Exo1: a new chemical inhibitor of the exocytic pathway

A phenotypic screen was used to search for drug-like molecules that can interfere with specific steps in membrane traffic. 2-(4-Fluorobenzoylamino)-benzoic acid methyl ester (Exo1), identified in this screen, induces a rapid collapse of the Golgi to the endoplasmic reticulum, thus acutely inhibiting the traffic emanating from the endoplasmic reticulum. Like Brefeldin A (BFA), Exo1 induces the rapid release of ADP-ribosylation factor (ARF) 1 from Golgi membranes but has less effect on the organization of the trans-Golgi network. Our data indicate that Exo1 acts by a different mechanism from BFA. Unlike BFA, Exo1 does not induce the ADP-ribosylation of CtBP/Bars50 and does not interfere with the activity of guanine nucleotide exchange factors specific for Golgi-based ARFs. Thus, Exo1 allows the fatty acid exchange activity of Bars50 to be distinguished from ARF1 activity in the control of Golgi tubulation.     

Subtype B and subtype C HIV type 1 recombinants in the northeastern state of Manipur, India

The predominant HIV-1 strain circulating in India is subtype C. However, subtype A and B strains of HIV-1 have also been reported in India. In 1999, the first A/C recombinant strain was reported from Pune in India. Intravenous drug users (IVDUs) from the northeastern region of India have a high HIV-1 seroprevalence. Studies carried out in intravenous drug users in the northeastern region of India have shown that HIV-1 subtype C is the predominant strain infecting IVDUs. Fourteen blood samples were collected from HIV-1-infected individuals from the northeastern region of India and screened by env and gag heteroduplex mobility assays (HMA). Where the env and gag HMA results from a sample yielded different subtypes, sequencing of env and gag PCR products was carried out to confirm the presence of HIV-1 recombinants. Of the 14 samples subtyped, nine samples belonged HIV-1 subtype C (gag C/env C), one to HIV-1 subtype B (gag B/env B), and the remaining were B/C recombinants (gag C/env B). This is the first report of HIV-1 B/C recombinants from India.     

A Proposed Methodology for In Vitro Evaluation of Bitterness in Drug Solutions and In Vitro Drug Release Samples

Purpose

Ethical and safety concerns, paediatric taste panels and predictivity in early drug development for strategic decisions are some of the reasons for seeking in vitro methods of bitterness evaluation for drugs and drug products. In this study, taste panel studies and in vitro drug release studies have been performed, correlated to each other and proposed as an analytical tool for evaluation of bitterness.

Methods

Bitterness threshold and bitterness scores for different solutions of ondansetron hydrochloride (ONS) were estimated by taste panel studies. In vitro drug release studies on taste-masked drug product in pharmacopoeial apparatus and an in-house-developed apparatus were performed and correlated to drug release studies in oral cavity.

Results

Concentration of 22 μg/ml and below was perceived bitterless by all the volunteers of taste panel. A second-order polynomial equation (y?=?0.6206x ²???0.2011x???0.7796; correlation coefficient R ²?=?0.991) was derived as a relationship between bitterness score and log ONS concentration. Drug release in in-house-assembled apparatus and oral cavity were not statistically different (α?=?0.05) at both 60 and 120 s.

Conclusions

Bitterness threshold and bitterness scores are helpful in evaluation of bitterness in drug solutions and samples obtained from drug release studies.     

Discovery of Cathepsin S Inhibitor LY3000328 for the Treatment of Abdominal Aortic Aneurysm

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Awake endotracheal retrograde intubation in restricted mouth opening: a ‘J’-tipped guide wire technique—a retrospective study

Introduction

Airway management in patient with restricted mouth opening is a great challenge, owing to the difficulty in laryngoscopy and visualisation of the vocal cords during the procedure of intubation. The term retrograde intubation refers to a technique in which a guide wire is passed into the trachea and then into the mouth or nose. A tracheal tube is then passed down over the guide until it enters the trachea.

Material and method

A retrospective audit was undertaken to determine the success and complication associated with retrograde intubation.

Results

The results show that in a sample of 20 patients in which retrograde intubation was done, only three developed sore throat and cough, one had bronchospasm and one developed infection at the site of insertion of a J-tipped catheter.

Conclusion

Retrograde tracheal intubation was easy to perform and had a high success rate and a low incidence of complications.     

Mucormycosis in COVID-19 patients

Mucormycosis, commonly known as ‘Black Fungus’ which was then a rare fungal infection, has suddenly come to light post the COVID-19- pandemic, more so during the second wave in India. It thus becomes important not only for the medical fraternity but also the general population to build awareness about the same. The present review will focus on the pathophysiology, etiology, outcomes of some case studies, and current treatment methods of mucormycosis infection. Major focus of the current article is on rhino-orbital-cerebral mucormycosis. All the studies included in the present review article was extracted from the PubMed database.     

Methionine epimerization in cyclic peptides

Bioactive flax cyclic octa- and nona-peptides containing single methionine (Met) and its oxidized forms were treated under mild alkaline conditions to perform regio-selective epimerization. Cyclic peptide epimerization at the Met α-proton in a single chemical step has not been reported previously. The epimerization rate varies among Met oxidation states and ring size. These d-amino isomers along with the developed Met alkylation strategy will enable an approach to novel chemical functionalization of biomolecules. The amino acid configurations were confirmed by Marfey derivatizations, and cytotoxicity studies show the difference among the isomers. These d-amino analogs can act as a potential biomarker in plant protein processing and biomedical applications.

One step regioselective methionine epimerization in cyclic peptides followed by selective functionalization leads to chemical novelty.     

A Qualitative Exploration to Understand the Sexual Behavior and Needs of Young Adults: A Study Among College Students of Pune,India

Indian Journal of Pediatrics - Youth and adolescents are the priority population to target the interventions as risky behaviors persist and they contribute to almost half of the new Human...