Steady-state pharmacokinetics of Nevirapine in HIV-1 infected adults in India

Background and Objectives: A variety of demographic factors, sex, and degree of immunosuppression can influence antiretroviral drug concentratians. The authors studied the influence of immune status, sex, and body mass index (BMI) on the steady-state pharmacokinetics of nevirapine delivered as a fixed-dose combination in HIV-1-infected patients in India. Methods: Twenty-six HIV-l-infected adult patients undergoing treatment with nevirapine-based highly active antiretroviral therapy regimens participated in the study. Pharmacokinetic variables were compared between patients divided based an CD4 cell counts, sex, and BMI. Results: Patients with higher BMI had lower peak and trough concentration and exposure of nevirapine than those with lower BMI; none of the differences in the pharmacokinetic variables of nevirapine between the various patient groups was statistically significant. Conclusions: Patients' immune status, sex, or BMI had no impact on the pharmacokinetics of nevirapine. Plasma nevirapine concentrations were maintained within the therapeutic range of the drug in the majority of the patients

Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy

Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy. One-third of patients have drug-refractory seizures and are left with suboptimal therapeutic options such as brain tissue-destructive surgery. Here, we report the development and characterization of a cell therapy alternative for drug-resistant MTLE, which is derived from a human embryonic stem cell line and comprises cryopreserved, post-mitotic, medial ganglionic eminence (MGE) pallial-type GABAergic interneurons. Single-dose intrahippocampal delivery of the interneurons in a mouse model of chronic MTLE resulted in consistent mesiotemporal seizure suppression, with most animals becoming seizure-free and surviving longer. The grafted interneurons dispersed locally, functionally integrated, persisted long term, and significantly reduced dentate granule cell dispersion, a pathological hallmark of MTLE. These disease-modifying effects were dose-dependent, with a broad therapeutic range. No adverse effects were observed. These findings support an ongoing phase 1/2 clinical trial (NCT05135091) for drug-resistant MTLE

Acute effects of maternal immune activation and its interaction with Gabrb3 on mouse fetal development

Autism spectrum disorder (ASD) is a group of neuro-developmental disorders characterized by social communication deficits and repetitive behaviors. ASD is believed to be caused by a number of genetic and environmental risk factors and complex interactions between them. Human clinical studies have shown an association between bacterial and viral infections in pregnant women during the first and second trimesters and ASD in their offspring. In addition, studies using animal models have linked an inflammatory state in the mother to ASD-relevant behaviors in the offspring, but the molecular mechanisms mediating the influence of these prenatal risk factors on behavior are unknown. To understand the acute effects of maternal immune activation (MIA) on embryonic neurobiological abnormalities, we administered bacterial mimetic lipopolysaccharide (LPS) and viral mimetic poly inosinic: cytidilic acid (Poly I:C) during mid-gestation in pregnant mice. In this period, the placenta, though vulnerable to environmental insults, allows for most fetuses to survive to term and for cortical neurogenesis to actively occur in the fetal brain. Twenty four hours after LPS and Poly I:C administration, we observed defects in neocortical neural progenitor proliferation and apical cytoarchitecture, differentiation and lineage specification. We also report variations in responses to LPS and Poly I:C, suggesting a differential vulnerability. Finally, we show a unique gene - environment interaction study with MIA and Gabrb3, one of the genes implicated in ASD, leading to synergistic adverse effects on pregnancy

Learner Perceptions Regarding the Lecture and the Small Group Discussion as Teaching/Learning Methods in Physiology”

Introduction: Physiology has traditionally been taught through lectures, but other methods are now being tried. One of these, the small group discussion (SGD), is considered to be more tuned to learners’ needs compared to the lecture.&#x0D; Aim: This study was undertaken to determine learner perceptions on the lecture and the SGD as teaching/learning methods in physiology.&#x0D; Methods: Ninety-seven first MBBS students were taught Physiology in both lecture and SGD formats for a whole year. Feedback was then obtained from the students using a validated and structured questionnaire. Data was entered in Excel sheet and analyzed using SPSS software.&#x0D; Results and Discussion: Learners felt that both the lecture and the SGD helped them understand basic principles well (93.4 and 93.3%), contributed effectively to the learning process (84.6 and 90%) and fostered critical thinking skills (64.9 and 68.9%). For delivery of basic concepts, learners preferred the lecture for its systematic presentation. SGDs were perceived to promote active participation of learners (85.6%), encourage facilitator-learner interaction (87.8), and retain student interest better (62.2%).Overall, learning was better-stimulated by the SGD (73.4%) rather than the lecture (35.2%).&#x0D; Conclusion: In the teaching/learning of physiology, appropriate use of both the lecture and the SGD will serve to nurture and sustain learner interest effectively.&#x0D; Bangladesh Journal of Medical Science Vol.18(2) 2019 p.274-278</jats:p

Differential interactions and structural stability of chitosan oligomers with human serum albumin and &#945;-1-glycoprotein

Chitosan is a naturally occurring deacetylated derivative of chitin with versatile biological activities. Here, we studied the interaction of chitosan oligomers with low degree of polymerization such as chitosan monomer (CM), chitosan dimer (CD), and chitosan trimer (CT) with human serum albumin (HSA) a major blood carrier protein and &#945;-1-glycoprotein (AGP). Since, HSA and AGP are the two important plasma proteins that determine the drug disposition and affect the fate of distribution of drugs. Fluorescence emission spectra indicated that CM, CD, and CT had binding constants of KCM = 6.2 ± .01 × 105 M−1, KCD = 5.0 ± .01 × 104 M−1, and KCT = 1.6 ± .01 × 106 M−1, respectively, suggesting strong binding with HSA. However, binding of chitooligomers with AGP was insignificant. Thermodynamic and molecular docking analysis indicated that hydrogen bonds and also hydrophobic interaction played an important role in stabilizing the HSA-chitooligomer complexes with free energies of −7.87, −6.35, and −8.4 Kcal/mol for CM, CD, and CT, respectively. Further, circular dichroism studies indicated a minor unfolding of HSA secondary structure, upon interaction with chitooligomers, which are supported with fluctuations of root mean square deviation (RMSD) and radius of gyration (Rg) of HSA. Docking analysis revealed that all three chitooligomers were bound to HSA within subdomain IIA (Site I). In addition, RMSD and Rg analysis depicted that HSA-chitooligomer complexes stabilized at around 4.5 ns. These results suggest that HSA might serve as a carrier in delivering chitooligomers to target tissues than AGP which has pharmacological importance