Gastrointestinal Motor Research Articles

Contribution of Serotonin 3A Receptor to Motor Function and Its Expression in the Gastrointestinal Tract

Introduction: The serotonin 3A receptor (5-HT_3AR) is involved in vomiting and gastrointestinal motility. However, it is not well understood the expression pattern of 5-HT_3AR in the gut immunohistochemically and how much contribution of 5-HT_3AR to upper or lower intestinal motility. Objectives: We investigated the contribution of 5-HT_3AR to gastrointestinal motor function by using 5-HT_3AR KO mice and sought to identify 5-HT_3AR-expressing cells via immunohistochemical staining using 5-HT_3AR-GFP reporter mice. Methods: The expression of 5-HT_3AR was measured in each section of the gut through real-time PCR. The motor function of the stomach and colon was assessed via the ¹³C-octanoic acid breath test and colonic bead expulsion test, respectively, using 5-HT_3AR KO mice. 5-HT_3AR-expressing cells in the muscle layer of the gut were identified by immunohistochemical staining using 5-HT_3AR-GFP reporter mice. Results: 5-HT_3AR was expressed throughout the digestive tract, and 5-HT_3AR expression in the stomach and lower digestive tract was higher than that in the other sections. Motor function in the stomach and colon was lower in 5-HT_3AR KO mice than in WT mice. As a result of immunohistochemical staining using GFP reporter mice, cholinergic neurons and PDGFRα⁺ cells were shown to express 5-HT_3AR. In contrast, 5-HT_3AR indicated by GFP fluorescence was rarely detected in ICC and smooth muscle cells. Conclusions: These results show that 5-HT_3AR is highly expressed in the stomach and large intestine and that the activation of 5-HT_3AR accelerates gastric emptying and large intestine transit. Additionally, 5-HT_3AR is highly expressed in cholinergic neurons and some interstitial cells, such as PDGFRα⁺ cells.

Irritable bowel syndrome in celiac disease - relationships to celiac disease antibodies and levels of pro-inflammatory cytokines

Background: Evidence indicates that low-grade inflammation can alter gastrointestinal motor and sensory function and might contribute to the genesis of symptoms in IBS. Objective: To examine relationships between IBS, disease antibodies and cytokine titers in celiac patients and a control group. Materials and methods: IBS, CD activity and serum levels of IL-6, IL-8 and IL12/23p40 were determined in celiac patients and controls. Results: 123 celiac patients were included, 89% were female. 59% demonstrated disease activity and 32% met IBS criteria. Prevalence of IBS was not different between patients who adhered or did not adhere to GFD as well as between patients with or without positive antibodies. Celiac patients had increased levels of IL-6, IL-8 and IL12/23p40 as compared to controls. Higher levels of cytokines were found in celiac patients with IBS than in those without IBS. No difference in levels of cytokines was found between patients with and without CD positive antibodies. A significant negative correlation between the mental component of QoL and IL-6 and IL12/23p40 levels was found, but not with IL-8. Conclusion: Higher levels of inflammatory cytokines were found in CD patients with IBS than in either those without IBS or controls, indicating that IBS symptoms are associated with an increase in the inflammatory response s. These differences in cytokine levels were not related to CD antibodies status gesting that IBS, in CD, is related to a different inflammatory process than that which is relevant to CD.

VF-13, a chimeric peptide of VD-hemopressin(α) and neuropeptide VF, produces potent antinociception with reduced cannabinoid-related side effects

