Emptying Rate Research Articles

Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers

Positive food effects may be observed for low aqueous soluble compounds, these effects could potentially be circumvented using lipid based formulations. However, as all compounds are not chemically stable in lipid based systems, alternative dosage regimes could be investigated to evade the stability issue. The two aims for this present study were therefore; i) to investigate if a nutritional drink, Fresubin Energy®, could induce food effect in humans for the poorly soluble compound cinnarizine; and ii) to investigate if co-administration of a self-nano-emulsifying drug delivery systems (SNEDDS) with a conventional cinnarizine tablet could reduce the observed food-effect.A commercial conventional cinnarizine tablet was dosed to 10 healthy volunteers in a cross-over design in both fasted and fed state, with and without co-administration of a SNEDDS, with a one week wash-out period between dosing. The fed state was induced using a nutritional drink (Fresubin Energy®) and gastric emptying was assessed by administration of paracetamol as a marker.The pharmacokinetic analysis showed that the nutritional drink delayed the uptake and increased the fraction of absorbed cinnarizine, indicative of a food effect on the compound. This was in agreement with a previous dog study and indicates that the nutritional drink can be used for inducing the same level of food effect in humans. Though not statistically significant, the co-administration of SNEDDS exhibited a tendency towards a reduction of the observed food effect and an increased absorption of cinnarizine in the fasted state; based upon the individual ratios, which was not reflected in the mean data. However, the co-administration of SNEEDS in the fasted state, also induce a slower gastric emptying rate, which was observed as a delayed tmax for both cinnarizine and paracetamol.

Gastrointestinal actions of glucagon‐like peptide‐1‐based therapies: glycaemic control beyond the pancreas

The gastrointestinal hormone glucagon-like peptide-1 (GLP-1) lowers postprandial glucose concentrations by regulating pancreatic islet-cell function, with stimulation of glucose-dependent insulin and suppression of glucagon secretion. In addition to endocrine pancreatic effects, mounting evidence suggests that several gastrointestinal actions of GLP-1 are at least as important for glucose-lowering. GLP-1 reduces gastric emptying rate and small bowel motility, thereby delaying glucose absorption and decreasing postprandial glucose excursions. Furthermore, it has been suggested that GLP-1 directly stimulates hepatic glucose uptake, and suppresses hepatic glucose production, thereby adding to reduction of fasting and postprandial glucose levels. GLP-1 receptor agonists, which mimic the effects of GLP-1, have been developed for the treatment of type 2 diabetes. Based on their pharmacokinetic profile, GLP-1 receptor agonists can be broadly categorized as short- or long-acting, with each having unique islet-cell and gastrointestinal effects that lower glucose levels. Short-acting agonists predominantly lower postprandial glucose excursions, by inhibiting gastric emptying and intestinal glucose uptake, with little effect on insulin secretion. By contrast, long-acting agonists mainly reduce fasting glucose levels, predominantly by increased insulin and reduced glucagon secretion, with potential additional direct inhibitory effects on hepatic glucose production. Understanding these pharmacokinetic and pharmacodynamic differences may allow personalized antihyperglycaemic therapy in type 2 diabetes. In addition, it may provide the rationale to explore treatment in patients with no or little residual β-cell function.

Pharmacological Profile of GPD-1116, an Inhibitor of Phosphodiesterase 4.

