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Biomedical subjects

G F Combs

Publications and source records attributed to G F Combs.

At least 19 recordsLinked to original sources
PubMed1992

The effects of topical and oral L-selenomethionine on pigmentation and skin cancer induced by ultraviolet irradiation.

This study was conducted to determine whether oral and/or topical selenium (Se) supplementation can reduce the incidence of acute and/or chronic damage to the skin (i.e., sunburn and pigmentation and/or skin cancer, respectively) induced by ultraviolet (UV) irradiation in mice. Groups of 38 BALB:c female mice or 16 Skh:2 hairless pigmented mice were treated with 1) lotion vehicle, 2) 0.02% L-selenomethionine (SeMet) lotion, or 3) vehicle and 1.5 ppm SeMet in the drinking water. Within each group, 30 BALB:c mice or 12 Skh:2 mice were given UV irradiation (Westinghouse FS 40 bulbs) three times per week in doses of 0.575 and 0.24 J/cm2, respectively. The animals' weights and food intakes and the Se concentrations of skin and liver were measured. Skin biopsies were taken from the backs and abdomens of all animals to evaluate the relative amounts of Se and the damage by UV irradiation. Skin pigmentation was scored, and the total number of clinically detectable skin tumors per animal was counted weekly. Results showed that the skin Se concentrations in areas of application of the lotion containing SeMet were greater than those of animals given comparable oral doses, while the Se concentrations of untreated skin and liver were similar to those of animals receiving oral Se. Mice treated with Se showed no signs of toxicity and had significantly less skin damage by UV irradiation, as indicated by reduced inflammation and pigmentation and by later onset and lesser incidence of skin cancer.

Administration, Cutaneous↗
PubMed1992

Penicillamine: pharmacokinetics and differential effects on zinc and copper status in chicks.

The pharmacokinetics of D(-)-penicillamine (PA) and the effects of PA on the nutritional status of Cu and Zn in chicks were studied. When administered by subcutaneous or intravenous injection, PA was eliminated from the plasma with biphasic kinetics: i.e., a fast (halftime: 6-7 min) and a slow (halftime: 52-55 min) component. The elimination of PA from the liver or pancreas showed only the slow (halftime: 42-46 min) component. When PA was administered orally, plasma PA concentrations responded over time in bimodal pattern, but the maximal level was only one-fifth that achieved by injection. The subcutaneous injection of PA elicited differential, transient changes in the concentrations of Zn and Cu in the plasma: plasma Zn concentration was decreased, and plasma Cu concentration was increased. Analyses of urine collected from ureter-cannulated chicks showed that PA was rapidly excreted via that route, and that urinary PA excretion was associated with increased urinary excretion of both Zn and Cu. These results show that PA treatment can alter tissue distributions particularly of Zn and, to a lesser extent, of Cu. J. Nutr.

Administration, Oral↗
PubMed1992

The effect of topical L-selenomethionine on minimal erythema dose of ultraviolet irradiation in humans.

The purpose of this study was to determine whether topical L-selenomethionine reduces the degree of acute damage to the skin (i.e., sunburn) induced by ultraviolet (UV) irradiation in humans. Eight women volunteers were treated for 2 weeks first with lotion vehicle then with topical L-selenomethionine for two weeks at each of three concentrations (0.002%, 0.02%, and 0.05%). At the end of each 2-week treatment period, the minimal erythema dose (MED) of UV irradiation was measured using a Multiport Solar Ultraviolet Simulator. It was found that topical L-selenomethionine was effective in protecting against acute UV damage to the skin. A response curve demonstrated that increasing concentrations of topical L-selenomethionine gave increasing MED, with a plateau of maximal protection attained at a concentration between 0.02% and 0.05%. Although previous studies in rats and mice demonstrated percutaneous absorption of selenium after application of L-selenomethionine, in the concentrations used here, the topical L-selenomethionine did not result in increased levels of selenium in the blood plasma of the patients tested.

Administration, Cutaneous↗
PubMed1991

Reporting the accuracy of biochemical measurements for epidemiologic and nutrition studies.

Procedures for reporting and monitoring the accuracy of biochemical measurements are presented. They are proposed as standard reporting procedures for laboratory assays for epidemiologic and clinical-nutrition studies. The recommended procedures require identification and estimation of all major sources of variability and explanations of laboratory quality control procedures employed. Variance-components techniques are used to model the total variability and calculate a maximum percent error that provides an easily understandable measure of laboratory precision accounting for all sources of variability. This avoids ambiguities encountered when reporting an SD that may taken into account only a few of the potential sources of variability. Other proposed uses of the total-variability model include estimating precision of laboratory methods for various replication schemes and developing effective quality control-checking schemes. These procedures are demonstrated with an example of the analysis of alpha-tocopherol in human plasma by using high-performance liquid chromatography.