Pharmacological evidence indicated a functional interaction between neuropeptide FF (NPFF) and cannabinoid systems, and the cannabinoids combined with the NPFF receptor agonist neuropeptide VF (NPVF) produced antinociception without tolerance. In the present study, VF-13, a chimeric peptide containing the pharmacophores of the endogenous cannabinoid peptide VD-hemopressin(α) (VD-Hpα) and NPVF, was synthesized and pharmacologically evaluated. In vitro, VF-13 significantly upregulated the phosphorylated level of extracellular signal-regulated kinase 1/2 (ERK1/2) in CHO cells stably expressing CB1 receptors and inhibited forskolin-induced cAMP accumulation in HEK293 cells stably expressing NPFF1 or NPFF2 receptors. Moreover, VF-13 induced neurite outgrowth in Neuro 2A cells via CB1 and NPFF receptors. These results suggest that VF-13 exhibits multifunctional agonism at CB1, NPFF1 and NPFF2 receptors in vitro. Interestingly, intracerebroventricular VF-13 produced dose-dependent antinociception in mouse models of tail-flick and carrageenan-induced inflammatory pain via the TRPV1 receptor. In contrast, the reference compound (m)VD-Hpα-NH2 induced CB1 receptor-mediated supraspinal antinociception. Additionally, subcutaneous injection of (m)VD-Hpα-NH2 and VF-13 produced significant antinociception in carrageenan-induced inflammatory pain model. In the tetrad assay, our data demonstrated that VF-13 elicited hypothermia, but not catalepsy and hypoactivity after intracerebroventricular injection. Notably, VF-13 produced non-tolerance forming antinociception over 6 days treatment in both acute and inflammatory pain models. Furthermore, VF-13 had no apparent effects on gastrointestinal transit, pentobarbitone-induced sedation, food intake, and motor coordination at the supraspinal level. In summary, VF-13, a novel chimeric peptide of VD-Hpα and NPVF, produced non-tolerance forming antinociception in preclinical pain models with reduced cannabinoid-related side effects.

Central neuropeptide-S administration alleviates stress-induced impairment of gastric motor functions through orexin-A.

The novel brain peptide neuropeptide-S (NPS) is produced exclusively by a small group of cells adjacent to the noradrenergic locus coeruleus. The NPSR mRNA has been detected in several brain areas involved in stress response and autonomic outflow, such as amygdala and hypothalamus, suggesting that central NPS may play a regulatory role in stress-induced changes in gastrointestinal (GI) motor functions. In rodents, exogenous central NPS was shown to inhibit stress-stimulated fecal output. Moreover, exogenous NPS was demonstrated to activate hypothalamic neurons that produce orexin-A (OXA), which has been shown to stimulate postprandial gastric motor functions via central vagal pathways. Therefore, we tested whether OXA mediates the NPS-induced alterations in gastric motor functions under stressed conditions. We investigated the effect of central exogenous NPS on solid gastric emptying (GE) and gastric postprandial motility in acute restraint stress (ARS)-loaded conscious rats. The OXA receptor antagonist SB-334867 was administered centrally prior to the central NPS injection. The expression of NPSR in the hypothalamus and dorsal vagal complex was analyzed by immunofluorescence. Central administration of NPS restored the ARS-induced delayed GE and uncoordinated postprandial antro-pyloric contractions. The alleviative effect of NPS on GE was abolished by pretreatment of the OX1R antagonist SB-334867. In addition to hypothalamus, NPSR was detected in the dorsal motor nucleus of vagus, which suggest a direct stimulatory action of exogenous NPS on gastric motility. NPS may be a novel candidate for the treatment of stress-related gastric disorders.

Simultaneous Measurement of Gastric Emptying of a Soup Test Meal Using MRI and Gamma Scintigraphy

Measurement of gastric emptying is of clinical value for a range of conditions. Gamma scintigraphy (GS) has an established role, but the use of magnetic resonance imaging (MRI) has recently increased. Previous comparison studies between MRI and GS showed good correlation, but were performed on separate study days. In this study, the modalities were alternated rapidly allowing direct comparison with no intra-individual variability confounds. Twelve healthy participants consumed 400 g of Technetium-99m (99mTc)-labelled soup test meal (204 kcal) and were imaged at intervals for 150 min, alternating between MRI and GS. The time to empty half of the stomach contents (T1/2) and retention rate (RR) were calculated and data correlated. The average T1/2 was similar for MRI (44 ± 6 min) and GS (35 ± 4 min) with a moderate but significant difference between the two modalities (p < 0.004). The individual T1/2 values were measured, and MRI and GS showed a good positive correlation (r = 0.95, p < 0.0001), as well as all the RRs at each time point up to 120 min. Gastric emptying was measured for the first time by MRI and GS on the same day. This may help with translating the use of this simple meal, known to elicit reliable, physiological, and pathological gastrointestinal motor, peptide, and appetite responses.

Gastrointestinal motility and morphology in mice: Strain-dependent differences.

