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Biomedical subjects

M Keelan

Publications and source records attributed to M Keelan.

105 records · Page 6Linked to original sources
PubMed1986

The aging gut.

A spectrum of changes occurs in the function of the gastrointestinal tract throughout the life of the animal. With aging, there is a decline towards newborn levels of the villus surface area and brush border membrane markers, but the absorption of some nutrients continues to increase (such as glucose and vitamin), whereas the absorption of some nutrients falls (such as cholesterol) and fatty acids). Clearly there is a distinction between age-related alterations in intestinal form and function, and some of the enzyme- or carrier-mediated changes are substrate specific. With aging, the structure and brush border membrane composition of the intestine tends to regress towards newborn levels. It remains to be clarified whether these changes are a benefit to the animal, whether they represent a degeneration of normal function, and whether these changes are the cause or the effect of various age-related alterations in metabolic and physiological function.

Aging↗
PubMed1986

Dietary fat content influences uptake of hexoses and lipids into rabbit jejunum following ileal resection.

After 6 weeks' feeding on a high-fat or low-fat diet, the in vitro uptake of hexoses and lipids was measured in control rabbits with an intact intestinal tract, and in animals submitted to the surgical removal of the distal half of their small intestine. Jejunal villus height, villus surface area and mucosal surface area were higher in unresected control rabbits fed the low- as compared with the high-fat diet, whereas dietary fat content had no effect on villus morphology in resected animals. Mucosal surface area was similar in control and in resected animals fed the high-fat diet, but was lower in resected than in control animals fed the low-fat diet. The active and passive transport properties of the jejunum were influenced by dietary fat manipulation. These absorption changes were qualitatively and/or quantitatively different in animals with an ileal resection from those in animals with an intact small intestine. Dietary fat manipulation had a different effect on the uptake of each lipid probe. The effective resistance of the intestinal unstirred water layer also adapted to changes in the dietary content of fat, but the changes in uptake of hexoses, fatty acids and cholesterol cannot be simply explained by alterations in this diffusion barrier, or by changes in the villus morphology. These findings indicate the importance of dietary fat on villus structure and transport function and their adaptation to ileal resection.

Adaptation, Physiological↗
PubMed1986

Adaptation of colonic uptake of hexoses and lipids following ileal resection: effect of variations in the fat content of the diet.

This study was undertaken to determine the effect of varying the dietary composition of fat (corn oil and lard) on the colonic uptake of lipids (medium-chain-length fatty acids, cholesterol and decanol) and hexoses (D-glucose, galactose and 3-O-methyl glucose) in control rabbits with an intact intestinal tract, and in animals submitted 6 weeks previously to the surgical removal of the distal half of their small intestine. Food intake was similar in the control and resected animals fed the high-fat (HF) or the low-fat (LF) diet. Body weight gain was lower in control animals fed LF than HF, but was lower in resected animals fed HF than LF. Colonic adherent mucosal fluid volume was unaffected by diet or by ileal resection, but colonic weight was lower in resected than control animals fed LF. Colonic uptake of glucose and 3-O-methyl glucose but not galactose was changed by ileal resection and by dietary fat changes. Colonic uptake of fatty acids and cholesterol was also different in HF than LF, and in resected as compared with control animals, but these changes were not explained by variations in the effective resistance of the colonic unstirred water layer. Thus colonic transport function is altered by the manipulation of the dietary content of fat and by resection of the ileum.

Adaptation, Physiological↗
PubMed1986

Dietary fat selectively alters transport properties of rat jejunum.

