Influence Of Gastric Emptying On The Control Of Postprandial Glycemia: Physiology And Therapeutic Implications.

The maintenance of glucose homeostasis is complex and involves, besides the secretion and action of insulin and glucagon, a hormonal and neural mechanism, regulating the rate of gastric emptying. This mechanism depends on extrinsic and intrinsic factors. Glucagon-like peptide-1 secretion regulates the speed of gastric emptying, contributing to the control of postprandial glycemia. The pharmacodynamic characteristics of various agents of this class can explain the effects more relevant in fasting or postprandial glucose, and can thus guide the individualized treatment, according to the clinical and pathophysiological features of each patient.

Effect Of Roux-en-y Gastric Bypass On Nonalcoholic Fatty Liver Disease Evaluated Through Nafld Fibrosis Score: A Prospective Study.

Nonalcoholic fatty liver disease (NAFLD) is common among subjects who undergo bariatric surgery and its postsurgical improvement has been reported. This study aimed to determine the evolution of liver disease evaluated through NAFLD fibrosis score 12 months after surgery. It is a prospective cohort study which evaluated patients immediately before and 12 months following Roux-en-Y gastric bypass (RYGB). Mean score decreased from 1.142 to 0.066; surgery led to a resolution rate of advanced fibrosis of 55 %. Resolution was statistically associated with female gender, percentage of excess weight loss, postsurgical body mass index, postsurgical platelet count, and diabetes resolution. As previously reported by studies in which postsurgical biopsies were performed, RYGB leads to a great resolution rate of liver fibrosis. Since postsurgical biopsy is not widely available and has a significant risk, calculation of NAFLD fibrosis score is a simple tool to evaluate this evolution through a noninvasive approach.

Myelodysplastic Syndrome With Synchronous Gastric Cancer: When The Symptoms Suggest Something Else.

Although myelodysplastic syndromes have a clear definition in theory, the morphologic dysplasia associated with ineffective hematopoiesis may be subtle and difficult to recognize and can commonly be mimicked by systemic conditions, such as infections, autoimmune disorders, nutritional deficiencies, toxic factors and non-hematological malignancies. However, myelodysplastic syndromes may truly coexist with other systemic diseases, which can be masked when the patient's symptoms are attributed exclusively to myelodysplastic syndromes without further investigation. To better illustrate this, we herein describe two cases associated with synchronous gastric cancers.

Neural Mechanisms And Delayed Gastric Emptying Of Liquid Induced Through Acute Myocardial Infarction In Rats.

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.Fundamento: Distúrbios da motilidade do intestino proximal no infarto agudo do miocárdio podem desencadear sintomas digestivos como náuseas e vômitos. O infarto do miocárdio ocasiona retardo do esvaziamento gástrico (EG) de líquido em ratos. Objetivo: Investigar se existe a influência do nervo vago (VGX), adrenoreceptores α-1, receptores GABAB do sistema nervoso central e participação do núcleo paraventricular (NPV) do hipotálamo no esvaziamento gástrico (EG) e complacência gástrica (CG) em ratos infartados. Métodos: Ratos Wistar (n = 8-15) foram divididos em: grupo infarto (INF), sham (SH) e subdivididos. O infarto foi realizado por ligadura da artéria coronária descendente anterior. A complacência gástrica foi estimada com curvas pressão-volume. Realizada vagotomia por secção dos ramos dorsal e ventral. Para verificar a ação dos receptores GABAB foi injetado baclofeno por via intra ventrículo-cerebral. Simpatectomia química foi realizada com prazosina intravenosa (iv), e na lesão do núcleo paraventricular do hipotálamo foi utilizada corrente elétrica de 1mA/10s, com esvaziamento gástrico determinado por medição da retenção gástrica (% RG) de uma refeição salina. Resultados: Não houve diferença significativa na CG. A vagotomia (VGX) reduziu significativamente a %RG; no grupo INF, o tratamento intra ventrículo-cerebral (ivc) com baclofeno reduziu significativamente a % RG; não houve conclusivamente envolvimento dos receptores GABAB em retardar o EG; o tratamento intravenoso com prazosina reduziu significativamente a %RG no grupo INF. A lesão do NPV aboliu o efeito do infarto do miocárdio no EG. Conclusão: O nervo vago, receptores α-adrenérgicos e núcleo paraventricular estão envolvidos no retardo do esvaziamento gástrico no infarto agudo do miocárdio em ratos.

