title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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[High rate of hepatitis B virus DNA positivity in anti-HBc only-positive patients]. | In hepatitis B virus (HBV) infections, detection of only anti-HBc in the absence of HBsAg and anti-HBs is known as 'anti-HBc only' situation. In this study we investigated the rate of HBV-DNA positivity in anti-HBc only-positive 45 patients (29 male, 16 female; mean age: 39.2 +/- 12.3 years) who were followed in the outpatient clinics of a University Hospital in Düzce (located at northern west part of Turkey). HBV markers were investigated by 3rd generation ELISA (MEIA Axsym-Abbott), and HBV-DNA were searched by real-time PCR [extraction: Minielute (Qiagen, Germany); PCR kits: Florion HBV (lontek, Turkey); detection: i-cycler IQ5 (BioRad, USA)] methods. As a result, 24.4% (11/45) of the patients were found HBV-DNA positive (> 10(3) copies/ml). There was no statistically significant difference of HBV-DNA positivity rates between males (9/29; 31%) and females (2/16; 12.5%), (p= 0.15). It was concluded that there may be a serious risk of HBV transmission from anti-HBc only-positive patients since the rate of HBV-DNA positivity was found high in our study. Thus HBV-DNA screening should be performed in 'anti-HBc only' patient groups. | 18,822,901 |
[Effect of sodium ferulate on hemodynamics in hepatic cirrhosis patients with portal hypertension]. | To observe the effect of sodium ferulate on the hemodynamics of hepatic cirrhosis patients. Eighty-two hepatic cirrhosis patients were randomly assigned to two groups, the 27 patients in the control group were treated by conventional liver protecting therapy, and the 55 patients in the treated group were treated with sodium ferulate besides the conventional therapy. The therapeutic course for both groups was two weeks. The following indexes were measured before treatment and two weeks after treatment respectively: inner diameter of portal vein (PV), inner diameter of splenic vein (SPV), maximum portal vein flow rate (PVX), maximum splenic vein flow rate (SPVX), portal vein blood flow (QPV) and endothelin-1 (ET-1) concentration. The adverse effect was observed meanwhile. In the treated group after treatment, levels of PV, SPV and ET-1 decreased (P < 0.01), PVX and SPVX increased significantly (P < 0.01), but QPV was unchanged; while no significant change of all the indexes was found in the control group (P > 0.05). Further analysis showed that in the treated group, PV, SPV and ET-1 decreased significantly in patients of Child grade A and B (P <0. 01), but QPV changed insignificantly (P > 0.05, and all indexes were unchanged in patients of Child grade C (P > 0.05). Sodium ferulate can effectively lower the pressure of portal vein in hepatic cirrhosis patients without any influence on the blood flow of portal vein, the effect is more significant on patients of Child grade A and B. | 18,822,917 |
[Effect of retention enema with combination of compound glutamine entero-soluble capsule and glucocorticoids for treatment of ulcerative colitis]. | To observe the therapeutic effect and safety of retention enema with compound glutamine entero-soluble Capsule (CGC) on active ulcerative colitis (UC). One hundred and sixty-eight patients with active UC were randomly assigned to the treatment group (86 patients) and the control group (82 patients). Besides the basic treatment of oral taking salicylazosulfapyridine or mesalazine, they were treated by retention enema with predisolone plus metronidazole injection. In addition, the patients in the treatment group were treated by retention enima with GGC and orally took CGC, 0.8 g each time, thrice a day. The efficacy of treatment and the changes in the principal symptoms 2 months after treatment were evaluated. The total effective rate in the treatment group was 94.2% (81/86 cases), and that in the control group was 82.9% (68/82 cases), the difference between the two groups was significant (P <0. 05). The symptoms of hemafecia and abdominal pain were improved, the disease active index (DAI) was lowered after treatment in both groups (P <0.01), but the improvement of hemafecia, time of disappearance of mucous bloody stool and decrease of DAI in the treatment group were superior to those in the control group (P <0.05 or P <0.01). No adverse reaction was found in all patients. The retention enema with glucocorticoid plus metronidazole combined with CGC shows an immediate effect obviously superior to that treated with glucocorticoids and metronidazole alone, and with no adverse reaction. | 18,822,919 |
Peak expiratory flow rate of rural school children from Wardha district, Maharashtra in India. | Peak expiratory flow rate (PEFR) recording is an essential measure in the management and evaluation of asthmatic children. The PEFR can be measured by a simple instrument--peak expiratory flow meter. The aim of this study was to determine the normal PEFR in rural school children from Wardha district of Maharashtra state, India. The PEFR was measured in 1078 healthy rural school children, living in Wardha district, Maharashtra using the Mini-Wright peak flow meter. All measurements were obtained in a standing position and the best out of three trials was recorded. Anthropometric measurements, weight, height, and mid-upper-arm circumference (MAC) were recorded, and body surface area (BSA) and body mass index (BMI) were calculated. Positive correlation was seen between age, height, weight and PEFR. The regression equations for PEFR were determined for boys and girls separately. The boys had higher values than the girls at all heights. The prediction equation for PEFR based on height was PEFR = 3.64 height (cm) - 257.86 (R=0.47, R2=0.22) for female; PEFR = 4.7 height (cm) - 346.51 (R=0.62, R2 =0.38) for male. PEFR is a reliable measurement, which can be used routinely and regularly in rural areas for assessment of airway obstruction and prediction formula derived for use in this population. | 18,822,931 |
[Quality of life in multiple sclerosis: relation to the clinical parameters of the disease]. | Multiple sclerosis is a chronic progressive disease with multiple neurological and psychological impairments. The object of this study was to investigate the relation between quality of life of MS patients and main clinical parameters of the disease. The study included 100 patients diagnosed with multiple sclerosis who were treated at the Department of Neurology, Clinical Center University in Sarajevo. Quality of life was evaluated by using MSQOL-54 questionnaire. Internal consistency of Bosnian MSQOL-54 version was evaluated. Associations between disability level (EDSS score), clinical type, disease duration, presence of pain and sphincteral problems and the MSQOL-54 physical and mental health composite scores were determined. The MSQOL -54 questionnaire, translated to Bosnian, proved to be highly reliable (Cronbach alfa > 0.75 on all scales). All clinical determinants used in the sudy proved to be significantly related to the quality of life scores based on the Mann-Whitney test (p < 0.05). Method of linear regression analysis showed presence of pain and EDSS score as the most significant independent predictive factors of the physical health composite score (R2 = 0.827). The presence of pain and clinical type of disease, proved to be independent predictive factors of the mental health composite score with present, but less significant role of EDSS score (R2 = 0.598). The presence of pain retained the most significant role in the prediction of both physical and mental composite scores, which proved the importance of pain management in treatment of MS patients. Disability level (EDSS score) showed minor importance in predicting mental health composite scores which proved deficiency of clinical scales and emphasize the importance of the quality of life measures as independent criteria in the evaluation of multiple sclerosis patients. | 18,822,940 |
[Dihydroartemisinin down-regulates the expression of transferrin receptor in myeloid leukemia cells]. | This article reports the effect of dihydroartemisinin (DHA) on transferrin receptor (TfR) in myeloid leukemia cells by establishing the model of normal iron HL60 and K562 cells and iron overload K562 cells in vitro. The TfR content of myeloid leukemia cells was determined by flow cytometry, and the effect of DHA on iron content in K562 cells was determined by atomic absorption spectrophotometric analysis. Furthermore, the inhibitory effect of DHA on the anti-proliferation and expression of TfR protein and mRNA in myeloid leukemia cells was studied. As a result, DHA effectively decreased the TfR content and down-regulated TfR protein expression in normal iron HL60 and K562 cells in a dose- and time-dependent manner and inhibited the cell proliferation. The IC50 were 1.74 and 11.33 micromol x L(-1), respectively. DHA exerted more pronounced inhibitory action on expression of TfR protein and mRNA in iron overload K562 cells. Compared to normal iron K562 cells, the TfR protein and mRNA levels were lowered by 28.1% (P < 0.01) and 26. 2% (P < 0. 05) , respectively, after DHA treatment for 48 h in iron overload K562 cells. Moreover, DHA decreased the iron content of iron overload K562 cells and inhibited the proliferation of iron overload K562 cells more potently. DHA effectively down-regulated the TfR content as well as expression of TfR protein and mRNA in normal iron myeloid leukemia cells. DHA also inhibited the proliferation of HL60 and K562 cells. The anti-proliferation effect of DHA on iron overload K562 cells was more striking. | 18,822,958 |
[Synthesis and central none-opioid analgesic activity of SIPI5047]. | Compound SIPI5047 was synthesize by using piperazine as starting material in five reaction steps, and its central none-opioid analgesic activity was studied. Its analgesic activity, pharmacological mechanism, action type and drug dependence were well studied in vivo and in vitro. The results show that SIPI5047 has potent analgesic activities in vivo, which is quite similar to morphine and also much more powerful than paracetamol. SIPI5047 has no efficacy to reduce fever or inflammation, but has an obvious action on central nervous system. SIPI5057 has no apparent affinity with the mu-receptor and it is an antagonist that acts on the polyamine site of the NMDA receptor. SIPI5057 appears no drug dependence. SIPI5047 is a novel central none-opioid analgesic agent and more worthy of further research as a new drug candidate. | 18,822,964 |
[Advances of studies on acupuncture reinforcing-reducing of twirling-rotating the needle]. | The theories and clinical and experimental studies about reinforcing-reducing manipulation of twirling rotating the needle in recent 15 years are reviewed and a brief account of manipulation methods, mechanisms and effects of reinforcing-reducing manipulation of twirling-rotating the needle is given, and it is indicated that the following several aspects in the studies at present need to be completed. Standardization and establishment of national standard of acupuncture manipulation must be enforced; quantitative parameters of acupuncture manipulation and mechanisms of acupuncture reinforcing-reducing of twirling-rotating the needle need to be further studied. | 18,822,992 |
Sequenced Treatment Alternatives to Relieve Depression (STAR*D). Part 1: study design. | This article describes the design of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. The main study objective was to compare the efficacy and tolerability of various antidepressant therapies through four sequential treatment levels. To maximize the generalizability of the results, broad inclusion and minimal exclusion criteria were used to recruit patients with major depression from a large number of real-world settings. The goal of treatment was to achieve full remission. A measurement-based care system was used to guide and optimize treatment at each level. Patients were treated for up to 12 weeks at each level (with an optional week 14 visit, if needed). All patients started with citalopram at Level 1. The three subsequent levels of treatment options were randomized and open label, and patients could accept or decline treatments as long as sufficient options were left that allowed randomization between at least two different options. For any treatment level, patients who reached full remission, and those with satisfactory response, could continue the same treatment during 1-year naturalistic follow up. Patients who did not reach full remission were encouraged to enter subsequent levels. | 18,822,996 |
Risk of radiation-related salivary gland carcinomas among survivors of Hodgkin lymphoma: a population-based analysis. | Radiotherapy for Hodgkin lymphoma (HL) increases the risk of salivary gland carcinomas (SGC). To the authors' knowledge, however, the magnitude of the risk has not been assessed to date. The risks of SGC among 20,928 1-year survivors of HL who were diagnosed between 1973 and 2003 were evaluated in 11 population-based cancer registry areas of the Surveillance, Epidemiology, and End Results (SEER) program. Observed-to-expected ratios (O/E) were assessed by radiation treatment, sex, age at the time of HL diagnosis, calendar year of diagnosis, attained age, time since HL diagnosis, histologic type of SGC, and site of occurrence in the major salivary glands. Among 11,047 HL patients who received radiotherapy as part of their initial treatment for HL, 21 developed subsequent invasive SGC (O/E = 16.9; 95% confidence interval [95% CI], 10.4-25.8). The risk of radiation-related SGC was highest for younger HL patients (age <20 years) (O/E = 45.5; 95% CI, 12.4-116.5) and among 10-year survivors (O/E = 23.9; 95% CI, 13.1-40.1), with risks remaining elevated for at least 2 decades after irradiation. Significant differences in risk by histologic type were observed, with a particularly high risk of developing mucoepidermoid carcinomas (O = 14; O/E = 44.2 [95% CI, 24.2-74.2]) and adenocarcinomas (O = 4; O/E = 30.6 [95% CI, 8.3-78.2]) noted. HL patients treated with radiotherapy experienced a significantly increased risk of SGC, particularly when exposed at young ages or for at least 2 decades after exposure. Although the results of the current study reflect the late effects of former HL treatment approaches, they point to the importance of long-term follow-up and a heightened awareness of SGC risk in this population. | 18,823,043 |
Clinical and genetic characterization of a large Dutch family with primary focal dystonia. | We describe a large family with a primary focal dystonia from a small Dutch village on a former island. Twenty-four individuals spanning three generations were examined by two movement-disorder neurologists. Two other movement-disorder neurologists evaluated the videos independently. Subjects were classified as "affected," "possibly affected," or "not affected." A diagnosis was defined if all the neurologists agreed on the definition. Eight definitely affected and four possibly affected subjects were detected. Clinical presentation consisted of mild cranio-cervical-brachial dystonia. Mean age at onset was 45.5 years (range, 39-56). Mean BFMDRS motor score was 4.4 (range, 1-8). Mean TWSTRS score (part I) was 11.3 (range, 8-23). Mutations in DYT1 gene and in the epsilon-sarcoglycan (SGCE) genes were not detected. We could not find linkage to the dominant DYT6, DYT7, DYT13, or the recessive DYT16 loci. The identification and accurate clinical evaluation of large dystonia families not linked to known genes is crucial for further advancement in molecular genetic characterization of focal dystonia. | 18,823,044 |
Monitoring intracellular labile iron pools: A novel fluorescent iron(III) sensor as a potential non-invasive diagnosis tool. | The physiological and pathophysiological importance of intracellular redox active "labile" iron has created a significant need for improved noninvasive diagnostic tools to reliably monitor iron metabolism in living cells. In this context, fluorescent iron-sensitive chemosensors in combination with digital fluorescence spectroscopic methods have proven to be highly sensitive and indispensable tools to determine cellular iron homeostasis. Recently, application of fluorescent iron sensors has led to the identification of a complex sub-cellular iron compartmentation. Cell organelle-specific iron sensors will significantly contribute to enhance fundamental knowledge of cellular iron trafficking, representing a crucial prerequisite for the future development of therapeutic strategies in iron dysregulatory diseases. Here we present physicochemical characterization and functional investigation of a new 3-hydroxypyridin-4-one based fluorescent iron(III) sensor, exclusively monitoring labile iron pools in the endosomal/lysosomal compartments. In vitro studies of the fluorescein labeled probe were carried out in murine bone marrow derived macrophages. Endosomal/lysosomal accumulation of the probe was revealed by confocal microscopy. Flow cytometry analyses demonstrated high sensitivity of the probe towards exogenous alterations of intracellular iron concentrations as well as in response to the chelation potency of iron chelators, clinically approved for treatment of iron-overload related diseases. | 18,823,046 |
