Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21.884
Filtrar
1.
Gen Comp Endocrinol ; 330: 114140, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36228737

RESUMO

The effects of newt motilin on the contractility of the isolated gastrointestinal (GI) tract from Japanese fire belly newts (newt) were examined to clarify whether motilin regulates GI motility in urodele amphibians. In addition, contractile responsiveness to motilins from seven species of vertebrates (human, chicken, turtle, alligator, axolotol, newt and zebrafish) were compared in GI preparations from three different animals (rabbit duodenum, chicken ileum and newt stomach) to determine the species-specific action of motilin. Newt motilin (10-10 M - 10-6 M) caused a contraction of cognate gastric strips, while the upper, middle, and lower intestinal strips were insensitive. The rank order of motilins for contractile activity in newt gastric strips was newt > alligator > axolotol > chicken > turtle > human ≫ zebrafish. On the other hand, newt motilin caused a weak contraction in the rabbit duodenum (human > alligator = chicken > turtle > newt ≧ axolotol > zebrafish), and it was ineffective in the chicken ileum (chicken > turtle > alligator > human ≫ newt, axolotol and zebrafish). This study demonstrates that motilin induces contraction in the GI tract of a urodele amphibian, the newt, in a region (stomach)-specific manner and further indicates that a ligand-receptor interaction of the motilin system is a species-specific manner probably due to differences in the amino acid sequence of motilin.


Assuntos
Motilidade Gastrointestinal , Trato Gastrointestinal , Motilina , Contração Muscular , Animais , Humanos , Coelhos , Galinhas , Trato Gastrointestinal/fisiologia , Motilina/química , Salamandridae , Estômago , Peixe-Zebra
2.
Zhongguo Zhen Jiu ; 42(11): 1299-303, 2022 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-36397230

RESUMO

From the perspective of autonomic nervous system, this paper analyzes the mechanism, current western medicine treatment methods and acupuncture-moxibustion treatment mechanism of gastroesophageal reflux disease (GERD). It is believed that the main cause of GERD is that the gastric acid goes to the wrong place due to gastrointestinal motility disorder, which belongs to "acid dislocation". At present, western medical treatment cannot effectively target the pathogenesis of the disease, and its effect is limited. Acupuncture-moxibustion could regulate the neuroendocrine immune network to regulate the function of autonomic nerve, restore the power of digestive tract to treat GERD, which is worthy of further research.


Assuntos
Terapia por Acupuntura , Refluxo Gastroesofágico , Gastroenteropatias , Moxibustão , Humanos , Refluxo Gastroesofágico/terapia , Sistema Nervoso Autônomo , Motilidade Gastrointestinal
3.
Front Cell Infect Microbiol ; 12: 1013952, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339343

RESUMO

Slow transit constipation is an intractable constipation with unknown aetiology and uncertain pathogenesis. The gut microbiota maintains a symbiotic relationship with the host and has an impact on host metabolism. Previous studies have reported that some gut microbes have the ability to produce 5-hydroxytryptamine (5-HT), an important neurotransmitter. However, there are scarce data exploiting the effects of gut microbiota-derived 5-HT in constipation-related disease. We genetically engineered the probiotic Escherichia coli Nissle 1917 (EcN-5-HT) for synthesizing 5-HT in situ. The ability of EcN-5-HT to secrete 5-HT in vitro and in vivo was confirmed. Then, we examined the effects of EcN-5-HT on intestinal motility in a loperamide-induced constipation mouse model. After two weeks of EcN-5-HT oral gavage, the constipation-related symptoms were relieved and gastrointestinal motility were enhanced. Meanwhile, administration of EcN-5-HT alleviated the constipation related depressive-like behaviors. We also observed improved microbiota composition during EcN-5-HT treatment. This work suggests that gut microbiota-derived 5-HT might promise a potential therapeutic strategy for constipation and related behavioral disorders.


