Proximal Gut Research Articles

Stage-Specific Control of Neural Crest Stem Cell Proliferation by the Small Rho GTPases Cdc42 and Rac1

The neural crest (NC) generates a variety of neural and non-neural tissues during vertebrate development. Both migratory NC cells and their target structures contain cells with stem cell features. Here we show that these populations of neural crest-derived stem cells (NCSCs) are differentially regulated by small Rho GTPases. Deletion of either Cdc42 or Rac1 in the NC results in size reduction of multiple NC target structures because of increased cell-cycle exit, while NC cells emigrating from the neural tube are not affected. Consistently, Cdc42 or Rac1 inactivation reduces self-renewal and proliferation of later stage, but not early migratory NCSCs. This stage-specific requirement for small Rho GTPases is due to changes in NCSCs that, during development, acquire responsiveness to mitogenic EGF acting upstream of both Cdc42 and Rac1. Thus, our data reveal distinct mechanisms for growth control of NCSCs from different developmental stages.

Risks of proton‐pump inhibitors: what every doctor should know

Medical Journal of AustraliaVolume 190, Issue 3 p. 109-110 Editorial Risks of proton-pump inhibitors: what every doctor should know Nicholas J Talley MD, PhD, FRACP, Corresponding Author Nicholas J Talley MD, PhD, FRACP Professor of Medicine and Epidemiology, and Chair of Department of Medicine talley.nicholas@mayo.edu Mayo Clinic, Jacksonville, Fla, USA.Correspondence: talley.nicholas@mayo.eduSearch for more papers by this author Nicholas J Talley MD, PhD, FRACP, Corresponding Author Nicholas J Talley MD, PhD, FRACP Professor of Medicine and Epidemiology, and Chair of Department of Medicine talley.nicholas@mayo.edu Mayo Clinic, Jacksonville, Fla, USA.Correspondence: talley.nicholas@mayo.eduSearch for more papers by this author First published: 02 February 2009 https://doi.org/10.5694/j.1326-5377.2009.tb02305.xCitations: 10Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume190, Issue3February 2009Pages 109-110 RelatedInformation

Starvation‐Induced Proximal Gut Mucosal Atrophy Diminished With Aging

Starvation induces small bowel atrophy with increased intestinal epithelial apoptosis and decreased proliferation. The authors examined these parameters after starvation in aged animals. Sixty-four 6-week-old and 26-month-old C57BL/6 mice were randomly assigned to either an ad libitum fed or fasted group. The small bowel was harvested at 12, 48, and 72 hours following starvation. Proximal gut mucosal height was measured and epithelial cells counted. Apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Proliferation was determined by immunohistochemical staining for proliferating cell nuclear antigen. Comparison of fed vs fasted and adult vs old groups was done by one-way ANOVA with Tukey's test and unpaired Student's t test. Significance was accepted at P < .05. Aged mice had higher proximal gut weights, mucosal heights, and cell numbers at baseline compared with the adult group (P < .05). The rate of apoptosis was lower in the aged (P < .05), but proliferation was not different between groups before starvation. After starvation, proximal gut wet weight decreased only in adult mice (P < .05). Gut mucosal height and mucosal cell number decreased more in adult than in aged mice (P < .05). This was related to decreased proliferation only in the adult group (P < .05). The fold of epithelial apoptosis that increased was higher in the aged group than in the adult group after starvation (P < .05). Gut mucosal kinetics change with age and have lower rates of apoptosis and greater mucosal mass; the character of starvation-induced atrophy is diminished with aging.

