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Introduction Intussusceptions diagnosed on computed tomography (CT) scans in Roux-en-Y gastric bypass (RYGB) patients could cause serious small bowel obstruction (SBO) or be an incidental finding. The objective of this study was to correlate radiological findings with clinical outcomes to differentiate intussusceptions requiring emergent surgery for SBO. Methods A search for acute abdominal CT scans reporting intussusceptions in RYGB patients between 2012 and 2019 at Skåne University Hospital, Malmö, Sweden, retrieved 35 scans. These were independently reevaluated by two radiologists for the length and location of the intussusception, whether oral contrast passed through, proximal bowel dilatation, and signs of internal herniation. Clinical outcome in terms of emergency surgery and the diagnosis was determined through chart review. Results Out of 35 acute patients, 9 patients required emergency surgery within 24 h. Intussusception caused SBO in five patients, and one patient had an internal herniation, while three patients had unremarkable findings. Eight patients were evaluated for intermittent pain with five unremarkable laparoscopies, while 18 patients had intussusceptions as incidental findings. Intussusception length on CT as measured by radiologists O.E. and D.L. predicted acute bowel obstruction (p = .014 and p p Conclusion Intussusception length > 100 mm on CT in RYGB patients is an easy and valuable sign indicating SBO that may require emergent surgery. Graphical Abstract

Background Artificial intelligence (AI) is gaining traction in medicine and surgery. AI-based applications can offer tools to examine high-volume data to inform predictive analytics that supports complex decision-making processes. Time-sensitive trauma and emergency contexts are often challenging. The study aims to investigate trauma and emergency surgeons’ knowledge and perception of using AI-based tools in clinical decision-making processes. Methods An online survey grounded on literature regarding AI-enabled surgical decision-making aids was created by a multidisciplinary committee and endorsed by the World Society of Emergency Surgery (WSES). The survey was advertised to 917 WSES members through the society’s website and Twitter profile. Results 650 surgeons from 71 countries in five continents participated in the survey. Results depict the presence of technology enthusiasts and skeptics and surgeons' preference toward more classical decision-making aids like clinical guidelines, traditional training, and the support of their multidisciplinary colleagues. A lack of knowledge about several AI-related aspects emerges and is associated with mistrust. Discussion The trauma and emergency surgical community is divided into those who firmly believe in the potential of AI and those who do not understand or trust AI-enabled surgical decision-making aids. Academic societies and surgical training programs should promote a foundational, working knowledge of clinical AI.

Diagnosing internal herniation (IH) in Roux-en-Y gastric bypass (RYGB) patients with acute abdominal pain poses a diagnostic challenge. Diagnostic laparoscopy is often required for a definitive diagnosis. We hypothesized that intestinal ischemia biomarkers would aid in the diagnosing of IH.To explore intestinal ischemia biomarkers in diagnosing IH.University Hospital, Sweden.Prospective inclusion of 46 RYGB patients admitted for acute abdominal pain between June 2015 and December 2017. Blood samples for analysis of citrulline, intestinal fatty acid-binding protein (I-FABP), and D-dimer were drawn72 hours from admission and compared between patients with IH (n = 8), small bowel obstruction (SBO) (n = 5), other specified diagnoses (n = 12), or unspecified abdominal pain (n = 21). Levels of white blood cell count (WBC), C-reactive protein (CRP), and lactate at admission were compared. A prospective pain questionnaire for time of pain onset and level of pain at onset and at admission was analyzed.None of the investigated biomarkers differed significantly between diagnosis categories. Most patients with IH had normal CRP, WBC, and D-dimer levels while their lactate levels were significantly lower (P = .029) compared with the rest of the cohort. Neither pain level nor pain duration differed between the groups.This study shows that citrulline, I-FABP, and D-dimer cannot be used to diagnose IH and indicates that CRP, D-dimer, and lactate are rarely elevated by an IH. Furthermore, pain intensity and duration cannot differentiate patients with IH. A diagnostic laparoscopy remains the gold standard to diagnose and rule out an IH.

Background Biliary complications during pregnancy is an important issue. The aim of this study was to examine if there is an increased risk to perform cholecystectomy during pregnancy in patients with previous bariatric surgery in comparison to other females subjected to cholecystectomy. Methods The Nationwide Swedish Registry for Gallstone Surgery (GallRiks) and the Scandinavian Obesity Surgery Registry (SOReg) were combined. Female patients 18–45 years old were included. The study group was patients with a history of bariatric surgery whom were pregnant at the time of cholecystectomy. This group was compared with pregnant patients without previous bariatric surgery and non-pregnant with and without previous bariatric surgery. Results In total, 21,314 patients were included and 292 underwent surgery during pregnancy. From 1282 patients identified in both registers, 16 patients were pregnant at the time of cholecystectomy. Acute cholecystectomy was performed in 5922 (28%) non-pregnant and 199 (68%) pregnant (p p = 0.031) and length of stay (p = 0.043), but no differences were seen when only comparing patients with an acute indication for surgery. There was no difference in complications comparing pregnant patients with previous bariatric surgery with non-pregnant, both with and without previous bariatric surgery. Conclusions Cholecystectomy during pregnancy in patients with previous bariatric surgery seems to be safe. The increased risk seen in the non-pregnant group after previous bariatric surgery is not seen in pregnancy, possibly due to an optimization of the circumstances at surgery.

Aims/hypothesis Salt-inducible kinase 2 (SIK2) is downregulated in adipose tissue from obese or insulin-resistant individuals and inhibition of SIK isoforms results in reduced glucose uptake and insulin signalling in adipocytes. However, the regulation of SIK2 itself in response to insulin in adipocytes has not been studied in detail. The aim of our work was to investigate effects of insulin on various aspects of SIK2 function in adipocytes. Methods Primary adipocytes were isolated from human subcutaneous and rat epididymal adipose tissue. Insulin-induced phosphorylation of SIK2 and HDAC4 was analyzed using phosphospecific antibodies and changes in the catalytic activity of SIK2 with in vitro kinase assay. SIK2 protein levels were analyzed in primary adipocytes treated with the proteasome inhibitor MG132. Results We have identified a novel regulatory pathway of SIK2 in adipocytes, which involves insulin-induced phosphorylation at Thr484. This phosphorylation is impaired in individuals with a reduced insulin action. Insulin stimulation does not affect SIK2 catalytic activity or cellular activity towards HDAC4, but is associated with increased SIK2 protein levels in adipocytes. Conclusion/interpretation Our data suggest that downregulation of SIK2 in the adipose tissue of insulin-resistant individuals can partially be caused by impaired insulin signalling, which might result in defects in SIK2 expression and function.

Activation of AMP-activated protein kinase (AMPK) is considered an attractive strategy for the treatment of type 2 diabetes. Favorable metabolic effects of AMPK activation are mainly observed in skeletal muscle and liver tissue, whereas the effects in human adipose tissue are only poorly understood. Previous studies, which largely employed the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), suggest an antilipolytic role of AMPK in adipocytes. The aim of this work was to reinvestigate the role of AMPK in the regulation of lipolysis, using the novel allosteric small-molecule AMPK activators A-769662 and 991, with a focus on human adipocytes. For this purpose, human primary subcutaneous adipocytes were treated with A-769662, 991, or AICAR, as a control, before being stimulated with isoproterenol. AMPK activity status, glycerol release, and the phosphorylation of hormone-sensitive lipase (HSL), a key regulator of lipolysis, were then monitored. Our results show that both A-769662 and 991 activated AMPK to a level that was similar to, or greater than, that induced by AICAR. In contrast to AICAR, which as expected was antilipolytic, neither A-769662 nor 991 affected lipolysis in human adipocytes, although 991 treatment led to altered HSL phosphorylation. Furthermore, we suggest that HSL Ser660 is an important regulator of lipolytic activity in human adipocytes. These data suggest that the antilipolytic effect observed with AICAR in previous studies is, at least to some extent, AMPK independent.

