Effects of motilin and ursodeoxycholic acid on gastrointestinal myoelectric activity of different origins in fasted rats

AIM: To investigate gastrointestinal migrating myoelectric complex (MMC) and the effects of porcine motilin and ursodeoxycholic acid (UDCA) on MMC of gastrointestinal tract of different origins in fasted rats. METHODS: Three bipolar silver electrodes were chronically implanted on the antrum, duodenum and jejunum. Seven days later 24 experimental rats were divided into 2 groups. One group was injected with porcine motilin via sublingual vein at a dose of 20 microg/kg, the other group was perfused into stomach with UDCA. The gastrointestinal myoelectric activity was recorded 1 h before and 2 h after the test substance infusions into the rats. RESULTS: In all fasted rats a typical pattern of MMC was observed. Among the totally 68 activity fronts recorded in fasted rats under control, 67% started in duodenum, and 33% in antrum. MMC cycle duration and duration of phase III of antral origin were longer than those of duodenal origin. Administration of 20 microg/kg porcine motilin induced a premature antral phase III of antral origin. But perfusion into stomach with UDCA resulted in shorter MMC cycle duration, longer duration of phase III of duodenal origin, which were followed with shorter cycle duration and duration of antral phase III. CONCLUSION: In fasted rats, MMC could originate from antrum and duodenum respectively. The characteristics of MMC of different origins may contribute to the large variations within subjects. The mechanisms of different origins of phase III may be different. Porcine motilin and UDCA could affect MMC of different origins of the gastrointestinal tract in fasted state, respectively.     

Obstructive jaundice, bacterial translocation and interdigestive small-bowel motility in rats

BACKGROUND/AIMS: Translocation of gut bacteria occurs in obstructive jaundice, the underlying mechanisms are unclear. We designed this experimental study to investigate the association between interdigestive motility and the pathogenesis of bacterial translocation during biliary obstruction. METHODS: Rats were fitted with jejunal myoelectrodes for the measurement of the interdigestive migrating motor complex (MMC) and with two cannulas in the proximal common bile duct (CBD) for exteriorization of biliary flow. This allowed measurement of MMCs under control conditions with an intact enterohepatic circulation and during 3 days of CBD obstruction without surgical intervention. Mesenteric lymph nodes, liver, spleen and segments of the duodenum, the jejunum and the caecum were removed for microbial culturing. RESULTS: The MMC cycle length increased from 17.3 min before CBD obstruction to 31.9, 34.1, and 25.3 min on days 1, 2 and 3, respectively, after CBD obstruction (p < 0.05 for all days). Bacterial levels in the jejunum were significantly higher in CBD-obstructed rats than in control rats. The translocation incidence was significantly higher in rats with CBD obstruction (6/8) than in control rats (1/8). The bacterial levels in the jejunum correlated significantly with the MMC cycle length (r = 0.60, p <0.05). CONCLUSION: Experimental biliary obstruction is associated with disturbance of MMCs, small-bowel bacterial overgrowth and increased bacterial translocation.     

Role of bile in regulation of gut motility

Abstract. Bile empties into the duodenum not only after a meal but also in the interdigestive state. In man, inter-digestive biliary emptying is related to fasting motor activity, the migrating motor complex (MMC), in the stomach and small bowel and generally occurs during phase 2 preceding a gastroduodenal phase 3 activity (activity front). It seems that the main regulatory peptide to initiate phase 3 is motilin. During a period with 13 phase 3 activities of MMC, 18 episodes of gall-bladder emptying and 19 motilin peaks were observed. Such a peak of plasma motilin usually took place 25 ± 11 min after onset of biliary emptying. In conclusion, data indicate that motilin is released to the circulation by the biliary output and induces phase 3 of MMC. The induced phase 3 propels bile acids along the gut to promote their absorption in the distal intestine. The choleretic action of recycling of bile acids may cause subsequent episodes of biliary emptying with motilin release by the action of the enterohepatic circulation of bile acids. In such a manner the MMC may be withheld as a recycling motility pattern.     

