Small Intestinal Motility Research Articles

Effects of morroniside isolated from Cornus officinalis fruits on functional gastrointestinal disorders and gastric ulcer in mice

The dried fruits of Cornus officinalis (Cornaceae) are used in Kampo medicine (e.g. Hachimigan and Goshajinkigan) to treat senile osteoporosis, diabetes, gastric atony, frequent urination, and diarrhea/constipation associated with aging. The present study investigated the effects of a C. officinalis fruit extract and morroniside, an iridoid compound from isolated these fruits, on the reduction in gastric emptying small intestinal motility caused by 5-hydroxytryptamine (5-HT) and 1-(3-chlorophenyl) biguanide (5-HT3 receptor agonist), and gastric ulcers induced by 150 or 75 mM HCl/90 % EtOH (HCl-EtOH) and/or 5-HT in mice. C. officinalis extract (500 mg/kg) and morroniside (20 and 50 mg/kg) suppressed the reduction in gastric emptying induced by 5-HT- and 5-HT3 agonist. C. officinalis extract, morroniside and 5-HT3 receptor antagonist (ramosetron) attenuated 5-HT-induced diarrhea. Furthermore, morroniside (20 and 50 mg/kg) prevented EtOH/HCl-induced gastric ulcers and those caused by 5-HT. Morroniside (20 and 50 mg/kg) attenuated elevations in the plasma levels of corticosterone, corticotropin-releasing factor (CRF), and adrenocorticotropic hormone (ACTH) in 75 mM HCl/90 % EtOH- and 5-HT-treated mice. The results obtained herein suggest the potential of morroniside as an effective treatment for irritable bowel syndrome, such as diarrhea and functional dyspepsia (reductions in gastric emptying and small intestinal motility), caused by 5-HT. The present study suggests a role for morroniside in the regulation of elevations in CRF, ACTH, and corticosterone levels through hypothalamic-pituitary-adrenal axis activity induced by stress loading, such as a 5-HT treatment and/or HCl/EtOH stimulation.

Quantitative Analysis of Small Intestinal Motility in 3D Cine-MRI Using Centerline-Aware Motion Estimation.

Currently available tools for noninvasive motility quantification of the small intestine are limited to dynamic 2D MRI scans, which are limited in their ability to differentiate between types of intestinal motility. To develop a method for quantification and characterization of small intestinal motility in 3D, capable of differentiating motile, non-motile and peristaltic motion patterns. Prospective. Fourteen healthy volunteers (127 small intestinal segments) and 10 patients with Crohn's disease (87 small intestinal segments). 3.0 T, 3D balanced fast field echo sequence, 1 volume per second. Using deformable image registration between subsequent volumes, the local velocity within the intestinal lumen was quantified. Average velocity and average absolute velocity along intestinal segments were used with linear classifiers to differentiate motile from non-motile intestines, as well as erratic motility from peristalsis. The mean absolute velocity of small intestinal content was compared between healthy volunteers and Crohn's disease patients, and the discriminative power of the proposed motility metrics for detecting motility and peristalsis was determined. The consensus of two observers was used as referenced standard. Student's t-test to assess differences between groups; area under the receiver operating characteristic curve (AUC) to assess discriminative ability. P < 0.001 was considered significant. A significant difference in the absolute velocity of intestinal content between Crohn's patients and healthy volunteers was observed (median [IQR] 1.06 [0.61, 1.56] mm/s vs. 1.84 [1.37, 2.43] mm/s), which was consistent with manual reference annotations of motile activity. The proposed method had a strong discriminative performance for detecting non-motile intestines (AUC 0.97) and discernible peristalsis (AUC 0.81). Analysis of 3D cine-MRI using centerline-aware motion estimation has the potential to allow noninvasive characterization of small intestinal motility and peristaltic motion in 3D. 3 TECHNICAL EFFICACY: Stage 2.

Secretin Inhibits Small Intestinal Motility via Interstitial Cells of Cajal and cAMP Mechanisms