Background Gastric bypass (GBP) is a surgical method with good evidence of sustainable weight loss, reduced obesity-related comorbidities, and improved health-related quality of life (HRQoL). However, long-term data post-GBP is scarce on HRQoL related to other factors than weight loss, such as impact of socio-economic, age, and gender. Aim To investigate long-term HRQoL in GBP patients. Methods The study was conducted as a cross-sectional study covering 3 to 9 years post-GBP measuring HRQoL using RAND-36. Association to weight loss, time since surgery, gender, educational level, occupation, and age was analyzed. The participants were included on the basis that they had received a GBP that was performed by Region Skåne, the southernmost administrative healthcare region in Sweden. Recruitment to the study was by mail invitation for an online survey. Results Of the total population of 5310 persons receiving the questionnaire, 1339 of the 1372 responders fulfilled the inclusion criteria. Those with low educational level, unemployed, persons on sick leave or disability support, and those with less weight loss reported the lowest HRQoL. The longer time since surgery, the lower the HRQoL. Conclusion Less weight loss, longer time since GBP, lower educational level, and lower degree of employment all affect HRQoL negatively after GBP surgery. Graphical abstract

Background Managing acute abdominal pain in the large and growing population of Roux-en-Y gastric bypass (RYGB)–operated patients poses a challenge to general surgeons, because of diagnostic limitations and the risk of internal herniation. Objective To investigate the diagnoses, management, and outcome of RYGB patients admitted for acute abdominal pain. Setting University Hospital, Sweden. Methods Prospective inclusion of 280 consecutive RYGB patients admitted for acute abdominal pain between April 2012 and June 2015. Readmissions, surgical procedures, and overall mortality were recorded until October 2018. Medical records were retrospectively reviewed for anthropometric measures, medical history, time from RYGB surgery, and previous closure of mesenteric gaps. Admissions were separated into early (≤30 d) or late (>30 d) after RYGB. Procedures performed were categorized as follows: RYGB complication, other surgery, or unremarkable laparoscopy. Patients discharged with diagnosis of unspecified abdominal pain were separately analyzed. Diagnostic investigations, bariatric competency, on call surgery, surgical complications, and length of stay were registered. Results In late admissions, the cause of the abdominal complaints remained unexplained in 127 of 262 (48%) patients despite 95 abdominal computed tomographies and 28 diagnostic laparoscopies. Emergency surgery was performed in 128 of 262 (49%) patients. RYGB complications (n = 66), mainly internal herniation (n = 42), were >2 times more frequent than other surgical procedures (n = 32), such as cholecystectomies (n = 23). Internal herniation could occur at any time interval from RYGB surgery and regardless of previously closed mesenteric gaps. Conclusion Better tools for evaluation of acute abdominal pain in RYGB patients are needed to reduce the number of unremarkable laparoscopies and admissions of patients with unspecified abdominal pain.

Gastric bypass surgery results in remission of type 2 diabetes in the majority of patients. The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been implicated in the observed remission. Most knowledge so far has been generated in obese subjects. To isolate the surgical effects of gastric bypass on metabolism and hormone responses from the confounding influence of obesity, T2D, or food intake, we performed gastric bypass in lean pigs, using sham-operated and pair-fed pigs as controls. Thus, pigs were subjected to Roux-en-Y gastric bypass (RYGB) or sham surgery and oral glucose tolerance tests (OGTT). RYGB pigs and sham pigs exhibited similar basal and 120-min glucose levels in response to the OGTT. However, RYGB pigs had approximately 1.6-fold higher 30-min glucose (p

Background: The benefit of haptic feedback in laparoscopic virtual reality simulators (VRS) is ambiguous. A previous study found 32% faster acquisition of skills with the combination of 3 D and haptic feedback compared to 2 D only. This study aimed to validate perception and effect on performance of haptic feedback by experienced surgeons in the previously tested VRS. Material and methods: A randomized single blinded cross-over study with laparoscopists (>100 laparoscopic procedures) was conducted in a VRS with 3 D imaging. One group started with haptic feedback, and the other group without. After performing the suturing task with haptics either enabled or disabled, the groups crossed over to the opposite setting. Face validity was assessed through questionnaires. Metrics were obtained from the VRS. Results: The haptics for ‘handling the needle’, ‘needle through tissue’ and ‘tying the knot’ was scored as completely realistic by 3/22, 1/22 and 2/22 respectively. Comparing the metrics for maximum stretch damage between the groups revealed a significantly lower score when a group performed with haptics enabled p = .027 (haptic first group) and p Conclusion: Haptic feedback in VRS has limited fidelity according to the tested laparoscopic surgeons. In spite of this, significantly less stretch damage was caused with haptics enabled.

Background. Laparoscopic skills training and evaluation outside the operating room is important for all surgeons learning new skills. To study feasibility, a video box trainer tracking 4-dimensional (4D) metrics was evaluated as a laparoscopic training tool. Method. Simball Box is a video box trainer with authentic surgical instruments and camera with video recording, equipped with 4D motion analysis registered through trocars using machine vision technology. Residents attending a 3-day laparoscopy course were evaluated performing a laparoscopic surgical knot at start, middle, and end. Metrics were obtained. Feedback data were presented in reference to expert/tutorial performance. Results. Ten right-handed residents were included. Median time (range) to finish the task was 359 (253-418), 129 (95-166), and 95 (52-156) seconds; 655%, 236%, and 174% of tutorial performance, with significance pre-/midcourse ( P < .0001), pre-/postcourse ( P < .0001), and mid-/postcourse ( P = .0050). Combined median total instrument motion decreased pre-/midcourse from 1208 (845-1751) to 522 cm (411-810 cm); P = .042 to 405 cm (246-864 cm) postcourse; pre-/postcourse P < .0001; 673%, 291%, 225% of tutorial performance. Total angular distance in radians (range) was 150 (87-251), 65 (42-116), and 50 (33-136) with significance pre-/midcourse ( P = .022) and pre-/postcourse ( P = .0002). Right-handed average speed (cm/s) increased: 1.94 (1.11-2.27) pre-, 2.39 (1.56-2.83) mid-, 2.60 (1.67-3.19) postcourse with significance pre-/midcourse ( P = .022) and pre-/postcourse ( P = .002). Average acceleration (mm/s2) and motion smoothness (µm/s3) failed to show any difference. Conclusion. For laparoscopic training and as a promising evaluation device, Simball Box obtained metrics mirroring progression well.