BALB/c and C57BL/6mice are widely used in biomedical research; however, the differences between strains are still underestimated.Our aims were to develop an experimental protocol to evaluate the duodenal contractility and gastrointestinal transit in miceusing theAlternating Current Biosusceptometry (ACB)techniqueand to compare gastrointestinal motor function and morphology between BALB/c and C57BL/6 strains. Male mice wereused inexperiments (a) duodenal contractility: animalswhich had a magnetic marker surgically fixed in the duodenum to determine the frequency and amplitude of contractions and (b) gastrointestinal transit: animals which ingested a magnetically marked chowto calculate theOro-Anal Transit Time (OATT) and the Fecal Pellet Elimination Rate (FPER). The animals were killedafter the experiments for organ collection andmorphometric analysis. BALB/c and C57BL/6 had two different duodenal frequencies (high and low)with similar amplitudes. After 10hours of monitoring, BALB/c eliminated around 89% of the ingestedmarker and C57BL/6 eliminated33%; OATT and FPER were slower for C57BL/6 compared with BALB/c. The OATT and amplitude of low frequencyhad a strong positive correlation in C57BL/6. For BALB/c, thegastric muscular layer was thickercompared to that measured for C57BL/6. The experimental protocolto evaluate duodenal contractility and fecal magnetic pellets output using the ACB techniquein micewas successfully established.BALB/c strains had higher duodenal frequencies and a shorter timeto eliminate the ingested marker. Our resultsshowed differences in bothmotor function and gastrointestinal morphology betweenBALB/c and C57BL/6 strains.

Abnormal gut motility in inflammatory bowel disease: an update.

There is substantial evidence linking disturbed gastrointestinal motility to inflammation. Thus, it is not surprising that abnormalities of gastrointestinal motility play a role in inflammatory bowel disease (IBD), affecting patient outcomes. We performed a review of the literature to investigate the relationship between abnormal gut motility and IBD. With an extensive literature search, we retrieved the pertinent articles linking disturbed gut motility to IBD in various anatomical districts. The evidence in the literature suggests that abnormal gastrointestinal motility plays a role in the clinical setting of IBD and may confuse the clinical picture. Abnormal gut motility may be important in the clinical setting of IBD. However, additional data obtained with modern techniques (e.g., magnetic resonance imaging) are needed to individuate in a more precise manner gastrointestinal motor dysfunctions, to understand the nature of clinical manifestations and properly tailor the treatment of patients.

Pathophysiology of Vomiting and Esophageal Perforation in Boerhaave’s Syndrome

Boerhaave's syndrome, involving esophagus rupture, is considered a pathological response to vomiting that may occur just before perforation. However, the mechanism of vomiting and occurrence of this disease have not been clearly demonstrated. We identified patients with esophageal perforation between 1995 and 2017 and reviewed endoscopic findings at retching during upper gastrointestinal endoscopy. Finally, we proposed a theory for the underlying pathological mechanism. We retrospectively investigated 10 patients with esophageal perforation between 1995 and 2017. All patients presented after vomiting associated with large volumes of food and alcohol intake. Nine were treated by primary closure of the perforation and drainage of the thoracic cavity, and one was conservatively treated. In all cases, the perforations were longitudinal tears (1-4cm) and located in the left of the esophagus, just above the gastric cardia. We hypothesize that vomiting occurred by retrograde propagation of gastrointestinal motor contraction from the jejunum to the gastric antrum, followed by prolapse of the gastric fornix mucosal into the esophagus. Subsequent esophageal perforation probably resulted from excessive prolapse due to strong contraction and destruction of the muscularis mucosa of the left side of abdominal esophagus, with longitudinal stretching of the whole left esophageal wall due to traction. We also propose that Boerhaave's syndrome is defined as "post-emetic esophageal perforation" to ensure broader recognition and more expedient diagnosis and treatment. Remaining conditions without any definite causes may be labeled "idiopathic" or "spontaneous" rupture of the esophagus.

RELATIONSHIP BETWEEN HELICOBACTER PYLORI INFECTION IN TYPE 2 DIABETES MELLITUS PATIENTS BASED ON ANTI IgA AND ANTI IgG HELICOBACTER PYLORI

Background Helicobacter Pylori (H. Pylori) infection is an infectious disease of the gastrointertinal tract especially the stomach and is currently associated with various systemic disorders in the body, one of which is hormonal disorders. Diabetes mellitus (DM) is an important cause of dyspepsia. Impaired gastrointestinal motor function is now recognized as a major problem in diabetes mellitus. The incidence of H. Pylori is increased in DM. Delayed gastric emptying and dysmotility are important causes of dyspepsia in diabetes. Methods This study was conducted by cross sectional method. The sample of the study was 39 patients who met the inclusion and exclusion criteria in the General Hospital H. Adam Malik Medan. Anti IgA and anti IgG H. Pylori examination by ELISA method using Chemwell. Results There were no difference in the incidence of anti IgA H. Pylori positive in patients with controlled DM and uncontrolled DM with p= 0,431. There was no difference in the incidence of anti IgA H. Pylori positive in patients with controlled DM and uncontrolled DM with p= 0,423. However, there were differences in H.Pylori infection in DM patients with dyspepsia and DM patients without dyspepsia with p = 0.001. Conclusion There were no relationship between H. Pylori infections in patients with type 2 DM.

