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Objective. Nitric oxide (NO) mechanisms have been shown to modulate fasting small intestinal motility in humans, but a role in the regulation of human postprandial small intestinal motility has not been assessed. The aim of this study was to evaluate the effect of the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) on the regulation of small intestinal nutrient transit and postprandial small intestinal motility in healthy humans. Material and methods. Seven healthy male volunteers (18–27 years) underwent antroduodenal manometry recordings for 4 h on 2 occasions after intraduodenal instillation of a 500 KJ [120 Kcal] test meal. The meal was administered 15 min after the commencement of a 60-min intravenous infusion of l-NMMA (4 mg kg?1 h?1) or saline (0.9%). Studies were separated, performed in randomized order and >3 days apart. The frequency and amplitude of duodenal pressure waves together with time to return of fasting motility (phase III) was determined. On each day, small intestinal transit was measured using a lactulose breath test. Results. The test meal interrupted fasting small intestinal motility in all subjects. The time to recurrence of fasting motility following its postprandial disruption was similar (l-NMMA versus saline 1.6±0.2 h versus 1.9±0.1 h; p>0.05). Duodenocaecal transit was delayed by infusion of l-NMMA compared with saline (l-NMMA versus saline 92.1±3.9 min versus 66.4±6.4 min; p<0.005). Infusion of l-NMMA significantly increased the frequency (l-NMMA versus saline 50.4±6.6 versus 34.8±5.5 waves per 30 min; p<0.05) and amplitude (l-NMMA versus saline 20.4±1.5 versus 15.5±1.1 mmHg; p<0.01) of duodenal pressure waves. Conclusions. These data suggest that endogenous NO may play a role in the regulation of small intestinal nutrient transit by regulating small intestinal motility in healthy individuals.  相似文献   

3.
目的 探讨接触性泻剂对小肠传输功能的影响及其病理学机制.方法 采用给大鼠饲料里添加接触性泻剂的方法使大鼠发生腹泻,45 d 后停止给药,52 d 后测量大鼠小肠传输功能的改变;并应用免疫组化的方法测定小肠肌间神经丛内血管活性肠肽(VIP) 、P物质和S- 100 蛋白的含量变化.结果 长期大剂量服用接触性泻剂可明显损伤小肠的传输功能,使小肠传输减慢;小肠肌间神经丛内SP 和S- 100 蛋白的含量增加,而VIP无明显变化.结论 长期服用接触性泻剂可明显损害小肠的传输功能,其机制可能是由于接触性泻剂损伤小肠肌间神经丛而致  相似文献   

4.
Summary The effects of hyperglycaemia on postprandial small intestinal motor activity are unclear. Duodenal and jejunal pressures and duodeno-caecal transit were measured in eight healthy male volunteers during euglycaemia (blood glucose 4–6 mmol/l) and hyperglycaemia (blood glucose 12–15 mmol/l). Duodenal and jejunal pressures were recorded with a manometric assembly during intraduodenal infusion of 100 ml nutrient liquid comprising 14% protein, 31.5% fat and 54.5% carbohydrate together with 15 g lactulose. Duodeno-caecal transit was determined by a breath hydrogen technique. The number of duodenal (p<0.05) and jejunal (p<0.01) pressure waves, excluding phase III episodes was reduced during hyperglycaemia compared to euglycaemia. Hyperglycaemia was associated with earlier onset of phase III activity (30±12 vs 132±20 min; p<0.05). Duodeno-caecal transit was slower during hyperglycaemia when compared to euglycaemia (114±17 vs 49±6 min, p<0.01). We conclude that induced hyperglycaemia has major effects on postprandial small intestinal motility. The reduction in duodenal and jejunal motor activity is likely to explain the retardation of small intestinal transit during hyperglycaemia.Abbreviations TMPD Transmusocal potential difference - MMC migrating myoelectric complex  相似文献   

5.
We studied the effects of a sphincter substitute on motility in the intestinal remnant following an extensive distal intestinal resection. Two groups of adult dogs were studied; each underwent a 75% resection of the distal small intestine, and in one group a nipple valve was fashioned at the distal end of the remnant. Nutritional status, absorptive function, motility, and transit were studied over a three-month period. While the nipple valve animals had less diarrhea, steatorrhea, and hypoalbuminemia, motor activity and transit were similar in both groups. Thus, in both groups, fasting motor activity was dominated by clusters of phasic pressure activity. (Cluster frequency, per hour, mean±se, resection vs resection with nipple valve: 4.8±1.05 vs 3.58±0.54, NS). We conclude that the beneficial effects of a sphincter substitute in ameliorating the short bowel syndrome in this dog model are not related to any modification of the motor response to resection but may simply reflect those of a low-grade mechanical obstruction.Presented in part at the American Gastroenterological Association Meeting, New Orleans, Louisiana, May 1991 and has appeared in abstract form inGastroenterology (100:A241, 1991).Supported by the Veterans Administration Merit Review Program.  相似文献   