Assuntos
Transtornos Mentais , Probióticos , Camundongos , Animais , Serotonina , Motilidade Gastrointestinal , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/terapia , Escherichia coli/metabolismo
6.
Radiographics ; 42(7): 2014-2036, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36206184

RESUMO

The motor function of the gastrointestinal tract relies on the enteric nervous system, which includes neurons spanning from the esophagus to the internal anal sphincter. Disorders of gastrointestinal motility arise as a result of disease within the affected portion of the enteric nervous system and may be caused by a wide array of underlying diseases. The etiology of motility disorders may be primary or due to secondary causes related to infection or inflammation, congenital abnormalities, metabolic disturbances, systemic illness, or medication-related side effects. The symptoms of gastrointestinal dysmotility tend to be nonspecific and may cause diagnostic difficulty. Therefore, evaluation of motility disorders requires a combination of clinical, radiologic, and endoscopic or manometric testing. Radiologic studies including fluoroscopy, CT, MRI, and nuclear scintigraphy allow exclusion of alternative pathologic conditions and serve as adjuncts to endoscopy and manometry to determine the appropriate diagnosis. Additionally, radiologist understanding of clinical evaluation of motility disorders is necessary for guiding referring clinicians and appropriately imaging patients. New developments and advances in imaging techniques have allowed improved assessment and diagnosis of motility disorders, which will continue to improve patient treatment options. Online supplemental material is available for this article. ©RSNA, 2022.


Assuntos
Gastroenteropatias , Motilidade Gastrointestinal , Humanos , Manometria/métodos , Motilidade Gastrointestinal/fisiologia , Esôfago , Diagnóstico por Imagem
7.
Biochem Biophys Res Commun ; 635: 19-29, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36252333

RESUMO

Nobiletin can regulate lipid metabolism and protect the central nervous system. However, its role in the enteric nervous system (ENS) of obese subjects is still unclear. To investigate the ENS protective effects and mechanism of nobiletin in obese mice, male C57BL/6 mice were fed a chow diet and a high-fat diet (HFD) for 8 weeks. The identified obese and control mice were grouped and administered vehicle, nobiletin 40 mg/kg, 100 mg/kg or 200 mg/kg daily for 4 weeks. The major indexes of obesity, intestinal transit rate, PGP9.5, nNOS, TNF-α, IL-1ß, IL-6, IL-10, Bcl2 and Bax were measured. The full-length transcriptome was used to analyze differentially expressed genes (DEGs) in the colon. The results indicated that nobiletin effectively improved major indexes of obesity and bowel motility function, suppressed the expression of TNF-α, IL-1ß, IL-6 and Bax, and upregulated the expression of IL-10, Bcl2, PGP9.5 and nNOS. Based on full-length transcriptome sequencing, nobiletin regulated lipid metabolism and inflammation via the PPAR and NOD-like receptor signaling pathways. Trem2 expression was significantly reduced in obese mice. However, Trem2 expression was significantly increased after nobiletin treatment in obese mice. The enrichment analysis showed that Trem2 plays an important role in enteric neuroinflammation. In conclusion, nobiletin regulates lipid metabolism and inflammation in obese mice. Trem2 is a potential target of nobiletin for ENS protection in obese mice.


Assuntos
Interleucina-10 , Fator de Necrose Tumoral alfa , Animais , Masculino , Camundongos , Proteína X Associada a bcl-2 , Dieta Hiperlipídica/efeitos adversos , Inflamação/tratamento farmacológico , Interleucina-6 , Glicoproteínas de Membrana , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Receptores Imunológicos , Motilidade Gastrointestinal
8.
Ter Arkh ; 94(2): 166-171, 2022 Feb 15.
Artigo em Russo | MEDLINE | ID: mdl-36286739

