Biomedical subjects

A B Thomson

Publications and source records attributed to A B Thomson.

At least 109 records · Page 6Linked to original sources

PubMed1995

Na(+)-K(+)-ATPase alpha 1- and beta 1-mRNA and protein levels in rat small intestine in experimental ileitis.

Na(+)-K(+)-adenosinetriphosphatase (ATPase) plays a key role in the absorption of electrolytes, water, and nutrients from the small intestine. The expression of Na(+)-K(+)-ATPase was examined in isolated enterocytes during the course of the ileal inflammatory response elicited by intraluminal administration of 2,4,6-trinitrobenzenesulfonic acid. The ileal inflammatory response was characterized by a marked cellular infiltrate, villous atrophy, and crypt hyperplasia along with fibrosis and smooth muscle hypertrophy. Peak levels of myeloperoxidase were observed at day 7, and ileal mucosal injury was paralleled by increases in ileal mucosal permeability. Ileal enterocytes were harvested from days 3 to 30 after the induction of ileitis. Decreases in Na(+)-K(+)-ATPase functional activity were observed from days 3 to 21 and were accompanied by corresponding decreases in Na(+)-K(+)-ATPase pump abundance, alpha 1- and beta 1-protein expression, and mRNA abundance, whereas Na(+)-K(+)-ATPase turnover, Michaelis-Menten constant values, and inhibition constant values for Na+ and ouabain, respectively, were unaltered. Alterations in transcriptional and posttranscriptional events may determine the changes in Na(+)-K(+)-ATPase activity in this particular model. Additionally observed increases in thymidine kinase and ornithine decarboxylase activities appear to signify alterations in the state of differentiation of the ileal epithelium and may determine the phenotypic expression of enterocyte transporters and permeability in the setting of inflammation.

Animals↗

PubMed1995

Small bowel permeability--a variable effect of NSAIDS.

The baseline permeability of small bowel in 57 healthy volunteers was assessed by measuring the mannitol and chromium-EDTA recovery in a 5-hour urine collection after ingestion of a drink containing a mixture of 1 g of mannitol and 3.7 MBq of 51Cr-EDTA. Subjects were treated with medication for 1 week followed by permeability studies as described above. The regimens used were diclofenac sodium (Voltaren) 50 mg po tid (21 subjects), Voltaren SR 75 mg bid for 1 week (34 subjects), indomethacin 50 mg tid (10 subjects), and tenoxicam (Mobiflex) 20 mg daily (13 subjects). There was no significant difference between the mannitol recoveries at baseline or after any of the drugs. The permeability was clearly increased by indomethacin and by Voltaren SR. Conventional-release Voltaren increased permeability, but the results were not significantly above baseline. Mobiflex had no influence on the measured permeability. Our results suggest that the SR preparation of diclofenac has a more pronounced effect than regular diclofenac sodium; thus different NSAIDs and different preparations of the same NSAID may have different effects on small bowel permeability.

Adult↗

PubMed1995

Role of a brush border membrane fatty acid binding protein in oleic acid uptake into rat and rabbit jejunal brush border membrane.

Oleic acid uptake was studied using adult rat and rabbit jejunal brush border membrane vesicles. The intestinal uptake of oleic acid is influenced by the activity of an amiloride-inhibitable brush border membrane Na+/H+ exchanger, NHE3: opposing Na+/H+ gradients (inward Na+ and outward H+ gradients) increased oleic acid uptake by about 40%, as compared with only an inward Na+ gradient, only an outward H+ gradient, or the absence of either Na+ or H+ gradients. This study was undertaken to test the hypothesis that a portion of oleic acid uptake is facilitated by a fatty acid binding protein in the brush border membrane (FABPPM) of adult rat jejunum. There was a reduction in the uptake of oleic acid when brush border membrane vesicles were incubated with a rat liver plasma membrane fatty acid binding protein antibody (anti-FABPPM-Ab) in the absence, but not in the presence, of opposing Na+/H+ gradients. Thus, oleic acid uptake occurs largely by partitioning of the lipid into the brush border membrane, as well as by a process which involves the activation of the brush border membrane Na+/H+ exchanger, and a membrane fatty acid binding protein.

