Structure-activity relationship in the gastric cytoprotective effect of several sesquiterpene lactones.

The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-experimental study on the potentially active centers is carried out. The biological evaluation of reduced analogues and the simulation of the molecular interactions between these compounds and an endogenous cysteine residue suggest that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytoprotective activity in this family of compounds. This observation suggests that cytoprotection is mediated through a Michael reaction between the sulfhydryl-containing peptides of the mucosa and Michael acceptors present in the molecules under study. This mechanism of action is in addition to and distinct from the one proposed in our previous paper, namely, that these sesquiterpenes stimulate endogenous synthesis of prostaglandins.     

Seroprevalence and risk factors for hepatitis C virus antibody in pregnant women.

OBJECTIVE: To better understand hepatitis C viropathies and seroprevalence by performing an epidemiologic analysis of pregnant women seropositive for antibody against hepatitis C. METHODS: We studied 1013 consecutive obstetric patients at Parkland Memorial Hospital who gave informed consent for detailed interviews and serotesting. Sera were analyzed for antibody to the hepatitis C virus using both C100-3 and RIBA-4 assays. Neonatal assessment was carried out in the immediate postpartum period. RESULTS: Hepatitis C antibody was detected in 2.28% (N = 23) of the 1005 women in whom analysis was completed. Factors associated with seropositivity included intravenous (IV) drug use, sexually transmitted diseases, hepatitis B infection, maternal age greater than 22.5 years, increased parity (eg, greater than 2.1), history of transfusion, and three or more different lifetime sexual partners or a sexual partner who used IV drugs. Maternal and neonatal outcome was not different between hepatitis C antibody-positive and -negative groups. CONCLUSIONS: Epidemiologic data are consistent with sexual and parenteral modes of transmission. Women with hepatitis C antibody did not have excessive perinatal complications compared with antibody-negative women. A model protocol and cost analysis for screening pregnant women for hepatitis C infection are presented. However, routine screening for hepatitis C is not advocated.     

Hypergonadotroper Hypogonadismus bei Galaktosämie

Classical galactosaemia due to galactose-1-phosphate-uridyltransferase deficiency is an inherited metabolic disorder with an estimated incidence of 1:40,000 in the Caucasian population. In neonates the disease presents as hepatopathy with cerebral involvement. Without treatment classic galactosaemia leads to cataract, hepatic insufficiency and failure to thrive, and may finally be fatal. Treatment consists of a lactose-free diet. Despite early initiation of dietary treatment and long-term compliance, more than 80% of female patients develop hypergonadotropic hypogonadism. This paper aims to give practical recommendations for diagnosis and treatment of hypergonadotropic hypogonadism in patients with classical galactosaemia.     

Hemocompatibility of medical connectors with biopassive or bioactive surface coatings

Although medical connectors compose very small parts of the extracorporeal circulation (ECC) system they represent a critical localization where early thromboembolic processes can manifest. In the present study we modified an in vitro closed-loop model with fresh human whole blood for the preclinical evaluation of the hemocompatibility of three types of medical connectors: non-coated (control); with silicone-, and heparin-coating. Each single loop consists of five polycarbonate connectors joined together by five pieces of silicone tubes. Thrombin-antithrombin-III, beta-thromboglobulin (beta-TG), PMN-Elastase, terminal complement complex, CD 11b expression, and surface-absorbed fibrinogen were measured. After 1 and 2 h recirculation, platelet loss, release of beta-TG, and adsorption of fibrinogen were significantly higher (p<0.05) within the non-coated connectors compared to the silicone- and heparin-coated groups. Following this experiment, the connectors were filled again with fresh heparinized whole blood from the same donor to evaluate the influence of prior blood contact. Here, the activation of platelets and coagulation was dependent on the duration of the blood preincubation period. Probably, the coated surfaces possess a reduced, or selective adsorption of plasma proteins, which in turn leads to a faster creation of a blood-friendly secondary superficial membrane, and prevents a further denaturation and hence activation of the adsorbed proteins.     

Colchicine prevents tumor necrosis factor-induced toxicity in vivo.

Tumor necrosis factor (TNF) toxicity was induced in vivo by intravenous administration of 15 micrograms of recombinant murine TNF-alpha per kg to galactosamine-sensitized mice. Within 8 h, the animals developed a fulminant hepatitis. Intravenous administration of 0.5 mg of colchicine per kg at 19 and 4 h prior to TNF challenge protected the animals against hepatitis. Lipopolysaccharide (LPS)-stimulated, bone marrow-derived macrophages from C3H/HeN mice released significant amounts of TNF in vitro. When such macrophages were intravenously given to LPS-resistant galactosamine-sensitized C3H/HeJ mice, these animals died within 24 h. Preincubation of these transferred macrophages with colchicine did not suppress the LPS-inducible TNF release from these cells. Concordantly, administration of macrophages exposed to colchicine in vitro resulted in full lethality. However, in vivo pretreatment of C3H/HeJ mice with colchicine 19 and 4 h prior to the transfer of LPS-stimulated macrophages prevented lethality. In LPS-responsive NMRI mice which had been protected against galactosamine-LPS-induced hepatitis by pretreatment with colchicine, TNF was still released into the blood. We conclude from our findings that the in vivo protection by colchicine is mediated by blocking TNF action on target cells while the effector cells of LPS toxicity, i.e., the macrophages, remain responsive.