We have previously reported that GPD-1116, an inhibitor of phosphodiesterase (PDE) 4, exhibits anti-inflammatory effects in a model of cigarette smoke-induced emphysema in senescence-accelerated P1 mice. In the present study, we further characterized the pharmacological profile of GPD-1116 in several experiments in vitro and in vivo. GPD-1116 and its metabolite GPD-1133 predominantly inhibited not only human PDE4, but also human PDE1 in vitro. Moreover, GPD-1116 was effective in several disease models in animals, including acute lung injury, chronic obstructive pulmonary disease (COPD), asthma and pulmonary hypertension; the effective doses of GPD-1116 were estimated to be 0.3-2 mg/kg in these models. With regard to undesirable effects known as class effects of PDE4 inhibitors, GPD-1116 showed suppression of gastric emptying in rats and induction of emesis in dogs, but showed no such suppression of rectal temperature in rats, and these side effects of GPD-1116 seemed to be less potent than those of roflumilast. These results suggested that GPD-1116 could be a promising therapeutic agent for the treatment of inflammatory pulmonary diseases. Furthermore, the inhibitory effects of GPD-1116 for PDE1 might be associated with its excellent pharmacological profile. However, the mechanisms through which PDE1 inhibition contributes to these effects should be determined in future studies.

Gastroparesis - causes, diagnosis and treatment

BACKGROUND Gastroparesis is a motility disorder of the stomach. The symptoms are non-specific: nausea and vomiting are most common. Stomach pains, early satiety, postprandial fullness and bloating are also frequent symptoms. Current diagnostic criteria require delayed gastric emptying in the absence of any detectable mechanical obstruction. In this review article we elucidate the causes, assessment and treatment options.MATERIAL AND METHOD Structured article search in Embase and PubMed.RESULTS A number of conditions can lead to gastroparesis. The most frequent somatic cause is diabetes mellitus. Gastroparesis may also be iatrogenically inflicted by means of surgery or drugs. It may be difficult to discriminate between functional dyspepsia and idiopathic gastroparesis. Examination is based on patient history, gastroscopy and measurement of the rate of gastric emptying. Biochemical tests are also relevant for differential diagnosis. The treatment is primarily symptomatic, and consists of dietary measures, fluid therapy, drugs, gastric electrical stimulation, or endoscopic or surgical intervention in the form of insertion of a feeding tube for nutrition and abdominal relief, pyloroplasty or gastrectomy.INTERPRETATION Gastroparesis is a serious motility disorder. The condition may have significant consequences for patients, entailing reduced quality of life, reduced workforce participation and a considerable need for health assistance.

The Effect of Hippocampal Cognitive Impairment and XIAP on Glucose and Lipids Metabolism in Rats

Background/Aims: To investigate the effect of cognitive impairment and X-linked inhibitor of apoptosis protein (XIAP) on glucolipid metabolism. Materials and Methods: β-amyloid (Aβ 1-42) was injected into the hippocampus of rats to establish a cognitive impairment model. Trans-activator of transcription (TAT)-XIAP fusion protein (the TAT-XIAP group), PBS (the model group), or XIAP antisense oligonucleotides (the ASODN group) was injected into the lateral ventricles of the rats to increase and decrease the activity of XIAP in the hippocampus. To determine the level of blood glucose and lipids, adenosine monophosphate-activated protein kinase (AMPK) expression of liver and hipppocamual neuronal apoptosis. Results: The levels of FPG, TG, TC and LDL were significantly higher in the TAT-XIAP group, the model group and the ASODN group than in the blank group (P < 0.05); however, the HDL level showed no significant change in all groups of rats. The apoptosis indexes of the rat hippocampal CA1 neuron were 68.44 ± 4.31%, 13.21 ± 2.30%, 56.68 ± 4.771%, and 87.51 ± 6.63% in the model group, the blank group, the TAT-XIAP group and the ASODN group, respectively. Gastrointestinal motility was less frequent (per time unit) in the model group, the ASODN group and the TAT-XIAP group than in the blank group. Compared with the model group, gastrointestinal motility was significantly less frequent in the ASODN group and was significantly more frequent in the TAT-XIAP group. Compared with the blank group, the model group had a significantly lower gastric emptying rate and intestinal propulsive rate. Compared with the model group, the gastric emptying rate and intestinal propulsive rate were significantly lower in the ASODN group and were significantly higher in the TAT-XIAP group. Compared with the blank group, the expressions of AMPK mRNA, and AMPK protein were significantly reduced in the model group, the TAT-XIAP group, and the ASODN group. AMPK expression was significantly increased in the TAT-XIAP group and was significantly decreased in the ASODN group than in the model group. Conclusion: Cognitive impairment and hippocampal neuron apoptosis can cause glucose and lipids metabolic abnormalities, possibly by regulating gastrointestinal motility and AMPK expression in the liver. The changes in the function of XIAP, which is an anti-apoptotic protein in the hippocampus, may affect the metabolism of glucose and lipids.

