Nobiletin, an active component of Wenyang Yiqi formula, alleviates constipation associated depression through targeting MAPT to inhibit the MAPK signaling pathway.

BACKGROUND: Slow transit constipation (STC) is a common gastrointestinal disorder that is often accompanied by depression. Nobiletin is a natural compound that has been shown to have anti-inflammatory and anti-depressant effects. PURPOSE: To study the effects of nobiletin extracted from Wenyang Yiqi Formula 19 (WYF) on STC accompanied by depression and the related mechanism in STC mouse models. METHODS: In this study, the effects of nobiletin on STC accompanied by depression were investigated in both an STC animal model and an in vitro study. The animal model was induced by loperamide, and the in vitro study used Interstitial cells of Cajal (ICCs) isolated from STC mice. The efficacy of nobiletin was assessed by comparing various parameters, including stool particle counts, moisture content, intestinal propulsive rate, colon histopathology, microtubule-associated protein-tau (MAPT) expression in colon tissue, serum levels of TNF-α, IL-1ß, IL-6, IFN-γ, and the levels of MAPK pathway-related proteins among three experimental groups. RESULTS: Nobiletin treatment significantly improved stool particle counts, moisture content, intestinal propulsive rate, and colon histopathology in the STC animal model. Nobiletin also decreased MAPT expression in colon tissue and serum levels of TNF-α, IL-1ß, IL-6, IFN-γ, and the levels of MAPK pathway-related proteins. In the in vitro study, nobiletin treatment reversed the increased cell proliferation and cell apoptosis observed in ICC isolated from the STC model. CONCLUSION: The findings of this study indicate that nobiletin exhibits promising therapeutic potential in addressing STC accompanied by depression. This potential may be attributed to its ability to regulate the function of ICC by targeting MAPT.

Transcutaneous Electrical Acustimulation Improves Constipation Symptoms and Accelerates Colonic Transit in Patients With Slow Transit Constipation Through Autonomic Mechanism.

OBJECTIVES: Nearly half of patients with slow transit constipation (STC) are not completely satisfied with their traditional remedies. We aimed to evaluate the therapeutic value and possible involved mechanism of transcutaneous electrical acustimulation (TEA) at ST36 in patients with STC. MATERIALS AND METHODS: Seventy patients with STC were randomly divided into TEA (n = 35) and sham-TEA (n = 35) to undergo a two-week treatment with TEA at ST36 or sham point. After the two-week treatment, 18 patients from each group randomly underwent a few physiological tests, including the electrocardiogram (ECG), anorectal manometry, colon transit test, and blood drawing. After a two-week washout period, TEA was performed in both groups for two weeks. RESULTS: Spontaneous bowel movements per week were increased, and scores of constipation symptoms were decreased, after a two-week blind TEA but not sham-TEA, which were sustained after a two-week washout period. Improvement in quality of life and psychologic states also was observed with blind TEA treatment. Mechanistically, the two-week blind TEA accelerated colon transit assessed by barium strip excretion rate (the effect was sustained after a two-week washout period), enhanced vagal nerve activity evaluated by the spectral analysis of heart rate variability derived from the ECG, and decreased circulating vasoactive intestinal peptide. CONCLUSIONS: Noninvasive TEA relieves constipation and improves quality of life and psychologic states in patients with STC, and the effects are sustained for ≥two weeks. The therapeutic effects of TEA may be attributed to the acceleration of colon transit and decrease of vasoactive intestinal peptide mediated through the vagal mechanism.

[Research progress of mechanisms of acupuncture in treating slow transit constipation].

As an important part of the traditional Chinese medicine treatment system, acupuncture therapy has been used in the treatment of slow transit constipation (STC) for a long time and has achieved good clinical effects. This article reviews research on the effects of acupuncture therapy on STC published in recent years, focusing on the mechanism of acupuncture on the enteric nervous system, neurotransmitters, interstitial cells of Cajal, smooth muscle cells, gastrointestinal motility, psychological factors and intestinal microecology of STC, in order to provide reference for the clinical application and mechanism research of acupuncture in the treatment of STC in the future.

Zhizhu decoction alleviates slow transit constipation by regulating aryl hydrocarbon receptor through gut microbiota.

