Motility Of Gastrointestinal Tract Research Articles

Synaptic cell adhesion molecule Cdh6 identifies a class of sensory neurons with novel functions in colonic motility.

Intrinsic sensory neurons are an essential part of the enteric nervous system (ENS) and play a crucial role in gastrointestinal tract motility and digestion. Neuronal subtypes in the ENS have been distinguished by their electrophysiological properties, morphology, and expression of characteristic markers, notably neurotransmitters and neuropeptides. Here we investigated synaptic cell adhesion molecules as novel cell type markers in the ENS. Our work identifies two Type II classic cadherins, Cdh6 and Cdh8, specific to sensory neurons in the mouse colon. We show that Cdh6+ neurons demonstrate all other distinguishing classifications of enteric sensory neurons including marker expression of Calcb and Nmu, Dogiel type II morphology and AH-type electrophysiology and I H current. Optogenetic activation of Cdh6+ sensory neurons in distal colon evokes retrograde colonic motor complexes (CMCs), while pharmacologic blockade of rhythmicity-associated current I H disrupts the spontaneous generation of CMCs. These findings provide the first demonstration of selective activation of a single neurochemical and functional class of enteric neurons, and demonstrate a functional and critical role for sensory neurons in the generation of CMCs.

A review of frequently used Kampo prescriptions. Part 5. Rikkunshito

AbstractBackgroundThe source of rikkunshito (RKT) is thought to be Yixuezhengzhuan by Yu Tuan. RKT was originally designed for many patients to treat gastrointestinal symptoms such as abdominal bloating, discomfort, nausea, and anorexia.Key FindingsRKT consists of eight types of crude drugs. Clinical studies including randomized clinical trials (RCT) for patients with non‐erosive reflux disease (NERD) refractory to proton‐pump inhibitor (PPI) have demonstrated that RKT improves not only acid‐related dysmotility symptoms, but also extra‐esophageal symptoms, and with RCT trial for functional dyspepsia (FD), RKT can simultaneously treat gastrointestinal and psychological symptoms. Moreover, RKT was recently applied to the day‐to‐day conditions, post‐operative management, and chemotherapy in cancer patients. Preclinical studies have also reported that various pharmacological functions of RKT such as its protective effect on mucosal injuries and its prokinetic effect on gastrointestinal tract motility have been elucidated. RKT was considered to increase plasma ghrelin levels by the inhibition of 5‐HT2B and 5‐HT2C receptor activities, enhanced ghrelin‐mediated signaling, inhibited degradation of acylated ghrelin to suppress decreases in plasma ghrelin levels by inhibiting the rate of degradation of acyl ghrelin to des‐acyl ghrelin, and inhibited PDE III activity. The incidence of adverse events associated with RKT was only 1.2%, and almost all adverse drug reactions were non‐serious reactions.ConclusionRKT is one of the very good candidates for beneficial medicines especially for patients presenting with intractable symptoms caused by gastrointestinal diseases such as disorders of gut–brain interaction or cancers.

Elimination of Intestinal Hypoxia in Complex Treatment of Intestinal Failure (Case Report)

INTRODUCTION: Currently, various approaches to the treatment of intestinal failure (IF) are considered. In search for pathogenetically justified therapy, it is possible to use oxygenated saline enteral solution (OSES). АIM: To demonstrate, by gas analysis of the introduced oxygenated saline enteral solution and the excreted intestinal fluid, the possibility of gas exchange in the intestine with increased oxygen extraction under hypoxic conditions. An 8-year-old child with burdened premorbid history and severe community–acquired bilateral pleuropneumonia kept on mechanical ventilation, had signs of IF (disorder in passage, absence of independent defecation for more than two days). During treatment and observation of the child, enteral feeding was attempted with pharmacological stimulation with prokinetics, and introduction of laxative sorbent with prebiotic effect (lactulose). Because of non-effectiveness of these measures, it was decided to perform intestinal lavage with OSES introduced through the nasogastral tube. In 30 minites after start of OSES introduction, the gastrointestinal tract motility notably enhanced, in 1.5 hour from the beginning of the procedure, fractional passage of a significant amount of thick fecal masses was noted, after which intestinate — liquid stool stained yellow with bile, was obtained. During the procedure, a comparative analysis of the gas composition of the introduced OSES and excreted intestinate was done. In the excreted solution, 97-fold decrease of рО2 from 659 to 6.8 mm Hg, and 3.6-fold increase in CO2 tension from 23 to 85.7 mm Hg, were noted. CONCLUSION: Oxygenation of the enteral environment by barbotage of a saline enteral solution introduced through a tube is an effective component of intensive therapy for intestinal failure syndrome, taking into account the ability of the gastrointestinal tract tissues to actively participate in gas exchange: extract oxygen and release carbon dioxide.