Predictors For Weight Loss Failure Following Roux-en-y Gastric Bypass.

Weight loss failure is a widely recognized occurrence following Roux-en-Y gastric bypass. This study aims to identify predictors associated with weight loss failure. It is a retrospective cohort which enrolled 187 subjects who underwent RYGB. Comparisons were made between patients' features at baseline and 24 months after surgery. A weight loss failure rate of 11.2% was found. Advanced age and diabetes were statistically associated with failure. The results found were close to previous reports. As weight loss failure represents an important concern, there is the possibility to perform revisional surgeries, which may emphasize the restrictive or malabsorptive characteristics of RYGB, leading to varied results. It is reinforced that weight loss cannot be used as the unique outcome to evaluate the success of surgery.

Chemoprotection Of Mnng-initiated Gastric Cancer In Rats Using Iranian Propolis.

Iranian propolis is a natural product of honeybees that has significant and varied anti-cancer benefits. The present study was designed to investigate the protective effects of Iranian propolis on gastric tissue carcinogenesis in an animal model.  Propolis samples were collected from Hamadan and Taleghan districts of Iran, followed by ultra performance liquid chromatography mass spectrometry analysis. Fifty-five rats were divided into three groups; control, Taleghan propolis and Hamadan propolis. All the animals received N-methyl-N-nitro-N-nitrosoguanidine (MNNG, 100 μg/ml) in drinking water ad libitum for 34 weeks. In the treated groups, nutrition with propolis was started two weeks before MNNG administration. At the end of the study, the entire gastrointestinal tract was scrutinized for tumors, and the rest of the body was assessed for metastatic deposits.  Results indicated that the incidence and number of tumors were significantly decreased by propolis in comparison with the control group (P < 0.05). The nuclear/cytoplasmic ratio, epithelial stratification, nuclear dispolarity, structural abnormality, and Beta-catenin and Bcl-2 proteins expression were significantly reduced in the propolis group compared to the control group (P < 0.05). In addition, Bax protein expression was significantly increased in the propolis group in comparison with the control group (P < 0.05).  The present study demonstrated the potential chemoprotective effects of the Iranian propolis against gastric cancer in a typical animal model. The results provide evidence for the hypothesis that Iranian propolis may exert a chemoprotective effect on MNNG-initiated gastric cancer through inhibition of cell proliferation and apoptosis induction.

Nitric Oxide Released From Luminal S-nitroso-n-acetylcysteine Increases Gastric Mucosal Blood Flow.

Nitric oxide (NO)-mediated vasodilation plays a key role in gastric mucosal defense, and NO-donor drugs may protect against diseases associated with gastric mucosal blood flow (GMBF) deficiencies. In this study, we used the ex vivo gastric chamber method and Laser Doppler Flowmetry to characterize the effects of luminal aqueous NO-donor drug S-nitroso-N-acetylcysteine (SNAC) solution administration compared to aqueous NaNO2 and NaNO3 solutions (pH 7.4) on GMBF in Sprague-Dawley rats. SNAC solutions (600 μM and 12 mM) led to a rapid threefold increase in GMBF, which was maintained during the incubation of the solutions with the gastric mucosa, while NaNO2 or NaNO3 solutions (12 mM) did not affect GMBF. SNAC solutions (600 μM and 12 mM) spontaneously released NO at 37 °C at a constant rate of 0.3 or 14 nmol·mL-1·min-1, respectively, while NaNO2 (12 mM) released NO at a rate of 0.06 nmol·mL-1·min-1 and NaNO3 (12 mM) did not release NO. These results suggest that the SNAC-induced GMBF increase is due to their higher rates of spontaneous NO release compared to equimolar NaNO2 solutions. Taken together, our data indicate that oral SNAC administration is a potential approach for gastric acid-peptic disorder prevention and treatment.

