The antioxidant probucol as a regulator of the intensity of free-radical lipid peroxidation processes in the blood of patients with coronary atherosclerosis

Two series of studies were made to assess probucol medicines (lipomal, "Alkaloid"; fenbutol "Akrikhin") effect on clinical symptoms, lipid metabolism, primary and secondary products of lipid peroxidation, activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase) in atherosclerotic patients with hyperlipidemia type IIA and IIB. In both series probucol reduced frequency of anginal attacks, content of total cholesterol and LDL cholesterol. HDL cholesterol remained unchanged or reduced insignificantly. Lipoperoxides and malonic dialdehyde levels in plasma progressively lowered against activation of antioxidant enzymes. These biochemical parameters returned to initial values within 3 months since the drug discontinuation. It is evident that antiatherogenic effect of probucol is due to indirect activation of natural defense systems responsible for enzymic detoxication of active oxygen forms and lipoperoxides rather than to direct interaction of this synthetic antioxidant with lipid radicals.     

Follow-up results of modified Glenn-Andersen operation in children with primary vesicoureteral reflux

A questionnaire survey covered 11 females with temporal arteritis (CA) and 20 healthy controls. Gastrointestinal, joint and spinal complaints were significantly more frequent in CA patients. Clinical characteristics of joint and spinal disorders in CA patients are close to those of chronic reactive arthritis. It is suggested that Horton's disease may be lacking as a stage of the infectious process in elderly patients (chronic intestinal and/or urinary infection-reactive arthritis-CA). A case is reported where CA developed after intestinal and urinary infection. Administration of antibiotics for treatment of the recurrence induced a continuous remission under reduced doses of glucocorticoids. In another case biseptol + glucocorticoids brought about a persistent remission allowing glucocorticoid discontinuation.     

Localization of the sites for Ca2+-binding proteins on G protein-coupled receptor kinases

Inhibition of G protein-coupled receptor kinases (GRKs) by Ca2+-binding proteins has recently emerged as a general mechanism of GRK regulation. While GRK1 (rhodopsin kinase) is inhibited by the photoreceptor-specific Ca2+-binding protein recoverin, other GRKs can be inhibited by Ca2+-calmodulin. To dissect the mechanism of this inhibition at the molecular level, we localized the GRK domains involved in Ca2+-binding protein interaction using a series of GST-GRK fusion proteins. GRK1, GRK2, and GRK5, which represent the three known GRK subclasses, were each found to possess two distinct calmodulin-binding sites. These sites were localized to the N- and C-terminal regulatory regions within domains rich in positively charged and hydrophobic residues. In contrast, the unique N-terminally localized GRK1 site for recoverin had no clearly defined structural characteristics. Interestingly, while the recoverin and calmodulin-binding sites in GRK1 do not overlap, recoverin-GRK1 interaction is inhibited by calmodulin, most likely via an allosteric mechanism. Further analysis of the individual calmodulin sites in GRK5 suggests that the C-terminal site plays the major role in GRK5-calmodulin interaction. While specific mutation within the N-terminal site had no effect on calmodulin-mediated inhibition of GRK5 activity, deletion of the C-terminal site attenuated the effect of calmodulin on GRK5, and the simultaneous mutation of both sites rendered the enzyme calmodulin-insensitive. These studies provide new insight into the mechanism of Ca2+-dependent regulation of GRKs.     

The drug prophylaxis of peptic ulcer exacerbations

453 patients with ulcer located in the duodenal bulb and pyloric part of the stomach in the presence of Helicobacter pylori were examined before and followed up after hospital treatment of the ulcer. The authors findings support the importance of maintenance with current antisecretory drugs and on-demand therapy as well as of combined antibacterial therapy against Helicobacter pylori. Adequate chemotherapy in the ulcer exacerbation was able to reduce the number of recurrences and complications.