Gangliosides protect bowel in an infant model of necrotizing enterocolitis by suppressing proinflammatory signals.

OBJECTIVES: Necrotizing enterocolitis (NEC) has high morbidity in premature infants. Hypoxia-ischemia, infection, and enteral feeding are risk factors associated with NEC, whereas feeding human milk is protective. Vasoactive and inflammatory mediators in NEC remain elusive. Gangliosides are found in human milk and enterocyte membranes. An infant bowel model of NEC was developed to test the hypothesis that gangliosides modulate the inflammatory response to infection and hypoxia. PATIENTS AND METHODS: Viable, noninflamed bowel was obtained from 9 infants between 26 and 40 weeks' gestational age. Infant bowel was treated in culture with Escherichia coli lipopolysaccharide (LPS) and hypoxia in the presence or absence of preexposure to gangliosides. Bowel necrosis and production of nitric oxide, endothelin-1, serotonin, eicosanoids, hydrogen peroxide, and proinflammatory cytokines were measured. RESULTS: Ganglioside preexposure reduced bowel necrosis and endothelin-1 production in response to LPS. Gangliosides suppressed infant bowel production of nitric oxide, leukotriene B4, prostaglandin E2, hydrogen peroxide, interleukin-1beta, interleukin-6, and interleukin-8 in response to LPS exposure and hypoxia. CONCLUSIONS: A bowel protective effect of gangliosides is indicated by modulation of vasoactive mediators and proinflammatory signal suppression.

Competitive nature of the intestinal transport mechanism for cobalt and iron in the rat.

Dose- and time-response studies were performed in iron-loaded and iron-deficient rats in order to define, (a) the kinetics of absorption of cobalt and iron, (b) the nature of the inhibitory effect of one metal on the absorption of the other, and (c) the effect of variations in body iron stores on these processes. The duodenum was perfused for 5-90 min with labeled solutions containing 5.0 mM iron or 5.0 mM cobalt. In iron-loaded rats, the rate of cobalt absorption was constant for 90 min whereas the rate of iron absorption fell after 30 min. In comparison to these results, the rate of absorption of both metals was increased in iron deficiency, and was more rapid in the first 30 min than in the 30-90 min period.To determine the response to varying doses of metal, we perfused duodenal loops for 30 min with 0.1-10.0 mM solutions of either iron or cobalt. In both iron-loaded and iron-deficient groups, a greater proportion of the metals was absorbed from smaller than from larger doses. When iron and cobalt were perfused together in iron-deficient animals, cobalt competitively inhibited iron absorption, and conversely, iron reduced cobalt absorption. The apparent maximum transport velocity was similar for both metals, but the affinity for cobalt was greater than iron. The results suggest that the absorption of cobalt and iron is mediated by a transport system in which two processes operate simultaneously; the first is limited largely by the concentration of available metal in the lumen of the intestine, whereas the second process depends upon the activity of a mechanism which displays saturation kinetics and competitive inhibition. The former process prevails when iron stores are replete, whereas the latter predominates when there is a need for iron, such as in iron deficiency.

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.

Psychotherapies for hypochondriasis.

BACKGROUND: Hypochondriasis is associated with significant medical morbidity and high health resource use. Recent studies have examined the treatment of hypochondriasis using various forms of psychotherapy. OBJECTIVES: To examine the effectiveness and comparative effectiveness of any form of psychotherapy for the treatment of hypochondriasis. SEARCH STRATEGY: 1. CCDANCTR-Studies and CCDANCTR-References were searched on 7/8/2007, CENTRAL, Medline, PsycINFO, EMBASE, Cinahl, ISI Web of Knowledge, AMED and WorldCat Dissertations; Current Controlled Trials meta-register (mRCT), CenterWatch, NHS National Research Register and clinicaltrials.gov; 2. Communication with authors of relevant studies and other clinicians in the field; 3. Handsearching reference lists of included studies and relevant review articles, and electronic citation search in ISI Web of Knowledge for all included studies. SELECTION CRITERIA: All randomised controlled studies, both published and unpublished, in any language, in which adults with hypochondriasis were treated with a psychological intervention. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two authors using a standardised extraction sheet. Study quality was assessed independently by the two authors qualitatively and using a standardised scale. Meta-analyses were performed using RevMan software. Standardised or weighted mean differences were used to pool data for continuous outcomes and odds ratios were used to pool data for dichotomous outcomes, together with 95% confidence intervals. MAIN RESULTS: Six studies were included, with a total of 440 participants. The interventions examined were cognitive therapy (CT), behavioural therapy (BT), cognitive behavioural therapy (CBT), behavioural stress management (BSM) and psychoeducation. All forms of psychotherapy except psychoeducation showed a significant improvement in hypochondriacal symptoms compared to waiting list control (SMD (random) [95% CI] = -0.86 [-1.25 to -0.46]). For some therapies, significant improvements were found in the secondary outcomes of general functioning (CBT), resource use (psychoeducation), anxiety (CT, BSM), depression (CT, BSM) and physical symptoms (CBT). These secondary outcome findings were based on smaller numbers of participants and there was significant heterogeneity between studies. AUTHORS' CONCLUSIONS: Cognitive therapy, behavioural therapy, cognitive behavioural therapy and behavioural stress management are effective in reducing symptoms of hypochondriasis. However, studies included in the review used small numbers of participants and do not allow estimation of effect size, comparison between different types of psychotherapy or whether people are "cured". Most long-term outcome data were uncontrolled. Further studies should make use of validated rating scales, assess treatment acceptability and effect on resource use, and determine the active ingredients and nonspecific factors that are important in psychotherapy for hypochondriasis.

