Gastrointestinal Motility Disorders Research Articles

Understanding the Biology of Human Interstitial Cells of Cajal in Gastrointestinal Motility

Millions of patients worldwide suffer from gastrointestinal (GI) motility disorders such as gastroparesis. These disorders typically include debilitating symptoms, such as chronic nausea and vomiting. As no cures are currently available, clinical care is limited to symptom management, while the underlying causes of impaired GI motility remain unaddressed. The efficient movement of contents through the GI tract is facilitated by peristalsis. These rhythmic slow waves of GI muscle contraction are mediated by several cell types, including smooth muscle cells, enteric neurons, telocytes, and specialised gut pacemaker cells called interstitial cells of Cajal (ICC). As ICC dysfunction or loss has been implicated in several GI motility disorders, ICC represent a potentially valuable therapeutic target. Due to their availability, murine ICC have been extensively studied at the molecular level using both normal and diseased GI tissue. In contrast, relatively little is known about the biology of human ICC or their involvement in GI disease pathogenesis. Here, we demonstrate human gastric tissue as a source of primary human cells with ICC phenotype. Further characterisation of these cells will provide new insights into human GI biology, with the potential for developing novel therapies to address the fundamental causes of GI dysmotility.

European Society for Neurogastroenterology and Motility recommendations for conducting gastrointestinal motility and function testing in the recovery phase of the COVID-19 pandemic.

BackgroundDuring the peak of the COronaVIrus Disease 2019 (COVID‐19) pandemic, care for patients with gastrointestinal motility and functional disorders was largely suspended. In the recovery phases of the pandemic, non‐urgent medical care is resumed, but there is a lack of guidance for restarting and safely conducting motility and function testing. Breath tests and insertion of manometry and pH‐monitoring probes carry a risk of SARS‐CoV‐2 spread through droplet formation.MethodsA panel of experts from the European Society for Neurogastroenterology and Motility (ESNM) evaluated emerging national and single‐center recommendations to provide the best current evidence and a pragmatic approach to ensure the safe conduct of motility and function testing for both healthcare professionals and patients.ResultsAt a general level, this involves evaluation of the urgency of the procedure, evaluation of the infectious risk associated with the patient, the investigation and the healthcare professional(s) involved, provision of the test planning and test units, education and training of staff, and use of personnel protection equipment. Additional guidance is provided for specific procedures such as esophageal manometry, pH monitoring, and breath tests.Conclusions and InferencesThe ESNM guidelines provide pragmatic and appropriate guidance for the safe conduct of motility and function testing in the COVID‐19 pandemic and early recovery phase.

Correction: Endoscopic management of gastrointestinal motility disorders - part 2: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

ESGE suggests flexible endoscopic treatment over open surgical treatment as first-line therapy for patients with a symptomatic Zenker’s diverticulum of any size. Weak recommendation, low quality of evidence, level of agreement 100 %. ESGE recommends that emerging treatments for Zenker’s diverticulum, such as Zenker’s peroral endoscopic myotomy (Z-POEM) and tunneling, be considered as experimental; these treatments should be offered in a research setting only. Strong recommendation, low quality of evidence, level of agreement 100 %. ESGE recommends against the widespread clinical use of transoral incisionless fundoplication (TIF) as an alternative to proton pump inhibitor (PPI) therapy or antireflux surgery in the treatment of gastroesophageal reflux disease (GERD), because of the lack of data on the long-term outcomes, the inferiority of TIF to fundoplication, and its modest efficacy in only highly selected patients. TIF may have a role for patients with mild GERD who are not willing to take PPIs or undergo antireflux surgery. Strong recommendation, moderate quality of evidence, level of agreement 92.8 %. ESGE recommends against the use of the Medigus ultrasonic surgical endostapler (MUSE) in clinical practice because of insufficient data showing its effectiveness and safety in patients with GERD. MUSE should be used in clinical trials only. Strong recommendation, low quality evidence, level of agreement 100 %. ESGE recommends against the use of antireflux mucosectomy (ARMS) in routine clinical practice in the treatment of GERD because of the lack of data and its potential complications. Strong recommendation, low quality evidence, level of agreement 100 %. ESGE recommends endoscopic cecostomy only after conservative management with medical therapies or retrograde lavage has failed. Strong recommendation, low quality evidence, level of agreement 93.3 %. ESGE recommends fixing the cecum to the abdominal wall at three points (using T-anchors, a double-needle suturing device, or laparoscopic fixation) to prevent leaks and infectious adverse events, whatever percutaneous endoscopic cecostomy method is used. Strong recommendation, very low quality evidence, level of agreement 86.7 %. ESGE recommends considering endoscopic decompression of the colon in patients with Ogilvie’s syndrome that is not improving with conservative treatment. Strong recommendation, low quality evidence, level of agreement 93.8 %. ESGE recommends prompt endoscopic decompression if the cecal diameter is > 12 cm and if the Ogilvie’s syndrome exists for a duration of longer than 4 – 6 days. Strong recommendation, low quality evidence, level of agreement 87.5 %.

