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Effects of intraduodenal coadministration of lauric acid and leucine on gut motility, plasma cholecystokinin, and energy intake in healthy men.
McVeay, C, Steinert, RE, Fitzgerald, PCE, Ullrich, SS, Horowitz, M, Feinle-Bisset, C
American journal of physiology. Regulatory, integrative and comparative physiology. 2020;(4):R790-R798
Abstract
The fatty acid, lauric acid (C12), and the amino acid, leucine (Leu) stimulate gut hormones, including CCK, associated with suppression of energy intake. In our recent study, intraduodenal infusion of a combination of C12 and l-tryptophan, at loads that individually did not affect energy intake, reduced energy intake substantially, associated with much greater stimulation of CCK. We have now investigated whether combined administration of C12 and Leu would enhance the intake-suppressant effects of each nutrient, when given at loads that each suppress energy intake individually. Sixteen healthy, lean males (age: 23 ± 2 yr) received, in randomized, double-blind fashion, 90-min intraduodenal infusions of control (saline), C12 (0.4 kcal/min), Leu (0.45 kcal/min), or C12+Leu (0.85 kcal/min). Antropyloroduodenal pressures were measured continuously and plasma CCK at 15-min intervals, and energy intake from a standardized buffet-meal, consumed immediately postinfusion, was quantified. All nutrient infusions stimulated plasma CCK compared with control (P < 0.05). Moreover, C12 and C12+Leu stimulated CCK compared with Leu (P < 0.05) (mean concentration, pmol/L; control: 2.3 ± 0.3, C12: 3.8 ± 0.3, Leu: 2.7 ± 0.3, and C12+Leu: 4.0 ± 0.4). C12+Leu, but not C12 or Leu, stimulated pyloric pressures (P < 0.05). C12+Leu and C12 reduced energy intake (P < 0.05), and there was a trend for Leu to reduce (P = 0.06) energy intake compared with control, with no differences between the three nutrient treatments (kcal; control: 1398 ± 84, C12: 1226 ± 80, Leu: 1260 ± 92, and C12+Leu: 1208 ± 83). In conclusion, combination of C12 and Leu, at the loads given, did not reduce energy intake beyond their individual effects, possibly because maximal effects had been evoked.
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Heated fennel therapy promotes the recovery of gastrointestinal function in patients after complex abdominal surgery: A single-center prospective randomized controlled trial in China.
Chen, B, He, Y, Xiao, Y, Guo, D, Liu, P, He, Y, Sun, Q, Jiang, P, Liu, Z, Liu, Q
Surgery. 2020;(5):793-799
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Abstract
BACKGROUND Postoperative gastrointestinal dysfunction remains a major determinant of the duration of stay after complex abdominal surgery. This study was performed to evaluate the effectiveness of heated fennel therapy in accelerating the recovery of gastrointestinal function. METHODS This surgeon-blinded, prospective randomized controlled study included 381 patients with hepatobiliary, pancreatic, and gastric tumors who were divided into 2 groups. The patients in the experimental groups received heated fennel therapy, and those in the control groups received heated rice husk therapy. We compared the baseline characteristics, time to first postoperative flatus and defecation, fasting time, duration of postoperative hospital stay, grading of abdominal pain, classification of abdominal distension, inflammatory markers, and nutritional status indicators. RESULTS The time to first flatus and first defecation and the fasting time were statistically significantly less in the heated fennel therapy group than those in the control groups (P < .05 each); and abdominal distension was also relieved in the experimental groups (P < .001). Heated fennel therapy had no obvious beneficial effect on inflammatory markers but improved the serum albumin (ALB) level of the patients at postop day 9 (P < .001). Among the patients with alimentary tract reconstruction, those in the heated fennel therapy group had a clinically important, lesser hospital stay than those in the control group (9.2 5 ± 5.1 versus 11.1 ± 6.4; P < .023). CONCLUSION Heated fennel therapy facilitated the gastrointestinal motility function of patients early postoperatively.
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Gastrointestinal pharmacology: practical tips for the esophagologist.
