Time period from onset of pain to hospital admission and patients' awareness in acute pancreatitis.

OBJECTIVES: This study aimed to explore the period between onset of pain and hospital-admission (pain-to-admission time) in patients with acute pancreatitis (AP), to investigate the prognostic value and associated factors of this time, and to ascertain the knowledge about the pancreas in these patients. METHODS: An analysis of a prospective multicenter study was done, which included 188 patients with AP. RESULTS: Median pain-to-admission time was 27 hours (interquartile range, 6.0-72.0). Median pain-to-admission time was significantly shorter in intensive care unit (ICU) patients (10 hours) compared to non-ICU patients (36 hours) (P = 0.045). Short pain-to-admission time was associated with high pain level. Median pain level (0, no pain; 10, maximal pain) was 8.0 (interquartile range, 7.0-10.0). Older age correlated with lower pain level (r = -0.26; P = 0.002). Multiple logistic regression analysis including the admission values for serum lipase and C-reactive protein and the corresponding interactions to the pain-to-admission time showed substantial discriminative ability regarding ICU admission (concordance index, 0.706; P = 0.006). 86% (112/130) knew that they have a pancreas, 72% (81/112) of these patients knew that AP exists, and 56% (45/81) recognized that AP is potentially fatal. CONCLUSIONS: Knowledge about AP in hospitalized AP patients is poor. Serum lipase and C-reactive protein in dependency of the pain-to-admission time might be a suitable predictor for severity of AP.

Low-dose ghrelin infusion--evidence against a hormonal role in food intake.

Ghrelin is the only peripheral orexigenic peptide of gastrointestinal origin. Its preprandial increase is supposed to initiate food intake. This assumption is based on studies with intravenously infused ghrelin in rather high doses and the correlation between ghrelin levels and hunger sensations. As yet it is unclear whether or not low dose ghrelin resulting in physiological and moderately supraphysiological plasma levels has an effect on hunger sensations, the wish for food intake and / or the quantity of the meal consumed. We examined 20 normal-weight males (age 25±1.7 years, BMI 24±0.5 kg/m(2)) in a prospective double-blind randomized fashion. On two different days they obtained a ghrelin infusion 1 ng/kg/min or intravenous saline starting one hour after a standardized meal. Hunger and satiety ratings were documented by visual analogue scales. A second meal was served on demand and consumed until feeling satiated. Time point of the second meal as well as ingested calories were registered. Prior to the start of i.v. ghrelin the postprandial decrease of active plasma ghrelin by 30 pg/ml was comparable. In the controls the postprandial reduction was significant until 210 min compared to basal. With i.v. ghrelin basal levels were reached within 10 min. The maximal rise was twice basal. No effect was observed on hunger and satiety ratings. The time period between the meals and the food quantity of the second meal were similar. During ghrelin infusion glucose and growth hormone but not insulin and cortisol levels were significantly higher after the second meal compared to saline. The present data demonstrate for the first time the effect of a low dose ghrelin infusion on food intake. Neither physiological nor moderably supraphysiological ghrelin levels were associated with any change of the various food intake parameters determined. These data do not favour a hormonal role of peripheral ghrelin in the regulation of food intake.

Incidence of acute pancreatitis does not increase during Oktoberfest, but is higher than previously described in Germany.

BACKGROUND & AIMS: Increased alcohol consumption can lead to acute pancreatitis (AP). We investigated whether the incidence of alcohol-induced AP increased during the Munich Oktoberfest in 2008, at which 6.6 million liters of beer were sold within 16 days. METHODS: We performed a multicenter, prospective study of 188 patients with AP (36.7% alcohol-induced, 34.6% biliary), treated at 27 hospitals in the greater area of Munich, Germany (2,970,000 inhabitants) during the 2008 Oktoberfest. Data were compared with that from two 18-day control periods. RESULTS: During the Oktoberfest, the overall incidence of AP was 42.8/100,000 person-years, which is 117% higher than previously reported. The incidence of acute attacks of alcoholic pancreatitis (AAP) did not increase during the Oktoberfest, compared with control periods. AAP was independently associated with repeated episodes of AP (P = .001), high levels of chronic alcohol intake (P = .001), low body-mass index (P = .007), male gender (P = .033), and acute alcohol excess (P = .037). Biliary AP was associated with increased levels of alanine-aminotransferase and aspartate-aminotransferase (P = .003), old age (P = .014), and low levels of chronic alcohol intake (P = .032). Death (5/188 patients) was associated with baseline levels of blood urea nitrogen, receiver operating characteristic-area under the curve (ROC-AUC = 0.918), alkaline phosphatase (ROC-AUC = 0.861), and C-reactive protein (ROC-AUC = 0.855). CONCLUSIONS: The incidence of AP does not increase during the Oktoberfest, compared with other time periods; the incidence of AP in Munich is higher than previously described in Germany. AAP was associated with long-term, heavy alcohol exposure rather than short-term, excessive alcohol drinking. Levels of blood urea nitrogen were associated with mortality.

