The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

Abstract Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 μg/ml (in cases). Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral effectiveness. Larger sample sized studies and longer follow-up are required to identify populations of individuals where the reduction in nevirapine concentration may result in lower ART response or shorter response duration

Location and Level of Etk Expression in Neurons Are Associated with Varied Severity of Traumatic Brain Injury

Much recent research effort in traumatic brain injury (TBI) has been devoted to the discovery of a reliable biomarker correlating with severity of injury. Currently, no consensus has been reached regarding a representative marker for traumatic brain injury. In this study, we explored the potential of epithelial/endothelial tyrosine kinase (Etk) as a novel marker for TBI.TBI was induced in Sprague Dawley (SD) rats by controlled cortical impact. Brain tissue samples were analyzed by Western blot, Q-PCR, and immunofluorescence staining using various markers including glial fibrillary acidic protein, and epithelial/endothelial tyrosine kinase (Etk). Results show increased Etk expression with increased number and severity of impacts. Expression increased 2.36 to 7-fold relative to trauma severity. Significant upregulation of Etk appeared at 1 hour after injury. The expression level of Etk was inversely correlated with distance from injury site. Etk and trauma/inflammation related markers increased post-TBI, while other tyrosine kinases did not.The observed correlation between Etk level and the number of impacts, the severity of impact, and the time course after impact, as well as its inverse correlation with distance away from injury site, support the potential of Etk as a possible indicator of trauma severity

Effect of semi-solid heat treatment on elevated temperature plasticity of 304L stainless steel

The present work explores the potential of semi-solid heat treatment technique by elucidating its effect on the plastic behavior of 304L SS in hot working domain. To accomplish this objective, hot isothermal compression tests on 304L SS specimens with semi-solid heat treatment and conventional annealing heat treatment have been carried out within a temperature range of 1273-1473 K and strain rates ranging from 0.01 to 1 s(-1). The dynamic flow behavior of this steel in its conventional heat-treated condition and semi-solid heat-treated condition has been characterized in terms of strain hardening, temperature softening, strain rate hardening, and dynamic flow softening. Extensive microstructural investigation has been carried out to corroborate the results obtained from the analysis of flow behavior. Detailed analysis of the results demonstrates that semi-solid heat treatment moderates work hardening, strain rate hardening, and temperature sensitivity of 304L SS, which is favorable for hot deformation. The post-deformation hardness values of semi-solid heat-treated steel and conventionally heat-treated steel were found to remain similar despite the pre-deformation heat treatment conditions. The results obtained demonstrate the potential of semi-solid heat treatment as a pre-deformation heat treatment step to effectively reduce the strength of the material to facilitate easier deformation without affecting the post-deformation properties of the steel

Role of grain boundary ferrite layer in dynamic recrystallization of semi-solid processed type 304L austenitic stainless steel

A semi-solid processed steel with well arranged delta-ferrite layer around the austenite-solid globules is found to show different dynamic recrystallization (DRX) pattern compared to its conventionally processed counterpart with ferrite stringers across the austenite grains. Analysis of experimental results indicates that the presence of delta-ferrite layer around austenite-globules delays the nucleation of new DRX grains. On the other hand, with increase in temperature, the delta-ferrite layer contributes to increase in DRX fraction by restricting the grain growth of the austenite matrix prior to deformation. (C) 2016 Elsevier B.V. All rights reserved

Bond graph modelling and simulation of fault scenarios in switched power electronic systems

A bond graph representation of switching devices known for a long time has been a modulated transformer with a modulus b(t)∈{0,1}∀t≥0 in conjunction with a resistor R:Ron accounting for the ON-resistance of a switch considered non-ideal. Besides other representations, this simple model has been used in bond graphs for simulation of the dynamic behaviour of hybrid systems. A previous article of the author has proposed to use the transformer–resistor pair in bond graphs for fault diagnosis in hybrid systems. Advantages are a unique bond graph for all system modes, the application of the unmodified standard Sequential Causality Assignment Procedure, fixed computational causalities and the derivation of analytical redundancy relations incorporating ‘Boolean’ transformer moduli so that they hold for all system modes. Switches temporarily connect and disconnect model parts. As a result, some independent storage elements may temporarily become dependent, so that the number of state variables is not time-invariant. This article addresses this problem in the context of modelling and simulation of fault scenarios in hybrid systems. In order to keep time-invariant preferred integral causality at storage ports, residual sinks previously introduced by the author are used. When two storage elements become dependent at a switching time instance ts, a residual sink is activated. It enforces that the outputs of two dependent storage elements become immediately equal by imposing the conjugate3 power variable of appropriate value on their inputs. The approach is illustrated by the bond graph modelling and simulation of some fault scenarios in a standard three-phase switched power inverter supplying power into an RL-load in a delta configuration. A well-developed approach to model-based fault detection and isolation is to evaluate the residual of analytical redundancy relations. In this article, analytical redundancy relation residuals have been computed numerically by coupling a bond graph of the faulty system to one of the non-faulty systems by means of residual sinks. The presented approach is not confined to power electronic systems but can be used for hybrid systems in other domains as well. In further work, the RL-load may be replaced by a bond graph model of an alternating current motor in order to study the effect of switch failures in the power inverter on to the dynamic behaviour of the motor