motilin and Chronic-Disease

Chronic constipation is a common digestive problem in North America, with significant psychosocioeconomic implications. Dietary and lifestyle measures and low-cost traditional over-the-counter laxatives are usually the first line of therapy but help only half of the patients. Several newer agents that act by increasing colonic peristalsis, altering colonic secretion, and/or antagonizing enteric opioid receptors have been developed that are effective in treating constipation and its related symptoms as well as improving quality of life. This article focuses on the pharmacology of traditional and newer agents for the treatment of constipation.

Topics: Alprostadil; Chronic Disease; Colchicine; Constipation; Guanylate Cyclase; Humans; Laxatives; Lubiprostone; Motilin; Narcotic Antagonists; Neurotrophin 3; Prebiotics; Probiotics; Receptors, Enterotoxin; Receptors, Guanylate Cyclase-Coupled; Receptors, Peptide; Surface-Active Agents

Chronic constipation (CC) is one of the most common functional gastrointestinal disorders. CC is estimated to affect up to 27% of the North American population. Although not life-threatening, CC can have profoundly negatively affects on quality of life and result in significant economic burden in terms of both direct and indirect healthcare costs. Possible etiologies for CC include alterations in gastrointestinal motility and secretion. Research efforts in CC have begun to identify multifactorial and often overlapping etiologies including abnormalities in myenteric neurons, alterations in neurotransmitters and their receptors, and incoordination of the muscles of the pelvic floor or anorectum. CC may be influenced by genetic predisposition, environmental factors and stress. In this article, the safety and efficacy of traditional and emerging therapies for CC are examined.

Topics: Analgesics, Opioid; Cathartics; Chloride Channel Agonists; Chronic Disease; Constipation; Drug Discovery; Gastrointestinal Motility; Humans; Motilin; Narcotic Antagonists; Natriuretic Peptides; Serotonin Agents

To observe the therapeutic efficacy of acupoint heat-sensitization moxibustion on chronic diarrhea patients as well as its effects on the levels of gastrointestinal neurotic mediators such as serum gastrin (GAS) and plasma motilin (MTL).. Sixty chronic diarrhea patients of Pi-Shen deficiency syndrome were randomly assigned to Group A (30 cases, treated with acupoint heat-sensitization moxibustion, once daily) and Group B (30 cases, treated with Changtai Oral Liquid, 10 mL each time, three times daily). The therapeutic course was 4 weeks. Another 20 healthy volunteers were recruited as the health control group. The levels of serum GAS and plasma MTL were detected using radioimmunoassay before and after treatment. The cured rate, the markedly effective case, the effective case, the ineffective case, and the total effective rate were calculated by the end of the treatment.. Before treatment the serum GAS level was lower and the plasma MTL level higher in the two patient groups than in the health control group with statistical difference (P<0.05). There was no statistical difference in the symptom integral between the two patient groups and the health control group (P>0.05). After treatment the serum GAS level increased, the plasma MTL level and the symptom integral decreased in the two patient groups, showing statistical difference when compared with the same group before treatment (P<0.05, P<0.01). After treatment the symptom integral was lower in the treatment group than in the control group with statistical difference (P<0.05). There was no statistical difference in the GAS and MTL levels between the two patient groups (P>0.05). The total effective rate for clinical symptoms was significantly higher in Group A than in Group B with statistical difference (93.3% vs 73.3%, P<0.05).. The therapy of acupoint heat-sensitization moxibustion was effective for chronic diarrhea patients of Pi-Shen deficiency syndrome. It could regulate the levels of serum GAS and plasma MTL and improve the patients' clinical symptoms.

Topics: Adult; Case-Control Studies; Chronic Disease; Diarrhea; Female; Gastrins; Humans; Male; Medicine, Chinese Traditional; Middle Aged; Motilin; Moxibustion; Single-Blind Method; Yang Deficiency; Yin Deficiency

This study explores the effects of fat-free milk supplementation on individuals with chronic constipation with regard to levels of motilin and acylated and des-acylated ghrelin (which affect intestinal motility) and compares them with data from control subjects given whole milk supplementation.. The investigation was designed according to the constipation severity test of individuals whose ages and body mass indexes were comparable. Individuals with mild constipation (n=10) were supplemented with 400 mL of fat-free milk daily; moderate constipation cases (n=10) were supplemented with 600 mL, and severe constipation cases (n=10) were supplemented with 800 mL of fat-free milk daily. Healthy control subjects were administered 400 mL of fat-free milk (group 1), which was followed a month later by administration of 400 mL of whole milk for 3 days (group 2). Blood samples were collected from the subjects before and after milk supplementation for hormone analyses. Motilin and acylated and des-acylated ghrelin were quantified with ELISA assay.. Supplementation of fat-free milk significantly increased levels of circulating motilin and ghrelin in all groups, including the control subjects, but whole milk supplementation led to a decrease in these hormone levels in the control subjects.. Drinking fat-free milk might be a new way of solving constipation.

