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Background Eating disorders during pregnancy can affect fetal growth and the child’s early development, but the underlying mechanisms have not been elucidated. The aim of the present study was to investigate serum biomarkers of nutrition and stress in pregnant women with previous eating disorders compared to controls and in relation to head circumference and early neurocognitive development of the offspring. Methods In a longitudinal cohort study, pregnant nulliparous non-smoking women with a history of anorexia nervosa (n = 20), bulimia nervosa (n = 17) and controls (n = 59) were followed during pregnancy and their children’s growth and neurocognitive development were followed up to five years of age. We investigated maternal serum biomarkers of nutrition and stress (ferritin, cortisol, thyroid-stimulating hormone, free thyroxine, insulin, insulin-like growth factor I (IGF-I) and IGF binding protein 1) in blood samples collected during early pregnancy and compared between groups (ANOVA, LSD post-hoc test). The results were related to previous data on head circumference at birth and neurocognitive development at five years of age of the offspring (Spearman rank correlation or Pearson correlation test). Results Serum levels of ferritin in the women with previous anorexia nervosa, but not in those with a history of bulimia nervosa, were significantly lower than in the controls (p < 0.01), and correlated strongly to impaired memory function in their children (rs = −0.70, p < 0.001). Maternal serum levels of free thyroxine were similar between groups but correlated positively to reduced head circumference at birth of the children in the bulimia nervosa group (r = 0.48, p < 0.05), and with the same tendency in the anorexia nervosa group (r = 0.42, p = 0.07), but not in the controls (r = 0.006). There were no significant differences in cortisol or the other biomarkers between groups. Conclusions Low maternal serum ferritin in women with previous anorexia nervosa may be of importance for impaired memory capacity in the offspring at five years of age. Our results also indicate that thyroxin levels in pregnant women with previous eating disorders are positively associated with fetal head growth. Electronic supplementary material The online version of this article (doi:10.1186/s12884-015-0741-7) contains supplementary material, which is available to authorized users.

The gastric emptying rate is a carefully regulated process consisting of different mathematically defined phases. The gastric metabolic load, as well as neural regulatory mechanisms and hormonal influences, cooperate in order to achieve a well-balanced emptying of contents from the stomach into the duodenum for absorption in the small intestine. This finely tuned regulation is primarily regulated by the release of gastrointestinal peptide hormones which serve to counteract the emptying process in the fed state and to stimulate sweeping contractions in the fasted state, most likely in order to prepare the stomach for another meal. We have found that the two peptide hormones ghrelin and glucagon-like peptide- I (GLP- I) have a great impact on the regulation of gastric emptying: ghrelin is a most potent stimulator of gastric contractions and emptying, and GLP- I profoundly inhibits this emptying process. These data suggest possibilities for governing the rate of gastric emptying as a natural step in achieving metabolic balance and control.

Beta-endorphin radioimmunoassays (RIAs) are widely performed following physical, emotional and environmental challenges in the rat. In the literature, a wide range of techniques have been described, but in the present study, we have focused on methodological aspects of beta-endorphin RIAs, investigating various characteristics of human and rat specific antibodies. Initial studies verified that the RIA outcome was not appropriate when using non-species compatible components. Novel rat beta-endorphin antibodies, r 4114 and r 4268, were raised in rabbits and characterised in terms of specificity, avidity and titer. Both of the new antisera showed 68.1% cross-reactivity with human beta-endorphin. The ED50 was 50+/-8 pmol/l, and the mean ED80 was 17 pmol/l for r 4268 but three-fold higher for r 4114. The intra-assay coefficient of variation (CV) was 7% at 100 pmol/l and the inter-assay CV was 10% at the same level for r 4268 and similar for r 4114. Using this novel rat beta-endorphin RIA for analyses of diurnal influence and removal from the Animal House cage, no significant changes were observed in either the hypothalamus or peri-aqueductal grey regions. These results suggest that rat beta-endorphin concentrations in these brain areas are not affected by order of removal or diurnal variation.

BACKGROUND Human inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis), is associated with leukocyte accumulation in the inflamed intestinal tissue. Recent studies strongly suggest a role of beta1 integrin receptors in regulating tissue damage and disease symptoms related to inflammatory bowel disease. The aim of this study was to investigate the role of the collagen-binding alpha2beta1 integrin (CD49b/CD29) in dextran sodium sulfate-induced colitis in mice. METHODS Colitis was induced in mice through oral administration of 2% dextran sodium sulfate in drinking water. Rectal administration of anti-alpha2-monoclonal antibody (mAb) in 1 group was compared with oral treatment with betamethasone in another group and rectal administration of a control antibody in a third group. Clinical and histological signs of colitis, neutrophil infiltration into the colon mucosa, and gene expression of metalloproteinases were assessed. RESULTS Rectal administration of anti-alpha2-mAb was found to significantly reduce weight loss from 13.5% +/- 6.5% to 2.2% +/- 0.2% (P = 0.013 versus control mAb) and mucosal neutrophil infiltration from 47.2 +/- 10.0 to 6.6 +/- 8.0 neutrophils per counted area (P < 0.05 versus control mAb). Metalloproteinase gene expression was suppressed through anti-alpha2-mAb treatment. The protective effect against colitis seen after anti-alpha2beta1 integrin treatment was found to be favorable to the effect seen after high-dose oral betamethasone. CONCLUSIONS We demonstrate an alleviating action of the collagen-binding alpha2beta1 integrin in experimental colitis in mice and suggest that this effect is mediated by inhibition of neutrophil migration and activation. Local administration of function-blocking antibodies against integrin alpha2beta1 may provide novel avenues to treat inflammatory bowel disease.

Ghrelin is a gut peptide that is secreted from the stomach and stimulates food intake. There are ghrelin receptors throughout the gut and intracerebroventricular ghrelin has been shown to increase gastric acid secretion. The aim of the present study was to examine the effects of peripherally administered ghrelin on gastric emptying of a non-nutrient and nutrient liquid, as well as, basal and pentagastrin-stimulated gastric acid secretion in awake rats. In addition, gastric contractility was studied in vitro. Rats equipped with a gastric fistula were subjected to an intravenous infusion of ghrelin (10-500 pmol kg(-1) min(-1)) during saline or pentagastrin (90 pmol kg(-1) min(-1)) infusion. After administration of polyethylene glycol (PEG) 4000 with 51Cr as radioactive marker, or a liquid nutrient with (51)Cr, gastric retention was measured after a 20-min infusion of ghrelin (500 pmol kg(-1) min(-1)). In vitro isometric contractions of segments of rat gastric fundus were studied (10(-9) to 10(-6) M). Ghrelin had no effect on basal acid secretion, but at 500 pmol kg(-1) min(-1) ghrelin significantly decreased pentagastrin-stimulated acid secretion. Ghrelin had no effect on gastric emptying of the nutrient liquid, but significantly increased gastric emptying of the non-nutrient liquid. Ghrelin contracted fundus muscle strips dose-dependently (pD2 of 6.93+/-0.7). Ghrelin IV decreased plasma orexin A concentrations and increased plasma somatostatin concentrations. Plasma gastrin concentrations were unchanged during ghrelin infusion. Thus, ghrelin seems to not only effect food intake but also gastric motor and secretory function indicating a multifunctional role for ghrelin in energy homeostasis.