Amiloride↗

PubMed1994

Orally administered immunosuppressants modify intestinal uptake of nutrients in rabbits.

The effect on intestinal nutrient transport of the immunosuppressive drugs cyclosporin A (CsA), cyclosporin G (CsG), and rapamycin (RAP) was determined in New Zealand white rabbits. Rabbits received oral doses of CsA (20 mg/kg/day), CsG (10 mg/kg/day), or RAP (1 mg/kg/day) for 10 days. Animals receiving RAP had decreased food intake and weight gain compared with controls. This correlated with a decrease in both total ileal weight and corresponding mucosal weight. CsA and CsG administration had no effect on food intake, total weight gain, or intestinal weight. Villus surface area was significantly decreased in all groups as compared with controls. Jejunal uptake of D-glucose as well as 1 medium and 4 long chain fatty acids was not affected by drug administration, while both mucosal-to-serosal and net 3-0-methylglucose fluxes were increased (P < 0.05) in the jejunum by all 3 drugs. In the ileum, the rates of uptake of D-glucose as well as stearic and linoleic acids were increased in animals treated with RAP compared with controls. There was an increase in the ileal values of the maximal transport rate (Vmax) and apparent Michaelis constant (Km*) in RAP, and a fall in the Vmax and Km* in CsG. CsG administration resulted in a decreased cholesterol uptake in both jejunum and ileum, and a decreased D-glucose uptake in the ileum compared with controls. These differences in glucose uptake among groups could not be attributed to variations in body, intestinal, or mucosal weights. It is unlikely that the changes observed in CsA- and CsG-treated animals would have nutritional importance, as these animals gained weight normally. In addition, in these animals the changes mainly occurred in the ileum, not in the jejunum, where most glucose is absorbed, and the associated alterations in the values of the Vmax and Km* would lead to reciprocal changes in the rates of uptake of varying luminal concentrations of glucose. In contrast, these changes are likely to be of more importance in RAP-treated animals, since they failed to gain weight normally. The significance of these findings needs to be established in chronically treated animals.

Administration, Oral↗

PubMed1994

Oral budesonide for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group.

BACKGROUND: Corticosteroids are the most efficacious drugs for inducing remission in active Crohn's disease, but their benefits are frequently offset by serious side effects. Budesonide is a corticosteroid with high topical antiinflammatory activity but low systemic activity because of extensive hepatic metabolism. We investigated the efficacy and safety of an oral controlled-ileal-release preparation of budesonide in patients with active Crohn's disease involving the ileum or ileum and proximal colon. METHODS: In a double-blind, multicenter trial, 258 patients were randomly assigned to receive placebo or one of three doses of budesonide--3, 9, or 15 mg daily. The primary outcome measure was clinical remission, as defined by a score of 150 or less on the Crohn's disease activity index. RESULTS: After eight weeks of treatment, remission occurred in 51 percent of the patients in the group receiving 9 mg of budesonide (95 percent confidence interval, 39 to 63 percent), 43 percent of those receiving 15 mg (95 percent confidence interval, 31 to 55 percent), and 33 percent of those receiving 3 mg (95 percent confidence interval, 21 to 44 percent), as compared with 20 percent of those receiving placebo (P < 0.001, P = 0.009, and P = 0.13, respectively). Improvements in the quality of life, as measured by the patients' responses to the inflammatory bowel disease questionnaire, paralleled these remission rates. Location of disease, prior surgical resection, and previous use of corticosteroids did not affect the outcome. A total of 119 patients (46 percent) were withdrawn from the study before the trial ended, 96 because of insufficient therapeutic effects, 13 because of adverse reactions, and 10 because of noncompliance. Budesonide caused a dose-related reduction in basal and corticotropin-stimulated plasma cortisol concentrations but was not associated with clinically important corticosteroid-related symptoms or other toxic effects. CONCLUSIONS: In an eight-week trial, an oral controlled-release preparation of budesonide at an optimal daily dose of 9 mg was well tolerated and effective against active Crohn's disease of the ileum and proximal colon.

Administration, Oral↗

PubMed1994

Crypt cell production rate, enterocyte turnover time and appearance of transport along the jejunal villus of the rat.