Intranasal Administration of Oxytocin Attenuates Stress Responses Following Chronic Complicated Stress in Rats.

Background/AimsGastrointestinal (GI) symptoms may develop when we fail to adapt to various stressors of our daily life. Central oxytocin (OXT) can counteract the biological actions of corticotropin-releasing factor (CRF), and in turn attenuates stress responses. Administration (intracerebroventricular) of OXT significantly antagonized the inhibitory effects of chronic complicated stress (CCS) on GI dysmotility in rats. However, intracerebroventricular administration is an invasive pathway. Intranasal administration can rapidly deliver peptides to the brain avoiding stress response. The effects of intranasal OXT on hypothalamus-pituitary-adrenal axis and GI motility in CCS conditions have not been investigated.MethodsA CCS rat model was set up, OXT 5, 10, or 20 μg were intranasal administered, 30 minutes prior to stress loading. Central CRF and OXT expression levels were analyzed, serum corticosterone and OXT concentrations were measured, and gastric and colonic motor functions were evaluated by gastric emptying, fecal pellet output, and motility recording system.ResultsRats in CCS condition showed significantly increased CRF expression and corticosterone concentration, which resulted in delayed gastric emptying and increased fecal pellet output, attenuated gastric motility and enhanced colonic motility were also recorded. OXT 10 μg or 20 μg significantly reduced CRF mRNA expression and the corticosterone concentration, OXT 20 μg also helped to restore GI motor dysfunction induced by CCS.ConclusionIntranasal administration of OXT has an anxiolytic effect and attenuates the hypothalamus-pituitary-adrenal axis in response to CCS, and gave effects which helped to restore GI dysmotility, and might be a new approach for the treatment of stress-induced GI motility disorders.

Adiponectin Decreases Gastric Smooth Muscle Cell Excitability in Mice

Some adipokines known to regulate food intake at a central level can also affect gastrointestinal motor responses. These are recognized to be peripheral signals able to influence feeding behavior as well. In this view, it has been recently observed that adiponectin (ADPN), which seems to have a role in sending satiety signals at the central nervous system level, actually affects the mechanical responses in gastric strips from mice. However, at present, there are no data in the literature about the electrophysiological effects of ADPN on gastric smooth muscle. To this aim, we achieved experiments on smooth muscle cells (SMCs) of gastric fundus to find out a possible action on SMC excitability and on membrane phenomena leading to the mechanical response. Experiments were made inserting a microelectrode in a single cell of a muscle strip of the gastric fundus excised from adult female mice. We found that ADPN was able to hyperpolarize the resting membrane potential, to enhance the delayed rectifier K+ currents and to reduce the voltage-dependent Ca2+ currents. Our overall results suggest an inhibitory action of ADPN on gastric SMC excitation–contraction coupling. In conclusion, the depressant action of ADPN on the gastric SMC excitability, here reported for the first time, together with its well-known involvement in metabolism, might lead us to consider a possible contribution of ADPN also as a peripheral signal in the hunger–satiety cycle and thus in feeding behavior.

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

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

Changes in the diet composition of fatty acids and fiber affect the lower gastrointestinal motility but have no impact on cardiovascular parameters: In vivo and in vitro studies.

