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Biomedical subjects

Alan B R Thomson

Publications and source records attributed to Alan B R Thomson.

At least 19 recordsLinked to original sources
PubMed2007

Nutritional modulation of the inflammatory response in inflammatory bowel disease--from the molecular to the integrative to the clinical.

Nutrient deficiencies are common in patients with inflammatory bowel disease (IBD). Both total parenteral and enteral nutrition provide important supportive therapy for IBD patients, but in adults these are not useful for primary therapy. Dietary intervention with omega-3 polyunsaturated fatty acids contained in fish oil may be useful for the care of IBD patients, and recent studies have stressed the role of PPAR on NFkappaB activity on the potential beneficial effect of dietary lipids on intestinal function.

Enteral Nutrition↗
PubMed2006

Aging and the intestine.

Over the lifetime of the animal, there are many changes in the function of the body's organ systems. In the gastrointestinal tract there is a general modest decline in the function of the esophagus, stomach, colon, pancreas and liver. In the small intestine, there may be subtle alterations in the intestinal morphology, as well as a decline in the uptake of fatty acids and sugars. The malabsorption may be partially reversed by aging glucagon-like peptide 2 (GLP2) or dexamethasone. Modifications in the type of lipids in the diet will influence the intestinal absorption of nutrients: for example, in mature rats a diet enriched with saturated as compared with polysaturated fatty acids will enhance lipid and sugar uptake, whereas in older animals the opposite effect is observed. Thus, the results of studies of the intestinal adaptation performed in mature rats does not necessarily apply in older animals. The age-associated malabsorption of nutrients that occurs with aging may be one of the several factors which contribute to the malnutrition that occurs with aging.

Aged↗
PubMed2006

Intestinal mucosal adaptation.

Intestinal failure is a condition characterized by malnutrition and/or dehydration as a result of the inadequate digestion and absorption of nutrients. The most common cause of intestinal failure is short bowel syndrome, which occurs when the functional gut mass is reduced below the level necessary for adequate nutrient and water absorption. This condition may be congenital, or may be acquired as a result of a massive resection of the small bowel. Following resection, the intestine is capable of adaptation in response to enteral nutrients as well as other trophic stimuli. Identifying factors that may enhance the process of intestinal adaptation is an exciting area of research with important potential clinical applications.

Adaptation, Physiological↗
PubMed2006

Intestinal sugar transport.

Carbohydrates are an important component of the diet. The carbohydrates that we ingest range from simple monosaccharides (glucose, fructose and galactose) to disaccharides (lactose, sucrose) to complex polysaccharides. Most carbohydrates are digested by salivary and pancreatic amylases, and are further broken down into monosaccharides by enzymes in the brush border membrane (BBM) of enterocytes. For example, lactase-phloridzin hydrolase and sucrase-isomaltase are two disaccharidases involved in the hydrolysis of nutritionally important disaccharides. Once monosaccharides are presented to the BBM, mature enterocytes expressing nutrient transporters transport the sugars into the enterocytes. This paper reviews the early studies that contributed to the development of a working model of intestinal sugar transport, and details the recent advances made in understanding the process by which sugars are absorbed in the intestine.

Animals↗
PubMed2006

Fatty acids in blood and intestine following docosahexaenoic acid supplementation in adults with cystic fibrosis.

UNLABELLED: The objective of this study was to investigate the effect of docosahexaenoic acid (DHA) supplementation on blood and intestinal DHA levels and lung function in mild/moderately affected adult CF patients with the DeltaF508 genotype. BACKGROUND: Cystic Fibrosis (CF) patients often present with plasma fatty acid levels indicating low levels of linoleic (18:2n-6) and docosahexaenoic (22:6n-3) acids and an increased level of arachidonic acid (20:4n-6). Improved dietary fat intake or reducing fat malabsorption with pancreatic enzymes has failed to normalize this biochemical deficiency of DHA. METHODS: Five CF patients, aged 18-43, received 70 mg of DHA/kg body weight/d for six weeks. At baseline and at six weeks a physical exam, lung function, 3-day dietary intake, duodenal mucosal biopsy and blood sample were assessed. The blood was analyzed for plasma vitamin A, D and E levels, liver function tests, clinical chemistry (CBC, differential and electrolytes). Plasma and red blood cell fatty acid levels were also analyzed. At three weeks, assessment included a physical exam, lung function test and fasting blood sample (vitamin levels, liver function and clinical chemistry only). RESULTS: Pre- and post-measurements were compared for the four subjects who completed the study. An increase in DHA content (% w/w) was observed in all phospholipid fractions of plasma, red blood cell and mucosal samples. No significant differences in vitamin levels, liver function or lung function were observed. CONCLUSIONS: The study proves the concept that an increase in tissue DHA levels in CF patients can be achieved by supplementing for six weeks with 70 mg/kg/d DHA.

