Gallbladder Contraction Research Articles

Ciliary Neurotrophic Factor Restores Gallbladder Contractility in Leptin-Resistant Obese Diabetic Mice 1,2

<h3>Background</h3> Obesity and diabetes are major risk factors for cholesterol gallstones, and the majority of obese people are leptin-resistant. Our previous work has shown that both leptin-deficient (Lep^ob) and leptin-resistant (Lep^db) obese diabetic mice have decreased <i>in vitro</i> gallbladder motility. Leptin administration to leptin-deficient (Lep^ob) animals restores gallbladder motility and reverses obesity and hyperinsulinemia. However, additional leptin in leptin-resistant obesity would not be expected to improve obesity-related parameters. Recent studies demonstrate that ciliary neurotrophic factor (CNTF) reduces weight and hyperinsulinemia in leptin-resistant obesity. Our hypothesis is that CNFT would cause weight loss, lower blood sugars, and restore gallbladder contractility in leptin-resistant (Lep^db) mice. <h3>Materials and methods</h3> 20 C57b/6J and 20 Lep^db 8-week-old female mice were injected daily with either intraperitoneal saline or 0.3 μg/g CNTF_Ax15 for 17 days. Gallbladders were mounted in muscle baths and stimulated with acetylcholine, neuropeptide Y, and cholecystokinin. Gallbladder volume, serum glucose, insulin, liver weight, liver fat, and gallbladder responses were measured. Data were analyzed by ANOVA. <h3>Results</h3> Saline treated obese mice had greater body weight and obesity parameters, but decreased gallbladder contractility to neurotransmitters compared to saline treated lean mice. CNTF administration to obese mice decreased body weight and obesity parameters, and restored gallbladder contractility. CNTF treated lean animals had weight loss and decreased gallbladder contraction to acetylcholine and cholecystokinin compared to saline treated lean animals. <h3>Conclusions</h3> Ciliary neurotrophic factor (CNTF) causes 1) weight loss, 2) improvement of diabetes, and 3) alterations in gallbladder motility that is improved in obese mice but decreased in lean mice. We conclude that CNTF may improve gallbladder contractility in leptin-resistant obesity with diabetes.

The cholecystokinin test: An assessment

A cholecystokinin (CCK) test was performed on 13 female patients who were thought to be having attacks of gallbladder pain and in whom at least one cholecystogram had been normal. In 10 of these patients the CCK test was performed during the course of a repeat cholecystogram in order to assess the effect of CCK on gallbladder contraction. There was no constant relationship between a positive test and gallbladder contraction as measured radiographically. Cholecystectomy was undertaken in 9 patients and of these, 4 had been CCK positive, 4 had been CCK negative and 1 had reacted equivocally. None of the CCK positive patients had stones at operation, whereas 2 of the CCK negative patients had one or two small stones. In this small series cholecystectomy relieved both the CCK negative and CCK positive patients of pain with equal frequency. It is concluded that a negative CCK test by no means excludes the presence of symptomatic gallstones in patients with X-ray negative gallbladder pain.

Periodic gallbladder contraction maintains bile acid circulation during the fasting period: a canine study.

Using a canine model we have studied the relationship between the interdigestive cycle in the small intestine, motility changes in the biliary tract and bile acid output into the duodenum from direct hepatic secretion and gallbladder emptying. Under anaesthesia catheters were inserted into the gallbladder, common bile duct and duodenum, and electrodes were attached to the small intestine in five dogs. These animals were subsequently studied conscious and fasting. A double marker technique was used to measure bile acid output from the gallbladder and liver while pressure in the gallbladder and common bile duct and electrical activity in the small intestine were monitored. Four complete interdigestive cycles were recorded in each dog. Output of bile acids from the gallbladder fluctuated with the phases of the cycle: being lowest in phase I (3.9 +/- 0.7 mumol/min); increasing significantly (P less than 0.005) in phase II (9.8 +/- 1.0 mumol/min); remaining elevated in phase III (13.9 +/- 1.7 mumol/min); and falling significantly (P less than 0.05) in phase IV (8.4 +/- 1.8 mumol/min). In contrast, hepatic secretion of bile acids directly into the duodenum remained fairly constant. Intraluminal pressure in the biliary tract paralleled the fluctuation in gallbladder bile acid output, being significantly increased (P less than 0.05) in phases II and III. Periodic contraction of the gallbladder would, therefore, appear to be the principal mechanism for the phasic output of bile during fasting.