Gastric bypass (GBP) has been the most common surgical way to treat obesity and its comorbidities. Late abdominal pain may occur by gastro-jejunal ulcers, gallstones, internal herniation or, rarely, intussusception. In an area with more than 1000 GBPs performed yearly, three patients with primary small bowel volvulus causing abdominal pain and requiring emergency or semi-urgent surgery were identified. Patients' histories, radiology, and surgery performed are presented. Weight loss followed by mesenteric narrowing of the root and thus relative elongation may make rotation of the small bowel mesentery possible. Such a torsion might be an overlooked differential diagnosis in obscure abdominal pain after GBP.

Obesity surgery is expanding, the quality of care is ever more important, and learning curve assessment should be established. A large registry cohort can show long-term effects on obesity and its comorbidities, complications, and long-term side effects of surgery, as well as changes in health-related quality of life (QoL). Sweden is ideally suited to the task of data collection and audit, with universal use of personal identification numbers, nation-wide registries permitting cross-matching to analyze causes of death, in-hospital care, and health-related absenteeism. In 2004, the Scandinavian Obesity Surgery Registry (SOReg) was initiated and government financing secured. A project group created a national database covering all public as well as private hospitals. Data entry was to be made online, operative definitions of comorbidity were formed, and complication severity scored. Several forms of audit were devised. After pilot studies, the system has been running in its present form since 2007. Since 15 January 2013, SOReg covers all bariatric surgery centers in Sweden. The number of operations in the database exceeded 40,000 (March 2014), with a median follow-up of 2.94 years. Audit shows that >98 % of data are correct. All results are publicized annually on the Internet. Using this systematic approach, it has been possible to cover >99 % of all bariatric surgery, cross-matching our data with nation-wide registries for in-hospital care, cause of death, and permitting regular nation-wide audit. Several scientific studies have used, or are using, what seems to be the most comprehensive database in obesity surgery.

BACKGROUND: The study investigated whether 3D vision and haptic feedback in combination in a virtual reality environment leads to more efficient learning of laparoscopic skills in novices.MATERIAL AND METHODS: Twenty novices were allocated to two groups. All completed a training course in the LapSim(®) virtual reality trainer consisting of four tasks: 'instrument navigation', 'grasping', 'fine dissection' and 'suturing'. The study group performed with haptic feedback and 3D vision and the control group without. Before and after the LapSim(®) course, the participants' metrics were recorded when tying a laparoscopic knot in the 2D video box trainer Simball(®) Box.RESULTS: The study group completed the training course in 146 (100-291) minutes compared to 215 (175-489) minutes in the control group (p = .002). The number of attempts to reach proficiency was significantly lower. The study group had significantly faster learning of skills in three out of four individual tasks; instrument navigation, grasping and suturing. Using the Simball(®) Box, no difference in laparoscopic knot tying after the LapSim(®) course was noted when comparing the groups.CONCLUSIONS: Laparoscopic training in virtual reality with 3D vision and haptic feedback made training more time efficient and did not negatively affect later video box-performance in 2D. [Formula: see text]. (Less)

BACKGROUND: A growing body of literature on Roux-en-Y gastric bypass surgery (RYGB) has generated inconclusive results on the mechanism underlying the beneficial effects on weight loss and glycaemia, partially due to the problems of designing clinical studies with the appropriate controls. Moreover, RYGB is only performed in obese individuals, in whom metabolism is perturbed and not completely understood.METHODS: In an attempt to isolate the effects of RYGB and its effects on normal metabolism, we investigated the effect of RYGB in lean pigs, using sham-operated pair-fed pigs as controls. Two weeks post-surgery, pigs were subjected to an intravenous glucose tolerance test (IVGTT) and circulating metabolites, hormones and lipids measured. Bile acid composition was profiled after extraction from blood, faeces and the gallbladder.RESULTS: A similar weight development in both groups of pigs validated our experimental model. Despite similar changes in fasting insulin, RYGB-pigs had lower fasting glucose levels. During an IVGTT RYGB-pigs had higher insulin and lower glucose levels. VLDL and IDL were lower in RYGB- than in sham-pigs. RYGB-pigs had increased levels of most amino acids, including branched-chain amino acids, but these were more efficiently suppressed by glucose. Levels of bile acids in the gallbladder were higher, whereas plasma and faecal bile acid levels were lower in RYGB- than in sham-pigs.CONCLUSION: In a lean model RYGB caused lower plasma lipid and bile acid levels, which were compensated for by increased plasma amino acids, suggesting a switch from lipid to protein metabolism during fasting in the immediate postoperative period.

Background Anastomotic leak is one of the most serious complications following bariatric laparoscopic Roux-en-Y gastric bypass (LRYGB), and associated with high morbidity rates and prolonged hospital stay. Timely management is of utmost importance for the clinical outcome. This study evaluated the approach to suspected leakage in a high-volume bariatric surgery unit. Methods All consecutive patients who underwent LRYGB performed by the same team of surgeons were registered prospectively in a clinical database from September 2005 to June 2012. Suspected leaks were identified based on either clinical suspicion and/or associated laboratory values, or by a complication severity grade of at least II using the Clavien–Dindo score. Results A total of 6030 patients underwent LRYGB during the study period. The leakage rate was 1·1 per cent (64 patients). Forty-five leaks (70 per cent) were treated surgically and 19 (30 per cent) conservatively. Eight (13 per cent) of 64 patients needed intensive care and the mortality rate was 3 per cent (2 of 64). Early leaks (developing in 5 days or fewer after LRYGB) were treated by suture of the defect in 20 of 22 patients and/or operative drainage in 13. Late leaks (after 5 days) were managed with operative drainage in 19 of 23 patients and insertion of a gastrostomy tube in 15. Patients who underwent surgical treatment early after the symptoms of leakage developed had a shorter hospital stay than those who had symptoms for more than 24 h before reoperation (12·5 versus 24·4 days respectively; P < 0·001). Conclusion Clinical suspicion of an anastomotic leak should prompt an aggressive surgical approach without undue delay. Early operative treatment was associated with shorter hospital stay. Delays in treatment, including patient delay, after symptom development were associated with adverse outcomes.

BACKGROUND: Internal hernias occur frequently after laparoscopic gastric bypass. We have found no data on the relative strength of the various techniques available for closing these defects. The present study was performed to obtain such data to form a theoretical basis for clinical studies. METHODS: Six piglets were operated laparoscopically and four loops of small bowel created in each. These mesenteric gaps were closed over a distance of 40 mm using (1) running 2-0 Ethibond® suture, (2) Endo Hernia stapler, (3) fibrin glue (Tisseel®) and (4) controls, where the mesenteric surfaces were rubbed with a sponge and approximated without further intervention. After 6 weeks, the different segments of the mesentery were excised. The tensile strength was measured using continuously increased traction until the closure ruptured. The ordinary mesentery served as the control. The breaking tension and total amount of energy transferred to the tissue were registered. RESULTS: Control areas with rubbed areas developed no adhesions. Suture and staple lines contracted by 30 % in length, whereas the fibrin glued lines were even shorter. Median tensile strength was greatest for the sutured lines (14,293 mN) and stapled lines (10,798 mN). Fibrin glued lines were significantly weaker (6,780 mN, p = 0.013 and p = 0.026), but as strong as ordinary mesentery (4,165 mN). CONCLUSIONS: If ongoing controlled randomized trials show closure to be beneficial, further studies should include staples as one of the options for the closure of mesenteric defects. The role of fibrin glue needs to be further investigated.

