Evaluation of the antidiarrheal activity of 80% methanol extract and solvent fractions of the leaf of Bersama abyssinica fresen (Melianthaceae) in mice

Introduction The use of traditional medicinal plants in the management of diarrhea has long been practiced in Ethiopia. B. abyssinica fresen is one of the plants traditionally used to treat diarrhea whereas an in vivo study had not yet been conducted. Thus, this study aimed to evaluate the antidiarrheal activity of crude extract and solvent fractions of the leaf of B. abyssinica in mice. Methods Cold maceration within 80% methanol was used to extract the leaf powder and extract of the leaf was fractionated using n-hexane, chloroform, and distilled water. The in vivo antidiarrheal activity of crude extracts and solvent fractions were tested in experimental models of castor oil-induced diarrhea, enteropooling, and antimotility test. Five groups each with 6 mice were used under the three antidiarrheal models. Positive controls were treated with loperamide 3 mg/kg and atropine 5 mg/kg and 2% tween 80 was used in the treatment of negative controls. The extract and solvent fractions were administered at doses of 100, 200, and 400 mg/kg. Time of onset of diarrhea, number and weight of total and wet feces, the percent reduction in the number of wet feces, weight and volume of intestinal contents, and percent inhibition of intestinal motility were recorded. Data were analyzed using SPSS version 20. Result Defecation of castor oil-induced diarrheal or loose stools was inhibited (p < 0.01 to p < 0.001) at 200 mg/kg and 400 mg/kg of crude extract and aqueous fraction. The crude extract and the aqueous fraction at three doses (p < 0.01 to p < 0.001), the chloroform fraction at 200 mg/kg and 400 mg/kg (p < 0.01 to p < 0.001), and the n-hexane fraction at 400 mg/kg (p < 0.05) reduced intraluminal fluid accumulation compared with the negative control. Castor oil-induced intestinal motility was significantly suppressed with the three-doses of aqueous fraction (p < 0.05 to p < 0.001), 200 mg/kg and 400 mg/kg of crude extract (p < 0.05 to p < 0.01), 400 mg/kg of chloroform and n-hexane (p < 0.01 to p < 0.001) compared with negative control. Conclusion The crude extract, aqueous, and chloroform fractions of B. abyyssinica leaves have promising anti-diarrheal effects, supporting the plant's traditional use to treat diarrhea.

Sedative effect and physiological changes in horses treated with intramuscular injection of detomidine and morphine

ABSTRACT: This study aimed to elucidate the sedative effect and physiological changes associated with the intramuscular injection of detomidine combined with morphine in horses. Six healthy crossbred horses, aged 2 to 10 years, were included. A crossover experimental design was used to compare the effects of intramuscular injection of 30 µg/kg of detomidine alone (IMD) and intramuscular administration of 30 µg/kg of detomidine and 0.1 mg/kg of morphine (IMDM). The degree of sedation, height of head above ground, were assessed at the time points before and 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, and 120 minutes after drug administration, and heart rate, respiratory rate, systolic blood pressure, rectum temperature and intestinal motility were assessed at the time points before and 10, 20, 30, 40, 50, 60, 75, 90, 105, and 120 minutes after drug administration. The physiological parameters were analyzed using the Kruskal-Wallis test with Dunn’s post-hoc test and analysis of variance with t-test for independent samples and the sedation scores using the Friedman test and Mann Whitney U-test. P-values <0.05 indicated a statistically significant difference. IMDM promoted a higher sedative effect as compared to IMD, but the sedation occurred inconsistently. Additionally, a reduction in intestinal motility was observed with IMDM at 60, 75, 90, and 105 minutes after administration. IMDM promoted more variable sedation and prolonged reduction in the intestinal motility in the horses as compared to IMD.