Intestinal nutrient absorption is subject to adaptation with, for example, diabetes, diet lipid variations (isocaloric semisynthetic diets enriched with saturated (S) or polyunsaturated (P) fatty acids), ileal resection and abdominal irradiation. These models were used in rats to assess dynamic morphology and distribution of amino acid transporter along the villus. The enterocyte migration rate (EMR) was measured using [3H]thymidine; the vincristine metaphase arrest technique was used to determine the crypt cell production rate (CCPR); quantitative autoradiography was used to assess the time and age of enterocytes when the uptake of 1 and 20 mM [3H]leucine and [3H]lysine was initiated along the villus. The enhanced jejunal uptake of nutrients which occurs after a 50% distal enterectomy was associated with a fall in EMR and CCPR, yet the enhanced nutrient uptake which occurs in diabetes is not associated with any alteration in EMR, CCPR, enterocyte transport pool (ETP), i.e., the length of the enterocyte column along with the villus containing amino acid transporter) or expression of transporter along the villus. The reduced uptake of nutrients in rats fed P as compared with S was associated with increased rather than decreased ETP and age of the enterocytes at the tip of the villus. The reduced nutrient uptake which occurs 3 days after abdominal irradiation was associated with increased EMR and CCPR, and reduced ETP and age of enterocytes of the tip of the villus. However, 14 days after irradiation when nutrient transport remains reduced, these parameters have returned to normal. Thus, alterations in nutrient transport may be associated with changes in the dynamic morphology of the intestine, but the two processes are not necessarily interdependent. We speculate that the changes in the dynamic morphology of the intestine, and the changes of amino acid transport which occurs in these models of intestinal adaptation, are independently controlled.

Amino Acid Transport Systems↗

PubMed1994

Dietary omega 3 fatty acids and cholesterol modify enterocyte microsomal membrane phospholipids, cholesterol content and phospholipid enzyme activities in diabetic rats.

Diabetes-associated changes in intestinal uptake of nutrients are modified by isocaloric variations in the type of dietary lipids, and are associated with alterations in the phospholipid and fatty acyl content of the intestinal brush border membrane. The present study was designed to test the hypothesis that diet- and diabetes-associated changes in enterocyte microsomal membrane phospholipids are due to variations in the activity of two phospholipid metabolizing enzymes, 1,2-diacylglycerol:CDPcholine cholinephosphotransferase (CPT) and phosphatidylethanolamine methyltransferase (PEMT). Adult female Wistar rats were fed one of four semisynthetic diets--beef tallow low in cholesterol (BT), beef tallow high in cholesterol (BTC), fish oil low in cholesterol (FO) or fish oil high in cholesterol. In half of the animals, diabetes mellitus was produced by injection of streptozotocin. Jejunal and ileal enterocyte microsomes (EMM) were isolated and analyzed for cholesterol and phospholipids, as well as for CPT and PEMT activities. In control animals, feeding FO reduced EMM total phospholipids including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol. Feeding FO resulted in a greater than 95% reduction in the activity of CPT. Diabetes was associated with increased jejunal EMM total phospholipids including sphingomyelin (SM) and PE, without associated changes in CPT or PEMT. Dietary cholesterol supplementation did not affect EMM total cholesterol or phosphlipid composition in control rats fed BT or FO, but was associated with an increase in EMM cholesterol in diabetic rats fed BT or FO. A decrease in total phospholipids due to a decline in SM, PC and PE in diabetic rats fed FO was not associated with changes in the activities of CPT or PEMT in EMM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Differential and interactive effects of calcium channel blockers and cholesterol content of the diet on jejunal uptake of lipids in rabbits.

