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J S Marway

Publications and source records attributed to J S Marway.

11 recordsLinked to original sources

Studies of gut mucosal protein synthesis in a non-steroidal anti-inflammatory drug (NSAID) model of inflammatory bowel disease.

The extent to which defects in protein synthesis occurred in an experimental indomethacin induced rat model of nonsteroidal enteropathy has been examined. Male rats (nine) were fed indomethacin (8 mg/kg/day) for three days mixed with a powdered form of chow. The control group of rats (nine) were fed the same diet for three days without indomethacin. After the feeding period, both groups were fed a normal solid diet for four days. At the end of this period, the fractional rates of intestinal protein synthesis was determined by the 'flooding dose' technique. The mucosal protein, RNA and DNA contents in the proximal ileum of animals with enteropathy were not significantly different from controls (p greater than 0.05). Experimental enteropathy induced selective increases in the fractional rates of protein synthesis (26% increase, p less than 0.03) and RNA activities (23% increase, p less than 0.04). There were no significant changes in any of these variables in the duodenum (p greater than 0.05 in all instances). These changes may partly reflect the activity of those processes responsible for the pathogenic changes in NSAID enteropathy.

Animals

Contractile and non-contractile proteins and nucleic acids in the stomach, whole jejunum and seromuscular layers of the duodenum, jejunum, ileum and large intestine in response to chronic ethanol feeding.

Rats were fed a nutritionally adequate liquid diet containing 35% of the total calories as ethanol (treated), or identical amounts of the same diet in which ethanol was replaced with isocaloric glucose (controls). At 6 weeks, rats were killed and the stomach (cardiac region), duodenum, jejunum, ileum and the large intestine (combined colon and rectum) were dissected. Seromuscular layers were prepared from the duodenum, jejunum, ileum and the large intestine. After 6 weeks of chronic ethanol feeding the wet weights of the stomach and whole jejunum were reduced by 31%. The wet weights of the duodenum, jejunum and distal ileum seromuscular layers were reduced by 19-25%. The wet weight of the large intestine seromuscular layer was unaltered. The total amounts of contractile and non-contractile protein in the small intestinal seromuscular layers were reduced by 16-52%. In jejunal serosa, the RNA contents were reduced by 29%, but total RNA contents in the serosa of the ileum and duodenum were not significantly altered. Total DNA content was reduced in jejunal and ileal serosal layers by 22 and 33%, respectively, but remained unchanged in duodenal serosa. In the stomach, total contractile and non-contractile protein was reduced by 26-52% and similarly total RNA and DNA were also decreased by 47 and 34%, respectively. Chronic ethanol feeding had no apparent effect on either contractile or non-contractile total protein, total RNA or DNA contents in colonic and rectal serosa. In the combined mucosal and seromuscular layers of the jejunum, much greater effects due to ethanol feeding were observed when compared with the jejunal seromuscular layer alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism

The effect of aminoguanidine treatment, with or without food restriction on the liver, stomach and small intestine of the rat.

A comparative investigation has been made into the effects of aminoguanidine treatment (60 mg kg-1 day-1) with or without dietary restriction (i.e. 50% reduction in food intake) on the protein, RNA and DNA composition of the liver, small intestine and stomach of young rats (0.1 kg body weight). After 3 weeks of dietary restriction the wet weights of the liver and small intestine decreased by 56 and 52%, respectively. There were significant reductions (approx 50%) in total hepatic and intestinal protein, RNA and DNA. Changes in ratios of RNA/protein, RNA/DNA and protein/DNA were only significant for intestinal RNA/DNA, where a 15% reduction was observed. In contrast, stomach wet weight and total protein content were unaltered by dietary deprivation. Stomach RNA and DNA contents were reduced by only 18-21%, and the protein/DNA ratio increased by 22%. Similar responses of liver, small intestine and stomach to dietary deprivation were observed in aminoguanidine-treated rats. Aminoguanidine-treatment of rats on an unrestricted diet for three weeks had no effect on the wet weights, total protein, RNA or DNA contents of the liver, stomach or small intestine. In dietary-restricted rats, and stomach were unaffected by the treatment. However, aminoguanidine treatment of dietary-restricted rats caused significant increases in the amounts of intestinal protein, RNA and DNA by approximately 15%. The treatment abolished the dietary restriction-induced decrease in total intestinal DNA/body weight. The wet weights of the lung, diaphragm, kidney, spleen and testes of both fed and dietary-restricted rats were also unaffected by aminoguanidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Ethanol-induced smooth and skeletal muscle myopathy: use of animal studies.

This article reviews the effects of ethanol on skeletal and smooth muscle. A brief summary of its clinical effects is provided, with a rationale for the use of suitable animal models to study ethanol-induced myotoxicity. Practical details are given for the animal feeding techniques to examine the chronic effects of ethanol toxicity. Information on acute ethanol dosage experiments are also provided. Our results have indicated that ethanol causes net loss of both skeletal and smooth muscle protein and an effect on protein synthesis and/or degradation was implicated. The theoretical and practical basis of measuring protein synthesis in intact laboratory animals is reviewed. However, there are no reliable methods for measuring rates of protein breakdown in vivo. The combined results of our studies indicated that disturbances in protein synthesis were causal mechanisms for ethanol-induced myo-dysfunction. Acute ethanol exposure was largely characterised by reductions in fractional rates of skeletal and smooth muscle contractile protein synthesis. The dominant characteristics of chronic treatments were loss of skeletal and smooth muscle proteins and RNA. Further laboratory animal studies will eventually elucidate the molecular mechanisms of these changes and provide valuable information on the regulation of protein mass.