BACKGROUND: Conversion operations after vertical banded gastroplasty (VBG) are sometimes performed because of vomiting and/or acid regurgitation. Primary operation with gastric bypass (GBP) is known to reduce gastroesophageal reflux (GERD). Previous studies have not been designed to differentiate between the effects of the altered anatomy and of the ensuing weight loss. No series has reported data on acid reflux before and after conversion from VBG to GBP. METHODS: We invited eight VBG patients with current symptoms of GERD. All had intact staple lines as assessed by barium meal and gastroscopy. Acid reflux was quantified using 48-h Bravo capsule measurements. Conversion operations were performed creating an isolated 15-20-ml pouch; the previously banded part of gastric wall was excised. Gastrojejunostomy was made end to end with a 28-mm circular stapler. The study is based on five patients consenting to early postoperative endoscopy and pH measurement. RESULTS: All patients were women with a mean age of 49.5 years and BMI of 36.3. Time since VBG was 132.1 months. Time from conversion to second measurement was 46.6 days and BMI at that time 32.7. There was no mortality and no serious morbidity. All patients improved clinically and no patient had to go back on proton pump inhibition or antacids. Total time with pH < 4.0 was reduced from 18.4% to 3.3% (p < 0.05). DeMeester score was reduced from 58.1 to 15.9 (p < 0.05). CONCLUSIONS: The effect of converting VBG-operated patients to GBP results in a near-normalisation of acid reflux parameters and a discontinuation of proton pump inhibitor medication.

Background: In most patients gastric bypass (GBP) causes remission of type 2 diabetes. It is established that plasma levels of gut hormones are affected by GBP, but it is not well understood how the enteroendocrine cells producing these gut hormones are affected by GBP. Objectives: We set out to investigate the effect of GBP on enteroendocrine cells in the stomach and intestine of pigs. Methods: Lean non-diabetic pigs were subjected to either GBP or sham-surgery and immunocytochemistry and morphometry for all major gut hormones in all parts of the GI-tract was performed. Sham-operated, pair-fed pigs were used as controls. Results: Postoperatively in the antrum, the density of gastrin-cells was lower (GBP 12.8±2.1 cells/μm2 versus sham 21.3±2.6 cells/μm2 ) while density of serotonin-cells was higher in GBP-pigs (GBP 21.6±2.3 cells/μm2 versus sham 10.6±0.7 cells/μm2). In the fundus, no effect of GBP was observed on any cell population. In the duodenum, densities of CCK- (GBP 5.1±1.0 cells/μm2 versus sham 2.6±0.4 cells/μm2), ghrelin- (GBP 3.4±0.5 cells/μm2 versus sham 1.4±0.2 cells/μm2), GIP- (GBP 5.5±0.3 cells/μm2 versus sham 2.3±0.3 cells/μm2) and neurotensin-cells (GBP 3.5±0.7 cells/μm2 versus sham 0.5±0.2 cells/μm2) were higher in the GBP-pigs. In the distal jejunum, density of ghrelin-cells was lower (GBP 0.7±0.2 cells/μm2 versus sham 2.3±0.4 cells/μm2) while densities of GIP- (GBP 3.5±0.3 cells/μm2 versus sham 2.4±0.2 cells/μm2) and secretin-cells (GBP 3.4±0.7 cells/μm2 versus sham 1.6±0.3 cells/ μm2) were higher in GBP-pigs compared to sham-pigs. In the ileum, densities of GIP-cells (GBP 5.4±0.4 cells/ μm2 versus sham 3.9±0.4 cells/μm2) and somatostatin-cells (GBP 3.3±0.4 cells/μm2 versus sham 2.1±0.3 cells/μm2) were higher, while densities of GLP-1-cells (GBP 5.0±0.5 cells/μm2 versus sham 8.8±1.4 cells/μm2) and PYYimmunoreactive cells (GBP 3.8±0.1 cells/μm2 versus sham 5.9±0.8 cells/μm2) were lower in the GBP-pigs. In the colon, densities of GIP- (GBP 2.8±0.3 cells/μm2 versus sham 1.4±0.2 cells/μm2), serotonin- (GBP 6.7±0.3 cells/μm2 versus sham 4.8±0.5 cells/μm2) and somatostatin-cells (GBP 1.9±0.2 cells/μm2 versus sham 1.3±0.1 cells/μm2) were higher in the GBP-pigs. GBP had no effect on villi length or total mucosa height in any of the intestinal segments analyzed, whereas duodenum (GBP 37.6±3.4 cells/μm2 versus sham 26.5±2.8 cells/μm2) and ileum (GBP 127±1.2 cells/μm2 versus sham 84.7±9.9 cells/μm2) of the GBP-pigs displayed higher proliferation, as assessed by Ki67 immunoreactivity. Conclusions: We conclude that GBP induces rapid and profound changes in the densities of gut hormoneproducing cells throughout the GI-tract in pigs. These changes seem to be the result of GBP per se and not a result of body weight or food intake. Also, GIP was increased in the GBP-pigs in all the intestinal segments analyzed.

Background Super-obesity, a body mass index>50 kg/m 2 , is difficult to treat. Many studies have focused on the anatomic changes of the intestines; the physiologic background is not clearly identified. It is established that Roux-en-Y gastric bypass (RYGB) augments secretion of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), and insulin, but other aspects of gut hormone cell function in the alimentary limb are unknown. Objective To study the effects of laparoscopic RYGB on enteroendocrine cells. Setting University-affiliated, high-volume bariatric surgery center. Methods Eighteen nondiabetic patients were drawn from the present study (NCT 01514799), randomizing between biliopancreatic (BP) limbs of either 60 cm (BP60) or 200 cm (BP200). Demographic characteristics did not differ at baseline or 12 months. Pouch and jejunal biopsies were obtained intraoperatively and using endoscopy at 12 months. Mucosal height and density of hormone-producing cell populations were assessed and mRNA expression measured with real-time polymerase chain reaction. Results In perianastomotic jejunum, a 4.9-fold increase in GLP-1 cell density was evident 12 months after RYGB, most pronounced in the BP200-group. The densities of glucose-dependent insulinotropic polypeptide (GIP) cells and PYY immunoreactive cells were doubled after 12 months. GIP mRNA was unaffected, but GLP-1 and PYY mRNA were lower 12 months after RYGB. RYGB had no impact on villi length or density of ghrelin-, cholecystokinin-, neurotensin-, secretin-, or serotonin-producing cells after 12 months. Pouch mucosal height and cell densities of ghrelin-, histamine-, serotonin-, and somatostatin-producing cells remained unaffected by RYGB in both groups. Conclusions RYGB selectively increased the density of incretin-producing cell populations in the jejunum. This may provide anatomic explanation for the observed increased plasma levels of incretins.

