Effect of preoperative supplementation with alpha-tocopherol and ascorbic acid on myocardial injury in patients undergoing cardiac operations

Augmentation of antioxidant defenses may help protect tissues against ischemia-reperfusion injury associated with operations involving cardiopulmonary bypass. In this study we examined the effect of pretreating patients with alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) or placebo on injury to the myocardium. Seventy-six subjects undergoing elective coronary artery bypass grafting participated in a prospective, double-blind, placebo-controlled randomized trial, receiving either placebo or both 750 IU dl-alpha-tocopherol per day for 7 to 10 days and 1 gm ascorbic acid 12 hours before the operation. Plasma alpha-tocopherol concentrations, raised fourfold by supplementation, fell by 70% after the operation in the supplemented group and to negligible levels in the placebo group. There were no significant differences between the groups with respect to release of creatine kinase MB isoenzyme over 72 hours, nor in the reduction of the myocardial perfusion defect determined by thallium 201 uptake. Electrocardiography provided no evidence of a benefit from antioxidant supplementation. Thus the supplementation regimen prevented the depletion of the primary lipid soluble antioxidant in plasma, but provided no measurable reduction in myocardial injury after the operation.     

The effect of phototherapy on psychoautonomic disorders of a neurotic nature

Bright white light therapy was applied to 51 patients with syndrome of autonomic dysfunction of neurotic origin (1 hour of light exposure every day in the morning, during 2 weeks, 60 sm from the lamp, 3300 lux). Improvement occurred in 52% of the patients (responders--group 1, nonresponders--2). Changes occurred in nearly all symptoms: neuroendocrine, motivation, psychoautonomic, pain, psychopathologic. After the treatment in group 1 there was an increase of power of EEG spectrum, intensification of manifestations of the slow activity and decrease of the fast one from the two sides, an approach of the coefficient of asymmetry to the control levels as well as elevation of the urine excretion of metabolites of both catecholamines and serotonin. Initially higher power of EEG spectrum in group 2, became still more increased due to intensification of manifestations of theta and beta-2 rhythms from the two sides. Meanwhile coefficient of asymmetry was sharply decreased as well as general secretory activity inhibited. There were such symptoms and indices which had changed either negatively or positively under the influence of phototherapy.     

Crohn's disease and ulcerative colitis mucosal T cells are stimulated by intestinal epithelial cells: implications for immunosuppressive therapy

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases, and their pathogenesis is attributed, in part, to alterations of the mucosal immune system. This study was designed to define the possible contribution of epithelial cells to the activation of lamina propria T lymphocytes (LPTs) in CD and UC. METHODS: LPTs isolated from CD, UC, and control surgical specimens were cocultured with freshly isolated allogeneic or autologous epithelial cells or epithelial cell lines. Resulting T-cell proliferation was evaluated by tritiated thymidine incorporation on day 5. RESULTS: When intestinal epithelial cells were used to stimulate mucosal T-cell proliferation, CD and UC LPTs were less responsive than control LPTs (p < 0.05 and p < 0.03, respectively). This difference between inflamed and control T cells was consistently observed by using a variety of different intestinal epithelial cell types. CONCLUSIONS: CD and UC mucosal T cells are hyporesponsive to activation by intestinal epithelial cells when compared with control LPTs. Elucidating the mechanism underlying the differential activation of CD and UC LPTs may help to better understand the immunopathogenesis of these conditions.     

The m1 muscarinic acetylcholine receptor transactivates the EGF receptor to modulate ion channel activity

Intracellular tyrosine kinases link the G protein-coupled m1 muscarinic acetylcholine receptor (mAChR) to multiple cellular responses. However, the mechanisms by which m1 mAChRs stimulate tyrosine kinase activity and the identity of the kinases within particular signaling pathways remain largely unknown. We show that the epidermal growth factor receptor (EGFR), a single transmembrane receptor tyrosine kinase, becomes catalytically active and dimerized through an m1 mAChR-regulated pathway that requires protein kinase C, but is independent of EGF. Finally, we demonstrate that transactivation of the EGFR plays a major role in a pathway linking m1 mAChRs to modulation of the Kv1.2 potassium channel. These results demonstrate a ligand-independent mechanism of EGFR transactivation by m1 mAChRs and reveal a novel role for these growth factor receptors in the regulation of ion channels by G protein-coupled receptors.     

Clinical and economic impact of implementing a comprehensive diabetes management program in managed care

Diabetes mellitus places a significant burden on the U.S. healthcare system. Because of the potential to reduce diabetic complications and costs through intensive management, diabetes has become a primary target for disease management programs. We performed a retrospective analysis of short-term baseline and follow-up clinical, economic, and member and provider satisfaction data from approximately 7,000 people with diabetes being treated through seven managed care plans using Diabetes Treatment Centers of America's Diabetes NetCare, (Nashville, TN), a comprehensive diabetes management program. Our analysis indicates that Diabetes NetCare achieved gross economic adjusted savings of $50 per diabetic member per month (12.3%), with gross unadjusted savings of $44 (10.9%) per diabetic member per month. Hospital admissions per 1,000 diabetic member years decreased by 18%, and bed days fell by 21%. Patients with diabetes were more likely to get HbAlc tests, foot exams, eye exams, and cholesterol screenings while enrolled in the program. These data suggest that implementation of a comprehensive healthcare management program for people with diabetes can lead to substantial improvements in costs and clinical outcomes in the short-term. It is expected that improvements will increase over time, with continuing improvements in health status and a reduction in the number of future diabetic complications.     

The prospects for using the genetically engineered surface antigen of the hepatitis B virus (HBsAg) expressed by recombinant poxvirus strains as the basis for vaccines against hepatitis B

The use of a recombinant poxvirus (RPV) strain, expressing HBsAg in the process of reproduction in different bioreactor systems under stationary and bioreactor conditions of cultivation, made it possible to obtain highly purified HBsAg. The identity and purity of HBsAg was confirmed by the analysis of its amino acid composition, SDS electrophoresis in polyacrylamide gel, electron microscopy and high-performance liquid chromatography. Good prospects of the use of RPV-expressed gene engineering HBsAg as the basis vaccines against hepatitis B was demonstrated in 10 experimental batches of vaccine. All batches of the preparation had pronounced immunogenicity and were safe and nontoxic in animal experiments. The ID50 of experimental batches did not exceed 211 ng/ml, which, according to the data of comparative experiments, was lower than, or equal to, corresponding values of analogous foreign commercial preparations, based on plasma or yeast HBsAg.