Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage

NSAIDs are among the most commonly used drugs worldwide and their beneficial therapeutic properties are thoroughly accepted. However, they are also associated with gastrointestinal (GI) adverse events. NSAIDs can damage the whole GI tract including a wide spectrum of lesions. About 1 to 2% of NSAID users experienced a serious GI complication during treatment. The relative risk of upper GI complications among NSAID users depends on the presence of different risk factors, including older age (>65 years), history of complicated peptic ulcer, and concomitant aspirin or anticoagulant use, in addition to the type and dose of NSAID. Some authors recently reported a decreasing trend in hospitalizations due to upper GI complications and a significant increase in those from the lower GI tract, causing the rates of these two types of GI complications to converge. NSAID-induced enteropathy has gained much attention in the last few years and an increasing number of reports have been published on this issue. Current evidence suggests that NSAIDs increase the risk of lower GI bleeding and perforation to a similar extent as that seen in the upper GI tract. Selective cyclooxygenase-2 inhibitors have the same beneficial effects as nonselective NSAIDs but with less GI toxicity in the upper GI tract and probably in the lower GI tract. Overall, mortality due to these complications has also decreased, but the in-hospital case fatality for upper and lower GI complication events has remained constant despite the new therapeutic and prevention strategies.     

Electrophoretic and biochemical studies of human aldehyde dehydrogenase isozymes in various tissues

Four major ALDH isozymes have been identified in human tissues using starch gel electrophoresis and isoelectric focusing. The isozyme bands have been termed as ALDH I, II, III and IV according to their decreasing electrophoretic migration and increasing isoelectric point. The isozymes have been partially purified via preparative isoelectric focusing. Kinetic characteristics of ALDH I and II were found to be quite similar to ALDH enzyme 2 and enzyme 1 described earlier by Greenfield and Pietruszko (Biochem Biophys Acta, $\text{483}$ 35–45 1977). ALDH III and IV showed a very high Km for propionaldehyde (1.0–1.5 mM at pH 9.5) and were not inhibited by disulfiram at pH 9.5. A variant phenotype of ALDH which lacked in isozyme I was detected in various tissues from Japanese individuals. Comparative kinetic properties of normal and variant enzyme are given.     

胆汁致消化道黏膜损伤机制的研究进展

胆汁是由肝细胞分泌的胆道内的消化液,为等渗溶液,主要成分包括胆盐、胆汁酸、胆红素、还原型谷胱甘肽及其结合物、氧化型谷胱甘肽等。在消化期,胆汁可由肝脏和胆囊大量排到十二指肠,将脂肪乳化成微滴以利于消化;还能促进脂肪酸及脂溶性维生素的吸收。生理状态下胆汁不会反流入胃及食管,也不会损伤肠道。病理状态下胆汁会反流入胃甚至反流到食管损伤胃及食管黏膜,在一些情况下胆汁甚至会损伤肠道的黏膜。目前认为胆汁是较明确的致癌因素,与消化道肿瘤的相关性较大,但仍缺乏针对性的防治方案。明确胆汁对消化道黏膜的损伤机制,有助探索消化道肿瘤防治的新靶点。本文回顾了近年来有关胆汁对食管黏膜、胃黏膜及肠黏膜损伤机制的研究进展,以期为进一步的研究提供思路。     

Bioconversion of arachidonic acid in the human gastrointestinal tract

The data presented demonstrate that the bioconversion of [14C]arachidonic acid in homogenates like these is very easily influenced by protein (enzyme) and substrate concentration as well as exogenous cofactors. This is not unexpected but variations will lead to artifactual differences. Neither quantitative nor qualitative differences could be detected between biopsies taken from healthy as compared to diseased individuals. No products other than PGE2, PGF2 alpha, TxB2, and 6-keto-PGF1 alpha (and metabolites thereof) could be demonstrated although special efforts were undertaken to determine whether there was any detectable lipoxygenase activity. Therefore it seems that future studies on the possible roles of prostaglandins in gastrointestinal physiology should be restricted to those compounds identified, primarily PGE2 and PGF2 alpha. The monotony in the pattern of products formed in homogenates from different tissues also suggests that in order to be able to detect possible differences between various conditions such studies should involve a minimum of tissue manipulation.     

Various aspects of structural studies of aspartate proteinases

The paper is a brief account of aspartic proteinases' structural studies developed in V.A. Engelhardt Institute of Molecular Biology during the last 3 years. The work on porcine pepsin has been finalized after the refinement of the monoclinic crystal form at 1.8 A resolution performed in collaboration with the group of protein structure and function studies of the University of Alberta in Canada. An important structural property of chymosin which explains the enzyme specificity has been found. Protein engineering work on chymosin is being developed. The structural template for aspartic proteinases has been elucidated and on the basis of this template the model of HIV-1 protease molecule has been built. Some approaches to the design of HIV-1 protease inhibitors were elucidated.     

Fluorescence studies on the active sites of proteinases

Summary Recent studies on the interaction of several proteinases (pepsin, papain, chymotrypsin, trypsin, thermolysin) with specific substrates or inhibitors bearing a fluorescent probe group have shown that the extended active sites of these enzymes differ in their conformational flexibility. In addition the use of such extrinsic probe groups, measurements of changes in the intrinsic tryptophan fluorescence, and of the energy transfer from tryptophan to a probe group, have given further information about the flexibility of the active sites of proteinases.     

Connexins in respiratory and gastrointestinal mucosal immunity

The mucosal lining forms the physical and chemical barrier that protects against pathogens and hostile particles and harbors its own population of bacteria, fungi and archea, known as the microbiota. The immune system controls tolerance of this population of microorganisms that have proven to be beneficial for its host. Keeping its physical integrity and a correct balance with the microbiota, the mucosa preserves its homeostasis and its protective function and maintains host’s health. However, in some conditions, pathogens may succeed in breaching mucosal homeostasis and successfully infecting the host. In this review we will discuss the role the mucosa plays in the defense against bacterial pathogens by considering the gap junction protein connexins. We will detail their implication in mucosal homeostasis and upon infection with bacteria in the respiratory and the gastrointestinal tracts.