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Biomedical subjects

R F Grimble

Publications and source records attributed to R F Grimble.

At least 55 records · Page 3Linked to original sources
PubMed1990

Dietary fat modifies some metabolic actions of human recombinant tumour necrosis factor alpha in rats.

To examine how fat might influence the metabolic effects of tumour necrosis factor alpha (TNF alpha), human recombinant TNF alpha was given intravenously to rats that had been fed for 12 weeks on diets containing (g/kg) 200 maize oil or 190 coconut oil + 10 maize oil. Rectal temperature and tissue composition measurements were made 8 and 24 h after injection. Ambient temperatures of 20 degrees and 25 degrees were employed to accentuate rectal temperature changes. Doses of 30 and 300 micrograms TNF alpha/kg body-weight were given, and brought about depression of serum zinc and albumin and elevation of copper. Muscle protein content was decreased and liver protein and Zn content enhanced by TNF alpha. Serum Zn and liver Zn content were negatively correlated 8 h after injections. Hypothermia developed within 1 h of injection. All responses except the rise in serum Cu and gain in liver Zn were more intense at the higher than at the lower dose of TNF alpha. Hypothermia was exacerbated by an environmental temperature of 20 degrees. The coconut-oil diet blunted the hypothermia and likewise the changes in serum albumin and Cu content 8 h after injections and in muscle and liver protein after 24 h. Changes in eicosanoid metabolism may be involved in the modulatory effects of the coconut-oil-enriched diet.

Animals↗
PubMed1990

Effect of methylxanthines on lactational performance of rats.

Caffeine, theophylline and theobromine are commonly consumed methylxanthines. There are conflicting reports that methylxanthines may adversely affect the outcome of pregnancy. The effects of methylxanthines on lactational performance were investigated by administration of pure alkaloids via drinking water to Wistar albino rats throughout pregnancy and lactation. Litter growth was used as an index of lactational performance in relation to maternal food and fluid intake, changes in weight, and lipid content of the carcass. Caffeine induced increased fluid intake (p less than 0.01). While theophylline produced no significant differences in litter growth, maternal weight and carcass fat during pregnancy/lactation compared with controls, caffeine and theobromine significantly enhanced litter growth (p less than 0.05 and 0.01, respectively). The enhancement in pup growth did not involve increases in maternal food intake or maternal lipid mobilization.

Animals↗
PubMed1989

Tumour necrosis factor-alpha and lymphotoxin have opposite effects on sympathetic efferent nerves to brown adipose tissue by direct action in the central nervous system.

Intracerebral injection of recombinant human tumour necrosis factor-alpha (rTNF alpha) decreased, whereas lymphotoxin increased the activity of the sympathetic efferent nerves to interscapular brown adipose tissue (IBAT). The changes in firing rates were accompanied by a significant dose-dependent change in IBAT and rectal temperatures (which were decreased with rTNF alpha and increased with lymphotoxin treatment). These results indicate that rTNF alpha and lymphotoxin act directly in the CNS to modulate the sympathetic outflow to IBAT. The opposite effects of the two peptides also suggest that in the CNS, separate receptor systems exist.

Action Potentials↗
PubMed1989

Effect of recombinant human tumour necrosis factor alpha on protein synthesis in liver, skeletal muscle and skin of rats.

Bacterial endotoxins cause enhanced protein metabolism in liver, and protein catabolism in muscle and skin. These effects may be mediated by cytokines such as interleukin 1 (IL1) and tumour necrosis factor (TNF). The study investigates the timing and magnitude of effects of recombinant human TNF alpha on protein synthesis and protein and RNA content of the liver, tibialis muscle and skin of Wistar rats. Intravenous doses of 30 and 300 micrograms/kg of body weight were used and effects examined 8 h and 24 h after injection. Muscle protein content and synthetic rate were reduced at 8 h post-injection by over 18% and 20% respectively. Protein synthesis returned to normal after the lowest dose but remained depressed 24 h after the highest dose due to the accompanying anorexia. Opposite effects were observed in liver. Protein fractional synthetic rate (FSR) was increased by over 26% at 8 h post-injection and remained elevated 24 h after the higher but not lower dose of TNF. Total protein and RNA contents were significantly higher than controls at this time. Skin protein synthesis was unaffected by TNF; however an increase in protein and RNA content was observed at 8 h post-injection with the lower dose of TNF. Liver and muscle respond in a similar but more rapid way to TNF than to endotoxin. The response of skin is however totally different. While muscle may contribute amino acids for enhanced hepatic protein synthesis following exposure to TNF, skin does not.