Mitigating Exertional Heat Illness in Military Personnel: The Science Behind a Rice-Based Electrolyte and Rehydration Drink.

Exertional heat illness continues to be prevalent among members of active duty personnel, especially those in specific military occupational specialties such as loadmasters, flight crew, flight maintainers, and Special Operations Forces. Therefore, the primary objective of this article was to elucidate the various oral rehydration solutions (ORSs) on the market that are used to mitigate exertional heat illness (EHI) in military personnel, and to focus on the science behind a ricebased electrolyte drink, CeraSport®, currently used by US military personnel in mitigating EHI during sustained training operations in high-heat environments. A search of the literature (through March 2016) was performed using PubMed and ProQuest, in addition to searching bibliographies and text books. We reviewed 63 articles and three texts. Articles were limited to those published in English and to studies that used only carbohydrates (e.g., no amino acids) and drinks reported to be used by the military in field training and deployment. Heat illness is prevalent among military personnel operating in high-heat environments and a variety of ORSs and sports drinks are available to help mitigate this. However, CeraSport, compared with other ORSs and sports drinks, may offer benefits such as faster gastric emptying rates and improved absorption from the gastrointestinal tract, which can provide rapidly available carbohydrate substrates for energy needs, and increased water retention for maintenance of blood plasma volume.

Meal sequence and glucose excursion, gastric emptying and incretin secretion in type 2 diabetes: a randomised, controlled crossover, exploratory trial.