Background: Mild cognitive impairment (MCI) has been considered a transitional state between normal aging and dementia, characterised by memory impairment but normal general cognitive functioning. Recently other cognitive deficits have been reported. This has led to a modification of MCI criteria. Objective: To examine which neuropsychological tests most clearly distinguish MCI subjects from normal controls. Methods: 112 consecutive MCI subjects and 35 controls were included in the study. The diagnosis of MCI was based on an objective history of cognitive decline and a neuropsychiatric examination, comprising instruments STEP, I-Flex, MMSE, and CDR. Participants were examined with 21 neuropsychological tests in the cognitive domains speed/attention, memory and learning, visuospatial function, language, and executive function. Results: Controls were significantly older. No differences were found in education or general intellectual capacity. Controls performed significantly better than MCI on tests within all five cognitive domains. The clearest differences were seen on language tests, followed by executive function, and learning and memory. Only two subjects (1.8%) were purely amnestic; 17% showed no impairment compared with controls, with a cut off of 1.5 SD below age mean. These subjects were better educated and performed significantly better on measures of general cognitive capacity. Conclusions: The results illustrate the heterogeneity of MCI, with a significant degree of impairment in all five cognitive domains. When examined with a comprehensive neuropsychological battery, very few subjects had an isolated memory impairment.

Previous studies using pancreatic polypeptide (PP) infusions in humans have failed to show an effect on gastric emptying, glucose metabolism, and insulin secretion. This might be due to the use of nonhuman sequences of the peptide.The objective of this study was to use synthetic human PP to study gastric emptying rates of a solid meal and postprandial hormone secretion and glucose disposal as well as the gastric emptying rate of water.This was a single-blind study.The study was performed at a university hospital.Fourteen healthy adult subjects were studied.Infusion of saline or PP at 0.75 or 2.25 pmol/kg.min was given to eight subjects (gastric emptying of solid food), and infusion of saline or PP at 2.25 pmol/kg.min was given to six subjects (gastric emptying of water).The main outcome measures were gastric emptying of solids (scintigraphy), hunger ratings (visual analog scale), and plasma concentrations of PP, insulin, glucagon, somatostatin, glucagon-like peptide 1, glucose, and gastric emptying of plain water (scintigraphy).PP prolonged the lag phase and the half-time of emptying of the solid meal. The change in hunger rating, satiety, desire to eat after the meal, or prospective consumption was not affected. The postprandial rise in plasma glucose was prolonged by PP. The postprandial rise in insulin was also delayed by PP. PP had no significant effect on the emptying of water.PP inhibits gastric emptying of solid food and delays the postprandial rise in plasma glucose and insulin. PP is suggested to have a physiological role in the pancreatic postprandial counterregulation of gastric emptying and insulin secretion.

Differentiating patients with functional bowel disorders from those with inflammatory bowel disease (IBD) can be difficult. Rectal luminal levels of nitric oxide (NO) are greatly increased in IBD. To further evaluate this disease marker, we compared NO in patients with irritable bowel syndrome (IBS) with those found in patients with active IBD and in healthy control subjects.Rectal NO was measured with chemiluminescence technique by using a tonometric balloon method in 28 healthy volunteers, 39 patients with IBS, 86 with IBD (Crohn's disease and ulcerative colitis), and 12 patients with collagenous colitis. In addition, NO was measured before and after a 4-week treatment period in patients with active ulcerative colitis and repeatedly during 2 weeks in healthy volunteers.NO was low in healthy control subjects (median, 45; 25th-75th percentile, 34-64 parts per billion [ppb]), and variations over time were small. In IBS patients NO was slightly increased (150, 53-200 ppb; P.001), whereas patients with active IBD or collagenous colitis had greatly increased NO levels (3475, 575-8850 ppb, and 9950, 4475-19,750 ppb, respectively; P.001). With a cutoff level of 250 ppb, NO had a sensitivity of 95% and a specificity of 91% in discriminating between active bowel inflammation and IBS. Rectal NO correlated with disease activity in IBD and collagenous colitis and decreased markedly in IBD patients responding to anti-inflammatory treatment.Rectal NO is a minimally invasive and rapid tool for discriminating between active bowel inflammation and IBS and a possibly useful add-on for monitoring patients with IBD.

Background & Aims: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. Methods: This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab/placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 6–8 if they fulfilled index criteria on day 5–7 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. Results: Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy ( P = .017; odds ratio, 4.9; 95% confidence interval, 1.4–17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. Conclusions: Infliximab 4–5 mg/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment.

Orexin A (OXA) is a novel peptide that appears to play a role in the regulation of food intake, arousal, and energy balance. The aim of this study was to study the effect of iv infusion of OXA on gastric emptying, appetite, leptin, ghrelin, and glucose metabolism in man (six normal men) and the localization of OXA and orexin receptors (OXRs) 1 and 2 in the human gut. Gastric emptying was studied scintigraphically after ingestion of a 99mTc-labeled omelet and iv infusion of OXA (10 pmol/kg.min). Appetite ratings and blood samples were obtained at regular intervals. The immunohistochemical distribution of OXA and OXRs was examined using antibodies recognizing OXA, OX1R, and OX2R in human gastrointestinal tissue. OXA had no effect on lag phase or gastric half-emptying time. However, the gastric emptying rate was significantly slower without affecting appetite ratings. Plasma concentrations of insulin were increased by OXA, whereas plasma leptin decreased and ghrelin was unchanged. OXA immunoreactivity was observed in a subset of neurons and varicose nerve fibers in the mucosa, ganglia, and circular muscle layer and mucosal endocrine cells in the stomach and small intestine. OXA-immunoreactive cells in the islets of Langerhans contained insulin with a subset expressing OX2R. In conclusion, peripheral OXA seems to slightly affect the regulation of gastric emptying in humans without affecting appetite ratings. OXA decreased plasma levels of leptin, suggesting a possible interaction between leptin and OXA in the regulation of energy homeostasis.

