cholecystokinin and Intestinal-Diseases

The liver adaptively responds to extra-intestinal and intestinal inflammation. In recent years, the role of the autonomic nervous system, intestinal failure and gut microbiota has been investigated in the development of hepatic, intestinal and extra-intestinal disease.. The autonomic nervous system can be stimulated via enteral fat leading to cholecystokinin release, stimulating receptors in the gut and in the brain. This promotes bowel integrity, dampening the inflammatory response to food antigens. Consensus exists that intravenously administered long-chain fatty acids can cause liver damage but randomized-controlled trials are lacking. Disruption of the enterohepatic circulation of bile salts can give rise to cholestasis and nonalcoholic fatty liver disease, which may progress to fibrosis and cirrhosis. Reduced intestinal availability of bile salts reduces stimulation of the farnesoid X receptor. This may induce hepatic bile salt overload and associated hepatotoxicity through reduced action of intestinal fibroblast growth factor 19. Evidence is put forward to suggest that the intestinal microbiota is associated with liver abnormalities.. Enteral lipids reduce inflammation and liver damage during stress or systemic inflammation, whereas parenteral lipid is associated with liver damage. Maintaining the enterohepatic circulation of bile salts limits hepatic cholestasis through an farnesoid X receptor feedback pathway. Changes in gut microbiota composition may induce liver disease.

Topics: Administration, Intravenous; Bile Acids and Salts; Cholecystokinin; Cholestasis; Chronic Disease; Fatty Acids; Fatty Acids, Omega-3; Fatty Liver; Gastrointestinal Tract; Humans; Intestinal Diseases; Liver; Metabolic Syndrome; Microbiota; Non-alcoholic Fatty Liver Disease

There is evidence that under various physiological circumstances long-term adaptation of structure and function of the gut occurs. The mechanisms of these changes are not clear but gastro-intestinal hormones may be involved. In particular, gastrin which has been shown experimentally to stimulate growth and development of parts of the gut, probably has a role in maintaining the structure of the normal upper alimentary tract. Cholecystokinin may be of major importance in producing adaptive changes in the pancreas in response to dietary modifications and enteroglucagon is possibly concerned with maintaining a normal small intestinal structure. The importance of the 'trophic' action of gatrointestinal hormones is becoming more widely recognised and as new gastro-intestinal hormones become established, this aspect of their physiological importance as well as their acute effects, will deserve attention.

Topics: Animals; Cholecystokinin; DNA; Duodenum; Female; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Intestinal Diseases; Intestine, Small; Kidney Failure, Chronic; Lactation; Pancreas; Pregnancy; Rats; Secretin; Starvation; Weaning; Zollinger-Ellison Syndrome

The intestinal mucosa plays a critical role in the organism, acting as an interface between the lamina propria and the harmful antigens in the lumen. Sepsis is associated with primary injury to the intestinal mucosa, which in turn induces bacterial translocation and hyperpermeability. Cholecystokinin (CCK) is a peptide synthesized by several cell types, whose immunomodulatory activity has been reported in experimental models of inflammation. We hypothesized that the CCK treatment could modulate the inflammatory response and protect the integrity of the intestinal barrier in endotoxemic rats. Ten minutes before the endotoxemia induction by lipopolysaccharide (LPS) administration, rats were pretreated with CCK at two doses (0.4 μg/kg or 40 μg/kg). Mucosal permeability, bacterial translocation, cytokines production, histology injury, and expression of tight junction (TJ) proteins were the parameters assessed. In the early phase of endotoxemia, rats exhibited impaired intestinal barrier function, increased mucosal permeability, bacterial translocation, and also hyperactivation of the inflammatory response. On the other hand, the pretreatment with CCK modulated the mucosal production of pro-inflammatory cytokines and increased the expression of seal-forming TJ proteins (occludin, claudin-1 and junctional adhesion molecule (JAM-A)) only in the colon and also, reduced the bacterial counts in the mesenteric lymph nodes. However, CCK has a site-specific mechanism of action in the colon via CCK-1R, which is upregulated by the CCK treatment. In synergy with previous findings from our research group, the present results demonstrated that CCK preserves the integrity of the intestinal mucosa and might be a promising hormonal adjuvant therapy for the treatment of sepsis.

