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Biomedical subjects

A B Thomson

Publications and source records attributed to A B Thomson.

At least 127 records · Page 7Linked to original sources
PubMed1993

Jejunum is preferable for construction of a Bianchi bowel-lengthening procedure in swine short bowel.

This study compared the efficacy of a Bianchi bowel-lengthening procedure performed in residual ileum and jejunum of a 75% short bowel model. Eighteen female piglets underwent a 75% mid small bowel resection. After a 6-week period, animal weights were similar and pigs were randomly assigned to one of three treatment groups: (1) a control group receiving no further therapy; (2) a group receiving a Bianchi procedure in the residual jejunal segment; and (3) a group receiving a Bianchi procedure in the residual ileal segment. All were followed for a further 12 weeks. Jejunal Bianchi-treated short bowel animals demonstrated a greater final weight gain (78.8 +/- 4.9 kg) compared with nontreated short bowel (63.0 +/- 6.6 kg) and ileal Bianchi-treated short bowel groups (69.3 +/- 6.9 kg) in addition to a larger jejunal diameter. The increased weight gain in the jejunal Bianchi-treated group was not a consequence of initial bowel length, food intake, changes in bowel length, digestibility of nitrogen or fat, or nutritional status. Furthermore, kinetic constants for D-glucose absorption following 18 weeks of short-bowel syndrome demonstrated a lowered glucose maximal transport rate (Vmax) in animals with nontreated short bowel compared with sham-operated controls. Additionally, jejunal and ileal glucose Vmax was further lowered in the presence of a Bianchi procedure. We conclude that: (1) during short-bowel syndrome, body weight gain was significantly higher in animals when the Bianchi procedure was performed in jejunum; (2) the short-bowel syndrome decreased intestinal glucose absorption; and (3) the Bianchi procedure itself further impaired glucose transport.

Animals↗
PubMed1993

Effect of intravenous infusion of ranitidine on intragastric acidity in fasting subjects: comparison with bolus or Gastrojet (pH-stat-adjusted) infusion.

This study was undertaken in nine fasting healthy volunteers to compare the effect of intravenous continuous infusion versus bolus injection of ranitidine on 12-h intragastric pH, and to compare the efficacy of these two modes of administration of pH-stat-adjusted infusion of ranitidine using the Gastrojet. Each volunteer had three study sessions with 12-h pH measurements. In the ranitidine infusion treatment arm (RAN-INF), ranitidine was continually infused intravenously using an IVAC-pump at a dose of 0.125 mg mg.kg over a 12-h period. In the ranitidine bolus treatment arm (RAN-BOL), ranitidine bolus 50 mg was given over 10 min, every 6 h. When ranitidine infusion was given by the pH stat method using the Gastrojet (RAN-JET), sufficient ranitidine was given to maintain a present value of pH > or = 5. The study was analysed with a 3 x 3 Latin square cross-over design with multiple measurements of each phase of the cross-over. No difference was found between RAN-INF and RAN-BOL in 12-h or in daytime (10.00-18.00 h) mean pH, median pH, or percentage of pH > or = 5. Using RAN-JET, 89.5% of the pH values were > or = 5., compared with 39.7% and 40.0% with RAN-INF or RAN-BOL. RAN-JET also gave higher (P < 0.05) mean and median 12-h or daytime pH values, as compared with RAN-INF or RAN-BOL. The mean doses of ranitidine given in the 12-h infusion periods were 100 mg, 109 mg and 112 mg (RAN-BOL, RAN-INF and RAN-JET, respectively). Thus, this superior inhibition of acid inhibition achieved with Gastrojet does not require higher mean doses of ranitidine. These findings cannot necessarily be applied to persons with duodenal ulcer disease or to patients in an intensive-care unit setting. However, the data do raise the possibility that much greater inhibition of acid inhibition can be achieved by individualizing the dose of ranitidine using the Gastrojet.

Adult↗
PubMed1993

Lipid absorption: passing through the unstirred layers, brush-border membrane, and beyond.

