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Biomedical subjects

A B Thomson

Publications and source records attributed to A B Thomson.

At least 253 records · Page 14Linked to original sources

Intestinal morphology, marker enzymes and lipid content of brush border membranes from rabbit jejunum and ileum: effect of aging.

Aging is associated with changes in the intestinal uptake of nutrients. This study was undertaken to determine whether the morphology, enzyme markers and the lipid content of the intestinal brush border membrane (BBM) was influenced by aging. There was an increase in the height of the jejunal villi and number of cells/villus, resulting in an age-related increase in the jejunal villus and mucosal surface area in young as compared with weanling rabbits. In mature 1-year-old animals, there was a decline in villus height, number of cells/villus, and mucosal surface area, so that the jejunal characteristics of the mature animals resembled those of the weanling rabbits. In the ileum, aging was associated with an increase (weanling vs. young), then a decrease (young vs. mature) in the height of the villi, and the number of cells/villus. Aging had no effect on the size of the villus cells. At all ages there was a direct positive relationship between the height of the villi and the mucosal surface area, and between villus surface area and sucrase activity. An established technique was used to purify rabbit BBM and to measure the BBM content of enzyme markers and lipids in weanling, young and mature animals. Both the BBM sucrase (S) and alkaline phosphatase (AP) increased in young as compared with weanling rabbits, and the ratio of AP/S remained unchanged. The S remained high in mature rabbits, but AP declined, so that AP/S fell. There was a positive linear correlation between S and villus surface area. In weanling rabbits, the total BBM phospholipid content and the ratio of total phospholipid/total cholesterol were lower in the ileum than in the jejunum. In the jejunal BBM of young animals, there was more total free fatty acids and cholesterol ester than in the weanling jejunum. The jejunal BBM total phospholipids and total cholesterol were higher in the mature than in the weanling animal jejunum when expressed as nmoles/mg protein, but the ratio of total phospholipid/total cholesterol was unaffected by aging. The greatest percentage of jejunal BBM phospholipid was comprised of lecithin and phosphatidyl ethanolamine. The increased BBM total phospholipid content in mature animals was associated with a higher amount and lower proportion of lecithin, but a higher proportion of sphingomyelin and phosphatidyl serine.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Intestinal uptake of fatty acids, cholesterol and decanol in ileal resected rabbits: effect of Isocal and Portagen.

Isocal, but not Portagen, is associated with increased villus surface area in control rabbits and in animals with an ileal resection. In control animals, Isocal feeding was associated with an increased in vitro jejunal uptake of short and medium-chain length fatty acids and cholesterol, whereas Portagen feeding was associated with a decline in the uptake of short-, medium- and long-chain fatty acids, but an increase in the uptake of cholesterol. In animals with an ileal resection both diets were associated with an increased uptake of long-chain fatty acids and cholesterol. These changes in lipid uptake are not explained by alterations in villus surface area or unstirred water layer resistance.

Animals↗

Insulin and islet cell transplantation in streptozotocin-diabetic rats: effect on intestinal uptake of hexoses.

A previously validated in vitro technique was used to determine the effect of once daily injections of NPH insulin (NPH) and/or islet cell transplantation on the jejunal uptake of 0.5-40 mM glucose and galactose into the jejunum of streptozotocin-diabetic rats. Glucose uptake was greater in untreated diabetic rats than in control animals due to a higher maximal transport rate and a higher passive permeability of the jejunum, and a lower value of the apparent Michaelis constant. Galactose uptake was greater in diabetic rats due to a higher maximal transport rate, but there was also a higher value of the apparent Michaelis constant. This enhanced uptake of glucose and galactose was reduced and normalized by daily injections of NPH insulin or by islet cell transplantation. It is concluded: the jejunal uptake of glucose and galactose is increased in diabetic rats, but the kinetic basis for this change was different for the two sugars; insulin therapy may correct the enhanced uptake of some nutrients in diabetic rats and islet cell transplantation may be at least as effective as exogenous insulin in modifying the intestinal adaptation to diabetes.

Animals↗

Intestinal brush border membrane marker enzymes, lipid composition and villus morphology: effect of fasting and diabetes mellitus in rats.