Glucagon-like peptide-2 (GLP-2) and peptide YY (PYY) are produced in endocrine L-cells of the intestine and secreted in response to food intake. GLP-2 has a trophic effect on the intestinal epithelium, whereas PYY has pro-absorptive effects. It can be speculated that, in inflammatory bowel disease (IBD), the production and secretion of GLP-2 and PYY could be affected as a part of a regulatory mechanism. Therefore, tissue levels and meal-stimulated secretion of GLP-2 and PYY were studied in IBD patients and compared to controls.Outpatients with IBD and control patients were included. Mucosal biopsies were taken from the ileum and colon and the content of GLP-2 and PYY was measured. After colonoscopy the patients took a mixed meal and plasma was collected for 90 min for plasma measurements of GLP-2 and PYY.Tissue levels of GLP-2 in control patients were highest in the terminal ileum (407+/-82 pmol/g tissue, n=10), whereas PYY was highest in the rectum (919+/-249 pmol/g tissue, n=10). In IBD patients with acute inflammation, the content of GLP-2 was similar to controls, whereas PYY was decreased to 72.1+/-17.7% (P=0.03, n=13) of control values. Neither the fasting plasma levels nor the meal responses of GLP-2 and PYY differed between controls and IBD patients.The similar responses of GLP-2 and PYY in patients and controls do not support the suggestion that L-cell secretion is altered in IBD. The decreased tissue PYY concentrations may contribute to the diarrhoea of some of these patients.

The worldwide increase in the incidence of obesity is a consequence of a positive energy balance, with energy intake exceeding expenditure. The signalling systems that underlie appetite control are complex, and the present review highlights our current understanding of key components of these systems. The pattern of eating in obesity ranges from over-eating associated with binge-eating disorder to the absence of binge-eating. The present review also examines evidence of defects in signalling that differentiate these sub-types. The signalling network underlying hunger, satiety and metabolic status includes the hormonal signals leptin and insulin from energy stores, and cholecystokinin, glucagon-like peptide-1, ghrelin and peptide YY3-36 from the gastrointestinal tract, as well as neuronal influences via the vagus nerve from the digestive tract. This information is routed to specific nuclei of the hypothalamus and brain stem, such as the arcuate nucleus and the solitary tract nucleus respectively, which in turn activate distinct neuronal networks. Of the numerous neuropeptides in the brain, neuropeptide Y, agouti gene-related peptide and orexin stimulate appetite, while melanocortins and α-melanocortin-stimulating hormone are involved in satiety. Of the many gastrointestinal peptides, ghrelin is the only appetite-stimulating hormone, whereas cholecystokinin, glucagon-like peptide-1 and peptide YY3-36 promote satiety. Adipose tissue provides signals about energy storage levels to the brain through leptin, adiponectin and resistin. Binge-eating has been related to a dysfunction in the ghrelin signalling system. Moreover, changes in gastric capacity are observed, and as gastric capacity is increased, so satiety signals arising from gastric and post-gastric cues are reduced. Understanding the host of neuropeptides and peptide hormones through which hunger and satiety operate should lead to novel therapeutic approaches for obesity; potential therapeutic strategies are highlighted.

Orexin A (OXA) is found in the central nervous system (CNS) and in the gut. Peripheral administration of OXA to rats results in an inhibition of fasting motility. Plasma OXA increases during fasting and central administration of OXA increases food intake. The aim of the present study was to assess the pharmacokinetic profile of OXA and the effect of intravenously (i.v.) administered OXA on plasma concentrations of insulin and glucagon concentrations. Rats were given OXA i.v. (100 pmol kg(-1) min(-1)) for time periods of 0, 10, 20, 30 min and for 10, 20, 30 min after ceasing a 30-min infusion. After each time period, rats were then sacrificed and blood obtained. OXA was also administered at increasing doses (0, 100, 300 and 500 pmol kg(-1) min(-1)) for 30 min and blood was obtained. Plasma OXA, insulin and glucagon levels were measured using commercially available radioimmunoassay (RIA) kits. The plasma half-life of OXA was 27.1+/-9.5 min. Stepwise increasing infusion rates of OXA confirmed a linear concentration-time curve and thus first-order kinetics. Its volume of distribution indicated no binding to peripheral tissues. Plasma glucagon decreased during infusion of OXA, while insulin was unaffected. Plasma OXA was raised fourfold after food intake. Thus, OXA has a longer plasma half-life than many other peptides found in the gut. This needs to be taken into account when assessing effects of OXA on biological parameters after peripheral administration.

Background: Several placebo controlled studies have demonstrated the efficacy of infliximab in inflammatory bowel disease (IBD) but the potential toxicity of this new biological compound has been less studied. Aim: To assess the use of infliximab in IBD in a population based cohort, with special emphasis on the occurrence of severe adverse events and mortality. Patients: All patients with IBD treated with infliximab between 1999 and 2001 in Stockholm County were evaluated. Methods: Prospective registration of clinical data was carried out. Retrospective analyses were made of possible adverse events occurring in relation to infliximab treatment. Adverse events requiring pharmacological treatment or hospitalisation were defined as severe. Clinical response was assessed as remission, response, or failure. Results: A cohort comprising 217 patients was assembled: 191 patients had Crohn’s disease (CD), and infliximab was used off label for ulcerative colitis (UC) in 22 patients. Four patients were treated for indeterminate colitis (IC). Mean age was 37.6 (0.9) years (range 8–79). The mean number of infliximab infusions was 2.6 (0.1) (range 1–11). Forty two severe adverse events were registered in 41 patients (CD, n = 35). Eleven of the severe adverse events occurred postoperatively (CD, n = 6). Three patients with CD developed lymphoma (of which two were fatal), opportunistic infections occurred in two patients (one with UC, fatal), and two patients with severe attacks of IBD died due to sepsis (one with CD, one postoperatively with UC). One additional patient with UC died from pulmonary embolism after colectomy. Mean age in the group with fatal outcome was 62.7 years (range 25–79). The overall response rate was 75% and did not differ between the patient groups. Conclusions: Infliximab was efficacious as an anti-inflammatory treatment when assessed in a population based cohort of patients with IBD. However, there appear to be a significant risk of deleterious and fatal adverse events, particularly in elderly patients with severe attacks of IBD. Off label use of infliximab in UC and IC should be avoided until efficacy is proven in randomised controlled trials. The underlying risk of developing malignancies among patients with severe or chronically active CD in need of infliximab treatment is not known but the finding of a 1.5% annual incidence of lymphoma emphasises the need for vigilant surveillance with respect to this malignant complication.

Proton pump inhibitors are used at different dosages for the treatment of acid-related gastrointestinal disorders, such as gastro-oesophaeal reflux and peptic ulcer disease. Comparisons of four different proton pump inhibitors: lansoprazole, omeprazole, pantoprazole, and rabeprazole show that they all have similar potency and efficacy. Rabeprazole, however, displays a slightly more rapid onset of acid inhibition than the others; the clinical advantage of this seems limited. The S-isomer of omeprazole, esomeprazole, exhibits a somewhat higher potency than the other proton pump inhibitors. Reports supporting a clinical advantage of this property are not convincing. To conclude, all inhibitors seem comparable as regards inhibition of gastric acid secretion.