Background: Secretin is a member of the secretin-glucagon-vasoactive intestinal peptide hormone superfamily and is a multifunctional gastrointestinal- (GI) and neuro- peptide hormone. Secretin is primarily secreted postprandially from the crypts of Lieberkühn of duodenal enteroendocrine S cells into circulation where it reaches secretin receptor targets in the central nervous system and periphery. This dynamic hormone has been shown to act as a key signaling molecule in the regulation of digestion, metabolism and energy expenditure, water retention, reproduction, thermogenesis in adipose tissue, and in gastric and intestinal motility. Secretin’s canonical role in the GI tract is to stimulate the secretion of bicarbonate and bile from pancreatic ducts and bile ducts to neutralize acidic chyme exiting the stomach. Secretin has also been shown to slow intestinal motility, but its targets and mechanism of action is poorly understood. Aims: Several studies have proposed that secretin acts to slow intestinal motility in the intestines primarily through the many secretin receptors present on vagal afferents in the GI tract, here we discuss new data that suggests an alternate and complementary signaling pathway via interstitial cells of Cajal (ICC). ICC act as a liaison to facilitate a reduction in force of GI smooth muscle contraction through the activation of the secretin receptor (SCTR) and subsequent stimulation of the second messenger, cyclic adenosine monophosphate (cAMP). Here we provide evidence to show how ICC mediates changes in myogenic activity and motility in the small intestine. Methods: Spinning-disk confocal microscopy was used to monitor Ca2+ signaling in ICC from small intestinal muscles of GCaMP6f x KitiCre mice. Additionally, cAMP levels were evaluated using CAMPER mice. Intestinal muscle contractility was assessed using muscle strip myography experiments. Results: Secretin reduced small intestinal force of contraction in the presence of tetrodotoxin (TTX) and dampened the effect of cholinergic transmission. The secretin receptor (SCTR) is expressed primarily on ICC, specifically ICC within the deep muscular plexus (ICC-DMP) in the small intestine and Ca2+ imaging confirmed the effects are primarily localized within ICC-DMP. Secretin reduced carbachol-induced contractions and Ca2+ transients in ICC-DMP in response to electrical field stimulation (EFS) in the presence of LNNA (NO synthase inhibitor) and MRS2500 (P2Y1 antagonist). Secretin caused an increase in cAMP levels in ICC-DMP in muscles from Kit-iCre-CAMPER mice. PKA inhibitors rescued some of the effects of secretin on ICC-DMP Ca2+ signaling. Measurements of diameter change in large, intact, intestinal segments (4-5 cm) showed a significant decrease in response to Secretin. Conclusions: Secretin can inhibit small intestinal motility through the activation SCTRs on ICC-DMP via cAMP-mediated mechanisms. These results show how novel secretin targets on ICC influence GI muscles and reduce propulsive and segmental motility to facilitate nutrient absorption and digestion after a meal. Funding: This project was supported by R01 DK-120759 from the National Institute of Diabetes and digestive and Kidney (NIDDK). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Garlic oil improves small intestinal motility in experimentally induced type II diabetes mellitus in female Wistar rats.

Diabetes mellitus adversely affects the contractile ability of the small intestine. However, there is a paucity of studies investigating the impact of garlic oil on small intestinal motility. This study aimed to evaluate the potential beneficial effects of garlic oil on type 2 diabetes mellitus in rats. Thirty-six adult female Wistar rats (n = 36) were divided into four groups: control, non-diabetic rats supplemented with garlic oil, diabetic rats, and diabetic rats treated with garlic oil. The rats were anesthetized using pentobarbitone (40 mg/kg BW); various motility parameters and oxidative markers were determined in small intestinal segments. Measurements were taken for naso-anal length, waist circumference, fasting blood glucose level (FBG), and plasma insulin level. Compared to the control group, the diabetic rats exhibited a reduction in the average force of contraction and motility index in all small intestinal segments. Furthermore, the rats exhibited a reduction in the average duration of muscle contraction only in the jejunum. The rats also exhibited hyperglycemia, insulin resistance, significant oxidative stress, and obesity. This was proven by changes in motility parameters, fasting blood glucose levels, HOMA-IR values, intestinal MDA levels, and waist circumference. The non-diabetic rats supplemented with garlic oil also exhibited a decrease in the average force of contraction and motility index in all small intestinal segments, despite having consistently higher Lee index and waist circumference values. However, the diabetic rats treated with garlic oil demonstrated improved small intestinal motility in nearly all small intestinal segments and a reduction in oxidative stress. In conclusion, rats with diabetes mellitus experienced a decrease in small intestinal motility, which is primarily driven by oxidative stress. Normal rats administered with garlic oil supplements exhibited similar effects. In contrast, garlic oil treatment in diabetic rats led to enhanced small intestinal motility and a notable anti-hyperglycemic effect, which can be attributed to the potent antioxidant properties of garlic oil.