Scarpignato, C, Sloan, JA, Wang, DH, Hunt, RH
Annals of the New York Academy of Sciences. 2020;(1):90-107
Abstract
Gastroesophageal reflux disease (GERD) is primarily a motor disorder, and its pathogenesis is multifactorial. As a consequence, treatment should be able to address the underlying pathophysiology. Proton pump inhibitors (PPIs) are the mainstay of medical therapy for GERD, but these drugs only provide the control of symptoms and lesions without curing the disease. However, continuous acid suppression with PPIs is recommended for patients with Barrett's esophagus because of their potential chemopreventive effects. In addition to the antisecretory activity, these compounds display several pharmacological properties, often overlooked in clinical practice. PPIs can indeed affect gastric motility, exert a mucosal protective effect, and an antioxidant, anti-inflammatory, and antineoplastic activity, also protecting cancer cells from developing chemo- or radiotherapeutic resistance. Even in the third millennium, current pharmacologic approaches to address GERD are limited. Reflux inhibitors represent a promise unfulfilled, effective and safe prokinetics are lacking, and antidepressants, despite being effective in selected patients, give rise to adverse events in a large proportion of them. While waiting for new drug classes (like potassium-competitive acid blockers), reassessing old drugs (namely alginate-containing formulations), and paving the new avenue of esophageal mucosal protection are, at the present time, the only reliable alternatives to acid suppression.
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The influence of gastric motility on the intraluminal behavior of fosamprenavir.
Braeckmans, M, Brouwers, J, Masuy, I, Servais, C, Tack, J, Augustijns, P
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2020;:105117
Abstract
In fasting conditions, the gastrointestinal system contracts according to the interdigestive migrating motor complex (MMC), in which phases of quiescence (MMC phase I) alternate with phases of medium (MMC phase II) to very strong (MMC phase III) contractions. The time of drug intake relative to this cyclic motility pattern may cause variations in formulation behavior. To explore this hypothesis, a cross-over study was performed in healthy volunteers with an immediate release tablet of fosamprenavir (Telzir) which was administered in either MMC phase I or MMC phase II, as determined by high-resolution manometry. In the intestinal tract, fosamprenavir is rapidly hydrolyzed to the active compound amprenavir by alkaline phosphatases. Drug concentrations of both prodrug and drug were determined in the stomach and duodenum and linked to simultaneously assessed systemic concentrations. In 5 out of 6 healthy volunteers, the gastric release of fosamprenavir and the systemic uptake of amprenavir were affected by the MMC phase in which the tablet was administered. The intragastric disintegration of the tablet was faster and less variable after administration in MMC phase II, resulting in faster and less variable uptake of amprenavir in the systemic circulation. Mean plasma tmax values were 157 (±72.0) and 73.3 (±27.3) min after administration in MMC phase I and MMC phase II, respectively. The study clearly identified the time of oral drug intake relative to the interdigestive motility pattern as a possible source of variation in gastrointestinal drug behavior and absorption.
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The impact of chewing gum on postoperative bowel activity and postoperative pain after total laparoscopic hysterectomy.
Turkay, Ü, Yavuz, A, Hortu, İ, Terzi, H, Kale, A
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 2020;(5):705-709
Abstract
We aimed to investigate the effects of chewing gum on bowel activity and postoperative pain in patients undergoing laparoscopic hysterectomy. Patients were randomised into two groups (n = 58, study; n = 51, control). In the study group, patients started chewing sugarless gum every 2 h for 15 min, beginning at the second postoperative hour. The control group did not chew gum, and they received standard postoperative care. Both groups were compared primarily in terms of the amount of time until the first bowel movement, the time of the first passage of flatus and the time of first defaecation. The amount of time until the first bowel movement, the time of the first passage of flatus and the time of the first defaecation were found to be significantly shorter in the chewing gum group (p < .001). The amount of postoperative analgesics that were needed and VAS scores at 6-hours and 24-hours postoperatively, were found to be lower in the study group than in the control group (p < .001). Chewing gum was found to have beneficial effects on bowel motility and postoperative pain in patients undergoing laparoscopic hysterectomy. This affordable and simple method could be recommended to patients after total laparoscopic hysterectomy.Impact statementWhat is already known on this subject? Postoperative gastrointestinal dysfunction remains a source of morbidity and the major determinant of length of stay after abdominal operation. The mechanism of enhanced recovery from postoperative gastrointestinal dysfunction with the help of chewing gum is believed to be the cephalic-vagal stimulation of digestion which increases the promotability of neural and humoral factors that act on different parts of the gastrointestinal tract.What do the results of this study add? The findings of previous randomised controlled studies have been inconsistent regarding the effect of chewing gum on postoperative bowel function following abdominal gynecological surgery. In this randomised prospective study, we found that chewing gum early in the postoperative period after total laparoscopic hysterectomy hastened time to bowel motility and flatus. To our knowledge this is the first study of the impact of chewing gum on bowel motility after total laparoscopic hysterectomy.What are the implications of these findings for clinical practice and/or further research? Chewing gum early in the postoperative period following laparoscopic hysterectomy hastens time to bowel motility and flatus. The use of chewing gum is a simple and cheap strategy for promoting the recovery of gastrointestinal functions.
