Emptying Rate Research Articles

당삼이 마우스 위장관 운동 기능에 미치는 영향

만삼(Codonopsis pilosula)의 뿌리를 말린 한약재인 당삼은 오래 전부터 우리나라와 중국 등지에서 위장관 기능항진에 전통적으로 쓰여 왔다. 본 연구에서는 당삼의 열수 및 에탄올 추출물을 제조하여 실험하였는데, 우선 마우스 단회 투여 경구 독성 시험 결과, 두 추출물 모두 5 g/kg의 고용량 투여 시에도 급성 독성을 나타내지 않았다. 당삼 추출물이 위장관 운동 기능에 미치는 영향을 검정하기 위해, 마우스에서 in vivo 위 배출 속도 및 위장관 이송률을 측정하는 실험을 수행하였다. 두 추출물 모두 마우스의 위 배출 속도에는 유의적인 영향을 주지 못한데 반해, 당삼 열수 추출물은 정상 및 실험적 위장관 운동 저해 마우스에서 모두 위장관 이송률을 유의적으로 증가시켰으며, 용량 의존적 증가 양상을 보였다. 이상과 같이, 본 연구에서는 당삼 열수 추출물이 정상 및 위장관 운동 기능 저해 상황의 마우스에서 모두 위장관 이송률을 증가시켰음을 최초로 보고하였으며, 이는 당삼 열수 추출물이 잠재적으로 인간의 위장관 운동 기능 저해 상황을 개선하는 신약 또는 건강 보조제로 개발될 수 있는 후보 물질임을 시사한다. Although major advances have been achieved in our understanding and treatment of diseases in many areas of medicine, relatively few improvements have been made in the area of gastrointestinal (GI) motor function. The dried root of Codonopsis pilosula (Franch.) Nannf. (CP) has been used as a traditional folk medicine for improving poor GI function in East Asia, including China and Korea. In the present study, neither aqueous (CP-W) nor ethanolic (CP-E) extracts of CP showed significant toxicity, even at an oral dose of 5 g/kg to mice. The effects of CP-W and CP-E on GI motor function were investigated by measuring in vivo the gastric emptying rate (GER) and intestinal transit rate (ITR) in mice. In normal mice, the ITR was significantly increased by CP-W in a dose-dependent manner, whereas the GER was not significantly affected by any CP extracts. The ITR was significantly retarded in the mice with experimental GI motility dysfunction (i.e., peritoneal irritation by acetic acid) compared with that in normal mice. However, the retardation was significantly recovered by the pre-treatment of CP-W in a dose-dependent manner. The above results suggest that CP-W might be a potential prokinetic agent preventing or alleviating GI motility dysfunctions in human patients.

Serum Leptin, Obestatin, and Ghrelin Levels and Gastric Emptying Rates of Liquid and Solid Meals in Non-obese Rats with Roux-en-Y Bypass Surgery or Prosthesis Placement: Implications for the Role of Vagal Afferents.

The present study aimed to investigate the effects of Roux-en-Y gastric bypass (RYGB) and prosthesis placement on gastric emptying rate in conjunction with serum ghrelin-obestatin-leptin responses in non-obese rats with intact or denervated afferent innervation. Under anesthesia, male Sprague-Dawley rats underwent either sham operation, RYGB, prosthesis, and/or Gregory cannula placement. Three weeks later, liquid or solid gastric emptying tests were performed and serum ghrelin, leptin and obestatin levels were measured. Both prosthesis placement and RYGB surgery delayed non-nutrient liquid emptying; while solid nutrient emptying was delayed only by RYGB. Nutrient-dependent (acid, hyperosmolal and peptone) delay in liquid emptying was abolished in rats with prosthesis. By vagal afferent denervation, delayed liquid emptying was abolished, while solid emptying was further delayed in rats with prosthesis. Ghrelin and obestatin levels were depressed in prosthesis-placed rats, but RYGB surgery had no impact on both levels. Leptin level was elevated in solid-food-given rats with prosthesis, but not changed in RYGB group, while it was reduced following liquid meal. All the changes observed in ghrelin, obestatin, or leptin levels in response to meal ingestion were reversed with vagal afferent denervation. Both RYGB and prosthesis placement had delaying effects on gastric emptying rate of non-obese rats. Our results indicate that the short-term changes in gastric motility and hormone responses induced by volume reduction are reversed by afferent denervation, suggesting that sparing the vagal innervation could be essential for reaching optimum motility and hormone changes expected after bariatric surgery.