Torsion of the spiral colon in cattle– a retrospective analysis of 58 cases

BackgroundTorsion of the spiral colon (TSC) describes twisting of the spiral colon around its mesentery. The present study reviewed the medical records of 58 cows and heifers with TSC and described the findings, treatment and outcome.ResultsAll cases had an abnormal general condition, and the main vital sign abnormalities were tachycardia (72.4%), tachypnoea (67.2%) and decreased rectal temperature (51.8%). Signs of colic were seen in 62.1% of the cows. The most common intestinal abnormalities were an empty or almost empty rectum (96.6%), reduced or absent rumen motility (93.2%), positive ballottement and/or percussion and simultaneous auscultation on the right side of the abdomen (87.9%), reduced or absent intestinal motility (84.5%) and dilatation of the large intestines (spiral colon and/or caecum, 70.7%) diagnosed by transrectal palpation. The main biochemical changes were hypermagnesaemia (70.8%), hypocalcaemia (70.8%), and acidosis (66.7%). Haemoconcentration was found in 63.8%. The main ultrasonographic findings were reduced to absent small intestinal motility (83.3%), dilated small intestines (69.6%) and ascites (66.7%). The spiral colon was dilated in 44.0% of the cows and the caecum in 24.0%. The actual site of torsion could not be visualised. Based on the clinical findings, TSC was diagnosed in 22.4% and caecal dilatation in 50.0% of the cows. A tentative diagnosis of small intestinal ileus was made in another 10.3% of the cows, and a definitive diagnosis of small intestinal ileus in 17.3%. Fifty-three cows underwent right flank laparotomy, and the TSC could be reduced in 26. Twenty-six of the 58 (44.8%) cows were discharged and 32 (55.2%) were euthanased before, during or after surgery.ConclusionsAcute illness, a sparse amount of faeces in the rectum and dilated spiral colon and caecum are characteristic findings of TSC. The final diagnosis often relies on the surgical or postmortem findings. Cattle with TSC should be treated surgically without delay. The prognosis is guarded with a survival rate of 44.8%.

Metformin And Vitamin B12 Deficiency: A Concise Exploration

Type 2 diabetes mellitus (T2DM) management with metformin, a first-line oral antidiabetic, is associated with emerging concerns about potential vitamin B12 deficiency. Approximately 6% to 30% of metformin users may experience this deficiency. Recent studies suggest interference in absorption and metabolism processes, prompting exploration of underlying mechanisms. Proposed mechanisms include disruption of calcium-dependent binding, alteration in small intestine motility, changes in bile acid metabolism, enhanced liver accumulation, and decreased intrinsic factor secretion. Inhibition of calcium-dependent absorption at the terminal ileum, reversible with calcium supplementation, is increasingly recognized as a key mechanism. Studies report varying prevalence rates of vitamin B12 deficiency with metformin use, emphasizing the need for careful monitoring. Daily dose appears more strongly associated with deficiency than duration. In conclusion, this mini-review underscores the intricate relationship between metformin and vitamin B12 deficiency, emphasizing the importance of vigilant monitoring and tailored interventions for comprehensive patient care.

Preliminary study to evaluate the use of fast abdominal ultrasonography of horses with colic in first opinion ambulatory practice

SummaryBackgroundColic is the commonest emergency in first opinion equine practice. Early referral is important for horses requiring surgery. Fast localised abdominal ultrasonography of horses (FLASH) is frequently used as a diagnostic tool in the investigation of colic at referral hospitals, but its use in first opinion practice has not been evaluated.ObjectiveTo assess the value of FLASH scanning in the primary assessment of horses with colic in the field, using a portable wireless ultrasound system.Study designProspective study (2018–2021).MethodsAny horse examined for colic as an emergency in a first opinion ambulatory practice was eligible for inclusion in the study. A FLASH examination was performed using a wireless handheld ultrasound scanner, with the images displayed on a smartphone or tablet. The findings on FLASH scans and the outcome of the case (recovered, referred for surgery or euthanised without referral) were recorded.ResultsIn total, 135 equids with acute colic were evaluated. Of the 135 horses, 49 (36%) had an abnormal finding on FLASH scanning, including distended loops of small intestine (n = 34), thickened small intestinal walls (n = 23) and/or distension of the stomach (n = 7). Reduced small intestinal motility was recorded in 52 animals (38%). Follow‐up information was available in all animals: 50 (37%) were euthanised due to clinical deterioration and the owners' decision not to undertake surgery; 85/135 (63%) survived, including 5/85 (6%) that underwent surgery and 80/85 (94%) that resolved with medical management.Main limitationsSmall number of cases. Lack of results of post‐mortem examination of horses that were euthanised. Potential selection bias.ConclusionThe FLASH technique can be valuable in the primary assessment of horses with colic in first opinion ambulatory practice. Further evaluation with more cases is required.