Impaired Incretin Secretion And Pancreatic Dysfunction With Older Age And Diabetes.

To estimate the impact of aging and diabetes on insulin sensitivity, beta-cell function, adipocytokines, and incretin production. Hyperglycemic clamps, arginine tests and meal tolerance tests were performed in 50 non-obese subjects to measure insulin sensitivity (IS) and insulin secretion as well as plasma levels of glucagon, GLP-1 and GIP. Patients with diabetes and healthy control subjects were divided into the following groups: middle-aged type 2 diabetes (MA-DM), aged Type 2 diabetes (A-DM) and middle-aged or aged subjects with normal glucose tolerance (MA-NGT or A-NGT). IS, as determined by the homeostasis model assessment, glucose infusion rate, and oral glucose insulin sensitivity, was reduced in the aged and DM groups compared with MA-NGT, but it was similar in the MA-DM and A-DM groups. Insulinogenic index, first and second phase insulin secretion and the disposition indices, but not insulin response to arginine, were reduced in the aged and DM groups. Postprandial glucagon production was higher in MA-DM compared to MA-NGT. Whereas the GLP-1 production was reduced in A-DM, no differences between groups were observed in GIP production. In non-obese subjects, diabetes and aging impair insulin sensitivity. Insulin production is reduced by aging, and diabetes exacerbates this condition. Aging associated defects superimposed diabetic physiopathology, particularly regarding GLP-1 production. On the other hand, the glucose-independent secretion of insulin was preserved. Knowledge of the complex relationship between aging and diabetes could support the development of physiopathological and pharmacological based therapies.

Gastroprotective Effects (in Rodents) Of A Flavonoid Rich Fraction Obtained From Syngonanthus Macrolepsis.

Syngonanthus macrolepis, popularly known in Brazil as 'sempre-vivas', is a plant from the family Eriocaulaceae, it is found in the states of Minas Gerais and Bahia. The species contains a variety of constituents, including flavonoids with gastroprotective effect. In this work, a flavonoid-rich fraction (Sm-FRF) obtained from scapes of S. macrolepis was investigated for preventing gastric ulceration in mice and rats. The activity was evaluated in models of induced gastric ulcer (absolute ethanol, stress, non-steroidal anti-inflammatory drugs and pylorus ligation). The cytoprotective mechanisms of the Sm-FRF in relation to sulfhydryl (SH) groups, nitric oxide (NO) and antioxidant enzymes were also evaluated. The Sm-FRF (100 mg/kg, p.o.) significantly reduced gastric injury in all models, and did not alter gastric juice parameters after pylorus ligation. The results indicate significant gastroprotective activity for the Sm-FRF, which probably involves the participation of both SH groups and the antioxidant system. Both are integral parts of the gastrointestinal mucosa's cytoprotective mechanisms against aggressive factors.

Micronutrient And Physiologic Parameters Before And 6 Months After Rygb.

Bariatric surgery is considered an effective method for sustained weight loss, but may cause various nutritional complications. The aim of this study was to evaluate the nutritional status of minerals and vitamins, food consumption, and to monitor physiologic parameters in patients with obesity before and 6 months after Roux-en-Y gastric bypass surgery (RYGB). Thirty-six patients who had undergone RYGB were prospectively evaluated before and 6 months after surgery. At each phase their weight, height, body mass index (BMI), Electro Sensor Complex (ES Complex) data, food consumption, and total protein serum levels, albumin, prealbumin, parathyroid hormone (PTH), zinc (Zn), B12 vitamin (VitB12), iron (Fe), ferritin, copper (Cu), ionic calcium (CaI), magnesium (Mg), and folic acid were assessed. The mean weight loss from baseline to 6 months after surgery was 35.34±4.82%. Markers of autonomic nervous system balance (P<.01), stiffness index (P<.01), standard deviation of normal-to-normal R-R intervals (SDNN) (P<.01), and insulin resistance (P<.001) were also improved. With regard to the micronutrients measured, 34 patients demonstrated some kind of deficiency. There was a high percentage of Zn deficiency in both pre- (55.55%) and postoperative (61.11%) patients, and 33.33% of the patients were deficient in prealbumin postoperatively. The protein intake after 6 months of surgery was below the recommended intake (<70 g/d) for 88.88% of the patients. Laboratory analyses demonstrated an average decrease in total protein (P<.05), prealbumin (P = .002), and PTH (P = .008) between pre- and postsurgery, and a decrease in the percentage of deficiencies for Mg (P<.05), CaI (P<.05), and Fe (P = .021). Despite improvements in the autonomic nervous system balance, stiffness index markers and insulin resistance, we found a high prevalence of hypozincemia at 6 months post-RYGB. Furthermore, protein supplements were needed to maintain an adequate protein intake up to 6 months postsurgery.

