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2,333,200 | Genomic sequence and expression profile of murine Bat1a and Nfkbil1. | In humans, susceptibility to several immunopathologic diseases maps to a conserved block encompassing the polymorphic BAT1, NFKBIL1 (IKBL) and TNF genes in the central MHC. As a pre-requisite for studies of these genes in animal models, we characterized Bat1a and Nfkbil1 in inbred mice differing in their H2 haplotype. We identified two indels and nine single nucleotide polymorphisms (SNP) upstream of Nfkbil1, one indel, nine SNP upstream of Bat1a and a synonymous SNP in exon 2 of Bat1a. H2(g7) and H2(b) mice yielded identical Bat1a and Nfkbil1 sequences. Real time PCR (RT-PCR) showed Bat1a was expressed in adult brain, heart, kidney, liver, lung, pancreas and spleen. Expression of Bat1a was higher in brain and liver of 15-day embryos compared to 1-day old mice and increased moderately in liver and lung of adult mice 2-4 h after LPS challenge. Nfkbil1 expression was low or undetetectable in all tissues and cell lines. |
2,333,201 | Heterogeneous ventricular chamber response to hypokalemia and inward rectifier potassium channel blockade underlies bifurcated T wave in guinea pig. | It was previously demonstrated that transmural electrophysiological heterogeneities can inscribe the ECG T wave. However, the bifurcated T wave caused by loss of inward rectifier potassium current (I(K1)) function is not fully explained by transmural heterogeneities. Since right ventricular (RV) guinea pig myocytes have significantly lower I(K1) than left ventricular (LV) myocytes, we hypothesized that the complex ECG can be inscribed by heterogeneous chamber-specific responses to hypokalemia and partial I(K1) blockade. Ratiometric optical action potentials were recorded from the epicardial surface of the RV and LV. BaCl(2) (10 micromol/l) was perfused to partially block I(K1) in isolated guinea pig whole heart preparations. BaCl(2) or hypokalemia alone significantly increased RV basal (RV(B)) action potential duration (APD) by approximately 30% above control compared with LV apical (LV(A)) APD (14%, P<0.05). In the presence of BaCl(2), 2 mmol/l extracellular potassium (hypokalemia) further increased RV(B) APD to a greater extent (31%) than LV(A) APD (19%, P<0.05) compared with BaCl(2) perfusion alone. Maximal dispersion between RV(B) and LV(A) APD increased by 105% (P<0.05), and the QT interval prolonged by 55% (P<0.05) during hypokalemia and BaCl(2). Hypokalemia and BaCl(2) produced an ECG with a double repolarization wave. The first wave (QT1) corresponded to selective depression of apical LV plateau potentials, while the second wave (QT2) corresponded to the latest repolarizing RV(B) myocytes. These data suggest that final repolarization is more sensitive to extracellular potassium changes in regions with reduced I(K1), particularly when I(K1) availability is reduced. Furthermore, underlying I(K1) heterogeneities can potentially contribute to the complex ECG during I(K1) loss of function and hypokalemia. |
2,333,202 | Cell death and apoptosis in osteoarthritic cartilage. | Osteoarthritis (OA) is the most common chronic joint disease in the elderly population, causing significant pain and disability. Because the cardinal feature of OA is a progressive loss of articular cartilage, a great portion of the research endeavour into the pathogenesis of OA has been focused on the regulation of matrix synthesis and degradation. The phenotypic stability and survival of the chondrocytes are essential for the maintenance of a proper cartilage matrix. This has lead to the long-standing assumption that cell death is a central feature in OA cartilage degeneration. The important role of apoptosis in OA has been demonstrated in in vitro and in vivo models. However, it should be noted that the relative contribution of apoptotic cell death in the pathogenesis of OA is still difficult to assess because of the chronic nature of the disease process. Therefore, the apoptosis of chondrocytes seems to be a potential target for therapeutic interventions in OA. The death receptor, mitochondrial and endoplasmic reticulum pathways are the major cellular pathways of apoptosis. Of all these elements involved in the apoptosis of chondrocytes, caspase inhibition has been studied with the most detail. Other molecules with the capacity to modulate mitochondria function, phosphatase (PP-1A/B) activity and pro-apoptosis stimuli (NO, prostaglandins, cytokines, ROS) could be excellent targets to block apoptosis of chondrocytes. Finally, the regulation of the natural inhibitors of apoptosis (c-FLIP, BAR, ARC and HC-gp39) could complement the other strategies to reduce cartilage degradation. |
2,333,203 | [Sedation and analgesia with propofol plus low-dose ketamine for retrobulbar block]. | To determine if adding ketamine to propofol provides better sedation than propofol alone for patients receiving a retrobulbar block for eye surgery.</AbstractText>Randomized double-blind trial enrolling 50 patients receiving a retrobulbar nerve block for eye surgery. Patients were randomly assigned to 2 groups. In the propofol group sedation was induced with 0.45 mg x kg(-1) of propofol. In the ketamine plus propofol group sedation was induced with 0.45 mg x kg(-1) of propofol plus 0.25 mg x kg(-1) of ketamine. We recorded patient characteristics (age, weight, ASA class, height, sex), hemodynamic variables (blood pressure, heart rate), puncture conditions, sedation (score on the Observer's Assessment of Alertness/Sedation [OAA/S] scale), ventilation (end-tidal carbon dioxide pressure, apneas, need for reanimation maneuvers, pulse oximetry), time until onset of effect, duration of effect, and amnesia.</AbstractText>No significant differences were observed in time to onset, duration of effect, patient characteristics, hemodynamic or respiratory variables, or amnesia. Sedation assessed on the OAA/S-scale was lower in the propofol group and the puncture conditions were significantly better in the ketamine plus propofol group. The only adverse psychomimetic reaction was transient agitation, observed in 2 propofol group patients.</AbstractText>Low doses of ketamine associated with propofol improve puncture conditions for performing a retrobulbar block without increasing unwanted side effects.</AbstractText> |
2,333,204 | Diabetes and hypoglycaemia in young children and mutations in the Kir6.2 subunit of the potassium channel: therapeutic consequences. | ATP-sensitive potassium channels (K(ATP)) couple cell metabolism to electrical activity by regulating potassium movement across the membrane. These channels are octameric complex with two kind of subunits: four regulatory sulfonylurea receptor (SUR) embracing four poreforming inwardly rectifying potassium channel (Kir). Several isoforms exist for each type of subunits: SUR1 is found in the pancreatic beta-cell and neurons, whereas SUR2A is in heart cells and SUR2B in smooth muscle; Kir6.2 is in the majority of tissues as pancreatic beta-cells, brain, heart and skeletal muscle, and Kir6.1 can be found in smooth vascular muscle and astrocytes. The K(ATP) channels play multiple physiological roles in the glucose metabolism regulation, especially in beta-cells where it regulates insulin secretion, in response to an increase in ATP concentration. They also seem to be critical metabolic sensors in protection against metabolic stress as hypo or hyperglycemia, hypoxia, ischemia. Persistent hyperinsulinemic hypoglycaemia (HI) of infancy is a heterogeneous disorder which may be divided into two histopathological forms (diffuse and focal lesions). Different inactivating mutations have been implicated in both forms: the permanent inactivation of the K(ATP) channels provokes inappropriate insulin secretion, despite low ATP. Diazoxide, used efficiently in certain cases of HI, opens the K(ATP) channels and therefore overpass the mutation effect on the insulin secretion. Conversely, several studies reported sequencing of KCNJ11, coding for Kir6.2, in patients with permanent neonatal diabetes mellitus and found different mutations in 30 to 50% of the cases. More than 28 heterozygous activating mutations have now been identified, the most frequent mutation being in the aminoacid R201. These mutations result in reduced ATP-sensitivity of the K(ATP) channels compared with the wild-types and the level of channel block is responsible for different clinical features: the "mild" form confers isolated permanent neonatal diabetes whereas the severe form combines diabetes and neurological symptoms such as epilepsy, deve-lopmental delay, muscle weakness and mild dimorphic features. Sulfonylureas close K(ATP) channels by binding with high affinity to SUR suggesting they could replace insulin in these patients. Subsequently, more than 50 patients have been reported as successfully and safely switched from subcutaneous insulin injections to oral sulfonylurea therapy, with an improvement in their glycated hemoglobin. We therefore designed a protocol to transfer and evaluate children who have insulin treated neonatal diabetes due to KCNJ11 mutation, from insulin to sulfonylurea. The transfer from insulin injections to oral glibenclamide therapy seems highly effective for most patients and safe. This shows how the molecular understan-ding of some monogenic form of diabetes may lead to an unexpected change of the treatment in children. This is a spectacular example by which a pharmacogenomic approach improves the quality of life of our young diabetic patients in a tremendous way. |
2,333,205 | Complete heart block associated with noncompaction, nail-patella syndrome, and mitochondrial myopathy. | Complete heart block has not been reported in association with left ventricular hypertrabeculation (LVHT)/noncompaction, nail-patella syndrome (NPS), and mitochondrial myopathy (MMP).</AbstractText>A 47-year-old man with congenital NPS from a 17-bp deletion in exon 5 of the LMX1B gene, MMP from the A3243G mitochondrial DNA transition, and LVHT was acutely admitted after a syncope followed by dizziness. Cardiological examinations revealed bradycardia. Blood pressure was 70/30 mm Hg. Blood work revealed a creatine kinase of 389 U/L (normal, <175 U/L), renal insufficiency, anemia, and reduced calcium, phosphorus, and magnesium. Electrocardiogram showed complete heart block with an escape rhythm of 30/min. A temporary pacemaker was inserted. During the procedure, the patient became asystole but was successfully resuscitated. One day later, he received a permanent pacemaker. Echocardiography showed normal systolic function and LVHT. The patient recovered without sequelae.</AbstractText>In single cases, LVHT may be associated with complete heart block. Most likely, complete heart block was due to MMP. Patients with NPS and MMP require multidisciplinary surveillance, including regular electrocardiograms, for indicating anticipatory intervention in time.</AbstractText> |
2,333,206 | Neuronal nitric oxide mediates cerebral vasodilatation during acute hypertension. | Parasympathetic nerves from the pterygopalatine ganglia provide nitroxidergic innervation to forebrain cerebral blood vessels. Disruption of that innervation attenuates cerebral vasodilatation seen during acute hypertension as does systemic administration of a non-selective nitric oxide synthase (NOS) inhibitor. Although such studies suggest that nitric oxide (NO) released from parasympathetic nerves participates in vasodilatation of cerebral vessels during hypertension, that hypothesis has not been tested with selective local inhibition of neuronal NOS (nNOS). We tested that hypothesis through these studies performed in anesthetized rats instrumented for continuous measurement of blood pressure, heart rate and pial arterial diameter through a cranial window. We sought to determine if the nNOS inhibitor propyl-L-arginine delivered directly to the outer surface of a pial artery would (1) attenuate changes in pial arterial diameter during acute hypertension and (2) block nNOS-mediated dilator effects of N-methyl-D-aspartate (NMDA) delivered into the window but (3) not block vasodilatation elicited by acetylcholine (ACh) and mediated by endothelial NOS dilator. Without the nNOS inhibitor arterial diameter abruptly increased 70+/-15% when mean arterial pressure (MAP) reached 183+/-3 mm Hg while with nNOS inhibition diameter increased only 13+/-10% (p<0.05) even when MAP reached 191+/-4 mm Hg (p>0.05). The nNOS inhibitor significantly attenuated vasodilatation induced by NMDA but not ACh delivered into the window. Thus, local nNOS inhibition attenuates breakthrough from autoregulation during hypertension as does complete interruption of the parasympathetic innervation of cerebral vessels. These findings further support the hypothesis that NO released from parasympathetic fibers contributes to cerebral vasodilatation during acute hypertension. |
2,333,207 | Different temporal expression of immunodominant Ro60/60 kDa-SSA and La/SSB apotopes. | Opsonization of apoptotic cardiocytes by maternal anti-Ro/SSA and anti-La/SSB antibodies contributes to tissue injury in the neonatal lupus syndrome. The objective of the current study was to quantify the surface membrane expression of Ro/La components during different phases of apoptosis and map the Ro/La apotopes (epitopes expressed on apoptotic cells) bound by cognate antibodies. Multi-parameter flow cytometry was used to define early and late apoptotic populations and their respective binding by monospecific anti-Ro and anti-La IgGs. Anti-Ro60 bound specifically to early apoptotic Jurkat cells and remained accessible on the cell surface throughout early and late apoptosis. In contrast, anti-La bound exclusively to late apoptotic cells in experiments controlled for non-specific membrane leakage of IgG. Ro52 was not accessible for antibody binding on either apoptotic population. The immunodominant NH2-terminal and RNA recognition motif (RRM) epitopes of La were expressed as apotopes on late apoptotic cells, confirming recent in vivo findings. An immunodominant internal epitope of Ro60 that contains the RRM, and is recognized by a majority of sera from mothers of children with congenital heart block (CHB) and patients with primary Sjögren's syndrome, was also accessible as an apotope on early apoptotic cells. The distinct temporal expression of the immunodominant Ro60 and La apotopes indicates that these intracellular autoantigens translocate independently to the cell surface, and supports a model in which maternal antibody populations against both Ro60 and La apotopes act in an additive fashion to increase the risk of tissue damage in CHB. |
2,333,208 | Physiological and subjective assessment of food grain handling workers in West Godavari district, India. | There are many rice mills and food grain depots where a large number of workers are engaged for processing paddy and rice, storage and distribution. Lifting, carrying and depositing sacs of food grain are the major jobs carried out by these workers. The present study was undertaken to evaluate the workers with respect to their nutritional status, workload, energy expenditure and musculoskeletal pain or discomfort resulting out of work practice. Average peak heart rate of the depot and rice mill workers suggested the workload as moderate to very heavy. Their average energy expenditure values also indicated the workload as moderate to heavy. Subjective assessment of the workers showed the workload as heavy for 60.7% depot workers and 23.1% rice mill workers. Musculoskeletal pain or discomfort was maximally reported in knee by 59% depot workers whereas low back and knee was reported by 61.5% rice mill workers. Besides the weight of the sac, awkward postures like bending and twisting of trunk adopted frequently causes the problem. Further studies and rationalization of work method may improve the health and safety of the workers. |
2,333,209 | Trendelenburg position with hip flexion as a rescue strategy to increase spinal anaesthetic level after spinal block. | When the level achieved by a spinal anaesthetic is too low to perform surgery, patients are usually placed in the Trendelenburg position. However, cephalad spread of the hyperbaric spinal anaesthetics may be limited by the lumbar lordosis. The Trendelenburg position with the lumbar lordosis flattened by hip flexion was evaluated as a method to extend the analgesic level after the administration of hyperbaric local anaesthetic.</AbstractText>When the pinprick block level was lower than T10 5 min after intrathecal injection of hyperbaric bupivacaine (13 mg), patients were recruited to the study and randomly allocated to one of the two positions: the Trendelenburg position with hip flexion (hip flexion group, n = 20) and the Trendelenburg position without hip flexion (control group, n = 20). Each assigned position was maintained for 5 min and then patients were returned to the horizontal supine position. Spinal block level was assessed by pinprick, cold sensation, and modified Bromage scale at intervals for the following 150 min.</AbstractText>The maximum level of pinprick and cold sensory block [median (range)] was higher in the hip flexion group [T4 (T8-C6) and T3 (T6-C2)] compared with the control group [T7 (T12-T4) and T5 (T11-T3)] (P < 0.001). The maximum motor blockade median (range) was not different between the two groups being 3 (3-3) in the hip flexion group vs 3 (0-3) in the control group.</AbstractText>When the level of spinal anaesthesia is lower than required, flexion of the hips in the Trendelenburg position may be useful as a strategy attempt to increase the level of the block.</AbstractText> |
2,333,210 | [Recombinant plasmid pIRES2-EGFP-HCN2 improved pacing function in canine model of sick sinus syndrome]. | To construct plasmid expressing pacemaker gene pIRES2-EGFP-HCN2 and study its effects in transfected atrial myocytes in vitro and in canine model of sick sinus syndrome (SSS).</AbstractText>mHCN2 gene was isolated from PTR plasmids and cloned into eukaryotic expression plasmid pIRES2-EGFP. Recombinant plasmids pIRES2-EGFP-HCN2 was transfected with by electroporation into neonatal atrial cardiomyocytes or injected to the sinoatrial (SA) region of canines with SSS induced by catheter and chemical ablation. pIRES2-EGFP-HCN2 expression was detected under fluorescence microscope and confirmed by reverse transcription-polymerase chain reaction (RT-PCR). Spontaneous beating rate in atrial cardiomyocytes was detected with light microscope.</AbstractText>EGFP expression was seen in transfected atrial cardiomyocytes 24 to 48 hours after transfection and the spontaneous beating rate was significantly increased than that in non-transfected atrial cardiomyocytes [(180 +/- 11) bpm vs (140 +/- 14) bpm, P < 0.05]. Heart rate was significantly increased 24 hours post recombinant plasmids pIRES2-EGFP-HCN2 injection compared to saline injection in canines with SSS [(150 +/- 13) bpm vs (105 +/- 17) bpm, P < 0.05]. Green fluorescence was also detected in frozen SA tissue sections of canines injected with recombinant plasmids pIRES2-EGFP-HCN2 and the production amplified by RT-PCR was about 300 bp which is consistent with mHCN2 gene fragment.</AbstractText>The recombinant eukaryotic expression plasmid pIRES2-EGFP-HCN2 can improve pacing function in atrial myocytes and in canine model of SSS.</AbstractText> |
2,333,211 | Screening for CHARGE syndrome mutations in the CHD7 gene using denaturing high-performance liquid chromatography. | Mutations in the CHD7 (chromodomain helicase DNA binding protein 7) gene cause CHARGE syndrome. At present, however, genetic testing of the CHD7 gene is not commonly applied in clinical settings because the currently available assays are technically and financially demanding, mainly because of the size of the gene. In the present study, we optimized the highly sensitive and specific mutation scanning method automated denaturing high-performance liquid chromatography (DHPLC) to analyze the entire coding region of CHD7. The coding region was amplified by 39 primer pairs, all of which have the same cycling conditions, aliquoted on a 96-well format polymerase chain reaction (PCR) plate. In this manner, all of the exons were amplified simultaneously using a single block in a thermal cycler. We then wrote a computer script to analyze each segment of the CHD7 gene by DHPLC in a serial manner using conditions that were optimized for each amplicon. The implementation of this screening method for CHD7 will help medical geneticists confirm their clinical impressions and provide accurate genetic counseling to the patients with CHARGE syndrome and their families. |
2,333,212 | Influence of swimming speed on metabolic rates of juvenile pacific bluefin tuna and yellowfin tuna. | Bluefin tuna are endothermic and have higher temperatures, heart rates, and cardiac outputs than tropical tuna. We hypothesized that the increased cardiovascular capacity to deliver oxygen in bluefin may be associated with the evolution of higher metabolic rates. This study measured the oxygen consumption of juvenile Pacific bluefin Thunnus orientalis and yellowfin tuna Thunnus albacares swimming in a swim-tunnel respirometer at 20 degrees C. Oxygen consumption (Mo2) of bluefin (7.1-9.4 kg) ranged from 235+/-38 mg kg(-1) h(-1) at 0.85 body length (BL) s(-1) to 498+/-55 mg kg(-1) h(-1) at 1.80 BL s(-1). Minimal metabolic rates of swimming bluefin were 222+/-24 mg O(2) kg(-1) h(-1) at speeds of 0.75 to 1.0 BL s(-1). Mo2 of T. albacares (3.7-7.4 kg) ranged from 164+/-18 mg kg(-1) h(-1) at 0.65 BL s(-1) to 405+/-105 mg kg(-1) h(-1) at 1.8 BL s(-1). Bluefin tuna had higher metabolic rates than yellowfin tuna at all swimming speeds tested. At a given speed, bluefin had higher metabolic rates and swam with higher tailbeat frequencies and shorter stride lengths than yellowfin. The higher M dot o2 recorded in Pacific bluefin tuna is consistent with the elevated cardiac performance and enhanced capacity for excitation-contraction coupling in cardiac myocytes of these fish. These physiological traits may underlie thermal-niche expansion of bluefin tuna relative to tropical tuna species. |
2,333,213 | Identification of an inhibitor of caspase activation from heart extracts; ATP blocks apoptosome formation. | By revealing the biochemistry of apoptosis it is expected we will both improve our understanding of diseases where apoptosis plays an important role and aid the development of therapies for these disorders. Caspases are a family of proteases whose activity is required for apoptosis. In this study, a cell-free system was used to investigate the mechanism of caspase-9 activation in extracts from heart cells. Unlike extracts from other cell types, heart extracts were found to activate caspases poorly. This could be explained by the low levels of Apaf-1 in heart cells. However, subsequent testing showed that heart extracts contained an inhibitor of caspase activation that could block caspase activation in extracts from different cell types. Subsequent purification of the inhibitor of caspase activation from these extracts identified ATP. Caspase-9 is activated by recruitment into a multi-protein complex, the apoptosome, which then activates downstream caspases that kill the cell. Importantly, size exclusion chromatography showed that ATP inhibits apoptosome formation at physiologically relevant concentrations. Together these data support the hypothesis that intracellular ATP concentration is a critical factor in determining whether an apoptotic stimulus can induce apoptosome formation. Thus, the well described fall in intracellular ATP apoptosis is not an epiphenomenon but may be a pro-apoptotic event contributing to cell death. |