Delayed Postprandial Gastric Emptying and Impaired Gallbladder Contraction Together With Elevated Cholecystokinin and Peptide YY Serum Levels Sustain Satiety and Inhibit Hunger in Healthy Elderly Persons

Altered gastric and cholecystic motility are risk factors for malnutrition in elderly persons, mainly through impaired satiety-appetite rhythm. Contrasting data have been published about this topic. The aim of this study was to evaluate, in healthy elderly participant, postprandial gastric and cholecystic emptying in relation to serum CCK (cholecystokinin) and PYY (peptide YY), as well as satiety and hunger sensations. We studied 10 community-dwelling elderly persons, (77 +/- 3 years old) and 9 younger adult persons (32 +/- 8 years old). Using ultrasonography, we measured gastric antrum area and cholecystic volume in fasting condition and after an 800-kcal mixed meal. Time for gastric and cholecystic emptying, and percentage of cholecystic emptying were calculated. Satiety and hunger were evaluated every 30 minutes using visual analogue scales. CCK and PYY serum levels were assayed 30 minutes before and at times 0, 30, 60, 120, and 240 minutes after the meal. Elderly participants showed a longer gastric emptying time compared to younger participants (448 +/- 104 vs 306 +/- 57 minutes, p <.002). Postprandial cholecystic emptying was significantly reduced in the older group (maximum contraction, 69% vs 84%; p <.05). After the meal, CCK and PYY levels showed higher, persistent elevation in elderly participants. In this group, postprandial satiety lasted significantly longer than in younger participants, and hunger was suppressed throughout the postprandial period. Antral area directly correlated with satiety and inversely with hunger. Gallbladder volume inversely correlated to satiety. This study showed, in a group of healthy elderly people, delayed gastric emptying associated to reduced cholecystic contractility together with higher CCK and PYY serum levels. These modifications facilitated long-lasting satiety and hunger suppression after a meal. This condition may lead to caloric restriction and finally to malnutrition at older ages.

Rho kinase expression and its central role in ovine gallbladder contractions elicited by a variety of excitatory stimuli

Rho kinase has contractile activity, which induces Ca 2+ sensitization in various cells. Several receptors are linked to the Rho/Rho-kinase pathway. Therefore, in this study we aimed to demonstrate the central importance of this novel pathway for diverse excitatory stimuli in the smooth muscle of the sheep gallbladder. Accordingly, the effects of a Rho kinase inhibitor, (+)-( R)- trans-4-(1-aminoethyl)- N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632, 10 − 8 –3 × 10 − 5 M), were investigated on cholecystokinin-8 (CCK-8, 10 − 8 M), endothelin-1 (10 − 8 M), carbachol (10 − 6 –10 − 5 M), 5-hydroxytryptamine (5-HT, 10 − 6 –10 − 5 M), histamine (10 − 6 –10 − 5 M), phenylephrine (10 − 5 –10 − 4 M), neurokinin A (10 − 7 –10 − 6 M), electrical field stimulation (40 V, 0.5 ms, 2, 4, 8, 16, 32 Hz, 15 s, 3 min intervals) and potassium chloride (KCl, 25–50 mM)-induced contractions as well as spontaneous contractile activity. Electrical field stimulation evoked tetrodotoxin (3 × 10 − 6 M)-sensitive reproducible contractions, which were inhibited by atropine (2 × 10 − 6 M) and potentiated by eserine (5 × 10 − 7 M). EFS-induced contraction was significantly inhibited by Y-27632 (10 − 5 M). In addition, spontaneous contractile activity was suppressed in the presence of the compound (10 − 6 –10 − 5 M). This Rho kinase inhibitor also dramatically decreased the contractions elicited by 5-HT, neurokinin A and carbachol. KCl-induced contraction, which was not atropine-sensitive, was also conspicuously attenuated by Y-27632. Moreover, Y-27632 (10 − 8 –3 × 10 − 5 M) relaxed gallbladder strips that were contracted by histamine, endothelin-1, CCK-8 and phenylephrine in a concentration-dependent manner. pEC 50 values for Y-27632 were 6.25 ± 0.10, 5.79 ± 0.12, 5.83 ± 0.09 and 5.70 ± 0.13 for the contraction elicited by histamine, CCK-8, endothelin-1 and phenylephrine, respectively. Furthermore, we also demonstrated Rho kinase protein expression (ROCK-1 and ROCK-2) by Western blot analysis. In conclusion, ROCK is expressed in the smooth muscle of the ovine gallbladder, and it has a central role in the contractile activity induced by diverse excitatory stimuli.

