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2,332,400 | Pulsioxymetry monitorization during lower third molar extraction. A comparative study of three local anesthetics with epinephrine 1:100,000. | A double-blind, parallel non-randomized study is made to compare the heart rate and oxygen saturation levels in healthy patients subjected to lower third molar extractions under the effect of three different local anesthetics (4% articaine, 2% lidocaine, 2% mepivacaine) with the same epinephrine concentration (1:100,000). The patients were divided into three groups of 15 subjects each, according to the anesthetic employed. Heart rate and oxygen saturation were determined in each patient before and immediately after anesthetic injection, and again one minute after motor application to perform the ostectomy, at the start of force application to extract the tooth, on completing suture, and one week later at suture removal (the latter being taken as baseline reference). Blood pressure was also recorded, calculating the mean arterial pressure and the rate-pressure product (RPP) and pressure-rate quotient (PRQ). Only heart rate showed variations during the intervention, regardless of the local anesthetic used (based on a multifactor analysis of variance and considering statistical significance for p < 0.05). It may be concluded that none of the local anesthetics studied exert important effects upon the variables analyzed in healthy patients, though significant variations may arise due to the stress and/or anxiety associated to certain moments of lower third molar extraction. |
2,332,401 | Isoflurane-induced protection against myocardial stunning is independent of adenosine 1 (A(1)) receptor in isolated rat heart. | Volatile anaesthetics can pharmacologically enhance the recovery of stunned myocardium, but the mechanism is still unknown. This study sought to determine whether isoflurane attenuates myocardial stunning, and whether the myocardial protection of isoflurane is mediated by adenosine A(1) receptors. Five groups (n=8) of isolated rat hearts were studied in the Langendorff apparatus. The control groups underwent 20-min ischaemia with or without adenosine receptor antagonist (DPCPX, A(1)()selective) treatment (Cont group and DPCPX group). In the isoflurane groups, isoflurane (1.5 MAC) was present throughout the experiment (Iso group) and DPCPX (200 nM) was administered from 10 min before ischaemia (Iso+DPCPX(pre-I) group) or the beginning of reperfusion (Iso+DPCPX(post-I) group) to the end of experiment. The isoflurane groups had a lower end-diastolic pressure than the control groups (P<0.05). Developed pressure recovered to 77, 76, and 82% in Iso, Iso+DPCPX(pre-I) and Iso+DPCPX(post-I) groups, respectively (P<0.05 compared with control groups). LV+dp/dt(max) recovered to 53, 86, 81, 84, and 60% of pre-ischaemic values in Cont, Iso, Iso+DPCPX(pre-I), Iso+DPCPX(post-I), and DPCPX groups. LV-dp/dt(min) recovered to 55, 84, 83, 81, and 62%, respectively. Both LV+dp/dt(max) and LV-dp/dt(min) were significantly different (P<0.05) between control and isoflurane groups during reperfusion. There were no significant differences among the isoflurane groups. Our data show that isoflurane enhances the post-ischaemic functional recovery of isolated rat heart and that block of A(1) receptors does not abolish the beneficial effects of isoflurane. We conclude that A(1)()receptors are not involved in isoflurane-induced myocardial protection in the isolated rat heart. |
2,332,402 | Adenosine 3',5'-cyclic monophosphate (cAMP)-dependent inhibition of IL-5 from human T lymphocytes is not mediated by the cAMP-dependent protein kinase A. | IL-5 is implicated in the pathogenesis of asthma and is predominantly released from T lymphocytes of the Th2 phenotype. In anti-CD3 plus anti-CD28-stimulated PBMC, albuterol, isoproterenol, rolipram, PGE2, forskolin, cholera toxin, and the cAMP analog, 8-bromoadenosine cAMP (8-Br-cAMP) all inhibited the release of IL-5 and lymphocyte proliferation. Although all of the above compounds share the ability to increase intracellular cAMP levels and activate protein kinase (PK) A, the PKA inhibitor H-89 failed to ablate the inhibition of IL-5 production mediated by 8-Br-cAMP, rolipram, forskolin, or PGE2. Similarly, H-89 had no effect on the cAMP-mediated inhibition of lymphocyte proliferation. Significantly, these observations occurred at a concentration of H-89 (3 microM) that inhibited both PKA activity and CREB phosphorylation in intact cells. Additional studies showed that the PKA inhibitors H-8, 8-(4-chlorophenylthio) adenosine-3',5'-cyclic monophosphorothioate Rp isomer, and a myristolated PKA inhibitor peptide also failed to block the 8-Br-cAMP-mediated inhibition of IL-5 release from PBMC. Likewise, a role for PKG was considered unlikely because both activators and inhibitors of this enzyme had no effect on IL-5 release. Western blotting identified Rap1, a downstream target of the cAMP-binding proteins, exchange protein directly activated by cAMP/cAMP-guanine nucleotide exchange factors 1 and 2, in PBMC. However, Rap1 activation assays revealed that this pathway is also unlikely to be involved in the cAMP-mediated inhibition of IL-5. Taken together, these results indicate that cAMP-elevating agents inhibit IL-5 release from PBMC by a novel cAMP-dependent mechanism that does not involve the activation of PKA. |
2,332,403 | Three thiadiazinone derivatives, EMD 60417, EMD 66430, and EMD 66398, with class III antiarrhythmic activity but different electrophysiologic profiles. | The thiadiazinone derivatives EMD 60417, EMD 66430, and EMD 66398 were developed as class III antiarrhythmic agents. Their chemical structure is closely related to that of their calcium-sensitizing congener [+]-EMD 60263, and EMD 66398 possesses the methylsulfonylaminobenzoyl moiety present in the prototypical IKr blocker E-4031. We compared the electrophysiologic effects of these compounds with standard drugs (almokalant, E-4031, quinidine) in cardiac myocytes from guinea-pig ventricle and human atrium by whole-cell patch-clamp technique. The test compounds' class III action, which is related to impairment of K+ channel function, was confirmed by action potential measurements. EMD 60417, EMD 66430, EMD 66398, and almokalant (1 microM each) reversibly prolonged the action potential duration in guinea-pig myocytes. In the same cells, the rapidly activating component IKr of the delayed rectifier K+ current, which has been defined by its sensitivity to E-4031, was reduced by EMD 60417, EMD 66430, EMD 66398, and almokalant. Inhibition of IKr was concentration-dependent as determined by attenuation of tail currents. The slowly activating component IKs of the delayed rectifier K+ current was not affected. The inward rectifier K+ current IK1 was not influenced at potentials close to the reversal potential. Transient and sustained outward K+ currents (Ito, Iso) measured in human atrial myocytes were not altered by any EMD compound. L-type Ca2+ current was hardly affected at concentrations of 1-10 microM, but sodium current was decreased. Action potential prolongation by EMD 60417, EMD 66430, and EMD 66398 is due to block of IKr. INa is inhibited at higher concentrations by EMD 66430 and EMD 60417. EMD 66398 is more potent and selective for IKr than EMD 60417 and EMD 66430, and thus resembles E-4031 in structure and function. |
2,332,404 | Dibenzylamine--a novel blocker of the voltage-dependent K+ current in myocardial mouse cells. | Ventricular myocytes of the mouse ventricle were voltage clamped with a patch-clamp technique in the whole-cell configuration. At depolarizing voltage pulses, these myocytes develop a large voltage-dependent K+ outward current. Application of the drug dibenzylamine (DBA) to the bath solution blocked the voltage-dependent K+ current. The concentration/response relationship for the peak current at +40 mV indicates a 1:1 binding of the drug to the receptor with a concentration of half maximum effect of 43.1 micromol/l. The block did not require activation of the channels by depolarizing pulses. At concentrations causing partial block (25 micromol/l), the block was independent of voltage. At the same concentration, DBA completely blocked the slow component of the recovery from inactivation (-80 mV) whereas steady-state inactivation was not altered. It is concluded that DBA is a novel blocker of the voltage-dependent K+ current in mouse cardiac myocytes which preferentially affects the current component generating the slow recovery from inactivation. |
2,332,405 | Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells. | <AbstractText Label="AIMS/HYPOTHESIS" NlmCategory="OBJECTIVE">Sulphonylureas stimulate insulin secretion by closing ATP-sensitive potassium (KATP) channels in the pancreatic beta-cell membrane. KATP channels are also found in other tissues, including heart and smooth muscle, where they link cellular metabolism to electrical activity. The sulphonylurea gliclazide blocks recombinant beta-cell KATP channels (Kir6.2/SUR1) but not heart (Kir6.2/SUR2A) or smooth muscle (Kir6.2/SUR2B) KATP channels with high potency. In this study, we examined the specificity of gliclazide for the native (as opposed to recombinant) KATP channels in beta cells, heart and smooth muscle.</AbstractText>The action of the drug was studied by whole-cell current recordings of native KATP channels in isolated pancreatic beta-cells and myocytes from heart and smooth muscle.</AbstractText>Gliclazide blocked whole-cell beta-cell KATP currents with an IC50 of 184 +/- 30 nmol/l (n = 6-10) but was much less effective in cardiac and smooth muscle (IC50s of 19.5 +/- 5.4 micromol/l (n = 6-12) and 37.9 +/- 1.0 micromol/l (n = 5-10), respectively). In all three tissues, the action of the drug on whole-cell KATP currents was rapidly reversible. In inside-out patches on beta-cells, gliclazide (1 micromol/l) produced a maximum of 66 +/- 13 % inhibition (n = 5), compared with more than 98 % block in the whole-cell configuration.</AbstractText><AbstractText Label="CONCLUSION/INTERPRETATION" NlmCategory="CONCLUSIONS">Gliclazide is a high-potency sulphonylurea which shows specificity for the pancreatic beta-cell KATP channel over heart and smooth muscle. In this respect, it differs from glibenclamide. The difference in the maximal block observed in the excised patch and whole-cell recordings from beta-cells, may be due to the absence of intracellular Mg-nucleotides in the excised patch experiments.</AbstractText> |
2,332,406 | Rate dependency of delayed rectifier currents during the guinea-pig ventricular action potential. | 1. The action potential clamp technique was exploited to evaluate the rate dependency of delayed rectifier currents (I(Kr) and I(Ks)) during physiological electrical activity. I(Kr) and I(Ks) were measured in guinea-pig ventricular myocytes at pacing cycle lengths (CL) of 1000 and 250 ms. 2. A shorter CL, with the attendant changes in action potential shape, was associated with earlier activation and increased magnitude of both I(Kr) and I(Ks). Nonetheless, the relative contributions of I(Kr) and I(Ks) to total transmembrane current were independent of CL. 3. Shortening of diastolic interval only (constant action potential shape) enhanced I(Ks), but not I(Kr). 4. I(Kr) was increased by a change in the action potential shape only (constant diastolic interval). 5. In ramp clamp experiments, I(Kr) amplitude was directly proportional to repolarization rate at values within the low physiological range (< 1.0 V s(-1)); at higher repolarization rates proportionality became shallower and finally reversed. 6. When action potential duration (APD) was modulated by constant current injection (I-clamp), repolarization rates > 1.0 V s(-1) were associated with a reduced effect of I(Kr) block on APD. The effect of changes in repolarization rate was independent of CL and occurred in the presence of I(Ks) blockade. 7. In spite of its complexity, the behaviour of I(Kr) was accurately predicted by a numerical model based entirely on known kinetic properties of the current. 8. Both I(Kr) and I(Ks) may be increased at fast heart rates, but this may occur through completely different mechanisms. The mechanisms identified are such as to contribute to abnormal rate dependency of repolarization in prolonged repolarization syndromes. |
2,332,407 | Spiradoline, a kappa opioid receptor agonist, produces tonic- and use-dependent block of sodium channels expressed in Xenopus oocytes. | Spiradoline, an arylacetamide kappa (kappa) opioid receptor agonist, produced a potent tonic block of rat neuronal (EC(50)= 34+/-5 microM) and heart (EC(50)= 183+/-13 microM) sodium channels and also blocked IFMQ3 mutant neuronal sodium channels (EC(50)= 130+/-34 microM) that lack fast inactivation when expressed in Xenopus oocytes. Spiradoline produced a hyperpolarizing shift in the voltage-dependence of sodium channel inactivation and exhibited a marked frequency-dependent component to blockade of sodium channels. The onset of open channel block of the IFMQ3 channel by spiradoline was best fit with a first-order blocking scheme, yielding an affinity constant of 116 +/- 33 microM. Thus, spiradoline blocks sodium channels by interacting with the major states of the channel which could result in local anesthetic action in nerves and antiarrhythmic action in the heart. |
2,332,408 | Effect of tetramethyl pyrazine on L-type calcium channel in rat ventricular myocytes. | To elucidate possible ionic mechanisms of antimyocardial ischemia and antiarrythmia of tetramethyl pyrazine (TP), we studied L-type Ca2+ currents (I(Ca.L)) in adult rat ventricular myocytes using the whole-cell patch-clamp technique. The results showed: (i) under physiological conditions, 0.25 mmol/L TP decreased amplitude of I(Ca.L) to 60.6% and this inhibition was increased with increasing concentration of TP. ID50 was 0.20 mmol/L. (ii) The Ca2+-antagonistic effect of TP was voltage-dependent. A marked negative shift of the steady-state inactivation curve was observed with long (10 s) conditioning prepulses, but not with short (350 ms) ones. (iii) The time course of inhibition during TP treatment was increased with an increase in drug concentration, and recovery from TP-induced inactivation of I(Ca.L) was slower than in control cases. (iv) Tonic block and use-dependent block with TP treatment, which was induced by increasing the frequency of stimulation, occurred. We suggest that TP inhibits the I(Ca.L) mainly by binding to inactivated Ca2+ channels. The high affinity of TP for the inactivated state of I(Ca.L) may play an important role in developing therapies for pathological conditions. |
2,332,409 | Clonidine prevents sevoflurane-induced agitation in children. | In a double-blinded trial, 40 male children (age 2-7 yr) undergoing circumcision were randomly assigned to receive clonidine 2 microg/kg IV or placebo after anesthetic induction. For induction and maintenance of anesthesia, we used sevoflurane as the sole anesthetic. For pain treatment, a penile block was performed before surgery. After surgery the incidence and severity of agitation was measured during an observation period of 2 h. Severe agitation was treated with midazolam. In 16 placebo and 2 clonidine-treated patients agitation was observed (P < 0.001). In 6 patients of the Placebo group, agitation was graded as severe, whereas none of the patients in the Clonidine group developed severe agitation (P = 0.02). During the postoperative period heart rate and blood pressure were significantly decreased in clonidine treated patients (P < 0.05). We conclude that clonidine effectively prevents agitation after sevoflurane anesthesia.</AbstractText>The recovery from sevoflurane anesthesia may be complicated by the presence of agitation in pediatric patients. Clonidine 2 microg/kg IV after anesthetic induction effectively reduces the incidence of agitation without resulting in clinically relevant bradycardia and hypotension.</AbstractText> |
2,332,410 | Isolation of a novel zinc finger repressor that regulates the kidney-specific CLC-K1 promoter. | CLC-K1 and CLC-K2, two kidney-specific CLC chloride channels, are transcriptionally regulated on a tissue-specific basis. We have shown that a GA element near their transcriptional start sites is important for basal and cell-specific activities of the CLC-K1 and CLC-K2 gene promoters. To identify the GA-binding proteins, a kidney cDNA library was screened by a yeast one-hybrid system. A novel member of the Cys2-His2 zinc finger gene designated as KKLF (kidney-enriched Krüppel-like factor) and the myc-associated zinc finger protein (MAZ) were cloned. KKLF was found to be abundantly expressed in the liver, kidney, heart, and skeletal muscle. In the kidney, KKLF protein was localized in interstitial cells, mesangial cells, and nephron segments where CLC-K1 and CLC-K2 were not expressed. Gel mobility shift assay revealed that recombinant KKLF and MAZ proteins exhibited sequence-specific binding to the CLC-K1 GA element and that the consensus sequence for the KKLF binding site was GGGGNGGNG. In transient transfection, MAZ had a strong activating effect on the CLC-K1-luciferase reporter gene transcription. On the other hand, KKLF coexpression with MAZ appeared to block the activating effect of MAZ. These results suggest that a novel set of zinc finger proteins may help regulate the strict tissue and nephron segment-specific expression of CLC-K1 and CLC-K2 channel genes through their GA cis element. |
2,332,411 | Painful regional anaesthesia induces an immunological stress reaction: the model of retrobulbar anaesthesia. | Laboratory stress studies found that acute psychological stresses may elicit changes in leukocyte numbers similar to those occurring in physical stresses. Both types of stress evoke - mainly by release of catecholamines - leukocytosis resulting from a release of natural killer cells (NK-cells), of CD8+ T-cells, of monocytes and of neutrophils. However, there is little proof that laboratory stress models can be applied to daily clinical routines. As a likely inductor of an immunological stress response the setting of retrobulbar anaesthesia prior to intraocular surgery permits the study of a short-term painful anaesthetic procedure under highly standardized conditions. This was examined in 16 female patients.</AbstractText>Counts of leukocyte subsets, serum cortisol and cardiovascular variables were measured 30 min and 1 min prior to retrobulbar anaesthesia as well as 2, 15 and 45 min afterwards.</AbstractText>The setting of retrobulbar anaesthesia induced an increase in total leukocytes [+380 cells microL-1; P < 0.01 (means; significance level)] mainly due to rising counts of neutrophils (+241 cells microL-1, P < 0.01). Of all lymphocyte subpopulations, natural killer cells increased most markedly (+64 cells microL-1; P < 0.01). Furthermore, the retrobulbar block induced an increase in systolic arterial pressure (+15.2 mmHg; P < 0.01).</AbstractText>These changes in immunological and cardiovascular variables are considered to be elements of a sympatho-adrenal stress reaction; catecholamines are considered to induce a demargination of leukocytes by binding to beta2-adrenoceptors and by modifying the avidity state of adhesion molecules.</AbstractText> |
2,332,412 | Epidural washout with high volumes of saline to accelerate recovery from epidural anaesthesia. | Prolonged postoperative blockade can follow neuraxial blocks for short surgical procedures. We investigated whether washout with a high volume of saline through an epidural catheter could provide a faster recovery after epidural anaesthesia.</AbstractText>Thirty patients were randomly assigned to a control group (no washout), to group 2x (epidural washout with twice the volume of 2% mepivacaine) and group 4x (epidural washout with four times that volume).</AbstractText>Recovery times from sensory blockade at L2 were 151+/-24, 122+/-29 and 116+/-24 min for control, 2x and 4x groups respectively. Significant differences were found in both saline groups when compared with control group, but not between group 2x and group 4x. No differences were found concerning motor blockade. One patient in group 4x demonstrated signs of intracranial hypertension. Mepivacaine plasma concentrations were increased by saline washout in group 4x.</AbstractText>Epidural washout with a high volume of saline can not be recommended since no clinically significant reduction in the recovery time can be achieved without risk.</AbstractText> |
2,332,413 | Addition of clonidine increases duration and magnitude of vasodilative effect induced by sympathetic block with mepivacaine in dogs. | The aim of this study is to examine the duration and magnitude of vasodilative effect induced by sympathetic block with the addition of clonidine to mepivacaine.</AbstractText>We measured mean arterial pressure (MAP), heart rate (HR), and right and left brachial artery blood flow (BABF) before and after stellate ganglion block (SGB) in dogs. The experimental protocol was designed as follows: (1) left SGB using 1.0 mL 0.5% mepivacaine (n = 6) and (2) left SGB using the addition of clonidine 0.5 microg to 1.0 mL 0.5% mepivacaine (n = 6).</AbstractText>MAP and HR did not change significantly throughout the study in either group. Left SGB with mepivacaine increased left BABF significantly from 10 minutes through 50 minutes after SGB (baseline, 100%; peak at 10 minutes after SGB, 176% +/- 28%; P <.01). Left SGB with the addition of clonidine to mepivacaine induced a significant increase of left BABF from 10 minutes through 70 minutes after SGB (baseline, 100%; peak at 10 minutes after SGB, 223% +/- 42%; P <.01). The values of left BABF after SGB with the addition of clonidine to mepivacaine were significantly higher than those of SGB with mepivacaine alone from 10 minutes through 80 minutes after SGB (P <.05). Right BABF decreased significantly after SGB throughout the study in both groups.</AbstractText>The addition of clonidine increases both duration and magnitude of the vasodilative effect induced by sympathetic block over that caused by mepivacaine alone.</AbstractText> |
2,332,414 | Interaction between 52 kDa SSA/Ro and deubiquitinating enzyme UnpEL: a clue to function. | The detection of isolated heart block in utero strongly predicts the presence of maternal autoantibodies reactive with 52 kDa SSA/Ro. The mechanisms that underlie this observation may be elucidated by defining the function of the target antigen. The initial approach was to identify proteins interactive with 52Ro using transcriptional activity in the yeast 2-hybrid system. A cDNA library was constructed using RNA isolated from human fetal hearts (12-23 weeks) and cloned into the HybriZAP vector encoding the activation domain of GAL4(AD) as target. Approximately 7 x 10(6) cDNAs were cotransformed with the bait into YRG-2. Plasmids from five interactive colonies were sequenced and three identified as the specific human deubiquitinating enzyme, UnpEL. UnpEL did not interact with bait plasmid encoding 52 beta, an alternative leucine zipper-minus form of 52 kDa SSA/Ro which is maximally expressed in fetal life. The mammalian 2-hybrid assay confirmed the interaction between full-length 52Ro and UnpEL. Further support for a biologic interaction was the marked redistribution in cellular localization of UnpEL following cotransfection of the two proteins into cultured human cardiocytes, human renal carcinoma cells (293 cells), and monkey kidney fibroblasts (COS-1). In conclusion, the interaction of full-length 52Ro and UnpEL implies that the former may also be involved in the ubiquitin pathway, an observation of particular interest since 52Ro contains a RING finger domain, a motif common to several recently reported proteins involved in modulating ubiquitination. The absence of an interaction with 52 beta raises the consideration that regulation of protein ubiquitination might differ in fetal life. |