Unexpected high frequency of neurofibroma in the celiac ganglion of German cattle

In a study originally designed to find potential risk factors for bovine spongiform encephalopathy (BSE) we examined tissues from 403 Holstein Frisian cattle in total. These included 20 BSE cattle and their 236 birth- and feeding cohort animals plus 32 offspring, 103 age, breed and district-matched control cattle and further twelve cattle with neurological signs. In addition to the obex, we examined the celiac ganglion, cervical cranial ganglion, trigeminal ganglion and proximal ganglion of the vagus nerve using histological techniques. Unexpectedly, we found a high number of neurofibroma, a benign peripheral nerve sheath tumor consisting of Schwann cells, fibroblasts and perineural cells. The neurofibroma were present only in the celiac ganglion and found during histologic examination. With a frequency of 9.91% in BSE cattle and their cohorts (case animals) and 9.09% in the age, breed and district matched control animals there seems to be no correlation between the occurrence of BSE and neurofibroma. Benign peripheral nerve sheath tumors have been described more often in cattle than in other domestic animals. Usually, they are incidental macroscopic findings in the thoracic ganglia during meat inspection. To our knowledge, there are no previous systematic histologic studies including bovine celiac ganglia at all. The high incidence of celiac ganglia neurofibroma may play a role in the frequently occurring abomasal displacements in Holstein Frisian cattle as the tumors might cause a gastrointestinal motility disorder. At present a genetic predisposition for these neoplasms cannot be ruled out.

RADIOGRAPHIC DETERMINATION OF GASTRIC EMPTYING AND GASTROINTESTINAL TRANSIT TIME IN COWNOSE RAYS (RHINOPTERA BONASUS) AND WHITESPOTTED BAMBOO SHARKS (CHILOSCYLLIUM PLAGIOSUM) AND THE EFFECT OF METOCLOPRAMIDE ON GASTROINTESTINAL MOTILITY.

Gastrointestinal (GI) pathology is common in elasmobranchs; however, information regarding normal GI transit time and the effect of therapeutics on GI motility is lacking. The objective of this study was to determine baseline gastric emptying and GI transit times in cownose rays (Rhinoptera bonasus) and whitespotted bamboo sharks (Chiloscyllium plagiosum) via radiographic barium sulfate contrast studies. Additionally, a pilot study was undertaken to determine the effect of metoclopramide on GI transit time in whitespotted bamboo sharks. Eight cownose rays and eight whitespotted bamboo sharks were administered a 98% w/w barium sulfate suspension at 8 ml/kg via orogastric tube. Post-contrast radiographs were obtained at 2 min, 3, 6, 12, and 23 hr for rays; and 2 min, 3, 6, 9, 12, 16, 25, 30, 36, and every 12 hr until complete gastric emptying occurred for sharks. In cownose rays, the mean and standard error were established for time of initial spiral colon filling (3.4 ± 0.4 hr), complete spiral colon opacification (12 ± 0 hr), initial spiral colon emptying (21.6 ± 1.4 hr), and complete gastric emptying (23 ± 0 hr). In bamboo sharks, the mean and standard error were established for time of initial spiral colon filling (5.3 ± 0.5 hr), complete spiral colon opacification (12.4 ± 1.3 hr), initial spiral colon emptying (22.5 ± 2.7 hr), and complete gastric emptying (39.9 ± 3.3 hr). Cownose rays had a significantly shorter time to spiral colon filling and complete gastric emptying compared with bamboo sharks (P < 0.05). Whitespotted bamboo sharks (n = 8) were administered metoclopramide (0.4 mg/kg orally once daily for 10 days) and the barium series was repeated. Complete gastric emptying time was significantly shorter in treated sharks compared with control (P < 0.05), suggesting that metoclopramide may be a useful therapeutic for GI motility disorders in elasmobranchs.

Peroral endoscopic myotomy for management of gastrointestinal motility disorder.