The present study was undertaken to determine the effects of two classes of calcium channel blockers (CCB), nisoldipine (N) and verapamil (V), on the jejunal uptake of lipids in rabbits. The uptake of cholesterol and long-chain fatty acids into rabbit jejunum was examined after 6 and 36 min of exposure to N or V in vitro ("acute" studies), and after 3-wk feeding of N or V ("chronic" studies). Animals were fed either a low (0.08%) cholesterol diet (LCD) or a high (2.8%) cholesterol diet (HCD), with or without N or V added. Acute in vitro exposure of the jejunum to N or V did not affect the uptake of cholesterol or palmitic acid in rabbits fed LCD or HCD. The effect of N or V feeding depended upon the cholesterol content of the diet; adding N or V to LCD increased cholesterol uptake while adding N or V to HCD enhanced or lowered cholesterol uptake, respectively. Both N and V increased the uptake of stearic acid in LCD. N in HCD had no effect on fatty acid uptake, whereas V lowered the uptake of stearic and linoleic acids and increased the uptake of oleic acid. These changes in lipid uptake were not due to variation in the animals' food intake, body weight gain, or intestinal mucosal surface area. The chronic administration of N or V results in an intestinal adaptative process that alters the jejunal uptake of lipids, the direction of which is influenced by the class of CCB, and by the cholesterol content of the diet. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Gradient for D-glucose and linoleic acid uptake along the crypt-villus axis of rabbit jejunal brush border membrane vesicles.

Glucose uptake into jejunal brush border membrane (BBM) varies along the crypt-villus axis (CVA). In the present study, the question was addressed whether uptake of the essential long-chain fatty acid linoleic acid also varies along the CVA. Using agitation techniques, five jejunal enterocyte fractions were sequentially isolated from female New Zealand white rabbits. A sixth and final fraction of lower-villus/crypt cells was obtained by the scraping of the remaining jejunal mucosa. Cell fraction along the CVA was proven histologically, by noting decreasing alkaline phosphatase activities in sequentially isolated fractions, and by demonstrating [3H-methyl]thymidine uptake mainly in the final fraction of the lower villus/crypt cells. BBM vesicles were prepared from the upper, mid- and lower-villus/crypt enterocyte fractions, using differential centrifugation and divalent ion precipitation. D-Glucose uptake into each fraction showed an Na(+)-gradient dependent time-course "overshoot" with linear uptake to 15 s and a subsequent decline to a steady-state plateau. Varying D-glucose concentrations from 50-1000 microM demonstrated saturation kinetics of uptake, with maximal transport rates (Vmax) and Michaelis affinity constants (Km) varying between fractions; the Km and Vmax were both lowest in the upper-villus fraction. A linear relationship existed between linoleic acid concentration (25-200 microM) and uptake in each fraction. Linoleic acid uptake was equivalent in all fractions when expressed per mg protein, but when expressed in terms of the estimated minimal BBM, vesicle surface area uptake was greater in the upper- than in the lower-villus/crypt fractions. Thus, BBM vesicle uptake of both linoleic acid and glucose vary along the crypt-villus axis of the rabbit jejunum.

Alkaline Phosphatase↗

PubMed1994

Effect of isradipine on the formation and regression of fatty streaks in cholesterol fed rabbits.

OBJECTIVE: The aim was to determine whether the antiatherogenic effect of the calcium channel blocker isradipine on fatty streak formation was dependent upon a temporal relationship between cholesterol feeding and administration of the drug. METHODS: The study was done in New Zealand White rabbits fed a diet supplemented with cholesterol (2.5% w/w) for three weeks. Such a regimen results in loss of endothelium dependent relaxation and accumulation of cholesterol in the aorta four weeks later. The calcium antagonist isradipine was given in a dose of 0.25 mg.kg-1.d-1 at specified periods during the study to seven subgroups of animals: (1) standard diet + 2.5% cholesterol for three weeks; (2) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks; (3) standard diet + 2.5% cholesterol for three weeks followed by standard diet for 12 weeks; (4) standard diet + 2.5% cholesterol+isradipine for three weeks followed by standard diet alone for four weeks; (5) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks with isradipine given throughout the seven weeks; (6) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks with isradipine given during the final four weeks only; (7) standard diet + 2.5% cholesterol for three weeks followed by standard diet for 12 weeks with isradipine given during the final eight weeks. Aortic tissue was removed for measurement of cholesterol content, endothelium dependent relaxation to acetylcholine and the calcium ionophore A23187, and relaxant responses to sodium nitrite. Serum was collected for measurement of cholesterol and triglyceride concentration. RESULTS: When isradipine was given either during cholesterol feeding and continued for four weeks following it (subgroup 5) or during the four weeks following cholesterol feeding (subgroup 6), loss of endothelium dependent relaxation and the accumulation of cholesterol in the aorta was prevented. However, administration of isradipine during the period of cholesterol feeding alone (subgroup 4) was without effect. Also, administration of isradipine after lesions of fatty acid streak type were established appeared to have a favourable effect on removal of cholesterol from the aorta. CONCLUSIONS: Isradipine protects against the development of fatty streaks in rabbits fed a diet supplemented with 2.5% cholesterol. Administration of this drug after fatty streaks are formed also promotes their resolution.