Topics: Acylation; Adult; Aged; Animals; Biological Products; Case-Control Studies; Chronic Disease; Constipation; Dietary Fats; Dietary Supplements; Enzyme-Linked Immunosorbent Assay; Female; Gastrointestinal Motility; Ghrelin; Humans; Male; Middle Aged; Milk; Motilin; Severity of Illness Index

Zoujin pill (ZJP), a medication used to treat gastrointestinal disorders since the 15th Century in China, have been reported to exert anti-depressant effects in various models.. To assess the effects of ZJP on gastrointestinal function and depressive behavior in rats under chronic unpredictable mild stress (CUMS), and to examine the underlying mechanisms related to brain-gut axis.. The rats suffered the stressor once daily for 5 weeks. ZJP (0.6 and 1.2 g/kg) and fluoxetine (15 mg/kg) as positive control were administered to the rats through gastric intubation once daily for 5 consecutive weeks. The anti-depression effects were compared by performing sucrose preference tests and open field tests. Gastrointestinal motility was investigated by determining the gastrointestinal transit rate and by electrogastrogram. The serum levels of the gastrointestinal hormone (GAS, MOT, VIP, SP), inflammatory cytokine (IL-1β, IL-6; , TNFα) and glucagon-like peptide-1 (GLP-1) were assayed by enzyme-linked immunosorbent assay. For monoamine neurotransmitters (NE, 5-HT, DA), the levels were determined by high-performance liquid chromatography and electrochemical detection in conjunction, which was applied on the samples taken from the hypothalamus, hippocampus, and striatum.. The depression-like symptoms among rats under CUMS were significantly relieved by ZJP administration (0.6 and 1.2 g/kg). Gastrointestinal motility was also improved by restoring gastric electrical rhythm and promoting gastrointestinal propulsion. The ZJP at 0.6 g/kg dosage obviously up-regulated 5-HT and DA levels in hippocampus. The ZJP at 1.2 g/kg dosage could increase 5-HT and DA levels in hypothalamus, striatum, and hippocampus, while down-regulated the NE level in hypothalamus and hippocampus. ZJP also reversed the alterations in serum gastrointestinal hormones. Furthermore, treatment with ZJP significantly reduced levels of IL-1β, IL-6 and TNF-α and increased serum GLP-1 compared with the CUMS group. Fluoxetine also exerted similar anti-depressant effects in the absence of effects on gastrointestinal motility and the levels of serum hormone, inflammatory cytokine and GLP-1.. ZJP imposed anti-depressant and gastrointestinal regulating functions in rats under CUMS, suggesting potential clinical application. .

Topics: Animals; Antidepressive Agents; Behavior, Animal; Biogenic Monoamines; Brain; Chronic Disease; Cytokines; Depression; Drugs, Chinese Herbal; Gastrins; Gastrointestinal Transit; Glucagon-Like Peptide 1; Intestine, Small; Male; Motilin; Rats, Sprague-Dawley; Stress, Psychological; Substance P; Vasoactive Intestinal Peptide

The aim of the study was to determine the clinical significance of intestinal functional and structural alterations in biliary pathology. Clinical, endoscopic, morphological, and morphometric methods were used. The subjects of the study were 62 patients with functional gall bladder disorder, 90 patients with chronic calculous cholecystitis, and 90 patients who had undergone cholecystectomy for cholelithiasis. The study found that biliary lithogenesis was associated with intestinal dysbiosis, changes in the qualitative density of erythrocytes immunopositive to motilin and substance P, and inflammatory changes in the intestines. After cholecystectomy, changes in intestinal microecology progressed, inflammatory and atrophic changes in the intestinal mucosa appeared or deepened, the qualitative density of erythrocytes immunopositive to motilin and substance P decreased, and colon polyps appeared more frequently.