2,333,214 | Metabolic domino: new concept in lifestyle medicine. | A new concept has been proposed to capture the flow of events and chain reactions associated with cardiovascular risk: the metabolic domino. The metabolic domino differs for each individual based on their genetic predisposition. Lifestyle changes are the first dominoes to fall, which lead to obesity and insulin resistance, followed by postprandial hyperglycemia, hypertension, and hyperlipidemia. Atherosclerosis then begins, and diabetes occurs once the domino for impairment of insulin secretion has toppled. Progression of the atherosclerotic process can lead to cardiovascular events such as ischemic heart diseases or cerebrovascular disorders. Preclinical and clinical data indicate that treatments which inhibit the renin angiotensin system, such as angiotensin receptor blockers, can suppress the onset of diabetes and, when administered even earlier in the metabolic domino, reduce the development of hypertension in at-risk individuals. The inhibition of inflammation with thiazolidinedione can also block the sequence of events leading to cardiovascular outcomes, as was shown with pioglitazone in the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive). |
2,333,215 | Effects of dexmedetomidine on the duration of anaesthesia and wakefulness in bupivacaine epidural block. | The purpose of this study was to examine the effects of intravenous dexmedetomidine on the duration of bupivacaine-induced epidural anaesthesia and level of wakefulness and the respective side-effects.</AbstractText>Sixty ASA I-II patients were included in the study. Consecutive patients were allocated to groups according to the last digit (odd/even) of their admission numbers. All patients had epidural anaesthesia with bupivacaine 0.5% performed by the same experienced anaesthesiologist. In the first group, the patients were administered intravenous dexmedetomidine infusion just after the epidural block and continued during the operation, while those in the second group were administered physiologic saline infusion at the same amount and duration.</AbstractText>The recovery time of sensory block was significantly longer in the first group. The bispectral index values were lower in the first group than in the second. Also, heart rate was significantly lower in Group I than in Group II. Regarding side-effects, shivering was significantly less frequent in the first group, whereas there was a significant increase in the requirement of atropine in the first group as dexmedetomidine caused bradycardia.</AbstractText>Intravenous administration of dexmedetomidine prolonged the duration of epidural anaesthesia, provided sedation and had few side-effects.</AbstractText> |
2,333,216 | RhoA/Rho kinase up-regulate Bax to activate a mitochondrial death pathway and induce cardiomyocyte apoptosis. | The small G-protein RhoA regulates the actin cytoskeleton, and its involvement in cell proliferation has also been established. In contrast, little is known about whether RhoA participates in cell survival or apoptosis. In cardiomyocytes in vitro, RhoA induces hypertrophic cell growth and gene expression. In vivo, however, RhoA expression leads to development of heart failure (Sah, V. P., Minamisawa, S., Tam, S. P., Wu, T. H., Dorn, G. W., Ross, J. Jr., Chien, K. R., and Brown, J. H. (1999) J. Clin. Investig. 103, 1627-1634), a condition widely associated with cardiomyocyte apoptosis. We demonstrate here that adenoviral overexpression of activated RhoA in cardiomyocytes induces hypertrophy, which transitions over time to apoptosis, as evidenced by caspase activation and nucleosomal DNA fragmentation. The Rho kinase inhibitors Y-27632 and HA-1077 and expression of a dominant negative Rho kinase block these responses. Caspase-9, but not caspase-8, is activated, and its inhibition prevents DNA fragmentation, consistent with involvement of a mitochondrial death pathway. Interestingly, RhoA expression induces a 3-4-fold up-regulation of the proapoptotic Bcl-2 family protein Bax. RhoA also increases levels of activated Bax and the amount of Bax protein localized at mitochondria. Bax mRNA is increased by RhoA, indicating transcriptional regulation, and the ability of a dominant negative p53 mutant to block Bax up-regulation implicates p53 in this response. The involvement of Bax in RhoA-induced apoptosis was examined by treatment with a Bax-inhibitory peptide, which was found to significantly attenuate DNA fragmentation and caspase-9 and -3 activation. The dominant negative p53 also prevents RhoA-induced apoptosis. We conclude that RhoA/Rho kinase activation up-regulates Bax through p53 to induce a mitochondrial death pathway and cardiomyocyte apoptosis. |
2,333,217 | Biological pacemaking: a concept whose time has come...or is coming. | "..when biological pacemakers reach clinical testing it is likely that some form of tandem therapy [with electronic pacemakers] will be used.." |
2,333,218 | The impact of aberration on high frame rate cardiac B-mode imaging. | In echocardiography, especially in 3D echocardiography, achieving high frame rates is a major challenge. A suggested solution is parallel receive beamforming. Without any compensation, this approach is known to produce block-like artifacts, where each block corresponds to one parallel receive group. In this work, in vitro imaging, in vivo imaging, and simulations were used to investigate the artifacts. In vitro, imaging a tissue phantom, the artifacts were successfully compensated for. However, in vivo, imaging the heart, the compensation techniques no longer sufficed and the artifacts persisted. With in vivo imaging, aberrating tissue layers are present between the heart and the probe. To investigate the effects of aberration on a parallel receive system, an in vitro experiment was performed with and without a silicon phase aberrator in front of the probe. The aberrator caused the artifacts to appear even when compensation techniques were applied. Simulations confirmed the measured results and indicated that distorted beam profiles and decorrelation between parallel receive groups caused the artifacts. To quantify the magnitude of the artifacts, a correlation-based indicator was developed. The indicator separated images with and without artifacts and confirmed that the artifacts appeared from the combination of parallel receive beams and aberration. |
2,333,219 | Attenuation of ischemia/reperfusion injury in rats by the anti-inflammatory action of resveratrol. | Resveratrol (trans-3,4',5-trihydroxystilbene, CAS 501-36-0), a natural antioxidant and polyphenol found in grapes and wine, has been found to pharmacologically precondition the heart in nitric oxide (NO)-dependent manner. In the vascular system, NO functions as an endogenous inhibitor of leukocyte chemotaxis, adherence, and activation. The present study was designed to determine if resveratrol, through NO, can block the proadhesive molecules generated in the ischemic reperfused myocardium. Isolated hearts were prepared from properly anesthetized rats, and mounted on a Langendorff apparatus. The hearts were randomly assigned to one of the three groups: (i) control, (ii) resveratrol, and (iii) resveratrol + NG-nitro-L-arginine ethyl ester (L-NAME). The hearts were perfused in the absence (n = 6) or presence of 10 micromol/L resveratrol (n=6) or resveratrol + L-NAME (n = 6) for 15 min. All the hearts were then subjected to 30 min ischemia followed by 2 h of reperfusion. Ventricular function was monitored, infarct size and apoptotic cell death measured, and the proadhesive molecules and malonaldehyde formation determined in the perfusate. Resveratrol significantly improved postischemic ventricular function and reduced myocardial infarct size compared to the non-treated control group. The amount of proadhesive molecules including soluble intracellular adhesion molecule-1 (sICAM-1), endothelial leukocyte adhesion molecule-1 (sE-Selectin) and vascular cell adhesion molecule-1 (sVCAM-1) were each significantly decreased during reperfusion in the resveratrol group. L-NAME, a NO blocker, completely abolished such beneficial effects of resveratrol. The results support an anti-inflammatory action of resveratrol through a NO-dependent mechanism. |
2,333,220 | Frequency-dependent effects of various IKr blockers on cardiac action potential duration in a human atrial model. | Rapidly activating K(+) current (I(Kr)) blockers prolong action potential (AP) duration (APD) in a reverse-frequency-dependent manner and may induce arrhythmias, including torsade de pointes in the ventricle. The I(Kr) blocker dofetilide has been approved for treatment of atrial arrhythmias, including fibrillation. There are, however, a limited number of studies on the action of I(Kr) blockers on atrial AP. When we tested a mathematical model of the human atrial AP (M Courtemanche, RJ Ramirez, S Nattel. Am J Physiol Heart Circ Physiol 275: H301-H321, 1998) to examine the effects of dofetilide-type I(Kr) blockade, this model could not reproduce the reverse-frequency-dependent nature of I(Kr) blockade on atrial APD. We modified the model by introducing a slowly activating K(+) current activation parameter. As the slow time constant was increased, dofetilide-type blockade induced more prominent reverse-frequency-dependent APD prolongation. Using the modified model, we also examined the effects of two more types of I(Kr) blockade similar to those of quinidine and vesnarinone. Voltage- and time-dependent block of I(Kr) through the onset of inhibition by quinidine is much faster than by vesnarinone. When we incorporated the kinetics of the effects of these drugs on I(Kr) into the model, we found that quinidine-type blockade caused a reverse-frequency-dependent prolongation of APD that was similar to the effect of dofetilide-type blockade, whereas vesnarinone-type blockade did not. This finding coincides with experimental observations. The lack of the reverse frequency dependence in vesnarinone-type blockade was accounted for by the slow development of I(Kr) blockade at depolarized potentials. These results suggest that the voltage- and time-dependent nature of I(Kr) blockade by drugs may be critical for the phenotype of the drug effect on atrial AP. |
2,333,221 | Autonomic effects of epidural and intravenous fentanyl. | We tested the hypothesis that there is greater suppression of autonomic reflexes during general anaesthesia when fentanyl is administered epidurally than when it is given intravenously.</AbstractText>Ten volunteers were anaesthetized with desflurane. Noxious stimuli of variable intensity were then delivered by tetanic electrical stimuli. Heart rate, arterial pressure, and pupillary dilation in response to these stimuli defined nociception. Seven of these volunteers participated twice using a crossover design: they received i.v. fentanyl on one study day and epidurally on the other. Autonomic responses to alternative tetanic stimuli at L4 and C5 dermatomes were measured every 5 min for 3 h after fentanyl administration.</AbstractText>After a brief redistribution period, plasma fentanyl concentrations were virtually identical on both days. After stimulation of the L4 dermatome only, block of pupillary reflex dilation was greater by 47 (22)% after epidural fentanyl compared with i.v. fentanyl. Time to maximal depression of reflex dilation after L4 stimulation was 41 (13) min. Arterial pressure and heart rate decreased after fentanyl by either route but there were no differences observed between L4 and C5 stimulations.</AbstractText>We conclude that during general anaesthesia, epidural fentanyl enhances antinociception by a spinal mechanism which can be detected by pupillary dilation but not by changes in arterial pressure or heart rate.</AbstractText> |
2,333,222 | Structure-based rational quest for potential novel inhibitors of human HMG-CoA reductase by combining CoMFA 3D QSAR modeling and virtual screening. | 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) catalyzes the formation of mevalonate. In many classes of organisms, this is the committed step leading to the synthesis of essential compounds, such as cholesterol. However, a high level of cholesterol is an important risk factor for coronary heart disease, for which an effective clinical treatment is to block HMGR using inhibitors like statins. Recently the structures of catalytic portion of human HMGR complexed with six different statins have been determined by a delicate crystallography study (Istvan and Deisenhofer Science 2001, 292, 1160-1164), which established a solid basis of structure and mechanism for the rational design, optimization, and development of even better HMGR inhibitors. In this study, three-dimensional quantitative structure-activity relationship (3D QSAR) with comparative molecular field analysis (CoMFA) was performed on a training set of up to 35 statins and statin-like compounds. Predictive models were established by using two different ways: (1) Models-fit, obtained by SYBYL conventional fit-atom molecular alignment rule, has cross-validated coefficients (q2) up to 0.652 and regression coefficients (r2) up to 0.977. (2) Models-dock, obtained by FlexE by docking compounds into the HMGR active site, has cross-validated coefficients (q2) up to 0.731 and regression coefficients (r2) up to 0.947. These models were further validated by an external testing set of 12 statins and statin-like compounds. Integrated with CoMFA 3D QSAR predictive models, molecular surface property (electrostatic and steric) mapping and structure-based (both ligand and receptor) virtual screening have been employed to explore potential novel hits for the HMGR inhibitors. A representative set of eight new compounds of non-statin-like structures but with high pIC(50) values were sorted out in the present study. |
2,333,223 | [Effect of electroacupuncture on bispectral index of electroencephalography in patients undergoing subtotal thyroidectomy]. | To investigate the effects of electroacupuncture on bispectral index (BIS) of electroencephalography in patients undergoing subtotal thyroidectomy.</AbstractText>Sixty patients were equally randomized into group A given electroacupuncture combined with cervical plexus block (CPB) and group B given CPB alone. After needling sensation was reached in bilateral "Hegu" and "Neiguan" acupoints, 5 min of high frequency electrical stimulation by electrical stimulation device followed with CPB was applied to group A, while only CPB was performed in group B. Visual analog scale (VAS) and verbal stress scale (VSS) were monitored, complication and adverse reaction were observed and BIS, mean arterial pressure (MAP), heart rate (HR) and arterial oxygen saturation (SaO2) were monitored continuously in the perioperative period.</AbstractText>HR increased and BIS decreased in group A, both were lower significantly than those in group B (P < 0.01); MAP, the complementary dosage of fentanyl and lidocaine used and scores of VAS and VSS were also lower in group A than those in group B (P < 0.01).</AbstractText>Electroacupuncture could enhance the anesthetic effect of CPB, lower the BIS value during subtotal thyroidectomy.</AbstractText> |
2,333,224 | Discovery of a small-molecule inhibitor for kidney ADP-ribosyl cyclase: Implication for intracellular calcium signal mediated by cyclic ADP-ribose. | ADP-ribosyl cyclase (ADPR-cyclase) produces a Ca2+-mobilizing second messenger, cyclic ADP- ribose (cADPR), from beta-NAD+. A prototype of mammalian ADPR-cyclases is a lymphocyte antigen CD38. Accumulating evidence indicates that ADPR-cyclases other than CD38 are expressed in various cells and organs. In this study, we discovered a small molecule inhibitor of kidney ADPR-cyclase. This compound inhibited kidney ADPR-cyclase activity but not CD38, spleen, heart or brain ADPR-cyclase activity in vitro. Characterization of the compound in a cell-based system revealed that an extracellular calcium-sensing receptor (CaSR)- mediated cADPR production and a later long-lasting increase in intracellular Ca2+ concentration ([Ca2+]i) in mouse mesangial cells were inhibited by the pre-treatment with this compound. In contrast, the compound did not block CD3/TCR-induced cADPR production and the increase of [Ca2+]i in Jurkat T cells, which express CD38 exclusively. The long-lasting Ca2+ signal generated by both receptors was inhibited by pre-treatment with an antagonistic cADPR derivative, 8-Br-cADPR, indicating that the Ca2+ signal is mediated by the ADPR-cyclase metabolite, cADPR. Moreover, among structurally similar compounds tested, the compound inhibited most potently the cADPR production and Ca2+ signal induced by CaSR. These findings provide evidence for existence of a distinct ADPR-cyclase in the kidney and basis for the development of tissue specific inhibitors. |
2,333,225 | Epithelial sodium channel inhibition in cardiovascular disease. A potential role for amiloride. | Amiloride was originally described in 1967 as a potassium-sparing diuretic, the mechanism of action of which is to block the epithelial sodium channel (ENaC) within the distal tubule of the kidney. In addition, higher doses of amiloride were found to be capable of inhibiting the Na(+)/H(+) exchangers (NHE) and the Na(+)/Ca(2+) exchangers. In time, several amiloride analogs have been synthesized to have a marked increase in their specificity to inhibit the ENaC, the NHE or the Na(+)/Ca(2+) exchangers. Although the NHE inhibitors have received the most recent attention, large-scale clinical trials using NHE inhibitors in ischemic cardiac states have shown them to be either ineffective or associated with an unacceptable risk profile. Aldosterone excess in animal models is known to cause cardiovascular injury, and blockade of mineralocorticoid receptors in human beings with heart disease improves outcomes. However, the exact mechanisms of aldosterone injury in animal models of hypertensive disease and protection with mineralocorticoid receptor antagonists in human trials of heart failure remain unknown. These effects are unexplained by changes in BP, potassium, or sodium balance. An additional possibility is that aldosterone action and mineralocorticoid receptor blockade is conferred by alterations in ENaC activity. Emerging experimental evidence suggests the possibility that systemic or central ENaC inhibition or both may be an alternative to the treatment of hypertension and cardiovascular disease states. Clinical trials to evaluate further the potential beneficial cardiovascular effects of ENaC blockade are needed. This article reviews the case for ENaC inhibition as a potential target for cardiovascular and renal protection in human beings. |
2,333,226 | Intrathecal plain vs hyperbaric bupivacaine for labour analgesia: efficacy and side effects. | Baricity is an important determinant of block characteristics of the spinal component of a combined spinal epidural (CSE) for labour analgesia. This study compares the analgesic efficacy and side effects of intrathecally administered plain and hyperbaric bupivacaine (both with fentanyl) during active labour.</AbstractText>Sixty-two women in active labour (cervical dilatation >or=5 cm and pain score > 5) were randomized in a prospective, single-blinded fashion to receive 2.5 mg of either hyperbaric or plain bupivacaine both combined with 15 microg of fentanyl as the spinal component of a CSE. The primary outcome was failure of satisfactory analgesia within ten minutes of the intrathecal injection as defined by a verbal pain score > 3. Secondary outcomes included need for rescue analgesia, hypotension, respiratory depression, nausea and vomiting, pruritus and sustained fetal bradycardia.</AbstractText>Sixty patients were analyzed. The failure rates were 20% in the hyperbaric group vs 0% in the plain group (P=0.024). The plain solution provided faster onset, higher sensory levels and less motor block at all times during the first 30 min. The incidence of both pruritus and sustained fetal bradycardia was 33% in the plain group and 10% in the hyperbaric group (P=0.03).</AbstractText>A plain rather than hyperbaric solution of bupivacaine 2.5 mg with fentanyl 15 microg provides a faster onset of analgesia, higher sensory levels and less motor block, while demonstrating an increased incidence of pruritus and sustained fetal bradycardia.</AbstractText> |
2,333,227 | Cardiomyopathy of Duchenne muscular dystrophy: pathogenesis and prospect of membrane sealants as a new therapeutic approach. | Duchenne muscular dystrophy (DMD) is a devastating progressive disease of striated muscle deterioration. This fatal X-linked disorder results from the loss of the protein dystrophin, which in turn causes striated muscle membrane instability. Cardiac dysfunction is a growing problem in patients with DMD, but relatively little is known about the pathophysiology of the dystrophic heart. At present, there is no effective treatment for DMD and the current clinical approaches are primarily supportive in nature. This review will discuss the pathogenesis of DMD in the heart and discuss how these pathogenic processes have led to a new class of agents directed specifically at restoring membrane integrity to dystrophic myocardium. The tri-block poloxamers, specifically poloxamer 188 (P188), are able to stabilize the membranes of dystrophic myocardium in animal models and may offer a new therapeutic approach for cardiac disease in DMD. |
2,333,228 | Hypoxia reoxygenation induces premature senescence in neonatal SD rat cardiomyocytes. | To investigate whether hypoxia reoxygenation induces premature senescence in neonatal Sprague-Dawley (SD) rat cardiomyocytes.</AbstractText>Cardiomyocytes were isolated from neonatal SD rat heart and identified by immunohistochemistry. The control cultures were incubated at 37 degree centigrade in a humidified atmosphere of 5% CO(2) and 95% air. The hypoxic cultures were incubated in a modular incubator chamber filled with 1% O(2), 5% CO(2), and balance N2 for 6 h. The reoxygenated cultures were subjected to 1% O(2) and 5% CO(2) for 6 h, then 21% oxygen for 4, 8, 12, 24, and 48 h, respectively. Cell proliferation was determined using bromodeoxyuridine labeling. The ultrastructure of cardiomyocytes was observed by using an electron microscope. beta-Galactosidase activity was determined by using a senescence beta-galactosidase Staining Kit. p16( INK4a ) and telomerase reverse transcriptase (TERT) mRNA levels were measured by real time quantitative PCR. TERT protein expression was determined by immunohistochemistry. Telomerase activities were assayed by using the Telo TAGGG Telomerase PCR ELISAplus kit.</AbstractText>The initial cultures consisted of pure cardiomyocytes identified by immunohistochemistry. The proportion of BrdU positive cells was reduced significantly in the hypoxia reoxygenation-treated group (P< 0.01). Under the condition of hypoxia reoxygenation, mitochondrial dehydration appeared; p16( INK4a ) and TERT mRNA levels, beta-galactosidase activity, TERT protein expression and telomerase activities were all significantly increased (P< 0.01 or P< 0.05).</AbstractText>These data indicate that premature senescence could be induced in neonatal SD rat cardiomyocytes exposed to hypoxia reoxygenation. Although TERT significantly increased, it could not block senescence.</AbstractText> |