2,332,415 | Response properties of baroreceptive NTS neurons. | Neurons in the nucleus of the solitary tract (NTS) responding to activation of arterial baroreceptors were recorded intracellularly using patch pipettes in an in situ arterially perfused working heart-brain stem preparation of rat. Seven of 15 (i.e., 46%) of NTS neurons showed adaptive (nonlinear) excitatory synaptic response patterns during baroreceptor stimulation followed by an "evoked hyperpolarization." This evoked hyperpolarization was stimulus intensity dependent and capable of shunting out a subsequent baroreceptor input. We suggest that this adaptive response behavior may be mediated, in part, by calcium-dependent potassium currents (IKCa) since neurons showed spike frequency adaptation during step depolarizations and an after-hyperpolarization after repetitive firing. Furthermore, in in vivo anesthetized rats, NTS microinjections of either charybdotoxin (225 fmol) or apamin (4.5 pmol) to block IKCa increased the baroreceptor reflex gain. Our data purport that the responsiveness of baroreceptive NTS neurons can be regulated by intrinsic membrane conductances such as IKCa. Modulation of such conductances during either physiological (exercise) or pathophysiological (essential hypertension) conditions may lead to changes in both the operating point and gain of the baroreceptor reflex. |
2,332,416 | The impact of emotions on coronary heart disease risk. | Coronary heart disease is now well recognized as a psychosomatic illness. Emotional disturbance increasingly appears to have an impact on both the development of coronary artery disease over time and the precipitation of acute coronary heart disease events.</AbstractText>This descriptive review is based on systematic literature reviews from 1980 to 2000 with an emphasis on predictive and prospective studies.</AbstractText>The empirical evidence linking emotional disturbances such as anxiety, depression and anger to coronary heart disease is now robust. There is also increasing evidence for the underlying pathophysiology that may link emotions to coronary heart disease.</AbstractText>Emotional disorders and coronary artery disease commonly coexist. Emotional disorders often follow events of coronary heart disease. Prospective studies, however, now show that emotional disturbance is also a significant risk factor for coronary artery disease and especially in those with pre-existing disease. It is important both to diagnose emotional disorders early in coronary heart disease patients and implement effective treatments with the likelihood of reducing subsequent morbidity and mortality.</AbstractText> |
2,332,417 | Nitric oxide limits coronary vasoconstriction by a shear stress-dependent mechanism. | Increases in shear stress promote coronary vasodilation by stimulating the production of nitric oxide (NO). Whether shear stress-induced NO production also limits vasoconstriction in the coronary microcirculation in vivo is unknown. Accordingly, we measured microvascular diameter and flow velocity in the beating heart along with estimated blood viscosity to calculate shear stress during vasoconstriction with endothelin or vasopressin. Measurements were repeated in the presence of NG-monomethyl-L-arginine (L-NMMA) to inhibit NO production and BQ-788 to block NO-linked endothelin type B receptors. BQ-788 did not augment steady-state constriction to endothelin, suggesting that NO production via activation of this receptor is inconsequential. L-NMMA potentiated constriction to both agonists, particularly in small arteries (inner diameter >120 microm). Shear stresses in small arteries were elevated during constriction and further elevated during constriction after L-NMMA. These observations suggest that NO production limits vasoconstriction in the coronary microcirculation and that the principal stimulus for this governance is elevated shear stress. The degree of shear stress moderation of constriction is heterogeneously distributed, with small arteries displaying a higher degree of shear stress regulation than arterioles. These results provide the strongest evidence to date that shear stress-mediated production of NO exerts a "braking" influence on constriction in the coronary microcirculation. |
2,332,418 | Heat shock preconditioning and pretreatment with glucocorticoid antagonist RU 486 protect rat myogenic cells H9c2 against glutamate-induced cell death. | We have observed that the treatment of rat-heart derived H9c2 myoblasts for 20 h with the excitatory amino acid glutamate resulted in cell death in a dose dependent manner as determined by LDH release. The optimum cardiotoxicity was seen at 25 mM glutamate. Preconditioning with either sublethal heat shock (42 degrees C for 30 min) or pretreatment with 500 nM of the glucocorticoid antagonist RU 486 for 24 h almost completely protected H9c2 cells against subsequent 20 h treatment with 25 mM lethal glutamate. In addition, we have observed that glutamate treatment resulted in intense nuclear localization of glucocorticoid receptors (GR) in H9c2 cells as judged by the confocal immunofluorescence microscopy. Furthermore, pretreatment with either heat shock or RU 486 followed by glutamate treatment resulted in dramatic decrease in GR nuclear localization which was almost comparable to that observed with control untreated cells. In conclusion, we have shown for the first time using H9c2 cells that (i) protection from glutamate cardiotoxicity occurs with prior treatment with sub lethal heat shock or RU 486 and (ii) these measures down regulate the intense nuclear localization of GR induced by glutamate. The block to GR nuclear localization is likely to be involved in cardioprotective effects offered against glutamate toxicity by pretreatment with heat shock or RU 486. |
2,332,419 | Neighborhood of residence and incidence of coronary heart disease. | Where a person lives is not usually thought of as an independent predictor of his or her health, although physical and social features of places of residence may affect health and health-related behavior.</AbstractText>Using data from the Atherosclerosis Risk in Communities Study, we examined the relation between characteristics of neighborhoods and the incidence of coronary heart disease. Participants were 45 to 64 years of age at base line and were sampled from four study sites in the United States: Forsyth County, North Carolina; Jackson, Mississippi; the northwestern suburbs of Minneapolis; and Washington County, Maryland. As proxies for neighborhoods, we used block groups containing an average of 1000 people, as defined by the U.S. Census. We constructed a summary score for the socioeconomic environment of each neighborhood that included information about wealth and income, education, and occupation.</AbstractText>During a median of 9.1 years of follow-up, 615 coronary events occurred in 13,009 participants. Residents of disadvantaged neighborhoods (those with lower summary scores) had a higher risk of disease than residents of advantaged neighborhoods, even after we controlled for personal income, education, and occupation. Hazard ratios for coronary events in the most disadvantaged group of neighborhoods as compared with the most advantaged group--adjusted for age, study site, and personal socioeconomic indicators--were 1.7 among whites (95 percent confidence interval, 1.3 to 2.3) and 1.4 among blacks (95 percent confidence interval, 0.9 to 2.0). Neighborhood and personal socioeconomic indicators contributed independently to the risk of disease. Hazard ratios for coronary heart disease among low-income persons living in the most disadvantaged neighborhoods, as compared with high-income persons in the most advantaged neighborhoods were 3.1 among whites (95 percent confidence interval, 2.1 to 4.8) and 2.5 among blacks (95 percent confidence interval, 1.4 to 4.5). These associations remained unchanged after adjustment for established risk factors for coronary heart disease.</AbstractText>Even after controlling for personal income, education, and occupation, we found that living in a disadvantaged neighborhood is associated with an increased incidence of coronary heart disease.</AbstractText> |
2,332,420 | Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress. | It is not clear whether the diurnal variation in the cutaneous circulatory response to heat stress is via the noradrenergic vasoconstrictor system or the nonadrenergic active vasodilator system. We conducted whole body heating experiments in eight male subjects at 0630 (AM) and 1630 (PM). Skin blood flow was monitored by laser-Doppler flowmetry at control sites and at sites pretreated with bretylium (BT) to block noradrenergic vasoconstriction. Noninvasive blood pressure was used to calculate cutaneous vascular conductance. The sublingual temperature (T(or)) threshold for cutaneous vasodilation was significantly higher in PM at control and at BT-treated sites (both P < 0.01), suggesting the diurnal shift in threshold depends on the active vasodilator system. The slope of cutaneous vascular conductance as a percentage of its maximum with respect to T(or) was significantly lower in AM at control sites only. Also, in the AM, the slope at control sites was significantly lower than that at BT-treated sites (P < 0.05), suggesting that the diurnal change in the sensitivity of cutaneous vasodilation depends on vasoconstrictor system function. Overall, the diurnal variation in the reflex control of skin blood flow during heat stress involves both vasoconstrictor and active vasodilator systems. |
2,332,421 | The mRNA level of the potassium-chloride cotransporter KCC2 covaries with seizure susceptibility in inferior colliculus of the post-ischemic audiogenic seizure-prone rat. | Cardiac arrest and resuscitation were used to induce brain damage and susceptibility to sound-triggered seizures in Sprague-Dawley rats. Glucose preloading was used to vary seizure susceptibility. Because loop diuretics can block these seizures, we investigated changes in KCC2, a potassium-chloride cotransporter, in the inferior colliculus - the origin of the seizures. Using polymerase chain reaction (PCR), we found that collicular KCC2 mRNA levels covaried with seizure susceptibility in these animals. Using quantitative PCR, we found that a fivefold increase in collicular KCC2 mRNA levels was associated with a doubling of seizure incidence. A hypothesis linking KCC2 activity to seizure susceptibility is presented. |
2,332,422 | Autoantibodies from mothers of children with congenital heart block downregulate cardiac L-type Ca channels. | Congenital heart block (CHB) affects offspring of mothers with autoantibodies (positive IgG) to intracellular SSA/Ro and SSB/La ribonucleoproteins and is associated with high morbidity and mortality. Here, we show that maternal anti-Ro/La antibodies immunoreact with human fetal cardiomyocyte sarcolemma, recognize human L-type Ca channel alpha(1C)-protein and functionally inhibit expressed current in oocytes injected with alpha(1C) cRNA and Purkinje L-type Ca current. Furthermore, cardiac myocytes from pups born to SSA/Ro-immunized mice exhibited reduced L-type Ca current density. All together, the data establish that L-type calcium channel is a target for maternal antibodies and may provide a functional basis for the electrocardiographic abnormalities seen in infants with CHB. |
2,332,423 | Comparison of caudal morphine and tramadol for postoperative pain control in children undergoing inguinal herniorrhaphy. | We compared the quality and duration of analgesia, the effect on perioperative sevoflurane requirement after a single, presurgical caudal block with either tramadol or morphine in children undergoing inguinal herniorrhaphy. Our study was also designed to evaluate the preemptive analgesic efficacy of morphine administered caudally in children.</AbstractText>Patients were randomly divided into three groups to receive 2 mg.kg-1 tramadol (group T, preemptive group) or morphine sulphate 0.03 mg.kg-1 (group M, preemptive group). The patients in control group (group C, postincisional group) received morphine sulphate 0.03 mg.kg-1 at the end of surgery, caudally. Cardiorespiratory data, sedation and pain were recorded for 24 h following recovery from anaesthesia.</AbstractText>There were no differences between the three groups in baseline blood pressure or heart rate; or duration of anaesthesia, surgery. The inhaled sevoflurane concentration was significantly lower in group M and group T than in the control group. The quality and duration of postoperative pain relief did not differ between the three groups. There were no intergroup differences in postoperative nausea, vomiting, or other complications.</AbstractText>Caudal tramadol (2 mg.kg-1) provided reliable postoperative analgesia similar to caudal morphine (0.03 mg.kg-1) in quality and duration of pain relief in our study children who were undergoing herniorrhaphy. We also concluded that presurgical caudal morphine or tramadol reduced perioperative sevoflurane requirements and either presurgical or postsurgical caudal morphine did not make any difference to postoperative analgesia.</AbstractText> |
2,332,424 | The apoptotic regulatory protein ARC (apoptosis repressor with caspase recruitment domain) prevents oxidant stress-mediated cell death by preserving mitochondrial function. | ARC is an apoptotic regulatory protein expressed almost exclusively in myogenic cells. It contains a caspase recruitment domain (CARD) through which it has been shown to block the activation of some initiator caspases. Because ARC also blocks caspase-independent events associated with apoptosis, such as hypoxia-induced cytochrome c release, we examined its role in cell death triggered by exposure to hydrogen peroxide (H(2)O(2)) in the myogenic cell line, H9c2. Cell death in this model was caspase-independent and characterized by dose-dependent reduction in ARC expression accompanied by disruption of the mitochondrial membrane potential (Delta psi(m)) and loss of plasma membrane integrity, typical of necrotic cell death. Ectopic expression of ARC prevented both H(2)O(2)-induced mitochondrial dysfunction and cell death without affecting the stress kinase response, suggesting that ARCs protective effects were downstream of early signaling events and not due to quenching of H(2)O(2). ARC was also effective in blocking H(2)O(2)-induced loss of membrane integrity and/or disruption of Delta psi(m) in two human cell lines in which it is not normally expressed. These results demonstrate that, in addition to its ability to block caspase-dependent and -independent events in apoptosis, ARC also prevents necrosis-like cell death via the preservation of mitochondrial function. |
2,332,425 | A comparison of five solutions of local anaesthetics and/or sufentanil for continuous, postoperative epidural analgesia after major urological surgery. | The aim of the present study was to compare and assess the quality of analgesia, the safety and the side-effects after the use of a continuous, thoracic epidural infusion of sufentanil (5 microg h(-1)), 0.25% bupivacaine (10 mL h(-1)), 0.2% ropivacaine (10 mL h(-1)) alone or in combination in patients who had undergone major urological surgery. This prospective, randomized, double-blinded study investigated the efficacy of thoracic epidural infusions after major urological surgery.</AbstractText>Patients received a 72-h continuous infusion (10 mL h(-1)) of 0.25% bupivacaine (B), 0.2% ropivacaine (R), 0.25% bupivacaine with 0.5 microg mL(-1) sufentanil (BS), 0.2% ropivacaine with 0.5 microg mL(-1) sufentanil (RS) or 0.5 microg mL(-1) sufentanil only (S). The analysis included 109 patients.</AbstractText>The mean visual analogue scale (VAS) scores for pain were highest in the groups R and S (P < 0.001). The PaCO2 values were significantly higher in the groups RS and S (P = 0.003). Motor block occurred more frequently in the groups B and BS than in the other groups (P < 0.001). Sedation, nausea and pruritus were more common in the groups that received sufentanil.</AbstractText>A continuous, epidural infusion with these drugs was safe and effective in our patients. The combination of 0.2% ropivacaine plus sufentanil appeared preferable because of the low incidence of motor block.</AbstractText> |
2,332,426 | Potent and use-dependent block of cardiac sodium channels by U-50,488H, a benzeneacetamide kappa opioid receptor agonist. | To determine whether the kappa opioid receptor agonist U-50,488H, a benzacetamide derivative of the cyclo-hexane-1,2-diamine analgesics, may be a useful molecular probe to define the structural requirements of this class of drugs for cardiac sodium channel blockade.</AbstractText>The electrophysiological effects of U-50,488H were compared with those of lidocaine, a clinically used class Ib antiarrhythmic agent, in rat heart sodium currents expressed in Xenopus laevis oocytes by using two-electrode voltage clamp.</AbstractText>Both U-50,488H and lidocaine produced a concentration-dependent tonic block of sodium current, but U-50,488H was approximately fourfold more potent than lidocaine. Both drugs produced a hyperpolarizing shift in the voltage dependence of sodium channel inactivation and both delayed recovery from inactivation. Both drugs exhibited use-dependent block, but U-50,488H showed a 1.8-fold increase in potency compared with lidocaine at a high frequency of stimulation (30 Hz).</AbstractText>The more potent tonic and use-dependent block of cardiac sodium channels by U-50,488H suggests that structural features of this molecule may provide it with a greater ability to block the channel. An understanding of these structural features may provide information needed in the development of novel arylacetamide-based antiarrhythmic drugs and insight into possible mechanisms describing channel block, resulting in a highly efficacious antiarrhythmic action in the heart.</AbstractText> |
2,332,427 | Cross-talk between the ERK and p70 S6 kinase (S6K) signaling pathways. MEK-dependent activation of S6K2 in cardiomyocytes. | The alpha(1)-adrenergic agonist phenylephrine (PE) and insulin each stimulate protein synthesis in cardiomyocytes. Activation of protein synthesis by PE is involved in the development of cardiac hypertrophy. One component involved here is p70 S6 kinase 1 (S6K1), which lies downstream of mammalian target of rapamycin, whose regulation is thought to involve phosphatidylinositol 3-kinase and protein kinase B (PKB). S6K2 is a recently identified homolog of S6K1 whose regulation is poorly understood. Here we demonstrate that in adult rat ventricular cardiomyocytes, PE and insulin each activate S6K2, activation being 3.5- and 5-fold above basal, respectively. Rapamycin completely blocked S6K2 activation by either PE or insulin. Three different inhibitors of MEK1/2 abolished PE-induced activation of S6K2 whereas expression of constitutively active MEK1 activated S6K2, without affecting the p38 mitogen-activated protein kinase and JNK pathways, indicating that MEK/ERK signaling plays a key role in regulation of S6K2 by PE. PE did not activate PKB, and expression of dominant negative PKB failed to block activation of S6K2 by PE, indicating PE-induced S6K2 activation is independent of PKB. However, this PKB mutant did partially block S6K2 activation by insulin, indicating PKB is required here. Another hypertrophic agent, endothelin 1, also activated S6K2 in a MEK-dependent manner. Our findings provide strong evidence for novel signaling connections between MEK/ERK and S6K2. |
2,332,428 | Electrophysiologic effects of an antiarrhythmic agent, bidisomide, on sodium current in isolated rat ventricular myocytes: comparison with mexiletine and disopyramide. | The effects of bidisomide, an antiarrhythmic agent, on sodium current (I(Na)) in isolated rat ventricular myocytes were investigated using a whole cell voltage clamp method. Bidisomide blocked I(Na) with a Ki of 214 microM at a holding potential of -140 mV. The blockade of I(Na) was enhanced at a less negative holding potential of -100 mV with a Ki of 21 microM. Bidisomide shifted the steady state inactivation curve to a negative potential direction by 20 mV without a significant change in the slope factor. Bidisomide slowed the time course of recovery of I(Na) at a holding potential of -140 mV with a slow recovery phase. The time constant of recovery phase for bidisomide, disopyramide and mexiletine were 2703, 1858 and 757 ms, respectively. The development of the block of I(Na) consisted of two phases in the presence of bidisomide. The fast and slow time constants were 11 and 648 ms. Bidisomide produced a use-dependent block of I(Na) when the depolarizing pulse was repeated at 1-3 Hz. Our results indicate that bidisomide binds to rat cardiac sodium channels and that the dissociation kinetics of bidisomide from the inactivated sodium channel is slower than that of disopyramide. |
2,332,429 | Electrophysiological effects of dronedarone (SR 33589), a noniodinated amiodarone derivative in the canine heart: comparison with amiodarone. | The electrophysiological effects of dronedarone, a new nonionidated analogue of amiodarone were studied after chronic and acute administration in dog Purkinje fibres, papillary muscle and isolated ventricular myocytes, and compared with those of amiodarone by applying conventional microelectrode and patch-clamp techniques. Chronic treatment with dronedarone (2x25 mg(-1) kg(-1) day p.o. for 4 weeks), unlike chronic administration of amiodarone (50 mg(-1) kg(-1) day p.o. for 4 weeks), did not lengthen significantly the QTc interval of the electrocardiogram or the action potential duration (APD) in papillary muscle. After chronic oral treatment with dronedarone a small, but significant use-dependent V(max) block was noticed, while after chronic amiodarone administration a strong use-dependent V(max) depression was observed. Acute superfusion of dronedarone (10 microM), similar to that of amiodarone (10 microM), moderately lengthened APD in papillary muscle (at 1 Hz from 239.6+/-5.3 to 248.6+/-5.3 ms, n=13, P<0.05), but shortened it in Purkinje fibres (at 1 Hz from 309.6+/-11.8 to 287.1+/-10.8 ms, n=7, P<0.05). Both dronedarone (10 microM) and amiodarone (10 microM) superfusion reduced the incidence of early and delayed afterdepolarizations evoked by 1 microM dofetilide and 0.2 microM strophantidine in Purkinje fibres. In patch-clamp experiments 10 microM dronedarone markedly reduced the L-type calcium current (76.5+/-0.7 %, n=6, P<0.05) and the rapid component of the delayed rectifier potassium current (97+/-1.2 %, n=5, P<0.05) in ventricular myocytes. It is concluded that after acute administration dronedarone exhibits effects on cardiac electrical activity similar to those of amiodarone, but it lacks the 'amiodarone like' chronic electrophysiological characteristics. |
