M. Keelan | University of Alberta (original) (raw)
Papers by M. Keelan
Emerging Infectious Diseases, 2005
The plasmid pVir may play a role in the virulence of Campylobacter jejuni, a leading cause of bac... more The plasmid pVir may play a role in the virulence of Campylobacter jejuni, a leading cause of bacterial gastroenteritis. The pVir plasmid was identified in 17% of 104 C. jejuni clinical isolates studied and was significantly associated with the occurrence of blood in patient stool, a marker of invasive infection. The pVir plasmid was not associated with greater occurrence of diarrhea, fever, pain, vomiting, or need for patient hospitalization. Isolates containing pVir were also associated with the presence of a tetracycline-resistance plasmid, but pVir did not transfer with tetracycline-resistance plasmids to recipient strains of C. jejuni. The association of pVir and bloody stool suggests that pVir may be clinically relevant in C. jejuni infections. C ampylobacter jejuni is a major foodborne pathogen and a leading cause of bacterial gastroenteritis (1,2). Infection with C. jejuni can result in a wide array of clinical symptoms, including diarrhea, fever, abdominal pain, and vomiting, as well as bloody stool with severe invasive infection (3). Various virulence factors, which allow for adherence, colonization, and invasion of the intestinal epithelium, have been proposed to contribute to the pathogenesis of C. jejuni (4). Potential virulence components include flagella (5,6), invasion proteins (7), and toxins (8,9). Although the genome of C. jejuni has been sequenced (10), its mechanisms of pathogenicity remain poorly understood (11). A number of bacterial enteric pathogens contain plasmids that contribute to pathogenesis, including Shigella sp. (12), Salmonella sp. (13), and enteropathogenic Escherichia coli (14). No evidence was seen for the involvement of plasmids in the virulence of C. jejuni until Bacon et al. (15) identified plasmid pVir in strain 81-176.
Diabetes research (Edinburgh, Scotland), 1990
This study was undertaken to determine the effects of feeding isocaloric semisynthetic diets high... more This study was undertaken to determine the effects of feeding isocaloric semisynthetic diets high in saturated fatty acids from beef tallow (BT) or high in polyunsaturated fatty acids from fish oil (FO), on the clinical control and the in vivo uptake of varying concentrations of D-glucose into perfused jejunal and ileal loops of intestine of rats with streptozotocin diabetes. Jejunal and ileal weights were greater in diabetic than in control rats fed BT or FO, but the percentage of the intestinal wall comprised of mucosa was lower, resulting in a similar mass of mucosa in diabetic and in control animals. Feeding FO increased the jejunal unstirred water layer (UWL) resistance in control rats but decreased ileal UWL in diabetic animals; UWL was lower in diabetic than in control rats fed FO but was similar in those fed BT. The passive permeability coefficient (Pd) of the intestine for L-glucose was greater in diabetic than in control rats fed BT but not in those fed FO; Pd was higher i...
Digestive Diseases and Sciences, 2003
The gastric pH-elevating effect of proton pump inhibitors such as omeprazole has been reported to... more The gastric pH-elevating effect of proton pump inhibitors such as omeprazole has been reported to be greater in the presence than in the absence of an H. pylori infection. It is unknown if this effect persists when a higher dose of omeprazole is taken. We undertook both 24-hr pH-metry and 24-hr aspiration studies in 12 H. pylori-positive patients with a history of duodenal ulcer (DU); (1) when not on omeprazole; (2) when on omeprazole 20 mg twice a day for 8 days; (3) two months after eradication of H. pylori and when not on omeprazole; and (4) after eradication of H. pylori and when on omeprazole twice a day. Eradication of H. pylori in DU results in lower mean and median pH; decreased percent pH > or = 3/ > or = 4, and greater median H+ after breakfast, after lunch, and overnight; and omeprazole appears to have less of a pH-elevating effect in the absence than in the presence of an H. pylori infection. The fall in gastric juice NH3 concentration as a result of eradicating H....