Brief exposure of Blattella germanica (Blattodea) to insecticides formulated in various microcapsule sizes and applied on porous and non-porous surfaces. | The authors explored how microcapsule size and brief exposure affected the bioavailability of five microencapsulated insecticide formulations, chlorpyrifos 23.1 g L(-1) CS (Detmol-PRO), chlorpyrifos 20 g L(-1) CS (Empire 20), fenitrothion 20 g L(-1) CS (Detmol-Mic), cyphenothrin 10 g L(-1) CS (Detmol-CAP) and diazinon 30 g L(-1) CS (Diacap), to Blattella germanica L. on porous and non-porous surfaces. The hypothesis was tested that microencapsulated (CS) insecticides comprising larger microcapsules show higher efficacy on porous surfaces than formulations with smaller microcapsules. Brief exposure was accomplished by allowing B. germanica to cross a 0.3 m insecticide barrier in 30 s (1.01 cm s(-1)). Such short exposure did not lead to 100% mortality in any formulation or surface tested. Significant differences in bioavailability on the porous and the non-porous surfaces were found: the largest difference was observed in Empire 20 and Detmol CAP, while bioavailability of Detmol MIC did not differ on porous and non-porous surfaces. Comparison of their microcapsule size spectra revealed that formulations containing larger microcapsules had higher efficacy on porous surfaces than formulations with smaller microcapsules. In order to explain the difference in efficacy, the variance of microcapsule sizes was regressed on the efficacy ratio on porous versus non-porous surfaces. Although negative correlation was evident between size of capsules and the efficacy ratio on porous and non-porous surfaces, the difference in the slope parameter was not statistically significant. Brief contact of B. germanica with insecticide spray residues, which is common in barrier treatment, may lead to low efficacy, especially on porous surfaces. The latter should be preferably treated with CS insecticides containing a fraction with large capsules. In addition to the size of the microcapsules, the role of other factors, such as wall capsule thickness and chemical composition, on CS insecticide activity on various surfaces should be examined in future work. | 18,823,064 |
Correlation between the molecular structure and photoresponse in aliphatic self-assembled monolayers with azobenzene tailgroups. | We have compared the structural and photoisomerization properties of self-assembled monolayers (SAMs) comprising either the trans or cis isomers of azobenzene terminated dithiolane with in-chain amide unit, viz., 4-(phenyldiazenyl)phenyl-4-(1,2-dithiolane-3-yl)-butylcarboxamide ( 1). These films were prepared on Au(111) from solutions of both isomers. Structure and composition of the SAMs were studied by X-ray photoelectron spectroscopy and near-edge X-ray absorption fine structure spectroscopy. The photoresponse of the films was monitored in real time by ellipsometry. SAMs fabricated from the trans isomer were found to be densely packed and highly ordered. These films did not show any discernible photoresponse upon irradiation with UV light, which, under favorable conditions, triggers the trans- cis isomerization. In contrast, films prepared from solutions containing predominantly the cis isomer were loosely packed and mostly disordered but exhibited reversible photoreactivity. The results confirm that steric effects, i.e., available free volume, play a dominant role for the photoresponse of aliphatic SAMs bearing the photoactive azobenzene group. The crystal structure of 1 ( trans isomer) exhibits a row-like aggregation of neighboring molecules by weak hydrogen bonds and can be taken as a model for the arrangement of 1 in the monolayer films. Further, in addition to the surface coordination behavior, we have also mimicked the chemisorption of the 1,2-dithiolane moiety onto the gold substrate in molecular coordination chemistry in oxidative addition reactions with the zero-valent platinum complex [Pt(PPh 3) 4]. | 18,823,085 |
Confinement of DNA in water-in-oil microemulsions. | The study of systems that allow DNA condensation in confined environments is an important task in producing cell-mimicking microreactors capable of biochemical activities. The water droplets formed in water-in-oil emulsions are potentially good candidates for such microcompartments. The anionic surfactant AOT was used here to stabilize the droplets. We have studied in detail the DNA distribution and the structural modifications of these microemulsion drops by varying the concentration and molecular weight of DNA and using various techniques such as light, X-ray, and neutron scattering, electrical conductivity, and surface tension. DNA induces the formation of large drops into which it is internalized. The size of these drops depends on the amount of DNA dissolved in water as well as on its molecular weight. The local DNA concentration is very high (>100 mg/mL). The large drops coexist with small empty drops (not containing DNA), similar to those found in the DNA-free microemulsion. | 18,823,088 |
Hippocampal response patterns during discriminative eyeblink/jaw movement conditioning in the rabbit. | Rabbits were given concurrent training in eyeblink (EB) and jaw movement (JM) conditioning in which 1 tone predicted an airpuff and another tone predicted water. After 10 days of discrimination training, the animals were given 10 days of reversal training. In the discrimination phase, acquisition of the 2 conditioned responses was not significantly different; however JM discrimination errors were much more frequent than were EB errors. In the reversal phase, correct performance on EB trials increased gradually, as was expected, whereas there was immediate behavioral reversal on JM trials. Differences in size and topography of dorsal CA1 multiple-unit responses reflected the ability of the hippocampus to discriminate between stimuli in trained animals, corresponding to the performance of the behavioral discrimination. During JM trials, the rhythmicity of the neural response was further modulated by the type of the prior trial, suggesting the coding of sequential events by the hippocampus. Thus, hippocampal conditioned activity can rapidly change its magnitude and pattern depending on the specific trial type during a concurrent EB/JM discrimination task and its reversal. (PsycINFO Database Record (c) 2008 APA, all rights reserved). | 18,823,166 |
Neural dynamics underlying impaired autonomic and conditioned responses following amygdala and orbitofrontal lesions. | A neural model is presented that explains how outcome-specific learning modulates affect, decision-making, and Pavlovian conditioned approach responses. The model addresses how brain regions responsible for affective learning and habit learning interact and answers a central question: What are the relative contributions of the amygdala and orbitofrontal cortex to emotion and behavior? In the model, the amygdala calculates outcome value while the orbitofrontal cortex influences attention and conditioned responding by assigning value information to stimuli. Model simulations replicate autonomic, electrophysiological, and behavioral data associated with three tasks commonly used to assay these phenomena: Food consumption, Pavlovian conditioning, and visual discrimination. Interactions of the basal ganglia and amygdala with sensory and orbitofrontal cortices enable the model to replicate the complex pattern of spared and impaired behavioral and emotional capacities seen following lesions of the amygdala and orbitofrontal cortex. | 18,823,167 |
Nicotine enhances context learning but not context-shock associative learning. | Nicotine has been found to enhance learning in a variety of tasks, including contextual fear conditioning. During contextual fear conditioning animals have to learn the context and associate the context with an unconditioned stimulus (footshock). As both of these types of learning co-occur during fear conditioning, it is not clear whether nicotine enhances one or both of these types of learning. To tease these two forms of learning apart, the authors made use of the context preexposure facilitation effect (CPFE). Acquisition of the CPFE requires that contextual and context-shock learning occurs on separate days, allowing for their individual manipulation. Nicotine (0.09 mg/kg) administered prior to contextual learning and retrieval enhanced the CPFE whereas administration prior to context-shock learning and retrieval had no effect. Thus, nicotine enhances contextual learning but not context-shock associative learning. Finally, the results are discussed in terms of a theory of how nicotine could alter hippocampal-cortical-amygdala interactions to facilitate contextual learning. | 18,823,171 |
What does it take to demonstrate memory erasure? Theoretical comment on Norrholm et al. (2008). | An issue of increasing interest in Pavlovian conditioning is to identify ways to facilitate the development and persistence of extinction. Both behavioral and molecular lines of evidence demonstrate that learning during extinction can be enhanced. Similar evidence has been offered to support the idea that extinction causes the original association to be unlearned, or erased. Differentiating between extinction and erasure accounts is extremely difficult and requires many assumptions about the fundamental nature of how memory storage maps into memory expression. In this issue of Behavioral Neuroscience, Norrholm et al. (see record 2008-13280-002) describe a study of extinction with humans that has the potential to serve as a translational bridge between rodent work and clinical applications. They find less recovery of a conditioned fear response when extinction occurs 10 min compared with 72 hr after conditioning; however, the recovery of subjects' expectancies of the fearful stimulus is independent of when extinction occurred. These findings and others discussed in this article demonstrate some of the challenges in making inferences about memory erasure during extinction. | 18,823,175 |
Object substitution masking: when does mask preview work? | When a target is enclosed by a 4-dot mask that persists after the target disappears, target identification is worse than it is when the mask terminates with the target. This masking effect is attributed to object substitution masking (OSM). Previewing the mask, however, attenuates OSM. This study investigated specific conditions under which mask preview was, or was not, effective in attenuating masking. In Experiment 1, the interstimulus interval (ISI) between previewed mask offset and target presentation was manipulated. The basic preview effect was replicated; neither ISI nor preview duration influenced target identification performance. In Experiment 2, mask configurations were manipulated. When the mask configuration at preview matched that at target presentation, the preview effect was replicated. New evidence of ineffective mask preview was found: When the two configurations did not match, performance declined. Yet, when the ISI between previewed mask offset and target presentation was removed such that the mask underwent apparent motion, preview was effective despite the configuration mismatch. An interpretation based on object representations provides an excellent account of these data. | 18,823,198 |
Active gaze, visual look-ahead, and locomotor control. | The authors examined observers steering through a series of obstacles to determine the role of active gaze in shaping locomotor trajectories. Participants sat on a bicycle trainer integrated with a large field-of-view simulator and steered through a series of slalom gates. Steering behavior was determined by examining the passing distance through gates and the smoothness of trajectory. Gaze monitoring revealed which slalom targets were fixated and for how long. Participants tended to track the most immediate gate until it was about 1.5 s away, at which point gaze switched to the next slalom gate. To probe this gaze pattern, the authors then introduced a number of experimental conditions that placed spatial or temporal constraints on where participants could look and when. These manipulations resulted in systematic steering errors when observers were forced to use unnatural looking patterns, but errors were reduced when peripheral monitoring of obstacles was allowed. A steering model based on active gaze sampling is proposed, informed by the experimental conditions and consistent with observations in free-gaze experiments and with recommendations from real-world high-speed steering. | 18,823,202 |
Impairments in the perception of odor-induced tastes and their relationship to impairments in taste perception. | Certain odors have tastelike qualities when sniffed. To the extent that these qualities are akin to real taste experiences, impairment in perception of odor-induced tastes should be accompanied by taste impairment, and vice versa. Twelve patients were selected with possible odor-induced taste impairments or general taste impairments via a screening test, along with a further 6 patients with a probable taste impairment (insular lesion). These 18 patients, along with 19 normal controls, completed a battery of odor, taste, visual control, and neuropsychological tests to assess impairments in odor-induced taste perception and general taste perception. Four patients had an odor-induced taste impairment and were also impaired on taste perception. A further analysis, using regression on the whole sample, indicated that taste impairments were associated with odor-induced taste abnormalities independent of other predictors. This pattern also held for the patient group alone. The insular patients also exhibited both taste and odor-induced taste impairments. This study is the first to demonstrate a relationship between impaired taste perception and the perception of odor-induced tastes and suggests that both may rely on certain common neural substrates. | 18,823,204 |
Combination antiplatelet agents for secondary prevention of ischemic stroke. | Stroke is a leading cause of death and the primary cause of serious, long-term disability in the United States. Joint guidelines from the American Heart Association (AHA) and American Stroke Association (ASA), as well as recent guidelines from the Eighth American College of Chest Physicians (ACCP) Conference on Antithrombotic and Antiplatelet Therapy, recommend aspirin, clopidogrel, or extended-release dipyridamole plus aspirin as acceptable first-line options for secondary prevention of ischemic events in patients with a history of ischemic stroke or transient ischemic attack (TIA). The ACCP strongly recommends the combination of extended-release dipyridamole plus aspirin over aspirin monotherapy (highest level of evidence) and suggests clopidogrel monotherapy over aspirin monotherapy (lower level of evidence). The AHA-ASA guidelines suggest that either extended-release dipyridamole plus aspirin or clopidogrel monotherapy should be used over aspirin monotherapy. Both guidelines recommend avoiding the combination of clopidogrel and aspirin for most patients with previous stroke or TIA. Results from recent trials evaluating combination antiplatelet therapy have been published that enhance the AHA-ASA recommendations and provide the foundation for the updated ACCP guideline. To identify pertinent combination antiplatelet trials, a MEDLINE search of the literature from 1967-2007 was performed. Two trials were identified--the European-Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) and Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA). The ESPRIT compared aspirin monotherapy with the combination of aspirin plus extended-release dipyridamole for prevention of secondary ischemic events in patients with a history of TIA or minor stroke. The CHARISMA trial compared aspirin plus clopidogrel with aspirin alone in a population at high risk for atherothrombotic events using the composite outcome of myocardial infarction, stroke, and death from cardiovascular causes. Data from ESPRIT add to evidence that the combination of aspirin plus extended-release dipyridamole is superior to aspirin alone. The findings of the CHARISMA trial reinforce recommendations from both AHA-ASA and ACCP that the combination of aspirin and clopidogrel be reserved for special populations requiring this antiplatelet combination (e.g., those who have had coronary artery stenting). | 18,823,219 |
Conceptual processing in music as revealed by N400 effects on words and musical targets. | The cognitive processing of concepts, that is, abstract general ideas, has been mostly studied with language. However, other domains, such as music, can also convey concepts. Koelsch et al. [Koelsch, S., Kasper, E., Sammler, D., Schulze, K., Gunter, T., & Friederici, A. D. Music, language and meaning: Brain signatures of semantic processing. Nature Neuroscience, 7, 302-307, 2004] showed that 10 sec of music can influence the semantic processing of words. However, the length of the musical excerpts did not allow the authors to study the effect of words on musical targets. In this study, we decided to replicate Koelsch et al. findings using 1-sec musical excerpts (Experiment 1). This allowed us to study the reverse influence, namely, of a linguistic context on conceptual processing of musical excerpts (Experiment 2). In both experiments, we recorded behavioral and electrophysiological responses while participants were presented 50 related and 50 unrelated pairs (context/target). Experiments 1 and 2 showed a larger N400 component of the event-related brain potentials to targets following a conceptually unrelated compared to a related context. The presence of an N400 effect with musical targets suggests that music may convey concepts. The relevance of these results for the comprehension of music as a structured set of conceptual units and for the domain specificity of the mechanisms underlying N400 effects are discussed. | 18,823,240 |