2,332,430 | Comparison of continuous thoracic epidural and paravertebral blocks for postoperative analgesia after minimally invasive direct coronary artery bypass surgery. | To compare continuous thoracic epidural analgesia (TEA) and paravertebral block (PVB) for postoperative analgesia in patients undergoing minimally invasive direct coronary artery bypass (MIDCAB) surgery for quality of analgesia, complications, compliance to chest physiotherapy, hemodynamics, and respiratory effects.</AbstractText>Prospective, randomized study.</AbstractText>Specialty research hospital.</AbstractText>Forty-one consenting patients undergoing MIDCAB surgery.</AbstractText>Patients in the TEA group had an epidural catheter inserted at the T4-5 interspace, whereas patients in the PVB group had a catheter inserted in the paravertebral space on the left side at the T4-5 level.</AbstractText>Parameters evaluated included visual analog scale pain scores at rest and while coughing, supplemental analgesic requirement, complications, hemodynamics, and respiratory parameters. Measurements were made at 2-hour intervals for 12 hours beginning at 10 minutes after endotracheal extubation. There was no statistically significant difference in visual analog scale scores and requirement of supplemental analgesia between the 2 groups. Cardiac index at 4 hours and 6 hours was significantly higher in the TEA group. Patients in the PVB group had significantly lower respiratory rates at 8, 10, and 12 hours. All other parameters were comparable. In 1 patient, the epidural space could not be catheterized. One patient in the TEA group had transient hypotension, and 1 patient complained of backache at the site of the epidural catheter insertion.</AbstractText>PVB is as effective as TEA for postoperative analgesia after MIDCAB surgery. PVB is technically easier than TEA and may be safer than TEA because no complications were seen in the PVB group.</AbstractText>Copyright 2001 by W.B. Saunders Company.</CopyrightInformation> |
2,332,431 | Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide. | The sulfonylurea glibenclamide (Glib) abolishes the cardioprotective effect of ischemic preconditioning (IP), presumably by inhibiting mitochondrial K(ATP) channel opening in myocytes. Glimepiride (Glim) is a new sulfonylurea reported to affect nonpancreatic K(ATP) channels less than does Glib. We examined the effects of Glim on IP and on the protection afforded by diazoxide (Diaz), an opener of mitochondrial K(ATP) channels.</AbstractText>Rat hearts were Langendorff-perfused, subjected to 35 minutes of regional ischemia and 120 minutes of reperfusion, and assigned to 1 of the following treatment groups: (1) control; (2) IP of 2x 5 minutes each of global ischemia before lethal ischemia; or pretreatment with (3) 30 micromol/L Diaz, (4) 10 micromol/L Glim, (5) 10 micromol/L Glib, (6) IP+Glim, (7) IP+Glib, (8) Diaz+Glim, or (9) Diaz+Glib. IP limited infarct size (18.5+/-1% vs 43.7+/-3% in control, P<0.01) as did Diaz (22.2+/-4.7%, P<0.01). The protective actions of IP or Diaz were not abolished by Glim (18.5+/-3% in IP+Glim, 22.3+/-3% in Diaz+Glim; P<0.01 vs control). However, Glib abolished the infarct-limiting effects of IP and Diaz. Patch-clamp studies in isolated rat ventricular myocytes confirmed that both Glim and Glib (each at 1 micromol/L) blocked sarcolemmal K(ATP) currents. However, in isolated cardiac mitochondria, Glim (10 micromol/L) failed to block the effects of K(ATP) opening by GTP, in contrast to the blockade caused by Glib.</AbstractText>Although it blocks sarcolemmal currents in rat cardiac myocytes, Glim does not block the beneficial effects of mitochondrial K(ATP) channel opening in the isolated rat heart. These data may have significant implications for the treatment of type 2 diabetes in patients with ongoing ischemic heart disease.</AbstractText> |
2,332,432 | [Anesthetic management of a patient with tetanus using epidural anesthesia]. | A 75-year-old woman with breast cancer complicated with tetanus was scheduled for mastectomy. Since severe bradycardia (17 beats.min-1) was detected by preoperative Holter monitoring, a temporary pacing catheter was inserted. She underwent mastectomy under general anesthesia using propofol combined with thoracic epidural anesthesia. She also received postoperative thoracic epidural block. Her perioperative heart rate was 80-105 beats.min-1 and the rhythm was sinus. There was no marked perioperative cardiovascular derangement. |
2,332,433 | Caudal bupivacaine-tramadol combination for postoperative analgesia in pediatric herniorrhaphy. | Administration of bupivacaine caudally has been used for postoperative analgesia after urogenital, rectal and lower abdominal surgery in children. Caudal opioids may offer analgesic advantages over bupivacaine alone but have been associated with side effects such as respiratory depression. Tramadol is an analgesic assumed to lack a respiratory depressant effect and has been shown to provide effective, long-lasting analgesia after epidural administration in adults and children. The aim of this study was to determine whether the addition of tramadol to bupivacaine caudally prolongs the duration of analgesia compared with bupivacaine alone, with respect to side effects, and whether caudal tramadol alone provides satisfactory analgesia.</AbstractText>Sixty boys, aged 12-84 months, undergoing unilateral herniorrhaphy, were allocated randomly to three groups. Children in group B received 0.25% plain bupivacaine 1 ml kg(-1), group BT received an identical local anesthetic dose mixed with tramadol 1.5 mg kg(-1) and group T received caudal tramadol 1.5 mg kg(-1) in 0.9% sodium chloride in the same total volume (1 ml kg(-1)). Pain and demeanour assessments were made 1, 2, 3, 4, 6, 12 and 24 h after recovery from anesthesia with reference to a three-point scale.</AbstractText>Analgesia time (time between caudal injection and first administration of analgesic) in group BT (13.5+/-2.2 h) was significantly longer than in the other two groups (P<0.05). In group T, more patients required additional analgesia after surgery than in the other two groups (P<0.05). Pain scores in the three groups were similar up to 4 h after operation but the mean score in group T was higher than groups B and BT 4 and 6 h after operation (P<0.05). Significantly more patients who had received caudal bupivacaine alone or with tramadol had lower pain and demeanour scores during the first 24 h after operation compared with those in the tramadol group.</AbstractText>Caudal administration of bupivacaine with the addition of tramadol resulted in superior analgesia with a longer period without demand for additional analgesics compared with caudal bupivacaine and tramadol alone without an increase of side effects.</AbstractText> |
2,332,434 | Chromanol 293B, a blocker of the slow delayed rectifier K+ current (IKs), inhibits the CFTR Cl- current. | The cystic fibrosis transmembrane conductance regulator (CFTR) and the sulphonylurea receptor subunit (SUR) of the KATP channel are both members of the ATP-binding cassette (ABC) protein superfamily. Many compounds that open or block the KATP channel by binding to SUR also inhibit the CFTR Cl- current (ICFTR); an example in point is the chromanol-type KATP channel opener, cromakalim. The structurally related chromanol 293B (trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chromane), a blocker of the slow component of the delayed rectifier K+ current (IKs) in the heart, is also a weak inhibitor of KATP. This suggests that 293B may affect also ICFTR- We have addressed this question with human CFTR expressed in Xenopus oocytes. In two-electrode voltage-clamp experiments, 293B inhibited ICFTR with an IC50-value of 19 microM and Hill coefficient of 1.0; the inhibition was weakened by increasing concentrations of isobutyl-methylxanthine (IBMX). Patch-clamp recordings gave an IC50-value of 30 microM but showed a unusual variability in the sensitivity to 293B. The data show that 293B inhibits ICFTR and suggest that the mechanism of inhibition may depend on the phosphorylation state of the CFTR protein. The concentrations required for inhibition of ICFTR are three- to fivefold higher than those reported for inhibition of KvLQT1 + minK expressed in Xenopus oocytes. Since CFTR is expressed also in cardiac myocytes, the effects of 293B in these cells must be analysed with caution. |
2,332,435 | FGF-8 in the ventral pharynx alters development of myocardial calcium transients after neural crest ablation. | Cardiac neural crest ablation results in depressed myocardial calcium transients and elevated proliferation in myocardium at a stage when cardiac neural crest cells are not in contact with the myocardium. To test the hypothesis that cardiac neural crest-derived cells, which migrate into the caudal, ventral pharynx at stage 14, block a signal from the ventral pharynx, we cultured stage 12 chick heart tube or myocardial strips in the presence or absence of ventral pharynx. We found that myocardium cultured with ventral pharynx that had not yet contacted neural crest cells had significantly reduced calcium transients and an increased rate of proliferation. Ventral pharynx from intact embryos at a stage when neural crest-derived cells had reached the pharynx had no effect on myocardial calcium transients. Ventral pharynx from neural crest-ablated embryos continued to suppress myocardial calcium transients at this later stage. Myocardium cultured with FGF-2 also showed a significant reduction in calcium transients. An FGF-2-neutralizing Ab reversed the deleterious effect of the ventral pharynx on myocardial calcium transients and proliferation. We therefore examined the expression of FGF-2 and similar FGFs in the ventral pharynx. Only FGF-8 was expressed in a temporospatial pattern that made it a viable candidate for altering the myocardial calcium transient during stages 14-18. In explant cultures, neutralizing Ab for FGF-8 rescued development of the myocardial calcium transient in neural crest-ablated chick embryos. |
2,332,436 | Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes. | Defects of the SCN5A gene encoding the cardiac sodium channel alpha-subunit are associated with both the long QT-3 (LQT-3) subtype of long-QT syndrome and Brugada syndrome (BrS). One previously described SCN5A mutation (1795insD) in the C terminus results in a clinical phenotype combining QT prolongation and ST segment elevation, indicating a close interrelationship between the two disorders. Here we provide additional evidence that these two disorders are closely related. We report the analysis of two novel mutations on the same codon, Y1795C (LQT-3) and Y1795H (BrS), expressed in HEK 293 cells and characterized using whole-cell patch clamp procedures. We find marked and opposing effects on channel gating consistent with activity associated with the cellular basis of each clinical disorder. Y1795H speeds and Y1795C slows the onset of inactivation. The Y1795H, but not the Y1795C, mutation causes a marked negative shift in the voltage dependence of inactivation, and neither mutation affects the kinetics of the recovery from inactivation. Interestingly, both mutations increase the expression of sustained Na+ channel activity compared with wild type (WT) channels, although this effect is most pronounced for the Y1795C mutation, and both mutations promote entrance into an intermediate or a slowly developing inactivated state. These data confirm the key role of the C-terminal tail of the cardiac Na+ channel in the control of channel gating, illustrate how subtle changes in channel biophysics can have significant and distinct effects in human disease, and, additionally, provide further evidence of the close interrelationship between BrS and LQT-3 at the molecular level. |
2,332,437 | Clinical characteristics and catheter ablation of left ventricular outflow tract tachycardia.<Pagination><StartPage>305</StartPage><EndPage>313</EndPage><MedlinePgn>305-13</MedlinePgn></Pagination><Abstract><AbstractText>Left ventricular outflow tract (LVOT) tachycardia is an uncommon form of idiopathic ventricular tachycardia (IVT). The underlying mechanism of this arrhythmia appears to be cyclic AMP-medicated triggered activity. The tachycardia occurs in the absence of structural heart disease and is generally benign, presenting commonly as palpitations and presyncope. It can manifest either a right or left bundle branch block morphology with an inferior axis. Subtle variations in the QRS morphology in leads I, V1, and V2 can help in localizing the anatomic site of origin (SOO). The arrhythmia is typically responsive to a variety of pharmacologic agents (beta-blockers, calcium channel blockers, Class I and II agents). Radiofrequency catheter ablation of LVOT tachycardia SOO as determined by pace mapping is quite efficacious (success rates of 90%). Magnetic electroanatomic mapping augments this by permitting three-dimensional catheter mapping and reproducible localization of the SOO. Catheter ablation should be considered relatively early in patients who experience severe symptoms with their arrhythmia and have failed, or are reluctant to take medications for the disorder.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Dixit</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, 9 Founders, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marchlinski</LastName><ForeName>F E</ForeName><Initials>FE</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Curr Cardiol Rep</MedlineTA><NlmUniqueID>100888969</NlmUniqueID><ISSNLinking>1523-3782</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D017115" MajorTopicYN="Y">Catheter Ablation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013610" MajorTopicYN="N">Tachycardia</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014694" MajorTopicYN="N">Ventricular Outflow Obstruction</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000601" 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IdType="pubmed">6650408</ArticleId></ArticleIdList></Reference><Reference><Citation>Am J Cardiol. 1991 Oct 1;68(9):897-900</Citation><ArticleIdList><ArticleId IdType="pubmed">1927948</ArticleId></ArticleIdList></Reference><Reference><Citation>J Am Coll Cardiol. 1997 Apr;29(5):1023-7</Citation><ArticleIdList><ArticleId IdType="pubmed">9120154</ArticleId></ArticleIdList></Reference><Reference><Citation>J Am Coll Cardiol. 1993 Nov 1;22(5):1344-53</Citation><ArticleIdList><ArticleId IdType="pubmed">8227790</ArticleId></ArticleIdList></Reference><Reference><Citation>Circulation. 1983 Nov;68(5):917-27</Citation><ArticleIdList><ArticleId IdType="pubmed">6137291</ArticleId></ArticleIdList></Reference><Reference><Citation>J Clin Invest. 1988 Dec;82(6):2127-35</Citation><ArticleIdList><ArticleId IdType="pubmed">3198769</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11406056</PMID><DateCompleted><Year>2002</Year><Month>02</Month><Day>28</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1469-493X</ISSN><JournalIssue CitedMedium="Internet"><Issue>2</Issue><PubDate><Year>2001</Year></PubDate></JournalIssue><Title>The Cochrane database of systematic reviews</Title><ISOAbbreviation>Cochrane Database Syst Rev</ISOAbbreviation></Journal>Cardioselective beta-blocker use in patients with reversible airway disease. | Left ventricular outflow tract (LVOT) tachycardia is an uncommon form of idiopathic ventricular tachycardia (IVT). The underlying mechanism of this arrhythmia appears to be cyclic AMP-medicated triggered activity. The tachycardia occurs in the absence of structural heart disease and is generally benign, presenting commonly as palpitations and presyncope. It can manifest either a right or left bundle branch block morphology with an inferior axis. Subtle variations in the QRS morphology in leads I, V1, and V2 can help in localizing the anatomic site of origin (SOO). The arrhythmia is typically responsive to a variety of pharmacologic agents (beta-blockers, calcium channel blockers, Class I and II agents). Radiofrequency catheter ablation of LVOT tachycardia SOO as determined by pace mapping is quite efficacious (success rates of 90%). Magnetic electroanatomic mapping augments this by permitting three-dimensional catheter mapping and reproducible localization of the SOO. Catheter ablation should be considered relatively early in patients who experience severe symptoms with their arrhythmia and have failed, or are reluctant to take medications for the disorder.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Dixit</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, 9 Founders, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marchlinski</LastName><ForeName>F E</ForeName><Initials>FE</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Curr Cardiol Rep</MedlineTA><NlmUniqueID>100888969</NlmUniqueID><ISSNLinking>1523-3782</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D017115" MajorTopicYN="Y">Catheter Ablation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013610" MajorTopicYN="N">Tachycardia</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="Y">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014694" MajorTopicYN="N">Ventricular Outflow Obstruction</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000601" 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IdType="pubmed">6650408</ArticleId></ArticleIdList></Reference><Reference><Citation>Am J Cardiol. 1991 Oct 1;68(9):897-900</Citation><ArticleIdList><ArticleId IdType="pubmed">1927948</ArticleId></ArticleIdList></Reference><Reference><Citation>J Am Coll Cardiol. 1997 Apr;29(5):1023-7</Citation><ArticleIdList><ArticleId IdType="pubmed">9120154</ArticleId></ArticleIdList></Reference><Reference><Citation>J Am Coll Cardiol. 1993 Nov 1;22(5):1344-53</Citation><ArticleIdList><ArticleId IdType="pubmed">8227790</ArticleId></ArticleIdList></Reference><Reference><Citation>Circulation. 1983 Nov;68(5):917-27</Citation><ArticleIdList><ArticleId IdType="pubmed">6137291</ArticleId></ArticleIdList></Reference><Reference><Citation>J Clin Invest. 1988 Dec;82(6):2127-35</Citation><ArticleIdList><ArticleId IdType="pubmed">3198769</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11406056</PMID><DateCompleted><Year>2002</Year><Month>02</Month><Day>28</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1469-493X</ISSN><JournalIssue CitedMedium="Internet"><Issue>2</Issue><PubDate><Year>2001</Year></PubDate></JournalIssue><Title>The Cochrane database of systematic reviews</Title><ISOAbbreviation>Cochrane Database Syst Rev</ISOAbbreviation></Journal><ArticleTitle>Cardioselective beta-blocker use in patients with reversible airway disease.</ArticleTitle><Pagination><StartPage>CD002992</StartPage><MedlinePgn>CD002992</MedlinePgn></Pagination><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Beta-blocker therapy has mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with reversible airway disease.<AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">To assess the effect of cardioselective beta-blockers on respiratory function of patients with reversible airway disease. Reversible airway disease was defined as asthma or chronic obstructive pulmonary disease with a reversible obstructive component.<AbstractText Label="SEARCH STRATEGY" NlmCategory="METHODS">A comprehensive search of EMBASE, MEDLINE and CINAHL was performed using the Cochrane Airways Group registry to identify randomized blinded placebo-controlled trials from 1966 to February, 2000. The search was completed using the terms: asthma*, bronchial hyperreactivity*, respiratory sounds*, wheez*, obstructive lung disease* or obstructive airway disease*, and adrenergic antagonist*, sympatholytic* or adrenergic receptor block*. We did not exclude trials on the basis of language.<AbstractText Label="SELECTION CRITERIA" NlmCategory="METHODS">Randomized, blinded, placebo-controlled trials of single dose or longer duration that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 second (FEV1), symptoms and use of short-acting inhaled beta-agonists, in patients with reversible airway disease. Reversible airway disease was documented by response to methacholine challenge, by an increase in FEV1 of at least 15% to beta-agonist administration, or the presence of asthma as defined by the American Thoracic Society.<AbstractText Label="DATA COLLECTION AND ANALYSIS" NlmCategory="METHODS">Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. Cardioselective beta-blockers were divided into 2 groups, those with or without intrinsic sympathomimetic activity (ISA). Two interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta-agonist given after the study drug.<AbstractText Label="MAIN RESULTS" NlmCategory="RESULTS">Nineteen studies for single-dose treatment and 10 for treatment of longer duration met selection criteria. The patients had mild-moderate airways obstruction. For cardioselective beta-blockers taken as a group, administration of a single dose was associated with a 7.98% (CI, 6.19 to 9.77%) reduction in FEV1, but with a 13.16% (CI, 10.76 to 15.56%) increase in beta-agonist response, as compared to placebo. There was no increase in symptoms. After treatment lasting a few days to a few weeks, there was no decrement in FEV1 compared to placebo and no increase in symptoms or inhaler use. Regular use of cardioselective beta-blockers without ISA produced a 13.13% (CI, 5.97 to 20.30) increase in beta-agonist response compared to placebo, a response not seen with beta-blockers containing ISA (-0.60% [CI, -11.7 to +10.5%]).<AbstractText Label="REVIEWER'S CONCLUSIONS" NlmCategory="CONCLUSIONS">Cardioselective beta-blockers, given to patients with mild-moderate reversible airway disease, do not produce clinically significant adverse respiratory effects in the short term. It is not possible to comment on their effects in patient with more severe or less reversible disease, or on their effect on the frequency or severity of acute exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should not be withheld from patients with mild-moderate reversible airway disease. |
2,332,438 | Apoptosis in the heart: about programmed cell death and survival. | Substantial evidence has accumulated that apoptosis, sometimes called "programmed cell death," is important in several cardiac diseases. Although most researchers focus on apoptosis in the hope that by understanding its mechanisms one can block this form of cell death, little attention has been given to programmed cell survival. |