Colitis-Induced Small Intestinal Hypomotility Is Dependent on Enteroendocrine Cell Loss in Mice

The abdominal discomfort experienced by patients with colitis may be attributable in part to the presence of small intestinal dysmotility, yet mechanisms linking colonic inflammation with small-bowel motility remain largely unexplored. We hypothesize that colitis results in small intestinal hypomotility owing to a loss of enteroendocrine cells (EECs) within the small intestine that can be rescued using serotonergic-modulating agents. Male C57BL/6J mice, as well as mice that overexpress (EECOVER) or lack (EECDEL) NeuroD1+ enteroendocrine cells, were exposed to dextran sulfate sodium (DSS) colitis (2.5% or 5% for 7 days) and small intestinal motility was assessed by 70-kilodalton fluorescein isothiocyanate-dextran fluorescence transit. EEC number and differentiation were evaluated by immunohistochemistry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining, and quantitative reverse-transcriptase polymerase chain reaction. Mice were treated with the 5-hydroxytryptamine receptor 4 agonist prucalopride (5 mg/kg orally, daily) to restore serotonin signaling. DSS-induced colitis was associated with a significant small-bowel hypomotility that developed in the absence of significant inflammation in the small intestine and was associated with a significant reduction in EEC density. EEC loss occurred in conjunction with alterations in the expression of key serotonin synthesis and transporter genes, including Tph1, Ddc, and Slc6a4. Importantly, mice overexpressing EECs revealed improved small intestinal motility, whereas mice lacking EECs had worse intestinal motility when exposed to DSS. Finally, treatment of DSS-exposed mice with the 5-hydroxytryptamine receptor 4 agonist prucalopride restored small intestinal motility and attenuated colitis. Experimental DSS colitis induces significant small-bowel dysmotility in mice owing to enteroendocrine loss that can be reversed by genetic modulation of EEC or administering serotonin analogs, suggesting novel therapeutic approaches for patients with symptomatic colitis.

Evaluating the Efficacy and Safety Profile of Good Morning™ Constipation Drops in a Loperamide-Induced Rat Model

Introduction: Constipation is a prevalent gastrointestinal condition globally, often managed with conventional laxatives that may cause side effects and dependency. Homeopathy, offering a holistic approach through diluted natural substances, aims to stimulate the body's self-healing mechanism. This study evaluates Good Morning™ drops, an innovative homeopathic formulation designed to safely and effectively manage constipation. Using a rat model of Loperamide-induced constipation, we evaluated its safety and efficacy, unveiling promising results.Materials and Methods: A rat model of Loperamide induced constipation was utilized to assess the efficacy and safety of Good Morning™ Constipation Drops. 3 unique formulations were prepared and employed to the animal model in 3 different doses. 72 rats were randomly assigned to 12 groups (3 control groups plus 3 formulations in 3 different doses totalling 9 groups), receiving specific variants or control treatments over the period of 21 days. Parameters including body weight, water intake, stool count, intestinal function, haematology, bleeding and clotting time, blood biochemistry, and organ weight were evaluated. Results and discussion: The results showed that all homeopathic formulations, particularly Variant 2, exhibited significant effects in Loperamide induced constipated rats. Across various parameters, Variant 2 consistently influenced food intake, stool characteristics, and small intestine motility. Safety assessments indicated overall well-being, withVariant 2 demonstrating superior survival outcomes. These findings position Variant 2 as a promising candidate for constipation management, emphasizing its consistent efficacy and safety in the rat model. Conclusion: In conclusion, Good Morning™ Constipation Drops exhibited a promising blend of safety, efficacy, and a multifaceted mechanism of action. The formulation, rich in botanical ingredients, demonstrates high safety with favorable survival rates. Efficacy is evident in improved stool counts, stool weights, Small Intestine Transition percentages, and impacts on lipid profiles and liver enzymes, highlighting its potential as a comprehensive solution for constipation relief.

Small intestinal strangulation in 60 cattle – clinical, laboratory and ultrasonographic findings, treatment and outcome

BackgroundIntestinal strangulation is constriction of the intestine by a band of tissue, ligament or blood vessel causing partial or complete intestinal obstruction. This retrospective study describes the clinical, laboratory and ultrasonographic findings, treatment and outcome of 60 cows with intestinal strangulation.ResultsThe general condition was abnormal in all cows (60/60), 23.3% (14/60) had nonspecific signs of pain, 40.0% (24/60) had signs of colic and 48.3% (29/60) had signs of somatic (parietal) pain. The most common digestive tract abnormalities were, in decreasing frequency, reduced or absent intestinal motility (100%, 60/60), reduced or absent faecal output (98.3%, 59/60), reduced or absent rumen motility (93.4%, 56/60), dilated small intestines on transrectal palpation (63.3%, 38/60), positive ballottement and swinging auscultation (BSA) and/or percussion and simultaneous auscultation (PSA) on the right side of the abdomen (58.3%, 35/60) and at least one positive foreign body test, most commonly the back grip, in 33.9% (20/59) of the cows. Other common findings were reduced skin surface temperature (67.8%, 40/59), reduced skin turgor (51.7%, 31/60), prolonged capillary refill time (49.2%, 29/59), enophthalmus (48.3%, 29/60) and moderate to severe scleral injection (46.6%, 27/58). The most common laboratory findings were hypokalaemia (58.3%, 35/60), haemoconcentration (57.6%, 34/59), base excess (51.1%, 24/47), hyperproteinaemia (45.8%, 27/59), hyperbilirubinaemia (43.3%, 26/60), acidosis (42.6%, 20/47) and azotaemia (38.3%, 23/60). The principal ultrasonographic findings were subjectively reduced or absent small intestinal motility and dilated small intestines, but the strangulation could not be visualised by ultrasonography. With one exception, all cows underwent a right flank laparotomy to resolve the strangulation by transection or resection of the impinging tissue. Forty-nine (81.7%) cows were discharged and 11 (18.3%) were euthanized before, during or after surgery.ConclusionsWithout laparotomy, intestinal strangulation could be clinically (transrectally) diagnosed in only 10% of the cows. A laparotomy is therefore essential for the correct diagnosis. The prognosis is good with prompt surgical treatment.

