THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

The Design and Analysis of Experiments

The first suggestion that physical exercise results in free radical-mediated damage to tissues appeared in 1978, and the past three decades have resulted in a large growth of knowledge regarding exercise and oxidative stress. Although the sources of oxidant production during exercise continue to be debated, it is now well established that both resting and contracting skeletal muscles produce reactive oxygen species and reactive nitrogen species. Importantly, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Furthermore, oxidants can modulate a number of cell signaling pathways and regulate the expression of multiple genes in eukaryotic cells. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, DNA repair proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species promote contractile dysfunction resulting in muscle weakness and fatigue. Ongoing research continues to probe the mechanisms by which oxidants influence skeletal muscle contractile properties and to explore interventions capable of protecting muscle from oxidant-mediated dysfunction.

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Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production

The importance of free radicals and catalytic metal ions in human diseases

Moderate exercise is an antioxidant: upregulation of antioxidant genes by training.

Oxygen free radicals and metallothionein

Experiments were conducted to determine the effects of exercise on rat glutathione peroxidase system enzymes and lipid peroxidation among animals supplemented and unsupplemented with selenium (Se) and vitamin E (E). Liver, muscle and blood were taken before, immediately after and 24 hours after exercising to exhaustion by swimming. No effect of exercise was found on muscle or liver enzymes, although exercise resulted in depressed glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) activities in erythrocytes immediately after exercise. Dietary Se supplementation did result in increased hepatic muscle and erythrocyte glutathione peroxidase activity, and decreased hepatic GR, G6PD and "malic enzyme" activities. Thiobarbituric acid reactive substances, and indicator of lipid peroxidation, increased in liver and muscle subsequent to exercise. This increase was reduced in liver, but not eliminated, by dietary E supplementation. The increase was not affected by dietary E in muscle, nor by dietary Se in either tissue.

Selenium, vitamin E and the response to swimming stress in the rat.

Glucose turnover and blood metabolites were measured in eight adult female beagles in the fed state, at 1 day of fasting, and at 7, 14, and 21 days of fasting. Glucose utilization decreased significantly from 1 to 7 days of fasting, but remained constant from 7 to 21 days, while blood ketones and plasma free fatty acids rose significantly during the same period. Plasma alanine, serine, and glycine fell with fasting, with the greatest decrease in alanine levels occurring between 7 to 14 days. Plasma branched chain amino acids rose significantly with fasting. It was con cluded that the shifts in plasma metabolites and decreased glucose utiliza tion could be indicative of decreased energy demands of the fasting dogs and/or a shift in substrate utilization with progressive fasting. J. Nutr. 107: 1053-1061,1977.

Influence of prolonged fasting in the dog on glucose turnover and blood metabolites.

Thirty-two adult female white-tailed deer were assigned to four complete pelleted diets (+/- 45 ppm vitamin E; +/- 0.2 ppm selenium). Selenium and vitamin E concentration in the unsupplemented diet was 0.04 and 5.5 ppm, respectively. Biochemical parameters of the erythrocyte (RBC) glutathione peroxidase system and survival of off-spring to weaning were followed for 2 years. At the end of the second year, 12 male young (3 per treatment) and the remaining adults were killed, and liver and muscle parameters of the glutathione system determined. Plasma selenium (Se) and vitamin E (E) were significantly lower among unsupplemented adults within 6 months of treatment and remained essentially constant from 10 months on. In vitro hemolysis and mortality of young were affected by dietary E but not by Se. Tissue glutathione peroxidase (GSH-Px) was correlated with tissue Se in all tissues measured (RBC, liver and muscle). Tissue Se, in turn, was related to dietary Se. Thus, dietary Se deficiency (Se = 0.04 ppm) resulted in biochemical deficiency (depressed GSH-Px). This was not reflected in gross lesions among the adults, nor in increased mortality among young.

The Effect of Dietary Selenium and Vitamin E on Biochemical Parameters and Survival of Young Among White-Tailed Deer (Odocoileus virginianus)

1. 1. Tritiated water was found to rapidly equilibrate with the body water of chicks after injection. 2. 2. The 3H also rapidly appeared in both liver and carcass fatty acids, with the greatest rates of incorporation occurring in the initial time periods of measurement. 3. 3. Incorporation of 3H into fatty acids in the liver appeared to proceed primarily via de novo synthesis whereas incorporation of 3H into fatty acids in the carcass occurred primarily via chain elongation.

In vivo estimation of fatty acid synthesis in the chicken (Gallus domesticus) utilizing 3H2O.

Two experiments were conducted to investigate the effect of riboflavin deficiency on the glutathione peroxidase system in erythrocyte, liver and muscle of the baby pig. In the first study, 15 one-week old pigs were assigned to three dietary regimens for 6 weeks. Pigs were either fed riboflavin-free (Râ€") or riboflavin-supplemented (25 mg/kg diet) diets. One-half of the supplemented pigs were pair-fed to the deficient pigs. At the end of the experiment, blood was sampled, pigs were killed and organ samples taken. Erythrocyte (RBC) active glutathione reductase (GR) was reduced by 75c/camong R- pigs without any change in RBC reduced gluta thione. Most importantly, hepatic glutathione peroxidase (GSH-Px) activity and selenium ( Se) concentration were markedly reduced by riboflavin deficiency while hepatic GR activity was unaltered. Muscle GSH-Px was reduced significantly but muscle Se was not. In the second study, 16 three- week old pigs were assigned to graded dietary levels of riboflavin (0, 2, 4 and 10 mg/kg) for 2 or 4 weeks. At 2 and 4 weeks, one-half of the pigs were killed, and blood and tissues taken. Hepatic GSH-Px was again depressed when pigs were fed the 0 mg/kg ivboflavin diet, but was essentially the same whether 2, 4 or 10 mg riboflavin/kg diet was fed. Muscle GSH-Px activity was more variable and did not respond to riboflavin deficiency in this study. RBC percent active GR plateaued between 2 and 4 mg ribo flavin per kg diet. J. Nutr. 709: 1615-1622, 1979.

Linda J. Brady

Papers

Selenium, vitamin E and the response to swimming stress in the rat.

Influence of prolonged fasting in the dog on glucose turnover and blood metabolites.

The Effect of Dietary Selenium and Vitamin E on Biochemical Parameters and Survival of Young Among White-Tailed Deer (Odocoileus virginianus)

In vivo estimation of fatty acid synthesis in the chicken (Gallus domesticus) utilizing 3H2O.

Effects of Riboflavin Deficiency on Growth and Glutathione Peroxidase System Enzymes in the Baby Pig