Amelioration of Dextran Sodium Sulfate-Induced Colitis in Mice through Oral Administration of Palmitoylethanolamide.

Inflammatory bowel disease (IBD) is a group of chronic disorders characterized by pain, ulceration, and the inflammation of the gastrointestinal tract (GIT) and categorized into two major subtypes: ulcerative colitis (UC) and Crohn's disease. The inflammation in UC is typically restricted to the mucosal surface, beginning in the rectum and extending through the entire colon. UC patients typically show increased levels of pro-inflammatory cytokines, leading to intestinal epithelial apoptosis and mucosal inflammation, which impair barrier integrity. Chronic inflammation is associated with the rapid recruitment and inappropriate retention of leukocytes at the site of inflammation, further amplifying the inflammation. While UC can be managed using a number of treatments, these drugs are expensive and cause unwanted side effects. Therefore, a safe and effective treatment for UC patients is needed. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide and an analog of the endocannabinoid anandamine. PEA administration has been found to normalize intestinal GIT motility and reduce injury in rodents and humans. In the current study, we examined the efficacy of PEA encapsulated in phytosomes following oral administration in experimental ulcerative colitis. Here, we showed that PEA at a human-equivalent dose of 123 mg/kg (OD or BID) attenuated DSS-induced experimental colitis as represented by the reduction in clinical signs of colitis, reduction in gross mucosal injury, and suppression of leukocyte recruitment at inflamed venules. These findings add to the growing body of data demonstrating the beneficial effects of PEA to control the acute phase of intestinal inflammation occurring during UC.

Хронічна інтестинальна псевдообструкція в дітей (огляд літератури)

Hirschsprung disease and chronic intestinal pseudo-obstruction (CIPO) in children are the most common and severe disorders of gastro-intestinal tract motility. While the problems connected with the Hirschsprung disease widely coverage in native literature, the publications that devoted the CIPO absent. Aim of the study was to analyze the literature data that devoted to the diagnosis and treatment of children with CIPO. Intestinal pseudo-obstruction refers to heterogeneous groups of disorders with a similar phenotypic presentation characterized by obstructive intestinal symptoms in the absence of true anatomical obstruction. CIPO classification based on the primary dysfunction: affected enteral nervous system (neuropathy), affected smooth muscle (myopathy) or interstitial cells Cajal (mesenchymopathy). Besides that, the intestinal pseudo-obstruction is divided into primary and secondary, congenital and acquired, total and segmentary. The main clinical features, methods of investigation in suspected CIPO such as radiological (roentgenography and roentgenoscopy, computed tomography, cine magnetic resonance), endoscopic, manometry, pathohistological, etc. were listed. The main principles of nutrition support, conventional therapy, and surgical management were presented. Conclusions. CIPO is a severe disorder of gastrointestinal motility that caused by various factors, which can be congenital and/or acquired. Diagnosis of CIPO based on the results of clinical, instrumental, and pathohistological investigation. The management of children with CIPO should include nutritional support, conventional therapy, and, for the clear indices, surgical correction. No conflict of interests was declared by the authors.

Modulating cecal microbiome and in silico amino acid metabolism of sanguinarine-based isoquinoline alkaloids supplements in natural heat stress broiler