CONTEXT: Slow transit constipation (STC), the most common type of constipation, seriously affects the life of patients. Zhizhu decoction (ZZD), a traditional Chinese medicine compound, has is effective against functional constipation, but the mechanism is still unclear. OBJECTIVE: This research explores the mechanism of ZZD on STC from the perspective of metabolomics and gut microbiota. MATERIALS AND METHODS: Fifty-four C57BL/6 mice were randomly divided into six groups (n = 9): control (control); STC (model); positive control (positive); low-dose (5 g/kg; L-ZZD), medium-dose (10 g/kg; M-ZZD), and high-dose (20 g/kg; H-ZZD) ZZD treatment. Following treatment of mice with ZZD for two weeks, the changes in intestinal motility, colon histology, intestinal neurotransmitters, and aryl hydrocarbon receptor (AHR) pathway determined the effects of ZZD on the pathophysiology of STC. LC-MS targeting serum metabolomics was used to analyze the regulation of ZZD on neurotransmitters, and 16S rRNA high-throughput sequencing was used to detect the regulation of the gut microbiome. RESULTS: ZZD had the highest content of naringin (6348.1 mg/L), and could significantly increase the 24 h defecations (1.10- to 1.42-fold), fecal moisture (1.14-fold) and intestinal transport rate (1.28-fold) of STC mice, increased the thickness of the mucosal and muscular tissue (1.18- to 2.16-fold) and regulated the neurotransmitters in the colon of STC mice. Moreover, ZZD significantly activated the AHR signaling pathway, and also affected the composition of gut microbiota in STC mice. DISCUSSION AND CONCLUSIONS: The beneficial effect and the possible mechanism of ZZD on STC could provide a theoretical basis for the broader clinical application of ZZD.

Clinical translation of advanced colonic drug delivery technologies.

Targeted drug delivery to the colon offers a myriad of benefits, including treatment of local diseases, direct access to unique therapeutic targets and the potential for increasing systemic drug bioavailability and efficacy. Although a range of traditional colonic delivery technologies are available, these systems exhibit inconsistent drug release due to physiological variability between and within individuals, which may be further exacerbated by underlying disease states. In recent years, significant translational and commercial advances have been made with the introduction of new technologies that incorporate independent multi-stimuli release mechanisms (pH and/or microbiota-dependent release). Harnessing these advanced technologies offers new possibilities for drug delivery via the colon, including the delivery of biopharmaceuticals, vaccines, nutrients, and microbiome therapeutics for the treatment of both local and systemic diseases. This review details the latest advances in colonic drug delivery, with an emphasis on emerging therapeutic opportunities and clinical technology translation.

Effects of Automatic Abdominal Massage Device in Treatment of Chronic Constipation Patients: A Prospective Study.

BACKGROUND AND AIM: Manual abdominal massage has been shown to effectively treat slow-transit constipation, but it is labor-intensive. To offer an alternative treatment option for constipation, the Bamk-001 automatic abdominal massage device was developed. The aim of this study was to assess the effect of the Bamk-001 device on symptom profiles and colon transit time (CTT) in patients with chronic constipation. METHODS: Thirty-seven patients with chronic functional constipation diagnosed using the Rome IV criteria were enrolled prospectively from December 2018 to February 2019. All patients received device-assisted automatic abdominal massage for 15 min twice daily, once in the morning before breakfast and once at night, for 14 days. CTT was measured before and at the end of the study period. Slow-transit constipation and very-slow-transit constipation were defined as CTT ≥ 48 h and ≥ 72 h, respectively. Patients' symptom profiles regarding overall defecation satisfaction and device-related adverse events were analyzed. RESULTS: Among the 37 patients, the mean age was 40.1 ± 11.8, and 5.4% (n = 2) were men. The Bamk-001 device significantly improved CTT from 54.0 (33.6-75.6) to 28.8 (18.0-52.8) h (p = 0.001) in patients with chronic constipation. In subgroup analysis, CTT improved significantly from 54.0 (33.6-75.6) to 28.8 (18.0-52.8) h (p = 0.003) and from 88.2 (74.4-124.8) to 45.6 (27.3-74.1) h (p = 0.005) in the slow-transit and very-slow-transit constipation groups, respectively (p = 0.001). Moreover, all patient symptoms were alleviated after treatment. No serious adverse events were reported. CONCLUSION: The Bamk-001 automatic abdominal massage device showed significant care efficacy, including the improvement in CTT and symptom profiles in patients with slow-transit constipation. The use of an automatic abdominal massage device as an adjunct in the management of constipation is a potentially beneficial intervention for patients with slow-transit constipation.