Neural correlates of stimulus reportability. | Most experiments on the "neural correlates of consciousness" employ stimulus reportability as an operational definition of what is consciously perceived. The interpretation of such experiments therefore depends critically on understanding the neural basis of stimulus reportability. Using a high volume of fMRI data, we investigated the neural correlates of stimulus reportability using a partial report object detection paradigm. Subjects were presented with a random array of circularly arranged disc-stimuli and were cued, after variable delays (following stimulus offset), to report the presence or absence of a disc at the cued location, using variable motor actions. By uncoupling stimulus processing, decision, and motor response, we were able to use signal detection theory to deconstruct the neural basis of stimulus reportability. We show that retinotopically specific responses in the early visual cortex correlate with stimulus processing but not decision or report; a network of parietal/temporal regions correlates with decisions but not stimulus presence, whereas classical motor regions correlate with report. These findings provide a basic framework for understanding the neural basis of stimulus reportability without the theoretical burden of presupposing a relationship between reportability and consciousness. | 18,823,251 |
Transgene expression of green fluorescent protein and germ line transmission in cloned pigs derived from in vitro transfected adult fibroblasts. | The pig represents the xenogeneic donor of choice for future organ transplantation in humans for anatomical and physiological reasons. However, to bypass several immunological barriers, strong and stable human genes expression must occur in the pig's organs. In this study we created transgenic pigs using in vitro transfection of cultured cells combined with somatic cell nuclear transfer (SCNT) to evaluate the ubiquitous transgene expression driven by pCAGGS vector in presence of different selectors. pCAGGS confirmed to be a very effective vector for ubiquitous transgene expression, irrespective of the selector that was used. Green fluorescent protein (GFP) expression observed in transfected fibroblasts was also maintained after nuclear transfer, through pre- and postimplantation development, at birth and during adulthood. Germ line transmission without silencing of the transgene was demonstrated. The ubiquitous expression of GFP was clearly confirmed in several tissues including endothelial cells, thus making it a suitable vector for the expression of multiple genes relevant to xenotransplantation where tissue specificity is not required. Finally cotransfection of green and red fluorescence protein transgenes was performed in fibroblasts and after nuclear transfer blastocysts expressing both fluorescent proteins were obtained. | 18,823,265 |
Glucose induces an autocrine activation of the Wnt/beta-catenin pathway in macrophage cell lines. | The canonical Wnt signalling pathway acts by slowing the rate of ubiquitin-mediated beta-catenin degradation. This results in the accumulation and subsequent nuclear translocation of beta-catenin, which induces the expression of a number of genes involved in growth, differentiation and metabolism. The mechanisms regulating the Wnt signalling pathway in the physiological context is still not fully understood. In the present study we provide evidence that changes in glucose levels within the physiological range can acutely regulate the levels of beta-catenin in two macrophage cell lines (J774.2 and RAW264.7 cells). In particular we find that glucose induces these effects by promoting an autocrine activation of Wnt signalling that is mediated by the hexosamine pathway and changes in N-linked glycosylation of proteins. These studies reveal that the Wnt/beta-catenin system is a glucose-responsive signalling system and as such is likely to play a role in pathways involved in sensing changes in metabolic status. | 18,823,284 |
Effect of a kappa-opioid agonist, i.v. JNJ-38488502, on sensation of colonic distensions in healthy male volunteers. | Kappa-opioid receptors are located on visceral pain fibres. JNJ-38488502 is a highly selective tetrapeptide kappa-opioid agonist with little access to the central nervous system and low risk of central nervous system side effects. The aim of the study was to evaluate the effects of i.v. JNJ-38488502 on sensations, including pain, during colonic distension. In a single-centre study, 23 healthy adult males underwent a single-dose, randomized, double-blind crossover study of JNJ-38488502 (0.42 mg kg(-1) i.v. infusion) vs placebo on left colon compliance, sensory thresholds and ratings during standard distensions. One participant could not undergo sensation studies. In the other 22, JNJ-38488502 increased colonic compliance (pressure at half-maximum volume 17.9 +/- 0.8 mmHg) compared to placebo (21.6 +/- 0.9 mmHg, P = 0.007). There was no significant effect on sensory thresholds which, however, were not reached by 44 mmHg in >50% of participants in both treatment phases. There were no significant treatment effects on sensory ratings to distensions at 8, 16, 24, 32 and 36 mmHg above baseline operating pressure. JNJ-38488502 was associated with increased urine output and plasma prolactin, consistent with kappa-opioid receptor activation. This study concluded that i.v. JNJ-38488502 induced kappa-opioid effects, but did not attenuate colonic sensations following random order colonic distension. Further studies of effects on pain sensations in health and disease are required. | 18,823,290 |
Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia. | To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites. Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m(-2) day(-1)). All patients were genotyped for polymorphisms in three enzymes involved in 6-MP metabolism. Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites. The developed model revealed considerable interindividual variability (IIV) in the clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-mMPNs)]. Body surface area explained a significant part of 6-TGNs clearance IIV when incorporated in the model (IIV reduced from 69.9 to 29.3%). The most influential covariate examined, however, was thiopurine methyltransferase (TPMT) genotype, which resulted in the greatest reduction in the model's objective function (P < 0.005) when incorporated as a covariate affecting the fractional metabolic transformation of 6-MP into 6-TGNs. The other genetic covariates tested were not statistically significant and therefore were not included in the final model. The developed pharmacokinetic model (if successful at external validation) would offer a more rational dosing approach for 6-MP than the traditional empirical method since it combines the current practice of using body surface area in 6-MP dosing with a pharmacogenetically guided dosing based on TPMT genotype. | 18,823,306 |
The PDE5 inhibitor sildenafil increases circulating endothelial progenitor cells and CXCR4 expression. | Endothelial progenitor cells (EPC) are a specific subtype of progenitor cells that can be isolated from circulating mononuclear cells, able to migrate from the bone marrow to the peripheral circulation where they contribute to vascular repair. CXC-motif chemochine receptor 4 (CXCR4) receptor seems to play a critical role in this process. To assess the effects of sildenafil (a type 5 phosphodiesterase [PDE5] inhibitor) administration in 20 healthy young men. Evaluation of CXCR4 expression in circulating EPC before and 4 hours after in vivo administration of 100 mg sildenafil by flow cytometry and colony-forming unit. We found that sildenafil increases circulating EPC number, the relative expression of CXCR4 on these cells and the ability to generate colonies in vitro. These data allow us to suppose an involvement of PDE5 in bone marrow release and peripheral homing of EPC. | 18,823,318 |
Activation of the ET-1/ETA pathway contributes to erectile dysfunction associated with mineralocorticoid hypertension. | The cavernosal tissue is highly responsive to endothelin-1 (ET-1), and penile smooth muscle cells not only respond to but also synthesize ET-1. Considering that ET-1 is directly involved in end-organ damage in salt-sensitive forms of hypertension, we hypothesized that activation of the ET-1/ET(A) receptor pathway contributes to erectile dysfunction (ED) associated with mineralocorticoid hypertension. Wistar rats were uninephrectomized and submitted to deoxycorticosterone acetate (DOCA)-salt treatment for 5 weeks. Control (Uni [uninephrectomized control]) animals were uninephrectomized and given tap water. Uni and DOCA-salt rats were simultaneously treated with vehicle or atrasentan (ET(A) receptor antagonist, 5 mg/Kg/day). Cavernosal reactivity to ET-1, phenylephrine (PE), ET(B) receptor agonist (IRL-1620) and electric field stimulation (EFS) were evaluated in vitro. Expression of ROCKalpha, ROCKbeta, myosin phosphatase target subunit 1 (MYPT-1), and extracellular signal-regulated kinase 1/2 (ERK 1/2) were evaluated by western blot analysis. ET-1 and ET(A) receptor mRNA expression was evaluated by real-time reverse-transcriptase polymerase chain reaction. Voltage-dependent increase in intracavernosal pressure/mean arterial pressure (ICP/MAP) was used to evaluate erectile function in vivo. ET(A) receptor blockade prevents DOCA-salt-associated ED. Cavernosal strips from DOCA-salt rats displayed augmented preproET-1 expression, increased contractile responses to ET-1 and decreased relaxation to IRL-1620. Contractile responses induced by EFS and PE were enhanced in cavernosal tissues from DOCA-salt hypertensive rats. These functional changes were associated with increased activation of the RhoA/Rho-kinase and ERK 1/2 pathways. Treatment of rats with atrasentan completely prevented changes in cavernosal reactivity in DOCA-salt rats and restored the decreased ICP/MAP, completely preventing ED in DOCA-salt rats. Activation of the ET-1/ET(A) pathway contributes to mineralocorticoid hypertension-associated ED. ET(A) receptor blockade may represent an alternative therapeutic approach for ED associated with salt-sensitive hypertension and in pathological conditions where increased levels of ET-1 are present. | 18,823,320 |
Escherichia coli tRNase Z can shut down growth probably by removing amino acids from aminoacyl-tRNAs. | In most organisms, tRNase Z is considered to be essential for 3' processing of tRNA molecules. The Escherichia coli tRNase Z gene, however, appears to be dispensable under normal growth conditions, and its existence remained an enigma. Here we intensively examined various (pre-)tRNAs for good substrates of E. coli tRNase Z in vitro, and found that the enzyme can remove the 3' terminal CCA residues from mature tRNAs regardless of their nucleotide modifications. Furthermore, we discovered that E. coli tRNase Z, when sufficiently expressed in the cell, can shut down growth probably by removing amino acids from aminoacyl-tRNAs. We confirmed in vitro that E. coli tRNase Z exceptionally possesses the activity that cleaves off the 3' terminal residues charging an amino acid from an aminoacyl-tRNA molecule. The current data suggest that tRNase Z might help modulate a cell growth rate by repressing translation under some stressful conditions. | 18,823,332 |
Indoor air disinfection using a polyester supported TiO2 photo-reactor. | Among the decontamination methods applicable to indoor air, heterogeneous photocatalysis has received increasing attention in recent years. This decontamination method is based on the UV irradiation of a solid catalyst, normally TiO2, aiming at the generation of highly reactive hydroxyl radicals. In this work, a novel way to prepare the photocatalyst was used, incorporating pure P-25 TiO2 (Degussa) into polyester orthophthalic polymer. The film was coated onto the walls of a PVC reactor with a concentric 30 W germicidal lamp (254 nm). The efficiency of this prototype was evaluated against fungi and bacteria elimination in a 67 m3 confined room. The system was very efficient for bacteria reduction, decreasing the bacterial count to below the detection limit (1 CFU/plate during 30-min sampling) after 2 h of operation at 195 l/min. For fungi, the gas-phase reactor showed to be less efficient and silver doping of the catalyst showed no increase in biocide activity. The use of a photocatalytic reactor based on TiO2 incorporated onto polyester orthophtalic polymer has been tested at 195 l/min, showing good performance in the air disinfection of a 67 m3 room. | 18,823,342 |
Mannose-binding lectin gene polymorphisms in relation to periodontitis. | To investigate the correlation of six functional polymorphisms in the MBL gene with MBL plasma levels in relation to periodontitis. A total of 92 periodontitis patients and 70 controls, all of Caucasian origin, were included. Patients and controls were genotyped for the L/H, X/Y, P/Q, A/D, A/B and A/C polymorphisms. Distributions of genotypes, rate of allele carriage and allele frequencies were compared between patients and controls. Patients and controls were subdivided in groups of genotypes. Plasma MBL levels were compared between different genotype groups. On the basis of genotyping, three phenotypes with regard to mannose-binding lectin (MBL) production were distinguished: high-producers, low-producers and deficient subjects. No differences in the genotype frequencies were observed between patients and controls. Within patients and controls, subjects with the high-producing genotypes had significantly higher MBL plasma levels than low-producers and deficient subjects (p<0.001). Plasma MBL was higher in low-producer patients compared with low-producer controls (p(adjusted)=0.021). No association could be observed between MBL gene polymorphisms and susceptibility to periodontitis in Caucasians. However, now that genotyping could distinguish the low producing and deficient subjects from the high-producers, it was observed, for the first time, that MBL acts as a weak acute-phase protein in periodontitis. | 18,823,346 |
Gender differences in the association of overweight and asthma morbidity among urban adolescents with asthma. | Asthma and obesity disproportionately affect US African-American youth. Among youth with asthma, obesity has been associated with poor control. The impact of gender on this association is unclear. We examined these relationships in a sample of urban, African-American adolescents with asthma. Questionnaires were used to identify high school students with asthma, and to examine the association of body mass index (BMI) to asthma morbidity, by gender. Of 5967 students completing questionnaires, 599 (10%) met criteria for asthma and 507 had data sufficient for inclusion in further analyses (46% male, mean age = 15.1 yr). Univariately, BMI > 85th percentile was significantly related only to reported emergency department visits (ED) and school days missed for any reason, Odds Ratio (95%Confidence Interval) = 1.7(1.1-2.7), p = 0.01 and 1.8(1.1-3.0), p = 0.01, respectively. A significant gender-BMI interaction (p < 0.05) was observed in multivariate models for ED visits, hospitalizations and school days missed for asthma. In gender-specific models, adjusted Risk Ratios for BMI > 85th and ED visits, hospitalizations, and school days missed because of asthma were 1.7(0.9-3.2), 6.6(3.1-14.6) and 3.6(1.8-7.2) in males. These associations were not observed in females. Gender modifies the association between BMI and asthma-related morbidity among adolescents with asthma. Results have implications for clinical management as well as future research. | 18,823,359 |
Persistent MDMA-induced dopaminergic neurotoxicity in the striatum and substantia nigra of mice. | Acute administration of repeated doses of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) dramatically reduces striatal dopamine (DA) content, tyrosine hydroxylase (TH), and DA transporter-immunoreactivity in mice. In this study, we show for the first time the spatiotemporal pattern of dopaminergic damage and related molecular events produced by MDMA administration in mice. Our results include the novel finding that MDMA produces a significant decrease in the number of TH-immunoreactive neurons in the substantia nigra (SN). This decrease appears 1 day after injection, remains stable for at least 30 days, and is accompanied by a dose-dependent long-lasting decrease in TH- and DA transporter-immunoreactivity in the striatum, which peaked 1 day after treatment and persisted for at least 30 days, however, some recovery was evident from day 3 onwards, evidencing sprouting of TH fibers. No change is observed in the NAc indicating that MDMA causes selective destruction of DA-containing neurons in the nigrostriatal pathway, sparing the mesolimbic pathway. The expression of Mac-1 increased 1 day after MDMA treatment and glial fibrillary acidic protein increased 3 days post-treatment in the striatum and SN but not in the NAc, in strict anatomical correlation with dopaminergic damage. These data provide the first evidence that MDMA causes persistent loss of dopaminergic cell bodies in the SN. | 18,823,368 |