Biopharmaceutical aspects of gastro-retentive dosage forms: the gabapentin paradigm

Gastro-retentive dosage form (GRDF) is a controlled-release modality of drug delivery technology that allows continuous administration to the upper part of the gastrointestinal tract. The manuscript summarizes various aspects that should be considered for the successful implementation of these region-specific delivery systems, including underlying physiological principles, technologies, and performance assessment approaches. In particular it focuses on characterization of potential drug candidates for GRDF and the anticipated pharmacokinetic and pharmacodynamic advantages associated with GRDF administration. These considerations are demonstrated using gabapentin as a representative narrow absorption window drug. The pharmacokinetic model that was developed for description of oral absorption of gabapentin in humans included variable intragastric input functions, saturable absorption kinetics and limited absorption window in the proximal gut. The pharmacokinetic profiles obtained via simulation demonstrated the potential benefits that can be accomplished by GRDF for gabapentin, including dose-proportional absorption, extended duration of absorption and thereby reduced dosing frequency and lowered total daily dose. Such pharmacokinetic modeling and simulation are shown to be an important and useful tool that can be used to optimize the selection of the mode of oral drug administration, including GRDF approach.

Short-Term Adaptation of Rat Intestine to Ileostomy: Implication for Pediatric Practice

Background: Surgical neonates with complex intestinal conditions, such as enterocolitis, midgut volvulus with bowel loss and multiple atresias, often require temporary stomas. Little is known on the postsurgical response of the altered gut segments, although adaptation is an important consideration in neonatal postoperative care, particularly after stoma closure. Materials and Methods: Rats underwent bowel resection at a point 15 cm proximal to the ileocecal valve, and a split ileostomy was performed. On the 6th postoperative day the mucosal thickness was calculated with Soft Imaging System Analysis Pro, the rate of proliferation was measured following Ki67 immunohistochemistry and the apoptotic index was determined on sections stained with ApopTag Plus. The intestinal motor activity was recorded on isolated gut segments. Neuronal nitric oxide synthase (nNOS) expression and distribution was examined with NADPH-diaphorase histochemistry and Western blot analysis. Results: An increased wet weight of the mucosa and a pronounced mucosal thickening were observed in the proximal functional bowel segment. Enterocyte proliferation rate was increased significantly, while the apoptotic index remained unchanged in the epithelial layer. The dilation of the gut lumen resulted in a morphological change in the nitrergic myenteric network with an overexpression of nNOS. As a consequence of the surgical procedure, the functional proximal gut segment showed strong and frequent contraction waves, with an enhanced responsiveness to cholinergic stimuli. Conclusions: The dilated functional bowel segment was characterized by hyperplasic changes in the mucosa and stronger mechanical activity with overproduction of nNOS. Although early restoration of intestinal continuity is recommended, our observations on adaptive changes may partly explain intestinal motility disorders after early stoma closure, suggesting the need for a careful approach to a redo-laparotomy.

Small bowel enterocutaneous fistulae: the merits of early surgery

The treatment of patients with small bowel enterocutaneous fistulas is complex and a challenge for every surgeon. The mortality and morbidity associated with only conservative management is often high and expensive because most patients cannot afford prolonged parenteral nutrition which itself carries a high incidence of complications. Although operations are difficult if performed early they may be lifesaving in our situation. The focus of our study was to determine whether, in patients with fistulae, early intervention resulted in low mortality and morbidity rates and to identify prognostic factors for fistula closure and mortality. Between August 1996 and July 2008 we treated 64 consecutive patients with small bowel enterocutaneous fistulae. There were 28 females and 36 males patients who had a mean age of 42.4 years. 49 (77%) of the fistulae resulted from surgical complications. Our policy was to intervene early once the patient was fit for a procedure. In 4 patients (6.2%) the fistulae arose from the jejunum and in the remaining 94% from the ileum. Octreotide was administered in 49 (77%) patients. To maintain the nutrition of the patients enteral feeding was used in 47 (73%) while re-feeding of the proximal gut fistula output into the distal stoma was used in 7 patients. Spontaneous closure occurred in 10 patients (16%). There were 9 deaths (14%). Fifty-two patients (81%) required surgical intervention at some stage. A strong relationship was found between their preoperative albumin levels and and mortality. Aggressive early surgical treatment with the judicious use of nutritional support, stoma care, octreotide, and control of sepsis results in a low mortality in patients with small intestinal fistulae. Preoperative hypoalbuminaemia is an important prognostic variable.

Paying the Price for Eating Ice Cream: Is Excessive GLP-1 Signaling in the Brain the Culprit?