Achalasia is a type of esophageal motility disorder, consisting of relaxation dysfunction of the lower esophagus and disturbed esophageal peristalsis. Related clinical symptoms include dysphagia, regurgitation, chest pain, and weight loss. Traditional treatment options include endoscopic botulinum toxin injection, endoscopic pneumatic dilation, and laparoscopic Heller's myotomy. These therapies mainly relieve symptoms by reducing the pressure on the lower esophageal sphincter and reducing blood flow resistance at the esophagogastric junction. Based on endoscopic submucosal dissection and natural orifice transluminal endoscopic surgery, peroral endoscopic myotomy (POEM) is a purely endoscopic method of myotomy with minimal invasiveness and a low rate of adverse events when performed by experienced operators. Since then, numerous studies have shown the significant clinical efficacy and safety of POEM. The purpose of this article is to introduce different modified POEMs, special indications for different POEMs, and their advantages as well as disadvantages.

Correction: Endoscopic management of gastrointestinal motility disorders – part 1: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

Correction: Endoscopic management of gastrointestinal motility disorders – part 1: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

Outcomes after enterostomies in children with and without motility disorders: A description and comparison of postoperative complications

PurposeTo provide an overview of complications after ileostomy or colostomy procedures in children, and to compare outcomes between patients with gastrointestinal motility disorders (i.e. functional constipation, Hirschsprung’s disease, pediatric intestinal pseudo-obstruction (PIPO)) and children without motility disorders (including necrotizing enterocolitis, anorectal malformation and inflammatory bowel disease). MethodsWe performed a retrospective study of children who underwent an enterostomy procedure at our institution. The number and type of complications and subsequent reoperations after ostomy formation were determined. Complications were scored using the Clavien–Dindo classification. A complication of ≥ grade III-b was considered a high-grade complication. Results129 children with an ileostomy and 61 children with a colostomy were included. Of these, 62 children (32.6%) had motility disorders; functional constipation (n=40), Hirschsprung’s disease (n=18) and PIPO (n=4). The total prevalence of complications was 73.2%. Comparing the perioperative data, children with motility disorders significantly more often underwent a laparoscopic procedure (59.7% vs. 10.9%, p=0.000) and had an end stoma-configuration (37.1% vs. 14.1%, p=0.000) as compared to children without motility disorders. Children with motility problems had a higher complication rate (88.7% vs. 65.5%, OR 4.1, 95% CI 1.7–9.8, p=0.001) compared to children without motility problems, and a larger proportion of complications was classified as high-grade complications (61.8% vs. 31.0% p =0.002). ConclusionA high complication rate after enterostomy formation was detected. Children with gastrointestinal motility disorders had more and more severe complications as compared to children without motility disorders. Level of evidenceLevel III Type of studyRetrospective comparative study

Endoscopic management of gastrointestinal motility disorders - part 2: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

ESGE suggests flexible endoscopic treatment over open surgical treatment as first-line therapy for patients with a symptomatic Zenker's diverticulum of any size.Weak recommendation, low quality of evidence, level of agreement 100 %.ESGE recommends that emerging treatments for Zenker's diverticulum, such as Zenker's peroral endoscopic myotomy (Z-POEM) and tunneling, be considered as experimental; these treatments should be offered in a research setting only.Strong recommendation, low quality of evidence, level of agreement 100 %.ESGE recommends against the widespread clinical use of transoral incisionless fundoplication (TIF) as an alternative to proton pump inhibitor (PPI) therapy or antireflux surgery in the treatment of gastroesophageal reflux disease (GERD), because of the lack of data on the long-term outcomes, the inferiority of TIF to fundoplication, and its modest efficacy in only highly selected patients. TIF may have a role for patients with mild GERD who are not willing to take PPIs or undergo antireflux surgery.Strong recommendation, moderate quality of evidence, level of agreement 92.8 %.ESGE recommends against the use of the Medigus ultrasonic surgical endostapler (MUSE) in clinical practice because of insufficient data showing its effectiveness and safety in patients with GERD. MUSE should be used in clinical trials only.Strong recommendation, low quality evidence, level of agreement 100 %.ESGE recommends against the use of antireflux mucosectomy (ARMS) in routine clinical practice in the treatment of GERD because of the lack of data and its potential complications.Strong recommendation, low quality evidence, level of agreement 100 %.ESGE recommends endoscopic cecostomy only after conservative management with medical therapies or retrograde lavage has failed.Strong recommendation, low quality evidence, level of agreement 93.3 %.ESGE recommends fixing the cecum to the abdominal wall at three points (using T-anchors, a double-needle suturing device, or laparoscopic fixation) to prevent leaks and infectious adverse events, whatever percutaneous endoscopic cecostomy method is used.Strong recommendation, very low quality evidence, level of agreement 86.7 %.ESGE recommends considering endoscopic decompression of the colon in patients with Ogilvie's syndrome that is not improving with conservative treatment.Strong recommendation, low quality evidence, level of agreement 93.8 %.ESGE recommends prompt endoscopic decompression if the cecal diameter is > 12 cm and if the Ogilvie's syndrome exists for a duration of longer than 4 - 6 days.Strong recommendation, low quality evidence, level of agreement 87.5 %.