Comparison of the effects of fasting morning, fasting evening and fed bedtime administration of tenatoprazole on intragastric pH in healthy volunteers: a randomized three-way crossover study.

BACKGROUND: The effectiveness of proton pump inhibitors is influenced by meals and administration time. AIM: To compare the effects on intragastric acidity of times of dosing of tenatoprazole, a novel imidazopyridine-based proton pump inhibitor with a prolonged plasma half-life. METHODS: This randomized three-period crossover study included 12 Helicobacter pylori-negative healthy subjects, who received tenatoprazole 40 mg either fasting at 7.00 AM, fasting at 7.00 PM or fed at 9.30 PM for 7 days, with a 2-week washout between periods. Twenty-four hour intragastric pH was monitored on day 7 of each period. RESULTS: On day 7, median 24-h pH was 4.7, 5.1 and 4.7 after breakfast, dinner and bedtime dosing, respectively (P = 0.11), whereas night-time pH was 4.2, 5.0 and 4.4 (P = 0.13). The mean 24-h percentage of time over pH 4 was 62, 72 and 64 after breakfast, dinner and bedtime dosing, respectively (N.S.), and 54, 68 and 56 during night-time (P = 0.06). Nocturnal acid breakthrough incidence decreased from 100% at baseline to 83%, 55% and 75% after 7.00 AM, 7.00 PM and 9.30 PM dosing, respectively (P = 0.18), and its mean duration dropped from 6.2 to 2.8, 1.0 and 2.2 h, respectively (P < 0.05). CONCLUSION: Seven-day administration of tenatoprazole provides a prolonged duration of acid suppression, especially during the night-time, with little effect of food or time of dosing.

Validation of a 7-point Global Overall Symptom scale to measure the severity of dyspepsia symptoms in clinical trials.

BACKGROUND: Currently there is no consensus on the optimal method to measure the severity of dyspepsia symptoms in clinical trials. AIM: To validate the 7-point Global Overall Symptom scale. METHODS: The Global Overall Symptom scale uses a 7-point Likert scale ranging from 1 = no problem to 7 = a very severe problem. Validation was performed in two randomized-controlled trials (n = 1121 and 512). Construct validity: Global Overall Symptom was compared with the Quality of Life in Reflux And Dyspepsia, Gastrointestinal Symptom Rating Scale, Reflux Disease Questionnaire and 10 specific symptoms using Spearman correlation coefficients. Test-retest reliability: The Intraclass Correlation Coefficient was calculated for patients with stable dyspepsia defined by no change in Overall Treatment Effect score over two visits. Responsiveness: effect size and standardized response mean were also calculated. RESULTS: Construct validity: Change in Global Overall Symptom score correlated significantly with Quality of Life for Reflux And Dyspepsia, Gastrointestinal Symptom Rating Scale, Reflux Disease Questionnaire and specific symptoms (all P < 0.0002). Reliability: The Intraclass Correlation Coefficient was 0.62 (n = 205) and 0.42 (n = 270). Responsiveness: There was a positive correlation between change in Global Overall Symptom and change in symptom severity. The effect size and standardized response mean were 1.1 and 2.1, respectively. CONCLUSION: The Global Overall Symptom scale is a simple, valid outcome measure for dyspepsia treatment trials.

