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Biomedical subjects

A B Thomson

Publications and source records attributed to A B Thomson.

At least 181 records · Page 10Linked to original sources
PubMed1989

Saturated fatty acid diet prevents radiation-associated decline in intestinal uptake.

Adult female Sprague-Dawley rats were fed isocaloric semipurified diets containing a high content of either polyunsaturated (P) or saturated (S) fatty acids; these diets were nutritionally adequate, providing for all known essential nutrient requirements. On day 3 after beginning S or P, one group of animals was exposed to a single 6-Gy dose of abdominal radiation, and the other half was sham irradiated. S or P diets were continued for a further 14 days. Brush-border membrane purification and sucrase-specific activities were unaffected by diet or by abdominal irradiation. In rats fed P, irradiation was associated with an increase in jejunal brush-border membrane total phospholipid and the ratio of phospholipid to cholesterol; these changes were not observed in animals fed S. In irradiated rats, ileal brush-border membrane phospholipid per cholesterol was high in animals fed S compared with P. In irradiated animals fed P, there was reduced jejunal and ileal uptake of several medium- and long-chain saturated and unsaturated fatty acids and cholesterol, and the ileal uptake of higher concentrations of glucose was reduced in irradiated animals fed P. In contrast, lipid uptake was similar in control and irradiated animals fed S except for cholesterol uptake, which was reduced. Ileal uptake of higher concentrations of glucose was increased in irradiated animals fed S. Quantitative autoradiography failed to demonstrate any change in the distribution of leucine or lysine transport sites along the villus 1 or 2 wk after abdominal irradiation or in response to feeding S or P. Also, these differences in transport achieved by feeding S to radiated animals were not explained by variations in the animals' food consumption or intestinal mucosal surface area. Thus the use of short-term feeding with a saturated fatty acid diet in the prevention of acute irradiation damage to the intestine warrants further investigation in humans.

Amino Acids↗
PubMed1989

Effect of oral enprostil, a synthetic prostaglandin E2, on intestinal brush border membrane lipid composition following abdominal irradiation in the rat.

Previous studies have demonstrated that external abdominal irradiation alters intestinal nutrient transport and brush border membrane (BBM) phospholipid content. This study was undertaken to assess the possible protective effect of oral dosing of enprostil, a synthetic E2 prostaglandin, on the BBM marker enzyme and lipid composition of non-irradiated control (CONT) animals and of rats exposed seven days perviously to a single dose of 600 cGy external abdominal irradiation (RAD). Half the CONT and RAD animals were orally dosed with enprostil 5 mcg/kg body weight, two and one mornings before the day of irradiation, and one hour before 600 cGy; the remaining half were dosed with placebo according to the same schedule. BBM were isolated and purified from the animals seven days post-irradiation for analysis of marker enzymes and lipid composition. Radiation was associated with a decline in jejunal and ileal BBM activity of sucrase. Enprostil was associated with a decline in the ratio of alkaline phosphatase/sucrase in jejunal BBM from irradiated rats, despite its preventing a radiation-associated decline in BBM sucrase activity. Radiation was associated with changes in ileal BBM phospholipids, and these alterations were not prevented with enprostil. Furthermore, enprostil given to non-radiated control rats altered BBM composition, such as increased jejunal and ileal lysophosphatidylethanolamine, and lowered ileal BBM sphingomyelin and phosphatidylethanolamine. Thus, enprostil failed to protect the intestine from the effects of abdominal irradiation on BBM phospholipids, but did partially prevent the effect of abdominal irradiation on jejunal sucrase activity.

Abdomen↗
PubMed1989

Endothelium-dependent relaxation to acetylcholine in the aorta of streptozotocin induced diabetic-rat and the BB-diabetic rat.