Paying the Price for Eating Ice Cream: Is Excessive GLP-1 Signaling in the Brain the Culprit?

SECOND HIT POST BURN INCREASED PROXIMAL GUT MUCOSA EPITHELIAL CELLS DAMAGE

Secondary infections after burn are common and are a major contributor to morbidity and mortality. We previously showed that burn disrupted proximal gut mucosal homeostasis through increased epithelial cell apoptosis. In the present study, we sought to determine whether proximal gut mucosal disruption is additively affected by secondary endotoxemia after a severe burn. C57BL/6 mice received 30% total body surface area full-thickness scald burns and were randomized to receive saline or LPS 1 mg/kg body weight given intraperitoneally 72 h after burn. Proximal small bowel was harvested 12 h after LPS injection. Mucosal height and epithelial cell number were assessed on hematoxylin-eosin sections, intestinal epithelial cell apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and cell proliferation by immunohistochemical staining for proliferating cell nuclear antigen. Results showed that proximal gut mucosa impairment occurred 12 h after injury, including significantly decreased proximal gut wet weight, gut mucosal height, and epithelial cell number associated with increased proximal gut epithelial apoptosis (P < 0.05). This impairment diminished 72 h after burn. Second-hit endotoxemia caused additional proximal gut mucosa damage with decreased proximal gut weight, cell number, and mucosal height (P < 0.05) and significantly increased small intestinal epithelial apoptosis and mucosal atrophy, even after the first event, indicating a second detrimental effect of endotoxemia after the initial injury.

Mechanisms of action of CCK to activate central vagal afferent terminals

Cholecystokinin [CCK] is a peptide released as a hormone by the proximal gut in response to the presence of peptones and fatty acid in the gut. Considerable evidence suggests that CCK inhibits feeding behavior and gastric function by acting as a paracrine modulator of vagal afferents in the periphery, especially in the duodenum. CCK is also widely distributed throughout the mammalian brain and appears to function as a neurotransmitter and neuromodulator. More recent studies have suggested that CCK may act directly within the CNS to activate central vagal afferent terminal inputs to the solitary nucleus. We have developed an in vitro calcium imaging method that reveals, for the first time, the direct effects of this peptide on vagal terminals in the solitary nucleus. In vitro imaging reveals that CCK provokes increases in intracellular calcium in vagal afferent terminals as a consequence of a complex interaction between protein kinase A [PKA] and phospholipase C [PLC] transduction mechanisms that open L-type calcium channels and causes endoplasmic reticular [ER] calcium release. The subsequent activation of PKC may be responsible for initiating calcium spiking which is dependent on a TTX-sensitive mechanism. Thus, imaging of the isolated but spatially intact hindbrain slice has allowed a more complete appreciation of the interdependent transduction mechanisms used by CCK to excite identified central vagal afferent fibers and varicosities.

Clinical Presentation and Patterns of Slow Transit Constipation Do Not Predict Coexistent Upper Gut Dysmotility

Slow transit constipation (STC) is associated with upper gastrointestinal tract motor abnormalities in a subset of patients. This could influence the clinical approach, particularly in those rare cases where surgical management is considered. To identify factors that predict proximal gut dysmotility in patients with STC. Esophageal and small bowel motor function were evaluated in 77 patients with STC. Severity and pattern of colonic transit delay, prevalence of a co-existent rectal evacuatory disorder, and type (if present), and duration, and onset of constipation symptoms were compared. Of the 77 patients studied, 43% exhibited altered motor function in the esophagus and/or small bowel. Frequency of defecation was lower in these patients than in those without upper gastrointestinal dysmotility (0.5 +/- 0.1 vs. 1.3 +/- 0.3 bowel movements/per week, respectively; P = 0.04). Severity and patterns of colonic transit delay and the mechanism associated with the onset of constipation symptoms or with their duration were similar in subjects with or without upper gastrointestinal tract dysmotility. Small bowel but not esophageal motor dysfunction was more frequently associated with a co-existent rectal evacuatory disorder (P = 0.01). Upper gastrointestinal tract dysmotility in patients with STC is frequent, but prediction on the basis of clinical history and characteristics of colonic transit is problematic.

