Atrial Natriuretic Peptide Protects against Histamine-Induced Endothelial Barrier Dysfunction in Vivo

Endothelial barrier dysfunction is a hallmark of many severe pathologies, including sepsis or atherosclerosis. The cardiovascular hormone atrial natriuretic peptide (ANP) has increasingly been suggested to counteract endothelial leakage. Surprisingly, the precise in vivo relevance of these observations has never been evaluated. Thus, we aimed to clarify this issue and, moreover, to identify the permeability-controlling subcellular systems that are targeted by ANP. Histamine was used as important pro-inflammatory, permeability-increasing stimulus. Measurements of fluorescein isothiocyanate (FITC)-dextran extravasation from venules of the mouse cremaster muscle and rat hematocrit values were performed to judge changes of endothelial permeability in vivo. It is noteworthy that ANP strongly reduced the histamine-evoked endothelial barrier dysfunction in vivo. In vitro, ANP blocked the breakdown of transendothelial electrical resistance (TEER) induced by histamine. Moreover, as judged by immunocytochemistry and Western blot analysis, ANP inhibited changes of vascular endothelial (VE)-cadherin, β-catenin, and p120ctn morphology; VE-cadherin and myosin light chain 2 (MLC2) phosphorylation; and F-actin stress fiber formation. These changes seem to be predominantly mediated by the natriuretic peptide receptor (NPR)-A, but not by NPR-C. In summary, we revealed ANP as a potent endothelial barrier protecting agent in vivo and identified adherens junctions and the contractile apparatus as subcellular systems targeted by ANP. Thus, our study highlights ANP as an interesting pharmacological compound opening new therapeutic options for preventing endothelial leakage

On the existence and uniqueness of solutions to stochastic differential equations driven by G-Brownian motion with integral-Lipschitz coefficients

In this paper, we study the existence and uniqueness of solutions to stochastic differential equations driven by G-Brownian motion (GSDEs) with integral-Lipschitz conditions on their coefficients

Stress induced hyperglycemia and the subsequent risk of type 2 diabetes in survivors of critical illness

OBJECTIVE: Stress induced hyperglycemia occurs in critically ill patients who have normal glucose tolerance following resolution of their acute illness. The objective was to evaluate the association between stress induced hyperglycemia and incident diabetes in survivors of critical illness. DESIGN: Retrospective cohort study. SETTING: All adult patients surviving admission to a public hospital intensive care unit (ICU) in South Australia between 2004 and 2011. PATIENTS: Stress induced hyperglycemia was defined as a blood glucose ≥ 11.1 mmol/L (200 mg/dL) within 24 hours of ICU admission. Prevalent diabetes was identified through ICD-10 coding or prior registration with the Australian National Diabetes Service Scheme (NDSS). Incident diabetes was identified as NDSS registration beyond 30 days after hospital discharge until July 2015. The predicted risk of developing diabetes was described as sub-hazard ratios using competing risk regression. Survival was assessed using Cox proportional hazards regression. MAIN RESULTS: Stress induced hyperglycemia was identified in 2,883 (17%) of 17,074 patients without diabetes. The incidence of type 2 diabetes following critical illness was 4.8% (821 of 17,074). The risk of diabetes in patients with stress induced hyperglycemia was approximately double that of those without (HR 1.91 (95% CI 1.62, 2.26), p<0.001) and was sustained regardless of age or severity of illness. CONCLUSIONS: Stress induced hyperglycemia identifies patients at subsequent risk of incident diabetes.Mark P. Plummer, Mark E. Finnis, Liza K. Phillips, Palash Kar, Shailesh Bihari, Vishwanath Biradar, Stewart Moodie, Michael Horowitz, Jonathan E. Shaw, Adam M. Dean

An evaluation of knowledge, attitude and practice of pharmacovigilance among interns in a tertiary care teaching hospital of North Maharashtra