The influence of dietary fatty acid composition on intestinal active and passive transport function, brush border membrane composition, and morphology was examined in rats. Animals fed a semisynthetic diet high in saturated fatty acids demonstrated enhanced in vitro jejunal uptake of decanoic, dodecanoic, palmitic, stearic, and linoleic acid, as well as cholesterol and chenodeoxycholic and taurochenodeoxycholic acid, as compared with uptake in animals fed a semisynthetic diet high in polyunsaturated fatty acids but equivalent in total content of fat and other nutrients, or as compared with Purina chow. Feeding the saturated fatty acid diet was also associated with reduced jejunal uptake of a range of concentrations of glucose, enhanced ileal uptake of leucine, unchanged uptake of galactose, and lower uptake of decanol. The semisynthetic diets did not alter brush border membrane protein, sucrase or alkaline phosphatase activities, cholesterol, or total phospholipids, although the percentage of jejunal amine phospholipids was higher than in rats fed chow. The morphologic differences between the jejunum and ileum were abolished in animals fed the high polyunsaturated fatty acid diet; in rats fed the high saturated fatty acid diet, there was reduced mean ileal villus height, width, thickness, surface area, cell size, and villus density, as well as reduced mucosal surface area. The changes in jejunal transport were not correlated with the alterations in morphology, unstirred layer resistance, food intake, or body weight gain. It is proposed that small changes in the percentage of total dietary lipids composed of essential and nonessential fatty acids (without concurrent alterations in dietary total fat, carbohydrate, or protein) influence active and passive intestinal transport processes in the rat.

Animals↗
PubMed1986

Effect of external abdominal irradiation on intestinal morphology and brush border membrane enzyme and lipid composition.

Previous studies have shown that external abdominal irradiation is associated with alterations in intestinal morphology and function. The activity of the jejunal brush border membrane (BBM) enzyme markers sucrase (S) and alkaline phosphate (AP) were not altered by 600 rad irradiation in the rat. In contrast, ileal BBM, AP, and AP/S were increased 3, 7/8, and 28 days postirradiation. The total lipid composition of the jejunal BBM was lower than in control animals only at 3 days postirradiation; this was due to a decrease in the total free fatty acid content. In addition to a lower total free fatty acid content, the ileal BBM contained an increased amount of total phospholipid (PL) which resulted in an increased phospholipid/cholesterol ratio at 3 days following irradiation. Variations in the BBM phospholipid composition occurred in both jejunum and ileum. In the jejunal BBM, the phospholipid composition changes did not alter the choline or amine phospholipid content; therefore, the choline/amine phospholipid ratio was unaffected by irradiation at 600 rad. In the ileal BBM, the phosphatidyl ethanolamine was increased at 3, 7/8, 14, and 28 days following irradiation. The choline/amine phospholipid ratio was not altered in the ileal BBM due to concomitant increases in lecithin content. Jejunal villus height, villus surface area, and the number of cells per villus were decreased at 3 days postirradiation, but increased by day 7/8 and 14 postirradiation to levels much higher than observed in control jejunal villi. The mucosal surface area was decreased at 3 and 7/8 days following irradiation but returned to control values by Day 14. Jejunal microvillus morphology was unaffected by irradiation. Few significant changes were observed in ileal villus morphology following irradiation at 600 rad. Ileal villus height, villus surface area, and mucosal surface area did not change, but the number of cells per villus initially decreased at 3 days and then increased beyond control values at 7/8 and 14 days postirradiation. Ileal microvillus height was significantly decreased only at 7 days postirradiation, while the number of microvilli per micron was increased only at 3 days postirradiation. This study suggests that changes in intestinal morphology and brush border composition may contribute to the altered passive permeation toward lipids which has been reported following abdominal radiation.

Abdomen↗
PubMed1985

Intestinal morphology, marker enzymes and lipid content of brush border membranes from rabbit jejunum and ileum: effect of aging.