Recombinant glucagon-like peptide-1 (7–36)amide (rGLP-1) was recently shown to cause significant weight loss in type 2 diabetics when administered for 6 weeks as a continuous subcutaneous infusion. The mechanisms responsible for the weight loss are not clarified. In the present study, rGLP-1 was given for 5d by prandial subcutaneous injections (PSI) (76nmol 30min before meals, four times daily; a total of 302·4nmol/24h) or by continuous subcutaneous infusion (CSI) (12·7nmol/h; a total of 304·8nmol/24h). This was performed in nineteen healthy obese subjects (mean age 44·2 (sem 2·5) years; BMI 39·0 (sem 1·2)kg/m2) in a prospective randomised, double-blind, placebo-controlled, cross-over study. Compared with the placebo, rGLP-1 administered as PSI and by CSI generated a 15% reduction in mean food intake per meal (P=0·02) after 5d treatment. A weight loss of 0·55 (sem 0·2) kg (PPP

Background: Glucagon-like peptide-1 (GLP-1) is secreted from L-cells after nutrient ingestion, inhibiting motility. Aims: To clarify whether infused GLP-1 inhibits in vivo prandial motility respons ...

Background We previously found that DNA synthesis of the colonic mucosa rises under protracted physical stress. At 8 stress weeks DNA values regained those of untreated animals, and was regarded as DNA adaptation to stress. Aims To assess whether the 8 weeks’ DNA adaptation to stress could be maintained following stress-free intervals, ending with a stress stimulus. Methods Sixty rats were transported to the stress laboratory. Thirty were water plunged and 30 sham handled once a day, 5 days a week, for 8 weeks. After 8 stress weeks, groups of five animals were allowed to rest for 1, 2, 3 and 4 weeks, ending with single water plunging or sham handling. Five additional rats were untreated. All 65 animals received an i.p. injection of 3H-thymidine before sacrifice. The ratio radioactive DNA/total DNA reflected the DNA synthesis of the colonic mucosa. Results Following DNA adaptation at 8 stress weeks, DNA replication in the right colon of the stressed rats significantly increased at 9, 10 and 11 weeks (P

The 5-HT 3 and 5-HT 4 receptor antagonists alosetron and piboserod, and the muscarinic receptor antagonists PNU-171990A (2-(diisopropylamino)ethyl 1-phenylcyclopentanecarboxylate, hydrochloride) and PNU-174708A (2-(diisopropylamino)ethyl 1-phenylcyclohexanecarboxylate) were studied by electromyography, defining the migrating myoelectric complex (MMC) after i.v. administration in conscious rats. Alosetron prolonged the MMC cycle length from 16.6 to maximally 30.4 min at the dose 0.5 mg kg −1 . Piboserod promptly abolished MMC pattern and prolonged cycle length from 16.5 to >60 min at 0.5 mg kg −1 . PNU-171990A and PNU-174708A had no effect on basal cycle length up to a dose of 20 mg kg −1 . In controls, saline did not change the MMC pattern, while l -hyoscyamine at the same dose, 20 mg kg −1 , prolonged cycle length from 17.6 to 29.0 min. None of the drugs affected duration or propagation velocity of phase III of MMC. Blockade of 5-HT 4 receptors seems to exert a powerful inhibitory effect on motility, 5-HT 3 receptor blockade is less efficient and muscarinic receptor blockade has low efficacy.

Background: transnational and psychometrically appropriate versions of instruments used in the diagnosis of dementia are essential for comparing information between different countries. The Cambridge Examination for Mental Disorders of the Elderly incorporates a brief neuropsychological test battery, Cambridge Cognitive Examination (recently revised version), which provides objective data on performance across a number of cognitive domains. Objective: to harmonise the Cambridge Cognitive Examination between seven European countries. Method: 40 patients with probable or possible Alzheimer's disease of each of the seven countries were administered the Cambridge Cognitive Examination. The Nurse Observation Scale for Geriatrics was used to assess concordance between cognitive and behavioural measures. Results: only small differences between the various Cambridge Cognitive Examination versions were found, and patterns of correlation between Cambridge Cognitive Examination and the Nurse Observation Scale for Geriatrics were consistent. Conclusion: these findings indicate that the harmonisation of the Cambridge Cognitive Examination was successful.

Background Gastrointestinal symptoms are common and important for the quality of life in patients with myotonic dystrophy (MD). Gastric emptying was studied in patients with MD who suffered from symptoms suggesting slow gastric emptying and the effect of prokinetic treatment was evaluated. Methods Gastric emptying was studied in 10 patients with MD who were suffering from nausea, early satiety, bloating, regurgitation, vomiting, or abdominal pain using a 99Tc-labelled test meal, and was compared with gastric emptying in a group of healthy controls. The patients were subsequently treated with erythromycin and their gastrointestinal symptoms were recorded and the gastric emptying test was repeated. Results Patients with MD had a significantly longer gastric lag phase (46·1 ± 4·3 vs. 31·9 ± 4·0 min, P = 0·03), a slower emptying phase (7·1 ± 0·9 vs. 10·2 ± 0·9 kJ min−1, P = 0·02) and a longer half-emptying time, T50 (141·7 ± 10·5 vs. 98·6 ± 8·7 min, P = 0·01) than a matched control group. Erythromycin did not stimulate the gastric emptying rate. The effect on gastrointestinal symptoms was modest, except for a reduction of diarrhoea. Conclusions Patients with MD suffering from nausea, vomiting and early satiety, displayed a slow gastric emptying. Treatment with erythromycin had only moderate effect on gastric emptying or gastric symptoms, but reduced diarrhoea in a majority of the patients.

LY315902 is an analogue of GLP-1 that yields a reduced clearance and longer half-life. The aim of the study is to assess the effect of LY315902 on fasting gastrointestinal motility, somatostatin and insulin release. Sprague–Dawley rats were fitted with three bipolar electrodes, 15, 25 and 35 cm distal to the pylorus. The effect of LY315902 and GLP-1 on migrating myoelectric complex (MMC) cycle length, duration and propagating velocity of activity fronts was studied for 60 min in conscious animals. The effect of LY315902 and GLP-1 on fasting small bowel motility was dose-dependent and treatment with exendin (9–39)amide, a GLP-1 receptor antagonist, together with LY315902 and GLP-1 completely antagonised the inhibitory effect of LY315902 and GLP-1 on fasting small bowel motility. Pretreatment with the nitric oxide (NO) synthase inhibitor N ω -nitro- l -arginine ( l -NNA) partly blocked the action of both LY315902 and GLP-1. Plasma insulin concentrations were not different from controls during infusion of LY315902 or GLP-1, while somatostatin concentrations were significantly higher during LY315902 and GLP-1 compared to saline. LY315902 has a longer duration of inhibitory action on the MMC than GLP-1, albeit similar effects on plasma insulin and somatostatin concentrations. The effect of LY315902 on motor control is mediated through the GLP-1 receptor and seems partly dependent on the l -arginine/NO pathway.