Application effect of catgut-embedding therapy combined with minimally invasive surgery for slow transit constipation: A protocol for systematic review and meta-analysis.

BACKGROUND: Catgut-embedding therapy combined with minimally invasive surgery has been used for treating slow transit constipation (STC) widely. However, the application effect of catgut-embedding therapy combined with minimally invasive surgery for STC are unclear. This study aims to evaluate the application effect of catgut-embedding therapy combined with minimally invasive surgery for STC. METHODS: Randomized controlled trials of catgut-embedding therapy combined with minimally invasive surgery in the treatment of STC will be searched in PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database from inception to July, 2020. And Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain more relevant studies comprehensively. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3. RESULTS: This study will summarize the present evidence by exploring the application effect of catgut-embedding therapy combined with minimally invasive surgery in the treatment of STC. CONCLUSIONS: The findings of the study will provide helpful evidence for the application effect of catgut-embedding therapy combined with minimally invasive surgery in the treatment of STC, facilitating clinical practice and further scientific studies. ETHICS AND DISSEMINATION: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/7HVZB.

Regulating the Enteric Nervous System against Obesity in Mice by Electroacupuncture.

BACKGROUND AND OBJECTIVES: The enteric nervous system (ENS) dominates the onset of obesity and has been shown to regulate nutrient absorption and energy metabolism. METHODS AND STUDY DESIGN: This study was performed to investigate the role of electroacupuncture in regulating ENS function in obese mice. Obese mice were obtained by high-fat diet. 16S rRNA pyrosequencing, Western blotting, quantitative PCR, and neurotransmitter analysis were used for this purpose. RESULTS: Body weight, Lee index, serum lipid, leptin, and adiponectin levels, and other basic indices were significantly ameliorated after electroacupuncture intervention. The pathological ENS scores, serum neurotransmitter levels, and intestinal transit rate were markedly changed in obese mice. Moreover, electroacupuncture promoted the diversity of gut microbiota. No significant differences were observed 21 and 28 days after electroacupuncture. CONCLUSIONS: These results suggested ENS may be a new treatment approach to obesity.

Pediococcus pentosaceus B49 from human colostrum ameliorates constipation in mice.

Constipation is a prevalent and burdensome gastrointestinal (GI) disorder that seriously affects the quality of human life. This study evaluated the effects of the P. pentosaceus B49 (from human colostrum) on loperamide (Lop)-induced constipation in mice. Mice were given P. pentosaceus B49 (5 × 109 CFU or 5 × 1010 CFU) by gavage daily for 14 days. The result shows that P. pentosaceus B49 treatment relieved constipation in mice by shortening the defecation time, increasing the GI transit rate and stool production. Compared with the constipation control group, the P. pentosaceus B49-treated groups showed decreased serum levels of inhibitory neurotransmitters (vasoactive intestinal peptide and nitric oxide), increased serum levels of excitatory neurotransmitters (acetylcholinesterase, motilin, and gastrin), and elevated cecal concentration of short chain fatty acids (SCFAs). Analysis of cecal microbiota reveals that P. pentosaceus B49 was colonized in the intestine of constipated mice, and altered the cecal microbiota by increasing beneficial SCFAs-producing bacteria (i.e., Lactobacillus, Ruminococcaceae_UCG-014, and Bacteroidales_S24-7) and decreasing potential pathogenic bacteria (i.e., Staphylococcus and Helicobacter). Moreover, transcriptome analysis of the colon tissue shows that P. pentosaceus B49 partly normalized the expression of genes related to GI peristalsis (i.e., Ache, Chrm2, Slc18a3, Grp, and Vip), water and electrolyte absorption and transport (i.e., Aqp4, Aqp8, and Atp12a), while down-regulating the expression of pro-inflammatory and pro-oncogenic genes (i.e., Lbp, Lgals2, Bcl2, Bcl2l15, Gsdmc2, and Olfm4) in constipated mice. Our findings indicate that P. pentosaceus B49 effectively relieves constipation in mice and is a promising candidate for treating constipation.

Purgative/laxative actions of Globularia alypum aqueous extract on gastrointestinal-physiological function and against loperamide-induced constipation coupled to oxidative stress and inflammation in rats.