Lipids are components of our diet and luminal secretions, with physicochemical characteristics that determine their digestion and absorption in the gastrointestinal tract. Lipids include triglycerides, phospholipids, and cholesterol. Dietary lipids contain approximately 97% triglycerides, with small amounts of phospholipids and cholesterol. These components are important in cell membrane composition, fluidity, peroxidation, prostaglandin and leukotriene synthesis, and cellular metabolic processes. Lipids are implicated in the mechanisms of brain development, inflammatory processes, atherosclerosis, carcinogenesis, aging, and cell renewal. Duodenal hydrolysis of dietary lipids and biliary phospholipids and cholesterol is carried out by pancreatic lipase, colipase, phospholipase A2, and cholesterol esterase. Bile acid solubilization results in mixed micelles and liposomes, in gel and liquid crystal phases. Lipid digestion products pass across the intestinal unstirred water layer. For long-chain fatty acids and cholesterol, passage across the unstirred water layer is rate limiting, whereas passage of short- and medium-chain fatty acids is limited by the brush-border membrane. Within the unstirred water layer, an acidic microclimate aids micellar dissociation so that protonated, and to a lesser extent, nonprotonated monomers then pass across the intestinal brush-border membrane. Absorptive mechanisms have been studied extensively in relation to lipid composition, fatty acid chain length, degree of unsaturation, essential fatty acid content, phospholipid components, and cholesterol. Enterocytes may take up lipids from the intestinal lumen or from lipoproteins of the bloodstream, but these pools are likely to be functionally distinct. Recent advances are reviewed, including recent advances in the area of microclimates, compartmentation, lipid binding proteins, intracellular trafficking, intestinal lipoproteins, release of lipids across the basolateral membrane, and dietary effects.

Bile Acids and Salts↗
PubMed1993

Islet transplantation improves glucose oxidation and mechanical function in diabetic rat hearts.

In poorly controlled diabetes an impairment of glucose use can contribute to a depression in mechanical function of rat hearts. In this study we determined the effects of islet transplantation on glucose use and heart function in streptozotocin-induced diabetic rats. Myocardial function, glycolysis, and glucose oxidation were measured in isolated working hearts obtained from control, diabetic, and islet-transplanted diabetic Wistar-Furth rats. Islets (1200) were transplanted beneath the kidney capsule 2 weeks after a single i.v. dose of streptozotocin (55 mg/kg). The study consisted of three groups: (i) islet-transplanted diabetic rats, (ii) untreated diabetic controls, and (iii) normal controls. Following 11 weeks of monitoring, working hearts were perfused at a 11.5-mmHg (1 mmHg = 133.3 Pa) preload and 80-mmHg afterload, with buffer containing 11 mM [5-3H,14C(U)]glucose, 1.2 mM palmitate, and 100 microU/mL insulin. In untreated diabetic rat hearts, glucose oxidation rates were markedly depressed compared with control hearts (30.4 +/- 4 and 510 +/- 68 nmol.g-1 dry wt..min-1, respectively). Low glucose oxidation rates in diabetic rats were significantly improved in islet-transplanted animals (234 +/- 39 nmol.g-1 dry wt..min-1). The low glucose oxidation rates in untreated diabetic rat hearts were accompanied by an impaired mechanical function compared with control hearts, which was improved by islet transplantation (heart rate x developed pressure x 10(-3) was 10.6 +/- 0.9, 14.8 +/- 1.3, and 14.8 +/- 1.5 beats.mmHg.min-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobiosis↗
PubMed1993

Fish oil modifies effect of high cholesterol diet on intestinal absorption in diabetic rats.

Omega-3 fatty acids ('fish oil') reduce the intestinal absorption of glucose and lipids in normal and in diabetic rats, but their effect is altered by the presence of saturated or poly-unsaturated omega-6 fatty acids in the diet. This study was undertaken to test the hypothesis that the influence of fish oil on the intestinal uptake of nutrients in diabetic rats is also influenced by the cholesterol content of the diet. Streptozotocin diabetic rats were raised for 2 wk on semisynthetic diets in which the lipid composition was derived mainly from beef tallow (BT), beef tallow plus cholesterol (BTC), fish oil (FO), or fish oil plus cholesterol (FOC). Food intake and weight gain was similar in the 4 diet groups, although the fasting blood glucose was lowest in diabetic rats fed BT. Cholesterol supplementation increased intestinal wall and mucosal weights when fed with BT, but the opposite effect was seen with FO, with lower wall and mucosal mass with FOC than with FO. Ileal uptake of D-glucose was lower in FO than in BT or FOC. Cholesterol feeding was associated with enhanced jejunal uptake of cholesterol when fed with BT, but the converse was observed with FO. Thus, 1) the reduction of glucose absorption associated with feeding fish oil is blunted in the presence of a supplemented intake of cholesterol; and 2) a fish oil diet reduces cholesterol uptake even in the presence of a high level of dietary cholesterol. It remains to be established what is the optimal ratio of dietary saturated, polyunsaturated omega-3 and omega-6 fatty acids, and cholesterol required to normalize intestinal transport function in diabetic rats.