Gut dysmotility in functional gastrointestinal disorders. Potential for therapeutic adjustment in terms of clinical case management

Gastrointestinal motility disorders can be a leading pathogenetic factor contributing to the development of many common gastroenterological diseases. Motor disorders can be a pathogenetic mechanism of development of both organic pathology (developmental abnormalities, acquired diseases, etc.), and functional gastrointestinal diseases associated with impaired nervous, humoral, metabolic and local regulation. (the latter are quite common in clinical practice). Correction of digestive motility disorders is determined by an understanding of the mechanisms of its complex regulation, which allows you to find the necessary points of application of drugs and select the necessary therapy. The motility of the gastrointestinal tract is primarily affected by prokinetics. Opioids used for many years are considered to be one of the most promising groups of prokinetics with proven effectiveness, they can both enhance and weaken the motor. A mu-, kappa-, and beta-receptor agonist, trimebutin, which acts on all receptors at the same time, coordinates the work of the intestines, and normalizes motility by reducing visceral sensitivity. Trimebutin favorably affects both hyperkinetic and hypokinetic forms of disorders of the motor activity of the gastrointestinal tract. This mechanism of action of trimebutin allows its effective use in patients with functional diseases of the digestive system, including those with the syndrome of their intersection. Trimebutin may be the drug of choice for such a combined pathology as irritable bowel syndrome and functional dyspepsia, the use of which is presented in the article on a clinical example of these two diseases.

Endoscopic management of gastrointestinal motility disorders – part 1: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

ESGE recommends the use of a graded pneumatic dilation protocol in achalasia, starting with a 30-mm dilation and followed by a 35-mm dilation at a planned interval of 2 - 4 weeks, with a subsequent 40-mm dilation when there is insufficient relief, over both a single balloon dilation procedure or the use of a larger balloon from the outset.Strong recommendation, high quality of evidence, level of agreement 100 %.ESGE recommends being cautious in treating spastic motility disorders other than achalasia with peroral endoscopic myotomy (POEM).Strong recommendation, very low quality of evidence, level of agreement 87.5 %.ESGE recommends against the routine use of botulinum toxin injections to treat patients with non-achalasia hypercontractile esophageal motility disorders (Jackhammer esophagus, distal esophageal spasm). However, if, in individual patients, endoscopic injection of botulinum toxin is chosen, ESGE recommends performing injections into four quadrants of the lower esophageal sphincter and in the lower third of the esophagus.Strong recommendation, low quality of evidence, level of agreement 78.6 %.ESGE recommends that endoscopic pylorus-directed therapy should be considered only in patients with symptoms suggestive of gastroparesis in combination with objective proof of delayed gastric emptying using a validated test, and only when medical therapy has failed.Strong recommendation, very low quality of evidence, level of agreement 100 %.ESGE recommends against the use of botulinum toxin injection in the treatment of unselected patients with gastroparesis. Strong recommendation, high quality of evidence, level of agreement 92.9 %.ESGE recommends consideration of gastric peroral endoscopic myotomy (G-POEM) in carefully selected patients only, because it is an emerging procedure with limited data on effectiveness, safety, and durability. G-POEM should be performed in expert centers only, preferably in the context of a clinical trial.Strong recommendation, low quality of evidence, level of agreement 100 %.

The impact of acute stress disorder on gallbladder interstitial cells of Cajal.

Physical and psychological stress exerts a substantial effect on gastrointestinal motility disorders, where trauma enhances symptoms of digestive dysfunction. Interstitial cells of Cajal (ICCs) act as pacemakers for gastrointestinal motility regulation and are likely important in stress-associated gastrointestinal motility disorders. This study explored the mechanisms underlying gallbladder ICCs function under acute stress conditions using a rabbit chest puncture and cholecystectomy model. The stem cell factor (SCF)/c-kit pathway is essential for the development of ICCs, and gene expression was investigated to identify stress-induced transcriptional alterations. Immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling assays were used to determine ICCs apoptosis, whereas western blot analysis and reverse-transcription polymerase chain reaction were used to detect changes in the SCF/c-kit signaling pathway. These methods revealed a reduction in ICCs via apoptosis following stress, and ICCs increased over time after stressor removal. Therefore, this study demonstrates the impact of stress on ICCs development and survival and further confirms the link between stress and gastrointestinal motility.