BACKGROUND: Chronic constipation is a gastrointestinal functional disorder which affects patient quality of life. Therefore, many studies were oriented to search herbal laxative agents. In this study, we investigated the effect of Globularia alypum L. leaves aqueous extract (GAAE) against loperamide (LOP)-produced constipation. METHODS: Animals were given LOP (3 mg/kg, b.w., i.p.) and GAAE (100, 200, and 400 mg/kg, b.w., p.o.) or yohimbine (2 mg/kg, b.w., i.p.), simultaneously, for 1 week. Gastric-emptying test and intestinal transit were determined. Colon histology was examined, and oxidative status was evaluated using biochemical-colorimetric methods. KEY RESULTS: GAAE ameliorates significantly gastric emptying (64% to 76.5%) and intestinal transit (66.65% to 84.73%). LOP negatively influenced defecation parameters and generated a stress situation. GAAE administration in contrast ameliorated those parameters and re-established oxidative balance. CONCLUSION: GAAE showed a modest action against oxidative stress and decreased LOP effect and thereby can be considered a pharmacological agent in constipation.

The Traditional Medicine Banhasasim-Tang Depolarizes Pacemaker Potentials of Cultured Interstitial Cells of Cajal through M3 Muscarinic and 5-HT3 Receptors in Murine Small Intestine.

BACKGROUND: Banhasasim-tang (BHSST) is a classic herbal formulation in traditional Chinese medicine widely used for gastrointestinal (GI) tract motility disorder. We investigated the effects of BHSST on the pacemaker potentials of cultured interstitial cells of Cajal (ICCs) in small intestine in vitro and its effects on GI motor functions in vivo. METHODS: We isolated ICCs from the small intestines and recorded pacemaker potentials in cultured ICCs with the whole-cell patch-clamp configuration in vitro. Intestinal transit rates (ITR%) were investigated in normal mice and GI motility dysfunction (GMD) mouse models in vivo. RESULTS: BHSST (20-50 mg/mL) depolarized pacemaker potentials and decreased their amplitudes in a concentration-dependent manner. Pretreatment with methoctramine (a muscarinic M2 receptor antagonist) did not inhibit BHSST-induced pacemaker potential depolarization. However, when we applied 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; a muscarinic M3 receptor antagonist), BHSST-induced effects were blocked. Pretreatment with Y25130 (a 5-HT3 receptor antagonist) blocked BHSST-induced effects in ICCs. In addition, when we applied 4-DAMP and Y25130 together, BHSST-induced effects were completely blocked. Pretreatment with Ca2+-free solution or thapsigargin inhibited BHSST-induced effects. Moreover, BHSST blocked both the transient receptor potential melastatin (TRPM) 7 and voltage-sensitive calcium-activated chloride (anoctamin-1, ANO1) channels. In normal mice, ITR% values were significantly increased by BHSST in a dose-dependent manner. The ITR% of GMD mice was significantly reduced relative to those of normal mice, which were significantly reversed by BHSST in a dose-dependent manner. CONCLUSION: These results suggested that BHSST depolarizes the pacemaker potentials of ICCs in a dose-dependent manner through the M3 and 5-HT3 receptors via internal and external Ca2+-dependent and TRPM7- and ANO1-independent pathways in vitro. Moreover, BHSST increased ITR% in vivo in normal mice and GMD mouse models. Taken together, the results of this study showed that BHSST had the potential for development as a prokinetic agent in GI motility function.

Sacral nerve stimulation in slow-transit constipation: effectiveness at 5-year follow-up.

AIM: The aim of this study is to evaluate the short- and long-term efficacy of sacral nerve stimulation (SNS) for treating slow-transit constipation (STC). METHOD: This is a retrospective cohort analysis of the efficacy of SNS in treating patients affected by STC, who previously failed to respond to conservative therapies. Only patients free of concomitant diseases were enrolled in our study. A temporary stimulation lead was initially implanted; patients with a > 50% symptom reduction were eventually deemed eligible for a permanent implant. RESULTS: This study enrolled 25 patients who underwent a SNS test stimulation; 21 patients (13 women; median age 32 years) eventually got a permanent implant. The median preoperative Cleveland Clinic Constipation Score (CCCS) was 21 (16-25). Preoperative colorectal transit time recorded a median of 10 markers (7-19) retained in the colorectal tract. At 6-month postoperative follow-up, the total number of markers retained in the colorectal tract decreased to 3 (0-4). The CCCS score improved during the first postoperative year (P < 0.001), but progressively worsened over the longer term. The SF-36 questionnaire showed an improvement in all 8 scales measuring physical and psycho-emotional states; all parameters recorded into the bowel diary also improved. Overall, at 60-month follow up, the overall neuromodulator removal rate was 48%. CONCLUSIONS: The SNS is a minimally invasive surgical procedure that we tested for treating STC. The short-term outcome was promisingly after 6 months; however, there was a declining trend beyond this interval. Thus, the long-term efficacy of SNS needs to be further assessed.