Regurgitation of bile acids in rat liver under bile drainage: quantitative analysis by taurine or ursodeoxycholate loading test

Abstract In rats with an interrupted enterohepatic circulation of bile acids, levels of serum taurine-conjugated bile acids were increased significantly 3 h after intravenous administration of taurine. Similarly, serum taurine- or glycine-conjugated ursodeoxycholic acid (UDCA) was increased significantly 2 h after UDCA administration. These findings suggested that the administered taurine or UDCA was taken up into hepatocytes and utilized to form conjugated bile acids, which were thereafter regurgitated into the systemic circulation from the liver. The proportion of regurgitated taurine-conjugated bile acids relative to total serum bile acids measured by taurine loading (30%) almost coincided with that of regurgitated taurine- or glycine-conjugated UDCA relative to total serum bile acids measured by UDCA loading (31.6%). Thus, the present study showed conclusively that at least 30% of serum bile acids are derived from newly conjugated bile acids that are regurgitated from the liver in rats with bile fistula.     

Effects of neurotrophins on gastrointestinal myoelectric activities of rats

AIM: To observe the effects of mouse nerve growth factor (NGF), rat recombinant brain derived neurotrophic factor (rm-BDNF) and recombinant human neurotrophin-3 (rh-NT3) on the gastrointestinal motility and the migrating myoelectric complex (MMC) in rat.METHODS: A randomized, double-blinded, placebo-controlled experiment was performed. 5-7 days after we chronically implanted four or five bipolar silver electrodes on the stomach, duodenum, jejunum and colon, 21 experimental rats were coded and divided into 3 groups and injected NGF, rm-BDNF, rh-NT-3 or placebo respectively via tail vein activity was recorded 2 hours before and after the test substance infusions in these consciously fasting rats.RESULTS: The neurotrophins-induced pattern of activity was characterized by enhanced spiking activity of different amplitudes at all recording sites, especially in the colon. In the gastric antrum and intestine, only rh-NT-3 had increased effects on the demographic characteristics of electrical activities (P＜0.05), but did not affect the intervals of MMCs.In the colon, all the three kinds of neurotrophins could significantly increase the frequency, amplitude and duration levels of spike bursts, and also rh-NT-3 could prolong the intervals of MMC in the transverse colon (25±11 min vs 19±6 min, P＜0.05). In the distal colon rh-NT-3 could evoke phase Ⅲ-like activity and disrupt the MMC pattern, which was replaced by a continuously long spike bursts (LSB) and irregular spike activity (ISA) for 48±6 min.CONCLUSION: Exogenous neurotrophic factors can stimulate gut myoelectric activities in rats.     

消化间期移行性复合运动对胆道调节作用的实验研究

目的 探讨消化间期移行性复合运动(MMC)与胆道运动的相互关系及两者间的相互调节作用，进一步阐明MMC的发生机制，并为胆石症的防治提供理论依据。方法 将45只成年豚鼠分为对照组，普卡比利组和地巴唑组，在胃窦、十二指肠上段、十二指肠中段、胆囊(GB)及Oddi括约肌(SO)等五处肌肉层内埋置银丝电极，用八导生理记录仪记录该部位肌电活动，胃内分别给予普卡比利和地巴唑后，观察肌电变化及MMC与GB、SO运动的关系。结果 各组动物给药前五个记录点的肌电活动频率和强度呈正相关(P＜0．05)。胃肠MMC的肌电活动被普卡比利增强后，GB、SO部位的肌电活动相应地加强。胃肠MMC的肌电活动被地巴唑抑制后，GB、SO部位的肌电活动相应地被抑制(P＜0．05)。结论 胃肠肌电活动的改变能引起胆道肌电活动的相应变化，提示胃肠MMC对胆道运动有调节作用。     

Effects of ghrelin on feeding regulation and interdigestive migrating complex in rats