Aims/hypothesisInvestigation of dietary therapy for diabetes has focused on meal size and composition; examination of the effects of meal sequence on postprandial glucose management is limited. The effects of fish or meat before rice on postprandial glucose excursion, gastric emptying and incretin secretions were investigated.MethodsThe experiment was a single centre, randomised controlled crossover, exploratory trial conducted in an outpatient ward of a private hospital in Osaka, Japan. Patients with type 2 diabetes (n = 12) and healthy volunteers (n = 10), with age 30–75 years, HbA1c 9.0% (75 mmol/mol) or less, and BMI 35 kg/m2 or less, were randomised evenly to two groups by use of stratified randomisation, and subjected to meal sequence tests on three separate mornings; days 1 and 2, rice before fish (RF) or fish before rice (FR) in a crossover fashion; and day 3, meat before rice (MR). Pre- and postprandial levels of glucose, insulin, C-peptide and glucagon as well as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide were evaluated. Gastric emptying rate was determined by 13C-acetate breath test involving measurement of 13CO2 in breath samples collected before and after ingestion of rice steamed with 13C-labelled sodium acetate. Participants, people doing measurements or examinations, and people assessing the outcomes were not blinded to group assignment.ResultsFR and MR in comparison with RF ameliorated postprandial glucose excursion (AUC−15–240 min-glucose: type 2 diabetes, FR 2,326.6 ± 114.7 mmol/l × min, MR 2,257.0 ± 82.3 mmol/l × min, RF 2,475.6 ± 87.2 mmol/l × min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 1,419.8 ± 72.3 mmol/l × min, MR 1,389.7 ± 69.4 mmol/l × min, RF 1,483.9 ± 72.8 mmol/l × min) and glucose variability (SD−15–240 min-glucose: type 2 diabetes, FR 1.94 ± 0.22 mmol/l, MR 1.68 ± 0.18 mmol/l, RF 2.77 ± 0.24 mmol/l [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 0.95 ± 0.21 mmol/l, MR 0.83 ± 0.16 mmol/l, RF 1.18 ± 0.27 mmol/l). FR and MR also enhanced GLP-1 secretion, MR more strongly than FR or RF (AUC−15–240 min-GLP-1: type 2 diabetes, FR 7,123.4 ± 376.3 pmol/l × min, MR 7,743.6 ± 801.4 pmol/l × min, RF 6,189.9 ± 581.3 pmol/l × min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 3,977.3 ± 324.6 pmol/l × min, MR 4,897.7 ± 330.7 pmol/l × min, RF 3,747.5 ± 572.6 pmol/l × min [p < 0.05 for MR vs RF and MR vs FR]). FR and MR delayed gastric emptying (Time50%: type 2 diabetes, FR 83.2 ± 7.2 min, MR 82.3 ± 6.4 min, RF 29.8 ± 3.9 min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 66.3 ± 5.5 min, MR 74.4 ± 7.6 min, RF 32.4 ± 4.5 min [p < 0.05 for FR vs RF and MR vs RF]), which is associated with amelioration of postprandial glucose excursion (AUC−15–120 min-glucose: type 2 diabetes, r = −0.746, p < 0.05; healthy, r = −0.433, p < 0.05) and glucose variability (SD−15–240 min-glucose: type 2 diabetes, r = −0.578, p < 0.05; healthy, r = −0.526, p < 0.05), as well as with increasing GLP-1 (AUC−15–120 min-GLP-1: type 2 diabetes, r = 0.437, p < 0.05; healthy, r = 0.300, p = 0.107) and glucagon (AUC−15–120 min-glucagon: type 2 diabetes, r = 0.399, p < 0.05; healthy, r = 0.471, p < 0.05). The measured outcomes were comparable between the two randomised groups.Conclusions/interpretationMeal sequence can play a role in postprandial glucose control through both delayed gastric emptying and enhanced incretin secretion. Our findings provide clues for medical nutrition therapy to better prevent and manage type 2 diabetes.Trial registration:UMIN Clinical Trials Registry UMIN000017434.Funding:Japan Society for Promotion of Science, Japan Association for Diabetes Education and Care, and Japan Vascular Disease Research Foundation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-015-3841-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Postoperative Complications, In-Hospital Mortality and 5-Year Survival After Surgical Resection for Patients with a Pancreatic Neuroendocrine Tumor: A Systematic Review.

Studies on postoperative complications and survival in patients with pancreatic neuroendocrine tumors (pNET) are sparse and randomized controlled trials are not available. We reviewed all studies on postoperative complications and survival after resection of pNET. A systematic search was performed in the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE from 2000–2013. Inclusion criteria were studies of resected pNET, which described postoperative complications separately for each surgical procedure and/or 5-year survival after resection. Prospective and retrospective studies were pooled separately and overall pooled if heterogeneity was below 75 %. The random-effect model was used. Overall, 2643 studies were identified and after full-text analysis 62 studies were included. Pancreatic fistula (PF) rate of the prospective studies after tumor enucleation was 45 %; PF-rates after distal pancreatectomy, pancreatoduodenectomy, or central pancreatectomy were, respectively, 14–14–58 %. Delayed gastric emptying rates were, respectively, 5–5–18–16 %. Postoperative hemorrhage rates were, respectively, 6–1–7–4 %. In-hospital mortality rates were, respectively, 3–4–6–4 %. The 5-year overall survival (OS) and disease-specific survival (DSS) of resected pNET without synchronous resected liver metastases were, respectively, 85–93 %. Heterogeneity between included studies on 5-year OS in patients with synchronous resected liver metastases was too high to pool all studies. The 5-year DSS in patients with liver metastases was 80 %. Morbidity after pancreatic resection for pNET was mainly caused by PF. Liver resection in patients with liver metastases seems to have a positive effect on DSS. To reduce heterogeneity, ISGPS criteria and uniform patient groups should be used in the analysis of postoperative outcome and survival.