Gastrointestinal motility and Intestinal structure following oral exposure to acrylamide in Wistar rats

Introduction: Acrylamide, a byproduct of the cooking process, has been reported to be a toxicant with likely carcinogenic properties. Its impairment of gastric function has been previously reported. In this study its effects on gastrointestinal motility and intestinal structure was investigated in male Wistar rats.Methods: Forty-five rats (120-180g) were divided into 3 equal groups (n=15) and treated p.o with either 0.2ml distilled-water, or acrylamide (7.5mg/kg and 15mg/kg respectively) for 28days. Thereafter, gastric emptying and intestinal motility was assessed. Intestinal structure (duodenum, jejunum and ileum), mucosal and intestinal cell counts were evaluated using histological techniques.Results: Gastric emptying and intestinal transit time increased (p<0.05) in the experimental (acrylamidetreated; 7.5mg/kg and 15mg/kg) groups compared to control. Mucosal cell counts (duodenum, jejunum and ileum) and ileum intestinal cell counts (p<0.05) were reduced in the experimental groups compared to control. Compared to control, duodenal samples of the experimental groups showed severe coagulative necrosis and sloughing off of the villi, luminal filling with necrotic debris, disruption and necrosis of the crypts of Lieberkühn, moderate polymorphonuclear cell infiltration and vascular congestion. These pathologies albeit with less severity were also observed in the jejunum and ileum of acrylamide treated groups.Conclusion: Increased oral exposure to acrylamide impairs gastric emptying, intestinal motility, mucus secretion and compromises digestive and absorptive functions of the small intestines, especially the duodenum. These observations may be ascribed to acrylamide-induced impaired neuronal signaling, autonomic neuropathy, oxidative stress, inflammation and cell necrosis. Keywords: Acrylamide, gastrointestinal tract, gastric emptying, intestinal motility, small intestines

Intestinal pseudo-obstruction in a patient with Kleefstra syndrome

Aim: To present a case of intestinal pseudo-obstruction in a paediatric patient with Kleefstra syndrome type 1 as a new clinical feature of this rare genetic disorder. Case report: A seven-year-old patient was admitted to the emergency department for nausea and vomiting. Clinical examination showed distended, meteoristic abdomen without detectable peristaltic sound. Abdominal X-ray revealed air-fluid levels and possible right subdiaphragmatic air collection. An urgent exploratory laparotomy was indicated. Intraoperatively, extremely dilated loops of small and large intestine up to the distal sigmoid colon were noted. No anatomical or mechanical causes of obstruction were found. The postoperative course was complicated by dysfunctional intestinal motility and urinary catheter-related infection which required prokinetics and intravenous antibiotic therapy. The patient was transferred to a paediatric centre specialized in intestinal motility disorders for further treatment. Conclusion: This is the first case of intestinal pseudo-obstruction described as a part of clinical presentation of Kleefstra syndrome type 1. Further research and re-evaluation of patients with KS1 is needed to determine if intestinal pseudo-obstruction is a new clinical manifestation depending on the size of the deletion or a repercussion of hypotonia sequential to an underlying syndrome.

Effect of gut microbiota from Henoch-Schönlein Purpura patients on acid-sensitive ion channel 3 expression and intestinal motility in germ-free rats

Background It has been proven that gut microbiota alterations are involved in the development of Henoch-Schönlein Purpura (HSP). However, the pathogenesis of HSP hasn’t been eluciated. This study was to investigate the impact of gut microbiota from HSP on ASIC3 expression and interactions between microbiota and ASIC3 expression in the development of HSP. Methods Feces collected from HSP and healthy children at the First Affiliated Hospital of Anhui Medical University were made into fecal microbial solutions. Germ-free rats were randomly assigned to either the control or HSP groups. The HSP group of rats were administered the fecal microbiota solution of HSP children, while the control group rats were administered the fecal microbiota solution of healthy children. Abdominal withdrawal reflex (AWR) and intestinal propulsion rate of the rats were used to determine visceral sensitivity. Composition of the gut microbiota of HSP children was determined using 16S rRNA gene sequencing. ASIC3 expression in the colon was ascertained through qRT-PCR as well as western blotting analysis. Results The results showed a reduction in the number of species and abundance in the intestinal microbiota of children with HSP. Visceral sensitivity and intestinal propulsion rate of HSP group rats increased significantly, compared with the control group. Colon ASIC3 mRNA and protein levels in the HSP group were found to be upregulated. The microbiota dysbiosis of HSP patients could stimulate ASIC3 expression in the colon of Germ-free rats, which in turn affected intestinal motility. Conclusions These results suggested that HSP children had intestinal microbiota disorder, which might affect gut motility by down-regulating colon ASIC3 expression in rats.