Diabetes mellitus is associated with enhanced passive intestinal uptake of cholesterol and fatty acids. In order to determine the basis for these changes in intestinal permeability, the jejunal morphology and the lipid content of purified brush border membranes (BBM) were measured in fasted and fed control (C) and streptozotocin diabetic (DM) rats. There was no difference between C and DM in BBM sucrase or alkaline phosphatase; fasting had no effect on BBM enzymes in C, but in DM fasting was associated with increased sucrase activity per length of jejunum. In C fasting was associated with higher levels of BBM total phospholipid, lecithin, choline and amine phospholipids, whereas fasting in DM was associated with higher BBM cholesterol and lower free fatty acids. In the fasting DM, there was a greater villus and mucosal surface area than in the fasting C. A previous study demonstrated that with fasting in DM versus C, cholesterol uptake was unchanged, but when animals were fed, cholesterol and fatty acid uptake were greater into the jejunum of fed DM as compared with fed C. In the BBM of fed DM as compared with C, there was a significant increase in total phospholipid, lecithin, phosphatidyl ethanolamine, choline and amine phospholipids, and phospholipid/cholesterol ratio. Thus, (1) fasting is associated with changes in intestinal morphology, BBM lipids; (2) the effect of fasting is different in DM and C; (3) the enhanced uptake of lipids into the jejunum of fed diabetic rats is not due to changes in villus morphology, but may be due to alterations in the BBM phospholipids.

Alkaline Phosphatase↗

Lack of pharmacokinetic interaction between cimetidine and pirenzepine.

The oral administration of pirenzepine (PRZ), an antimuscarinic agent, has a variable effect on gastric acid secretion in patients with duodenal ulcer, and it seems to potentiate cimetidine-induced inhibition of secretion. The possibility of a pharmacokinetic interaction between these drugs was examined in eight patients who received cimetidine and PRZ alone and in combination in a crossover fashion. Cimetidine, 600 mg b.i.d., PRZ, 50 mg b.i.d., or combination therapy were each given for 1 week before the study. Serum samples were serially drawn during each dosing interval for determination of cimetidine and PRZ concentrations by HPLC and RIA, respectively. Cimetidine given alone or with PRZ exhibited diurnal variation, as the peak serum concentration was lower after the nighttime dose than after the morning dose. PRZ showed intersubject variation. However, each drug failed to alter the pharmacokinetic indices of the other. The times to attain the peak serum concentration were not significantly different for cimetidine alone or with PRZ, arguing against an effect of PRZ on gastric motility in the doses we used. The greater and prolonged acid inhibition with the combination of cimetidine and PRZ, therefore, may stem from a synergistic action of both drugs on receptor sites on gastric parietal cells.

Administration, Oral↗

Comparative study of cimetidine and Mylanta II in the 6-week treatment of gastric ulcer.

The efficacy of antacid in the treatment of benign gastric ulcer is less well established than in the treatment of duodenal ulcer. The objective of this study was to monitor ulcer healing and symptom relief in 38 patients with gastric ulceration treated for 6 weeks with cimetidine (Tagamet) 300 mg q.i.d. or an aluminum-magnesium containing antacid (Mylanta II) 10 ml q.i.d. (acid neutralizing capacity 203.2 mEq/day). The study was single-blind; the study physicians and those providing endoscopic assessments were not aware of the patients' treatment. Entered into the study were 19 male and 19 female patients ranging in age from 17 to 70 years, with a mean age of 52 years. None of the patients had taken cimetidine in the previous month, and none abused alcohol or nonsteroidal anti-inflammatory agents, but two-thirds of the patients were smokers. Five patients in the antacid group withdrew for numerous reasons including continued pain, noncompliance, and side effects. All patients in the cimetidine group completed the study, and no side effects were noted. There was no difference between the antacid- and the cimetidine-treated patients in the relief of symptoms. There was a significant difference in the 6-week ulcer healing between the groups, with 14/19 (74%) healed in the cimetidine group compared with only 6/14 (43%) healed in the antacid group (p less than 0.025). Thus, Mylanta II, 10 ml four times daily, is comparable to cimetidine 300 mg q.i.d. in the symptomatic relief of benign gastric ulceration, but ulcer healing was superior using cimetidine.