RESUMO

AIM: To assess the psychoemotional status and the state of the autonomic nervous system and their importance in the violation of the motor-evacuation function of the gastrointestinal tract in chronic duodenal insufficiency (CDI). MATERIALS AND METHODS: A prospective study of 40 patients with CDI was carried out. The control group consisted of 30 healthy individuals. Anamnestic and physical data, results of X-ray and endoscopic studies, and intracavitary manometry were used to verify CDI. The study of the gastrointestinal tract was carried out using the "Gastroscan-GEM". Assessment of autonomic homeostasis was carried out using cardiac rhythmographic research and analysis of heart rate variability using the "Varicard 2.51" complex. To assess personal and situational anxiety test questionnaire SpielbergerKhanin. Eysenck's test questionnaire was used to determine the type of temperament. RESULTS AND DISCUSSION: We revealed a postprandial decrease in the contribution of the frequency spectrum of the duodenum (Pi/Ps 1.70.07; p=0.000) and the colon (Pi/Ps 39.622.45; p=0.000) in the total spectrum in comparison with the starving study, at the same time there is an aberrant significant increase in the contribution of the stomach to the total spectrum (46.55.8%; p=0.00). In patients with CDI, the prevalence of the sympathetic division of the autonomic nervous system AMo was noted 94.0 [92.5; 97.5]% with an asymptotic type of autonomic reactivity (IN2/IN1=1.1 [1.05; 1.17]) and insufficient adaptation reserve coefficients (0.32 [0.2; 0.4]) in relation to the control group. The psychoemotional state in patients with chronic duodenal stasis is in direct correlation with changes in the postprandial ratio of the electrical activity of the stomach and duodenum (r=0.7, p=0.021), and in reverse with the coefficient of the ratio of intraduodenal pressure to intragastric pressure (r=-0,8, p=0.000). CONCLUSION: In patients with CDI, changes in the functional state of the stomach and duodenum are of a systemic nature, which is due to stimulating (parasympathetic) and inhibitory (sympathetic) effects. The relationship between the motor-evacuation activity of the stomach and duodenum and the psychoemotional state in patients with CDI was revealed.


Assuntos
Duodeno , Estômago , Humanos , Estudos Prospectivos , Sistema Nervoso Autônomo , Manometria , Motilidade Gastrointestinal
9.
Comput Math Methods Med ; 2022: 1653290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36188104

RESUMO

Gastrointestinal dysfunction (GD) is a common complication after endotoxemia, which can further aggravate the progress of infection. Acupuncture uses metal needles of different shapes and techniques to stimulate specific points on the human body, which are effective in treating various diseases, including gastrointestinal diseases. We aimed at exploring the clinical effect of acupuncture on the recovery of visceral sensation, proximal gastric compliance, and autonomic nervous function in patients with septic GD. A total of 73 sepsis with GD patients were selected using modified single section ultrasonography combined with clinical symptoms in the First People's Hospital of Lanzhou City during 2019. The participants were randomly allocated to routine-treatment (control group) and study group receiving acupuncture. The indexes before and after treatment included gastric residue, gastric dilatation, pressure and volume, gastric compliance, autonomic nerve function, APACHE II score, and infection index were measured and compared. Before treatment, there was no significant difference in the basic information of the two groups, including gastric volume and pressure, gastric residue, gastric compliance, autonomic nerve function, and APACHE II score. After treatment, the maximum gastric volume and pressure, gastric residue, and APACHE II score of the two groups were significantly improved (P < 0.05). In addition, the maximum gastric volume and pressure of the study group were significantly higher, while gastric residual, autonomic nerve function, and APACHE II were significantly lower than those of the control group (P < 0.05). However, our results showed that acupuncture did not further reduce inflammatory markers, including white blood cells, C-reactive protein, and procalcitonin. To sum up, on the basis of basic treatment, the application of acupuncture can further improve the clinical symptoms of GD in patients with sepsis, enhance gastrointestinal motility, and improve autonomic nervous function, which is worthy of clinical application and promotion.