Digestive Diseases and Sciences, 2001
In the past year there have been many advances in the area of small bowel physiology and patholog... more In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) glucose absorption mediated by SGLT1 is controlled by mRNA abundance, as well as by posttranscriptional processes including protein trafficking; (2) inducers of cytochrome P-450 decrease glucose and fructose absorption and increase glucose consumption in the intestine; (3) the regulated release of nutrients from the stomach into the upper intestine ensures that the modest intestinal transport reserve capacity is not exceeded; (4) hepatocyte growth factor and short-chain fatty acids may enhance intestinal adaptation and prevent the atrophy seen when total parenteral nutrition is infused; (5) inhibitors of pancreatic lipase and phospholipase H2 may...
Diabetes research, 1992
Nutrient absorption is increased in rats with streptozotocin-induced diabetes mellitus (DM). This... more 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 bene...
Diabetes research, 1989
Short-term (two weeks) feeding of isocaloric diets supplemented with polyunsaturated fatty acids ... more Short-term (two weeks) feeding of isocaloric diets supplemented with polyunsaturated fatty acids (PUFA) is useful for the prevention or treatment of the enhanced uptake of glucose which occurs in rats with streptozotocin-induced diabetes, as compared with animals fed a diet supplemented with saturated fatty acids (SFA). The study was undertaken to compare the effects of long-term (seven weeks) feeding PUFA or SFA to diabetic rats. We have previously reported that diabetic animals fed PUFA had superior body weight gain, lower hemoglobin AlC values, lower plasma cholesterol and triglyceride levels, lower percentage decline in glucose (K value) following intravenous glucose tolerance testing, near-normal values of hepatic microsomal glucose-6-phosphatase activity and near-normal concentrations of 18:2(6) and 20:4(6) in liver microsomal phosphatidylcholine and phosphatidylserine. However, jejunal and ileal uptake of varying concentrations of glucose were similar in the three diet groups...
Glucose uptake is increased into the intestine of diabetic rats, and this adaptation can be modif... more 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...
Female Wistar rats were fed for 8 weeks a high polyunsaturated fatty acid diet (P) enriched with ... more Female Wistar rats were fed for 8 weeks a high polyunsaturated fatty acid diet (P) enriched with 18:2w6 and 18:3w3, or a high saturated fatty acid diet (S) enriched with 16:0, 18:0 and 18:1w9. There was a similar jejunal BBM fatty acid profile in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) composition in animals fed P. However, feeding S altered the fatty acid composition of BBM phospholipids: for PC, feeding S increased total monounsaturated fatty acids (e.g. 18:1(9)) and reduced total polyunsaturated fatty acids, especially the total w6 fatty acids. For PE, feeding S increased only the total monounsaturated fatty acids. The ratio of monounsaturated/saturated fatty acids was increased for PC and PE. Fatty acid changes were more pronounced in the jejunal than ileal BBM. It is concluded that alterations in dietary fatty acid saturation: (a) influences intestinal BBM phospholipid fatty acid composition; (b) these changes are quantitatively and qualitatively different fo...
Handbook of Nutrition in the Aged, Third Edition
American Journal of Physiology-Gastrointestinal and Liver Physiology
Adult female Sprague-Dawley rats were fed isocaloric semipurified diets containing a high content... more Adult female Sprague-Dawley rats were fed isocaloric semipurified diets containing a high content of either polyunsaturated (P) or saturated (S) fatty acids; these diets were nutritionally adequate, providing for all known essential nutrient requirements. On day 3 after beginning S or P, one group of animals was exposed to a single 6-Gy dose of abdominal radiation, and the other half was sham irradiated. S or P diets were continued for a further 14 days. Brush-border membrane purification and sucrase-specific activities were unaffected by diet or by abdominal irradiation. In rats fed P, irradiation was associated with an increase in jejunal brush-border membrane total phospholipid and the ratio of phospholipid to cholesterol; these changes were not observed in animals fed S. In irradiated rats, ileal brush-border membrane phospholipid per cholesterol was high in animals fed S compared with P. In irradiated animals fed P, there was reduced jejunal and ileal uptake of several medium- ...