Acetylcholine↗

PubMed1994

A dose-ranging study of ranitidine and its effect on intragastric and intra-oesophageal acidity in subjects with gastro-oesophageal reflux disease.

METHODS: This randomized, double-blind, single-centre, crossover study was designed to assess the effects of three regimens of ranitidine (150 mg b.d., 300 mg b.d. and 300 mg q.d.s.) and placebo on intra-oesophageal and intragastric pH in subjects with gastro-oesophageal reflux disease (GERD). Twenty-six subjects were screened, and 9 were evaluable by the admission criteria. These 9 subjects received each of the regimens for 72 h, and a wash-out period of at least 48 h followed each dosing period. Standard meals and beverages were provided. RESULTS: With increasing doses of ranitidine, 24-h intragastric mean H+ and integrated H+ fell, and the percentage of the time the pH was equal to or greater than 4 (% time pH > or = 4) rose: the minimum effective dose for these effects was ranitidine 300 mg daily. With increasing doses of ranitidine there was also a progressive decline in mean 24-h intra-oesophageal H+ and integrated H+, and increasing % time pH > or = 4. The minimal effective dose was 300 mg daily for intra-oesophageal mean H+ and integrated H+, and 600 mg for % time pH > or = 4. The minimal effective dose to decrease the number of reflex episodes was 1200 mg ranitidine. For the daytime upright position, a dose effect of increasing ranitidine was also seen, with minimal effective ranitidine doses of 300 mg for a decrease in mean H+, and 1200 mg for % time pH > or = 4. CONCLUSION: If these higher doses of ranitidine are confirmed to be more effective than the standard 150 mg b.d. regimen for the treatment of patients with gastro-oesophageal reflux disease, then the mechanism of this action probably relates to the lower exposure of the oesophageal mucosa to acid.

Adult↗

PubMed1994

Feeding trans fatty acids to rats has no effect on the intestinal uptake of glucose, fatty acids or cholesterol.

Trans fatty acids are produced in the manufacture of margarine, and these hydrogenated fatty acids may have a deleterious effect on the reduction in fasting levels of serum cholesterol anticipated from the feeding of cis polyunsaturated fatty acids. We undertook this study in rats to test the effect of feeding trans fatty acids on the intestinal uptake of glucose, fatty acids and cholesterol. Adult female Wistar rats were fed for 2 weeks semisynthetic, isocaloric diets containing no oleic acid (18:1), cis 18:1 or trans 18:1. There was no difference between the three dietary groups in the animals' food consumption or body weight gain. Rats fed trans 18:1 had an approximately 20% decline in the total weight of the ileum as compared with controls fed no 18:1, and therefore there was also a decline in the percentage of the ileal tissue comprised of mucosa. When comparing rats fed trans 18:1 with those fed cis 18:1 or no 18:1, there was no difference in the uptake of varying concentrations of D-glucose when expressed as nmol.100 mg tissue-1.min-1 or nmol.100 mg mucosal-1.min-1 for jejunum or for ileum. Also, there was no difference in the value of the maximal transport rate (Vmax), Michaelis constant (Km), or the contribution of passive uptake of glucose assessed with L-glucose. There was no diet-associated change in the jejunal or ileal uptake of a medium-chain length fatty acid (lauric acid), a long-chain length saturated fatty acid (palmitic acid), a monounsaturated fatty acid (oleic acid), two polyunsaturated fatty acids (linoleic and linolenic acids), or cholesterol. Thus, we conclude that 2 weeks' feeding of trans fatty acid to rats has no influence on the jejunal or ileal uptake of glucose, fatty acids or cholesterol.

Absorption↗

PubMed1994

Dietary omega-3 fatty acids and cholesterol modify desaturase activities and fatty acyl constituents of rat intestinal brush border and microsomal membranes of diabetic rats.