Assuntos
Terapia por Acupuntura , Gastroenteropatias , Sepse , Proteína C-Reativa , Gastroenteropatias/terapia , Motilidade Gastrointestinal/fisiologia , Humanos , Pró-Calcitonina , Sepse/complicações , Sepse/terapia
10.
Am J Physiol Gastrointest Liver Physiol ; 323(6): G562-G570, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36255075

RESUMO

Chronic nausea is a widespread functional disease in children with numerous comorbidities. High-resolution electrogastrogram (HR-EGG) has shown sufficient sensitivity as a noninvasive clinical marker to objectively detect distinct gastric slow wave properties in children with functional nausea. We hypothesized that the increased precision of magnetogastrogram (MGG) slow wave recordings could provide supplementary information not evident on HR-EGG. We evaluated simultaneous pre- and postprandial MGG and HR-EGG recordings in pediatric patients with chronic nausea and healthy asymptomatic subjects, while also measuring nausea intensity and nausea severity. We found significant reductions in postprandial dominant frequency and normogastric power, and higher levels of postprandial bradygastric power in patients with nausea in both MGG and HR-EGG. MGG also detected significantly lower preprandial normogastric power in patients. A significant difference in the mean preprandial gastric slow wave propagation direction was observed in patients as compared with controls in both MGG (control: 180 ± 61°, patient: 34 ±72°; P < 0.05) and HR-EGG (control: 240 ± 39°, patient: 180 ± 46°; P < 0.05). Patients also showed a significant change in the mean slow wave direction between pre- and postprandial periods in MGG (P < 0.05). No statistical differences were observed in propagation speed between healthy subjects and patients in either MGG or HR-EGG pre/postprandial periods. The use of MGG and/or HR-EGG represents an opportunity to assess noninvasively the effects of chronic nausea on gastric slow wave activity. MGG data may offer the opportunity for further refinement of the more portable and economical HR-EGG in future machine-learning approaches for functional nausea.NEW & NOTEWORTHY Pediatric chronic nausea is a difficult-to-measure subjective complaint that requires objective diagnosis, clinical assessment, and individualized treatment plans. Our study demonstrates that multichannel MGG used in conjunction with custom HR-EGG detects key pathological signatures of functional nausea in children. This quantifiable measure may allow more personalized diagnosis and treatment in addition to minimizing the cost and potential radiation associated with current diagnostic approaches.


Assuntos
Motilidade Gastrointestinal , Estômago , Humanos , Criança , Período Pós-Prandial , Biomarcadores , Náusea/diagnóstico
11.
Phys Rev Lett ; 129(13): 138101, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36206418

RESUMO

Small intestine motility and its ensuing flow of luminal content impact both nutrient absorption and bacterial growth. To explore this interdependence we introduce a biophysical description of intestinal flow and absorption. Rooted in observations of mice we identify the average flow velocity as the key control of absorption efficiency and bacterial growth, independent of the exact contraction pattern. We uncover self-regulation of contraction and flow in response to nutrients and bacterial levels to promote efficient absorption while restraining detrimental bacterial overgrowth.


Assuntos
Absorção Intestinal , Nutrientes , Animais , Bactérias , Motilidade Gastrointestinal/fisiologia , Absorção Intestinal/fisiologia , Camundongos
12.
Neurogastroenterol Motil ; 34(11): e14442, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36054796

RESUMO

BACKGROUND: In most animal species, opioids alter colonic motility via the inhibition of excitatory enteric motor neurons. The mechanisms by which opioids alter human colonic motility are unclear. The aim of this study was to describe the effects of loperamide on neuromuscular function in the human colon. METHODS: Tissue specimens of human colon from 10 patients undergoing an anterior resection were divided into three inter-taenial circular muscle strips. Separate organ baths were used to assess: (1) excitatory transmission (selective blockade of inhibitory transmission: L-NOARG/MRS2179); (2) inhibitory transmission (selective blockade of excitatory transmission: hyoscine hydrobromide); and (3) a control bath (no drug additions). Neuromuscular function was assessed using force transducer recordings and electrical field stimulation (EFS; 20 V, 10 Hz, 0.5 ms, 10 s) prior to and following loperamide and naloxone. KEY RESULTS: In human preparations with L-NOARG/MRS2179, loperamide had no significant effects on isometric contractions. In preparations with hyoscine hydrobromide, loperamide reduced isometric relaxation during EFS (median difference + 0.60 g post-loperamide, Z = -2.35, p = 0.019). CONCLUSIONS AND INFERENCES: Loperamide had no effect on excitatory neuromuscular function in human colonic circular muscle. These findings suggest that loperamide alters colonic function by acting primarily on inhibitory motor neurons, premotor enteric neurons, or via alternative non-opioid receptor pathways.


