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Biomedical subjects

A B Thomson

Publications and source records attributed to A B Thomson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Intravenous fish oil emulsion attenuates total parenteral nutrition-induced cholestasis in newborn piglets.

Total parenteral nutrition (TPN) causes intrahepatic cholestasis and membrane phospholipid changes. Fatty acid (FA) composition of bile and hepatocyte phospholipid is influenced by dietary FA composition. We hypothesized that altering FA composition of i.v. lipid emulsions modifies 1) severity of TPN-induced cholestasis; 2) hepatocyte membrane composition and function; 3) bile flow and composition. Newborn piglets received either sow's milk, TPN with i.v. soybean oil or TPN with i.v. fish oil (FO). After 3 wk, basal and stimulated bile flow were measured after bolus injections of 20, 50, and 100 micromol/kg of taurocholate (TCA). Bile was analyzed for bile acids, cholesterol, phospholipids, and phospholipid-FA. Sinusoidal and canalicular membrane PL-FA, fluidity, and Na+/K+-ATPase were measured. Although the soybean oil-fed animals developed cholestasis, the FO and milk group had similar liver and serum bilirubin. Basal and stimulated bile flow rates were impaired in the soybean oil but not in the FO group. Hepatocyte membrane FA composition reflected dietary FA. Changes in sinusoidal and canalicular membrane fluidity and sinusoidal Na+/K+-ATPase activity did not explain the effect of FO on TPN-induced cholestasis. Intravenous FO reduces TPN-induced cholestasis by unknown mechanisms.

Animals↗
PubMed1998

Characterization of a cDNA encoding a novel plant poly(A) polymerase.

We have isolated cDNA clones encoding a novel factor (PAP-I) that is a component of a multi-subunit poly(A) polymerase from pea seedlings. The encoded protein, when isolated from appropriately engineered Escherichia coli, was active as a poly(A) polymerase, either with an associated RNA binding cofactor (PAP-III) or with free poly(A) as an RNA substrate. The latter observation indicates that PAP-I is in fact a poly(A) polymerase. PAP-I bore a striking resemblance to an as yet uncharacterized cyanobacterial protein. This observation suggested a possible chloroplast localization for PAP-I. This hypothesis was tested and found to be substantiated; immunoblot analysis identified PAP-I in chloroplast but not nuclear extracts. Our results suggest that PAP-I is a component of the machinery that adds poly(A) to chloroplast RNAs.

Amino Acid Sequence↗
PubMed1998

Oral administration of rapamycin and cyclosporine differentially alter intestinal function in rabbits.

The immunosuppressive drugs rapamycin (Rap) and cyclosporine A (CsA) are used clinically to modify or abolish immune-mediated functions. This study examined the effect of orally administered regimens of Rap, CsA, and a combination of Rap/CsA on intestinal function in male New Zealand white rabbits. Animals received oral doses of CsA (15 mg/kg/body weight/day), low-dose (LD) and high-dose (HD) Rap (0.25 or 1 mg/kg/body wt/day, respectively), or Rap/CsA (0.25 and 5 mg/kg/body wt/day, or 0.5 and 5 mg/kg/body wt/day, respectively) for 20 days. We measured in vitro uptake of nutrients and permeability, and morphometric measurements in the jejunum and ileum were made. Animals receiving HD-Rap or HD-Rap/CsA had decreased food intake, body weight, and intestinal weight, when compared with LD-Rap, LD-Rap/CsA, CsA, or controls. The maximal transport rate (Vmax) for the active jejunal uptake of D-glucose was increased in HD-Rap and CsA, but not in the HD-Rap/CsA-treated animals. The jejunal Vmax of D-glucose in the LD-Rap- or -Rap/CsA-treated animals was no different from controls. In the HD-Rap- and HD-Rap/ CsA-treated animals, jejunal rates of uptake of stearic, linoleic, and linolenic acids were reduced when compared with controls. Jejunal and ileal permeability (as assessed by the passive uptake of L-glucose, tissue conductance, and mucosal-to-serosal flux of [3H]inulin) was increased in animals treated with HD-Rap or HD-Rap/CsA, when compared with CsA or controls. These parameters of permeability were no different at lower doses of Rap or Rap/CsA. The jejunal and ileal villous surface area was increased in CsA, but decreased in HD-Rap or HD-Rap/CsA animals. Thus, HD-Rap given alone or in combination with CsA reduced body weight gain, in part due to reduced food intake and malabsorption of lipids, which was due at least in part to reduced intestinal surface area. The relevance of these findings to patients undergoing chronic immunosuppressive drug therapy needs to be established.