American Journal of Physiology-Gastrointestinal and Liver Physiology
Intestinal absorption is altered in rats by diabetes and by dietary manipulation. For 5 wk rats w... more Intestinal absorption is altered in rats by diabetes and by dietary manipulation. For 5 wk rats were fed chow (C) or semisynthetic diets containing isocaloric amounts of a high content of either polyunsaturated (P) or saturated (S) fatty acids; then half were rendered hyperglycemic with streptozotocin while the remaining half served as nondiabetic controls. Studies were performed after a total of 8 wk on C, P, or S. Jejunal villous surface area was greater in diabetic rats than in control rats fed C or S, whereas the jejunal mucosal surface area was significantly greater in diabetic animals than in control animals only when they were fed S. Ileal mucosal surface area was similar in diabetic and in control rats fed C, S, or P; although ileal villous surface area was greater in diabetic than in control rats only when they were fed C. The jejunal and ileal uptake of varying concentrations of glucose and galactose was higher in diabetic rats than controls fed C or S. In contrast, the en...
American Journal of Physiology-Gastrointestinal and Liver Physiology
This study was undertaken to test the hypothesis that a change in the mother’s diet at the time o... more 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 ...
American Journal of Physiology-Gastrointestinal and Liver Physiology
Alterations in dietary lipids of the nursing mother result in variations in the lipid content of ... more Alterations in dietary lipids of the nursing mother result in variations in the lipid content of her milk. Maternal rats, weanlings, and 10-wk-old animals were fed chow or a semisynthetic isocaloric diet enriched with either saturated fatty acids (S) or polyunsaturated fatty acids (P). The jejunal and ileal in vitro uptake of varying concentrations (4-64 mM) of D-glucose and D-fructose or single concentrations of medium- and long-chain fatty acids and cholesterol were assessed in 18- to 21-day-old suckling rats, in 5-wk-old weanling animals, and in 12-wk-old young adults. The rate of uptake of D-glucose and D-fructose was unaffected in suckling rats by changing the lipid content of the diet of the nursing dams, whereas sugar uptake was greater in weanlings or adults fed S compared with P. The jejunal uptake of long-chain fatty acids was not influenced in suckling by changing the mother's diet, whereas in weanlings the uptake of 18:0 and 18:3 was higher with feeding S vs. P. In summary, jejunal uptake of cholesterol was greater in sucklings than in weanlings fed S vs. P. In suckling animals there are different adaptive patterns between the jejunum and the ileum and varying patterns of adaptation in response to alterations in the lipids in the diet when comparing suckling vs. weanling rats. These differences in nutrient uptake could not be explained by age- or diet-associated alterations in villus height. It is concluded that the age of the rat influences the intestinal adaptation of nutrient transport, which occurs in response to changes in dietary lipids, and dietary lipids fed to nursing dams and their offspring are important in the development of the intestine.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism
2-week Isoc~oric modifications in the dietary ratio of polyunsaturated/saturated fatty acids (P/S... more 2-week Isoc~oric modifications in the dietary ratio of polyunsaturated/saturated fatty acids (P/S) alters intestinal trmuport in rats. This study was undertaken to test the hypotheses that (1) the fatty acid composition of a nutritionally adequate diet in early life has lasting consequences for active and passive intestinal transport processes; and (2) early life feedin8 experiences with diets of varying fatty acid composition Influence the intestines' ability to adaptively up-or down-regulate Intestinal transport in later life. Female Sprague-Dawley rats were weaned onto S or P and were maintained on these diets for 2, 10 or 12 weeks. An in vitro uptake technique was used in which the bulk phase was vigorously stirred to reduce the effective resistance of the intestinal unstirred water layer. P decreased and S increased the uptake