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Biomedical subjects

K Karpinski

Publications and source records attributed to K Karpinski.

26 records · Page 2Linked to original sources

Pharmacokinetic disposition in sheep of various vitamin E preparations given orally or intravenously.

1. Increases in plasma tocopherol concentrations were compared in sheep after a single oral administration of (per kg body-weight): 67 mg D- and 91 mg DL-epimers of alpha-tocopherol, and 74 mg D- and 100 mg DL-epimers of alpha-tocopheryl acetate, or intravenous administration of DL-alpha-tocopherol and DL-epimers of DL-alpha-tocopheryl acetate. 2. The results showed that biological availability was higher after D-alpha-tocopherol dosing than after the other forms. Intravenous administration of D-alpha-tocopherol acetate was a more effective way of dosing in sheep than equivalent intravenous amounts of DL-alpha-tocopheryl acetate or DL-alpha-tocopherol.

Administration, Oral↗

Vitamin E kinetics in sheep.

1. Kinetics of physiological doses of D-alpha-[5-Me-3H]tocopherol (200 microCi) administered to twenty-four sheep were studied using one of four routes: intravenous, oral (capsules), intraruminal and intramuscular. 2. Blood samples were withdrawn from the jugular vein periodically for 96 h after the intravenous and oral administrations, for 168 h after the intraruminal administration and for 216 h after the intramuscular administration. 3. The study indicated that the biological availability of alpha-tocopherol followed the order intravenous greater than intramuscular greater than oral greater than intraruminal. 4. The rate of elimination was in the order intravenous greater than oral greater than intraruminal approximately intramuscular. 5. The intravenous route was fitted with a three-compartment model, whereas the other routes exhibited a good fit for either a one- or two-compartment model.

Administration, Oral↗

Short-term effects of various phenols and acids on the Fischer 344 male rat forestomach epithelium.

A series of phenols and acids was fed to rats for 9 days to determine effects on the [methyl-3H]thymidine labelling index and the histological appearance of the forestomach. A variety of proliferative effects in the rat forestomach were observed which paralleled changes in the [methyl-3H] thymidine labelling index. The 3-tert-butyl isomer of butylated hydroxyanisole (BHA) was as effective as the food grade mixture. In the 4-hydroxybenzoic acid ester series, activity was not found either with the free acid or the methyl ester. With the ethyl, n-propyl and n-butyl esters activity in the perfundic region of the forestomach increased with alkyl chain length, the n-butyl ester being nearly as effective as BHA. In contrast, 4-methoxyyphenol and propionic acid demonstrated their greatest effects in the midregion of the forestomach, the action of propionic acid not being apparent until 21 or 27 days of treatment. It was also found that after a 9-day treatment involving coadministration of BHA and acetylsalicyclic acid, the overall effect of the antioxidant on the forestomach was greatly reduced.

Animals↗

A 13-week feeding study of butylated hydroxyanisole: the subsequent regression of the induced lesions in male Fischer 344 rat forestomach epithelium.

Feeding butylated hydroxyanisole (BHA) to male Fischer 344 rats at concentrations of 2, 0.5, 0.25, 0.1 and 0% for 13 weeks led to proliferative lesions developing in the forestomach epithelium of the 2%-treated rats but not in other groups. The [methyl-3H]thymidine labelling index was raised in the 2%- and 0.5%-treated groups and showed an apparent no observable effect level at 0.25%. Within 1 week after withdrawal of BHA the labelling indexes in all treated groups returned to near the values in the controls. The induced mucosal lesions, however, reverted more slowly and even after 9 weeks on the basal diet, the stratified squamous epithelium along the lesser curvature, was still slightly thicker than the control. There were multilayered basal cell processes in the lamina propria with connections to the basal cell layer. The possible significance of these results to the ultimate development of cancer is discussed.

Animals↗

Fetal distribution of styrene in rats after vapor phase exposures.