Gallbladder Disorder in Type 2 Diabetes Mellitus Cases

The present paper reports the prevalence of gallbladder disorder in type 2 diabetic patients and their correlation with sex, age, weight and duration of diabetes. 30 type2 diabetic patients and 20 healthy controls underwent real time ultrasonography to study the prevalence of gallbladder disorder. The fasting gallbladder volume and contraction 60 min. after a fatty meal of the diabetic subjects were compared with 30-35 age and sex match volunteers. The age, sex weight, duration of diabetes and control of diabetes were correlated to the prevalence of gallbladder disorder in diabetic patients. 29% percent of the diabetic patients had ultrasonographic evidence of gallstones as compared to 3.7% in healthy subjects. 67.5% of the diabetic patients with gallbladder disorder were females which is more than in males. Mean fasting gallbladder volume increased in diabetic patients (23.5 cm3) as compared to non diabetic healthy subjects (13.8 cm3). Mean fasting gallbladder volume of diabetic patients with gallbladder disorder was found to be larger then healthy persons. Mean percentage of contraction of gallbladder 60 min. after fatty meal was reduced in diabetic patients (48.5%) and also further reduced in the patients with gallbladder disorder (35%). Mean duration of diabetes was longer in diabetic patients with gallbladder disorder. But no significant effect of age, sex and weight was observed. It is concluded that type2 diabetic patients have increased prevalence of gallbladder disorder.

Role of cholecystokinin in appetite control and body weight regulation

Summary Cholecystokinin (CCK), a peptide that is distributed widely throughout the gastrointestinal tract and the central nervous system, has a number of physiological effects including the stimulation of gallbladder contraction and pancreatic and gastric acid secretion, slowing of gastric emptying and suppression of energy intake. This review focuses on current knowledge relating to (i) the effects of CCK on energy intake; (ii) the role for CCK in the pathophysiology of obesity; and (iii) the therapeutic potential for strategies which modulate the action or secretion of CCK in the management of obesity. While CCK plays a role in the acute regulation of appetite and energy intake, there is little evidence to suggest that specific CCK receptor agonists, or modulation of the actions of endogenous CCK by dietary manipulation, have sustainable inhibitory effects on energy intake. Hence, it appears unlikely that manipulating the pathways by which CCK modulates energy intake will prove to be an effective strategy in the long term management of obesity.

Gallbladder contraction, gastric emptying and antral motility: Single visit assessment of upper GI function in untreated celiac disease using echo‐planar MRI

To assess gallbladder contraction, gastric emptying, and antral motility in untreated celiac patients and healthy controls using a single MRI examination. Gallbladder emptying, gastric emptying, and antral motility were measured in 15 celiac patients and 15 age/sex-matched healthy controls following a 323-kcal test meal using EPI techniques. Postprandial dyspepsia scores were recorded on a questionnaire. Fasting gallbladder volume (P=0.01) and the volume of bile ejected postprandially (P=0.014) were increased in celiacs. Gastric emptying tended to be slower in celiacs (P=0.142). Three celiac patients with severe postprandial dyspepsia and total villous atrophy had pathologically delayed gastric emptying and increased fasting gallbladder volume. Antral contractions were absent in five out of 14 patients (36%) five minutes after the meal, but in none of 10 volunteers in whom the antrum could be visualized (P=0.128). This study shows that using MRI, multiple parameters related to upper gastrointestinal function in celiac disease can be measured in a single noninvasive study, whereas previously three separate visits would have been required. Celiacs have increased fasting gallbladder volumes and tend to have slower gastric emptying.