of glucose, and ~i~ effect was wowessive from 2 to 12 weeks. Switching from a P to an S diet decreased jejunal but increased Heal uptake of glucose, whereas switching from an S to a P diet was associated with a decline in both the jejunal and the Heal uptake of 8htcose. The Heal uptake of galactese increased as the animals grew on either P or S. SwlW.Mng from P to S resulted in a decline in ileal uptake of galactose, whereas the opposite effect was observed when switeMng from S to P. The effect of feeding P or S on hexoee uptake was influenced by the animals' dietary histo~. Ileal glucese and 8alactese uptake was lower in animals fed P at an early age (PSP) than in animals fed P for the first time in later life (SSP). Jejunal glucose and plactese uptake was also lower in animals fed S at an early age (SIPS) than in those fed S for the first time in later life (PPS). The alterations in the uptake of long-chain saturated and unsaturated fatty acids and cholesterol did not wowess with longer periods of feeding, and in the jejunum, lipid uptake did not change when switching from P to S or S to P. Early feeding with P (PSP vs. SSP) was associated with lower Jejunal ~ Of 18:3 and lower Ueal upteke of 12:0, whereas previous feeding with S (SPS vs. PPS) was associated with ~ Ileal uptake of cholesterol. The changes in uptake of hexoses and Itplds was not explained by differences in the ealmals' foed cmmmap41o~ body or int~tinal weight or mucosal surface area. Thus, (1) the effect of changes in the P/S ratio on hexose uptake are fast, wowesalve and irreversible, wl~as the general effect on lipid uptake is nonpNIp~ve and irreversible; and (2) the intestinal uptake of hexoses and some Iipids is subject to critical-period lnPmuming. This late effect of early nutrition signifies that the adaptability of intestinal transport is subject to dietary vadatiuu shoray after wean~g. lntrmluct~ Some physiological responses occur rapidly, reversibly and repeatedly, whereas other adaptive changes Abbt~'~tions: CPP, critial,.i~iod p~n8; p, diet high in polyunsaturated fat content; S, diet high in saturated fat content (see also Tabk i).
Canadian Journal of Gastroenterology
The recent advances in clinically important diseases of the small intestine have been reviewed ho... more The recent advances in clinically important diseases of the small intestine have been reviewed however, the basis for many of these clinical advances rests with important observations on alterations in the physiology of the small intestine, as well as mechanistic observations of alterations in small 1nrestinal function in models of human disease. In this review a summary of the past year's literature is presented which will draw attention to the considerable progress in small bowel physiology which will soon be translated into an improved understanding of the pathophysiology of a variety of intestinal disorders.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism
Chow-fed rats were given 15% ethanol in their drinking water for 4 weeks, and then for the next 2... more 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.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism
The rate of desaturation of linoleic acid (18:2(n - 6)) and level of arachidonic acid (20: 4(n - ... more 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.
Canadian Journal of Gastroenterology, 1997
The small bowel has undergone intense study. Part I of this two-part review of the small bowel fo... more The small bowel has undergone intense study. Part I of this two-part review of the small bowel focuses on gastrointestinal peptides; intestinal infections and human immunodeficiency virus; drugs; intestinal growth - mucosal proliferation and differentiation; nucleic acids, nucleotides and nucleosides; vitamins and minerals; Whipple's disease; radiation; and early development.
Aging of the Organs and Systems, 2003
Page 165. Aging of the Gastrointestinal System L. Drozdowski, M. Keelan, MT Clandinin and ABR Tho... more Page 165. Aging of the Gastrointestinal System L. Drozdowski, M. Keelan, MT Clandinin and ABR Thomson 519 Newton Research Building, University of Alberta, Edmonton, Alberta T6G 2C2, Canada Introduction All multicellular organisms undergo change with time. ...