2,333,229 | Novel point mutation in the NKX2-5 gene in a Moroccan family with atrioventricular conduction disturbance and an atrial septal defect in the oval fossa.<Pagination><StartPage>107</StartPage><EndPage>109</EndPage><MedlinePgn>107-9</MedlinePgn></Pagination><Abstract><AbstractText>Defects of the oval fossa usually occur as isolated malformations, but can show an autosomal dominant pedigree in familial cases. Several mutations have been described for the transcription factor NKX2-5, and co-segregate with varied cardiac anomalies. We have identified by sequence analysis a novel missense heterozygous mutation in the NKX2-5 gene, specifically a substitution of glutamine for proline at codon 160, in a Moroccan family, the affected members having a deficiency of the floor of the oval fossa and atrioventricular block.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rifai</LastName><ForeName>Laïla</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Medical Genetics, National Institute of Health, Rabat, Morocco. laila.rifai@gmail.com</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maazouzi</LastName><ForeName>Wajih</ForeName><Initials>W</Initials></Author><Author ValidYN="Y"><LastName>Sefiani</LastName><ForeName>Abdelaziz</ForeName><Initials>A</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2006</Year><Month>12</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Cardiol Young</MedlineTA><NlmUniqueID>9200019</NlmUniqueID><ISSNLinking>1047-9511</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000072576">Homeobox Protein Nkx-2.5</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018398">Homeodomain Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C095552">NKX2-5 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014157">Transcription Factors</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001283" MajorTopicYN="N">Atrioventricular Node</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006329" MajorTopicYN="N">Heart Conduction System</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006344" MajorTopicYN="N">Heart Septal Defects, Atrial</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000072576" MajorTopicYN="N">Homeobox Protein Nkx-2.5</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018398" MajorTopicYN="N">Homeodomain Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009018" MajorTopicYN="N">Morocco</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010375" MajorTopicYN="N">Pedigree</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017354" MajorTopicYN="N">Point Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014157" MajorTopicYN="N">Transcription Factors</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="accepted"><Year>2006</Year><Month>4</Month><Day>5</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>12</Month><Day>23</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>5</Month><Day>4</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>12</Month><Day>23</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17184575</ArticleId><ArticleId IdType="doi">10.1017/S1047951106001338</ArticleId><ArticleId IdType="pii">S1047951106001338</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17184062</PMID><DateCompleted><Year>2007</Year><Month>02</Month><Day>12</Day></DateCompleted><DateRevised><Year>2006</Year><Month>12</Month><Day>22</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>5</Issue><PubDate><Year>2006</Year><Season>Sep-Oct</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Subarachnoidal anesthesia in patients with concomitant diseases of the cardiovascular system]. | Defects of the oval fossa usually occur as isolated malformations, but can show an autosomal dominant pedigree in familial cases. Several mutations have been described for the transcription factor NKX2-5, and co-segregate with varied cardiac anomalies. We have identified by sequence analysis a novel missense heterozygous mutation in the NKX2-5 gene, specifically a substitution of glutamine for proline at codon 160, in a Moroccan family, the affected members having a deficiency of the floor of the oval fossa and atrioventricular block.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rifai</LastName><ForeName>Laïla</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Medical Genetics, National Institute of Health, Rabat, Morocco. laila.rifai@gmail.com</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maazouzi</LastName><ForeName>Wajih</ForeName><Initials>W</Initials></Author><Author ValidYN="Y"><LastName>Sefiani</LastName><ForeName>Abdelaziz</ForeName><Initials>A</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2006</Year><Month>12</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Cardiol Young</MedlineTA><NlmUniqueID>9200019</NlmUniqueID><ISSNLinking>1047-9511</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000072576">Homeobox Protein Nkx-2.5</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018398">Homeodomain Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C095552">NKX2-5 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014157">Transcription Factors</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001283" MajorTopicYN="N">Atrioventricular Node</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006329" MajorTopicYN="N">Heart Conduction System</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006344" MajorTopicYN="N">Heart Septal Defects, Atrial</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000072576" MajorTopicYN="N">Homeobox Protein Nkx-2.5</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018398" MajorTopicYN="N">Homeodomain Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009018" MajorTopicYN="N">Morocco</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010375" MajorTopicYN="N">Pedigree</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017354" MajorTopicYN="N">Point Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014157" MajorTopicYN="N">Transcription Factors</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="accepted"><Year>2006</Year><Month>4</Month><Day>5</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>12</Month><Day>23</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>5</Month><Day>4</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>12</Month><Day>23</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17184575</ArticleId><ArticleId IdType="doi">10.1017/S1047951106001338</ArticleId><ArticleId IdType="pii">S1047951106001338</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17184062</PMID><DateCompleted><Year>2007</Year><Month>02</Month><Day>12</Day></DateCompleted><DateRevised><Year>2006</Year><Month>12</Month><Day>22</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>5</Issue><PubDate><Year>2006</Year><Season>Sep-Oct</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal><ArticleTitle>[Subarachnoidal anesthesia in patients with concomitant diseases of the cardiovascular system].</ArticleTitle><Pagination><StartPage>44</StartPage><EndPage>48</EndPage><MedlinePgn>44-8</MedlinePgn></Pagination><Abstract>Age-related changes limit blood circulatory reserves in vital organs, by increasing the risk of ischemic and hypoxic lesions. Patients from a peripheral vascular surgery department form a high cardiac risk group. Subarachnoidal anesthesia is the most optimal anesthetic support (if there are no absolute contraindications) during operations for lower extremity varicose veins. Thirty patients operated on for this condition were examined to solve the problem associated with the effectiveness and safety of this method of anesthesia and to define the pattern of hemodynamic rearrangement more precisely. All the patients had concomitant cardiovascular diseases, which forced them to be referred to as ASA Classes III-IV. The authors monitored basic hemodynamic parameters, such as systolic blood pressure (BP), diastolic BP, mean BP (BP(mean)), heart rate, and cardiac output, by using a noninvasive procedure by means of a computer equipped with a Doppler flowmetric transducer, and ST-segment changes by ECG). The values of total and specific peripheral vascular resistance and cardiac index were estimated by a calculating method. Analysis of hemodynamic changes revealed no significant differences between the groups of elderly and senile patients. On examination, all the patients were divided into 2 groups by the type of circulation: 1) those with eukinetic circulation and 2) those with hypokinetic circulation. Hyperkinetic circulation was not found in the study groups of patients. The patients with cardiac disease were observed to have increased vascular resistance, in those with hypokinetic circulation, this increase being more marked (p < 0.05). In addition, ST-segment had a more stable position in patients with hypokinetic circulation. There was a great scatter in ST-segment changes in patients with eukinetic circulation in the presence of decreased peripheral resistance under preganglionic sympathetic block. With the described changes, noteworthy was the stability of BP(mean) values that did not decreased below the critical ones. This fact permitted the authors to state that the compensatory reserves of the cardiovascular system were preserved under subarachnoidal blockade, which in turn suggests the effectiveness and safety of the used anesthetic procedure. |
2,333,230 | Altered Ca(2+) handling by ryanodine receptor and Na(+)-Ca(2+) exchange in the heart from ovariectomized rats: role of protein kinase A. | Our previous study has demonstrated that ovariectomy (Ovx) significantly increased the left ventricular developed pressure (LVDP) and the maximal rate of developed pressure over time (+/-dP/dt(max)) in the isolated perfused rat heart and the effects were reversed by female sex hormone replacement. In the present investigation, we studied the effects of Ovx for 6 wk on Ca(2+) homeostasis that determines the contractile function. Particular emphasis was given to Ca(2+) handling by ryanodine receptor (RyR) and Na(+)-Ca(2+) exchange (NCX). (45)Ca(2+) fluxes via the RyR, NCX, and Ca(2+)-ATPase (SERCA) were compared with their expression in myocytes from Ovx rats with and without estrogen replacement. Furthermore, we correlated the handling of Ca(2+) by these Ca(2+) handling proteins with the overall Ca(2+) homeostasis by determining the Ca(2+) transients induced by electrical stimulation and caffeine, which reveals the dynamic changes of cytosolic Ca(2+) concentration ([Ca(2+)](i)) in the heart. In addition, we determined the expression and contribution of protein kinase A (PKA) to the regulation of the aforementioned Ca(2+) handling proteins in Ovx rats. It was found that after Ovx there were 1) increased Ca(2+) fluxes via RyR and NCX, which were reversed not only by estrogen replacement, but more importantly by blockade of PKA; 2) an increased expression of PKA; and 3) no increase in expression of NCX and SERCA. We suggest that hyperactivities of RyR and NCX are a result of upregulation of PKA. The increased release of Ca(2+) through RyR and removal of Ca(2+) by NCX are believed to be responsible for the greater contractility and faster relaxation after Ovx. |
2,333,231 | [Chronic progressive external ophthalmoplegia: clinical and electromyographic manifestations in a series of cases]. | Chronic progressive external ophthalmoplegia (CPEO) is a common mitochondrial disease. The different conditions in this group of diseases overlap clinically, enzymatically and genetically. There is no effective treatment. Ptosis improves with corrective surgery involving tarsorrhaphy as a palliative measure.</AbstractText>Code numbers were examined in a retrospective study conducted in order to search for patients with ptosis or ophthalmoplegia who had either visited or been admitted to the neurology department over the last 10 years. Data concerning these patients' clinical features and results of complementary tests were collected. Six patients with CPEO were identified, five of whom were females. Ages ranged from 44 to 72 years. All the patients had ptosis, although 50% were asymmetric. Half of them reported mild dysphagia while swallowing liquids. Levels of creatine phosphokinase and acetylcholine antireceptor antibodies were normal. Half the patients showed increased jitter and a muscle biopsy revealed that five of them had ragged red fibres. The most frequent enzyme deficit was complex I and IV deficiency. There were no familial forms; the most common genetic anomaly was single deletion in the mitochondrial deoxyribonucleic acid.</AbstractText>In cases of ptosis and ophthalmoplegia that do not respond to anticholinesterases, knowledge of this condition makes it possible to avoid the use of immunosuppressant drugs, which have important side effects.</AbstractText> |
2,333,232 | [Torasemide--new generation loop diuretic: clinical pharmacology and therapeutic application]. | Peculiarities of clinical pharmacology of new generation loop diuretic torasemide and its possible place in the treatment of arterial hypertension, chronic heart failure (CHF) and liver cirrhosis are considered. Main advantage of torasemide over loop diuretics of furosemide and bumetamide type is that in addiction to powerful diuretic and natriuretic actions it produces potassium sparing effect that is explainded by ability its of to tosasimide to block aldosterone receptors in renal tubules. Moreover torasemide exerts longer action than furosemide and bumetamide what allows to take it once a day. In low doses torasemide produces pronounced antihypertensive effect without augmentation of excretion of potassium and water with urine. Because of this it can be used as antihypertensive drug for monotherapy or in combination with other drugs. Contrary to thiazide and loop diuretics prescription of subdiuretic doses of torasemide usually does not require control of potassium content in the blood or addition of potassium preparations. In higher doses (10 mg/day or more) torasemide acts as typical loop diuretic and can be used in the treatment of CHF and liver cirrhosis with ascites. Due to potassium sparing action it more rarely than furosemide and bumetamide causes hypokalemia. Comparative studies have shown than in CHF torasemide exerts more favorable effect on clinical signs of disease and functional status of patients than furosemide. Total mortality, cardiovascular mortality and requirements in hospitalization of patients receiving torasemide is substantially less than of patients receiving furosemide. |
2,333,233 | Comparison between spinal anaesthesia and sciatic-femoral block for arthroscopic knee surgery. | We compared spinal anesthesia and sciatic-femoral block for arthroscopic knee surgery in terms of hemodynamic changes, intraoperative anesthesia, postoperative analgesia, postoperative motor block and bladder function, side effects, and patient satisfaction.</AbstractText>Thirty-two patients were randomised into 2 groups: Group B (sciatic-femoral block with mepivacaine 1% 15 + 25 mL, 120 mm/35 mm 22-gauge needles and ElectroNerve Stimulator) and Group S (unilateral spinal anesthesia with 7 mg of hyperbaric bupivacaine 0.5% and 25-gauge Sprotte needle in L2-L3 space). We recorded pain, together with hemodynamic parameters (baseline, 5, 10, 15, 30 min), utilising Numerical Rating Scale (NRS) during the tourniquet application and during the surgical procedures, anesthesia quality, orthopedic evaluation for intraoperative liberty of knee movement. During the postoperative period we recorded at 2, 4 and 6 h: postoperative analgesia, motor block, first urine output, side effects, first requirement for analgesic drug, patient satisfaction and costs.</AbstractText>The only significant differences between the 2 groups (P<0.05) were the heart rate changes at 10, 15, 30 min with an increase in Group B and a decrease in Group S, and the first urine output at 200+/-69 min in Group B versus 269+/-66 min in Group S.</AbstractText>In conclusion the sciatic-femoral nerve block is a valid alternative to spinal anesthesia for arthroscopic knee surgery, leading to a faster discharging from the hospital.</AbstractText> |
2,333,234 | Fluid challenge in patients submitted to spinal block. | The practice of routinely prehydrating patients by infusing a colloid solution for prevention of spinal anesthesia-induced hypotension has been challenged recently. The aim of the study was to evaluate the influence of a 15 mL/kg pre-emptive bolus of colloids (6% hydroxyhethyl starch) on heart rate (HR), mean arterial blood pressure (MAP), cardiac index (CI) in patients submitted to subarachnoid block with hyperbaric bupivacaine 0.5%, 0.2 mg/kg for orthopedic surgery of the lower limb.</AbstractText>Patients were monitored by a Model Flow method. Forty patients (ASA I-II) scheduled to undergo to spinal anesthesia for elective orthopedic surgery of the lower limb were enrolled in the study. The 20 patients in Group A were treated with a preanesthetic infusion of 15 mL/kg of hydroxyhaethyl starch 6%, Group B (20 untreated patients) was the control group. HR, MAP, CI were collected at T0 (first relevation); T1 (after 5 min from the spinal block); T2 (after 10 min); T3 (after 15 min); T4 (after 20 min); T5 (after 25 min); T6 (after 30 min); T7 (after 35 min).</AbstractText>Our data show that MAP value is higher in treated patients than in control group (ANOVA: P<0.001) and at T1 in Group B MAP was lower than at T0 (P<0.05). HR and CI trend appear similar in the 2 groups. Our results show that heart rate is not affected by colloid infusion. This may be due to the substantial cardiovascular stability of the selective spinal anesthesia, which does not activate a clinical relevant compensatory vagal effect. Fluid prehydration would expand the vascular space and hence compensate for the reduction in systemic vascular resistance, although MAP reduction following the induction of spinal anesthesia is present in both treated and control groups.</AbstractText>Our data show that despite to fluid challenge, we could not prevent MAP decrease in Group A, even if it is more marked in Group B.</AbstractText> |
2,333,235 | Ketamine inhibits fetal ACTH responses to cerebral hypoperfusion. | The present study tested the effect of ketamine on the fetal reflex responses of late-gestation sheep to brachiocephalic occlusion (BCO), a stimulus that mimics the reduction in cerebral blood flow that results from severe fetal hypotension. Ketamine, a dissociative anesthetic and known noncompetitive antagonist of N-methyl D-aspartate (NMDA) receptors, has previously been shown to impair chemoreceptor responsiveness. Studies from this laboratory suggest that fetal reflex ACTH responses to hypotension are largely mediated by chemoreceptors; therefore, we hypothesized that ketamine would inhibit the reflex hormonal response to BCO. Chronically catheterized fetal sheep were subjected to acute cerebral hypoperfusion through occlusion of the brachiocephalic artery. Fetal blood pressure and heart rate were continuously recorded, and fetal blood samples drawn during the experiment were analyzed with specific hormone assays. Our results demonstrate that ketamine attenuates hemodynamic responses to cerebral hypoperfusion and is a potent inhibitor of ACTH and proopiomelanocortin (POMC)/pro-ACTH release. These data support the hypothesis that fetal reflex responses hypotension are chemoreceptor mediated. Given the potency with which ketamine inhibits ACTH response to fetal hypotension, we suggest that the use of ketamine or other anesthetic or analgesic drugs that block or otherwise interact with the NMDA-glutamate pathways, in late pregnancy or in preterm newborns be reconsidered. |
2,333,236 | Mitochondrial DNA deletions inhibit proteasomal activity and stimulate an autophagic transcript. | Deletions within the mitochondrial DNA (mtDNA) cause Kearns Sayre syndrome (KSS) and chronic progressive external opthalmoplegia (CPEO). The clinical signs of KSS include muscle weakness, heart block, pigmentary retinopathy, ataxia, deafness, short stature, and dementia. The identical deletions occur and rise exponentially as humans age, particularly in substantia nigra. Deletions at >30% concentration cause deficits in basic bioenergetic parameters, including membrane potential and ATP synthesis, but it is poorly understood how these alterations cause the pathologies observed in patients. To better understand the consequences of mtDNA deletions, we microarrayed six cell types containing mtDNA deletions from KSS and CPEO patients. There was a prominent inhibition of transcripts encoding ubiquitin-mediated proteasome activity, and a prominent induction of transcripts involved in the AMP kinase pathway, macroautophagy, and amino acid degradation. In mutant cells, we confirmed a decrease in proteasome biochemical activity, significantly lower concentration of several amino acids, and induction of an autophagic transcript. An interpretation consistent with the data is that mtDNA deletions increase protein damage, inhibit the ubiquitin-proteasome system, decrease amino acid salvage, and activate autophagy. This provides a novel pathophysiological mechanism for these diseases, and suggests potential therapeutic strategies. |
2,333,237 | Impact of in utero environment on the offspring of lupus patients. | The number of patients affected by systemic lupus erythematosus (SLE) that decide to have children has greatly increased probably because of recent improvements in the diagnosis and management of the disease. This has stimulated our interest in defining the outcome of children, focusing both on neonatal problems and long term development. SLE patients still carry a risk of pregnancy loss. However, due to careful monitoring and treatment by a multidisciplinary team, the number of losses has dramatically decreased, but an increased number of preterm deliveries is still a problem. Neonatal lupus is linked to the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in the mother, although other factors probably of fetal origin are important. Neonatal lupus is a complex condition whose most serious manifestation is the congenital heart block (CHB). Usually, children with complete CHB need permanent pacing, but apparently do not have neuropsychological problems. Studies focusing on the neuropsychological development of SLE offspring show an increased number of learning disabilities in children with normal intelligence levels. Fetal consequence of maternal treatment need to be considered choosing non teratogenic drugs, but the withdrawal of medications just because the patient is pregnant should be avoided to avoid SLE flares. |
2,333,238 | The lack of cardiotrophin-1 alters expression of interleukin-6 and leukemia inhibitory factor mRNA but does not impair cardiac injury response. | Cardiotrophin-1 (CT-1) was identified as a growth factor for cardiac myocytes and CT-1 protects myocytes from cell death. Adult CT-1(-/-) mice exhibit neural deficits including the loss of preganglionic sympathetic neurons, but their autonomic and cardiac parameters have not been examined. We used these mice to determine if the absence of CT-1 or loss of preganglionic sympathetic input altered heart rate, left ventricular pressure, cardiac contractility (dP/dt), or cell death following ischemia-reperfusion. Basal heart rate was increased in CT-1(-/-) mice, and this difference was abolished by ganglionic block. Left ventricular pressure and dP/dt were unchanged. Dobutamine stimulated similar increases in heart rate and dP/dt in both genotypes, but ventricular pressure was significantly lower in CT-1 nulls. Cardiac expression of interleukin-6 (IL-6) mRNA was increased significantly in CT-1 null mice, while leukemia inhibitory factor (LIF) mRNA was unchanged. Infarct size normalized to area at risk was no different in CT-1(-/-) mice (33.8+/-1.0% vs. 37.7+/-3.2% WT) 24h after ischemia-reperfusion. Induction of IL-6 mRNA after infarct was significantly abrogated in CT-1 null mice compared to wild-type mice, but LIF mRNA-induction remained significant in CT-1 null mice and might contribute to cardiac protection in the absence of CT-1. |