Pan-enteric neuropathy and dysmotility are present in a mouse model of short-segment Hirschsprung disease and may contribute to post-pullthrough morbidity

PurposeHirschsprung disease (HSCR) is characterized by distal intestinal aganglionosis. While surgery is lifesaving, gastrointestinal (GI) motility disorders persist in many patients. Our objective was to determine whether enteric nervous system (ENS) abnormalities exist in the ganglionated portions of the GI tract far proximal to the aganglionic region and whether these are associated with GI dysmotility. MethodsUsing Ednrb-null mice, a model of HSCR, immunohistochemical analysis was performed to evaluate quantitatively ENS structure in proximal colon, small intestine, and stomach. Gastric emptying and intestinal transit were measured in vivo and small and large bowel contractility was assessed by spatiotemporal mapping ex vivo. ResultsProximal colon of HSCR mice had smaller ganglia and decreased neuronal fiber density, along with a marked reduction in migrating motor complexes. The distal small intestine exhibited significantly fewer ganglia and decreased neuronal fiber density, and this was associated with delayed small intestinal transit time. Finally, in the stomach of HSCR mice, enteric neuronal packing density was increased and gastric emptying was faster. ConclusionsENS abnormalities and motility defects are present throughout the ganglionated portions of the GI tract in Ednrb-deficient mice. This may explain the GI morbidity that often occurs following pull-through surgery for HSCR.

Proceedings of the 2018 Advances In Motility and In NeuroGastroenterology: AIMING for the Future Single Topic Symposium.

Motility and functional disorders are common in children and often debilitating, yet these disorders remain challenging to treat effectively. At the 2018 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the Neurogastroenterology and Motility Committee held a full day symposium entitled, 2018 Advances In Motility and In NeuroGastroenterology - AIMING for the future. The symposium aimed to explore clinical paradigms in pediatric gastrointestinal motility disorders and provided a foundation for advancing new scientific and therapeutic research strategies. The symposium brought together leading experts throughout North America to review the state of the art in the diagnosis and management of motility and functional disorders in children. Presentations were divided into esophageal, antral duodenal, and colorectal modules. Each module included oral presentations by experts in the respective fields, leading to thought-provoking discussions. There were 2 breakout sessions with small group discussions on select topics, focusing on defining scientific insights into the diagnosis and management of pediatric functional gastrointestinal and motility disorders in a systematic, segment-based approach. The field of neurogastroenterology has made remarkable progress in the last decade. The current report summarizes the major learning points from the symposium highlighting the diagnosis and promising therapies on the horizon for pediatric neurogastrointestinal and motility disorders.

Trypanosoma Cruzi Induces Phospho‐proteome Profile in Primary Colon Epithelial Cells During Early Infection

Trypanosoma cruzi, an obligate intracellular protozoan parasite, is the etiological agent of Chagas Disease. Due to globalization, the disease is now present in all economically advanced countries of the world. About 30% of T. cruzi infected individuals will develop cardiac, neurological, and/or gastrointestinal pathology, particularly megacolon. Megacolon, one of Chagas disease major pathologies, is accompanied by gastrointestinal motility disorders that have been attributed to alterations in the number of interstitial cells of Cajal and enteric nervous system defects. The objective of this study is to begin to define early molecular mechanisms that contribute to chagasic megacolon that can be exploited for development of molecular intervention strategies. In order to do this, we challenged primary colon epithelial cells (HCoEpiC) with invasive T. cruzi trypomastigotes at different time points to decipher changes in levels of phosphorylated proteins. Using a proteome profiler Human phospho‐kinase array, we show that T. cruzi induced a unique phospho‐proteome profile. We validated the phospho‐kinase array data via immunoblotting and immunofluorescence. Modulators of host immune response such JAK2, STAT1, and NF‐kB showed increased activation. Increased phosphorylated levels of kinases such, as p‐Src and p‐Fyn and the Heat Shock protein (p‐HSP27) chaperone illustrate dysregulation of intracellular signaling. We found that p‐JNK and p‐AKT exhibited increased phosphorylation and their downstream effectors p‐CREB and p‐c‐Jun showed increased nuclear colocalization. Early infection also induced increase thrompsopondin‐1 expression, a known fibrogenic protein. We generated a biological interaction network using Ingenuity Pathway Analysis (IPA) to further characterize protein‐protein interactions within the phospho‐proteome profile. In conclusion, we demonstrate a unique phospho‐proteome profile induced by T. cruzi during early infection of HCoEpiC and illustrate biological networks and signal transduction pathways that are activated during infection.Support or Funding InformationThis work was supported by NIH grants SC1AI127352, 5U54MD007586 (The RCMI Program in Health Disparities Research), and 5R25GM059994‐19 (RISE).