Analysis of Variance↗
PubMed1991

Report on the Fourth Conference for Federally Supported Human Nutrition Research Units and Centers.

The Fourth Conference for Federally Supported Human Nutrition Research Units and Centers, sponsored by the Interagency Committee on Human Nutrition Research, addressed two topics: nutrition and function, and nutrient interactions and toxicities. This article summarizes the conference's introductory remarks and the contents of the 34 papers presented. Future meetings of federally supported nutrition research units and centers will focus on other human nutrition research topics and will be held biennially.

Humans↗
PubMed1991

Selenium in pediatric nutrition.

Se is an essential nutrient that provides antioxidant protection in concert with vitamin E. Several selenoproteins have been identified, but only one, SeGSHpx, has a known function, that of neutralizing toxic hydroperoxides. Plasma Se concentration, being responsive to changes in Se intake, is the most practical and widely used measure of nutritional Se status. The plasma Se concentrations of the majority of healthy infants and children fall within the range of 50 to 150 micrograms/L. Although SeGSHpx activity measures the metabolically functional form of Se, the lack of a standardized analytical method has limited its usefulness as an index of nutritional Se status. Se deficiency was first observed in animals, but it is now recognized to occur in humans. Two human diseases associated with severe nutritional Se deficiency have been reported from China: a juvenile cardiomyopathy named Keshan disease and a chondrodystrophy named Kaschin-Beck disease. Long-term TPN, which provides negligible amounts of intrinsic Se, has been demonstrated in some cases to result in biochemical and clinical impairment. Although there are no consistent signs and symptoms characteristic of TPN-associated Se deficiency in addition to the low blood selenium levels, some patients will experience leg muscle pain and altered serum transaminase and creatine kinase activities. These manifestation of Se deficiency usually take years to develop. Recent information about the amount of dietary Se needed to maximize plasma SeGSHpx activity in adult men has allowed for better estimates of the Se requirement for humans. Recommended daily dietary allowances published recently by the National Academy of Sciences have been revised for infants and children in this paper by making appropriate adjustments for the protein requirements of these age-groups. These recommended intakes for Se can generally be met by consuming adequate amounts of cereals, meat, eggs, dairy products, human milk, and infant formula, which are good sources of highly available Se and are of low risk of providing excess amounts of Se. Suboptimal Se intakes by pregnant women may predispose their infants to low Se status at birth, which in turn may affect the infants ability to maintain adequate Se status during the first few months of life. In those situations where protein intake is restricted, such as in phenylketonuria and maple syrup urine disease, Se-supplemented formulas should be used. The most critical situation for Se supplementation is in pediatric patients receiving long-term TPN therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Diet↗
PubMed1990

Time-course studies of pancreatic exocrine damage induced by excess dietary zinc in the chick.

Experiments were conducted to determine the time course of Zn-induced changes in the exocrine status of the chick pancreas. In experiments 1 and 2, chicks killed at intervals after the addition of excess Zn (500 mg/kg as ZnO) to a purified diet containing 70 mg Zn/kg showed a rapid increase in plasma Zn concentration that reached a plateau within 1 h. The pancreatic soluble Zn level increased linearly for 24 h, but then its rate of accumulation diminished. The same pattern of accumulation was shown by pancreatic metallothionein (MT), which correlated highly with pancreatic Zn; that is, MT-associated Zn consistently accounted for 70 to 80% of pancreatic Zn. Plasma amylase activity started to increase 8-10 h after Zn introduction and reached a maximum by 24 h. Two critical levels of pancreatic soluble Zn (1 and 2.7 micrograms Zn/mg of protein, respectively) were observed at which amylase activities increased in the plasma and decreased in the pancreas. In experiment 3, feeding excess Zn reduced the incorporation of [3H]leucine into pancreatic amylase protein. This was associated with a reduction of tracer incorporation into total pancreatic proteins, that is, the fraction that is precipitable by trichloracetic acid (TCA). In experiment 4, the enzyme (or potential) activities of the exportable Zn-containing enzymes procarboxypeptidases A and B and ribonuclease were not affected by excess Zn intake, indicating the selective nature of the effect of excess Zn on pancreatic function.

Amylases↗
PubMed1989

Potentiation of atherosclerotic lesions in rabbits by a high dietary level of vitamin E.