NO EFFECT OF PRE-EXERCISE SUCRALOSE INGESTION ON GASTRIC EMPTYING RATE OF A CARBOHYDRATE-ELECTROLYTE SOLUTION

Ingestion of carbohydrate during exercise is common in order to provide an exogenous substrate for oxidation and to improve performance. The rate at which a solution is emptied from the...

Intrauterine growth-restricted piglets have similar gastric emptying rates but lower rectal temperatures and altered blood values when compared with normal-weight piglets at birth.

Intrauterine growth-restricted (IUGR) piglets have lower survival rates and are more likely to have empty stomachs 24 h after birth than normal piglets. Although hypoglycemia may result from low colostrum intake per se, it is not known if slow gastric emptying may be an additional risk factor for poor immunization and glucose absorption in IUGR piglets. It is estimated that IUGR piglets consume less colostrum per kilogram BW than normal-weight piglets within the first 24 h, which could be due to a slower gastric emptying rate and a compromised energy metabolism. Therefore, we hypothesized that the gastric emptying rate and blood glucose would be lower in IUGR piglets. We investigated gastric emptying rates in normal and IUGR piglets and blood glucose and rectal temperatures at birth and after 15, 30, 60, and 120 min. In addition, blood parameters relevant for metabolism were studied. Forty-eight piglets (24 normal and 24 IUGR) were classified at birth as either normal or IUGR on the basis of head morphology. Piglets were removed from the sow at birth before suckling, and birth weight was recorded. Pooled porcine colostrum was tube-fed to all piglets at 12 mL/kg BW as soon as possible after birth (t = 0 min). The piglets were randomly allocated to be euthanized at 15, 30, 60, and 120 min (all groups, = 6) after bolus feeding, and the weights of the stomach and its residuals were recorded. There was no difference in gastric emptying rates between normal and IUGR piglets ( = 0.129); however, gastric DM residuals tended to by greater in IUGR piglets than normal piglets ( = 0.085). Overall, IUGR piglets had lower rectal temperatures (36.2°C ± 0.2°C vs. 37.5°C ± 0.2°C; < 0.001) and plasma glucose levels (2.8 ± 0.2 vs. 4.1 ± 0.2 mmol; < 0.001) than normal piglets. Interactions between piglet classification and time were observed in plasma values for NEFA, -3-hydroxybutyrate, albumin, aspartate, and alanine amino transferase, with greater levels in normal piglets at 15 min ( < 0.05) and 30 min for bile acid ( < 0.05) compared to IUGR piglets. In conclusion, the gastric emptying rates between normal and IUGR piglets were similar, but gastric DM residuals tended to be greater in IUGR piglets. Differences were observed in blood values and rectal temperatures, with lower values in IUGR piglets. Therefore, it is likely that factors like hypothermia and possibly reduced metabolic function are more important during the first hours after birth than gastric retention per se.

Preoperative liquid gastric emptying rate does not predict outcome after fundoplication

Aim of the studyPreoperative gastric emptying (GE) rate in patients with gastrointestinal reflux disease (GERD) was evaluated as a predictor of outcome after antireflux surgery. Methods and patientsGE was assessed using radionuclide scintigraphy and a standardized meal with cow's milk. GE half time (T1/2), patient demographics and GERD symptoms including vomiting (>4days/week), retching (>4days/week), prolonged feeding time (>3h/day), and discomfort after meals were recorded pre- and postoperatively. A standardized follow-up included a 24-h pH-monitoring and an upper gastrointestinal contrast study. Of 74 patients undergoing Nissen fundoplication between 2003 and 2009, 35 underwent a preoperative GE study. The remaining 39 patients were not examined owing to volume intolerance, cow's milk intolerance or allergy, inability to lie still, or parents refusing participation. Main resultsMedian age at fundoplication was 4.9 [range 1.1–15.4] years, and follow-up time was median 4.3 [1.9–8.9] years. GERD recurred in 7 (20%) patients. Preoperative T1/2 in the seven patients with recurrent GERD was median 45 [21–87] min compared to 44 [16–121] min in the 28 patients without recurrent GERD (p=0.92). There was no significant difference between the one third of patients with the slowest GE [T1/2 54–121min] and the remaining patients [T1/2 16–49min] regarding GERD recurrence or postoperative vomiting, retching, prolonged feeding time, or discomfort after meals. ConclusionPreoperative GE rate did not predict outcome after antireflux surgery, as slow GE was not associated with recurrent GERD or postoperative troublesome symptoms such as vomiting, retching, or meal discomfort.