Animals↗
PubMed1992

Desaturation of linoleic acid in the small bowel is increased by short-term fasting and by dietary content of linoleic acid.

The rate of desaturation of linoleic acid (18:2(n - 6)) and level of arachidonic acid (20: 4(n - 6)) in mucosal microsomes from small intestine of rats fasted for 24 h or fed diets of different fatty acid composition was examined. Fasting or feeding a diet high in linoleic acid increased delta 6-desaturase activity, a rate-limiting enzyme in the arachidonic acid biosynthetic pathway in the jejunum. After fasting, delta 6-desaturase activity was also enhanced in the ileum. Feeding a diet rich in n - 3 fatty acids had no significant effect on delta 6-desaturase activity in jejunal or ileal mucosal microsomes. Following fasting, arachidonic acid content of microsomal total phospholipids increased in the jejunum with a concomitant decrease in linoleic acid content. Arachidonic acid and 18:2(n - 6) concentration remained unchanged in ileal microsomes after short-term food withdrawal. Feeding a diet containing n - 3 fatty acids lowered the content of 20:4(n - 6) and increased 20:5(n - 3) and 22:6(n - 3) levels in both jejunal and ileal microsomes. These data indicate that the level of 20:4(n - 6) and the biosynthesis of 20:4(n - 6) by desaturation-chain elongation of 18:2(n - 6) in the rat enterocyte responds rapidly to change in physiological conditions such as fasting and dietary fat composition.

Animals↗
PubMed1992

Effect of intravenous and oral omeprazole on 24-hour intragastric acidity in duodenal ulcer patients.

Nine patients with duodenal ulcer were on separate occasions given omeprazole, 20 mg orally, 10 mg intravenously (IV), and 40 mg IV once daily for 5 days. On day 1, the median reduction of 24-hour intragastric acidity was 42.2% for the 20-mg oral dose and 54.8% and 88.4% for the two IV doses, respectively, but the between-patient variability was considerable for all three doses. On day 5, the degree of reduction had increased for all three doses to a median value of 99.9% for the 20-mg oral dose and 95.7% and 99.9% for the two IV doses, respectively. Plasma omeprazole concentrations increased significantly from day 1 to day 5 only for the 20-mg oral and 40-mg IV doses. Thus, the increased pharmacological effect of omeprazole during repeated once daily administration can only partly be explained by increased plasma concentrations, suggesting that some additional factor(s) must influence the degree of reduction of 24-hour intragastric acidity. Thus, when determining the optimal dose of omeprazole for acid inhibition, the route and duration of administration must be taken into consideration; after 5 days of once-daily administration of doses as low as 10 mg IV and 20 mg orally are effective and dependable in reducing 24-hour intragastric acidity in patients with duodenal ulcer. However, a daily dose of 40 mg IV omeprazole is not sufficient to keep intragastric pH above 4 in all patients during the first day of treatment.

Administration, Oral↗
PubMed1992

Intestinal function following allogeneic small intestinal transplantation in the rat.