Efficacy of Polydextrose Supplementation on Colonic Transit Time, Bowel Movements, and Gastrointestinal Symptoms in Adults: A Double-Blind, Randomized, Placebo-Controlled Trial.

The addition of fiber is one of the most important dietary means to relieve constipation through lifestyle modification. Polydextrose (PDX) has been reported in several studies to increase fecal bulk, soften stools, and increase the number of defecations. However, there are few studies on the effect of PDX on colonic transit time (CTT). Therefore, the aim of this study was to demonstrate the effect of PDX on CTT and other aspects of gastrointestinal function during two weeks (Day 1 to Day 14), preceded by a 2-week run-in period (Day -14 to Day -1). A total of 192 adults who were diagnosed with functional constipation per Rome III criteria were recruited for the study. Participants were randomized equally into 4 groups (12 g, 8 g, or 4 g of PDX or placebo per day). The primary endpoint was CTT, assessed using radio-opaque markers and abdominal X-rays on Day 0, the baseline; and Day 15, the end of the intervention. Secondary outcomes that were measured using inventories were the patient assessment of constipation symptoms and quality of life, bowel function index, relief of constipation, bowel movement frequency (BMF), stool consistency, degree of straining, and proportion of bowel movements. Ancillary parameters and harms were also evaluated. The recruited population was not sufficiently constipated (e.g., baseline values for CTT and BMF of 42 h and 8.7 BMF/week, respectively). Despite this limitation, our results demonstrated an increased number of bowel movements when supplemented with PDX at a dosage of 12 g per day for 2 weeks. This dosage also consistently improved the secondary outcomes that were measured using inventories at Day 15, compared with the baseline. No serious or significant adverse events were reported during the study.

[Effects of the endosperm of tara seeds and powder of Agave Americana leaves on body weight and intestinal transit time in holtzman rats]. / Efecto del endospermo de semilla de tara y polvo de hojas de Agave americana en el peso corporal y velocidad de tránsito intestinal en ratas.

OBJECTIVE: To evaluate the effects of endosperm of tara seeds (ETS) and powder of Agave americana leaves (AAL) on body weight and intestinal transit time in Holtzman rats. MATERIALS AND METHODS: Twenty-five male Holtzman rats, individually caged, and distributed into five groups were fed for 21 days with one of the following treatments: T1, diet with 6% alpha cellulose (Control); T2, diet with 6% ETS; T3, diet with 6% AAL; T4, diet with 10% ETS; and T5, Diet with 10% AAL. Feed intake, body weight gain, apparent digestibility of fat, characteristics of feces (fat content, weight, moisture, volume, and pH) and intestinal transit time were recorded. One-way analyses of variance (ANOVA) were performed, as well as Tukey's multiple means comparison. RESULTS: Diets with 6% and 10% of ETS resulted in a reduction of feed intake, apparent digestibility of fat, and fecal pH, and said results had an effect in the reduction of body weight gain of 37.0% (p=0.008) and 50.9% (0.001), compared with the control diet. The diet with 10% of AAL powder reduced the intestinal transit time from 642 min (control) to 532 min (p=0.242). CONCLUSIONS: Diets containing EST regulated body weight gain, while the diet with AAL powder had no effects on the intestinal transit time in rats.