Inter-regulation of gastric emptying and incretin hormone secretion: implications for postprandial glycemic control.

The GI tract is central to the regulation of postprandial glycemia, with the rate of gastric emptying and the secretion of the incretin hormones, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, being key determinants. Gastric emptying exhibits a large interindividual variation; the latter not only accounts for differences in postprandial glycemia but also determines postprandial incretin profiles. Accordingly, the rate of gastric emptying may affect the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors. In contrast, glucagon-like peptide-1 receptor agonists lower postprandial glycemia predominantly by their action to slow gastric emptying. This review discusses the inter-relationship between gastric emptying and the incretin axis in the context of changes in blood glucose, with an emphasis on the relevant clinical implications.

Small Intestinal Glucose Delivery Affects the Lowering of Blood Glucose by Acute Vildagliptin in Type 2 Diabetes.

The rate of gastric emptying is an important determinant of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) secretion and may influence the magnitude of glucose lowering by dipeptidyl peptidase-4 (DPP-4) inhibitors. To evaluate the effects of the DPP-4 inhibitor, vildagliptin (VILD), during intraduodenal (ID) glucose infusion at 2 different rates within the physiological range of gastric emptying, in type 2 diabetes. A total of 16 diet-controlled type 2 diabetic patients were studied on 4 separate days in double-blind, randomized, fashion. On each day, either 5-mg VILD or placebo (PLBO) was given 60 minutes before a 120-minute ID glucose infusion at 2 or 4 kcal/min (ID2 or ID4). Plasma glucose and hormones were measured frequently. Plasma glucose, insulin, C-peptide, glucagon, total GIP, and total and intact GLP-1 concentrations were higher during ID4 than ID2 (P < .01 for each). Compared with PLBO, VILD was associated with higher intact GLP-1, insulin, and C-peptide and lower glucose and total GIP and GLP-1 (P < .01 for each), without affecting glucagon. There were significant interactions between the rate of ID glucose and VILD treatment on plasma glucose, intact and total GLP-1, and GIP (P < .05 for each) but not insulin, C-peptide, or glucagon. The reduction in glucose and the increment in intact GLP-1 after VILD vs PLBO were 3.3- and 3.8-fold greater, respectively, during ID4 compared with ID2. These observations warrant further study to clarify whether type 2 diabetic patients with relatively more rapid gastric emptying have greater glucose lowering during treatment with DPP-4 inhibitors.

The role of proximal versus distal stomach resection in the weight loss seen after vertical sleeve gastrectomy.

The mechanisms involved in the weight loss seen after vertical sleeve gastrectomy (VSG) are not clear. The rat stomach has two morphologically and functionally distinct proximal and distal parts. The rat model for VSG involves complete removal of the proximal part and 80% removal of the distal part along the greater curvature. The purpose of this study was to understand the potential independent contributions of removal of these distinct gastric sections to VSG outcomes. We prepared four surgical groups of male Long-Evans rats: VSG, sham surgery (control), selective proximal section removal (PR), and selective distal section removal (DR). Gastric emptying rate (GER) was highest after VSG compared with all other groups. However, PR, in turn, had significantly greater GER compared with both DR and sham groups. The surgery-induced weight loss followed the same pattern with VSG causing the greatest weight loss and PR having greater weight loss compared with DR and sham groups. The results were robust for rats fed regular chow or a high-fat diet. Body mass analysis revealed that the weight loss was due to the loss of fat mass, and there was no change in lean mass after the surgeries. In conclusion, removal of the proximal stomach contributes to most, but not all, of the physiological impact of VSG.

What is the manner of gastric emptying after ingestion of liquids with differences in the volume under uniform glucose-based energy content?