Broilers reared under tropical conditions are exposed to Heat Stress (HS) yielding adverseness in production. The study aimed to evaluate the effect of plant-derived sanguinarine-based Isoquinoline alkaloids (IQ) on integrating performance of growth with the cecal microbiome and functional metabolism profiles of amino acid metabolism for either precision nutrition or productivity promotion using nutrition strategies with intestinal microecological balance in broilers of 14-and 35-day of age under HS conditions. IQ significantly improved performance, body weight, average daily weight gain, feed intake, and mortality. IQ significantly modulated the cecum microbiome (14- and 35-dayo of age) by enriching microbiome diversity with increase in Bacteriodetes and Cyanobacteria, but decrease in Firmicutes and Proteobacteria. It was found on 14-day of age that abundances of Turicibactor sanguinis, Lactobacillus salivarious, Lactobacillus sacidophilus, and Akkermansia municiphila in the cecum of boiler fed with IQ60 were higher than in that of the control group. While abundances of Enteroccucus cecorum, Enteroccuus villorum, Escherichia fergusonii, and Helicobacter pullorum were lower in broiler fed with IQs demonstrating the potential to suppress Antimicrobial-Resistant (AMR) reservoirs in the cecum. IQs significantly increased amino acid metabolism namely, l-arginine degradation VII and l-tryptophan degradation I, l-tryptophan degradation VI on day 14, and l-alanine degradation VII, l-tryptophan biosynthesis, l-methionine biosynthesis I, l-methionine salvage cycle, and l-threonine degradation II on day 35 (Kruskal-Wallis p-value < 0.05) in which positively correlated with BW and FI but negative correlation with FCR (Pearson correlation, P < 0.05). It is the first finding that IQs potentially modulated the crosstalk between host and microbiota via the microbiome-gut-brain axis for gut homeostasis by improving Turicibacter sanguini, that promoted serotonin biosynthesis from colonic Enterochromaffin Cells (EC) in modulating Gastro-Intestinal tract (GI) motility. It can be concluded that IQ exhibited the potential to modulate cecal microbiota to improve functional amino acid pathways supporting growth performance in stress broilers. The phenotypic activity related to genotype prediction under in silico model of functional microbiome systems with multi-Omics methods relating with microbiome community is worthwhile to be further investigated leading to discovering potential phytogenic compounds for precision feed additives in stress broilers.

Complementary transcriptomic and proteomic analyses elucidate the toxicological molecular mechanisms of deoxynivalenol-induced contractile dysfunction in enteric smooth muscle cells

Deoxynivalenol (DON) is one of the frequent Fusarium mycotoxins and poses a serious threat to public health worldwide. DON-induced weight loss is tightly connected with its ability to decrease feed intake by influencing gastrointestinal tract (GIT) motility. Our previous reports indicated that DON interfered with intestinal motility by injuring the contractility of enteric smooth muscle cells (SMC). Here, we further explored the potential mechanisms by employing a complementary method of transcriptomics and proteomics using the porcine enteric smooth muscle cell line (PISMC) as an experimental model. The transcriptomic and proteomic data uncover that the expression of numerous extracellular matrix (ECM) proteins and multiple integrin subunits were downregulated in PISMC under DON exposure, suppressing the ECM-integrin receptor interaction and its mediated signaling. Furthermore, DON treatment could depress actin polymerization, as reflected by the upregulated expression of Rho GTPase-activating proteins and cofilin in PISMC. Meanwhile, the expression levels of downstream contractile apparatus genes were significantly inhibited after challenge with DON. Taken together, the current results suggest that DON inhibits enteric SMC contractility by regulating the ECM-integrin-actin polymerization signaling pathway. Our findings provide novel insights into the potential mechanisms behind the DON toxicological effects in the GIT of humans and animals.

Integrated resonance Rayleigh scattering approach utilizing Box-Behnken experimental design for the facile quantification of prucalopride in pharmaceutical tablets and human urine with sustainability assessment.

Prucalopride (PCP) is one of the recent drugs used for the regulation of gastrointestinal tract motility and the treatment of constipation. A new, highly sensitive and fast resonance Rayleigh scattering (RRS) approach was suggested for PCP determination. The approach was based on its reaction of PCP with eosin Y in buffered medium (pH 3.5) to form an ion pair association complex which had a significant enhancement in RRS compared to that of eosin Y or PCP alone. The enhancement of RRS intensity had straight correlation to PCP concentration ranging from 150 to 2000 ng mL-1 with 38 ng mL-1 as LOD and 125 ng mL-1 as LOQ. The measurements were done at a wavelength of 365 nm that provided the maximum sensitivity. All the experimental parameters were studied carefully and optimized via Box-Behnken experimental design. The International Council for Harmonization (ICH) guidelines were employed to validate the suggested method and the obtained results proved the appropriate method performance. The method was efficiently utilized to determine PCP in pure form, pharmaceutical tablets and spiked urine samples with no interferences from the surrounding matrices. Furthermore, the greenness of the suggested procedure was confirmed using different green metric approaches.