6.
目的探讨选择性5羟色胺再摄取抑制剂对小肠传递功能的影响。方法8名健康志愿者连续5天口服帕罗西丁,20mg/天,于用药前一天和停药次日进行乳果糖氢呼气试验测定口-盲肠通过时间。结果口-盲肠通过时间从用药前86±23分钟降至用药后的68±20分钟,差异显著(t=3.439,P<0.05)。结论5羟色胺参与胃肠道动力调节,选择性5羟色胺再摄取抑制剂具有促小肠动力作用。  相似文献   

7.
BACKGROUND AND AIMS: Prostaglandin analogs have the pharmacologic effect of speeding up small intestinal transit (SIT). It remains unknown whether some gut peptides also mediate this enhancement. We studied the effect of misoprostol on rat SIT and looked at the role of vasoactive intestinal polypeptide (VIP) release during its action. METHODS: A group of rats initially received oral misoprostol treatment of 1, 10, 50 and 100 microg/kg, respectively. By using orally fed charcoal as a motility marker, the SIT was assessed at 30 min following oral misoprostol treatment. Another group of rats received misoprostol as an intraperitoneal injection in similar doses to the group above. The small intestinal transit was computed for this group at 30 min following misoprostol injection via an instilled radiochromium motility marker that went through a previously placed intraduodenal catheter. The plasma VIP level was measured by using a radioimmunoassay kit. RESULTS: Neither charcoal evaluated transit nor the plasma VIP level was influenced by the lower doses of oral misoprostol treatment (1 and 10 microg/kg), whereas other doses enhanced SIT and diminished the plasma VIP level (P< 0.01).The similar effects on radiochromium computed SIT (P< 0.01) and plasma VIP levels were obtained in tubed rats following misoprostol intraperitoneal treatment. The SIT results correlated negatively with plasma VIP levels. CONCLUSIONS: Enhanced SIT and diminished VIP levels are found in rats following misoprostol treatment. It appears that inhibited VIP release is one of the mechanisms in misoprostol-enhanced SIT.  相似文献   

8.
We measured the effect of misoprostol (M), a PGE1 analog, on duodenojejunal postprandial motor activity and orocecal transit in eight healthy volunteers. Intestinal motility was studied by an intraluminal catheter with three strain gauge transducers connected to a solid-state datalogger, and transit time was measured by a hydrogen breath test. Subjects were studied for two consecutive days and fed twice a day with a similar, 600-kcal meal. Misoprostol (M) at 800, 400, or 200 g or placebo were taken orally before every one of the four meals. Transit time was measured after the morning meal on both days, after ingestion of either 800 g of M or placebo. On four occasions, following M, the normal fed pattern was not established and the migrating motor complex (MMC) was not interrupted by the meal. In all other occasions, when the higher doses of M were given, the first 1–2 hr after the meal revealed a hypoactive bowel. This effect was inconsistently seen following 200 g of M. Orocecals transit time was consistently and significantly shorter after M than placebo: 48.3±9.5 min vs 104.4±4.8 min,P<0.0001. Four subjects had diarrhea during the study. We conclude that misoprostol, particularly at higher doses, has a profound effect on intestinal postprandial motility and results in accelerated transit time. The motility changes induced by M may be responsible, in part, for its effect on transit.A preliminary report of this work was given at the annual meeting of the American Gastroenterological Association, May 1991, and was published as an abstract inGastroenterology 100:496, 1990. This study was supported in part by Searle.  相似文献   

9.
Orogastric feeding of a charcoal meal to rats was employed to measure whether the various stages of pregnancy could influence gastrointestinal transit. The oestrous cycle of female Sprague-Dawley rats was checked daily. If pro-oestrus occurred, the first day of pregnancy was defined to be on the next day after the copulation. Gastrointestinal transit studies were conducted on day 7 (first trimester), day 14 (second) and day 21 (third), respectively. The rats were killed 15 min after the successful feeding of a calorie-free, charcoal-containing test meal via a transiently placed orogastric catheter. Gastrointestinal transit was defined as the per cent of charcoal transit divided by the total length of the small intestine. These results were compared with the data obtained from non-pregnant female rats. Mean percentages of transit for the first, second and third trimester, and for controls were 42.8 ± 1.9, 45.3 ± 4.1, 35.7 ± 1.7 and 42.6 ± 1.4%, respectively (mean ± s.e.). Late pregnancy elicited a marked inhibition of transit (P < 0.01). A significant negative correlation between transit and uterine weight of all pregnant rats was seen (r= -0.50, P < 0.05). The present study indicates that inhibited gastrointestinal transit occurs in the late pregnant rat.  相似文献   