Pico145 inhibits TRPC4-mediated mICAT and postprandial small intestinal motility

In intestinal smooth muscle cells, receptor-operated TRPC4 are responsible for the majority of muscarinic receptor cation current (mICAT), which initiates cholinergic excitation-contraction coupling. Our aim was to examine the effects of the TRPC4 inhibitor Pico145 on mICAT and Ca2+ signalling in mouse ileal myocytes, and on intestinal motility. Ileal myocytes freshly isolated from two month-old male BALB/c mice were used for patch-clamp recordings of whole-cell currents and for intracellular Ca2+ imaging using Fura-2. Functional assessment of Pico145’s effects was carried out by standard in vitro tensiometry, ex vivo video recordings and in vivo postprandial intestinal transit measurements using carmine red. Carbachol (50 µM)-induced mICAT was strongly inhibited by Pico145 starting from 1 pM. The IC50 value for the inhibitory effect of Pico145 on this current evoked by intracellularly applied GTPγS (200 µM), and thus lacking desensitisation, was found to be 3.1 pM, while carbachol-induced intracellular Ca2+ rises were inhibited with IC50 of 2.7 pM. In contrast, the current activated by direct TRPC4 agonist (-)-englerin A was less sensitive to the action of Pico145 that caused only ∼43 % current inhibition at 100 pM. The inhibitory effect developed rather slowly and it was potentiated by membrane depolarisation. In functional assays, Pico145 produced concentration-dependent suppression of both spontaneous and carbachol-evoked intestinal smooth muscle contractions and delayed postprandial intestinal transit. Thus, Pico145 is a potent GI-active small-molecule which completely inhibits mICAT at picomolar concentrations and which is as effective as trpc4 gene deficiency in in vivo intestinal motility tests.

FRI643 Tirzepatide Associated Partial Small Bowel Obstruction: A Case Report

Abstract Disclosure: A. Mathew: None. H. Hannoodee: None. Glucagon-like peptide-1 receptor agonists (GLP1 RA) are quickly becoming an adjunctive treatment modality for people with type-2 diabetes and is approved for chronic weight management. Tirzepatide has a dual GIP/GLP-1 RA action and has a synergistic effect when administered together. GLP-1 RA are associated with improved cardiovascular and all-cause mortality outcomes in patients with type-2 diabetes. Tirzepatide is associated with gastrointestinal (GI) side effects like nausea, diarrhea, abdominal pain, decreased appetite, and constipation. This case report discusses a case of small bowel obstruction (SBO) that was noted after patient was changed from dulaglutide to tirzepatide. Mr. X is a 61 y/o male with PMHx of type-2 DM, HTN, and HLD who presented to ER for severe epigastric pressure- like 7/10 abdominal pain. No association with food intake. He had 1 episode of semi-loose stools. Denied any abdomen cramping, sick contacts, nausea/vomiting, fever/chills, or constipation. His previous endoscopy was only relevant for benign colonic polyps, which were removed. He had been on GLP1 RA for more than a year, and previously on dulaglutide 3mg, which was switched to tirzepatide 2.5mg 5 weeks ago. He was able to tolerate the medication without significant side effects and was recently up-titrated to 5 mg. Labs showed WBC 7.2, Hb 13.6, Cr 1.45, BUN 12, lipase 25, and normal LFTs. Abdominal X-ray and CT abdomen were noted to be significant for a partial vs evolving SBO without any identifiable small bowel intrinsic pathology. Mr. X was managed conservatively with fluids, NPO diet, and pain medications. Serial abdominal images were obtained, and he was eventually advanced to soft diet. Tirzepatide was discontinued on discharge. As a response to enteral nutrition, distal small bowel and colon release GLP-1 hormone. Exogenous and endogenous GLP-1 are associated with reduced gastric motility. GLP 1 RA and dual GIP/GLP-1 RA are advised to be used with caution in patients with established gastroparesis, as they can worsen the symptoms. GLP-1 effect on small intestinal motility is not extensively studied, however, small bowel motility inhibition was noted in animal models. Some of these actions were dose-dependent. There are some case reports of SBO due to GLP-1 RA. An observational cohort study noted an increased incidence of SBO with GLP1 RA when compared to SGLT2i. They noted most incidents of SBO happened early within the initiation of therapy (within 3 months). At the time of writing this abstract, there are no published SBO case reports associated with tirzepatide. Further large-scale clinical trials need to be conducted to explore the association of SBO in patients with GIP/GLP-1 and GLP-1 RA. These studies will help guide if these drugs should be contraindicated or used with caution in people with a previous history of SBO or colonic obstruction. Presentation: Friday, June 16, 2023

Dilated small and large intestines combined with a severely abnormal demeanor are characteristic of mesenteric torsion in cattle.