Prebiotic prevents the development of gastrointestinal motility disorders caused by omeprazole

The synthetic disaccharide lactulose, consisting of fructose and galactose, after oral administration in an unchanged form reaches the lower part of the gastrointestinal tract, where under the action of normal flora it is broken down into short-chain fatty acids that stimulate colon motility. The effect of lactulose on gastrointestinal tract motility in the conditions of its long-term suppression by omeprazole has not been investigated. We studied the influence of lactulose on spontaneous and carbachol-stimulated gastric and colonic motility in rats treated with omeprazole for 28 days. The animals were divided into 3 groups. The first group of animals served as a control. The animals in the second group were administered omeprazole intraperitoneally at a dose of 14 mg/kg orally once a day for 28 days. The animals in the third group were simultaneously injected intraperitoneally with omeprazole and prebiotic lactulose at a dose of 0.2 g/kg orally once a day for 28 days. On the day after the last injections of drugs, we investigated the spontaneous and carbachol-stimulated contractions in the stomach and colon by the balloon graphic method. It was found that the frequency of spontaneous and stimulated contractions in the stomach and colon did not change significantly after 28 days of omeprazole treatment. The amplitude and index of spontaneous and carbachol-stimulated contractions in the stomach and colon were significantly weaker compared to the control. One day after the 28-day simultaneous administration of omeprazole and lactulose the amplitude and index of spontaneous and stimulated contractions in the stomach and colon increased compared with the group of rats treated with omeprazole alone. We concluded that the positive effect of lactulose on gastric and colon motility is a result of the prebiotic properties of lactulose which leads to the normalization of the microbiocenosis in the gastrointestinal tract and the elimination of the inflammatory process in it.

Anoctamin 1 and c-Kit immunohistochemical study of interstitial cells of Cajal in the muscularis externa of human gastrointestinal tract.

Interstitial cells of Cajal (ICC) are widely distributed in human gastrointestinal (GI) tract, especially in the layer of muscularis externa between neurons and smooth muscles. They play a very important role of coordination of GI tract motility. The aims of this research were to study the morphology and distribution of ICC in the muscularis externa of the GI tract, using immunohistochemistry staining methods, to determine the distribution of immune reactivity of anoctamin 1 (Ano1) compared with c-Kit, and to determine if Ano1 is a reliable marker for ICC in human GI tract. Specimens from the wall of stomach, small intestine, and colon were taken from human cadavers and processed for histological and immunohistochemical study using c-Kit and Ano1 primary antibodies. Interstitial cells of Cajal appeared as bipolar cells, not forming network, in both the circular and longitudinal muscle layers, while in the myenteric area they appeared as multipolar interconnected cells. They were unevenly distributed in and between the muscle layers of the muscularis externa of human GI tract. They were more numerous in the stomach followed by the colon then the small intestine, and more numerous in the myenteric area followed by the circular muscle layer then the longitudinal muscle layer, in the three organs. Our results also showed that Ano1 is a more reliable marker for human ICC than c-Kit. Interstitial cells of Cajal differed in morphology and were unevenly distributed between muscle layers of muscularis externa and between different parts of human GI tract.

A model for gastrointestinal tract motility in a 4D imaging phantom of human anatomy.

