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Biomedical subjects

R F Grimble

Publications and source records attributed to R F Grimble.

At least 37 records · Page 2Linked to original sources
PubMed1995

Endotoxin induced production of interleukin-6 is enhanced by vitamin E deficiency and reduced by black tea extract.

Studies were performed to investigate the effect of a polyphenol rich extract from black tea and vitamin E on bacterial lipopolysaccharide (endotoxin) induced IL-6 production, alterations in liver glutathione and antioxidant acute phase protein (caeruloplasmin) concentration, in rats fed on a synthetic diet for 21 days. In the vitamin E sufficient group a significantly lower IL-6 concentration than in vitamin E deficient animals was observed. Addition of tea extract to the diet produced a similar reduction in IL-6, but no synergism occurred in the presence of both vitamin E and tea extract. However, a significantly lower caeruloplasmin and a significantly higher liver glutathione concentration was observed in rats fed both substances. It is suggested that consideration of dietary components which alter antioxidant/oxidant status may contribute towards treatment of inflammatory/autoimmune diseases.

Analysis of Variance↗
PubMed1995

Comparison of the modulatory influence of maize and olive oils and butter on metabolic responses to endotoxin in rats.

1. n-3 polyunsaturated fatty acids decrease responses to cytokines and inflammatory agents. The present study examines how different intakes of n-6 and n-9 fatty acids influence the metabolic response to endotoxin in Wistar rats. 2. Weanling male rats were, for 4 weeks, fed diets containing 50, 100 or 200 g/kg fat in the form of maize oil (rich in linoleic acid), butter (poor in linoleic acid, rich in oleic acid) or olive oil (adequate in linoleic acid, rich in oleic acid) or standard laboratory chow. All butter and olive oil diets included 10 g/kg maize oil, in total fat, to avoid essential fatty acid deficiency. 3. Rats subsequently received 800 micrograms/kg Escherichia coli endotoxin or sterile saline subcutaneously. Twenty-four hours after injection, the rate of tissue protein synthesis was measured in liver, lung, kidney, tibialis muscle and spleen by the 'flooding dose' method. Protein and zinc concentrations were assayed in all tissues and serum albumin and caeruloplasmin measured. 4. In animals fed chow, protein synthetic rate increased by 18%, 29% and 27% in liver, lung and kidney respectively. Tissue zinc concentrations increased by 33% in kidney, and tissue protein increased by 17%, 23% and 17% in liver, lung and kidney respectively. Serum caeruloplasmin increased by 60% and albumin concentration fell by 14%. 5. In animals consuming the 50 g/kg maize oil diet, protein synthetic rate increased by 56%, 36% and 34% in liver, lung and kidney respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Cigarette smoking influences cytokine production and antioxidant defences.

1. Smoking exerts an inflammatory stimulus on lung macrophages, and smokers generally have low intakes of antioxidant micronutrients. This study was performed to investigate the relationship between whole-blood tumour necrosis factor production, plasma interleukin-6 and acute-phase protein concentration and antioxidant vitamins in smokers and non-smokers. 2. Measurement of tumour necrosis factor was conducted in whole blood stimulated with endotoxin (lipopolysaccharide), and interleukin-6 concentrations were measured in the plasma of smokers and non-smokers. Enzyme and dietary antioxidant concentrations and acute-phase proteins were determined in the two groups. 3. Tumour necrosis factor production and plasma interleukin-6 concentrations were 38% (P = 0.01) and 16% (P = 0.07) greater, respectively, in smokers than in non-smokers. Plasma vitamin A and E concentrations were unaffected by smoking; however, a 21% lower plasma vitamin C (P = 0.04) concentration was observed in smokers, than in non-smokers despite a similar intake of this vitamin by the two groups. 4. Concentrations of the acute-phase proteins alpha 1-acid glycoprotein, caeruloplasmin and alpha 2-macroglobulin were increased in the plasma of smokers compared with non-smokers by 39%, 28% and 12% respectively (P < 0.01). Our studies indicate that smokers have a compromised antioxidant status and elevated concentrations of tumour necrosis factor and interleukin-6 as a consequence of smoking. 5. These observations may provide some insight into the biological mechanisms underlying the pathology associated with smoking.

Acute-Phase Proteins↗
PubMed1994

Complex modulation of cytokine induction by endotoxin and tumour necrosis factor from peritoneal macrophages of rats by diets containing fats of different saturated, monounsaturated and polyunsaturated fatty acid composition.

