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.     

Differential transforming growth factor-beta secretion in adenocarcinoma and squamous cell carcinoma of the uterine cervix

Tumor cells from eight freshly isolated cervical cancers (i.e., four adenocarcinomas and four squamous carcinomas) were analyzed for their production of the immune-inhibitory cytokine transforming growth factor-beta (TGF-beta) in vitro. All fresh adenocarcinomas secreted significant levels of TGF-beta (mean 397, range between 207 and 782 pg/ml/10(5) cells/48 hr). In contrast, no detectable TGF-beta was present in the supernatants from the four fresh squamous carcinoma cultures (P < 0.001). These data suggest that major differences in the secretion of the immunoinhibitory cytokine TGF-beta exist between squamous cell carcinomas and adenocarcinomas of the uterine cervix. Furthermore, these findings suggest that at least some of the differences in the natural biologic behavior, as well as in the response to radiation treatment, between these two histologic types of cervical cancer could be related to differences in secretion of this immune-inhibitory cytokine.     

Effect of transluminal angioplasty on cerebral blood flow in the management of symptomatic vasospasm following aneurysmal subarachnoid hemorrhage

In this study the authors have examined the effects of transluminal angioplasty on cerebral blood flow (CBF) in the management of intractable vasospasm following aneurysmal subarachnoid hemorrhage (SAH). Fourteen consecutively enrolled patients underwent attempted angioplasty with or without intraarterial infusion of papaverine. Twelve patients underwent pre- and postangioplasty xenon-enhanced computerized tomography (Xe-CT) scanning to measure regional CBF in 55 to 65 regions of interest (ROIs) per patient. Angioplasty was possible in 13 (93%) of 14 patients, with angiographically demonstrated improvement in all 13. Twelve (92%) of the 13 patients were neurologically improved following angioplasty; seven (58%) of the 12 patients who improved had a complete reversal of all delayed ischemic deficits. Angioplasty significantly decreased the mean number of ROIs at risk (11.4 ROIs pre- and 0.9 ROIs postangioplasty) (p < 0.00005, t-test). All patients had a reduction in the number of ROIs at risk after angioplasty; six (50%) of 12 no longer had any ROIs remaining at risk after angioplasty. Angioplasty significantly increased the mean CBF within at-risk ROIs (13 ml/100 g/minute pre- and 44 ml/100 g/minute postangioplasty) (p < 0.00005, t-test). All patients experienced an improvement in mean CBF in at-risk ROIs after angioplasty, with the mean CBF improving to above 20 ml/100 g/minute in all cases. No differences in the degree of improvement were found in patients who received intraarterial papaverine compared with those who did not. In the majority of patients with refractory vasospasm following SAH, angioplasty effectively dilated spastic arteries, reversed delayed neurological deficits, and significantly improved CBF in areas of brain at risk of infarction.     

Effects of the glucocorticoid agonist, RU28362, and the antagonist RU486 on lung phosphatidylcholine and antioxidant enzyme development in the genetically obese Zucker rat

The biochemical maturation of the lung in late gestation and in the young animal is regulated by glucocorticoids. The present study was aimed at dissociating the different glucocorticoid receptor sites involved in these regulatory functions. The obese Zucker rat was selected as a model for this study as it exhibits hypersensitivity to glucocorticoid hormone action by virtue of its elevated receptor numbers and activity. Two synthetic steroid analogues were administered to obese animals; RU28362, a specific type II receptor agonist, and the type II antagonist RU486. RU28362 promoted a strong catabolic effect, which was associated with reduced food intake and the abolition of growth in the rats. The agonist, RU28362, attenuated developmental increases in antioxidant enzyme activities, and altered the growth of the tissue. At the age studied, development of the lung phosphatidylcholine (PC) system was almost complete, but RU28362 increased disaturated PC 16:0/16:0 concentrations by almost 2-fold, and altered the molecular composition of total pulmonary PC. RU486 attenuated the growth of the rats and reduced their food intake. Treatment with the type II antagonist attenuated lung growth and increased the activities of pulmonary copper zinc (Cu/Zn) and manganese (Mn) superoxide dismutases. RU486 had no effect on lung PC concentrations and molecular composition. The data suggest a role for type I glucocorticoid receptors in the regulation of the antioxidant enzyme system in the lung, as type II antagonism will channel endogenous glucocorticoid binding to the type I site. Type II receptor binding would appear to play a role in regulating the lung PC content.     