Experiments were designed to investigate the phenomenon of endothelium-dependent relaxation (EDR) to acetylcholine in two animal models of insulin dependent diabetes mellitus. Thoracic aortas obtained from streptozotocin diabetic rats and genetically diabetic biobreeding rats (BB rats) were used in this study. Concentration-effect curves to acetylcholine were carried out on aortic rings under isometric tension. Following the induction of diabetes with streptozotocin, half of the animals were treated with daily intermediate acting insulin and the other half maintained without insulin for a period of 12 weeks before the experiment. The diabetic BB rats were also maintained on insulin. The EDR to acetylcholine was not impaired in the aortas of streptozotocin diabetic rats (insulin treated as well as untreated) compared to nondiabetic controls. The scanning electron microscopic (SEM) appearances of the aortic endothelium did not differ among the three groups of animals. However, the EDR to acetylcholine was found to be impaired in the aortas of diabetic BB rats. (Maximum relaxation: 25.3 +/- 5.0% of the contraction to norepinephrine compared to 52.2 +/- 5.3% in controls.) The SEM appearances of the aortic endothelium in the diabetic BB rats were found to be abnormal with edema and loss of definition of cell margins compared to nondiabetic controls. The differences in EDR to acetylcholine seen between the two animal models of diabetes may be related to the different aetiologies of diabetes in the animals.

Acetylcholine↗
PubMed1989

Improved intestinal form and function in diabetic rats fed long-term with a polyunsaturated fatty acid diet.

Short-term (two weeks) feeding of isocaloric diets supplemented with polyunsaturated fatty acids (PUFA) is useful for the prevention or treatment of the enhanced uptake of glucose which occurs in rats with streptozotocin-induced diabetes, as compared with animals fed a diet supplemented with saturated fatty acids (SFA). The study was undertaken to compare the effects of long-term (seven weeks) feeding PUFA or SFA to diabetic rats. We have previously reported that diabetic animals fed PUFA had superior body weight gain, lower hemoglobin AlC values, lower plasma cholesterol and triglyceride levels, lower percentage decline in glucose (K value) following intravenous glucose tolerance testing, near-normal values of hepatic microsomal glucose-6-phosphatase activity and near-normal concentrations of 18:2(6) and 20:4(6) in liver microsomal phosphatidylcholine and phosphatidylserine. However, jejunal and ileal uptake of varying concentrations of glucose were similar in the three diet groups. Thus, the potential long-term beneficial effects of feeding diets with a high PUFA/SFA ratio probably have their explanation in metabolic effects distant to their uptake by the intestine.

Animals↗
PubMed1989

Rechallenge following an early life exposure to a high-cholesterol diet enhances diet-associated alterations in intestinal permeability.

This study was undertaken to test the hypothesis that the intestinal transport response to a high-cholesterol (2%) diet (HCD) is influenced by prior exposure to HCD at an earlier age. Uptake was assessed using an in vitro technique, and rabbits were fed one of four dietary regimens: chow for 20 weeks, chow for 14 weeks followed by HCD for 6 weeks, chow for 2 weeks followed by 4 weeks HCD followed by chow for 14 weeks, or 2 weeks chow followed by 4 weeks HCD followed by 8 weeks chow and then 6 further weeks with HCD. The passive jejunal uptake of octanoic, lauric, cholic, and taurocholic acids was greater in animals previously exposed at an earlier age to HCD, as compared with those first exposed to HCD at a later age. Furthermore, the effect of HCD on the passive permeability properties of the intestine lasted for as long as 14 weeks after the animals were switched from HCD back to chow. These alterations in permeability properties occurred in the absence of changes in the intestinal mucosal surface area and were not explained by differences in the rabbits' body weight gain, food consumption, or mucosal surface area of the jejunum or ileum. Thus, (a) early changes in animals' dietary content of cholesterol may have prolonged effects on intestinal transport function, and (b) this early feeding experience with cholesterol may alter the adaptive pattern of the intestine when animals are exposed to a dietary cholesterol challenge at a later age.

Animals↗
PubMed1988

Dietary cholesterol and/or n-3 fatty acid modulate delta 9-desaturase activity in rat liver microsomes.