Animals↗
PubMed1989

Temperature and metabolic changes in rats after various doses of tumour necrosis factor alpha.

1. Sub-lethal doses of recombinant of tumour necrosis factor alpha (TNF alpha) were administered i.v. to young conscious male Wistar rats. Temperature changes and alterations in serum zinc and albumin concentrations and weight and composition of liver, kidney, spleen, tibialis muscle and skin were measured. Temperatures were monitored for 8 h and tissue parameters 8 and 22 h post-injection. 2. Doses above 10 micrograms/kg caused fevers of increasing magnitude and duration with latencies of 2 h. At doses of 200 micrograms/kg or more fevers were preceded by a fall in rectal temperature of up to 1.1 degrees C. 3. Weight loss by skin and tibialis and gain by liver occurred 22 h post-injection. Spleen and kidney weight and zinc and spleen protein contents were unaffected. Serum albumin and zinc fell 22 and 8 h after injection respectively. Liver zinc was elevated at both times and inversely correlated at 8 h with serum values. A degree of dose dependence of zinc and albumin changes existed. A gain in protein was evident in liver 8 h post-injection and a loss by muscle at 22 h. Paradoxical effects were observed in skin protein concentration. 4. TNF alpha mimicked many of the metabolic effects of E. coli endotoxin reported in the literature and showed similar effects to those described for interleukin 1 (IL1).

Animals↗
PubMed1988

Effects of urethane, ambient temperature and injection route on rat body temperature and metabolism due to endotoxins.

1. We have investigated the influence of environmental temperature, anaesthesia and route of administration on rectal temperature and other metabolic responses to two preparations of bacterial endotoxin in male adult Wistar rats. 2. Urethane anaesthesia, environmental temperatures of 20 and 28 degrees C, subcutaneous (S.C.) and intraperitoneal (I.P.) routes of administration and butanol and trichloroacetic acid (TCA) extracts of E. coli endotoxin (1.2 mg/kg) were used. 3. In addition to rectal temperature, serum zinc, albumin and urea concentrations and liver protein, RNA and zinc contents were measured. 4. Fevers were produced by injections of both endotoxins, by either route at 28 degrees C. Butanol-extracted endotoxin produced a more rapid response than the TCA extract via the I.P. route whereas the TCA extract produced a higher temperature than the butanol extract when the S.C. route was used. 5. Fevers were inhibited at an environmental temperature of 20 degrees C and by anaesthesia, while the former had no effect on compositional changes the latter inhibited the fall in serum zinc in response to subcutaneous doses of either endotoxin and the increase in liver zinc content in response to the butanol extract of endotoxin. 6. At 20 degrees C a marked fall in rectal temperature occurred in conscious rats 2 h after receiving the TCA but not the butanol extract of endotoxin. Temperature depression was more severe when endotoxin was administered by the I.P. route. 7. Serum urea was elevated in conscious rats by the TCA extract of endotoxin via both routes but only by the I.P. route for the butanol extract of endotoxin. In anaesthetized animals only the TCA extract of endotoxin raised serum urea concentration when given intraperitoneally. 8. Serum albumin and liver protein and RNA were unaffected by endotoxin injections over the 7 h time course of the study. 9. Rectal temperature responses to endotoxins were influenced in direction and magnitude by all variables employed in the study, while compositional changes were unaffected by environmental temperature but influenced to varying degrees by urethane anaesthesia and the route of administration employed.

Anesthesia↗
PubMed1987

Effect of dietary linoleate content on the metabolic response of rats to Escherichia coli endotoxin.