Hypobaric hypoxia causes body weight reduction in obese subjects.

The reason for weight loss at high altitudes is largely unknown. To date, studies have been unable to differentiate between weight loss due to hypobaric hypoxia and that related to increased physical exercise. The aim of our study was to examine the effect of hypobaric hypoxia on body weight at high altitude in obese subjects. We investigated 20 male obese subjects (age 55.7 +/- 4.1 years, BMI 33.7 +/- 1.0 kg/m(2)). Body weight, waist circumference, basal metabolic rate (BMR), nutrition protocols, and objective activity parameters as well as metabolic and cardiovascular parameters, blood gas analysis, leptin, and ghrelin were determined at low altitude (LA) (Munich 530 m, D1), at the beginning and at the end of a 1-week stay at high altitude (2,650 m, D7 and D14) and 4 weeks after returning to LA (D42). Although daily pace counting remained stable at high altitude, at D14 and D42, participants weighed significantly less and had higher BMRs than at D1. Food intake was decreased at D7. Basal leptin levels increased significantly at high altitude despite the reduction in body weight. Diastolic blood pressure was significantly lower at D7, D14, and D42 compared to D1. This study shows that obese subjects lose weight at high altitudes. This may be due to a higher metabolic rate and reduced food intake. Interestingly, leptin levels rise in high altitude despite reduced body weight. Hypobaric hypoxia seems to play a major role, although the physiological mechanisms remain unclear. Weight loss at high altitudes was associated with clinically relevant improvements in diastolic blood pressure.

Plasma ghrelin levels during exercise - effects of intensity and duration.

Ghrelin, a recently discovered hormone of gastric origin has been shown to stimulate appetite and food intake. In man it is considered to play a role in energy homeostasis and regulation of somatropic function. As exercise affects hunger/satiety sensations and food intake, at least under some experimental conditions, we investigated the effect of exercise intensity and duration on ghrelin release and subsequent ad libitum food intake in normal weight subjects. Bicycle exercise on an ergometer for 30 min at 50 W which was below the aerob-anaerobic threshold led to an increase of ghrelin which remained unchanged during the higher intensity at 100 W. Respective hunger/satiety ratings and subsequent food intake and postprandial ghrelin suppression were identical and not different from controls. In a second group 7 subjects cycled at 50 W for 30, 60 and 120 min, respectively. Ghrelin concentrations rose significantly by 50-70 pg/ml above baseline for the respective period of exercise. While postexercise premeal ghrelin levels were not significantly different subsequent food intake after 120 min of cycling was significantly greater compared to control, 30 min and 60 min exercise, respectively. The present data suggest that low rather than high-intensity exercise stimulates ghrelin levels independent of exercise duration. Stimulation of food intake during prolonged exercise is most likely not due to changes of ghrelin.

Food intake and plasma ghrelin response during potato-, rice- and pasta-rich test meals.

OBJECTIVE: Complex carbohydrates such as potato, rice and pasta are frequently consumed accompaniments of meat meals and have different effects on satiety, food intake, glucose, and insulin concentrations. The orexigenic gastric hormone ghrelin contributes to feeding regulation and as yet it is unknown whether there is any differential ghrelin response to these starchy food items corresponding to their effects on food intake. METHODS: In 11 subjects the effect of satiating amounts of potatoes, rice or pasta consumed together with 150 g pork steak was examined on hunger/satiety ratings, food intake, plasma insulin, glucose and ghrelin concentrations. RESULTS: All meals led to comparable quantities of food intake while energy intake was significantly lower after potatoes. Satiety/hunger ratings were significantly different from basal for the entire 4 h period after rice and pasta meals, while they had returned to basal during the 4th hour after potatoes. After rice and pasta insulin rose significantly for 4 h. Ghrelin decreased during the 2nd and 3rd hour. In contrast potatoes stimulated insulin for the initial 2 h only while ghrelin rose significantly by 120 pg/ml over the 4 h period. A significant correlation was observed between ghrelin and hunger ratings while subsequent second meal food and energy intake did not differ irrespective of the preceding ghrelin concentration. CONCLUSION: Compared to rice and pasta satiating amounts of potatoes coingested with meat result in lower energy intake and postprandial insulin concentrations, which is not counterbalanced during subsequent food intake despite higher ghrelin concentrations. The present data support the concept that ghrelin can affect hunger sensations but not necessarily food and energy intake.