1. Responses to cytokines and other inflammatory stimuli have been shown to be enhanced by fats rich in n-6 polyunsaturated fatty acids and suppressed by fats rich in n-3 polyunsaturated fatty acids and oleic acid or poor in n-6 polyunsaturated fatty acids. 2. Corn oil is rich and coconut oil, olive oil and butter are poor in n-6 polyunsaturated fatty acids. Olive oil and butter are rich in oleic acid. Fish oil is rich in n-3 polyunsaturated fatty acids. 3. The present study examines the effects of feeding standard chow or corn, coconut, fish and olive oils and butter for 4 and 8 weeks on subsequent cytokine production by peritoneal macrophages of rats. 4. Tumour necrosis factor production in response to a lipopolysaccharide stimulus and interleukin-1 and interleukin-6 production in response to a tumour necrosis factor challenge were studied. 5. All fats produced a small, but statistically insignificant, reduction in tumour necrosis factor production, which was greatest for olive oil at 8 weeks. 6. After 4 weeks, fish and olive oil significantly reduced interleukin-1 production. After 8 weeks, coconut oil suppressed production of the cytokine, and the inhibitory effect of fish oil was still apparent. After 8 weeks, corn and olive oil enhanced interleukin-1 production. 7. After 4 weeks of feeding, fish and olive oil enhanced interleukin-6 production. After 8 weeks, the enhancement by these fats increased, and corn oil and butter also enhanced production. Coconut oil produced no modulatory effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Cysteine and methionine supplementation modulate the effect of tumor necrosis factor alpha on protein synthesis, glutathione and zinc concentration of liver and lung in rats fed a low protein diet.

The synthesis of cysteine-rich compounds such as glutathione and metallothionein is an integral part of the response to cytokines. To examine the essentiality of an adequate supply of sulfur amino acids during a response to tumor necrosis factor alpha (TNF) we fed rats a low protein (8% casein) diet supplemented with either cysteine and alanine, methionine and alanine, or alanine alone, or a normal protein (20% casein) diet for 8 d before injection with TNF or saline. Those animals injected with saline were pair-fed the intake of their TNF-injected counterparts for the 24 h after injection. In a second experiment, control groups fed the same diets but receiving no treatment were also examined to establish baseline values. Although few significant differences between the non-injected animals consuming food ad libitum were apparent, TNF injection and pair-feeding resulted in differences between the dietary groups. Supplementation of the low protein diet with either cysteine or methionine improved growth and increased liver and lung glutathione concentration, zinc concentration, protein concentration and protein synthesis compared with results for the alanine-supplemented group. Lung polymorphonuclear cells were proportionally elevated in the TNF-treated, alanine-supplemented group compared with the other dietary groups treated with TNF. The changes in protein synthesis and glutathione concentration of the liver in response to TNF showed that sulfur amino acids may be partitioned to a greater extent into hepatic protein than into glutathione when sulfur amino acid intake is low. Consequently the adequacy of dietary sulfur amino acids will determine the extent to which antioxidant defenses are maintained during inflammation.

Animals↗
PubMed1994

The acute phase response of adult rats is altered by in utero exposure to maternal low protein diets.

The immune system has been previously demonstrated to be under the influence of maternal nutrition in pregnancy. Assessment was made of the effects of low protein diets (12, 9 and 6 g casein/100 g diet) fed before conception and during pregnancy on the immune system of the resulting offspring in early adulthood. Control animals were fed a diet containing 18 g casein/100 g. At the end of pregnancy all dams were fed a nonpurified diet containing 18.3 g protein/100 g. Male pups were weaned onto this diet, which they consumed until the age of 7 wk. Rats exposed to 18 g casein/100 g diet in utero mounted a typical acute phase response following E. coli endotoxin challenge at age 7 wk. Food intake was 75% lower, hepatic zinc concentrations 25% greater, and serum albumin 15% lower than in saline-injected controls. Pulmonary glutathione levels were 35% greater in endotoxin-treated rats than in saline-treated controls. In rats exposed to low protein diets in utero the trend was for the acute phase response to be blunted. This was most noticeable with respect to the anorectic response, hepatic zinc uptake and pulmonary glutathione uptake. In rats not challenged with endotoxin, maternal diet had pronounced effects on tissue zinc status at the age of 7 wk. Liver zinc concentrations were 21% and 16% lower in the groups exposed to 9 and 6 g casein/100 g diets relative to the control group exposed to 18 g casein/100 g diet. Glutathione status was altered in all groups exposed to low dietary protein in utero.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗
PubMed1994

Nutritional antioxidants and the modulation of inflammation: theory and practice.