delta 9-Desaturase activity and fatty acid composition of liver microsomal phospholipids in rats fed diets enriched with either saturated (hydrogenated beef tallow) or alpha-linolenic (linseed oil) or eicosapentaenoic and docosahexaenoic (fish oil) acids with or without 2% cholesterol supplementation were investigated. Both the linseed oil and the fish oil diets inhibited delta 9-desaturase activity in the rat liver microsomes. The inhibition was greater when feeding fish oil (90%) compared with the linseed oil (60%) diet. Dietary cholesterol feeding accelerated conversion of palmitic (16:0) to palmitoleic (16:1) acid, irrespective of the fatty acid supplement. Feeding the linseed oil diet decreased, while feeding the fish oil diet increased synthesis of the monounsaturated fatty acids of n-7 series (palmitoleic and vaccenic acid) and decreased 18:1(n-9) in microsomal membrane lipids when compared with animals fed beef tallow. Addition of 2% cholesterol to the otherwise low cholesterol diets led to accumulation of 16:1(n-7), and 18:1(n-9) in microsomal membranes. These results suggest that delta 9-desaturase activity is dependent on the cholesterol contents as well as the n-3 fatty acid content of microsomal membranes on which it is localized.

Animals↗
PubMed1988

Fish oil reduces cholesterol and arachidonic acid content more efficiently in rats fed diets containing low linoleic acid to saturated fatty acid ratios.

Rats were fed diets containing a high level of saturated fatty acids (hydrogenated beef tallow) versus a high level of linoleic acid (safflower oil) at both low and high levels of fish oil containing 7.5% (w/w) eicosapentaenoic and 2.5% (w/w) docosahexaenoic acids for a period of 28 days. The effect of feeding these diets on the cholesterol content and fatty acid composition of serum and liver lipids was examined. Feeding diets high in fish oil with safflower oil decreased the cholesterol content of rat serum, whereas feeding fish oil had no significant effect on the cholesterol content of serum when fed in combination with saturated fatty acids. The serum cholesterol level was higher in animals fed safflower oil compared to animals fed saturated fat without fish oil. Consumption of fish oil lowered the cholesterol content of liver tissue regardless of the dietary fat fed. Feeding diets containing fish oil reduced the arachidonic acid content of rat serum and liver lipid fractions, the decrease being more pronounced when fish oil was fed in combination with hydrogenated beef tallow than with safflower oil. These results suggest that dietary n-3 fatty acids of fish oil interact with dietary linoleic acid and saturated fatty acids differently to modulate enzymes of cholesterol and fatty acid metabolism.

Animals↗
PubMed1988

Dietary fat and the diabetic state alter insulin binding and the fatty acyl composition of the adipocyte plasma membrane.

Control and diabetic rats were fed on semi-purified high-fat diets providing a polyunsaturated/saturated fatty acid ratio (P/S) of 1.0 or 0.25, to examine the effect of diet on the fatty acid composition of major phospholipids of the adipocyte plasma membrane. Feeding the high-P/S diet (P/S = 1.0) compared with the low-P/S diet (P/S = 0.25) increased the content of polyunsaturated fatty acids in membrane phospholipids in both control and diabetic animals. The diabetic state decreased the content of polyunsaturated fatty acids, particularly arachidonic acid, in adipocyte membrane phospholipids. The decrease in arachidonic acid in membrane phospholipids of diabetic animals tended to be normalized to within the control values when high-P/S diets were given. For control animals, altered plasma-membrane composition was associated with change in insulin binding, suggesting that change in plasma-membrane composition may have physiological consequences for insulin-stimulated functions in the adipocyte.

Adipose Tissue↗
PubMed1988

Fatty acid desaturation in the intestinal mucosa.

Information as to the ability of the enterocyte to desaturate fatty acids is lacking. This is important in understanding whether the source of intestinal arachidonic (20:4(n-6) acid is biliary or from de novo synthesis. Delta 9- and delta 6-desaturase enzymes were assayed in homogenates of rat jejunum, ileum and liver. Rat small intestine possesses desaturase activity to convert palmitic (16:0) to palmitoleic (16:1) and linoleic (18:2(n-6) to linolenic (18:3(n-6) acid. Enzyme activities were highest in liver relative to activity in jejunal and ileal homogenates. It is concluded that delta 9- and delta 6-desaturase activities may have an important role in determining physico-chemical properties and thus transport properties of enterocyte membranes.

Animals↗
PubMed1988

Delta 6-desaturase activity in liver microsomes of rats fed diets enriched with cholesterol and/or omega 3 fatty acids.

