Successful renal transplantation in a family with a novel mutation in COL4A3 gene and autosomal recessive Alport syndrome

Alport syndrome (AS) is an inherited disorder of basement membranes caused by mutations affecting specific proteins of the type IV collagen family, presenting with nephropathy and extrarenal manifestations such as sensorineural deafness and ocular anomalies. Ten percentage to 15% of the patients with AS have autosomal recessive (ARAS) due to mutation in either COL4A3 or COL4A4 gene. We report a novel mutation in the COL4A3 gene in an Indian family with ARAS. The above‐mentioned genetic anomaly was a missense variation in exon 26 of the COL4A3 gene (chr2:228137797G>A; c.1891G>A) that resulted in the amino acid substitution of Arginine for Glycine at codon 631 (p.Gly631Arg) that was present in the heterozygous state in the asymptomatic parents and homozygous state in the male offspring who presented with early‐onset end‐stage renal disease, lenticonus and hearing loss. The patient (male offspring) underwent successful renal transplantation with his mother as a donor.     

Cardioprotective effect of fenugreek on isoproterenol-induced myocardial infarction in rats

Objectives:

This study is designed to evaluate the cardioprotective effect of fenugreek on isoproterenol- induced myocardial infarction and is investigated by an in vivo method in rats.

Materials and Methods:

Male Wistar albino rats were divided into four groups (n=10). Group I received 0.5% CMC treated as normal control group. Group II received isoproterenol (85 mg/kg body weight) intraperitoneal (i.p.) for two consecutive days (14^th and 15^th days). Group III received fenugreek (250 mg/kg body weight) intragastric intubation for 15 days. Group IV rats received fenugreek as in Group III and additionally isoproterenol was given for two consecutive days (14^th and 15^th days).

Results:

The results described the cardioprotective effect that observed in Group IV showed significantly (P< 0.05) decreased levels of TBARS and enhanced the activities of both enzymatic and non-enzymatic antioxidants (SOD, CAT, GPx and GSH) in myocardial infarcted rats when compared to Groups II and III. Histopathological studies were also co-relating with the above biochemical parameters.

Conclusion:

These findings concluded the cardioprotective effect of fenugreek on lipid peroxidation and antioxidant defense system during isoproterenol-induced myocardial infarction in rats.     

Peripheral CD4+/CD8+ T-lymphocyte counts estimated by an immunocapture method in the normal healthy south Indian adults and HIV seropositive individuals.

BACKGROUND: Flow cytometry is the standard method for the estimation of CD4/CD8 counts, but the high initial investment for this instrument and costly reagents make it unaffordable to most of the centers in a developing country like India. OBJECTIVES: To evaluate the feasibility of an alternate system for the estimation of CD4 and CD8 counts in normal south Indian adults and validate the usefulness of this assay to monitor the counts in HIV seropositive individuals. STUDY DESIGN: Forty-six normal healthy adults and 68 HIV seropositive individuals both belonging to south Indian linguistic groups were enrolled in this cross-sectional study. The HIV seropositive individuals included 54 HIV-1, 9 HIV-2 and 5 HIV 1&2 infected individuals serologically confirmed by one of the commercial Immunoblot kits. The Capcellia CD4/CD8 whole blood assay, an immuno-capture ELISA based kit from Sanofi DIAGNOSTICS Pasteur, (France) was used with a few modifications in the procedure to measure the CD4 and CD8 counts. RESULTS: The mean CD4 cell counts were 1048 (central 95 centile only), 746 and 424 for the normal healthy adults, asymptomatic HIV seropositives and symptomatic HIV patients, respectively, and the mean CD8 counts were 595, 889 and 732, respectively. Statistically significant differences were observed in the CD4 cell counts between HIV seronegative healthy adults and asymptomatic (P < 0.001) as well as asymptomatic and symptomatic (P < 0.05) HIV infected individuals. The mean CD4 counts of asymptomatic HIV-2 infected individuals was significantly higher than the counts of asymptomatic HIV-1 infected individuals (P < 0.05). CONCLUSIONS: This is an user friendly test and can be an alternate to flow cytometry for the estimation of peripheral T-lymphocyte subsets in developing countries. The assay system has certain limitations inherent to ELISA techniques.     

Joongpoongtang 05 (JP05) confers neuroprotection via anti-apoptotic activities in Neuro-2a cells during oxygen-glucose deprivation and reperfusion

To evaluate the anti-apoptotic effects of Joongpoongtang 05 (JP05), a mixture of plant extracts, on a Neuro-2a (N2a) cell model of oxygen and glucose deprivation (OGD)/reperfusion (OGDR), a neuroblastoma cell injury model was induced by OGDR. This model allowed us to investigate cerebral ischemic changes and the protective effects of JP05. JP05 treatment significantly enhanced cell viability and reduced the levels of lactate dehydrogenase, nitric oxide, reactive oxygen species and the oxidants/antioxidants balance in neuronal cells as compared to the untreated OGDR group. Here, JP05 reduced OGDR-induced expressions of heme oxygenase-1 and nitric oxide synthase, which may contribute to the neuroprotection. JP05 also partially reversed the effects of OGDR on NF-κB and activated Akt production. Our findings suggest that JP05 confers neuroprotective effects via anti-apoptotic property against OGDR-induced free radical injury in N2a cells.     

Breakdown of the first hyperpolarizability/bond-length alternation parameter relationship

We have investigated the dependence of the static first hyperpolarizability on the bond-length alternation (BLA) parameter. Our analysis indicates that the validity of the first hyperpolarizability/BLA parameter relationship is restricted to the no-field, vacuum, limit, while it successively breaks down along with increasing polarity of a surrounding medium, becoming invalid, for instance, in an aqueous solution. This contention is based on a series of TD-DFT, TD-DFT/PCM and hybrid TD-DFT/MM calculations of the first hyperpolarizability for a set of molecular configurations generated from Car–Parrinello hybrid QM/MM simulations of the stilbazolium merocyanine chromophore in chloroform and water solvents, and on a rationalization by means of the two-state model for the first hyperpolarizability. The BLA dependence of the three parameters entering the two-state model is shown to be qualitatively different in vacuum and in solvents. Particularly, in the vacuum case, the difference between ground and excited state dipole moments goes to zero for a vanishing BLA, which is not true in the presence of an aqueous medium. In the aqueous medium, an opposing behavior of the parameters involved in the two-state model results in an almost constant first hyperpolarizability with varying BLA parameter.     

Design and in vitro testing of a floatable gastroretentive tablet of metformin hydrochloride

Metformin hydrochloride, which is better absorbed in the upper intestine, was formulated as a floating (buoyant) matrix tablet using a gas generating agent (sodium bicarbonate) and a gel forming hydrophilic polymer (hydroxypropyl methylcellulose). The formulation was optimized on the basis of floating ability and in vitro drug release. The resulting formulation produced robust tablets with optimum hardness, consistent weight uniformity and low tablet friability. All tablets but one exhibited satisfactory (gradual and near complete) drug release and buoyancy. In vitro drug release tests of these tablets indicated controlled sustained release of metformin hydrochloride and 96-99% released at the end of 8 h. Two formulations of fabricated tablets containing metformin hydrochloride (500 mg), sodium bicarbonate (75 mg), hydroxypropyl methylcellulose-K 4M (170-180 mg), citric acid (between 15 and 20 mg) and polyvinyl pyrrolidone K90 (32-40 mg) with hardness between 6.8 to 7.5 kg/cm2 showed a floating time of more than 8 h and promising drug release results. The release followed the Higuchi kinetic model, indicating diffusion dominated drug release.