Emerging Infectious Diseases, 2005
The plasmid pVir may play a role in the virulence of Campylobacter jejuni, a leading cause of bac... more The plasmid pVir may play a role in the virulence of Campylobacter jejuni, a leading cause of bacterial gastroenteritis. The pVir plasmid was identified in 17% of 104 C. jejuni clinical isolates studied and was significantly associated with the occurrence of blood in patient stool, a marker of invasive infection. The pVir plasmid was not associated with greater occurrence of diarrhea, fever, pain, vomiting, or need for patient hospitalization. Isolates containing pVir were also associated with the presence of a tetracycline-resistance plasmid, but pVir did not transfer with tetracycline-resistance plasmids to recipient strains of C. jejuni. The association of pVir and bloody stool suggests that pVir may be clinically relevant in C. jejuni infections. C ampylobacter jejuni is a major foodborne pathogen and a leading cause of bacterial gastroenteritis (1,2). Infection with C. jejuni can result in a wide array of clinical symptoms, including diarrhea, fever, abdominal pain, and vomiting, as well as bloody stool with severe invasive infection (3). Various virulence factors, which allow for adherence, colonization, and invasion of the intestinal epithelium, have been proposed to contribute to the pathogenesis of C. jejuni (4). Potential virulence components include flagella (5,6), invasion proteins (7), and toxins (8,9). Although the genome of C. jejuni has been sequenced (10), its mechanisms of pathogenicity remain poorly understood (11). A number of bacterial enteric pathogens contain plasmids that contribute to pathogenesis, including Shigella sp. (12), Salmonella sp. (13), and enteropathogenic Escherichia coli (14). No evidence was seen for the involvement of plasmids in the virulence of C. jejuni until Bacon et al. (15) identified plasmid pVir in strain 81-176.
Diabetes research (Edinburgh, Scotland), 1990
This study was undertaken to determine the effects of feeding isocaloric semisynthetic diets high... more This study was undertaken to determine the effects of feeding isocaloric semisynthetic diets high in saturated fatty acids from beef tallow (BT) or high in polyunsaturated fatty acids from fish oil (FO), on the clinical control and the in vivo uptake of varying concentrations of D-glucose into perfused jejunal and ileal loops of intestine of rats with streptozotocin diabetes. Jejunal and ileal weights were greater in diabetic than in control rats fed BT or FO, but the percentage of the intestinal wall comprised of mucosa was lower, resulting in a similar mass of mucosa in diabetic and in control animals. Feeding FO increased the jejunal unstirred water layer (UWL) resistance in control rats but decreased ileal UWL in diabetic animals; UWL was lower in diabetic than in control rats fed FO but was similar in those fed BT. The passive permeability coefficient (Pd) of the intestine for L-glucose was greater in diabetic than in control rats fed BT but not in those fed FO; Pd was higher i...
Digestive Diseases and Sciences, 2003
The gastric pH-elevating effect of proton pump inhibitors such as omeprazole has been reported to... more The gastric pH-elevating effect of proton pump inhibitors such as omeprazole has been reported to be greater in the presence than in the absence of an H. pylori infection. It is unknown if this effect persists when a higher dose of omeprazole is taken. We undertook both 24-hr pH-metry and 24-hr aspiration studies in 12 H. pylori-positive patients with a history of duodenal ulcer (DU); (1) when not on omeprazole; (2) when on omeprazole 20 mg twice a day for 8 days; (3) two months after eradication of H. pylori and when not on omeprazole; and (4) after eradication of H. pylori and when on omeprazole twice a day. Eradication of H. pylori in DU results in lower mean and median pH; decreased percent pH > or = 3/ > or = 4, and greater median H+ after breakfast, after lunch, and overnight; and omeprazole appears to have less of a pH-elevating effect in the absence than in the presence of an H. pylori infection. The fall in gastric juice NH3 concentration as a result of eradicating H....