Actomyosin

Protein synthesis in bone and skin of the rat are inhibited by ethanol: implications for whole body metabolism.

The acute effects of ethanol (75 mmol/kg body weight, intraperitoneal) on rates of protein synthesis in bone tibia) and skin of young (approximately 100 g body weight) laboratory rats was investigated. Plasma ethanol levels were raised to approximately 40 mmol/liter. At 2.5 hr, rates of protein synthesis were measured with a flooding dose of L-[4-3H]phenylalanine. In bone the protein-bound specific radioactivities, fractional synthesis rates, and synthesis rates relative to RNA and DNA were significantly reduced by approximately 30%. In skin these variables similarly decreased in response to ethanol treatment, by approximately 25%. The reduction in absolute rates of protein synthesis in bone (delta, 0.7 g protein/day/kg body weight) and skin (delta, 3.4 g protein/day/kg body weight) were comparable to the reductions in liver and skeletal muscle in response to acute ethanol. As bone and skin contribute to a quarter of whole body protein synthesis, it was concluded that these observations may have important implications for whole body protein homeostasis.

Animals

Measurement of protein synthesis by the phenylalanine flooding dose technique: effect of phenylalanine and anaesthesia on plasma electrolyte, enzyme and metabolite levels.

Ten minutes after an intravenous flooding dose of phenylalanine to rats, plasma sodium and calcium concentrations were slightly reduced (by 2-7%) but no effects on potassium or phosphate were observed. Creatine kinase activities were significantly increased by phenylalanine injection (by 39%), but alkaline phosphatase, alanine aminotransferase, lactate dehydrogenase and aspartate aminotransferase activities were unaltered. Plasma concentrations of total proteins, albumin, cholesterol, triglycerides, urea, creatinine and glucose were also unaffected. In the presence of anaesthesia, phenylalanine injection had almost identical effects, although the increase in creatine kinase activities did not reach statistical significance. Anaesthesia for 10 min reduced plasma potassium concentrations (by 27%), and calcium (by 5%), though phosphate and sodium were unaltered. The activities of lactate dehydrogenase, creatine kinase and aspartate aminotransferase were reduced by between 36-52%, but alkaline phosphatase and alanine aminotransferase activities were unaltered by anaesthesia. Plasma concentrations of total proteins and albumin were also reduced (both by 9%), but glucose concentrations were increased (by 33%). Anaesthesia had no other significant effects on cholesterol, triglycerides, urea or creatinine concentrations. The qualitative effects of anaesthesia in the presence of raised free phenylalanine concentrations were similar. It was concluded that, except for creatine kinase, determinations of plasma constituents in phenylalanine-injected rats could be made without overt interpretational errors. However, caution is required in interpreting data on plasma constituents from anaesthetized rats.

Alanine Transaminase

Experimental alcoholic skeletal muscle myopathy is characterised by a rapid and sustained decrease in muscle RNA content.

An investigation was made into the effects of ethanol feeding (36% of total calories) on skeletal muscle. From 7 to 42 days, muscle weights and protein and DNA contents of alcohol-treated rats were significantly lower (10-23%) than pair-fed controls (with glucose as 36% of total calories). Ethanol feeding markedly reduced muscle RNA content by 22-34%, when compared to controls. Muscle RNA content of ethanol-fed rats at 7, 14, 28 and 42 days of treatment was significantly lower than initial values (i.e. at 3 days) by 22-38%. Thus, ethanol feeding caused an initial net loss and thereafter a reduction in the rate of accretion of RNA. The marked and sustained loss in the muscle protein synthetic apparatus may be a precipitating event in the development of experimental skeletal muscle myopathy.

Alcoholism

Use of the Lieber-DeCarli liquid feeding regime with specific reference to the effects of ethanol on rat skeletal muscle RNA.

This communication discusses the ways in which parameters of tissue injury in chronic ethanol-fed rats can be presented. These are: concentration (amount per unit wet weight), absolute amount (total quantity per organ or tissue) or relative to body weight (total quantity per unit body weight). Specific reference is made to the amount of RNA in skeletal muscles from rats fed the Lieber-DeCarli liquid diet containing ethanol for 6 weeks. Comparisons were made with data from rats which were pair-fed the same diet in which ethanol was substituted by iso-caloric glucose. Chronic ethanol-feeding had no statistically significant effect on the concentration of skeletal muscle RNA, though the absolute amount was reduced by 20%. When expressed relative to body weight the magnitude of this decline was reduced, to only 10%. Due to the nature of the liquid feeding regime the animals showed variable alterations in body weight. The amount of liquid diet consumed by control and ethanol-fed rats over a 24 hr period can comprise as much as 40% (w/w) of body weight. It is therefore suggested that data expressed relative to body mass may, on occasions, be erroneous. Episodic engorgement with food may also have an influence on other metabolic processes such as the kinetics of protein, fat or carbohydrate metabolism. These issues may have important implications for other studies using the Lieber-DeCarli liquid diet to examine the effects of ethanol on muscle or non-muscle tissues.

Animal Feed