Adolescent↗

Massive gastrointestinal hemorrhage cecal ulcers and salmonella colitis.

A 65-year-old man presented with massive lower gastrointestinal tract hemorrhage. Minimal changes were noted on sigmoidoscopy, no bleeding lesions were identified on arteriography or red blood cell scan, and barium enema examination demonstrated only diverticular disease and minimal cecal deformity, interpreted as secondary to a recent appendectomy. Colonoscopy demonstrated multiple deep cecal ulcers. These were presumed to be due to an infectious etiology, since the stools were culture-positive for Salmonella typhimurium. The hemorrhage stopped within 24 hours of treatment with Ampicillin, Flagyl, and Gentamicin. The patient has remained well over a 12-month follow-up period. Repeat colonoscopy demonstrated healing of the cecal ulcers and there was also clearing of the Salmonella from the stools. This case report serves to remind us of the different methods used to diagnose lower gastrointestinal tract hemorrhage, and the importance of considering infectious causes of colitis.

Aged↗

Cholesterol feeding impairs endothelium-dependent relaxation of rabbit aorta.

Experiments were designed to assess the effect of cholesterol feeding on the endothelium-mediated relaxation of the rabbit aorta to acetylcholine. Age-matched male New Zealand white rabbits were fed either a 2% cholesterol diet or standard rabbit chow. The animals were anaesthetized with sodium pentobarbitone and sacrificed after 4 and 8 weeks on these diets. Rings were prepared from the proximal thoracic aorta and examined in tissue baths. These rings were contracted first with norepinephrine (-6 log mol/L) and acetylcholine was added to demonstrate the endothelium-mediated relaxation. The endothelium-dependent relaxation was significantly less in aortas from rabbits fed the 2% cholesterol diet than in aortas from animals fed the conventional diet. This impairment of relaxation was apparent after both 4 and 8 weeks of cholesterol feeding. In both groups of animals no relaxation was seen in rings from which the endothelium was removed. These results show that cholesterol feeding leads to an impairment of endothelium-mediated relaxation of the rabbit aorta to acetylcholine.

Acetylcholine↗

Effect of chronic ethanol and food deprivation on intestinal villus morphology and brush border membrane content of lipid and marker enzymes.

Brush border membranes (BBM) were isolated from the jejunum and ileum of control, ad libitum (CAL); control, food-restricted (CFR); control, weight gain (CWG); and ethanol-fed (EF) rabbits. Jejunal alkaline phosphatase activity was similar among control groups, but higher in CAL than EF animals. Sucrase activity was higher in EF and CWG animals than in CAL and CFR. The alkaline phosphatase/sucrase ratio was lower in EF than control animals. Ileal enzyme marker activity was similar among EF and control animals. Sucrase (S) activity was lower in the ileum than in the jejunum. Jejunal free fatty acid and phospholipid/cholesterol (PL/C) were lower in EF than control animals, whereas ileal lipid content was generally similar among all animal groups. Total phospholipid content was similar between sites, but the cholesterol and free fatty acid content were lower in the ileum than the jejunum. The phospholipid/cholesterol ratio was increased only in the ileum of EF animals. The amount of lecithin was decreased in the jejunal BBM of EF animals resulting in a decreased choline/amine phospholipid ratio as compared with control animals. The ileal phospholipid composition was similar among all groups. A large increase in villus height is observed in the jejunum of EF animals. Villus surface area and mucosal surface area are altered with ethanol feeding and food deprivation. Thus, (i) there is a gradient of S and cholesterol between the BBM of jejunum and ileum; (ii) changes in food intake are associated with changes in the morphology as well as the enzyme marker and lipid content of BBM.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

Jejunal uptake of sugars, cholesterol, fatty acids, and fatty alcohols in vivo in diabetic rats.