Digestive Diseases and Sciences, 2001
In the past year there have been many advances in the area of small bowel physiology and patholog... more In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) glucose absorption mediated by SGLT1 is controlled by mRNA abundance, as well as by posttranscriptional processes including protein trafficking; (2) inducers of cytochrome P-450 decrease glucose and fructose absorption and increase glucose consumption in the intestine; (3) the regulated release of nutrients from the stomach into the upper intestine ensures that the modest intestinal transport reserve capacity is not exceeded; (4) hepatocyte growth factor and short-chain fatty acids may enhance intestinal adaptation and prevent the atrophy seen when total parenteral nutrition is infused; (5) inhibitors of pancreatic lipase and phospholipase H2 may...
Diabetes research, 1992
Nutrient absorption is increased in rats with streptozotocin-induced diabetes mellitus (DM). This... more 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 bene...
Diabetes research, 1989
Short-term (two weeks) feeding of isocaloric diets supplemented with polyunsaturated fatty acids ... more Short-term (two weeks) feeding of isocaloric diets supplemented with polyunsaturated fatty acids (PUFA) is useful for the prevention or treatment of the enhanced uptake of glucose which occurs in rats with streptozotocin-induced diabetes, as compared with animals fed a diet supplemented with saturated fatty acids (SFA). The study was undertaken to compare the effects of long-term (seven weeks) feeding PUFA or SFA to diabetic rats. We have previously reported that diabetic animals fed PUFA had superior body weight gain, lower hemoglobin AlC values, lower plasma cholesterol and triglyceride levels, lower percentage decline in glucose (K value) following intravenous glucose tolerance testing, near-normal values of hepatic microsomal glucose-6-phosphatase activity and near-normal concentrations of 18:2(6) and 20:4(6) in liver microsomal phosphatidylcholine and phosphatidylserine. However, jejunal and ileal uptake of varying concentrations of glucose were similar in the three diet groups...
Glucose uptake is increased into the intestine of diabetic rats, and this adaptation can be modif... more 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...
Female Wistar rats were fed for 8 weeks a high polyunsaturated fatty acid diet (P) enriched with ... more Female Wistar rats were fed for 8 weeks a high polyunsaturated fatty acid diet (P) enriched with 18:2w6 and 18:3w3, or a high saturated fatty acid diet (S) enriched with 16:0, 18:0 and 18:1w9. There was a similar jejunal BBM fatty acid profile in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) composition in animals fed P. However, feeding S altered the fatty acid composition of BBM phospholipids: for PC, feeding S increased total monounsaturated fatty acids (e.g. 18:1(9)) and reduced total polyunsaturated fatty acids, especially the total w6 fatty acids. For PE, feeding S increased only the total monounsaturated fatty acids. The ratio of monounsaturated/saturated fatty acids was increased for PC and PE. Fatty acid changes were more pronounced in the jejunal than ileal BBM. It is concluded that alterations in dietary fatty acid saturation: (a) influences intestinal BBM phospholipid fatty acid composition; (b) these changes are quantitatively and qualitatively different fo...
Handbook of Nutrition in the Aged, Third Edition
American Journal of Physiology-Gastrointestinal and Liver Physiology
Adult female Sprague-Dawley rats were fed isocaloric semipurified diets containing a high content... more Adult female Sprague-Dawley rats were fed isocaloric semipurified diets containing a high content of either polyunsaturated (P) or saturated (S) fatty acids; these diets were nutritionally adequate, providing for all known essential nutrient requirements. On day 3 after beginning S or P, one group of animals was exposed to a single 6-Gy dose of abdominal radiation, and the other half was sham irradiated. S or P diets were continued for a further 14 days. Brush-border membrane purification and sucrase-specific activities were unaffected by diet or by abdominal irradiation. In rats fed P, irradiation was associated with an increase in jejunal brush-border membrane total phospholipid and the ratio of phospholipid to cholesterol; these changes were not observed in animals fed S. In irradiated rats, ileal brush-border membrane phospholipid per cholesterol was high in animals fed S compared with P. In irradiated animals fed P, there was reduced jejunal and ileal uptake of several medium- ...
