The Effects of Interferon alpha 2b on Chemically-induced Peritoneal Fibrosis and on Peritoneal Tissue MMP-2 and TIMP-2 Levels in Rats

This study investigated the effect of interferon alpha 2b on chlorhexidine gluconate (CH)-induced peritoneal fibrosis (PF) in rats and assessed peritoneal tissue levels of metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinases (TIMP)-2. Wistar albino rats (n = 8 per group) were treated as follows: control group, 3 ml/day of 0.9% saline intraperitoneally for 28 days; CH group, 0.1% CH (200 g [3 ml]/day) in 15% ethanol and 0.9% saline intra-peritoneally for 28 days; CH + interferon (IFN) group, CH (as above) plus pegylated IFN-alpha 2b 1.5 mu g/kg per week subcutaneously on days 0, 7, 14, 21 and 28; IFN group, pegylated IFN-alpha 2b (as above). Parietal peritoneum samples were obtained from the left anterior abdominal wall after 35 days. Parietal thickness, degree of vascular proliferation and inflammation, and MMP-2 and TIMP-2 levels were determined. The mean peritoneal thicknesses of the control, CH, CH + IFN and IFN groups were 7.02 +/- 3.89, 156.86 +/- 29.13, 59.88 +/- 22.1, 9.27 +/- 2.03 mu m, respectively. Pegylated IFN-alpha 2b decreased CH-induced expression of MMP-2 in the parietal peritoneum, but had no effect on TIMP-2 levels. Further studies are needed to determine the optimal dosage and duration for pegylated IFN-alpha 2b treatment

The Effects of Interferon α2b on Chemically-Induced Peritoneal Fibrosis and on Peritoneal Tissue MMP-2 and TIMP-2 Levels in Rats

This study investigated the effect of interferon alpha 2b on chlorhexidine gluconate (CH)-induced peritoneal fibrosis (PF) in rats and assessed peritoneal tissue levels of metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinases (TIMP)-2. Wistar albino rats (n = 8 per group) were treated as follows: control group, 3 ml/day of 0.9% saline intraperitoneally for 28 days; CH group, 0.1% CH (200 g [3 ml]/day) in 15% ethanol and 0.9% saline intra-peritoneally for 28 days; CH + interferon (IFN) group, CH (as above) plus pegylated IFN-alpha 2b 1.5 mu g/kg per week subcutaneously on days 0, 7, 14, 21 and 28; IFN group, pegylated IFN-alpha 2b (as above). Parietal peritoneum samples were obtained from the left anterior abdominal wall after 35 days. Parietal thickness, degree of vascular proliferation and inflammation, and MMP-2 and TIMP-2 levels were determined. The mean peritoneal thicknesses of the control, CH, CH + IFN and IFN groups were 7.02 +/- 3.89, 156.86 +/- 29.13, 59.88 +/- 22.1, 9.27 +/- 2.03 mu m, respectively. Pegylated IFN-alpha 2b decreased CH-induced expression of MMP-2 in the parietal peritoneum, but had no effect on TIMP-2 levels. Further studies are needed to determine the optimal dosage and duration for pegylated IFN-alpha 2b treatment

Genome-wide association study and meta-analysis identify loci associated with ventricular and supraventricular ectopy

Abstract The genetic basis of supraventricular and ventricular ectopy (SVE, VE) remains largely uncharacterized, despite established genetic mechanisms of arrhythmogenesis. To identify novel genetic variants associated with SVE/VE in ancestrally diverse human populations, we conducted a genome-wide association study of electrocardiographically identified SVE and VE in five cohorts including approximately 43,000 participants of African, European and Hispanic/Latino ancestry. In thirteen ancestry-stratified subgroups, we tested multivariable-adjusted associations of SVE and VE with single nucleotide polymorphism (SNP) dosage. We combined subgroup-specific association estimates in inverse variance-weighted, fixed-effects and Bayesian meta-analyses. We also combined fixed-effects meta-analytic t-test statistics for SVE and VE in multi-trait SNP association analyses. No loci reached genome-wide significance in trans-ethnic meta-analyses. However, we found genome-wide significant SNPs intronic to an apoptosis-enhancing gene previously associated with QRS interval duration (FAF1; lead SNP rs7545860; effect allele frequency = 0.02; P = 2.0 × 10−8) in multi-trait analysis among European ancestry participants and near a locus encoding calcium-dependent glycoproteins (DSC3; lead SNP rs8086068; effect allele frequency = 0.17) in meta-analysis of SVE (P = 4.0 × 10−8) and multi-trait analysis (P = 2.9 × 10−9) among African ancestry participants. The novel findings suggest several mechanisms by which genetic variation may predispose to ectopy in humans and highlight the potential value of leveraging pleiotropy in future studies of ectopy-related phenotypes