Preparation, Characterization And In Vitro Digestibility Of Gellan And Chitosan-gellan Microgels.

Gellan microgels with potential application in delivery systems were obtained by physically cross-linked gellan gum. The microgels were produced by atomization followed by ionotropic gelation using CaCl2 (gellan/Ca) or KCl (gellan/K) as hardening agent and part of them were coated with chitosan in order to improve their resistance to gastric digestion. Size distribution, morphology and zeta potential of microgels were evaluated before and after in vitro digestion process. The long term stability was also evaluated. Spherical microparticles were obtained at gellan concentration above 0.6% w/w, showing average size among 70-120 μm. Most of the coated and uncoated microgels showed stability in aqueous media, except the uncoated gellan/K microgel. The in vitro digestion evaluation showed that all particles maintained their size and shape after the gastric digestion step. However, the enteric digestion caused disintegration of microgels indicating their potential application for enteric delivery systems. The chitosan-coated microgels showed lower degree of fragmentation when compared to the uncoated microgels, indicating that the coating process enable a better control of microgels releasing properties during the enteric digestion.

Surgical Treatment Of Type 2 Diabetes In Subjects With Mild Obesity: Mechanisms Underlying Metabolic Improvements.

This study aims to assess the clinical and physiological effects of Roux-en-Y gastric bypass (RYGBP) on type 2 diabetes associated with mild obesity (body mass index [BMI] 30-34.9 kg/m(2)) over 24 months postsurgery. In this prospective trial, 36 mildly obese subjects (19 males) with type 2 diabetes using oral antidiabetic drugs with (n = 24) or without insulin (n = 12) underwent RYGBP. Follow-up was conducted at baseline and 3, 6, 12, and 24 months postsurgery. The following endpoints were considered: changes in HbA1c, fasting glucose and insulin, antidiabetic therapy, BMI, oral glucose insulin sensitivity [OGIS, from meal tolerance test (MTT)], beta-cell secretory function [ΔCP(0-30)/ΔGlu(0-30) (ΔC-peptide/Δglucose ratio, MTT 0-30 min), disposition index (DI = OGIS [Symbol: see text] ΔCP(0-30)/ΔGlu(0-30)], glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) [incremental area under the curve (AUCi)], adiponectin, C-reactive protein, and lipids. All subjects achieved normal-to-overweight BMI after 3 months. Over 24 months, 31/36 (86 %) subjects presented HbA1c <7 % [complete and partial remission of diabetes in 9/36 (22 %) and 1/36 (3 %), respectively]. Since 3 months postsurgery, improvements were observed in OGIS [290 (174) to 373 (77) ml/min/m(2), P = 0.009], ΔCP(0-30)/ΔGlu(0-30) [0.24 (0.19) to 0.52 (0.34) ng/mg, P = 0.001], DI [7.16 (8.53) to 19.8 (15.4) (ng/mg) (ml/min/m(2)), P = 0.001], GLP-1 AUCi [0.56 (0.64) to 3.97 (3.86) ng/dl [Symbol: see text] 10 min [Symbol: see text] 103, P = 0.000], and GIP AUCi [30.2 (12.6) to 27.0 (20.2) ng/dl [Symbol: see text] 10 min [Symbol: see text] 103, P = 0.004]. At baseline and after 12 months, subjects with diabetes nonremission had longer diabetes duration, higher HbA1c, lower beta-cell secretory function, and higher first 30-min GIP AUCi, compared with those with remission. RYGBP improves the glucose metabolism in subjects with type 2 diabetes and mild obesity. This effect is associated with improvement of insulin sensitivity, beta-cell secretory function, and incretin secretion.