Ghrelin response to protein and carbohydrate meals in relation to food intake and glycerol levels in obese subjects.

Obese subjects have lower basal and an attenuated decrease of postprandial plasma ghrelin following carbohydrate-rich meals, while the response to protein is unknown. Therefore, plasma ghrelin levels were examined after ingestion of satiating amounts of a protein- or carbohydrate-rich meal in relation to food and energy intake and hunger/satiety ratings in 30 obese subjects followed 240 min later by ad lib sandwiches. Food intake and hunger/satiety ratings were identical while energy intake was significantly greater after bread (861 +/- 62.7 vs. 441 +/- 50.4 kcal, p < 0.001). Second meal food and energy intake were not different. Ghrelin decreased after bread, but increased by 50 pg/ml (p < 0.001) after meat. The corresponding increase of insulin was 55 vs. 9 microU/ml (p < 0.001). Glycerol levels decreased significantly less after the protein meal compared to carbohydrates. After protein glycerol was significantly correlated to the rise of ghrelin but not insulin. These data demonstrate that, in obese subjects, protein has no different satiating effect than carbohydrate despite divergent ghrelin levels. Energy intake corresponds to energy density of the respective food items. Ghrelin response to both meals is qualitatively similar but quantitatively attenuated compared to normal weight subjects. The relationship between ghrelin and glycerol would support recent observations of a possible role of ghrelin in fat metabolism.

Differential association of basal and postprandial plasma ghrelin with leptin, insulin, and type 2 diabetes.

To gain further insight into the regulatory role of insulin and leptin on plasma ghrelin, 56 normal weight, 128 normoinsulinemic obese, 121 hyperinsulinemic obese, and 30 type 2 diabetic normoinsulinemic and 75 type 2 diabetic hyperinsulinemic obese patients were examined. In the obese subjects, basal hyperinsulinemia was associated with significantly lower ghrelin independent of BMI, age, and leptin. In normoinsulinemic (normal weight and normoinsulinemic obese) subjects, ghrelin was inversely related to stepwise increasing leptin. Multiple regression analysis and matching for insulin revealed a significant negative interaction of ghrelin with leptin but not insulin. In type 2 diabetic normoinsulinemic subjects, ghrelin was significantly lower compared with that in normoinsulinemic obese subjects. In type 2 diabetic hyperinsulinemic subjects, ghrelin was significantly lower than in normoinsulinemic subjects, whereas no further reduction was observed compared with hyperinsulinemic obese subjects. The postprandial decrease was significantly attenuated in normoinsulinemic obese and hyperinsulinemic obese subjects (-214.8 +/- 247 pg/ml [normal weight], -137.6 +/- 107 pg/ml [normoinsulinemic obese], -85.5 +/- 69 pg/ml [hyperinsulinemic obese], P < 0.001; mean +/- SD), whereas type 2 diabetes had no independent postprandial effect. In conclusion, the present data support the concept that leptin could be of importance for suppression of basal ghrelin during moderate weight gain in normoinsulinemic subjects, whereas hyperinsulinemia but not leptin is responsible in more severe obesity. Postprandial suppression of ghrelin is attenuated by as yet unknown mechanisms that are related to body weight but not to insulin or type 2 diabetes.

Postprandial response of plasma ghrelin levels to various test meals in relation to food intake, plasma insulin, and glucose.

Ghrelin is an orexigenic gastric hormone that decreases in peripheral blood after carbohydrate-rich meals but increases after protein ingestion. In the present study plasma ghrelin was determined together with hunger and satiety ratings and with insulin and glucose concentrations after the ingestion of satiating quantities of carbohydrate-, fat-, protein-, fruit-, and vegetable-rich meals in 14 healthy subjects. Four hours later, standardized sandwiches were consumed. After carbohydrate, ghrelin decreased, whereas fat, protein, fruit, and vegetable ingestion significantly increased ghrelin levels. Considering all test meals, no significant correlation existed between changes of ghrelin levels and satiety ratings (r = 0.05; not significant), whereas a significant inverse relationship was observed between plasma ghrelin and insulin levels (r = -0.44; P < 0.001). During the second meal, sandwich consumption was significantly greater after the preceding fruit and vegetable meals, which was significantly correlated with the fourth-hour increase of ghrelin (r = 0.44; P < 0.001). In conclusion, after an overnight fast, ghrelin release depends on the ingested macronutrients and is most likely not a major regulator of acute food intake, although it is of greater importance for the recurrence of hunger and subsequent meal size.