This study tests the hypothesis that small bowel transplantation alters the function of the intestine. The function of the small intestine was investigated after syngeneic (BN----BN or Lew----Lew) and fully allogeneic (BN----Lew) orthotopic total small intestinal transplantation (SIT) using a two-stage model. All animals were treated with cyclosporine A throughout the 60-day study period. Syngeneic transplantation reduced weight gain in the (BN----BN) rats, but not in the (Lew----Lew) animals. Allogeneic transplantation caused a reduction in weight gain for the first 30 days posttransplantation, which may have been associated with graft-versus-host disease. Thereafter, the rate of growth of allogeneic SIT animals was normal. Dietary fat absorption was reduced in all groups of transplanted animals. Intestinal permeability to mannitol and polyethylene glycol 400 (PEG-400) was increased by syngeneic transplantation in all groups, with further permeability increases to mannitol, lactulose, PEG-400, and 51Cr-EDTA after allogeneic SIT. The glucose-stimulated intestinal short circuit current was reduced by both syngeneic and allogeneic SIT, but the maximal active transport rate for glucose uptake was increased, as was the passive uptake of fatty acids. These functional alterations were not associated with changes in intestinal morphology or evidence of rejection. These findings demonstrate that: (1) SIT results in significant changes in the transport characteristics of the bowel, but these have a minimal impact on the well-being of the animal overall; (2) SIT induces an increase in intestinal permeability to mannitol and PEG-400, with a further increase in permeability to all markers following allogeneic SIT; (3) following SIT, and the immune events associated with allogeneic SIT, significant adaptation of the transplanted intestine occurs. We suggest that denervation of the small intestine after SIT is the underlying cause of the changes observed.

Animals↗
PubMed1992

Reduction of nutrient absorption in normal rats by cyclosporine.

The indications for using cyclosporine are expanding rapidly beyond immune suppression for transplantation. We have previously described reduced active glucose uptake by small bowel following CsA treatment in rats. This study examined the effect of varying the dose and route of administration of CsA on bowel function. Male Lewis rats were given CsA via subcutaneous injection at doses of 5 mg/kg or 30 mg/kg on alternate days, or orally via gavage at 0 (control solvent oil), 7.5 mg/kg, or 30 mg/kg daily. Weight gain and feed intake were followed for 1 month when a balance study was performed to quantify in vivo nutrient absorption from the feed. In vitro studies of glucose and fatty acid uptake studies were then performed. Weight gain was reduced by high-dose CsA whether given orally or by subcutaneous injection. Oral CsA reduced in vivo fat and energy absorption from the diet, and all doses and routes of administration of CsA caused a reduction in both active glucose uptake and passive fatty acid absorption by the bowel in vitro. Thus, CsA has significant effects on bowel function in the normal rat. We suggest that further studies are indicated to determine the effects of CsA in man, especially in conditions with already-impaired bowel function.

Animals↗
PubMed1992

Characterization of lipid intake into rabbit jejunal brush border membrane vesicles.

The absorption of lipids is generally accepted to be mediated by a process of passive diffusion, although some recent data have raised the possibility of a mediated component. Brush border membrane vesicles (BBMV) have been widely used to study nutrient transport, but have only recently been used to examine the uptake of lipids. Using a BBMV technique validated with studies of the uptake of D-glucose, we examined the uptake of linoleic acid into the jejunum of adult rabbits. The uptake of 100 microM linoleic acid was constant between 2 and 20 min, with no overshoot observed at earlier periods. Linoleic acid uptake was suppressed by 88% with 0.6 mM phloridzin and by 58% with 0.2 mM phloretin, but uptake of linoleic acid was unaffected by the absence of sodium, by the presence of a sodium gradient, or by varying the osmolarity of the buffer. Lysis of the BBMV incubated with linoleic acid by the addition of ice-cold deionized water did not alter the amount of linoleic acid associated with the BBMV. The linoleic acid concentration curve was linear up to 160 microM, when carried out under initial rate conditions and in the presence of 2 mM taurocholic acid. These results are compatible with the process of passive uptake of linoleic acid into BBMV of rabbit jejunum, but do not exclude the possible physiological importance of a membrane fatty acid binding protein.

Animals↗
PubMed1992

Small bowel transplantation: past, present and future.

As techniques for immune suppression improve, the clinical utility of small bowel transplantation will increase. Recent reports of long-term (over 1 year) survival with totally enteral nutrition following bowel transplantation have increased interest in this area and prompted the present review of the state of the art of small bowel transplantation. Background methodology is emphasized, in order to allow for more critical review of reported models, and to provide a framework for comparing results. The functional capacity of bowel following transplantation, and the effects of immune suppression on bowel function are reviewed in detail. Prospects for future direction in basic and clinical research are discussed.

Animals↗
PubMed1992

Two weeks of oral synthetic E2 prostaglandin (Enprostil) improves the intestinal morphological but not the absorptive response in the rat to abdominal irradiation.

