Protective effects of N-acetylcysteine on acetic acid-induced colitis in a porcine model

BACKGROUND: Ulcerative colitis is a chronic inflammatory disease and involves multiple etiological factors. Acetic acid (AA)-induced colitis is a reproducible and simple model, sharing many characteristics with human colitis. N-acetylcysteine (NAC) has been widely used as an antioxidant in vivo and in vitro. NAC can affect several signaling pathways involving in apoptosis, angiogenesis, cell growth and arrest, redox-regulated gene expression, and inflammatory response. Therefore, NAC may not only protect against the direct injurious effects of oxidants, but also beneficially alter inflammatory events in colitis. This study was conducted to investigate whether NAC could alleviate the AA-induced colitis in a porcine model. METHODS: Weaned piglets were used to investigate the effects of NAC on AA-induced colitis. Severity of colitis was evaluated by colon histomorphology measurements, histopathology scores, tissue myeloperoxidase activity, as well as concentrations of malondialdehyde and pro-inflammatory mediators in the plasma and colon. The protective role of NAC was assessed by measurements of antioxidant status, growth modulator, cell apoptosis, and tight junction proteins. Abundances of caspase-3 and claudin-1 proteins in colonic mucosae were determined by the Western blot method. Epidermal growth factor receptor, amphiregulin, tumor necrosis factor-alpha (TNF-α), and toll-like receptor 4 (TLR4) mRNA levels in colonic mucosae were quantified using the real-time fluorescent quantitative PCR. RESULTS: Compared with the control group, AA treatment increased (P < 0.05) the histopathology scores, intraepithelial lymphocyte (IEL) numbers and density in the colon, myeloperoxidase activity, the concentrations of malondialdehyde and pro-inflammatory mediators in the plasma and colon, while reducing (P < 0.05) goblet cell numbers and the protein/DNA ratio in the colonic mucosa. These adverse effects of AA were partially ameliorated (P < 0.05) by dietary supplementation with NAC. In addition, NAC prevented the AA-induced increase in caspase-3 protein, while stimulating claudin-1 protein expression in the colonic mucosa. Moreover, NAC enhanced mRNA levels for epidermal growth factor and amphiregulin in the colonic mucosa. CONCLUSION: Dietary supplementation with NAC can alleviate AA-induced colitis in a porcine model through regulating anti-oxidative responses, cell apoptosis, and EGF gene expression

Community collectivization and its association with consistent condom use and STI treatment-seeking behaviors among female sex workers and high-risk men who have sex with men/transgenders in Andhra Pradesh, India

We examine community collectivization among female sex workers (FSWs) and high-risk men who have sex with men and transgenders (HR-MSM) following several years of HIV prevention programming with these populations, and its association with selected outcome indicators measuring individual behaviors (condom use with different partners and sexually transmitted infection [STI] treatment-seeking from government health facilities). Data for this study were collected from a large-scale cross-sectional survey conducted in 2010–2011 among FSWs (sample size: 3557) and HR-MSM (sample size: 2399) in Andhra Pradesh, India. We measured collectivization among FSWs in terms of three binary (low, high) indices of collective efficacy, collective agency, and collective action. Collectivization among HR-MSM was measured by participation in a public event (no, yes), and a binary (low, high) index of collective efficacy. Adjusted odds ratios (adjusted OR) and their 95% confidence intervals (CI) were computed to assess the relationships between collectivization and outcome indicators directly and through mediation of variables such as self-efficacy for condom use and utilization of government health facilities. Results show that among FSWs, high levels of collective efficacy (adjusted OR: 1.3, 95% CI: 1.1–1.7) and collective action (adjusted OR:1.3, 95% CI: 1.1–1.8) were associated with consistent condom use (CCU) with regular clients. Among HR-MSM, participation in a public event (adjusted OR: 2.7, 95% CI: 2.0–3.6) and collective efficacy (adjusted OR: 1.9, 95% CI: 1.5–2.3) were correlated with condom use with paying partners. The association between collectivization and outcome indicators continued to be significant in most cases even after adjusting for the potential mediators. Indicators of collectivization exhibited significant positive association with self-efficacy for condom use and service utilization from government health facilities among both FSWs and HR-MSM. The association of high levels of collectivization with CCU, STI treatment- seeking from government health facilities, ability to negotiate for condom use, and self-efficacy in utilizing government health facilities is relevant to effort to improve the effectiveness and sustainability of HIV prevention programs in India and beyond