Food and diet are central issues for proper functioning of the cardiovascular (CV) system and gastrointestinal (GI) tract. We hypothesize that different types of dietary FAs affect CV parameters as well as GI motor function and visceral sensitivity. Male Wistar rats were fed with control diet (CTRL), diet supplemented with 7% soybean oil (SOY), SOY+3.5% virgin coconut oil (COCO), and SOY+3.5% evening primrose oil (EP) for 4weeks. The content of insoluble fiber in CTRL was higher than in SOY, COCO, or EP. Body weight gain and food/water intake were measured. At day 28, biometric, biochemical, CV parameters, GI motor function (X-ray and colon bead expulsion test), and visceral sensitivity were evaluated. Changes in propulsive colonic activity were determined in vitro. The colon and adipose tissue were histologically studied; the number of mast cells (MCs) in the colon was calculated. SOY, COCO, and EP had increased body weight gain but decreased food intake vs CTRL. Water consumption, biometric, biochemical, and CV parameters were comparable between groups. SOY increased the sensitivity to colonic distention. All groups maintained regular propulsive neurogenic contractions; EP delayed colonic motility (P<0.01). SOY, COCO, and EP displayed decreased size of the cecum, lower number and size of fecal pellets, and higher infiltration of MCs to the colon (P<0.001). Dietary FAs supplementation and lower intake of insoluble fiber can induce changes in the motility of the lower GI tract, in vivo and in vitro, but CV function and visceral sensitivity are not generally affected.

Radiographic dose-dependency study of loperamide effects on gastrointestinal motor function in the rat. Temporal relationship with nausea-like behavior.

Loperamide is a potent mu opioid receptor agonist available over the counter to treat diarrhea. Although at therapeutic doses loperamide is devoid of central effects, it may exert them if used at high doses or combined with drugs that increase its systemic and/or central bioavailability. Recently, public health and scientific interest on loperamide has increased due to a growing trend of misuse and abuse, and consequent reports on its toxicity. Our aim was to evaluate in the rat the effects of increasing loperamide doses, with increasing likelihood to induce central effects, on gastrointestinal motor function (including gastric dysmotility and nausea-like behavior). Male Wistar rats received an intraperitoneal injection of vehicle or loperamide (0.1, 1, or 10mgkg-1 ). Three sets of experiments were performed to evaluate: (a) central effects (somatic nociceptive thresholds, immobility time, core temperature, spontaneous locomotor activity); (b) general gastrointestinal motility (serial X-rays were taken 0-8hours after intragastric barium administration and analyzed semiquantitatively, morphometrically, and densitometrically); and (c) bedding intake (a rodent indirect marker of nausea). Animals from sets 1 and 3 were used to evaluate gastric dysmotility ex vivo at 2 and 4hours after administration, respectively. Loperamide significantly induced antinociception, hypothermia, and hypolocomotion (but not catalepsy) at high doses and dose-dependently reduced gastrointestinal motor function, with the intestine exhibiting higher sensitivity than the stomach. Whereas bedding intake occurred early and transiently, gastric dysmotility was much more persistent. Our results suggest that loperamide-induced nausea and gastric dysmotility might be temporally dissociated.

Patient-reported outcomes (PROs) in adult survivors of childhood hematopoietic cell transplant (HCT): A report from the St. Jude lifetime cohort study.

10049 Background: We examined PROs including symptom prevalence and quality of life (QOL) in adult survivors of childhood HCT compared to those treated with conventional therapy and non-cancer controls, and risk factors of impaired PROs. Methods: Physical and psychological symptoms and QOL were reported by 112 survivors of hematologic malignancies treated with HCT, 1106 treated with conventional therapy, and 242 non-cancer controls. PROs were self-reported using a survey, which included demographics, Brief Symptom Inventory and 36-Item Short Form Survey. Each participant completed a clinical physical health assessment and chronic health conditions (CHCs) were graded using a modified Common Terminology Criteria for Adverse Events. Multivariable logistic regression was conducted to estimate odds ratios (OR) and 95% confidence intervals (CI) for PROs using demographics and CHCs as predictors. Results: HCT and conventional therapy survivors’ mean age at survey and time since diagnosis were 28 and 29 years, and 19 and 20 years, respectively. The mean age at survey for non-cancer controls was 35 years. HCT survivors reported high prevalence of pain (64%), sensory (39%) and memory problems (29%), anxiety (29%), and depression (24%), which was not significantly different from survivors treated with conventional therapy. Compared to non-cancer controls, HCT survivors had more sensory (OR 3.2; 95% CI 1.5-6.8), motor (OR 4.3; 95% CI 1.2-15.4), and memory (OR 3.7; 95% CI 1.5-8.9) problems, and worse physical QOL (OR 5.4; 95% CI 1.6-18.6). Presence of PROs were associated with organ-specific CHCs (grade 3-4 vs. grade 0-2) not receipt of HCT: cardiac symptoms with cardiovascular CHCs (OR 3; 95% CI 1.8-4.9), pulmonary symptoms with pulmonary CHCs (OR 2.5; 95% CI 1.4-4.3), nausea with gastrointestinal CHCs (OR 2; 95% CI 1.2-3.1), and sensory (OR 1.9; 95% CI 1.2-3.1) and motor (OR 3.3; 95% CI 2-5.5) problems with neurological CHCs. Conclusions: Prevalence of symptoms and impaired QOL in HCT survivors is comparable to survivors treated with conventional therapy, but higher than non-cancer controls. PROs may have a role in facilitating identification of adverse events in survivors.