Administration, Oral↗
PubMed1998

Review article: olestra and its gastrointestinal safety.

Olestra is a fat substitute made from sucrose and vegetable oil. Olestra is neither digested nor absorbed, and therefore adds no calories or fat to the diet. Because the gut is the only organ that is exposed to olestra, the potential for olestra to affect gastrointestinal structure and function, and the absorption of nutrients from the gut, has been investigated. Histological evaluations performed after long-term feeding studies have shown no indications that olestra causes injury to the gastrointestinal mucosa. Olestra is not metabolized by the colonic microflora, and has no meaningful effects on the metabolic function of these organisms. Studies of gastrointestinal transit have shown that the consumption of olestra with food does not affect gastric emptying, or small or large bowel transit times. Olestra does not affect the absorption of macronutrients, water-soluble vitamins or minerals. It causes a dose-responsive decrease in the availability of the fat-soluble vitamins A, D, E and K; however, this potentially adverse effect is offset by the addition of vitamins to olestra-containing foods. Olestra has no consistent effect on the amount of total bile acids excreted in the faeces, and therefore probably has no significant effect on bile acid absorption. The occurrence of gastrointestinal symptoms, including diarrhoea, loose stools, gas and abdominal cramping, after consumption of olestra under ordinary snacking conditions is comparable to that following consumption of triglyceride-containing snacks.

Animals↗
PubMed1998

Short-chain fatty acid-supplemented total parenteral nutrition alters intestinal structure, glucose transporter 2 (GLUT2) mRNA and protein, and proglucagon mRNA abundance in normal rats.

Intestinal adaptation is a complex physiologic process that is not completely understood. Intravenous short-chain fatty acids (SCFAs) enhance intestinal adaptation after 80% enterectomy in rats. The purpose of this study was to examine rapid responses to SCFA-supplemented total parenteral nutrition (TPN) in the normal small intestine. After jugular catheterization, 31 Sprague-Dawley rats (weighing 258 +/- 3 g) were randomly assigned to receive standard TPN or an isoenergetic, isonitrogenous TPN solution supplemented with SCFAs (TPN+SCFA). Intestinal samples were obtained after 24 or 72 h of nutrient infusion. TPN+SCFA for 24 h increased (P < 0.05) the ileal RNA concentration (microg RNA/mg ileum) whereas TPN+SCFA for 72 h increased (P < 0.05) the ileal DNA concentration (microg DNA/mg ileum) and decreased (P < 0.05) the ileal protein concentration (microg protein/mg ileum). Ileal proglucagon mRNA abundance was elevated (P < 0.05) after 24 h of TPN+SCFA infusion and returned to levels seen with control TPN by 72 h. Glucose transporter 2 (GLUT2) mRNA was significantly higher (P < 0.05) in the TPN+SCFA groups at both time points when compared with control TPN groups. Ileal GLUT2 protein abundance in the 72-h TPN+SCFA group was significantly higher (P < 0.05) than that of all other groups. Sodium-glucose cotransporter (SGLT-1) mRNA and protein abundance and uptake of D-fructose and D-glucose did not differ between groups. Jejunal uptake of L-glucose and lauric acid was significantly higher (P < 0.05) after 72 h of TPN+SCFA than after 24 h, whereas the 24- and 72-h TPN groups did not differ. In summary, SCFAs led to rapid changes in ileal proglucagon and glucose transporter expression in rats receiving TPN and provide insights into therapeutic management of individuals with short bowel syndrome or intestinal malabsorption syndromes.

Animal Nutritional Physiological Phenomena↗
PubMed1998

Fermentable dietary fiber increases GLP-1 secretion and improves glucose homeostasis despite increased intestinal glucose transport capacity in healthy dogs.