Background: Adverse Drug Reactions (ADRs) are considered as one of the leading cause throughout the world resulting in significant increase in mortality and morbidity, therefore its monitoring is very essential in today's practice of medicine. Spontaneous reporting of ADRs have played a major role in the detection of unsuspected, serious and unusual ADRs previously undetected during the phases of clinical trials. Under-reporting of ADRs is considered as one of the major hurdle for the success of pharmacovigilance. Aims and objectives were to assess the knowledge, attitude and practice of pharmacovigilance among interns in a tertiary care teaching hospital.Methods: A cross sectional, observational, questionnaire based study was carried out using a predesigned Knowledge Attitude Practice (KAP) questionnaire. Study was conducted after the permission of Institutional Ethical Committee (IEC). The study included 100 interns who had completed at least ten months of their internship. The KAP questionnaire was assessed and analyzed and data was presented as percentages.Results: On an average only 31.17% interns answered correctly related with knowledge about pharmacovigilance. 88.63% interns agreed that ADRs reporting is necessary. According to 85.22% interns, pharmacovigilance must be taught in details to healthcare professionals. Only 34.09% had ever seen the ADR reporting form. Only 17.04% interns had knowledge about how to report ADR?Conclusions: Our study revealed that there was lack of awareness related with knowledge, attitude and practice of pharmacovigilance among the interns. There is need of implementation of pharmacovigilance awareness programs for undergraduates

The effect of riluzole alone and in combination with sodium valproate on pentylenetetrazole induced seizures in swiss-albino rats

Background: Riluzole- a glutamate antagonist is known to enhance antiepileptic effects of various other antiepileptic drugs. The present study was undertaken to evaluate anticonvulsant effect of riluzole alone and in combination with sodium valproate on pentylenetetrazole (Metrazol) induced seizures in swiss-albino rats.Methods: Pentylenetetrazole (PTZ) 50 mg/kg intraperitonially (ip) was used to induce seizure in swiss- albino rats. Anticonvulsant effect of riluzole (at 5 mg/kg and 10 mg/kg) and sodium valproate (at 75 mg/kg, 150 mg/kg and 300 mg/kg) was studied on PTZ induced seizures in albino rats. Also effect of riluzole (10mg/kg) in combination with sodium valproate (75 mg/kg, 150 mg/kg and 300 mg/kg) was studied.  Parameters such as time of onset of first clonic convulsion in seconds, frequency of clonic convulsion in 60 minute and total duration of entire convulsion in minutes were studied. For statistical analysis unpaired t test was used.Results: At 5 mg/kg and 10 mg/kg doses riluzole per se was not found to produce any significant effect in PTZ induced seizures (P>0.05). Sodium valproate at 300 mg/kg dose was found to produce significant antiepileptic effect (P0.05). Interestingly significant antiepileptic effect was noted with combination of riluzole (at 10 mg/kg) with sodium valproate at 150 mg/kg and 300 mg/kg dose (P<0.001).Conclusions: Riluzole alone was not found to produce any significant protective effect against PTZ induced seizures in albino rats. However riluzole (10 mg/kg) was found to enhance the antiepileptic activity of sodium valproate

What scientific applications can benefit from hardware transactional memory?

Achieving efficient and correct synchronization of multiple threads is a difficult and error-prone task at small scale and, as we march towards extreme scale computing, will be even more challenging when the resulting application is supposed to utilize millions of cores efficiently. Transactional Memory (TM) is a promising technique to ease the burden on the programmer, but only recently has become available on commercial hardware in the new Blue Gene/Q system and hence the real benefit for realistic applications has not been studied, yet. This paper presents the first performance results of TM embedded into OpenMP on a prototype system of BG/Q and characterizes code properties that will likely lead to benefits when augmented with TM primitives. We first, study the influence of thread count, environment variables and memory layout on TM performance and identify code properties that will yield performance gains with TM. Second, we evaluate the combination of OpenMP with multiple synchronization primitives on top of MPI to determine suitable task to thread ratios per node. Finally, we condense our findings into a set of best practices. These are applied to a Monte Carlo Benchmark and a Smoothed Particle Hydrodynamics method. In both cases an optimized TM version, executed with 64 threads on one node, outperforms a simple TM implementation. MCB with optimized TM yields a speedup of 27.45 over baseline