To describe the clinical, laboratory, and ultrasonographic findings; treatment; and outcome of cattle with mesenteric torsion (MT). 61 cattle with MT between November 1, 1986, and December 31, 2019. Medical records were retrospectively reviewed. Results were compared for cattle that survived versus did not survive to hospital discharge. All cattle had abnormal demeanor. The most common clinical signs were tachycardia (80.3% [49/61]), tachypnea (65.0% [39/60]), and lower rectal temperature (59.3% [35/59]). Signs of colic occurred in 65.6% (40/61). The most common gastrointestinal findings were an empty or almost empty rectum (100% [59/59]), reduced or absent motility of the small intestines (96.6% [57/59]) or rumen (93.2% [55/59]), positive ballottement and/or percussion and simultaneous auscultation on the right side (91.7% [55/60]), and dilated small (49.2% [29/59]) and large intestines (spiral colon and/or cecum, 44.1% [26/59]) detected during transrectal examination. The most common laboratory findings were acidosis (82.6%, [38/46]) hypermagnesemia (74.5% [35/47]). Ultrasonographic findings included reduced or absent small intestinal motility (86.7% [26/30]) and dilated small intestines (83.8% [31/37]). The spiral colon was dilated in 32.4% (12/37) of the cattle. Eighty-two percent (50/61) of the cattle underwent right flank laparotomy and the MT could be reduced in 34.4% (21/61). Twenty-three percent (14/61) of the cattle survived to hospital discharge, and 77.0% (47/61) were euthanized before hospital discharge. Dilated small and large intestines (spiral colon, cecum) combined with a severely abnormal demeanor and tachycardia are characteristic findings in cows with MT. Immediate surgical treatment is paramount.

Comparative study of purgative pharmacological effects and mechanisms of Moringa oleifera leaves and Rhei Radix et Rhizoma

Moringa oleifera leaves are known for their &quot;Virechana&quot;(purgative) effect in Ayurvedic medicine in India. This study compared the purgative effects and mechanisms of M. oleifera leaves with the reference Rhei Radix et Rhizoma to establish a foundation for the further application of M. oleifera leaves in traditional Chinese medicine(TCM). Using network pharmacology and molecular docking methods, this study identified the material basis, common targets, and signaling pathways through which Rhei Radix et Rhizoma and M. oleifera leaves exerted their purgative pharmacological effects. A low-fiber diet-induced constipation mouse model was established to measure fecal parameters and small intestinal propulsion rate, and histological changes in the colon were observed using HE staining. Relative expression levels of relevant genes and target proteins were assessed using RT-qPCR and immunohistochemistry, respectively. The results showed that mapping the targets of Rhei Radix et Rhizoma and M. oleifera leaves onto the biological process network of constipation revealed close proximity, indicating that they may exert their therapeutic effects on constipation through similar biological processes. Molecular docking results indicated that compounds such as sennoside C and isoquercitrin could target serine/threonine protein kinases(AKT1) and mitogen-activated protein kinase 3(MAPK3), thereby affecting MAPK and calcium signaling pathways to promote defecation. Animal experiments demonstrated that both M. oleifera leaves and Rhei Radix et Rhizoma increased the number of fecal pellets and water content in constipated mice, improved small intestine motility, colon mucosal thickness, and muscle layer thickness, upregulated the gene expression levels of AKT1 and MAPK3 in the colon, and downregulated the expression of AQP3 protein. These findings suggest that M. oleifera leaves and Rhei Radix et Rhizoma share similarities in their therapeutic efficacy and mechanisms for treating constipation. Using Rhei Radix et Rhizoma as a reference can provide a better understanding of the characteristics of the &quot;Virechana&quot;(purgative) effect of M. oleifera leaves in TCM.

Effects of Multiple High-Dose Methamphetamine Administration on Enteric Dopaminergic Neurons and Intestinal Motility in the Rat Model.