Effect of GIP, GLP-1, insulin and gastrin on ghrelin release in the isolated rat stomach.

Ghrelin release in man depends on the macronutrient composition of the test meal. The mechanisms contributing to the differential regulation are largely unknown. To elucidate their potential role, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), insulin, gastrin and somatostatin were examined on isolated rat stomach ghrelin secretion, which offers the advantage of avoiding systemic interactions. Basal ghrelin secretion was in a range that did not permit to consistently evaluate inhibiting effects. Therefore, the effect of gastrointestinal hormones and insulin was analyzed during vagal prestimulation. GLP-1(7-36)amide 10(-8) and 10(-7) M decreased ghrelin secretion significantly. In contrast, GIP 10(-8) and 10(-7) M augmented not only prestimulated, but also basal ghrelin secretion (p<0.05). Insulin reduced ghrelin at 10(-10), 10(-8) and 10(-6) M (p<0.05). Both gastrin 10(-8) M and somatostatin 10(-6) M also significantly inhibited ghrelin secretion. These data demonstrate that GLP-1(7-36)amide, insulin, gastrin and somatostatin are potential candidates to contribute to the postprandially observed inhibition of ghrelin secretion with insulin being the most effective inhibitor in this isolated stomach model. GIP, on the other hand, could attenuate the postprandial decrease. Because protein-rich meals do not effectively stimulate GIP release, other as yet unknown intestinal factors must be responsible for protein-induced stimulation of ghrelin release.

Absorption of the mycotoxin patulin from the rat stomach.

The mycotoxin patulin (PAT), which frequently occurs in apple juices, has previously been shown to be toxic and teratogenic. However, there is almost no data about its absorption and metabolism. Therefore, the enrichment of PAT in the tissue of perfused rat stomachs after luminal application and its vascular appearance was quantified by stable isotope dilution assays. After application of juices enriched with PAT at concentrations of 350 and 3.5 mg/l, respectively, the mycotoxin appeared almost instantly in the perfusate. Twenty-six to twenty-nine percent of PAT were removed from the gastric lumen over 55 min. From this quantity, 17% and 2% were transferred into vascular circulation and 3% and 0.06% were detectable in gastric tissue for the high and the low PAT dose, respectively. The disappearance of 8400 microg and 700 microg PAT, respectively, could be attributed in part to its reaction with intracellular glutathione (GSH). Regarding the GSH content in the tissue, a decrease of 87% compared to that of control stomachs was observed for the high PAT dose, whereas in the case of the low PAT dose no significant GSH degradation occurred. Thus our results show that even low concentrations of patulin penetrate the gastric wall. Toxic effects, however, are unlikely as most of the patulin is disintegrated.

Differential effect of protein and fat on plasma ghrelin levels in man.

Ghrelin, a gastric hormone that stimulates food intake is decreased after ingestion of carbohydrate-rich meals. The acute effect of fat- and protein-rich meals on plasma ghrelin levels is still unknown. Accordingly, plasma ghrelin levels were determined in 10 healthy volunteers after ingestion of the three macronutrients and during vagal stimulation by modified sham feeding and following gastric distension with a highly viscous guar solution. After a solid carbohydrate-rich test meal ghrelin levels fell from 559+/-59.3 pg/ml to a nadir of 449+/-47.4 pg/ml within 60 min (p<0.05). Following an oral glucose load (75 g in 300 ml water), a similar decrease was observed (p<0.05). A fat-rich meal also decreased plasma ghrelin levels (p<0.05) leading to a nadir towards the end of the study period at 180 min. Protein intake, however, stimulated plasma ghrelin levels from 449+/-68.1 to a plateau of 520 pg/ml (p<0.05). There was no significant change of ghrelin levels after modified sham feeding or gastric distension. In conclusion, the decrease of ghrelin levels after fat ingestion shows a different time pattern compared to carbohydrate, while protein ingestion stimulated ghrelin levels. This suggests that different and as yet unknown mechanisms contribute to the regulation of postprandial ghrelin release in man depending on the ingested macronutrients. Cephalic-vagal and intragastric neural mechanisms most likely do not contribute to the postprandial regulation of ghrelin secretion.