2,333,239 | Effects of epidural analgesia using ropivacaine on the mother and the newborn during labor. | To evaluate the effects of epidural analgesia using 0.2% Ropivacaine on the mother, newborn and during labor.</AbstractText>This study was conducted at the Zeynep Kamil Obstetric, Gynecology, and Pediatric Research and Training Hospital in Istanbul, Turkey, between July 2003 and April 2004. Eighty pregnant women of 37-41 weeks' gestation were enrolled in the study. Forty cases received epidural analgesia (group 1) and the control group composed 40 cases (group 2). Duration of labor, systolic and diastolic blood pressures at initial, 15th, 30th, 45th and 60th minutes, and number of breathing per minute, pulse rates, fetal heart rates and presence of motor block were recorded. Blood gas assessments from the umbilical cord, 1st and 5th minute Apgar scores were noted following the delivery. Way of delivery, adverse effects and complications of the epidural analgesia were recorded.</AbstractText>Mean age of the cases was 24.79 +/- 4.72 years. Duration between full cervical dilation and delivery (phase 2) was significantly longer in group 1 (p<0.01). Sixty minutes systolic arterial pressure was significantly lower in group 1 (p<0.05). In group 1, diastolic arterial pressures at 15th, 45th, 60th minutes (p<0.01) and 30th minute (p<0.05) were significantly lower when compared to the initial values. No significant differences were recorded in terms of breathing rates, umbilical cord CO2, O2, pH levels and Apgar scores between the 2 groups. The most common adverse effect of epidural analgesia was sedation (59%). The second dose of Ropivacaine was needed in 24 (61.5%) cases in group 1. In group 1, 29 (74.4%) patients expressed their pleasure as very good regarding the epidural analgesia.</AbstractText>Epidural analgesia, if administered by a specialist to a properly selected patient at proper time, leads to a comfortable delivery by relieving the pain. It can be performed safely after taking an informed consent.</AbstractText> |
2,333,240 | The influence of restorative treatment approaches and the use of local analgesia, on the children's discomfort. | The aim is to investigate possible differences in discomfort during treatment with the atraumatic restorative treatment (ART) or the Conventional restorative method with and without local analgesia (LA).</AbstractText>The study group consisted of 6 and 7 year old children with no dental experience (mean age 6.98, SD +/- 0.52) randomly divided into four treatment groups: Conventional method with and without LA and ART with and without LA. One or two proximal lesions in primary molars were treated. The heart rate and the behaviour (Venham) were measured.</AbstractText>Statistical analysis was performed in SPSS version 10.0.</AbstractText>In a first session 300 children were treated and 109 children for a second time in the same way as at the first visit. During the first session ART without LA gave the least discomfort while the Conventional method without LA gave the most discomfort. During the second treatment the least discomfort was observed with ART without LA and the most discomfort in the Conventional way with LA.</AbstractText>There is a constant preference for hand instruments; the bur is increasingly accepted. The experience with LA is the reverse.</AbstractText> |
2,333,241 | Increase in skin temperature after spinal anesthesia in infants. | The relatively stable hemodynamics during spinal anesthesia in infants have been attributed to a less active sympathetic nervous system in comparison with adults. Thus, the authors evaluated sympathetic block primarily by measurement of skin temperature and secondarily by determination of noninvasive blood pressure as an indirect sign of sympatholysis.</AbstractText>In 15 infants (postconceptual age: 45.0 +/- 4.8 weeks; weight: 4.0 +/- 1.2 kg) scheduled for repair of inguinal hernia under spinal anesthesia, skin temperature at the T4 level and at the plantar foot was measured before and after spinal anesthesia. Spinal anesthesia was induced at the L4/L5 interspace with 0.5% hyperbaric bupivacaine 1 mg/kg with 10 microg/kg adrenaline added.</AbstractText>Temperature at the plantar foot after spinal anesthesia rose significantly from 33.0 degrees C +/- 1.3 degrees C to 34.7 degrees C +/- 1.4 degrees C within 10 minutes and to 35.6 degrees C +/- 0.9 degrees C after 20 minutes (P < .0001), whereas the temperature at the thorax remained constant at 35 degrees C to 36 degrees C. Systolic and diastolic blood pressure decreased by 15.9 +/- 11.4 mm Hg and 9.0 +/- 9.2 mm Hg, respectively (P < .01), but remained within normal range in all cases.</AbstractText>The authors found a significant increase in skin temperature of the feet within 10 minutes as a sign of sympatholysis, whereas trunk temperature remained constant. Blood pressure decreased but remained within the normal range, despite the observed sympatholysis.</AbstractText> |
2,333,242 | Comparison of ropivacaine and bupivacaine for intrathecal anesthesia during outpatient arthroscopic surgery. | To compare the effects of intrathecal ropivacaine with bupivacaine in a dose ratio of 2:1 for outpatient arthroscopic knee surgery.</AbstractText>Randomized, single-blinded study.</AbstractText>University-affiliated hospital.</AbstractText>90 patients scheduled for outpatient arthroscopic knee surgery.</AbstractText>Patients were randomized and assigned in single-blinded fashion to receive a 3-mL solution of either 15 mg of isobaric ropivacaine (group R; n = 45) or 7.5 mg of isobaric bupivacaine (group B; n = 45) through a 27-gauge Quincke spinal needle at the L(3) to L(4) interspace, while placed in the lateral decubitus position.</AbstractText>Onset and offset times for sensory and motor block; highest level of sensory block; duration of the sensory and motor block; first ambulation, urination, and discharge time; mean arterial pressure; and heart rate were all recorded.</AbstractText>Onset time for sensory block (mean +/- SD) to L1 and time until sensory block regressed to L2 were shorter in group R. Complete motor block occurred in 40 patients with ropivacaine and 45 patients with bupivacaine. First ambulation and first urination and discharge times were similar between the two groups. Cephalad spread of sensory block was higher with ropivacaine (P < 0.05). The median (range) upper sensory level obtained with bupivacaine was T11 (T6-L1) and T8 (T6-T10) with ropivacaine. Hemodynamic changes were similar between the groups (P > 0.05).</AbstractText>Isobaric ropivacaine 15 mg provided a higher sensory block level and shorter sensorial onset and offset times than did 7.5 mg of isobaric bupivacaine.</AbstractText> |
2,333,243 | Adjuvant bupivacaine scalp block facilitates stabilization of hemodynamics in patients undergoing craniotomy with general anesthesia: a preliminary report. | To evaluate the effect of 0.25% bupivacaine scalp block on alterations in hemodynamics and plasma catecholamine metabolites during general anesthesia in patients undergoing frontotemporal craniotomy.</AbstractText>Prospective, clinical study.</AbstractText>Operating room of a university hospital.</AbstractText>16 ASA physical status II and III patients who were scheduled for frontotemporal craniotomy.</AbstractText>Patients were prospectively randomized to receive a saline control (C group) or bupivacaine scalp block (SB group) as an adjuvant to general anesthesia using isoflurane in 50% N(2)O-O(2).</AbstractText>Routine monitoring of electrocardiogram, heart rate (HR), and mean arterial blood pressure (MAP) were recorded at two-minute intervals from the beginning of anesthesia until 10 minutes after incision, followed by 5-minute intervals throughout the remaining course of the surgery. By prospective design, increases in MAP or HR by 20% above the mean baseline values were treated with 2.5 mg/kg of thiopental combined with 2 mug/kg of fentanyl. Arterial blood was sampled at 5 minutes before and after skin incision and at the start of dural opening for measuring serum catecholamine metabolites by high-performance liquid chromatography.</AbstractText>Only two patients in the SB group needed additional anesthetics for stabilizing their hemodynamics during the course of anesthesia. In contrast, all C group patients required supplemental anesthesia for controlling the abrupt rise in hemodynamic parameters. In addition, absolute MAP and HR values were significantly higher in the C group than in the SB group during the surgical period between incision and dural opening. The differences in hemodynamics observed between the two groups were, however, not accompanied with a significant change in plasma catecholamine metabolites at each predetermined time interval measured.</AbstractText>Pretreatment with 0.25% bupivacaine scalp block appeared to be an effective adjuvant treatment for maintaining stable hemodynamics for patients undergoing craniotomy during general anesthesia especially at the time of skin incision and dural opening. This study design was unable to discern any correlation between elevation in hemodynamic parameters and a rise in serum catecholamine levels.</AbstractText> |
2,333,244 | Incomplete myocardial rupture following inferior myocardial infarction: a case report. | In an era of early and invasive therapeutic approaches, myocardial rupture has become an uncommon complication of myocardial infarction. While septal wall rupture most often leads to devastating haemodynamic consequences, free wall rupture is usually fatal. We report a case of a 48-year-old man in whom an incomplete myocardial rupture located in the inferior part of the interventricular septum was promptly detected during the acute phase of an inferior myocardial infarction treated by early percutaneous coronary angioplasty. A conservative rather than a surgical approach was decided with a favourable short-term outcome. |
2,333,245 | In vitro preclinical cardiac assessment of tolterodine and terodiline: multiple factors predict the clinical experience. | Terodiline and tolterodine are drugs used to treat urinary incontinence. Terodiline was removed from the market in 1991 for proarrhythmia, whereas tolterodine has a generally benign clinical cardiac profile. To assess differences in the electrophysiologic actions of these drugs, we evaluated their effects on hERG current (HEK cells) and cardiac Purkinje fiber repolarization. The IC50 for hERG block (37 degrees C) by tolterodine was 9.6 nM and by terodiline was 375 nM, values near or below clinical concentrations. Tolterodine elicited concentration-dependent prolongation of the action potential duration (APD90). In contrast, terodiline depressed the action potential plateau and induced triangulation without affecting APD90. The triangulation ratios (normalized ratio of APD50 over APD90) for terodiline were 0.94 and 0.59 for 1.0 and 10 microM and for tolterodine, were 0.99 and 0.97 at 7 and 70 nM. In summary, tolterodine, a potent hERG blocker, has a benign clinical cardiac profile at therapeutic concentrations that may be due to its lack of triangulation, as well as extensive plasma protein binding. However, at supratherapeutic concentrations, preclinical data predict risk of QT prolongation. These data suggest that hERG block and triangulation are among multiple factors that must be considered in preclinical cardiac safety assessments. |
2,333,246 | Pharmacological evidence that alpha2A- and alpha2C-adrenoceptors mediate the inhibition of cardioaccelerator sympathetic outflow in pithed rats. | It has been suggested that the alpha(2)-adrenoceptors mediating cardiac sympatho-inhibition in pithed rats closely resemble the pharmacological profile of the alpha(2A)-adrenoceptor subtype. However, several lines of evidence suggest that more than one subtype may be involved. Thus, the present study has pharmacologically re-evaluated the receptor subtype(s) involved in the inhibitory effect of the alpha(2)-adrenoceptor agonist, B-HT 933, on the tachycardic responses elicited by selective cardiac sympathetic stimulation (0.03, 0.1, 0.3, 1 and 3 Hz) in desipramine-pretreated pithed rats. I.v. continuous infusions of B-HT 933 (30 microg/kg min), which failed to modify the tachycardic responses to exogenous noradrenaline, inhibited those induced by preganglionic (C(7)-T(1)) stimulation of the cardiac sympathetic outflow at all frequencies of stimulation (0.03-3 Hz). This cardiac sympatho-inhibitory response to B-HT 933 was: (1) unaltered by saline (1 ml/kg) or the antagonists BRL44408 (100 microg/kg; alpha(2A)) or imiloxan (3000 and 10,000 microg/kg; alpha(2B)); (2) partially antagonized by BRL44408 (300 microg/kg) or MK912 (10 microg/kg; alpha(2C)) given separately; and (3) completely antagonized by rauwolscine (300 microg/kg; alpha(2)), MK912 (30 microg/kg) or the combination of BRL44408 (300 microg/kg) plus MK912 (10 microg/kg). Moreover, the above doses of antagonists, which are high enough to block their respective receptors, failed to block per se the tachycardic responses to sympathetic stimulation. These results suggest that the cardiac sympatho-inhibition induced by B-HT 933 in pithed rats is mainly mediated by stimulation of alpha(2A)- and alpha(2C)-adrenoceptors. |
2,333,247 | Successful ablation of a concealed parahisian accessory pathway using a remote magnetic navigation system following failure by conventional methods. | Using conventional catheters, ablation of concealed parahisian accessory pathways may be difficult and high risk for heart block.</AbstractText>We describe the case of a concealed parahisian accessory pathway with three prior attempts to ablate using conventional methods (RF and cryotherapy). Using a remote magnetic navigation system, successful ablation occurred following a single RF lesion (total fluoroscopy time 17 min). In contrast to previous attempts, the patient remained asymptomatic during follow-up (12 months).</AbstractText>This is the first report of successful remote magnetic catheter ablation of a concealed parahisian AP. Magnetic catheter stability during RF application likely contributed to the success of this procedure and may have minimized the risk of AV block.</AbstractText> |
2,333,248 | Growth characteristics of calves fed an intensified milk replacer regimen with additional lactoferrin. | The objective of this study was to evaluate the effect of lactoferrin addition to milk replacer varying in crude protein (CP) on dry matter intake, growth, and days medicated. Thirty-four Holstein heifer calves were assigned to 4 treatments in a 2 x 2 factorial arrangement of treatments in a randomized complete block design. Treatments were as follows: 562 g daily of a nonmedicated conventional milk replacer (20% CP:20% fat) feeding regimen with or without 1 g of supplemental bovine lactoferrin (n = 9 for both treatments) or a nonmedicated intensified milk replacer feeding regimen (28% CP:20% fat) fed on a metabolizable energy basis (0.2 Mcal/kg BW(0.75)) from d 2 to 9, and at 0.27 Mcal/kg BW(0.75) from d 10 to 42 with or without 1g supplemental bovine lactoferrin (n = 8 for both treatments). Calves were fed pelleted starter (25% CP) in 227.5-g increments beginning on d 2 and had free access to water. Calves remained on the study for 14 d postweaning. Dry matter intake was determined daily. Growth measurements were taken weekly. Blood samples were taken twice weekly for determination of blood urea N. On d 10 of life, calves were subjected to a xylose challenge. Calves on conventional treatments ate more starter preweaning, during weaning, and postweaning. Preweaning, intensively fed calves had higher dry matter intakes. Weights of intensified-fed calves were greater at weaning. Intensified milk replacer-fed calves had greater average daily gain preweaning and overall and higher gain:feed ratios preweaning, but conventionally fed calves had higher gain:feed ratios during weaning. Intensified milk replacer-fed calves had greater hip heights during weaning and postweaning and greater heart girths preweaning, weaning, and postweaning. Days medicated were greater preweaning and overall for intensified-fed calves. There were no differences among treatments for xylose absorption. Calves on conventional treatments had increased blood urea nitrogen concentrations preweaning. There were no effects of lactoferrin on any experimental variable. Intensified milk replacer-fed calves consumed less starter but had higher average daily gains overall and larger frames and greater BW than conventionally fed calves. An intensified milk replacer feeding regimen promotes faster growth during the preweaning period when compared with calves fed conventional treatments, but supplemental bovine lactoferrin was not beneficial under these experimental conditions. |
2,333,249 | Combined blockade of the Na+ channel and the Na+/H+ exchanger virtually prevents ischemic Na+ overload in rat hearts. | Blocking either the Na(+) channel or the Na(+)/H(+) exchanger (NHE) has been shown to reduce Na(+) and Ca(2+) overload during myocardial ischemia and reperfusion, respectively, and to improve post-ischemic contractile recovery. The effect of combined blockade of both Na(+) influx routes on ionic homeostasis is unknown and was tested in this study. [Na(+)](i), pH(i) and energy-related phosphates were measured using simultaneous (23)Na- and (31)P-NMR spectroscopy in isolated rat hearts. Eniporide (3 muM) and/or lidocaine (200 muM) were administered during 5 min prior to 40 min of global ischemia and 40 min of drug free reperfusion to block the NHE and the Na(+) channel, respectively. Lidocaine reduced the rise in [Na(+)](i) during the first 10 min of ischemia, followed by a rise with a rate similar to the one found in untreated hearts. Eniporide reduced the ischemic Na(+) influx during the entire ischemic period. Administration of both drugs resulted in a summation of the effects found in the lidocaine and eniporide groups. Contractile recovery and infarct size were significantly improved in hearts treated with both drugs, although not significantly different from hearts treated with either one of them. |
2,333,250 | Mycophenolate acid inhibits endothelial NAD(P)H oxidase activity and superoxide formation by a Rac1-dependent mechanism. | Endothelial dysfunction precedes hypertension and atherosclerosis and predicts cardiac allograft vasculopathy and death in heart transplant recipients. Endothelial overproduction of reactive oxygen species, such as superoxide anions produced by NAD(P)H oxidase, induces endothelial dysfunction. Because immunosuppressive drugs have been associated with increased reactive oxygen species production and endothelial dysfunction, we sought to elucidate the underlying mechanisms. Reactive oxygen species, release of superoxide anions, and NAD(P)H oxidase activity were studied in human umbilical vein endothelial cells and in polymorphonuclear neutrophils. Gp91ds-tat was used to specifically block NAD(P)H oxidase. Transcriptional activation of different subunits of NAD(P)H oxidase was assessed by real-time RT-PCR. Rac1 subunit translocation and activation were studied by membrane fractionation and pull-down assays. Calcineurin inhibitors significantly increased endothelial superoxide anions production because of NAD(P)H oxidase, whereas mycophenolate acid (MPA) blocked it. MPA also attenuated the respiratory burst induced by neutrophil NAD(P)H oxidase. Because transcriptional activation of NAD(P)H oxidase was not affected, but addition of guanosine restored endothelial superoxide anions formation after MPA treatment, we speculate that the inhibitory effect of MPA was mediated by depletion of cellular guanosine triphosphate content. This prevented activation of Rac1 and, thus, of endothelial NAD(P)H oxidase. Because all heart transplant recipients are at risk for cardiac allograft vasculopathy development, these differential effects of immunosuppressants on endothelial oxidative stress should be considered in the choice of immunosuppressive drugs. |
2,333,251 | Novel strategies to delineate matrix metalloproteinase (MMP)-substrate relationships and identify targets to block MMP activity. | Adverse extracellular matrix (ECM) remodeling contributes to fibrotic disorders in the kidney, lung, and heart. Matrix metalloproteinases (MMPs) are key enzymes regulating ECM turnover, and MMP inhibition attenuates remodeling. Recent technological developments allow MMP-substrate relationships to be identified and explored as novel therapeutic targets. This review summarizes current and novel strategies to block MMP activity. |
2,333,252 | Identification of two types of ATP-sensitive K+ channels in rat ventricular myocytes. | The ATP-sensitive K(+) (K(ATP)) channels are known to provide a functional linkage between the electrical activity of the cell membrane and metabolism. Two types of inwardly rectifying K(+) channel subunits (i.e., Kir6.1 and Kir6.2) with which sulfonylurea receptors are associated were reported to constitute the K(ATP) channels. In this study, we provide evidence to show two types of K(ATP) channels with different biophysical properties functionally expressed in isolated rat ventricular myocytes. Using patch-clamp technique, we found that single-channel conductance for the different two types of K(ATP) channels in these cells was 57 and 21 pS. The kinetic properties, including mean open time and bursting kinetics, did not differ between these two types of K(ATP) channels. Diazoxide only activated the small-conductance K(ATP) channel, while pinacidil and dinitrophenol stimulated both channels. Both of these K(ATP) channels were sensitive to block by glibenclamide. Additionally, western blotting, immunochemistry, and RT-PCR revealed two types of Kir6.X channels, i.e., Kir6.1 and Kir6.2, in rat ventricular myocytes. Single-cell Ca(2+) imaging also revealed that similar to dinitrophenol, diazoxide reduced the concentration of intracellular Ca(2+). The present results suggest that these two types of K(ATP) channels may functionally be related to the activity of heart cells. |
2,333,253 | Remifentanil preventing hemodynamic changes during laparoscopic adrenalectomy for pheochromocytoma. | In this prospective case-series study, a balanced anesthetic scheme of sevoflurane in nitrous oxide supplemented with remifentanil and sustained neuromuscular block was applied in nine patients scheduled for laparoscopic adrenalectomy for pheochromocytoma. Laparoscopic adrenalectomy to treat pheochromocytoma results in marked catecholamine release during pneumoperitoneum and tumor manipulation. Remifentanil infusion was adjusted to maintain systolic arterial pressure between 120-170 mmHg. Increased infusion rate of remifentanil was used (up to 3 microg/kg/min) to prevent and treat marked hemodynamic changes from catecholamine release during tumor manipulation. Hpotension after tumor removal was treated with additional colloids fluids and decreasing the remifentanil infusion rate by 25-50%. |
2,333,254 | Opioid antagonism of cannabinoid effects: differences between marijuana smokers and nonmarijuana smokers. | In non-human animals, opioid antagonists block the reinforcing and discriminative-stimulus effects of Delta(9)-tetrahydrocannabinol (THC), while in human marijuana smokers, naltrexone (50 mg) enhances the reinforcing and subjective effects of THC. The objective of this study was to test a lower, more opioid-selective dose of naltrexone (12 mg) in combination with THC. The influence of marijuana-use history and sex was also investigated. Naltrexone (0, 12 mg) was administered 30 min before oral THC (0-40 mg) or methadone (0-10 mg) capsules, and subjective effects, task performance, pupillary diameter, and cardiovascular parameters were assessed in marijuana smoking (Study 1; n=22) and in nonmarijuana smoking (Study 2; n=21) men and women. The results show that in marijuana smokers, low-dose naltrexone blunted the intoxicating effects of a low THC dose (20 mg), while increasing ratings of anxiety at a higher THC dose (40 mg). In nonmarijuana smokers, low-dose naltrexone shifted THC's effects in the opposite direction, enhancing the intoxicating effects of a low THC dose (2.5 mg) and decreasing anxiety ratings following a high dose of THC (10 mg). There were no sex differences in these interactions, although among nonmarijuana smokers, men were more sensitive to the effects of THC alone than women. To conclude, a low, opioid-selective dose of naltrexone blunted THC intoxication in marijuana smokers, while in nonmarijuana smokers, naltrexone enhanced THC intoxication. These data demonstrate that the interaction between opioid antagonists and cannabinoid agonists varies as a function of marijuana use history. |