OBJETIVOS.: Evaluar el efecto del endospermo de semilla de tara (EST) y polvo de hojas del Agave americana (HAA) sobre el peso corporal y velocidad de tránsito intestinal en ratas Holtzman. MATERIALES Y MÉTODOS: Veinticinco ratas machos Holtzman distribuidas en cinco grupos y alojadas en jaulas individuales, fueron alimentadas durante 21 días con uno de los siguientes tratamientos: T1, dieta con 6% de alfa celulosa (control); T2, dieta con 6% de EST; T3, dieta con 6% de HAA; T4, dieta con 10% de EST y T5, dieta con 10% de HAA. Se registraron el consumo de alimento, ganancia de peso corporal, digestibilidad aparente de la grasa, características de las heces (contenido de grasa, peso, humedad, volumen y pH) y tiempo de tránsito intestinal. Se realizaron análisis de varianza (ANOVA) de una vía y a través de la comparación múltiple de medias de Tukey. RESULTADOS: Dietas con 6% y 10% del EST exhibieron una reducción en el consumo de alimento, digestibilidad aparente de la grasa y pH fecal, cuyos resultados tuvieron efectos en la reducción de la ganancia del peso corporal de 37,0% (p=0,008) y 50,9% (p=0,001) comparados con la dieta control. Dieta con 10% del polvo de HAA redujo el tiempo de tránsito intestinal de 642 min (control) a 532 min (p=0,242). CONCLUSIONES: Dietas que contienen EST regulan la ganancia del peso corporal; en cambio, dieta con polvo de HAA, no tuvo efectos sobre la velocidad de tránsito intestinal en ratas.

Efecto del endospermo de semilla de tara y polvo de hojas de Agave americana en el peso corporal y velocidad de tránsito intestinal en ratas / Effects of the endosperm of tara seeds and powder of Agave Americana leaves on body weight and intestinal transit time in holtzman rats

RESUMEN Objetivos. Evaluar el efecto del endospermo de semilla de tara (EST) y polvo de hojas del Agave americana (HAA) sobre el peso corporal y velocidad de tránsito intestinal en ratas Holtzman. Materiales y métodos Veinticinco ratas machos Holtzman distribuidas en cinco grupos y alojadas en jaulas individuales, fueron alimentadas durante 21 días con uno de los siguientes tratamientos: T1, dieta con 6% de alfa celulosa (control); T2, dieta con 6% de EST; T3, dieta con 6% de HAA; T4, dieta con 10% de EST y T5, dieta con 10% de HAA. Se registraron el consumo de alimento, ganancia de peso corporal, digestibilidad aparente de la grasa, características de las heces (contenido de grasa, peso, humedad, volumen y pH) y tiempo de tránsito intestinal. Se realizaron análisis de varianza (ANOVA) de una vía y a través de la comparación múltiple de medias de Tukey. Resultados Dietas con 6% y 10% del EST exhibieron una reducción en el consumo de alimento, digestibilidad aparente de la grasa y pH fecal, cuyos resultados tuvieron efectos en la reducción de la ganancia del peso corporal de 37,0% (p=0,008) y 50,9% (p=0,001) comparados con la dieta control. Dieta con 10% del polvo de HAA redujo el tiempo de tránsito intestinal de 642 min (control) a 532 min (p=0,242). Conclusiones Dietas que contienen EST regulan la ganancia del peso corporal; en cambio, dieta con polvo de HAA, no tuvo efectos sobre la velocidad de tránsito intestinal en ratas.

ABSTRACT Objective To evaluate the effects of endosperm of tara seeds (ETS) and powder of Agave americana leaves (AAL) on body weight and intestinal transit time in Holtzman rats. Materials and Methods Twenty-five male Holtzman rats, individually caged, and distributed into five groups were fed for 21 days with one of the following treatments: T1, diet with 6% alpha cellulose (Control); T2, diet with 6% ETS; T3, diet with 6% AAL; T4, diet with 10% ETS; and T5, Diet with 10% AAL. Feed intake, body weight gain, apparent digestibility of fat, characteristics of feces (fat content, weight, moisture, volume, and pH) and intestinal transit time were recorded. One-way analyses of variance (ANOVA) were performed, as well as Tukey's multiple means comparison. Results Diets with 6% and 10% of ETS resulted in a reduction of feed intake, apparent digestibility of fat, and fecal pH, and said results had an effect in the reduction of body weight gain of 37.0% (p=0.008) and 50.9% (0.001), compared with the control diet. The diet with 10% of AAL powder reduced the intestinal transit time from 642 min (control) to 532 min (p=0.242). Conclusions Diets containing EST regulated body weight gain, while the diet with AAL powder had no effects on the intestinal transit time in rats.

