Jejunal brake

Optimal absorption of fat requires adequate time of contact with the absorptive sites of the small intestine. In order to prevent steatorrhea, intestinal transit must be slowed in response to the fat that has emptied into the small intestine. Intestinal transit is known to be inhibited by fat in the ileum via the ileal brake. This response has suggested that the regulation of intestinal transit is a function of the distal small intestine. However, clinical observations suggest that the ileal brake is not the only control mechanism for intestinal transit. In short bowel patients with resection of the ileum, the proportion of fecal fat recovery remained constant even after the fat intake was increased threefold. In these patients, optimal fat absorption based on the slowing of intestinal transit must have been triggered by an inhibitory mechanism located outside of the distal small intestine. To test the hypothesis that fat in the proximal small intestine inhibited intestinal transit, we compared intestinal transit during perfusion of the proximal half of the small intestine with 0 (buffer only), 15, 30, or 60 mM oleate in dogs equipped with duodenal and mid-intestinal fistula. Intestinal transit across a 150-cm test segment (between fistulas) was measured by counting for the recovery of a radioactive marker in the output of the mid-intestinal fistula during the last 30 min of a 90-min perfusion. We found that oleate inhibited intestinal transit in a load-dependent fashion (P<0.005). Specifically, while the mean cumulative recovery of the transit marker was 95.5% during buffer perfusion, the recovery decreased when 15 mM (64.3%), 30 mM (54.7%), or 60 mM oleate (38.7%) was perfused into the proximal half of the small intestine. We conclude that fat in the proximal small intestine inhibits intestinal transit as the jejunal brake.     

Intestinal Transit Is More Potently Inhibited by Fat in the Distal (Ileal Brake) than in the Proximal (Jejunal Brake) Gut

Fat in the proximal and distal gut inhibitsintestinal transit as the jejunal brake and the ilealbrake. It is unknown, however, whether the intestinaltransit response to fat in the proximal vs distal gut is different. Since surgical removal of thedistal small intestine induced faster transit andgreater steatorrhea than removal of the proximal smallintestine, we hypothesized that the ileal brakeinhibited intestinal transit more potently than thejejunal brake. In six dogs equipped with duodenal (10 cmfrom pylorus) and midintestinal (160 cm from pylorus)fistulas, we compared intestinal transit across an isolated 150-cm test segment (betweenfistulas), while 0 (buffer), 15, 30, or 60 mM oleate wasdelivered into either the proximal (between fistulas) orthe distal (beyond the midintestinal fistula) half of the gut. The half of the gut not receivingoleate was perfused with buffer. Buffer perfused intoboth the proximal and the distal half of the gut servedas the control. A meal was administered and diverted completely out of the duodenal fistula so thatthe studies were all done in the fed state. Intestinaltransit was measured by counting for the recovery of aradioactive marker from the temporarily diverted output of the midintestinal fistula. We foundthat (1) intestinal transit was inhibited more potentlyby oleate in the distal than in the proximal half of thegut (region effect; P < 0.01), (2) oleate inhibited intestinal transit in a load-dependent fashion(dose effect; P < 0.05), and (3) load-dependentinhibition of intestinal transit by oleate depended onthe region of exposure (interaction between load and region; P < 0.01). We conclude that intestinaltransit is more potently inhibited by fat-induced ilealthan jejunal brake.     

Electrical pacing accelerates intestinal transit slowed by fat-induced ileal brake

Previous studies on intestinal electrical stimulation were aimed at achieving a delay in intestinal transit. The aim of this study was to test the hypothesis that the physiological slowing of intestinal transit by the fat-induced ileal brake might be accelerated with intestinal electrical stimulation. This study was performed in five dogs prepared with eight serosal electrodes in the jejunum and two chronic intestinal fistulas located in the duodenum and at the midpoint of the small intestine. To slow transit by triggering the ileal brake, oleate was delivered into the distal half of the gut while buffer was perfused into the proximal half of the gut. Intestinal transit between the fistulas was measured by the recovery of [^99mTc]DTPA. To test for the effect of pacing, transit was compared with vs. without continuous forward electrical stimulation (frequency: 24 cycles/min; pulse duration: 50 msec, pulse amplitude 1–3 mA). Electrical stimulation completely entrained intestinal pacesetter potentials as measured from the seven recording electrodes distal to the pacing electrode. A substantial and significant increase in intestinal transit was observed with intestinal electrical stimulation with the percentage of marker recovery increasing from 19.2 ± 9.3% to 84.6 ± 11.3% (P < 0.01). In conclusion, intestinal electrical stimulation accelerates intestinal transit slowed by ileal brake.     