Aging is associated with changes in the intestinal uptake of nutrients. This study was undertaken to determine whether the morphology, enzyme markers and the lipid content of the intestinal brush border membrane (BBM) was influenced by aging. There was an increase in the height of the jejunal villi and number of cells/villus, resulting in an age-related increase in the jejunal villus and mucosal surface area in young as compared with weanling rabbits. In mature 1-year-old animals, there was a decline in villus height, number of cells/villus, and mucosal surface area, so that the jejunal characteristics of the mature animals resembled those of the weanling rabbits. In the ileum, aging was associated with an increase (weanling vs. young), then a decrease (young vs. mature) in the height of the villi, and the number of cells/villus. Aging had no effect on the size of the villus cells. At all ages there was a direct positive relationship between the height of the villi and the mucosal surface area, and between villus surface area and sucrase activity. An established technique was used to purify rabbit BBM and to measure the BBM content of enzyme markers and lipids in weanling, young and mature animals. Both the BBM sucrase (S) and alkaline phosphatase (AP) increased in young as compared with weanling rabbits, and the ratio of AP/S remained unchanged. The S remained high in mature rabbits, but AP declined, so that AP/S fell. There was a positive linear correlation between S and villus surface area. In weanling rabbits, the total BBM phospholipid content and the ratio of total phospholipid/total cholesterol were lower in the ileum than in the jejunum. In the jejunal BBM of young animals, there was more total free fatty acids and cholesterol ester than in the weanling jejunum. The jejunal BBM total phospholipids and total cholesterol were higher in the mature than in the weanling animal jejunum when expressed as nmoles/mg protein, but the ratio of total phospholipid/total cholesterol was unaffected by aging. The greatest percentage of jejunal BBM phospholipid was comprised of lecithin and phosphatidyl ethanolamine. The increased BBM total phospholipid content in mature animals was associated with a higher amount and lower proportion of lecithin, but a higher proportion of sphingomyelin and phosphatidyl serine.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1985

Intestinal brush border membrane marker enzymes, lipid composition and villus morphology: effect of fasting and diabetes mellitus in rats.

Diabetes mellitus is associated with enhanced passive intestinal uptake of cholesterol and fatty acids. In order to determine the basis for these changes in intestinal permeability, the jejunal morphology and the lipid content of purified brush border membranes (BBM) were measured in fasted and fed control (C) and streptozotocin diabetic (DM) rats. There was no difference between C and DM in BBM sucrase or alkaline phosphatase; fasting had no effect on BBM enzymes in C, but in DM fasting was associated with increased sucrase activity per length of jejunum. In C fasting was associated with higher levels of BBM total phospholipid, lecithin, choline and amine phospholipids, whereas fasting in DM was associated with higher BBM cholesterol and lower free fatty acids. In the fasting DM, there was a greater villus and mucosal surface area than in the fasting C. A previous study demonstrated that with fasting in DM versus C, cholesterol uptake was unchanged, but when animals were fed, cholesterol and fatty acid uptake were greater into the jejunum of fed DM as compared with fed C. In the BBM of fed DM as compared with C, there was a significant increase in total phospholipid, lecithin, phosphatidyl ethanolamine, choline and amine phospholipids, and phospholipid/cholesterol ratio. Thus, (1) fasting is associated with changes in intestinal morphology, BBM lipids; (2) the effect of fasting is different in DM and C; (3) the enhanced uptake of lipids into the jejunum of fed diabetic rats is not due to changes in villus morphology, but may be due to alterations in the BBM phospholipids.

Alkaline Phosphatase↗
PubMed1985

Effect of chronic ethanol and food deprivation on intestinal villus morphology and brush border membrane content of lipid and marker enzymes.

Brush border membranes (BBM) were isolated from the jejunum and ileum of control, ad libitum (CAL); control, food-restricted (CFR); control, weight gain (CWG); and ethanol-fed (EF) rabbits. Jejunal alkaline phosphatase activity was similar among control groups, but higher in CAL than EF animals. Sucrase activity was higher in EF and CWG animals than in CAL and CFR. The alkaline phosphatase/sucrase ratio was lower in EF than control animals. Ileal enzyme marker activity was similar among EF and control animals. Sucrase (S) activity was lower in the ileum than in the jejunum. Jejunal free fatty acid and phospholipid/cholesterol (PL/C) were lower in EF than control animals, whereas ileal lipid content was generally similar among all animal groups. Total phospholipid content was similar between sites, but the cholesterol and free fatty acid content were lower in the ileum than the jejunum. The phospholipid/cholesterol ratio was increased only in the ileum of EF animals. The amount of lecithin was decreased in the jejunal BBM of EF animals resulting in a decreased choline/amine phospholipid ratio as compared with control animals. The ileal phospholipid composition was similar among all groups. A large increase in villus height is observed in the jejunum of EF animals. Villus surface area and mucosal surface area are altered with ethanol feeding and food deprivation. Thus, (i) there is a gradient of S and cholesterol between the BBM of jejunum and ileum; (ii) changes in food intake are associated with changes in the morphology as well as the enzyme marker and lipid content of BBM.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1985