Total parenteral nutrition (TPN) is often crucial for patients not being able to feed enterally or having intestinal absorptive deficits. Enteral nutrition is, however, frequently regarded vital for maintaining functional and structural intestinal integrity. The aim of this study was to investigate possible effects of TPN on rat distal small intestine compared to enterally fed identically housed controls, regarding the enteric nervous system (ENS), motility in vitro, and morphology. This study shows that motor responses evoked by electrical stimulation or exposure to vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide-27 (PACAP-27), and nitric oxide (NO) donor were unchanged. By using immunohistochemistry, the numbers of submucous (P < 0.05) and myenteric (P < 0.05) nerve cells were found to increase, expressed as numbers per unit length. The percentage of neurons expressing VIP, PACAP-27, NO-synthase, and galanin remained unchanged, however. By in situ hybridization the number of submucous neurons expressing neuropeptide Y-mRNA was found to decrease (P < 0.05); the other populations were unaltered. Morphometry revealed an increased submucosal thickness (P < 0.05), while intestinal circumference markedly decreased (P < 0.0001) in TPN-treated rats. In conclusion, TPN treatment resulted in reduced intestinal circumference leading to condensation of enteric neurons. No marked changes in neurotransmitter expression of the enteric neurons or in motor activity were noted.

Gastric bypass (GBP) results in rapid type 2 diabetes (T2D) remission in most cases. Consequences of GBP reversal are unknown. A GBP-operated T2D patient was given mixed-meal tests before (MMTpre), 2 months (MMT2-M) and 12 months (MMT12-M) after GBP reversal. Glucose, hormones and metabolite profiles were assessed. MMT2-M displayed slightly lower glucose levels; MMT12-M displayed higher glucose and insulin levels, indicating deteriorating glycaemia. Homeostasis model assessment (HOMA)-β was higher at MMT2-M, but reduced at MMT12-M. Matsuda index revealed slightly reduced insulin sensitivity at MMT2-M, which deteriorated further at MMT12-M. Markers for metabolic stress and insulin resistance were elevated at MMT12-M. Gastric inhibitory polypeptide (GIP) levels were increased at MMT2-M and decreased at MMT12-M. Glucagon-like peptide-1 (GLP-1) decreased at MMT2-M and further decreased at MMT12-M. In conclusion, in this patient, GBP reversal provoked deteriorating glycaemia and long-term development of insulin resistance.

The most frequently used and effective treatment for morbid obesity is Roux-en-Y gastric bypass surgery (RYGB), which results in rapid remission of type 2 diabetes in most cases. To what extent this is accounted for by weight loss or other factors remains elusive. To gain insight into these mechanisms, we investigated the effects of RYGB on β-cell function and β-cell mass in the pig, a species highly reminiscent of the human. RYGB was performed using linear staplers during open surgery. Sham-operated pigs were used as controls. Both groups were fed a low-calorie diet for 3 weeks after surgery. Intravenous glucose tolerance tests were performed 2 weeks after surgery. Body weight in RYGB pigs and sham-operated, pair-fed control pigs developed similarly. RYGB pigs displayed improved glycemic control, which was attributed to increases in β-cell mass, islet number, and number of extraislet β-cells. Pancreatic expression of insulin and glucagon was elevated, and cells expressing the glucagon-like peptide 1 receptor were more abundant in RYGB pigs. Our data from a pig model of RYGB emphasize the key role of improved β-cell function and β-cell mass to explain the improved glucose tolerance after RYGB as food intake and body weight remained identical.

Salt-inducible kinase 2 (SIK2) is an AMP-activated protein kinase (AMPK) related kinase abundantly expressed in adipose tissue. Our aim was to identify molecular targets and functions of SIK2 in adipocytes, and to address the role of PKA-mediated phosphorylation of SIK2 on Ser358. Modulation of SIK2 in adipocytes resulted in altered phosphorylation of CREB-regulated transcription co-activator 2 (CRTC2), CRTC3 and class IIa histone deacetylase 4 (HDAC4). Furthermore, CRTC2, CRTC3, HDAC4 and protein phosphatase 2A (PP2A) interacted with SIK2, and the binding of CRTCs and PP2A to wild-type but not Ser358Ala SIK2, was reduced by cAMP elevation. Silencing of SIK2 resulted in reduced GLUT4 (also known as SLC2A4) protein levels, whereas cells treated with CRTC2 or HDAC4 siRNA displayed increased levels of GLUT4. Overexpression or pharmacological inhibition of SIK2 resulted in increased and decreased glucose uptake, respectively. We also describe a SIK2–CRTC2–HDAC4 pathway and its regulation in human adipocytes, strengthening the physiological relevance of our findings. Collectively, we demonstrate that SIK2 acts directly on CRTC2, CRTC3 and HDAC4, and that the cAMP–PKA pathway reduces the interaction of SIK2 with CRTCs and PP2A. Downstream, SIK2 increases GLUT4 levels and glucose uptake in adipocytes.

Colonic permeability was studied in vitro in patients subjected to colectomy because of ulcerative colitis and in control patients undergoing colonic resections for cancer.The mucosal layer from fresh colonic segments was stripped and mounted in Ussing diffusion chambers containing modified Krebs buffer solution. The mucosa to serosa passage of the marker molecules 14C-mannitol and ovalbumin was measured for 120 min.Marker passage was significantly increased in colitis patients compared with control patients, irrespective of age, sex, duration of disease, and treatment. Marker passage was further increased in patients with acute colitis. The increased colonic permeability may be explained by inflammation and the resultant loss of mucosal integrity. The increased permeability to ovalbumin implies that permeability to luminal macromolecules, such as bacterial products and other antigenic substances, might be increased in colitis.The results suggest a derangement of the colonic barrier, as evidenced by an increased mucosal permeability in both chronic and acute colitis.

The occurrence of islet amyloid polypeptide (IAPP) in the gut and pancreas of several species and during ontogeny of the rat, was studied using immunocytochemistry. Effects of IAPP on rat ileal smooth muscle were assessed in vitro. Islets of most, but not all, species examined, displayed IAPP in insulin cells and, in some species, also in somatostatin- and peptide YY (PYY)-containing cells. In the gut, expression of IAPP varied among species; when present, IAPP was most abundant in the proximal part and co-localized with somatostatin, PYY, gastrin/cholecystokinin, enteroglucagon or serotonin. IAPP was first demonstrated at embryonic day 12 and 16 in islet and gastrointestinal endocrine cells, respectively. IAPP relaxed gut muscle and reduced electrical field stimulation-evoked contractions, presumably by inhibiting acetylcholine release. Thus, IAPP expression in islets is consistent with an important role for IAPP in fuel metabolism; the gastrointestinal expression and motor effects of IAPP suggest that IAPP may modulate gastrointestinal function.

Objective: To elucidate the activity and expression of cyclic nucleotide phosphodiesterase (PDE) families in omental (OM) and subcutaneous (SC) adipose tissue and adipocytes, and to study alterations in their activity in human obesity. Design: Cross-sectional, translational research study. Patients: In total, 25 obese and 9 non-obese subjects undergoing gastrointestinal surgery participated in the study. Results: Inverse correlations between PDE activities and body mass index (BMI) were seen in both SC and OM adipose tissue. Inverse correlations between total PDE and PDE3 activity and BMI were seen in OM adipocytes but not in SC adipocytes. In both SC and OM adipose tissue of obese patients, total PDE and PDE3 activities were decreased compared with the controls. In SC adipose tissue of Type 2 diabetes (T2D) patients, the PDE activity not inhibitable by PDE3 or PDE4 inhibitors (PDEn) was increased compared with obese non-diabetic patients. In addition to PDE3 and 4 isoforms, PDE7B, PDE9A and PDE10A proteins were also detected in adipose tissue or adipocytes. Conclusions: Multiple PDE families are present in human adipose tissue and their activities are differentially affected by obesity and T2D.