Administration, Oral↗
PubMed2006

A combination of dexamethasone and glucagon-like peptide-2 increase intestinal morphology and glucose uptake in suckling rats.

OBJECTIVES: Glucagon-like peptide (GLP)-2 enhances nutrient uptake in adult animals. Glucocorticosteroids accelerate intestinal ontogeny and increase nutrient uptake in adult animals. We hypothesized that administering GLP-2 and dexamethasone (DEX) to suckling rats will enhance sugar uptake and that this effect persists into the postweaning period. METHODS: Suckling rats were treated for 10 days with GLP-2 (0.1 microg/g/d, twice daily), DEX (0.128 microg/g/d, once daily), GLP-2 + Dex (same doses as above), or placebo. The rate of intestinal uptake of glucose and fructose in sucklings (19-21 days old) and weanlings (49 days old) was assessed using an in vitro ring technique. RESULTS: DEX reduced body weight in weanlings, whereas GLP-2 + DEX prevented this effect. In sucklings, GLP-2 + DEX increased ileal villous height and jejunal and ileal villous width and crypt depth. In sucklings, GLP-2 + DEX increased the maximal transport rate (Vmax) for jejunal glucose uptake, whereas DEX reduced the ileal Vmax. In weanlings, GLP-2 + DEX increased jejunal villous height, whereas ileal villous width and crypt depth were reduced. DEX increased the ileal Vmax and apparent affinity constant for glucose in weanlings. CONCLUSIONS: The combination of these hormones may be useful in stimulating glucose uptake in the developing intestine, and giving DEX to sucklings may enhance glucose uptake in later life.

Animals↗
PubMed2006

Dietary gangliosides enhance in vitro lipid uptake in weanling rats.

BACKGROUND: The intestine adapts morphologically or functionally in response to environmental stimuli. Dietary lipids modify brush border membrane (BBM) permeability and nutrient transporter activities. Gangliosides (GANG) are glycolipids in human milk that are present only in low amounts in infant formula. Exogenous GANG are incorporated into cell membranes and increase their permeability. The objective of this study was to determine whether feeding a GANG-enriched diet alters in vitro intestinal lipid absorption. METHODS: Weanling rats were fed either (1) GANG-enriched diet; (2) diet enriched with polyunsaturated long-chain fatty acids; or (3) isocaloric control diet for 2 weeks, after which in vitro intestinal lipid uptake was measured. RESULTS: Feeding GANG did not alter weight gain or intestinal morphology. Enhanced uptake of stearic acid (18:0) in the ileum and stearic and linoleic acid (18:2) in the jejunum was not associated with a change in the abundance of the ileal lipid binding protein (ILBP), the intestinal fatty acid binding protein (I-FABP), or the liver fatty acid binding protein (L-FABP). CONCLUSION: We speculate that the enhanced uptake of long-chain fatty acids in weanling rats fed GANG may be caused by a modification in physical properties of the BBM.

Adaptation, Physiological↗
PubMed2005

Dietary gangliosides increase the content and molecular percentage of ether phospholipids containing 20:4n-6 and 22:6n-3 in weanling rat intestine.

This study was conducted to determine whether dietary ganglioside (GG) increases the content of ether phospholipids (EPL) in intestinal mucosa. Weanling Sprague-Dawley rats were fed a semipurified diet consisting of 20% fat as a control diet. Two experimental diets were formulated by adding either 0.1% (w/w fat) GGs (GG diet) or 1.0% (w/w fat) sphingomyelin (SM diet) to the control diet. Fatty acid methyl esters from the alkenylacyl, alkylacyl and diacyl subclasses of phospholipids were measured to determine total and molecular percentage of EPL comprising the choline phosphoglyceride (CPG) and ethanolamine phosphoglyceride (EPG) fraction. Animals fed the GG diet significantly increased total EPL content both in CPG (by 36%) and in EPG (by 66%), and the molecular percentage of EPL in CPG (by 76%) and in EPG (by 59%) compared to animals fed the control diet. Dietary GG-induced increase in EPL resulted in a higher level of polyunsaturated fatty acids (PUFA) specifically in 20:4n-6 and 22:6n-3 compared to control animals, leading to a decrease in the ratio of saturated fatty acids (SFA) to PUFA both in CPG and in EPG. Feeding animals the SM diet showed a higher level of EPL than control animals with a concomitant increase in 22:6n-3 in EPL. The present data demonstrate that dietary GG increases the content and composition of EPL containing PUFA in the weanling rat intestine.