New cine magnetic resonance imaging parameters for the differential diagnosis of chronic intestinal pseudo-obstruction

Chronic intestinal pseudo-obstruction (CIPO) is a severe and refractory intestinal motility disorder whose diagnosis currently relies on subjective imaging assessments. Cine magnetic resonance imaging (MRI) may potentially improve the quantitative analysis of gastrointestinal motility; however, suitable CIPO detection parameters should be determined. Cine MRI was performed in seven patients with CIPO and 11 healthy controls. The logarithm of the Mahalanobis distance (x1) and distance variation per time (x2) were used as the original parameters to determine CIPO diagnostic thresholds. Furthermore, the correlation between cine MRI findings and CIPO severity was investigated. Threshold values of α = 1.10 and β = 0.15 for x1 and x2, respectively, produced a CIPO diagnosis sensitivity of 1.00 (7/7) and specificity of 0.82 (9/11). The resulting error was 0.11 (2/18). The two parameters were correlated (Pearson’s correlation coefficient: − 0.52). Any of the intestinal tracts of patients with severe CIPO requiring home parenteral nutrition belonged to the region defined by x1 ≥ 1.10 and x2 ≤ 0.15. Cine MRI is effective for the quantitative evaluation of small intestinal motility and CIPO diagnosis when using the abovementioned parameters and can be useful for treatment decision-making. However, these parameters have a wide distribution in healthy volunteers; this may complicate the detection of other disorders.

Contributions of Bile Acids to Gastrointestinal Physiology as Receptor Agonists and Modifiers of Ion Channels

BAs are known to be important regulators of intestinal motility and epithelial fluid and electrolyte transport. Over the past two decades, significant advances in identifying and characterizing the receptors, transporters, and ion channels targeted by bile acids (BAs) has led to exciting new insights into the molecular mechanisms involved in these processes. Our appreciation of BAs, their receptors and BA-modulated ion channels as potential targets for the development of new approaches to treat intestinal motility and transport disorders is increasing. In the current review, we aim to summarize recent advances in our knowledge of the different BA receptors and BA-modulated ion channels present in the gastrointestinal system. We discuss how they regulate motility and epithelial transport, their roles in pathogenesis and their therapeutic potential in a range of gastrointestinal diseases.

Reactive Enteric Glial Cells Participate in Paralytic Ileus by Damaging Nitrergic Neurons During Endotoxemia

BackgroundParalytic ileus is common in patients with septic shock, which may cause high morbidity and mortality. Enteric neurons and enteric glial cells (EGCs) participate in the regulation of intestinal motility, but little is known about their role. We aimed to prove whether reactive EGCs have harmful effects on enteric neurons during endotoxemia and lead to intestinal motility disorder in mice. MethodsIn this study, lipopolysaccharide (LPS) was used to induce endotoxemia in mice, and intraperitoneal injections of fluorocitrate (FC) twice per day (9 AM and 6 PM) for 7 days before LPS injections to prevent the activation of EGCs. The effects of reactive EGCs on intestinal motility were analyzed by motility assays in vivo and colonic migrating motor complexes (CMMCs) in vitro. The changes of enteric neurons were evaluated by immunofluorescent staining HuCD, nNOS, CHAT, and TUNEL.ResultsThe expression of glial fibrillary acidic protein (GFAP) was significantly upregulated in LPS-injected animals, indicating EGCs were transformed into a reactive state. The administration of FC could significantly prevent it. Meanwhile, inhibition of reactive EGCs can improve intestinal motility and peristaltic reflex. The density of the general neuronal population (HuC/D-immunoreactive) in the colonic myenteric plexus was significantly increased after suppressing reactive EGCs. The population of nNOS neurons was increased significantly, but there was no significant difference in the number of ChAT neurons. Furthermore, the apoptotic rate of enteric neurons significantly increased, when incubated with the conditional medium of reactive EGCs in vitro. At the same time, the dendritic complexity and the number of primary neuritis neurons were significantly reduced.ConclusionReactive enteric glial cells participated in paralytic ileus by damaging nitrergic neurons during endotoxemia. It may provide a novel therapeutic strategy for intestinal motility disorders during endotoxemia or sepsis.