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Biomedical subjects

G F Combs

Publications and source records attributed to G F Combs.

At least 73 records · Page 4Linked to original sources
PubMed1986

Synthetic seleno-organic compound with glutathione peroxidase-like activity in the chick.

The glutathione peroxidase activity catalyzed by the seleno-organic anti-inflammatory drug Ebselen (registered under the trademark of the Natterman Corp. Cologne, FRG) [PZ51, 2-phenyl-1,2-benzisoselenazol-3(2H)on], as measured by NADPH oxidation, was inhibited in vitro by the selenium-dependent glutathione peroxidase (SeGSHpx) inhibitors aurothioglucose and D-(-)penicillamine HCl. Vitamin E- and selenium-deficient chicks were given 0, 80 or 320 ppm PZ51 in diets devoid of vitamin E and supplemented with low levels of sodium selenite (0.04 ppm selenium added to the basal diet containing ca. 0.015 ppm selenium) when a small number of chicks (ca. 13%) had exudative diathesis (ED). By 24 hr, the high PZ51 dose (320 ppm) delayed the onset of ED compared to untreated controls. Similarly, vitamin E-deficient chicks fed diets containing 0, 80, 160, 320, 640 or 1280 ppm PZ51 and supplemented with 0.04 ppm selenium showed ED in inverse proportion to log PZ51 dose. Plasma and liver post-mitochondrial supernatant samples from these chicks also exhibited log-linear relationships between dietary PZ51 level and selenium content or SeGSHpx-like activity. The amount of SeGSHpx-like activity for chicks given PZ51 above that determined for untreated chicks was extractable into ethanol, indicating that those PZ51-associated increases were not due to protein-bound selenium or SeGSHpx. This suggests that selenium from PZ51 was not available to support synthesis of SeGSHpx. Dietary PZ51 (1280 ppm) or selenium (0.1 ppm) alone or in combination decreased the acute lethalities of nitrofurantoin or paraquat in vitamin E-adequate chicks. The results indicate that SeGSHpx-like activity in selenium-deficient chicks is increased by oral administration of PZ51, which appears to mimic the true enzyme by affording protection against clinical signs of selenium deficiency (i.e. ED) and pro-oxidant drug lethality.

Animals↗
PubMed1986

Selenium-dependent glutathione peroxidase inhibitors increase toxicity of prooxidant compounds in chicks.

The acute lethality of paraquat (1, 1'-dimethyl-4,4'-bipyridinium dichloride; also methyl viologen) for chicks was reduced in a dose-dependent manner by adding to a selenium-deficient torula-yeast-based diet low concentrations (0.02-0.04 ppm) of selenium (Se) as either Na2SeO3, selenomethionine or a high Se yeast without significantly increasing plasma Se-dependent glutathione peroxidase (Se GSH-Px) activity. Similarly, chicks orally dosed with 100 mg nitrofurantoin [N-(5-nitro-2 furfurylidine)-1-aminohydantoin] per kilogram had highest mortalities in the Se-deficient (unsupplemented) group; lowest mortalities occurred in chicks supplemented with 0.2 ppm Se; chicks supplemented with 0.02 ppm Se survived at rates not statistically different from chicks either unsupplemented or supplemented with 0.2 ppm Se. The activities of SeGSH-px in various vital organs were significantly elevated by supplementation of 0.2 ppm Se to Se-deficient chicks; but only kidney SeGSH-Px increased with 0.02 ppm Se. Additionally, no histopathology was observed in the vital organs of moribund chicks 5 or 24 h following nitrofurantoin administration at any dietary level of Se tested. Exposure of chicks to oxygen enhanced the toxicity of nitrofurantoin, but the protective effect of dietary Se was still evident. Two inhibitors of SeGSH-Px, D(-)-penicillamine X HCl and aurothioglucose, were found to increase the lethalities of both nitrofurantoin and paraquat. Aurothioglucose was most effective when administered simultaneously with the prooxidant compounds; penicillamine increased toxicities only when administered at least 24 h before paraquat or nitrofurantoin (it decreased nitrofurantoin lethality and did not significantly alter paraquat toxicity if given simultaneously). These data support an hypothesis that the protection offered by dietary Se against the acute toxicities of the prooxidant compounds paraquat and nitrofurantoin may be provided by SeGSH-Px in the chick.