Animals↗
PubMed2005

Dietary ganglioside decreases cholesterol content, caveolin expression and inflammatory mediators in rat intestinal microdomains.

Membrane microdomains rich in cholesterol and sphingolipids, including gangliosides (GGs), are known to be important regions for cell signaling and binding sites for various pathogens. Cholesterol depletion inhibits the cellular entry of pathogens and also reduces inflammatory signals by disrupting microdomain structure. Our previous study showed that dietary gangliosides increased total ganglioside incorporation while decreasing cholesterol in the intestinal mucosa. We hypothesized that diet-induced reduction in cholesterol content in the intestinal mucosa disrupts microdomain structure resulting in reduced pro-inflammatory signals. Male weanling Sprague-Dawley rats were fed semipurified diets for 2 weeks. Experimental diets were formulated to include either ganglioside-enriched lipid (GG diet, 0.02% gangliosides [w/w of diet] ) or polyunsaturated fatty acid (PUFA diet, 1% arachidonic acid and 0.5% docosahexaenoic acid, w/w of total fat), in a control diet containing 20% fat. Levels of cholesterol, GG, caveolin, platelet activating factor (PAF), and diglyceride (DG) were measured in the microdomain isolated from the intestinal brush border. The GG diet increased total gangliosides by 50% with a relative increase in GD3 and a relative decrease in GM3. Cholesterol content was also reduced by 23% in the intestinal microdomain. These changes resulted in a significant decrease in the ratio of cholesterol to ganglioside. The GG diet and the PUFA diet were both associated with reduction in caveolin, PAF, and DG content in microdomains, whereas no change occurred in the ganglioside profile of animals fed the PUFA diet. Dietary gangliosides decrease the cholesterol/ganglioside ratio, caveolin, PAF and DG content in microdomains thus exerting a potential anti-inflammatory effect during gut development.

Animals↗
PubMed2005

Lipid malabsorption persists after weaning in rats whose dams were given GLP-2 and dexamethasone.

Glucagon-like peptide-2 (GLP-2) enhances intestinal growth and absorption in mature animals, and glucocorticosteroids (GC) increase the sugar and lipid uptake in adult animals. However, the role of GC and GLP-2 in the ontogeny of lipid absorption is unknown. We hypothesized that GLP-2 and the GC dexamethasone (DEX), when administrated to rat dams during pregnancy and lactation, would enhance lipid uptake in the offspring. Rat dams were treated in the last 10 d of pregnancy and during lactation with GLP-2 [0.1 microg/g/d subcutaneous (sc)], DEX (0.128 microg/g/d sc), GLP-2 + DEX, or a placebo. Sucklings were sacrificed at 19-21 d of age, and weanlings were sacrificed 4 wk later. Lipid uptake was assessed using an in vitro ring uptake method. Although DEX and GLP-2 + DEX increased the jejunal mass, the jejunal lipid uptake was unchanged. In contrast, GLP-2, DEX, and GLP-2 + DEX reduced the ileal lipid uptake in suckling and weanling rats. This reduction was not due to alterations in intestinal morphology or to changes in fatty acid-binding protein abundance, but it was partially explained by an increase in the effective resistance of the intestinal unstirred water layer. In sucklings, DEX dramatically reduced the jejunal lipid uptake to levels similar to those seen in weanlings, such that the normal ontogenic decline in lipid uptake was not observed. Giving dams GLP-2 or DEX during pregnancy and lactation reduced lipid uptake in the offspring, and this persisted for at least 1 mon. The impact this may have on the nutritional well-being of the animal in later life is unknown.

Animals↗
PubMed2005

Tumor necrosis factor receptor gene polymorphisms in Crohn's disease: association with clinical phenotypes.