Subclass composition and J-chain expression of the‘compensatory’ gastrointestinal IgG cell population in selective IgA deficiency

The subclass distribution of IgG-producing immunocytes was examined by two-colour immunohistochemistry in gastrointestinal mucosa of 14 patients with selective serum IgA deficiency providing the following biopsy material: gastric (n = 1); jejunal (n = 12); colonic (n = 1); and rectal (n = 2). All except two patients suffered from various infections, and coeliac disease was observed in six of them. Control reference data were based on biopsies from immunologically intact subjects, including histologically normal jejunal (n = 10) and large bowel (n = 10) mucosa and stomach mucosa with slight chronic gastritis (n = 8). The total mucosal population of immunoglobulin-producing cells per 500 microns gut length unit was only slightly decreased in IgA deficiency because of an increased number of IgG (30%) and especially IgM (71%) immunocytes. The IgG1 immunocyte proportion in the proximal gut (median 87%) was higher than that in the comparable controls (gastric 69%, jejunal 66%). A similar trend was seen in the distal gut (69%) compared with controls from the large bowel mucosa (55%). Conversely, IgG2 and IgG3 cell proportions were significantly decreased compared with the respective controls from the proximal gut. The same was true for IgG4, which also was significantly reduced in jejunal mucosa. Paired staining for cytoplasmic J chain and immunoglobulin isotype showed 71% positivity for jejunal IgG-producing cells in IgA deficiency, which was somewhat reduced compared with comparable controls (89%). J chain appeared to be preferentially expressed by IgG1 cells (75%), but was also found in IgG2 (70%), IgG3 (32%) and IgG4 cells (33%). IgM-producing cells showed a J-chain positivity (99%) in IgA deficiency similar to normal (100%). Our results suggested that the block in mucosal B cell differentiation to IgA expression in the proximal gut is mainly located immediately upstream to the CH alpha 1 gene, giving excessive terminal maturation of J-chain-positive IgG1 immunocytes.

Gut Microbiota and Its Possible Relationship With Obesity

Obesity results from alterations in the body's regulation of energy intake, expenditure, and storage. Recent evidence, primarily from investigations in animal models, suggests that the gut microbiota affects nutrient acquisition and energy regulation. Its composition has also been shown to differ in lean vs obese animals and humans. In this article, we review the published evidence supporting the potential role of the gut microbiota in the development of obesity and explore the role that modifying the gut microbiota may play in its future treatment. Evidence suggests that the metabolic activities of the gut microbiota facilitate the extraction of calories from ingested dietary substances and help to store these calories in host adipose tissue for later use. Furthermore, the gut bacterial flora of obese mice and humans include fewer Bacteroidetes and correspondingly more Firmicutes than that of their lean counterparts, suggesting that differences in caloric extraction of ingested food substances may be due to the composition of the gut microbiota. Bacterial lipopolysaccharide derived from the intestinal microbiota may act as a triggering factor linking inflammation to high-fat diet-induced metabolic syndrome. Interactions among microorganisms in the gut appear to have an important role in host energy homeostasis, with hydrogen-oxidizing methanogens enhancing the metabolism of fermentative bacteria. Existing evidence warrants further investigation of the microbial ecology of the human gut and points to modification of the gut microbiota as one means to treat people who are over-weight or obese.