Background A novel 14 C-urea breath test (UBT) was developed to detect the presence of Helicobacter pylori by bench analysis in office, enabling the practitioner to readily reveal H. pylori infection. Aim To validate the novel UBT (Heliprobe) versus conventional UBT. Methods Pretreatment (n = 203) and post-treatment (n = 147) detection of H. pylori. Additional tests with encapsulated 14 C-urea (n = 37) were validated. After intake of liquid or encapsulated 14 C-urea, exhaled 14 CO 2 in breath was trapped in benzethoniumhydroxide/ethanol, or adsorbed to LiOH-soaked pads on a dry cover surface (Heliprobe BreathCard). The amount of adsorbed 14 C was detected using a β-scintillator or two Geiger - Muller counters operating in parallel (Heliprobe Analyzer). Results For pretreatment detection, we found full concordance between the UBTs, with 100% sensitivity and specificity (Cl 95-100% and 97-100%, respectively) and strong agreement (r= 0.80, Cl 0.75-0.85; K = 1, Cl 0.86-1.14; P < 0.0001). Similarly, for post-treatment follow-up detection, sensitivity and specificity were 100% (Cl 85-100% and 97-100%, respectively) with significant agreement (r = 0.48, Cl 0.34-0.59; K = 1, Cl 0.84-1.16; P< 0.0001). The use of encapsulated 14 C-urea did not change agreement between the tests. Sensitivity and specificity were 100% (Cl 72-100% and 87-100%, respectively) with strong agreement between the tests (r = 0.71, Cl 0.50 -0.84; K = 1, Cl 0.68-1.32; P < 0.0001). Conclusion The novel Heliprobe UBT, with either liquid or encapsulated 14 C-urea, seems equi-efficacious to conventional UBT in fulfilling its role as the non-invasive gold standard for detection of H. pylori.

Tachykinins stimulate motility whereas NO inhibits motility in the gastrointestinal tract. Aim: To investigate if inhibition of NO production sensitizes myoelectric activity to subthreshold doses of tachykinins in the small intestine of awake rats. Methods: Rats were supplied with a venous catheter and bipolar electrodes at 5, 15 and 25 cm distal to pylorus for electromyography of small intestine. The motor responses were evaluated using pattern recognition. Substance P and neurokinin A dose-dependently stimulated gut motility, with neurokinin A being more potent than substance P. Therefore, neurokinin A was chosen and administered under baseline conditions and 45–60 min after Nω-nitro-l-arginine (l-NNA) 1 mg kg−1, with or without pretreatment with l-arginine 300 mg kg−1. In addition, myoelectric activity effects of neurokinin A in conjunction with l-NNA were studied before and after administration of the tachykinin receptor antagonists, SR140333 (NK1), SR48968 (NK2) and SR142801 (NK3), each at 2.5 mg kg−1. Results: Dose-finding studies verified 10 pmol kg−1 min−1 to be the threshold dose at which NKA caused phase II-like activity in a low percentage of experiments (12%, n=41). This dose was therefore used in combination with l-NNA for sensitization experiments of gut myoelectric activity. In experiments where NKA-induced no response, pretreatment with l-NNA led to phase II-like activity in 9 of 18 (50%, p

The orexins [orexin A (OXA) and orexin B (OXB)] are novel neuropeptides that increase food intake in rodents. The aim of this study was to determine the distribution of orexin and orexin receptors (OX1R and OX2R) in the rat duodenum and examine the effects of intravenous orexin on fasting gut motility. OXA-like immunoreactivity was found in varicose nerve fibers in myenteric and submucosal ganglia, the circular muscle, the mucosa, submucosal and myenteric neurons, and numerous endocrine cells of the mucosa. OXA neurons displayed choline acetyltransferase immunoreactivity, and a subset contained vasoactive intestinal peptide. OXA-containing endocrine cells were identified as enterochromaffin (EC) cells based on the presence of 5-hydroxytryptamine immunoreactivity. OX1R was expressed by neural elements of the gut, and EC cells expressed OX2R. OXA at 100 and 500 pmol · kg−1 · min−1significantly increased the myoelectric motor complex (MMC) cycle length compared with saline. Similarly, OXB increased the MMC cycle length at 100 pmol · kg−1 · min−1, but there was no further effect at 500 pmol · kg−1 · min−1. We postulate that orexins may affect the MMC through actions on enteric neurotransmission after being released from EC cells and/or enteric neurons.

BACKGROUND Luminal nitric oxide increases in ulcerative colitis and Crohn disease. The authors have previously used a minimally invasive method to demonstrate increased luminal nitric oxide in ulcerative colitis and Crohn disease of the colon. The aim of the current study was to determine whether this method could be applied to identify inflammatory activity in ulcerative colitis and Crohn disease in children. METHODS Thirty-six children (18 of whom had active disease) with inflammatory bowel disease localized to the colon were studied. The control group comprised 12 healthy children. To measure nitric oxide, a silicon catheter with an inflatable balloon was inserted into the rectum and inflated with 10 mL of nitric oxide-free air. After a 10-minute incubation time, the air was withdrawn and nitric oxide concentrations were immediately analyzed using a chemiluminescence technique. RESULTS Children with active ulcerative colitis and Crohn disease of the colon had greatly increased luminal nitric oxide concentrations in the rectum (8,840 +/- 5,120 and 15,170 +/- 4,757 parts per billion [ppb], respectively) compared with controls (77 +/- 17 ppb) (P < 0.001). Children with nonactive ulcerative colitis or Crohn disease displayed low concentrations of rectal nitric oxide (356 +/- 110 and 188 +/- 55 ppb, respectively), which was not different from that of healthy controls. CONCLUSION Rectal nitric oxide measurement is a feasible and useful method for monitoring disease activity in inflammatory bowel disease, especially in children.

BACKGROUND: There is interest in ultimately combining endoscopy and motility assessments. Gastric emptying (GET), small bowel (SBTT), colon (CTT) and whole gut transit (WGTT) times are conveniently ...

It has been established that the human gut microbiome is commensal, helps to digest our food, and is involved in metabolic processes in the gut and in the development and maintenance of our immune ...