American Journal of Physiology-Gastrointestinal and Liver Physiology
Intestinal absorption is altered in rats by diabetes and by dietary manipulation. For 5 wk rats w... more Intestinal absorption is altered in rats by diabetes and by dietary manipulation. For 5 wk rats were fed chow (C) or semisynthetic diets containing isocaloric amounts of a high content of either polyunsaturated (P) or saturated (S) fatty acids; then half were rendered hyperglycemic with streptozotocin while the remaining half served as nondiabetic controls. Studies were performed after a total of 8 wk on C, P, or S. Jejunal villous surface area was greater in diabetic rats than in control rats fed C or S, whereas the jejunal mucosal surface area was significantly greater in diabetic animals than in control animals only when they were fed S. Ileal mucosal surface area was similar in diabetic and in control rats fed C, S, or P; although ileal villous surface area was greater in diabetic than in control rats only when they were fed C. The jejunal and ileal uptake of varying concentrations of glucose and galactose was higher in diabetic rats than controls fed C or S. In contrast, the en...
American Journal of Physiology-Gastrointestinal and Liver Physiology
This study was undertaken to test the hypothesis that a change in the mother’s diet at the time o... more 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 ...
American Journal of Physiology-Gastrointestinal and Liver Physiology
Alterations in dietary lipids of the nursing mother result in variations in the lipid content of ... more Alterations in dietary lipids of the nursing mother result in variations in the lipid content of her milk. Maternal rats, weanlings, and 10-wk-old animals were fed chow or a semisynthetic isocaloric diet enriched with either saturated fatty acids (S) or polyunsaturated fatty acids (P). The jejunal and ileal in vitro uptake of varying concentrations (4-64 mM) of D-glucose and D-fructose or single concentrations of medium- and long-chain fatty acids and cholesterol were assessed in 18- to 21-day-old suckling rats, in 5-wk-old weanling animals, and in 12-wk-old young adults. The rate of uptake of D-glucose and D-fructose was unaffected in suckling rats by changing the lipid content of the diet of the nursing dams, whereas sugar uptake was greater in weanlings or adults fed S compared with P. The jejunal uptake of long-chain fatty acids was not influenced in suckling by changing the mother's diet, whereas in weanlings the uptake of 18:0 and 18:3 was higher with feeding S vs. P. In summary, jejunal uptake of cholesterol was greater in sucklings than in weanlings fed S vs. P. In suckling animals there are different adaptive patterns between the jejunum and the ileum and varying patterns of adaptation in response to alterations in the lipids in the diet when comparing suckling vs. weanling rats. These differences in nutrient uptake could not be explained by age- or diet-associated alterations in villus height. It is concluded that the age of the rat influences the intestinal adaptation of nutrient transport, which occurs in response to changes in dietary lipids, and dietary lipids fed to nursing dams and their offspring are important in the development of the intestine.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism
2-week Isoc~oric modifications in the dietary ratio of polyunsaturated/saturated fatty acids (P/S... more 2-week Isoc~oric modifications in the dietary ratio of polyunsaturated/saturated fatty acids (P/S) alters intestinal trmuport in rats. This study was undertaken to test the hypotheses that (1) the fatty acid composition of a nutritionally adequate diet in early life has lasting consequences for active and passive intestinal transport processes; and (2) early life feedin8 experiences with diets of varying fatty acid composition Influence the intestines' ability to adaptively up-or down-regulate Intestinal transport in later life. Female Sprague-Dawley rats were weaned onto S or P and were maintained on these diets for 2, 10 or 12 weeks. An in vitro uptake technique was used in which the bulk phase was vigorously stirred to reduce the effective resistance of the intestinal unstirred water layer. P decreased and S increased the uptake