Melatonin protection against burn-induced hepatic injury by down-regulation of nuclear factor kappa B activation.

Melatonin exhibits a wide variety of biological activity including antioxidant and anti-inflammatory effects. We have previously reported its protective effect on hepatic oxidative hepatic injury in burns. In this study, we investigated the role of nuclear factor kappa B (NF-κB) in melatonin-mediated protection against liver injury by using the burned-rat model. Melatonin (N-acetyl-5-methoxytriptamin, 10mg/kg (-1), i.p.) was administered immediately and 12 hours after thermal skin injury. Hepatic NF-κB expression was determined by Western blotting. TNF-α level in liver homogenate was quantified using enzyme-linked immunosorbent assay (ELISA) kit. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver injury at the 24th hour after burns. Thermal skin injury caused significant elevation of hepatic NF-κB expression by 48 percent, TNF-α level by 55 percent and plasma AST and ALT activities by 2- and 3-fold, respectively, in comparison with normal control rats. Treatment with melatonin decreased significantly elevated hepatic NF-κB activity and TNF-α, maintaining the levels close to the control values Melatonin suppressed the elevation of plasma AST and ALT activities (p less than 0.001), which remained significantly increased compared to controls. In conclusion, thermal skin injury causes hepatic NF-κB activation that may mediate the release of hepatic TNF-α and contribute to liver damage. Melatonin protects against burn-induced hepatic injury as to a certain extent this effect may result from the suppression of NF-κB-mediated inflammatory response.

Risk and protective factors for development of colorectal polyps and cancer (Bulgarian experience).

BACKGROUND/AIMS: Colorectal cancer takes third place among all malignancies in the Varna region. The present study aims to determine the typical and distinguishing risk and protective factors for colorectal polyps and cancer formation. METHODOLOGY: 166 patients with large bowel polyps and 107 patients with colorectal cancer were questioned, examined endoscopically and histologically. Logistic regression analysis was used to find a possible correlation between alimentary habits, way of life, and risk for colorectal polyps and cancer formation. The latter have been used to define a strategy for their prevention. RESULTS: Our results showed that fried, preserved, and grilled meat, consumption of animal fats, sugar, and being overweight are positively associated with colorectal polyps. In contrast, consumption of fruit, vegetables, rye- and brown bread, green tea, vegetable food, yoghourt, vegetarian food, fish, lamb, hare, garlic, boiled food, and mineral water, have strong protective effect against large bowel polyps. We have confirmed the role of the well-known risk factors for colorectal cancer, and discovered an association between H. pylori infection, age, villous component in the adenomatous polyps, and family history for any neoplasia and large bowel carcinoma. CONCLUSIONS: We suggest the following protective factors for CRC: vegetarian food, plant oil, rural life, aspirin intake, legumes, fish, fruit and vegetable consumption. We observe a similarity between the risk factors for colorectal polyps and cancer formation. They act simultaneously and depend on genetic predisposition. A combination of endoscopic treatment and correction of the alimentary factors could be used as a means of cancer prevention.

Chronic HBV infection. Immunomodulation with levamisole in viremic HBeAg positive or anti-HBe positive patients--a pilot study.

BACKGROUND/AIMS: We evaluated the effect of immunomodulatory treatment with levamisole in HBeAg positive or anti-HBe positive patients with chronic HBV infection and ongoing viral replication. The majority of patients had an expected poor response to IFN-alpha. METHODOLOGY: Twenty-five viremic patients (15 males and 10 females) with chronic HBV infection were treated with Levamisole for 12 months or until negative serum HBV DNA occurred for at least 3 months. Viral replication and aminotransferase activity were controlled at the end of 3, 6, 9 and 12 months during the treatment. RESULTS: A decrease of serum HBV DNA was noted when serum HBV DNA levels before and after treatment with levamisole were compared, by t-test for dependent samples (p < 0.05). There was a significant reduction of ALT activity, too. HBV DNA fell below the detection limit of our assay at the end of 3, 6, 9 and 12 months in 7, 7, 8 and 10 of the patients, respectively. In 3 of 16 initially HBeAg positive patients, seroconversion to anti-HBe antibody occurred. At the end of 12 months 10 patients were with negative serum HBV DNA and normal ALT activity. Two of them lost HBsAg during the treatment. Ten patients were without any effect from the therapy. The potential responder initially is anti-HBe positive, with low serum HBV DNA < 500 pg/ml and low ALT activity (< 3 times the upper limit of normal). CONCLUSIONS: Immunomodulation with levamisole may benefit some patients with chronic ongoing viral replication including patients with expected poor response to IFN-alpha. This treatment could be used as an alternative therapeutic schedule in patients contraindicated for IFN-alpha, and also because it lowers treatment costs.