The effect of feeding semipurified diets enriched in linseed (rich in C18:3, omega 3 fatty acid) or fish (rich in C20:5, omega 3 and C22:6, omega 3 fatty acid) oil with and without cholesterol supplementation on the desaturation of linoleic acid (C18:2, omega 6) by rat liver microsomal fractions was investigated. Animals fed diets supplemented with beef tallow were used as equal-energy controls. Both linseed-oil and fish-oil diets, without added cholesterol, decrease conversion of C18:2, omega 6 fatty acid to gamma-linolenic acid (C18:3, omega 6). Reduction in delta 6-desaturation was significantly greater for animals fed the diet containing fish oil than with animals fed the linseed-oil diet. The major effect of cholesterol supplementation was to decrease the rate of desaturation of C18:2, omega 6, when fed in combination with the beef-tallow diet, whereas delta 6-desaturation was unaffected when cholesterol was fed along with diets high in omega 3 fatty acids (linseed oil or fish oil). The activity of the delta 6-desaturase in vitro is consistent with the fatty acid composition observed for the microsomal membranes on which this enzyme is localized. Dietary linseed oil and fish oil lowered the arachidonic (C20:4, omega 6) acid content of rat liver microsomes, with an accompanying increase in membrane eicosapentaenoic (C20:5, omega 3) and docosahexaenoic (C22:6, omega 3) acid content, in comparison with the group fed beef tallow. Inclusion of cholesterol into the beef-tallow or linseed-oil diets resulted in decreased membrane C20:4, omega 6-fatty-acid content, with concomitant increase in C18:2, omega 6-fatty-acid content. However, addition of cholesterol to the fish-oil diet did not alter the microsomal membrane content of C20:4, omega 6 fatty acid. Thus it is suggested that (1) the decrease in prostaglandin E2, thromboxane and prostacyclin levels generally observed after fish-oil consumption may be at least partly due to inhibition of C20:4, omega 6-fatty-acid synthesis from C18:2, omega 6 fatty acid; and (2) consumption of fish oil prevents the further decrease in C20:4, omega 6-fatty-acid levels by dietary cholesterol that is apparent when cholesterol is fed in combination with diets high in saturated fat or C18:3, omega 3 fatty acid.

Animals↗
PubMed1988

Differential effects of dietary linoleic and alpha-linolenic acid on lipid metabolism in rat tissues.

Comparative effects of feeding dietary linoleic (safflower oil) and alpha-linolenic (linseed oil) acids on the cholesterol content and fatty acid composition of plasma, liver, heart and epididymal fat pads of rats were examined. Animals fed hydrogenated beef tallow were used as isocaloric controls. Plasma cholesterol concentration was lower and the cholesterol level in liver increased in animals fed the safflower oil diet. Feeding the linseed oil diet was more effective in lowering plasma cholesterol content and did not result in cholesterol accumulation in the liver. The cholesterol concentration in heart and the epididymal fat pad was not affected by the type of dietary fatty acid fed. Arachidonic acid content of plasma lipids was significantly elevated in animals fed the safflower oil diet and remained unchanged by feeding the linseed oil diet, when compared with the isocaloric control animals fed hydrogenated beef tallow. Arachidonic acid content of liver and heart lipids was lower in animals fed diets containing safflower oil or linseed oil. Replacement of 50% of the safflower oil in the diet with linseed oil increased alpha-linolenic, docosapentaenoic and docosahexaenoic acids in plasma, liver, heart and epididymal fat pad lipids. These results suggest that dietary 18:2 omega 6 shifts cholesterol from plasma to liver pools followed by redistribution of 20:4 omega 6 from tissue to plasma pools. This redistribution pattern was not apparent when 18:3 omega 3 was included in the diet.

Adipose Tissue↗
PubMed1988

Effect of dietary cholesterol and/or omega 3 fatty acids on lipid composition and delta 5-desaturase activity of rat liver microsomes.