Animals↗
PubMed1986

Effect of selenium and vitamin E dietary deficiencies on chick lymphoid organ development.

Diets specifically deficient in selenium (Se) and/or vitamin E or adequate in both nutrients were fed to chicks from the time of hatching. Lymphoid organs (bursa, thymus, and in some instances, spleen) were collected from chicks 7-35 days of age. Growth of the chicks fed these diets was monitored over the experimental period as was lymphoid organ growth. The development of the primary lymphoid organs was further assessed by histological techniques and the organ contents of vitamin E (alpha-tocopherol) and Se were determined. Specific deficiencies of either Se or vitamin E were found to significantly impair bursal growth as did a combined deficiency. Thymic growth was impaired only by the combined deficiency diet. Severe histopathological changes in the bursa resulted from the combined deficiency and these were detectable by 10-14 days after hatching. These changes were characterized by a gradual degeneration of the epithelium and an accompanying depletion of lymphocytes. Similar changes, although slower to develop and less severe, were observed in the thymus as a result of the combined deficiency. When both serum and tissue levels of vitamin E and Se were monitored, it was observed that these were rapidly and independently depleted by the specific deficiency diets. These data suggest that the primary lymphoid organs are major targets of Se and vitamin E dietary deficiencies and provide a possible mechanism by which immune function may be impaired.

Animals↗
PubMed1986

The lack of effect of a pyridoxine deficiency on the utilization of the hydroxyl analogue of methionine by the chick.

The purpose of this study was to determine whether a vitamin B6 deficiency affects the utilization of 2-hydroxy-4-(methylthio) butanoic acid (HMB), an analogue of methionine. The basal diet used for this purpose was based on peas, peanut meal, and glucose monohydrate and was low in both methionine and pyridoxine. Supplemental pyridoxine hydrochloride and L-methionine or HMB resulted in significant increases in growth rate and efficiency of feed utilization; supplemental pyridoxine also produced significant increases in the activity of glutamic-oxaloacetic transaminase (PGOT, EC 2.6.1.1.) in plasma. There was no discernible effect of change in vitamin B6 status on the utilization of HMB as compared with L-methionine.

Animals↗
PubMed1986

Studies of the renal excretion of the hydroxyl analogue of methionine by the chick.

Athens-Canadian Random Bred adult cockerels and chicks were used to compare the metabolism of the free acid form of the methionine hydroxyl analogue (HMB-FA) to L-methionine (LMET). The first experiment was to determine whether HMB-FA was excreted by the kidneys, thus reducing the amount available for protein synthesis. Fasted adult male chickens were given a single oral dose of HMB-FA or LMET containing a radioactive tracer. Urine was collected and analyzed for the amount of radioactive tracer present; blood samples were subjected to blood gas analyses to assess the physiological status of the bird. It was concluded that LMET was the major methionine analogue excreted from roosters dosed with either HMB-FA or LMET, and that HMB-FA was not excreted by the avian kidney. The second experiment was to determine whether the acid-base status of the diet influences the utilization of HMB-FA. Two levels of dietary LMET or HMB-FA and six levels of dietary base were fed to chicks in a complete 2 X 2 X 6 factorial design for a period of 20 days, after which weight gain and feed consumption were determined. The results indicated that the acid-base status of the diet can play a role in maximizing the gain of chicks fed HMB-FA. Optimal dietary conditions for comparing the efficacy of HMB-FA with LMET and the poor performance of HMB-FA in crystalline amino acid diets are discussed.

Acid-Base Equilibrium↗
PubMed1985

Drug-induced changes in selenium-dependent glutathione peroxidase activity in the chick.