Adipocytes-released Peptides Involved in the Control of Gastrointestinal Motility.

The present review focuses on adipocytes-released peptides known to be involved in the control of gastrointestinal motility, acting both centrally and peripherally. Thus, four peptides have been taken into account: leptin, adiponectin, nesfatin-1, and apelin. The discussion of the related physiological or pathophysiological roles, based on the most recent findings, is intended to underlie the close interactions among adipose tissue, central nervous system, and gastrointestinal tract. The better understanding of this complex network, as gastrointestinal motor responses represent peripheral signals involved in the regulation of food intake through the gut-brain axis, may also furnish a cue for the development of either novel therapeutic approaches in the treatment of obesity and eating disorders or potential diagnostic tools.

Gastrointestinal defects in gallstone and cholecystectomized patients.

Several gallstone patients complain of dyspeptic symptoms, irrespective of the presence of typical colicky pain. Symptoms often persist after a cholecystectomy. Systematic studies on dyspepsia and dynamic gastrointestinal motor function are missing in gallstone patients with preserved gallbladder or after a cholecystectomy. Forty-six gallstone patients (age 55±2years; 15M, 31F) and 24 cholecystectomized patients (age 57±2years; 6M, 18F) (no difference in type and volume of gallstones between the two groups) were compared against a group of 65 healthy controls (age 51±2years; 30M, 35F). Dyspepsia occurring in the prior months was assessed by a questionnaire, gastric and gallbladder emptying by functional ultrasonography and orocecal transit time by a hydrogen breath test using a lactulose-enriched standard liquid meal. Gallstone patients had significantly greater dyspepsia, fasting and residual gallbladder volumes, and slower gallbladder emptying, gastric emptying and small intestinal transit time than controls. In cholecystectomized patients, gastric emptying further delayed, compared to gallstone patients and controls. Gallstone patients with the gallbladder "in situ" or after a cholecystectomy display dyspeptic symptoms. Symptoms are associated with multiple gastrointestinal motility defects involving the gallbladder, stomach and small intestine. After cholecystectomy, gastric emptying worsens.

The Role of Prostaglandins in Disrupted Gastric Motor Activity Associated With Type 2 Diabetes.

Patients with diabetes often develop gastrointestinal motor problems, including gastroparesis. Previous studies have suggested this gastric motor disorder was a consequence of an enteric neuropathy. Disruptions in interstitial cells of Cajal (ICC) have also been reported. A thorough examination of functional changes in gastric motor activity during diabetes has not yet been performed. We comprehensively examined the gastric antrums of Lepob mice using functional, morphological, and molecular techniques to determine the pathophysiological consequences in this type 2 diabetic animal model. Video analysis and isometric force measurements revealed higher frequency and less robust antral contractions in Lepob mice compared with controls. Electrical pacemaker activity was reduced in amplitude and increased in frequency. Populations of enteric neurons, ICC, and platelet-derived growth factor receptor α+ cells were unchanged. Analysis of components of the prostaglandin pathway revealed upregulation of multiple enzymes and receptors. Prostaglandin-endoperoxide synthase-2 inhibition increased slow wave amplitudes and reduced frequency of diabetic antrums. In conclusion, gastric pacemaker and contractile activity is disordered in type 2 diabetic mice, and this appears to be a consequence of excessive prostaglandin signaling. Inhibition of prostaglandin synthesis may provide a novel treatment for diabetic gastric motility disorders.