Symptoms and Pathophysiological Correlations in Patients with Constipation and Functional Dyspepsia

Introduction: Patients with constipation often report dyspeptic symptoms, but whether constipation is associated with specific dyspeptic symptoms and altered gastrointestinal (GI) motility, remains to be established. Our aim was to study symptoms association and GI motility parameters in patients with constipation and functional dyspepsia. Patients and Method: 42 patients with different symptoms and severity of constipation and dyspepsia were enrolled. Scintigraphic gastric emptying, colonic transit time and gallbladder contraction were studied in all subjects. Results: No significant association was observed between individual symptoms of constipation and dyspepsia. Patients with more severe constipation did not have higher dyspepsia severity scores. Colonic transit time, gastric half emptying and gallbladder contraction were not significantly correlated. Although patients with severe nausea had faster colonic transit than those with absent/mild symptom (19 ± 2 vs. 48 ± 7 h; p < 0.05), the multivariate analysis only revealed a significant association between severe postprandial fullness, delayed t_1/2 (OR 1.05, CI 1–1.1) and impaired gallbladder contraction (OR 0.94, CI 0.89–0.99). Conclusions: Constipation was not associated with severity, or any particular dyspeptic symptom. Although motor abnormalities of both colon and proximal GI tract regions existed in the subset of constipated dyspeptic patients, they did not seem associated with the genesis of different dyspeptic symptoms.

μ‐Opiate receptor agonist loperamide blocks bethanechol‐induced gallbladder contraction, despite higher cholecystokinin plasma levels in man

mu-Opiate receptor agonists, such as loperamide, influence biliary excretion and suppress cholecystokinin (CCK)-induced gallbladder contraction. Loperamide decreases cholinergic mechanisms, like pancreatic polypeptide (PP) release, while muscarinic agonist (bethanechol)-induced PP release remains unaffected. The effects of loperamide on gallbladder contraction and peptide release were performed to resolve this discrepancy. Six subjects (27.6 +/- 2.0 years) received bethanechol (12.5, 25 and 50 microg kg(-1) h(-1) continuously over 40 min) after oral 16 mg loperamide (vs placebo) in a crossover design. Gallbladder volume and plasma levels of CCK, PP, motilin, gastrin, neurotensin, cholylglycine were measured regularly. Bethanechol significantly reduced gallbladder volume (26.7 +/- 1.9 to a nadir of 15.3 +/- 2.2 mL, P < or = 0.05), and this action was inhibited by loperamide. Basal CCK levels increased significantly after loperamide. Incremental integrated CCK release after bethanechol was higher under loperamide (P < or = 0.05), as placebo CCK release was significantly decreased under bethanechol (2.0 +/- 0.4-0.8 +/- 0.3 pmol L(-1)). In both settings, PP levels were significantly increased after bethanechol, while release of neurotensin, motilin, gastrin and cholylglycine was unaffected. The mu-opiate receptor agonist loperamide inhibits bethanechol-induced gallbladder contraction. This effect is not mediated by inhibition of CCK release, as loperamide even enhances basal CCK plasma levels. As cholinergic mechanisms, like bethanechol-induced incremental PP release, were unaffected, mu-opiate agonists might influence gallbladder contraction via vagal-cholinergic pathways.

Free phytosterols facilitate excretion of endogenous cholesterol in gerbils

To determine whether phytosterols (PST) facilitate excretion of whole body cholesterol and whether dietary fat or enhancing gallbladder contraction with curcumin might influence this process, four experiments were conducted in gerbils. In Experiment 1, naïve gerbils received cholesterol-free purified diets with 30% energy from fat and 0% or 0.75% free PST from tall oil for 4 weeks. In Experiment 2, body cholesterol pools were expanded by feeding a diet containing 0.3% cholesterol for 3 weeks. Subsequently, PST was provided in either fat-free or normal-fat diets without cholesterol for only 2 h each morning, followed by a low-fat diet for the rest of the day and food restriction overnight. In Experiment 3, gerbils were preloaded with cholesterol, followed by either PST alone or PST+curcumin to enhance gallbladder contraction. In Experiment 4, curcumin or curcumin+PST were fed with 30% as fat and 0.15% cholesterol throughout the study. Because of the small whole body cholesterol pool in Experiment 1, the impact of PST was limited. When whole body cholesterol was expanded in Experiments 2 and 3, subsequent reductions of liver esterified cholesterol by PST were significant. In the presence of dietary fat, PST caused a greater reduction (23%) than in a fat-free diet (8%) compared to respective controls. Curcumin (Experiments 3 and 4) proved ineffective in reducing liver or plasma cholesterol pools, and the 3:1 ratio between PST/diet cholesterol was less effective at blocking cholesterol absorption than a 5:1 ratio previously employed. Thus, free PST removed whole body cholesterol, which was enhanced by concomitant fat intake, but was unaffected by a gallbladder contracting agent.