2,332,439 | In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy. | Although the current clinical formulation of paclitaxel (Taxol) has a promising clinical activity against a wide variety of tumors, it has significant toxic side effects, some of which are associated with its formulation in a 1:1 (v/v) mixture of Cremophor EL and dehydrated alcohol. One of the problems associated with the intravenous administration of paclitaxel is its low solubility in water. Our study was designed to evaluate the pharmacokinetics, tissue distribution, toxicity and efficacy of a paclitaxel (Genexol)-containing biodegradable polymeric micellar system (Genexol-PM) in comparison to Taxol. Genexol-PM was newly developed by using a low molecular weight, nontoxic and biodegradable amphiphilic diblock copolymer, monomethoxy poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA) and paclitaxel (Genexol, Samyang Genex Co., Seoul, Korea). In a human cancer cell line model, Genexol-PM and Taxol showed comparable in vitro cytotoxicity against human ovarian cancer cell line OVCAR-3 and human breast cancer cell line MCF7. The maximum tolerated dose (MTD) of Genexol-PM and Taxol in nude mice was determined to be 60 and 20 mg/kg, respectively. The median lethal dose (LD(50)) in Sprague--Dawley rats was 205.4 mg/kg (male) and 221.6 mg/kg (female) for Genexol-PM, while 8.3 mg/kg (male) and 8.8 mg/kg (female) for Taxol. After intravenous administration of Genexol-PM in murine B16 melanoma-induced female SPF C57BL/6 mice at a dose of 50 mg/kg, the area under the plasma concentration-time curve (AUC) was similar to Taxol((R)) at a dose of 20 mg/kg, but biodistribution of paclitaxel after administration of Genexol-PM showed 2 to 3-fold higher levels in tissues including liver, spleen, kidneys, lungs, heart and tumor as compared to Taxol. The in vivo antitumor efficacy of Genexol-PM as measured by reduction in tumor volume of SKOV-3 human ovarian cancer implanted in nude (nu/nu) athymic mice and MX-1 human breast cancer implanted in Tac:Cr:(NCr)-nu athymic mice was significantly greater than that of Taxol. The results of cytotoxicity, MTD, LD(50) and antitumor efficacy suggest that Genexol-PM may have a great advantage over present-day chemotherapy with Taxol. |
2,332,440 | Novel mutations in the emerin gene in Israeli families. | Emery-Dreifuss Muscular Dystrophy (EMD or EDMD) is a rare X-linked recessive disorder, characterized by progressive muscle wasting and weakness, contractures, and cardiomyopathy, manifesting as heart block. Mutation analysis at the EMD gene locus was performed in 4 unrelated Israeli families with X-linked EMD and in one sporadic case. In the 4 families 4 different mutations were found, 3 of which were novel. These included two frame shift mutations in exon 2 (333delT and 412insA) and one base pair substitution at the consensus +1 donor splice in intron 5 (1429G-->A). The fourth mutation in exon 6 (1675-1678delTCCG) has been previously described. No mutations were identified in the one sporadic case. Two of the three novel mutations were found in exon 2. A summary of the previously published mutations described in the EMD Mutation Database (http://www.path.cam.ac.uk/emd/) as well as the mutations described in our study suggest that the distribution of mutations in EMD gene is not entirely random and that exon 2 is prone to mutations. Hum Mutat 17:522, 2001. |
2,332,441 | Beat dependent alteration of Ca2+-activated Cl- current during rapid stimulation in rabbit ventricular myocytes. | The transient outward currents (Ito) play an important role in action potential repolarization in cardiac myocytes. Two components of Ito have been identified as 4-AP-sensitive but Ca2+-insensitive Ito carried by K, and Ca2+-sensitive but 4-AP insensitive Ito carried by Cl- (I(Cl(Ca))). It is known that the amplitudes of Ito change depending on the stimulation frequency. In this study we investigated the beat dependent alteration of I(Cl(Ca)) during rapid stimulation using the whole cell patch clamp technique in rabbit ventricular myocytes. The cells were internally perfused with a solution containing 0.1 microM free Ca2+ to develop I(Cl(Ca)) and all internal K+ was replaced with Cs+ to block 4-AP-sensitive Ito and other K+ currents. By applying depolarizing pulses at a high frequency of 2.5 Hz, the amplitudes of I(Cl(Ca)) gradually increased as the number of pulses increased following a transient decrease in the 2nd pulse and reached a plateau level at the 20th pulse. The shape of the current-voltage curve of I(Cl(Ca)) was not overly different for different numbers of preceding pulses. The recovery from inactivation of I(Cl(Ca)) could be fitted to a single exponential curve and full recovery was achieved after > 1 sec with a time constant of 368 ms. The ramp clamp experiments showed that the conductance of the background I(Cl(Ca)) increased with the preceding pulse numbers, indicating that the resting level of [Ca2]i increased with the pulses applied. From these results, we conclude that beat dependent alteration of I(Cl(Ca)) is determined by not only its apparent kinetic property, but also the resting level of [Ca2+]i during rapid stimulation. |
2,332,442 | Effects of ketamine and its isomers on ischemic preconditioning in the isolated rat heart. | Ischemic preconditioning protects the heart against subsequent ischemia. Opening of the adenosine triphosphate-sensitive potassium (KATP) channel is a key mechanism of preconditioning. Ketamine blocks KATP channels of isolated cardiomyocytes. The authors investigated the effects of ketamine and its stereoisomers on preconditioning.</AbstractText>Isolated rat hearts (n = 80) underwent 30 min of no-flow ischemia and 60 min of reperfusion. Two groups with eight hearts each underwent the protocol without intervention (control-1 and control-2), and, in eight hearts, preconditioning was elicited by two 5-min periods of ischemia before the 30 min ischemia. In the six treatment groups (each n = 8), ketamine, R(-)- or S(+)-ketamine were administered at concentrations of 2 or 20 microg/ml before preconditioning. Eight hearts received 20 microg/ml R(-)-ketamine before ischemia. Left ventricular (LV) developed pressure and creatine kinase (CK) release during reperfusion were determined as variables of ventricular function and cellular injury.</AbstractText>Baseline LV developed pressure was similar in all groups: 104 +/- 28 mmHg (mean +/- SD). Controls showed a poor recovery of LV developed pressure (17 +/- 8% of baseline) and a high CK release (70 +/- 17 IU/g). Ischemic preconditioning improved recovery of LV developed pressure (46 +/- 14%) and reduced CK release (47 +/- 17 IU/g, both P < 0.05 vs. control-1). Ketamine (2 microg/ml) and 2 or 20 microg/ml S(+)-ketamine had no influence on recovery of LV developed pressure compared with preconditioning (47 +/- 18, 43 +/- 8, 49 +/- 36%) and CK release (39 +/- 8, 30 +/- 14, 41 +/- 25 IU/g). After administration of 20 microg/ml ketamine and 2 or 20 microg/ml R(-)-ketamine, the protective effects of preconditioning were abolished (LV developed pressure-recovery, 16 +/- 14, 22 +/- 21, 18 +/- 11%; CK release, 67 +/- 11, 80 +/- 21, 82 +/- 41 IU/g; each P < 0.05 vs. preconditioning). Preischemic treatment with R(-)-ketamine had no effect on CK release (74 +/- 8 vs. 69 +/- 9 IU/g in control-2, P = 0.6) and functional recovery (LV developed pressure 12 +/- 4 vs. 9 +/- 2 mmHg in control-2, P = 0.5).</AbstractText>Ketamine can block the cardioprotective effects of ischemic preconditioning. This effect is caused by the R(-)-isomer.</AbstractText> |
2,332,443 | Class III antiarrhythmics and phenytoin: teratogenicity due to embryonic cardiac dysrhythmia and reoxygenation damage. | Class III antiarrhythmic drugs, like almokalant, dofetilide and ibutilide, cause a spectrum of malformations in experimental teratology studies. The pattern of developmental toxic effects is very similar to those reported for phenytoin, which is an established human and animal teratogen. The toxic effects are characterised by embryonic death, decreased fetal weights, and stage specific malformations, such as distal digital reductions, orofacial clefts and cardiovascular defects. Class III antiarrhythmics decrease the excitability of cardiac cells by selectively blocking the rapid component of the delayed rectified potassium channel (IKr), resulting in prolongation of the repolarisation phase of the action potential. Phenytoin, which decrease the excitability of neurones, has recently also been shown to block IKr, in addition to its known blockade of sodium channels. Animal studies indicate that IKr is expressed in the embryo and that the embryonic heart is extremely susceptible to IKr-blockers during a restricted period in early development. At concentrations not affecting the maternal heart, the embryonic heart reacts with bradycardia, arrhythmia and cardiac arrest when exposed to such drugs. Available studies strongly support the idea that birth defects after in utero exposure to both selective and non-selective IKr-blockers (like phenytoin) are initiated by concentration dependent embryonic bradycardia/arrhythmia resulting in 1) hypoxia; explaining embryonic death and growth retardation, 2) episodes of severe hypoxia, followed by generation of reactive oxygen species within the embryo during reoxygenation, causing orofacial clefts and distal digital reductions, and 3) alterations in embryonic blood flow and blood pressure, inducing cardiovascular defects. |
2,332,444 | An interior point iterative maximum-likelihood reconstruction algorithm incorporating upper and lower bounds with application to SPECT transmission imaging. | The algorithm we consider here is a block-iterative (or ordered subset) version of the interior point algorithm for transmission reconstruction. Our algorithm is an interior point method because each vector of the iterative sequence [x(k)], k = 0, 1, 2, ... satisfies the constraints a(j) < x(j)k < b(j), j = 1, ..., J. Because it is a block-iterative algorithm that reconstructs the transmission attenuation map and places constraints above and below the pixel values of the reconstructed image, we call it the BITAB method. Computer simulations using the three-dimensional mathematical cardiac and torso phantom, reveal that the BITAB algorithm in conjunction with reasonably selected prior upper and lower bounds has the potential to improve the accuracy of the reconstructed attenuation coefficients from truncated fan beam transmission projections. By suitably selecting the bounds, it is possible to restrict the over estimation of coefficients outside the fully sampled region, that results from reconstructing truncated fan beam projections with iterative transmission algorithms such as the maximum-likelihood gradient type algorithm. |
2,332,445 | Severe hypomagnesemia and hypoparathyroidism in Kearns-Sayre syndrome. | Kearns-Sayre syndrome (KSS) is a multisystem mitochondrial disorder characterized by the invariant triad: onset before 20, progressive external ophthalmoplegia and pigmentary retinal degeneration, plus at least one of the following: complete heart block, cerebellar dysfunction and CSF protein >100 mg/dl. Autopsies from patients with KSS revealed widespread tissue distribution of mitochondrial (mt) DNA deletions. These deletions result in significantly lower activities of the enzymes of the respiratory chain. KSS has been associated with a variety of endocrine and metabolic disorders in <10% of patients, while renal tubular involvement is extremely rare. We present an 18-year-old girl with KSS who developed hypoparathyroidism and renal tubular dysfunction with inappropriate mangesiuria and kaliuria. We further discuss the renal tubular damage in KSS emphasizing its pathophysiology and clinical phenotype, and review the possible mechanisms of hypoparathyroidism in KSS. |
2,332,446 | Block of Kcnk3 by protons. Evidence that 2-P-domain potassium channel subunits function as homodimers. | KCNK subunits have two pore-forming P domains and four predicted transmembrane segments. To assess the number of subunits in each pore, we studied external proton block of Kcnk3, a subunit prominent in rodent heart and brain. Consistent with a pore-blocking mechanism, inhibition was dependent on voltage, potassium concentration, and a histidine in the first P domain (P1H). Thus, at pH 6.8 with 20 mm potassium half the current passed by P1H channels was blocked (apparently via two sites approximately 10% into the electrical field) whereas channels with an asparagine substitution (P1N) were fully active. Furthermore, pore blockade by barium was sensitive to pH in P1H but not P1N channels. Although linking two Kcnk3 subunits in tandem to produce P1H-P1H and P1N-P1N channels bearing four P domains did not alter these attributes, the mixed tandems P1H-P1N and P1N-P1H were half-blocked at pH approximately 6.4, apparently via a single site. This implicates a dimeric structure for Kcnk3 channels with two (and only two) P1 domains in each pore and argues that P2 domains also contribute to pore formation. |
2,332,447 | Shear stress-induced vasodilation in porcine coronary conduit arteries is independent of nitric oxide release. | The present study was performed to determine the importance of nitric oxide in eliciting epicardial coronary artery dilation during sustained increases in shear stress in the absence of pulsatile flow. Isolated first-order porcine epicardial coronary conduit arteries (approximately 500 microm) were preconstricted (U-46619) and subjected to steady-state changes in flow in vitro. Nonpulsatile flow (shear stress range from 0 to approximately 100 dyn/cm2) produced a graded dilation of epicardial arteries. Inhibiting nitric oxide synthase with 10(-5) M N(omega)-nitro-L-arginine methyl ester (L-NAME) blocked bradykinin-induced vasodilation but did not affect the flow-diameter relation or the maximum change in diameter from static conditions (67 +/- 10 microm in control vs. 71 +/- 8 microm after L-NAME, P = not significant). The addition of indomethacin (10(-5) M) had no effect on flow-mediated vasodilation. Depolarizing vascular smooth muscle with KCl (60 mM) or removing the endothelium blocked bradykinin vasodilation and completely abolished flow-mediated responses. The K+ channel blocker tetraethylammonium chloride (TEA; 10(-4)M) attenuated flow-mediated vasodilation (maximum diameter change was 110 +/- 18 microm under control conditions vs. 58 +/- 10 microm after TEA, P < 0.001). These data indicate that epicardial coronary arteries dilate to steady-state changes in nonpulsatile flow via a mechanism that is independent of nitric oxide production. The ability to completely block this with KCl and attenuate it with TEA supports the hypothesis that epicardial coronary arteries dilate to steady levels of shear stress through hyperpolarization of vascular smooth muscle. This may be secondary to the release of an endothelium-dependent hyperpolarizing factor. |
2,332,448 | Human cardiac sodium channels are affected by pentobarbital. | To investigate the response to general anaesthetics of different sodium channel subtypes, we examined the effects of pentobarbital, a close thiopental analogue, on single sodium channels from human ventricular muscle and compared them with existing data from human brain channels.</AbstractText>Sodium channels from preparations of human ventricular muscle were incorporated into planar lipid bilayers in the presence of batrachotoxin, a sodium channel activator. Single channel currents were recorded in symmetrical 100 mmol L-1 and 500 mmol L-1 NaCl before and after the addition of the anaesthetic pentobarbital (0.34-1.34 mmol L-1).</AbstractText>The blocking effect of pentobarbital on the fractional open time had an IC50 of 690 micromol L-1 in 500 mmol L-1 NaCl, whereas it had a significantly lower IC50 of 400 micromol L-1 in 100 mmol L-1 NaCl. Pentobarbital caused a significant shift of steady-state activation to hyperpolarized potentials (fmax = -42 mV, IC50 = 2 mmol L-1). This effect was independent of NaCl concentration.</AbstractText>Despite pharmacological and electrophysiological differences between human cardiac and human brain sodium channels their responses to pentobarbital are similar. The finding of channel block being dependent on the electrolyte concentration is novel for sodium channels.</AbstractText> |
2,332,449 | Neostigmine added to lidocaine axillary plexus block for postoperative analgesia. | We have assessed the analgesic efficacy and side-effects of neostigmine when added to lidocaine for axillary brachial plexus block, in a prospective, randomized, double-blind, placebo-controlled study.</AbstractText>We studied 34 ASA I or II patients undergoing elective ambulatory carpal tunnel release. Axillary brachial plexus block was performed using a peripheral nerve stimulator to locate the median nerve. All patients were administered 1.5% lidocaine 450 mg and epinephrine 5 microg mL-1. Patients were allocated randomly to one of two groups. Neostigmine 500 microg was added in group N, and saline 1 mL in group S.</AbstractText>The duration of analgesia did not significantly differ between groups [mean (SD)]: 812.5 (456.9) for group S vs. 746.7 (474.1) min for group N (P > 0.05). The need for supplementary analgesia did not significantly differ between groups: 4.4 (1.5) extra doses for group S vs. 3.8 (2.2) extra doses for group N (P > 0.05). Visual analogue pain scores and occurrence of side-effects did not significantly differ between groups.</AbstractText>Neostigmine does not seem to be of clinical value for peripheral nerve blocks.</AbstractText> |
2,332,450 | Hemodynamic assessment of local anesthetic administration by laser Doppler flowmetry. | The hemodynamic effects of local anesthetic administration with and without a vasoconstrictor were compared by using laser Doppler flowmetry.</AbstractText>Seventeen people participated in a single study session in which they were given 2 intraoral injections. The injections, which were administered in random order, consisted of 1.8 mL lidocaine (2%) with epinephrine (1:100,000) and mepivacaine (3%). Hemodynamic parameters consisting of blood pressure, heart rate, and laser Doppler flowmetry were reordered at regular intervals.</AbstractText>The laser Doppler flowmeter detected changes in the peripheral perfusion of the finger that were not detected by changes in blood pressure and heart rate. The greatest change was associated with anxiety and occurred just before the injection. The inclusion of epinephrine in the local anesthetic resulted in a persistence of these changes.</AbstractText>This investigation has confirmed the sensitivity of laser Doppler flowmetry as an investigational tool for assessing hemodynamic changes associated with anxiety and the administration of local anesthesia.</AbstractText> |
2,332,451 | The effects of atropine and methotrimeprazine on the epinephrine-induced arrhythmias in halothane-anesthetized dogs. | The effects of atropine and methotrimeprazine on epinephrine-induced ventricular arrhythmias were evaluated in halothane-anesthetized dogs. Ten mixed-breed dogs were assigned to 3 treatments (saline, atropine, and methotrimeprazine) in a randomized complete block design. Anesthesia was induced and maintained with halothane (1.5 minimum alveolar concentration) in oxygen. Controlled ventilation was used throughout to maintain eucapnia. Saline, atropine (0.05 mg/kg, i.v.) or methotrimeprazine (0.5 mg/kg, i.v.) were administered and, 5 minutes later the arrhythmogenic dose of epinephrine (ADE) was measured by i.v. infusion of progressively increasing infusion rates of epinephrine, until the ventricular arrhythmia criterion was met (at least 4 ectopic ventricular contractions (EVCs) during a 15-second period). Data were analyzed using a student's t-test for ADE values and multivariate profile analysis for heart rate (HR), arterial blood pressure (ABP), and rate pressure product (RPP). The ADE increased in atropine- and methotrimeprazine-treated groups, whereas 1 and 4 animals from these groups did not develop any ventricular arrhythmia, respectively. Epinephrine induced multiform premature ventricular contractions (PVCs) in the atropine group, whereas ventricular escape beats were observed in the control and methotrimeprazine groups. Heart rate and RPP decreased, and ABP increased at the time of ADE observation in the control group. Epinephrine infusion in the atropine group caused marked increases in HR, ABP, and RPP, which were associated with pulsus alternans in 2 animals. It was concluded that 1) the presence of cholinergic blockade influences the type of ventricular arrhythmia induced by epinephrine; 2) increased ADE values recorded following atropine administration must be cautiously interpreted, since in this situation the PVCs were associated with signs of increased myocardial work and ventricular failure; and 3) the use of a broader arrhythmia criterion (EVCs instead of PVCs) may not allow a direct comparison between ADE values, since it includes ventricular arrhythmias mediated by different mechanisms. |
2,332,452 | Long-term graft acceptance in rat heart transplantation by CTLA4Ig gene transfection combined with FTY720 treatment. | CTLA4Ig strongly adheres to B7 molecules on antigen-presenting cells to block intracellular signal transduction via CD28 on helper T cells, which eventually inhibits immune responses. We have demonstrated that the administration to recipient animals of adenoviral vectors containing CTLA4Ig gene (adCTLA4Ig) prolonged graft survival, although the gene expression diminished in a time-dependent manner and the grafts were finally rejected. In addition, recipient animals treated with FTY720, a new immunosuppressant, exhibited a decrease in the number of peripheral lymphocytes due to apoptosis. In this study, we performed adCTLA4Ig transfection combined with FTY720 treatment in heart-grafted rats to determine if the combination could induce a mutual effect on graft survival. The recipient animals were given injections of 1 x 10(9) plaque-forming units of adCTLA4Ig via the tail vein immediately after grafting. On the day before transplantation we administered FTY720 orally to some of these animals at a dosage of 5 mg/kg and again on the day of transplantation. The median graft survival period in the adCTLA4Ig-only group was 27 days, whereas that in the combination group was markedly prolonged to 56 days. Of 15 grafts, 5 survived indefinitely. In these groups we observed detectable levels of CTLA4Ig in the sera 49 days after grafting; the levels were always higher in the combination group than in the adCTLA4Ig-only group. As a result, this study revealed that FTY720 and adCTLA4Ig have a potent mutual effect on graft survival during rat heart transplantation. Furthermore, it is highly possible that FTY720 enhances gene expression of adCTLA4Ig, which may be related to the long-term acceptance of grafts. |
2,332,453 | Late sodium current is a novel target for amiodarone: studies in failing human myocardium. | V. A. Maltsev, H. N. Sabbah and A. I. Undrovinas. Late Sodium Current is a Novel Target for Amiodarone: Studies in Failing Human Myocardium. Journal of Molecular and Cellular Cardiology (2001) 33, 923-932. The authors recently reported the existence of a novel late Na(+)current (I(NaL)) in ventricular cardiomyocytes (VC) isolated from both normal and failing human hearts. Both in failing human and canine VC, partial block of I(NaL)normalized action potential (AP) duration and abolished early after depolarizations (EADs). The most recent computer simulation studies indicate a significant contribution of the persistent Na(+)current into the ion current balance on the plateau of VC AP as well as its important role in the dispersion of AP duration across the ventricular wall. The data thus indicate a possibility for I(NaL)to be a new therapeutic target. The present study tested a hypothesis that I(naL)could be a novel target for amiodarone (AMIO). Midmyocardial VC isolated from left ventricle of explanted failing human hearts were measured by a whole-cell clamp. I(NaL)was effectively blocked by AMIO in therapeutic concentrations, with IC(50)being 6.7+/-1.1 microM (mean+/-S.E.M., n=16 cells). At the same time, AMIO (5 microM ) produced almost no effect on the transient Na(+)current (IC(50)=87+/-28 microM, n=8). AMIO significantly shifted the steady-state inactivation (SSI) curve of I(NaL)towards more negative potentials and accelerated decay time course in a dose-dependent manner. At 5 microM, AMIO shifted SSI by 21+/-3 mV (n=7) and decreased the decay time constant from 0.67+/-0.05 s to 0.37+/-0.04 s (n=5, P<0.004). Evaluation of AMIO binding to different Na(+)channel (NaCh) states by means of mathematical models describing dose-dependent SSI shift and decay acceleration was consistent with an action that AMIO blocks NaCh preferentially in inactivated and activated states rather than in resting state. The authors conclude that the late Na(+)current is effectively blocked by AMIO and represents a new target for the drug in patients with chronic heart failure (HF). |