Male weanling rats were fed for 28 d a purified diet containing 20% (wt/wt) fat providing high levels of either saturated fat or alpha-linolenic acid or eicosapentaenoic and docosahexaenoic acids with or without 2% (wt/wt) cholesterol supplementation. Effect of diet on rate of desaturation of eicosatrienoic acid (20:3 omega 6) and lipid composition of liver microsomal membranes was examined. The desaturation of 20:3 omega 6 to arachidonic acid (20:4 omega 6) was higher in rats fed linseed oil and lower in rats fed fish oil than in control animals fed the beef tallow diet. The desaturation of 20:3 omega 6 was lower in rats fed beef tallow or linseed oil diets supplemented with cholesterol than in the respective unsupplemented diet. Inclusion of 2% (wt/wt) cholesterol in the fish oil diet failed to affect synthesis of 20:4 omega 6 from 20:3 omega 6. These in vitro changes in delta 5-desaturase activity are consistent with the diet-induced alterations observed in the fatty acid composition of microsomal membranes. Both free cholesterol and cholesterol ester in the microsomal membrane were higher in rats fed beef tallow or linseed oil diets supplemented with exogenous cholesterol than in the respective unsupplemented diet, and only free cholesterol was higher in rats fed the fish oil diet supplemented with cholesterol. Feeding fish oil appears to prevent both the inhibition of 20:4 omega 6 biosynthesis and the accumulation of cholesterol ester that were apparent when 2% cholesterol was added to either beef tallow or linseed oil diets.

8,11,14-Eicosatrienoic Acid↗
PubMed1988

Discriminant function analysis to calculate a Crohn's activity group scale to predict future inactive or active disease.

A discriminant function analysis was performed on several demographic, anthropometric, clinical, and laboratory data of 685 observations performed over 12 months on 137 patients with Crohn's disease. A Crohn's activity group scale (CAGS) was calculated. The CAGS has two advantages over the usual Crohn's disease activity index: it is objective, but more important is the fact that the values, when calculated longitudinally, have predictive value. Thus, calculation of CAGS is useful for counseling purposes and may also be useful in the design of future trials assessing therapy for Crohn's disease by allowing prerandomization stratification of patients with high or low probability of future recurrences of symptomatic disease activity.

Crohn Disease↗
PubMed1988

Inflammatory bowel disease in northern Alberta. An epidemiologic study.

The Medical Record departments of the five teaching hospitals in Edmonton, plus the 37 community hospitals in the eight census districts of the northern half of the province of Alberta, Canada, were contacted, and a search was made of all patients with a discharge diagnosis of Crohn's disease or ulcerative colitis. Also, the patient records of all Edmonton gastroenterologists were reviewed to discover patients with Crohn's disease or ulcerative colitis who had never been hospitalized within these census areas. From January 1, 1977, to December 31, 1981 (which was the prevalence date), the population was 1,295,360. Of the 2,419 patients with inflammatory bowel disease, 48.5% had definite Crohn's disease and 33% had definite ulcerative colitis. There were 1,716 (70.9%) patients analyzed in this study. The factorial analysis of disease prevalence per 10(5) population revealed that significant differences were found for location of residence, sex, and age. The prevalence of Crohn's disease was higher in urban than in rural areas and in females than in males, whereas the prevalence of ulcerative colitis was unaffected by these variables. The peak prevalence of Crohn's disease was below age 29 in males and females, and the prevalence in young women at this age was approximately twice that in males. The highest prevalence of Crohn's disease was in urban females aged 20-39 (greater than 234 cases/10(5) population), with similar prevalence rates in urban males and rural females, and with the lowest prevalence rates in rural males. The incidence of Crohn's disease was greater than for ulcerative colitis, began to increase in about 1965, and reached a plateau in the late 1970s. In conclusion, the demonstration of an age, location of residence, or effect of sex on the prevalence of inflammatory bowel disease requires multiple factorial analyses. When the sample is extrapolated to the total diseased population of the region, a prevalence value of 330/10(5) was derived for young female urban individuals residing in this northern area.

Age Factors↗
PubMed1988

Twenty-four-hour intragastric measurements in twenty healthy subjects: effect of enisoprost, a novel and potent antisecretory and antipeptic synthetic E1 prostaglandin.

Gastric aspiration was performed continuously overnight and at hourly intervals during the daytime in 20 healthy male volunteers. Medications used included enisoprost 100, 200 or 400 micrograms, misoprostol 200 micrograms and placebo, given at bedtime. Each dose of enisoprost markedly inhibited nocturnal mean acid output, hydrogen ion activity, pH and peptic activity. The duration of these effects was up to 10 h. Misoprostol, given at bedtime, also decreased acid secretion, but the effect was significantly less than that observed with any of the doses of enisoprost. A dose-response effect for enisoprost was found for the mean nocturnal hydrogen ion activity and pH, as well as for maximum pH attained. Although enisoprost, given at bedtime, had a marked inhibitory effect on acid and pepsin secretion for the overnight interval, this did not result in rebound hyperacidity or a rise in serum total gastrin concentration. The results of this study suggest that enisoprost should be tested by clinical trial for the treatment of peptic ulcer disease.