OBJECTIVES: Crohn's disease (CD) is a chronic multifactorial disorder with diverse clinical features that are influenced by a heterogeneous set of genetic factors. TNF-alpha/TNF receptor interactions play a pivotal role in the pathogenesis of the inflammatory response. Our purpose was to determine whether single nucleotide polymorphisms (SNPs) in the TNF receptors confer susceptibility to Crohn's disease and whether they are associated with clinical phenotype. METHODS: A cohort of 205 consecutively identified and unrelated patients with CD and 106 controls were recruited. Subjects were genotyped for polymorphisms in TNFRSF1A (position +36, -609), TNFRSF1B (+196, +1466), along with the three common CARD15 variants and phenotyped for disease behavior. Genotypic and allelic frequencies were compared between CD and controls and a logistic regression model was constructed to determine independent associations with specific clinical phenotypes. RESULTS: Only the TNFRSF1A +36 and TNFRSF1B +196 SNPs were associated with CD (p= 0.0019 and 0.034, respectively). The TNFRSF1A +36 mutation was negatively associated with stricturing disease phenotype (OR = 0.384; CI = 0.166-0.887). In contrast, the TNFRSF1B +196 was negatively associated with colitis (OR = 0.410; CI = 0.191-0.880). These associations were independent of CARD15 mutation status. Finally, TNFRSF1B +196 was negatively associated with surgery in CARD15 negative patients. CONCLUSIONS: These data constitute the first report of an association of TNFRSF1A and TNFRSF1B polymorphisms with CD in a Caucasian population and address the role of TNFR mutations in determining clinical heterogeneity in CD.

Adenine↗
PubMed2005

Treatment of suckling rats with GLP-2 plus dexamethasone increases the ileal uptake of fatty acids in later life.

Glucocorticosteroids such as dexamethasone (Dex) increase sugar and lipid uptake in adult animals and accelerate the development of the immature intestine. The effect of Dex on the ontogeny of lipid absorption is unknown. In adult rats, glucagon-like peptide-2 (GLP-2) has a trophic effect on the intestine and enhances nutrient absorption. This study was undertaken to determine the effect of GLP-2 and Dex on the intestine uptake of lipids in suckling rats and to determine whether any such effect persists into the postweanling period. Sixty-four suckling rats were randomized into four groups. They were treated from days 11 to 21 with GLP-2 (0.1 microg.g(-1).day(-1) sc), Dex (0.128 microg.g(-1).day(-1) sc), GLP-2 plus Dex (GLP-2 0.1 microg.g(-1).day(-1) sc + Dex 0.128 microg.g(-1).day(-1) sc), or placebo. One-half the pups were killed at days 19-21 ("sucklings"), and one-half were killed 4 wk later ("weanlings"). The rate of intestinal uptake of six fatty acids (12:0, lauric; 16:0, palmitic; 18:0, stearic; 18:1, oleic; 18:2, linoleic; and 18:3, linolenic) and cholesterol was assessed using an in vitro ring technique. GLP-2 had no effect on lipid uptake. Dex increased the uptake of 18:3 in sucklings, and the ileal uptake of 18:0 was increased in weanlings. The combination of GLP-2 plus Dex had no effect in sucklings and increased the ileal uptake of 12:0, 18:0, 18:1, 18:2, and 18:3 in weanlings. The enhanced uptake of fatty acids with GLP-2 plus Dex was not explained by alterations in the animals' body or intestinal weights, intestinal morphology, or intestinal- or liver-fatty acid binding proteins. Unlike adults, GLP-2 does not enhance lipid uptake in sucklings. Dex has a modest enhancing effect on selected fatty acid uptake both in sucklings as well as weanlings. GLP-2 plus Dex has an enhancing effect on the ileal uptake of fatty acids in weanlings 4 wk after their previous injection with GLP-2 plus Dex. It remains to be established what is the nutritional importance of this late effect of prior exposure to Dex or GLP-2 plus Dex on the intestinal uptake of lipids.

Absorption↗
PubMed2004

An isocaloric PUFA diet enhances lipid uptake and weight gain in aging rats.

