Cell-mediated cytotoxicity and humoral immune response in ascorbic acid-deficient guinea pigs.

Guinea pigs were divided into three dietary groups: ascorbic-acid deficient, pair-fed, and ad libitum control. Two weeks later guinea pigs were immunized intradermally with 5 x 10(8) chicken erythrocytes in Freund's complete adjuvant. Hemagglutinating antibody titers to chicken erythrocytes 2 weeks after immunization were comparable in all three dietary groups. In vitro 51Cr release from labeled chicken erythrocyte target cells incubated with lymphoid cells from spleens of ascorbic acid-deficient guinea pigs was significantly less than with spleen cells from pair-fed and ad libitum control guinea pigs. The percentage of splenic lymphoid cells that formed rosettes with rabbit erythrocytes, a T cell marker, was the same in all three dietary groups. The defect of ascorbic acid deficiency may reflect an impairment of T lymphocytes function in cell-mediated cytotoxicity or a change in number or function of another cell type.

A quantitative analysis of fine structure and drug metabolism in livers of clofibrate-treated young adult and retired breeder rats.

The effects of clofibrate on the fine structure and drug-metabolizing capacity of livers of normolipidemic young adult virgin (YA) and hypercholesterolemic retired breeder (RB) male rats were measured by morphometric and biochemical procedures. The oral administration of clofibrate for 7 days significantly increased liver weight and reduced the cholesterol concentrations in the serum and liver tissue in both groups of animals. The hepatic triglyceride (TG) concentration and the volume of cytoplasmic lipid droplets, presumably TG, as well as the serum TG concentration, increased only in the drug-treated RB rats. Clofibrate treatment resulted in significant increases in the volumes of the hepatocytes and their constituent mitochondria and microbodies and caused a proliferation of the smooth-surfaced endoplasmic reticulum. Although the magnitude of the hypocholesterolemic response was considerably greater in the RB animals, the morphological changes were much more marked in the YA group. However, the surface area of the rough-surfaced endoplasmic reticulum was reduced in the livers of the drug-treated RB rats. NADPH cytochrome c reductase specific activity was significantly increased in both the RB and YA animals, but the concentration of cytochrome P-450 (per mg microsomal protein) increased only in the YA rats. Neither the cytochrome b5 concentration nor the rate of ethylmorphine N-demethylation was significantly affected by clofibrate administration. The results suggest that there is no positive correlation between the hypocholesterolemic response to clofibrate and the degree of subcellular changes in the hepatocytes and that this hypolipidemic drug elicits a minimal effect on the concentrations of the components of the hepatic microsomal drug-metabolizing system.

Experimental protein and energy in the rat.

Young male rats (100-130 g) were fed diets of equal energy content containing o.5, 1,2,3,5, and 18% lactalbumin consumed either freely or in restricted amounts. The rats receiving low protein diets failed to grow and mature. Those consuming the 0.5 and1% protein diets given freely developed the characteristic features of kwashiorkor including edema, while those receiving the diets in restricted amounts developed the characteristic features of marasmus. The rats fed low protein diets had low plasma levels of essential amino acids; however, the lysine level was well maintained. The plasma levels of nonessential amino acids, especially glycine, alanine, and aspartic and glutamic acids were raised in marasmic rats but were reduced in rats fed low protein diets ad libitum. Young and severly malnourished rats appeared to have limited ability to synthesize urea. Therefore, they excreted more ammonia and other nitrogenous substances such as ethanolamine, and when given an amino acid load, intermediary metabolites of the ingested amino acids. Rats fed low protein diets showed diminution of total liver DNA, RNA, and protein. In addition to the reduction of protein synthesis resulting from decreased cellular RNA, ribosomes from the livers of protein-deficient rats had reduced ability to synthesize proteins. This defect was associated with the detatchment of the ribosomes from endoplasmic reticulum membrane and the elevation of the proportion of monosomes to polyribosomes. Malnutrition did not produce any change in the turnover rate of liver RNA. Protein deficiency caused significant depression of serum insulin, thyroxine, and corticosterone levels. Theoverall conclusion is that mammalian metabolism is well adapted to dietary intake and that this adaptation is achieved through dietary control of synthesis and release of key metabolic hormones.