Alterations in rat intestinal transit by morphine promote bacterial translocation

Translocation of enteric microorganisms from the intestinal tract to extraintestinal sites has been proposed as an early step in the development of gram-negative sepsis. This study examined the role of altered bowel transit in influencing intestinal bacteriostasis and bacterial translocation using morphine as a pharmacologic inhibitor of such transit. In the first experiment, either normal saline (N=8) or morphine sulfate (20 mg/kg;N=8) was injected subcutaneously. Two hours later, morphine (7.5 mg/kg) was infused subcutaneously for an additional 22 hr; control animals received saline alone. After completion of this regimen, a volume of 0.2 ml of 2.5 mM FITC dextrans (10,000 daltons) were injected intraduodenally in each group. The bowel was removed 25 min later, divided into 5-cm segments, and the content of dextrans measured. Small bowel propulsion was expressed as the geometric center of the distribution of dextrans throughout the intestine (in percentage length of small bowel). Gut propulsion was significantly reduced after morphine treatment as compared to controls (32.8±8.2% vs 55.8±4.0%;P<0.01). In 16 additional rats, saline or morphine was again administered as described. After 24 hr, samples were obtained from the mesenteric lymph node (MLN) complex, blood, spleen, liver, duodenum, jejunum, ileum, and cecum for standard bacteriology. The bacterial counts increased significantly in each intestinal segment following morphine treatment. Microorganisms translocated to the MLN complex in 5, and to distant sites in four of eight morphine-treated animals, respectively. Translocation to the MLN complex occurred in only one of eight controls (P<0.05); no translocation to distant sites occurred in control animals. We conclude that the morphine-induced prolongation in bowel transit promotes bacterial translocation secondary to an overgrowth of enteric bacteria in the intestinal lumen.Supported by NIH grant GM 38529 and the DFG grant Ru 387/1-2.     

Lipids infused into the jejunum accelerate small intestinal transit but delay ileocolonic transit of solids and liquids

Background—Various nutrients areknown to alter small intestinal motility patterns although their effecton transit of fluids and solids in man is not clear.
Aims—To determine small intestinaltransit of solids and liquids during perfusion with lipids, protein,and non-energy solutions.
Methods—Twenty eight healthyvolunteers received a jejunal infusion (1 ml/ minute for 30 minutes) ofone of four solutions: a lipid or a protein solution (4.18 J/ml), anon-absorbable electrolyte solution containing polyethylene glycol, or0.9% sodium chloride. As solid phase marker 1 g of amberlite resinpellets labelled with ¹¹¹InCl₃ was added;^99mTc DTPA was used as a fluid phase marker. Images wereobtained on a gamma camera at 10 minute intervals for four hours oruntil all radiolabel was detected in the colon.
Results—Intestinal transit ofsolids and liquids from the duodenojejunal junction to the caecum wassimultaneous, and independent of the energy content of the solutioninfused. Lipid infusion accelerated transit through the small intestinebut delayed transport of chyme along the ileocolonic junction. Afterprotein small intestinal transit was slowest; ileocolonic transit onthe other hand was fastest with protein. Transit of the non-energysolutions was in between that of the nutrient solutions.
Conclusions—Transit times throughthe small intestine and the ileocolonic junction were influenced by theluminal contents. In the small intestine fat induced significantlyfaster transit compared with proteins, but delayed ileocolonic transit.Once in the small intestine, solids and liquids transit the small bowel together, independent of the luminal content.