2,332,454 | Electrocardiogram interpretation. Case 1: permanent pacemaker malfunction?<Pagination><StartPage>231</StartPage><MedlinePgn>231</MedlinePgn></Pagination><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sporton</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Cardiology, St Bartholomew's Hospital, London EC1A 7BE.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Holdright</LastName><ForeName>D</ForeName><Initials>D</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Hosp Med</MedlineTA><NlmUniqueID>9803882</NlmUniqueID><ISSNLinking>1462-3935</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001281" MajorTopicYN="N">Atrial Fibrillation</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002037" MajorTopicYN="N">Bundle-Branch Block</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004868" MajorTopicYN="N">Equipment Failure</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010138" MajorTopicYN="Y">Pacemaker, Artificial</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2001</Year><Month>5</Month><Day>8</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2001</Year><Month>6</Month><Day>2</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2001</Year><Month>5</Month><Day>8</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11338955</ArticleId><ArticleId IdType="doi">10.12968/hosp.2001.62.4.1555</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11338519</PMID><DateCompleted><Year>2001</Year><Month>09</Month><Day>20</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>1</Issue><PubDate><Year>2001</Year><Season>Jan-Feb</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Combined anesthesia with blockade of nn.dorsalis penis and inhalation anesthetics in surgery of the penis in children]. | The studies were carried out in 21 patients with abnormalities of the penis (coronal and penile hypospadia, webbed penis) aged 5-15 years. Central hemodynamics, heart rate, and arterial pressure were evaluated at 6 stages of anesthesia and surgery. Premedication, induction, and maintenance anesthesia were carried out routinely. Laryngeal mask was used during maintenance anesthesia. The nn. dorsalis penis was blocked with 0.25% marcaine in a dose of 0.1 ml/kg for each side. The results indicate that penile blockade in combination with inhalation anesthesia is an effective method for anesthesiological protection of children operated on the penis. |
2,332,455 | Ryanoid modification of the cardiac muscle ryanodine receptor channel results in relocation of the tetraethylammonium binding site. | The interaction of ryanodine and derivatives of ryanodine with the high affinity binding site on the ryanodine receptor (RyR) channel brings about a characteristic modification of channel function. In all cases, channel open probability increases dramatically and single-channel current amplitude is reduced. The amplitude of the ryanoid-modified conductance state is determined by structural features of the ligand. An investigation of ion handling in the ryanodine-modified conductance state has established that reduced conductance results from changes in both the affinity of the channel for permeant ions and the relative permeability of ions within the channel (Lindsay, A.R.G., A. Tinker, and A.J. Williams. 1994. J. Gen. Physiol. 104:425-447). It has been proposed that these alterations result from a reorganization of channel structure induced by the binding of the ryanoid. The experiments reported here provide direct evidence for ryanoid-induced restructuring of RyR. TEA+ is a concentration- and voltage-dependent blocker of RyR in the absence of ryanoids. We have investigated block of K+ current by TEA+ in the unmodified open state and modified conductance states of RyR induced by 21-amino-9alpha-hydroxyryanodine, 21-azido-9alpha-hydroxyryanodine, ryanodol, and 21-p-nitrobenzoylamino-9alpha-hydroxyryanodine. Analysis of the voltage dependence of block indicates that the interaction of ryanoids with RyR leads to an alteration in this parameter with an apparent relocation of the TEA+ blocking site within the voltage drop across the channel and an alteration in the affinity of the channel for the blocker. The degree of change of these parameters correlates broadly with the change in conductance of permeant cations induced by the ryanoids, indicating that modification of RyR channel structure by ryanoids is likely to underlie both phenomena. |
2,332,456 | Capsaicin increases modulation of sympathetic nerve activity in rats: measurement using power spectral analysis of heart rate fluctuations.<Pagination><StartPage>638</StartPage><EndPage>643</EndPage><MedlinePgn>638-43</MedlinePgn></Pagination><Abstract><AbstractText>We assessed the sympatho-vagal activities of the heart after administration of capsaicin by measuring the power spectral analysis in rats. There were major two frequency components of heart rate variability, which we defined as high (1.0 Hz <, HF) and low (LF, < 1.0 Hz) frequency components. Vagal blockade by atropine abolished the high frequency component, and lowered the amplitude of the low frequency component. On the other hand, under conditions of sympathetic blockade by propranolol, the low frequency component was reduced. Combined vagal and sympathetic blockade abolished all heart rate fluctuations. We analyzed the low and high frequency components by integrating the spectrum for the respective band width. The rats administered capsaicin had a higher heart rate and sympathetic nervous system index (LF/HF) than the control group of rats. These results suggest that power spectral analysis is an effective and noninvasive method for detecting subtle changes in autonomic activity in response to the intake of foods or drugs.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ohnuki</LastName><ForeName>K</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moritani</LastName><ForeName>T</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Ishihara</LastName><ForeName>K</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Fushiki</LastName><ForeName>T</ForeName><Initials>T</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Biosci Biotechnol Biochem</MedlineTA><NlmUniqueID>9205717</NlmUniqueID><ISSNLinking>0916-8451</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>7C0697DR9I</RegistryNumber><NameOfSubstance UI="D001285">Atropine</NameOfSubstance></Chemical><Chemical><RegistryNumber>9Y8NXQ24VQ</RegistryNumber><NameOfSubstance UI="D011433">Propranolol</NameOfSubstance></Chemical><Chemical><RegistryNumber>S07O44R1ZM</RegistryNumber><NameOfSubstance UI="D002211">Capsaicin</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001016" MajorTopicYN="N">Aortic Bodies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001285" MajorTopicYN="N">Atropine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001340" MajorTopicYN="N">Autonomic Nerve Block</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002211" MajorTopicYN="N">Capsaicin</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006321" MajorTopicYN="N">Heart</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013058" MajorTopicYN="N">Mass Spectrometry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009407" MajorTopicYN="N">Nerve Block</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011433" MajorTopicYN="N">Propranolol</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017208" MajorTopicYN="N">Rats, Wistar</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013564" MajorTopicYN="N">Sympathetic Nervous System</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2001</Year><Month>5</Month><Day>2</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2001</Year><Month>10</Month><Day>26</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2001</Year><Month>5</Month><Day>2</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11330680</ArticleId><ArticleId IdType="doi">10.1271/bbb.65.638</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11279715</PMID><DateCompleted><Year>2001</Year><Month>12</Month><Day>07</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1469-493X</ISSN><JournalIssue CitedMedium="Internet"><Issue>1</Issue><PubDate><Year>2001</Year></PubDate></JournalIssue><Title>The Cochrane database of systematic reviews</Title><ISOAbbreviation>Cochrane Database Syst Rev</ISOAbbreviation></Journal>Dietary advice given by a dietitian versus other health professional or self-help resources to reduce blood cholesterol. | We assessed the sympatho-vagal activities of the heart after administration of capsaicin by measuring the power spectral analysis in rats. There were major two frequency components of heart rate variability, which we defined as high (1.0 Hz <, HF) and low (LF, < 1.0 Hz) frequency components. Vagal blockade by atropine abolished the high frequency component, and lowered the amplitude of the low frequency component. On the other hand, under conditions of sympathetic blockade by propranolol, the low frequency component was reduced. Combined vagal and sympathetic blockade abolished all heart rate fluctuations. We analyzed the low and high frequency components by integrating the spectrum for the respective band width. The rats administered capsaicin had a higher heart rate and sympathetic nervous system index (LF/HF) than the control group of rats. These results suggest that power spectral analysis is an effective and noninvasive method for detecting subtle changes in autonomic activity in response to the intake of foods or drugs.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ohnuki</LastName><ForeName>K</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moritani</LastName><ForeName>T</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Ishihara</LastName><ForeName>K</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Fushiki</LastName><ForeName>T</ForeName><Initials>T</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Biosci Biotechnol Biochem</MedlineTA><NlmUniqueID>9205717</NlmUniqueID><ISSNLinking>0916-8451</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>7C0697DR9I</RegistryNumber><NameOfSubstance UI="D001285">Atropine</NameOfSubstance></Chemical><Chemical><RegistryNumber>9Y8NXQ24VQ</RegistryNumber><NameOfSubstance UI="D011433">Propranolol</NameOfSubstance></Chemical><Chemical><RegistryNumber>S07O44R1ZM</RegistryNumber><NameOfSubstance UI="D002211">Capsaicin</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001016" MajorTopicYN="N">Aortic Bodies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001285" MajorTopicYN="N">Atropine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001340" MajorTopicYN="N">Autonomic Nerve Block</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002211" MajorTopicYN="N">Capsaicin</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006321" MajorTopicYN="N">Heart</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013058" MajorTopicYN="N">Mass Spectrometry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009407" MajorTopicYN="N">Nerve Block</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011433" MajorTopicYN="N">Propranolol</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017208" MajorTopicYN="N">Rats, Wistar</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013564" MajorTopicYN="N">Sympathetic Nervous System</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2001</Year><Month>5</Month><Day>2</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2001</Year><Month>10</Month><Day>26</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2001</Year><Month>5</Month><Day>2</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11330680</ArticleId><ArticleId IdType="doi">10.1271/bbb.65.638</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11279715</PMID><DateCompleted><Year>2001</Year><Month>12</Month><Day>07</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1469-493X</ISSN><JournalIssue CitedMedium="Internet"><Issue>1</Issue><PubDate><Year>2001</Year></PubDate></JournalIssue><Title>The Cochrane database of systematic reviews</Title><ISOAbbreviation>Cochrane Database Syst Rev</ISOAbbreviation></Journal><ArticleTitle>Dietary advice given by a dietitian versus other health professional or self-help resources to reduce blood cholesterol.</ArticleTitle><Pagination><StartPage>CD001366</StartPage><MedlinePgn>CD001366</MedlinePgn></Pagination><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">The average level of blood cholesterol is an important determinant of the risk of coronary heart disease. Blood cholesterol can be reduced by dietary means. Although dietitians are trained to provide dietary advice, for practical reasons it is also given by other health professionals and occasionally through the use of self-help resources.<AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">To assess the effects of dietary advice given by a dietitian compared with another health professional, or the use of self-help resources, in reducing blood cholesterol in adults.<AbstractText Label="SEARCH STRATEGY" NlmCategory="METHODS">We searched The Cochrane Library (to Issue 2 1999), MEDLINE (1966 to January 1999), EMBASE (1980 to December 1998), Cinahl (1982 to December 1998), Human Nutrition (1991 to 1998), Science Citation Index, Social Sciences Citation Index, hand searched conference proceedings on nutrition and heart disease, and contacted experts in the field.<AbstractText Label="SELECTION CRITERIA" NlmCategory="METHODS">Randomised trials of dietary advice given by a dietitian compared with another health professional or self-help resources. The main outcome was difference in blood cholesterol between dietitian groups compared with other intervention groups.<AbstractText Label="DATA COLLECTION AND ANALYSIS" NlmCategory="METHODS">Two reviewers independently extracted data and assessed study quality.<AbstractText Label="MAIN RESULTS" NlmCategory="RESULTS">Eleven studies with 12 comparisons were included, involving 704 people receiving advice from dietitians, 486 from other health professionals and 551 people using self-help leaflets. Four studies compared dietitian with doctor, seven with self-help resources, and one compared dietitian with nurse. Participants receiving advice from dietitians experienced a greater reduction in blood cholesterol than those receiving advice only from doctors (-0.25 mmol/L (95% CI -0.37, -0.12 mmol/L)). There was no statistically significant difference in change in blood cholesterol between dietitians and self-help resources (-0.10 mmol/L (95% CI -0.22, 0.03 mmol/L)). No statistically significant differences were detected for secondary outcome measures between any of the comparisons with the exception of dietitian versus nurse for HDLc, where the dietitian groups showed a greater reduction (-0.06 mmol/L (95% CI -0.11, -0.01)). No significant heterogeneity between the studies was detected.<AbstractText Label="REVIEWER'S CONCLUSIONS" NlmCategory="CONCLUSIONS">Dietitians were better than doctors at lowering blood cholesterol in the short to medium term, but there was no evidence that they were better than self-help resources. The results should be interpreted with caution as the studies were not of good quality and the analysis was based on a limited number of trials. More evidence is required to assess whether change can be maintained in the longer term. There was no evidence that dietitians provided better outcomes than nurses. |
2,332,457 | Diazoxide-induced cardioprotection requires signaling through a redox-sensitive mechanism. | Diazoxide, a selective opener of the mitochondrial ATP-sensitive potassium channel, has been shown to elicit tolerance to ischemia in cardiac myocytes and in perfused heart. However, the mechanism of this cardioprotection is poorly understood. Because reactive oxygen species (ROS) are recognized as important intracellular signaling molecules and have been implicated in ischemic preconditioning, we examined diazoxide-induced ROS production in adult cardiomyocytes. Cells treated with 50 micromol/L diazoxide showed a 173% increase in ROS production relative to baseline. 5-Hydroxydecanoate was found to attenuate the diazoxide-induced increase in ROS generation. The diazoxide-induced increase in ROS also was abrogated by the addition of either the antioxidant N-acetylcysteine (NAC) or N-mercaptopropionylglycine. We also examined the ability of NAC to block the protective effects of diazoxide in the perfused rat heart. After 20 minutes of global ischemia and 20 minutes of reflow, hearts perfused with 100 micromol/L diazoxide before ischemia showed significantly improved postischemic contractile function relative to untreated hearts (84% versus 29% of initial left ventricular developed pressure, respectively). Hearts treated with diazoxide in the presence of 4 mmol/L NAC recovered 53% of initial left ventricular developed pressure, whereas hearts treated with NAC alone recovered 46% of preischemic function. Using (31)P NMR spectroscopy, we found that, similar to preconditioning, diazoxide significantly attenuated ischemia-induced intracellular acidification and enhanced post- ischemic recovery of phosphocreatine levels, both of which were blocked by cotreatment with NAC. These data suggest that the cardioprotective actions of diazoxide are mediated by generation of a pro-oxidant environment. |
2,332,458 | Glimepiride block of cloned beta-cell, cardiac and smooth muscle K(ATP) channels. | 1. We examined the effect of the sulphonylurea glimepiride on three types of recombinant ATP-sensitive potassium (K(ATP)) channels. 2. K(ATP) channels share a common pore-forming subunit, Kir6.2, which associates with different sulphonylurea receptor isoforms (SUR1 in beta-cells, SUR2A in heart and SUR2B in smooth muscle). 3. Kir6.2 was coexpressed with SUR1, SUR2A or SUR2B in Xenopus oocytes and macroscopic K(ATP) currents were recorded from giant inside-out membrane patches. Glimepiride was added to the intracellular membrane surface. 4. Glimepiride inhibited Kir6.2/SUR currents by interaction with two sites: a low-affinity site on Kir6.2 (IC(50)= approximately 400 microM) and a high-affinity site on SUR (IC(50)=3.0 nM for SUR1, 5.4 nM for SUR2A and 7.3 nM for SUR2B). The potency of glimepiride at the high-affinity site is close to that observed for glibenclamide (4 nM for SUR1, 27 nM for SUR2A), which has a similar structure. 5. Glimepiride inhibition of Kir6.2/SUR2A and Kir6.2/SUR2B currents, but not Kir6.2/SUR1 currents, reversed rapidly. 6. Our results indicate that glimepiride is a high-affinity sulphonylurea that does not select between the beta-cell, cardiac and smooth muscle types of recombinant K(ATP) channel, when measured in inside-out patches. High-affinity inhibition is mediated by interaction of the drug with the sulphonylurea receptor subunit of the channel. |
2,332,459 | Continuous fascia iliaca compartment block in children: a prospective evaluation of plasma bupivacaine concentrations, pain scores, and side effects. | We sought to determine the plasma concentrations of bupivacaine and its main metabolite after continuous fascia iliaca compartment (FIC) block in children. Twenty children (9.9 +/- 4 yr, 38 +/- 19 kg) received a continuous FIC block for either postoperative analgesia (n = 16) or femoral shaft fracture (n = 4). A bolus dose of 0.25% bupivacaine (1.56 +/- 0.3 mg/kg) with epinephrine was followed by a continuous administration of 0.1% bupivacaine (0.135 +/- 0.03 mg. kg(-)(1). h(-)(1)) for 48 h. Plasma bupivacaine levels were determined at 24 h and 48 h by using gas liquid chromatography. Heart rate, arterial blood pressure, respiratory rate, side effects, and pain scores were recorded at 4-h intervals during 48 h. No significant differences were found between mean plasma bupivacaine levels at 24 h (0.71 +/- 0.4 microg/mL) and at 48 h (0.84 +/- 0.4 microg/mL) (P = 0.33). FIC block provided adequate analgesia in most cases. No severe adverse effects were noted. We conclude that the bupivacaine plasma concentrations during continuous FIC block in children are within the safety margins. FIC block is well tolerated, and provides satisfactory pain relief in most cases.</AbstractText>In this study, we have shown that, in children, continuous fascia iliaca compartment block, a technique providing neural blockade of the thigh and the anterior part of the knee, was associated with safe plasma bupivacaine concentrations, was well tolerated, and provided satisfactory pain scores in most cases.</AbstractText> |
2,332,460 | Apheresis for lupus erythematosus: state of the art. | PP is a safe, expensive, labor-intensive procedure. Its absolute SLE indications include hyperviscosity, cryoglobulinemia, pulmonary hemorrhage and TTP. PP may be useful in cyclophosphamide-resistant, serious, organ-threatening disease. It may be potentially useful in the antiphospholipid syndrome or mothers or children at risk for congenital heart block. Refinements in apheresis technology may expand the indications for PP. |
2,332,461 | Induction of anaesthesia with desflurane and isoflurane in the rabbit. | The characteristics of two techniques of face-mask induction of desflurane anaesthesia (rapid or slow) were compared with the effects of slow isoflurane induction in five New Zealand White (NZW) rabbits. Slow induction used stepwise increments in vapour setting of 2% for desflurane and 0.5% for isoflurane at 30 s intervals. All animals were anaesthetized using each technique according to a randomized block design with one week between treatments. Observations were made of the quality of induction (any struggling or periods of apnoea) and the latency to, and the duration of loss of the righting and toe pinch reflexes recorded. Changes in respiratory rate, arterial blood gas and cardiovascular parameters were also recorded. Induction and recovery times were shorter with rapid desflurane induction in comparison to isoflurane (loss of righting reflex: 139+/-27 s cf. 205+/-48 s), but both techniques were associated with struggling and long periods of apnoea (> 1 min) during the first 4 min after administration. During this period a significant degree of bradycardia, hypercapnia and hypoxaemia occurred with both techniques, but these and the subsequent effects of rapid desflurane administration were less severe than with isoflurane. Slow induction with desflurane was tolerated best, with little or no deleterious behavioural or physiological effects, however excessively prolonged induction times (loss of righting reflex 337+/-160 s) limits the application of this method. Desflurane, administered rapidly, appears to be a more suitable agent than isoflurane. However, as with isoflurane, anaesthesia should only be induced following oxygen supplementation. |