1. Two experiments were conducted to determine whether or not high dietary levels of vitamin E affect the development of atherosclerotic lesions in aortas of cholesterol-fed (5 g/kg diet) rabbits that were mechanically deendothelialized by balloon catheterization. 2. In the first experiment, the aortas of rabbits fed 2000 mg vitamin E/kg diet (i.e. 50-fold their nutritional requirement) for 8 weeks showed no gross morphological differences, either within or outside experimentally damaged areas, from those of rabbits fed the nutritionally adequate control level (40 mg/kg) of the vitamin. 3. In the second experiment, rabbits fed 10,000 mg vitamin E/kg diet (i.e. 250-fold requirement) for 14-15 weeks showed significantly greater endothelial loss and plaque formation at aortic sites outside of the mechanically damaged area than did controls. Plasma cholesterol levels were very high (9000-14,000 mg/l) and were not affected by dietary vitamin E level until 10-12 weeks when they were reduced moderately (18%). 4. It is concluded that very high levels of vitamin E can potentiate spontaneous atherosclerotic lesions, and it is suggested that this effect may depend on high cholesterol status.

Animals↗
PubMed1988

Excess dietary zinc decreases tissue alpha-tocopherol in chicks.

Experiments were conducted to determine the basis of the reduction in tissue alpha-tocopherol concentrations by excess dietary zinc (Zn) in chicks fed purified diets. These reductions were preceded by elevations in the Zn concentrations of plasma and pancreas, and in the amylase activity of plasma and by reductions of exportable enzymes of the pancreas. Chicks fed similar levels of Zn as supplements to a non-purified diet showed no such impairments in either exocrine pancreatic function or tissue alpha-tocopherol concentrations. Depression of feed intake and subsequent changes of concentrations of tissue lipid components by excess dietary Zn accounted for only a minor portion of the reduction of tissue alpha-tocopherol concentrations. Tissue alpha-tocopherol concentrations were moderately correlated with tissue lipid concentrations. The rate of appearance of radioactivity from an oral dose of all-rac-alpha-tocopherol-[3,4-3H]2 in plasma was reduced by 64% by addition of 500 mg Zn/kg to the purified diet for 2 wk. These results indicate that impaired enteric absorption and/or transport of vitamin E as a consequence of Zn-induced pancreatic insufficiency is a major cause of reduced tissue concentrations of alpha-tocopherol produced by excess dietary Zn.

Amylases↗
PubMed1988

Effect of excess dietary zinc on pancreatic exocrine function in the chick.

The effects of excess dietary zinc (Zn) on exocrine pancreatic function were studied in chicks. A purified diet based on crystalline amino acids and sucrose was employed in several experiments, and a practical type of diet based on corn and soybean meal was used in one experiment for the purpose of comparison. Additions of as little as 100 mg Zn/kg as ZnO to the purified diet markedly elevated pancreatic Zn concentration, whereas liver and plasma Zn were moderately increased. Histological examination of the pancreas showed alterations in acinar structure due to Zn intoxication. The activities of the pancreatic exportable enzymes amylase, lipase, trypsinogen and chymotrypsinogen were each decreased by such levels of Zn feeding. Reductions of pancreatic enzyme activities were associated with reductions in the digestibility of dietary starch and in tissue alpha-tocopherol concentrations. Chicks fed the nonpurified (i.e., soy-containing) diet accumulated much less Zn in the pancreas (about one-tenth as compared with the purified diet); the addition of as much as 2000 mg Zn/kg as ZnO to this diet produced only a small increase in pancreas Zn concentration, and did not affect exportable pancreatic enzyme activities or tissue alpha-tocopherol concentrations. These results indicate that dietary factors that reduce Zn availability may also reduce Zn toxicity. Chicks fed the purified diet with excess Zn had slightly higher liver selenium (Se) concentrations, but this effect was not associated with changes in the activity of Se-dependent glutathione peroxidase in that organ. Nutritional deprivation of Se did not affect the extent of Zn-induced acinar damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1988

Disruption of endoplasmic reticulum is the primary ultrastructural lesion of the pancreas in the selenium-deficient chick.

Severe uncomplicated selenium (Se) deficiency was produced in chicks by feeding, from 1 day of age, a purified diet that contained 0.010 ppm Se but was adequate with respect to all other known nutrients. The deficiency was characterized by depressions in rate of growth and efficiency of feed utilization and by reductions in the plasma activity of Se-dependent glutathione peroxidase (SeGSHpx) by 85-97% from levels in chicks fed the basal diet supplemented with 0.20 ppm Se as Na2SeO3. Histological observations of the target organ of Se deficiency in the chick, i.e., the pancreas, using transmission electron microscopy, showed severe losses of endoplasmic reticulum (ER) and absence of secretory granules in acinar cells of Se-deficient animals. These effects were not uniform within individuals, as Se-deficient pancreases also showed areas of unaffected acini. By 14 days of age, Se-deficient pancreases contained many apparently undifferentiated cells, which were absent from pancreases of Se-fed chicks. It is noteworthy that abnormal mitochondria were not observed in any pancreas sections. It is concluded that the metabolic consequences of severe uncomplicated Se deficiency in the chick result from the disruption of ER and loss of functional acinar cells, rather than to damage to mitochondria as previously suggested.