10.
This study presents a method of brush border membrane (BBM) preparation from the human small intestine using polyethylene glycol (PEG) precipitation and also looks at the effect of in vitro oxidant exposure on structural and functional alterations in the membrane. Isolated BBM were relatively pure as judged by 10- to 14-fold enrichment of marker enzymes with less than 1% contamination by other subcellular organelles. These membranes showed uphill transport of glucose and lipid analysis showed a cholesterol–phospholipid (C/P) ratio of 1.19. Isolated BBM were found to be susceptible to superoxide generated by xanthine oxidase (XO), resulting in lipid and protein oxidation along with altered glucose uptake. Superoxide exposure also resulted in phospholipid alterations, especially generation of lyso phospholipids. These changes were prevented by inhibiting XO by allopurinol or scavenging superoxide by superoxide dismutase (SOD). Other oxidants studied did not have significant affect on these membranes. These studies suggest that PEG can be used for preparation of BBM from the human small intestine and these membranes undergo structural and functional alterations on exposure to superoxide.  相似文献   

11.
Antagonists of 5-hydroxytryptamine type 3 (5HT3) receptors reduce the nausea induced by cisplatinum, but the effects of these agents on 5HT3 receptors in the human gut remain to be defined. We examined the actions of one of these drugs (Glaxo GR 38032F) on small intestinal transit and mouth-to-cecum transit times in healthy man. We also quantified its effects on the release of peptide YY (PYY), neurotensin, human pancreatic polypeptide, gastrin-cholecystokinin, and motilin. Ten healthy volunteers were enrolled in a randomized, double-blind, placebo-controlled crossover study. Following a single intravenous dose of GR 38032F (0.15 mg/kg), we measured the time to appearance in plasma of sulfapyridine after injection of salicylazosulfapyridine into the duodenum. This was used as a measure of duodenocecal transit. The appearance of hydrogen in breath after ingestion of a meal containing lactulose was also correspondingly used to quantify the mouth-to-cecum transit of the head of the meal. Gastrointestinal hormones were assayed in plasma by specific RIAs; samples were drawn fasting (10 min after injection) and after breakfast (358 calories: 15.7 g protein, 55.4 g carbohydrate, 8.1 g fat). The postprandial integrated response and peak release of PYY was decreased by GR 38032F. There was also a trend for the peak release of neurotensin to be reduced. GR 38032F did not significantly alter small intestinal transit times or mouth-to-cecum transit times. We conclude that GR 38032F does not have a major effect on small intestinal transit in health.Supported in part by grants from Glaxo Inc., USA, and from the National Institutes of Health (RR585, DK34988, and DK32121).  相似文献   

12.
Summary Massive bleeding from jejunal varices in a young alcoholic with cirrhosis and portal hypertension ceased following a portocaval shunt. Although rare, bleeding from small or large bowel varices has a high mortality. In 62 cases, small or large bowel varices are almost always associated with a predisposing condition including previous abdominal surgery and portal hypertension from cirrhosis or other causes. Hematochezia without hematemesis and nonbleeding esophageal varices generally occur. Angiography is the best diagnostic test.  相似文献   

13.
Radiation with doses >7.5 Gy damages the canine intestinal mucosa, and pretreatment with WR2721 reduces this damage. However, the effects of radiation and of WR2721 onin vivo intestinal transport are unclear. Therefore, we determined canine survival, intestinal transport, and mucosal histology following unilateral abdominal irradiation. Isoperistaltic ileostomies were prepared in 23 dogs under general anesthesia and aseptic conditions. After a three-week recovery period, animals were given either placebo or WR2721, 150 mg/kg intravenously, 30 min prior to 10 Gy cobalt-60 abdominal irradiation. Ileal transport and histology were determined in both groups before exposure and one, four, and seven days after irradiation. Seven-day survival was significantly improved by pretreatment with WR2721 (91% vs 33%,P<0.02). On day 4, both mucosal integrity and net intestinal absorption were significantly better (P<0.05) after WR2721 than after placebo. Thus, radiation-induced damage to the ileal mucosa is accompanied by a reduction in net ileal absorption of water and electrolytesin vivo. In addition, pretreatment with WR2721 improves animal survival while reducing ileal damage and improving intestinal absorption.Supported by the Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under work units B3161 and 00082. Views presented in this paper are those of the authors; no endorsement by the Defense Nuclear Agency or the Uniformed Services University of the Health Sciences has been given or should be inferred. Research was conducted according to the principles enunciated in the Guide of the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources, National Research Council.  相似文献   