2,333,255 | Does adding intravenous fentanyl to caudal block in children enhance the efficacy of multimodal analgesia as reflected in the plasma level of catecholamines? | Several studies showed that single analgesic modality management can attenuate perioperative stress, but little is known about the effect of multimodal analgesia on catecholamine responses to surgical trauma in children.</AbstractText>Fifty children (American Society of Anesthesiologists Grade I or II) were randomly allocated to one of two groups: one received general anaesthesia and a caudal block (control group), and one group was given general anaesthesia, caudal block and intravenous (i.v.) fentanyl 2 microg kg(-1) (fentanyl group). Plasma epinephrine and norepinephrine concentrations were measured three times during the perioperative period: at induction time (T(0)), at the end of surgery (T(1)) and when the children were fully awake in the postanaesthesia care unit (T(2)).</AbstractText>There was a significant reduction in the catecholamine levels in the two groups when (T(1)) and (T(2)) were compared with T(0). When plasma epinephrine levels (at T(0), T(1) and T(2)) between the two groups were compared, a statistically significant reduction at T(2) was obtained in the fentanyl group, when compared with the control group. However, plasma norepinephrine levels showed no statistically significant difference between the two groups (at T(0), T(1) and T(2)).</AbstractText>These findings suggest that the multimodal analgesic approach of adding i.v. low-dose fentanyl to a caudal block may decrease the plasma epinephrine release in children undergoing inguinal herniotomy.</AbstractText> |
2,333,256 | Characterization of T-cell population in children with prolonged fetal exposure to dexamethasone for anti-Ro/SS-A antibodies associated congenital heart block. | The objectives of the study were to characterize the production, function and survival of T lymphocytes of children with prolonged fetal exposure to dexamethasone for anti-Ro/SS-A antibodies associated congenital complete heart block. The analysis of thymic function, studied by measuring the level of T-cell receptor excision circles, was performed by real time PCR, the composition of T-cell subpopulation was evaluated by flow cytometry and the T-cell diversity was assayed by heteroduplex analysis. T-cell competence was gauged at two functional levels by determining the proliferation and the number of T-cell divisions and by measuring gamma-interferon production after mitogenic stimulation. We observed that the thymic output, distribution of T-cell subsets, thymidine incorporation, number of T-cell divisions, and y-interferon production were comparable to those of age-matched control. On the contrary, heteroduplex analysis demonstrated the presence of both polyclonal and oligoclonal peripheral T-cell repertoires. In conclusion, the analysis of the T-cell compartment in children with prolonged intrauterine exposure to high dose dexamethasone did not disclose any relevant abnormality, except a restriction of T-cell receptor diversity in some patients. |
2,333,257 | Benztropine pretreatment does not affect responses to acute cocaine administration in human volunteers. | Benztropine (Cogentin ) was evaluated for its ability to block cocaine's physiological and subjective effects in humans. In healthy, recreational users of cocaine, placebo, or benztropine (1, 2, and 4 mg orally) was given 2 hr before subjects self-administered 0.9 mg/kg of cocaine intranasally. Measurements were made for 2 hr following cocaine administration, and plasma cocaine and cocaine metabolites were assayed. Cocaine produced typical increases in heart rate and alterations in self-reports measured by visual analog scales (VAS). Benztropine alone did not produce changes on any of these measures. Responses to cocaine with and without benztropine pretreatment were similar: benztropine did not change cocaine's effects. This study of one of the tropane-ring analogs that is approved for human use suggests this compound does not alter cocaine-induced effects, but just as importantly, does not produce any adverse behavioral or physiological effects. The exact therapeutic application of benztropine as a possible adjunct treatment for cocaine abuse in humans require further exploration. |
2,333,258 | A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice. | Pentosan polysulfate (PPS) is a heparin-like polysaccharide that can affect the binding interactions of fibroblast growth factor (FGF-2) with its high-affinity receptors. Patients with angiogenic tumors frequently show high levels of FGF-2 in the circulation. Since FGF-2 is a heparin-binding angiogenic growth factor, PPS has been used successfully to block its activity in patients with angiogenic tumors. However, because of its heparin-like activity, the major toxic effect of PPS is the development of bleeding disorders. The role that circulating FGF-2 plays in the pathogenesis of bleeding disorders in patients treated with PPS is currently unknown. Here we hypothesized that FGF-2 might play a physiological role in the pathogenesis of intestinal bleeding induced by PPS. This hypothesis is supported by previous studies showing that PPS is accumulated in the intestine and that circulating FGF-2 specifically binds to and modulates the angiogenic activity of intestinal submucosal endothelial cells. We used recombinant adenoviral vectors carrying a secreted form of FGF-2 and LacZ control vectors to determine whether high levels of circulating FGF-2 facilitate the development of intestinal bleeding disorders in FVB/N and C57BL/6J mice treated with PPS. We found that PPS, acting together with FGF-2, induced structural changes in intestinal vessels leading to the development of lethal intestinal hemorrhages. These findings might have wider clinical implications for the systemic use of PPS and other heparinoids in the treatment of patients with angiogenic diseases associated with high levels of circulating FGF-2. |
2,333,259 | Clonidine as an analgesic adjuvant to continuous paravertebral bupivacaine for post-thoracotomy pain.<Pagination><StartPage>586</StartPage><EndPage>591</EndPage><MedlinePgn>586-91</MedlinePgn></Pagination><Abstract><AbstractText>We prospectively evaluated the effect of clonidine as an adjuvant to bupivacaine for continuous paravertebral intercostal nerve block, measuring pain and sedation scores and pulmonary function tests. Thirty patients scheduled to undergo thoracotomy were randomized to receive either a bolus of 0.125% bupivacaine 2 mg/kg (group BUP) or 0.125% bupivacaine 2 mg/kg with clonidine 2 microg/kg (group BUP+CLO), followed by an infusion of 0.125% bupivacaine at 0.5 mg/kg/h, or 0.125% bupivacaine at 0.5 mg/kg/h with clonidine at 2 microg/kg/h, in respective groups, through a paravertebral intercostal catheter. Haemodynamic parameters, pain and sedation scores and pulmonary function tests were recorded at 6, 12, 24 and 48 hours after arrival in postoperative care unit. There were significantly lower pain scores at rest and on coughing in group BUP+CLO compared with group BUP (P <0.01). Multiple comparisons revealed a significant reduction in pain score at each time point (P<0.01), except at 12h to 24h, in group BUP+CLO. Sedation scores were significantly higher in group BUP+CLO compared with group BUP at each time point (all P<0.01). There was a linear effect of time on sedation score in group BUP whereas in group BUP+CLO, the effect was quadratic. Patients in the clonidine group had a higher incidence of hypotension (P < 0.01). There was no significant difference in pulmonary function between the groups. We conclude that using clonidine as an adjunct to bupivacaine for continuous paravertebral intercostal nerve block improves pain relief after thoracotomy, but hypotension and sedation are adverse effects interfering with its clinical application.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bhatnagar</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Anaesthesiology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mishra</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Madhurima</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Gurjar</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Mondal</LastName><ForeName>A S</ForeName><Initials>AS</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Anaesth Intensive Care</MedlineTA><NlmUniqueID>0342017</NlmUniqueID><ISSNLinking>0310-057X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000316">Adrenergic alpha-Agonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000779">Anesthetics, Local</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D006993">Hypnotics and Sedatives</NameOfSubstance></Chemical><Chemical><RegistryNumber>MN3L5RMN02</RegistryNumber><NameOfSubstance UI="D003000">Clonidine</NameOfSubstance></Chemical><Chemical><RegistryNumber>Y8335394RO</RegistryNumber><NameOfSubstance UI="D002045">Bupivacaine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000316" MajorTopicYN="N">Adrenergic alpha-Agonists</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000779" MajorTopicYN="N">Anesthetics, Local</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001794" MajorTopicYN="N">Blood Pressure</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002045" MajorTopicYN="N">Bupivacaine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003000" MajorTopicYN="N">Clonidine</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003371" MajorTopicYN="N">Cough</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004311" MajorTopicYN="N">Double-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006993" MajorTopicYN="N">Hypnotics and Sedatives</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007278" MajorTopicYN="N">Injections, Spinal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007367" MajorTopicYN="N">Intercostal Nerves</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009407" MajorTopicYN="N">Nerve Block</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010147" MajorTopicYN="N">Pain Measurement</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010149" MajorTopicYN="N">Pain, Postoperative</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011446" MajorTopicYN="N">Prospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012129" MajorTopicYN="N">Respiratory Function Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013908" MajorTopicYN="Y">Thoracotomy</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>1</Month><Day>12</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17061632</ArticleId><ArticleId IdType="doi">10.1177/0310057X0603400507</ArticleId><ArticleId IdType="pii">2005395</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17061591</PMID><DateCompleted><Year>2007</Year><Month>01</Month><Day>04</Day></DateCompleted><DateRevised><Year>2006</Year><Month>10</Month><Day>25</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2006</Year><Season>Jul-Aug</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Impact of subarachnoidal block on cardiac rhythm variability in children].<Pagination><StartPage>64</StartPage><EndPage>67</EndPage><MedlinePgn>64-7</MedlinePgn></Pagination><Abstract><AbstractText>The impact of spinal anesthesia on cardiac rhythm variability was studied in 36 children aged 13-17 years who had been operated on for urological, orthopedic, and vascular diseases. The findings were compared with the results obtained in 83 children with the same pathology at the age of 7-15 years, who had been operated under general anesthesia. A spectral cardiac sinus rhythm analysis demonstrated a steady state of stress-limiting systems during spinal block. Unlike general anesthesia, spinal anesthesia was ascertained to reduce the likelihood of intraoperative arrhythmias, by producing an adequate analgesic effect.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kuliov</LastName><ForeName>A G</ForeName><Initials>AG</Initials></Author><Author ValidYN="Y"><LastName>Aleksandrovich</LastName><ForeName>Iu S</ForeName><Initials>IuS</Initials></Author><Author ValidYN="Y"><LastName>Ul'rikh</LastName><ForeName>G E</ForeName><Initials>GE</Initials></Author><Author ValidYN="Y"><LastName>Zabolotskiĭ</LastName><ForeName>D V</ForeName><Initials>DV</Initials></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Anesteziol Reanimatol</MedlineTA><NlmUniqueID>7705399</NlmUniqueID><ISSNLinking>0201-7563</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000775" MajorTopicYN="N">Anesthesia, Spinal</DescriptorName><QualifierName UI="Q000592" MajorTopicYN="Y">standards</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D050723" MajorTopicYN="N">Fractures, Bone</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009407" MajorTopicYN="N">Nerve Block</DescriptorName><QualifierName UI="Q000592" MajorTopicYN="Y">standards</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013346" MajorTopicYN="N">Subarachnoid Space</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014570" MajorTopicYN="N">Urologic Diseases</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014652" MajorTopicYN="N">Vascular Diseases</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>1</Month><Day>5</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17061591</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17061590</PMID><DateCompleted><Year>2007</Year><Month>01</Month><Day>04</Day></DateCompleted><DateRevised><Year>2006</Year><Month>10</Month><Day>25</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2006</Year><Season>Jul-Aug</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Regional anesthesia and sedation during extremity operations in children].<Pagination><StartPage>62</StartPage><EndPage>64</EndPage><MedlinePgn>62-4</MedlinePgn></Pagination><Abstract><AbstractText>Twenty-five studies were made in patients aged 12 to 15 years, who had been operated on for extremity injuries. The patients were divided into 2 groups: (1) those who had been given regional anesthesia with sedation (n=10) and (2) those who had received apparatus-mask anesthesia (n=15). The following parameters: heart rate, blood pressure, stroke volume, cardiac output were estimated. The study included 6 steps: (1) premedication; (2) postmedication; (3) postblock; (4) 20 min after block; (5) during skin incision; (6) after consciousness recovery. The findings suggest that there are insignificant hemodynamic changes when regional anesthesia is made in combination with drug sedation as compared with fluorotane-oxide-oxygen anesthesia.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chizhov</LastName><ForeName>D A</ForeName><Initials>DA</Initials></Author><Author ValidYN="Y"><LastName>Pivovarov</LastName><ForeName>S A</ForeName><Initials>SA</Initials></Author><Author ValidYN="Y"><LastName>Babaev</LastName><ForeName>B D</ForeName><Initials>BD</Initials></Author><Author ValidYN="Y"><LastName>Shishkov</LastName><ForeName>M V</ForeName><Initials>MV</Initials></Author><Author ValidYN="Y"><LastName>Ostreĭkov</LastName><ForeName>I F</ForeName><Initials>IF</Initials></Author><Author ValidYN="Y"><LastName>Shein</LastName><ForeName>V N</ForeName><Initials>VN</Initials></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Anesteziol Reanimatol</MedlineTA><NlmUniqueID>7705399</NlmUniqueID><ISSNLinking>0201-7563</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000765" MajorTopicYN="N">Anesthesia, Conduction</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001794" MajorTopicYN="N">Blood Pressure</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002648" MajorTopicYN="N">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016292" MajorTopicYN="N">Conscious Sedation</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005121" MajorTopicYN="N">Extremities</DescriptorName><QualifierName UI="Q000293" MajorTopicYN="Y">injuries</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008991" MajorTopicYN="N">Monitoring, Physiologic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013318" MajorTopicYN="N">Stroke Volume</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>1</Month><Day>5</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17061590</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17061580</PMID><DateCompleted><Year>2007</Year><Month>01</Month><Day>04</Day></DateCompleted><DateRevised><Year>2006</Year><Month>10</Month><Day>25</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2006</Year><Season>Jul-Aug</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Modes of balanced regional anesthesia in patients with lower extremity injuries].<Pagination><StartPage>34</StartPage><EndPage>36</EndPage><MedlinePgn>34-6</MedlinePgn></Pagination><Abstract><AbstractText>The basic hemodynamic (systolic blood pressure (BP), diastolic BP, heart rate, stroke volume, cardiac output, RPP) and respiratory parameters (respiratory rate, tidal volume, respiratory minute volume) during operations on the lower extremities under epidural anesthesia (n=24; Group 1) versus lumbar plexus block by the 3-in-1 technique (n= 23; Group 2) were studied in 47 traumatological patients. With balanced epidural anesthesia, there was a short-term decrease in hemodynamic parameters and a worse external respiratory function; in 5 patients requiring its performance WL, balanced block of peripheral nerves of the lumbar plexus was, on the contrary, marked by a greater hemodynamic and respiratory stability.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sabirov</LastName><ForeName>D M</ForeName><Initials>DM</Initials></Author><Author ValidYN="Y"><LastName>Narziev</LastName><ForeName>M M</ForeName><Initials>MM</Initials></Author><Author ValidYN="Y"><LastName>Batirov</LastName><ForeName>U B</ForeName><Initials>UB</Initials></Author><Author ValidYN="Y"><LastName>Valiev</LastName><ForeName>E Iu</ForeName><Initials>EIu</Initials></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Anesteziol Reanimatol</MedlineTA><NlmUniqueID>7705399</NlmUniqueID><ISSNLinking>0201-7563</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000765" MajorTopicYN="N">Anesthesia, Conduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000767" MajorTopicYN="Y">Anesthesia, Epidural</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016292" MajorTopicYN="Y">Conscious Sedation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D035002" MajorTopicYN="N">Lower Extremity</DescriptorName><QualifierName UI="Q000293" MajorTopicYN="Y">injuries</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008160" MajorTopicYN="Y">Lumbosacral Plexus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008991" MajorTopicYN="N">Monitoring, Physiologic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012119" MajorTopicYN="N">Respiration</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>1</Month><Day>5</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17061580</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17061576</PMID><DateCompleted><Year>2007</Year><Month>01</Month><Day>04</Day></DateCompleted><DateRevised><Year>2015</Year><Month>11</Month><Day>19</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2006</Year><Season>Jul-Aug</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Epidural anesthesia during operations on the heart in patients with obesity]. | We prospectively evaluated the effect of clonidine as an adjuvant to bupivacaine for continuous paravertebral intercostal nerve block, measuring pain and sedation scores and pulmonary function tests. Thirty patients scheduled to undergo thoracotomy were randomized to receive either a bolus of 0.125% bupivacaine 2 mg/kg (group BUP) or 0.125% bupivacaine 2 mg/kg with clonidine 2 microg/kg (group BUP+CLO), followed by an infusion of 0.125% bupivacaine at 0.5 mg/kg/h, or 0.125% bupivacaine at 0.5 mg/kg/h with clonidine at 2 microg/kg/h, in respective groups, through a paravertebral intercostal catheter. Haemodynamic parameters, pain and sedation scores and pulmonary function tests were recorded at 6, 12, 24 and 48 hours after arrival in postoperative care unit. There were significantly lower pain scores at rest and on coughing in group BUP+CLO compared with group BUP (P <0.01). Multiple comparisons revealed a significant reduction in pain score at each time point (P<0.01), except at 12h to 24h, in group BUP+CLO. Sedation scores were significantly higher in group BUP+CLO compared with group BUP at each time point (all P<0.01). There was a linear effect of time on sedation score in group BUP whereas in group BUP+CLO, the effect was quadratic. Patients in the clonidine group had a higher incidence of hypotension (P < 0.01). There was no significant difference in pulmonary function between the groups. We conclude that using clonidine as an adjunct to bupivacaine for continuous paravertebral intercostal nerve block improves pain relief after thoracotomy, but hypotension and sedation are adverse effects interfering with its clinical application.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bhatnagar</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Anaesthesiology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mishra</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Madhurima</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Gurjar</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Mondal</LastName><ForeName>A S</ForeName><Initials>AS</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Anaesth Intensive Care</MedlineTA><NlmUniqueID>0342017</NlmUniqueID><ISSNLinking>0310-057X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000316">Adrenergic alpha-Agonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000779">Anesthetics, Local</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D006993">Hypnotics and Sedatives</NameOfSubstance></Chemical><Chemical><RegistryNumber>MN3L5RMN02</RegistryNumber><NameOfSubstance UI="D003000">Clonidine</NameOfSubstance></Chemical><Chemical><RegistryNumber>Y8335394RO</RegistryNumber><NameOfSubstance UI="D002045">Bupivacaine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000316" MajorTopicYN="N">Adrenergic alpha-Agonists</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000779" MajorTopicYN="N">Anesthetics, Local</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001794" MajorTopicYN="N">Blood Pressure</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002045" MajorTopicYN="N">Bupivacaine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003000" MajorTopicYN="N">Clonidine</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003371" MajorTopicYN="N">Cough</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004311" MajorTopicYN="N">Double-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006993" MajorTopicYN="N">Hypnotics and Sedatives</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007278" MajorTopicYN="N">Injections, Spinal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007367" MajorTopicYN="N">Intercostal Nerves</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009407" MajorTopicYN="N">Nerve Block</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010147" MajorTopicYN="N">Pain Measurement</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010149" MajorTopicYN="N">Pain, Postoperative</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011446" MajorTopicYN="N">Prospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012129" MajorTopicYN="N">Respiratory Function Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013908" MajorTopicYN="Y">Thoracotomy</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>1</Month><Day>12</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17061632</ArticleId><ArticleId IdType="doi">10.1177/0310057X0603400507</ArticleId><ArticleId IdType="pii">2005395</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17061591</PMID><DateCompleted><Year>2007</Year><Month>01</Month><Day>04</Day></DateCompleted><DateRevised><Year>2006</Year><Month>10</Month><Day>25</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2006</Year><Season>Jul-Aug</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal><ArticleTitle>[Impact of subarachnoidal block on cardiac rhythm variability in children].