Context: Gastric bypass surgery (GBP) results in the rapid resolution of type 2 diabetes. Most studies aiming to explain the underlying mechanisms are limited to data obtained after a postsurgical recovery period, making assessment of confounding influences from, for example, weight loss and altered nutrient intake difficult. Objective: To examine the impact of GBP on hormonal and metabolite profiles under conditions of identical nutrient intake independent of weight loss, we studied GBP patients fitted with a gastrostomy tube to enable the administration of nutrients to bypassed segments of the gut. Thus, this model allowed us to simulate partially the preoperative condition and compare this with the postoperative situation in the same patient. Design: Patients (n = 4) were first given a mixed meal test (MMT) orally and then via the gastrostomy tube, preceded by overnight and 2-hour fasting, respectively. Blood samples were assessed for hormones and metabolites. Results: The oral MMT yielded 4.6-fold increase in plasma insulin (P < .05), 2-fold in glucagon-like peptide-1 (P < .05), and 2.5-fold in glucose-dependent insulinotropic peptide (P < .05) plasma levels, compared with the gastrostomy MMT. The changes in hormone levels were accompanied by elevated branched-chain amino acid levels (1.4–2-fold, P < .05) and suppressed fatty acid levels (∼50%, P < .05). Conclusions: These data, comparing identical nutrient delivery, demonstrate markedly higher incretin and insulin responses after oral MMT than after gastric MMT, thereby providing a potential explanation for the rapid remission of type 2 diabetes observed after GBP. The simultaneous increase in branched-chain amino acid questions its role as a marker for insulin resistance.

Anaesthetized animals are often used in studies of gastric secretion. We have examined the effect of anaesthetics on the acid output in gastric fistula rats and pylorus-ligated rats, both vagally intact and denervated. Diethyl ether, chloral hydrate, and mebumal effectively reduced both basal and stimulated acid output in fistula rats. The acid output in pylorus-ligated rats was greatly reduced by the anaesthetics. In vagally denervated rats local nervous reflexes are thought to play an important role in the acid secretory response to pylorus ligation. Anaesthetic drugs suppressed acid output in both vagally intact and vagally denervated rats. The possibility of an action on intramural neurons cannot be excluded. The neuro-suppressive effect of anaesthesia should be considered in studies of gastric acid secretion.

The histamine-storing enterochromaffinlike cells, which are numerous in the oxyntic mucosa of the rat stomach, are known to proliferate in response to long-lasting hypergastrinaemia. In addition, portacaval shunting, which is not associated with elevated serum gastrin, causes an increase in enterochromaffinlike cell density. The present study shows that the combination of portacaval shunting and omeprazole-evoked, long-lasting hypergastrinemia results in enhanced enterochromaffinlike cell hyperplasia despite the fact that the hypergastrinemia was not significantly greater than in intact omeprazoletreated rats. The mechanism behind the enhanced response to gastrin of the enterochromaffinlike cells in rats with portacaval shunts is unknown. When results from untreated and omeprazole-treated rats were plotted, there was a linear correlation between the serum gastrin concentration and the enterochromaffinlike cell density in both sham-operated rats and rats with portacaval shunts. We conclude that gastrin plays a role in the development of enterochromaffinlike cell hyperplasia following omeprazole treatment in rats with portacaval shunts but that other as yet unidentified agents may also promote the response.

Total parenteral nutrition (TPN) is held to cause intestinal atrophy and weaken mechanical and immunological barriers. To monitor the degree of atrophy caused by TPN, female Sprague-Dawley rats were, for 8 days, maintained on TPN (n = 6) and compared to identically housed controls given food and water ad libitum (n = 6). Specimens from jejunum, ileum, and colon were taken for histology and morphometric analysis. Topographic distribution and presence of eosinophils, by eosinophil peroxidase (EPO) staining, were examined in the gastric fundus, jejunum, ileum, and colon. Atrophy in terms of a markedly reduced circumference was noted throughout the intestinal tract in all rats subjected to TPN. The width of jejunal and ileal villi was narrowed and the length of jejunal villi was decreased. Furthermore, submucosal thickness in the jejunum and ileum increased. The height of ileal enterocytes remained unaltered. The number of goblet cells decreased in jejunal but not in ileal villi. The Paneth cells, suggested to play important roles in innate defense, increased in size. In the gastric fundus a marked increase in eosinophils was revealed predominantly in the mucosa and submucosa. The number and distribution of jejunal and ileal eosinophils were identical to those of controls. In colon from TPN rats, a redistribution of eosinophils was noted, causing a "band-like" accumulation of eosinophils in the basal portion of the mucosa. In conclusion, TPN causes gut atrophy and an increase in Paneth cell size. Eosinophils increase in number in the gastric fundus and a topographic redistribution occurs in the colon.

Gestational diabetes mellitus is a heterogeneous disorder characterised by impaired insulin secretion and action. Our aim was to study whether autoimmunity, variations in genes affecting insulin secretion and action, or both, contribute to the development of gestational diabetes and whether the pathogenesis of the disease differs between women with a Scandinavian or Arabian background.We studied a total of 500 unrelated women with gestational diabetes (400 Scandinavian and 100 Arabian) and 550 unrelated pregnant non-diabetic control women (428 Scandinavian and 122 Arabian) matched for ethnicity.Arabian women with gestational diabetes were 50% more insulin resistant for the same BMI compared with Scandinavian women with the disease (homeostasis model assessment [HOMA-IR]; 3.2+/-0.3 vs 2.2+/-0.2, p=0.02). Both Scandinavian (4.2% vs 0.9%, p=0.008) and Arabian (4.6% vs 0.0%, p=0.03) women with gestational diabetes had a higher frequency of GAD antibodies (GAD65Ab) than the matched controls. The frequency of HLA-DQB1 risk genotypes was slightly higher in Scandinavian women with gestational diabetes than in the Scandinavian controls (46.3% vs 38.8%, p=0.03) but no significant difference was found between the Arabian women with gestational diabetes and the Arabian controls (47% vs 51.6%, p=0.47). There were no significant differences in the frequency of the insulin gene variable number of tandem repeat ( INS VNTR) alleles and genotypes or the peroxisome proliferator-activated receptor-gamma 2 ( PPAR gamma 2-Pro12Ala) polymorphism between the women with gestational diabetes and the control women either in Arabian or in Scandinavian women.Gestational diabetes mellitus was associated with the presence of GAD65Ab in both study groups. Scandinavian women with gestational diabetes may share some genetic features with Type 1 diabetes. In addition, Arabian women with gestational diabetes are more insulin resistant than Scandinavian women with gestational diabetes and with the same BMI.

In Sweden, penetrating injuries to the lung and especially to the heart are fortunately rare. We hereby present a case-report on a young man who was stabbed in the right lung and heart. The paramedics arrived at the scene one minute after the alarm and instituted mechanical ventilation and fluid infusion. Ten minutes later the young man arrived at the emergency department. By then the patient was in deep shock without spontaneous breathing, was darkly cyanotic, showed indeterminately palpable pulses and non-reacting pupils. ECG-monitoring showed sinus-rhythm. Massive fluid infusion was initiated and the adolescent was immediately transported to the operating room. On the way to the operating room the patient's heart arrested. A lateral thoracotomy was performed to relieve the cardiac tamponade, and internal heart massage was initiated. Injuries to the lung and heart were reached through sternotomy. Thanks to prompt initial handling by the paramedics and emergency personnel, a trauma-trained senior surgeon and rather direct lines of communication at the small hospital, the young man could return to ordinary activities with neither physical nor neurological deficit.

