The effect of tobacco, XPC, ERCC2 and ERCC5 genetic variants in bladder cancer development

<p>Abstract</p> <p>Background</p> <p>In this work, we have conducted a case-control study in order to assess the effect of tobacco and three genetic polymorphisms in <it>XPC, ERCC2 and ERCC5 </it>genes (rs2228001, rs13181 and rs17655) in bladder cancer development in Tunisia. We have also tried to evaluate whether these variants affect the bladder tumor stage and grade.</p> <p>Methods</p> <p>The patients group was constituted of 193 newly diagnosed cases of bladder tumors. The controls group was constituted of non-related healthy subjects. The rs2228001, rs13181 and rs17655 polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique.</p> <p>Results</p> <p>Our data have reported that non smoker and light smoker patients (1-19PY) are protected against bladder cancer development. Moreover, light smokers have less risk for developing advanced tumors stage. When we investigated the effect of genetic polymorphisms in bladder cancer development we have found that ERCC2 and ERCC5 variants were not implicated in the bladder cancer occurrence. However, the mutated homozygous genotype for XPC gene was associated with 2.09-fold increased risk of developing bladder cancer compared to the control carrying the wild genotype (p = 0.03, OR = 2.09, CI 95% 1.09-3.99). Finally, we have found that the XPC, ERCC2 and ERCC5 variants don't affect the tumors stage and grade.</p> <p>Conclusion</p> <p>These results suggest that the mutated homozygous genotype for XPC gene was associated with increased risk of developing bladder. However we have found no association between rs2228001, rs13181 and rs17655 polymorphisms and tumors stage and grade.</p

Acidic Digestion in a Teleost: Postprandial and Circadian Pattern of Gastric pH, Pepsin Activity, and Pepsinogen and Proton Pump mRNAs Expression

Two different modes for regulation of stomach acid secretion have been described in vertebrates. Some species exhibit a continuous acid secretion maintaining a low gastric pH during fasting. Others, as some teleosts, maintain a neutral gastric pH during fasting while the hydrochloric acid is released only after the ingestion of a meal. Those different patterns seem to be closely related to specific feeding habits. However, our recent observations suggest that this acidification pattern could be modified by changes in daily feeding frequency and time schedule. The aim of this study was to advance in understanding the regulation mechanisms of stomach digestion and pattern of acid secretion in teleost fish. We have examined the postprandial pattern of gastric pH, pepsin activity, and mRNA expression for pepsinogen and proton pump in white seabream juveniles maintained under a light/dark 12/12 hours cycle and receiving only one morning meal. The pepsin activity was analyzed according to the standard protocol buffering at pH 2 and using the actual pH measured in the stomach. The results show how the enzyme precursor is permanently available while the hydrochloric acid, which activates the zymogen fraction, is secreted just after the ingestion of food. Results also reveal that analytical protocol at pH 2 notably overestimates true pepsin activity in fish stomach. The expression of the mRNA encoding pepsinogen and proton pump exhibited almost parallel patterns, with notable increases during the darkness period and sharp decreases just before the morning meal. These results indicate that white seabream uses the resting hours for recovering the mRNA stock that will be quickly used during the feeding process. Our data clearly shows that both daily illumination pattern and feeding time are involved at different level in the regulation of the secretion of digestive juices

Decellularized Matrix from Tumorigenic Human Mesenchymal Stem Cells Promotes Neovascularization with Galectin-1 Dependent Endothelial Interaction

BACKGROUND: Acquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC) strain (hMSC-TERT20) immortalized by retroviral vector mediated human telomerase (hTERT) gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative qRT-PCR analysis revealed similar mRNA levels for genes encoding the angiogenic cytokines VEGF and Angiopoietin-1 in both clones. However, clone-BD11 produced a denser extracellular matrix that supported stable ex vivo capillary morphogenesis of human endothelial cells and promoted in vivo neovascularization. Proteomic characterization of the -BD11 decellularized matrix identified 50 extracellular angiogenic proteins, including galectin-1. siRNA knock down of galectin-1 expression abrogated the ex vivo interaction between decellularized -BD11 matrix and endothelial cells. More stable shRNA knock down of galectin-1 expression did not prevent -BD11 tumorigenesis, but greatly reduced endothelial migration into -BD11 cell xenografts. CONCLUSIONS: Decellularized hMSC matrix had significant angiogenic potential with at least 50 angiogenic cell surface and extracellular proteins, implicated in attracting endothelial cells, their adhesion and activation to form tubular structures. hMSC -BD11 surface galectin-1 expression was required to bring about matrix-endothelial interactions and for xenografted hMSC -BD11 cells to optimally recruit host vasculature

Diagnosis and management of catheter-related infected intracardiac thrombosis in premature infants