Topics: Adult; Aged; Atrophy; Cholecystitis; Cholelithiasis; Chronic Disease; Colonic Polyps; Diagnosis, Differential; Erythrocyte Count; Erythrocytes; Female; Humans; Inflammation; Intestinal Mucosa; Male; Middle Aged; Motilin; Predictive Value of Tests; Prognosis; Substance P

Erythromycin has been shown to have profound prokinetic effects on the gastrointestinal tract of humans and animals, probably through its action on endogenous motilin receptors. The purpose of this study was to determine both the direct and indirect effects ('off contraction') of erythromycin and motilin on ex vivo circular muscle strips of the distal colon from patients with or without idiopathic chronic constipation (ICC).. Cumulative concentrations of erythromycin (1-20 microM) and motilin (0.05-1 microM) were tested in both control and ICC preparations in order to evaluate the direct drugs effect. A range doses of both erythromycin (0.5-10 microM) and motilin (0.05-0.5 microM) were tested on their ability to affect the off-contraction that follows the typical inhibitory response evoked by low frequencies of Electrical Field Stimulation (EFS) (1-5 Hz, 20 V, 1 msec pulse trains lasting 1 min).. The direct effect of both erythromycin and motilin was a slight increase (less than 10% of the maximal ACh-induced contraction) in the basal tension, with no dose-response relationship. The off-contraction, evoked by EFS, was not affected by drugs pretreament in control preparations. Conversely, in ICC preparations both drugs significantly increased the off-contraction (about 30%).. Erythromycin causes mainly an indirect contractile effect in circular muscle strips from ICC patients. This effect may be related to the activation of inhibitory neuronal motilin receptors. This activation might potentiate NANC relaxation, proportionally increasing the circumferential reflex contraction that follows the EFS-induced relaxation.

Topics: Adult; Aged; Anti-Bacterial Agents; Chronic Disease; Colon; Constipation; Erythromycin; Humans; In Vitro Techniques; Middle Aged; Motilin; Muscle Contraction; Muscle, Smooth

A disturbed intraduodenal milieu and pancreatic scarring in advanced chronic pancreatitis (CP) may lead to changes of gut and pancreatic hormones. In the present study, the gastroduodenal mucosal content of several regulatory peptides was determined in 8 patients with severe calcific CP and 8 healthy volunteers. In addition, hormone release into the bloodstream was estimated after intraduodenal acid/glucose stimulation in the control subjects and 8 CP patients each with or without secondary diabetes mellitus (DM), and in 8 patients with juvenile DM, so that disturbed gut hormone release could be attributed either to CP or DM. While VIP release into the circulation was similar in all participants, mucosal levels of VIP and substance P were significantly elevated in the duodenal bulb and descending duodenum of CP patients. The somatostatin content of gastroduodenal mucosa in CP was at least as high as in normals. Gastrin was significantly more abundant only in the duodenal bulb of CP patients, while plasma gastrin was normal. Duodenal CCK concentrations tended to be elevated in the duodenal bulb, but not significantly. The release of secretin seemed to be higher in type-1 diabetics than in CP patients. The mucosal pattern of GIP was nearly identical in CP patients and controls. Compatible with this finding, the GIP release did not show any peculiarities in CP with or without DM or in DM. Basal and stimulated plasma levels of motilin were abnormally high in CP. Pancreatic polypeptide plasma levels were normal in DM, but significantly reduced in CP, especially in CP with DM. Fasting PP and stimulated pancreatic enzyme outputs were linearly related.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Chronic Disease; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Intestinal Mucosa; Male; Middle Aged; Motilin; Neurotensin; Pancreatic Polypeptide; Pancreatitis; Secretin; Somatostatin; Substance P; Vasoactive Intestinal Peptide

The plasma motilin levels were studied in seven patients with severe long-standing idiopathic constipation before and after a fat-rich test meal. The results were compared with those of a control group consisting of 10 apparently healthy persons with normal bowel function. The constipated patients had reduced basal motilin levels and a reduced motilin release after the test meal. Motilin is known to stimulate intestinal motility by inducing interdigestive descending contractions in the stomach and small intestine. A defective motilin release may therefore play a part in the pathogenesis of idiopathic constipation.

Topics: Adult; Chronic Disease; Constipation; Dietary Fats; Female; Food; Gastrointestinal Motility; Humans; Middle Aged; Motilin; Radioimmunoassay

Topics: Adolescent; Child; Cholestasis; Chronic Disease; Diarrhea, Infantile; Humans; Infant; Motilin; Pancreatic Polypeptide