Ileal proglucagon gene expression and postprandial plasma concentrations of proglucagon-derived peptides are reported to change with the type and quantity of dietary fiber ingested by rats. Within the intestine, proglucagon encodes several proglucagon-derived peptides known to modulate intestinal absorption capacity and pancreatic insulin secretion. To determine whether the chronic ingestion of fermentable dietary fiber regulates the expression and synthesis of proglucagon-derived peptides in the distal intestine to modulate glucose homeostasis, the following study was conducted: 16 adult dogs (23 +/- 2 kg) were fed isoenergetic, isonitrogenous diets containing a mixture of high fermentable dietary fibers (HFF) or low fermentable (LFF) wood cellulose for 14 d in a randomized cross-over design. Food was withheld for 16 h before an oral glucose tolerance test was conducted supplying 2 g of glucose/kg body wt, and peripheral blood was collected via a hind-leg catheter at 0, 15, 30, 45, 60, 90 and 120 min for plasma glucose, insulin and glucagon-like peptide-1(7-36)NH2 (GLP-1) analyses. Intestinal samples were collected after the second dietary treatment. Ileal proglucagon mRNA, intestinal (GLP-1) concentrations and the integrated area under the curves (AUC) for plasma GLP-1 and insulin were greater and plasma glucose AUC was reduced when dogs were fed the HFF diet compared to the LFF diet (P < 0.05). Intestinal villi heights, brush border and basolateral glucose transporter protein abundance and jejunal transport capacities were significantly greater when dogs were fed the HFF diet than when fed the LFF diet. In conclusion, improvements in glucose homeostasis are observed in healthy dogs when they ingest fermentable fibers.

Animals↗
PubMed1998

Optimization of acid suppression for patients with peptic ulcer bleeding: an intragastric pH-metry study with omeprazole.

OBJECTIVE: To study whether an intravenous infusion dose of omeprazole (80 mg + 8 mg/h) during 24 h can be subsequently reduced with maintained effect. Second, to study the effect of oral omeprazole 20 mg given once or twice daily up to day 10, after cessation of a 3-day intravenous infusion (80 mg + 8 mg/h). DESIGN: Prospective, randomized, partly blinded study. METHODS: Twelve Helicobacter pylori(+) patients and 12 H. pylori(-) subjects were included. In part I the patients received omeprazole, 80 mg + 8 mg/h, during 24 h followed by 8, 4 or 2 mg/h. In part II the subjects received 80 mg + 8 mg/h during 3 days followed by 20 mg omeprazole orally, once or twice daily until day 10. Intragastric pH was measured. RESULTS: All H. pylori(+) patients showed a rapid increase of intragastric pH with a mean intragastric pH of 6.7 during the second half of the first day. After the subsequent dose reduction, the mean pH decreased to 6.1-6.2. Patients continuing on 8 mg/h showed the best results. Likewise, all H. pylori(-) subjects showed a rapid and sustained reduction of intragastric acidity during the infusion. Subsequent dose reduction to 20 mg once daily led to a stable fraction of time with pH > 3 of 72%. CONCLUSIONS: Omeprazole given as a continuous infusion of 80 mg + 8 mg/h for 72 h followed by omeprazole 20 mg once daily raised the intragastric pH to and above levels alleged to allow haemostasis in patients with peptic ulcer bleeding and subsequent healing of the ulcer.

Adult↗
PubMed1998

The utility of endoscopy in the management of patients with gastroesophageal reflux symptoms.

OBJECTIVE: The utility of endoscopy in the management of patients with symptoms of gastroesophageal reflux disease (GERD) is unclear. The purpose of this prospective study was to assess the impact of endoscopy on the subsequent management of patients with uncomplicated reflux symptoms. METHODS: A total of 742 patients underwent endoscopy for symptoms of GERD. Endoscopists recorded the therapy before endoscopy, the findings of endoscopy, and the treatment recommendations after endoscopy. RESULTS: There was no difference in pre-endoscopy therapy or grade of esophagitis in subjects undergoing endoscopy for failed therapy versus GERD symptoms alone. After endoscopy, the most common strategy for patients taking omeprazole was to maintain or increase the dose. For those taking an H2 blocker before endoscopy, the most common outcome was to switch the patient to omeprazole, independent of the grade of esophagitis. CONCLUSIONS: Most patients undergoing endoscopy for symptoms of GERD were switched to omeprazole regardless of the endoscopic findings. No esophageal cancer was identified and the incidence of Barrett's esophagus was low. It appears that endoscopy itself did not change the management of patients receiving H2-blocker therapy. A trial of a proton pump inhibitor before endoscopy should be considered.

Adolescent↗
PubMed1998

Stanniocalcin: a novel protein regulating calcium and phosphate transport across mammalian intestine.