OBJECTIVE: Ghrelin is an orexigenic peptide with remarkable prokinetic effects. However, its mechanisms in regulating feeding and gastrointestinal migrating myoelectrical complex (MMC) are not fully understood. The aim of this study was to examine the effects of ghrelin on feeding regulation and duodenal motility in rats. MATERIAL AND METHODS: Feeding regulation was investigated at different times after intravenous injection of ghrelin and its receptor antagonist (D-Lys3)GHRP-6 in fasted rats. Rats were supplied with a pair of silver bipolar electrodes embedded in the duodenal serosa for electromyography. Ghrelin was injected intravenously into the rats during the fed state or fasted state. Some rats were pretreated with atropine, phentolamine, propranolol, L-arginine, the 5-hydroxytryptamine3 receptor antagonist ondansetron, and (D-Lys3)GHRP-6. RESULTS: Ghrelin had little effect on food intake in the first 30 min after administration, but was found to increase feeding during the subsequent hours. (D-Lys3)GHRP-6 decreased feeding and antagonized the effect of ghrelin. Ghrelin induced duodenal MMC after administration in the fed state, and shortened the duodenal MMC cycle length and the duration of phase III during fasting. The amplitude and frequency of phase III were increased without affecting the percentage of phase III in the MMC cycle. Pretreatment with atropine, L-arginine, ondansetron, and (D-Lys3)GHRP-6 inhibited the effects of ghrelin. Propranolol and phentolamine had little influence on these effects. CONCLUSIONS: Ghrelin appears to be closely related to feeding and intestinal motility. The excitatory effects of ghrelin are dependent on the cholinergic pathway, and it has a close relationship with the NOS-NO or 5-HT pathway. The ghrelin receptor is involved in its activities.     

Abnormalities of gastrointestinal motility in children with nonulcer dyspepsia and in children with gastroesophageal reflux disease

In 11 children (mean age 44.2 months) with symptoms suggesting upper intestinal dysfunction (nonulcer dyspepsia), in nine children (mean age 27.3 months) with gastroesophageal reflux (GER) disease, and in seven controls (mean age 20.4 months) we investigated fasting [for 3 hr or until two migrating motor complexes (MMC) were observed] and fed (90 min) antroduodenal motility by means of perfused catheter system; furthermore, we measured both gastric emptying of a radiolabeled milk formula and fasting duodenogastric reflux during manometry by assessing bile salt concentration in gastric aspirates. No structural abnormalities of gastrointestinal tract and organic disorders were detected in the patients. In a high proportion of both groups of patients we found manometric abnormalities of interdigestive and fed motor patterns that were not seen in the controls: absence of antral phase III of MMC; significant decrease of antral and/or duodenal motor activity during fasting and/or fed periods; abnormal propagation or configuration of MMC phase III that was signficantly shorter than in controls; bursts of sustained fasting and/or fed phasic duodenal activity, frequently uncoordinated with adjacent gut segments. When compared to controls, the mean intragastric concentration of bile salts during all MMC phases and the mean 1-hr percent gastric activity of the radiolabeled milk were significantly higher in the two groups of patients. We conclude that in a high proportion of children with nonulcer dyspepsia and of children with GER disease, gastrointestinal manometry may reveal significant irregularities of antral and duodenal motility, which are associated with increased duodenogastric reflux and delayed gastric emptying.     

Effects of intraduodenal bile on interdigestive gastrointestinal and gallbladder motility in healthy subjects

BACKGROUND/AIMS: The enterohepatic circulation of bile acids is related to normal inter-digestive gastrointestinal motility, with the gut peptide motilin also being involved. This study aimed to investigate the effect of intraduodenal artificial bile infusion on antroduodenal and gallbladder motility so as to further elucidate the controlling factors. METHODS: Twelve fasting, healthy male volunteers received artificial bile (80 mol% bile acids; 15 mol% phospholipids; 5 mol% cholesterol) or placebo (saline) intraduodenally for 10 min starting 30 min after the end of phase III, according to a double-blind, randomised, cross-over design. Antroduodenal motility, gallbladder volumes, and plasma motilin levels were measured. All values are means +/- SEM. RESULTS: The interval between infusion and the subsequent phase III, as well as the origin of this phase III were not significantly different between bile and saline. Antral pressure waves were significantly more frequent during and immediately after bile infusion compared with saline infusion (p < 0.05). The duration of phase I following infusion was significantly longer after bile (24.8 +/- 3.7 min) than after saline infusion (13.1 +/- 1.7 min; p < 0.05). The mean gallbladder volume tended to increase in the hours following bile infusion, but to decrease after saline infusion (p = 0.06). Plasma motilin increased after bile and saline infusion in an almost identical way. CONCLUSION: This study provides no clear evidence for a role of intraduodenal artificial bile (i.e. its main constituents) in the regulation of migrating motor complex cycling or feedback inhibition of inter-digestive gallbladder emptying.     

