The VEGF +405 G>C 5' untranslated region polymorphism and risk of PCOS: a study in the South Indian Women

Purpose

The aim of this study was to investigate the association between two common single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene (−460C/T and +405G/C) and polycystic ovary syndrome (PCOS) risk in south Indian women.

Methods

This study involves clinically confirmed PCOS patients (n = 126) and non-PCOS controls (n = 130) of south Indian origin (Dravidian linguistic group). Genotyping of the VEGF gene −460C/T and +405G/C SNPs were performed by PCR and sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D'') for pairwise linkage disequilibrium (LD) were assessed by Haploview Software.

Results

The frequencies of +405G/G genotype (P = 0.03) and +405G alleles (P = 0.006) were significantly higher in patients compared to controls. Whereas the genotype and allele frequencies of −460C/T SNP were not significantly different between patients and controls. In addition, LD analysis revealed no significant difference between patients and controls.

Conclusion

Our findings suggest that the VEGF +405G/C polymorphism may constitute an inheritable risk factor for PCOS in south Indian women.     

Estimating the risk of rabies transmission to humans in the U.S.: a delphi analysis

Background  

In the United States, the risk of rabies transmission to humans in most situations of possible exposure is unknown. Controlled studies on rabies are clearly not possible. Thus, the limited data on risk has led to the frequent administration of rabies post-exposure prophylaxis (PEP), often in inappropriate circumstances.     

Development of aceclofenac nanovesicular system using biomaterial for transdermal delivery: physical characterization,ex vivo,in vivo,and anti-inflammatory studies

Context: Aceclofenac is an important NSAID; however, it causes GI disturbances whereas employing transdermal route would require permeation enhancer for systemic application, thereby causing skin damage. Ceramide 2 is a natural lipid having an important role in the maintenance of skin. Objective: Aceclofenac-loaded nanovesicles of ceramide-2, cholesterol, palmitic acid, and cholesteryl sulfate were formulated and analyzed for physical and biological properties. Materials and method: Film hydration method was used to prepare the vesicles and physical parameters, in vitro drug release and stability were evaluated. Then, they were formulated into gel and evaluated against a commercial formulation (CF) and gel-containing plain drug (CPG) for ex vivo, in vivo drug permeation, and anti-inflammatory activity. Results: The developed formulations showed best physical profile and ACV-1 gave 92.89% drug release in in vitro studies. Ex vivo studies showed drug permeation between 15.32–31.12?μg/cm², whereas CPG and CF released 0.47 and 2.81?μg/cm², respectively. ACVG-1 and CF showed C_max of 8.1 and 1.2?μg/ml at 8 and 4?h, respectively. ACVG-1 showed 11.6 times AUC than CF. ACVG-1 inhibited edema by 44% in first hour itself. Discussion: Ceramide 2 and palmitic acid played an important role in the formulation and promotes the drug permeation through stratum corneum and dermis. Ceramide content of the formulation also contributes towards stability and skin protection. Conclusion: The composition of the vesicle formulation performs an important role in physical properties and drug permeation, thereby producing an optimum formulation.     

Comparative genomics of Papaya ringspot virus pathotypes P and W from India

Archives of Virology -     

Development of hollow/porous calcium pectinate beads for floating-pulsatile drug delivery.

The purpose of this work was to develop hollow calcium pectinate beads for floating-pulsatile release of diclofenac sodium intended for chronopharmacotherapy. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. To overcome limitations of various approaches for imparting buoyancy, hollow/porous beads were prepared by simple process of acid-base reaction during ionotropic crosslinking. The floating beads obtained were porous (34% porosity), hollow with bulk density<1 and had Ft50% of 14-24 h. In vivo studies by gamma scintigraphy determined on rabbits showed gastroretention of beads up to 5 h. The floating beads provided expected two-phase release pattern with initial lag time during floating in acidic medium followed by rapid pulse release in phosphate buffer. This approach suggested the use of hollow calcium pectinate microparticles as promising floating-pulsatile drug delivery system for site- and time-specific release of drugs acting as per chronotherapy of diseases.     

A recombinant adenovirus expressing p7(Kip1) induces cell cycle arrest and apoptosis in human 786-0 renal carcinoma cells

PURPOSE: We evaluated the effects of the over expression of p27Kip1, a cyclin dependent kinase inhibitor and tumor suppressor protein, on the 786-0 human renal carcinoma cell line. MATERIALS AND METHODS: The recombinant adenovirus Adp27Kip1 was evaluated for the induction of p27 protein expression in 786-0 renal carcinoma cells. Expression time and optimal vector concentration were determined. Growth curve studies, cell cycle analysis and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling were done to determine the effects of p27Kip1 on the cell cycle. Cyclin dependent protein kinase (Cdk) inhibitor (CDKI) activity assays were done to determine the expression/activities of Cdks and Western blot analysis was performed to determine the presence of CDKIs and other cell cycle regulator proteins. Nude mouse xenografts were established to demonstrate the in vivo efficacy of Adp27Kip1. RESULTS: p27Kip1 protein expression was detected within 12 hours after Adp27Kip1 infection and it remained stable for at least 48 hours. Growth studies demonstrated that Adp27Kip1 infection resulted in the inhibition of proliferation by 3 days after infection and cell death was detected by day 5. Cell cycle analysis of DNA content indicated an accumulation of cells in the G1 phase of Adp27Kip1 infected cells and a corresponding decrease in S phase cells within 48 hours after infection. Cdk activity was determined, and Cdk2, Cdk4 and Cdc2 kinase activities were inhibited, consistent with p27Kip1 over expression. The levels of the CDKIs p16 and p18 were elevated 24 hours after Adp27Kip1 infection, while p21 levels remained unchanged. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling revealed that Adp27Kip1 infection but not infection by control virus induced detectable apoptosis within 24 hours. Adp27Kip1 significantly caused the reduction in the size of tumors of the renal cell carcinoma xenografts. CONCLUSIONS: This study demonstrates the potential effectiveness of Adp27Kip1 as a vector for gene therapy studies of renal cell carcinoma.