Neurogastroenterology and Motility最新文献

Background: Cyclic vomiting syndrome (CVS) is defined by its episodic patterning. Furthermore, CVS is associated with other episodic disorders such as migraine and epilepsy. Indeed, many of the medications that are known to be useful for prophylaxis and abortive therapy in CVS are also effective in preventing and aborting migraines and seizures. These observations strongly suggest that CVS has a neural basis, but the precise pathophysiological mechanisms that operate in CVS remain unclear.

Purpose: This brief review describes recent neurophysiological insights and opportunities to further advance the understanding of pathophysiological neural mechanisms that are present in patients with CVS. These insights are poised to translate into the next generation of neurotherapeutic strategies for CVS using central neuromodulation. Additionally, the development of neurophysiological tests of neural excitability could be positioned to shape management decisions in future CVS care.

Background: The shear rheology of ingested fluids influences their pharyngo-esophageal transit during deglutition. Thus, swallowed fluids elicit differing physiological responses due to their shear-thinning profile.

Methods: Two hydrocolloid fluids, xanthan gum (XG) and sodium carboxymethylcellulose gum (CMC), were compared in 10 healthy adults (mean age 39 years). Manometry swallowing assessments were performed using an 8-French catheter. Swallows were analyzed using the Swallow Gateway web application (www.swallowgateway.com). Grouped data were analyzed by a mixed statistical model. The coefficient of determination (r²) assessed the relationship between measures and bolus viscosity (SI units, mPa.s) at shear rates of 1-1000 s^-1.

Key results: Rheology confirmed that the thickened fluids had similar viscosities at 50 s^-1 shear rate (XG IDDSI Level-1, 2, and 3 respectively, 74.3, 161.2, and 399.6 mPa.s vs. CMC Level-1, 2, and 3 respectively 78.0, 176.5, and 429.2 mPa.s). However, at 300 s^-1 shear, CMC-thickened fluids exhibited approximately double the viscosity (XG Level-1, 2, and 3 respectively 19.5, 34.4, and 84.8 mPa.s vs. CMC Level-1, 2, and 3 respectively, 41.3, 80.8, and 160.2 mPa.s). In vivo swallows of CMC, when compared to XG, showed evidence of greater flow resistance, such as increased intrabolus pressure (p < 0.01) and UES Integrated Relaxation Pressure (UESIRP, p < 0.01) and shorter UES Relaxation Time (p < 0.05) and Bolus Presence Time (p < 0.001). The apparent fluid viscosity (mPa.s) correlated most significantly with increasing UESIRP (r² 0.69 at 50 s^-1 and r² 0.97 at 300 s^-1, p < 0.05).

Conclusion: Fluids with divergent shear viscosities demonstrated differences in pharyngeal function. These physiological responses were linked to the shear viscosity and not the IDDSI level.

Introduction: Gastrointestinal (GI) magnetic resonance imaging (MRI) enables simultaneous assessment of gastric peristalsis, emptying, and intestinal filling and transit. However, GI MRI in animals typically requires anesthesia, which complicates physiology and confounds interpretation and translation to humans. This study aimed to establish GI MRI in conscious rats, and for the first time, characterize GI motor functions in awake versus anesthetized conditions.

Methods: Fourteen Sprague-Dawley rats were acclimated to remain awake, still, and minimally stressed during MRI. GI MRI was performed under both awake and anesthetized conditions following voluntary consumption of a contrast-enhanced test meal.

Results: Awake rats remained physiologically stable during MRI, giving rise to gastric emptying of 23.7% ± 1.4% at 48 min and robust peristaltic contractions propagating through the antrum at 0.72 ± 0.04 mm/s, with a relative amplitude of 40.7% ± 2.3% and a frequency of 5.1 ± 0.1 cycles per minute. Under anesthesia, gastric emptying was approximately halved, mainly due to a significant reduction in peristaltic contraction amplitude, rather than the change in propagation speed, whereas the contraction frequency remained unchanged. Additionally, the small intestine showed faster filling and stronger motility in awake rats.

Conclusion: This study demonstrates the feasibility of GI MRI in awake rats and highlights notable differences in gastric and intestinal motility between awake and anesthetized states. Our protocol provides a novel and valuable framework for preclinical studies of GI physiology and pathophysiology.

Normal anal sensibility can be present in ARM patients diagnosed with all types of ARM after they have been treated with corrective surgery. Anal sensibility was better in those with a functional IAS. This means that the IAS, present in the distal end of the fistula, should be spared as much as possible to preserve anal sensibility. In this way, aiming to maintain the best possible fecal continence. Furthermore, the outcomes of this study demonstrate that anal sensibility is regulated by transmural nerves.

Background: Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder characterized by discomfort with constipation and/or diarrhea with unclear pathophysiology. We aimed to determine the activities of colorectal eosinophils, neutrophils and epithelial cells by biomarkers in feces reflecting these activities.

