Incidence of diabetes mellitus is dramatically growing in the world. Oxidative stress, advanced glycation end products (AGEs) and receptor for AGE (RAGE) play key role in the pathogenesis of diabetes. Little is known about resveratrol effects on the liver. We hypothesize that resveratrol may exert a hepatoprotective effect in diabetic rats. Male rats with diabetes were treated with or without resveratrol at 1, 5 and 10 mg/kg body weight for 30 days. Total AGEs and malondialdehyde (MDA) levels in liver tissues were determined by spectrofluorimetric methods. Total antioxidant capacity and total oxidant contents in the liver and glucose in plasma were measured by a colorimetric assay. Expression of RAGE was assayed in liver of all animals using quantitative polymerase chain reaction. In liver tissue extract of resveratrol-treated rats with diabetes, MDA levels, total oxidant, plasma glucose and expression of RAGE were significantly reduced compared to the untreated group. Moreover, total antioxidant levels were significantly increased in treated rats. There was no significant difference in AGE contents among all groups. These results revealed that resveratrol had beneficial effects on the liver by extenuating oxidative stress and down regulation of RAGE expression.

Smoking is the most important cause of lung cancer as well as an important determinant of other neoplasms and nonneoplastic diseases. 2 In Pakistan, a nation-wide survey found that 21.6% of the subjects aged 15 or above were smokers, with a higher proportion among men (36%) than women (9%). In addition to cigarettes and bidis, tobacco is also smoked in local ways such as a hookah (a clay pot containing burning coal over a layer of tobacco fixed to a second pot containing water with two pipes, one for smoking and the other to filter smoke through water). 3 It is worth noting that Pakistani cigarettes contain high levels of tar and nicotine. 4 Furthermore, other possible risk factors of lung cancer, such as exposure to indoor air pollution from cooking fumes have been poorly investigated in countries from Southern Asia.To our knowledge, no studies had conducted to investigate the causes of lung cancer in Pakistan, the seventh most populated country in the world.All newly diagnosed patients of lung cancer treated at the Liaquat National Post Graduate Medical Centre, the Jinnah Post Graduate Medical Center (JPMC) and the Civil Hospital were enrolled without any restriction according to age, sex, residence or diagnostic procedure. A small number of patients diagnosed and treated at other hospitals were identified from the records of the population-based cancer registry of South Karachi. 1 Two groups of controls were selected in the same hospitals as the cases, to whom they were individually matched by sex and age. The first group comprised hospital patients undergoing minor surgical operations (e.g., hernia, appendicitis, bone fracture), the second one visitors to patients other than cases.Trained interviewers administered the questionnaire, which was designed to gather information on smoking habits, chewing, use of snuff (naswar) and residential history (including sources of indoor air pollution).Smokers were defined as having smoked at least once a day for at least 6 months. In order to combine the consumption of different tobacco products, we calculated cigarette-equivalents by using the following weights: 0.75 for bidi, 3 for pipe, 4 for cigar and 20 for hookah. Cigarette-equivalents approximate grams of tobacco. 2 Cumulative consumption of tobacco products was then calculated by multiplying the average daily consumption of cigarette-equivalents by the duration of smoking.Never smokers were chosen as the reference category for the main analyses on smoking. In some analyses, we excluded never smokers and used the least exposed group as baseline in order to assess simultaneously the effect of different aspects of smoking (e.g., duration and consumption).Most chewers used betel quid (pan), which contains betel leaf, lime, areca nut and, in most cases, tobacco. Snuff (naswar) consists of a blend of sun-cured tobacco, lime ashes of plants and variable flavoring agents. It is usually placed behind the lower lip or below the tongue.The subjects were asked about their places of residence, including fuels commonly used fo...

Background:Millions of people in the world have diabetes mellitus and its prevalence is growing. Oxidative stress, advanced glycation end-products (AGEs) and receptor for advanced glycation end-products (RAGE) play key role in the pathogenesis of diabetes. New and safe strategies of remedy are needed for this disease.Objectives:We hypothesized that resveratrol may exert a renal protective effect on diabetic rats.Materials and Methods:Male rats with diabetes were treated with or without resveratrol as 1, 5, 10 mg/kg of body weight for 30 days. The total AGEs and malondialdehyde levels in kidney tissues were determined by spectrofluorimetric method and the insulin level was assayed using ELISA. The total antioxidant capacity contents in kidney and the glucose in plasma were measured by a colorimetric assay. The expression of RAGE was assayed in kidneys of all animals using quantitative PCR.Results:In resveratrol-treated rats with diabetes, malondialdehyde levels, plasma glucose and expression of RAGE were significantly reduced compared with the untreated group. Moreover, the total antioxidant and insulin levels significantly increased in treated rats. There was no significant difference in the AGEs contents among all the groups.Conclusions:These results revealed that resveratrol has beneficial effects on kidney by extenuating the oxidative stress and down-regulation of RAGE expression.

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Tyrosine kinase inhibitors (TKIs) have been developed as therapeutic compounds for inhibiting the progression of liver fibrosis. In the present study, the simultaneous treatment of Nilotinib (TKIs) and Losartan was studied. Forty rats were divided into eight groups of fibrosis induced by carbon tetrachloride (CCl) and therapeutics (Nilotinib, Losartan, and combination therapy). In the end, serum parameters of the liver and gene expression analysis of transforming growth factor-β, its receptors (TβRII), platelet-derived growth factor, its receptors (PDGFR), matrix metalloproteinases (MMP-2 and MMP-9), tumor necrosis factor-α, cytochrome P450 2E1, and collagen1 type 1 were performed. The oxidant/antioxidant factors were also analyzed. Histopathology analysis along with α-SMA immunohistochemistry and hydroxyproline evaluation was also conducted for a more in-depth study. The overall results indicated a better therapeutic effect of co-treatment of Nilotinib-Losartan in comparison with the treatment of each of them alone. Interestingly, some gene and protein factors and fibrotic indices were reduced even to the normal levels of the control group. The results of this study suggest that co-administration of these two combinations, strengthens their anti-fibrotic properties and, due to the routine use of these compounds against AML and blood pressure, these compounds can be used with caution against human liver fibrosis.

Brucellosis remains a major zoonosis worldwide; therefore, better understanding of its immunology is a priority for the development of new therapeutic and vaccination strategies. Genetic factors appear to have an important role in the pathogenesis of infectious diseases such as brucellosis. Adhesion molecules, such as members of the selectin family, participate in the interaction between leukocytes and the endothelium, as well as in inflammatory cell recruitment. The impact of L-selectin polymorphisms on brucellosis has not so far been investigated. The aim of this study was to assess an L-selectin Phe206Leu (F206L) polymorphism in patients with active brucellosis, and to analyse its possible relationship with disease progression. A case-control association study was carried out on 619 subjects, including 374 patients with brucellosis and 245 age-and sex-matched healthy controls. Genomic DNA was isolated, and amplification of L-selectin genomic regions was performed by PCR incorporating sequence-specific primers (PCR-SSP) to distinguish the genotypes. The frequencies of the F206L polymorphism were studied. A significant difference in F206L polymorphism was found between patients with brucellosis and controls. The 206Leu allele was more frequent in patients than in healthy individuals (36?6 versus 28 %, P=0?003). In addition, there was an association between the presence of the 206Leu allele and a relapse of brucellosis (odds ratio 6?53, 95 % confidence interval 1?5-28?8, P=0?005). The higher frequency of L-selectin genotypes in patients with brucellosis than in control individuals, as well as the association between the 206Leu allele and the occurrence of brucellosis relapse, suggest that the F206L polymorphism could make individuals more vulnerable to brucellosis.

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