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.     

Kinetic evidence for low chemical processivity in ncd and Eg5

We have examined the formation of hydroxyphenols, nitrophenols, and the minor products 4-nitrosophenol, benzoquinone, 2,2'-biphenol, and 4,4'-biphenol from the reaction of peroxynitrite with phenol in the presence and absence of added carbonate. In the absence of added carbonate, the product yields of nitrophenols and hydroxyphenols have different pH profiles. The rates of nitration and hydroxylation also have different pH profiles and match the trends observed for the product yields. At a given pH, the sum of the rate constants for nitration and hydroxylation is nearly identical to the rate constant for the spontaneous decomposition of peroxynitrite. The reaction of peroxynitrite with phenol is zero-order in phenol, both in the presence and absence of added carbonate. In the presence of added carbonate, hydroxylation is inhibited, whereas the rate of formation and yield of nitrophenols increase. The combined maximum yield of o- and p-nitrophenols is 20 mol% (based on the initial concentration of peroxynitrite) and is about fourfold higher than the maximal yield obtained in the absence of added carbonate. The o/p ratio of nitrophenols is the same in the presence and absence of added carbonate. These results demonstrate that hydroxylation and nitration occur via two different intermediates. We suggest that the activated intermediate formed in the isomerization of peroxynitrous acid to nitrate, ONOOH*, is the hydroxylating species. We propose that intermediate 1, O=N-OO-CO2-, or secondary products derived from it, is (are) responsible for the nitration of phenol. The possible mechanisms responsible for nitration are discussed.     

Effect of exercise and dietary restraint on energy intake of reduced-obese women

Self-selected food intake of 15 reduced-obese women living in a metabolic ward was studied for 14 consecutive days to determine the effect of exercise and other metabolic and behavioral variables on energy intake. A choice of prepared food items were offered at breakfast, lunch and dinner, and a variety of additional food items were available continuously 24 h/day. Subjects performed either moderate intensity aerobic exercise (A-EX) (n = 8) expending 354 +/- 76 kcal/session or low intensity resistance weight training (R-EX)(n =7) expending 96 +/- kcal/session, 5 days/week. Mean energy intakes (kcal/day, +/- SEM) of the exercise groups were similar: 1867 +/- 275 for A-EX, 1889 +/- 294 for R-EX. Mean energy intakes of individuals ranged from 49 to 157% of the predetermined level required for weight maintenance. Resting metabolic rate per kg 0.75 and the Eating Inventory hunger score contributed significantly to the between subject variance in energy intake, whereas exercise energy expenditure did not. Regardless of exercise, eight women consistently restricted their energy intake (undereaters), and seven other consumed excess energy (overeaters). Overeaters were distinguished by higher Eating Inventory disinhibition (P = 0.023) and hunger (p = 0.004) scores. The overeaters' diet had a higher fat content 34 +/- 1% (p = 0.007). Also, overeaters took a larger percentage of their daily energy, than that of undereaters, 27 +/- 1 energy intake in the evening, 13 +/- 2%, compared to undereaters, 7 +/- 1% (p = 0.005). We conclude that the Eating Inventory is useful for identifying reduced-obese women at risk of overeating, and these individuals may benefit from dietary counseling aimed at reducing fat intake and evening snacking.     

A role for B cells in the development of T cell helper function in a malaria infection in mice

B cell knockout mice are unable to clear a primary erythrocytic infection of Plasmodium chabaudi chabaudi. However, the early acute infection is controlled to some extent, giving rise to a chronic relapsing parasitemia that can be reduced either by drug treatment or by adoptive transfer of B cells. Similar to mice rendered B-cell deficient by lifelong treatment with anti-mu antibodies, B cell knockout mice (muMT) retain a predominant CD4+ Th1-like response to malarial antigens throughout a primary infection. This contrasts with the response seen in control C57BL/6 mice in which the CD4+ T-cell response has switched to that characteristic of Th2 cells at the later stages of infection, manifesting efficient help for specific antibodies in vitro and interleukin 4 production. Both chloroquine and adoptive transfer of immune B cells reduced parasite load. However, the adoptive transfer of B cells resulted in a Th2 response in recipient muMT mice, as indicated by a relative increase in the precursor frequency of helper cells for antibody production. These data support the idea that B cells play a role in the regulation of CD4+ T subset responses.     

Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors

Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.     

International developments in solar thermal testing

A methodology of the design of solar energy test facilities is presented. In the design of the test facilities, careful attention has been paid to the availability of local materials and skilled labour to perform tests on solar energy equipment to international standards. Outdoor test results are presented for collector tests performed to ASHRAE standards on site in Egypt. The results are compared with indoor tests from the UK National Test Laboratory using the SERC solar simulator at University of Wales College of Cardiff, UK. Data analysis has been carried out on the outdoor and indoor results to determine the performance of these collectors. The indoor and outdoor results agreed very well. The indoor results have been corrected in accordance with International Standards to yield an ‘equivalent outdoor’ peformance characteristic. The emerging international standards for solar thermal testing are discussed, particularly in a developing country context.     

Does genetic variance for cognitive abilities account for genetic variance in educational achievement and occupational status? A study of twins reared apart and twins reared together

Studies of brothers and twins have shown that about 50 per cent of the variance in educational achievement and 40 per cent of the variance in occupational status reflects between-family variance. About half of the between-family variance for educational achievement and even more for occupational status is due to genetic effects and the remainder is due to sharing the same environment. With data on 35 pairs of male twins reared apart and 56 pairs reared together we investigated the extent to which genetic variance in SES can be attributed to genetic variance for cognitive abilities. For both educational achievement and occupational status there was significant genetic variance both in common with and independent of genetic variance for cognitive abilities. Thus, there are genetic effects contributing to familial similarity for SES that are not the same as those of importance for cognitive abilities. Candidate traits that may account for this remaining genetic variance in SES are personality, interests, or talents not represented in standard cognitive tests.     

Toward a scalable, silicon-based quantum computing architecture

Advances in quantum devices have brought scalable quantum computation closer to reality. We focus on the system-level issues of how quantum devices can be brought together to form a scalable architecture. In particular, we examine promising silicon-based proposals. We discover that communication of quantum data is a critical resource in such proposals. We find that traditional techniques using quantum SWAP gates are exponentially expensive as distances increase and propose quantum teleportation as a means to communicate data over longer distances on a chip. Furthermore, we find that realistic quantum error-correction circuits use a recursive structure that benefits from using teleportation for long-distance communication. We identify a set of important architectural building blocks necessary for constructing scalable communication and computation. Finally, we explore an actual layout scheme for recursive error correction, and demonstrate the exponential growth in communication costs with levels of recursion, and that teleportation limits those costs.