Non‐invasive Targeted Gastric Vagal Complex Stimulation: Preliminary in Human Cutaneous Measures of Gastric Slow Wave Function

Gastric slow wave abnormalities have been associated with upper gastrointestinal motility disorders. Invasive studies in humans have described normal and abnormal propagation of the gastric slow wave, and recent non‐invasive studies have shown that multi‐electrode cutaneous measures of gastric slow wave function correlate with symptom severity in patients with gastroparesis and functional dyspepsia (Gharibans et al, Clinical Gastroenterology and Hepatology, 2019). Invasive Neurostimulation of gastric Vagal complexes are thought to result in satiety (Abiliti, Transcend), anti‐nausea (Entera) and general weight loss (vBLOC), but effects of invasive neuromodulation on gastric motility are not clear. Our group developed: 1) a wearable non‐invasive electrogastrography (EGG) device that reliably records gastric slow wave function and 2) a new non‐invasive targeted gastric Vagus nerve stimulation (ntG‐VNS) system. The challenge is to further develop a combined ntG‐VNS/EGG system that may be used as a tool to probe Gastric disease states, and eventually diagnose and or treat gastric motility disorders.MethodsA 10 lead ambulatory high resolution electrogastrogram (AHR‐EGG) system for ambulatory use (Gharibans et al, Scientific Reports, 2018) was used to record gastric myolectric activity cutaneously (Fig 1A). The gastric proximal fundus was visualized at a depth of 2cm using a Butterfly high frequency transducer at 1–5MHz (Fig 1b) and guided stimulator electrode placement. After fundus localization ntG‐VNS was applied inferior to the lower sternum with 2 (0.5 inch) disk electrodes 0.5 inch apart in rostral caudal orientation (Fig 1A) utilizing short pulsed intermittent stimulation for 14 minutes during simultaneous EGG. Cutaneous recordings were sampled at 250Hz, filtered below 0.15Hz and down‐sampled to 1Hz. Artifact rejection methods as described in (Gharibans et al, Scientific Reports, 2018) were next applied, followed by median filtering of the 0.05Hz power derived from spectrograms across all electrodes to derive EGG power. Baseline activity was derived from percentiles of power across the recording, and was subtracted to derive normalized EGG power to be used for subsequent analysis.ResultsEGG power prior to nTG‐VNS showed a center frequency of .0493 Hz (Fig 2A). Post nTG‐VNS EGG showed highly significant reduction of slow wave power (Fig 2B), below the baseline pre‐stimulation levels.ConclusionntG‐VNS immediately abolishes gastric slow wave propagation as measured by non‐invasive AHR‐EGG over a 14 min time period. Taken together, targeted non‐invasive gastric vagus nerve stimulation technology may prove to be a valuable human research tool, focused on improving our fundamental understanding of gastric motility vagal reflexes.Support or Funding InformationThis work was in part supported by the U.S. Department of Health and Human Services, Biological Advanced Research and Development Authority, BARDA: (75A50119C00038)Figure 1Figure 2

Transcutaneous Electrical Stimulation Rescues Gastric Emptying in Lung Transplant Patients with Moderate to Severe Gastroparesis