2,332,462 | PTOV1, a novel protein overexpressed in prostate cancer containing a new class of protein homology blocks. | In a search for molecular markers of progression in prostate cancer by means of differential display, we have identified a new gene, which we have designated PTOV1. Semiquantitative RT-PCR has established that nine out of 11 tumors overexpress PTOV1 at levels significantly higher than benign prostatic hyperplasia or normal prostate tissue. The human PTOV1 protein consists almost entirely of two repeated blocks of homology of 151 and 147 amino acids, joined by a short linker peptide, and is encoded by a 12-exon gene localized in chromosome 19q13.3. A Drosophila melanogaster PTOV1 homolog also contains two tandemly arranged PTOV blocks. A second gene, PTOV2, was identified in humans and Drosophila, coding for proteins with a single PTOV homology block and unrelated amino- and carboxyl-terminal extensions. A 1.8-Kb PTOV1 transcript was detected abundantly in normal human brain, heart, skeletal muscle, kidney and liver, and at low levels in normal prostate. Immunocytochemical analysis and expression of chimeric GFP-PTOV1 proteins in cultured cells showed a predominantly perinuclear localization of PTOV1. In normal prostate tissue and in prostate adenomas, PTOV1 was undetectable or expressed at low levels, whereas nine out of 11 prostate adenocarcinomas showed a strong immunoreactivity, with a focal distribution in areas of carcinoma and prostatic intraepithelial neoplasia. Therefore, PTOV1 is a previously unknown gene, overexpressed in early and late stages of prostate cancer. The PTOV homology block represents a new class of conserved sequence blocks present in human, rodent and fly proteins. |
2,332,463 | Similar haemodynamic, respiratory and metabolic changes with the use of sevoflurane or halothane in children breathing spontaneously via a laryngeal mask airway. | In preschool children, short-lasting surgical procedures are often performed under combined inhalational and regional anaesthesia with the child breathing spontaneously via a laryngeal mask airway (LMA). Despite widespread use, only limited data are available on haemodynamic, respiratory and metabolic effects of sevoflurane and halothane during LMA anaesthesia.</AbstractText>In an open-label, randomised, controlled study, 49 children (aged 3-8 years) were allocated to receive either sevoflurane or halothane in 60% nitrous oxide. After insertion of the LMA, end-tidal concentrations of sevoflurane or halothane were maintained at 1 MAC with the child ventilating spontaneously throughout the entire procedure. Analgesia was provided by caudal block. Haemodynamic and respiratory parameters were recorded, and capillary blood-gas samples were obtained repeatedly.</AbstractText>Changes in heart rate (HR) and systolic blood pressure were similar in both groups during all observed periods, apart from a significantly higher increase in HR during inhalational induction with sevoflurane (P<0.05). Regression slope analysis during anaesthesia revealed a decrease of the respiratory rate of 5 breaths h-1 (P<0.001) and an increase of end-tidal PCO2 and capillary PCO2 of about 0.25 kPa h-1 (P<0.001), with no significant difference between the two groups. Base excess, calculated in capillary blood gas samples, did not change over time (P>0.5) in either group.</AbstractText>The use of approximately 1 MAC sevoflurane or halothane in 60% N2O in children breathing spontaneously via LMA resulted in comparable haemodynamic, respiratory and metabolic changes, and clinically relevant deteriorations did not occur during the 65-min study period.</AbstractText> |
2,332,464 | Serpin protein CrmA suppresses hypoxia-mediated apoptosis of ventricular myocytes. | In this study, we ascertain whether caspase 8 activation and mitochondrial defects underlie apoptosis of ventricular myocytes during hypoxia. As an approach to circumvent the potential shortcomings surrounding the limited permeability and short half-life of the synthetic peptide inhibitors designed to block caspase activation, we constructed a replication-defective adenovirus encoding the serpin caspase inhibitor protein CrmA to ensure efficient and continual inhibition of caspase 8 activity during chronic hypoxia.</AbstractText>In contrast to normoxic cells, oxygen deprivation of postnatal ventricular myocytes for 24 hours resulted in a 9-fold increase (P<0.05) in apoptosis as determined by Hoechst 33258 staining and nucleosomal DNA laddering. Moreover, hypoxia provoked a 1.5-fold increase (P<0.01) in caspase 8-like activity. Furthermore, hypoxia provoked perturbations to mitochondria consistent with the mitochondrial death pathway, including permeability transition pore (PT) opening, loss of mitochondrial membrane potential ((m)), and cytochrome c release. Importantly, CrmA suppressed caspase 8 activity, PT pore changes, loss of (m), and apoptosis but had no effect on hypoxia-mediated cytochrome c release. Furthermore, Bongkrekic acid, an inhibitor of PT pore, prevented hypoxia-induced PT pore changes, loss of (m), and apoptosis but had no effect on hypoxia-mediated cytochrome c release.</AbstractText>To our knowledge, we provide the first direct evidence for the operation of CrmA as an antiapoptotic factor in ventricular myocytes during prolonged durations of hypoxia. Furthermore, our data suggest that perturbations to mitochondria including PT pore changes and (m) loss are caspase-regulated events that appear to be separable from cytochrome c release.</AbstractText> |
2,332,465 | Prenatal diagnosis of persistent fetal bradycardia: report of four cases. | Persistent fetal bradycardia is infrequent in prenatal life and difficult to manage optimally. It is generally attributable to sinus bradycardia due to fetal distress, blocked atrial extrasystoles, and congenital complete heart block. We reported four cases of persistent fetal bradycardia from 1995 to 1999 in our hospital. The first, second, and third cases of sustained fetal bradycardia had congenital complete heart block with positive titers for anti-Ro/SSA antibodies in both mothers and fetuses. Because of progressive fetal hydrops in the second case, the pregnancy was terminated. The first and third cases were isolated congenital complete heart block without structural anomaly. After prenatal examination the babies were followed up closely until term and both had a good prognosis without any implantation of pacemaker. In the fourth case there was no clinically known etiology associated with sustained fetal bradycardia. The fetal heart rate returned to normal after 6 weeks of follow-up and the baby was delivered without any cardiac problems. Congenital complete heart block is the most common cause of persistent fetal bradycardia. Prenatal detailed monitoring until delivery is necessary before heart failure develops. Treatment strategies (corticosteroids, ritodrine, and plasmapheresis) are debatable and may include prophylactic therapy for high-risk pregnant women. |
2,332,466 | Effects of soluble TNF receptor treatment on lipopolysaccharide-induced myocardial cytokine expression. | Tumor necrosis factor (TNF)-alpha plays a key role in the pathogenesis of septic shock syndrome, and myocardial TNF-alpha expression may contribute to this pathophysiology. We examined the myocardial expression of TNF-alpha-related cytokines and chemokines in mice exposed to lipopolysaccharide (LPS) and tested the effects of anti-TNF therapy on myocardial cytokine expression. Cytokine mRNA levels were measured by RNase protection assay, and protein levels in the plasma and myocardium were assessed by enzyme-linked immunosorbent assays. LPS (4 microg/g body wt ip) induced marked cytokine expression, including TNF-alpha, interleukin (IL)-1beta, IL-6, and monocyte chemotactic protein (MCP)-1, in both the plasma and myocardium. Pretreatment with adenovirus-mediated TNF receptor fusion protein (AdTNFR1; 10(9) plaque-forming units iv) decreased plasma cytokine levels. In contrast, whereas myocardial IL-1beta expression was also suppressed, expression of IL-6 and MCP-1 was not inhibited by AdTNFR1. In summary, anti-TNF treatment differentially altered the cytokine expression in the plasma and myocardium during endotoxemia. Inability to block myocardial expression of IL-6 and MCP-1 suggests a possible mechanism for the failure of anti-TNF therapies in the treatment of endotoxin shock. |
2,332,467 | Large-conductance calcium-activated potassium channels in neonatal rat intracardiac ganglion neurons. | The properties of single Ca2+-activated K+ (BK) channels in neonatal rat intracardiac neurons were investigated using the patch-clamp recording technique. In symmetrical 140 mM K+, the single-channel slope conductance was linear in the voltage range -60/+60 mV, and was 207+/-19 pS. Na+ ions were not measurably permeant through the open channel. Channel activity increased with the cytoplasmic free Ca2+ concentration ([Ca2+]i) with a Hill plot giving a half-saturating [Ca2+] (K0.5) of 1.35 microM and slope of approximately equals 3. The BK channel was inhibited reversibly by external tetraethylammonium (TEA) ions, charybdotoxin, and quinine and was resistant to block by 4-aminopyridine and apamin. Ionomycin (1-10 microM) increased BK channel activity in the cell-attached recording configuration. The resting activity was consistent with a [Ca2+]i <100 nM and the increased channel activity evoked by ionomycin was consistent with a rise in [Ca2+]i to > or =0.3 microM. TEA (0.2-1 mM) increased the action potential duration approximately equals 1.5-fold and reduced the amplitude and duration of the afterhyperpolarization (AHP) by 26%. Charybdotoxin (100 nM) did not significantly alter the action potential duration or AHP amplitude but reduced the AHP duration by approximately equals 40%. Taken together, these data indicate that BK channel activation contributes to the action potential and AHP duration in rat intracardiac neurons. |
2,332,468 | Molecular identification of a TTX-sensitive Ca(2+) current. | The TTX-sensitive Ca(2+) current [I(Ca(TTX))] observed in cardiac myocytes under Na(+)-free conditions was investigated using patch-clamp and Ca(2+)-imaging methods. Cs(+) and Ca(2+) were found to contribute to I(Ca(TTX)), but TEA(+) and N-methyl-D-glucamine (NMDG(+)) did not. HEK-293 cells transfected with cardiac Na(+) channels exhibited a current that resembled I(Ca(TTX)) in cardiac myocytes with regard to voltage dependence, inactivation kinetics, and ion selectivity, suggesting that the cardiac Na(+) channel itself gives rise to I(Ca(TTX)). Furthermore, repeated activation of I(Ca(TTX)) led to a 60% increase in intracellular Ca(2+) concentration, confirming Ca(2+) entry through this current. Ba(2+) permeation of I(Ca(TTX)), reported by others, did not occur in rat myocytes or in HEK-293 cells expressing cardiac Na(+) channels under our experimental conditions. The report of block of I(Ca(TTX)) in guinea pig heart by mibefradil (10 microM) was supported in transfected HEK-293 cells, but Na(+) current was also blocked (half-block at 0.45 microM). We conclude that I(Ca(TTX)) reflects current through cardiac Na(+) channels in Na(+)-free (or "null") conditions. We suggest that the current be renamed I(Na(null)) to more accurately reflect the molecular identity of the channel and the conditions needed for its activation. The relationship between I(Na(null)) and Ca(2+) flux through slip-mode conductance of cardiac Na(+) channels is discussed in the context of ion channel biophysics and "permeation plasticity." |
2,332,469 | Inhibitory effect of YC-1 on the hypoxic induction of erythropoietin and vascular endothelial growth factor in Hep3B cells. | YC-1 is a newly developed agent that inhibits platelet aggregation and vascular contraction. Although its effects are independent of nitric oxide (NO), it mimics some of the biological actions of NO. For example, it stimulates soluble guanylate cyclase (sGC) and increases intracellular cGMP concentration. Here, we tested the possibility that YC-1 inhibits hypoxia-inducible factor (HIF)-1-mediated hypoxic responses, as does NO. Hep3B cells were used during the course of this work to observe hypoxic induction of erythropoietin (EPO) and vascular endothelial growth factor (VEGF), and the effects of YC-1 were compared with those of a NO donor, sodium nitropurruside (SNP). In hypoxic cells, YC-1 blocked the induction of EPO and VEGF mRNAs, and inhibited the DNA-binding activity of HIF-1. It suppressed the hypoxic accumulation of HIF-1alpha, but not its mRNA level. It also reduced HIF-1alpha accumulation induced by cobalt and desferrioxamine. Treatment with antioxidants did not recover the HIF-1alpha suppressed by YC-1. We examined whether these effects of YC-1 are related to the sGC/cGMP signal transduction system. Two sGC inhibitors examined failed to block the effects of YC-1, and 8-bromo-cGMP did not mimic actions of YC-1. The effects of YC-1 on the hypoxic responses were comparable with those of SNP. These results suggest that YC-1 and SNP suppressed the hypoxic responses by post-translationally inhibiting HIF-1alpha accumulation. The YC-1 effect may be linked with the metal-related oxygen sensing pathway, and is not due to the stimulation of sGC. This observation implies that the inhibitory effects of YC-1 on hypoxic responses can be developed to suppress EPO-overproduction by tumor cells and tumor angiogenesis. |
2,332,470 | Effect of halothane on the cerebral circulation in young children: a hysteresis phenomenon. | To determine the effect of halothane on the cerebral blood flow velocity (CBFV) with increasing then decreasing concentrations, 11 children scheduled for minor surgery were studied. Anaesthesia consisted of halothane, vecuronium, nitrous oxide in oxygen and a caudal block. End-tidal carbon dioxide, temperature, heart rate and systolic arterial pressure were maintained constant. CBFV increased significantly between 0.5 and 1.0 MAC (p <0.001), and 0.5 and 1.5 MAC of halothane (p <0.001), but was not different after increasing concentration from 1.0 to 1.5 MAC. During the decreasing phase, CBFV decreased significantly from 1.5 to 1.0 MAC of halothane (p <0.001), whereas there was no difference in CBFV when decreasing halothane MAC from 1.0 to 0.5 MAC. In children, the decrease in CBFV during decreasing halothane concentration is not superimposable to the increase in CBFV seen when increasing halothane concentration, suggesting the presence of cerebrovascular hysteresis to halothane. |
2,332,471 | Phenytoin-induced cleft palate: evidence for embryonic cardiac bradyarrhythmia due to inhibition of delayed rectifier K+ channels resulting in hypoxia-reoxygenation damage. | Phenytoin (PHT) teratogenicity has been related to embryonic arrhythmia due to the capacity of PHT to block I(K) channels pharmacologically, resulting in hypoxia-reoxygenation damage. The aim of this study was to further elucidate the proposed mechanism.</AbstractText>Pregnant CD-1 mice were given PHT (85 mg/kg) or saline intraperitoneally on gestational days 10-11. Embryonic heart rhythm and presence of hemorrhage in orofacial region was recorded on day 12, fetuses were examined for malformations on day 18. Embryonic heart rate was also recorded on individual days after dosing days 9-16. In addition, PHT was given at doses of 10, 25, or 85 mg/kg on day 12 for analysis of plasma concentrations.</AbstractText>PTH-induced bradycardia and arrhythmia in approximately 20% of the embryos, 48% showed hemorrhage in the orofacial region; 39% of the fetuses had cleft palate. The region in which hemorrhages were visible in the embryo corresponded with the region where tissue deficiency (cleft palate) was visible in the fetus at term. None of the controls showed hemorrhages, dysrhythmia, or cleft palate. PHT affected embryonic heart rates on days 9-13, but not on days 14-16. Single dose administration on day 12, the most sensitive day, resulted in a dose-dependent decrease in embryonic heart rate (12-34%). Embryonic arrhythmia occurred at 25 and 85, but not at 10 mg/kg or in the controls. Mean maternal free plasma concentrations were 6 and 14 micromol/L in the 10- and 25-mg/kg groups, respectively.</AbstractText>PHT-induced cleft palate was preceded by embryonic dysrhythmia and hemorrhage in the orofacial region. Embryonic heart rhythm was phase specifically affected, as described for selective I(Kr) channel blockers, at clinically relevant concentrations. The results support the idea that PHT teratogenicity is a consequence of pharmacologically induced dysrhythmia and hypoxia-related damage.</AbstractText>Copyright 2001 Wiley-Liss, Inc.</CopyrightInformation> |
2,332,472 | Comparison of cloned Kir2 channels with native inward rectifier K+ channels from guinea-pig cardiomyocytes. | The aim of the study was to compare the properties of cloned Kir2 channels with the properties of native rectifier channels in guinea-pig (gp) cardiac muscle. The cDNAs of gpKir2.1, gpKir2.2, gpKir2.3 and gpKir2.4 were obtained by screening a cDNA library from guinea-pig cardiac ventricle. A partial genomic structure of all gpKir2 genes was deduced by comparison of the cDNAs with the nucleotide sequences derived from a guinea-pig genomic library. The cell-specific expression of Kir2 channel subunits was studied in isolated cardiomyocytes using a multi-cell RT-PCR approach. It was found that gpKir2.1, gpKir2.2 and gpKir2.3, but not gpKir2.4, are expressed in cardiomyocytes. Immunocytochemical analysis with polyclonal antibodies showed that expression of Kir2.4 is restricted to neuronal cells in the heart. After transfection in human embryonic kidney cells (HEK293) the mean single-channel conductance with symmetrical K+ was found to be 30.6 pS for gpKir2.1, 40.0 pS for gpKir2.2 and 14.2 pS for Kir2.3. Cell-attached measurements in isolated guinea-pig cardiomyocytes (n = 351) revealed three populations of inwardly rectifying K+ channels with mean conductances of 34.0, 23.8 and 10.7 pS. Expression of the gpKir2 subunits in Xenopus oocytes showed inwardly rectifying currents. The Ba2+ concentrations required for half-maximum block at -100 mV were 3.24 M for gpKir2.1, 0.51 M for gpKir2.2, 10.26 M for gpKir2.3 and 235 M for gpKir2.4. Ba2+ block of inward rectifier channels of cardiomyocytes was studied in cell-attached recordings. The concentration and voltage dependence of Ba2+ block of the large-conductance inward rectifier channels was virtually identical to that of gpKir2.2 expressed in Xenopus oocytes. Our results suggest that the large-conductance inward rectifier channels found in guinea-pig cardiomyocytes (34.0 pS) correspond to gpKir2.2. The intermediate-conductance (23.8 pS) and low-conductance (10.7 pS) channels described here may correspond to gpKir2.1 and gpKir2.3, respectively. |
2,332,473 | Volatile anaesthetic effects on Na+-Ca2+ exchange in rat cardiac myocytes. | We examined the influence of two clinically relevant concentrations (1 and 2 MAC (minimum alveolar concentration)) of halothane and sevoflurane on both efflux and reverse modes of Na+-Ca2+ exchange (NCX) in enzymatically dissociated adult rat cardiac myocytes. We hypothesised that a volatile anaesthetic-induced decrease in myocardial contractility is mediated by a reduction in intracellular calcium concentration ([Ca2+]i) via inhibition of NCX. Cells were exposed to cyclopiazonic acid and zero extracellular Na+ and Ca2+ to block sacroplasmic reticulum (SR) re-uptake and NCX efflux, respectively. As [Ca2+]i increased under these conditions, extracellular Na+ was rapidly (< 300 ms) reintroduced in the presence or absence of a volatile anaesthetic to selectively promote Ca2+ efflux via NCX. Other cells exposed to cyclopiazonic acid and ryanodine to inhibit SR Ca2+ re-uptake and release were Na+ loaded in zero extracellular Ca2+. The reintroduction of extracellular Ca2+ was used to selectively activate Ca2+ influx via NCX. Compared to controls, both 1 and 2 MAC halothane as well as sevoflurane reduced NCX-mediated efflux. The reduction in NCX-mediated influx was concentration dependent, but comparable between the two anaesthetics. Both anaesthetics at each concentration also shifted the relationship between extracellular Na+ (or extent of Na+ loading) and NCX-mediated efflux (or influx) to the right. These data indicate that despite inhibition of NCX-mediated Ca2+ efflux, volatile anaesthetics produce myocardial depression. However, the inhibition of NCX-mediated Ca2+ influx may contribute to decreased cardiac contractility. The overall effect of volatile anaesthetics on the [Ca2+]i profile is likely to be determined by the relative contributions of influx vs. efflux via NCX during each cardiac cycle. |
2,332,474 | Extracellular calcium modulates the effects of protamine on rat myocardium. | We studied the effects of protamine (10-300 microg. mL(-1)) as well as its interaction with heparin in rat left ventricular papillary muscles in vitro at calcium concentrations of 0.5 and 1 mM under low (isotony) and high (isometry) loads. Protamine induced a negative inotropic effect that was less pronounced at calcium 0.5 mM (active force at protamine 300 microg/mL, 84 +/- 20 vs 57 +/- 15% of baseline, P: < 0.05); whereas at calcium 1 mM there was a marked contracture of the muscle. For the smallest concentrations of protamine and at calcium 0.5 mM, we observed a moderate positive inotropic effect that was suppressed by nifedipine. Protamine induced a negative lusitropic effect under low load and decreased postrest potentiation, suggesting an impairment in the functions of the sarcoplasmic reticulum. Heparin was able to inhibit and reverse the negative inotropic effect of protamine. The negative inotropic effect of protamine is enhanced by an increase in extracellular calcium concentration. This negative inotropic effect is probably related to calcium overload and impairment in sarcoplasmic reticulum functions, and heparin can block these effects.</AbstractText>The negative inotropic effect of protamine is enhanced by an increase in extracellular calcium concentration. This negative inotropic effect is probably related to calcium overload and impairment in sarcoplasmic reticulum functions, and heparin can block these effects.</AbstractText> |
2,332,475 | Kearns Sayre syndrome: an atypical presentation. | Kearns Sayre syndrome is a rare presentation which usually involves a triad of factors: external ophthalmoplegia, retinal pigmentary degeneration, and heart block. We present a clinically and histopathologically confirmed case of Kearns Sayre syndrome that involved no retinal pathology. |