of glucose, and ~i~ effect was wowessive from 2 to 12 weeks. Switching from a P to an S diet decreased jejunal but increased Heal uptake of glucose, whereas switching from an S to a P diet was associated with a decline in both the jejunal and the Heal uptake of 8htcose. The Heal uptake of galactese increased as the animals grew on either P or S. SwlW.Mng from P to S resulted in a decline in ileal uptake of galactose, whereas the opposite effect was observed when switeMng from S to P. The effect of feeding P or S on hexoee uptake was influenced by the animals' dietary histo~. Ileal glucese and 8alactese uptake was lower in animals fed P at an early age (PSP) than in animals fed P for the first time in later life (SSP). Jejunal glucose and plactese uptake was also lower in animals fed S at an early age (SIPS) than in those fed S for the first time in later life (PPS). The alterations in the uptake of long-chain saturated and unsaturated fatty acids and cholesterol did not wowess with longer periods of feeding, and in the jejunum, lipid uptake did not change when switching from P to S or S to P. Early feeding with P (PSP vs. SSP) was associated with lower Jejunal ~ Of 18:3 and lower Ueal upteke of 12:0, whereas previous feeding with S (SPS vs. PPS) was associated with ~ Ileal uptake of cholesterol. The changes in uptake of hexoses and Itplds was not explained by differences in the ealmals' foed cmmmap41o~ body or int~tinal weight or mucosal surface area. Thus, (1) the effect of changes in the P/S ratio on hexose uptake are fast, wowesalve and irreversible, wl~as the general effect on lipid uptake is nonpNIp~ve and irreversible; and (2) the intestinal uptake of hexoses and some Iipids is subject to critical-period lnPmuming. This late effect of early nutrition signifies that the adaptability of intestinal transport is subject to dietary vadatiuu shoray after wean~g. lntrmluct~ Some physiological responses occur rapidly, reversibly and repeatedly, whereas other adaptive changes Abbt~'~tions: CPP, critial,.i~iod p~n8; p, diet high in polyunsaturated fat content; S, diet high in saturated fat content (see also Tabk i).
Canadian Journal of Gastroenterology
The recent advances in clinically important diseases of the small intestine have been reviewed ho... more The recent advances in clinically important diseases of the small intestine have been reviewed however, the basis for many of these clinical advances rests with important observations on alterations in the physiology of the small intestine, as well as mechanistic observations of alterations in small 1nrestinal function in models of human disease. In this review a summary of the past year's literature is presented which will draw attention to the considerable progress in small bowel physiology which will soon be translated into an improved understanding of the pathophysiology of a variety of intestinal disorders.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism
Chow-fed rats were given 15% ethanol in their drinking water for 4 weeks, and then for the next 2... more 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.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism
The rate of desaturation of linoleic acid (18:2(n - 6)) and level of arachidonic acid (20: 4(n - ... more 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.
Canadian Journal of Gastroenterology, 1997
The small bowel has undergone intense study. Part I of this two-part review of the small bowel fo... more The small bowel has undergone intense study. Part I of this two-part review of the small bowel focuses on gastrointestinal peptides; intestinal infections and human immunodeficiency virus; drugs; intestinal growth - mucosal proliferation and differentiation; nucleic acids, nucleotides and nucleosides; vitamins and minerals; Whipple's disease; radiation; and early development.
Aging of the Organs and Systems, 2003
Page 165. Aging of the Gastrointestinal System L. Drozdowski, M. Keelan, MT Clandinin and ABR Tho... more Page 165. Aging of the Gastrointestinal System L. Drozdowski, M. Keelan, MT Clandinin and ABR Thomson 519 Newton Research Building, University of Alberta, Edmonton, Alberta T6G 2C2, Canada Introduction All multicellular organisms undergo change with time. ...