Search

Objective: Despite a number of studies in the past decades, the role of Cholecystokinin (CCK) in anorexia nervosa (AN) has remained uncertain. In this study a highly specific assay for the biologically active part of CCK was used in patients with bulimic as well as with the restricting type of AN who were followed over the course of weight gain., Methods: Ten patients with restricting and 13 with bulimic AN were investigated upon admission (T0), after a weight gain of at least 2 kg on two consecutive weighting dates (T1), and during the last week before discharge (T2) from inpatient treatment in a specialized clinic. Blood samples were drawn under fasting conditions and 20 and 60 minutes following a standard meal (250 kcal). Data were compared to those of eight controls matched for sex and age. Gastrointestinal complaints of patients were measured by a questionnaire at each of the follow-up time points., Results: At admission, AN patients exhibited CCK-levels similar to controls both prior to and after a test meal. Pre and post-meal CCK levels increased significantly after an initial weight gain but decreased again with further weight improvement. CCK release was somewhat lower in bulimic than in restricting type AN but both subgroups showed a similar profile. There was no significant association of CCK release to either initial weight or BMI, or their changes, but CCK levels at admission predicted gastrointestinal symptom improvement during therapy., Conclusions: Normal CCK profiles in AN at admission indicates hormonal responses adapted to low food intake while change of eating habits and weight gain results in initially increased CCK release (counteracting the attempts to alter eating behavior) that returns towards normal levels with continuous therapy.

Acute mountain sickness (AMS) is characterized by headache often accompanied by gastrointestinal complaints that vary from anorexia through nausea to vomiting. The aim of this study was to investigate the influence of high altitude on plasma levels of gastroenteropancreatic (GEP) peptides and their association to AMS symptoms. Plasma levels of 6 GEP peptides were measured by radioimmunoassay in 11 subjects at 490 m (Munich, Germany) and, after rapid passive ascent to 3454 m (Jungfraujoch, Switzerland), over the course of three days. In a second study (n = 5), the same peptides and ghrelin were measured in subjects who consumed standardized liquid meals at these two elevations. AMS symptoms and oxygen saturation were monitored. In the first study, both fasting (morning 8 a.m.) and stimulated (evening 8 p.m.) plasma levels of pancreatic polypeptide (PP) and cholecystokinin (CCK) were significantly lower at high altitude as compared to baseline, whereas gastrin and motilin concentrations were significantly increased. Fasting plasma neurotensin was significantly enhanced whereas stimulated levels were reduced. Both fasting and stimulated plasma motilin levels correlated with gastrointestinal symptom severity (r = 0.294, p = 0.05, and r = 0.41, p = 0.006, respectively). Mean O(2)-saturation dropped from 96% to 88% at high altitude. In the second study, meal-stimulated integrated (= area under curve) plasma CCK, PP, and neurotensin values were significantly suppressed at high altitude, whereas integrated levels of gastrin were increased and integrated VIP and ghrelin levels were unchanged. In summary, our data show that acute exposure to a hypobaric hypoxic environment causes significant changes in fasting and stimulated plasma levels of GEP peptides over consecutive days and after a standardized meal. The changes of peptide levels were not uniform. Based on the inhibition of PP and neurotensin release a reduction of the cholinergic tone can be postulated.