TNF-alpha induces apoptosis of parietal cells.

Helicobacter pylori infection can be associated with chronic gastric inflammation and hypochlorhydria with increased levels of the proinflammatory cytokines. The current study investigated the effects of TNF-alpha on programmed death of gastric parietal cells. TNF-alpha induced apoptosis of parietal cells in isolated perfused rat stomachs at 10ng/mL. In isolated and highly enriched rat parietal cells, 10ng/mL TNF-alpha induced a 2.6-fold increase in the apoptotic rate. The 55kDa protein of TNFR-1 but not the 75kDa of TNFR-2 was detected by Western blot analysis. TNF-alpha-induced apoptosis of isolated parietal cells was inhibited by pretreatment with different NF-kappaB-inhibitors, nitric oxide synthase inhibitors and with antisense-oligodeoxynucleotides against the p65 subunit of NF-kappaB. Investigation of downstream signaling pathways of apoptosis revealed that TNF-alpha induced the expression of iNOS, but failed to stimulate the activity of caspase 3. The TNF-alpha effect on gastric parietal cells may contribute to the atrophy and hypochlorhydria of the gastric mucosa observed during chronic H. pylori infection.

Superior mesenteric artery syndrome: diagnosis and treatment from the gastroenterologist's view.

BACKGROUND: Superior mesenteric artery syndrome (SMAS) is caused by compression of the third part of the duodenum between the superior mesenteric artery and the aorta. It occurs most frequently in patients with rapid weight loss. METHODS: We report two young patients, who each presented with a longstanding history of postprandial abdominal pain, nausea, and voluminous vomiting. The diagnosis of SMAS was established by digital fluoroscopy and contrast-enhanced spiral computed tomography (CT) scan. The findings obtained by endoscopic ultrasound (EUS) at the site of duodenal compression, using a miniprobe, were of substantial diagnostic value and in good agreement with the radiological observations. RESULTS: Both patients, once diagnosed, were treated conservatively by providing enteral or parenteral high caloric nutrition. Weight gain was accompanied by the complete relief of symptoms. CONCLUSIONS: Pathogenesis, diagnostic procedures, and therapy are reviewed in order to draw attention to this rare entity.

Inhibitory effect of nociceptin on somatostatin secretion of the isolated perfused rat stomach.

The heptadecapeptide nociceptin/orphanin FQ (N/OFQ) has recently been isolated from porcine and rat brain and identified as the endogenous ligand of the N/OFQ receptor (NOP). It shows structural similarity with opioid peptides. N/OFQ has also been demonstrated in the gastrointestinal tract, where it inhibits gastrointestinal motility. The effect of N/OFQ on gastric neuroendocrine function is unknown as yet. In the isolated perfused rat stomach, N/OFQ 10(-6) M shows a small, but not significant decrease of basal somatostatin (SRIF) secretion. At the doses of 10(-12) M, 10(-10) and 10(-8) M N/OFQ has neither an effect on basal SRIF nor on basal vasoactive intestinal polypeptide (VIP), gastrin, substance P or bombesin secretion, respectively. However, gastric inhibitory polypeptide (GIP) 10(-9) M prestimulated SRIF secretion is significantly inhibited by N/OFQ 10(-8) M (-45+/-11%; p<0.05 vs. GIP). During concomitant infusion of the specific competitive NOP receptor antagonist [Nphe(1)]nociceptin(1-13)NH(2) 10(-6) M, the effect of N/OFQ is abolished (6+/-11%; p<0.05 vs. GIP and N/OFQ) while the opiate receptor antagonist naloxone 10(-6) M has no significant effect (-32+/-9%; ns vs. GIP and N/OFQ). At the higher concentration of N/OFQ 10(-6) M, the inhibition of prestimulated SRIF secretion (-58+/-6%; p<0.05 vs. GIP) is not influenced by the NOP receptor antagonist at the concentration of 10(-6) M (-49+/-9%; ns vs. GIP and N/OFQ) and 10(-5) M (-69+/-10%; ns vs. GIP and N/OFQ), respectively. On the other hand, infusion of naloxone 10(-6) M attenuates the inhibitory effect of N/OFQ 10(-6) M significantly (-21+/-6%; p<0.05 vs. GIP and N/OFQ).Thus, N/OFQ is an inhibitor of gastric somatostatin secretion. At the lower dose, this effect is transmitted via NOP receptors, while at the higher dose of 10(-6) M, the effect is at least in part mediated via opiate receptors.