Effects of Various Selective Phosphodiesterase Inhibitors on Carbachol-Induced Contraction and Cyclic Nucleotide Contents in the Guinea Pig Gall Bladder

The effects of various selective phosphodiesterase (PDE) inhibitors on muscle contractility and cyclic nucleotide contents in the guinea pig gall bladder were investigated. Various selective PDE inhibitors, vinpocetine (type 1), erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, type 2), milrinone (type 3), Ro20-1724 (type 4), and zaprinast (type 5), inhibited CCh-induced contractions in a concentration-dependent manner. The rank order of potency for the gall bladder was Ro20-1724 > vinpocetine > EHNA > milrinone > zaprinast, which was different from that of the trachea, taenia coli, and aorta. In the presence of CCh (0.3 muM), vinpocetine, milrinone, and Ro20-1724 each increased cAMP content, but not cGMP. By contrast, zaprinast increased cGMP content, but not cAMP, and EHNA increased both cAMP and cGMP contents. These results suggest that vinpocetine-, milrinone-, and Ro20-1724-induced relaxation was correlated with cAMP, zaprinast-induced relaxation was correlated with cGMP, and that EHNA-induced relaxation was correlated with cAMP and cGMP in the guinea pig gall bladder. In conclusion, the effect of PDE inhibitors in the guinea pig gall bladder was different from those in smooth muscles, such as the trachea, taenia coli, and aorta.

Cholecystokinin

Cholecystokinin (CCK) is a peptide hormone discovered in the small intestine. Together with secretin and gastrin, CCK constitutes the classical gut hormone triad. In addition to gallbladder contraction, CCK also regulates pancreatic enzyme secretion and growth, intestinal motility, satiety signalling and the inhibition of gastric acid secretion. CCK is, however, also a transmitter in central and intestinal neurons. Notably, CCK is the most abundant neuropeptide in the human brain. Owing to difficulties in developing accurate assays, knowledge about CCK secretion in disease is limited. Available data indicate, however, that proCCK is expressed in certain neuroendocrine tumours and sarcomas, whereas the secretion of CCK is impaired in celiac disease and bulimia nervosa. Stimulation with exogenous CCK has proved useful in diagnostic tests of gallbladder and pancreatic diseases, as well as medullary thyroid carcinomas.

Fat in the intestine as a regulator of appetite—role of CCK

The present review summarizes the appetite-suppressing effects of intestinal fat in the regulation of food intake in humans, with a special focus on the role of cholecystokinin (CCK). Current evidence supports a role for intestinal fat (especially long-chain free fatty acids) acting via the peptide CCK as a physiological satiety pathway. The regulation of satiety is, however, complex and it is not surprising that multiple control systems exist. It is interesting to note that nutrients, such as hydrolysis products of fat in the small intestine, stimulate the release of satiety peptides, such as CCK or PYY, that serve as satiety signals. CCK, released from the gastrointestinal tract by the local action of digested food, exerts various functions: stimulation of gallbladder contraction and exocrine pancreatic secretion, inhibition of gastric emptying, and inhibition of appetite. CCK functions therefore (1) as a positive feedback signal to stimulate digestive processes and (2) as negative feedback signal to limit the amount of food consumed during an individual meal.