Aims: Stress hormones might be involved in motion sickness. The influence of loperamide on kinetosis-induced nausea and stress hormone release was investigated in a placebo-controlled, cross-over study., Methods: Standardized rotation around the vertical axis combined with head movements was used to induce nausea 3 h after 16 mg loperamide or placebo (n = 8). Plasma antidiuretic hormone (ADH), adrenocorticotropic hormone (ACTH) and nausea ratings were investigated., Results: After loperamide nausea was significantly lower (P < 0.02). ACTH (P < 0.05) and ADH levels (P < 0.02) increased significantly in both settings, but were lower after loperamide., Conclusions: The susceptibility to develop kinetosis-induced nausea and stress hormone release is decreased by loperamide, although the site of action remains speculative.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of motor neurons. However, ALS has been recognized to involve several non-motor systems, subclinically. Cardiac and sudomotor autonomic involvement in ALS has been described. Recently, delayed gastric emptying was reported. The aim of this study was to assess colonic transit time in patients with ALS. Therefore, measurement of total and segmental colonic transit times using radio-opaque markers was performed in 14 patients with ALS and 14 healthy age-matched volunteers. Multiple-ingestion, single-radiograph technique was used. Segmental and colonic transit times were calculated from the number of retained markers. Nine of 14 patients with ALS showed markedly delayed colonic transit times if compared to healthy controls. Colonic transit in ALS patients was significantly delayed in the right and left colon; the rectosigmoid transit did not show major delay. The colonic transit times did not correlate with bulbar involvement, Norris score, walking disability or duration of the disease. In summary, colonic dysfunction in ALS may be a result of inactivity or inadequate fiber intake. However, it also may represent a gastrointestinal autonomic involvement due to nerval degeneration. Considering ALS as a multisystem disorder including the autonomic nervous system may have implications for research into pathogenesis and therapy of neurodegenerative disease.

Background: The effect of commonly ingested alcoholic beverages on gastric acid output and release of gastrin in humans is unknown., Aim and Methods: In 16 healthy humans the effect of some commonly ingested alcoholic beverages produced by fermentation plus distillation (for example, whisky, cognac, calvados, armagnac, and rum) or by alcoholic fermentation (beer, wine, champagne, martini, and sherry) on gastric acid output and release of gastrin was studied. Gastric acid output was determined by the method of intragastric titration. Plasma gastrin was measured using a specific radioimmunoassay., Results: None of the alcoholic beverages produced by fermentation plus distillation had any significant effect on gastric acid output and release of gastrin compared with control (isotonic glucose and distilled water). Alcoholic beverages produced only by fermentation significantly (p < 0.05) increased the gastric acid output by 57% to 95% of maximal acid output (MAO) and release of gastrin up to 5.1-fold compared with control. If beer, wine, and sherry were distilled, only their remaining parts increased gastric acid output by 53% to 76% of MAO and increased release of gastrin up to 4.3-fold compared with control., Conclusions: (1) Alcoholic beverages produced by fermentation but not by distillation are powerful stimulants of gastric acid output and release of gastrin; (2) the alcoholic beverage constituents that stimulate gastric acid output and release of gastrin are most probably produced during the process of fermentation and removed during the following process of distillation.

The aim of the study was to investigate whether cholecystokinin, neurotensin, and cholinergic mechanisms act as mediators of bile salt-stimulated exocrine pancreatic secretion. Ten fasting healthy subjects provided with a double-lumen tube received 2, 4, and 6 g cattle bile and 200, 400, and 600 mg Na-taurodeoxycholate (TDC) into the duodenum at 65-min intervals, respectively. The application of TDC was repeated in another 10 subjects after intravenous bolus injection of 2.5 micrograms/kg b.w. atropine followed by continuous infusion of 5 micrograms/kg.h. Secretions of volume, bicarbonate, trypsin, and lipase were determined in 10-min fractions of duodenal juice. Plasma samples were analysed for cholecystokinin-like immunoreactivity (CCK-LI) and neurotensin with radioimmunoassays. Volume, bicarbonate, trypsin, and lipase secretion rates were significantly increased by 4 g and 6 g bile and by all doses of TDC. Incremental volume and bicarbonate output was dose-dependently enhanced by bile and TDC, and trypsin and lipase output by bile. Atropine significantly decreased the baseline values and all responses to TDC. Plasma concentrations and integrated CCK-LI and neurotensin significantly increased after 4 and 6 g bile and after 400 and 600 mg TDC. Atropine did not significantly influence peptide release. It is concluded that both hydrokinetic and ecbolic pancreatic secretion stimulated by intraduodenal bile and TDC are dependent on a cholinergic tone. CCK and probably also neurotensin act as further mediators of the ecbolic effect.