Several studies have identified the effects of methamphetamine (MA) on central dopaminergic neurons, but its effects on enteric dopaminergic neurons (EDNs) are unclear. The aim of this study was to investigate the effects of MA on EDNs and intestinal motility. Male Sprague-Dawley rats were randomly divided into MA group and saline group. The MA group received the multiple high-dose MA treatment paradigm, while the controls received the same saline treatment. After enteric motility was assessed, different intestinal segments (i.e., duodenum, jejunum, ileum, and colon) were taken for histopathological, molecular biological, and immunological analysis. The EDNs were assessed by measuring the expression of two dopaminergic neuronal markers, dopamine transporter (DAT) and tyrosine hydroxylase (TH), at the transcriptional and protein levels. We also used c-Fos protein, a marker of neural activity, to detect the activation of EDNs. MA resulted in a significant reduction in TH and DAT mRNA expression as well as in the number of EDNs in the duodenum and jejunum (p < 0.05). MA caused a dramatic increase in c-Fos expression of EDNs in the ileum (p < 0.001). The positional variability of MA effects on EDNs paralleled the positional variability of its effect on intestinal motility, as evidenced by the marked inhibitory effect of MA on small intestinal motility (p < 0.0001). This study found significant effects of MA on EDNs with locational variability, which might be relevant to locational variability in the potential effects of MA on intestinal functions, such as motility.

Effect of cholecystokinin on small intestinal motility in suncus murinus

In a fasting gastrointestinal tract, a characteristic cyclical rhythmic migrating motor complex (MMC) occur that comprises of three phases: I, II, and III. Among these, phase III contractions propagate from the stomach to the lower intestine in mammals, including humans, dogs, and Suncus murinus (suncus). Apart from the phase III of MMC propagating from the stomach, during the gastric phase II, small intestine-originated strong contractions propagate to the lower small intestine; however, the mechanism of contractions originating in the small intestine has not been clarified. In this study, we aimed to elucidate the role of cholecystokinin (CCK) in small intestinal motility. Administration of sulfated CCK-8 in phase I induced phase II-like contractions in the small intestine, which lasted for approximately 10–20 min and then returned to the baseline, while no change was observed in the stomach. Contractions of small intestine induced by CCK-8 were abolished by lorglumide, a CCK1 receptor antagonist. Gastrin, a ligand for the CCK2 receptor, evoked strong contractions in the stomach, but did not induce contractions in the small intestine. To examine the effect of endogenous CCK on contractions of small intestinal origin, lorglumide was administered during phase II. However, there was no change in the duodenal motility pattern, and strong contractions of small intestinal origin were not abolished by treatment with lorglumide. These results suggest that exogenous CCK stimulates contractions of small intestine via CCK1 receptors, whereas endogenous CCK is not involved in the strong contractions of small intestinal origin.

Houpo Paiqi Mixture Promotes Intestinal Motility in Constipated Rats by Modulating Gut Microbiota and Activating 5-HT-cAMP-PKA Signal Pathway.

Constipation is a common functional gastrointestinal disorder which needs more effective treatment approaches. Houpo Paiqi Mixture (HPPQM) is a type of Chinese patent medicine developed from a classical formula that has been widely applied to the treatment of intestinal motility disorder. Here we aim to assess the effectiveness of HPPQM in the treatment of constipation in rat models and its potential mechanism. UPLC-MS/MS was performed to investigate the chemical component of HPPQM. Rats were randomly divided into normal control, constipation model (CM), HPPQM (low, middle and high dose) and mosapride groups. Loperamide 8mg/kg was given orally to induce constipation model. The small intestine motility, colonic contraction, rectum propulsion and histological feature of the colon were significantly improved in HPPQM group, compared with CM group (P<0.05). Results of 16S rRNA sequencing revealed that HPPQM treatment strikingly restructured intestinal microbiota in constipated rats by increasing the relative abundances of Bacteroides and Akkermansia and decreasing the relative abundances of Prevotella and Lactobacillus. The levels of GPR43, 5-HT, 5-HT4R, cAMP, PKA were decreased while SERT was increased in constipated rats (P<0.05), which could be restored to normal levels by treatment with HPPQM (P<0.05). Differences in amplitude between experimental CLSMs (with HPPQM added) and control CLSMs were discovered, starting at the concentration of 40 nL/mL (P<0.05). It was found that GLPG0974 and GR113808 could significantly reduce this reactivity (P<0.05). HPPQM manifested a curative effect in constipated rats by promoting intestinal motility. The underlying mechanisms might be related to modulating gut microbiota and activating 5-HT-cAMP-PKA signal pathway.

Small Bowel Transit Scintigraphy in Children With Pediatric Intestinal Pseudo-Obstruction.