Laparoscopic sleeve gastrectomy with ileal transposition (SGIT): A new surgical procedure as effective as gastric bypass for weight control in a porcine model

Bariatric surgery has evolved into multiple forms in the last decades, combining food restriction and malabsorption. The aim of this study was to develop a new technique based on food restriction and early stimulation of the distal gut, thus maintaining the alimentary tract continuity. Thirty-two Yorkshire pigs, weight 22.2 +/- 5.4 kg (mean +/- SD) were randomly assigned to four laparoscopic procedures: ileal transposition (IT, n = 8); sleeve gastrectomy with ileal transposition (SGIT, n = 8); Roux-en-Y gastric bypass (GBP, n = 8); sham operation (SHAM, n = 8). Firing 45-mm linear staplers over a 60-F bougie, resecting the greater curvature and fundus, constituted a sleeve gastrectomy. Ileal transposition was performed by isolating a 100-cm ileal segment proximal to the ileocecal valve and by dividing the proximal jejunum 15 cm distal to the ligament of Treitz and performing re-anastomosis. Gastric bypass consisted of creating a proximal gastric pouch and a 300 cm alimentary limb. Sham operation was performed by bowel transections and re-anastomosis in the ileum and proximal jejunum together with gastrotomy and closure. Animals were evaluated weekly for weight increase and food intake. We performed a logistic regression analysis to compare weight progression curves, and analysis of variance (ANOVA) and Bonferroni (Dunn) tests to detect differences in weight and food intake. We observed significant differences in mean weight after 18 weeks between SGIT (30.9 +/- 13.4 kg) and SHAM (72.5 +/- 10.7 kg) (p = 0.0002), and GBP (28.6 +/- 2.5 kg) and SHAM (p = 0.0001), and IT (56.1 +/- 13.4 kg) and SHAM (p = 0.0081). No differences were observed between RYGB and SGIT. We also observed significant differences in food intake (grams per day) in the third month between SGIT (1668 +/- 677 g) versus SHAM (3252 +/- 476 g) (p = 0.0006), and GBP (2011 +/- 565 g) versus SHAM (p = 0.039). No differences were observed in food intake between SGIT and GBP. SGIT proved to be as effective in the short term as GBP on weight progression with no bypass of the proximal gut.

Severe Copper Deficiency in a Patient with History of Gastric Bypass Leading to CNS Demyelinaton, Severe Ataxia and Peripheral Neuropathy

Copper is an essential micronutrient necessary for the hematologic and neurologic systems. Acquired copper deficiency in humans has been described, causing a syndrome similar to the subacute combined degeneration of vitamin B12 deficiency. Copper deficiency is being increasingly recognized in adult populations due to various causes including high zinc levels, copper chelating agents and after gastric bypass surgery. We present a case patient with sever hypocupremia leading to profound neurological symptoms to stress the importance of this clinical entity and its early diagnosis and treatment. We present a 52 year-old white male who had Roux-en-Y gastric bypass surgery. He was maintained on multivitamin supplements including Vitamin B12, iron and zinc. Fifteen years after his gastric bypass he started having worsening sensory ataxia and worsening paresthesias of the lower extremities, and was hospitalized for severe weakness in his lower extremities. On admission his nutritional evaluation revealed normal serum levels for Vitamin B12, zinc and iron. However he was found to have an extremely low serum copper level. MRI of the spine showed T-2 hyperintensity within the dorsal spinal cord from C2 through C5 which has been described in patients with copper deficiency. The patient was started on copper supplements, showed significant clinical improvement, and was maintained on copper supplements after his discharge. Copper deficiency is a rare complication following gastric bypass surgery. Copper is primarily absorbed from stomach and proximal small bowel. It is not clear why copper deficiency occurs in some but not all patients after gastric surgery. Iron and zinc have been described to inhibit copper uptake in the proximal bowel. Zinc and copper compete for absorption in the digestive tract so that a diet that is excessive in one of these minerals may result in a deficiency in the other. Bariatric procedures such as gastric bypass surgery result in a similar functional anatomy of the proximal gut and may place more patients at increased risk of copper deficiency. Early recognition and therapy with copper supplements may lead to a decrease in both neurologic and other known hematologic consequences of hypocupremia. Oral copper should to be taken in a different time preferably earlier to the oral multivitamins or oral zinc to prevent the chelating effect of zinc on copper.