The ability of aurothioglucose and D(-)-penicillamine hydrochloride to inhibit selenium-dependent glutathione peroxidase (SeGSH-Px) in vitro and to increase exudative diathesis in vitamin E-deficient chickens was studied. Aurothioglucose and penicillamine competitively inhibited SeGSH-Px in inverse proportion to the concentration of hydrogen peroxide and reduced glutathione, respectively, in chick liver postmitochondrial supernatant assay preparations. Neither drug inhibited glutathione reductase or superoxide dismutase at the concentrations tested; however, both inhibited catalase in a semilogarithmic fashion. This was true for both the purified bovine enzyme and chick liver homogenate. Aurothioglucose and penicillamine injected subcutaneously at the back of the neck increased exudative diathesis in vitamin E-deficient chickens fed 0.1 ppm Se, and effectively overcame the protective effect of selenium 72 h after injection in chicks fed vitamin E-free, low selenium diets supplemented with 0.0-0.1 ppm Se. Assays of plasma and of liver, lung and kidney postmitochondrial supernatants indicated that all observed reductions in SeGSH-Px activity preceded increases in exudative diathesis. Plasma and liver SeGSH-Px activities were lower at early times (6-24 h) after treatment with high doses of either drug. Lung SeGSH-Px activities were only lower in chicks receiving 240 mg penicillamine/kg 6 h after treatment; kidney SeGSH-Px activities were only lower in chicks treated with the highest dose of aurothioglucose 48 h after treatment. Brain SeGSH-Px activities were unaffected by drug treatment and the heart had higher SeGSH-Px activities only at 6 h after treatment with the highest dose of either drug compared to saline controls. Catalase activities in liver homogenates were only significantly altered by penicillamine; the highest dose caused the activity to be higher than that in saline-treated chicks. The cause of the lower SeGSH-Px activities could be either lower enzyme concentrations in tissues of the drug-treated groups and/or direct inhibition. Whatever the mechanism, it is concluded that exudative diathesis can be used to determine which drugs reduce SeGSH-Px activity in the chick.

Administration, Oral↗
PubMed1984

Report on Clinical Nutrition Research Units.

The National Institutes of Health support seven Clinical Nutrition Research Units, which are designed to create or strengthen nutrition research, training, and education through coordinated effort, intellectual stimulation, and use of shared resources. Research at the participating institutions focuses on the role of nutrition in cancer, cardiovascular disease, renal disease, digestive diseases, cystic fibrosis, diabetes, and other illnesses. Contributing substantially to the development of this nutrition research base have been Clinical Nutrition Research Unit-supported pilot studies, core laboratories, and new investigators. In the clinical setting, Clinical Nutrition Research Unit Nutritional Support Services assist in the care of patients receiving total parenteral nutrition and those with anorexia nervosa, burns, cancer, and a spectrum of nutrition-related problems. Participation of Clinical Nutrition Research Unit staff in training activities range from undergraduate, graduate, and postgraduate education courses for medical students and other health professionals to continuing education workshops, lecture series, and information programs for professional and lay audiences.

Government Agencies↗
PubMed1984

Uncomplicated selenium deficiency produced in chicks fed a corn-soy-based diet.

Day-old chicks were fed a practical-type diet based on corn- and soybean meal produced in a severely Se-deficient area of northeastern China. The diet contained 0.007 ppm Se and resulted in marked decreases in the activities of Se-dependent glutathione peroxidase in plasma and pancreas within 6 days of feeding. Chicks fed this basal diet showed histological signs of acinar atrophy of the pancreas, hyaline body formation, vacuolation and cytoplasmic shrinkage by 18 days and significantly elevated activities of amylase in plasma by 30 days. Each of these changes was prevented by supplementing the basal diet with Se to bring it to a level of 0.20 ppm. Chicks fed a Se-deficient purified diet based on crystalline amino acids also showed decreased Se-dependent glutathione peroxidase activities in plasma and pancreas, pancreatic damage as evidenced by histological examination and increases in plasma amylase activities. However, these signs of nutritionally induced pancreatic atrophy occurred sooner and were of greater magnitude than those observed in Se-deficient chicks fed the practical diet within the 30-day experimental period. These results, therefore, constitute the first report of nutritionally induced pancreatic atrophy in Se-deficient chicks fed a diet containing intact protein, and we suggest that a factor(s) associated with the practical diet acts to partially protect the chicks from this pathological consequence of severe Se deficiency.