Nonobese diabetic mice have diminished gallbladder motility and shortened crystal observation time

Diabetes and obesity are strongly associated and are risk factors for cholesterol gallstone disease. Leptin-deficient and leptin-resistant diabetic obese mice have enlarged, hypomotile gallbladders. In addition, bile from gallbladders of leptin-deficient mice has enhanced cholesterol crystal formation, whereas bile from gallbladders of leptin-resistant mice has delayed crystal observation time. To determine the effect of diabetes alone, we hypothesized that leptin-normal, nonobese diabetic (NOD) mice would have reduced biliary motility and rapid crystal formation. Twenty control and 9 prediabetic and 11 diabetic NOD, 12- to 26-week-old mice underwent glucose measurement and cholecystectomy for muscle bath stimulation with neurotransmitters. An additional group of 200 control and 78 NOD 12-week-old mice underwent microscopic bile examination for cholesterol crystal formation. Compared with control mice, prediabetic NOD mice had similar glucose levels and gallbladder volumes. Diabetic NOD mice had higher sugar levels and larger gallbladder volumes (P < 0.001) than control mice. Prediabetic NOD gallbladders had less contractility (P < 0.01) than control gallbladders, and contractility worsened (P < 0.01) in diabetic NOD mice. NOD mice formed cholesterol crystals earlier than did control mice (P < 0.05). Nonobese diabetic NOD mice have (1) decreased gallbladder contraction to neurotransmitters, which worsens with development of diabetes, and (2) rapid crystal formation. We conclude that diabetes alone alters gallbladder motility and cholesterol crystal formation.

Characterization of intracellular Ca2+ stores in gallbladder smooth muscle

The existence of functionally distinct intracellular Ca(2+) stores has been proposed in some types of smooth muscle. In this study, we sought to examine Ca(2+) stores in the gallbladder by measuring intracellular Ca(2+) concentration ([Ca(2+)](i)) in fura 2-loaded isolated myocytes, membrane potential in intact smooth muscle, and isometric contractions in whole mount preparations. Exposure of isolated myocytes to 10 nM CCK caused a transient elevation in [Ca(2+)](i) that persisted in Ca(2+)-free medium and was inhibited by 2-aminoethoxydiphenylborane (2-APB). Application of caffeine induced a rapid spike-like elevation in [Ca(2+)](i) that was insensitive to 2-APB but was abolished by pretreatment with 10 muM ryanodine. These data support the idea that both inositol trisphosphate (IP(3)) receptors (IP(3)R) and ryanodine receptors (RyR) are present in this tissue. When caffeine was applied in Ca(2+)-free solution, the [Ca(2+)](i) transients decreased as the interval between Ca(2+) removal and caffeine application was increased, indicating a possible leakage of Ca(2+) in these stores. The refilling of caffeine-sensitive stores involved sarcoendoplasmic reticulum Ca(2+)-ATPase activation, similar to IP(3)-sensitive stores. The moderate Ca(2+) elevation caused by CCK was associated with a gallbladder contraction, but caffeine or ryanodine failed to induce gallbladder contraction. Nevertheless, caffeine caused a concentration-dependent relaxation in gallbladder strips either under resting tone conditions or precontracted with 1 muM CCK. Taken together, these results suggest that, in gallbladder smooth muscle, multiple pharmacologically distinct Ca(2+) pools do not exist, but IP(3)R and RyR must be spatially separated because Ca(2+) release via these pathways leads to opposite responses.

Pancreatic enzyme supplement improves dysmotility in chronic pancreatitis patients.

Impaired gallbladder contraction and rapid gastric emptying in patients with chronic pancreatitis may be the result of depleted pancreatic exocrine function. The authors tested whether oral pancreatic enzymes can improve the dysmotility or not. Study subjects consisted of 15 patients with chronic pancreatitis and 18 healthy controls. The gastric emptying time and gallbladder contraction were studied. All patients were initially studied using a test meal without pancreatic enzymes, followed on separate days by a test meal with a single and a triple dose of pancreatic enzymes. Blood samples were taken before and 2 h after the test meal to determine the pancreatic polypeptide levels. In patients with chronic pancreatitis, gallbladder contraction at 15 min after the meal was impaired. The gastric emptying time was faster and the ratio of pre- to postprandial pancreatic polypeptide levels was enhanced. A single dose and a triple dose of oral enzymes further improved the gastric emptying time and the pancreatic polypeptide ration, but did not improve the gallbladder contraction rate at 15 min. It was demonstrated that the oral pancreatic enzymes improved the gastric dysmotility, confirming the previous findings that suggested the depleted pancreatic enzyme output caused the dysmotility.