</ArticleTitle><Pagination><StartPage>64</StartPage><EndPage>67</EndPage><MedlinePgn>64-7</MedlinePgn></Pagination><Abstract>The impact of spinal anesthesia on cardiac rhythm variability was studied in 36 children aged 13-17 years who had been operated on for urological, orthopedic, and vascular diseases. The findings were compared with the results obtained in 83 children with the same pathology at the age of 7-15 years, who had been operated under general anesthesia. A spectral cardiac sinus rhythm analysis demonstrated a steady state of stress-limiting systems during spinal block. Unlike general anesthesia, spinal anesthesia was ascertained to reduce the likelihood of intraoperative arrhythmias, by producing an adequate analgesic effect.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kuliov</LastName><ForeName>A G</ForeName><Initials>AG</Initials></Author><Author ValidYN="Y"><LastName>Aleksandrovich</LastName><ForeName>Iu S</ForeName><Initials>IuS</Initials></Author><Author ValidYN="Y"><LastName>Ul'rikh</LastName><ForeName>G E</ForeName><Initials>GE</Initials></Author><Author ValidYN="Y"><LastName>Zabolotskiĭ</LastName><ForeName>D V</ForeName><Initials>DV</Initials></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Anesteziol Reanimatol</MedlineTA><NlmUniqueID>7705399</NlmUniqueID><ISSNLinking>0201-7563</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000775" MajorTopicYN="N">Anesthesia, Spinal</DescriptorName><QualifierName UI="Q000592" MajorTopicYN="Y">standards</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D050723" MajorTopicYN="N">Fractures, Bone</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009407" MajorTopicYN="N">Nerve Block</DescriptorName><QualifierName UI="Q000592" MajorTopicYN="Y">standards</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013346" MajorTopicYN="N">Subarachnoid Space</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014570" MajorTopicYN="N">Urologic Diseases</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014652" MajorTopicYN="N">Vascular Diseases</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>1</Month><Day>5</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17061591</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17061590</PMID><DateCompleted><Year>2007</Year><Month>01</Month><Day>04</Day></DateCompleted><DateRevised><Year>2006</Year><Month>10</Month><Day>25</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2006</Year><Season>Jul-Aug</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal><ArticleTitle>[Regional anesthesia and sedation during extremity operations in children].</ArticleTitle><Pagination><StartPage>62</StartPage><EndPage>64</EndPage><MedlinePgn>62-4</MedlinePgn></Pagination><Abstract>Twenty-five studies were made in patients aged 12 to 15 years, who had been operated on for extremity injuries. The patients were divided into 2 groups: (1) those who had been given regional anesthesia with sedation (n=10) and (2) those who had received apparatus-mask anesthesia (n=15). The following parameters: heart rate, blood pressure, stroke volume, cardiac output were estimated. The study included 6 steps: (1) premedication; (2) postmedication; (3) postblock; (4) 20 min after block; (5) during skin incision; (6) after consciousness recovery. The findings suggest that there are insignificant hemodynamic changes when regional anesthesia is made in combination with drug sedation as compared with fluorotane-oxide-oxygen anesthesia.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chizhov</LastName><ForeName>D A</ForeName><Initials>DA</Initials></Author><Author ValidYN="Y"><LastName>Pivovarov</LastName><ForeName>S A</ForeName><Initials>SA</Initials></Author><Author ValidYN="Y"><LastName>Babaev</LastName><ForeName>B D</ForeName><Initials>BD</Initials></Author><Author ValidYN="Y"><LastName>Shishkov</LastName><ForeName>M V</ForeName><Initials>MV</Initials></Author><Author ValidYN="Y"><LastName>Ostreĭkov</LastName><ForeName>I F</ForeName><Initials>IF</Initials></Author><Author ValidYN="Y"><LastName>Shein</LastName><ForeName>V N</ForeName><Initials>VN</Initials></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Anesteziol Reanimatol</MedlineTA><NlmUniqueID>7705399</NlmUniqueID><ISSNLinking>0201-7563</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000765" MajorTopicYN="N">Anesthesia, Conduction</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001794" MajorTopicYN="N">Blood Pressure</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002648" MajorTopicYN="N">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016292" MajorTopicYN="N">Conscious Sedation</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005121" MajorTopicYN="N">Extremities</DescriptorName><QualifierName UI="Q000293" MajorTopicYN="Y">injuries</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008991" MajorTopicYN="N">Monitoring, Physiologic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013318" MajorTopicYN="N">Stroke Volume</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>1</Month><Day>5</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17061590</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17061580</PMID><DateCompleted><Year>2007</Year><Month>01</Month><Day>04</Day></DateCompleted><DateRevised><Year>2006</Year><Month>10</Month><Day>25</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2006</Year><Season>Jul-Aug</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal><ArticleTitle>[Modes of balanced regional anesthesia in patients with lower extremity injuries].</ArticleTitle><Pagination><StartPage>34</StartPage><EndPage>36</EndPage><MedlinePgn>34-6</MedlinePgn></Pagination><Abstract>The basic hemodynamic (systolic blood pressure (BP), diastolic BP, heart rate, stroke volume, cardiac output, RPP) and respiratory parameters (respiratory rate, tidal volume, respiratory minute volume) during operations on the lower extremities under epidural anesthesia (n=24; Group 1) versus lumbar plexus block by the 3-in-1 technique (n= 23; Group 2) were studied in 47 traumatological patients. With balanced epidural anesthesia, there was a short-term decrease in hemodynamic parameters and a worse external respiratory function; in 5 patients requiring its performance WL, balanced block of peripheral nerves of the lumbar plexus was, on the contrary, marked by a greater hemodynamic and respiratory stability.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sabirov</LastName><ForeName>D M</ForeName><Initials>DM</Initials></Author><Author ValidYN="Y"><LastName>Narziev</LastName><ForeName>M M</ForeName><Initials>MM</Initials></Author><Author ValidYN="Y"><LastName>Batirov</LastName><ForeName>U B</ForeName><Initials>UB</Initials></Author><Author ValidYN="Y"><LastName>Valiev</LastName><ForeName>E Iu</ForeName><Initials>EIu</Initials></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Anesteziol Reanimatol</MedlineTA><NlmUniqueID>7705399</NlmUniqueID><ISSNLinking>0201-7563</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000765" MajorTopicYN="N">Anesthesia, Conduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000767" MajorTopicYN="Y">Anesthesia, Epidural</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016292" MajorTopicYN="Y">Conscious Sedation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D035002" MajorTopicYN="N">Lower Extremity</DescriptorName><QualifierName UI="Q000293" MajorTopicYN="Y">injuries</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008160" MajorTopicYN="Y">Lumbosacral Plexus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008991" MajorTopicYN="N">Monitoring, Physiologic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012119" MajorTopicYN="N">Respiration</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>1</Month><Day>5</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>10</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17061580</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17061576</PMID><DateCompleted><Year>2007</Year><Month>01</Month><Day>04</Day></DateCompleted><DateRevised><Year>2015</Year><Month>11</Month><Day>19</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2006</Year><Season>Jul-Aug</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal><ArticleTitle>[Epidural anesthesia during operations on the heart in patients with obesity].</ArticleTitle><Pagination><StartPage>21</StartPage><EndPage>24</EndPage><MedlinePgn>21-4</MedlinePgn></Pagination><Abstract>The paper estimates an anesthetic appliance using an epidural block during cardiac operations in obese patients. It shows the advantage of this type of anesthesia in reducing the dose of used narcotic analgesics, in early activating patients, and decreasing the length of stay in a cardiac intensive care unit. |
2,333,260 | Cloning and expression pattern of chicken Ror2 and functional characterization of truncating mutations in Brachydactyly type B and Robinow syndrome. | Ror2 is a receptor tyrosine kinase mutated in the human syndromes Brachydactyly type B (BDB) and recessive Robinow syndrome (RS). In this study, we used the chick as a model to investigate the role of Ror2 in skeletogenesis and to elucidate the functional consequences of Ror2 mutations. For this purpose, we cloned chicken Ror2 and analyzed its expression pattern at various embryonic stages by in situ hybridization and immunolabeling. We document expression of cRor2 in several organs, including mesonephros, heart, nervous system, intestine and cartilage. The high conservation of expression when compared with the mouse underlines the validity of the chick as a model system. Using replication-competent retroviral vector-mediated overexpression, we analyzed the functional consequences of truncating BDB and RS mutations in the developing chick limb. Overexpression of Ror2 mutants led to a disturbance of growth plate architecture and a severe block of chondrocyte differentiation, demonstrating the functional importance of Ror2 in skeletogenesis. |
2,333,261 | The effects of spinal anesthesia on QT interval in preeclamptic patients. | In this study, we measured the effects of spinal anesthesia on the corrected QT (QTc) interval in women with severe preeclampsia. Twenty-five preeclamptic (preeclamptic group) and 25 healthy pregnant women with normal arterial blood pressure and QTc interval (control group) were enrolled in this prospective, case-controlled study. Arterial blood pressure, heart rate, and QTc interval values were obtained before (baseline value) and at 5, 10, 20, 30, 60, and 120 min after initiation of spinal anesthesia. Total ephedrine dose, time elapsed until sensory block, and Apgar scores were recorded. Prior to spinal anesthesia, QTc interval values were significantly higher in the preeclamptic group (452 +/- 17.5 ms) when compared with that in controls (376 +/- 21.4 ms). Although the QTc interval shortened during spinal anesthesia when compared with baseline value in the preeclamptic group (P < 0.05), it showed no significant change in the control group. In conclusion, the QTc interval may be prolonged in severe preeclamptic patients who have hypertension and hypocalcemia. Spinal anesthesia for cesarean delivery may normalize that prolonged QTc interval due to sympathetic blockade. |
2,333,262 | Articaine for supplemental intraosseous anesthesia in patients with irreversible pulpitis. | The purpose of this study was to determine the anesthetic efficacy and heart rate effect of 4% articaine with 1:100,000 epinephrine for supplemental intraosseous injection in mandibular posterior teeth diagnosed with irreversible pulpitis. Thirty-seven emergency patients, diagnosed with irreversible pulpitis of a mandibular posterior tooth, received an inferior alveolar nerve block and had moderate-to-severe pain upon endodontic access. The Stabident system was used to administer 1.8 ml of 4% articaine with 1:100,000 epinephrine. Success of the intraosseous injection was defined as none or mild pain upon endodontic access or initial instrumentation. The results demonstrated that anesthetic success was obtained in 86% (32 of 37) of the patients. Maximum mean heart rate was increased 32 beats/minute during the intraosseous injection. We can conclude that when the inferior alveolar nerve block fails to provide profound pulpal anesthesia, the intraosseous injection of 4% articaine with 1:100,000 epinephrine would be successful 86% of the time in achieving pulpal anesthesia in mandibular posterior teeth of patients presenting with irreversible pulpitis. |
2,333,263 | Effect of haloperidol on transient outward potassium current in rat ventricular myocytes. | Although sigma ligand haloperidol is known to affect repolarization in heart, its effect on potassium currents in cardiomyocytes has not yet been studied. We analyzed the effect of 1 micromol/l haloperidol on transient outward K(+) current (I(to)) in enzymatically isolated rat right ventricular cardiomyocytes using the whole-cell patch-clamp technique at room temperature. Haloperidol induced a decrease of amplitude and an acceleration of apparent inactivation of I(to), both in a voltage-independent manner. The averaged inhibition of I(to), evaluated as a change of its time integral, was 23.0+/-3.2% at stimulation frequency of 0.1 Hz. As a consequence of slow recovery of I(to) from the haloperidol-induced block (time constant 1482+/-783 ms), a cumulation of the block up to about 40% appeared at 3.3 Hz. We conclude that haloperidol causes a voltage-independent block of I(to) that cumulates at higher stimulation frequencies. Based on the computer reconstruction of experimental data, a block of I(to)-channels in both open and open-inactivated states appears to be likely mechanism of haloperidol-induced inhibition of I(to). |
2,333,264 | A comparison of nerve stimulator guided paravertebral block and ilio-inguinal nerve block for analgesia after inguinal herniorrhaphy in children. | The aim of this study was to compare the efficacy of nerve stimulator guided paravertebral block with ilio-inguinal nerve block in children undergoing inguinal herniorrhaphy. Eighty children were randomly allocated to receive either paravertebral block or ilio-inguinal nerve block. Each block was evaluated in terms of intra-operative haemodynamic stability, postoperative pain scores at rest, on movement and during activity, requirement for supplemental analgesia and parental satisfaction. Haemodynamic stability was maintained significantly better during sac traction in the paravertebral block group (p < 0.005). Pain scores and analgesic consumption were significantly lower in the paravertebral block group during the postoperative follow-up period (p < 0.05). Parental satisfaction (93%vs 69%) and surgeon satisfaction (93%vs 64%) were significantly higher in the paravertebral block group (p < 0.05). Paravertebral blockade improved and prolonged postoperative analgesia, and was associated with greater parental and surgeon satisfaction when compared to ilio-inguinal nerve block. |
2,333,265 | Mechanisms of vasoactive intestinal peptide-elicited coronary vasodilation in the isolated perfused rat heart. | The present study investigated the potential role of vasoactive intestinal peptide (VIP) receptors, VPAC1 and VPAC2, in VIP-elicited coronary vasodilation of the isolated perfused rat heart. Additional studies determined the role of ATP-sensitive (K(ATP)) and voltage-gated K(+) (K(V)) channels in the VIP-elicited coronary vasodilation. Both the selective VPAC1 agonist, K15,R16,L27VIPl-7GRF8-27, and the selective VPAC2 agonist, RO25-1553, decreased coronary vascular resistance (CVR) in a dose-dependent manner, with EC(50) values of 1.67x10(-9)M and 7.11x10(-9)M, respectively (VPAC1 vs VPAC2 agonist, P<0.05). K15,R16,L27VIP1-7GRF8-27 and RO25-1553 maximally reduced CVR by -42+/-4% and -39+/-6% at 1x10(-8) and 3x10(-8)M, respectively. VIP at 1x10(-10)M decreased CVR by -14+/-2% in the absence (vehicle), by -11+/-3% in the presence of the nonselective VIP receptor antagonist VIP10-28 (1x10(-7)M; P>0.05 vs. vehicle) and by only -4+/-2% in the presence of the selective VPAC2 receptor antagonist PACAP6-38 (1x10(-7)M; P<0.05 vs. vehicle). In additional studies, VIP at 1x10(-10)M decreased CVR by -22+/-1% in the absence (control) and by only -10+/-2% in the presence of the nonselective K(+) channel blocker tetrabutylammonium (3x10(-4)M; P<0.05 vs. control). VIP reduced CVR by -4+/-1% in the presence of the K(ATP) channel blocker glibenclamide (3x10(-6)M; P<0.05 vs control) and by -28+/-2% in the presence of the K(V) channel blocker 4-aminopyridine (3x10(-4)M; P>0.05 vs control). Thus, selective VPAC1 and VPAC2 receptor activation in the coronary circulation produces vasodilation and the VIP-elicited coronary vasodilation involves activation of VPAC2 receptors and K(ATP) but not K(V) channels. In addition, VIP10-28 does not effectively block coronary vascular VIP receptors. |
2,333,266 | Early pregnancy diagnosis by palpation per rectum: influence on embryo/fetal viability in dairy cattle. | The objective was to estimate the effect of palpation per rectum (for early pregnancy diagnosis) on embryo/fetal viability in dairy cattle. A controlled, randomized block-design experiment with two blocks, one by category, and the other by number of embryos, was conducted. Five-hundred-and-twenty pregnant dairy cows and heifers with a viable embryo detected by transrectal ultrasonography (TRUS) between days 29 and 32 after AI were included. The pregnant females were randomly allocated into two nearly equal groups: palpation per rectum (PAL group; n=258) and no palpation per rectum (NPAL group; n=262). The PAL group was submitted to palpation per rectum (PPR) using the fetal membrane slip (FMS) technique once between days 34 and 41 of pregnancy. The fetal membrane slip consisted of compressing the pregnant uterine horn and allowing the chorioallantoic membrane to slip between the fingers. Both groups were submitted to two additional TRUS at days 45 and 60 of pregnancy, to monitor the potential immediate and delayed deleterious effects of PPR on embryo and fetal viability, respectively. A diagnosis of embryo/fetal death was made when there was no embryo/fetal heart beat or the absence of positive signs of pregnancy in an animal previously diagnosed pregnant, or the presence of signs of embryo/fetal degeneration. The overall rate of embryo/fetal death was 14.0% (73/520). Embryonic death (10%; 52/520) was higher than fetal death (4.5%; 21/468; P<0.001). Embryo/fetal mortality was higher in cows (16.4%; 59/360) than in heifers (8.8%; 14/160; P<0.025) and in cattle with twin (25.5%; 12/47) versus singleton pregnancies (12.9%; 61/473; P<0.025), but was not different (P>0.05) between PAL (14.7%; 38/258) and NPAL (13.4%; 35/262). In conclusion, PPR between days 34 and 41 of pregnancy using the fetal membrane slip technique did not affect embryo/fetal viability. |
2,333,267 | Ethnicity modifies the association between diabetes mellitus and ischaemic heart disease in Chinese, Malays and Asian Indians living in Singapore. | <AbstractText Label="AIMS/HYPOTHESIS" NlmCategory="OBJECTIVE">The aim of the study was to determine whether the risk of ischaemic heart disease (IHD) associated with diabetes mellitus differs between ethnic groups.</AbstractText>Registry linkage was used to identify IHD events in 5707 Chinese, Malay and Asian Indian participants from three cross-sectional studies conducted in Singapore between the years 1984 and 1995. The study provided a median of 10.2 years of follow-up with 240 IHD events experienced. We assessed the interaction between diabetes mellitus and ethnicity in relation to the risk of IHD events using Cox proportional hazards regression.</AbstractText>Diabetes mellitus was more common in Asian Indians. Furthermore, diabetes mellitus was associated with a greater risk of IHD in Asian Indians. The hazard ratio when comparing diabetes mellitus with non-diabetes mellitus was 6.41 (95% CI 5.77-7.12) in Asian Indians and 3.07 (95% CI 1.86-5.06) in Chinese (p = 0.009 for interaction). Differences in the levels of established IHD risk factors among diabetics from the three ethnic groups did not appear to explain the differences in IHD risk.</AbstractText><AbstractText Label="CONCLUSIONS/INTERPRETATION" NlmCategory="CONCLUSIONS">Asian Indians are more susceptible to the development of diabetes mellitus than Chinese and Malays. When Asian Indians do develop diabetes mellitus, the risk of IHD is higher than for Chinese and Malays. Consequently, the prevention of diabetes mellitus amongst this ethnic group is particularly important for the prevention of IHD in Asia, especially given the size of the population at risk. Elucidation of the reasons for these ethnic differences may help us understand the pathogenesis of IHD in those with diabetes mellitus.</AbstractText> |
2,333,268 | Inhibition of cardiac voltage-gated sodium channels by grape polyphenols. | The cardiovascular benefits of red wine consumption are often attributed to the antioxidant effects of its polyphenolic constituents, including quercetin, catechin and resveratrol. Inhibition of cardiac voltage-gated sodium channels (VGSCs) is antiarrhythmic and cardioprotective. As polyphenols may also modulate ion channels, and possess structural similarities to several antiarrhythmic VGSC inhibitors, we hypothesised that VGSC inhibition may contribute to cardioprotection by these polyphenols.</AbstractText>The whole-cell voltage-clamp technique was used to record peak and late VGSC currents (INa) from recombinant human heart NaV1.5 channels expressed in tsA201 cells. Right ventricular myocytes from rat heart were isolated and single myocytes were field-stimulated. Either calcium transients or contractility were measured using the calcium-sensitive dye Calcium-Green 1AM or video edge detection, respectively.</AbstractText>The red grape polyphenols quercetin, catechin and resveratrol blocked peak INa with IC50s of 19.4 microM, 76.8 microM and 77.3 microM, respectively. In contrast to lidocaine, resveratrol did not exhibit any frequency-dependence of peak INa block. Late INa induced by the VGSC long QT mutant R1623Q was reduced by resveratrol and quercetin. Resveratrol and quercetin also blocked late INa induced by the toxin, ATX II, with IC50s of 26.1 microM and 24.9 microM, respectively. In field-stimulated myocytes, ATXII-induced increases in diastolic calcium were prevented and reversed by resveratrol. ATXII-induced contractile dysfunction was delayed and reduced by resveratrol.</AbstractText>Our results indicate that several red grape polyphenols inhibit cardiac VGSCs and that this effect may contribute to the documented cardioprotective efficacy of red grape products.</AbstractText> |