Dopaminergic system dysregulation in the mrsk2_KO mouse, an animal model of the Coffin-Lowry syndrome. | The Coffin-Lowry syndrome, a rare syndromic form of X-linked mental retardation, is caused by loss-of-function mutations in the hRSK2 (RPS6KA3) gene. To further investigate RSK2 (90-kDa ribosomal S6 kinase) implication in cognitive processes, a mrsk2_KO mouse has previously been generated as an animal model of Coffin-Lowry syndrome. The aim of the present study was to identify possible neurochemical dysregulation associated with the behavioral and morphological abnormalities exhibited by mrsk2_KO mice. A cortical dopamine level increase was found in mrsk2_KO mice that was accompanied by an over-expression of dopamine receptor of type 2 and the dopamine transporter. We also detected an increase of total and phosphorylated extracellular regulated kinase that may be responsible for the increased level of tyrosine hydroxylase phosphorylation also observed. By taking into consideration previously reported data, our results strongly suggest that the dopaminergic dysregulation in mrsk2_KO mice may be caused, at least in part, by tyrosine hydroxylase hyperactivity. This cortical hyperdopaminergia may explain some non-cognitive but also cognitive alterations exhibited by mrsk2_KO mice. | 18,823,370 |
Enhancement of apoptotic damage of squamous cell carcinoma cells by inhibition of the mitochondrial DNA repairing system. | Mitochondrial DNA (mtDNA) repair systems are thought to be associated with the susceptibility of cancer cells to anticancer agents. The present study investigated the relationship between the susceptibility to gamma-rays and the mtDNA repair ability of oral squamous cell carcinoma (OSC) cell lines. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and mtDNA common deletion in both nuclear and mitochondrial DNA of OSC-2, OSC-3 and OSC-6 cells (radio-sensitive cell lines) after gamma-ray-irradiation were higher than those of OSC-1, OSC-4 and OSC-5 cells (radio-resistant cell lines). Compared with OSC-2, OSC-3 and OSC-6 cells, OSC-1, OSC-4 and OSC-5 cells had higher levels of activity of phosphoinositide-3 kinase (PI-3K)/Akt and more strongly expressed 8-hydroxyguanine DNA glycosylase (OGG1), DNA polymerase gamma (POLG) and mitochondrial transcription factor A (Tfam). Down-regulation of these mtDNA-repair-associated molecules by the RNA interference technique enhanced the susceptibility of OSC-2 and OSC-5 cells to gamma-rays, and the expression of Tfam and POLG was down-regulated by inhibitors of PI-3K/Akt signaling. These results indicate that the inhibition of mtDNA repair capacity by PI-3K/Akt signal inhibitors and OGG1 down-regulator in cancer cells may be a useful strategy for cancer treatment when combined with ionizing irradiation and chemotherapeutic drugs. | 18,823,381 |
Leishmania donovani depletes labile iron pool to exploit iron uptake capacity of macrophage for its intracellular growth. | Intracellular pathogens employ several strategies for iron acquisition from host macrophages for survival and growth, whereas macrophage resists infection by actively sequestering iron. Here, we show that instead of allowing macrophage to sequester iron, protozoan parasite Leishmania donovani (LD) uses a novel strategy to manipulate iron uptake mechanisms of the host and utilizes the taken up iron for its intracellular growth. To do so, intracellular LD directly scavenges iron from labile iron pool of macrophages. Depleted labile iron pool activates iron sensors iron-regulatory proteins IRP1 and IRP2. IRPs then bind to iron-responsive elements present in the 3' UTR of iron uptake gene transferrin receptor 1 by a post-transcriptional mRNA stability mechanism. Increased iron-responsive element-IRP interaction and transferrin receptor 1 expressions in spleen-derived macrophages from LD-infected mice confirm that LD employs similar mechanism to acquire iron during infection into mammalian hosts. Increased intracellular LD growth by holo-transferrin supplementation and inhibited growth by iron chelator treatment confirm the significance of this modulated iron uptake pathway of host in favour of the parasite. | 18,823,384 |
The classification and diagnosis of erythrocytosis. | An absolute erythrocytosis is present when the red cell mass is raised and the haematocrit is elevated above prescribed limits. Causes of an absolute erythrocytosis can be primary where there is an intrinsic problem in the bone marrow and secondary where there an event outside the bone marrow driving erythropoiesis. This can further be divided into congenital and acquired causes. There remain an unexplained group idiopathic erythrocytosis. Investigation commencing with thorough history taking and examination and then investigation depending on initial features is required. Clear simple criteria for polycythaemia vera are now defined. Those who do not fulfil these criteria require further investigation depending on the clinical scenario and initial results. The erythropoietin level provides some guidance as to the direction in which to proceed and the order and extent of investigation necessary in an individual patient. It should thus be possible to make an accurate diagnosis in the majority of patients. | 18,823,397 |
Introduction to hydromechanical well tests in fractured rock aquifers. | This article introduces hydromechanical well tests as a viable field method for characterizing fractured rock aquifers. These tests involve measuring and analyzing small displacements along with pressure transients. Recent developments in equipment and analyses have simplified hydromechanical well tests, and this article describes initial field results and interpretations during slug and constant-rate pumping tests conducted at a site underlain by fractured biotite gneiss in South Carolina. The field data are characterized by displacements of 0.3 microm to more than 10 microm during head changes up to 10 m. Displacements are a hysteretic function of hydraulic head in the wellbore, with displacements late in a well test always exceeding those at similar wellbore pressures early in the test. Displacement measurements show that hydraulic aperture changes during well tests, and both scaling analyses and field data suggest that T changed by a few percent per meter of drawdown during slug and pumping tests at our field site. Preliminary analyses suggest that displacement data can be used to improve estimates of storativity and to reduce nonuniqueness during hydraulic well tests involving single wells. | 18,823,402 |
Transverse patterning dissociates human EEG theta power and hippocampal BOLD activation. | Theta oscillations (4-8 Hz) are often modulated in human electroencephalogram (EEG) studies of memory, whereas overlapping frequencies dominate rodent hippocampal EEG. An emerging parallelism between theta reactivity and hippocampal functional magnetic resonance imaging activation has suggested a homology between theta activity in humans and rodents, representing a process of cortico-hippocampal interaction involved in memory. In the present study, we investigated EEG reactivity during performance of a relational memory task that induces a negative hippocampal blood oxygenation level dependent (BOLD) signal change, compared to a nonrelational control condition. Relational trials induced theta increases and alpha decreases. Low Resolution Electromagnetic Brain Tomography estimates localized theta and alpha modulation to frontal midline and parietal midline cortices, respectively, both of which exhibit negative BOLD responses in this task. Thus, theta and alpha dynamics are dissociable from positive BOLD activation, and may, in fact, colocalize with negative BOLD responses. | 18,823,411 |
Cardiovascular dynamics in blood phobia: evidence for a key role of sympathetic activity in vulnerability to syncope. | This study was aimed at clarifying the mechanism predisposing people with blood phobia to syncope by investigating the complete hemodynamic response pattern and the underlying autonomic control. Blood phobics and controls were shown 3 film-clips: phobia-related, phobia-unrelated, and neutral. Hemodynamic responses were recorded using impedance cardiography and Finapres. Preejection period and respiratory sinus arrhythmia were employed as indices of cardiac sympathetic and parasympathetic activity. Self-ratings of emotion were also collected. Blood phobics displayed global heart rate and cardiac output increases to the phobic film, mediated by augmented cardiac sympathetic activity. Systolic blood pressure and total peripheral resistance markedly declined, with no evidence of diphasic reaction or parasympathetic activation. An impaired vasomotor response under sympathetic control might be the key mechanism underlying the phobic dysfunctional response. | 18,823,415 |
Perceiving age and gender in unfamiliar faces: brain potential evidence for implicit and explicit person categorization. | We used repetition priming to investigate implicit and explicit processes of unfamiliar face categorization. During prime and test phases, participants categorized unfamiliar faces according to either age or gender. Faces presented at test were either new or primed in a task-congruent (same task during priming and test) or incongruent (different tasks) condition. During age categorization, reaction times revealed significant priming for both priming conditions, and event-related potentials yielded an increased N170 over the left hemisphere as a result of priming. During gender categorization, congruent faces elicited priming and a latency decrease in the right N170. Accordingly, information about age is extracted irrespective of processing demands, and priming facilitates the extraction of feature information reflected in the left N170 effect. By contrast, priming of gender categorization may depend on whether the task at initial presentation requires configural processing. | 18,823,419 |
L-Ornithine-l-aspartate in the management of hepatic encephalopathy: a meta-analysis. | Hepatic encephalopathy continues to be a major clinical problem and the current decade has not witnessed major therapeutic breakthroughs in this area. L-ornithine-l-aspartate (LOLA) is not frequently used as there are still some reservations about its benefits. The present study aimed to assess the effectiveness and safety of LOLA in the management of hepatic encephalopathy. We used the method recommended by the Cochrane Collaboration to perform a meta-analysis of randomized controlled trials of LOLA therapy for hepatic encephalopathy including three randomized controlled trials. Three randomized trials randomizing 212 patients were included. LOLA versus placebo had a significant effect on improvement of hepatic encephalopathy (relative risk 1.89; 95% CI 1.32 to 2.71; P = 0.0005). This comparison showed no statistical heterogeneity (P = 0.85 and chi(2) = 0.09). Subgroup analysis showed that LOLA could be effective versus placebo in trials with grade I or II overt hepatic encephalopathy patients (relative risk 1.87; 95% CI 1.30 to 2.68; P = 0.0007) and had no significant effect in trials with subclinical hepatic encephalopathy patients (relative risk 1.69; 95% CI 0.72 to 3.94; P = 0.23). Adverse effects were observed in only three patients treated with LOLA in one report. LOLA benefited patients with overt hepatic encephalopathy (I or II), whereas these data do not support the use of LOLA for patients with subclinical hepatic encephalopathy. | 18,823,442 |
Genetically engineered rice containing larger amounts of nicotianamine to enhance the antihypertensive effect. | Nicotianamine (NA), a metal chelator ubiquitous in higher plants, serves as an antihypertensive substance in humans. To engineer a novel antihypertensive rice that contains larger amounts of NA, the barley NA synthase gene, HvNAS1, was introduced into rice via Agrobacterium-mediated transformation. The introduced HvNAS1 was driven by pGluB-1, which induces strong gene expression in the endosperm of rice seeds. The NA content in transgenic rice seeds was up to fourfold greater than that in non-transgenic rice seeds. The Cre/loxP DNA excision (CLX) system was used to remove the selectable marker gene for antibiotic resistance. Furthermore, the transgenic rice was crossed with a cleistogamous mutant to prevent gene transfer via pollen dispersal. These two modifications may minimize public concern with regard to the use of this transgenic rice. | 18,823,453 |
Meta-analysis of the diagnostic accuracy of transesophageal echocardiography for assessment of atherosclerosis in the ascending aorta in patients undergoing cardiac surgery. | Stroke after cardiac surgery may be caused by emboli emerging from an atherosclerotic ascending aorta (AA). Epiaortic ultrasound scanning (EUS), the current 'gold' standard for detecting AA atherosclerosis, has not gained widespread use because there is a lack of optimized ultrasound devices, it lengthens the procedure, it endangers sterility, and there is a false belief by many surgeons that palpation is as sensitive as EUS. Furthermore there is no clear evidence proving that the use of epiaortic scanning changes outcome in cardiac surgery. Various researchers investigated the ability of transesophageal echocardiography (TEE) to discriminate between the presence and absence of AA atherosclerosis. It is acknowledged that TEE has limited value in this, but it has never been supported by a meta-analysis estimating the true diagnostic accuracy of TEE based on all quantitative evidence. We aimed to do this using state-of-the-art methodology of diagnostic meta-analyses. We searched multiple databases for studies comparing TEE vs. EUS for detection of atherosclerosis. A random-effects bivariate meta-regression model was used to obtain summary estimates of sensitivity and specificity, incorporating the correlation between sensitivity and specificity as well as covariates to explore heterogeneity across studies. We extracted six studies with a total of 346 patients, of whom 419 aortic segments were analyzed, including 100 segments with atherosclerosis [median prevalence 25% (range 17-62%)]. Summary estimates of sensitivity and specificity were 21% (95% CI 13-32%) and 99% (96-99%), respectively. Because of the low sensitivity of TEE for the detection of AA atherosclerosis, a negative test result requires verification by additional testing using epiaortic scanning. In case of a positive test result, AA atherosclerosis can be considered as present, and less manipulative strategies might be indicated. | 18,823,455 |
Early time course of altered leukocyte response to lipopolysaccharide and peptidoglycan in porcine gunshot injury. | Penetrating injuries are frequently combined with polybacterial soiling. Clearance of the microorganisms depends on the ability to activate immune responses, but post-traumatic hyporeactivity of immune cells is almost universal. The aim of this study was to map the early time course of this altered leukocyte reactivity, and to compare the reactions to subsequent Gram-positive or Gram-negative challenges. Twelve juvenile pigs sustained two standardized rounds, one through the right femur and one through the left upper abdomen. First aid treatment and acute surgery were started immediately. Blood samples were drawn before trauma and after 10, 30, 60, and 90 min, and thereafter stimulated in ex vivo whole blood for 3 h with lipopolysaccharide (LPS, 10 ng/ml), peptidoglycan (PepG, 1 microg/ml), or an equivalent amount of normal saline. The leukocyte response was evaluated by measurement of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and IL-10 in the supernatant. In the post-traumatic in vivo serum, the concentration of TNF-alpha increased steadily (significant after 60 min). A reduced ex vivo reaction to LPS was evident after 10 min, and was statistically significant after 30 min. The lowest levels were reached after 90 min. The ex vivo synthesis of TNF-alpha after stimulation with PepG remained unaltered. A similar development was seen for IL-6. IL-1 beta levels did not change, while IL-8 increased significantly only after 60 and 90 min. Trauma almost instantaneously reprogrammed circulating leukocytes. As measured with TNF-alpha, a profound hyporeactivity to LPS, but not to PepG, was induced. In addition, no global down-regulation of leukocyte function was found after stimulation with LPS. | 18,823,462 |
Silence of ClC-3 chloride channel inhibits cell proliferation and the cell cycle via G/S phase arrest in rat basilar arterial smooth muscle cells. | Previously, we have found that the ClC-3 chloride channel is involved in endothelin-1 (ET-1)-induced rat aortic smooth muscle cell proliferation. The present study was to investigate the role of ClC-3 in cell cycle progression/distribution and the underlying mechanisms of proliferation. Small interference RNA (siRNA) is used to silence ClC-3 expression. Cell proliferation, cell cycle distribution and protein expression were measured or detected with cell counting, bromodeoxyuridine (BrdU) incorporation, Western blot and flow cytometric assays respectively. ET-1-induced rat basilar vascular smooth muscle cell (BASMC) proliferation was parallel to a significant increase in endogenous expression of ClC-3 protein. Silence of ClC-3 by siRNA inhibited expression of ClC-3 protein, prevented an increase in BrdU incorporation and cell number induced by ET-1. Silence of ClC-3 also caused cell cycle arrest in G(0)/G(1) phase and prevented the cells' progression from G(1) to S phase. Knockdown of ClC-3 potently inhibited cyclin D1 and cyclin E expression and increased cyclin-dependent kinase inhibitors (CDKIs) p27(KIP) and p21(CIP) expression. Furthermore, ClC-3 knockdown significantly attenuated phosphorylation of Akt and glycogen synthase kinase-3beta (GSK-3beta) induced by ET-1. Silence of ClC-3 protein effectively suppressed phosphorylation of the Akt/GSK-3beta signal pathway, resulting in down-regulation of cyclin D1 and cyclin E, and up-regulation of p27(KIP) and p21(CIP). In these BASMCs, integrated effects lead to cell cycle G(1)/S arrest and inhibition of cell proliferation. | 18,823,498 |