Gastrointestinal (GI) tract motility is one of the main sources for intra/inter-fraction variability and uncertainty in radiation therapy for abdominal targets. Models for GI motility can improve the assessment of delivered dose and contribute to the development, testing, and validation of deformable image registration (DIR) and dose-accumulation algorithms. To implement GI tract motion in the 4D extended cardiac-torso (XCAT) digital phantom of human anatomy. Motility modes that exhibit large amplitude changes in the diameter of the GI tract and may persist over timescales comparable to online adaptive planning and radiotherapy delivery were identified based on literature research. Search criteria included amplitude changes larger than planning risk volume expansions and durations of the order of tens of minutes. The following modes were identified: peristalsis, rhythmic segmentation, high amplitude propagating contractions (HAPCs), and tonic contractions. Peristalsis and rhythmic segmentations were modeled by traveling and standing sinusoidal waves. HAPCs and tonic contractions were modeled by traveling and stationary Gaussian waves. Wave dispersion in the temporal and spatial domain was implemented by linear, exponential, and inverse power law functions. Modeling functions were applied to the control points of the nonuniform rational B-spline surfaces defined in the reference XCAT library. GI motility was combined with the cardiac and respiratory motions available in the standard 4D-XCAT phantom. Default model parameters were estimated based on the analysis of cine MRI acquisitions in 10 patients treated in a 1.5T MR-linac. We demonstrate the ability to generate realistic 4D multimodal images that simulate GI motility combined with respiratory and cardiac motion. All modes of motility, except tonic contractions, were observed in the analysis of our cine MRI acquisitions. Peristalsis was the most common. Default parameters estimated from cine MRI were used as initial values for simulation experiments. It is shown that in patients undergoing stereotactic body radiotherapy for abdominal targets, the effects of GI motility can be comparable or larger than the effects of respiratory motion. The digital phantom provides realistic models to aid in medical imaging and radiation therapy research. The addition of GI motility will further contribute to the development, testing, and validation of DIR and dose accumulation algorithms for MR-guided radiotherapy.

Toward a consensus nomenclature for ghrelin, its non-acylated form, liver expressed antimicrobial peptide 2 and growth hormone secretagogue receptor.

The stomach-derived octanoylated peptide ghrelin was discovered in 1999 and recognized as an endogenous agonist of the growth hormone secretagogue receptor (GHSR). Subsequently, ghrelin has been shown to play key roles in controlling not only growth hormone secretion, but also a variety of other physiological functions including, but not limited to, food intake, reward-related behaviors, glucose homeostasis and gastrointestinal tract motility. Importantly, a non-acylated form of ghrelin, desacyl-ghrelin, can also be detected in biological samples. Desacyl-ghrelin, however, does not bind to GHSR at physiological levels, and its physiological role has remained less well-characterized than that of ghrelin. Ghrelin and desacyl-ghrelin are currently referred to in the literature using many different terms, highlighting the need for a consistent nomenclature. The variability of terms used to designate ghrelin can lead not only to confusion, but also to miscommunication, especially for those who are less familiar with the ghrelin literature. Thus, we conducted a survey among experts who have contributed to the ghrelin literature aiming to identify whether a consensus may be reached. Based on the results of this consensus, we propose using the terms "ghrelin" and "desacyl-ghrelin" to refer to the hormone itself and its non-acylated form, respectively. Based on the results of this consensus, we further propose using the terms "GHSR" for the receptor, and "LEAP2" for liver-expressed antimicrobial peptide 2, a recently recognized endogenous GHSR antagonist/inverse agonist.

Effect of early postoperative feeding on gastrointestinal tract motility after cesarean section

Effect of early postoperative feeding on gastrointestinal tract motility after cesarean section

A Model for Gastrointestinal Tract Motility in a 4D Imaging Phantom of Human Anatomy

<h3>Purpose/Objective(s)</h3> Gastrointestinal (GI) tract motility is one of the main sources for intra/inter-fraction variability and uncertainty in validating deformable image registration (DIR) algorithms. We present an implementation of four modes of GI motility in the 4D extended cardiac-torso (XCAT) digital phantom. <h3>Materials/Methods</h3> We consider motility modes that exhibit large amplitude changes in the diameter of the GI tract and may persist over timescales comparable to online adaptive planning and radiotherapy delivery. The following modes are modeled: peristalsis, rhythmic segmentation, high amplitude propagating contractions (HAPC), and tonic contractions. The models are intended for the organ of origin (i.e., peristalsis in esophagus and small intestine; HAPCs in colon) but can be applied to any user-specified GI tract organ. Peristalsis and rhythmic segmentations are modeled by traveling and standing sinusoidal waves. HAPCs and tonic contractions are modeled by traveling and stationary Gaussian waves. Spatial and temporal dispersion are implemented by exponential functions. The model is applied at the control points of the nonuniform rational B-spline (NURBS) surfaces defined in the reference XCAT phantom. The reference NURBS surfaces are dynamically updated at each timepoint based on the user-defined parameters shown in Table 1. GI motility is combined with the respiratory and cardiac motion available in XCAT. Cine MRI acquisitions from 50 fractions of 10 patients treated in a 1.5 T MR-Linac were analyzed to estimate default parameters for each model. <h3>Results</h3> We demonstrate the ability to generate realistic 4D MRI images that simulate four modes of GI motility combined with respiratory and cardiac motion. All modes of motility, except tonic contractions, were observed in the analysis of our cine MRI acquisitions. Peristalsis was the most common. Default parameters estimated from cine MRI data or from literature (if not observed in our measurements) are used as initial values for simulation experiments. <h3>Conclusion</h3> The digital phantom provides realistic models to aid in multimodality imaging research. The addition of GI motility will further contribute to the development, testing, and validation of DIR algorithms for MR-guided radiotherapy.