Discovery and SAR of N-(1-((substituted piperidin-4-yl)methyl)-3-methoxypiperidin-4-yl)-2-methoxybenzamide derivatives: 5-Hydroxytryptamine receptor 4 agonist as a potent prokinetic agent

A series of novel benzamide derivatives, altering the 4-fluorophenylalkyl moiety in cisapride, were synthesized as 5-HT4 receptor agonists, and SAR of these analogs was examined on in vitro and in vivo prokinetic activities. These compounds were synthesized for high 5-HT4 receptor binding affinities and low hERG affinities. Several types of analogs were obtained and screened for 5-HT4 binding, hERG blocking, agonism, and gastric emptying assessment. Among the analogues, compound 23g showed promising results compared with the other analogs with respect to gastric emptying rates in rats. Therefore, we suggest that it may be a clinical candidate for the development of a potent prokinetic agent to treat GI disorders.

Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia.

Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here.

Development of a hydration index: a randomized trial to assess the potential of different beverages to affect hydration status.

Background: The water content of ingested beverages enters the body water pool at a rate dictated by the rates of gastric emptying and intestinal absorption. Water is subsequently lost from the body by various routes, primarily urine in the absence of sweating. The post-ingestion diuretic response following prior hypohydration is influenced by several characteristics of the drink, including primarily volume, energy density, electrolyte content, and the presence of diuretic agents. Objective: This study investigated the effects of 13 different commonly-consumed drinks on urine output and fluid balance when ingested in a euhydrated state, with a view to establishing a Hydration Index (HI; i.e. volume of urine produced after drinking expressed relative to a standard treatment [still water]). Design: Each subject (n = 72, euhydrated and fasted males) ingested 1 L of still water or one of three other commercially-available beverages over a period of 30 minutes. Urine output was then collected for the subsequent 4 h. HI was corrected for water content of drinks and was calculated as the amount of water retained at 2 h after ingestion, relative to that observed following ingestion of still water. Results: Total urine masses (mean (SD)) over 4 h were smaller than the still water control (1337(330) g) after oral rehydration solution (ORS, 1038(333) g, P=0.004), full-fat milk (1052(267) g, P=0.006) and skimmed milk (1049(334) g, P=0.005). Cumulative urine output at 4h after ingestion of cola, diet cola, tea, cold tea, coffee, lager, orange juice, sparkling water and a sports drink were not different from the response to water ingestion. The mean HI at 2 h was 1.53(0.74) for ORS, 1.32(0.51) for full-fat milk, and 1.44(0.54) for skimmed milk. Conclusions: An HI may be a useful measure to identify the short-term hydration potential of different beverages when ingested in a euhydrated state.

Acute load-dependent effects of oral whey protein on gastric emptying, gut hormone release, glycemia, appetite, and energy intake in healthy men

In healthy individuals, intraduodenal whey protein load-dependently modulates gastrointestinal motor and hormonal functions and suppresses energy intake. The effect of oral whey, particularly the impact of load, has not been evaluated. The purpose of this study was to quantify gastric emptying of 30 and 70 g of oral whey protein loads and their relation to gastrointestinal hormone, glycemic, and appetitive responses. On 3 separate occasions in a randomized, double-blind order, 18 lean men [mean ± SEM age: 24.8 ± 1.4 y; body mass index (in kg/m(2)): 21.6 ± 0.5] received iso-osmolar, equally palatable drinks (∼450 mL) containing 30 g pure whey protein isolate (L), 70 g pure whey protein isolate (H), or saline (control). Gastric emptying (with the use of 3-dimensional ultrasound), plasma cholecystokinin, glucagon-like peptide 1, glucose-dependent insulinotropic peptide, insulin, glucagon, total amino acids, and blood glucose were measured for 180 min after consumption of the drinks, and energy intake at a buffet-style lunch was quantified. Gastric emptying of the L and H drinks was comparable when expressed in kilocalories per minute (L: 2.6 ± 0.2 kcal/min; H: 2.9 ± 0.3 kcal/min) and related between individuals (r = 0.54, P < 0.01). Gastrointestinal hormone, insulin, and glucagon responses to the L and H drinks were comparable until ∼45-60 min after ingestion, after which time the responses became more differentiated. Blood glucose was modestly reduced after the H drink between t = 45 and 150 min when compared with the L drink (all P < 0.05). Energy intake was suppressed by both L and H drinks compared with control (P < 0.05) (control: 1174 ± 91 kcal; L: 1027 ± 81 kcal; and H: 997 ± 71 kcal). These findings indicate that, in healthy lean men, the rate of gastric emptying of whey protein is independent of load and determines the initial gastrointestinal hormone response. This study was registered at www.anzctr.org.au as 12611000706976.