Keywords:small intestine; ileocolonic junction; transit; nutrients; lipids; proteins

     

Centrally administered neuropeptide Y (NPY) inhibits gastric emptying and intestinal transit in the rat

Neuropeptide Y is distributed abundantly not only in the brain, but also in the gastrointestinal tract and suppresses intestinal muscle contraction in isolated muscle preparations. The purpose of the present study was to determine whether centrally administered neuropeptide Y modulated gastric emptying and intestinal transit in conscious rats. Graded doses of neuropeptide Y were administered intracisternally 1 min before ingestion of test meals through an oral tube. Four hours after ingestion of 60 Amberlite pellets, the rats were sacrificed and residual pellets in the stomach and the small intestine segments were counted to calculate the solid meal transit rate. The liquid meal transit rate was calculated 1 hr after 0.07% phenol red ingestion by determining the residual phenol red in the stomach and the small intestine segments. Neuropeptide Y elicited potent suppression of gastric emptying and intestinal transit of both solid and liquid meals. Pretreatment with propranolol antagonized, whereas phentolamine did not affect, the suppressive effect of central neuropeptide Y. Although carbachol blocked the effects of neuropeptide Y, neither atropine nor hexamethonium altered the actions of neuropeptide Y. In conclusions, centrally administered neuropeptide Y strongly inhibited gastrointestinal transit by stimulating a beta-adrenergic pathway.     

Stimulation of intestinal lipase secretion by porcine cholecystokinin in the hagfish, Eptatretus stouti.

Mammalian gastrointestinal hormones and related peptides were tested in hagfish for effects on gallbladder muscle contraction in vivo and in vitro, intestinal muscle contraction in vitro, and intestinal release of lipase and alkaline phosphatase in vivo. No stimulation of contraction of gallbladder or intestinal muscle was observed in response to porcine cholecystokinin-33 (CCK-33), porcine gastrins-17-I and -II, caerulein, or pentagastrin. CCK-33 stimulated release of lipase but not of alkaline phosphatase from the hagfish intestine. Porcine secretin, vasoactive intestinal peptide, and glucagon had no effect on enzyme release. It is suggested that stimulation of pancreatic enzyme release arose earlier than stimulation of intestinal brush border enzyme release or stimulation of gallbladder muscle contraction as an action of CCK in vertebrates.     

Nitric oxide synthase inhibition results in immediate postoperative recovery of gastric, small intestinal and colonic motility in awake rats

Background Nitric oxide (NO) is known to inhibit gastrointestinal motility. However, no detailed analysis of gastric, small intestinal and colonic motor effects, including effects on contraction frequency, has, as yet, been reported after NO inhibition in awake rats. We therefore investigated the effects of NO synthase inhibition on gastric, small intestinal and colonic motility in awake rats under baseline conditions and in a postoperative ileus model.Methods In Sprague–Dawley rats, strain gauge transducers were sutured either to the gastric corpus, the small intestine or the colon. After 3 days, l-NMMA (NO synthase inhibitor), d-NMMA or vehicle was given i.v., while the motility was recorded continuously. In addition, postoperative gastric, small intestinal or colonic motility was investigated after l-NMMA or vehicle treatment prior to abdominal surgery. The motility index, the contraction amplitude, the area under the contraction amplitude and the contraction frequency were analysed.Results l-NMMA decreased gastric motility to 60±8% for about 15 min, but continuously increased small intestinal motility to 221±22% and colonic motility to 125±7% compared to baseline (baseline=100%; p<0.01 for all comparisons). l-NMMA increased the contraction frequency throughout the gastrointestinal tract (stomach, 13±2%; small intestine, 8±1%; colon, 16±5%; p<0.01 vs. baseline for all comparisons). l-NMMA injection prior to surgery did not prohibit intraoperative inhibition of gastrointestinal motility, but did result in immediate recovery of gastric, small intestinal and colonic motility postoperatively (l-NMMA vs. vehicle, 0–60 min postoperatively; stomach, 90±9% vs. 53±3%; small intestine, 101±5% vs. 57±3%; colon, 134±6% vs. 60±5%; p<0.01 for all comparisons; no significant difference between preoperative baseline motility and l-NMMA treated rats postoperatively).Conclusions Under baseline conditions, endogenous NO inhibits small intestinal and colonic motility and gastric, small intestinal and colonic contraction frequency in awake rats. In the early postoperative period, endogenous NO is a major inhibitory component that seems to constitute the common final pathway of mediators and the neural pathways inhibiting gastrointestinal motility in rats.     