Topics: Animals; Cholecystokinin; Intestinal Diseases; Intestinal Mucosa; Lipopolysaccharides; Male; Rats; Rats, Wistar; Tight Junctions

Undiagnosed food allergies have been proposed as possible causes of promoting and perpetuating irritable bowel syndrome . Our aim was to find out if sensitization could induce chronic functional motor disturbances in the intestine and the mechanisms implicated. Rats were sensitized to ovalbumin (OVA) following three hypersensitivity induction protocols, two parenteral and one oral. Rat mast cell protease II (RMCP II) release in response to OVA challenge and immunoglobulin E (IgE) concentration were measured in serum. At least 1 week after challenge, small intestinal motility was evaluated using strain gauges. Intestinal tissue samples from orally sensitized rats were checked for in vitro stimulation with OVA. Mucosal mast cells were counted from duodenum sections. All sensitized rats showed intestinal hypermotility. Only rats sensitized by parenteral procedure showed an increase in RMCP II after OVA challenge in serum. IgEs increased only in the Bordetella pertussis sensitized group. Small intestine sections from orally sensitized rats released more RMCP II than sections from control rats. All sensitized rats showed an increase in the number of mucosal mast cells in duodenum. In conclusion, hypersensitivity to food proteins induces chronic motor alteration that persists long after antigen challenge and an excited/activated state of sensitized mucosal mast cells.

Topics: Animals; Bordetella pertussis; Cholecystokinin; Duodenum; Food Hypersensitivity; Gastrointestinal Motility; Ileum; Immunoglobulin E; Immunohistochemistry; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Male; Mast Cells; Muscle Tonus; Ovalbumin; Rats; Rats, Sprague-Dawley; Serine Endopeptidases

The aims of this study were: 1) to obtain an experimental model reproducing the characteristics of chronicity and spontaneous relapses found in inflammatory bowel disease (IBD) and 2) to correlate these changes with intestinal motility and bacteria translocation. For this purpose, two groups of Sprague-Dawley rats were used: a treated group that received two subcutaneous injections of indomethacin (7.5 mg/kg) 48 h apart and a control group that received saline. Blood leukocytes, TNF, and fecal parameters were monitored for 90 days after treatment. In treated rats, a cyclic oscillation of blood leukocytes and TNF concomitant with an inverse correlation of fecal output was observed. Treated rats were then selected either during their highest or lowest blood leukocyte values for motor activity and microbiological evaluation. Controls were obtained in age-matched rats. Rats with high leukocyte levels showed a decrease of motor activity. In contrast, animals with low leukocyte levels presented hypermotility. Bacterial overgrowth accompanied by bacterial translocation was found in the group with high leukocytes, whereas no differences were observed between the control and indomethacin groups during the lowest leukocyte phase. We obtained a model of IBD characterized by a chronic cyclic oscillation of intestinal motility, flora, and inflammatory blood parameters. During the high-leukocyte stage, motor activity decrease is related to bacterial translocation. This phase is followed by a reactive one characterized by hypermotility associated with a decrease in both bacterial growth and leukocytes. However, as in IBD, this reaction seems unable to prevent a return to relapse.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bacteria; Bacterial Infections; Bacterial Translocation; Cholecystokinin; Chronic Disease; Enteritis; Enzyme Inhibitors; Gastrointestinal Motility; Indomethacin; Injections, Subcutaneous; Intestinal Diseases; Leukocyte Count; Male; Nitroarginine; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

The neurally programmed APUD-cells from ectodermal origin are of peculiar significance in two respects: 1. They represent the largest endocrine gland of the whole organism and the peptides, which are secreted by the different APUD-cells, exercise a great influence on most of the motoric and secretory processes within the whole gastrointestinal tract just as on many metabolic processes as demonstrated on the so-called "enteropancreatic axis". Neoplasias of these APUD-cells, the "Apudomes", give rise to peculiar clinical syndromes. Early diagnosis of an apudome can be reached today by radioimmunologic detection of high concentrations of the responsible peptide in the blood enabling us to initiate an effective therapy at least for some of the known apudomes. 2. Beyond that the APUD-cells and their corresponding peptides are representing the so-called "peptidergic" division of the nervous system which acts as third-line effector to modulate not only the actions of the autonomic division but also of each other. The given example of the modulating effect of substance P or of the endorphines on the perception of pain is only one single aspect of the broad functional spectrum of these neuropeptides. The discovery, that the very same peptide can be detected in endocrine cells as well as in neurones, has opened one of the most fascinating and provocative developments in biology of the present time and some surprising new details can be expected in the next future.