The Efficacy of the GLP-1 Agonist Exenatide in the Treatment of Short Bowel Syndrome

Purpose: Short bowel syndrome (SBS) is a serious medical problem resulting in severe diarrhea and nutritional deprivation. The symptoms result from lack of absorptive surface and loss of the braking mechanisms controlling the proximal gut. One of the missing, distally produced, peptides that control the proximal gut is glucagon-like peptide-1 (GLP-1). In this study we test the effect of the GLP-1 receptor agonist, exenatide, on short bowel syndrome. Methods: SBS subjects were selected based on clinical symptoms and greater than 50% distal small bowel resection. Before beginning exenatide treatment, each patient completed a questionnaire documenting stool frequency and consistency. In addition, SBS symptoms, CBC, chemistries and BMI were also obtained. An antroduodenal manometry study was performed during fasting, after exenatide, and after a subsequent test meal. Each patient was then started on exenatide 5 to 10 mcg subcutaneously twice a day. Over the following month the baseline parameters measured were repeated. Results: The subjects consisted of 4 males and 1 female, ages 46 to 69 (mean: 57.2). At baseline, all patients had severe diarrhea that ranged from 7 to 15 bowel movements per day, often occurring within 15 minutes of eating. After exenatide, all 5 patients had an immediate improvement in bowel frequency and form. In the most severely affected patient, the bowel movements reduced from 15 watery bowel movements per day to 2–3 formed stool. In all subjects, bowel movements were no longer meal related and often occurred hours after any meal. At baseline nutritional parameters were stable due to total parenteral nutrition (TPN) in most cases (N = 3). However, after exenatide, all 3 patients no longer needed TPN. Despite the lack of TPN, no weight loss or biochemical nutritional deterioration was observed in any case. Previous attempts at ceasing TPN had resulted in immediate and life-threatening dehydraton and malnutrition. Using normal bowel function as a goal, subjects described their improvement with exenatide as 65–100% improved. Antroduodenal manometry in 2 out of 5 subjects demonstrated continuous low amplitude gastric contractions during fasting which completely normalized after exenatide. Conclusion: Exenatide is a novel and safe treatment option for SBS. It normalizes bowel function and maintains nutritional status. Successful treatment with exenatide may significantly reduce the need for parenteral nutrition.

Profound Copper Deficiency in a Patient with History of Gastric Bypass

Copper deficiency (hypocupremia) is a rare entity that can lead to serious morbidity. With advent of gastric bypass surgery, hypocupremia is being increasingly recognized in adult populations. We present a case patient with hypocupremia and profound neurological symptoms to stress the importance of this entity and its early diagnosis and treatment. We present a case of a 62 year-old white female who had Roux-en-Y gastric bypass surgery. Due to multiple nutritional deficiencies following surgery, she was receiving multivitamin supplements including iron and zinc supplementation as well as vitamin B12 injections. Ten years after her gastric bypass, she began having progressively worsening ataxia, paresthesias of lower extremities and hands, and generalized weakness. Her weakness continued to progress resulting in significant proximal muscle weakness as demonstrated by her difficulty in rising from seated position. Patient eventually became hospitalized for severe weakness requiring mechanical ventilation. On admission, an extensive nutritional evaluation was significant for undetectable copper level and elevated zinc level. MRI of spine showed abnormal T2 hyperintensity within the posterior columns of the spinal cord from the C7-T1 level to the skull base which has been previously described in patients with hypocupremia. Intravenous copper infusions were given to the patient during her hospitalization. She had dramatic clinical improvement which correlated with the normalization of serum copper level. The patient was eventually weaned from the ventilator and began demonstrating further improvement in her muscle weakness. Direct percutaneous endoscopic jejunostomy tube was placed and patient fed enterally. The patient was ambulatory prior to her discharge from the hospital. Hypocupremia is a rare complication following gastric bypass operation. Copper is primarlily absorbed in the stomach and proximal small bowel, however, it is uncertain why hypocupremia occurs only in certain patients following gastric bypass. Previous literature has established an association with zinc overload state and hypocupremia. Zinc and iron supplementation have already been demonstrated in animal models to inhibit copper uptake in the proximal gut. The combination of gastric bypass and zinc overload likely caused our patient's hypocupremia. Her dramatic improvement after aggressive copper replacement stresses the importance of the timely diagnosis and treatment of hypocupremia.