Morphine tissue levels and reduction of gastrointestinal transit in rats. Correlation supports primary action site in the gut

Overnight-fasted male rats given a single dose of tritium-labeled morphine either intraperitoneally or intravenously were fed a charcoal test meal by stomach tube. The drug remaining in tissues was assayed by liquid scintillation counting of thin-layer chromatograms from homogenates, and gastrointestinal transit was tested by measuring the portion of the small intestine traversed by charcoal in 5 min. Morphine, 0.15 mg/kg, given intraperitoneally either 10 min or 30 min before testing substantially reduced gastrointestinal transit (to 23% and 55% of drug-free controls, respectively), and produced maximum drug levels 5 min after administration in small intestine longitudinal muscle with attached myenteric plexus (500 +/- 42 ng/g, mean +/- SE, n = 4). Intact small intestine, plasma, and brain, respectively, contained decreasing drug concentrations that, in the latter, never exceeded 2%-3% of that in longitudinal muscle. Rats receiving 0.15 mg/kg morphine intravenously presented only minor and short-lived inhibition of gastrointestinal transit that was significantly below (approximately 35%) that of drug-free controls at 10 min, but not 30 min, after drug administration. Morphine levels in the brain and plasma of these rats were up to five times higher, and in the intact small intestine longitudinal muscle were up to 20 times lower than in intraperitoneally treated rats. Morphine concentration in the tissues assayed was plotted against the effect on gastrointestinal transit at the same interval for individual rats regardless of dose, administration route, and observation time: data analysis, in small intestine longitudinal muscle, but not in the brain or plasma, indicated a highly significant correlation and fitting of computer-generated curves described by a currently accepted equation according to the receptor occupation theory of drug response. In view of these findings, and of the complete prevention by the "peripherally selective" narcotic antagonist N-methyl naloxone of gastrointestinal transit inhibition after an intravenous analgesic dose of morphine (1 mg/kg), the investigated animal model is consistent with the primary role of a gut-located action site in opiate-induced constipation.     

Stress-induced changes in intestinal transit in the rat: a model for irritable bowel syndrome

Stress in humans commonly results in gastrointestinal dysfunction, which is characterized by its symptomatology because the etiology is completely unknown. We developed an animal model in which to study the effects of stress on the gastrointestinal tract, and characterized the model as a stressor by evaluating endocrine and analgesic responses to mild restraint. Mild restraint (wrap restraint) elevated plasma levels of adrenocorticotropic hormone and beta-endorphin, and caused analgesia. The different regions of the gastrointestinal tract responded differently to the stress stimulus. Gastric emptying was not affected, small intestinal transit was inhibited, and large intestinal transit was stimulated by stress, and there was an associated increase in fecal excretion. Wrap-restraint stress did not result in the formation of ulcers. There was a strong correlation between stress-induced adrenocorticotropic hormone release and stress-induced intestinal dysfunction over a 24-h period that suggested a circadian influence. However, neither exogenous adrenocorticotropic hormone nor beta-endorphin had any effect on intestinal transit. Furthermore, neither adrenalectomy nor hypophysectomy prevented the response of the intestine to stress, suggesting that neither adrenal nor pituitary-derived factors are responsible for mediating the effects of stress on the gut. We conclude that wrap-restraint stress produces different effects on different regions of the intestine, suggesting that the small and large intestines are independently regulated and can respond differently to different stimuli. There were similarities between the intestinal effects of wrap-restraint stress in rats and intestinal symptoms associated with stress and irritable bowel syndrome in humans. Therefore, wrap restraint may be an appropriate animal model in which to study stress-related intestinal dysfunction. The mechanisms by which stress affects intestinal transit are still unresolved; however, the intestinal effects of stress are not mediated by either pituitary or adrenally derived factors.     

The effect of flufenamic acid on gastrointestinal myoelectrical activity and transit time in dogs

Background—Flufenamic acid, a fenamate, has beenshown to alter markedly the membrane potential of small intestinalsmooth muscle and increase intracellular calcium in single cells.
Aims—To determine the effects of flufenamic acidon myoelectrical motor activity and gastrointestinal transit in theintact animal.
Methods—Myoelectrical motor activity was recordedvia seromuscular platinum electrodes sutured at regular intervals inthe stomach and throughout the small intestine. Fasted and fedgastrointestinal transit was assessed using technetium-99m(^99mTc) as the radioactive marker linked to 1 mm amberlitepellets or added to the meal.
Results—Flufenamic acid (600 mg, intravenously)induced intense spike activity in the small intestine. The meanduration of irregular spike activity was 250 (7) minutes. Spikeactivity was more pronounced in the lower small intestine. Flufenamicacid also accelerated initial gastric emptying and markedly shortened transit time in the small intestine. In the fasted state the 50% transit time in the small intestine was 54 (8) minutes with infusion offlufenamic acid compared with 105 (10) minutes in the control group; inthe fed state ^99mTc first reached the colon at 220 (10)minutes compared with 270(12) minutes in the control group.
Conclusions—Flufenamic acid had marked effects onboth myoelectrical motor complex activity and small intestinal transitin the dog. The observed effects suggest that flufenamic acid may be ofpotential use as a prokinetic agent.