Resection of rabbit ileum: effect on brush border membrane enzyme markers and lipids.

Alterations in transport function have been described 6 weeks after surgical resection of 50% of the distal small intestine. Previous studies demonstrated a modest increase in the jejunal uptake of medium chain length fatty acids following resection, while the uptake of many other lipids (cholesterol, bile acids, fatty alcohols, short and long chain length fatty acids) appears to be unaffected. Marked changes in the kinetic constants for the carrier-mediated uptake of four sugars and leucine were observed following resection, but the changes in transport were not associated with changes in the mucosal surface area. This study was undertaken to examine the possible adaptive mechanisms that occur with ileal resection in the rabbit. A 29% increase in the wet weight of jejunal mucosal scrapings and a 53% increase in jejunal brush border membrane (BBM) protein was observed following resection. The jejunal BBM sucrase (S) was unchanged following ileal resection, but alkaline phosphatase (AP) total activities were increased in the resected rabbits. This resulted in a 45% increase in the ratio of AP/S with resection. The lipid composition (total free fatty acids, total bile acids, total cholesterol, total phospholipids, individual phospholipids, and the ratio of total phospholipids/total cholesterol) of BBM was similar in control and resected rabbits. This suggests that quantitative rather than qualitative changes in the membrane composition may be responsible for the transport changes observed in resected animals.

Animals↗
PubMed1980

Aspergillus terreus infective endocarditis on a porcine heterograft valve.

We present the first reported case of Aspergillus endocarditis occurring on a porcine heterograft prosthesis and discuss the literature regarding both Aspergillus endocarditis and endocarditis on a porcine valve. A 65-year-old man underwent aortic valve replacement with a porcine heterograft. Several weeks later he exhibited signs of infection and then of valve failure. Upon removal, the porcine valve substance was found to be grossly infiltrated and destroyed by the Aspergillus organism. The porcine valve has an excellent reputation of being resistant to infection and relatively easy to sterilize by medical management alone. Several surveys attest to the low incidence of endocarditis. Because of our experience with the destruction caused by Aspergillus, however, and because antimicrobials generally fail to eradicate this organism, we urge prompt operation to remove the heterograft valve involved with infection by this organism. The valve diseased with Aspergillus should be replaced with a mechanical prosthesis. In the aortic position, extra-anatomic replacement should be considered to facilitate eradication of periannular infection postoperatively.

Aged↗
PubMedDate not supplied

Early nutrition with a high-cholesterol diet alters normal age-related changes in intestinal active transport.

This study was undertaken in the young and growing rabbit to establish the effect of feeding a high-cholesterol (2%) diet on the intestinal in vitro uptake of glucose, galactose, leucine, and cholic acid. Three groups of animals were fed standard Purina chow for 14, 28, and 42 days. A fourth group was fed chow for 14 days followed by high-cholesterol diet for 10 days followed by chow for 4 days. A fifth group was fed chow for 14 days followed by the high-cholesterol diet for 10 days followed by chow for 18 days. Short-term feeding with a high-cholesterol diet reversed the normal developmental decline in the jejunal uptake of some nutrients (e.g., glucose), enhanced the age-related uptake of other nutrients (e.g., galactose and leucine), but had no effect on others (e.g., jejunal uptake of cholic acid). Two weeks after stopping the high-cholesterol diet, there was enhanced jejunal uptake of all nutrients. Colonic uptake of glucose, galactose, and leucine was unresponsive to the effects of early development or of a high-cholesterol diet, whereas the colonic uptake of cholic acid did increase. This altered uptake is not explained by nonspecific mechanisms such as changes in body weight gain, intestinal mass, or effective resistance of the intestinal unstirred water layer. In summary, early feeding of rabbits for a short interval with a high-cholesterol diet is associated with transport changes that may persist, progress, or appear for the first time when the animals are switched from the high-cholesterol diet back to chow. Thus, early feeding with a high-cholesterol diet alters the normal development of intestinal transport function.