2,332,476 | Congenital complete heart block. | Congenital complete heart blocks (CCHB) are mostly related to the neonatal lupus syndrome. The purpose of this paper was to assess the clinical spectrum of CCHB in our hospital. Nine patients were retrospectively enrolled between 1994 and 1999. The birth history, electrocardiography, 24-hour Holter monitoring, pacemaker insertion and its complications, maternal disease, and maternal and infant autoantibody levels were studied. All nine cases were diagnosed prenatally. Hydrops fetalis was noted in five (55.6%). Six cases were live births and the other three were terminated. No anatomical heart defects were noted. Initial electrocardiography revealed the atrial rates ranged from 150 to 166 beats per minute. The minimal ventricular rates ranged from 46 to 80 beats per minute. VVI mode pacemakers were inserted through xyphoid approach in all live-birth infants. Complications were noted in three of them (50%). Antinuclear antibody and anti-SSA/Ro antibody were positive in all 8 mothers (100%). The anti-SSB/La antibody was positive in 6 of the eight mothers (75%). Five infants tested positive for anti-SSA/Ro antibody. None of the infants tested positive for anti-SSB/La antibody. In conclusion, all CCHBs in our series were associated with maternal autoantibodies. Because of high complication rate of permanent pacemaker insertion during the neonatal period, it should be restricted in certain conditions. |
2,332,477 | Transplantation of lungs from a non-heart-beating donor. | In animals, we have previously done successful lung transplantations using organs from non-heart-beating donors. We have also developed an ex-vivo system of assessing the function of such organs before transplantation. The next stage was to try the technique in human beings. Bearing in mind the sensitive ethical issues involved, our first aim was to find out what procedures would be acceptable, and to use the results to guide a clinical lung transplantation from a non-heart-beating donor.</AbstractText>The ethical acceptability of the study was gauged from the results of a broad information programme directed at the general public in Sweden, and from discussions with professionals including doctors, nurses, hospital chaplains, and judges. The donor was a patient dying of acute myocardial infarction in a cardiac intensive-care unit after failed cardiopulmonary resuscitation. The next of kin gave permission to cool the lungs within the intact body, and intrapleural cooling was started 65 min after death. Blood samples were sent for virological testing and cross matching. The next of kin then had time to be alone with the deceased. After 3 h, the body was transported to the operating theatre and the heart-lung block removed. The lungs were assessed ex vivo, and the body was transported to the pathology department for necropsy.</AbstractText>No contraindications to transplantation were found, and the right lung was transplanted successfully into a 54-year-old woman with chronic obstructive pulmonary disease. The donor lung showed excellent function only 5 min after reperfusion and ventilation, and during the first 5 months of follow-up, the function of the transplanted lung has been good.</AbstractText>About half the deaths in Sweden are caused by cardiac and cerebrovascular disease. This group could be a potential source of lung donors. When all hospitals and ambulance personnel in Sweden have received training in non-heart-beating lung donation, we hope that there will be enough donor lungs of good quality for all patients needing a lung transplant.</AbstractText> |
2,332,478 | Long-term outcome of mothers of children with isolated heart block in Finland. | To study the long-term outcome of mothers of children with isolated heart block in a defined population.</AbstractText>We reviewed the Finnish hospital registries for patients born between 1950 and 1999 who had been diagnosed as having isolated heart block before the age of 15 years. We identified 101 children with isolated congenital heart block (CHB) and 55 with isolated heart block detected after the newborn period. Eighty-three (91%) of the 91 mothers of children with CHB and 48 (87%) of the 55 mothers of children with heart block detected after the newborn period were studied according to a protocol defining clinical characteristics (mean 9.9 years, range 0-49 years, and mean 22.9 years, range 4-47 years after the index delivery, respectively). Maternal survival was compared with survival in an age-matched population of normal Finnish women.</AbstractText>Before the index delivery, 29 (37%) of the 78 surviving mothers of children with CHB had a self-reported clinical diagnosis of a chronic autoimmune disease, and 55 (71%) had had symptoms, signs, or abnormal laboratory findings suggesting an underlying subclinical disease. Of the 23 mothers who were completely asymptomatic before the index delivery, 10 (13% of the surviving mothers) remained so after a mean followup of 9.6 years (range 0-21 years). In mothers of children with CHB, clinical characteristics different from those of healthy mothers were photosensitivity, fatigue, dry eyes, and dry mouth. Forty-eight (58%) of these 83 mothers developed an autoimmune disease during followup. The most common diagnosis was primary Sjögren's syndrome (22 definite, 11 probable), followed by systemic lupus erythematosus (SLE). The standardized mortality ratio of mothers of children with CHB was 5.1, and 3 of the 5 deaths were associated with SLE. Mothers of children with heart block detected after the newborn period had similar symptoms and signs of autoimmune diseases as the healthy controls, and their standardized mortality ratio was 1.9.</AbstractText>Primary Sjögren's syndrome, either definite or subclinical, is the predominant autoimmune disorder in mothers of children with CHB. Mothers of children with isolated heart block detected after the newborn period do not, as a group, have clinical features suggestive of autoimmune diseases.</AbstractText> |
2,332,479 | Inhibitory effects of dauricine on potassium currents in guinea pig ventricular myocytes. | To study the effects of dauricine(Dau) on the rapidly activating component (IKr), the slowly activating component (IKs) of the delayed rectifier potassium current, and the inward rectifier potassium current (IKl) in guinea pig ventricular myocytes.</AbstractText>Single myocytes were dissociated by enzymatic dissociation method. The currents were recorded with the whole-cell configuration of the patch-clamp technique.</AbstractText>(1) Dau 1, 3, 10, 30, and 100 mumol.L-1 blocked IKr and tail current (IKr-tail) in a concentration-dependent manner. The IC50 for block of IKr-tail was 16 (95% confidence limits: 13-22) mumol.L-1. The time constant of IKr-tail deactivation was (140 +/- 38) ms in the control and (130 +/- 26) ms in the presence of Dau 30 mumol.L-1 (n = 6 cells from 3 animals, P > 0.05). (2) Dau 1-100 mumol.L-1 produced concentration-dependent blocks of IKs and tail current (IKs-tail). The IC50 value for block of IKs-tail was 33 (95% confidence limits: 24-46) mumol.L-1. The time constant of IKs-tail deactivation was (92 +/- 18) ms in the control and (84 +/- 16) ms in the presence of Dau 30 mumol.L-1 (n = 8 cells from 4 animals, P > 0.05). (3) Addition of Dau 30 mumol.L-1 induced block of IKs and IKs-tail (n = 7 cells from 3 animals). The degree of block of IKs and IKs-tail depended on test potentials, increasing with more positive depolarizations. (4) Dau 20 mumol.L-1 blocked mainly inward component of IKl and reduced the reversal potential from -72 mV (control) to -78 mV (n = 6 cells from 3 animals).</AbstractText>(1) Dau inhibited IKs, but not the process of IKs deactivation. (2) Dau blocked IKr, but not the process of deactivation. (3) Dau had a blocking effect on IKl.</AbstractText> |
2,332,480 | Pediatric caudal block with mepivacaine, bupivacaine or a mixture of both drugs: requirement for postoperative analgesia and plasma concentration of local anesthetics. | To assess the effects of pediatric caudal block using mepivacaine, bupivacaine, or a mixture of both drugs on postoperative analgesia, and to examine plasma concentrations of the local anesthetics after caudal injection.</AbstractText>Prospective, randomized, double-blind study.</AbstractText>Operating room and pediatric surgical ward.</AbstractText>60 ASA physical status I children weighing 10 to 20 kg (26 females, 34 males), and scheduled for inguinal herniorrhaphy.</AbstractText>Patients randomly received caudal block with 1 mL/kg of mepivacaine 1% (Group M, n = 20), 1 mL/kg of bupivacaine 0.25% (Group B, n = 20), or a mixture of 0.5 mL/kg of mepivacaine 1% and 0.5 mL/kg of bupivacaine 0.25% (Group MB, n = 20) after induction of anesthesia with sevoflurane in 50% oxygen (O2). Anesthesia was maintained with 66% nitrous oxide in O2 supplemented with sevoflurane at an end-tidal concentration of less than 1%.</AbstractText>Postoperative pain scores using a pediatric pain scale and plasma concentration of each local anesthetic were measured. In Group M, four patients required postoperative analgesics within the first 24 hours. However, no patients required postoperative analgesics in Groups B and MB. In Group M, the plasma concentration of mepivacaine of two patients exceeded 5 microg/kg of the level of toxicity. However, these patients did not show any toxic symptoms. Because a mixture of two local anesthetics halves the concentration of each local anesthetic, the plasma concentrations of mepivacaine and bupivacaine in Group MB were significantly lower than those of Groups M and B.</AbstractText>Pediatric caudal block with a mixture of mepivacaine and bupivacaine is effective for intraoperative and postoperative analgesia.</AbstractText> |
2,332,481 | Blockade of currents by the antimalarial drug chloroquine in feline ventricular myocytes. | The effects of the antimalarial drug chloroquine on cardiac action potential and membrane currents were studied at clinically relevant concentrations. In cat Purkinje fibers, chloroquine at concentrations of 0.3 to 10 microM increased action potential duration, and reduced maximum upstroke velocity. At concentrations of 3 and 10 microM, chloroquine increased automaticity and reduced maximum diastolic potential, and after 60 min of perfusion with a concentration 10 microM, spontaneous activity was abolished. In isolated cat ventricular myocytes, chloroquine also increased action potential duration in a concentration-dependent manner, and reduced resting membrane potential at 3 and 10 microM. In voltage-clamped cat ventricular myocytes, chloroquine blocked several inward and outward membrane currents. The order of potency was inward rectifying potassium current (I(K1)) > rapid delayed rectifying potassium current (I(Kr)) > sodium current (I(Na)) > L-type calcium current (I(Ca-L)). Only tonic block of I(Na) and I(Ca-L) was observed at a stimulation frequency of 0.1 Hz and no additional blockade was observed during stimulation trains applied at 1 Hz. The effect of chloroquine on I(K1) was voltage-dependent, with less pronounced blockade at negative test potentials. In addition, unblock was achieved by hyperpolarizing pulses to potentials negative to the current reversal potential. Chloroquine blocked the rapid component of the delayed rectifying outward current, I(Kr,) but not the slow component, I(Ks). These findings provide the cellular mechanisms for the prolonged QT interval, impaired ventricular conduction, and increased automaticity induced by chloroquine, which have been suggested as responsible for the proarrhythmic effects of the drug. |
2,332,482 | Negative inotropic effect of diazepam in isolated guinea pig heart. | The inotropic effect of diazepam, a benzodiazepine derivative, and its mechanism of action were examined using guinea pig heart and single ventricular cell preparations. In Langendorff hearts and right ventricular free-wall preparations, diazepam (10 to 100 microM) produced a monophasic negative inotropic effect in a concentration dependent manner. Neither a central type (flumazenil 1 microM) nor a peripheral type (PK11195 10 microM) of benzodiazepine receptor antagonist antagonized the monophasic negative inotropic effects of diazepam. Diazepam (10 to 100 microM) shortened action potential duration of papillary muscle in a concentration dependent manner. In isolated single ventricular cells, diazepam (30 and 100 microM) inhibited the calcium current (I(Ca)) in a concentration dependent manner. Diazepam produced a significant decrease in I(Ca) elicited by first depolarizing pulses, however, the decrease of I(Ca) was not augmented during a train of depolarizing pulses. Thus, diazepam appears to produce a tonic block of cardiac calcium channels and the mode of inhibition is clearly different from the use-dependent block of verapamil. From these results, it was concluded that diazepam produces a monophasic negative inotropic effect that is independent of the benzodiazepine receptor, and is probably mediated through an inhibition of I(Ca) in guinea pig heart preparations. |
2,332,483 | Direct inhibition of expressed cardiac l- and t-type calcium channels by igg from mothers whose children have congenital heart block. | Congenital heart block (CHB) is a disease that affects the offspring of mothers with autoimmune diseases. We recently reported that maternal sera containing antibodies against SSA/Ro and SSB/La ribonucleoproteins (positive IgG) inhibited L-type Ca current in isolated cardiac myocytes and induced sinus bradycardia in a murine model of CHB. The direct interaction of positive IgG with L-type Ca channel proteins and the possible inhibition of T-type Ca current that could account for the sinus bradycardia remain unknown.</AbstractText>The 2-electrode voltage-clamp technique was used to record currents via L-type (I(Ba)-alpha(1C) or I(Ba)-alpha(1C)+beta(2a)+alpha(2)/delta) and T-type (I(Ba)-alpha(1H)) Ca channels, Na channels (I(Na)-hH1), and K channels (I(Ks)-minK+KvLQT1) expressed in Xenopus oocytes. Positive IgG (350 microgram/mL) inhibited I(Ba)-alpha(1C) by 50.6+/-4.7% (P<0.01) and I(Ba)-alpha(1C)+beta(2a)+alpha(2)/delta by 50.9+/-4.2% (P<0.01); I(Ba)-alpha(1H) was reduced by 18.9+/-1.0% (P<0.01). Immunoblot data show cross-reactivity of positive IgG with alpha(1C) subunit. Pretreatment of oocytes with atropine (1 micromol/L) or acetylcholine (10 micromol/L) did not affect the inhibitory effect of IgG on I(Ba)-alpha(1C) and I(Ba)-alpha(1C)+beta(2a)+alpha(2)/delta (P<0.05). Positive IgG had no effect, however, on either I(Na)-hH1 or I(Ks)-minK+KvLQT1.</AbstractText>Positive IgG inhibited expressed L-type I:(Ba) and cross-reacted with the alpha(1C) subunit in Xenopus oocytes, providing strong evidence that maternal antibodies interact directly with the pore-forming alpha(1)-subunit of Ca channels. In addition, we show for the first time that positive IgG also inhibited T-type I(Ba) but not I(Na)-hH1 or I(Ks)-minK+KvLQT1. This could provide, in part, the ionic basis of sinus bradycardia reported in animal models of CHB and clinically in humans.</AbstractText> |
2,332,484 | Development of antisense oligodeoxynucleotides for transplantation. | Over last ten years antisense technology has been improved to provide powerful tools to selectively inhibit production of different mRNAs. This technology has been applied in transplantation to prolong the survival of organ allografts and to prevent development of ischemic/reperfusion injury in grafts. The present review describes technological progress in chemical modifications from antisense phosphodiester oligonucleotides to phosphorothioate oligonucleotides and the most advanced chimeric oligonucleotides with methoxyethyl groups attached at both ends or at one end of the oligonucleotide. Results indicate that phosphorothioate oligonucleotides, designed to block intercellular adhesion molecule-1 (ICAM-1), extended the survival of heart and kidney allografts when administered to donors or recipients. Combination of ICAM-1 antisense phosphorothioate oligonucleotide and cyclosporine (CsA) produced a potent synergistic interaction on allograft survival in comparison with each drug alone. The same ICAM-1 phosphorothioate oligonucleotide used for perfusion of kidney grafts prevented development of ischemic/reperfusion injury. We also compared the effect of c-raf mRNA inhibition on heart allograft survival by phosphorothioate oligonucleotide or phosphorothioate/methoxyethyl oligonucleotide used alone or in combination with CsA or sirolimus (SRL). The results documented that addition of methoxyethyl modifications at both ends or at one end of oligonucleotides significantly improved the in vivo antisense activity. Combined therapy with c-raf antisense phosphorothioate/methoxyethyl oligonucleotide and SRL synergistically extended the survival of heart allografts. Thus, antisense technology may provide not only tools to examine the effects of selective inhibition of different molecules involved in allograft rejection but also act as potential therapeutic agents. |
2,332,485 | Autoantibodies against neonatal heart M1 muscarinic acetylcholine receptor in children with congenital heart block. | Isolated congenital heart block may be associated with autoimmune disorder such as Sjögren Syndrome and systemic lupus erythematosus. In this work we demonstrate circulating autoantibodies against neonatal heart M1 muscarinic acetylcholine receptor (mAChR) in the sera of children with congenital heart block. This antibody were able to react with the second extracellular loop of the human M1 mAChR as demonstrated using a synthetic peptide in enzyme immune assay and binding assay. Affinity purified anti-peptide IgG as well as total IgG from children with congenital heart block, interfered with the specific radioligand occupancy from neonatal heart M1 mAChR, interacting irreversibly. The antipeptide antibodies also displayed an 'agonist-like' activity, i.e. decreased contractility, activated nitric oxide synthase activity and increased production of cyclic GMP. All of these effects were selectively blunted by pirenzepine and neutralized by the synthetic M1 peptide. Both binding and biological effects were obtained using neonatal rat heart instead adult heart and were independent of Ro/SS-A and La/SS-B antibodies and were also absent in the sera of normal children. A clinical relevance of these findings is demonstrated by a strong association between the existence of circulating M1 mAChR antipeptide antibodies and the presence of isolated congenital heart block, making these antibodies a proper marker of this disease. |
2,332,486 | Effect of vagal cooling on the counterregulatory response to hypoglycemia induced by a low dose of insulin in the conscious dog. | We previously demonstrated, using a nerve-cooling technique, that the vagus nerves are not essential for the counterregulatory response to hypoglycemia caused by high levels of insulin. Because high insulin levels per se augment the central nervous system response to hypoglycemia, the question arises whether afferent nerve fibers traveling along the vagus nerves would play a role in the defense of hypoglycemia in the presence of a more moderate insulin level. To address this issue, we studied two groups of conscious 18-h-fasted dogs with cooling coils previously placed on both vagus nerves. Each study consisted of a 100-min equilibration period, a 40-min basal period, and a 150-min hypoglycemic period. Glucose was lowered using a glycogen phosphorylase inhibitor and a low dose of insulin infused into the portal vein (0.7 mU.kg(-1) min(-1)). The arterial plasma insulin level increased to 15 +/- 2 microU/ml and the plasma glucose level fell to a plateau of 57 +/- 3 mg/dl in both groups. The vagal cooling coils were perfused with a 37 degrees C (SHAM COOL; n = 7) or a -20 degrees C (COOL; n = 7) ethanol solution for the last 90 min of the study to block parasympathetic afferent fibers. Vagal cooling caused a marked increase in the heart rate and blocked the hypoglycemia-induced increase in the arterial pancreatic polypeptide level. The average increments in glucagon (pg/ml), epinephrine (pg/ml), norepinephrine (pg/ml), cortisol (microg/dl), glucose production (mg.kg(-1). min(-1)), and glycerol (micromol/l) in the SHAM COOL group were 53 +/- 9, 625 +/- 186, 131 +/- 48, 4.63 +/- 1.05, -0.79 +/- 0.24, and 101 +/- 18, respectively, and in the COOL group, the increments were 39 +/- 7, 837 +/- 235, 93 +/- 39, 6.28 +/- 1.03 (P < 0.05), -0.80 +/- 0.20, and 73 +/- 29, respectively. Based on these data, we conclude that, even in the absence of high insulin concentrations, afferent signaling via the vagus nerves is not required for a normal counterregulatory response to hypoglycemia. |
2,332,487 | Absence of conduction defects in the electrocardiograms [correction of echocardiograms] of mothers with children with congenital complete heart block. | To investigate the association between complete congenital heart block (CCHB) in the fetus and adult disease.</AbstractText>We prospectively studied 111 consecutive patients with systemic lupus erythematosus (SLE) or a positive extractable nuclear antigen (Ro, La, or RNP) attending a connective tissue disease (CTD) clinic and 19 patients who had had children with CCHB. Electrocardiographs were recorded on all patients and subsequently analyzed blindly.</AbstractText>There was a significantly shorter PR interval in the mothers of children with CCHB compared to patients attending the CTD clinic (p < 0.02). There was no significant difference in PR interval between Ro positive and Ro negative patients in the CTD clinic. There were no significant differences in QRS or QTc duration between mothers with CCHB children and Ro positive or Ro negative patients attending the CTD clinic. The shorter PR interval in the mothers with CCHB children may be explained by their significantly younger age compared to patients in the CTD clinic (p < 0.02, 95% CI) and the lower incidence of CTD.</AbstractText>We were unable to confirm the association between anti-Ro antibodies and cardiac conduction defects in adults. This supports theories that CCHB is due to vulnerability peculiar to the fetal heart during a particular stage of development between 16 and 30 weeks of gestation.</AbstractText> |
2,332,488 | Safety and efficacy of peribulbar block as adjunct to general anaesthesia for paediatric ophthalmic surgery. | Fifty children (age 5-14 years, ASA I-II) undergoing elective ophthalmic surgery were chosen for the study. Of these, 25 received intravenous pethidine (control group) and 25 received a peribulbar block (block group) for perioperative analgesia, and were monitored intraoperatively and postoperatively by an investigator blinded to the analgesic technique.</AbstractText>Intraoperative values of haemodynamic variables were significantly higher in the control group (P < 0.01). Requirement for intraoperative rescue analgesic and postoperative analgesia was higher in the control group (P < 0.05 and P < 0.001, respectively). Children in the block group had lower postoperative pain scores at all times. Incidence of oculocardiac reflex was significantly higher (P < 0.001) in the control group. Seventy-six percent of children in the control group had postoperative nausea and vomiting compared to 20% children in the block group (P < 0.001).</AbstractText>There were no complications related to the block. Peribulbar block appears to be a safe and useful analgesic technique for paediatric ophthalmic surgery.</AbstractText> |