Simulations of the mobile phase of polyethylene

Results are presented from atomistic molecular dynamics simulations of the mobile pseudo-hexagonal phase of polyethylene, which occurs under conditions of elevated pressure and temperature. Three different types of model are considered, all of which employ periodic boundary conditions. The first model consists of n-alkane sequences (48×-C₂₄H₄₈-) that are bonded across the simulation box boundaries to produce chains that are effectively infinite in extent. On heating, at high pressure, this system displays a rotator phase, in which the chains retain an all-trans conformation, and rotate as semi-rigid units. A second model, consisting of finite n-alkanes (48×C₂₄H₅₀) displays the same behaviour at low temperatures, but at high temperature and pressure forms a conformationally disordered rotator phase, characterised by a large proportion of gauche defects and a significant lattice expansion. The final model considered contains long n-alkanes (24×C₁₀₂H₂₀₆) which contain jog defects and each pass twice through the simulation box. This model forms a conformationally disordered rotator phase at high temperature and ambient pressure. The behaviour of the three models, in terms of the variations in chain conformation and rotational and translational dynamics, are compared. The conformationally disordered phases provide useful representations of the experimentally observed mobile phase.     

Effects of manufacturing defects on the mechanical properties of carbon fibre reinforced polyethersulphone laminates

The effects of defects on the mechanical properties of carbon fibre reinforced polyethersulphone laminates have been measured. The defects studied were cut fibre plies, omission of polymer films and local delamination produced by the inclusion of foreign matter. Of these it was found that only cut plies had a significant detrimental effect on the strength of a laminate. For specimens with two cut plies, the failure stress, tensile, flexural and compressive in the remaining continuous plies was the same as in the defect-free material, provided that the cut plies were widely separated. However the failure stresses were 15–18% lower in the continuous plies in the specimens containing two cut plies which were more closely spaced and in specimens containing four cut plies.     

Regional differences in triacylglycerol synthesis in adipose tissue and in cultured preadipocytes

The initial suspicion that obesity increases coronary risk has been much sharpened with the demonstration that risk is more tightly linked to abdominal than to peripheral obesity, and tighter yet again when the mass of omental adipose tissue is taken into account. These data suggest that important metabolic differences might exist between adipocytes from different regions, and indeed, it has long been appreciated that triacylglycerol hydrolysis can be stimulated to a greater extent in omental than in subcutaneous adipocytes. The present study focuses on triacylglycerol synthesis in human subcutaneous and omental adipocytes, a process which, by contrast, has received relatively little attention. Experiments were done on adipose tissue removed at laparotomy and on cultured preadipocytes. With the former, triacylglycerol synthesis was measured in the presence and absence of oleate added to the medium using radiolabeled glucose and oleate as tracers. The results demonstrate that under all conditions examined triacylglycerol synthesis in subcutaneous adipose tissue exceeded that in deep omental adipose tissue. To study the cells in more detail, preadipocytes were cultured and triacylglycerol synthesis was examined again under basal conditions and with stimulation with insulin and acylation stimulating protein (ASP). Under basal conditions, particularly when oleate was added to the medium, clear differences were present such that triacylglycerol synthesis was substantially greater in subcutaneous preadipocytes than in omentally derived preadipocytes. These differences were more pronounced when the cells were stimulated with either insulin or acylation stimulating protein. Overall, triacylglycerol synthetic capacity in subcutaneous tissue exceeded that in omental tissue. As a consequence, omental tissue as compared to subcutaneous adipose tissue would have a limited capacity to prevent fatty acids from reaching the liver and stimulating hepatic lipoprotein synthesis.