Gastroparesis (GP) is prevalent after lung transplant (Ltx) (50-68%). GP has been associated with symptoms and delayed absorption of medications. Of particular concern after Ltx, GP can predispose to gastroesophageal reflux disease considered the main culprit for chronic allograft dysfunction. Therefore, early diagnosis and treatment is recommended in Ltx patients. Pharmacologic intervention for GP is not efficacious to improve gastric emptying and can induce potential serious side effects. Transcutaneous electric stimulation (TES) has been proposed to improve motility in various gastrointestinal motility disorders METHODS: We tested the hypothesis that TES may improve gastric emptying in Ltx patients. A 4-hour solid-phase gastric emptying study was done for worsening lung function before and after TES. Surveillance gastric emptying study (GEE) was done 2-12 weeks after TES. Five patients (4 female, age 48 ± 8), interval post-transplant (1-10 years), underwent TES as rescue therapy for moderate to severe GP (gastric retention >25% at 4 hours) that failed standard pharmacologic and dietary interventions. TES was delivered in continuous square wave, pulse rate 120 Hz, pulse width 220 µs, and pulse intensity to the maximum tolerated level without pain or muscle twitching. Two cutaneous electrodes were placed between T6 and T10 spinal levels (gastric autonomic segment) over the spine. Patients were instructed to use TES for 30 min after meals and for 30 min at bedtime RESULTS: Following TES, the percentage of gastric retention at 4 hours improved in the majority of patients (42 median, 25-73 min-max before TES; 20 median 7-43 min-max) after TES, p=0.01; figure 1). Three patients reported GP symptoms. Only one patient reported no significant improvement in the severity of symptoms CONCLUSION: TES appears to modulate symptom perception and significantly improves gastric emptying in Ltx patients with moderate to severe gastroparesis.

ПЕРЕБІГ ЗАГРОЗИ ПЕРЕРИВАННЯ ВАГІТНОСТІ ПРИ РІЗНИХ ТИПАХ ХРОНІЧНИХ ГАСТРИТІВ

Переривання вагітності – одна з важливих медико-соціальних проблем в усьому світі. Функціонально-морфологічні зміни в статевій сфері, які супроводжують нормальний ріст і розвиток плода при фізіологічній вагітності обумовлюють в різній мірі участь інших органів і систем материнського організму, сприяють зміні процесів обміну і підтримці гомеостазу в нових умовах для збереження вагітності. Розлади моторики шлунково-кишкового тракту можуть бути провідним патогенетичним чинником, що сприяє розвитку багатьох поширених гастроентерологічних розладів. Під час вагітності відзначається зниження перистальтичної активності кишечника, що може відігравати патогенетичну роль при вагітності як чинника, що призводить до зниження моторно-евакуаторної функції кишечника і, в свою чергу, здійснювати негативний вплив на перебіг вагітності. Метою дослідження було визначення особливостей клінічного перебігу загрози переривання в ранні терміни гестації у жінок з різними типами хронічних гастритів для оптимізації тактики ведення вагітності. Обстежено 67 вагітних із загрозою переривання в терміни 8-12 тижнів гестації, які становили 2 групи: 1 група- 35(52,2%) жінок з хронічними гастритами та 2 група – 32(47,8%) пацієнтки, які не мали гастритів. На початок вагітності всі жінки з хронічними гастритами були в стадії ремісії. Для визначення ролі моторно-евакуаторної функції ШКТ у розвитку загрози переривання у вагітних з гастритами проведена порівняльна оцінка частоти і виразності проявів даного ускладнення в ранні терміни за провідними клінічними ознаками: больовий синдром, кров’янисті виділення, наявність ретрохоріальної гематоми в поєднанні з основними гастроентерологічними проявами (блювання, закрепи) моторно-евакуаторної функції ШКТ при різних типах гастритів. Підтвердження типу гастриту проводилося за визначенням рівня базальної секреції гастрину 17 (G-17) в сироватці крові на тлі стимулюючого тесту. Результати оброблені методами математичного і статистичного аналізу з визначенням середніх величин (М ± m), критерія Стьюдента та показника достовірності (статистично достовірними вважали різницю р ˂ 0,05).Результати. Всі обстежені жінки знаходились в репродуктивному віці, середній вік вагітних в групах не мав статистичної різниці. Аналіз частоти клінічних проявів загрози переривання показав, що серед пацієнток 1 групи 35(100%) мали больову симптоматику, 30(85,7%) – кров’яністі виділення та 10(28,6%) – ретрохоріальну гематому, в 2 групі –відповідно: 32(100%), 12 (37,5%), 5(15,6%). Оцінка інтенсивності симптомів загрози переривання показала, що найчастіше відмічався помірний рівень болю при всіх типах гастритів Слабка інтенсивність мала місце при нормоацидному стані у жінок як 1групи (11,4%), так і 2 групи (9,4%). Сильний за інтенсивністю біль відмічали 2,9% вагітних 1 групи з гіперацидним станом та 3,1% жінок 2 групи з гіпоацидним станом. Аналіз характеру та інтенсивності кров’янистих виділень показав, що у жінок 1 групи при всіх типах гастритів були мажучі виділення: при гіперацидному типі у 11,4%, нормоацидному – 20,0% та гіпоацидному типі – у 11,4%.У жінок 2 групи мажучі виділення відмічені в 9,4% пацієнток з нормоацидним станом. Наявність помірних кров’янистих виділень була значно високою (в 7,4 рази вище) при гіперацидному стані у вагітних 1 групи в порівнянні з 2 групою. Ретрохоріальні гематоми реєструвались у вагітних 1 групи і становили 14,3% у пацієнток з гіперацидним типом, 5,7% - при нормоацидному типі і 8,6% - при гіпоацидному типі. Наявність ретрохоріальних гематом в 2,5 рази була вищою при гіперацидному гастриті в порівнянні з жінками з нормоацидним та в 1,7 рази вищою в порівнянні з гіпоацидним гастритом. Оцінка частоти поєднаних клінічних проявів функціональних захворювань ШКТ у вагітних із загрозою переривання вагітності показала, що прояви тільки загрози переривання спостерігались у 65,6% вагітних без гастритів, серед вагітних з гастритами їх відсоток становив лише 5,7%. Різні варіанти поєднаних клінічних проявів функціональних розладів ШКТ і загрози переривання суттєво переважали у жінок з хронічними гастритами: загроза переривання і блювання вагітних в 3 рази, загроза, блювання і закрепи – в 4,3 рази, загроза переривання і закрепи – в 1,6 рази. Найчастіше відмічено поєднання загрози переривання і блювоти вагітних при гіперацидному стані у жінок 1 групи (в 2,7 разів частіше ніж у жінок 2 групи). Варіант співвідношення загрози переривання, блювання вагітних та закрепів при гіперацидному стані в 3,6 разів частіше зустрічався серед жінок 1 групи, ніж 2 групи. Варіант загрози переривання із закрепами реєструвався у 17,1% жінок 1 групи при гіперацидному стані, що було в 2,7 разів частіше, ніж у жінок 2 групи. Найчастіше клінічні прояви загрози переривання і функціональні розлади ШКТ проявлялись в вагітних з хронічними гастритами при гіперацидному стані. Висновки. В клінічному перебігу загрози переривання вагітності важливу роль відіграє дисфункція моторно-евакуаторної діяльності ШКТ в залежності від типу хронічного гастриту, опосередкованого різною кислотоутворюючою функцією шлунку, що свідчить про необхідність оптимізації лікувальної тактики загрози переривання у вагітних з різними типами гастритів.