Anaemia and iron deficiency in gastroenterology : a Scandinavian prospective, observational study of iron isomaltoside in clinical practice

Indirect burden of patients with moderate inflammatory bowel disease in Uppsala County Council, Sweden : a retrospective study using real-world data

Here we have investigated the pharmacokinetics, pharmacodynamics and safety of single doses of camicinal in type 1 diabetes mellitus (T1DM) patients with a history of slow gastric emptying with symptoms consistent with gastroparesis.In a randomized, double-blind, placebo-controlled, incomplete block, three-period, two-centre crossover study, patients received oral administration of placebo and two of the three possible doses of camicinal (25, 50 or 125 mg). Gastric emptying ((13) C-octanoic acid breath test), pharmacokinetics and safety were primary outcomes.Nine of the 10 patients enrolled completed the study. Gastric half-emptying time decreased by -95 min (95% CI: -156.8, -34.2) after a single dose of camicinal 125 mg compared with placebo (52 vs. 147 min, P 0.05), representing a 65% improvement. A decrease of the gastric half-emptying time compared with placebo (approximately 39 min) was observed with camicinal 25 and 50 mg, representing a 27% reduction for both doses (not statistically significant). A positive exposure-response relationship was demonstrated across all doses. The effects of camicinal on gastric half-emptying time were not influenced by fasting glucose levels. Single doses up to 125 mg were well tolerated. Camicinal was well absorbed, exhibiting linear and approximately dose-proportional pharmacokinetic characteristics and a clear exposure-response relationship with gastric emptying.Camicinal significantly accelerated gastric emptying of solids in T1DM patients following administration of a single oral dose. Camicinal was well tolerated and exhibited similar pharmacokinetic characteristics in diabetic patients to those previously reported in healthy volunteers.

An integrated understanding of the physiological mechanisms involved in the genesis of nausea remains lacking. We aimed to describe the psychophysiological changes accompanying visually induced motion sickness, using a motion video, hypothesizing that differences would be evident between subjects who developed nausea in comparison to those who did not. A motion, or a control, stimulus was presented to 98 healthy subjects in a randomized crossover design. Validated questionnaires and a visual analogue scale (VAS) were used for the assessment of anxiety and nausea. Autonomic and electrogastrographic activity were measured at baseline and continuously thereafter. Plasma vasopressin and ghrelin were measured in response to the motion video. Subjects were stratified into quartiles based on VAS nausea scores, with the upper and lower quartiles considered to be nausea sensitive and resistant, respectively. Twenty-eight subjects were exposed to the motion video during functional neuroimaging. During the motion video, nausea-sensitive subjects had lower normogastria/tachygastria ratio and cardiac vagal tone but higher cardiac sympathetic index in comparison to the control video. Furthermore, nausea-sensitive subjects had decreased plasma ghrelin and demonstrated increased activity of the left anterior cingulate cortex. Nausea VAS scores correlated positively with plasma vasopressin and left inferior frontal and middle occipital gyri activity and correlated negatively with plasma ghrelin and brain activity in the right cerebellar tonsil, declive, culmen, lingual gyrus and cuneus. This study demonstrates that the subjective sensation of nausea is associated with objective changes in autonomic, endocrine and brain networks, and thus identifies potential objective biomarkers and targets for therapeutic interventions.

Changes in food reward have been implicated in exercise-induced compensatory eating behaviour. However, the underlying mechanisms of food reward, and the physiological correlates of exercise-induced changes in food reward, are unknown.Methods.Forty-six overweight and obese individuals completed 12 weeks of aerobic exercise. Body composition, food intake, and fasting metabolic-related hormones were measured at baseline, week six, and postintervention. On separate days, the reward value of high-and-low-fat food (explicit liking and implicit wanting) was also assessed at baseline, week six, and postintervention.Results.Following the intervention, FM, FFM, andVO2peakimproved significantly, while fasting leptin decreased. However, food intake or reward did not change significantly. Cross-sectional analyses indicated that FM (P=0.022) and FFM (P=0.046) were associated with explicit liking for high-fat food, but implicit wanting was associated with FM only (P=0.005). Fasting leptin was associated with liking (P=0.023) and wanting (P=0.021) for high-fat food. Furthermore, a greater exercise-induced decline in fasting leptin was associated with increased liking (P=0.018).Conclusion.These data indicate that food reward has a number of physiological correlates. In particular, fasting leptin appears to play an active role in mediating food reward during exercise-induced weight loss.

Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose. Electronic supplementary material The online version of this article (doi:10.1007/s12325-014-0112-1) contains supplementary material, which is available to authorized users.

The slowing of gastric emptying is an important mechanism for the satiating effect of gut peptide signaling. After food intake, cholecystokinin (CCK), as well as glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), are released from the gastrointestinal tract to mediate satiety. In humans, CCK and the GLP-1 have been found to cause satiety in both normal and obese subjects. This satiating effect may be caused by the peptides circulating as hormones with direct effects in the central nervous system, or indirect effects through signals mediated either via the vagus nerve or by activation of vagal afferent fibers due to slow gastric emptying. These peptides also cause gastric relaxation, considered an additional component in the satiating effect of the peptides. To conclude, after food intake, gut peptides may act in concert as neurohormonal satiety signals acting directly in the brain or indirectly via the vagus nerve, as well as through gastric sensory mechanisms to limit food intake.

1. MEN 11420 (nepadutant) is a potent, selective and competitive antagonist of tachykinin NK2 receptors. 2. The objective of the present study was to assess the capability of the drug to antagonize ...

Seven studies have now been published pertaining to the acute effect of iv administration of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake. In four of these studies energy intake was significantly reduced following the glucagon-like peptide-1 infusion compared with saline. In the remaining studies, no significant effect of glucagon-like peptide-1 could be shown. Lack of statistical power or low glucagon-like peptide-1 infusion rate may explain these conflicting results. Our aim was to examine the effect of glucagon-like peptide-1 on subsequent energy intake using a data set composed of subject data from previous studies and from two as yet unpublished studies. Secondly, we investigated whether the effect on energy intake is dose dependent and differs between lean and overweight subjects. Raw subject data on body mass index and ad libitum energy intake were collected into a common data set (n = 115), together with study characteristics such as infusion rate, duration of infusion, etc. From four studies with comparable protocol the following subject data were included if available: plasma concentrations of glucagon-like peptide-1, subjective appetite measures, well-being, and gastric emptying rate of a meal served at the start of the glucagon-like peptide-1 infusion. Energy intake was reduced by 727 kJ (95% confidence interval, 548-908 kJ) or 11.7% during glucagon-like peptide-1 infusion. Although the absolute reduction in energy intake was higher in lean (863 kJ) (634-1091 kJ) compared with overweight subjects (487 kJ) (209-764 kJ) (P = 0.05), the relative reduction did not differ between the two groups (13.2% and 9.3%, respectively). Stepwise regression analysis showed that the glucagon-like peptide-1 infusion rate was the only independent predictor of the reduction in energy intake during glucagon-like peptide-1 (7-36) amide infusion (r = 0.4, P < 0.001). Differences in mean plasma glucagon-like peptide-1 concentration on the glucagon-like peptide-1 and placebo day (n = 43) were related to differences in feelings of prospective consumption (r = 0.40, P < 0.01), fullness (r = 0.38, P < 0.05), and hunger (r = 0.26, P = 0.09), but not to differences in ad libitum energy intake. Gastric emptying rate was significantly lower during glucagon-like peptide-1 infusion compared with saline. Finally, well-being was not influenced by the glucagon-like peptide-1 infusion. Glucagon-like peptide-1 infusion reduces energy intake dose dependently in both lean and overweight subjects. A reduced gastric emptying rate may contribute to the increased satiety induced by glucagon-like peptide-1.