Late‐breaking abstracts

Late‐breaking abstracts

Effect of Electro-acupuncture on Ultrastructure in Diabetic Gastroparesis Model Rats

Abstract Objective: To observe the effects of electro-acupuncture (EA) on ultrastructure of gastric antrum smooth muscle cells (GASMCs) in diabetic gastroparesis (DGP) model rats, and to explore the possible mechanism underlying the therapeutic effects of EA. Methods: Sixty Sprague Dawley rats were randomly divided into 5 groups: blank control (group A), DGP model (group B), EA point (group C), EA non-point (group D), Metoclopramide control (group E). DGP rat model was established by 2% STZ intraperitoneal injection at once, and then being fed with high-sugar-high-fat (HSHF) for 8wks. Phenol red lavage method was employed to measure gastric emptying rate (GER) and intestinal migration rate (IMR). The ultrastructure of GASMCs was observed under the electronic microscope. Results: Compared with the blank control group, the GER and IMR in model group were decreased significantly (P＜0.05 or P＜0.01). Compared with the model group, the GER and IMR in EA point group were increased significantly(P＜0.05 or P＜0.01). Electro-acupuncture on “Zu San Li”(ST36) point, etc. has been observed improving the ultrastructure of GASMCs, as well as increasing the number of interstitial cells of Cajal (ICCs). Conclusion: Electro-acupuncture can improve the GI motility promisingly, based on a potential underlying mechanism that the electro-acupuncture can improve the ultrastructure of gastric smooth muscle, and increase the number of ICCs.

Gastroparesis.

This review summarizes recent progress in the epidemiology, pathophysiology, and treatment of gastroparesis. The relationship between delayed gastric emptying and symptom pattern in gastroparesis and, related to it, its separation from functional dyspepsia remains an area of controversy and uncertainty. Pathophysiological studies have focused on the role of pyloric resistance and duodenal motility in generation of symptoms. In diabetic patients, glycemic control did not determine short-term changes in gastric emptying rate in type 2 diabetes, but poor glycemic control was a major risk factor for long-term development of gastroparesis in type 1 diabetes. At the cellular level, diabetic gastroparesis is characterized by loss of interstitial cells of Cajal (ICCs), and this is inversely correlated to the number of CD206+ macrophages, which are thought to have a protective effect on ICCs. Treatment trials have focused on dietary factors and a nasal spray formulation of metoclopramide. A meta-analysis of prokinetic studies found no association between symptom improvement and enhancement of gastric emptying in gastroparesis. Two controlled studies showed no benefit of tricyclic antidepressants (nortriptyline, amitriptyline) in idiopathic gastroparesis and functional dyspepsia with delayed emptying. The relationship between delay in gastric emptying, symptom pattern, and response to prokinetic therapy in gastroparesis is poor. In diabetes, gastroparesis is characterized by loss of ICCs, and this is inversely correlated to the number of CD206+ macrophages. Dietary interventions may help to alleviate symptoms. Tricyclic antidepressants do not provide symptomatic benefit to patients with idiopathic gastroparesis.

A family caregiver's relaxation enhances the gastric motility function of the patient: a crossover study.