Keywords:prokinetic agents; transit studies; migrating motorcomplex

     

Effects of Several Endothelin Receptor Antagonists on Gastrointestinal Transit of Guinea Pigs

This study was undertaken to investigate the effects of endothelin_A receptor antagonist (ET_A-RA) BQ485; ET_B-RA BQ788, and nonselective ET_A/B-RA Bosentan on the gastrointestinal transit of guinea pigs. We further analyzed the distribution of ET-R subtypes on smooth muscle cells (SMC) of the gastrointestinal tract to investigate their direct involvement on SMC in gastrointestinal tract transit. A guinea pig model was used to measure intestinal transit. The effects of Bosentan (100 mg/kg, per os), BQ485 (1 mg/kg, intraperitoneally) and BQ788 (1 mg/kg, intraperitoneally) on transit in stomach, small intestine, and colon were evaluated. We separated SMC from stomach, small intestine, cecum, and colon by collagenase and analyzed the distribution of ET-R subtypes in each part by binding assay. Gastric transit and colon transit were significantly inhibited by BQ485, BQ788, and Bosentan. Small intestinal transit was not affected by any of these agents. ET_A-R and ET_B-R were widely distributed on SMC of stomach, small intestine, cecum, and colon. The ratio of ET_A-R to ET_B-R was 1:3 in stomach, small intestine, and cecum, but was 1:10 in colon. The ratio of the total number of ET-R on SMC of stomach, small intestine, cecum, and colon was 1:3:9:1. These results indicate that both ET_A-R and ET_B-R are strongly involved in the transit in the stomach and colon. However, the discrepancy between the effects of the various ET-R antagonists on gastrointestinal transit and the distribution of ET-R on SMC of the gastrointestinal tract suggests that ET-R on SMC of the gastrointestinal tract is not directly involved in gastrointestinal transit.     

Biofeedback provides long term benefit for patients with intractable, slow and normal transit constipation

Background—Many patients with idiopathicconstipation do not respond to conventional medical treatments.Recently biofeedback has been proposed as an alternative treatment butthe long term results, and which patients benefit, are unknown.Treatment has usually been restricted to patients with normal colonictransit and impaired pelvic floor coordination on straining.
Aims—To determine the efficacy and long termoutcome of biofeedback treatment in idiopathic constipation.
Methods—One hundred consecutive contactablepatients who had completed a course of biofeedback more than 12 monthspreviously were identified. Pretreatment details of bowel function andsymptoms, whole gut transit time, and anorectal physiological testing,which had been previously prospectively collected, were collated.Follow up consisted of structured interview. Sixty five per cent had slow transit and 59% had paradoxical pelvic floor contraction on straining.
Results—Median follow up was 23 months (range12-44). On long term follow up 55% felt that biofeedback had helpedand 57% felt their constipation was improved. There was a significant reduction in need to strain, abdominal pain, bloating, and oral laxative use. Spontaneous bowel frequency was significantly improved bytreatment. Patients with slow and normal transit, males and females,and those with and without paradoxical contraction of the analsphincter on straining, benefited equally from treatment. Anorectaltesting did not predict outcome.
Conclusion—This study suggests that biofeedbackis an effective long term treatment for the majority of patients withidiopathic constipation unresponsive to traditional treatments. Pelvicfloor abnormalities and transit time should not form selection criteria for treatment.