Infected right atrial thrombosis is an uncommon but severe complication of the use of central indwelling catheters in children. Massive thrombi around a right atrial catheter were seen in two critically ill premature infants after 3 weeks of parenteral nutrition. A catheter-related sepsis had previously occurred and had been treated by antibiotics. Subsequently, protracted thrombocytopenia, fluctuating hepatomegaly and increasing respiratory distress were found in both cases. A right atrial mass was detected by 2 dimensional echocardiography. Cardiotomies for removal of the infected thrombus were performed with success in both cases. In one infant, weighing only 900 gm, surgical removal was accomplished with the aid of inflow stasis. Premature infants with catheter-related sepsis appear at greater risk for intracardiac thrombosis and should undergo echocardiography as part of their evaluation. Infected atrial thrombi can be safely removed by cardiotomy even in the very small premature infant

Purification, Structural Characterization and Antiproliferative Properties of Chondroitin Sulfate/Dermatan Sulfate from Tunisian Fish Skins

Chondroitin sulfate/dermatan sulfate GAGs were extracted and purified from the skins of grey triggerfish (GTSG) and smooth hound (SHSG). The disaccharide composition produced by chondroitinase ABC treatment showed the presence of nonsulfated disaccharide, monosulfated disaccharides \u394Di6S and \u394Di4S, and disulfated disaccharides in different percentages. In particular, the nonsulfated disaccharide \u394Di0S of GTSG and SHSG were 3.5% and 5.5%, respectively, while monosulfated disaccharides \u394Di6S and \u394Di4S were evaluated to be 18.2%, 59% and 14.6%, 47.0%, respectively. Capillary elecrophoresis analysis of GTSG and SHSG contained 99.2% and 95.4% of chondroitin sulfate/dermatan sulfate, respectively. PAGE analysis showed a GTSG and SHSG having molecular masses with average values of 41.72KDa and 23.8KDa, respectively. HCT116 cell proliferation was inhibited (p&lt;0.05) by 70.6% and 72.65% at 200\u3bcg/mL of GTSG and SHSG respectively. Both GTSG and SHSG demonstrated promising antiproliferative potential, which may be used as a novel, effective agent

Prevalence and determinants of the metabolic syndrome among Tunisian adults : results of the Transition and Health Impact in North Africa (TAHINA) project

Objective: To determine the prevalence of metabolic syndrome (MetS) and its components and to evaluate the relationship between this diagnosis and cardiovascular risk factors, demographic and socio-economic variables. Design: A cross-sectional study using a questionnaire including information on sociodemographic and CVD risk factors. Blood pressure, anthropometric indices, fasting glucose and lipid profile were measured. MetS was defined according to the criteria of the National Cholesterol Education Program, Adult Treatment Panel III. Setting: The whole Tunisian territory; Transition and Health Impact in North Africa (TAHINA) project. Subjects: A total of 4654 individuals (1840 men and 2814 women), aged 35 to 74 years, who participated in the Tunisian national survey. Results: The overall prevalence of MetS was 30.0%, higher in women (36.1%) than in men (20.6%; P<0.001). In both genders MetS prevalence increased significantly with age (P<0.001), but this increase was more important in women. Multiple regression analyses showed that the odds for MetS increased significantly with urban area for both men and women (P<0.05 and P<0.001, respectively). The multivariate models showed also that the odds for MetS increased significantly with increasing level of education and in those with a family history of CVD for men (both P<0.05) and after the menopausal transition for women (P<0.05). Conclusions: The study highlights the MetS problem in a middle-income developing country. There is an urgent need for a comprehensive, integrated, population-based intervention programme to ameliorate the growing problem of MetS in Tunisians

Prevalence of diabetes in Northern African countries : the case of Tunisia

Background: Although diabetes is recognized as an emerging disease in African and Middle East, few population-based surveys have been conducted in this region. We performed a national survey to estimate the prevalence of type 2 diabetes (T2D) and to evaluate the relationship between this diagnosis, demographic and socioeconomic variables. Methods: The study was conducted on a random sample of 6580 households (940 in each region). 7700 subjects adults 35-70 years old were included in the analyses. T2D was assessed on the basis of a questionnaire and fasting blood glucose level according to the WHO criteria. Access to health care and diabetes management were also assessed. Results: Overall, the prevalence of T2D was 15.1%. There were sharp urban vs. rural contrasts, the prevalence of diabetes being twice higher in urban area. However, the ratio urban/rural varied from 3 in the less developed region to 1.6 in the most developed ones. A sharp increase of prevalence of T2D with economic level of the household was observed. For both genders those with a family history of T2D were much more at risk of T2D than those without. Awareness increase with age, economic level and were higher amongst those with family history of T2D. Drugs were supplied by primary health care centers for 57.7% with a difference according to gender, 48.9% for men vs. 66.0% women (p < 0.001) and area, 53.3% on urban area vs. 75.2% on rural one (p < 0.001). Conclusions: Through its capacity to provide the data on the burden of diabetes in the context of the epidemiological transition that North Africa is facing, this survey will not only be valuable source for health care planners in Tunisia, but will also serve as an important research for the study of diabetes in the region where data is scarce. In this context, NCDs emerge as an intersectoral challenge and their social determinants requiring social, food and environmental health policy