We previously demonstrated that the gastric emptying rate of liquids chiefly depended on the total amount of calories (energy content) in a uniform volume. The aim of the present study was to examine the effects of different volumes of liquids with a uniform energy content on gastric emptying. Three types of test solutions were prepared with a uniform amount of calories (200kcal provided by glucose) and step-wise increments in volume (200ml, 400ml, and 600ml). The gastric volume of each solution was determined by ultrasound measurements of the gastric antral cross-sectional area after their ingestion by 8 healthy volunteers. The mean gastric volume decreased exponentially to nearly 0ml 70min after ingestion in the 200ml group, 90min in the 400ml group, and 100min in the 600ml group. Each gastric emptying curve converged with identical slopes on the graph when the points at which the gastric emptying curves of the 200ml and 400ml groups reached the zero point on the Y-axis (mean gastric volume) were shifted toward 110min on the X-axis (time scale). The volume of liquid ingested with a uniform glucose-based energy content is a critical determinant of liquid gastric emptying. The gastric emptying time may be predicted following the ingestion of an isocaloric liquid with any volume over a predefined range once a gastric emptying curve following the ingestion of a liquid has been plotted on a graph. UMIN000014930.

Oral Administration of Collagen Hydrolysates Improves Glucose Tolerance in Normal Mice Through GLP-1-Dependent and GLP-1-Independent Mechanisms.

The aim of this study was to evaluate the antidiabetic properties of collagen hydrolysates (CHs). CHs exhibited dipeptidyl peptidase-IV inhibitory activity and stimulated glucagon-like-peptide-1 (GLP-1) secretion in vitro. We also determined whether CHs improve glucose tolerance in normal mice. Oral administration of CHs suppressed the glycemic response during the oral and intraperitoneal glucose tolerance tests (OGTT and IPGTT), but the effects were weaker in IPGTT than in OGTT. CHs had no effect on the gastric emptying rate. A pretreatment with the GLP-1 receptor antagonist, exendin 9-39 (Ex9), partially reversed the glucose-lowering effects of CHs, but only when coadministered with glucose. CHs administered 45 min before the glucose load potentiated the glucose-stimulated insulin secretion. This potentiating effect on insulin secretion was not reversed by the pretreatment with Ex9, it appeared to be enhanced. These results suggest that CHs improve glucose tolerance by inhibiting intestinal glucose uptake and enhancing insulin secretion, and also demonstrated that GLP-1 was partially involved in the inhibition of glucose uptake, but not essential for the enhancement of insulin secretion.

L-Arginine L-Glutamate Enhances Gastric Motor Function in Rats and Dogs and Improves Delayed Gastric Emptying in Dogs.

Amino acids are not only constituents of proteins, but also have multiple physiologic functions. Recent findings have revealed that ingested amino acids either activate luminal receptors or are metabolized, causing physiologic reactions in the gastrointestinal (GI) tract. We examined the effect of oral L-arginine L-glutamate (ArgGlu), a pharmaceutical amino acid salt used i.v. for the treatment of hyperammonemia, on gastric motor function in rats and dogs. Gastric emptying was determined using phenol red and 13C-breath test methods, whereas gastric relaxation was determined using the barostat method. ArgGlu (10-30 mg/kg, p.o.) dose-dependently promoted gastric emptying in rats. This effect was dependent on vagus nerve activation and comparable to that of the prokinetic mosapride. Intragastric ArgGlu (3-30 mg/kg intragastrically) also dose-dependently enhanced adaptive relaxation of rat stomachs, which was negated not by vagotomy of gastric branches, but by pretreatment with N omega-nitro-L-arginine methyl ester (20 mg/kg i.v.), a nitric oxide synthase inhibitor. Its relaxing effect on the stomach was also confirmed in dogs and was equally as efficacious as treatment with sumatriptan (1-3 mg/kg s.c.). ArgGlu (30 mg/kg p.o.) significantly reduced the half gastric emptying time in clonidine-induced delayed gastric emptying of solids in dogs, and its effect was comparable to that of cisapride (3 mg/kg p.o.). This study demonstrated that the pharmaceutical ingredient ArgGlu, currently used i.v., enhanced gastric motor function when administered orally, suggesting that it could be a new oral medicine indicated for treatment of upper GI hypofunction or dysfunction like functional dyspepsia.

