Review: peroxisome proliferator-activated receptor-gamma and its role in the development and treatment of diabetes

Since its identification as the receptor for antidiabetic thiazolidinedione drugs, peroxisome proliferator-activated receptor-gamma (PPARgamma) has been the focus of pharmaceutical drug discovery programs directed toward finding better drugs for the treatment of diabetes, as well as the object of basic research aimed at understanding its role in the regulation of metabolism. We now understand a great deal about the crucial role that PPARgamma plays in adipocyte differentiation and development, and are rapidly gaining knowledge about the role of the receptor in the regulation of metabolism. However, many crucial aspects of the molecular mechanism by which modulation of PPARgamma activity affects insulin resistance and glucose homeostasis are still not clearly understood. Here the authors review the current status of PPARgamma research, with an emphasis on its role in the causes and treatment of type 2 diabetes.     

Hemophilia A: role of FVIIIC/vWF Ag in assisting linkage analysis for carrier detection.

Carrier detection for hemophilia A was carried out in 52 females from 30 families presenting to the Haematology Department AIIMS, using linkage analysis and factor VIIIC (FVIIIC)-von Willebrand factor (vWF) antigen assay. The allelic frequency for the marker Bcl 1 and Xba 1 was 0.58 and 0.54, respectively, for the positive alleles and 0.42 and 0.46, respectively, for the negative alleles. The heterozygosity frequency of Bcl I and Xba 1 was 0.65 and 0.55, respectively. Of the 52 females, 30 were mothers of hemophilic patients and 22 were sisters of hemophilic patients. Of the 30 mothers, positive family history was present in 14. In these patients, the defective X chromosome was tracked in 10, and in four the defective X chromosome could not be tracked because the mothers were homozygous for the marker used. Of the 16 mothers without a family history of disease, three were observed to be carriers based on linkage analysis and reduced factor VIII levels in mother/sister. Possible defective X chromosome was tracked in 11 mothers and five were noninformative because they did not show heterozygosity for the markers used. Using linkage analysis, nine of the 22 sisters were found to be definite carriers, 10 noncarriers, and three were noninformative. It is thus concluded that using Bcl 1 and Xba 1 linkage analysis, carrier status can be definitely ascertained in 50% females and this level of information can be increased to 61.5% by measuring FVIIIC/vWF antigen levels in them.     

De novo development of antibodies to kidney‐associated self‐antigens angiotensin II receptor type I,collagen IV,and fibronectin occurs at early time points after kidney transplantation in children

Chronic rejection is the leading cause of graft loss following pediatric kidney transplantation. Our group and others have demonstrated an association between the development of Abs to self‐antigens and chronic rejection following adult lung and heart transplantation. The goal of this study was to determine whether Abs to kidney‐associated self‐antigens develop following pediatric renal transplantation. We investigated post‐transplant development of Abs to kidney‐associated self‐antigens angiotensin II receptor type I, Fn, and collagen IV in a pediatric cohort. Using ELISA, we measured Abs to kidney‐associated self‐antigens in serum. Our cohort included 29 subjects with samples collected pretransplant and for 12 months post‐transplant. No samples had Abs to kidney‐associated self‐antigen pretransplant. In contrast, 50% (10/20) of subjects developed Abs to one or more kidney‐associated self‐antigen post‐transplantation. The median time to antibody appearance and duration of persistence were 103 and 61 days, respectively. Development of Abs did not correlate with graft function. Half of subjects developed Abs to kidney‐associated self‐antigens angiotensin II receptor type I, Fn, or collagen IV in the first year after kidney transplantation—a higher rate of early antibody development than expected. In this small study, Abs did not correlate with worse clinical outcomes.     

Experimental infection of the leaf-monkeys, Presbytis cristata and Presbytis melalophos with subperiodic Brugia malayi

The leaf-monkeys, Presbytis cristata and Presbytis melalophos, experimentally infected with subperiodic Brugia malayi, have been used for studies on the pathoimmunology of the infection and the screening of potential filaricides during the last 6-8 years, and considerable information on the pattern of microfilaraemia and adult worm recoveries have been obtained. The prepatent periods in 97 P. cristata and 45 P. melalophos, each infected with about 200 infective larvae, were similar, these being approximately 70 and 68 days respectively. Although all infected animals became microfilaraemic, the peak geometric mean count was much higher in P. cristata than in P. melalophos, this being 182.0 and 65.8 per ml blood respectively. Mean adult worm recovery expressed as the percentage of the infective dose was 4.7% and 2.5%, respectively. Most worms were recovered from the sacral nodes/thoracic duct or inguinal lymph nodes in these animals. In view of the higher worm recovery and the higher peak microfilaraemia attained, it is concluded that P. cristata is a better model for the infection than P. melalophos.     