Previous in vitro studies have demonstrated enhanced active and passive intestinal uptake of nutrients in streptozotocindiabetic rats, but the effect of diabetes on the in vivo absorption of glucose and amino acids remains controversial, and the effect of diabetes on the in vivo uptake of lipids has not been reported. Accordingly, an in vivo perfusion technique was used in rats to examine the uptake of nutrients from the intestinal lumen, their transfer to the body, their mucosal and submucosal content, and the percentage of uptake transferred. Diabetes was associated with reduced uptake of fatty alcohols, indicating that the effective resistance of the unstirred water layer in vivo is higher in diabetic than in nondiabetic control rats. The mucosal and submucosal content of dodecanol was lower in diabetic than in control rats, but the percentage of the dodecanol uptake transferred to the body was higher. Although the uptake of varying concentrations of D-galactose was similar in diabetic and in control animals, kinetic analysis corrected for unstirred layer effects demonstrated lower mean values of the passive permeability coefficients (Pd) for galactose in diabetic than in control animals, with lower values of the Michaelis constant (Km) and higher values of the maximal transport rate (Jmd). The uptake of lauric acid was reduced in diabetic rats, whereas the uptake of deconoic acid and of cholesterol was unchanged. With correction for unstirred layer effects, it was apparent that the jejunum of diabetic rats was in fact more permeable to decanoic and lauric acid as well as to cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Resection of rabbit ileum: effect on brush border membrane enzyme markers and lipids.

Alterations in transport function have been described 6 weeks after surgical resection of 50% of the distal small intestine. Previous studies demonstrated a modest increase in the jejunal uptake of medium chain length fatty acids following resection, while the uptake of many other lipids (cholesterol, bile acids, fatty alcohols, short and long chain length fatty acids) appears to be unaffected. Marked changes in the kinetic constants for the carrier-mediated uptake of four sugars and leucine were observed following resection, but the changes in transport were not associated with changes in the mucosal surface area. This study was undertaken to examine the possible adaptive mechanisms that occur with ileal resection in the rabbit. A 29% increase in the wet weight of jejunal mucosal scrapings and a 53% increase in jejunal brush border membrane (BBM) protein was observed following resection. The jejunal BBM sucrase (S) was unchanged following ileal resection, but alkaline phosphatase (AP) total activities were increased in the resected rabbits. This resulted in a 45% increase in the ratio of AP/S with resection. The lipid composition (total free fatty acids, total bile acids, total cholesterol, total phospholipids, individual phospholipids, and the ratio of total phospholipids/total cholesterol) of BBM was similar in control and resected rabbits. This suggests that quantitative rather than qualitative changes in the membrane composition may be responsible for the transport changes observed in resected animals.

Animals↗

A comparative trial of ranitidine 300 mg at night with ranitidine 150 mg twice daily in the treatment of duodenal and gastric ulcer.

A multicenter double-blind comparative trial of oral ranitidine, 300 mg hs versus 150 mg bid, was conducted in 89 patients with duodenal ulcer (DU) and 54 with gastric ulcer (GU). Antacid tablets were prescribed prn. After 4 wk of treatment there were no statistically significant differences in the ulcer healing rates associated with the once daily (DU 86.4%, GU 62.5%) and the twice daily (DU 84.4%, GU 73.3%) regimens. Antacid consumption, by both DU and GU patients, was higher in the 150 mg bid group, but the differences did not achieve statistical significance. Further improvement in cumulative healing rates in response to both treatment regimens was observed following a second 4-wk treatment for those patients whose ulcers had failed to heal during the 1st month. Smoking adversely affected the rate of ulcer healing in DU patients, but had no significant effect on GU healing. No serious adverse effects or biochemical abnormalities were observed. Ranitidine 300 mg hs appears to be equally safe and effective as the standard regimen of 150 mg bid in the short-term treatment of uncomplicated gastroduodenal ulcer.

Adult↗

Cimetidine therapy for gastroesophageal reflux disease.

In a Canadian multicenter trial, a new dosing regimen of cimetidine (Tagamet)-600 mg given twice a day-was compared with the standard regimen of 300 mg four times a day in 118 evaluable patients with endoscopically proved esophagitis. More than 90% of the patients evaluated had clinically moderate to severe esophagitis. After four weeks of therapy, both regimens had significantly reduced the number of episodes and the severity and duration of the worst episodes of daytime and nighttime heartburn, as evaluated by visual analogue scales. After eight weeks of therapy, this improvement persisted. There was no difference between the regimens. Healing was observed endoscopically in 57% of patients receiving cimetidine 300 mg four times a day and in 55% of those receiving 600 mg twice a day. Side effects were infrequent and minor.