To test the discriminatory potential of certain indices of pancreatic function we performed duodenal perfusion studies and measured trypsin, bicarbonate, and lactoferrin outputs, and plasma concentrations of pancreatic polypeptide and motilin in the basal state and during continuous intravenous stimulation with 100 ng kg-1h-1 Ceruletide and 1 CU kg-1h-1 secretin. The following groups were studied: 12 normal volunteers (NV), seven patients with chronic pancreatitis with steatorrhea (CPS), and seven without steatorrhea (CP). Stimulated trypsin outputs, after 45 min of stimulation, were the best discriminant among the groups (NV versus CPS, p less than 0.0005; NV versus CP, p less than 0.005; CP versus CPS, p less than 0.05). Basal trypsin outputs showed similar patterns but failed to discriminate between NV and CP. Bicarbonate outputs were less discriminatory than trypsin outputs. Lactoferrin outputs failed to discriminate, but transient high peak outputs occurred in the initial stimulation period in all four patients with calcific chronic pancreatitis, suggesting a washout phenomenon. Basal motilin levels were elevated in both groups of pancreatitis (p less than 0.05). Stimulated pancreatic polypeptide levels were lower in CPS (NV versus CPS, p less than 0.05) but higher in CP (NV versus CP, p less than 0.005). These differences were also apparent in the basal state. We conclude that the best discrimination among the three groups was achieved by measurement of trypsin outputs, after 45 min of stimulation. In addition, the pancreatic polypeptide response may be used as a marker of residual pancreatic function in chronic pancreatitis.

Topics: Adult; Aged; Bicarbonates; Celiac Disease; Ceruletide; Chronic Disease; Female; Humans; Islets of Langerhans; Lactoferrin; Male; Middle Aged; Motilin; Pancreas; Pancreatic Polypeptide; Pancreatitis; Secretin; Trypsin

The gut hormone motilin can initiate the interdigestive migrating motor complex. There are synchronous cyclic changes in plasma motilin-like immunoreactivity (MLI) levels and pancreatico-biliary secretion during the interdigestive period which may be causally related. The purpose of this study was to investigate the role of pancreatico-biliary secretion into the gut as a modulator of plasma MLI concentrations. In six healthy subjects, the mean basal plasma MLI level was 130 +/- 16 pg/ml. Infusion of cholecystokinin octapeptide (CCK-8) stimulated MLI secretion, with an integrated (30 min) response of 2028 +/- 340 pg/min X ml. Intraduodenal perfusion of pancreatico-biliary juice produced a similar increase in plasma MLI, with a 30 min integrated response of 2190 +/- 270 pg/min X ml. Neither enzyme activity, osmolarity, or pH accounted for the response. In six patients with exocrine pancreatic insufficiency, although their mean basal plasma MLI concentration of 205 +/- 44 pg/ml was significantly higher than that observed in healthy subjects, there was no significant plasma MLI increase after CCK-8 infusion. Pancreatic exocrine secretion was severely compromised in these patients, as evidenced by the markedly reduced peak lipase (3.8 +/- 0.6 kU/h) and trypsin (2.4 +/- 0.5 kU/h) outputs. In contrast, infusion of pancreatico-biliary juice obtained from healthy subjects caused a rise in plasma MLI, with a 60 min integrated response of 3912 +/- 1031 pg/min X ml, which was similar to that of 3947 +/- 472 pg/min X ml in healthy subjects. We conclude that there is an undefined factor in pancreatico-biliary juice that stimulates MLI release. A deficiency of pancreatic exocrine secretion may be responsible for the impaired MLI response to CCK-8 stimulation in chronic pancreatitis. Since MLI is known to initiate the formation of the interdigestive migrating motor complexes, diminished motilin release secondary to pancreatic exocrine deficiency may result in disordered gastrointestinal motor activity in patients with chronic pancreatitis.

Topics: Adolescent; Adult; Bile; Chronic Disease; Gastrointestinal Hormones; Humans; Kinetics; Lipase; Middle Aged; Motilin; Pancreatic Juice; Pancreatitis; Sincalide; Trypsin

Pancreatic and gut hormones have been measured in 39 patients with chronic pancreatitis, 16 of whom had severe pancreatic insufficiency. Patients with pancreatic insufficiency had significantly diminished fasting levels and postprandial rises of pancreatic polypeptide which were less than 20% of normal. Patients with chronic pancreatitis, with or without exocrine insufficiency, had two- to threefold higher plasma levels of motilin and enteroglucagon than controls. Plasma levels of insulin, pancreatic glucagon, gastric inhibitory polypeptide and gastrin were similar to normal in these patients. The pattern of response of these hormones to a test breakfast differs markedly from those seen in other gut disease states and may reflect pathophysiological mechanisms.

Topics: Adult; Blood Glucose; Chronic Disease; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Insulin; Male; Middle Aged; Motilin; Pancreatic Hormones; Pancreatic Polypeptide; Pancreatitis