BackgroundThe primary purpose of this study was to assess the effect of a caregiver’s relaxation on the gastric motility function of the patient. The secondary purpose was to evaluate changes in the caregiver’s willingness to perform self-care following feedback on the results of the primary purpose.MethodsSubjects were 26 patients with a decreased level of consciousness who received gastrostomy tube feeding and their 26 family caregivers. We compared the patient’s gastric motility under the condition of having his or her hand held with and without caregiver relaxation (crossover study). Changes in the caregiver’s willingness to perform self-care following feedback on the results was evaluated using self-administered questionnaires. Hypnosis was used for relaxation. The outcomes assessed for gastric motility function were the motility index and gastric emptying rate by ultrasonography examination.ResultsHand-holding by the family caregiver while he or she was receiving relaxation enhanced the patient’s gastric motility function. By giving feedback on the results, the caregiver’s willingness to adopt self-care was increased and his or her sense of guilt was reduced.ConclusionsThis study suggested that a caregiver’s relaxation increases the gastric motility function of the patient and that gettinng feedback including the positive results increases the caregiver’s willingness to perform self-care, which consequently reduce the caregiver burden.

In silico modelling of mass transfer & absorption in the human gut

An in silico model has been developed to investigate the digestion and absorption of starch and glucose in the small intestine. The main question we are aiming to address is the relative effect of gastric empting time and luminal viscosity on the rate of glucose absorption. The results indicate that all factors have a significant effect on the amount of glucose absorbed. For low luminal viscosities (e.g. lower than 0.1 Pas) the rate of absorption is controlled by the gastric emptying time. For viscosities higher than 0.1 Pas a 10 fold increase in viscosity can result in a 4 fold decrease of glucose absorbed. Our model, with the simplifications used to develop it, indicate that for high viscosity luminal phases, gastric emptying rate is not the controlling mechanism for nutrient availability. Developing a mechanistic model could help elucidate the rate limiting steps that control the digestion process.

Efficacy of itopride combined with alpha-lipoic acid for patients with diabetic gastroparesis

Objective To evaluate the efficacy of itopride hydrochloride combined with alpha-lipoic acid in treatment of diabetic gastroparesis. Methods One hundred and ten patients with diabetic gastroparesis were randomly assigned to two groups. Sixty patients received α-lipoic acid plus itopride (α-lipoic acid 0.6 g intravenously for 14 d plus itopride 50 mg orally t. i.d), and 50 cases received oral itopride only.The clinical symptoms including postprandial abdominal fullness, belching, acid reflux, anorexia, nausea and vomiting were observed; the gastric emptying rate was tested, and plasma motilin and serum ganstrin levels were measured groups, before and after two weeks of treatment. Results The clinical symptom scores of combination therapy group (4.62±3.46 vs. 12.26±3.43) and control groups (5.43±3.65 vs. 12.31±3.37) were improved after treatment. The overall effective rate of combination group was 91.6% and that of itopride therapy group was 78.0% (χ2=4.098, P<0.05). Gastric emptying rate of combination group [(76.9±9.7)% vs. (37.3±10.2) %] was increased more markedly than that of itopride group[(57.2±10.4)% vs. (36.8±11.2)%] (t=10.221, P<0.05). Plasma motilin and serum ganstrin levels in combination group [(640.2±64.4)ng/L vs. (554.0±67.6)ng/L, (152.6±20.3)ng/L vs. (96.8±22.2)ng/L] were reduced more markedly than those in itopride group [(636.3±66.4)ng/L vs. (589.4±48.3)ng/L, (153.5±19.4)ng/L vs. (120.9±19.7)ng/L] respectively (t=3.100, 5.959, all P<0.05). Conclusion For patients with diabetic gastroparesis, α-lipoic acid and itopride combination therapy can significantly improve symptoms and gastric emptying rate, decrease motlin and gastrin levels; and the efficacy of combination therapy is better than that of itopride monotherapy. Key words: Diabetes mellitus; Gastroparesis; Tiapride; Thioctic acid