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An increasingly complex view of intestinal motility.
Rao, M
Nature reviews. Gastroenterology & hepatology. 2020;(2):72-73
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GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals.
Gasbjerg, LS, Helsted, MM, Hartmann, B, Sparre-Ulrich, AH, Veedfald, S, Stensen, S, Lanng, AR, Bergmann, NC, Christensen, MB, Vilsbøll, T, et al
The Journal of clinical endocrinology and metabolism. 2020;(3)
Abstract
CONTEXT The actions of both endogenous incretin hormones during a meal have not previously been characterized. OBJECTIVE Using specific receptor antagonists, we investigated the individual and combined contributions of endogenous glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism, energy expenditure, and gallbladder motility. DESIGN Randomized, double-blinded, placebo-controlled, crossover design. SETTING On four separate days, four liquid mixed meal tests (1894 kJ) over 270 minutes (min). PATIENTS OR OTHER PARTICIPANTS Twelve healthy male volunteers. INTERVENTIONS Infusions of the GIP receptor antagonist GIP(3-30)NH2 (800 pmol/kg/min), the GLP-1 receptor antagonist exendin(9-39)NH2 (0-20 min: 1000 pmol/kg/min; 20-270 min: 450 pmol/kg/min), GIP(3-30)NH2+exendin(9-39)NH2, or placebo/saline. MAIN OUTCOME MEASURE Baseline-subtracted area under the curve (bsAUC) of C-peptide. RESULTS Infusion of GIP(3-30)NH2+exendin(9-39)NH2 significantly increased plasma glucose excursions (bsAUC: 261 ± 142 mmol/L × min) during the liquid mixed meals compared with GIP(3-30)NH2 (180 ± 141 mmol/L × min; P = 0.048), exendin(9-39)NH2 (171 ± 114 mmol/L × min; P = 0.046), and placebo (116 ± 154 mmol/L × min; P = 0.015). Correspondingly, C-peptide:glucose ratios during GIP(3-30)NH2+exendin(9-39)NH2 infusion were significantly lower than during GIP(3-30)NH2 (P = 0.0057), exendin(9-39)NH2 (P = 0.0038), and placebo infusion (P = 0.014). GIP(3-30)NH2 resulted in significantly lower AUCs for glucagon than exendin(9-39)NH2 (P = 0.0417). Gallbladder ejection fraction was higher during GIP(3-30)NH2 compared with placebo (P = 0.004). For all interventions, energy expenditure and respiratory quotient were similar. CONCLUSIONS Endogenous GIP and GLP-1 lower postprandial plasma glucose excursions and stimulate insulin secretion but only endogenous GIP affects gallbladder motility. The two incretin hormones potentiate each other's effects in the control of postprandial glycemia in healthy men.
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Manometric demonstration of duodenal/jejunal motor function consistent with the duodenal brake mechanism.
Dent, J, Deloose, E, Dinning, P, Corsetti, M, Rommel, N, Tack, J, Wiklendt, L, Papageorgiou, AW, Arkwright, JW
Neurogastroenterology and motility. 2020;(10):e13835
Abstract
BACKGROUND High-resolution manometric studies below the stomach are rare due to technical limitations of traditional manometry catheters. Consequently, specific motor patterns and their impact on gastric and small bowel function are not well understood. High-resolution manometry was used to record fed-state motor patterns in the antro-jejunal segment and relate these to fasting motor function. METHODS Antro-jejunal pressures were monitored in 15 healthy females using fiber-optic manometry (72 sensors at 1 cm intervals) before and after a high-nutrient drink. KEY RESULTS Postprandial motility showed a previously unreported transition point 18.8 cm (range 13-28 cm) beyond the antro-pyloric junction. Distal to the transition, a zone of non-propagating, repetitive pressure events (11.5 ± 0.5 cpm) were dominant in the fed state. We have named this activity, the duodeno-jejunal complex (DJC). Continuous DJC activity predominated, but nine subjects also exhibited intermittent clusters of DJC activity, 7.4 ± 4.9/h, lasting 1.4 ± 0.55 minutes, and 3.8 ± 1.2 minutes apart. DJC activity was less prevalent during fasting (3.6 ± 3.3/h; P = .04). 78% of fed and fasting state propagating antro-duodenal pressure events terminated proximally or at the transition point and were closely associated with DJC clusters. CONCLUSIONS AND INFERENCES High-resolution duodeno-jejunal manometry revealed a previously unrecognized transition point and associated motor pattern extending into the jejunum, consistent with the duodenal brake previously identified fluoroscopically. Timing suggests DJC activity is driven by chyme stimulating duodenal mucosal chemosensors. These findings indicate that the duodenum and proximal jejunum consists of two major functional motor regions.