Dietary fat influences many aspects of immune function. Escherichia coli endotoxin is a potent stimulator of interleukin 1 production from macrophages. The present study examines the effect of feeding with fat diets rich (corn oil) and poor (coconut oil) in linoleate at high and low concentrations on responses to endotoxin. Spleen phosphatidylcholine linoleate contents were higher in the corn oil than in the coconut oil group and arachidonate concentrations were highest in the group fed a high concentration of corn oil. Coconut oil completely abolished the responses to endotoxin. The inhibitory effects of coconut oil could largely be due to reduced prostaglandin and leukotriene synthesis.

Animals↗
PubMed1987

Effects in rats of dietary protein inadequacy on lactose production, milk volume and components of the lactose synthetase complex (EC 2.4.1.22).

Lactose synthetase (LS) is a complex of alpha-lactalbumin and N-acetylglucosamine galactosyl transferase (GT). LS is the rate-limiting enzyme in lactose biosynthesis. Lactose is the main osmotic component of milk and may thereby affect milk volume. Dietary protein inadequacy reduces milk volume and lactose content. The study investigates the role of LS activity in these phenomena. Lactating rats were fed adequate and inadequate amounts of protein of high (milk protein) and low (cereal protein) quality. After 14 days LS and GT activity of mammary tissue was measured. Milk volume and lactose content was determined. While GT activity was unaffected by diet, LS activity was reduced by low dietary protein quality. Addition of bovine alpha-lactalbumin to tissue incubates largely restored the reduced LS activities. Milk volume was affected in a parallel manner to LS activity. A highly significant positive correlation existed between LS activity and total lactose production (r = 0.794; p less than 0.001). Dietary protein inadequacy indirectly reduces milk volume by means of a direct effect on the lactalbumin part of the LS complex and, subsequently, lactose biosynthesis.

Animals↗
PubMed1983

Changes in protein turnover during gestation in the foetuses, placentas, liver, muscle and whole body of rats given a low-protein diet.

(1) Protein synthesis and content have been studied in skeletal muscle, liver, foetuses and placentas of pregnant rats given a protein-deficient diet. Changes which occurred during the anabolic and subsequent catabolic phases of pregnancy are compared with those in well-fed pregnant and in protein-deficient non-pregnant rats. (2) The normal increase in liver protein did not occur during pregnancy in the protein-deficient group. (3) Protein deficiency affected protein content of the placenta earlier and more severely than that of the foetus. (4) Rates of protein synthesis in liver, placentas and foetuses were enhanced above control values by protein deficiency. (5) Muscle protein increased normally during the anabolic phase of pregnancy but fell during the catabolic phase, unlike values for well-fed animals. (6) Muscle protein synthesis rates rose by similar amounts in well-fed and protein-deficient animals during the anabolic phase of pregnancy. The fall to starting values during the catabolic phase was sharper and earlier in protein-deficient animals, which could reduce demands on the body amino acid pool by an amount equivalent to over 50% of the needs for protein deposition in foetuses and placentas. Thus, changes in muscle protein synthesis in both anabolic and catabolic phases of pregnancy may afford some protection to foetal protein synthesis.

Animals↗
PubMed1983

Double metabolic balances on low birthweight infants fed formulae of differing composition.

The comparative nutritional merits of two infant milk formulae, Ready-to-Feed Premium Babyfood (Cow and Gate Ltd.) and Prematalac (Cow and Gate Ltd.) were examined--Prematalac is modified in an attempt to meet the specific requirements of the low birthweight infant. Nine premature infants were enrolled for two metabolic balance periods in a cross-over experimental design. At the onset the infants were randomly allocated one of two milks. Various anthropometric data were collected at the start and end of each 4 day balance. All infants received more energy and protein per kg body weight per day on Prematalac compared with Premium. Incremental weight, though satisfactory for both milks over the balance periods, was greater when Prematalac was fed compared with Premium (mean and (range) 46 (25-93), 19 (9-44) g per day respectively). No differences were detected for gain in length between the two milks. Mean percent digestibility of energy intake was similar for both milks (92%). Infants retained more nitrogen when fed Prematalac compared with Premium (mean (+SD) 477 (59) and 299 (30) mg per kg per day respectively). Neither milk was considered ideal, and we conclude that standard formulae are unable to support the potential for gain in lean body tissue of the premature infant.