Topics: APUD Cells; Cholecystokinin; Hormones; Humans; Intestinal Diseases; Neoplasms; Nervous System Diseases; Neurotensin; Neurotransmitter Agents; Peptides; Substance P

A secretin-pancreozymin test was conducted with 43 gastroenterologically healthy children and 12 patients with subtotal atrophy of intestinal mucosa. While the pancreas enzymes were normal, the patients with coeliac disease reacted to the injection of the peptide hormones by producing a larger volume of secretion than did the control group. Despite the increased secretion there was at the same time a significantly higher concentration of bile acids in the duodenal juice. Analysis of the bile acid distribution indicated no deviation from the norm. There was, however, a striking discrepancy between the bile acid and the bilirubin excretion in the children with subtotal atrophy, whose bilirubin secretion, compared to that of the control group, was greatly reduced.

Topics: Adolescent; Atrophy; Bile Acids and Salts; Celiac Disease; Child; Child, Preschool; Cholecystokinin; Giardiasis; Humans; Ichthyosis; Infant; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Psoriasis; Secretin

The availability of pure intestinal hormones and the development of radioimmunoassays for their measurement has expedited research into many aspects of gastrointestinal endocrinology. A complex balance evidently exists between the different intestinal hormones and also the rest of the endocrine system. Polyendocrinopathies have been described, and, so far, two diseases due to intestinal hormone excess (Zollinger-Ellison syndrome and the syndrome of watery diarrhea, hypokalemia and achlorhydria) elucidated. It seems likely that many more gastrointestinal endocrine diseases await discovery.

Topics: Cholecystokinin; Diagnosis, Differential; Diarrhea; Digestive System; Endocrine Glands; Esophagogastric Junction; Gastrins; Gastrointestinal Hormones; Humans; Hypoglycemia; Intestinal Diseases; Intestine, Large; Pancreas; Peptic Ulcer; Prostaglandins; Pylorus; Secretin; Syndrome; Zollinger-Ellison Syndrome

Topics: Amylases; Bicarbonates; Celiac Disease; Cholecystokinin; Diet; Folic Acid Deficiency; Humans; Intestinal Diseases; Intestine, Small; Malabsorption Syndromes; Nutrition Disorders; Pancreas; Protein Deficiency; Secretin; Serum Albumin

Ileal disease or resection causes bile salt malabsorption and a reduction in the bile salt content of bile. Since cholesterol solubility requires adequate bile salt concentrations, depletion of the bile salt content of bile might, therefore, jeopardize cholesterol solubility and predispose to cholesterol gallstone formation. To study this, we examined biliary lipid composition in 10 patients with ileal dysfunction and in 25 healthy controls. Biliary lipid composition, as analysed in cholecystokinin-stimulated, bile-rich duodenal fluid, was shown to be representative of gallbladder bile and reproducible on repeat duodenal intubation. Nine of the 10 patients with ileal dysfunction had an abnormal, supersaturated bile in which the limits of cholesterol solubility were exceeded, and while nine of 25 control subjects also had an unstable bile, the mean bile composition in the ileal dysfunction group was significantly different from the control population. These studies provide a physicochemical explanation for the clinical observation that patients with ileal dysfunction have an increased incidence of gallstones.

Topics: Adult; Aged; Bile; Bile Acids and Salts; Cholecystokinin; Cholelithiasis; Cholesterol; Female; Humans; Ileum; Intestinal Diseases; Male; Middle Aged; Phospholipids

Topics: Barium Sulfate; Celiac Disease; Cholecystokinin; Colectomy; Colitis, Ulcerative; Enteritis; Gastrointestinal Motility; Humans; Ileostomy; Intestinal Diseases; Intestine, Small; Radiography

Topics: Bile Acids and Salts; Blood Chemical Analysis; Celiac Disease; Cholecystokinin; Feces; Gastrectomy; Gastrointestinal Hormones; Intestinal Absorption; Intestinal Diseases; Iodine Isotopes; Lipid Metabolism; Pancreatectomy; Pancreatic Juice; Pancreatitis; Pharmacology; Physiology; Salts; Sprue, Tropical; Triolein