Methods: Fecal samples were collected from 185 patients with IBS before and after 8 weeks of placebo or mesalazine treatment and from 40 healthy subjects. Calprotectin, eosinophil derived neurotoxin (EDN), eosinophil cationic protein (ECP), human neutrophil lipocalin (HNL) (pab/765) or dimer, human phospholipase BII-precursor (HPLBII-P) and myeloperoxidase (MPO) were measured by ELISA. Symptom scores were evaluated by diaries.

Results: HPLBII-P, HNL (pab/765) and EDN, proteins secreted by intestinal epithelial cells, were elevated in IBS patients as compared to healthy subjects (p < 0.0001-p = 0.008). In contrast, the neutrophil proteins calprotectin, MPO and HNL dimer were unaltered. The eosinophilic protein ECP was lower in IBS (p = 0.001). HNL (pab/765) (p = 0.01) and EDN (p = 0.004) increased in IBS patients after mesalazine treatment. Colo-rectal mucosa showed strong staining of HPLBII-P and western blotting of fecal extracts showed the presence of mainly monomeric, epithelial-associated HNL.

Conclusions: The absence of signs of involvement of neutrophils and eosinophils in IBS suggests that activity of local epithelial cells rather than inflammation may be a major determinant of the disease. The measurements of EDN, HNL (pab/765), and HPLBII-P may serve as potential fecal biomarkers in the study and monitoring of IBS.

Background: Cancer is a major global cause of morbidity and mortality. Survivorship is increasing, bringing new challenges. Cancer treatment, including chemotherapeutic drugs, immunotherapy, and radiotherapy, can have severe and impactful gastrointestinal side effects occurring shortly after treatment (acute toxicity) or persisting for years after treatment ends (late/chronic toxicity).

Purpose: The aim of this article is to review the neurotoxic effects of chemotherapy on the enteric nervous system (ENS) and the gut extrinsic innervation. These effects could contribute to the development of long-term gastrointestinal dysfunctions. Research, primarily conducted in animal models, indicates that antitumoral drugs can lead to chemotherapy-induced enteric neuropathy (CIEN). Studies, mainly performed in the myenteric plexus, show that CIEN is characterized by a reduced density of nerve cells and fibers, as well as an imbalanced representation of neuronal subpopulations or their markers, with enteric glial cells also affected. These alterations underlie changes in neuronal activity and gastrointestinal motor function. Although research on the submucosal plexus remains limited, evidence suggests that CIEN affects the entire ENS. Furthermore, scarce studies show that CIEN also occurs in humans. Moreover, emerging experimental data on chemotherapy-induced alterations in visceral sensitivity suggest that the extrinsic innervation of the gut is also affected, but this has received little attention thus far. Nevertheless, this could contribute to the development of chemotherapy-induced brain-gut axis (BGA) disorders in the long term. Cancer chemotherapy (and probably also immunotherapy and radiotherapy) seems to cause neuropathic effects on the intrinsic and extrinsic innervation of the gastrointestinal tract, with an important impact on gastrointestinal and BGA functions. This is a relatively neglected area deserving further investigation.

Background: The gut, the ureter, or the Fallopian tube all transport biological fluids by generating trains of propagating smooth muscle constrictions collectively known as peristalsis. These tubes connect body compartments at different pressures. We extend here Poiseuille's experiments on liquid flow in inert tubes to an active, mechanosensitive tube: the intestine.

Methods: We use as a miniature myogenic peristaltic pump model, the fetal chicken gut, and measured the flow and contractile wave propagation as a function of the initially applied pressures and pressure gradients. We dissect the molecular pathways of smooth muscle mechanosensitivity by measuring the force generated by gut rings in different pharmacological conditions.

Results: We demonstrate that smooth muscle contractions in response to stretch or pressure is mediated by L-type Ca²⁺ channels and IP3 receptors. We show that this positive-feedback mechanosensitive behavior can spontaneously generate pressure gradients across gut segments initially subject to equal pressure; this same mechanism tends to stabilize initially applied pressure gradients; it can act jointly or compete with the pressure gradient induced by directional peristaltic waves. We demonstrate that high pressure differentials can reverse the physiological propagation direction of contractile waves imparted by interstitial cell of Cajal pacemaker activity. We find that flow rate increases with tube length, but that the maximum pressure differential generated depends solely on smooth muscle contractile force and on the initial resting pressure applied inside the organ.

Conclusions: We provide fundamental mechanical and hydrodynamic insight into the myogenic mechanisms of transport in the gastrointestinal tract. We scale up our results to other human peristaltic organs and discuss their implications for pathophysiology of intestinal obstruction, vesicoureteral reflux and endometriosis.