Objective evidence of small intestinal dysmotility is a key criterion for the diagnosis of pediatric intestinal pseudo-obstruction (PIPO). Small bowel scintigraphy (SBS) allows for objective measurement of small bowel transit (SBT), but limited data are available in children. We aimed to evaluate the utility of SBS in children suspected of gastrointestinal dysmotility. Patients undergoing gastric emptying studies for suspected foregut dysmotility, including PIPO, from 2016 to 2022 at 2 tertiary children's hospitals were recruited to an extended protocol of gastric emptying studies to allow for assessment of SBT. PIPO was classified based on antroduodenal manometry (ADM). SBT was compared between PIPO and non-PIPO patients. Scintigraphic parameters were assessed and correlated against ADM scores. Fifty-nine patients (16 PIPO and 43 non-PIPO diagnoses) were included. SBS was performed with liquid and solid meals in 40 and 26 patients, respectively. As compared to the non-PIPO group, PIPO patients had a significantly lower median percentage of colonic filling at 6 hours, with both liquid (48% vs 83%) and solid tests (5% vs 65%). SBT in PIPO patients with myopathic involvement was significantly slower than in patients with neuropathic PIPO, both for liquid and solid meal. A significant correlation was found between solid SBT and ADM scores (r = -0.638, P = 0.036). SBS provides a practically feasible assessment of small intestinal motility. It shows a potential utility to help diagnose and characterize PIPO. SBS seems most discriminative in PIPO patients with myopathic involvement. Studies in a larger pediatric population and across different ages are required.

A novel beneficial role of humanin on intestinal apoptosis and dysmotility in a rat model of ischemia reperfusion injury

A prevalent clinical problem including sepsis, shock, necrotizing enterocolitis, and mesenteric thrombosis is intestinal ischemia/reperfusion (I/R) injury. Humanin (HN), a recently identified mitochondrial polypeptide, exhibits antioxidative and antiapoptotic properties. This work aimed to study the role of HN in a model of experimental intestinal I/R injury and its effect on associated dysmotility. A total of 36 male adult albino rats were allocated into 3 equal groups. Sham group: merely a laparotomy was done. I/R group: for 1 h, clamping of the superior mesenteric artery was done, and then reperfusion was allowed for 2 h later. HN-I/R group: rats underwent ischemia and reperfusion, and 30 min before the reperfusion, they received an intraperitoneal injection of 252 μg/kg of HN. Small intestinal motility was evaluated, and jejunal samples were got for biochemical and histological analysis. I/R group showed elevation of intestinal NO, MDA, TNF- α, and IL-6 and decline of GPx and SOD levels. Furthermore, histologically, there were destructed jejunal villi especially their tips and increased tissue expression of caspase-3 and i-NOS, in addition to reduced small intestinal motility. Compared to I/R group, HN-I/R group exhibited decrease intestinal levels of NO, MDA, TNF- α, and IL-6 and increase GPx and SOD. Moreover, there was noticeable improvement of the histopathologic features and decreased caspase-3 and iNOS immunoreactivity, beside enhanced small intestinal motility. HN alleviates inflammation, apoptosis, and intestinal dysmotility encouraged by I/R. Additionally, I/R-induced apoptosis and motility alterations depend partly on the production of nitric oxide.

GutMap: A New Interface for Analysing Regional Motility Patterns in ex vivo Mouse Gastrointestinal Preparations.

Different regions of the gastrointestinal tract have specific functions and thus distinct motility patterns. Motility is primarily regulated by the enteric nervous system (ENS), an intrinsic network of neurons located within the gut wall. Under physiological conditions, the ENS is influenced by the central nervous system (CNS). However, by using ex vivo organ bath experiments, ENS regulation of gut motility can also be studied in the absence of CNS influences. The current technique enables the characterisation of small intestinal, caecal, and colonic motility patterns using an ex vivo organ bath and video imaging protocol. This approach is combined with the novel edge detection script GutMap, available in MATLAB, that functions across Windows and Mac platforms. Dissected intestinal segments are cannulated in an organ bath containing physiological saline with a camera mounted overhead. Video recordings of gut contractions are then converted to spatiotemporal heatmaps and analysed using the GutMap software interface. Using data analysed from the heatmaps, parameters of contractile patterns (including contraction propagation frequency and velocity as well as gut diameter) at baseline and in the presence of drugs/treatments/genetic mutations can be compared. Here, we studied motility patterns of female mice at baseline and in the presence of a nitric oxide synthase inhibitor (Nω-Nitro-L-arginine; NOLA) (nitric oxide being the main inhibitory neurotransmitter of gut motility) to showcase the application of GutMap. This technique is suitable for application to a broad range of animal models of clinical disorders to understand underlying biological pathways contributing to gastrointestinal dysfunction. Key features • Enhanced video imaging analysis of gut contractility in rodents using a novel software interface. • New edge detection algorithm to accurately contour curvatures of the gastrointestinal tract. • Allows for output of high-resolution spatiotemporal heatmaps across Windows and Mac platforms. • Edge detection and analysis method makes motility measurements accessible in different gut regions including the caecum and stomach.