2,333,269 | [Perinatal consequences of maternal connective tissue diseases: a prospective study of 73 cases]. | To describe a group of newborns born from mothers with connective tissue diseases, to determine their perinatal characteristics and the neonatal morbidity, and to assess the possible role of drugs received by mothers on the obstetrical and neonatal morbidity.</AbstractText>During a 34-month period, newborns born from mothers with connective tissue diseases and followed in a single center were prospectively included in the study. In all cases, maternal treatments (i.e. hydroxychloroquine and/or prednisone) were continued during pregnancy.</AbstractText>Among the 73 included infants, 18 (25%) were born before 37 weeks of gestation and 3 (4%) were small for gestational age. A neonatal lupus syndrome with facial rash and thrombopenia was observed in 1 case. No neonatal congenital heart block was observed and maternal treatment did not significantly influence the mean PR or QT intervals. Four infants had minor congenital abnormalities and 3 had feto-maternal infection.</AbstractText>These data show that perinatal morbidity is lower than that previously published. We postulate that a strict follow-up during pregnancy may have played a significant positive role in these results.</AbstractText> |
2,333,270 | Electrophysiological effects of brompheniramine on cardiac ion channels and action potential. | Some antihistamines (mainly terfenadine and astemizole) have been demonstrated to cause QT interval prolongation and, in some cases, torsade-de-pointes. We investigated the cardiac electrophysiological effects of brompheniramine, a conventional antihistamine. Brompheniramine was reported to prolong QT interval in isolated hearts. To evaluate the electrophysiological effects of brompheniramine, we used whole-cell patch clamp techniques in human ether-a-go-go related gene (hERG)-stably transfected CHO cells, the SCN5A sodium channel transiently transfected CHO cells, and rat myocytes and conventional microelectrode recording techniques in isolated guinea pig papillary muscles. As for the I(hERG), the IC(50) value of brompheniramine was found to be 0.90+/-0.14microM with a Hill coefficient (n(H)) of 1.75+/-0.42. Action potential duration at 90% repolarization (APD(90)) was slightly prolonged by brompheniramine at 10 and 100microM, but APD(50) was shortened by 100microM. Moreover, despite the potent hERG current block, reductions of the V(max) and total amplitude of action potential were observed at high concentrations of brompheniramine. The change in action potential parameters and poor correlations between hERG and APD assay indicated additional effects of brompheniramine on non-hERG channels. In agreement with this hypothesis, the inhibition of I(Na) (IC(50) values: 21.26+/-2.52microM) and I(Ca) (IC(50) values: 16.12+/-9.43microM) by brompheniramine was observed. The results of this study suggest that brompheniramine may possess classes III, Ib and IV properties, especially at high concentrations and that additional studies on non-hERG channels will be necessary to elucidate the complex electrophysiological effects of brompheniramine on the heart. |
2,333,271 | Intrinsic tyrosine kinase activity is required for vascular endothelial growth factor receptor 2 ubiquitination, sorting and degradation in endothelial cells. | The human endothelial vascular endothelial growth factor receptor 2 (VEGFR2/kinase domain region, KDR/fetal liver kinase-1, Flk-1) tyrosine kinase receptor is essential for VEGF-mediated physiological responses including endothelial cell proliferation, migration and survival. How VEGFR2 kinase activation and trafficking are co-coordinated in response to VEGF-A is not known. Here, we elucidate a mechanism for endothelial VEGFR2 response to VEGF-A dependent on constitutive endocytosis co-ordinated with ligand-activated ubiquitination and proteolysis. The selective VEGFR kinase inhibitor, SU5416, blocked the endosomal sorting required for VEGFR2 trafficking and degradation. Inhibition of VEGFR2 tyrosine kinase activity did not block plasma membrane internalization but led to endosomal accumulation. Lysosomal protease activity was required for ligand-stimulated VEGFR2 degradation. Activated VEGFR2 codistributed with the endosomal hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)/signal-transducing adaptor molecule (STAM) complex in a ligand and time-dependent manner, implying a role for this factor in sorting of ubiquitinated VEGFR2. Increased tyrosine phosphorylation of the Hrs subunit in response to VEGF-A links VEGFR2 activation and Hrs/STAM function. In contrast, VEGFR2 in quiescent cells was present on both the endothelial plasma membrane and early endosomes, suggesting constitutive recycling between these two compartments. This pathway was clathrin-linked and dependent on the AP2 adaptor complex as the A23 tyrphostin inhibited VEGFR2 trafficking. We propose a mechanism whereby the transition of endothelial VEGFR2 from a constitutive recycling itinerary to a degradative pathway explains ligand-activated receptor degradation in endothelial cells. This study outlines a mechanism to control the VEGF-A-mediated response within the vascular system. |
2,333,272 | Signaling pathways regulating murine cardiac CREB phosphorylation. | Using the mouse Langendorff heart perfusion model, the signaling pathways that regulate cardiac CREB-S133 phosphorylation have been defined. In mouse hearts stimulated with isoproterenol (ISO) (10(-8) M), endothelin-1 (ET-1) (10(-8) M), and phorbol 12-myristate 13-acetate (TPA) (10(-7) M), CREB-S133 phosphorylation was attained only by TPA-treatment. Activation of protein kinase A (PKA) was achieved by ISO. ISO- and ET-1-stimulation activated Ca2+/calmodulin-dependent kinase II (CaMKII). Protein kinase C (PKC) and p90(RSK) were activated with all three stimuli. Inhibition of ERK1/2 with PD98059 (10(-5) M) completely inhibited the activation of p90(RSK), but did not block CREB-S133 phosphorylation in TPA-perfused heart, indicating that PKA, CaMKII, and p90(RSK) do not phosphorylate CREB-S133 in the murine heart. PKC activation is signal specific. Analyses of PKC isoforms suggest that CREB phosphorylation is mediated by PKC epsilon translocating into nucleus only with TPA stimulation. These results, unlike those reported in other tissues, demonstrate that cardiac CREB is not a multi-signal target. |
2,333,273 | Connective tissue diseases and pregnancy. | Connective tissue diseases (CTD) such as systemic lupus erythematosus diffuse or limited systemic sclerosis and numerous others affect women frequently during the childbearing period. Every pregnancy in a patient with CTD should be regarded as high-risk pregnancy, and requires intensive monitoring and immediate treatment of clinical problems. For these reasons, for women suffering from CTD, who are pregnant or who intend to become pregnant, an interdisciplinary setting addressing all aspects of rheumatology, ob-gyn and neonatalogy needs to be provided. This setting includes particular diagnostic tools and laboratory parameters prior to and during pregnancy as well as in the post-partal period. Aside overt organ dysfunction, key problems in pregnant CTD patients consist mainly of haemostaseological problems such as antiphospholipid antibodies, neonatal lupus erythematosus, congenital heart block and drug therapy of the underlying disease, which will be outlined in this review. |
2,333,274 | [Isoflavones in menopause women]. | Phytoestrogens are composed derivatives of vegetables. The 2 main classes of interest to human health are lignans and isoflavones. Isoflavones exist in at least 15 different chemical forms and their effect on human health has been investigated to some extent (particularly, genistein and daidzein as high levels of these compounds are present in soybean). Isoflavones have similar structure to oestrogen and have the capacity to exert both oestrogenic and anti oestrogenic effects. They may block the effects of oestrogen in some tissues (e. g., the breast and endometrium), but act like an oestrogen in providing possible protection against bone loss and heart disease. Lignans are much more widespread in plant foods but investigation has been limited due to the complexity of measurement. The increasing interest in the use of the soybean and the phytoestrogens derived from the soybean is due to the results published on experimental animal actions, and in human case-control studies. There are many observational and epidemiologists studies that suggest the potential benefit of isoflavones on the menopause symptoms, the cardiovascular system, the osteoporosis and the estrogen dependent cancers, but many open questions exist. We must be very strict with certain observational studies by the possible influences of collateral factors to the isoflavones (exercise, type of diet, etc.), and attribute the beneficial effects may be due to own treatment. |
2,333,275 | Role of Cav1.2 L-type Ca2+ channels in vascular tone: effects of nifedipine and Mg2+. | Ca(2+) entry via L-type voltage-gated Ca(2+) channels (LVGCs) is a key factor in generating myogenic tone (MT), as dihydropyridines (DHPs) and other LVGC blockers, including Mg(2+), markedly reduce MT. Recent reports suggest, however, that elevated external Mg(2+) concentration and DHPs may also inhibit other Ca(2+)-entry pathways. Here, we explore the contribution of LVGCs to MT in intact, pressurized mesenteric small arteries using mutant mice (DHP(R/R)) expressing functional but DHP-insensitive Ca(v)1.2 channels. In wild-type (WT), but not DHP(R/R), mouse arteries, nifedipine (0.3-1.0 microM) markedly reduced MT and vasoconstriction induced by high external K(+) concentrations ([K(+)](o)), a measure of LVGC-mediated Ca(2+) entry. Blocking MT and high [K(+)](o)-induced vasoconstriction by <1 microM nifedipine in WT but not in DHP(R/R) arteries implies that Ca(2+) entry via Ca(v)1.2 LVGCs is obligatory for MT and that nifedipine inhibits MT exclusively by blocking LVGCs. We also examined the effects of Mg(2+) on MT and LVGCs. High external Mg(2+) concentration (10 mM) blocked MT, slowed the high [K(+)](o)-induced vasoconstrictions, and decreased their amplitude in WT and DHP(R/R) arteries. To verify that these effects of Mg(2+) are due to block of LVGCs, we characterized the effects of extracellular and intracellular Mg(2+) on LVGC currents in isolated mesenteric artery myocytes. DHP-sensitive LVGC currents are inhibited by both external and internal Mg(2+). The results indicate that Mg(2+) relaxes MT by inhibiting Ca(2+) influx through LVGCs. These data provide new information about the central role of Ca(v)1.2 LVGCs in generating and maintaining MT in mouse mesenteric small arteries. |
2,333,276 | C2C12 skeletal muscle cells adopt cardiac-like sodium current properties in a cardiac cell environment. | Intracardiac transplantation of undifferentiated skeletal muscle cells (myoblasts) has emerged as a promising therapy for myocardial infarct repair and is already undergoing clinical trials. The fact that cells originating from skeletal muscle have different electrophysiological properties than cardiomyocytes, however, may considerably limit the success of this therapy and, in addition, cause side effects. Indeed, a major problem observed after myoblast transplantation is the occurrence of ventricular arrhythmias. The most often transient nature of these arrhythmias may suggest that, once transplanted into cardiac tissue, skeletal muscle cells adopt more cardiac-like electrophysiological properties. To test whether a cardiac cell environment can indeed modify electrophysiological parameters of skeletal muscle cells, we treated mouse C(2)C(12) myocytes with medium preconditioned by primary cardiocytes and compared their functional sodium current properties with those of control cells. We found this treatment to significantly alter the activation and inactivation properties of sodium currents from "skeletal muscle" to more "cardiac"-like ones. Sodium currents of cardiac-conditioned cells showed a reduced sensitivity to block by tetrodotoxin. These findings and reverse transcription PCR experiments suggest that an upregulation of the expression of the cardiac sodium channel isoform Na(v)1.5 versus the skeletal muscle isoform Na(v)1.4 is responsible for the observed changes in sodium current function. We conclude that cardiomyocytes alter sodium channel isoform expression of skeletal muscle cells via a paracrine mechanism. Thereby, skeletal muscle cells with more cardiac-like sodium current properties are generated. |
2,333,277 | Determination of the optimal angle for needle insertion during caudal block in children using ultrasound imaging. | Using ultrasound imaging, the optimal angle for needle insertion during caudal epidural injection in children was estimated. After general anaesthesia, ultrasonography was performed at the sacral hiatus in 130 children aged 2-84 months positioned in the lateral position. The median [range] values for the intercornual, caudal space depth and the distance from skin to the posterior sacral bony surface were 17.0 [9.6-24] mm, 3.5 [1-8] mm and 21.0 [10-39] mm, respectively. The optimal angle showed no significant correlation with age, weight, height or body surface area. The median [range] calculated optimal angle for the needle was 21.0 [10-38] degrees. We conclude that the needle should be inserted at about 20 degrees to the skin to avoid puncture of the bone and potential intra-osseous injection. |
2,333,278 | Crystal structure of monomeric native antithrombin reveals a novel reactive center loop conformation. | The poor inhibitory activity of circulating antithrombin (AT) is critical to the formation of blood clots at sites of vascular damage. AT becomes an efficient inhibitor of the coagulation proteases only after binding to a specific heparin pentasaccharide, which alters the conformation of the reactive center loop (RCL). The molecular basis of this activation event lies at the heart of the regulation of hemostasis and accounts for the anticoagulant properties of the low molecular weight heparins. Although several structures of AT have been solved, the conformation of the RCL in native AT remains unknown because of the obligate crystal contact between the RCL of native AT and its latent counterpart. Here we report the crystallographic structure of a variant of AT in its monomeric native state. The RCL shifted approximately 20 A, and a salt bridge was observed between the P1 residue (Arg-393) and Glu-237. This contact explains the effect of mutations at the P1 position on the affinity of AT for heparin and also the properties of AT-Truro (E237K). The relevance of the observed conformation was verified through mutagenesis studies and by solving structures of the same variant in different crystal forms. We conclude that the poor inhibitory activity of the circulating form of AT is partially conferred by intramolecular contacts that restrain the RCL, orient the P1 residue away from attacking proteases, and additionally block the exosite utilized in protease recognition. |
2,333,279 | Individual differences in drug abuse vulnerability: d-amphetamine and sensation-seeking status. | While the personality dimensions of novelty seeking and sensation seeking are associated with drug abuse vulnerability, the mechanisms associated with this vulnerability remain obscure.</AbstractText>This study examined the behavioral effects of d-amphetamine in healthy volunteers scoring in the upper and lower quartiles based on age- and gender-adjusted population norms on the impulsive Sensation-Seeking Scale (SSS) of the Zuckerman-Kuhlman personality questionnaire (ZKPQ).</AbstractText>Participants completed 7-day outpatient studies examining the subjective, performance, and cardiovascular effects of d-amphetamine (0, 7.5, and 15 mg/70 kg, p.o.) under double-blind conditions according to a randomized block design. Performance tasks included behavioral measures of impulsivity, including attention, inhibition, and risk-taking behavior.</AbstractText>No differences in baseline performance or d-amphetamine effects on measures of attention, inhibition, and risk-taking behavior were observed. High impulsive sensation seekers reported greater increases on several subjective report measures associated with drug abuse potential, including visual analog scales feel drug, like drug, and high.</AbstractText>Healthy adults scoring in the top quartile on the population of the impulsive SSS of the ZKPQ may be vulnerable to the abuse potential of d-amphetamine.</AbstractText> |
2,333,280 | Combined hERG channel inhibition and disruption of trafficking in drug-induced long QT syndrome by fluoxetine: a case-study in cardiac safety pharmacology. | Drug-induced prolongation of the rate-corrected QT interval (QTCI) on the electrocardiogram occurs as an unwanted effect of diverse clinical and investigational drugs and carries a risk of potentially fatal cardiac arrhythmias. hERG (human ether-à-go-go-related gene) is the gene encoding the alpha-subunit of channels mediating the rapid delayed rectifier K+ current, which plays a vital role in repolarising the ventricles of the heart. Most QTCI prolonging drugs can inhibit the function of recombinant hERG K+ channels, consequently in vitro hERG assays are used widely as front-line screens in cardiac safety-testing of novel chemical entities. In this issue, Rajamani and colleagues report a case of QTCI prolongation with the antidepressant fluoxetine and correlate this with a dual effect of the drug and of its major metabolite norfluoxetine on hERG channels. Both compounds were found to produce an acute inhibition of the hERG channel by pharmacological blockade, but in addition they also were able to disrupt the normal trafficking of hERG protein to the cell membrane. Mutations to a key component of the drug binding site in the S6 region of the channel greatly attenuated channel block, but did not impair disruption of trafficking; this suggests that channel block and drug effects on trafficking were mediated by different mechanisms. These findings add to growing evidence for disruption of hERG channel trafficking as a mechanism for drug-induced long QT syndrome and raise questions as to possible limitations of acute screening methods in the assessment of QTcI prolonging liability of drugs in development. |
2,333,281 | Identification of Clostridium difficile toxin B cardiotoxicity using a zebrafish embryo model of intoxication. | Clostridium difficile toxin B (TcdB) has been studied extensively by using cell-free systems and tissue culture, but, like many bacterial toxins, the in vivo targets of TcdB are unknown and have been difficult to elucidate with traditional animal models. In the current study, the transparent Danio rerio (zebrafish) embryo was used as a model for imaging of in vivo TcdB localization and organ-specific damage in real time. At 24 h after treatment, TcdB was found to localize at the pericardial region, and zebrafish exhibited the first signs of cardiovascular damage, including a 90% reduction in systemic blood flow and a 20% reduction in heart rate. Within 72 h of exposure to TcdB, the ventricle chamber of the heart became deformed and was unable to contract or pump blood, and the fish exhibited extensive pericardial edema. In line with the observed defects in ventricle contraction, TcdB was found to directly disrupt coordinated contractility and rhythmicity in primary cardiomyocytes. Furthermore, using a caspase-3 inhibitor, we were able to block TcdB-related cardiovascular damage and prevent zebrafish death. These findings present an insight into the in vivo targets of TcdB, as well as demonstrate the strength of the zebrafish embryo as a tractable model for identification of in vivo targets of bacterial toxins and evaluation of novel candidate therapeutics. |
2,333,282 | Progressive increase in conduction velocity across human mesenchymal stem cells is mediated by enhanced electrical coupling. | The purpose of the study was to investigate the development of electrical transmission across human adult bone marrow-derived mesenchymal stem cells (hMSCs) during long-term co-incubation with cardiomyocytes (CMCs).</AbstractText>Neonatal rat CMCs were cultured in multi-electrode array dishes. A conduction block was induced by creating a central acellular channel, yielding two asynchronously beating CMC fields. Enhanced green fluorescent protein (eGFP)-labeled hMSCs from ischemic heart disease patients (n=8), eGFP-labeled hMSCs having RNA interference-mediated connexin43 (Cx43) knockdown (n=6), 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (Dil)-labeled CMCs (n=6), or no cells (n=9) were seeded in the channel. Assessment of conduction velocity (CV), Cx expression and localization, gap junctional coupling, and intracellular electrical recordings were performed for up to 14 days.</AbstractText>Resynchronization of the two CMC fields occurred within 24 h after seeding of hMSCs. CV across hMSCs increased from 1.4+/-0.4 cm/s at day 7 to 3.5+/-0.1 cm/s (p<0.05) at day 14. CV across seeded CMCs was 16.8+/-0.2 cm/s throughout this period. No resynchronization occurred in the absence of seeded cells. Knockdown of Cx43 in hMSCs abolished conduction across the channel completely. Time-dependent increase of CV across hMSCs was associated with increased Cx43 mRNA and protein expression resulting in increased gap junctional coupling. Intracellular recordings in coupled hMSCs showed increased conducted action potential (AP) amplitude, lower resting membrane potential, and decreased duration of conducted AP (p<0.05, day 14 versus day 1).</AbstractText>CV across hMSCs increases progressively after 7 days of co-incubation with CMCs, most likely via improved electrotonic interaction. This is associated with increased Cx43 expression, increased functional gap junctional coupling, and enhanced intercellular electrical coupling between hMSCs and CMCs.</AbstractText> |
2,333,283 | Association of Duke prognostic treadmill scores with change in P-wave duration during exercise tolerance tests in patients with interatrial block and coronary heart disease. | Interatrial block (IAB), as denoted by P waves > or =110 ms in duration, is believed to be associated with underlying ischemia, particularly with that of its principal interatrial conduction pathway, the Bachmann bundle. In this study, the association between Duke prognostic treadmill (DPT) scores and change in P-wave duration in IAB was investigated in patients who underwent cardiopulmonary exercise tolerance tests (CPETTs). Twenty-seven patients with IAB and 42 control patients without IAB on electrocardiography at rest who had evidence of myocardial ischemia on coronary angiography after CPETTs were identified consecutively. P-wave measurements were obtained independently at the beginning of every CPETT stage and also when P-wave changes occurred. Increments in P-wave durations were measured to the nearest 20 ms. DPT scores were calculated for the 2 groups. There was no significant difference between the groups in mean values for DPT scores and for exercise capacity. However, change in P-wave duration in patients with IAB was significantly associated with mean DPT score. As the change in P-wave duration increased, the DPT score was significantly less (p = 0.003). DPT scores were more significant with P-wave changes of >20 ms compared with P-wave changes of < or =20 ms (p = 0.00001). In conclusion, in patients with coronary heart disease and IAB at rest, increases in P-wave durations during CPETTs are inversely associated with DPT scores. |