Aging is associated with a change in the morphology and absorptive capacity of the small intestine. In young rats, feeding a semisynthetic diet containing saturated FA (SFA) increases nutrient uptake, as compared with an isocaloric diet containing polyunsaturated FA (PUFA). We tested the hypotheses that (i) aging is associated with a decline in lipid absorption in the Fischer 344 rat; (ii) this decline can be corrected by manipulating the fat composition of the diet; and (iii) the age- and diet-associated variations in lipid uptake are associated with changes in the ileal lipid-binding protein (ILBP) or the intestinal or liver FA-binding proteins (I- or L-FABP, respectively) in the cytosol of the enterocyte. In rats fed SFA or PUFA, aging was associated with a decline in the in vitro uptake of stearic acid (18:0) when expressed on the basis of intestinal or mucosal weight. In contrast, age had no effect on lipid uptake when expressed on the basis of serosal surface area, whereas lipid uptake increased with age when expressed on the basis of mucosal surface area. The age-associated variations in lipid uptake were not associated with changes in protein abundance and/or expression of ILBP, I-FABP, or L-FABP. In 24-mon-old rats, when uptake of lipids was expressed on the basis of mucosal surface area, feeding PUFA enhanced lipid uptake and body weight gain as compared with rats fed SFA. Future studies must determine whether the enhanced lipid uptake and body weight gain observed in older animals fed PUFA have any therapeutic benefit.

Aged↗
PubMed2004

The age-related decline in intestinal lipid uptake is associated with a reduced abundance of fatty acid-binding protein.

Aging is associated with changes in the absorptive capacity of the small intestine. We tested the hypotheses that (i) aging is associated with a decline in lipid absorption, and that (ii) this decreased lipid absorption is due to a decline in the abundance of mRNA and/or the enterocyte cytosolic intestinal FA-binding protein (I-FABP), the liver FA-binding protein (L-FABP), and the ileal lipid-binding protein (ILBP). In vitro uptake studies were performed on Fischer 344 rats at ages 1, 9, and 24 mon. Northern blotting (L-FABP, ILBP) and immunohistochemistry (I-FABP, ILBP) were performed. Aging was associated with decreased animal weights, but the surface area of the intestine was not significantly altered with age. The rates of ileal uptake of 16:0, 18:0, 18:1, and 18:2 were reduced by greater than 50% with aging when expressed on the basis of mucosal weight. This decline was not associated with reduced expression of mRNA for L-FABP or ILBP but was associated with a 50% decrease in the abundance of I-FABP and a 40% decrease in the abundance of ILBP. Thus, the decrease with aging in the ileal uptake of some FA when rates were expressed on the basis of mucosal weight was associated with a reduced abundance of I-FABP and ILBP.

Aging↗
PubMed2004

Age-associated changes in intestinal fructose uptake are not explained by alterations in the abundance of GLUT5 or GLUT2.

A reduction in nutrient absorption may contribute to malnourishment in the elderly. The objectives of this study were to determine the effects of aging on the absorption of fructose in rats, as well as the mechanisms of these adaptive changes. Male Fischer 344 rats aged 1, 9, and 24 months were fed standard Purina chow for 2 weeks (PMI #5001, PMI Nutritionals, Brentwood, MO). The uptake of (14)C-labeled D-fructose was determined in vitro using the intestinal sheet method. Intestinal samples were taken for RNA isolation and for brush border membrane (BBM) and basolateral membrane (BLM) preparation. Northern blotting, Western blotting, and immunohistochemistry were used to determine the effects of age and diet on GLUT5 and GLUT2. When expressed on the basis of intestinal or mucosal weights, aging was associated with a decline in jejunal and ileal fructose uptake, whereas jejunal fructose uptake was increased when expressed on the basis of serosal or mucosal surface area. The alterations in fructose uptake were not paralleled by changes in GLUT5 or GLUT2 abundance. These results indicate that 1) the effect of age on fructose uptake depends on the method used to express results, and 2) the age-associated changes in uptake are not explained by alterations in GLUT5 and GLUT2.

Aging↗
PubMed2004

Effect of Helicobacter pylori infection and NSAIDs on the risk of peptic ulcer bleeding.

Peptic ulcer bleeding remains an important emergency situation with a high incidence and carries significant morbidity and mortality. Current evidence suggests that H. pylori and NSAIDs increase the risk of peptic ulcer bleeding and these two factors seem to act independently. Testing for, and cure of, H. pylori infection is recommended in patients prior to the initiation of NSAID therapy and in those who are currently receiving NSAIDs and have a history of peptic ulcer bleeding. For patients who present with peptic ulcer bleeding but require NSAIDs long-term, H. pylori eradication therapy should be considered, followed by continuous proton pump inhibitor prophylaxis to prevent re-bleeding, regardless of which kind of NSAID (nonselective NSAID/coxib) is being prescribed. The success of eradication should always be confirmed because of the risk of peptic ulcer recurrences and bleeding complication.

Anti-Inflammatory Agents, Non-Steroidal↗