The prevalence of Barrett's oesophagus in a cohort of 1040 Canadian primary care patients with uninvestigated dyspepsia undergoing prompt endoscopy.

BACKGROUND: The prevalence of Barrett's oesophagus in patients undergoing gastroscopy may be influenced by possible referral bias. AIM: To present the prevalence of Barrett's oesophagus from the the Canadian Adult Dyspepsia Empirical Therapy Prompt Endoscopy study and to explore potential risk factors for its presence. METHODS: Patients had not been on treatment for dyspepsia for 2-4 weeks prior to endoscopy, which was performed within 10 working days of presentation. RESULTS: Barrett's oesophagus was endoscopically suspected in 53 of 1040 cases (5%) and histologically confirmed by the presence of intestinal metaplasia in 25 (2.4%). The prevalence of biopsy-proven Barrett's oesophagus was 4% in patients with dominant reflux-like symptoms. Sixty-four percent with confirmed Barrett's oesophagus had dominant reflux-like symptoms compared with 37% without Barrett's oesophagus. Barrett's oesophagus was more common in patients >50 years of age; 68% of cases were males. The mean duration of symptoms was 10 years, yet 16% had symptoms of <1-year duration. Endoscopic reflux oesophagitis was present in 68% of confirmed Barrett's oesophagus patients. CONCLUSIONS: Barrett's oesophagus is confirmed on biopsy in about half of endoscopically suspected Barrett's oesophagus patients. Barrett's oesophagus is more common in males, in those with dominant reflux-like symptoms, and in patients with a longer symptom history.

Intestinal uptake of hexoses and fatty acids in tumor-bearing rats.

An in vitro technique was used to examine the rate of uptake of varying concentrations of glucose, galactose, and a homologous series of saturated fatty acids into the jejunum of control rats and Noble rats bearing prostatic tumor variants of primary human prostatic adenocarcinoma 52. Both groups of animals were healthy, eating and gaining weight normally. The uptake of acetic and butyric acid was reduced in tumor-bearing rats, but the uptake of four medium chain-length fatty acids was unchanged. The similar value of the incremental change in free energy in the control and tumor-bearing animals indicates similar passive permeability properties of the jejunum in the two groups. The uptake of varying concentrations of glucose and galactose was similar in the control and in the tumor-bearing animals. It is concluded that there are only subtle changes in nutrient uptake in tumor-bearing rats that are eating and gaining weight normally. It is suggested that any alteration in nutrient absorption which might occur in the cachectic tumor-bearing animal is probably due to alterations in food intake or body weight, rather than due to a direct effect of the tumor on the intestine.

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

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

Use of percollTM in the isolation and purification of rabbit small intestinal brush border membranes.

(1) Intestinal absorption is altered under a variety of circumstances in health and disease and to determine a possible relationship between intestinal absorptive function and intestinal brush border membrane composition, we undertook the isolation and purification of rabbit jejunal and ileal brush borders, to allow further studies of their lipid composition under varied experimental conditions. (2) A modification of an established method (Schmitz, J., Preiser, H., Maestracci, D., Ghosh, B.K., Cerda, J.J. and Crane, R.K. (1973) Biochim. Biophys. Acta 323, 98-112) utilized CaCl2 aggregation and sequential centrifugation followed by purification of the brush border pellet (P2) at 27,000 X g on a PercollTM (Pharmacia) self-forming gradient. The PercollTM was removed by ultracentrifugation for 30 min at 100 000 X g, utilizing a batch rotor in the Beckman airfugeTM. (3) Pure brush border membrane vesicles were obtained and characterized by specific marker analysis and electron microscopy. Comparative marker analyses performed on P2 and final PercollTM preparations from animals showed that the purification achieved was 8-11-fold greater when compared to the original homogenates. Verification of purity was also demonstrated by the absence of DNA and very low levels of Beta-gluconridase and (Na+ + K+)-ATPase in the PercollTM preparations. (4) Comparative lipid analyses of P2 and final PercollTM preparations showed that levels of total phospholipid and free fatty acids were several-fold higher in the PercollTM preparations on a per mg protein basis. (5) A comparison of the activity of enzyme markers and the levels of total free fatty acids in P2 pellets obtained after Cacl2 and MgCl2 aggregation showed that CaCl2 aggregation gave the more consistently reproducible results. (6) Although standard procedures of membrane preparations not involving density gradient separation provide membranes of reasonable purity for the estimation of lipid components, we consider the final purification step of density gradient separation using PercollTM is essential for determining small quantitative changes which might occur in the membrane lipid composition under experimental conditions were intestinal absorptive function is altered.