Aging↗
PubMedDate not supplied

Small bowel review: Part II.

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

Humans↗
PubMedDate not supplied

Nutritional effects of surgical and medical treatment for short bowel syndrome.

BACKGROUND: The choice of treatment options in short bowel syndrome (SBS) is hampered by a lack of comparative studies. This study uses a previously validated juvenile pig model of SBS to compare nontreated controls (C), surgical treatment with either proximal colon interposition (CI) or bowel lengthening (BL), with medical treatment with codeine and cimetidine (M). METHODS: Treatment was initiated 6 weeks after resection of 75% of the small bowel, and animals were followed until sacrifice at week 16. Feed intake and weight gain were monitored throughout; in vivo nutrient absorption, in vitro nutrient transport, sodium-glucose cotransporter activity, and intestinal morphology (gross and microscopic) were examined at the end of treatment. RESULTS: BL and M treatments resulted in improved rates of weight gain; this improvement was associated with improved absorption of dietary fat. The treatments did not affect carbohydrate or protein absorption in vivo. In vitro fatty acid absorption was not increased in any group. Active uptake of glucose was increased in the colon interposition group, but phlorizin binding (reflecting sodium glucose cotransporter activity) did not differ between groups. Gross serosal and microscopic mucosal surface areas increased in all groups; however, there were no significant differences between the treatment groups. CONCLUSIONS: These results demonstrate that bowel lengthening and medical treatment improved the rate of weight gain in this model of SBS. This appeared to be due to improvement in the absorption of dietary fat, which was not caused by alterations in in vitro uptake or mucosal surface area, suggesting these treatments have their affects by altering motility or intraluminal digestion. These findings suggest that these treatments are worthy of further study in treating patients (primary pediatric) with SBS.

Animals↗
PubMedDate not supplied

Lipids in total parenteral nutrition solutions differentially modify lipids in piglet intestinal brush border and microsomal membranes.

BACKGROUND: Fats in the diet modify the lipid composition and function of the intestinal brush border membrane (BBM) as well as the enterocyte microsomal membrane (EMM). METHODS: This study was undertaken in pigs to establish the effect of 3 weeks of total parenteral nutrition (TPN) on the fatty acids in the major phospholipids, (phosphatidylcholine [PC] and phosphatidylethenolamine [PE] in the jejunal and ileal BBM and EMM. RESULTS: In a comparison of 21-day-old milk-fed piglets and newborn animals, there were differences in the major fatty acids (palmitic, 16:0; stearic, 18:0; oleic, 18:1 omega 9, and linoleic acid, 18:2 omega 6) in PC and PE in BBM and EMM. Age-matched (3-week-old) animals fed a lipid-free glucose-containing TPN solution had different membrane fatty acids than did milk-fed piglets, or animals given a soybean oil-containing TPN solution for 21 days. Substituting fish oil or fish oil plus soybean oil altered BBM and EMM fatty acids, compared with the soybean oil-based TPN solutions. These changes varied between the class of phospholipids (PC vs PE), between intestinal site (jejunum vs ileum), and between the type of membrane (BBM vs EMM). CONCLUSIONS: The jejunum and ileum have distinctive control mechanisms for varying their membrane lipids in response to TPN. There is some postmicrosomal modification of lipids between the EMM and BBM. It remains to be established whether the lipid content of the membranes of other organs, and therefore their function, is modified by the lipid composition of parenterally infused lipids.

Aging↗