Keywords:constipation; biofeedback; follow up; laxatives; transit time

     

Loperamide abolishes exercise-induced orocecal liquid transit acceleration

Previous work in our laboratory has found that mild physical activity accelerates mouth-to-large intestinal transit of lactulose in a mixed liquid meal. Because loperamide is commonly used as an antidiarrheal agent, we wondered if it would blunt the orocecal transit acceleration provoked by mild exercise. We investigated this equation in 12 healthy persons by comparing orocolonic liquid transit at rest and in mild exercise. Each subject ingested 8 mg loperamide 1 hr prior to study under both resting and exercise conditions. With loperamide treatment, exercise (walking at 5.6 km/hr) failed to hasten increased H₂ excretion (mean transit time 72±12 min at rest, 90±15 min in exercise;P=NS). This result contrasts sharply with previously reported controls: loperamide completely abolished exercise-induced orocecal transit acceleration (?23±5 min in controls +18±13 min with loperamide;P<0.05). Compared with these same controls, resting transit was not significantly slowed by the drug, while transit in exercise was retarded (64±5 min in controls, 90±15 min with loperamide;P=0.06). Loperamide left unchanged the heart rate and oxygen uptake rises associated with exercise. In summary, by showing that loperamide blocks an exercise effect on the upper gut, these results suggest that the drug might prove effective in treating some gut symptoms induced by physical activity.     

Alterations in intestinal motility and microflora in experimental acute pancreatitis

Summary Conclusion A delay in intestinal transit time appears as an early event in acute pancreatitis, preceding intestinal bacterial overgrowth and translocation. Background Septic complications, primarily caused by bacteria of enteric origin, are frequent in severe acute pancreatitis. Impairment in intestinal motility probably plays a pathophysiological role in the development of bacterial overgrowth and ensuing translocation. Methods In the present study, the influence of acute pancreatitis on intestinal motility was evaluated by measuring small intestinal transit time in the rat. Acute pancreatitis was induced by the retrograde intraductal infusion of 0.2 mL taurodeoxycholate. Intestinal transit time was studied by intraduodenal injection of Krebs’ phosphate-buffered solution labeled with Na₂ ⁵¹CrCO₄, and 1 h small intestinal transit was measured at 1, 3, 12, and 24 h, after induction of pancreatitis. Bacterial overgrowth was evaluated by measuringEscherichia coli counts in the colon and distal small intestine, and bacterial translocation to mesenteric lymph nodes, the liver, spleen, and pancreas was determined. Results A delayed small intestinal transit time was noted from 3 h on after induction of acute pancreatitis, with most of the radioactivity retained in the first two intestinal segments. Overgrowth ofE. coli was noted 12 h after induction of pancreatitis in both the colon and distal small intestine, and at the same time-point, a significant increase in the incidence of bacterial translocation to mesenteric lymph nodes was seen.     

Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction

AIM: To investigate whether dimethyl sulfoxide(DMSO) inhibits gut inflammation and barrier dysfunction following zymosan-induced systemic inflammatoryresponse syndrome and multiple organ dysfunction syndrome.METHODS: Sprague-Dawley rats were randomly divided into four groups: sham with administration of normal saline(SS group); sham with administration of DMSO(SD group); zymosan with administration of normal saline(ZS group); and zymosan with administration of DMSO(ZD group). Each group contained three subgroups according to 4 h,8 h,and 24 h after surgery. At 4 h,8 h,and 24 h after intraperitoneal injection of zymosan(750 mg/kg),the levels of intestinal inflammatory cytokines [tumor necrosis factor-alpha(TNF-α) and interleukin(IL)-10] and oxides(myeloperoxidase,malonaldehyde,and superoxide dismutase) were examined. The levels of diamine oxidase(DAO) in plasma and intestinal mucosal blood flow(IMBF) were determined. Intestinal injury was also evaluated using an intestinal histological score and apoptosis of intestinal epithelial cells was determined by deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) assay. The intestinal epithelial tight junction protein,ZO-1,was observed by immunofluorescence.RESULTS: DMSO decreased TNF-α and increased IL-10 levels in the intestine compared with the ZS group at the corresponding time points. The activity of intestinal myeloperoxidase in the ZS group was higher than that in the ZD group 24 h after zymosan administration(P 0.05). DMSO decreased the content of malondialdehyde(MDA) and increased the activity of superoxide dehydrogenase(SOD) 24 h after zymosan administration. The IMBF was lowest at 24 h and was 49.34% and 58.26% in the ZS group and ZD group,respectively(P 0.05). DMSO alleviated injury in intestinal villi,and the gut injury score was significantly lower than the ZS group(3.6 ± 0.2 vs 4.2 ± 0.3,P 0.05). DMSO decreased the level of DAO in plasma compared with the ZS group(65.1 ± 4.7 U/L vs 81.1 ± 5.0 U/L,P 0.05). DMSO significantly preserved ZO-1 protein expression and localization 24 h after zymosan administration. The TUNEL analysis indicated that the number of apoptotic intestinal cells in the ZS group was much higher than the ZD group(P 0.05).CONCLUSION: DMSO inhibited intestinal cytokines and protected against zymosan-induced gut barrier dysfunction.     