Aging↗
PubMed1987

Influence of dietary vitamin E on nutritional pancreatic atrophy in selenium-deficient chicks.

Studies were conducted to determine the relationship between dietary vitamin E (VE) and the development of nutritional pancreatic atrophy (NPA) in selenium (Se)-deficient chicks. Selenium- and VE-depleted chicks reared on a low Se, amino acid-based diet containing 100 IU VE (as all-rac-alpha-tocopheryl acetate) per kilogram were found to have exceedingly low pancreatic activities of Se-dependent glutathione peroxidase (SeGSHpx) at 8 d of age. Supplementation of the purified diet with 500 or 1,000 IU VE/kg prevented both NPA and the associated growth depression. Use of graded dietary VE levels showed that addition of at least 300 IU/kg was required to overcome the growth depression associated with severe Se deficiency. Although tissue alpha-tocopherol concentrations increased linearly with increasing dietary levels of VE, the response in pancreas was less than (about one-half of) those in liver and heart and, unlike the response in heart, was not affected by dietary Se level. That protection against NPA involved the antioxidant action of VE was suggested by results showing that NPA is promoted by high dietary levels of linoleic acid, that high VE levels correct membrane unsaturated fatty acid losses due to Se deficiency and that NPA is prevented by high levels of other antioxidants. It is suggested that the normally low activities of SeGSHpx and concentrations of alpha-tocopherol in the pancreas may predispose that organ to lesions due to oxidative stress under conditions of severe nutritional Se deficiency that results in further depletion of SeGSHpx. This situation may be overcome by feeding VE at 15-20-fold excesses over the levels normally regarded as nutritionally required.

Animals↗
PubMed1987

Mercaptans decrease selenium-dependent glutathione peroxidase activity in the chick.

A variety of mercaptans, especially the beta-mercaptocarboxylic acids, inhibited the selenium (Se)-dependent glutathione peroxidase (SeGSHpx) activity of chick liver postmitochondrial supernatant or cytosol and of purified bovine erythrocyte SeGSHpx. The effects of mercaptans and a glutathione analogue on Se utilization were determined by subcutaneous injection of test compounds into vitamin E-deficient chicks fed diets containing 0.1 ppm Se (as Na2SeO3) at times when greater than 50% of vitamin E- and Se-deficient chicks showed the vitamin E-, Se-deficiency disease exudative diathesis (ED). D-(-)-Penicillamine hydrochloride (the positive control model compound), sodium beta-mercaptopyruvate, t-butyl mercaptan and S-methylglutathione (nonmercaptan glutathione analogue) decreased SeGSHpx activity in chick liver postmitchondrial supernatants within 24 h of injection and increased the incidence of ED within 4 d. Other mercaptans tested did not increase ED incidence or affect liver, kidney or plasma SeGSHpx activities. Although mercaptosuccinic acid, N-(2-mercaptopropionyl)glycine and sodium thioglycolate each strongly inhibited SeGSHpx in vitro, each also significantly increased chick mortality in the dosage range tested; therefore, their effects on SeGSHpx in vivo could not be evaluated. It appears that the beta-mercaptocarboxylic acids, mercaptans with a high degree of steric hinderance in close proximity to the thiol group and a close structural analogue of glutathione are capable of altering selenium status in chicks.

Animals↗
PubMed1987

Response to divergent selection for early growth of chickens fed a diet deficient in selenium.

Three generations of divergent selection for 21-day growth response to a diet deficient in selenium (-Se) were bred using a meat-type chicken. The Athens-Canadian Randombred (AC) population of chickens served as the base population for this study. Mass selection was used to establish a -Se refractory line (SDR) and a -Se susceptible line (SDS). A genetic control line was maintained during the selection process to facilitate evaluation of the responses of the selected lines. The SDR males and females had an average of 17% increase in weight gain at 21 days of age when fed the -Se diet compared with the control line males and females fed the same diet for the three generations of selection. The SDS line had an average reduction in weight gain of 27% during the same period of selection. A difference of 25 g was observed between the mean body weights of SDR males and females and between the SDS males and females after one generation of selection. By the third generation of selection, the difference between SDR and SDS males had increased to 31 g, whereas the SDR and SDS females differed by 41 g. Early response to selection was asymmetrical because the response was greater in the SDS than in the SDR line. Response to selection, however, generally declined after the first generation. Realized heritability estimates for individual generations for this trait were variable (ranging from -.26 to .95), but cumulative estimates (.15 to .39) for growth through three generations were similar to those reported for chickens and quail.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