Intraduodenally applied bile salts and essential amino acids are known to stimulate exocrine pancreatic secretion. There are contradictory reports, however, about an interaction of both stimuli with respect to pancreatic function. The intention of the study was to compare the effects of equimolar amounts of taurodeoxycholate and L-phenylalanine used singularly and combined on pancreatic secretion and on gastroenteropancreatic peptide release. In 12 healthy subjects, 0.8 mmol of Na-taurodeoxycholate (410 mg) and L-phenylalanine (130 mg) were separately and combined applied into the duodenum in a randomized order. Volume, bicarbonate, trypsin, lipase, and amylase secretion as well as cholecystokinin, pancreatic polypeptide, and somatostatin plasma levels were measured. Volume and bicarbonate secretion was significantly enhanced by taurodeoxycholate. The effect was stronger compared to L-phenylalanine. The increase of enzyme secretion was comparable. After combined application, the ecbolic effect was insignificantly smaller, whereas the hydrokinetic effect was between those of the single stimuli. Plasma levels of cholecystokinin, pancreatic polypeptide, and somatostatin rose concomitantly with the pancreatic response. On an equimolar basis taurodeoxycholate results in a stronger hydrokinetic effect than L-phenylalanine. Their ecbolic effects, however, are comparable. In addition to cholinergic mechanisms, as indicated by the PP release observed, cholecystokinin may also act as a mediator. In combined application, the stimuli interfere with each other. Somatostatin and pancreatic polypeptide are not responsible for this mutual inhibition.

1. Morphine suppresses the release of pancreatic polypeptide, a hormone under vagal cholinergic control. The intention of the study was to detect whether the mu-opiate receptor agonist loperamide is also able to inhibit pancreatic polypeptide release, and to define its site of action. 2. In groups of healthy subjects (n = 6 each) stimulation of pancreatic polypeptide was assessed in five different tests: (i) insulin-hypoglycaemia; (ii) modified sham feeding; (iii) intravenous infusion of the cholecystokinin analogue ceruletide; (iv) injection of corticotropin releasing hormone; (v) infusion of the muscarinic acetylcholine agonist bethanechol. All tests were performed after oral application of either a placebo or loperamide (16 mg), tests (ii) and (iii) were repeated with loperamide in smaller doses (2 and 6 mg), with loperamide plus naloxone, with naloxone alone, and with infusion of atropine. Plasma concentrations of pancreatic polypeptide were measured radioimmunologically. 3. Release of pancreatic polypeptide in test (i) to (iv) was completely blocked by 16 mg loperamide, whereas bethanechol-stimulated release (test 5) was not influenced. Tests (ii) and (iii) showed that the inhibition was dose-dependent and could be attenuated by naloxone. The inhibitory effect of loperamide was comparable with that of atropine. 4. We conclude that loperamide causes a dose-dependent inhibition of pancreatic polypeptide release mediated by vagal-cholinergic pathways, but does not have an atropine-like peripheral action.

Long-term normalization of glucose metabolism is necessary to prevent or ameliorate diabetic complications. Although pancreatic grafting is able to restore normal blood glucose and glycated haemoglobin, the degree of normalization of the deranged diabetic metabolism after pancreas transplantation is still questionable. Consequently glucose, insulin, C-peptide, glucagon, and pancreatic polypeptide responses to oral glucose and i.v. arginine were measured in 36 Type 1 (insulin-dependent) diabetic recipients of pancreas and kidney allografts and compared to ten healthy control subjects. Despite normal HbA1 (7.2 +/- 0.2%; normal less than 8%) glucose disposal was normal only in 44% and impaired in 56% of the graft recipients. Normalization of glucose tolerance was achieved at the expense of hyperinsulinaemia in 52% of the subjects. C-peptide and glucagon were normal, while pancreatic polypeptide was significantly higher in the graft recipients. Intravenous glucose tolerance (n = 21) was normal in 67% and borderline in 23%. Biphasic insulin release was seen in patients with normal glucose tolerance. Glucose tolerance did not deteriorate up to 7 years post-transplant. In addition, stress hormone release (cortisol, growth hormone, prolactin, glucagon, catecholamines) to insulin-induced hypoglycaemia was examined in 20 graft recipients and compared to eight healthy subjects. Reduced blood glucose decline indicates insulin resistance, but glucose recovery was normal, despite markedly reduced catecholamine and glucagon release. These data demonstrate the effectiveness of pancreatic grafting in normalizing glucose metabolism, although hyperinsulinaemia and deranged counterregulatory hormone response are observed frequently.