Ventilation/Perfusion SPECT for diagnostics of pulmonary embolism in clinical practice. | The aim of this retrospective study is to illustrate clinical utility and impact of pulmonary embolism (PE) diagnostics of up to date Ventilation/Perfusion SPECT (V/P (SPECT)) applying holistic interpretation criteria. During a 2-year period 2328 consecutive patients referred to V/P(SPECT) for clinically suspected PE were examined. Final diagnosis was established by physicians clinically responsible for patient care. To establish the performance of V/P(SPECT) negative for PE, patients were followed up by medical records for 6 months. Ventilation/Perfusion SPECT was feasible in 99% of the patients. Data for follow-up were available in 1785 patients (77%). PE was reported in 607 patients (34%). Normal pattern was described in 420 patients (25%). Pathology other than PE such as a pneumonia, left heart failure, obstructive lung disease, tumour was described in 724 patients (41%). Report was nondiagnostic in 19 patients (1%). Six cases were classified as falsely negative because PE was diagnosed at follow-up and was fatal in one case. Six cases were classified as falsely positive because the clinician decided not to treat. In 608 patients with final PE diagnosis, 601 patients had positive V/P(SPECT) (99%). In 1177 patients without final PE diagnosis 1153 patients had negative V/P(SPECT) (98%). Holistic interpretation of V/P(SPECT,) yields high negative and positive predictive values and only 1% of nondiagnostic findings and was feasible in 99% of patients. It is a responsibility and a challenge of nuclear medicine to provide optimal care of patients with suspected PE by making V/P(SPECT) available. | 18,823,506 |
Gene products of chromosome 11q and their association with CCND1 gene amplification and tamoxifen resistance in premenopausal breast cancer. | The amplification event occurring at chromosome locus 11q13, reported in several different cancers, includes a number of potential oncogenes. We have previously reported amplification of one such oncogene, namely CCND1, to be correlated with an adverse effect of tamoxifen in premenopausal breast cancer patients. Over-expression of cyclin D1 protein, however, confers tamoxifen resistance but not a tamoxifen-induced adverse effect. Potentially, co-amplification of an additional 11q13 gene, with a resulting protein over-expression, is required to cause an agonistic effect. Moreover, during 11q13 amplification a deletion of the distal 11q region has been described. In order to assess the potential impact of the deletion we examined a selected marker for this event. Array comparative genomic hybridization analysis was employed to identify and confirm changes in the gene expression of a number of different genes mapping to the 11q chromosomal region, associated with CCND1 amplification. The subsequent protein expression of these candidate genes was then examined in a clinical material of 500 primary breast cancers from premenopausal patients who were randomly assigned to either tamoxifen or no adjuvant treatment. The protein expression was also compared with gene expression data in a subset of 56 breast cancer samples. Cortactin and FADD (Fas-associated death domain) over-expression was linked to CCND1 amplification, determined by fluorescence in situ hybridization, but was not associated with a diminished effect of tamoxifen. However, deletion of distal chromosome 11q, defined as downregulation of the marker Chk1 (checkpoint kinase 1), was associated with an impaired tamoxifen response, and interestingly with low proliferative breast cancer of low grade. For Pak1 (p21-activated kinase 1) and cyclin D1 the protein expression corresponded to the gene expression data. The results indicate that many 11q13 associated gene products are over-expressed in conjunction with cyclin D1 but not linked to an agonistic effect of tamoxifen. Finally, the deletion of distal 11q, linked to 11q13 amplification, might be an important event affecting breast cancer outcome and tamoxifen response. | 18,823,530 |
Human embryonic stem cell research, justice, and the problem of unequal biological access. | In 2003, Ruth Faden and eighteen other colleagues argued that a "problem of unequal biological access" is likely to arise in access to therapies resulting from human embryonic stem cell research. They showed that unless deliberate steps are taken in the United States to ensure that the human embryonic stem cell lines available to researchers mirrors the genetic diversity of the general population, white Americans will likely receive the benefits of these therapies to the relative exclusion of minority ethnic groups. Over the past five years the problem of unequal biological access has not received much attention from politicians, bioethicists and even many researchers in the United States, in spite of the widely held belief in the country that there is an obligation to prevent and correct ethnic disparities in access to medical care. The purpose of this paper is to increase awareness of the problem of unequal biological access and of the need to do more than is currently being done to ensure that ethnic disparities in access to human embryonic stem cell-based therapies do not arise. Specifically, this paper explains why the problem of unequal biological access will likely arise in the United States in such a way that white Americans will disproportionately receive most of the benefits of the therapies resulting from human embryonic stem cell research. It also argues for why there is an obligation to prevent these ethnic disparities in access from happening and outlines four steps that need to be taken towards meeting this obligation. | 18,823,539 |
Prevalence and determinants of child maltreatment among high school students in Southern China: a large scale school based survey. | Child maltreatment can cause significant physical and psychological problems. The present study aimed to investigate the prevalence and determinants of child maltreatment in Guangzhou, China, where such issues are often considered a taboo subject. A school-based survey was conducted in southern China in 2005. 24 high schools were selected using stratified random sampling strategy based on their districts and bandings. The self-administered validated Chinese version of parent-child Conflict Tactics Scale (CTSPC) was used as the main assessment tool to measure the abusive experiences encountered by students in the previous six months. The response rate of this survey was 99.7%. Among the 6592 responding students, the mean age was 14.68. Prevalence of parental psychological aggression, corporal punishment, severe and very serve physical maltreatment in the past 6 months were 78.3%, 23.2%, 15.1% and 2.8% respectively. The prevalence of sexual abuse is 0.6%. The most commonly cited reasons for maltreatment included 'disobedience to parents', 'poor academic performance', and 'quarrelling between parents'. Age, parental education, places of origins and types of housing were found to be associated with physical maltreatments whereas gender and fathers' education level were associated with sexual abuse. Though largely unspoken, child maltreatment is a common problem in China. Identification of significant determinants in this study can provide valuable information for teachers and health professionals so as to pay special attention to those at-risk children. | 18,823,544 |
Tissue proteomics for cancer biomarker development: laser microdissection and 2D-DIGE. | Novel cancer biomarkers are required to achieve early diagnosis and optimized therapy for individual patients. Cancer is a disease of the genome, and tumor tissues are a rich source of cancer biomarkers as they contain the functional translation of the genome, namely the proteome. Investigation of the tumor tissue proteome allows the identification of proteomic signatures corresponding to clinico-pathological parameters, and individual proteins in such signatures will be good biomarker candidates. Tumor tissues are also a rich source for plasma biomarkers, because proteins released from tumor tissues may be more cancer specific than those from non-tumor cells. Two-dimensional difference gel electrophoresis (2D-DIGE) with novel ultra high sensitive fluorescent dyes (CyDye DIGE Fluor satulation dye) enables the efficient protein expression profiling of laser-microdissected tissue samples. The combined use of laser microdissection allows accurate proteomic profiling of specific cells in tumor tissues. To develop clinical applications using the identified biomarkers, collaboration between research scientists, clinicians and diagnostic companies is essential, particularly in the early phases of the biomarker development projects. The proteomics modalities currently available have the potential to lead to the development of clinical applications, and channeling the wealth of produced information towards concrete and specific clinical purposes is urgent. | 18,823,585 |
Acrolein, the toxic endogenous aldehyde, induces neurofilament-L aggregation. | Acrolein is a highly reactive by product of lipid peroxidation and individuals with neurodegenerative disorders have been shown to contain elevated concentrations of this molecule in the brain. In the present study, we examined the pattern of neurofilament-L (NF-L) modification elicited by acrolein. When NF-L was incubated with acrolein, protein aggregation occurred in a acrolein concentration-dependent manner. Exposure of NF-L to acrolein also led to the generation of protein carbonyl compounds. Through the addition of free radical scavengers we observed a significant decrease in acrolein-mediated NF-L aggregation. These results indicate that free radicals may be involved in the modification of NF-L by acrolein. In addition, dityrosine crosslink formation was observed in acrolein-mediated NF-L aggregates and these aggregates displayed thioflavin T reactivity, reminiscent of amyloid. This study suggests that acrolein-mediated NF-L aggregation might be closely related to oxidative reactions, thus these reactions may play a critical role in neurodegenerative diseases. | 18,823,586 |
Taurine protects the antioxidant defense system in the erythrocytes of cadmium treated mice. | The present study was undertaken to investigate the protective role of taurine (2-aminoethanesulfonic acid) against cadmium (Cd) induced oxidative stress in murine erythrocytes. Cadmium chloride (CdCl(2)) was chosen as the source of Cd. Experimental animals were treated with either CdCl(2) alone or taurine, followed by Cd exposure. Cd intoxication reduced hemoglobin content and the intracellular Ferric Reducing/Antioxidant Power of erythrocytes, along with the activities of antioxidant enzymes, glutathione content, and total thiols. Conversely, intracellular Cd content, lipid peroxidation, protein carbonylation, and glutathione disulphides were significantly enhanced in these cells. Treatment with taurine before Cd intoxication prevented the toxin-induced oxidative impairments in the erythrocytes of the experimental animals. Overall, the results suggest that Cd could cause oxidative damage in murine erythrocytes and that taurine may play a protective role in reducing the toxic effects of this particular metal. | 18,823,590 |
Preferential recognition of peroxynitrite modified human DNA by circulating autoantibodies in cancer patients. | Peroxynitrite (ONOO(-)) has been vastly implicated in mutagenesis and cancer development. Present study probes the antigenicity of peroxynitrite damaged DNA (ONOO(-)-DNA) in cancer patients. Purified human placental DNA was damaged by the synergistic action of sodium nitroprusside (SNP) and Pyrogallol for 3h at 37 degrees C. Binding characteristics of cancer autoantibodies as well as experimentally induced anti-peroxynitrite-DNA (anti-ONOO(-)-DNA) antibodies were assessed by ELISA and band shift assay. DNA modifications produced single strand breaks, decreased melting temperature (T(m)), hyperchromicity in UV spectrum and decreased fluorescence intensity. The ONOO(-)-DNA induced high titre antibodies in experimental animals. Cancer autoantibodies exhibited enhanced binding with the modified DNA as compared to the native form. Lymphocyte DNA from cancer patients showed appreciable recognition of anti-ONOO(-)-DNA IgG as compared to the DNA from healthy subjects. The peroxynitrite modified DNA presents unique epitopes which may be one of the factors for the autoantibody induction in cancer patients. | 18,823,620 |
A quantitative method for representing balance strategies of goal-directed human motions. | A movement index termed balance strategy vector (BSV) was developed as a research tool for studying human balance strategies during goal-directed motions. For a given motion (motion capture data), the BSV index quantitatively represents its balance strategy by computing how available body joint DoFs' angular motions affect the formation of the wholebody center-of-mass trajectory. The index facilitates easy and intuitive understanding of balance strategies of various human motions and can assist scientific investigations on human balance strategies. As an example demonstrating the utility of the index, the index was used to explore balance strategies of free-style, sagittal-plane load lifting motions. | 18,823,622 |
Removal of ammonia from contaminated air in a biotrickling filter - denitrifying bioreactor combination system. | The removal of gaseous ammonia in a system consisting of a biotrickling filter, a denitrification reactor and a polishing bioreactor for the trickling liquid was investigated. The system allowed sustained treatment of ammonia while preventing biological inhibition by accumulating nitrate and nitrite and avoiding generation of contaminated water. All bioreactors were packed with cattle bone composite ceramics, a porous support with a large interfacial area. Excellent removal of ammonia gas was obtained. The critical loading ranged from 60 to 120 gm(-3)h(-1) depending on the conditions, and loadings below 56 gm(-3)h(-1) resulted in essentially complete removal of ammonia. In addition, concentrations of ammonia, nitrite, nitrate and COD in the recycle liquid of the inlet and outlet of each reactor were measured to determine the fate of nitrogen in the reactor, close nitrogen balances and calculate nitrogen to COD ratios. Ammonia absorption and nitrification occurred in the biotrickling filter; nitrate and nitrite were biologically removed in the denitrification reactor and excess dissolved COD and ammonia were treated in the polishing bioreactor. Overall, ammonia gas was very successfully removed in the bioreactor system and steady state operation with respect to nitrogen species was achieved. | 18,823,641 |
Methane oxidation in a boreal climate in an experimental landfill cover composed from mechanically-biologically treated waste. | The present study evaluated microbial methane (CH4) oxidation in a boreally located outdoor landfill lysimeter (volume 112 m3, height 3.9 m) filled with mechanically-biologically treated waste (MBT residual) and containing a cover layer made from the same MBT residual. The calculations based on gas emission and pore gas measurements showed that, between April and October 2005, a significant proportion (> 96%) of the methane produced (< 23 l CH4 m(-2) d(-1)) in the lysimeter was oxidized. Methane was oxidized mainly at the depths of 35-75 cm, as indicated by the upward decrease both in the methane concentration and in the methane-to-carbon dioxide ratio in the pore gas. Lower methane oxidation (< 0.8 CH4 m(-2) d(-1); this was < 22% of the methane produced) was observed only during the coldest time of the year (January 2006), apparently due to the fall in temperature at the depths of 25-70 cm (from 9-25 degrees C during April to October to 2-9 degrees C in January). Unexpectedly, the highest methane oxidation potential (MOP) was observed in samples from the top layer where exposure to methane was low. Overall, the results show that MBT residual is a suitable support medium for methane oxidation in landfill covers in field conditions in a boreal climate. | 18,823,644 |
Duration of anticoagulant therapy for patients with venous thromboembolism. | In principle, the answer to this question is obvious: "as long as the risk of continued therapy is outweighed by the benefit." In practice, determining an individual patient's risk of recurrent venous thromboembolism (VTE) without warfarin or other vitamin K antagonists is difficult. However, there are many factors (both intrinsic and environmental) that can alter the risk of VTE recurrence. This paper will discuss evidence and considerations (including the issue of bleeding risk) that may be relevant to decisions about duration of anticoagulant therapy for patients with VTE. | 18,823,648 |