Fecal imaging demonstrates that low-methoxyl pectin supplementation normalizes gastro-intestinal transit in mice given a liquid diet.

This study has the following aims: (1) to confirm a methodology for a fecal indocyanine green (ICG) imaging test for measuring gastro-intestinal transit time (GITT); and (2) to compare GITT in mice given a liquid diet in which viscosity increases under acidic conditions to that in mice given stable liquid diets with comparable viscosity or regular chow. To address Aim 1, mice received ICG orally along with intraperitoneal injection of atropine in Study 1, and mice were given ICG orally with concurrent carmine red for Study 2. Fluorescence imaging of feces collected for 8 h thereafter was used to detect the first feces with fluorescence and thereby determine GITT. To address Aim 2, mice were fed ad libitum for 1 week with either liquid diet or regular chow for Study 3, or with liquid diet containing low-methoxyl (LM) pectin or high-methoxyl (HM) pectin, or regular chow for Study 4. GITT was then determined by fecal ICG imaging. Atropine delayed GITT in a dose-dependent manner. The GITT of ICG completely corresponded to that of carmine red (correlation coefficient, 1.00). The first ICG excretion in the loose/some diarrheal feces of mice given a liquid diet was seen at 170 min. Feces of mice given liquid diet were loose with LM pectin and loose/some diarrhea with HM pectin. GITT of mice given liquid diet with HM pectin was significantly delayed (280 min) compared to that of mice given liquid diet with LM pectin (111 min) or regular chow (130 min). Fecal imaging of ICG enables measurements of GITT. LM pectin supplementation in a liquid diet may normalize GITT in mice to that of a normal meal and may be associated with changes in fecal properties.

Short-Term Interferential Transabdominal Electrical Stimulation Did Not Change Oral-Rectal Transit Time in Piglets.

BACKGROUND: Transcutaneous electrical stimulation (TES) using interferential current (IFC) is a new therapeutic treatment for constipation. Clinical studies show that TES-IFC for 3-6 months improves colonic transit, but it is not clear if short-term stimulation affects transit or the effect requires longer to develop. The aim of this study was to determine if TES-IFC for only four days affects oral-rectal transit time in healthy pigs. METHODS: Twenty-two 4-5-week old large white female piglets had transit studies during week 4 and week 5 by placing a capsule containing 18 radiopaque plastic markers in the esophagus under anesthetic followed by x-rays at 6, 30, 54, and 78 hours. Animals were randomly assigned to active or control groups. The active group received TES for 30 min daily for four days. Interferential current was applied through four electrodes (4 × 4 cm), with two para-spinal just below the last rib and two on the belly at the same level. Stimulation was at 4000 Hz and 4080-4160 Hz with currents crossing through the abdominal cavity. RESULTS: Whole bowel transit times ranged from 7.7 to 72.2 hours, stomach transit from <1 to 63 hours, and bowel with rectum transit time from 5 to 53 hours. Transit times were the same for the control (median 28.4 hours) and TES-IFC (23.0 hours) groups in the prestimulation and stimulation weeks (control 23.0, TES-IFC 19.8 hours) with no change within or between groups. CONCLUSION: Four days of half-hour TES-IFC daily in healthy 5-week-old piglets did not change oral-rectal transit time.

Sacral neuromodulation versus personalized conservative treatment in patients with idiopathic slow-transit constipation: study protocol of the No.2-trial, a multicenter open-label randomized controlled trial and cost-effectiveness analysis.

PURPOSE: The evidence regarding the (cost-)effectiveness of sacral neuromodulation (SNM) in patients with therapy-resistant idiopathic slow-transit constipation is of suboptimal quality. The Dutch Ministry of Health, Welfare and Sports has granted conditional reimbursement for SNM treatment. The objective is to assess the effectiveness, cost-effectiveness, and budget impact of SNM compared to personalized conservative treatment (PCT) in patients with idiopathic slow-transit constipation refractory to conservative treatment. METHODS: This study is an open-label, multicenter randomized controlled trial. Patients aged 14 to 80 with slow-transit constipation, a defecation frequency (DF) < 3 per week and meeting at least one other Rome-IV criterion, are eligible. Patients with obstructed outlet, irritable bowel syndrome, bowel pathology, or rectal prolapse are excluded. Patients are randomized to SNM or PCT. The primary outcome is success at 6 months (DF ≥ 3 a week), requiring a sample size of 64 (α = 0.05, ß = 0.80, 30% difference in success). Secondary outcomes are straining, sense of incomplete evacuation, constipation severity, fatigue, constipation specific and generic quality of life, and costs at 6 months. Long-term costs and effectiveness will be estimated by a decision analytic model. The time frame is 57 months, starting October 2016. SNM treatment costs are funded by the Dutch conditional reimbursement program, research costs by Medtronic. CONCLUSIONS: The results of this trial will be used to make a final decision regarding reimbursement of SNM from the Dutch Health Care Package in this patient group. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov , identifier NCT02961582, on 12 October 2016.

