Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease

There is experimental evidence that inhibition of cyclooxygenase with nonsteroidal anti-inflammatory drugs may decrease cholesterol gall-stone formation and mitigate biliary pain in gall-stone patients. The mechanisms by which NSAIDs exert these effect are unclear. In a prospective, controlled clinical trial we examined the effects of oral indomethacin on the composition of human gall-bladder bile. The study included 28 patients with symptomatic cholesterol or mixed gallstones. Of these, 8 were treated with 3 × 25 mg indomethacin daily for 7 days prior to elective cholecystectomy while 20 received no treatment and served as controls. Bile and tissue samples from the gallbladder were obtained during cholecystectomy. Indomethacin tissue levels in the gallbladder mucosa, as assessed by HPLC, were 1.05±0.4 ng/mg wet weight, a concentration known to inhibit effectively cyclooxygenase activity. Nevertheless, no differences between the treated and untreated groups were found in the concentrations of biliary mucus glycoprotein (0.94±0.27 versus 0.93±0.32 mg/ml) or total protein (5.8±0.9 versus 6.4±1.3 mg/ml), cholesterol saturation (1.3±0.2 versus 1.5±0.2), or nucleation time (2.0±3.0 versus 1.5±2.0 days). However, biliary viscosity, measured using a low-shear rotation viscosimeter, was significantly lower in patients receiving indomethacin treatment (2.9±0.6 versus 5.6±1.2 mPa.s; P < 0.02). In conclusion, in man oral indomethacin decreases bile viscosity without alteration of bile lithogenicity or biliary mucus glycoprotein content. Since mucus glycoproteins are major determinants of bile viscosity, an alteration in mucin macromolecular composition may conceivably cause the indomethacin-induced decrease in biliary viscosity and explain the beneficial effects of nonsteroidal anti-inflammatory drugs in gallstone disease

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Oxidative Cyclisierungsreaktionen von 1-(3-Nitro-3-phenylpropyl)piperidin

The title compound 2 - prepared by Komblum reaction - reacted with Hg(II)-edta in a two electron withdrawal to a bicyclic compound 6, which showed in solution an equilibrium of two species probably of diastereomers, which was deduced from NMR-measurements. Additionally, resulting of an threefold dehydrogenation two diastereomeric bicyclic lactams 11A and 11B were isolated

Knowledge database and case-based reasoning

Nuclear emergencies are characterised by severe disruptions in society's functionality and adverse impacts on human, environment and economy. Decision-making in times of such crises is complex and usually accompanied by acute time pressure. Environment can change rapidly and decisions may have to be made based on uncertain information. IT-based decision support can systematically help to identify response and recovery measures, especially when time for decision-making is sparse, when numerous options exist or when events are not completely anticipated. This paper reviews the case- and scenario-based approach implemented in the so-called analytical platform to support the management of nuclear events in different accident phases. Important information needed for decision-making as well as approaches to reusing experience from previous events and the fictitious scenarios calculated by Java version of the Real-time On-line Decision Support System are discussed. Suitable management options based on similar historic events and scenarios might be identified to support disaster management

Laser components

The chapter covers In P-based laser diodes (1300-1650nm wavelength range) deployed as transmitter devices in today's optical communication systems. Only discrete directly modulated devices are considered in this chapter which is followed by two other laser-related articles dealing specifically with ultra-fast and wavelength-tunable devices. In the first part, a description of basic laser structures and technology, of relevant gain materials and their impact on lasing properties, and of fundamental characteristics of Fabry-Pérot devices will be presented. The second part is devoted to single-wavelength lasers focusing on design rules and various implementations. Essentially, distributed feedback (DFB) devices are treated but other options such as the so-called discrete mode laser diodes will also be outlined. In the third part, surface-emitting laser diodes are addressed including vertical cavity surface-emitting lasers (VCSEL) and horizontal cavity DFB structures design ed for surface emission