Background: This study aimed to evaluate the efficacy and safety of linaclotide in patients with chronic constipation (CC) or irritable bowel syndrome with constipation (IBS-C) who did not respond to treatment with magnesium oxide (MgO).

Methods: This study was designed as a multicenter, open-label, single-arm, exploratory study. Patients with CC or IBS-C who took MgO and those meeting the medication initiation criteria were administered linaclotide at a daily dosage of 500 μg for 12 weeks. The primary endpoint was a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score from baseline, which was evaluated by using a paired t-test.

Key results: The patients' mean age (± standard deviation) was 67.6 ± 13.82 years. The full analysis set included 61 patients. The JPAC-QOL total score was 1.60 at baseline and 0.70 at 12 weeks, with a significant mean change of -0.89 ± 0.721 (p < 0.001). Several secondary endpoints also showed improvement. The frequency of spontaneous bowel movement (SBM) and complete SBM increased by 2.70 ± 7.254 (p < 0.01) and 2.81 ± 5.254 times, respectively (p < 0.001). The Bristol Stool Form Scale, abdominal bloating severity, and straining severity scores improved by 1.33 ± 1.274 (p < 0.001), -0.16 ± 0.563 (p < 0.05), and -0.46 ± 0.795 (p < 0.001) points, respectively. The safety analysis set included 65 patients, 7 of whom had diarrhea, which improved with dose reduction and drug withdrawal.

Conclusion & inferences: The study was conducted in an older adult population, similar to real clinical practice. Linaclotide may be an option for treating CC that shows an inadequate response to conventional therapy.

Background: Behavioral therapy has proved effective as rumination therapy. Our objective was to treat rumination patients using multidisciplinary behavioral therapy aimed at reducing ≥2 of the rumination score.

Methods: All patients fulfilled Rome IV criteria for rumination and were referred to speech therapy for psychoeducation, diaphragmatic breathing exercises and guided eating, physiotherapy for exercises to relax the thoracic and abdominal muscles, and consultation with the psychologist and the dietitian. Symptoms, depression, anxiety, health-related quality of life (HRQoL), and functional capacity were evaluated by questionnaires (Rome IV, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), 15D, and World Health Organization Disability Assessment Schedule (WHODAS) 2.0) at baseline and at 6-month control. Esophageal manometry was performed at 6-month control.

Key results: The study enrolled 11 patients (19-64 years, 10 female). Rumination score: 6.5 (5-8) at baseline, 4.0 (3-5) at the 6-month control, p = 0.005. BDI/8 (6-13), BAI/15 (8-29) at baseline; BDI/7 (4-8), BAI/15 (7-27) at the 6-month control, NS. 15D score: 0.800 at baseline, 0.845 at the 6-month control, NS. WHODAS 2.0 score: 15 (7-33) at baseline, 11 (7-26) at the 6-month control, NS. Rumination could be evoked in manometry in six of nine (67%) patients at 6-month control.

Conclusions and inferences: Behavioral multidisciplinary therapy significantly reduces the self-assessed frequency of rumination. These patients have more depression, anxiety and a lower HRQoL compared to the normal population.

Background: The prompt development of obesity/constipation is the most serious problem for both children and adults. Limited studies suggested an association between them but lacked preclinical studies. This study allows to evaluate their crosslink and to compare the aqueous extracts laxative actions of two edible wild fruits of Arbutus unedo (AUAE) and Crataegus monogyna (CMAE) in constipated high-fat diet (HFD) rats.

Methods: Wistar rats were divided into experimental groups for 13 weeks: standard (SD) and HFD groups. SD-rats were randomly redivided into 2 groups: SD and SD + Loperamide (LOP, 3 mg/kg, b.w.). HFD-rats were randomly reseparated into HFD-group, (HFD + LOP)-group, [HFD + Yohimbine (YOH, 2 mg/kg, b.w.)]-group, [HFD+ LOP]-groups+ various doses of AUAE or CMAE (75, 150, and 300 mg/kg, b.w.). Diversified indicators were investigated to achieve the expected objectives, including; fecal parameters, gastrointestinal transit (GIT), gastric emptying (GE), oxidative stress-(OxS), blood biochemical analysis, and accompanied small/large bowel histological modification.

Key results: The liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS) analysis of AUAE and CMAE allowed the identification of 11 and 6 phenolic compounds, respectively. In HFD-rats, the subsequent dysregulation of GI motility was markedly aggravated. More importantly, with the same way (CMAE and AUAE)-treated groups showed alleviated outcomes for the following: most stool parameters, GIT, and GE were remarkably recovered; a similar recovery pattern was observed in the histopathological structure, OxS, and blood biochemical indicators.

Conclusions & inferences: Our results experimentally confirmed the crosslink between overweight and constipation and both fruits have potential as functional foods to reduce metabolic risk of the obesity associated with bowel dysmotility.