S152 Gastrointestinal Tract Injuries Associated With Sevelamer: A Systematic Review

Introduction: Sevelamer is a phosphate binder that is used to treat hyperphosphatemia in patients with chronic kidney disease. Sevelamer is known to cause multiple gastrointestinal side effects including nausea, vomiting, constipation, and abdominal pain. However, sevelamer crystals were observed in rare cases in the gastrointestinal tract (GIT) with associated serious injuries including inflammation, ulceration, ischemia, and perforation. In this study, we conducted a systematic review to investigate the association of sevelamer with GIT injuries. Methods: We conducted a systematic search in MEDLINE, EMBASE, Scopus, and Cochrane Central Register of Controlled Trials to identify eligible reports of sevelamer-associated gastrointestinal tract injuries. The bibliographies of identified articles, Goggle scholars, and websites of relevant professional associations were also searched for relevant studies. Two independent reviewers identified eligible studies and data were extracted in Excel. Only studies that had sevelamer crystals seen in the histopathological exams were included. (Table) Results: We included 58 studies describing a total of 77 patients with a mean age of 58.8 years. Diabetes was present in 27% of cases and at least one risk factor to have slow GIT motility was identified in 63.3% of patients. Both sevelamer carbonate and sevelamer hydrochloride were reported to be associated with GIT injury. Gastrointestinal bleeding (44.2 %) and abdominal pain (37.7 %) were the most common presenting symptoms. The large intestines were the most common area of involvement (74 %), especially in the rectosigmoid area (36.4 %). Ulceration (52 %) and inflammation (48.1 %) were the most common histopathological findings. Stopping sevelamer was the most common pharmacological intervention. 20.8% of patients required surgical intervention, while 6.5% had an endoscopic intervention. Full recovery was reported in 45.5% while 6.5% of patients died. Conclusion: While sevelamer crystals can be found incidentally in the mucosa of the GIT, there is growing evidence that sevelamer use can be associated with GIT injury. Slow GIT motility can be an important risk factor to develop sevelamer-associated GIT injury. If a GIT injury was found during endoscopy and sevelamer crystals were identified on histopathological exam, discontinuing sevelamer and using an alternative phosphate binder should be considered. Further studies are needed to identify risk factors and the best approaches for primary and secondary prevention. Table 1. - Characteristics of included studies GIT: gastrointestinal tract, GIB: Gastrointestinal bleeding Demographics Age (years)Malesfemales 58.88 ± 10.934 (44.2 %)35 (44.5 %) Comorbidities DiabetesConstipationPrevious abdominal surgeryBlood thinnersPossible Slow GIT motility 27 (35.5 %)4 (5.2 %)15 (19.5 %)16 (20.8 %)49 (63.3%) Sevelamer treatment Sevelamer carbonateSevelamer hydrochlorideBothAverage doseMedian doseDuration 16 (20.8 %)12 (15.6 %)1 (1.3%)4,176.29 mg3,200.00 mg5 days – 7 years Symptoms GIBAbdominal painDiarrheaNausea/vomitingEsophageal dysphagia 34 (44.2 %)29 (37.7 %)12 (15.6 %)10 (13%)1 (1.3%) Location of GIT injury EsophagusStomachSmall IntestinesIleocecal valveLarge intestinesCecum and/or ascending colonTransverse ColonDescending colonRectosigmoidDiffuse colonic or unspecifiedAppendix 8 (10.4 %)8 (10.4 %)3 (3.9 %)3 (3.9 %)57 (74 %)8 (10.4 %)7 (9.1 %)1 (1.3%)28 (36.4 %)15 (19.5 %)2 (2.6 %) Histopathological abnormalities* UlcerationInflammationPerforationNecrosisIschemiaStrictureInflammatory polyp 40 (52 %)37 (48.1 %)14 (18.2 %)11 (14.3 %)6 (7.8 %)3 (3.9 %)3 (3.9 %) Pharmacological interventions Stopped SevelamerDecreased sevelamer doseContinued Sevelamer 35 (45.5 %)1 (1.3 %)1 (1.3 %) Procedural interventions Surgical interventionEndoscopic treatmentEndovascular intervention 16 (20.8)5 (6.5 %)1 (1.3 %) Outcomes RecoveredDeathNot reported 35 (45.5 %)5 (6.5 %)37 (48.1 %) *Includes both microscopic and macroscopic findings.