The aim of the study was to evaluate both morphologically and functionally the distal large intestine from the aganglionic lethal spotted (ls/ls) mutant mouse and their healthy litter mates. Immunohistochemically, the aganglionic murine distal large intestine showed an absence of nerve cell bodies, and a reduction or absence of nerve fibers displaying immunoreactivity (IR) for protein gene product (PGP), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), substance P (SP), galanin and calcitonin gene-related peptide (CGRP), while in the ganglionic large intestine these neuronal populations were abundantly present throughout the gut wall. Pathological nerve trunks within the afflicted intestinal segment were found to harbour PGP- and neuropeptide Y (NPY)-IR nerve fibers. Smooth muscle specimens from the distal part of the murine distal large intestine were mounted as ring preparations in vitro and subjected to electrical field stimulation (EFS). EFS (4-20 Hz) caused a contraction in both ganglionic and aganglionic intestine. After pretreatment with atropine EFS (20 Hz) evoked a biphasic motor response, a relaxation followed by a contraction in control specimens, while no motor response was seen in aganglionic intestine. Addition of the NOS-inhibitor N-nitro-L-arginine methyl ester (L-NAME) caused per se a weak and transient contraction and reduced the amplitude of the EFS-induced relaxation in control intestine.

The occurrence of islet amyloid polypeptide (IAPP) in the gut and pancreas of several species and during ontogeny of the rat, was studied using immunocytochemistry. Effects of IAPP on rat ileal smooth muscle were assessed in vitro. Islets of most, but not all, species examined, displayed IAPP in insulin cells and, in some species, also in somatostatin- and peptide YY (PYY)-containing cells. In the gut, expression of IAPP varied among species; when present, IAPP was most abundant in the proximal part and co-localized with somatostatin, PYY, gastrin/cholecystokinin, enteroglucagon or serotonin. IAPP was first demonstrated at embryonic day 12 and 16 in islet and gastrointestinal endocrine cells, respectively. IAPP relaxed gut muscle and reduced electrical field stimulation-evoked contractions, presumably by inhibiting acetylcholine release. Thus, IAPP expression in islets is consistent with an important role for IAPP in fuel metabolism; the gastrointestinal expression and motor effects of IAPP suggest that IAPP may modulate gastrointestinal function.

Helospectins I and II are two non-amidated, vasoactive intestinal peptide (VIP)-like peptides, isolated from the salivary gland venom of the lizard Heloderma horridum . Helospectin I has 38 amino acid residues and differs from helospectin II in that it has an additional serine residue at the C-terminus. The study was based on an antiserum that recognizes both helospectins I and II (but recognizes VIP only poorly). Immunocytochemistry of the digestive tract revealed helospectin-immunoreactive nerve fibers in the muscle layers, submucosa and mucosa of mouse, rat, hamster, guinea-pig and man. Myenteric and submucous ganglia in all species contained helospectin-immunoreactive nerve fibers and cell bodies. The distribution of helospectin-like immunoreactivity in the gut resembled that of VIP. Double immunostaining for helospectin and VIP revealed their co-existence in the same population of nerve fibers and cell bodies throughout the gut of all species tested. In addition, helospectin (but not VIP) immunoreactivity was observed in a population of endocrine cells in the intestines. The existence of helospectin-like material in the gut was confirmed by immunochemistry. The helospectin-like immunoreactivity in the extracts diluted in parallel to the helospectin standard curve. Analysis by high performance liquid chromatography of extracts of rat intestine revealed one predominant helospectin-immunoreactive peak that eluted close to authentic helospectins I and II. The helospectin-immunoreactive material in the gut may constitute a novel neuropeptide that co-exists with VIP. The distribution of the VIP-helospectin-immunoreactive neurons and fibers indicates their possible involvement in the regulation of gut motor and secretory activities.

The lower esophagus of guinea-pig, cat, sheep and man was analyzed for pituitary adenylate cyclase activating peptide (PACAP), a novel vasoactive intestinal peptide (VIP)-like peptide, using immunocytochemistry and radioimmunoassay. PACAP-immunoreactive nerve fibers were numerous in the longitudinal and circular muscle layers of sheep and man, moderate in numbers in cat, while being few in the esophagus of guinea-pig. A few PACAP-immunoreactive nerve cell bodies and numerous nerve fibers were seen in the myenteric ganglia of the esophagus of cat, sheep and man. In the lower esophagus of cat, sheep and man all PACAP-containing nerve cell bodies and nerve fibers stored VIP. The results of radioimmunoassay of PACAP in extracts of speciments from man were in good agreement with the immunocytochemical findings. High performance liquid chromatography revealed one major peak of PACAP-like immunoreactivity in extracts of human esophagus. We suggest that neuronal PACAP may serve to modulate motor activity and secretion in the lower esophageal sphincter region.

Background Paraesophageal hernias are quite common and sometimes feared due to the risk of incarceration and strangulation of any herniated organ. The hereby reported combination of an incarcerated paraesophageal hernia containing a perforated peptic ulcer is extremely rare. Case presentation An elderly man with multiple medical conditions was admitted due to severe upper abdominal pain. The patient was found to have a paraesophageal hernia and underwent a laparotomy. In the hernia, a perforated benign peptic duodenal ulcer was found. The duodenal defect was over-sewn, the hernial defect was closed and the former hernial cavity was drained by a right-sided chest tube. The patient was discharged one month after surgery and was found to do well at follow-up one month after discharge. Conclusion This is the first report of a patient surviving the extremely rare and life-threatening combination of a perforated peptic duodenal ulcer in a paraesophageal hernia.

The use of sedation for upper gastrointestinal endoscopy varies greatly. It is uncommon in Scandinavia and Japan, whereas other European endoscopy units employ sedation as a routine. Much has been written about the danger of adverse cardiopulmonary events such as oxygen desaturation, induced by endoscope insertion and/or sedation 1 . Serious complications are, however, very rare and the need for monitoring has been refuted 2 . A much greater hazard is perforation, with reported mortality rates of up to 48 and 62 per cent 3 , and an incidence of at least 0.03 per cent 4 . A recent report by Quine et al. 5 gave a perforation rate of 0.05 per cent in a collected series of 14149 upper gastrointestinal endoscopies. The present study analysed the experience from one endoscopy unit which routinely uses unsedated endoscopy. Oxygen saturation monitoring is not employed and oxygen supplementation is given on clinical grounds only.

Bilateral subdiaphragmatic truncal vagotomy results in great functional changes in the stomach although the changes in the gastric mucosal architecture are small. A trophic effect of the vagus on the stomach is revealed after unilateral vagal sectioning, taking advantage of the fact that, in the rat, each vagal trunk innervates only one side of the stomach, and that denervation of one side does not impair the functional capacity of the other. The denervated side of the stomach displayed atrophy that was reflected in reduced weight and height of the oxyntic mucosa and a reduced density of argyrophil cells. The lack of atrophy after bilateral vagotomy can be explained by counteracting forces, in that the subsequent rise in gastrin secretion (due to lack of acid feedback inhibition of gastrin release) probably masks antitrophic effects of the vagotomy per se. Interestingly, the number of somatostatin cells in the oxyntic mucosa was not reduced after unilateral vagotomy, nor was the weight of the antral mucosa or the density of enterochromaffin and gastrin cells in the antrum on the denervated side.