Home-Based Transabdominal Interferential Electrical Stimulation for Six Months Improves Paediatric Slow Transit Constipation (STC).

BACKGROUND: Transcutaneous electrical stimulation (TES) for one to two months has produced some improvement in treatment-resistant slow-transit constipation (STC) in children. Optimal parameters for treatment are not known. It is possible that more improvement would occur with stimulation for longer. This study examined the effectiveness of stimulation for six months. METHODS: Children with STC confirmed by nuclear transit study (NTS) were enrolled prospectively. All had chronic constipation for greater than two years and had failed medical treatment. TES was performed for one hour/day for six months using the INF 4160 (Fuji Dynamics) portable stimulator and 4 cm × 4 cm electrodes near the belly button and on the back. Families kept bowel diaries and completed PEDSQLCore QOL (4.0) questionnaires before and at end of treatment. RESULTS: Sixty-two children (34 females; seven years, 2-16 year) with STC were studied. Defecation frequency increased in 57/62 (91%, mean ± SEM pre- 1.49 ± 0.20 vs. post- 3.25 ± 0.25 defecation/week, p < 0.0001) with the number with ≥3BA increasing from 6 to 37 (10-59%). Soiling frequency decreased from 4.8 to 1.1 days/week (p <0.001). Abdominal pain decreased from 1.7 to 0.3 days/week (<0.0001), and spontaneous urge to defecate improved. Quality of life (p < 0.01), mean transit index and gastric emptying on NTS improved (p < 0.005). CONCLUSION: Treatment-resistant STC responds to TES using interferential current across the abdomen when given daily for many months. Battery operated stimulators allowed stimulation at home for an hour each day. Stimulation for six months produced clinically significant improvement in defecation frequency, soiling, abdominal pain, urge to defecate, and quality of life in half of these chronic patients.

[Clinical observation of slow transit constipation treated with acupuncture and modified weitong xiaopi formula].

OBJECTIVE: To compare the difference in the clinical therapeutic effects on slow transit constipation (STC) among the combined therapy of acupuncture and herbal medicine, simple use of herbal medicine and simple use of western medication. METHODS: Ninety patients of STC were randomized into three groups, 30 cases in each one. In the combined therapy group, acupuncture was used in combination with the modified weitong xiaopi formula. In the Chinese herbal medicine group, the modified weitong xiaopi formula was adopted. In the western medication group, mosapride citrate capsules were used. The duration of the treatment was 28 days. Before and after treatment, the colonic transit test was applied, the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were selected for assessment. The clinical therapeutic effects were compared among the three groups. RESULTS: The total effective rate was 96.7% (29/30) in the combined therapy group, better than 90.0% (27/30) in the Chinese herbal medicine group and 76.7% (23/30) in the western medication group (P<0.05). In each group, before and after treatment, the residual marker amount was reduced apparently in the colonic transit test (all P<0.01). After treatment, the residual marker amount in the combined therapy group was less than that in the Chinese herbal medicine group (P<0.05) and that in the western medication group (P<0.01). The residual marker amount in the Chinese herbal medicine group was less than that in the western medication group (P<0.01). Compared with those before treatment, the scores of SAS and SDS were decreased in the combined therapy group and Chinese herbal medicine group (both P<0.01). After treatment, the scores of SAS and SDS in the combined therapy group were lower obviously than those in the other two groups (both P<0.01). CONCLUSIONS: Under the guidance of xuanfu theory, the combination of acupuncture and Chinese herbal medicine improve appa-rently colonic function and relieve the conditions of anxiety and depression in STC patients. The therapeutic effects are better than those treated with simple use of Chinese herbal medicine and simple use of western medication.