Hepatoprotection in ethinylestradiol-treated rats is provided by tauroursodeoxycholic acid,but not by ursodeoxycholic acid*

Abstract Ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) have been suggested as potential treatments for drug-induced cholestasis. It was therefore decided to study the effects of administration of UDCA or TUDCA on individual serum bile acid concentrations, conventional liver tests and associated hepatic ultrastructural changes in ethinylestradiol-treated (EE) rats (5 mg/kg per day). Control rats were treated s.c. with propylene glycol. EE-treated rats were randomly assigned to receive daily i.p. injections of placebo, TUDCA or UDCA. Four rats in each group were treated for 4 consecutive days, and a second four for 14 days. After 4 days of treatment, the serum levels of cholic acid and taurocholic acid were significantly increased in EE-treated rats. None of the conventional liver tests were significantly different among the four groups. After 14 days of treatment the serum levels of cholic acid, chenodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, bilirubin, alkaline phosphatase and gamma glutamyltransferase were significantly raised in EE and EE plus UDCA treated rats. EE plus TUDCA treated rats, however, had no significant changes in these individual serum bile acids or conventional liver tests. The ultrastructure of livers from EE plus TUDCA treated rats was similar to those of controls. On the other hand, EE and EE plus UDCA rats both showed a significant reduction in sinusoidal microvilli. These results show that treatment of rats for 4 days with EE induces significant rises in the serum concentrations of two individual bile acids and that TUDCA protects against this. On treatment over 14 days TUDCA provides protection against changes in several biochemical liver tests as well as ultrastructural hepatoprotection. Treatment with UDCA, however, afforded no such protection.     

急性肝衰竭大鼠消化间期移行性运动复合波的变化特点

目的 观察急性肝衰竭大鼠胃肠消化间期移行性运动复合波(MMC)的变化及其特点. 方法 采用D-氨基半乳糖急性肝衰竭大鼠模型,用多道生理记录仪分别记录正常对照组和急性肝衰竭模型组大鼠的胃肠消化间期MMC,并对两组大鼠胃肠消化间期MMC的各项指标进行比较分析. 结果 大鼠胃窦和十二指肠MMCⅡ相:急性肝衰竭组分别为(1519.00±831.14)s和(1535.86±930.50)s,正常对照组分别为(573.61±409.98)s和(541.09±342.30)s,急性肝衰竭组比正常对照组显著延长,t值分别为-3.97和-3.85,P值均<0.05.大鼠胃窦和十二指肠MMCⅢ相:急性肝衰竭组分别为(23.39±6.36)s和(27.02±11.50)s,正常对照组分别(53.32±14.01)s和(53.81±1 3.64)s,急性肝衰竭组比正常对照组明显缩短,u值分别为-4.99和4.66,P值均<0.05.胃窦Ⅲ相频率:急性肝衰竭组为(0.04±0.01)HZ,正常对照组为(0.22±0.01)HZ,u=-4.73,P<0.05,差异有统计学意义.大鼠空肠MMC周期和MMCⅡ相:急性肝衰竭组分别为(1897.71±815.77)s和(1870.90±1010.35)s,正常对照组分别为(1384.17±449.34)s和(643.04±450.67)s,两组比较,u=-1.63和t=-4.94,P值均<0.05.大鼠空肠MMCⅢ相持续时间:急性肝衰竭组为(31.41土11.17)s,正常对照组为(53.11±14.74)s,t=5.10,P<0.05.大鼠胃窦和十二指肠MMC周期、十二指肠MMCⅢ相频率和空肠Ⅲ相频率变化,两组大鼠比较,差异无统计学意义.结论 急性肝衰竭大鼠MMCⅡ相显著延长,呈移行性簇状收缩,MMCⅢ相缩短,空肠MMC周期延长,可能是导致急性肝衰竭大鼠胃肠动力障碍的主要原因.     

Effect of ursodeoxycholic acid administration on bile duct proliferation and cholestasis in bile duct ligated rat