Outcomes of pancreaticoduodenectomy in elderly patients

Although the mortality and morbidity of pancreaticoduodenectomy (PD) have improved significantly over the past years, the concerns for elderly patients undergoing PD are still present. Furthermore, the frequency of PD is increasing because of the increasing proportion of elderly patients and the increasing incidence of periampullary tumors. This study aimed to analyze the outcomes of PD in elderly patients. We studied all patients who had undergone PD in our center between January 1995 and February 2015. The patients were divided into three groups based on age: group I (patients aged <60 years), group II (those aged 60 to 69 years) and group III (those aged ≥70 years). The primary outcome was the rate of total postoperative complications. Secondary endpoint included total operative time, hospital mortality, length of postoperative hospital stay, delayed gastric emptying, re-exploration, and survival rate. A total of 828 patients who had undergone PD for resection of periampullary tumor were included in this study. There were 579 (69.9%) patients in group I, 201 (24.3%) in group II, and 48 (5.8%) in group III. The overall incidence of complications was higher in elderly patients (25.9% in group I, 36.8% in group II, and 37.5% in group III; P=0.006). There were more patients complicated with delayed gastric emptying in group II compared with the other two groups. There was no significant difference in the incidence of postoperative pancreatic fistula, biliary leakage, pancreatitis, pulmonary complications and hospital mortality. PD can be performed safely in selected elderly patients. Advanced age alone should not be a contraindication for PD. The outcome of elderly patients who have undergone PD is similar to that of younger patients, and the increased rate of complications is due to the presence of associated comorbidities.

Exploring the Feasibility of Biowaiver Extension of BCS Class III Drugs with Site-Specific Absorption Using Gastrointestinal Simulation Technology.

The US Food and Drug Administration, World Health Organization and European Medicines Agency have allowed biowaiver for some BCS class III drugs, but shortened the requisite dissolution time of BCS class III drugs from 30 to 15min, considering their site-specific absorption and others risk. The objective of this study was to assess the effects of site-specific absorption, low absorbed fraction (F a) and gastric emptying rate on the biowaiver extension of BCS class III drugs. The oral absorption of BCS class III drugs nadolol, acebutolol and atenolol which were P-gp substrates, was simulated using GastroPlus software with physiological parameters reflecting site-specific and site-independent absorption. Then, the simulation results were compared with the experimental data in literature. Simulation with different dissolution rates (>85% solubility, T 85%=15-180min) was performed to predict absorption (maximum concentration, C max and area under the concentration-time curve from time 0 to infinity, AUC0-inf) of the above model/virtual drugs (F a 3.81-80.14%). The results of this study indicated that the site-specific absorption and low F a magnified the effect of dissolution rate on C max and AUC0-inf. However, the oral absorption of model drugs was not sensitive to the change of gastric emptying rate from 0.1, 0.25, 0.5 to 1h. Based on the results of this study, we suggest that for BCS class III drug with high F a (about >80%), the biowaiver should extend to rapid dissolution (T 85%=30min), and 30% of F a as the boundary of intermediate permeability class (30%<F a<85%).

Pancreatic polypeptide stimulates mouse gastric motor activity through peripheral neural mechanisms.

Pancreatic polypeptide (PP) is supposed to be one of the major endogenous agonists of the neuropeptide Y4 receptor. Pancreatic polypeptide can influence gastrointestinal motility, acting mainly through vagal mechanisms, but whether PP acts directly on the stomach has not been explored yet. The aims of this study were to investigate the effects of PP on mouse gastric emptying, on spontaneous tone of whole stomach in vitro and to examine the mechanism of action. Gastric emptying was measured by red phenol method after i.p. PP administration (1-3nmol per mouse). Responses induced by PP (1-300mmolL-1 ) on gastric endoluminal pressure were analyzed in vitro in the presence of different drugs. Gastric genic expression of Y4 receptor was verified by RT-PCR. Pancreatic polypeptide dose-dependently increased non-nutrient liquid gastric emptying rate. In vitro, PP produced a concentration-dependent contraction that was abolished by tetrodotoxin, a neural blocker of Na+ voltage-dependent channels. The contractile response was significantly reduced by atropine, a muscarinic receptor antagonist, and by SR48968, an NK2 receptor antagonist, while it was potentiated by neostigmine, an inhibitor of acetylcholinesterase. The joint application of atropine and SR48968 fully abolished PP contractile effect. Reverse transcriptase-polymerase chain reaction analysis revealed the presence of Y4 receptor mRNA in mouse stomach with a greater expression in antrum than in fundus. The present findings demonstrate that exogenous PP stimulates mouse gastric motor activity, by acting directly on the stomach. This effect appears due to the activation of enteric excitatory neurons releasing acetylcholine and tachykinins.