Culture on electrospun polyurethane scaffolds decreases atrial natriuretic peptide expression by cardiomyocytes in vitro. | The function of the mammalian heart depends on the functional alignment of cardiomyocytes, and controlling cell alignment is an important consideration in biomaterial design for cardiac tissue engineering and research. The physical cues that guide functional cell alignment in vitro and the impact of substrate-imposed alignment on cell phenotype, however, are only partially understood. In this report, primary cardiac ventricular cells were grown on electrospun, biodegradable polyurethane (ES-PU) with either aligned or unaligned microfibers. ES-PU scaffolds supported high-density cultures and cell subpopulations remained intact over two weeks in culture. ES-PU cultures contained electrically-coupled cardiomyocytes with connexin-43 localized to points of cell:cell contact. Multi-cellular organization correlated with microfiber orientation and aligned materials yielded highly oriented cardiomyocyte groupings. Atrial natriuretic peptide, a molecular marker that shows decreasing expression during ventricular cell maturation, was significantly lower in cultures grown on ES-PU scaffolds than in those grown on tissue culture polystyrene. Cells grown on aligned ES-PU had significantly lower steady state levels of ANP and constitutively released less ANP over time indicating that scaffold-imposed cell organization resulted in a shift in cell phenotype to a more mature state. We conclude that the physical organization of microfibers in ES-PU scaffolds impacts both multi-cellular architecture and cardiac cell phenotype in vitro. | 18,823,659 |
Demethylating agent 5-aza-2'-deoxycytidine activates HLA-G expression in human leukemia cell lines. | HLA-G is a non-classical HLA class I antigen primarily expressed in the extravillous cytotrophoblast. HLA-G can also be expressed at some pathological circumstances and may thus contribute to inhibition of efficient immune responses. Complex regulation of HLA-G expression also involves epigenetic mechanisms as DNA methylation. Here we demonstrate that treatment with demethylating agent 5-aza-2'-deoxycytidine (AdC) resulted in HLA-G transcription in 18 out of 20 examined leukemia cell lines. HLA-G protein synthesis was detected in 10 cell lines expressing significant level of HLA-G transcripts following AdC treatment. | 18,823,661 |
Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial. | Diabetic retinopathy remains a leading cause of visual loss in people of working age. We examined whether candesartan treatment could slow the progression and, secondly, induce regression of retinopathy in people with type 2 diabetes. We did a randomised, double-blind, parallel-group, placebo-controlled trial in 309 centres worldwide. We recruited normoalbuminuric, normotensive, or treated hypertensive people with type 2 diabetes with mild to moderately severe retinopathy and assigned them to candesartan 16 mg once a day or placebo. After a month, the dose was doubled to 32 mg once per day. Investigators and patients were unaware of the treatment allocation status. Progression of retinopathy was the primary endpoint, and regression was a secondary endpoint. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00252694. 1905 participants (aged 37-75 years) were randomised to candesartan (n=951) or placebo (n=954). 161 (17%) patients in the candesartan group and 182 (19%) in the placebo group had progression of retinopathy by three steps or more on the Early Treatment Diabetic Retinopathy Study scale. The risk of progression of retinopathy was non-significantly reduced by 13% in patients on candesartan compared with those on placebo (hazard ratio [HR] 0.87, 95% CI 0.70-1.08, p=0.20). Regression on active treatment was increased by 34% (1.34, 1.08-1.68, p=0.009). HRs were not attenuated by adjustment for baseline risk factors or changes in blood pressure during the trial. An overall change towards less severe retinopathy by the end of the trial was observed in the candesartan group (odds 1.17, 95% CI 1.05-1.30, p=0.003). Adverse events did not differ between the treatment groups. Treatment with candesartan in type 2 diabetic patients with mild to moderate retinopathy might induce improvement of retinopathy. | 18,823,658 |
Enhanced short-term improvement of insulin response to a low-caloric diet in obese carriers the Gly482Ser variant of the PGC-1alpha gene. | The Gly482Ser missense mutation of the transcriptional coactivator, peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) has been involved in insulin function impairments, with conflicting results. The current study investigated the relationships of carrying this polymorphism with insulin resistance (IR) during a short-term weight-loss and the subsequent weight follow-up. The Gly482Ser was genotyped in 180 Spanish volunteers [body mass index: 31.4+/-3.2kg/m(2); age: 35+/-5 years]. Specific phenotypical measurements were determined at baseline, following an 8-week low-calorie diet (LCD) as well as after 6-month and 1-year of follow-up. At baseline the Ser482Ser genotype was associated with higher HOMA-IR and insulin concentrations than the other genotypes (p<0.05), which was accompanied by an increased higher risk of IR (OR: 2.97; 95% CI: 1.24-7.15). After following the LCD, such increased risk of insulin insensitivity in Ser482Ser carriers was toned down (p>0.05). This outcome was sustained after 6-month and 1-year of follow-up (p>0.05). These data show an increased risk of IR in obese carrying the rs8192673 Ser482Ser genotype. This risk was markedly reduced by an energy-restricted diet, which was sustained 6 months and 1 year after the diet therapy. This observation allows identifying obese subjects who might personally profit most from an energy-restrictive treatment concerning insulin response and lead to more individualized prognostic and therapeutic decisions. | 18,823,672 |
Scope and design of the Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements (FREEDOM) Study. | Conventional thrice-weekly hemodialysis (HD) has limited the ability to generate further improvements in patient quality of life, morbidity, and mortality. Daily HD (DHD) offers the promise of providing clinical and economic benefits. The objectives of the Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements Study are to evaluate outcomes of DHD (6 times/wk) with the NxStage System One (NxStage Medical Inc, Lawrence, MA) device. Cohort study with matched control group. The DHD group will include up to 500 participants at 70 clinical sites, enrolling for 3 years with a minimum of 1-year follow-up. Study candidates include adult patients (age >or= 18 years) with end-stage renal disease who are considered suitable candidates for DHD with the NxStage System One device by the treating physician and who have Medicare as their primary insurance payer. The control group will consist of a matched thrice-weekly in-center HD cohort derived from the US Renal Data System database using a 10:1 ratio, totaling 5,000 patients. Treatment with DHD and "standard of care" thrice-weekly HD. The primary intent-to-treat analysis compares hospitalization days/patient-year between the DHD and thrice-weekly HD groups. Other outcomes recorded in both groups include non-treatment-related medical expenditures. In addition, in the DHD cohort, changes in quality-of-life measures (baseline, 4 and 12 months, and every 6 months thereafter); urea kinetics; parameters related to anemia, bone and mineral metabolism, and nutrition; vascular access interventions; and use of medications will be examined. This study has the potential to elucidate the health and economic benefits of DHD and complement results of current clinical trials. | 18,823,688 |
Approaches for the treatment of waste streams of the aluminium anodising industry. | The aluminium anodising industry is an important industrial sector that invariably generates great amounts of different waste streams. Classical and especially new-developing technologies dealing with them are reviewed. Innovative methods are mainly based on engineering geochemical processes, looking for the recovery of resource materials and the reduction of emissions to the environment. These represent a promising alternative to the classical method (neutralisation process and anodising mud disposal) which is an end-of-pipe solution. Among the treatments recently proposed, there are the use of anodising mud in the manufacture of refractory bodies, and the synthesis of useful minerals from the wastewaters arising from the etching, anodising and brightening processes. The viability of the application of such methods in the treatment of waste streams of the aluminium anodising industry is discussed, pointing out the main shortcomings and benefits of each of them. For those methods appearing environmentally friendly the process cost and the actual marketability of the final products should be determinant on their near future applicability. | 18,823,703 |
Infections with weakly haemolytic Brachyspira species in pigs with miscellaneous chronic diseases. | The prevalence of infections with different Brachyspira species was assessed in 202 pigs with various chronic herd problems using different methods. Twenty-seven pigs (13.4%) were positive for Brachyspira spp. with at least one of the methods used. The highest number of positives was identified with mucosal scraping-PCR (23), followed by PET-PCR (22) and bacteriological-biochemical analysis (15). With the exception of three cases of B. pilosicoli infections, only weakly pathogenic Brachyspira species were identified. The majority was B. murdochii, followed by B. innocens and B. intermedia. Concurrent infections with two or more Brachyspira species were common and accounted for 37.1% of the total. Presence of weakly haemolytic Brachyspira was associated with wasting and diarrhoea in a number of cases. This investigation shows that infections with weakly haemolytic Brachyspira spp. may contribute to colonic pathology in pigs with chronic herd problems and that mixed infections seem to occur more frequently than previously noticed. | 18,823,725 |
Cocaine-induced agitated delirium with associated hyperthermia: a case report. | "Cocaine-induced agitated delirium with associated hyperthermia" is a rare, almost uniformly fatal syndrome. The incidence of the disease is not known, however, it is believed to have markedly increased since the late 1980s with widespread popularity of crack cocaine. Recent literature is lacking regarding this rare syndrome. Although almost uniformly fatal, we present a neurologically intact survivor due to a multidisciplinary team approach. We are reporting a 41-year-old African-American man who arrived at the trauma center with a rectal temperature of 42.6°C (108.6°F) and a toxicology screen positive for cocaine. The patient manifested many of the known complications of cocaine-induced agitated delirium with associated hyperthermia, including renal failure and coagulation panel abnormalities. With early application of cooling techniques, including ice pack, gastric lavage, and bilateral chest cavity lavage using multiple chest tubes, the patient's core temperature was quickly lowered. This case demonstrated how a multidisciplinary team approach, including emergency medicine and critical care specialists, and aggressive treatment of hyperthermia using bilateral tube thoracostomy and chest cavity lavage enabled our patient's core temperature to be effectively lowered. We were unable to find prior reports of using tube thoracostomy in this manner. | 18,823,733 |
Metal-on-metal hip resurfacing: the effect of cup position and component size on range of motion to impingement. | The aim of this dry bone study was to determine the range of hip motion to impingement for different hip resurfacing cup positions and component sizes. The maximum angles of hip flexion, extension, abduction, and adduction were calculated from 3-dimensional coordinates for: 1. Cup inclination of 30 degrees , 40 degrees , 50 degrees , 60 degrees , and 70 degrees with fixed anteversion; 2. Cup anteversion of 0 degrees , 10 degrees , 25 degrees , 35 degrees , and 45 degrees with fixed inclination; and 3. 3 different component sizes on the same size dry bones. An acetabular component inclination of 50 degrees and an anteversion of 25 degrees allowed the most physiologic range of hip motion. A larger-diameter femoral component relative to the native femoral neck diameter resulted in a greater range of hip motion to impingement. | 18,823,742 |
Monte-Carlo simulations of elastically backscattered neutrons from hidden explosives using three different neutron sources. | Calculations of elastically backscattered (EBS) neutrons from hidden explosives buried in soil were performed using Monte-Carlo N-particle transport code MCNP5. Three different neutron sources were used in the study. The study re-examines the performance of the neutron backscattering methods in providing identification of hidden explosives through their chemical composition. The EBS neutron energy spectra of fast and slow neutrons of the major constituent elements in soil and an explosive material in form of TNT have shown definite structures that can be used for the identification of a buried landmine. | 18,823,788 |
Rupture of the left atrial 'basal' appendage due to blunt trauma in an elderly patient. | Blunt traumatic cardiac rupture is associated with a high mortality rate. Motor vehicle accidents account for most cardiac ruptures, but crush injury is relatively rare. We describe a case of a 77-year-old man who had the left atrial 'basal' appendage ruptured through blunt trauma due to a fall. He was surgically treated and recovered without complication. | 18,823,789 |
Ultrasound of the peripheral nerves. | Peripheral nerves disorders are common in the rheumatologic practice and can mimic a variety of musculoskeletal diseases. Clinical evaluation remains the mainstay for diagnosing nerve disorders of the extremities. A careful history and an accurate physical examination lead in most patients to a high diagnostic suspicion. Nevertheless several imaging techniques are usually obtained to confirm the clinical data and in the preoperative workup. Although standard radiographs and computed tomography do not visualize the nerves directly, they can reveal the adjacent anatomic structures such as bones and joints and can add additional information that frequently is essential in the choice of adequate treatment. Magnetic resonance imaging and ultrasound show peripheral nerves directly and can reveal their size and internal structure. With the new developments in high resolution, electronic broadband transducers, ultrasound (US) is now considered an optimal imaging technique to evaluate the normal anatomy and disorders of peripheral nerves. Well recognized advantages of this technique in this field are: the possibility of realizing a dynamic examination and assessing long nerves segments in a short time; it is non-invasive and low cost. In addition US is better accepted by the patients. In this article we present a brief description of the normal and US anatomy of the peripheral nerves followed by a description of the US appearance of the most frequent disorders: entrapment neuropathies (EN), tumor and cystic lesions. | 18,823,807 |
Development of working reference materials for clinical virology. | Nucleic acid amplification technique (NAT)-based assays are replacing traditional diagnostic methods in clinical laboratories. However, many of these assays are developed in-house and the lack of standardised reference materials has hindered assay implementation and control. Consequently, in the UK, the Clinical Virology Network (CVN), the National Institute for Biological Standards and Control (NIBSC), and the Health Protection Agency (HPA), are working in collaboration to develop working standards or 'run controls' for diagnostic NAT-based assays, particularly real-time PCR. These run controls are intended for use in microbiology laboratories and are designed to be extracted and amplified in the same way as clinical samples and included in each assay run. The aim is to enable clinical laboratories to continuously monitor the performance of their diagnostic NAT assays on a run-by-run basis allowing inter-laboratory comparisons, and ultimately improving the consistency of results. At present, eight candidate run controls representing clinically relevant viral targets have been prepared for evaluation by CVN laboratories. Data have been returned on the performance of each run control in routine diagnostic assays. Preliminary results presented here indicate a high level of variability in intra- and inter-assay detection of these targets, highlighting the need for standardisation of assays within molecular diagnostics. | 18,823,817 |
Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer. | We previously identified a novel exogenous gammaretrovirus (xenotropic murine leukemia virus-related gammaretrovirus (XMRV)) using a pan-viral microarray. XMRV is the first MLV-related virus found in human infection. Forty percent (8/20) of familial prostate cancer patients homozygous for a mutation in RNase L (R462Q) were positive for XMRV, while the virus was rarely (1/66) detected in familial prostate cancer patients heterozygous for R462Q or carrying the wild type allele. To determine the presence of XMRV in non-familial prostate cancer samples. RNA from prostate tissue was analyzed for XMRV using nested RT-PCR. In all samples, RNase L (R462Q) genotyping was performed using an allele-specific PCR. XMRV-specific sequences were detected in one of 105 tissue samples from non-familial prostate cancer patients and from one of 70 tissue samples from men without prostate cancer. The two XMRV-positive patients were wild type or heterozygous for the R462Q mutation and thus carried at least one fully functional RNase L allele. XMRV was rarely detected in non-familial prostate cancer samples from Northern European patients. The homozygous mutation R462Q (QQ) was significantly underrepresented (<6%) in this cohort when compared to other studies (11-17%). | 18,823,818 |