Stanniocalcin (STC) is an anti-hypercalcemic glycoprotein hormone previously identified in the corpuscles of Stannius in bony fish and recently in the human genome. This study undertook to express human STC in Chinese hamster ovary (CHO) cells and to determine its effects on calcium and phosphate absorption in swine and rat intestine. Unidirectional mucosal-to-serosal (Jm-->s) and serosal-to-mucosal (Js-->m) 45Ca and 32P fluxes were measured in vitro in duodenal tissue in voltage-clamped Ussing chambers. Addition of STC (10-100 ng/ml) to the serosal surface of the duodenum resulted in a simultaneous increase in calcium Jm-->s and Js-->m fluxes, with a subsequent reduction in net calcium absorption. This was coupled with an STC-stimulated increase in phosphate absorption. Intestinal conductance was increased at the highest dose of STC (100 ng/ml) in swine tissue. The addition of STC to the mucosal surface had no effect on calcium and phosphate fluxes. STC at doses of 10-1,000 ng/ml had no effect on short-circuit current in any region of the rat intestine. In conclusion, human recombinant STC decreases the absorption of calcium and stimulates the absorption of phosphate in both swine and rat duodenum. STC is a novel regulatory protein that regulates mammalian intestinal calcium and phosphate transport.

Animals↗
PubMed1998

Early dietary experience influences ontogeny of intestine in response to dietary lipid changes in later life.

This study was undertaken to test the hypothesis that a change in the mother's diet at the time of birth and continued during suckling modifies the intestinal transport of nutrients in the suckling offspring. Pregnant rat dams were fed one of four semisynthetic diets during pregnancy [high or low n-6/n-3 diet or a diet enriched with arachidonic acid (AA) or docosahexaenoic acid (DHA)] and were fed the same diet at the time of birth or switched to another diet. The greatest body weight gain was in the suckling rats (15-16 days of age) fed a low n-6/n-3 diet. Switching from this diet caused weight loss, and the observed weight gain with the low n-6/n-3 diet was prevented by previous exposure of the mother to the high n-6/n-3 diet or the AA- or DHA-containing diet. Although continuous feeding of a high n-6/n-3 diet to the mother during pregnancy and lactation was associated with the lowest in vitro rates of fructose uptake, switching the mother to another diet during lactation did not necessarily correct the low absorption. In contrast, continuous feeding of a high n-6/n-3 diet to the mother during pregnancy and lactation is associated with the highest maximal transport rate of glucose uptake into the jejunum and ileum. Jejunal uptake of fatty acids 12:0, 18:0, 18:3(n-3), and cholesterol was less with the low n-6/n-3 diet compared with the high n-6/n-3 diet, whereas the ileal uptake of 18:0 and 18:3(n-3) was higher with the low n-6/n-3 diet. Thus the ontogeny of the intestine is critically influenced by the mother's diet during gestation as well as during the nursing period. Some of the diet-associated changes in nutrient uptake resulting from the mother's diet during pregnancy could be corrected by dietary interventions introduced after birth.

Aging↗
PubMed1998

Cholestatic hepatocellular injury with azathioprine: a case report and review of the mechanisms of hepatotoxicity.

Azathioprine is a drug commonly used for the treatment of inflammatory bowel disease, organ transplantation and various autoimmune diseases. Hepatotoxicity is a rare, but important complication of this drug. The cases reported to date can be grouped into three syndromes: hypersensitivity; idiosyncratic cholestatic reaction; and presumed endothelial cell injury with resultant raised portal pressures, venoocclusive disease or peliosis hepatis. The components of azathioprine, 6-mercaptopurine and the imidazole group, may play different roles in the pathogenesis of hepatotoxicity. The strong association with male sex, and perhaps with human leukocyte antigen type, suggests a genetic predisposition of unknown type. Many of the symptoms of hepatotoxicity, such as nausea, abdominal pain and diarrhea, can be nonspecific and can be confused with a flare-up of inflammatory bowel disease. As well, the subtype resulting in portal hypertension can occur without biochemical abnormalities. A 63-year-old man with Crohn's disease who is presented developed the rare idiosyncratic form of azathioprine hepatotoxicity, but also had a severe disabling steroid myopathy, peripheral neuropathy, resultant deep venous thrombosis and pulmonary embolism related to immobility, and a nosocomial pneumonia. His jaundice and liver enzyme levels improved markedly on withdrawal of the drug, returning to almost normal in five weeks. Treating inflammatory bowel disease effectively while trying to limit iatrogenic disease is a continuous struggle. Understanding the risks of treatment is the first important step. There must be a low threshold for obtaining liver function tests, especially in men, and alertness to the need to discontinue the drug or perform a liver biopsy should patients on azathioprine develop liver biochemical abnormalities, unexplained hepatomegaly or signs of portal hypertension.

Azathioprine↗
PubMed1998

From bench to bedside and back--report on the European Helicobacter pylori Study Group Xth International Workshop on Gastroduodenal Pathology and Helicobacter pylori.