Adolescent↗
PubMed1988

Impairment of endothelium-dependent relaxation: an early marker for atherosclerosis in the rabbit.

1. Cholesterol feeding of rabbits impairs the endothelium-dependent relaxation (EDR) evoked by acetylcholine (ACh) in the aorta. The experiments described in this paper were undertaken to examine the influence of age upon this phenomenon. 2. Rabbits aged 8 weeks and 46 weeks were fed a diet containing 2% cholesterol and other lipids for 4 weeks. Age-matched control animals were fed a standard rabbit diet. The concentrations of cholesterol and triglycerides in plasma were measured and the extent of atherosclerosis was estimated by staining the aortae with Sudan Red. Light and electron microscopy were undertaken also. 3. Rings of aorta were prepared for recording isometric tension. They were contracted with noradrenaline (NA) and EDR elicited by adding ACh. 4. The young rabbits showed weight gain, hypercholesterolaemia, prominent Sudan Red staining, together with scanning and transmission electron microscopic (SEM and TEM) features of cholesterol-induced atherosclerosis. The older animals showed significant weight loss and hypercholesterolaemia. The aortae of these animals showed no significant sudanophilia or light microscopic features of atherosclerosis. The SEM appearances were similar to the young animals fed cholesterol. 5. EDR to ACh was significantly impaired in both groups of cholesterol-fed rabbits. The maximal relaxations to ACh in young control and cholesterol-fed rabbits were 46.4 +/- 2.9% and 24.0 +/- 4.3% (mean +/- s.e. mean, n = 8, P less than 0.05) of the contractile response to NA (1 mumol 1(-1]. The corresponding results in the age control and cholesterol-fed rabbits were 31.8 +/- 3.9% and 9.1 +/- 1.5% (n = 9, P less than 0.05). 6. The young rabbits were far more susceptible to cholesterol-induced atherosclerosis than older animals and these changes were accompanied by loss of EDR. In the older animals and these changes were accompanied by loss of EDR. In the older animals the loss of the latter property was not accompanied by a significant degree of atherosclerosis although hypercholesterolaemia was present.

Acetylcholine↗
PubMed1988

Antacid maintenance therapy in the prevention of duodenal ulcer relapse.

The effectiveness of antacid maintenance therapy in preventing duodenal ulcer (DU) relapse was investigated. Two hundred and fifty one asymptomatic patients with healed DU were stratified into smokers and non-smokers and randomised to receive for one year either placebo, or Maalox TC three tablets (81 mmol) at bedtime (hs), or Maalox TC three tablets in the morning plus three tablets at bedtime (bd) (162 mmol), or cimetidine 400 mg at bedtime. A double dummy technique was used to render the study double blind. In 176 patients evaluable for efficacy, the cumulative relapse at one year was: placebo 57%; Maalox TC hs 39%; Maalox TC bd 23%; cimetidine 25%. Maalox TC bd and cimetidine were equally effective and superior to placebo (p less than 0.01) and bedtime Maalox TC (p less than 0.04). The benefit of treatment was significant for the overall sample and for the subgroup of smokers. The results for the non-smokers also supported efficacy for these two treatments but, perhaps because of small sample sizes, these comparisons were not significant. All 251 patients were assessed for safety. Approximately half the patients in each treatment group had adverse events, leading to withdrawal in three, seven, 12, and four patients on placebo, Maalox hs, Maalox bd, and cimetidine respectively. Diarrhoea occurred in 12 patients in Maalox TC bd and eight in each other group. Serum magnesium concentrations were unchanged; aluminium concentrations were higher than baseline at six and 12 months in both antacid groups and at 12 months in the cimetidine group but the differences were not significant. Maalox TC three tablets bd are as effective as cimetidine 400 mg at bedtime in reducing DU relapse and both are superior to placebo.

Adult↗