Enprostil, a synthetic E2 prostaglandin, was administered in a dose of 5 micrograms/kg body weight by gastric tube to rats for 14 days following abdominal irradiation with a single dose of 600 cGy from a 137Cs source. Enprostil prevented the body weight loss and the reduced food intake observed in irradiated animals given placebo, and also prevented the irradiation-associated decline in the mucosal weight and surface area of the ileum. Enprostil given to nonirradiated animals reduced the maximal transport rate (Vmax) and the apparent Michaelis constant (Km*) for the ileal uptake of D-glucose, but did not prevent the irradiation-associated decline in the ileal uptake of glucose. Thus, there is a dissociation of the effects of Enprostil on the morphological and the absorptive properties of the intestine. It is concluded that a 2-week course of a daily oral dose of E2 prostaglandin begun shortly after a single exposure to nonlethal abdominal irradiation prevents the radiation-associated reduction in the intestinal mucosal surface area and the animal's body weight, but does not prevent the malabsorption of glucose.

Animals↗
PubMed1992

Dietary lipid content influences the clinical and intestinal adaptive responses to islet transplantation in diabetic rats.

Nutrient absorption is increased in rats with streptozotocin-induced diabetes mellitus (DM). This intestinal adaptive response is modified by isocaloric manipulations of the dietary content of fatty acids, and separate studies have shown a normalization of the enhanced uptake of glucose and lipids when DM rats are treated with transplantation of 3000 syngeneic pancreatic islets of Langerhans. These studies were undertaken to test the hypothesis that modification of the type of fatty acids in the triglycerides in isocaloric semisynthetic diets (S, saturated fatty acids from beeftallow; or F, polyunsaturated fatty acids from fish oil) fed to DM recipients influences the ability of syngeneic transplanted islets to normalize the clinical indices of glycemic control and the intestinal adaptive response. A suboptimal number of islets was transplanted (1200) under the renal capsule, so that the clinical parameters of diabetic control would be modestly abnormal and so that any possible beneficial influence of this dietary manipulation might better be able to demonstrate a further improvement of clinical endpoints. Adult Male Wistar-Furth rats were rendered diabetic, transplanted with 1200 syngeneic islets, and were then fed for 6 weeks a chow or a isocaloric semisynthetic diet enriched with either S or F. Islet transplantation reduced the diabetes-associated abnormalities in food consumption, body weight gain, intestinal weight, urine glucose concentrations, urine volume, oral glucose tolerance, hemoglobin A1c and blood urea nitrogen concentration; these changes were all similar in transplanted animals fed S, F, or chow. Plasma concentrations of cholesterol and triglycerides were significantly elevated in transplanted rats fed S as compared to those fed F or chow. Transplanted DM rats had reduced in vitro intestinal uptake of stearic, oleic, linoleic and linolenic fatty acids, and cholesterol as compared with untreated DM rats, but the uptake of lipids was similar in transplanted DM rats fed S, F, or chow diets. Feeding rats S prevented the decline in the value of the jejunal maximal transport rate (Vmax) and apparent Michaelis affinity constant (Km) observed in transplanted DM rats fed F, but the lack of difference in glycemic control in transplanted DM rats fed F was likely due to their higher ileal Vmax for glucose uptake. Thus, intestinal adaptive function and clinical glycemic control are influenced by the type of fatty acids fed to syngeneic islet-transplanted DM rats.

Animals↗
PubMed1992

Medical treatment of gastroesophageal reflux disease: options and priorities.

Gastroesophageal reflux disease (GERD) represents a spectra of symptoms and of reflux damage to the esophagus. This reflux damage is due to a prolonged acid exposure of the esophagus arising from an imbalance between protective motility factors and aggressive acid secretory factors. Initially, patients may be managed by modifying their food intake and by supportive anti-gravity measures. However, many individuals will require drug therapy. Symptomatic relief can be achieved with pro-kinetic agents, antacids, sucralfate suspension, H2-receptor antagonists and H(+)-K+ ATPase pump blockers. There are limitations in the study design of experiments which have compared one agent with another. Accepting these design limitations, it would appear that pump blockers lead to higher rates of endoscopic healing than the use of standard doses of H2-receptor antagonists. However, higher doses of H2-receptor antagonists will likely give higher rates of symptomatic relief and endoscopic healing of GERD. Recurrence of symptoms and esophagitis occur in a high proportion of patients with GERD, and some patients may need to be considered for maintenance therapy.