Impairment of working memory maintenance and response in schizophrenia: functional magnetic resonance imaging evidence. | Comparing prefrontal cortical activity during particular phases of working memory in healthy subjects and individuals diagnosed with schizophrenia might help to define the phase-specific deficits in cortical function that contribute to cognitive impairments associated with schizophrenia. This study featured a spatial working memory task, similar to that used in nonhuman primates, that was designed to facilitate separating brain activation into encoding, maintenance, and response phases. Fourteen patients with schizophrenia (4 medication-free) and 12 healthy comparison participants completed functional magnetic resonance imaging while performing a spatial working memory task with two levels of memory load. Task accuracy was similar in patients and healthy participants. However, patients showed reductions in brain activation during maintenance and response phases but not during the encoding phase. The reduced prefrontal activity during the maintenance phase of working memory was attributed to a greater rate of decay of prefrontal activity over time in patients. Cortical deficits in patients did not appear to be related to antipsychotic treatment. In patients and in healthy subjects, the time-dependent reduction in prefrontal activity during working memory maintenance correlated with poorer performance on the memory task. Overall, these data highlight that basic research insights into the distinct neurobiologies of the maintenance and response phases of working memory are of potential importance for understanding the neurobiology of cognitive impairment in schizophrenia and advancing its treatment. | 18,823,880 |
The kynurenines are associated with oxidative stress, inflammation and the prevalence of cardiovascular disease in patients with end-stage renal disease. | Increased oxidative stress (SOX), inflammation and prevalence of cardiovascular disease (CVD) have been reported in end-stage renal disease (ESRD), but their associations with kynurenine (KYN) pathway activation remain unknown. We determined the plasma concentrations of tryptophan (TRP), KYN, 3-hydroxykynurenine (3-HKYN); two distinct SOX markers: Cu/Zn superoxide dismutase (Cu/Zn SOD) and total peroxide; and high sensitivity C-reactive protein (hs CRP) as a indicator of inflammation in 146 ESRD patients and healthy controls. Analysis of TRP degradation through the KYN pathway demonstrated that in uremia the concentrations of this aminoacid were decreased by 40-60% in comparison with controls. In contrast, the plasma levels of KYN and 3-HKYN in ESRD patients were increased by 32-96% and 184-306%, respectively. These changes were accompanied by significant increase in the kyn/trp ratios by 140-240%, and 3-hkyn/kyn ratios by 40-154% in uremics compared to controls. ESRD patients showed a significant increase in Cu/Zn SOD, total peroxide and hs CRP levels between controls and all patients group. KYN and 3-HKYN were positively associated with inflammation and SOX markers in uremics. Logistic regression analysis showed that age, gender, presence of DM (all p<0.001), elevated hs CRP (p<0.01) and 3-HKYN levels (p<0.05) were independently associated with the presence of CVD in this population. These results suggest a relationship between KYN pathway activation and increased SOX, inflammation and CVD prevalence in ESRD patients. | 18,823,890 |
Preparation of a sulfoxide group and ammonium-salt bonded silica stationary phase for separation of polychlorinated biphenyls from mineral oils. | In this study, a silica stationary phase modified with sulfoxide group and ammonium-salt was prepared for the separation of polychlorinated biphenyls (PCBs) from mineral oils, and its properties were investigated. Organic sulfide was attached to a diamino (primary and secondary amino) bonded silica surface by an amide bond, and the bonded sulfide groups were oxidized with periodate to afford sulfoxide groups bonded to the stationary phase. The secondary amino groups in the spacer chain were converted to ammonium-salt by the addition of hydrochloric acid. The sulfoxide group and ammonium-salt bonded stationary phase was tested for their suitability as adsorbent for SPE-type preparative short columns and for an analytical HPLC-type separation. The new stationary phase (1.2 mmol of sulfur bonded per gram) separated PCBs from mineral oils (paraffin-based transformer oils) more efficiently than previously reported stationary phases including sulfoxide group or ammonium-salt bonded ones. The quantitative chromatographic parameters for an aliphatic hydrocarbon (eicosane) and some PCB congeners also indicated strong retention of highly chlorinated biphenyls by the sulfoxide and ammonium-salt bonded silica compared with simple aminopropyl, sulfoxide group or ammonium-salt bonded ones. A cleanup procedure was established for simple determination of PCBs in mineral oil samples using sulfoxide group and ammonium-salt bonded silica packed column fractionation. The analytical method, combination of the cleanup procedure, and measurement with a GC-high resolution (magnetic sector) MS or a GC-quadrupole MS were validated using mineral oil certified reference materials. | 18,823,892 |
Parental assessments of internalizing and externalizing behavior and executive function in children with primary hypertension. | To determine the relations between hypertension and parental ratings of behavior and executive functions in children with primary hypertension and to examine the potential moderating influence of obesity. Hypertensive and normotensive control groups were matched for age, sex, race, intelligence quotient, maternal education, household income, and obesity. Parents completed the Child Behavior Checklist to assess Internalizing and Externalizing problems and the Behavior Rating Inventory of Executive Function to assess behavioral correlates of executive function. Thirty-two hypertensive subjects and 32 normotensive control subjects (aged 10 to 18 years) were enrolled. On the Child Behavior Checklist, hypertensives had higher Internalizing T-scores (53 vs 44.5, P = .02) with 37% falling within the clinically significant range vs 6% of control subjects (P = .005). Internalizing score increased with increasing body mass index percentile in hypertensive but not normotensive subjects. Hypertensives had worse Behavior Rating Inventory of Executive Function Global Executive Composite T-scores compared with control subjects (50 vs 43, P = .009). Children with both hypertension and obesity demonstrate higher rates of clinically significant internalizing problems, and hypertensives (irrespective of obesity) demonstrate lower parental ratings of executive function compared with normotensive control subjects. | 18,823,913 |
Advanced post-processing for scanned ultrasonic arrays: application to defect detection and classification in non-destructive evaluation. | This paper describes a number of array post-processing methods developed for scanning applications in non-destructive evaluation. The approach is to capture and process the full matrix of all transmit-receive time-domain signals from the array. Post-processing the data in this way enables a multitude of imaging modalities to be implemented, including many that could not feasibly be achieved using conventional parallel firing techniques. The authors have previously published work on imaging algorithms for improving the characterisation of defects in solids by post-processing the data from a static linear ultrasonic array. These algorithms are extended and applied to data from a scanned array. This allows the effective aperture and range of probing angles to be increased, hence improving imaging and defect characterisation performance. Practical implementation issues such as scanning speed and data transfer are discussed. | 18,823,924 |
Advanced treatment of the reverse osmosis concentrate produced during reclamation of municipal wastewater. | The work investigated the treatment of the concentrate produced from the reverse osmosis treatment of an MBR effluent. Two conventional chemical processes, coagulation and activated carbon adsorption, and three advanced oxidation processes (electrochemical treatment, photocatalysis and sonolysis) were applied. Coagulation with alum gave dissolved organic carbon (DOC) removals up to 42%, while FeCl(3) achieved higher removals (52%) at lower molar doses. Adsorption with granular activated carbon showed the highest DOC removals up to 91.3% for 5 g/L. The adsorption isotherm was linear with a non-adsorbable organic fraction of around 1.2 mg/L DOC. The three oxidation methods employed, electrolytic oxidation over a boron-doped diamond electrode, UVA/TiO2 photocatalysis and sonolysis at 80 kHz, showed similar behavior: during the first few minutes of treatment there was a moderate removal of DOC followed by further oxidation at a very slow rate. Electrolytic oxidation was capable of removing up to 36% at 17.8A after 30 min of treatment, sonolysis removed up to 34% at 135W after 60 min, while photocatalysis was capable of removing up to 50% at 60 min. | 18,823,926 |
Role of integrin-linked kinase for functional capacity of endothelial progenitor cells in patients with stable coronary artery disease. | Number and function of endothelial progenitor cells (EPCs) are down-regulated in patients with coronary artery disease (CAD). Integrin-linked kinase (ILK) is a signal and adaptor protein that regulates survival of mature endothelial cells and vascular development. Here we show that EPC dysfunction in patients with CAD is paralleled by down-regulation of ILK while restoration of ILK expression rescues the migratory defect of CAD-EPCs. Human EPCs transduced with dominant-negative ILK (DN-ILK) display significantly reduced expression of CD34(+)/VEGFR-2(+), DiI-Ac-LDL uptake, and Ulex europaeus lectin binding. Mechanistically, DN-ILK-transfected EPCs are characterized by decreased proliferation, while proliferation is increased in wild-type ILK-transfected EPCs. These effects are paralleled by changes in cyclin D1 expression, colony forming units, and cytoskeletal rearrangement. Functionally, ILK is necessary and sufficient for SDF-1-triggered migration and adhesion in EPCs. These data extend current knowledge about the role of ILK in EPC biology and implicate ILK as a therapeutic target in CAD. | 18,823,942 |
Differential effects of glutamate transporter inhibitors on the global electrophysiological response of astrocytes to neuronal stimulation. | Astrocytes are responsible for regulating extracellular levels of glutamate and potassium during neuronal activity. Glutamate clearance is handled by glutamate transporter subtypes glutamate transporter 1 and glutamate-aspartate transporter in astrocytes. DL-threo-beta-benzyloxyaspartate (TBOA) and dihydrokainate (DHK) are extensively used as inhibitors of glial glutamate transport activity. Using whole-cell recordings, we characterized the effects of both transporter inhibitors on afferent-evoked astrocyte currents in acute cortical slices of 3-week-old rats. When neuronal afferents were stimulated, passive astrocytes responded by a rapid inward current followed by a persistent tail current. The first current corresponded to a glutamate transporter current. This current was inhibited by both inhibitors and by tetrodotoxin. The tail current is an inward potassium current as it was blocked by barium. Besides inhibiting transporter currents, TBOA strongly enhanced the tail current. This effect was barium-sensitive and might be due to a rise in extracellular potassium level and increased glial potassium uptake. Unlike TBOA, DHK did not enhance the tail current but rather inhibited it. This result suggests that, in addition to inhibiting glutamate transport, DHK prevents astrocyte potassium uptake, possibly by blockade of inward-rectifier channels. This study revealed that, in brain slices, glutamate transporter inhibitors exert complex effects that cannot be attributed solely to glutamate transport inhibition. | 18,823,961 |
Use of ProteinChip technology for identifying biomarkers of parasitic diseases: the example of porcine cysticercosis (Taenia solium). | Taenia solium cysticercosis is a significant public health problem in endemic countries. The current serodiagnostic techniques are not able to differentiate between infections with viable cysts and infections with degenerated cysts. The objectives of this study were to identify specific novel biomarkers of these different disease stages in the serum of experimentally infected pigs using ProteinChip technology (Bio-Rad) and to validate these biomarkers by analyzing serum samples from naturally infected pigs. In the experimental sample set 30 discriminating biomarkers (p<0.05) were found, 13 specific for the viable phenotype, 9 specific for the degenerated phenotype and 8 specific for the infected phenotype (either viable or degenerated cysts). Only 3 of these biomarkers were also significant in the field samples; however, the peak profiles were not consistent among the two sample sets. Five biomarkers discovered in the sera from experimentally infected pigs were identified as clusterin, lecithin-cholesterol acyltransferase, vitronectin, haptoglobin and apolipoprotein A-I. | 18,823,977 |
Trypanosoma cruzi: Induction of benznidazole resistance in vivo and its modulation by in vitro culturing and mice infection. | Through a continuous in vivo drug pressure protocol, using mice as experimental model, we induced benznidazole resistance in Trypanosoma cruzi stocks. Full resistance was obtained for four out of five T. cruzi stocks analyzed. However, the number of benznidazole doses (40-180), as well as the time (4-18 months) necessary to induce resistance varied among the different T. cruzi stocks. The resistance phenotype remained stable after T. cruzi stocks has been maintained by 12 passages in mice (six months) and in acellular culture for the same time. However, the maintenance of resistant parasite for 12 months in acellular culture induces a reduction in its level of benznidazole resistance, while no alteration was detected in parasite maintained for the same time in mice. The data showed the stability of the resistance acquired by drug pressure, but suggest the possibility of reversible changes in the resistance levels after maintenance for long time in acellular culture. | 18,823,980 |
Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in postoperative Crohn's disease. | The benefit of therapy for prevention of postoperative recurrence of Crohn's disease (CD) is limited. Clinical relapse and severe endoscopic recurrence are the main outcomes in the evaluation of trials on prevention of recurrence. The aim of this meta-analysis was to focus on knowledge of the placebo rates of relapse and recurrence in postoperative CD and to identify factors influencing these rates. We performed a meta-analysis of placebo-controlled, randomized clinical trials, evaluating therapies for postoperative maintenance of CD identified on MEDLINE from 1990 to 2006. Primary outcomes were clinical relapse and severe endoscopic recurrence. The pooled estimate of the placebo relapse rate was 23.7% (95% confidence interval [CI], 13-35; range 0-78). There was a statistically significant heterogeneity among studies (P < .0001). Heterogeneity in clinical relapse was present even if the trials were stratified according to the time of outcome. The pooled estimate of the severe endoscopic recurrence rate was 50.2% (95% CI, 28-73; range, 30-79). There was significant heterogeneity among the studies (P = .00038). This heterogeneity was less apparent in studies carried out within 12 months. The logistic analysis identified only duration of follow-up as a variable associated with different placebo relapse rates. No variable was identified as a predictor of a placebo endoscopic recurrence rate. There is significant heterogeneity among placebo rates in postoperative CD. No single design variable was identified that explained the heterogeneity in placebo outcomes for clinical or endoscopic recurrence. | 18,823,987 |
Several major antiepileptic drugs are substrates for human P-glycoprotein. | One of the current hypotheses of pharmacoresistant epilepsy proposes that transport of antiepileptic drugs (AEDs) by drug efflux transporters such as P-glycoprotein (Pgp) at the blood-brain barrier may play a significant role in pharmacoresistance in epilepsy by extruding AEDs from their intended site of action. However, several recent in vitro studies using cell lines that overexpress efflux transporters indicate that human Pgp may not transport AEDs to any relevant extent. In this respect it has to be considered that most AEDs are highly permeable, so that conventional bi-directional transport assays as used in these previous studies may fail to identify AEDs as Pgp substrates, particularly if these drugs are not high-affinity substrates for Pgp. In the present study, we used a modified transport assay that allows evaluating active transport independently of the passive permeability component. In this concentration equilibrium transport assay (CETA), the drug is initially added at identical concentration to both sides of a polarized, Pgp-overexpressing cell monolayer instead of applying the drug to either the apical or basolateral side for studying bi-directional transport. Direct comparison of the conventional bi-directional (concentration gradient) assay with the CETA, using MDR1-transfected LLC cells, demonstrated that CETA, but not the conventional assay, identified phenytoin and phenobarbital as substrates of human Pgp. Furthermore, directional transport was determined for lamotrigine and levetiracetam, but not carbamazepine. Transport of AEDs could be completely or partially (>50%) inhibited by the selective Pgp inhibitor, tariquidar. However, transport of phenobarbital and levetiracetam was also inhibited by MK571, which preferentially blocks transport by multidrug resistance transporters (MRPs), indicating that, in addition to Pgp, these AEDs are substrates of MRPs. The present study provides the first direct evidence that several AEDS are substrates of human Pgp, thus further substantiating the transporter hypothesis of pharmacoresistant epilepsy. | 18,824,002 |
