Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal TGF-ß1 mRNA expression in gastritis patients.

OBJECTIVE: Helicobacter pylori (H. pylori) infection is the main cause of gastric inflammation. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. TGF-ß1 was shown to be secreted in a subset of Treg cells known as 'Th3 cells'. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa. In this study we therefore, aimed to investigate the expression of TGF-ß1 in the context of H. pylori colonization in chronic gastritis, to examine the relationship between it and histopathologic findings and to compare it with virulence factors. PATIENTS AND METHODS: Total RNA was extracted from gastric biopsies of 48 H. pylori-infected patients and 38 H. pylori-negative patients with gastritis. Mucosal TGF-ß1 mRNA expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. Presence of vacA, cagA, iceA, babA2 and oipA virulence factors was evaluated using PCR. RESULTS: TGF-ß1 mRNA expression was significantly increased in biopsies of H. pylori-infected patients compared to H. pylori-uninfected patients. There was association between virulence factors and TGF-ß1 mRNA expression. TGF-ß1 mRNA expression in mucosa was significantly higher in patients with vacA s1 and s1m1. CONCLUSIONS: TGF-ß1 may play an important role in the inflammatory response and promote the chronic and persistent inflammatory changes in the gastric. This may ultimately influence the outcome of H. pylori-associated diseases that arise within the context of gastritis and vacA may suffice to induce expression of TGF-ß1 mRNA.

Early prevention by L-Arginine attenuates coronary atherosclerosis in a model of hypercholesterolemic animals; no positive results for treatment.

BACKGROUND: Endothelial dysfunction (ED) is an independent predictor of cardiovascular events. ED is also a reversible disorder, and nitric oxide donors like L-arginine may promote this process. Despite the positive results from several studies, there are some studies that have shown that L-arginine administration did not improve endothelium-dependent dilation or the inflammatory state of patients. In this study the early and the late effects of L-arginine on coronary fatty streak formation and ED biomarkers were considered in hypercholesterolemic rabbits. METHODS: 36 white male rabbits randomly assigned in 3 groups. Rabbits were fed 1% high-cholesterol diet (LP group, n = 15), or high-cholesterol diet with oral L-arginine (3% in drinking water) (EP group, n = 15) or standard diet (control group, n = 6) for 4 weeks (phase I). Afterward, all animals were fed normal diet for 4 weeks (phase II). In the second phase, L-arginine was discontinued for EP group and was begun for LP group. The plasma levels of lipids, von Willebrand factor (vWF), and nitrite were compared before and after 4 and 8 weeks of experiment. Coronary fatty streak formation was measure after 4 and 8 weeks of experiment. RESULTS: The plasma levels of lipids were increased significantly in both groups of LP and EP after phase I. The hypercholesterolemia induced significant increased vWF release in LP group. The L-arginine supplementation led to significant plasma nitrite increment in EP group. The vWF in LP group was higher than other groups (p < 0.05). By the end of phase II, despite of start of L-arginine supplementation for LP group and L-arginine discontinuation in EP group, there were significantly more fatty streaks lesions in LP group coronary arteries than EP group. Furthermore, L-arginine supplementation did not result in significant nitrite increment in LP group. CONCLUSION: Early prevention by L-arginine may be helpful to prevent the ED, but our study did not suggest the treatment. It seems reasonable to consider ED-aside from control the cardiovascular risk factors in primary prevention of atherosclerosis and its clinical outcomes before development of irreversible vascular damage.