The gastric anti-secretagogue effects of cimetidine (a histamine H2-receptor antagonist) and of atropine (a non-selective muscarinic receptor antagonist) and pirenzepine (a selective muscarinic M1-receptor antagonist) were examined in conscious gastric fistula rats both under basal conditions and after stimulation with maximal doses of pentagastrin and histamine. Cimetidine blocked basal as well as stimulated acid secretion. The cimetidine dose-response curves and the calculated ED50 values were similar in the different experimental situations. Atropine blocked equally effectively the basal and the stimulated acid secretion. The antisecretagogue and pupil dilating effects were compared. The ED50 values for the anti-secretagogue effect and for the pupil dilating effect were in the same range though not identical. Pirenzepine blocked acid secretion, whether basal or stimulated, with similar potency. It was much more potent to block acid secretion than to cause pupil dilatation. The greater potency of pirenzepine to block acid secretion than to cause pupil dilatation suggests that the cholinergic pathway of acid secretion involves neuronal muscarinic M1-receptors within the intramural ganglia of the stomach wall. In conclusion, cimetidine, atropine and pirenzepine effectively blocked basal as well as pentagastrin- and histamine-stimulated acid secretion, indicating that both histamine and acetylcholine are important in the control of the parietal cell. Histamine has been claimed to be the final common chemical mediator of acid secretion. This view is at odds with the fact that muscarinic blocking agents also inhibit basal and stimulated acid secretion.

Sympathectomy has been used to study the role of the sympathetic nervous system in the control of gastric acid secretion. Conflicting results may reflect differences in the sympathectomy procedures used. In a previous study we showed a reduction of catecholamines by more than 90% in the gut wall of the rat after surgical upper abdominal sympathectomy. The aim of the present investigation was to ascertain whether chemical sympathectomy was equally effective and whether total denervation, including combined chemical and surgical sympathectomy together with bilateral truncal vagotomy, would lower the catecholamine levels further. The results showed that chemical sympathectomy reduced noradrenaline levels in fundus (oxyntic) and antrum mucosa to levels similar to those after surgical sympathectomy (less than 5%), but the reduction was less pronounced in the muscle layer of the fundus and antrum and in the pancreas and spleen. Combined surgical and chemical sympathectomy did not reduce noradrenaline more effectively than surgical sympathectomy alone. Vagotomy reduced catecholamines in the stomach by about 50%; in extragastric tissues vagotomy was without effect. Total denervation, including combined surgical and chemical sympathectomy plus vagotomy, did not reduce noradrenaline levels more than surgical sympathectomy alone, suggesting that the proportion of adrenergic fibers that derive from the vagus is quantitatively insignificant but that the vagus exerts a local control of the sympathetic stores of gastric catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

In portacaval-shunted rats, basal but not pentagastrin-stimulated acid secretion was higher than in sham-operated controls. The basal serum gastrin concentration was unchanged and the postprandial serum gastrin concentration lowered following portacaval shunt. Thus, gastrin is not responsible for the elevated basal acid secretion. The present study provides evidence that there is no trophic effect on the oxyntic mucosa as a whole and that there is no change in parietal cell-associated gastrin receptors after portacaval shunting. Interestingly, however, endocrine cells in the oxyntic mucosa (the histamine-containing ECL cells) proliferated greatly and the pentagastrin- and cholecystokinin octapeptide-induced activation of the histamine-forming enzyme, histidine decarboxylase, in these cells was much greater than in control rats. Analysis of the dose-response curves for the enzyme-activating effect of pentagastrin and cholecystokinin-octapeptide indicated that the D50 values for these two stimulants were not altered by shunting but that the maximal enzyme activation was greatly elevated. The enhanced enzyme activation can be partly, but not fully, explained by the fact that the ECL cells were increased in number. The enhanced response following portacaval shunt probably reflects also an increased number of gastrin receptors per ECL cell. The effect of portacaval shunting on gastric ECL cells can perhaps be explained by impaired degradation in the liver of intestinal substance(s) exerting a highly specific trophic effect on the ECL cells or, alternatively, causing an enrichment of gastrin receptors on these cells, thereby making them more sensitive to the trophic effect of gastrin. The ECL cell hyperplasia is manifest about 4 weeks after the shunting. A modified procedure for portacaval shunting which left the gastroduodenal vein (otherwise ligated) drained to the liver produced the same trophic effect as conventional portacaval shunt, suggesting an intestinal rather than gastroduodenal origin of the agent(s) responsible for the trophic action.

Immunoreactive neuropeptide Y (NPY) was demonstrated in neuronal elements in the gut and pancreas of the rat. Immunoreactive endocrine cells could not be detected. The occurrence of NPY-containing nerve-cell bodies in the submucosal and myenteric ganglia indicates an intrinsic origin of the NPY fibers. However, an additional extrinsic supply of NPY fibers is suggested by the finding that abdominal sympathectomy caused the disappearance of some NPY fibers, notably those around blood vessels. The distribution of NPY fibers in all layers of the gut wall suggests multiple functions of NPY, including a role in the regulation of intramural neuronal activities, smooth muscle tone, and local blood flow.

EKELUND, M., EL MUNSHID, H.A., HAKANSON, R. & REHFELD, J.F. 1985. Mechanism of hypergastrinaemia after nephrectomy in the rat. Acta Physiol Scand 125, 383–388. Received 17 September 1984, accepted 1 May 1985. ISSN 0001–6772. Departments of Pharmacology and Surgery, University of Lund, Lund, Sweden, and Department of Clinical Chemistry, Rigshospitalet, Copenhagen, Denmark. Bilateral nephrectomy in the rat is followed by hypergastrinaemia and by activation of gastric histidine decarboxylase. The enzyme activity is thought to reflect the concentration of circulating gastrin. While there is general agreement that post-nephrectomy hypergastrinaemia is primarily the result of loss of renal elimination of gastrin, it remained to be determined whether gastrin secretion could be stimulated in the hypergastrinaemic state and whether it contributed to the hypergastrinaemia. Histamine, but not pentagastrin, is known to evoke gastric acid secretion in the nephrectomized rat, and histamine, but not pentagastrin, was found to lower the serum gastrin level and the gastric histidine decarboxylase activity, indicating that after nephrectomy gastrin was still secreted and that the secretion could be suppressed by increased acid output. The importance of gastrin secretion for post-nephrectomy hypergastrinaemia was assessed further by investigating the effect of nephrectomy on the serum gastrin concentration in rats previously subjected to operations that had either reduced (e.g. antrectomy) or raised (e.g. antrum exclusion) the serum gastrin concentration. Post-nephrectomy serum gastrin levels co-varied with the levels before nephrectomy. Thus, the capacity to secrete gastrin was not abolished by nephrectomy. Finally, nephrectomy greatly affected the linear correlation between the serum gastrin concentration and the gastric histidine decarboxylase activity in a manner suggesting the operation of a gastrin-independent factor capable of activating the enzyme.