The origin, mechanism, and significance of the bile duct proliferation (BDP) associated with cholestasis remain unexplained. This study examined the effect of oral administration of ursodeoxycholic acid (UDCA) on both BDP and cholestasis in the rat. After bile duct ligation, male Sprague-Dawley rats were treated for 30 days with either UDCA (5 mg/day) (group A) or saline solution (group B). Animals were sacrificed at day 30. The serum activity of aminotransferase (ALT, AST), alkaline phosphatase, and -glutamyltransferase (GGT) was significantly lower (P<0.01) in the UDCA-treated rats. Total serum bilirubin and total serum bile acids were lower (P<0.001) in group A. Moreover, the control of BA in bile was reduced also (P<0.02). Conversely, serum cholesterol levels were not different between the two groups. Histological examination showed that the number of ductular cells in the portal areas was significantly (P<0.001) reduced in UDCA-treated as compared to saline-treated rats. The replication activity, assessed as the number of bromodeoxyuridine-positive cells, was also significantly lower in treated animals (33±11 vs 64±22 per 1000 cells;P<0.001). Lobular bile ductules were three times larger in group B, and extrahepatic duct measurements confirmed this increase in size of the larger biliary ducts (P<0.001). These findings demonstrate that UDCA reduces BDP in response to BD ligation. Although the mechanism(s) of this effect is still hypothetical, UDCA may reduce the level of irritating bile salts such as chenodeoxycholic acid and lithocolate and increase periductular bile acid recirculation. These data support the beneficial effect of UDCA treatment in chronic cholestatic disease.     

Duodenal nutrients inhibit canine jejunal fasting motor patterns through a hormonal mechanism

Ingestion of a meal converts the fasting motor pattern, the migrating motor complex (MMC), to a fed pattern of motility. The role of specific anatomic gut regions involved in these changing patterns of motility and the neurohormonal factors which mediate these changes, however, are unknown. Our aim was to determine the neurohormonal mechanisms by which nutrients within the duodenal lumen alter proximal jejunal motility. Fifteen dogs were prepared with a gastric cannula, duodenal infusion catheter, duodenal and proximal jejunal manometry catheters, and a totally diverting cannula in the most proximal portion of the jejunum. Ten of the dogs also underwent completein situ neural isolation of the entire jejunoileum. Experiments were performed in the fasting state with no infusion (0 ml/min) and during a 5-hr duodenal infusion (3 ml/min) of either a nonnutrient electrolyte solution or a mixed nutrient solution while diverting distal duodenal chyme from the jejunum. During sham infusion (0 ml/min), the MMC was present in neurally intact dogs (group 1) and dogs with neurally isolated jejunoileum (group 2). Nonnutrient infusion did not inhibit or consistently alter the MMC in either group. Nutrient infusion limited to the duodenum inhibited the MMC in both duodenum and jejunum in dogs with neurally intact and neurally isolated jejunoileum. Latency of onset of the fed pattern in the duodenum and jejunum did not differ between groups. We conclude that postprandial inhibition of the MMC in the jejunum is mediated, in part, by a hormonal mechanism induced by duodenal lumenal nutrients.This work was supported in part by the USPHS (NIH Grant DK39337), the Ethicon Corporation, and Mayo Foundation.This work was presented at the Annual Meeting of the Association of Academic Surgeons on November 11, 1993, in Hershey, Pennsylvania.     

Ursodeoxycholic acid limits liver histologic alterations and portal hypertension induced by bile duct ligation in the rat.

Chronic administration of ursodeoxycholic acid (UDCA) has recently been suggested as a potential treatment for cholestatic liver disease. The purpose of this study was to examine the effects of chronic oral administration of UDCA on the histological, biochemical, and hemodynamic abnormalities induced by bile duct ligation in the rat. Fifty-one rats with ligation-section of the common bile duct were randomly and blindly assigned to receive UDCA (25 mg/kg each day) or placebo by gavage for 4 weeks. At the end of the treatment period, morphometric analysis showed that in rats treated with UDCA, hepatocyte and sinusoidal volume fractions were significantly higher than in rats receiving placebo [41.9 +/- 3.2% vs. 28.1 +/- 1.8%, (mean +/- SE) and 7.4 +/- 0.1% vs. 4.3 +/- 0.3%, respectively], whereas bile duct volume fraction (reflecting bile ductular proliferation) and connective tissue fraction were significantly lower in rats treated with UDCA than in rats receiving placebo (14.2 +/- 1.5% vs. 20.0 +/- 1.0% and 35.4 +/- 2.4% vs. 47.6 +/- 1.7%, respectively). Serum aminotransferase and alkaline phosphatase activities, and total serum bile acids and individual bile acid concentrations were not significantly different between the two groups. Portal pressure (12.7 +/- 0.5 mm Hg vs. 17.1 +/- 0.5 mm Hg), portal tributary blood flow (5.7 +/- 0.4 vs. 9.3 +/- 0.4 mL.min-1.100 g-1 body weight), and cardiac index (41.1 +/- 1.8 vs. 50.6 +/- 1.4 mL.min-1.100 g-1 body weight) were significantly lower in UDCA-treated rats than in placebo-treated animals. In portal vein stenosed rats, chronic administration of UDCA had no hemodynamic effects, a finding that suggests UDCA has no direct vasoactive effect on splanchnic circulation. It is concluded that in rats with bile duct ligation UDCA limits the severity of liver disease and consequently of portal hypertension and hyperkinetic circulation.     