The Xth International Workshop on Gastroduodenal Pathology and Helicobacter pylori was held in Lisbon, Portugal, from September 12 to 14, 1997. State-of-the-art reviews and research findings were presented to over 2000 participants. This review focuses on important new developments and serves as a rapid communication of clinically relevant material.

Drug Therapy, Combination↗
PubMed1998

Overview of olestra: a new fat substitute.

Olestra is a mixture of hexa-, hepta- and octa-esters formed from the reaction of sucrase and long chain fatty acids isolated from edible oils. Olestra has properties similar to those of traditional triglycerides but is not hydrolyzed by pancreatic lipases and, therefore, serves as a noncaloric replacement for fats in the diet. The safety of olestra has been established in over 100 studies in seven different species of animals, with confirmatory safety data coming from approximately 75 human studies; consumption of olestra at levels typical for savoury snacks does not result in reports of gastrointestinal problems in humans. This is consistent with the results of studies of the physiological and morphological effects of olestra in animals and in humans. It is anticipated that olestra will be available in Canada in the near future. Patients will soon be asking their physicians about its use. This article provides an overview of olestra.

Canada↗
PubMed1998

Small bowel review: Part I.

In the past year there have been many advances in the area of small bowel physiology and pathology. In preparation for this review, over 500 papers were assessed, and some have been selected and reviewed, with a particular focus on presenting clinically useful information for the practising gastroenterologist.

Celiac Disease↗
PubMed1997

Polyunsaturated fat in the diet may improve intestinal function in patients with Crohn's disease.

To investigate the effect of increasing dietary polyunsaturated fat intake on fat absorption in Crohn's patients, normal subjects and subjects with inactive Crohn's disease consumed a high polyunsaturated to saturated fat ratio diet. Subjects participated in breath tests before and after six months of a high polyunsaturated to saturated (P/S) fat ratio diet to measure their response to [1-13C] 10:0 and [1-13C] 16:0 ingested with a test meal. Whole body absorption-oxidation of C10:0 was not affected by the diet treatment. Before diet treatment, whole body absorption-oxidation of C16:0 in Crohn's patients was 80% of that observed for control subjects. After consuming a high polyunsaturated to saturated fatty acid ratio diet, subjects increased oxidation of C16:0 by 85% compared to before the diet treatment period. It is concluded that (1) absorption of labelled C16:0 from a test meal is reduced in Crohn's patients, and (2) consumption of a high polyunsaturated to saturated fatty acid ratio diet improves the utilization of dietary C16:0 by Crohn's patients.

Body Weight↗
PubMed1997

Refeeding varying fatty acid and cholesterol diets alters phospholipids in rat intestinal brush border membrane.

Refeeding a diet initially given shortly after weaning results in a different adaptive change in the in vitro intestinal uptake of sugars and lipids than if the diet is given for the first time at a later age. This study was undertaken in rats to test the hypothesis that changes in nutrient uptake associated with refeeding diets containing beef tallow (S), beef tallow plus 1% cholesterol (Sc), fish oil (F), or fish oil plus cholesterol (Fc) are associated with changes in the brush border membrane (BBM) phospholipids and phospholipid fatty acids. Weanling Sprague-Dawley rats were fed ad libitum one of the four diets. At 35 d of age (about 2 wk after weaning), the rats were maintained on either the same diet used at weaning, or were switched to one of the other semisynthetic diets which were then fed for a further 7 wk. At week nine (2 + 7) the rats were either continued on the same diet or were switched back to the original diet for 2 wk (2 + 7 + 2). The groups of animals which were compared included SSSc vs. ScSSc; ScScS vs. SScS; FFFc vs. FcFFc; and FcFcF vs. FFcF. Refeeding S, Sc, F, or Fc had no effect on food consumption or on body weight gain. Refeeding Fc resulted in increased ileal BBM total phospholipids, whereas rechallenge with F resulted in a decline in the jejunal BBM ratio of phospho-lipid/cholesterol. Refeeding Sc resulted in a decrease in the ileal BBM phosphatidylcholine (PC). In rats rechallenged with Fc, there was increased ileal BBM sphingomyelin (SM), increased ileal BBM phosphatidylethanolamine (PE), decreased ileal BBM PC/PE, and an increased ileal BBM SM/PC. Refeeding had no effect on the fatty acyl constituents of the jejunal of ileal BBM PC or PE. These results suggest that there are late effects of the early introduction of dietary cholesterol on intestinal BBM phospholipid content and composition that may contribute to the previously reported changes in intestinal nutrient absorption.

Age Factors↗