Severe Ataxia, Myelopathy, and Peripheral Neuropathy Due to Acquired Copper Deficiency in a Patient With History of Gastrectomy

In animal studies, copper absorption has been demonstrated to occur in the proximal gut via duodenal enterocytes. Acquired copper deficiency is known as "swayback" in ruminant animals and Menkes' disease in humans. Copper is an essential micronutrient necessary for the hematologic and neurologic systems. Acquired copper deficiency in humans has been described, causing a syndrome similar to the subacute combined degeneration of vitamin B(12) deficiency. This is a single case report. Our patient developed a neurologic constellation of ataxia, myelopathy, and peripheral neuropathy similar to vitamin B(12) deficiency many years after gastrectomy for severe peptic ulcer disease. The patient was maintained for decades with enteral feedings via jejunostomy that provided the recommended dietary allowance (RDA) for copper. Copper deficiency was suspected, identified, and treated. Over 3 months of follow-up, serum copper levels increased from 4 microg/dL to 20 microg/dL (70-150 microg/dL), and ceruloplasmin increased from 6 mg/dL to 8 mg/dL (14-58 mg/dL). During this short time of follow-up, the patient has had no further progression of his neurologic symptoms. Ataxia and myelopathy secondary to acquired copper deficiency are rare complications of major gastric resection. This is quite similar to the syndrome of vitamin B(12) deficiency. Vitamin B(12) repletion does not improve symptoms. Bariatric procedures such as gastric bypass surgery result in a similar functional anatomy of the proximal gut and may place more patients at increased risk. Early recognition and therapy with oral or parenteral copper may lead to a decrease in both neurologic and hematologic consequences.

Dietary Synergies in Appetite Control: Distal Gastrointestinal Tract

AbstractWOODS, STEPHEN C. Dietary synergies in appetite control: distal gastrointestinal tract.

Oxytocin is expressed throughout the human gastrointestinal tract

Background/Aim Several studies have described that oxytocin exerts stimulatory or inhibitory effects on gut functions. Recently, mRNA for oxytocin and its receptor was found throughout the entire human gastrointestinal (GI) tract. The aim of this study was to examine the cellular localization and distribution of the corresponding proteins. Material and methods Full-thickness biopsies from 24 patients, covering the entire GI tract, were collected during operations at the Department of Surgery in Malmö and Lund. The biopsies were taken from non_affected margins. The biopsies were fixed by immersion, rinsed in buffered sucrose, and kept frozen at 70 °C. Indirect immunofluorescence with primary antibodies to oxytocin and its receptor was used. Results Oxytocin was expressed in nerve cell bodies and nerve fibres in the myenteric and submucous ganglia all along the GI tract. Immunoreactive nerve cell bodies in myenteric ganglia predominated in the proximal (antrum and duodenum) and distal gut, while those in the submucous ganglia were more numerous in the ileum and colon. The oxytocin receptor was not detectable by two different antibodies in any tissue in the GI tract. Conclusion Oxytocin is expressed in the myenteric and submucous ganglia and nerve fibres along the entire human GI tract. The role for oxytocin in the physiology and pathophysiology of the bowel remains to be settled.

Review article: a critical view on impaired accommodation as therapeutic target for functional dyspepsia

Several important pathophysiological mechanisms have been identified in functional dyspepsia, however a complete understanding of these mechanisms and beneficial therapeutic strategies are still lacking. Based on the currently available literature we aimed at providing a critical view on one of these pathophysiological mechanisms, impaired accommodation. Although impaired gastric accommodation is identified as a major pathophysiological mechanism, the clinical evidence supporting its role as an important therapeutic target is currently still lacking. Treatment with fundic relaxant drugs has shown conflicting results and has been rather disappointing in general. These negative findings could be explained by the fact that impaired fundic accommodation is part of a more complex disorder involving other regions of the proximal gut or by the increasing insight that central mechanisms may play an important role. Future studies of impaired accommodation should take these considerations into account.