Providing Oral Nutrition to Women in Labor: American College of Nurse-Midwives.

Historically, oral intake for women during labor has been limited to nothing by mouth or clear liquids only. These restrictions are based on the risk of aspiration during or after the administration of general anesthesia. While aspiration can be life threatening, older methods of anesthesia are rarely used in current intrapartum care, and evidence is inconclusive that withholding oral nutrition reduces the risk of gastric aspiration. Additionally, withholding oral nutrition may result in the development of ketosis and may potentially contribute to a woman's stress and dissatisfaction with the birth experience. The purpose of this Clinical Bulletin is to review the evidence related to this practice and provide recommendations to promote informed, shared decision making regarding oral intake during labor with women at low risk for gastric aspiration.

The Effect of Body Mass Index on Surgical Outcomes in Patients Undergoing Pancreatic Resection: A Systematic Review and Meta-Analysis.

Previous studies that investigated the association between body mass index (BMI) and pancreatectomy outcomes have produced conflicting conclusions. We conducted this meta-analysis to assess the association between them. We searched PubMed, EMBASE, and Cochrane Library databases up to December 28, 2014. Patients were divided into high-BMI group (BMI ≥ 25 kg/m) and normal-BMI group (BMI < 25 kg/m). Postoperative and intraoperative outcomes were evaluated. Meta-regression and subgroup analysis were performed to evaluate any factors accountable for the heterogeneity. Meta-analysis was performed using a random-effect model. We included 22 studies involving 8994 patients. Patients in the high-BMI group had significantly increased postoperative pancreatic fistula rate (odds ratio [OR],1.96; 95% confidence interval [CI], 1.43-2.67), delayed gastric emptying rate (OR, 1.62; 95% CI, 1.15-2.29), wound infection rate (OR, 1.43; 95% CI, 1.07-1.93), operation time (mean difference [MD],15; 95% CI, 13.40-16.60), blood loss (MD, 270.71; 95% CI, 248.93-292.49), and length of hospital stay (MD, 2.87; 95% CI, 1.51-4.24). For modest heterogeneity in postoperative pancreatic fistula, regional distribution tended to be the contributor. High BMI not only increased the surgical difficulty but also decreased the surgical safety for pancreatectomy.

Delayed gastric emptying in diabetic rats caused by decreased expression of cystathionine gamma lyase and H2 S synthesis: in vitro and in vivo studies.

This study aimed to evaluate the role of H2 S on gastric emptying rate (GER) and also to determine the effect of gastric distention on mRNA and protein expression of cystathionine β-lyase (CBS) and cystathionine γ-synthase (CSE) in diabetic-gastroparetic and normal rats. Adult normal rats intraperitoneally received either propargylglycine (PAG), L-cysteine or NaHS 30 min prior to GER marker (acetaminophen) to investigate H2 S involvement in GER and the same protocols were performed in diabetes-induced gastroparesis rats. The role of calcitonin gene related peptide (CGRP) neurons in the prokinetic effect of endogenous H2 S on GER was determined. The level of CBS and CSE expressions in response to gastric distention were also determined. The effect of H2 S on frequency and tension of spontaneous contractions of gastric smooth muscle strips was investigated. Our results showed that: (i) H2 S and L-cysteine increased GER in gastroparetic and normal rats. (ii) The increased levels of CSE expression in response to gastric distention in diabetic rats were lower than in normal rats. (iii) PAG inhibited the excitatory effect of capsaicin on GER and on tension of spontaneous contractions of strips. (iv) Hydrogen sulphide increased the frequency and tension of spontaneous contractions of gastric strip muscles in normal and diabetic rats. The results showed that delayed GER in diabetic rats can be due to down-regulation of H2 S biosynthesis enzyme, CSE and suggested that a potential prokinetic role for H2 S to treat the delayed gastric emptying in diabetic patients.

Model-based dietary optimization for late-stage, levodopa-treated, Parkinson's disease patients.