Pregnant rats were subjected to a 5-hour exposure of either 2,000 or 1,000 ppm atmospheres of styrene. Concentrations of styrene in the maternal blood and in each fetus were measured. The fetal concentrations in the 2,000 ppm exposure group were significantly more than double that in the 1,000 ppm group. Fetal weight and distribution of styrene appear to be related to the fetal position on the uterine horn. Those at the ovarian and cervical ends of the uterine horn were of lowest weight and those at the ovarian end had the highest concentration of styrene. Concentrations of styrene appeared to be much lower in the fetuses than in maternal organs and tissues after similar exposures.

Aerosols↗

The fetal distribution of some aliphatic chlorinated hydrocarbons in the rat after vapor phase exposure.

Rats, on the 17th day of pregnancy, were exposed for five h to several different concentrations, ranging from about 100 to 3,000 ppm, of methylene chloride, 1,2-dichloroethane, chloroform and trichloroethylene. Immediately following exposure, the concentrations of these compounds were determined in each fetus and in the maternal blood and characterized as a function of the administered dose. Fetal weights and fetal concentrations were related to their position on the two horns of the uterus. Fetal weight distribution conformed with observations previously reported [Withey and Karpinski 1983, Barr et al. 1969]. Fetuses at either end of each branch of the uterine horns had the lowest concentration of trichloroethylene. The data for methylene chloride and dichloroethane revealed a linear decrease in fetal concentration with the location of the fetus from the ovarian to the cervical end of the uterine horns. These relationships were consistent across doses. Fetal chloroform concentrations did not appear to be related to fetal position. Good linear relationships between the mean fetal concentrations and the maternal blood concentrations with exposure level were observed for the four compounds used in this study.

Aerosols↗

Effect of deoxynivalenol (vomitoxin) on the humoral immunity of mice.

The effects of vomitoxin (deoxynivalenol; DON) on the immune system were studied in groups of weanling male Swiss Webster mice administered by gavage 0.75, 2.5, and 7.5 mg of vomitoxin per kg body weight. Untreated controls and solvent controls (propylene glycol, ethanol, and distilled water in a ratio of 4:1:5) were also included in this study. Serum antibody (IgM) levels to sheep red blood cells (SRBC) were significantly reduced in the treatment groups compared to the control groups. Plaque-forming cell (PFC) numbers were also lower in the treated groups compared to the control groups. Furthermore, vomitoxin at a dose of 0.75 mg/kg resulted in a significant increase in the albumin, albumin/globulin ratio and a decrease in the alpha-2 globulin fraction compared to the control groups. Administration of 7.5 mg/kg of vomitoxin resulted in deaths, due to toxicity, in all animals of this group within 3 weeks. These preliminary findings are indicative of a potential effect of vomitoxin on the immune system which could have serious implications to man.

Animals↗

Histopathological and radioautographical studies on the forestomach of F344 rats treated with butylated hydroxyanisole and related chemicals.

Butylated hydroxyanisole, when fed to male Fischer 344 rats for periods of 9 days or more, led to forestomach epithelial cell necrosis and regeneration. Both the induced proliferation and the histopathological changes were considerably more prevalent in the prefundic region of the forestomach than in the mid-region. Using [Me-3H]thymidine, a specific DNA precursor, and radioautography it was shown that the effect of the antioxidant was apparently threshold at 0.25% in the diet after both 9 days and 3 months of treatment and that the proliferation was dependent on the continuous presence of the antioxidant in the diet at 3 and 6 months. Some other phenols and acids were investigated after 9-27 days' feeding; most induced some degree of epithelial cell proliferation in the rat forestomach, although some had a greater effect on the mid-region than on the prefundic region. These observations are discussed in terms of the likely relevance of butylated hydroxyanisole-induced forestomach tumours to the possibility that the antioxidant may lead to cancer in humans exposed to lower levels in their diet.

Administration, Oral↗