Intestinal Transit in Dogs is Accelerated by Volume Distension During Fat-Induced Jejunal Brake

Intestinal transit is accelerated by volume distension and slowed by nutrient load. We hypothesized that the accelerating effect of volume distension might overcome the slowing effect of nutrient. To test this hypothesis, we compared intestinal transit in five dogs equipped with duodenal and mid-intestinal fistulas. The proximal half of the small intestine was perfused with 60 mM oleate, while the distal half of the small intestine was either perfused with buffer (with distension) or left unperfused (without distension). We found that intestinal transit was slowed by oleate (with marker recovery reduced from 85.8 ± 5.3 to 39.4 ± 7.5%) (P < 0.01) and that volume distension accelerated intestinal transit so that marker recovery increased from 39.4 ± 7.5 without distension to 60.8 ± 6.3% with distension (P < 0.05). We concluded that intestinal transit is accelerated by volume distension during fat-induced jejunal brake.     

Intestinal transit of fat depends on accelerating effect of cholecystokinin and slowing effect of an opioid pathway

Fat has been described to both accelerate and slow intestinal transit. We hypothesized that the fat-induced jejunal brake depends on the combined accelerating effect of CCK and the slowing effect of an opioid pathway. Using a multifistulated model, intestinal transit was measured in four dogs, while 60 mM oleate was delivered into the proximal gut with either 0 or 6 mg naloxone, and 0.1 mg/kg devazepide (a peripheral CCK-A-receptor antagonist) administered intraluminally and intravenously, respectively. In a second study, intestinal transit was measured in seven dogs, while naloxone was delivered intraluminally at 0-, 3-, 6-, or 12-mg doses. Compared to the jejunal brake (marker recovery of 50.1 ± 2.6%), intestinal transit was slowed by the CCK-A antagonist (36.4 ± 8.3%; P < 0.05) and accelerated by naloxone (82.0 ± 6.8%; P < 0.05). The accelerating effect of CCK occurred early in the transit response, while the dose-dependent effect (P < 0.05) of naloxone occurred later. We conclude that fat-induced jejunal brake depends on the early accelerating effect of CCK and the later slowing effect of a naloxone-sensitive opioid pathway.     

Gastrointestinal transit times and motility in patients with cystic fibrosis

Abstract

Objective. Patients with cystic fibrosis (CF) often suffer from gastrointestinal (GI) dysfunction including obstructive symptoms, malabsorption and pain, but the underlying pathophysiology remains obscure. Aim. To compare GI motility and transit times in CF patients and healthy controls. Material and methods. Ten CF patients (five women, median age 23) with pancreatic insufficiency were studied. Total gastrointestinal transit time (GITT) and segmental colonic transit times (SCTT) were assessed by radiopaque markers. Gastric emptying and small intestinal transit were evaluated using the magnet-based motility tracking system (MTS-1). With each method patients were compared with 16 healthy controls. Results. Basic contraction frequencies of the stomach and small intestine were normal, but the pill reached the cecum after 7 h in only 20% of CF patients while in 88% of controls (p = 0.001). Paradoxically, velocity of the magnetic pill through the upper small intestine tended to be faster in CF patients (median 1.1 cm/min, range 0.7–1.7) compared with controls (median 1.0 cm/min, range 0.6–1.7) (p = 0.09). No statistically significant differences were found in median gastric emptying time (CF: 58 min, range 6–107 vs. healthy: 41 min, range 4–125 (p = 0.24)), GITT (CF: 2 days, range 0.5–3.3 vs. healthy: 1.5 days, range 0.7–2.5 (p = 0.10)), right SCTT (CF: 0.5 day, range 0–1.1 vs. healthy: 0.4 day, range 0–1.0 (p = 0.85)), or left SCTT (CF: 1.0 day, range 0–2.2 vs. healthy 0.6 day, range 0.2–1.2 (p = 0.10)). Conclusions. In spite of normal contraction patterns, overall passage through the small intestine is significantly delayed in CF patients while upper small intestinal transit may be abnormally fast.