Ultrasensitive and bifunctional ZnO nanoplates for an oxidative electrochemical and chemical sensor of NO2: implications towards environmental monitoring of the nitrite reaction

Herein, we focused on the one pot synthesis of ZnO nanoplates (NP edge thickness of ∼100 nm) using a chemical emulsion approach for chemical (direct) and electrochemical (indirect) determination of NO₂. The structural and morphological elucidation of the as-synthesized ZnO NPs was carried out by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive analysis of X-ray (EDAX), thermogravimetric analysis (TGA) and BET-surface area measurements. The XRD studies of the as-synthesised NPs reveal that ZnO NPs have a Wurtzite type crystal structure with a crystallite size of ∼100 nm. Such ZnO NPs were found to be highly sensitive to NO₂ gas at an operating temperature of 200 °C. Electrocatalytic abilities of these ZnO NPs towards NO₂/NO₂⁻ were verified through cyclic voltammetry (CV) and linear sweep voltammetry (LSV) using aqueous 1 mM NO₂⁻ (nitrite) in phosphate buffer (pH 7) solution. The results revealed enhanced activity at an onset potential of 0.60 V vs. RCE, achieved at a current density of 0.14 mA cm⁻². These ZnO NPs show selective NO₂ detection in the presence of other reactive species including CO, SO₂, CH₃OH and Cl₂. These obtained results show that this chemical route is a low cost and promising method for ZnO NPs synthesis and recommend further exploration into its applicability towards tunable electrochemical as well as solid state gas sensing of other toxic gases.

Herein, we focused on the one pot synthesis of ZnO nanoplates (NP edge thickness of ∼100 nm) using a chemical emulsion approach for chemical (direct) and electrochemical (indirect) determination of NO₂.      

Hierarchical CdMoO4 nanowire–graphene composite for photocatalytic hydrogen generation under natural sunlight

Herein, a facile in situ solvothermal technique for the synthesis of a CdMoO₄/graphene composite photocatalyst is reported. Graphene oxide (GO) was synthesised by an improved Hummers'' method and was further used for the in situ synthesis of graphene via GO reduction and the formation of a CdMoO₄ nanowire/graphene composite. The structural phase formation of tetragonal CdMoO₄ was confirmed from X-ray diffraction measurements. The small nanoparticle assembled nanowires, prismatic microsphere morphology and crystalline nature of the synthesized material were investigated using field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). Due to its unique morphology and stability, the CdMoO₄/graphene composite was used as a photocatalyst for H₂O splitting. In comparison to pristine CdMoO₄, the CdMoO₄/graphene composite showed the best hydrogen evolution rate, i.e. 3624 μmole h⁻¹ g⁻¹, with an apparent quantum yield of 30.5%. The CdMoO₄/graphene composite has a higher photocatalytic activity due to the inhibition of charge carrier recombination. H₂ production measurements showed that the ternary semiconductor/graphene composite has enhanced photocatalytic activity for H₂ generation.

Herein, a facile in situ solvothermal technique for the synthesis of a CdMoO₄/graphene composite photocatalyst for hydrogen generation under natural solar light.     

Essential Medicines: An Indian Perspective

The concept of defining essential medicines and establishing a list of them was aimed to improve the availability of affordable medicines for the world''s poor. Access to essential medicines is a major determinant of health outcomes. Several countries have made substantial progress towards increasing access to essential medicines, but access to essential medicines in developing countries like India is not adequate. In this review we have tried to present the Indian scenario in respect to availability and accessibility of essential medicines over last one decade. To enhance the credibility of Indian healthcare system, procurement and delivery systems of essential medicines have to be strengthened through government commitment, careful selection, adequate public sector financing, efficient distribution systems, control on taxes and duties, and inculcating a culture of rational use of medicines in current and future prescribers.