Highly potent substances are produced by the immune system. These substances include cytokines and oxidant molecules, such as hydrogen peroxide, free radicals, and hypochlorous acid. The purpose of immune cell products is to destroy invading organisms and damaged tissue, bringing about recovery. However, oxidants and cytokines can damage healthy tissue. Excessive or inappropriate production of these substances is associated with mortality and morbidity after infection and trauma, and in inflammatory diseases. Oxidants enhance interleukin-1, interleukin-8, and tumor necrosis factor production in response to inflammatory stimuli by activating the nuclear transcription factor, NF kappa B. Sophisticated antioxidant defenses directly and indirectly protect the host against the damaging influence of cytokines and oxidants. Indirect protection is afforded by antioxidants, which reduce activation of NF kappa B, thereby preventing up-regulation of cytokine production by oxidants. Cytokines increase both oxidant production and antioxidant defenses, thus minimizing damage to the host. While antioxidant defenses interact when a component is compromised, the nature and extent of the defenses are influenced by dietary intake of sulfur amino acids, for glutathione synthesis, and vitamins E and C. In animal studies, in vivo and in vitro responses to inflammatory stimuli are influenced by dietary intake of copper, zinc, selenium, N-acetylcysteine, cysteine, methionine, taurine, and vitamin E. Information from animal studies has yet to be fully translated into a clinical context. However, N-acetylcysteine, vitamin E, and a cocktail of antioxidant nutrients have reduced inflammatory symptoms in inflammatory joint disease, acute and chronic pancreatitis, and adult respiratory distress syndrome. Impaired antioxidant defenses may contribute to disease progression after infection with human immunodeficiency virus. Powerful arguments have been advanced for treatment with antioxidants to slow progression of acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Influence of butter and of corn, coconut and fish oils on the effects of recombinant human tumour necrosis factor-alpha in rats.

1. Tumour necrosis factor-alpha is produced in response to inflammatory stimuli. Fish oil can suppress the production and actions of cytokines. Little information is available on the effects of other fats on cytokine biology. We compared the effects of fats, with a wide range of fatty acid characteristics, on the effects of tumour necrosis factor-alpha on protein and zinc metabolism in rats. 2. Weanling rats were fed for 8 weeks on diets containing 10% fat in the form of corn, fish or coconut oils or butter before an intraperitoneal injection of recombinant human tumour necrosis factor-alpha was given. Measurements were made 24h after the injection. 3. In rats fed corn oil, food intake was reduced by 62% and rates of protein synthesis were increased by 86, 32 and 39% in the liver, lung and kidney, respectively. Zinc concentrations increased by 23% in the liver but decreased by 10% in the kidney. Plasma caeruloplasmin and complement C3 levels increased by 25% and 28%, respectively, and plasma albumin level decreased by 24%. 4. Fish oil prevented the increase in hepatic protein synthesis and changed the response of protein synthesis in lung and kidney to a decrease. Changes in hepatic and renal zinc concentrations were prevented. The response of the plasma caeruloplasmin level was unaltered but those of the plasma complement C3 and albumin concentrations were prevented. 5. Coconut oil and butter, although similarly low in linoleic acid, differed in their modulatory effects. With the exception of the rise in the plasma complement C3 concentration, all responses were prevented or greatly inhibited in rats fed butter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cysteine and glycine supplementation modulate the metabolic response to tumor necrosis factor alpha in rats fed a low protein diet.

Responses to cytokines entail synthesis of substances rich in cysteine and glycine, such as glutathione (GSH), metallothionein and some plasma proteins. To examine the importance of an adequate supply of cysteine and glycine, we fed rats a low protein diet supplemented with L-cysteine and glycine, separately or in combination, or L-alanine, or a high protein diet for 1 wk before injection with tumor necrosis factor alpha (TNF) or saline. The high protein diet-fed group had greater liver weight and zinc and GSH concentrations after TNF than the group fed the low protein diet supplemented with alanine. Glycine and cysteine supplementation resulted in greater liver weight after TNF treatment than did alanine supplementation. Cysteine supplementation had a similar influence on GSH concentration. Ceruloplasmin, alpha-2-macroglobulin and alpha-1-acid glycoprotein were higher in TNF-treated rats than in saline controls in each dietary group. However, feeding supplementary glycine and cysteine and the high protein diet often resulted in different values than seen in animals fed the low protein diet supplemented with alanine. Paradoxically, lower ceruloplasmin concentrations were observed in animals fed the former diets than in those fed the latter. alpha-2-Macroglobulin concentration was lower in all animals fed low protein diets than in those fed the high protein diet. alpha-1-Acid glycoprotein was lowest in groups fed cysteine-supplemented diets and highest in the glycine-supplemented group.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1992

Taurine and serine supplementation modulates the metabolic response to tumor necrosis factor alpha in rats fed a low protein diet.

