A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Risk factors for breast cancer in Turkish women: a hospital-based case-control study

The aim of this study was to investigate the association between risk factors and breast cancer in Turkish women. In a hospital-based case-control study in Istanbul, 405 patients with histologically confirmed breast cancer were compared with 1050 controls, who were admitted to different departments of the same hospital. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each risk factor were obtained from logistic regression analyses. Risk factors for breast cancer were found to be early menarche age (OR 3.87, 95% CI 2.46-6.08), use of alcohol (OR 3.87, 95% CI 1.79-8.37), history of diabetes (OR 3.31, 95% CI 2.36-4.64) or hypertension (OR 3.44, 95% CI 2.07-5.71), oral contraceptive use (OR 1.98, 95% CI 1.38-2.85) and hormone replacement therapy (HRT) use (OR 1.94, 95% CI 1.15-3.29). The findings of the present study indicated that history of diabetes or hypertension, use of alcohol, oral contraceptive and HRT, never having breastfed and delayed age at first birth associated with changing of lifestyle led to an increased risk of breast cancer in Turkish women

Views of Turkish health professionals on gamete donation

28th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE) -- JUL 01-04, 2012 -- Istanbul, TURKEYWOS:00032529960067328th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE). Meeting AbstractEuropean Soc Human Reprod & Embryo

Intestinal volvulus: Aetiology, morbidity and mortality in Tunisian children

Background: Intestinal volvulus (IV) can occur at various sites of the gastrointestinal tract. In Europe, IV in children is most frequently due to malrotation but in Asia Ascaris infestation is a common cause. This report reviews the experience with IV in children in Tunisia; analyzes the aetiologies as well as the clinical presentations and the benefi ts of the Ladd’s procedure in the treatment of the IV. Patients and Methods: The authors retrospectively reviewed the case records of all children with IV from January 2000 to December 2009 at the Tunis Children’s Hospital. Results: There were 22 boys and nine girls with an age range of one day to four years. Twenty-fi ve (80%) patients presented during the neonatal period. The most common presentation was bilious vomiting and dehydration. The aetiology was identifi ed in all patients: Anomalies in rotation (n=22), omphalomesenteric duct (n=3), internal hernia (n=3), cystic lymphangioma (n=2), caocal volvulus (n=1). The bowel resection rate for gangrene was 16%. All patients with malrotation had Ladd’s procedure performed. Five patients (19%) developed wound infections. One patient presented with adhesive small bowel obstruction. There were no recurrences following Ladd’s procedure for malrotation. Two neonates (6%) died from overwhelming infections. Intestinal volvulus in our environment differs in aetiology from other reports. The resection rates are not similar, however. Conclusion: Early diagnosis reduced the high morbidity and mortality in our study.Key words: Children, intestinal volvulus, malrotation, outcom

Status of vitamins A and E in schoolchildren in the centre west of Tunisia : a population-based study

Objective: The present study was undertaken to assess the status of vitamins A and E (VA and VE, respectively) and their main determinants in Tunisian children. Design: Cross-sectional population-based study. Setting: Kasserine Governorate in the centre west of Tunisia. Subjects: A total of 7407 children attending the first grade of elementary school were included. VA and VE were assessed by HPLC. Results: The prevalence of moderate VA deficiency (VAD; < 0.70 mu mol/l) was 2.3% and VE deficiency (VED; < 6.97 mu mol/l) was 5.4%. Low status in VA (0.70-1.05 mu mol/l) and VE (6.97-11.61 mu mol/l) was observed in 17% and 20.2% of children, respectively. No child exhibited severe VA or VE deficiency (< 0.35 and < 2.32 mu mol/l, respectively). The main predictors of VAD were advanced age (OR = 1.65; 95% CI 1.13, 2.41; P=0.05) and sickness within the past 2 weeks (OR = 1.51; 95% CI 1.09, 2.09; P=0.01). Predictors of VED were living in the pen-urban region (OR = 1.60; 95% CI 1.28, 2.01; P < 0001) and sickness within the past 2 weeks (OR = 0.75; 95% CI 0.60, 0.94; P=0.01). Conclusions: Moderate VAD and VED were uncommon in Tunisian children. However, low status in VA and/or VE remains frequent. A reinforcement of the national strategies for children's nutrition and health is needed, particularly in disadvantaged regions. Supplementation of VA and VE is not necessary in Tunisia, but food fortification may be beneficial