PP‐14 EFFECTS OF BODY MASS INDEX ON GASTRIC MOTILITY IN CHILDREN WITH ABDOMINAL PAIN‐PREDOMINANT FUNCTIONAL GASTROINTESTINAL DISORDERS

Introduction:There is evidence that overweight children have a higher prevalence of functional gastrointestinal disorders (FGIDs) than normal‐weight children. Objective of this study was to assess the effects of body mass index (BMI) on gastric motility abnormalities in children with abdominal pain‐predominant FGIDs (AP‐FGIDs).Methods:Gastric motility parameters of 100 children with AP‐FGIDs (61(61%) girls, mean age 8.0 years [SD 2.1years] and 50 healthy controls (30 (30%) boys, mean age 8.6 years [SD 1.9 years]) were assessed at the Gastroenterology Research Laboratory of Faculty of Medicine, University of Kelaniya, Sri Lanka, using a previously validated ultrasound method. AP‐FGIDs were diagnosed using Rome III criteria. Fifty‐four had functional abdominal pain, 23 had irritable bowel syndromes, 9 had functional dyspepsia, 8 had abdominal migraine and 6 had more than one AP‐FGID.Results:Patients with AP‐FGIDs had significantly lower gastric emptying rate (44.9% vs. 59.5% in controls, p &lt; 0.0001), frequency of antral contractions (8.29 vs. 9.44, p &lt; 0.0001), amplitude of antral contraction (48.6% vs. 58.1%, p &lt; 0.0001) and antral motility index (4.0 vs. 6.4, p = 0.001). Fasting antral size (FA) and antral area at 1minute (AA1) and antral area at 15 minutes (AA15) after ingestion of the liquid test meal were not significantly different. BMI of children with AP‐FGIDs and controls were respectively 15.2 and 15.6 (p = 0.42). The correlations between BMI and AA1 (r = 0.29, p = 0.007), AA15 (r = 0.32, p = 0.003) and MI (r = 0.22, p = 0.038) in children with AP‐FGIDs were significant. Patients with BMI &lt;15Kg/m2 had a lower FA (1.5cm2 vs. 2.1cm2, p = 0.03), AA1 (8.9 cm2 vs. 10.7 cm2, p = 0.003) and AA15 (4.6 cm2 vs. 5.8 cm2, p = 0.01) than patients with BMI &gt;15Kg/m2.Conclusions:BMI has an impact on certain gastric motility parameters in children with AP‐FGIDs. However, it does not contribute to abnormalities seen in main gastric motility parameters such as gastric emptying.

Role of Amylin in Type 1 and Type 2 Diabetes

The pathophysiology of diabetes has historically focused on alterations in insulin secretion and function; however, diabetes involves multiple hormonal alterations, including abnormal regulation of amylin. This review discusses the physiologic functions of amylin in glucose homeostasis and the rationale for amylin replacement in type 1 and 2 diabetes. The use of pramlintide, a synthetic amylin analog, is also discussed. Amylin, formed primarily in pancreatic islet β cells, is cosecreted with insulin in response to caloric intake. Patients with type 1 diabetes have lower baseline amylin serum concentrations, and amylin response to caloric intake is absent. Patients with type 2 diabetes requiring insulin also have a diminished amylin response to caloric intake, potentially related to the degree of β-cell impairment. Key physiologic functions of amylin in maintaining glucose homeostasis include suppressing glucagon release in response to caloric intake, delaying the rate of gastric emptying, and stimulating the satiety center in the brain to limit caloric intake. Pramlintide is indicated for adults with type 1 and 2 diabetes who have not achieved adequate glucose control despite optimal insulin therapy. As an adjunct to insulin therapy, pramlintide demonstrated significant reductions in A1C in patients with type 1 and 2 diabetes, with favorable effects on body weight. It is administered subcutaneously before each major meal. There is an increased risk of hypoglycemia with insulin when used in combination with pramlintide. Other adverse effects may include nausea, vomiting, anorexia, reduced appetite, and headache. Proper patient selection and education are essential to successful pramlintide use.