Recovery Of The Incretin Effect In Type 2 Diabetic Patients After Biliopancreatic Diversion.

Context: Bariatric surgery often results in remission of the diabetic state in obese patients. Increased incretin effect seems to play an important role in the glycemic improvements after Roux-en-Y gastric bypass, but the impact of biliopancreatic diversion (BPD) remains unexplored. Objective: To elucidate the effect of BPD on the incretin effect and its interplay with beta-cell function and insulin sensitivity (IS) in obese subjects with type 2 diabetes (T2DM). Design, Setting and Patients: Twenty-three women were studied: a control group of 13 lean, normal glucose-tolerant women (lean NGT) studied once and 10 obese patients with T2DM studied before, 1 and 12 months after BPD. Intervention: The ObeseT2DM group underwent BPD. Main Outcome Measures: The change in incretin effect as measured by the isoglycemic intravenous glucose infusion test. Secondary outcomes encompassed IS and beta-cell function. Results: At baseline, the incretin effect was lower in obese T2DM compared to lean NGT (p<0.05). One month after BPD, the incretin effect was not changed, but at 12 months it reached the level of the lean NGT group (p>0.05). IS improved (p<0.05) 1 month after BPD and at 12 months it resembled the levels of the lean NGT group. Insulin secretory rate and beta-cell glucose sensitivity increased after BPD and achieved levels similar to lean NGT group 1 month after BPD and even higher levels at 12 months (p<0.05). Conclusions: BPD has no acute impact on the reduced incretin effect, but 12 months after surgery the incretin effect normalizes alongside normalization of glucose control, IS and beta-cell function.

Preparative separation of flavonoids from the medicinal plant Davilla elliptica St. Hill. by high-speed counter-current chromatography

High-speed counter-current chromatography (HSCCC) is a major tool for the fast separation of natural products from plants. It was used for the preparative isolation of the flavonoid monoglucosides present in the aerial parts of the Davilla elliptica St. Hill. (Dilleniaceae). This species is used in Brazilian folk medicine for the treatment of gastric disorders. The optimum solvent system used was composed of a mixture of ethyl acetate-n-propanol-water (140:8:80, v/v/v) and led to a successful separation of quercetin-3-O-alpha-L-rhamnopyranoside and myricetin-3-O-alpha-L-rhamnopyranoside in approximately 3.0 hours with purity higher than 95%. Identification was performed by ¹H NMR, 13C NMR and HPLC-UV-DAD analyses.

Long-term follow-up of an 8-year-old boy with insulinoma as the first manifestation of a familial form of multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary cancer syndrome characterized mostly by parathyroid, enteropancreatic, and anterior pituitary tumors. We present a case of an 8-year-old boy referred because of hypoglycemic attacks. His diagnosis was pancreatic insulinoma. Paternal grandmother died due to repeated gastroduodenal ulcerations and a paternal aunt presented similar manifestations. At a first evaluation, the father presented only gastric ulceration but subsequently developed hyperparathyroidism and lung carcinoid tumor. During almost 15 years of follow-up, three brothers and the index case presented hyperparathyroidism and hyperprolactinemia. Molecular study showed a G to A substitution in intron 4, at nine nucleotides upstream of the splicing acceptor site, causing a splicing mutation. All affected members of the family have the same mutation. Paternal grandmother and aunt were not studied and the mother does not carry any mutation. MEN1 is a rare condition that requires permanent medical assistance. Early clinical and genetic identification of affected individuals is essential for their own surveillance and also for genetic counseling.