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The effect of gum chewing on the return of bowel motility after planned cesarean delivery: a randomized controlled trial.
Altraigey, A, Ellaithy, M, Atia, H, Abdelrehim, W, Abbas, AM, Asiri, M
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2020;(10):1670-1677
Abstract
Objective: To endorse the impact of chewing gum on the intestinal functions' restoration, hospital stay and gastrointestinal complications after planned cesarean delivery (CD).Methods: Women aged between 20 and 35 years scheduled for planned CD; either first or repeated, with term, singleton, viable and healthy pregnancy at obstetrics and gynecology department, Armed Forces Hospital Southern Region, Khamis Mushayt, Saudi Arabia were invited to participate and randomized if eligible into three groups. The first group chewed sugar-free gum 2 h after recovery at least for half an hour and at 2-h interval during daytime. The second group received oral fluids 6 h postoperatively, while the third group was the control group. The primary outcome measure was the time to first passage of stool. The secondary outcomes included the time of the first passage of flatus, the first hearing of normal intestinal sounds, the duration of hospital stay the duration of parenteral therapy by intravenous fluids, the time of initiating breast-feeding and the cost of hospital stay. The study was prospectively registered at ClinicalTrials.gov (NCT02386748).Results: The study included 372 women randomized into three groups (124 women in each group). Chewing gum significantly improved intestinal recovery with faster onset of bowel movements, first audible intestinal sounds, passage of flatus and passage of stool (p = .0001). It was associated with significantly shorter duration of hospital stay and parenteral therapy duration (p = .0001). Abdominal distension, vomiting and ileus postoperatively were significantly higher in nonchewing gum groups. Neither paralytic ileus nor side effects were recorded with gum use.Conclusion: Chewing gum, within 2 h postoperatively, is a simple, safe and well-tolerated intervention that can boost rapid intestinal recovery and shorten hospital stay after planned cesarean deliveries.
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Promotion of Regular Oesophageal Motility to Prevent Regurgitation and Enhance Nutrition Intake in Long-Stay ICU Patients. A Multicenter, Phase II, Sham-Controlled, Randomized Trial: The PROPEL Study.
Heyland, DK, Marquis, F, Lamontagne, F, Albert, M, Turgeon, AF, Khwaja, KA, Garland, A, Hall, R, Chapman, MG, Kutsiogannis, DJ, et al
Critical care medicine. 2020;(3):e219-e226
Abstract
OBJECTIVES To evaluate the effect of esophageal stimulation on nutritional adequacy in critically ill patients at risk for enteral feeding intolerance. DESIGN A multicenter randomized sham-controlled clinical trial. SETTING Twelve ICUs in Canada. PATIENTS We included mechanically ventilated ICU patients who were given moderate-to-high doses of opioids and expected to remain alive and ventilated for an additional 48 hours and who were receiving enteral nutrition or expected to start imminently. INTERVENTIONS Patients were randomly assigned 1:1 to esophageal stimulation via an esophageal stimulating catheter (E-Motion Tube; E-Motion Medical, Tel Aviv, Israel) or sham treatment. All patients were fed via these catheters using a standardized feeding protocol. MEASUREMENTS AND MAIN RESULTS The co-primary outcomes were proportion of caloric and protein prescription received enterally over the initial 7 days following randomization. Among 159 patients randomized, the modified intention-to-treat analysis included 155 patients: 73 patients in the active treatment group and 82 in the sham treatment group. Over the 7-day study period, the percent of prescribed caloric intake (± SE) received by the enteral route was 64% ± 2 in the active group and 65% ± 2 in sham patients for calories (difference, -1; 95% CI, -8 to 6; p = 0.74). For protein, it was 57% ± 3 in the active group and 60% ± 3 in the sham group (difference, -3; 95% CI, -10 to 3; p = 0.30). Compared to the sham group, there were more serious adverse events reported in the active treatment group (13 vs 6; p = 0.053). Clinically important arrhythmias were detected by Holter monitoring in 36 out of 70 (51%) in the active group versus 22 out of 76 (29%) in the sham group (p = 0.006). CONCLUSIONS Esophageal stimulation via a special feeding catheter did not improve nutritional adequacy and was associated with increase risk of harm in critically ill patients.