Helicobacter pylori is recognized as the main etiological factor for chronic gastritis, peptic ulcer and possibly also gastric malignancies. A 14C-urea breath test was successively refined to correctly diagnose the presence of H. pylori.After intake of a 14C-urea cocktail, 14CO2 in breath was trapped in benzethoniumhydroxide/ethanol. Serology by ELISA, followed by Western blot, was used as reference method for confirmation of presence or absence of H. pylori.Breath measurements at 10 and 20 min were determined to be optimal for diagnostic purposes. With 2.5 microCi of 14C-urea, a sensitivity of 86% and specificity of 100% was obtained for the 10-min values. Corresponding data for the 20-min values were 86% and 99%, respectively. When 50 mmol L(-1) citric acid was added to the 2.5 microCi 14C-urea cocktail, separation between positive and negative results became more distinct along with improved sensitivity of 91% and specificity of 100%. As the isotope amount was reduced to 1.0 microCi in the citric acid-containing cocktail, a sensitivity of 93% and specificity of 100% were obtained at both 10 and 20 min.Diagnostic urea breath test has a high concordance with H. pylori serology, combining ELISA and Western blot. Stepwise refinements proved the optimal urea breath test cocktail to include 1.0 microCi 14C-urea in citric acid solution with breath measurement at 10 min.

BACKGROUND Myotonic dystrophy (MD) is a systemic disease affecting striated, cardiac and smooth muscles, as well as nerve structures and endocrine glands. Patients with MD may suffer from slow gastric emptying. OBJECTIVE To study electrogastrograms (EGG) and postprandial gut hormone profiles in MD in order to evaluate whether disturbances in these regulatory mechanisms could explain, or contribute to, the delayed gastric emptying. SUBJECTS Ten patients with MD complaining of symptoms consistent with slow gastric emptying, and ten healthy matched controls. METHODS After an overnight fast, the patients and the control subjects were examined with standard EGG using surface electrodes before and during intake of a standard meal. Blood tests were drawn at regular time intervals for hormone analyses. RESULTS The EGG in MD showed a reduced amount of normal three cycles per minute activity compared with controls (P < 0.04). The dominant frequency in MD was less stable than in controls (P < 0.03), and the power of the signal showed less increase after a meal. The postprandial increase in plasma motilin (P < 0.05) and glucagon-like peptide-1 (GLP-1) (P < 0.001) was significantly less pronounced in MD compared with controls, whereas the plasma concentrations of cholecystokinin (CCK), neurotensin (NT), peptide YY (PYY) and somatostatin (SOM) did not differ significantly. CONCLUSION Disturbed electrophysiological control of the stomach and impaired secretion of gastrointestinal peptide hormones could contribute to slow gastric emptying in MD. Combined impairment of gastric pacing and gastrointestinal hormone responses was found in patients with the most prominent retardation of gastric emptying.

BACKGROUND Glucagon-like peptide-1 (GLP-1) has been shown to inhibit gastric emptying of a caloric load but the effect on a non-caloric load is unknown. METHODS Seven healthy men were studied after an over-night fast. Thirty min before the intake of 330 ml radioactively labeled water either GLP-1 (0.75 pmol/kg/min) or saline was administered intravenously and continued for 75 min. Scintigraphic gastric emptying was performed for 45 min and plasma samples were obtained for analysis of vasopressin, sodium, osmolality, GLP-1, insulin, and glucose. In addition, electric field stimulation of human gastric muscle strips was done. RESULTS The median (range) percent water retained in the stomach, 45 min after intake of water, was 96% (68%-98%) and 12% (2%-42%) (P = 0.02) during infusion of GLP-1 and saline, respectively. Additionally, GLP-1 did not affect basal tone or contractile response of gastric muscle strips to electric field stimulation or acetylcholine (ACh). There was no change in plasma concentrations of vasopressin, sodium, or plasma osmolality during GLP-1 compared to saline infusion. CONCLUSION GLP-1 has a profound inhibitory effect on the gastric emptying of water in man, but no short-term effect on water homeostasis. No effect was seen on contractility of gastric muscle strips suggesting an indirect action on gastric emptying.

Background: Tachykinins and acetylcholine are main physiological motility stimulators in the gut by their effects exerted through neurokinin and muscarinic receptors. Methods

Naslund E, Andersson I, Degerblad M, Kogner P, Kral JG, Rossner S, Hellstrom PM (Danderyd Hospital, Huddinge University Hospital and Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden; and the Health Science Center at Brooklyn, New York, USA). Associations of leptin, insulin resistance and thyroid function with long-term weight loss in dieting obese men. J Intern Med 2000; 248: 299–308. Objective. The aim of the present study was to identify predictors of weight loss in obese men participating in a 2-year behaviour modification programme. Design. Longitudinal, clinical intervention study of a behaviour modifying weight loss program. Setting. University Hospital, Stockholm, Sweden Subjects. Forty-four obese men (age, 42.7 ± 1.1 years; BMI, 37.1 ± 0.6 kg m–2, mean ± SEM) followed for 2 years. Interventions. Behaviour modification weight loss programme. Main outcome measures. Associations between plasma leptin and thyroid function tests, insulin resistance by homeostatic model assessment (HOMA), dietary recall and anthropometrically determined body composition. Results. At baseline, there were significant correlations between plasma leptin and body mass index (BMI), fat-free mass (FFM) and insulin resistance. Median weight loss over 2 years was 4.9 kg (range, – 27.2 to + 11.9). Baseline serum leptin concentrations adjusted for BMI (leptin/BMI ratio) were significantly correlated with 2-year weight change (r = 0.34, P = 0.04). A subset of seven of the 44 men gained weight over the 2 years. These ‘gainers’ differed significantly in initial leptin/BMI ratio (0.62 ± 0.07) compared with the 37 ‘losers’ (0.42 ± 0.03, P

By means of a standardised procedure, reference values for scintigraphic gastric emptying were established. The influence of gender, age, menstrual cycle, body mass index (BMI) and smoking habits was also evaluated. Eight centres recruited 20 healthy subjects each. The meal consisted of a technetium-99m labelled omelet (1,300 kJ) and of 150 ml unlabelled soft drink. Geometric means of frontal and dorsal acquisitions were utilised in a linear fit model for determination of the linear emptying rate, and by using the intercepts of the regression line with the 90% and 50% levels, the lag phase and half-emptying time, respectively, were defined. All individuals showed an initial lag phase and subsequent linear emptying. Because of a longer lag phase and a slower linear emptying rate, premenopausal women had a slower gastric emptying than postmenopausal women and men of all ages. The gastric emptying rate increased with age in the women, mainly due to a shortened lag phase, while the emptying rate remained almost unchanged with age in the males. There were no significant differences in results between the centres. The menstrual cycle, BMI and smoking habits did not affect emptying. In conclusion, the fact that the results showed a slower gastric emptying rate in younger women compared with older women and men indicates that it is necessary to use separate reference values for fertile females.