DIGESTIVE ORGANS STATUS IN CHILDREN WITH ATOPIC DERMATITIS

In 93,7% of children with atopic dermatitis, a wide range of gastroenterological complaints were detected, including abdominal pain, nausea and stool disorders, indirect signs of intestinal absorption disorders, gastrointestinal motility disorders in the form of hypermotorics, hypomotorics of the colon, as well as changes in intestinal microbiocenosis (52%).

In vivo and in vitro effects of Salsola collina on gastrointestinal motility in rats.

Objective(s): Salsola collina is widely distributed along the Bohai coast and consumed as an edible plant by native residents. We have found surprisingly that S. collina extracts promoted gastrointestinal motility in mice previously. In the present study, effects of S. collina on gastrointestinal motility in rats and its underlying mechanism were explored.Materials and Methods: In vivo, different fraction extracts from S. collina were prepared and the effects on gastric emptying and small intestinal propulsion in normal rats were measured. Plasma ghrelin (GRL), motilin (MTL), gastrin (GAS) and vasoactive intestinal peptide (VIP) and expressions of GRL receptor (GHSR), MTL receptor (MTLR), VIP receptor 2 (VIPR2) in the duodenum were also detected. In vitro, gastric antrum strips were prepared and activities of different extracts on gastric smooth muscle contractions were evaluated.Results:Results showed that the ethyl acetate extract (EAE) was the most effective fraction to promote gastric emptying and intestinal propulsion, showing a dose-dependent manner. EAE increased plasma GRL and GAS, elevated GHSR expression and restrained VIPR2 expression in the duodenum. In vitro, EAE promoted contraction of normal gastric antrum strips as well as relaxed strips induced by atropine.Conclusion:These data indicate that EAE has a significant prokinetic activity via a mechanism that mainly involves in modulating plasma GRL and GAS, expressions of GSHR and VIPR2 in the duodenum and activating M-cholinergic receptor. Our study provides a pharmacological basis for the use of S. collina extract in treating gastrointestinal motility disorders.