Gallbladder motility in children with Down syndrome.

The aim of this study was to investigate gallbladder motility in children with Down syndrome by measuring gall-bladder volume and contraction index. This study, performed between January 2001 and December 2002 at the Ondokuz Mayis University, School of Medicine, Department of Paediatric Neurology, Samsun, Turkey, included 21 patients with Down syndrome (study group) and 22 healthy children (control group). After an 8-hour fast, gallbladder diameters in both groups were measured in length, width, and height by ultrasonography before and 30 minutes after a test meal. The volume of gallbladder before and after a test meal was determined, and the contraction index was calculated. Blood triglyceride and cholesterol levels were measured, and 5-hydroxyindoleacetic acid (5-HIAA) levels in urine were determined. Mean gallbladder volume before test meal in the study group and controls was 8,412.4 +/- 5,174 mm and 16,516.8 +/- 6,796.1 mm (P < 0.001), respectively. The mean contraction index of the study group was 41.2% +/- 19.4% and of controls, 75.0% +/- 12.3% (P < 0.001). The mean triglyceride level of the study group was significantly higher than controls (P < 0.05). The mean urine 5-HIAA level of the study group was lower than controls (P < 0.05). CI was lower in patients with Down syndrome, suggesting gallbladder hypomotility. Hypomotility may be a feature associated with the high prevalence of gallstones in Down syndrome.

Bethanechol provocation testing does not predict symptom relief after cholecystectomy for acalculous biliary pain

Background. The currently accepted hypothesis to explain acalculous gallbladder pain is the lack of contractile co-ordination between the body and neck. We have previously shown that bethanechol, a muscarinic stimulant causes differential stimulation of these two regions. Aim. To evaluate the reliability of bethanechol-induced gallbladder contraction in predicting symptom relief after cholecystectomy in patients with acalculous gallbladder disease. Methods. Fifty-one patients underwent a bethanechol provocation test together with serial ultrasound to determine gallbladder emptying. McGill pain questionnaires were completed, and patients positive for pain (bethanechol provocation test +ve) were offered cholecystectomy, and patients negative for pain (bethanechol provocation test −ve) were reassessed at 6 months and offered cholecystectomy if symptoms persisted. All patients answered pain questionnaires either 6 months after surgery or as follow-up. Results. There was no difference in the percentage of gallbladder emptying between the bethanechol provocation test +ve and bethanechol provocation test −ve groups. Fifty-three percent of bethanechol provocation test +ve patients and 54% of bethanechol provocation test −ve patients still remained symptomatic 6 months after surgery. Conclusion. Gallbladder pain provoked by bethanechol does not predict symptom relief after cholecystectomy.

Involvement of endogenous CCK and CCK1 receptors in colonic motor function.

Cholecystokinin (CCK) is a brain-gut peptide; it functions both as a neuropeptide and as a gut hormone. Although the pancreas and the gallbladder were long thought to be the principal peripheral targets of CCK, CCK receptors are found throughout the gut. It is likely that CCK has a physiological role not only in the stimulation of pancreatic and biliary secretions but also in the regulation of gastrointestinal motility. The motor effects of CCK include postprandial inhibition of gastric emptying and inhibition of colonic transit. It is now evident that at least two different receptors, CCK(1) and CCK(2) (formerly CCK-A and CCK-B, respectively), mediate the actions of CCK. Both localization and functional studies suggest that the motor effects of CCK are mediated by CCK(1) receptors in humans. Since CCK is involved in sensory and motor responses to distension in the intestinal tract, it may contribute to the symptoms of constipation, bloating and abdominal pain that are often characteristic of functional gastrointestinal disorders in general and irritable bowel syndrome (IBS), in particular. CCK(1) receptor antagonists are therefore currently under development for the treatment of constipation-predominant IBS. Clinical studies suggest that CCK(1) receptor antagonists are effective facilitators of gastric emptying and inhibitors of gallbladder contraction and can accelerate colonic transit time in healthy volunteers and patients with IBS. These drugs are therefore potentially of great value in the treatment of motility disorders such as constipation and constipation-predominant IBS.