Regulation of cytochrome P4501A1 expression by hyperoxia in human lung cell lines: Implications for hyperoxic lung injury. | Supplemental oxygen, used to treat pulmonary insufficiency in newborns, contributes to the development of bronchopulmonary dysplasia (BPD). Cytochrome P4501A enzymes are induced by hyperoxia in animal models, but their role in human systems is unknown. Here we investigated the molecular mechanisms of induction of CYP1A1 by hyperoxia in human lung cell lines. Three human lung cell lines were exposed to hyperoxia (95% O2) for 0-72 h, and CYP1A1 activities, apoprotein contents, and mRNA levels were determined. Hyperoxia significantly induced CYP1A1 activity and protein contents (2-4 fold), and mRNA levels (30-40 fold) over control in each cell line. Transfection of a CYP1A1 promoter/luciferase reporter construct, followed by hyperoxia (4-72 h), showed marked (2-6 fold) induction of luciferase expression. EMSA and siRNA experiments strongly suggest that the Ah receptor (AHR) is involved in the hyperoxic induction of CYP1A1. MTT reduction assays showed attenuation of cell injury with the CYP1A1 inducer beta-naphthoflavone (BNF). Our results strongly suggest that hyperoxia transcriptionally activates CYP1A1 expression in human lung cell lines by AHR-dependent mechanisms, and that CYP1A1 induction is associated with decreased toxicity. This novel finding of induction of CYP1A1 in the absence of exogenous AHR ligands could lead to novel interventions in the treatment of BPD. | 18,824,009 |
Expression profiles of cloned channel catfish (Ictalurus punctatus) lymphoid cell lines and mixed lymphocyte cultures. | Clonal channel catfish lymphoid cell lines and mixed lymphocyte cultures (MLCs) have proven extremely useful in examining immune responses at the cellular and molecular levels. To date clonal catfish cell lines and MLCs have been biologically and phenotypically characterized using a variety of techniques including reverse transcription polymerase chain reaction (RT-PCR), as well as Northern and Southern blotting. To expand the molecular characterization of these cultures, microarray analysis was employed. Clonal B (3B11), macrophage (42TA), and cytotoxic T cell (TS32.15 and TS32.17) lines and MLCs were examined using a cDNA array containing approximately 2500 probes derived from EST libraries prepared from the 42TA macrophage cell line, a MLC, and 5-14-day-old catfish fry. Analysis showed that each cell line displayed a unique RNA expression profile that included a variety of immune-related genes. Pearson correlation analysis indicated that one cytotoxic T cell line (TS32.15) clustered with the MLC, whereas a second cytotoxic T cell line (TS32.17) was more closely associated with a second cluster containing B cells and macrophages. This study illustrates the utility of microarray analyses in profiling RNA expression patterns in catfish lymphoid cell lines and will serve as a platform for examining catfish immune responses following virus infection or poly [I:C] treatment. | 18,824,023 |
Proteomic analysis of curdlan-producing Agrobacterium sp. in response to pH downshift. | During batch cultivation of Agrobacterium sp. ATCC 31750, proteome analysis in response to a pH downshift from 7.0 to 5.5 was carried out using two-dimensional electrophoresis and matrix-assisted laser desorption-ionization-time of flight mass spectrometry. When the pH of the exponentially growing Agrobacterium sp. culture was downshifted to pH 5.5, the synthesis level of 27 intracellular proteins showed significant changes in level over a prolonged period of time compared with the batch culture controlled at pH 7.0. In particular, the intracellular protein level of the beta-1,3-glucan synthase catalytic subunit, UTP-glucose-1-phosphate uridylyltransferase, and phosphoglucomutase, which are key metabolic enzymes in the curdlan biosynthesis pathway, were more than 10-, 3- and 17-times higher in the low pH culture. On the other hand, the level of orotidine5-phosphate decarboxylase (conversion of OMP to UMP) was significantly up-regulated after pH downshift. The accumulation of UMP may direct the metabolic flow towards the biosynthetic route of UTP, which is a key metabolic precursor for UDP-glucose. Therefore, it is possible that increase of cellular metabolic enzymes during pH downshift culture can enhance the metabolic flux of the biosynthesis of key precursor, such as UTP- and UDP-glucose, resulting in an increase in curdlan biosynthesis. | 18,824,044 |
Does vivid emotional imagery depend on body signals? | The recall and re-experiencing of a personal emotional event (emotional imagery) are thought to evoke neural activity in the central nervous system that can affect the physiology of bodily states. It has been proposed that the more active the neural systems previously engaged in the emotional experience, and the more active the bodily state associated with that experience, the more vivid the emotional imagery is. The sympathetic nervous system (SNS) and the gastrointestinal system (GI) are engaged in emotional reactions. On this basis, we hypothesized that vivid emotional imagery would be accompanied by strong increases in gastrointestinal and sympathetic nervous system activity. To test this hypothesis, 17 healthy participants performed emotional imagery of strong autobiographical memories involving various emotional states (happy, fear, disgust, sadness, anger). SNS and GI changes, measured by skin conductance and electrogastrogram, respectively, correlated positively with subjective ratings of arousal during the imagery. However, the SNS changes did not correlate with ratings of emotional imagery vividness, and even more intriguingly, the GI changes correlated strongly and negatively with vividness ratings. To account for these findings, we propose that in highly vivid imagery experience, the central nervous system is simulating the whole emotional experience strongly, and bodily information plays a lesser role. In low vivid imagery experience, the central nervous system is not simulating very strongly the emotional experience, and information coming from the body (including the GI system) plays a greater role. This interpretation is set forth in the context of Damasio's [Damasio, A., (1999) The feeling of what happens: body and emotion in the making of consciousness, Orlando, Fl, Harcourt.] theoretical framework, which predicts such a dissociation between a "body loop" and an "as if body loop" for the experiencing and re-experiencing of emotions and feelings. | 18,824,045 |
Analysis of cyanogens with resorcinol and picrate. | The total cyanogenic potential of various substrates (flax seed, stones of peach, plum, nectarine and apricot as well as apple seeds, and various model compounds) was investigated by using the acid hydrolysis method, picrate method, and a novel method based on the reaction of cyanide liberated from plants with resorcinol and picrate. The hydrocyanic acid liberated from cyanogens was trapped by using a 1% sodium bicarbonate. Then, 1 ml of extract was mixed with 1 ml of working reagent containing 160 microg of resorcinol, 320 microg of picric acid, and 30 mg of sodium carbonate, and heated on a boiling water bath for 10 min. The absorbance was measured at 488 nm in 1cm glass cuvettes at room temperature. The color system obeys Beer's law in the range of 0-5 microg ml(-1) total HCN. Using model compounds and real samples including replicate analyses on prunasin, the resorcinol method proved to be more accurate, reproducible, and especially more sensitive than the known spectrophotometric methods such as the acid hydrolysis method and the picrate method. | 18,824,068 |
A novel SNP in a vitamin D response element of the CYP24A1 promoter reduces protein binding, transactivation, and gene expression. | The active form of vitamin D (1alpha,25(OH)(2)D(3)) is known to have antiproliferative effects and has been implicated in cancers of the colon, breast, and prostate. These cancers occur more frequently among African Americans than Caucasians, and individuals with African ancestry are known to have approximately twofold lower levels of serum vitamin D (25(OH)D) compared with individuals of European ancestry. However, epidemiological studies of the vitamin D receptor (VDR) have shown inconsistent associations with cancer risk, suggesting that differences in other genes in the pathway may be important. We sought to identify functionally significant polymorphic variants in CYP24A1, a gene that is highly inducible by 1alpha,25(OH)(2)D(3) and that encodes the primary catabolic enzyme in the pathway. Here we report the identification of six novel SNPs in the human CYP24A1 promoter, including one at nucleotide -279 occurring within the distal vitamin D response element (VDRE2). Our experiments demonstrate that the VDRE2 variant results in decreased protein binding and transactivation in vitro, and reduced expression of CYP24A1 in cultured primary human lymphocytes provides evidence for an effect in vivo. This variant was only observed in our African American population, and represents a first step toward understanding differences in disease risk among racial/ethnic groups. | 18,824,104 |
CB(1) receptor antagonism: biological basis for metabolic effects. | The endocannabinoid system (ECS) is a complex physiologic system that affects metabolic pathways. A dysregulated ECS has been demonstrated in animal models of obesity and the expression of the cannabinoid type 1 (CB(1)) receptor in both brain and peripheral tissues suggests that selective antagonism at this receptor could target multiple tissues involved in metabolic homeostasis. In clinical trials with obese patients, treatment with the CB(1) receptor antagonist rimonabant was associated with clinically meaningful weight loss, as well as improved serum lipids and glycemic control. The biological basis for the metabolic effects of rimonabant (SR141716) appears to involve the modulation of metabolism through antagonism at a single receptor with several target organs. | 18,824,122 |
Targeting virulence traits: potential strategies to combat extraintestinal pathogenic E. coli infections. | Extraintestinal pathogenic Escherichia coli (ExPEC) are able to colonize, invade and induce disease in body niches outside the gastrointestinal tract. The emergence of (multi)resistant ExPEC variants calls for alternative antimicrobial strategies with a reduced pressure on selection of antibiotic resistances. We report on recent research efforts to target such virulence traits or to interfere with ExPEC colonization of extraintestinal niches in order to prevent or treat ExPEC infections and reduce the risk of further emergence of antibiotic resistances. | 18,824,126 |
Small-molecule catalysts of oxidative protein folding. | Oxidative protein folding occurs both in vivo and in vitro and involves the formation and rearrangement of protein disulfide bonds (SS bonds). In vivo these reactions are catalyzed by enzymes, including the eukaryotic enzyme protein disulfide isomerase (PDI). Using the physical properties of PDI as a guide, several small-molecule catalysts of oxidative protein folding have been designed, synthesized, and tested. These small molecules can improve the folding rate of the model substrate ribonuclease A by a factor of over 10 and improve the yield by up to a factor of 3 over traditional conditions. The molecules have also been demonstrated to significantly improve the in vivo folding of proteins as well. | 18,824,127 |
Long-term effects of candesartan and amlodipine on cardiovascular mortality and morbidity in Japanese high-risk hypertensive patients: rationale, design, and characteristics of candesartan antihypertensive survival evaluation in Japan extension (CASE-J Ex). | Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial was conducted to compare the effects of the angiotensin II receptor blocker (ARB) candesartan and the calcium channel blocker (CCB) amlodipine on the incidence of cardiovascular (CV) events in Japanese high-risk hypertensive patients. After 3.2years follow-up, CV events rate was 17.6-17.7 per 1000 person-years in each group, which was much lower than we expected. Since it has not been known whether the same efficacy of two drugs is sustained beyond the current trial, a longer follow-up period will be needed. The Steering Committee of CASE-J trial decided to extend the trial for 3years as an observational study (CASE-J Ex). In CASE-J Ex, the primary end point is a composite of CV events and the secondary endpoints are all-cause death and new-onset diabetes. After Committee's decision, 245 doctors agreed to participate in CASE-J Ex and 2236 patients (1141 with candesartan-based regimens and 1095 with amlodipine-based regimens) were re-enrolled. The baseline characteristics of CASE-J Ex participants were similar to CASE-J participants and still balanced well between candesartan and amlodipine. Recently, the interest of antihypertensive treatment has focused to differentiation of the effects of antihypertensive agents on the incidence of CV events as well as blood pressure lowering effect. CASE-J Ex will clarify the long-term effects of ARB and CCB on CV mortality and morbidity. Additionally, because the number of diabetic patients is increased, the evidences from CASE-J Ex will be valuable. | 18,824,134 |
Clinical correlations of human cytomegalovirus strains and viral load in kidney transplant recipients. | Little is known about clinical differences associated with cytomegalovirus (CMV) infection by distinct strains in renal transplant patients. Different clinical pictures may be associated with specific viral genotypes, viral load, as well as host factors. The objective of this study was to identify CMV strains to determine viral load (antigenemia), and their correlation with clinical data in renal transplant recipients. Seventy-one patients were enrolled, comprising 91 samples. After selection, polymorphonuclear cells were used to amplify and sequence the gB region of CMV DNA. The sequences were analyzed to ascertain the frequency of different genotypes. Additionally, the results of this study showed that the gB coding gene presents a great variability, revealing a variety of patterns: classical gB1 (1.4%), gB1V (46.4%), classical gB2 (35.2%), gB2V (2.8%), gB3 (1.4%), classical gB4 (4.9%) and gB4V (4.9%). The mean viral load in kidney transplant patient was 75.1 positive cells (1-1000). A higher viral load was observed in patients with genotype 4 infection. Statistically significant differences were detected between gB1 and gB4 (p=0.010), and between gB2 and gB4 (p=0.021). The average numbers of positive cells in relation to clinical presentation were: 34.5 in asymptomatic, 49.5 in CMV associated syndrome and 120.7 in patients with invasive disease (p=0.048). As a group, gB1 was the most frequent strain and revealed a potential risk for developing invasive disease. Viral load also seemed to be important as a marker associated with clinical presentation of the disease. | 18,824,137 |
Rat visceral yolk sac (VYS) and placenta mitochondrial features during the placentation period. | The transference of the nutritional function from the VYS to the chorioallantoic placenta during middle pregnancy is a key event for the activation of embryo oxidative metabolism. However, the metabolic adaptations occurring in these tissues during this critical period have not been studied to date. Herein, we investigate the VYS and placenta mitochondrial adaptations throughout gestational days 11, 12 and 13. The results reflect that, during the placentation period, mitochondrial proliferation predominates over differentiation in placenta. Besides, VYS development and mitochondriogenesis show a slowdown despite maintaining the mitochondrial OXPHOS capacities, hence becoming a supporting tissue until the placenta functions are completely available. | 18,824,141 |
Integrated farming: why organic farmers should use transgenic crops. | The concept of organic farming is summarised and compared as an example to farming with biotechnology-derived crops. If done within an ecological concept, both methods can be seen as environmentally acceptable. Organic farming does not offer consistent arguments for the rejection of transgenic crops. Some arguments (from genomics to biodiversity) are discussed in order to demonstrate that the contrast between both farming systems is rated too high and that it is possible to overcome the divide. In this way the ground is prepared for a proposal on how to merge those otherwise incompatible agricultural management systems, a proposal that also will have to build on a new concept of sustainability. It will be dealt with in the second part of the article in the next issue of New Biotechnology. | 18,824,150 |
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