Plasma taurine and serine decrease following trauma and in severe inflammatory disease. These changes may signify an increase in requirements for sulfur amino acids. We previously demonstrated that cysteine supplementation can restore the impaired ability of rats fed an 8% casein diet to increase hepatic zinc, glutathione (GSH) and protein concentrations in response to tumor necrosis factor alpha (TNF alpha). Here we examined whether serine or taurine produces a similar effect, because serine provides the carbon skeleton of cysteine and taurine is its major metabolite. After 7 d of receiving either a 20% casein diet supplemented with cysteine or an 8% casein diet supplemented with alanine, serine or taurine, rats received an intraperitoneal injection of human TNF alpha. Tumor necrosis factor caused no change in hepatic GSH but resulted in a lower GSH concentration in lung in rats fed the alanine-supplemented diet. Neither taurine nor serine increased liver GSH relative to that in rats fed alanine, but the depression in lung due to TNF injection was lessened. The absolute increase in ceruloplasmin in response to TNF was enhanced in rats fed the alanine-supplemented diet relative to those fed the 20% casein diet. Serine normalized this response. This observation--the effects of taurine and serine on lung GSH and a significant negative correlation between ceruloplasmin and liver and lung GSH concentration in rats fed TNF--suggests that supplemental serine and taurine may improve antioxidant defenses when dietary supplies of cysteine are low but do not influence cysteine availability for a normal response to TNF.

Acute-Phase Proteins↗
PubMed1991

Effect of age on hypothalamic prostaglandin E2 production and fever in response to tumour necrosis factor (cachectin) and endotoxin in rats.

1. Decreased febrile responses to interleukin-1 and endotoxin have been noted in a number of species with ageing. 2. The present study extends these observations by examining the pyrogenic response to intravenous recombinant human tumour necrosis factor-alpha (50 micrograms/kg) using conscious rats aged 7,20 and 80 weeks. 3. The febrile response decreased in magnitude and duration with age. Fevers of 0.9 degree C and of 5 h duration were observed in the youngest rats, whereas those aged 80 weeks were afebrile. The depression in serum zinc level and the elevation in liver zinc level, which occurred 7 h after injection, were unaffected by age. 4. The mechanism of the reduced pyrogenic response was examined by assessing prostaglandin E2 production in vitro from hypothalami of rats, aged 10 and 24 weeks, in response to Escherichia coli endotoxin and tumour necrosis factor. 5. Whereas the production of prostaglandin E2 increased by 47% and 52%, respectively, in hypothalami from 10-week-old rats, no response to either pyrogen was obtained in tissue from rats aged 24 weeks. 6. Maturity brings about a decreased responsiveness of hypothalamic prostaglandin E2 production to pyrogens, which may explain the decreased febrile responses observed.

Aging↗
PubMed1990

Tumour necrosis factor-alpha and endotoxin induce less prostaglandin E2 production from hypothalami of rats fed coconut oil than from hypothalami of rats fed maize oil.

1. The primary aim of the study was to determine whether the stimulatory effect of tumour necrosis factor-alpha and endotoxin on hypothalamic prostaglandin E2 production was influenced by dietary fats containing different amounts of linoleic acid. Rats received diets containing 20% (w/w) maize oil or 19% (w/w) coconut oil plus 1% (w/w) maize oil for 8 weeks. 2. A subsidiary part of the study examined the effect of tumour necrosis factor-alpha on the ability of the calcium ionophore A23187 to stimulate prostaglandin E2 and leukotriene C4 production by hypothalami from chow-fed rats. 3. While tumour necrosis factor-alpha enhanced prostaglandin E2 production in response to A23187, neither agent had an effect on leukotriene C4 production. 4. Hypothalami from rats fed maize oil exhibited increased prostaglandin E2 production in response to both pyrogens. This did not occur with hypothalami from rats fed coconut oil. 5. Coconut oil might exert its modulatory effect by bringing about a reduction in membrane phospholipid arachidonic acid content.

Animals↗
PubMed1990

The effect of methylxanthines on milk volume and composition, and growth of rat pups.

A study was conducted to investigate the effect of differential dose levels of methylxanthines on lactational performance, with respect to milk volume and composition and pup growth. The methylxanthines; caffeine, theophylline and theobromine, were administered via drinking water in the proportions occurring in tea, at a dose of 50, 1 and 2 mg/kg body-weight respectively to Wistar albino rats throughout pregnancy and for up to the 14th day of lactation. A fourth group received a mixture of all three methylxanthines. Maternal food and fluid intake and weight changes, as well as weight gain in the litter were monitored thrice weekly. Milk samples were collected from the dams on days 7 and 14 of lactation, while milk volume was measured on days 12-13 by a method using tritiated water. Results showed that caffeine and theobromine significantly enhanced litter weight (P less than 0.01 and 0.05 respectively). In the caffeine group, enhanced litter growth was due to a significant increase (P less than 0.05) in milk volume, consequent to increased maternal food intake (P less than 0.05). In the theobromine group there was only a weak association between increased litter weight and milk volume. Theophylline had no effect on the volume or composition of milk, or litter weight. The combination of all three methylxanthines also failed to produce any of the positive effects observed with separate drug treatments.

Animals↗