Cyclic motor activity and trophicity after jejunal resection and bypass in rats

The aim of the study was to examine the changes in intestinal motility induced by an extensive jejunal resection and bypass in rats using an electromyographic technique. The relationship, if any, between the development of motility and adaptive modifications of intestinal trophicity was also studied. A massive jejunal resection, preserving a 7-cm segment distal to the ligament of Treitz, was performed in one group of animals. In a second group, the jejunum was bypassed as a self-emptying blind loop. Two sham-operated groups underwent transection and reanastomosis on the proximal jejunum or ileum. Electromyographic activity was studied at the 10th and 30th postoperative days by means of electrodes implanted throughout the remaining or bypassed bowel and was expressed by means of the pattern of recurrence of the migrating myoelectric complex (MMC). After a month, the animals were sacrificed. Mucosal and muscular wet weight and protein content (mg/cm) of the intestine were then determined. The results showed that 10 days after the jejunal resection in the fasting state, MMC cycle duration is different in the remaining jejunum and in the ileum. However, the distribution of MMC phases in the jejunum was modified and was similar to the one in the ileum. Thirty days after resection, MMC cycle duration, as well as phase distribution in the remaining jejunum, resemble the MMC patterns in the ileum. These changes were not observed after bypass. After the return of MMCs after postprandial inhibition produced by a meal, MMC duration in the ileum was greatly decreased until a month after jejunal resection. In contrast, the jejunal bypass did not produce this modification.     

Maintenance of hepatic bile acid secretion rate during overnight fasting by bedtime bile acid administration

We have tested the hypothesis that the greater clinical efficacy of bedtime administration of bile acid in gallstone dissolution is due to prevention of the reduction in hepatic bile acid secretion that normally accompanies overnight interruption of the enterohepatic circulation, thus also reducing the secretion of supersaturated hepatic bile. We measured the hepatic bile acid secretion rate by combining duodenal perfusion of a nonabsorbable recovery marker (polyethylene glycol) with continuous intravenous infusion of a hepatic bile marker (indocyanine green). We studied 6 subjects with gallstones before and during administration of ursodeoxycholic acid (UDCA, 675 mg) at bedtime. Duplicate pretreatment studies revealed good reproducibility. Mean values for hepatic bile acid secretion rate were uninfluenced by chronic UDCA administration before the acute bedtime dose, but during the 4-h period after acute administration of UDCA the total bile acids secreted increased by a mean value of 2.2 mmol (p less than 0.01). Before treatment, nine of the 78 hourly samples were secreted at a hepatic bile acid secretion rate of less than 5 mumol/kg.h in the 6 patients studied, compared with only one hourly sample during UDCA administration. Super-saturated hepatic bile was secreted for a mean of 9.5 h before treatment, and for 1.2 h during UDCA treatment (p less than 0.005). We conclude that if UDCA is administered at bedtime, this maintains the hepatic bile acid secretion rate overnight, thus reducing secretion of supersaturated hepatic bile, in addition to the well-established effect of UDCA on cholesterol secretion.     

Role of Bile Acids in Duodenal Migrating Motor Complexes in Dogs

Previous studies have suggested thatenterohepatic circulation of bile acids is essential forregular cycling of duodenal migrating motor complexes(MMCs). The present study was an attempt to clarify the role of bile acids in the enterohepaticcirculation system in initiating duodenal MMCs. Sevendogs underwent total external biliary diversion thatresulted in the loss of MMCs originating from theduodenum. Sodium ursodeoxycholate (6 mg/kg/hr) was thengiven either through the portal vein or a peripheralvein, and motility of the gastrointestinal tract wasserially recorded. When sodium ursodeoxycholate was given either through the portal vein or aperipheral vein during external biliary diversion,duodenal MMCs restarted. The cyclic change in plasmamotilin levels during an MMC cycle as induced by sodium ursodeoxycholate was almost the same as in anormal MMC cycle. Total bile acid concentration in theportal vein changed cyclically with MMC cycles when bileflow was intact but did not change cyclically with MMC cycles restarted by intravenous bilesalt infusion. Bile acid stimulation of putativereceptors existing between the portal vein andintrahepatic bile ducts may be involved in initiatingnormal duodenal MMC cycles.     

