H2S biosynthesis and catabolism: new insights from molecular studies

Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissue

Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field

Ventricular tachyarrhythmia during pregnancy in women with heart disease: Data from the ROPAC, a registry from the European Society of Cardiology

Objectives: To describe the incidence, onset, predictors and outcome of ventricular tachyarrhythmia (VTA) in pregnant women with heart disease. Background: VTA during pregnancy will cause maternal morbidity and even mortality and will have impact on fetal outcome. Insufficient data exist on the incidence and outcome of VTA in pregnancy. Methods and results: From January 2007 up to October 2013, 99 hospitals in 39 countries enrolled 2966 pregnancies in women with structural heart disease. Forty-two women (1.4%) developed clinically relevant VTA during pregnancy, which occurred mainly in the third trimester (48%). NYHA class > 1 before pregnancy was an independent predictor for VTA. Heart failure during pregnancy was more common in women with VTA than in women without VTA (24% vs. 12%, p = 0.03) and maternal mortality was respectively 2.4% and 0.3% (p = 0.15). More women with VTA delivered by Cesarean section than women without VTA (68% vs. 47%, p = 0.01). Neonatal death, preterm birth (< 37 weeks), low birthweight (< 2500 g) and Apgar score < 7 occurred more often in women with VTA (4.8% vs. 0.3%, p = 0.01; 36% vs. 16%, p = 0.001; 33% vs. 15%, p = 0.001 and 25% vs. 7.3%, p = 0.001, respectively). Conclusions: VTA occurred in 1.4% of pregnant women with cardiovascular disease, mainly in the third trimester, and was associated with heart failure during pregnancy. NYHA class before pregnancy was predictive. VTA during pregnancy had clear impact on fetal outcome

Profound Chemopreventative Effects of a Hydrogen Sulfide-Releasing NSAID in the APC(Min/+) Mouse Model of Intestinal Tumorigenesis

Canadian Institutes of Health Research grant to JL

Risk of diabetes after para-aortic radiation for testicular cancer

Background: While the risk of diabetes is increased following radiation exposure to the pancreas among childhood cancer survivors, its association among testicular cancer (TC) survivors has not been investigated. Methods: Diabetes risk was studied in 2998 1-year TC survivors treated before 50 years of age with orchidectomy with/without radiotherapy between 1976 and 2007. Diabetes incidence was compared with general population rates. Treatment-specific risk of diabetes was assessed using a case–cohort design. Results: With a median follow-up of 13.4 years, 161 TC survivors were diagnosed with diabetes. Diabetes risk was not increased compared to general population rates (standardised incidence ratios (SIR): 0.9; 95% confidence interval (95% CI): 0.7–1.1). Adjusted for age, para-aortic radiotherapy was associated with a 1.66-fold (95% CI: 1.05–2.62) increased diabetes risk compared to no radiotherapy. The excess hazard increased with 0.31 with every 10 Gy increase in the prescribed radiation dose (95% CI: 0.11–0.51, P = 0.003, adjusted for age and BMI); restricted to irradiated patients the excess hazard increased with 0.33 (95% CI: −0.14 to 0.81, P = 0.169) with every 10 Gy increase in radiation dose. Conclusion: Compared to surgery only, para-aortic irradiation is associated with increased diabetes risk among TC survivors

Exercise-induced ventricular fibrillation: Seven years follow-up

We present a 7-year follow-up of a 55-year-old male who experienced ventricular fibrillation during the recovery period of exercise testing and refused implantation of an ICD. Normal left ventricular systolic function was found on echocardiographic examination, and coronary angiography revealed only a side branch disease with a vessel diameter of less than 2 millimeters. The patient was discharged on metoprolol and ASA in addition to his previous treatment with lisinopril and simvastatin. Outpatient cardiac evaluation by repeated 24-hour ECG monitorizations (Holter) revealed normal findings. On follow up visits every six months for the past seven years, the patient was found to be asymptomatic. © Trakya University Faculty of Medicine