Anthropometry↗
PubMed1982

Tyrosine oxidation and protein turnover in maternal tissues and the fetus during pregnancy in rats.

Protein metabolism was examined in rats during the anabolic and subsequent catabolic phase of pregnancy. Protein synthesis in maternal muscle and liver, whole body amino acid flux and [14C]tyrosine oxidation was measured twice during each phase. Protein fractional synthesis and breakdown rates in the fetus and placenta were determined. 1. Muscle protein synthetic rate increased during the anabolic phase and fell during the catabolic phase. Muscle protein increased during the anabolic phase. 2. Liver protein increased by the end of pregnancy with no change in synthetic rates indicating reduced rates of breakdown. 3. Amino acid flux increased during the catabolic phase of pregnancy indicating increases in whole body protein synthesis. The increases were of sufficient magnitude to permit the deposition of protein occurring in fetuses and placentas during this period. 4. 14CO2 production from infused [14C]tyrosine remained unchanged during the anabolic phase of pregnancy but fell during the catabolic phase due mainly to dilution of label by increased amino acid flux. 5. Maternal protein anabolism is mediated by increased muscle protein synthesis rather than by decreased amino acid catabolism. 6. A 61% fall in protein breakdown rate assists fetal protein deposition during the last 4 days of pregnancy.

Amino Acids↗
PubMed1981

The effect of dietary protein concentration and quality on the hormonal status, protein metabolism and milk protein concentrations of rats.

Lactating rats were fed casein or cereal protein at one of two concentrations. Milk volume was severely reduced by poor dietary protein quality. Milk fat, lactose and free amino acid nitrogen were unaffected by the diets, whereas total milk protein was reduced by 20% on the cereal diets. Lactalbumin concentrations showed a greater decrease than that of other milk proteins. Changes in maternal serum insulin, corticosterone, albumin and body weight suggest maternal metabolism changes to provide substrate for milk synthesis. Total milk protein and serum albumin synthesis show similar sensitivity to dietary protein adequacy.

Animals↗
PubMed1979

The relationship between protein turnover and energy balance in lean and genetically obese (ob/ob) mice.

1. Groups of lean and genetically obese (ob/ob) mice were adapted to varying energy intakes and the rates of total protein turnover in liver, gut and kidney were measured. 2. Lean mice gained less weight when fed above maintenance and lost less weight when fed below maintance than obese mice. 3. Hepatic protein turnover (mg/d) was sigmoidally related to digestible energy intake in lean mice but showed no significant changes with dietary intake in obese mice. 4. The changes in protein turnover resulted from changes in both the half-lives of protein synthesis and catabolism and in tissue protein content. 5. In the lean mice, protein turnover in kidney and gut was not significantly changed with increasing energy intake until the highest level was reached. 6. The findings suggest that protein turnover may be an important cycle for the regulation of energy balance in mice and that this cycle is impaired in the genetically obese (ob/ob) mice.

Animals↗
PubMed1978

A new technique for measuring protein turnover in the gut, liver and kidneys of lean and obese mice with [3H] glutamic acid.

1. We have measured the incorporation of an intraperitoneal injection of [3H] glutamate into the protein of the gut, liver and kidney of lean and obese siblings of the genetically obese mouse. 2. Recycling of the 3H was minimized by using glutamate labelled at the C-2 position. Loss of label from the amino acid pool by transamination and deamination was rapid, with a half-life of 4 h. 3. In tissue protein the amino acid showing the highest 3H radioactivity was glutamate. 4. The half-lives for protein synthesis and catabolism were calculated from the decay curves of both specific and total radioactivity of [3H] glutamate in tissue protein. No significant differences were found between kidney, liver and gut in lean and obese mice.

Animals↗