14.
The effect of transplantation on small intestinal absorption, digestive capacity, myoelectric activity, and morphology was assessed in inbred Lewis rats. Electrodes were sutured to the duodenum and isografted jejunoileum or to the native jejunoileum in controls. The frequency of migrating myoelectric complexes (MMCs) in the duodenum was 3.3±0.3/hr in controls and 1.8±0.4/hr in transplants (P<0.05). MMC frequency in the jejunoileum was 5.1±1.3/hr in controls and 3.2±0.9/hr in transplants (P>0.05). MMCs appeared to migrate from the duodenum to the jejunoileum 80±3% of the time in controls and 59±7% of the time in transplant rats (P<0.05). Absorption in the transplanted jejunoileum demonstrated a 35–40% decrease in glucose and electrolytes absorption. Villus height and number of nuclei per villus was reduced. Intestinal length (dry) was 103±6 cm for controls and 51±3 cm for transplant rats (P<0.05). Brush border sucrase activity was unchanged. We conclude that small intestinal isografts display similar myoelectric activity as controls, but the decreased absorptive capacity and villus height may require longer segments of intestine to be transplanted in order to support normal nutrition.Supported by the Veterans Administration Research Service.  相似文献   

15.
BACKGROUND: Polyethylene glycol 3350 increases stool frequency and accelerates colonic transit. Used as a laxative, it proved effective in patients with normal and slow transit. Although free of severe side effects, it may cause nausea and vomiting. The effect of this substance on upper gut transit has not been studied. AIM: To investigate the effect of polyethylene glycol 3350 on gastric emptying and oro-caecal transit in 12 healthy subjects. METHODS: In a randomised controlled study, isosmotic polyethylene glycol 3350 electrolyte balanced solution, in the maximal recommended dose or isosmotic electrolyte solution, was administered after breakfast and lunch on separate days. Gastric half-emptying time and oro-caecal transit time were measured using [13C]-octanoate and lactose-[13C] ureide breath tests. RESULTS: Isosmotic polyethylene glycol 3350 electrolyte solution, as compared to isosmotic electrolyte solution, decreased oro-caecal transit time from 424+/-28 to 314+/-17 min (P = 0.001). Gastric half-emptying time was significantly increased (84+/-6 min versus 127+/-14 min; P = 0.006). CONCLUSION: Polyethylene glycol 3350 accelerate oro-caecal transit in healthy subjects, but also cause an important delay in gastric emptying. The delay in gastric emptying may be of clinical significance in patients who have associated gastroparesis.  相似文献   

16.
Glycoprotein and glycolipid constituents were examined in purified microvillus and basolateral membranes isolated from rat small intestinal epithelial cells. SDS—polyacrylamide gel electrophoresis showed that the molecular weights of most of the major proteins from microvillus membranes were over 100 kD, whereas the majority of those from basolateral membranes tended to have lower molecular weights. Glycoprotein profiles were also examined using three labeling methods, and in each case marked differences were observed between microvillus and basolateral membranes. In both membranes, lectins with a specificity toward N-linked sugar chains bound to the majority of the glycoproteins, in contrast to those lectins which preferentially bind to O-linked sugar chains. Glycolipids were labeled in vivo and isolated from both membrane fractions. Some differences were observed in the fucolipids and neutral glycolipids suggesting a more complex pattern in microvillus membranes. These results indicate that there are differences in the glycoprotein and glycolipid compositions of microvillus and basolateral membranes that may reflect the functional polarity of intestinal epithelial cells.This work was supported by grant AM17938 from the National Institutes of Health and by the Veterans Administration Medical Research Service.  相似文献   