The diabetes-associated changes in intestinal uptake of nutrients are modified by isocaloric alterations in the type of dietary lipids, and is associated with alterations in the phospholipid and fatty acyl content of the intestinal brush border membrane. We wished to test the hypothesis that diet- and diabetes-associated changes in brush border membrane phospholipid fatty acids are due to alterations in the activity of enterocyte microsomal delta-5, delta-6 and delta-9 desaturases. Adult female Wistar rats were divided into two groups. In half of the animals, diabetes was produced with the injection of streptozotocin, and the other half of the animals served as nondiabetic controls. Both groups were raised on chow for two weeks and were then randomized to one of four semisynthetic diets for two weeks: beef tallow low in cholesterol (BT), beef tallow high in cholesterol (BTC), fish oil low in cholesterol (FO), or fish oil high in cholesterol (FOC). Feeding a high cholesterol diet increased the activity of jejunal enterocyte microsomal membrane activity of delta-5 and delta-9-desaturases when fed with FO in non-diabetic control rats, increased delta-5-desaturase in diabetic rats fed FO, and increased the ileal activity of delta-5 and delta-6-desaturases in control and diabetic animals fed FO. Dietary fatty acids, cholesterol and diabetes did not produce the changes in the amount of fatty acids in BBM phosphatidylcholine or phosphatidylethanolamine expected from the measured alterations in delta-5 (20:4 omega 6 and 20:5 omega 3), in delta-6 (18:3 omega 6 and 18:4 omega 3), or in delta-9 desaturase (18:1 omega 9 and 16:1 omega 7). In summary, 1) the activities of enterocyte microsomal membrane delta-5, delta-6 and delta-9-desaturases are independently influenced by dietary fatty acids or cholesterol, or by diabetes; 2) changes in dietary fatty acids, cholesterol and diabetes are associated with alterations in the fatty acyl constituents of brush border membrane phosphatidylcholine and phosphatidylethanolamine, but these fatty acyl changes are not explained on the basis of variations in the activities of the microsomal desaturases. Thus, the intestinal brush border membrane and the enterocyte microsomal desaturases are capable of adapting in response to changes in dietary lipids or diabetes, but the two alterations are not necessarily causally interrelated.

Animals↗

PubMed1994

Feeding an isocaloric omega-3 fatty acid diet reduces the brush border membrane vesicle uptake of glucose in streptozotocin-diabetic rats.

Glucose uptake is increased into the intestine of diabetic rats, and this adaptation can be modified further by manipulation of the type of fatty acids in the triglycerides in the diet. Jejunal brush border membrane vesicles were used to examine the uptake of D-glucose into the jejunum of non-diabetic control and streptozotocin-diabetic rats fed for two weeks in isocaloric semisynthetic diet enriched with saturated fat (beef tallow) or polyunsaturated omega-3 fatty acids (fish oil). The time-course of uptake of 100 microM glucose demonstrated an overshoot which peaked at approximately 30 seconds and declined thereafter to an equilibrium plateau. In concentration studies, glucose uptake was greater into brush border membrane vesicles of diabetic as compared with control rats. The maximal transport rate (Vmax) was increased approximately 9-fold in diabetics as compared with control rats fed beef tallow (p < 0.05), and was increased approximately 6-fold in diabetic rats fed fish oil. In diabetic rats, feeding fish oil reduced the value of the Vmax by approximately 50% as compared with diabetic rats fed beef tallow. Thus, the enhanced glucose uptake into BBM vesicles of streptozotocin-diabetic rats can be partially corrected by feeding an isocaloric semisynthetic diet enriched with polyunsaturated omega-3 fish oils.

Animals↗

PubMed1994

Intestinal absorption of vitamin A in streptozotocin-induced diabetic rats.