Prolonged Ambulatory Duodeno-Jejunal Manometry in Humans: Normal Values and Gender Effect

Objective: The aim of this study was to provide a detailed comparison of motor activity in the duodenum and jejunum and between men and women studied by prolonged ambulatory manometry.
Methods: Thirty healthy volunteers (17 males) underwent prolonged ambulatory recording of duodeno-jejunal motility using a catheter with five built-in strain-gauge transducers (two duodenal and three jejunal). Manometric data was obtained during an extended period of fasting, the postprandial period and during sleep.
Results: There was a wide range of durations of the migrating motor complex (MMC), but at least one phase III was detected during 6 h of fasting, or 6 h of sleep in each subject (0.52 ± 0.04 phase III/hour during fasting vs 0.59 ± 0.04 during sleep,   p = 0.1  ). There was marked variation in the duration and pattern of phase III. Postprandially, frequency of contractions and motility index were maximal in the first 2 h after the meal, in both the duodenum and jejunum. There were no substantive differences between males and females or between the duodenum and jejunum.
Conclusion: We conclude that upper small bowel motility is little affected by gender or segment.     

Changes of gastrointestinal myoelectric activity and bile acid pool size after cholecystectomy in guinea pigs

AIM: To investigate the bile acid pool size after cholecystectomy whether or not correlated to the gastrointestinal migrating myoeiectric complex (MMC) in guinea pigs. METHODS: Gallbladder motilities were assessed before cholecystectomy. Furthermore, we continuously monitored interdigestive gastrointestinal motilities using bipolar electrodes in conscious guinea pigs before and after surgery at 4 wk in standard diet group and high cholesterol diet (cholesterol gallstone) group. Total bile acid pool sizes were measured by isotope dilution method at meantime. RESULTS: After cholecystectomy, there were parallel falls in duration of phase Ⅰ, Ⅱ, Ⅲ and MMC cycle duration but increase in amplitude in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones. However, There were not significantly differences. On the other hand, the bile acid pool was definitely small in the GS guinea pigs compared to normal guinea pigs and became slightly smaller after cholecystectomy. Similarly, bile acid in gallbladder bile, fecal bile acid was slightly increased in GS guinea pigs after cholecystectomy, to the same degree as normal. These differences, however, were not significant. CONCLUSION: It is concluded that in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones: (1) Cholecystectomy produce a similar but less marked trend in bile acid pool; and (2) MMC are linked to enterohepatic circulation of bile acids, rather than surgery, which is consistent with changes of the bile acid pool size. As a result, gastrointestinal dyskinesia is not involved in occurrence of postchole cystectomy syndrome.     

Effect of ursodeoxycholic acid on liver iron stores and distribution in rats with normal or iron-supplemented diet

Abstract: Iron excess is a potential liver-damaging factor, and bile salts can increase iron digestive absorption and iron biliary excretion. The aim of this study was to investigate in rats the effect of ursodeoxycholic acid, a bile salt used in the treatment of chronic liver disease, on the hepatic iron stores in normal and iron-overload conditions. UDCA was administered by gavage to Sprague-Dawley rats. Iron hyperabsorption and overload were obtained by 5% carbonyl iron addition in diet. Hepatic iron stores and distribution were evaluated by liver iron concentration measurement and histologic assessment, respectively. Whatever the iron content of the diet, liver iron concentration was not modified by UDCA administration compared with the control groups. Iron distribution was not modified by UDCA in rats with normal diet. The total iron score was only transiently lowered by UDCA in iron supplemented rats compared with the control group at 1 month. In conclusion, chronic UDCA administration does not modify liver iron stores and distribution in rats with both normal or increased digestive iron absorption. These data suggest that UDCA is unlikely to increase hepatic iron stores in treated patients and that the benefit of UDCA treatment is probably not related to a decreasing effect of liver iron content.