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

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

Oleic acid uptake into rat and rabbit jejunal brush border membrane.

Oleic acid uptake was studied using adult rabbit and rat jejunal brush border membrane vesicles. There was a reduction of oleic acid uptake following trypsin-treatment. Opposing Na+/H+ gradients (inward Na+ and outward H+ gradients) increased oleic acid uptake by about 40%, as compared with only an inward Na+ gradient, only an outward H+ gradient, or the absence of either Na+ or H+ gradients. The addition of mucin further increased the enhanced uptake of oleic acid observed in the presence of opposing Na+/H+ gradients. Amiloride, an inhibitor of the Na+/H+ exchanger, reduced by about 40% the uptake of oleic acid into sheets of rat jejunum, and this inhibitory effect was observed over a range of rates of stirring of the bulk phase. In rabbit jejunal brush border membrane vesicles, amiloride reduced oleic acid uptake in the presence but not in the absence of opposing Na+/H+ gradients, with a Ki of approx. 36 microM. Thus, oleic acid uptake occurs largely by partitioning of the lipid into the brush border membrane, influenced by a process which involves the activation of the brush border membrane Na+/H+ exchanger.

Substrate specificity in the stimulation of intestinal ornithine decarboxylase activity by refeeding after starvation.

Jejunal loops in 3-day-fasted rats were perfused with hexoses and amino acids to test for their ability to stimulate intestinal ornithine decarboxylase activity. Intraluminal L- and D-glucose, galactose and 3-O-methylglucose were potent stimulants, while D-fructose and L-leucine were not. Intravenously infused D-glucose was also without effect. Induction of ornithine decarboxylase therefore appears to involve a receptor-mediated event which is probably located at the luminal cell surface.

Fish oil reduces cholesterol and arachidonic acid content more efficiently in rats fed diets containing low linoleic acid to saturated fatty acid ratios.

Rats were fed diets containing a high level of saturated fatty acids (hydrogenated beef tallow) versus a high level of linoleic acid (safflower oil) at both low and high levels of fish oil containing 7.5% (w/w) eicosapentaenoic and 2.5% (w/w) docosahexaenoic acids for a period of 28 days. The effect of feeding these diets on the cholesterol content and fatty acid composition of serum and liver lipids was examined. Feeding diets high in fish oil with safflower oil decreased the cholesterol content of rat serum, whereas feeding fish oil had no significant effect on the cholesterol content of serum when fed in combination with saturated fatty acids. The serum cholesterol level was higher in animals fed safflower oil compared to animals fed saturated fat without fish oil. Consumption of fish oil lowered the cholesterol content of liver tissue regardless of the dietary fat fed. Feeding diets containing fish oil reduced the arachidonic acid content of rat serum and liver lipid fractions, the decrease being more pronounced when fish oil was fed in combination with hydrogenated beef tallow than with safflower oil. These results suggest that dietary n-3 fatty acids of fish oil interact with dietary linoleic acid and saturated fatty acids differently to modulate enzymes of cholesterol and fatty acid metabolism.

Dietary cholesterol and/or n-3 fatty acid modulate delta 9-desaturase activity in rat liver microsomes.

delta 9-Desaturase activity and fatty acid composition of liver microsomal phospholipids in rats fed diets enriched with either saturated (hydrogenated beef tallow) or alpha-linolenic (linseed oil) or eicosapentaenoic and docosahexaenoic (fish oil) acids with or without 2% cholesterol supplementation were investigated. Both the linseed oil and the fish oil diets inhibited delta 9-desaturase activity in the rat liver microsomes. The inhibition was greater when feeding fish oil (90%) compared with the linseed oil (60%) diet. Dietary cholesterol feeding accelerated conversion of palmitic (16:0) to palmitoleic (16:1) acid, irrespective of the fatty acid supplement. Feeding the linseed oil diet decreased, while feeding the fish oil diet increased synthesis of the monounsaturated fatty acids of n-7 series (palmitoleic and vaccenic acid) and decreased 18:1(n-9) in microsomal membrane lipids when compared with animals fed beef tallow. Addition of 2% cholesterol to the otherwise low cholesterol diets led to accumulation of 16:1(n-7), and 18:1(n-9) in microsomal membranes. These results suggest that delta 9-desaturase activity is dependent on the cholesterol contents as well as the n-3 fatty acid content of microsomal membranes on which it is localized.