Levodopa has been the gold standard for Parkinson’s disease treatment for more than 40 years. Its bioavailability is hindered by dietary amino acids, leading to fluctuations in the motor response particularly in late-stage (stage 3 and 4 on Hoehn and Yahr scale) patients. The routine dietary intervention consists of low-protein (<0.8 g/kg) diets or the redistribution of daily protein allowance to the last meal. Computational modeling was used to examine the fluctuation of gastrointestinal levodopa absorption under consideration of the diet by (i) identifying the group of patients that could benefit from dietary interventions, (ii) comparing existing diet recommendations for their impact on levodopa bioavailability, and (iii) suggesting a mechanism-based dietary intervention. We developed a multiscale computational model consisting of an ordinary differential equations-based advanced compartmentalized absorption and transit (ACAT) gut model and metabolic genome-scale small intestine epithelial cell model. We used this model to investigate complex spatiotemporal relationship between dietary amino acids and levodopa absorption. Our model predicted an improvement in bioavailability, as reflected by blood concentrations of levodopa with protein redistribution diet by 34% compared with a low-protein diet and by 11% compared with the ante cibum (a.c.) administration. These results are consistent with the reported better outcome in late-stage patients. A systematic analysis of the effect of different amino acids in the diet suggested that a serine-rich diet could improve the bioavailability by 22% compared with the a.c. administration. In addition, the slower gastric emptying rate in PD patients exacerbates the loss of levodopa due to competition. Optimizing dietary recommendations in quantity, composition, and intake time holds the promise to improve levodopa efficiency and patient’s quality of life based on highly detailed, mechanistic models of gut physiology endowed with improved extrapolative properties, thus paving the way for precision medical treatment.

Clinical effect of low-frequency electrical pulse therapy combined with α-lipoic acid on diabetic gastroparesis in elderly patients with type 2 diabetes

Objective To investigate the clinical effect of low-frequency electrical pulse therapy combined with α-lipoic acid on diabetic gastroparesis in elderly patients with type 2 diabetes. Methods A total of 65 patients diagnosed as diabetic gastroparesis were selected from our hospital and divided into three groups according to random number table: the control group(n=23, the α-lipoic acid treatment), the conventional treatment group(n=16), and the experimental group(n=26, treating with α-lipoic acid combined with low-frequency electrical pulse therapy). All patients received the conventional diabetic therapy. Clinical effects, gastric emptying rate and serum gastrin(GAS) and fasting blood glucose levels were compared before versus after treatment among the three groups. Results The cure and total effective rates were higher in the experimental group than in the control group 〔46.15%(12 cases) vs. 30.43%(7 cases), 80.76%(20 cases) vs. 65.21%(15 cases), χ2=0.867, P<0.05〕. There were significant differences in gastric emptying rate, serum gastrin and fasting plasma glucose levels among the 3 treatment groups before versus after treatment. And the gastric emptying rate and serum gastrin level were better improved in the experimental groups compared with the conventional treatment and control groups. Conclusions The low-frequency electrical pulse therapy combined with α-lipoic acid has a significant clinical efficacy, which can improve clinical effects, promote gastric emptying, decrease fasting plasma glucose levels in elderly patients with type 2 diabetes. Key words: Diabetes mellitus, type 2; Thioctic acid; Pulse therapy, drug

A Mechanistic Model of Intermittent Gastric Emptying and Glucose-Insulin Dynamics following a Meal Containing Milk Components.

To support decision-making around diet selection choices to manage glycemia following a meal, a novel mechanistic model of intermittent gastric emptying and plasma glucose-insulin dynamics was developed. Model development was guided by postprandial timecourses of plasma glucose, insulin and the gastric emptying marker acetaminophen in infant calves fed meals of 2 or 4 L milk replacer. Assigning a fast, slow or zero first-order gastric emptying rate to each interval between plasma samples fit acetaminophen curves with prediction errors equal to 9% of the mean observed acetaminophen concentration. Those gastric emptying parameters were applied to glucose appearance in conjunction with minimal models of glucose disposal and insulin dynamics to describe postprandial glycemia and insulinemia. The final model contains 20 parameters, 8 of which can be obtained by direct measurement and 12 by fitting to observations. The minimal model of intestinal glucose delivery contains 2 gastric emptying parameters and a third parameter describing the time lag between emptying and appearance of glucose in plasma. Sensitivity analysis of the aggregate model revealed that gastric emptying rate influences area under the plasma insulin curve but has little effect on area under the plasma glucose curve. This result indicates that pancreatic responsiveness is influenced by gastric emptying rate as a consequence of the quasi-exponential relationship between plasma glucose concentration and pancreatic insulin release. The fitted aggregate model was able to reproduce the multiple postprandial rises and falls in plasma glucose concentration observed in calves consuming a normal-sized meal containing milk components.