2,333,284 | Does gamma-tocopherol play a role in the primary prevention of heart disease and cancer? A review. | Vitamin E consists of a group of eight isomers, four tocopherols (alpha-, beta-, gamma-, delta-tocopherol) and four tocotrienols (alpha-, beta-, gamma-, delta-tocotrienol). While extensive literature has been published on the potential health benefits of alpha-tocopherol, little is known about gamma-tocopherol, the major form of vitamin E in food in the U.S. gamma-tocopherol has recently received more research attention based on findings from in vitro and animal studies indicating that it has potent anti-inflammatory and antioxidant properties. Based on these recent studies, it is important to investigate the possible health benefits of gamma-tocopherol in humans. In this article, we review publications on dietary gamma-tocopherol intake, plasma gamma-tocopherol levels, cardiovascular disease and cancer risk in humans. |
2,333,285 | If current inhibition: cellular basis and physiology. | The slow diastolic depolarization phase in cardiac pacemaker cells is the electrical basis of cardiac automaticity. The hyperpolarization-activated current (I(f)) is one of the key mechanisms underlying diastolic depolarization. Particularly, I(f) is unique in being activated on membrane hyperpolarization following the repolarization phase of the action potential. I(f) has adapted biophysical properties and voltage-dependent gating to initiate pacemaker activity. I(f) possibly constitutes the first voltage-dependent trigger of the diastolic depolarization. For these reasons, I(f) is a natural pharmacological target for controlling heart rate in cardiovascular disease. In this view, I(f) inhibitors have been developed in the past, yet the only molecule to have reached the clinical development is ivabradine. At the cellular level, the remarkable success of ivabradine is to be ascribed to its relatively high affinity for f-channels. Furthermore, ivabradine is the most I(f)-specific inhibitor known to date, since moderate inhibition of other voltage-dependent ionic currents involved in automaticity can be observed only at very high concentrations of ivabradine, more than one order of magnitude from that inhibiting I(f). Finally, the mechanism of block of f-channels by ivabradine has particularly favorable properties in light of controlling heart rate under variable physiological conditions. In this article, we will discuss how I(f) inhibition by ivabradine can lead to reduction of heart rate. To this aim, we will comment on the role of I(f) in cardiac automaticity and on the mechanism of action of ivabradine on f-channels. Some aspects of the cardiac pacemaker mechanism that improve the degree of security of ivabradine will also be highlighted. |
2,333,286 | Blocking expression of AHR2 and ARNT1 in zebrafish larvae protects against cardiac toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. | The zebrafish (Danio rerio) has become an attractive vertebrate model for studying developmental processes, and is emerging as a model system for studying the mechanisms by which xenobiotic compounds perturb normal development. Embryos treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) shortly after fertilization exhibit a range of adverse effects on the heart: an early reduction in cardiac myocyte number, followed by a change in heart looping and morphology, with an apparent compaction of the ventricle and overall decrease in heart size. These changes are accompanied by impaired cardiac function including a decrease in cardiac output and eventually irreversible ventricular standstill. The mechanisms involved in mediating effects of TCDD on the heart remain unknown. However, it is widely accepted that aryl hydrocarbon receptor (AHR) activation mediates endpoints of TCDD toxicity in vertebrates. In zebrafish, there are multiple forms of AHR and AHR nuclear translocator protein (ARNT) raising the question about whether different endpoints of TCDD toxicity are mediated by different components of the AHR/ARNT pathway. To address this question we used morpholino oligonucleotide technology to specifically block the expression of zfAHR2, zfARNT1, zfARNT2, and zfCYP1A, and assessed the previously described effects of TCDD on heart morphology, size, and function in the developing morphants. We report that blocking zfAHR2 and zfARNT1 expression provided protection against the TCDD-mediated alteration in heart morphology, reduced cardiac myocyte number, decreased cardiac output and ventricular standstill in zebrafish larvae, while the zfarnt2 and zfcyp1a morpholinos did not block the TCDD-induced cardiac toxicity. |
2,333,287 | Metabolic fate of administered [13C]galactose in tissues of galactose-1-phosphate uridyl transferase deficient mice determined by nuclear magnetic resonance. | The pattern of distribution of galactose and its metabolites was determined in tissues of mice deficient in galactose-1-phosphate uridyl transferase (G/G) 4 h after the administration of 1mg/g of [13C]galactose. Labeled galactose was found in all the tissues examined, the highest amounts in liver and kidney. Each of the tissues had its own pattern of labeling of galactose-1-phosphate (gal-1-P), galactitol and galactonate. [13C]gal-1-P and galactonate concentration was highest in liver while [13C]galactitol was higher in kidney and heart than in other tissues. Muscle had the lowest amounts of these compounds. In contrast, no galactose was found in tissues of normal mice (N/N) except for a minute amount in muscle. No [13C]gal-1-P was found in liver, kidney or brain and only minute amounts in heart and muscle of N/N animals. Barely detectible, labeled galactitol was observed in these tissues except liver, where none was found. [13C]Galactonate was formed in liver comparable to G/G mice. Almost all of the accumulating 13C isotope was found in liver and kidney glucose and lactate in the normal animals. [13C]Glucose and lactate was also found in liver of the G/G animals, but to a lesser extent than in normals, indicating the presence of a pathway in G/G animals for circumventing the block at GALT for the normal conversion of galactose to glucose. |
2,333,288 | L-Theanine reduces psychological and physiological stress responses. | L-Theanine is an amino acid contained in green tea leaves which is known to block the binding of L-glutamic acid to glutamate receptors in the brain. Because the characteristics of L-Theanine suggest that it may influence psychological and physiological states under stress, the present study examined these possible effects in a laboratory setting using a mental arithmetic task as an acute stressor. Twelve participants underwent four separate trials: one in which they took L-Theanine at the start of an experimental procedure, one in which they took L-Theanine midway, and two control trials in which they either took a placebo or nothing. The experimental sessions were performed by double-blind, and the order of them was counterbalanced. The results showed that L-Theanine intake resulted in a reduction in the heart rate (HR) and salivary immunoglobulin A (s-IgA) responses to an acute stress task relative to the placebo control condition. Moreover, analyses of heart rate variability indicated that the reductions in HR and s-IgA were likely attributable to an attenuation of sympathetic nervous activation. Thus, it was suggested that the oral intake of L-Theanine could cause anti-stress effects via the inhibition of cortical neuron excitation. |
2,333,289 | A computational system to optimise noise rejection in photoplethysmography signals during motion or poor perfusion states. | Photoplethysmography (PPG) signals can be used in clinical assessment such as heart rate (HR) estimations and extraction of arterial flow waveforms. Motion artefact and/or poor peripheral perfusion can contaminate the PPG during monitoring. A computational system is presented here to minimise these two intrinsic weaknesses of the PPG signals. Specifically, accelerometers are used to detect the presence of motion artefacts and an adaptive filter is employed to minimise induced errors. Zero-phase digital filtering is engaged to reduce inaccuracy on the PPG signals when measured from a poorly perfused periphery. In this system, a decision matrix adopts the appropriate technique to improve the PPG signal-to-noise ratio dynamically. Statistical analyses show promising results (maximum error < 7.63%) when computed HR is compared to corresponding estimates from the electrocardiogram. Hence, the results here suggest that this dual-mode approach has potential for use in relevant clinical measurements. |
2,333,290 | Is there an increased risk of local recurrence under the heart block in patients with left-sided breast cancer? | Tangential radiotherapy for left-sided breast cancer may be cardiotoxic. Shaping the field with a heart block reduces cardiac exposure but may under-dose the breast and/or chest wall. We compared the incidence and location of local recurrences in patients irradiated with and without a heart block.</AbstractText>Between 1994 and 1998, 180 patients irradiated to the left breast and/or chest wall were retrospectively reviewed. The local recurrence rates in patients treated with and without a heart block were compared using a 2-tailed Fisher exact test. An in-depth dosimetric analysis was performed in 23 patients to assess the percentage of breast tissue under-dosed by inclusion of the heart block.</AbstractText>Overall, the local recurrence rates in patients with or without a heart block were similar. In postlumpectomy patients with inferiorly located tumors, the rates of local recurrence with and without a heart block were 2 of 6 patients versus 0 of 19 patients, respectively. In the dosimetric analysis, the average percentage of breast tissue under-dosed by the inclusion of a heart block was 2.8% (range, 0%-11%).</AbstractText>A heart block is a reasonable method to limit cardiac dose but should be used cautiously following a lumpectomy in patients with inferiorly located tumors. Additional study with larger numbers of patients is warranted.</AbstractText> |
2,333,291 | Enhancement of bupivacaine local anesthesia with the potassium channel blocker ibutilide. | In some clinical settings it is necessary to inject large volumes of local anesthetic--and consequently very high doses--in order to provide an adequate level of block. Subsequent absorption of these high doses, or inadvertent intravenous administration of even small doses, has led to systemic toxicity. Thus, it is desirable to develop adjuvants that are inert alone, but would enhance the potency and/or efficacy of local anesthetics to improve their safety. Adelta/C fibers possess K(+) channels identified as sustained delayed rectifier type K(DR) currents and transient A-type K(A) currents. In the heart, the class III antiarrhythmic drug ibutilide blocks the cardiac component of the rapid delayed rectifying K(+) current (IKr). Experiments were conducted to determine whether co-administration of the K(+) channel blocker ibutilide would enhance the local anesthetic bupivacaine in mice. After injecting bupivacaine mixed with vehicle or ibutilide in the popliteal region of mice, paw withdrawal latencies were determined by applying the plantar aspect of a single hind-paw to the surface a 55 degrees C hot-plate device. 0.5% Bupivacaine+ibutilide (7.8x10(-5) M) elicited significantly longer hot-plate latencies than 0.5% bupivacaine+vehicle. In addition, bupivacaine was 2.6-fold more potent when co-administered with ibutilide rather than vehicle. Epinephrine extends the tissue concentrations of local anesthetics by inducing localized vasoconstriction. Epinephrine augmented the enhancement by ibutilide of bupivacaine's potency by 6.8-fold. In summary, ibutilide may enhance the effects of bupivacaine by blocking K(+) channels on sensory nociceptive nerves. |
2,333,292 | In vitro study of the safety limits of bronchoscopic argon plasma coagulation in the presence of airway stents. | The purpose of this study was to identify the safety limits of bronchoscopic argon plasma coagulation (APC) around indwelling airway stents.</AbstractText>This is an experimental in vitro study simulating a patient-care environment. Uncovered and covered Nitinol (Ultraflex), uncovered and covered Wallstent and studded silicone stents were deployed in the tracheobronchial tree of a ventilated and oxygenated heart-lung block from an expired pig. APC was performed at power settings of 40 and 80 W using F(I)O(2) of 0.21, 0.40 and 1.00 and an argon gas-flow rate of 0.8 L/min through a flexible fiberoptic bronchoscope. The primary outcome was the time taken for the APC to cause stent damage. Stent damage was defined as discoloration, ignition or rupture.</AbstractText>Airway fires involving all five stents consistently occurred in the presence of 100% oxygen at powers of 40 W and 80 W. At lower F(I)O(2) (0.21 and 0.40) silicone stents were not damaged at 40 W and 80 W. Uncovered Ultraflex stents were undamaged using 40 W at either F(I)O(2) (0.21 and 0.40), but could be damaged using both F(I)O(2) levels when the power was increased to 80 W. Covered Ultraflex and both uncovered and covered Wallstents were damaged at both power settings (40 W and 80 W) and F(I)O(2) (0.21 and 0.40) levels, with a trend towards earlier damage using higher F(I)O(2) and power.</AbstractText>Working within the parameters identified in this study (power 40 W, F(I)O(2) 0.21, APC flow-rate 0.8 L/min), APC is a safe method for tissue devitalization and destruction and avoids the risk of airway stent ignition, especially if short bursts of APC are employed. The safety limits identified using an F(i)O(2) of 0.4, however, are also important because some patients undergoing resection may require oxygen therapy.</AbstractText> |
2,333,293 | The role of the hyperpolarization-activated inward current If in arrhythmogenesis: a computer model study. | Atrial fibrillation is the most common cardiac arrhythmia. Structural cardiac defects such as fibrosis and gap junction remodeling lead to a reduced cellular electrical coupling and are known to promote atrial fibrillation. It has been observed that the expression of the hyperpolarization-activated current If is increased under pathological conditions. Recent experimental data indicate a possible contribution of If to arrhythmogenesis. In this paper, the role of If in action potential propagation in normal and in pathological tissue is investigated by means of computer simulations. The effect of diffuse fibrosis and gap junction remodeling is simulated by reducing cellular coupling nonuniformly. As expected, the conduction velocity decreases when cellular coupling is reduced. In the presence of If the conduction velocity increases both in normal and in pathological tissue. In our simulations, ectopic activity is present in regions with high expression of If and is facilitated by cellular uncoupling. We conclude that an increased If may facilitate propagation of the action potential. Hence, If may prevent conduction slowing and block. Overexpression of If may lead to ectopic activity, especially when cellular coupling is reduced under pathological conditions. |
2,333,294 | Tolerogenic protocol for intestinal transplantation. | Transplantation is standard therapy for many patients suffering from kidney, liver, or heart failure. In contrast, transplantation of the intestine remains a high-risk procedure, which is performed in a minority of patients with short bowel syndrome. The difficulty is the strong alloimmune response caused by intestinal grafts and the complications of the profound immunosuppression. We tested a new clinical immunomodulatory protocol using donor-specific blood transfusion, a strategy that was popular before the introduction of cyclosporine and was recently shown to promote development of regulatory cells. Low-dose steroids and low-dose tacrolimus were administered based on previous observations that tolerance requires an intact immune system, that over-immunosuppression is counterproductive, and that high doses of calcineurin inhibitors block development of regulatory cells whereas low doses promote it. Finally, inflammation within the intestinal graft was minimized to reduce the additional stimulants that the innate immunity of the transplanted intestine exert on the adaptive immune response. Under this protocol, freedom from rejection was achieved in four consecutive intestinal transplant recipients using extremely low immunosuppression. |
2,333,295 | Impaired clearance of apoptotic cardiocytes is linked to anti-SSA/Ro and -SSB/La antibodies in the pathogenesis of congenital heart block. | The role of cardiocytes in physiologic removal of apoptotic cells and the subsequent effect of surface binding by anti-SSA/Ro and -SSB/La antibodies was addressed. Initial experiments evaluated induction of apoptosis by extrinsic and intrinsic pathways. Nuclear injury and the translocation of SSA/Ro and SSB/La antigens to the fetal cardiocyte plasma membrane were common downstream events of Fas and TNF receptor ligation, requiring caspase activation. As assessed by phase-contrast and confirmed by confocal microscopy, coculturing of healthy cardiocytes with cardiocytes rendered apoptotic via extrinsic pathways revealed a clearance mechanism that to our knowledge has not previously been described. Cultured fetal cardiocytes expressed phosphatidylserine receptors (PSRs), as did cardiac tissue from a fetus with congenital heart block (CHB) and an age-matched control. Phagocytic uptake was blocked by anti-PSR antibodies and was significantly inhibited following preincubation of apoptotic cardiocytes with chicken and murine anti-SSA/Ro and -SSB/La antibodies, with IgG from an anti-SSA/Ro- and -SSB/La-positive mother of a CHB child, but not with anti-HLA class I antibody. In a murine model, anti-Ro60 bound and inhibited uptake of apoptotic cardiocytes from wild-type but not Ro60-knockout mice. Our results suggest that resident cardiocytes participate in physiologic clearance of apoptotic cardiocytes but that clearance is inhibited by opsonization via maternal autoantibodies, resulting in accumulation of apoptotic cells, promoting inflammation and subsequent scarring. |
2,333,296 | Role of cyclic GMP and calcineurin in homologous and heterologous desensitization of natriuretic peptide receptor-A. | The natriuretic peptide receptor-A (NPR-A) mediates natriuretic, hypotensive, and antihypertrophic effects of natriuretic peptides through the production of cGMP. In pathological conditions such as heart failure, these effects are attenuated by homologous and heterologous desensitization mechanisms resulting in the dephosphorylation of the cytosolic portion of the receptor. In contrast with natriuretic peptide-induced desensitization, pressor hormone-induced desensitization is dependent on protein kinase C (PKC) stimulation and (or) cytosolic calcium elevation. Mechanisms by which PKC and Ca(2+) promote NPR-A desensitization are not known. The role of cGMP and of the cytosolic Ca(2+) pathways in NPR-A desensitization were therefore studied. In contrast with the activation of NPR-A by its agonist, activation of soluble guanylyl cyclases of LLC-PK1 cells by sodium nitroprusside also leads to a production of cGMP but without altering NPR-A activation. Consequently, cGMP elevation per se does not appear to mediate homologous desensitization of NPR-A. In addition, cytosolic calcium increase is required only for the heterologous desensitization pathway since the calcium chelator BAPTA-AM blocks only PMA or ionomycin-induced desensitization. Calcineurin inhibitors block the NPR-A guanylyl cyclase heterologous desensitization induced by ionomycin, suggesting an essential role for this Ca(2+)-stimulated phosphatase in NPR-A desensitization. In summary, the present report demonstrates that neither cGMP nor Ca(2+) cytosolic elevation cause NPR-A homologous desensitization. Our results also indicate for the first time a role for calcineurin in NPR-A heterologous desensitization. |
2,333,297 | Hypocretin/orexin type 1 receptor in brain: role in cardiovascular control and the neuroendocrine response to immobilization stress. | Hypocretin/orexin acts pharmacologically in the hypothalamus to stimulate stress hormone secretion at least in part by an action in the hypothalamic paraventricular nucleus, where the peptide's receptors have been localized. In addition, orexin acts in the brain to increase sympathetic tone and, therefore, mean arterial pressure and heart rate. We provide evidence for the role of endogenously produced hypocretin/orexin in the physiological response to immobilization stress and identify the receptor subtype responsible for this action of the peptide. Antagonism of the orexin type 1 receptor (OX(1)R) in the brain prevented the ACTH-stimulating effect of centrally administered hypocretin/orexin. Furthermore, pretreatment of animals with the OX(1)R antagonist blocked the ACTH response to immobilization/restraint stress. The OX(1)R antagonist did not, however, block the pharmacological or physiological release of prolactin in these two models. Antagonism of the OX(1)R also blocked the central action of orexin to elevate mean arterial pressures and heart rates in conscious rats. These data suggest receptor subtype-selective responses to hypocretin/orexin and provide further evidence for the importance of endogenously produced peptide in the physiological control of stress hormone secretion. |
2,333,298 | [Correlation between succinate-dependent Ca2+ accumulation and transamination in the heart and the liver mitochondria of experimental animals]. | Glutamate (GLU) and alpha-ketoglutarate (KGL), the substrates involved in transamination, have reciprocal effects on succinate-dependent respiration, NADH reduction, as well as on the accumulation and stable retention of Ca2+ in heart and liver mitochondria and homogenates from experimental animals. The succinate-dependent Ca2+ accumulation was shown to be highly sensitive to changes of the concentration ratios of GLU and KGL within the range 1:10 mM. GLU activated this process by transamination of oxalacetate (OAA) to aspartate. The predomination of KGL blocked the activating effect of GLU. The predomination of GLU eliminated the block produced by KGL or phosphoenolpyruvate (sources of OAA and GTP) but did not eliminate the Ca2+ accumulation-suppressing effect of aminoacetate, inhibitor of transaminases. |
2,333,299 | Comparison between neurotropin and mepivacaine for stellate ganglion injection. | Neurotropin, a nonproteinaceous extract from the inflamed skin of rabbits inoculated with vaccinia virus, is reported to decrease pain effectively when used for stellate ganglion (SG) injection. We compared the effects of neurotropin SG injection with those of mepivacaine on pain relief, as well as comparing the side effects. One hundred and eighty-eight SG injections in 15 patients (5 with postherpetic neuralgia and 10 with sudden deafness) were performed either with 1% mepivacaine 6 ml or with neurotropin 3 ml combined with saline 3 ml in turn. Fifteen min before and after the injection, the pain score, according to a visual analog scale (VAS; only in patients with postherpetic neuralgia); blood pressure; and heart rate were checked, and the number of procedures with Horner's sign was determined. VAS scores decreased significantly with both injections. Horner's sign was observed on the block side in all procedures with the mepivacaine injection, but it was seen in only 48 procedures with the neurotropin injection. Blood pressure and heart rate did not change. In conclusion, the SG injection of neurotropin decreased the VAS score in postherpetic neuralgia to the same extent as mepivacaine. The incidence of Horner's sign was significantly lower with neurotropin than with mepivacaine. |
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