Progesterone inhibitory role on gastrointestinal motility.

Progesterone is a steroidal hormone that is produced from the corpus luteum of the ovaries and from the placenta. The main function of progesterone is to promote the secretory differentiation in the endometrium of the uterus and to maintain pregnancy by inhibiting uterine contractions throughout pregnancy. Progesterone performs its actions by activating the classical progesterone nuclear receptors that affect gene transcription and by the non-classical activation of cell surface membrane receptors that accounts for the rapid actions of progesterone. Besides the reproductive roles of progesterone, it exerts functions in many tissues and systems such as the nervous system, the bone, the vascular system, and the gastrointestinal (GI) tract. This review will summarize the recent literature that investigated the role of progesterone in GI tract motility. Most literature indicates that progesterone exerts an inhibitory role on gut smooth muscle cells in part by elevating nitric oxide synthesis which induces relaxation in smooth muscle. Moreover, progesterone inhibits the signaling pathways that lead to contraction such as Rho kinase inhibition. These data serve as a quick resource for the future directions of progesterone research that could lead to better understanding and more effective treatment of gender-related GI tract motility disorders.

BR-bombesin: a novel bombesin-related peptide from the skin secretion of the Chaco tree frog (Boana raniceps) with physiological gastric effects.

Bombesin mediates several biological activities in the gastrointestinal (GI) tract and central nervous system in mammals, including smooth muscle contraction, secretion of GI hormones and regulation of homeostatic mechanisms. Here, we report a novel bombesin-like peptide isolated from Boana raniceps. Its amino acid sequence, GGNQWAIGHFM-NH2, was identified and structurally confirmed by HPLC, MS/MS and 454-pyrosequencing; the peptide was named BR-bombesin. The effect of BR-bombesin on smooth muscle contraction was assessed in ileum and esophagus, and its anti-secretory activity was investigated in the stomach. BR-bombesin exerted significant contractile activity with a concentration-response curve similar to that of commercially available bombesin in ileum strips of Wistar rats. In esophageal strips, BR-bombesin acted as an agonist, as many other bombesin-related peptides act, although with different behavior compared to the muscarinic agonist carbachol. Moreover, BR-bombesin inhibited stomach secretion by approximately 50% compared to the untreated control group. This novel peptide has 80% and 70% similarity with the 10-residue C-terminal domain of human neuromedin B (NMB) and human gastrin releasing peptide (GRP10), respectively. Molecular docking analysis revealed that the GRP receptor had a binding energy equal to -7.3kcal.mol-1 and -8.5kcal.mol-1 when interacting with bombesin and BR-bombesin, respectively. Taken together, our data open an avenue to investigate BR-bombesin in disorders that involve gastrointestinal tract motility and acid gastric secretion.

Возможности регионарной анестезии при радикальной цистэктомии у больных мышечно-инвазивным раком мочевого пузыря