17.
To compare differentiation along the crypt-villus axis in adult rats with changes observed in postnatal maturation with respect to binding capacities for lectins and food proteins, crypts and villi were isolated byin vivo perfusion andin vitro incubation. Brush border membranes were prepared from adults and newborns, and binding of125I-labeled lectins and food proteins was assessed by airfuge ultracentrifugation. Crypt and villus membrane protein patterns looked almost identical, unlike newborn membranes. Considerable shifts in lectin binding to membranes were observed during postnatal maturation, but not in crypt-villus differentiation. For instance, fucose-specific lectin binding patterns in both preparations resembled the general adult mode. Contrary to differences in food protein binding between newborn and adult membranes, food protein binding did not show a consistent significant difference between membranes of crypt and villus origin in adult animals. In conclusion, membrane differentiation along the crypt-villus axis was found to follow a pattern dissimilar from neonatal maturation as far as protein and carbohydrate composition and food protein binding were concerned.Supported by Deutsche Forschungsgemeinschaft DFG Ste 305.  相似文献   

18.
Mitomycin C (MMC) therapy often causes toxicity affecting the small intestine. We investigated the relationship between pathological manifestations and cell death, or the proliferation of small intestinal villi in rats treated with MMC. The length of the villi, apoptosis, and cell proliferation were evaluated in the small intestine at 3, 7, and 11 days after MMC treatment by the TUNEL method, BrdU-immunohistochemistry, and transmission electron microscopy. In MMC-treated rats, the body weight decreased until day 7 and recovered from day 8, while most rats had watery stools from days 4 to 7. The villi were the shortest on day 7 and were still shorter on day 11 than in the control group. The highest incidence of TUNEL-positive cells in the small intestinal crypts was observed on day 3, and the number decreased thereafter to reach the control level on day 11. The percentage of BrdU-labeled cells was the highest on day 3 and the lowest on day 7, but recovered to the control level on day 11. The clinical symptoms caused by MMC treatment are consistent with the changes of villous length that reflect the viability of stem cells in the small intestinal crypts about 4 days earlier.  相似文献   

19.
Intestinal permeability was assessed before and 1, 2, 4, 8 and 12 weeks after commencing a gluten-free diet (GFD) in eight coeliac subjects. Intestinal morphology was quantified in six coeliac subjects on a normal diet, six coeliac subjects on a GFD, and 21 normal subjects. T-cell activity was measured in the eight coeliac subjects by soluble interleukin-2 receptor (sIL-2R) concentration (normal less than 477 U/mL). Intestinal permeability was increased 10-fold with a geometric mean value of 0.72 on a normal diet, and decreased to 0.17 at 4 weeks (P = 0.04), to 0.07 at 8 weeks (P = 0.010), and to 0.20 at 12 weeks (P = 0.015) of a GFD. Two of the eight subjects showed a poor response to gluten withdrawal. Quantitative intestinal morphology showed no significant improvement after 3 to 6 months of a GFD. Mean +/- s.d. sIL-2R concentrations in the eight subjects were increased 5-fold higher than control values at 1400 +/- 530 U/mL on a normal diet and decreased to 750 +/- 200 U/mL after 12 weeks of a GFD (P = 0.004). We conclude that intestinal permeability improves rapidly in the majority of coeliac subjects after commencing a GFD, although some abnormal permeability and increased T-cell activity persists. This may be due to varying degrees of gluten ingestion resulting in continued immune activation.  相似文献   

20.
Antidepressants are used in irritable bowel syndrome (IBS) and may have effects on the gut independent of improving mood. We have investigated the actions of a tricyclic antidepressant on small intestinal motor function in eight healthy volunteers and in six patients with diarrhea-predominant IBS. Fasting ambulatory motility was recorded from six small intestinal sites for 16–18 hr while on no drug (baseline) and while taking imipramine for five days. Orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, during baseline and imipramine administration. Imipramine did not alter migrating motor complex periodicity, but slowed jejunal phase III propagation velocity in controls from 7.5±1.1 to 3.6±0.5 cm/min (P<0.01) and in IBS from 7.8±0.6 to 4.4±0.5 cm/min (P<0.0001). Phase III duration at each site was increased, and total recorded phase III was greater during imipramine than baseline studies. Imipramine increased the amplitude of phase III contractions. There was no effect of imipramine on non-phase-III motility index or discrete clustered contractions. Imipramine prolonged OCTT from 73±6 min to 97±8 min in controls (P<0.05) and from 61±9 min to 89±8 min in IBS (P<0.05). Although OCTT was shorter in this IBS group, no motility differences were seen between controls and IBS. This demonstration that a tricyclic antidepressant can modify small intestinal motor function in health and in IBS supports the view that these drugs may have therapeutic actions in IBS unrelated to mood improvement.This work was supported by the Priory Hospitals Group.  相似文献   

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