Adenosine Triphosphatases↗
PubMed1991

Feeding rats a diet enriched with saturated fatty acids prevents the inhibitory effects of acute and chronic ethanol exposure on the in vitro uptake of hexoses and lipids.

Chow-fed rats were given 15% ethanol in their drinking water for 4 weeks, and then for the next 2 weeks of ethanol exposure they were fed isocaloric semisynthetic diets enriched in either saturated (S) or polyunsaturated (P, linoleic acid) fats. Food intake was lower in ethanol-fed (ETH) than in control (C) rats, but the average body weight gain was similar in ETH and C fed S or P. Intestinal dry weight and the percentage of the intestinal wall comprised of mucosa were more than 2-fold higher in ETH than C fed P, whereas these values were 50% lower in ETH than C fed S. The in vitro jejunal uptake of glucose and galactose was higher in ETH than C fed S, whereas the converse was true when feeding P. These effects were due to differences in the values of the maximal transport rate (Vmax), the Michaelis constant (Km), and the contribution of passive permeation. The relative permeability of the intestine to lipids was unchanged by giving ethanol or by feeding S or P, but the individual rates of uptake of most medium- and long-chain fatty acids and cholesterol were lower in ETH fed P as compared with S. In a second series of studies the acute effect of ethanol exposure was examined: animals were fed S or P for 2 weeks and the intestine was then removed: when 5% ethanol was added directly to the test solutions, there was lower in vitro jejunal and ileal uptake of glucose and higher jejunal uptake of 18:2 when rats were previously fed P, but not in those fed S. In summary; (1) feeding an isocaloric polyunsaturated fatty acid diet has a trophic effect on the intestinal mucosa of animals chronically drinking ethanol; and (2) feeding rats a diet enriched with saturated fatty acids prevents the inhibitory effects of acute and chronic ethanol exposure on the in vitro jejunal uptake of glucose, galactose and lipids observed in animals fed a polyunsaturated diet. Thus, the effect of chronic consumption of ethanol on the active and passive jejunal uptake of nutrients is influenced by the type of lipids in the animal's diet.

Alcoholism↗
PubMed1991

Lipid composition and peroxide levels of mucosal cells in the rat large intestine in relation to dietary fat.

To examine whether dietary fat alters membrane lipid composition and peroxidation of polyunsaturated fatty acids in "non-proliferative" and "proliferative" cells in the large intestine, Sprague-Dawley rats were fed diets providing a polyunsaturated-to-saturated fatty acid ratio of 1.2 or 0.3 at a high or low level of fat intake for a 25-day period. Cell populations were isolated and the effect of dietary fat on membrane polyunsaturated fatty acid content and peroxide levels was determined. Neither fat level nor fatty acid composition of diet influenced total cholesterol, total phospholipids, and percentage of phospholipid classes in membrane phospholipids. Feeding the high fat and/or high polyunsaturated-to-saturated fatty acid ratio diet increased polyunsaturated fatty acid content of mucosal cell phospholipids. Increase in polyunsaturated fatty acid content was paralleled by a decrease in the monounsaturated fatty acid content of mucosal cell phospholipids. Membrane content of total saturated fatty acids was not significantly affected by diet. Variation in phospholipid fatty acid composition between "non-proliferative" and "proliferative" cells was observed. Lipid peroxide levels in mucosal cell lipid fractions were altered by dietary fat treatment. Animals fed high fat diets, compared to groups fed low fat diets, exhibited higher membrane peroxide levels when results are expressed as nmol/mg protein. Higher peroxide levels were observed in mucosal cells for rats fed high polyunsaturated-to-saturated fatty acid ratio diets when results were expressed per nmol of phospholipid. It is concluded that changes in fat level and fatty acid composition of the diet alters the mucosal cell membrane lipid composition in the rat large intestine and influences susceptibility of mucosal cell lipid to peroxidation. Further research is required to delineate which dietary factors--fat level, polyunsaturated-to-saturated fatty acid ratio, or both--have a primary influence on the degree of lipid peroxidation.

Animals↗