На сегодняшний день регионарная анестезия при радикальной цистэктомии у пациентов с раком мочевого пузыря выполняется в качестве компонента общей анестезии в условиях искусственной вентиляции легких. Цель работы — оценить безопасность и преимущества выполнения радикальной цистэктомии на фоне комбинированной спинально-эпидуральной анестезии при сохраненном самостоятельном дыхании c последующей оценкой течения послеоперационного периода. Материалы и методы. С 2008 по 2012 г. 96 пациентам в возрасте 67,0 ± 6,5 года произведена радикальная цистэктомия с расширенной тазовой лимфаденэктомией и различными видами деривации мочи с использованием комбинированной спинально-эпидуральной анестезии. Послеоперационная анальгезия включала продленную инфузию наропина 0,2% — 6–8 мл/ч в комбинации с системным введением нестероидных противовоспалительных средств. Оценивали характеристики вариабельности сердечного ритма в частотной области. Результаты и выводы. Развитие спинального блока сопровождалось снижением общей спектральной мощности, преимущественно спектра активности симпатического отдела (LF) — вследствие симпатической блокады, менее выраженным угнетением парасимпатического отдела вегетативной нервной системы. Плотность спектра активности подкорковых нервных центров и процессов гуморальной регуляции (VLF) достоверно не изменялась до момента седации больного. Гемодинамика характеризовалась повышением сердечного индекса на 15,9 %, снижением индекса общего периферического сосудистого сопротивления на 23,2 %.Введение гипнотиков приводило к дальнейшему уменьшению спектральной мощности в диапазоне LF и достоверному подавлению в общей спектральной мощности спектра VLF. Эти изменения вегетативного гомеостаза сопровождались снижением артериального давления, сердечного индекса на фоне недостоверного повышения индекса общего периферического сосудистого сопротивления.Применение субгипнотических доз пропофола с целью достижения медикаментозного сна обеспечивало более стабильное состояние гемодинамики и вегетативного гомеостаза по сравнению с применением бензодиазепинов. Комбинированная спектрально-эпидуральная анестезия является методом выбора анестезиологического пособия при выполнении радикальной цистэктомии. Продленная послеоперационная эпидуральная анальгезия 0,2% наропином обеспечивает максимально раннюю активизацию пациентов, сопровождается ранним восстановлением моторики желудочно-кишечного тракта и пассажа, снижает риск развития респираторных и тромбоэмболических осложнений.

The Advantages and Disadvantages of Prokinetics

Prokinetics are medications that enhance gastrointestinal contractility; they improve the symptoms of patients with delayed gastrointestinal motility. Prokinetics have conventionally been used to stimulate gastrointestinal propulsion and to treat symptoms correlated with motility problems, including gastroparesis and constipation. 5-Hydroxytryptamine receptor 4 (5-HT4) agonists, such as cisapride, very effectively increased human gastrointestinal tract motility. However, cisapride sometimes induced serious tachyarrhythmia; the drug was thus withdrawn from the market. Thereafter, many prokinetics have been developed to treat delayed gastrointestinal motility. However, some exhibit serious side-effects. Recently, a new, highly selective serotonin receptor agonist, prucalopride, has been introduced; there is as yet no evidence of serious cardiac side- effects. The drug has been approved by the Food and Drug Administration to treat chronic constipation. Thus, recently introduced, highly selective agents appear to show promise as treatments for gastrointestinal dysmotility; there seem to be no serious side-effects.

Oropharyngeal Dysphagia and Impaired Motility of the Upper Gastrointestinal Tract-Is There a Clinical Link in Neurocritical Care?

Patients in the neurological ICU are at risk of suffering from disorders of the upper gastrointestinal tract. Oropharyngeal dysphagia (OD) can be caused by the underlying neurological disease and/or ICU treatment itself. The latter was also identified as a risk factor for gastrointestinal dysmotility. However, its association with OD and the impact of the neurological condition is unclear. Here, we investigated a possible link between OD and gastric residual volume (GRV) in patients in the neurological ICU. In this retrospective single-center study, patients with an episode of mechanical ventilation (MV) admitted to the neurological ICU due to an acute neurological disease or acute deterioration of a chronic neurological condition from 2011–2017 were included. The patients were submitted to an endoscopic swallowing evaluation within 72 h of the completion of MV. Their GRV was assessed daily. Patients with ≥1 d of GRV ≥500 mL were compared to all the other patients. Regression analysis was performed to identify the predictors of GRV ≥500 mL/d. With respect to GRV, the groups were compared depending on their FEES scores (0–3). A total of 976 patients were included in this study. A total of 35% demonstrated a GRV of ≥500 mL/d at least once. The significant predictors of relevant GRV were age, male gender, infratentorial or hemorrhagic stroke, prolonged MV and poor swallowing function. The patients with the poorest swallowing function presented a GRV of ≥500 mL/d significantly more often than the patients who scored the best. Conclusions: Our findings indicate an association between dysphagia severity and delayed gastric emptying in critically ill neurologic patients. This may partly be due to lesions in the swallowing and gastric network.