2,332,489 | Neurogenic inflammation in the airways. | Release of neuropeptides, including tachykinins and calcitonin gene-related peptide, from sensory nerves via an axon or local reflex may have inflammatory effects in the airways. This neurogenic inflammation may be initiated by activation of sensory nerves by inflammatory mediators and irritants. Neurogenic inflammation is well developed in rodents and may contribute to the inflammatory response to allergens, infections and irritants in animal models. However, the role of neurogenic inflammation in airway inflammatory diseases, such as asthma and COPD is still uncertain as there is little direct evidence for the involvement of sensory neuropeptides in human airways. Initial clinical studies using strategies to block neurogenic inflammation have not been encouraging, but it is important to study more severe forms of airway disease in more prolonged studies in the future to explore the role of neurogenic inflammation. |
2,332,490 | Role of adenosine and glycogen in ischemic preconditioning of rat hearts. | We tested whether ischemic preconditioning of the rat heart is mediated by reduced glycogenolysis during ischemia, an event triggered by adenosine A1 receptor activation. Rat hearts (n=40) were studied with [31P] and [13C] nuclear magnetic resonance (NMR) spectroscopy, using the Langendorff perfusion technique (5.5 mM [1-13C]glucose, 10 U/l insulin). In parallel experiments, hearts (n=43) were freeze-clamped at different time-points throughout the protocol. They were subjected to either ischemic preconditioning (PC), PC in the presence of 50 microM adenosine receptor antagonist, 8-(p-sulfophenyl)-theophylline (SPT), or intermittent infusion of 0.25 microM adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA). After 30 min ischemia and reperfusion, recovery of heart ratexpressure product was improved in hearts treated with preconditioning (33+/-13%) or CCPA (58+/-14%) compared with the SPT and ischemic control (IC) groups, which both failed to recover (P<0.05). CCPA administration induced a 58% increase in pre-ischemic [13C]glycogen (P<0.05 vs. all groups). In the PC and SPT groups, [13C]glycogen decreased by 25 and 47%, respectively (P<0.05) due to the short bouts of ischemia, resulting in lower pre-ischemic glycogen compared to ischemic control and CCPA hearts (P<0.05). The rate of [13C]glycogen utilization during the first 15 min of ischemia (in micromol/min g wwt) was not statistically different between IC (0.42+/-0.03), PC (0.30+/-0.04), and CCPA (0.38+/-0.05) hearts, but was reduced in SPT hearts (0.24+/-0.05; P<0.05). Total glycogen depletion during 30-min ischemia was reduced in PC hearts (0.61 mg/g wwt) compared to IC (1.84 mg/g wwt) and CCPA (1.75 mg/g wwt) hearts; SPT did not block reduced glycogenolysis during ischemia in PC hearts (0.77 mg/g wwt vs. IC). This study adds further strong evidence that in rat hearts, adenosine is involved in ischemic preconditioning. However, protection is unrelated to pre-ischemic glycogen levels and glycogenolysis during ischemia. |
2,332,491 | Cardiomyocytes bind and activate native human prorenin : role of soluble mannose 6-phosphate receptors. | Cardiomyocytes bind, internalize, and activate recombinant human prorenin through mannose 6-phosphate/insulin-like growth factor II (M6P/IGFII) receptors. To investigate whether this also applies to native human prorenin, neonatal rat myocytes were incubated for 4 hours at 37 degrees C with various prorenin-containing human body fluids. Uptake and activation by M6P/IGFII receptors were observed for plasma prorenin from subjects with renal artery stenosis and/or hypertension and for follicular fluid prorenin. The total amount of cellular renin and prorenin (expressed as percentage of the levels of renin and prorenin in the medium) after 4 hours of incubation was 4 to 10 times lower than after incubation with recombinant human prorenin. Although plasma contains alkaline phosphatases capable of inactivating the M6P label as well as soluble M6P/IGFII receptors that block prorenin binding in a competitive manner and proteins (eg, insulin, IGFII) that increase the number of cell-surface M6P/IGFII receptors, these factors were not responsible for the modest uptake of native human prorenin. Uptake did not occur during incubation of myocytes with plasma prorenin from anephric subjects or with amniotic fluid prorenin, and this was not due to the presence of excessively high levels of M6P/IGFII receptors and/or phosphatase activity in these fluids. In conclusion, myocytes are capable of binding, internalizing, and activating native human prorenin of renal and ovarian origin through M6P/IGFII receptors. Differences in prorenin glycosylation and/or phosphorylation as well as the concentration of soluble M6P/IGFII receptors and growth factors affecting cell-surface M6P/IGFII receptor density determine the amount of prorenin entering the heart and thus cardiac angiotensin II production. |
2,332,492 | [Single-lead DDD cardiac pacing: state of the art and future perspectives].<Pagination><StartPage>1553</StartPage><EndPage>1560</EndPage><MedlinePgn>1553-60</MedlinePgn></Pagination><Abstract><AbstractText>The electrical treatment of advanced atrioventricular block, with normal sinus node function, can be successfully and safely performed with single-lead atrial floating electrode VDD pacing. In comparison with two-lead DDD pacing, it offers some important advantages: easier and less time-consuming implantation procedures, simpler follow-up controls, and lower medium and long-term complication rates. However, should sinus node dysfunction develop, the atrium cannot be paced with this special kind of cardiac stimulation. For this reason, in the last few years, a particular research field has developed to overcome this problem. In this paper, the literature is reviewed, with special attention to the studies analyzing the commercially available leads and some prototypes implanted, outlining the pros and cons. The high stimulation energy, the inconstant atrial capture, and phrenic nerve stimulation are still unresolved problems. The reliability and efficacy of single-lead DDD pacing will presumably depend, in the future, on the development of preshaped, new-designed electrodes, with stable contact with the atrial wall, and on new stimulation waveforms. In this context, however, particular attention should be devoted to the correct atrial signal detection.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Romanò</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Divisione di Cardiologia, Azienda Ospedaliera G. Salvini, Garbagnate Milanese (MI). max.romano@tiscalinet.it</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Spinelli</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Grieco</LastName><ForeName>A</ForeName><Initials>A</Initials></Author></AuthorList><Language>ita</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><VernacularTitle>La stimolazione DDD monocatetere: stato dell'arte e prospettive future.</VernacularTitle></Article><MedlineJournalInfo><Country>Italy</Country><MedlineTA>Ital Heart J Suppl</MedlineTA><NlmUniqueID>101223651</NlmUniqueID><ISSNLinking>1129-4728</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002304" MajorTopicYN="N">Cardiac Pacing, Artificial</DescriptorName><QualifierName UI="Q000639" MajorTopicYN="Y">trends</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005544" MajorTopicYN="N">Forecasting</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006327" MajorTopicYN="N">Heart Block</DescriptorName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading></MeshHeadingList><NumberOfReferences>48</NumberOfReferences></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2001</Year><Month>2</Month><Day>28</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2001</Year><Month>4</Month><Day>3</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2001</Year><Month>2</Month><Day>28</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11221584</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11220947</PMID><DateCompleted><Year>2001</Year><Month>04</Month><Day>26</Day></DateCompleted><DateRevised><Year>2017</Year><Month>11</Month><Day>16</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>5</Issue><PubDate><Year>2000</Year><Season>Sep-Oct</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Hazards and complications of central segmental blockade. I. Epidural anesthesia (retrospective analysis)]. | The electrical treatment of advanced atrioventricular block, with normal sinus node function, can be successfully and safely performed with single-lead atrial floating electrode VDD pacing. In comparison with two-lead DDD pacing, it offers some important advantages: easier and less time-consuming implantation procedures, simpler follow-up controls, and lower medium and long-term complication rates. However, should sinus node dysfunction develop, the atrium cannot be paced with this special kind of cardiac stimulation. For this reason, in the last few years, a particular research field has developed to overcome this problem. In this paper, the literature is reviewed, with special attention to the studies analyzing the commercially available leads and some prototypes implanted, outlining the pros and cons. The high stimulation energy, the inconstant atrial capture, and phrenic nerve stimulation are still unresolved problems. The reliability and efficacy of single-lead DDD pacing will presumably depend, in the future, on the development of preshaped, new-designed electrodes, with stable contact with the atrial wall, and on new stimulation waveforms. In this context, however, particular attention should be devoted to the correct atrial signal detection.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Romanò</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Divisione di Cardiologia, Azienda Ospedaliera G. Salvini, Garbagnate Milanese (MI). max.romano@tiscalinet.it</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Spinelli</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Grieco</LastName><ForeName>A</ForeName><Initials>A</Initials></Author></AuthorList><Language>ita</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><VernacularTitle>La stimolazione DDD monocatetere: stato dell'arte e prospettive future.</VernacularTitle></Article><MedlineJournalInfo><Country>Italy</Country><MedlineTA>Ital Heart J Suppl</MedlineTA><NlmUniqueID>101223651</NlmUniqueID><ISSNLinking>1129-4728</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002304" MajorTopicYN="N">Cardiac Pacing, Artificial</DescriptorName><QualifierName UI="Q000639" MajorTopicYN="Y">trends</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005544" MajorTopicYN="N">Forecasting</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006327" MajorTopicYN="N">Heart Block</DescriptorName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading></MeshHeadingList><NumberOfReferences>48</NumberOfReferences></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2001</Year><Month>2</Month><Day>28</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2001</Year><Month>4</Month><Day>3</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2001</Year><Month>2</Month><Day>28</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11221584</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11220947</PMID><DateCompleted><Year>2001</Year><Month>04</Month><Day>26</Day></DateCompleted><DateRevised><Year>2017</Year><Month>11</Month><Day>16</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>5</Issue><PubDate><Year>2000</Year><Season>Sep-Oct</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal><ArticleTitle>[Hazards and complications of central segmental blockade. I. Epidural anesthesia (retrospective analysis)].</ArticleTitle><Pagination><StartPage>84</StartPage><EndPage>93</EndPage><MedlinePgn>84-93</MedlinePgn></Pagination><Abstract>A total of 700 reports about complications of epidural anesthesia over more than 30 years are analyzed. Four groups of complications have been distinguished: 1) errors and complications caused by technological errors; 2) complications caused by atypical dissemination of an anesthetic; 3) complications caused by side and toxic effects of local anesthetics or effects of epidural block; and 4) complications caused by damage to nerve structures. Causes, pathogenesis, prevention and treatment of complications are discussed. The cause-and-effect analysis of complications of epidural anesthesia helped objectively formulate and validate the relative and absolute contraindications to the use of this method. |
2,332,493 | High concentrations of isoflurane do not block the sympathetic nervous system activation from desflurane. | The volatile anesthetic desflurane has been associated with neurocirculatory responses that have been relatively refractory to adjuvant treatment. We have employed desflurane to evaluate the integrity of the sympathetic nerve recording after establishment of the anesthetized state with another anesthetic agent. This retrospective evaluation of data from volunteers determined if higher concentrations of isoflurane that were sufficient to block the neurocirculatory response to laryngeal and tracheal stimulation would abolish the neurocirculatory response to desflurane.</AbstractText>Data from eight, healthy, young volunteers met our criteria for inclusion. They had been anesthetized with propofol or thiopental and intubated after neuromuscular blockade. Each subject was monitored with radial artery blood pressure (BP), heart rate (HR)(ECG), and sympathetic microneurography. Isoflurane had been administered to achieve a steady state concentration of 1.5 MAC (minimum alveolar concentration) while oxygenation and carbon dioxide were monitored with pulse oximetry and infrared spectrometry, respectively. A deep level of anesthesia was confirmed when laryngoscopy and endotracheal tube movement failed to elicit a neurocirculatory response. A brief exposure to 11% desflurane in the inspired gas was then provided.</AbstractText>The responses to desflurane included significant increases in HR, range 32-84 b/min, and BP, range 15-72 mm Hg (P < 0.05). Sympathetic nerve activity increased substantially in the three volunteers with functional nerve recordings.</AbstractText>In healthy volunteers receiving 1.5 MAC isoflurane, which was sufficient to block the neurocirculatory response to laryngoscopy and tracheal stimulation, there were striking increases in sympathetic outflow, HR and BP when 11% desflurane was substituted for isoflurane.</AbstractText> |
2,332,494 | Pregnancy in systemic lupus erythematosus. | Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women of reproductive age. Pregnancy and its outcome is a major concern to most SLE patients. Queries regarding the risk of disease flares during pregnancy, chance of fetal loss, and the safety of various drugs are often raised. With the improvement in the understanding of the pathogenesis of SLE and the judicious use of immunosuppressive drugs, better disease control can now be achieved and SLE patients should not be deprived of the opportunity for bearing children. Prepregnancy counselling and close collaboration with other specialists such as the obstetricians and the perinatologists is essential in optimising the maternal and fetal outcome in lupus pregnancies. In this review, important issues regarding the fertility rate, optimal timing of conception, risk of disease flares during lupus pregnancy, pregnancy course, fetal outcome, safety of various drugs used for disease control during pregnancy and lactation, and contraceptive advice are discussed. |
2,332,495 | Reorganisation of respiratory network activity after loss of glycinergic inhibition. | gamma-Aminobutyric acid (GABA)-ergic and glycinergic inhibition is believed to play a major role in the respiratory network. In the present study we tested whether specific blockade of glycinergic inhibition resulted in changes in respiratory network interaction and function. Using the working heart-brainstem preparation from adult mice, we recorded phrenic nerve activity and the activity of different types of respiratory neurones located in the ventrolateral medulla. Strychnine (0.03-0.3 microM) was given systemically to block glycine receptors (Gly-R). During exposure to strychnine, post-inspiratory (PI) neurones shifted their onset of discharge into the inspiratory phase. As a consequence, the post-inspiratory phase failed and the rhythm changed from a three-phase cycle (inspiration, post-inspiration, expiration, with a frequency of about. 0.24 Hz) to a faster, two-phased cycle (inspiration expiration, frequency about 0.41 Hz). Inspiratory and expiratory neurones altered their augmenting membrane potential pattern to a rapidly peaking pattern. Smaller voltage oscillations at approximately 10 Hz and consisting of excitatory and inhibitory postsynaptic potential sequences occurred during the expiratory interval. Due to their high frequency and low amplitude, such oscillations would be inadequate for lung ventilation. We conclude that, under physiological conditions, glycinergic inhibition does indeed play a major role in the generation of a normal respiratory rhythm in adult mice. After failure of glycinergic inhibition a faster respiratory rhythm seems to operate through reciprocal GABAergic inhibition between inspiratory and expiratory neurones, while phase switching is organised by activation of intrinsic membrane properties. |
2,332,496 | Low molecular weight dextran sulfate prevents complement activation and delays hyperacute rejection in pig-to-human xenotransplantation models. | Dextran sulfate of 5000 molecular weight (DXS 5000) is known to block complement activation as well as the intrinsic coagulation cascade by potentiation of C inhibitor. The effect of DXS 5000 on hyperacute rejection (HAR) was tested in pig-to-human xenotransplantation models. For in vitro testing, a cytotoxicity assay was used with the pig kidney cell line PK15 as target cells and fresh, undiluted human serum as antibody and complement source. Ex vivo pig lung perfusion was chosen to assess DXS 5000 in a physiologic model. Pig lungs were perfused with fresh, citrate-anticoagulated whole human blood to which 1 or 2 mg/ml DXS 5000 were added; the lungs were ventilated and the blood de-oxygenated. Pulmonary vascular resistance (PVR) and blood oxygenation (deltapO2) were monitored throughout the experiment. Autologous pig blood and human blood without DXS 5000 served as controls. In the PK 15 assay DXS 5000 led to a complete, dose-dependent inhibition of human serum cytotoxicity with an average IC50 of 43 +/- 18 microg/ml (n=8). Pig lungs perfused with untreated human blood (n=2) underwent HAR within 105 +/- 64 min, characterized by increased PVR, decrease of deltapO2, and generalized edema. Microscopically, capillary bleeding as well as deposition of human antibodies, complement and fibrin could be observed. Addition of DXS 5000 (n=4) prolonged lung survival to 170 +/- 14 min for 1 mg/ml and 250 +/- 42 min for 2 mg/ml. and PVR values as well as edema formation were comparable to control lungs that were perfused with autologous pig blood (n=2). Activation of complement (activation products in serum, deposition on lung tissue) and the coagulation system (fibrin monomers) were significantly diminished as compared to human blood without DXS 5000. Binding of anti-Gal antibodies was not influenced, and in vitro experiments showed no evidence of complement depletion by DXS 5000. In conclusion, DXS 5000 is an efficient complement inhibitor in pig-to-human xenotransplantation models and therefore a candidate for complement-inhibitory/anti-inflammatory therapy either alone or in combination with other substances and warrants further investigation. |
2,332,497 | Translation is regulated via the 3' untranslated region of alpha-myosin heavy chain mRNA by calcium but not by its localization. | Posttranscriptional regulation plays an important role in alpha-myosin heavy chain (alpha-MyHC) protein synthesis in cardiac muscle cells. In the present study, we test the effects of calcium and mRNA mislocalization on alpha-MyHC translation in order to determine the mechanism(s) contributing to translational block via the 3' untranslated region (3'UTR). Neonatal rat cardiac myocytes were treated for 6 h with L-isoproterenol (10 microM) to enhance beating, with 10 microM verapamil to block beating and mislocalize mRNA, or with 3 microM colchicine to enhance beating but mislocalize mRNA by depolymerization of the microtubules. In order to determine whether translation is regulated by the 3'UTR, either a control (SV40 3'UTR) or the experimental (alpha-MyHC 3'UTR) was placed after a luciferase reporter gene and transfected into the myocytes. The amount of luciferase protein only decreased significantly in verapamil arrested cells transfected with the alpha-MyHC 3'UTR construct (P < 0.01). To control for the possibility that pharmacological treatments might affect transcription or message stability, we analyzed neomycin and luciferase mRNA levels transcribed from the same transfected plasmid. No significant changes were found with an RNase protection assay. These results suggest that calcium but not mRNA localization regulates protein synthesis and further, this is mediated by the 3' untranslated region of alpha-MyHC. |
2,332,498 | Endothelin: what does the radiologist need to know? | Endothelin (ET) is a potent endogenous vasoconstrictor peptide. It has been implicated in various pathological states since its discovery in 1988. The cardiovascular system and the kidneys are important sites for the action of this peptide. Two types of ET receptor, ETA and ETB, govern the biological effects of ET. Drugs that can prevent the endogenous synthesis of ET or block its binding to receptors may offer important therapeutic impact to patients with congestive heart failure, pulmonary hypertension and acute renal failure. Areas of particular interest to the radiologist include the role of ET in mediating some of the side effects of contrast media, particularly contrast medium nephropathy, and the involvement of ET in the pathogenesis of restenosis following angioplasty. This review outlines the basic biology of this important mediator and its role in health and disease. |
2,332,499 | Venous pooling during nitrate-stimulated tilt testing in patients with vasovagal syncope. | To investigate the importance of venous pooling and variation in venous tone during nitrate-stimulated tilt testing in patients.</AbstractText>Ten patients with a history of vasovagal syncope underwent an upright tilt test after an injection of 99mTc-labelled albumin. A gamma camera was positioned at the level of the lower legs. The patients were tilted to 90 degrees for 30 min or until symptoms developed. In those subjects who did not show any symptoms before the end of the 30-min period, isosorbide dinitrate (ISDN) 5 mg was given sublingually and the test was prolonged for a maximum of 15 min.</AbstractText>Nine of 10 patients needed nitrate stimulation to develop symptoms, and one patient remained symptom free following ISDN administration. Measurement of radioactivity revealed no significant increase in calf volume after nitrate stimulation (the mean volume increase was 77% before ISDN stimulation and a further 0.9% afterwards).</AbstractText>The higher sensitivity for vasovagal syncope during upright tilt testing after administration of sublingual ISDN is not due to an increase in venous pooling in the lower extremities.</AbstractText> |
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