We evaluated small intestinal motility, secretion, and mucosal permeability in fasted Sprague–Dawley rats following administration of luminal Escherichia coli heatstable enterotoxin (500 ng ml −1 ) alone or in combination with intravenous endotoxin (100 μg kg −1 ). Systemic endotoxin alone, or in combination with enterotoxin, caused a disruption of the regular interdigestive myoelectric complex as well as induction of spike bursts and diarrhea. Enterotoxin alone produced only minimal effects on intestinal myoelectric activity. Exposure of the intestine to systemic endotoxin and luminal enterotoxin in combination, led to a 2-fold increase in intestinal secretion in comparison with controls. This effect was significantly greater than the increase observed with enterotoxin (64±51%, P P P

Objective To evaluate if impaired gastric emptying of digestible solids can explain the disturbed eating behavior in continuous ambulatory peritoneal dialysis (CAPD) patients, and if predialytic and dialytic (CAPD and hemodialysis) patients with impaired gastric emptying have a higher prevalence of electrogastrographic (EGG) abnormalities. Design Cross-sectional study. After ingestion of a 99mTc-labeled test meal, anterior and posterior 1-minute scintigraphic acquisitions were collected every 5 minutes during the first 50 minutes and thereafter every 10 minutes until 2 hours had elapsed. Simultaneously, cutaneous EGG recorded gastric myoelectric activity. Setting The Division of Nephrology and the Department of Nuclear Medicine at the same academic teaching hospital. Participants Thirty outpatients participated in both the gastric emptying and the EGG studies. Dialysis patients should have been on dialysis for more than 3 months. For comparison, 160 healthy control subjects participated in the gastric emptying study. Main Outcome Measures The following parameters were used to describe gastric emptying: lag phase 90%, half-emptying time ( T50), gastric retention at 90 and 120 minutes (Ret 90/120) and gastric emptying rate (GER, %/min). Electrogastrographic measurements were expressed as percentages of normal slow waves [2.4 – 3.6 cycles/min (cpm)], bradygastria (1.5 – 2.4 cpm), and tachygastria (3.6 – 10 cpm). Results T50 was prolonged, Ret 90 and Ret 120 were higher, and GER was slower in male CAPD patients compared to male controls. No significant differences were found in postprandial EGG. Conclusion Gastric emptying is impaired in male non-diabetic CAPD patients. However, abnormalities in postprandial EGG cannot explain this finding.

1. The non-selective endothelin (ET) receptor antagonist bosentan has been shown to restore systemic and gut oxygen delivery and reverse intestinal mucosal acidosis in porcine endotoxin shock. 2. To further elucidate the specific role of the ETA as opposed to the ETB receptor and their effects in the splanchnic region a non-selective (ET(MIX)ra) A-182086 and selective ETA (ET(A)ra) PD155080 and ETB (ET(B)ra) A-192621 receptor antagonists were administered, separately or simultaneously (ET(A+B)ra) 2 h after onset of endotoxin shock. These four groups were compared to a control group receiving only endotoxin and vehicle. 3. Thirty-nine pigs were anaesthetized and catheterized for measurement of central and regional haemodynamics. A tonometer in the distal ileum was used for measurement of mucosal PCO2. Blood gases and plasma ET-1-LI levels as well as histological samples from the gut were assessed. Intervention was started 2 h after onset of endotoxemia and the experiments were terminated after 5 h. 4. Endotoxin-induced changes in systemic, gut oxygen delivery and portal hepatic vascular resistance and systemic acidosis were effectively counteracted by both ET(A+B)ra an ET(MIX)ra. ET(A)ra administration was not effective while ET(B)ra proved to be fatal as all animals in this group died prior to full time of the experiment. While both ET(A+B)ra and ET(MIX)ra improved gut oxygen delivery only the latter attenuated the profound endotoxin-induced ileal mucosal acidosis. 5. The lethal effect seen from selective ETB receptor antagonism in the current study may be due to increased ETA receptor activity as plasma levels of ET-1 is increased several fold by blocking the ETB receptor and thereby the plasma-ET-1-clearing function. Furthermore, a loss of endothelial ETB receptor vasodilating properties may also have contributed to the lethal course in the ET(B)ra group. 6. The findings in this study suggest that ET is involved in the profound endotoxin-induced disturbances in splanchnic homeostasis in porcine endotoxaemia. Furthermore, antagonism of both ETA and ETB receptors is necessary to effectively counteract these changes.

We have investigated the effect of 5-hydroxytryptamine (5-HT) and different 5-HT-receptor antagonists and atropine on the migrating myoelectric complex in the rat small intestine. Infusion of 5-HT dose-dependently shortened the interval between phase III of the migrating myoelectric complex (MMC). In untreated animals the interval in upper jejunum was 19.1 (16.0–22.1) min. At doses of 10 and 20 nmol kg–1 min–1, the interval decreased to 15.2 (12.0–18.4) and 10.2 (9.4–11.0) min, respectively. The 5-HT3-receptor antagonist ondansetron (0.5 mg kg–1) alone increased the MMC interval from 20.8 (15.1–26.5) to 33.9 (19.4–48.4) min. Neither methiothepin (0.5 mg kg–1) nor ketanserin (0.5 mg kg–1), selective for 5-HT15-HT2-and 5-HT2-receptors, respectively, changed the MMC interval. The 5-HT4-receptor antagonist GR 113808 (0.5 mg kg–1) disrupted the MMC and induced irregular spiking activity. Ondansetron and atropine antagonized the 5-HT-induced shortening of the MMC interval. Neither methiothepin nor ketanserin affected the response to 5-HT. GR 113808 did not block the response to 5-HT in half of the animals; however, in the remaining ones MMC was disrupted and irregular spiking induced. In conclusion, these results show that 5-HT dose-dependently stimulates the cycling of the MMC in the small intestine via 5-HT3-receptors and a cholinergic final pathway. Our findings encourage further studies on the role of the 5-HT3-receptor in the control of gastrointestinal motility.