Amylases↗
PubMed1984

Effects of dietary protein level and level of feed intake on the apparent bioavailability of selenium for the chick.

Experiments were conducted to determine the effects of dietary protein level and level of feed intake on the apparent bioavailability of Se from Na2SeO3 and selenomethionine (DL-Se-Met) for protection from exudative diathesis (ED) of the Se- and vitamin E-depleted chick. Level of dietary protein (22.5 vs. 16.9%) significantly (P less than .01) affected the incidence of ED at several levels of dietary Se from each source. At each level of Se, the low protein diet resulted in a lower incidence of ED and, thus, an increase in the apparent bioavailability of Se; Se from Na2SeO3 was more available than that from Se-Met. Further experiments were conducted to determine whether the effect of dietary protein level on the incidence of ED was due to effects on growth rate or feed intake. Chicks were fed the high or low protein basal diets at 75% of ad libitum rate of feed consumption. Sodium selenite was added to make Se intakes equivalent, either on a per day or a per unit gain basis, to ad libitum feeding controls receiving the Se-supplemented diets. Results showed that both a low level of dietary protein and a restricted level of feeding markedly reduced the incidence and severity of ED. The activity of Se-dependent glutathione peroxidase (SeGSHpx) in plasma and liver varied inversely with the incidence of ED and was increased by feed restriction. These results suggest that growth rate affects both the clinical and biochemical manifestations of Se-deficiency in the chick. Because both parameters are used to assess the bioavailability of Se in feeds and foods, bioassays in which growth rate is different between test and reference treatments may yield incorrect results.

Animals↗
PubMed1984

Fluorosis in the laying hen.

One hundred fifty Single Comb White Leghorn hens of two strains previously selected for either high eggshell strength (HES strain) or low eggshell strength (LES strain) were treated for 8 weeks with sodium fluoride added to a practical-type corn-soybean meal basal diet at 0, 300, 600, 900, or 1200 ppm. The HES strain was found to be more sensitive to fluorosis than the LES strain. High levels of dietary fluoride produced greater decreases in feed consumption, egg production, eggshell breaking strength, eggshell weight, and eggshell thickness in the HES strain than in the LES strain, despite the fact that the absolute intake of fluoride was greatest in the LES strain. Fluoride treatment significantly increased bone magnesium content in both strains and plasma phosphorus in the HES strain but did not significantly affect bone breaking strength or the concentrations of total calcium, ionized calcium, or magnesium in plasma of either strain. High fluoride treatment (1200 ppm) reduced the growth of HES progeny after 8 weeks of treatment of the hens, but LES progeny were not affected. These results suggest that the decreased sensitivity of the LES strain to fluoride may relate to its relatively greater (ca. 14%) volume of bone in which most absorbed fluoride is deposited.

Animals↗
PubMed1983

Selenium and mitochondrial integrity in the pancreas of the chick.

The activity of selenium-dependent glutathione peroxidase (SeGSH-Px) in the pancreas was found to decline in response to Se depletion in the chick at approximately the same time as the appearance of histopathological changes in the acinar cells of the pancreas, indicative of the onset of nutritional pancreatic atrophy. Oral administration of 10 micrograms of Se as Na2SeO3 to Se-deficient chicks increased SeGSH-Px activity in liver and plasma within 12 hours but not in pancreas until 36 hours. Histological signs of regeneration were not observed within 48 hours of Se repletion; however, acinar nuclei were significantly larger within 12 hours of Se repletion. The apparent rates of synthesis of DNA, RNA, and protein in liver, and of DNA in pancreas, were not affected by Se deficiency. The apparent rates of synthesis of pancreatic RNA and protein were depressed in Se-deficient chicks and were increased within 24 and 36 hours, respectively, upon Se repletion. Electron microscopic observation of pancreatic acinar cells from Se-deficient chicks revealed disruption of inner and outer mitochondrial membranes. However, no impairment was noted in rate of oxygen uptake, respiratory control index, or ADP:oxygen ratio of pancreatic mitochondria due to Se deficiency. The mitochondrial protein yield of the Se-deficient chick pancreases was 27% less than that of Se-adequate chicks. These data suggest that a decreased number of functional acinar mitochondria may result in nutritional pancreatic atrophy in the Se-deficient chick.