Hypotriglyceridemic effect of dietary n - 3 fatty acids in rats fed low versus high levels of linoleic acid.

The effect of dietary alpha-linolenic acid (linseed oil) or eicosapentaenoic acid (fish oil) on serum and liver triacylglycerol levels in rats fed diets rich in saturated fatty acids (hydrogenated beef tallow) versus high in linoleic acid (safflower oil) was examined. Feeding fish oil with hydrogenated tallow lowered the serum triacylglycerol concentration while the combination of fish oil and safflower oil failed to do so. Inclusion of fish oil in the hydrogenated tallow diet lowered the triacylglycerol constant in level tissue whereas inclusion of linseed oil had no significant effect. Feeding of linseed oil or fish oil in the safflower oil diet resulted in lowering of the liver triacylglycerol levels. These results suggest that dietary fish oil may have greater hypotriglyceridemic effects in individuals/populations eating diets high in saturated fats compared with those consuming mainly polyunsaturated vegetable oils rich in n - 6 fatty acids.

Evidence for critical-period programming of intestinal transport function: variations in the dietary ratio of polyunsaturated to saturated fatty acids alters ontogeny of the rat intestine.

2-week isocaloric modifications in the dietary ratio of polyunsaturated/saturated fatty acids (P/S) alters intestinal transport 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 feeding 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 this effect was progressive from 2 to 12 weeks. Switching from a P to an S diet decreased jejunal but increased ileal uptake of glucose, whereas switching from an S to a P diet was associated with a decline in both the jejunal and the ileal uptake of glucose. The ileal uptake of galactose increased as the animals grew on either P or S. Switching from P to S resulted in a decline in ileal uptake of galactose, whereas the opposite effect was observed when switching from S to P. The effect of feeding P or S on hexose uptake was influenced by the animals' dietary history: ileal glucose and galactose 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 galactose uptake was also lower in animals fed S at an early age (SPS) 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 progress 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 uptake of 18:3 and lower ileal uptake of 12:0, whereas previous feeding with S (SPS vs. PPS) was associated with lower ileal uptake of cholesterol. The changes in uptake of hexoses and lipids was not explained by differences in the animals' food consumption, body or intestinal weight or mucosal surface area.(ABSTRACT TRUNCATED AT 400 WORDS)

Alternate models for shared carriers or a single maturing carrier in hexose uptake into rabbit jejunum in vitro.

The uptake (tissue accumulation) of three hexoses into rabbit jejunum was measured in a flux chamber in conditions of effective stirring. Glucose uptake was inhibited by galactose or 3-O-methylglucose: 1-40 mM galactose caused a progressive decline in glucose uptake; 1-5 mM 3-O-methylglucose inhibited glucose uptake but higher concentrations of 3-O-methylglucose had no further effect. When 1-40 mM 3-O-methylglucose was added to glucose plus galactose there was a further decrease in the uptake of glucose; adding 1-40 mM galactose to glucose plus 3-O-methylglucose also produced a decrease in glucose uptake. Both glucose and 3-O-methylglucose inhibited uptake of galactose but the pattern of inhibition varied between the two sugars. The uptake of 3-O-methylglucose was also inhibited by glucose and by galactose, but the uptake of 3-O-methylglucose in the presence of either galactose or glucose was no further reduced by adding the third hexose. Graphical analysis and analysis by non-linear regression both showed that neither the single Michaelis-Menten function, nor the single Michaelis-Menten-plus-competitive-inhibition function was appropriate for any of these data. The results are consistent with the hypothesis that either there are multiple (at least three) intestinal carriers for hexoses; alternatively that there is a single carrier whose transport properties for the three hexoses change differentially during cell maturation and migration up the villus.

Fatty acid desaturation in the intestinal mucosa.

Information as to the ability of the enterocyte to desaturate fatty acids is lacking. This is important in understanding whether the source of intestinal arachidonic (20:4(n-6) acid is biliary or from de novo synthesis. Delta 9- and delta 6-desaturase enzymes were assayed in homogenates of rat jejunum, ileum and liver. Rat small intestine possesses desaturase activity to convert palmitic (16:0) to palmitoleic (16:1) and linoleic (18:2(n-6) to linolenic (18:3(n-6) acid. Enzyme activities were highest in liver relative to activity in jejunal and ileal homogenates. It is concluded that delta 9- and delta 6-desaturase activities may have an important role in determining physico-chemical properties and thus transport properties of enterocyte membranes.

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

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