A preliminary pharmacokinetic study of the enantiomers of the terfenadine acid metabolite in humans

A stereoselective and sensitive achiral/chiral method for the determination of terfenadine acid metabolite in human plasma was developed. The metabolite was separated and quantitated using an achiral chromatographic procedure with a cyano column. The mobile phase was 1 mM sodium acetate buffer (pH 4.0) and acetonitrile (25:75% v/v) at a flow rate of 2 ml/min, at ambient temperature. The stereospecific resolution was accomplished using a chiral-AGP column and a mobile phase consisting of sodium acetate (0.01 M): methanol (98.7:1.3% v/v), and 20 mM di-n-butylamine at a flow rate of 1.2 ml/min. The column temperature was maintained at 32°C. The eluent was monitored at 230 nm (excitation) and 300 nm (emission) with a cut-off filter at 270 nm. This assay was used for a pharmacokinetic study in five subjects after administration of a single dose of 60 mg of terfenadine. The t_½ values of the two enantiomers were similar, but the AUC values of the (+)-enantiomer were 2.05–2.35 times higher than those of (?)-enantiomer. © 1994 Wiley-Liss, Inc.     

Pathophysiology of dyslipidemia and increased cardiovascular risk in HIV lipodystrophy: a model of 'systemic steatosis'

PURPOSE OF REVIEW: This review addresses a syndrome of dyslipidemia and lipodystrophy that has emerged in HIV-infected patients receiving highly active antiretroviral therapy (HAART). The term 'HIV/HAART associated dyslipidemic lipodystrophy (HADL)' describes this syndrome. Although HAART increases patient survival rates, their increased longevity and dyslipidemias place them at risk for cardiovascular disease. Identification of rationally based therapies requires an understanding of the mechanistic basis of HADL. RECENT FINDINGS: A case definition for HIV lipodystrophy, based on age, gender, duration of HIV disease, serum HDL cholesterol and anthropometry, provides high diagnostic sensitivity and specificity. The dyslipidemias, mainly hypercholesterolemia, hypertriglyceridemia and low-plasma HDL cholesterol, among HIV-infected patients in the pre- and post-HAART eras are summarized. Clinical studies of HADL patients show increased lipolysis, which increases free fatty acid transfer to liver for incorporation into lipoprotein triglycerides that are secreted, and to skeletal muscle where they impair normal insulin signaling. A model of HADL that includes preferential lipolysis in femoral-gluteal fat depots is presented. Relevant therapies include those that inhibit lipolysis (niacin) or increase hepatic fatty acid oxidation (fibrates). SUMMARY: HADL is one of several disorders characterized by dyslipidemia, insulin resistance, and lipodystrophy. The relative acuteness of HADL should facilitate identification of the sequence of metabolic changes that gives rise to the syndrome. Current evidence suggests that deranged energy storage in femoral-gluteal and other peripheral sites is important; the molecular details for the derangement are unknown but are under scrutiny by many investigators.     

Design and synthesis of a novel enediynyl pentapeptide with predominantly beta-turn structural motif and its potential as a fluorescence-based chemosensor

A novel enediynyl pentapeptide in the protected form 1 was synthesized and characterized. It exists predominantly in beta-turn structural motif as revealed by variable temperature NMR and CD spectroscopy. In the presence of transition metal ions and gold nanoparticles, the fluorescence intensity of the peptide got enhanced with remarkable quantum yield with the Z-enediynyl -amino acid acting as a fluorophoric reporter. The interesting photophysical behaviors with alkali and alkaline earth metal ions are also reported.     

A database for Plasmodium falciparum protein models

There is an urgent need for developing alternate strategies to combat Malaria caused by Plasmodium falciparum (P. falciparum) because of growing drug resistance and increased incidents of infection in humans. 3D models of P. falciparum annotated proteins using molecular modeling techniques will enhance our understanding about the mechanism of host parasite interactions for the identification of drug targets and malarial vaccine design. Potential structural templates for P. falciparum annotated proteins were selected from PDB (protein databank) using BLASTP (basic local alignment search tool for proteins). This exercise identified 476 Plasmodium proteins with one or more known structural templates (>or= 40 % identity) for further modeling. The pair-wise sequence alignments generated for protein modeling were manually checked for error. The models were then constructed using MODELLER (a comparative protein modelling program for modelling protein structures) followed by energy minimization in AMBER force field and checked for error using PROCHECK. AVAILABILITY: http://bioinfo.icgeb.res.in/codes/model.html.     

Use of chromomycin A3 staining in bovine sperm cells for detection of protamine deficiency

Sperm chromatin integrity is essential for accurate transmission of male genetic information, and normal sperm chromatin structure is important for fertilization. Protamine is a nuclear protein that plays a key role in sperm DNA integrity, because it is responsible for sperm DNA stability and packing until the paternal genome is delivered into the oocyte during fertilization. Our aim was to investigate protamine deficiency in sperm cells of Bos indicus bulls (Nelore) using chromomycin A₃ (CMA₃) staining. Frozen semen from 14 bulls were thawed, then fixed in Carnoy's solution. Smears were prepared and analyzed by microscopy. As a positive control of CMA₃ staining, sperm from one bull was subjected to deprotamination of nuclei. The percentage of CMA₃-positive bovine sperm did not vary among batches. Only two bulls showed a higher percentage of CMA₃-positive sperm cells compared to the others. CMA₃ is a simple and useful tool for detecting sperm protamine deficiency in bulls.