Adult↗

Erosive gastroduodenitis with marked epithelial atypia after hepatic arterial infusion chemotherapy.

We report the case of a 59-year-old man who was treated with intraarterial chemotherapy for metastatic colonic adenocarcinoma. After the second course he developed persistent symptoms of nausea, vomiting, and pain. Endoscopic examination demonstrated severe erosive gastritis and duodenitis, and histological examination of the antral tissue showed severe atypia and histological appearances suggestive of in situ carcinoma. A 2-month course of sucralfate and cimetidine was used and successfully produced symptomatic relief as well as complete normalization of the dysplastic changes.

Adenocarcinoma↗

Protein-energy malnutrition in gastroenterology outpatients: increased risk in Crohn's disease.

A screening study was conducted to identify malnutrition in gastroenterology outpatients and to ascertain whether poor food intake is a contributing factor. A 48-hour recall method was used to collect dietary data from 154 patients (87 women and 67 men). Fourteen (16%) of the women and 8 (12%) of the men were classified as having protein-energy malnutrition (PEM) on the basis of abnormal anthropometric measurements or low serum albumin concentration. PEM was found in several diagnostic groups, but 9 of the 14 malnourished women had Crohn's disease. Protein undernutrition was more evident in women; calorie undernutrition was more evident in men. More women than men had low serum albumin levels. Low hemoglobin levels were particularly prevalent among patients with Crohn's disease. Many of the patients, especially women, had "inadequate" and "marginal" intakes of folate, vitamin A, thiamin, and calcium according to Nutrition Canada interpretive standards. The intake of iron was particularly poor among women: 59% of the intakes of female patients were classified as inadequate (less than 10 mg/day). Ten of the 14 female patients with PEM had inadequate iron intakes. Serum folates of less than 5 ng/ml were present in 72% of the women and 77% of the men. The data suggest that gastrointestinal outpatients are at high risk of malnutrition and that one of the factors contributing to the problem is inadequate food intake.

Adult↗

The effects of abdominal irradiation on intestinal transport in the rat as assessed with isolated epithelial cells.

The time course of the effect of exposure to sublethal irradiation on transport of several substrates by the intestine has been studied using isolated enterocytes. Rats received a single dose of 6 Gy to the abdomen, and isolated intestinal epithelial cells were prepared 3, 7, and 14 days later. The ability of the cells to take up D-glucose, L-leucine, and glycyl-L-leucine was assessed using 2.5-min incubation periods and was compared with the uptake in control cells. It was found that the protein content of the cells increased after irradiation, and although some of this was the result of increased binding of albumin to the cells there was also a nonspecific increase in most cell proteins. Consequently uptake data were expressed per unit number of cells and not per milligram of cell protein. Comparison of uptake expressed in this way showed that D-glucose and glycyl-L-leucine uptake was elevated 3 days after irradiation while that of L-leucine was unaffected. By 14 days after irradiation the glucose and glycyl-L-leucine uptake had returned to normal but the L-leucine transport was depressed. These data indicate that the effects of irradiation upon substrate transport in the intestines are not uniform and that although the cell population is initially reduced the remaining cells can compensate by increasing their transport capacity.

Animals↗

Intestinal uptake of hexoses and fatty acids in tumor-bearing rats.

An in vitro technique was used to examine the rate of uptake of varying concentrations of glucose, galactose, and a homologous series of saturated fatty acids into the jejunum of control rats and Noble rats bearing prostatic tumor variants of primary human prostatic adenocarcinoma 52. Both groups of animals were healthy, eating and gaining weight normally. The uptake of acetic and butyric acid was reduced in tumor-bearing rats, but the uptake of four medium chain-length fatty acids was unchanged. The similar value of the incremental change in free energy in the control and tumor-bearing animals indicates similar passive permeability properties of the jejunum in the two groups. The uptake of varying concentrations of glucose and galactose was similar in the control and in the tumor-bearing animals. It is concluded that there are only subtle changes in nutrient uptake in tumor-bearing rats that are eating and gaining weight normally. It is suggested that any alteration in nutrient absorption which might occur in the cachectic tumor-bearing animal is probably due to alterations in food intake or body weight, rather than due to a direct effect of the tumor on the intestine.

Adenocarcinoma↗