Condition of the gastrointestinal tract motor function in abdominal injury

Introduction. Injuries are a large medical and social problem. It takes many lives and is often a cause of disability. Objectives. The work is devoted to the study of the motor-evacuation function (MEF) of the gastrointestinal tract (GIT) in patients with closed abdominal injury of varying severity. Materials and methods. 125 patients with isolated or combined blunt abdominal trauma were under observation. The main criterion for the inclusion of patients in the study was the presence of injury to the abdomen and / or retroperitoneal space, confirmed while surgery or using instrumental methods of examination. The structure of injuries was dominated by a combined trauma, which was observed in 104 (83.2%) victims; in 21 (16.8%) patients abdominal injury was isolated or multiple. Evaluation of the MEF of the gastrointestinal tract was carried out using a technique developed with the participation of the author on the basis of the available indicators widely used in practice. The severity of the injury was determined on an ISS scale. Results. The results showed that the predominant part of patients with abdominal trauma (62.4%) had a violation of gastrointestinal MEF upon admission; in 21% of patients, the state of function at the border of functional compensation was noted, and only in 16% of persons, the MEF of the gastrointestinal tract was rated as moderately and completely compensated. By severity of injury, a group of patients with moderate severity (47.2%) prevailed; a mild injury was observed in 35.2% of patients, severe injury was diagnosed in 16%, and a super-severe one was in 1.6% of injured people. Conclusions. The possibility of using the MEF indicators of the gastrointestinal tract as one of diagnostic criteria for the severity of a blunt abdominal injury is assumed.

Prediction of the Risk of Early Gestational Complications in Women with Chronic Gastritis

The objective: to determine the risk factors for the development of early gestational complications and their prognostic value in pregnant women with chronic gastritis.Material and methods. 120 pregnant women at 8–12 weeks of gestation with early gestational complications (threatened abortion (TA), emesis gravidarum, spontaneous miscarriage, missed abortion) were studied. They were divided into two groups: Group 1 included 58 pregnant women with chronic gastritis and Group 2 included 62 women without gastritis. 6 parameters were analysed for factorial attributes: gastritis, gastrin-17 (G-17), progesterone, estradiol, chorionic gonadotropin (HCG), and H.pylory. The method of stepwise inclusion/exclusion was used for the selection of significant factors (Stepwise at the critical threshold for inclusion at p&lt;0,1 and the threshold for exclusion at р&gt;0,2).Results. When the attributes associated with the risk of threatened abortion were selected, 3 factors have been identified: gastritis, gastrin (G-17), progesterone. The risk prediction model based on these attributes is adequate c2=25,7; p&lt;0,001). There was an increase (p=0,01) of the risk of TA with increased progesterone levels, OR = 1,4 (95% CІ 1,1–1,7) for every 10 units of the parameter increase. There was a higher (p&lt;0,001) risk of TA in pregnant women with gastritis, OR = 5,4 (95% CІ 2,2–13,2) compared with pregnant women without gastritis. When the attributes associated with the risk of emesis gravidarum, 2 factors were identified: the presence of gastritis and H. pylori. The risk prediction model built on these attributes is adequate (c2=13,8; p=0,001). There was an increase (p=0,03) in the risk of emesis gravidarum in the presence of H.pylori, OR = 2,9 (95% CІ 1,1–7,6) compared with pregnant women without H. pylori. When the attributes associated with the risk of spontaneous miscarriage were selected, 2 factors were identified: gastritis and HCG. The risk prediction model built on these attributes is adequate (c2=7,7; p=0,02). According to the results of the analysis, there was a decrease (p=0,04) in the risk of spontaneous miscarriage with increasing chorionic gonadotropin, OR = 0,94 (95% CІ 0,89–0,99) for every 1000 units of the parameter increase. A higher (p=0,05) risk of spontaneous miscarriage for pregnant women with gastritis was found, OR = 2,7 (95% CI 1,0–7,1) compared with non-gastric pregnant women. When the attributes associated with the risk of missed abortion were selected, 1 factor was identified (progesterone level). The risk prediction model constructed on this basis is adequate (c2=4,1; p=0,04). A tendency to decrease (p=0,06) in the risk of missed abortion with increasing progesterone, OR = 0,75 (95% CІ 0,55 1,02) for every 10 units of the parameter increase was found.Conclusions. The risk factors for the development of early gestational complications in pregnant women with chronic gastritis are hormonal and infectious factors which may contribute to changes in the gastrointestinal motor and evacuation function, cause changes in the acidity of gastric acid and lead to the development of constipation and endogenous intoxication, which cause nausea and vomiting. The nature of the changes and the degree of their severity determine the various clinical manifestations of gestational complications: emesis gravidarum, spontaneous miscarriage, missed abortion.