Animals↗
PubMed1983

Protection against acute paraquat toxicity by dietary selenium in the chick.

Experiments were conducted to determine whether both dietary vitamin E and selenium (Se) affect the acute toxicity of paraquat in the chick. Paraquat significantly stimulated the rate of NADPH-supported consumption of oxygen by the microsomal fractions of chick liver and lung, and this stimulation was decreased by addition of superoxide dismutase and/or catalase. The acute oral LD50 of paraquat in the 8-day-old vitamin E- and Se-deficient chick (131 mg/kg body weight) was increased more than threefold by supplementing the diet with 0.10 ppm Se as Na2SeO3, (419 mg/kg body weight) but was not significantly affected by supplementing the diet with vitamin E (148 mg/kg body weight). A high fat (20%) diet did not alter the protective effect of Se against the acute toxicity of paraquat; however exposure to an oxygen-enriched atmosphere did reduce the protection by dietary Se. Dietary Se at 0.01 ppm protected against acute paraquat toxicity, whereas 0.08 ppm Se produced detectable increases in the Se-dependent glutathione peroxidase. These results indicate that the acute toxicity of paraquat in the chick is highly responsive to nutritional Se status and not vitamin E status.

Animals↗
PubMed1983

Effects of vitamin E and aspirin on the incidence of encephalomalacia, fatty acid status and serum thromboxane levels in chicks.

This study was initiated to examine the role of prostanoids (thromboxane) in the development of nutritional encephalomalacia (NE). Chicks were fed diets deficient in or supplemented with vitamin E in the presence or absence of a known prostaglandin inhibitor, acetylsalicylic acid (ASA). When the incidence of NE was approximately 50% in the vitamin E--deficient group without ASA supplement, the chicks were killed, and serum thromboxane B2 (TxB2) and serum and brain fatty acid (FA) composition were determined. The incidence of NE was not altered by ASA treatment. Plasma arachidonate levels were increased by ASA treatment on the vitamin E--deficient diet. Furthermore, the serum TxB2 levels in vitamin E--deficient versus vitamin E--adequate chicks, unlike changes noted for rats, were decreased. Aspirin treatment drastically reduced TxB2 levels in all groups but did not alter the incidence of NE. Therefore, it is unlikely that the development of NE is a result of thromboxane-mediated thrombosis.

Animals↗
PubMed1983

Evidence of a hereditary factor affecting the chick's response to uncomplicated selenium deficiency.

Experiments were conducted to determine whether a hereditary factor accounted for part of the variation observed in the growth responses of young chicks to uncomplicated selenium (Se) deficiency. Results showed that such a factor influenced the growth of chicks fed a Se-deficient diet. Those chicks most susceptible (SUS) to the growth depressing effects of Se-deficiency oxidized 14CH3-methionine to 14CO2 at a greater rate when fed the Se-deficient diet than did chicks that appeared refractory (REF) (i.e., grew at near normal rates) to Se-deficiency. When diets were supplemented with Se, both lines exhibited equivalent rates of 14CH3-methionine oxidation. The SUS chicks appeared to have lower levels of free homocystine and cystathionine in plasma compared to REF chicks or to Se-supplemented chicks of both lines. These results provide evidence for an impairment in sulfur-amino acid metabolism as the basis of the hereditary effect.

Amino Acids↗