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.     

Expression studies of delta-globin gene alleles associated with reduced hemoglobin A2 levels in Greek Cypriots

We previously identified five delta-globin gene alleles associated with reduced hemoglobin (Hb) A2 (Trifillis, P., Ioannou, P., Schwartz, E., and Surrey, S. (1991) Blood 78, 3298-3305). We have now evaluated functional consequences of the changes after expression in COS-1 cells to monitor effects on RNA splicing. In addition, variant Hb A2 tetramers were expressed in yeast to assess effects of amino acid changes on oxygen binding and stability to heat and mechanical agitation. The G --> T change at codon 27 and the A --> G change in IVS-2 both affect RNA splicing, whereas the C --> T change at codon 97 and the AT deletion in IVS-2 have no effect. Oxygen equilibrium curves of the Hb A2 variants expressed in yeast were similar to that of wild type Hb A2. None of the three variant Hb A2 tetramers (Thr --> Ile at codon 4 (Hb deltaT4I), Ala --> Ser at codon 27 (Hb deltaA27S), and Arg --> Cys at codon 116 (Hb deltaR116C)) showed decreased heat stability compared with Hb A2, whereas the Hb deltaT4I variant showed highest instability to mechanical agitation. Co-expression in yeast of alpha-globin chain and the delta-chain variant containing a Leu --> Pro change at codon 141 yielded no identifiable tetramers, suggesting lack of assembly or severe tetramer instability. These studies show the probable cause for decreased Hb A2 for two alleles is due to defective splicing, whereas decreased protein stability, increased tetramer association with red cell membranes, increased interdisulfide bond formation of delta-chains, which inhibits assembly with alpha-chains, and/or reduced assembly is suggested for the other three alleles.     

Adverse environmental conditions in the respiratory and medical ICU settings

Sleep deprivation and fragmentation occurring in the hospital setting may have a negative impact on the respiratory system by decreasing respiratory muscle function and ventilatory response to CO2. Sleep deprivation in a patient with respiratory failure may, therefore, impair recovery and weaning from mechanical ventilation. We postulate that light, sound, and interruption levels in a weaning unit are major factors resulting in sleep disorders and possibly circadian rhythm disruption. As an initial test of this hypothesis, we sampled interruption levels and continuously monitored light and sound levels for a minimum of seven consecutive days in a medical ICU, a multiple bed respiratory care unit (RCU) room, a single-bed RCU room, and a private room. Light levels in all areas maintained a day-night rhythm, with peak levels dependent on window orientation and shading. Peak sound levels were extremely high in all areas representing values significantly higher than those recommended by the Environmental Protection Agency as acceptable for a hospital environment. The number of sound peaks greater than 80 decibels, which may result in sleep arousals, was especially high in the intensive and respiratory care areas, but did show a day-night rhythm in all settings. Patient interruptions tended to be erratic, leaving little time for condensed sleep. We conclude that the potential for environmentally induced sleep disruption is high in all areas, but especially high in the intensive and respiratory care areas where the negative consequences may be the most severe.     

Special issue on women, psychoanalysis, and gender: Editors' introduction.

Introduces this special issue of Psychoanalytic Psychology. This special issue on Women, Psychoanalysis, and Gender is a commemoration of the capability, influence, acceptance, and authority of women in the community of psychoanalysis. In this issue, we turn to both new and more established voices in an expanded arena of gender, culture, and psychoanalysis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reprocessing of Microcrystalline Cellulose Spheres with Low Drug Concentrations

Spherical dosage forms have been reported to be an efficient and effective method for delivering drugs into the body and controlling their dissolution rate. Substantial work has been conducted in these laboratories illustrating the advantages of microcrystalline cellulose-based spheres for these purposes. Through various methodologies, but most routinely the extrusion and marumerization technique, it has been determined by Funck, et al. that not more than 50% drug can be incorporated into a sphere formulation without the addition of other binders.

Because of the nature of the extrusion and marumerization manufacturing process, the type of drug being processed and the resultant particle size requirements of the spheres, the percent of spheres falling outside the desired particle size can range from between 3% and 20%. For this reason and the possibility of operator errors, our objective was to determine the parameters which needed monitoring when reprocessing was necessary.