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1.
Gastrointestinal Dysfunction in Parkinson's Disease.
Safarpour, D, Sharzehi, K, Pfeiffer, RF
Drugs. 2022;(2):169-197
Abstract
There has been exponential growth in the awareness and understanding of gastrointestinal (GI) dysfunction in Parkinson's disease (PD) over the past 3 decades. The clinical features of GI dysfunction in PD have been clearly identified and innovative research has demonstrated the presence of pathology within the enteric nervous system (ENS) in individuals with PD, leading to suggestions that the GI system may be ground zero for the genesis and the portal of entry of PD pathology, which then ascends via the vagus nerve to the central nervous system (CNS). This theory, as well as the more recent recognition of the association of PD with dysbiosis within the gut microbiota, has been the object of intense study and scrutiny. Since most PD medications are absorbed through the GI system, the need for better understanding of changes within the GI tract that may potentially affect the pattern of response to medications has become evident. In this review, current knowledge of the pathophysiology of changes within the GI tract and the gut microbiome of individuals with PD, including changes that occur with progression of the disease, will be addressed. We focus on common clinical GI problems in PD that can arise from different segments of the GI tract. Relevant diagnostic evaluations and treatment options for each of these problems will be reviewed.
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Gastric accommodation: Physiology, diagnostic modalities, clinical relevance, and therapies.
Febo-Rodriguez, L, Chumpitazi, BP, Sher, AC, Shulman, RJ
Neurogastroenterology and motility. 2021;(12):e14213
Abstract
BACKGROUND Gastric accommodation is an essential gastric motor function which occurs following ingestion of a meal. Impaired gastric fundic accommodation (IFA) is associated with dyspeptic symptoms. Gastric accommodation is mediated by the vagal pathway with several important physiologic factors such as duodenal nutrient feedback playing a significant role. IFA has been described as a pathophysiologic factor in several gastrointestinal disorders including functional dyspepsia, diabetic gastropathy, post-Nissen fundoplication, postsurgical gastrectomy, and rumination syndrome. Modalities for gastric accommodation assessment include gastric barostat, intragastric meal distribution via scintigraphy, drinking tests (eg, water load), SPECT, MRI, 2D and 3D ultrasound, and intragastric high-resolution manometry. Several treatment options including sumatriptan, buspirone, tandospirone, ondansetron, and acotiamide may improve symptoms by increasing post-meal gastric volume. PURPOSE Our aim is to provide an overview of the physiology, diagnostic modalities, and therapies for IFA. A literature search was conducted on PubMed, Google Scholar, and other sources to identify relevant studies available until December 2020. Gastric accommodation is an important gastric motor function which if impaired, is associated with several upper gastrointestinal disorders. There are an increasing number of gastric accommodation testing modalities; however, each has facets which warrant consideration. Evidence regarding potentially effective therapies for IFA is growing.
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3.
Effect of obesity on gastrointestinal transit, pressure and pH using a wireless motility capsule.
Steenackers, N, Wauters, L, Van der Schueren, B, Augustijns, P, Falony, G, Koziolek, M, Lannoo, M, Mertens, A, Meulemans, A, Raes, J, et al
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2021;:1-8
Abstract
BACKGROUND Despite the increasing prevalence and medical burden of obesity, the understanding of gastrointestinal physiology in obesity is scarce, which hampers drug development. AIM: To investigate the effect of obesity and food intake on gastrointestinal transit, pressure and pH. MATERIAL AND METHODS An exploratory cross-sectional study using a wireless motility capsule (SmartPill©) was performed in 11 participants with obesity and 11 age- and gender-matched participants with normal weight (group) in fasted and fed state (visit). During the first visit, the capsule was ingested after an overnight fast. During a second visit, the capsule was ingested after a nutritional drink to simulate fed state. Linear mixed models were constructed to compare segmental gastrointestinal transit, pressure and pH between groups (obesity or control) and within every group (fasted or fed). RESULTS Food intake slowed gastric emptying in both groups (both P < 0.0001), though food-induced gastric contractility was higher in participants with obesity compared to controls (P = 0.02). In the small intestine, a higher contractility (P = 0.001), shorter transit (P = 0.04) and lower median pH (P = 0.002) was observed in participants with obesity compared to controls. No differences were observed for colonic measurements. CONCLUSION Obesity has a profound impact on gastrointestinal physiology, which should be taken into account for drug development.
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4.
Gastric Sensory and Motor Functions and Energy Intake in Health and Obesity-Therapeutic Implications.
Cifuentes, L, Camilleri, M, Acosta, A
Nutrients. 2021;(4)
Abstract
Sensory and motor functions of the stomach, including gastric emptying and accommodation, have significant effects on energy consumption and appetite. Obesity is characterized by energy imbalance; altered gastric functions, such as rapid gastric emptying and large fasting gastric volume in obesity, may result in increased food intake prior to reaching usual fullness and increased appetite. Thus, many different interventions for obesity, including different diets, anti-obesity medications, bariatric endoscopy, and surgery, alter gastric functions and gastrointestinal motility. In this review, we focus on the role of the gastric and intestinal functions in food intake, pathophysiology of obesity, and obesity management.
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5.
Pharmacological effects of Pugionium cornutum (L.) Gaertn. extracts on gastrointestinal motility are partially mediated by quercetin.
Su, C, Li, H, Chen, B, Li, C, Zhang, C, Xu, L, Lan, M, Shen, Y
BMC complementary medicine and therapies. 2021;(1):223
Abstract
BACKGROUND The majority of global population suffer from various functional gastrointestinal disorders. Pugionium cornutum (L.) Gaertn. (PCG) is used to relieve indigestive symptoms in traditional Chinese medicine. However, little is known about the effects of bioactive components from PCG extracts on gastrointestinal motility. METHODS Crude ethanol extract of PCG (EEP) was prepared from Pugionium cornutum (L.) Gaertn. Different solvents were used to prepare fine extracts from EEP, including water extract of PCG (WEP), petroleum ether extract of PCG (PEEP), dichloromethane extract of PCG (DEP) and ethyl acetate extract of PCG (EAEP). Smooth muscle cell model and colonic smooth muscle stripe model were used to test the bioactive effects and mechanisms of different PCG extracts on contraction and relaxation. Diverse chromatographic methods were used to identify bioactive substances from PCG extracts. RESULTS EEP was found to promote the relaxation of gastric smooth muscle cell and inhibit the contraction of colonic smooth muscle strip. Among the fractions of EEP, EAEP mainly mediated the relaxation effect by stimulating intracellular calcium influx. Further evidences revealed that EAEP was antagonistic to acetylcholine. In addition, COX and NO-GC-PKC pathways may be also involved in EAEP-mediated relaxation effect. Quercetin was identified as a bioactive compound from PCG extract for the relaxation effect. CONCLUSION Our research supports the notion that PCG extracts promote relaxation and inhibits contraction of gastrointestinal smooth muscle at least partially through the effect from quercetin.
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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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7.
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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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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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.
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10.
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.