Diabetes mellitus is known to be associated with enhanced intestinal absorption of lipids. A validated in vitro technique was used to examine the uptake of (3H) retinol (a lipid soluble vitamin) into the jejunum and ileum of streptozotocin (STZ)-induced diabetic rats. In addition, availability of vitamin A in the plasma and liver of diabetics which were pair-fed to non-diabetic control rats was investigated. The relationship between the duration of incubation and retinol uptake was curvilinear in both the jejunum and the ileum, but no difference in intestinal uptake was observed between the two groups of animals. A linear relationship was noted between the concentration of retinol and uptake into both the jejunum and ileum. There was no difference in the uptake of retinol between the diabetic and control animals. The hepatic concentration of vitamin A also remained unaffected by diabetes as indicated by similar values found between pair-fed diabetic and non-diabetic control rats. Unlike the liver, plasma retinol level was decreased in the diabetic animals; this effect does not appear to be caused by any change in the intestinal absorption of the vitamin.

Animals↗

PubMed1994

The future of clinical investigators and of academic medicine in Canada.

Health is part of our own personal well-being, as well as that of the community and of our nation: clinician-investigators lead us forward in new medical developments, and may even be of assistance in developing innovative programs of cost control and outcome analysis. Canada now devotes close to 10% of its gross national product to health expenditures, second only to the United States, and yet there is still the widespread perception within this country that "there is not enough." The issues are how to do more with less, and how to recruit more clinician-investigators from the diminishing pool of potential recruitees. Academic medicine, with its research focus, is well-suited to bring together newer perspectives of education and health, and these clinician-investigators may improve major areas of our health care partnership.

Attitude↗

PubMed1993

Delayed effects of early nutrition with cholesterol plus saturated or polyunsaturated fatty acids on intestinal morphology and transport function in the rat.

This study was undertaken to test the hypotheses that: (1) the fatty acid and/or cholesterol composition of a nutritionally adequate isocaloric semisynthetic diet given in early life has lasting consequences for intestinal nutrient uptake and morphology; and (2) early life feeding experiences with diets of varying fatty acid or cholesterol composition influence the ability of the intestine to adapt to an altered nutrient uptake in later life. Weanling female Sprague-Dawley rats were fed nutritionally adequate isocaloric semisynthetic diets enriched with beef tallow, beef tallow plus 1% cholesterol, fish oil or fish oil plus 1% cholesterol. Animals fed fish oil or fish oil plus cholesterol for 11 weeks had a lower food intake but greater weight gain than animals fed beef tallow or beef tallow plus cholesterol. The age of the animals influenced lipid and hexose uptake. The uptake of these nutrients could also be changed by the addition of cholesterol to the diet. This cholesterol-related effect depended on the type of fat in the diet (saturated vs. polyunsaturated). These changes in nutrient uptake were associated with but not necessarily explained by alterations in food intake, body weight gain, intestinal mucosal weight or surface area. Finally, these changes in nutrient uptake and morphology may or may not be reversible. We speculate that dietary lipids may affect the ability of the intestine to adapt to an altered nutrient intake in later life.

Adaptation, Physiological↗

PubMed1993

Different mechanisms of uptake of stearic acid and cholesterol into rabbit jejunal brush border membrane vesicles.

The rate of uptake of stearic acid and cholesterol solubilized in taurocholic acid (TC) was examined in rabbit jejunal brush border membrane vesicles (BBMV). For stearic acid (18:0) or cholesterol there was an initial rapid rate of uptake, which reached a plateau within approximately 1 min and remained stable thereafter. At low concentrations of 18:0 and 20 mM, but not 2 mM, TC, there was a curvilinear relationship between the concentration of 18:0 and uptake, whereas the relationship between cholesterol uptake and concentration was linear over a wide range of values. When the concentration of TC was held constant at increasing concentrations of 18:0 or cholesterol, there was a linear increase in the rate of uptake. When the concentration of 18:0 or cholesterol was held constant and the concentration of TC was increased from 2 to 20 mM, the uptake of 18:0 declined, but the rate of uptake of cholesterol increased. When the concentrations of 18:0 plus TC, or cholesterol plus TC, were both increased in unison and their ratio was held constant, their rate of uptake increased. Thus, (i) BBMV may be used to assess the rate of uptake of lipids; (ii) the partitioning of cholesterol from bile acid micelles into the BBMV appears to be by way of "collision" of the cholesterol with the membrane. In contrast, the uptake of 18:0 from the micelle into the membrane vesicles may be by both the collision and the aqueous/dissociation models; and (iii) 18:0 uptake may be mediated by both a concentration-dependent and a concentration-independent component.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