Primary cultures of prostate epithelial cells and their ability to activate carcinogens.

Differences in the incidence of prostate cancer (CaP) amongst different migrant populations point to causative agents of dietary and/or environmental origin. Prostate tissues were obtained following transurethral resection of the prostate (TURP) or radical retropubic prostatectomy. After surgery, TURP-derived or tumour-adjacent tissue fragments were minced in warm PFMR-4A medium (37?C) and suspensions pipetted into collagen-coated petri dishes. Non-adherent material was removed by washing with fresh medium after 12 h. Adhered cells subsequently reacted positively with monoclonal antibodies to prostate specific antigen (PSA). PSA was also detected in the medium. The genotoxicities of the chemical carcinogens 2-amino-1-methyl-6-phenylimidazo4,5-b pyridine (PhIP), its N-hydroxy metabolite (N-OH-PhIP) and benzoapyrene (BaP) in adherent cell populations from different donors (n=8) were examined. Cells were treated in suspension for 30 min at 37?C in the presence of the DNA repair inhibitors hydroxyurea (HU) and cytosine arabinoside (ara-C). DNA single-strand breaks were detected in cells by the alkaline single cell-gel electrophoresis ('Comet') assay and quantified by measuring comet tail length (CTL) in m. All three carcinogens induced dose-related increases in CTLs (P{\ensuremath{<}}0.0001) in cells from four donors 24 h post-seeding. However, in cells from a further two donors the genotoxic effects of PhIP, N-OH-PhIP and BaP were much less apparent after 48 h than after 24 h in culture. After 96 h in culture, cells from these donors appeared to be resistant to the comet-forming activity of the compounds. However, BaP-DNA adducts were still measurable by 32P-postlabelling for up to 14 days following a 24-h exposure to 50 M BaP in adhered cells from another two donors. This study shows that primary cultures of cells derived from the prostate can activate members of two classes of chemical carcinogens. Further development may provide a robust model system in which to investigate the aetiology of CaP

The Economic Determinants of the Olympic Performance in Communist and Post-Communist Countries

International audienceThe chapter first reminds the statist model of sport, its overshooting Olympic performance, and reforms before its final collapse. Moving towards a market-compatible sport system during the transformational economic crisis was not without hindrances ending up into a hybrid sports industry. All these changes affected Olympic performance downwards. Econometric modelling explains all nations’ medal totals at Summer Olympic Games by GDP per capita, population, a host country effect, regional sport specialisation, and a political regime variable taking on board communist and post-communist specificity. A similar model is adapted to Winter Games by adding two variables, snow coverage and endowment in winter sports resorts. Both models provide a statistically significant explanation of how medal totals have evolved in post-communist nations. Used for forecasting, the Winter Olympics model enables checking the impact of doping on Olympic performance with a natural experiment at the 2014 Sochi Games

Causes and consequences of ischemic-type biliary lesions after liver transplantation

Biliary complications are a major source of morbidity, graft loss, and even mortality after liver transplantation. The most troublesome are the so-called ischemic-type biliary lesions (ITBL), with an incidence varying between 5% and 15%. ITBL is a radiological diagnosis, characterized by intrahepatic strictures and dilatations on a cholangiogram, in the absence of hepatic artery thrombosis. Several risk factors for ITBL have been identified, strongly suggesting a multifactorial origin. The main categories of risk factors for ITBL include ischemia-related injury; immunologically induced injury; and cytotoxic injury, induced by bile salts. However, in many cases no specific risk factor can be identified. Ischemia-related injury comprises prolonged ischemic times and disturbance in blood flow through the peribiliary vascular plexus. Immunological injury is assumed to be a risk factor based on the relationship of ITBL with ABO incompatibility, polymorphism in genes coding for chemokines, and pre-existing immunologically mediated diseases such as primary sclerosing cholangitis and autoimmune hepatitis. The clinical presentation of patients with ITBL is often not specific; symptoms may include fever, abdominal complaints, and increased cholestasis on liver function tests. Diagnosis is made by imaging studies of the bile ducts. Treatment starts with relieving the symptoms of cholestasis and dilatation by endoscopic retrograde cholangiopancreaticography (ERCP) or percutaneous transhepatic cholangiodrainage (PTCD), followed by stenting if possible. Eventually up to 50% of the patients with ITBL will require a retransplantation or may die. In selected patients, a retransplantation can be avoided or delayed by resection of the extra-hepatic bile ducts and construction of a hepaticojejunostomy. More research on the pathogenesis of ITBL is needed before more specific preventive or therapeutic strategies can be developed