Assuntos
Loperamida , Escopolamina , Animais , Colo , Estimulação Elétrica , Motilidade Gastrointestinal , Humanos , Loperamida/farmacologia , Contração Muscular/fisiologia , Naloxona/farmacologia , Nitroarginina/farmacologia , Escopolamina/farmacologia
13.
Physiol Rep ; 10(18): e15462, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36117310

RESUMO

Severe systemic inflammation is associated with nausea, loss of appetite, and delayed gastric emptying, which increases hospitalization admission length and mortality rate. There is a lack of human controlled studies exploring gastric emptying rates and underlying mechanisms during inflammatory conditions. We aimed to investigate if systemic inflammation in young men delays gastro-intestinal transit times, lowers motility, and affects gastrointestinal hormone secretion. This substudy of a randomized crossover trial investigated eight healthy young men on two separate occasions; (I) following an overnight fast (healthy conditions/HC) and (II) fasting and bedrest combined with two lipopolysaccharide (LPS) injections of 1 ng kg-1 following an overnight fast and 0.5 ng kg-1 following another 24 h (systemic inflammation/SI). A standardized protein beverage and a SmartPill capsule (a wireless gastrointestinal monitoring system) were swallowed during each occasion. Whole gut transit time was comparable between HC and SI. SI decreased gastric mean pressure peak amplitude (p = 0.04) and increased pH rise across the pylorus and small bowel pH (p = 0.02) compared with HC. Glucagon-like peptide-1 was elevated during SI compared with HC (p = 0.04). Peptide YY was lower during SI compared with HC (p = 0.007). Prolonged LPS exposure combined with fasting and bedrest elevated glucagon-like peptide 1 concentrations, which may play a role for the nausea and loss of appetite typically associated with SI.


Assuntos
Hormônios Gastrointestinais , Peptídeo YY , Estudos Cross-Over , Motilidade Gastrointestinal , Peptídeo 1 Semelhante ao Glucagon , Humanos , Inflamação , Lipopolissacarídeos , Masculino , Náusea/induzido quimicamente
14.
Sci Rep ; 12(1): 15310, 2022 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-36130988

RESUMO

Despite its physiological and pathological importance, the mechanical relationship between glucose uptake in the intestine and intestinal flows is unclear. In the intestine of the nematode Caenorhabditis elegans, the defecation motor program (DMP) causes reciprocating intestinal flows. Although the DMP is frequently activated in the intestines, its physiological function is unknown. We evaluated the mechanical signature of enhanced glucose uptake by the DMP in worms. Glucose uptake tended to increase with increasing flow velocity during the DMP because of mechanical mixing and transport. However, the increase in input energy required for the DMP was low compared with the calorie intake. The findings suggest that animals with gastrointestinal motility exploit the reciprocating intestinal flows caused by peristalsis to promote nutrient absorption by intestinal cells.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/fisiologia , Motilidade Gastrointestinal , Glucose , Intestinos/fisiologia
15.
Am J Physiol Gastrointest Liver Physiol ; 323(5): G477-G487, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36126271

RESUMO

Gastrointestinal motility is crucial to gut health and has been associated with different disorders such as inflammatory bowel diseases and postoperative ileus. Despite rat and mouse being the two animal models most widely used in gastrointestinal research, minimal studies in rats have investigated gastrointestinal motility. Therefore, our study provides a comparison of colonic motility in the mouse and rat to clarify species differences and assess the relative effectiveness of each animal model for colonic motility research. We describe the protocol modifications and optimization undertaken to enable video imaging of colonic motility in the rat. Apart from the broad difference in terms of gastrointestinal diameter and length, we identified differences in the fundamental histology of the proximal colon such that the rat had larger villus height-to-width and villus height-to-crypt depth ratios compared with mouse. Since gut motility is tightly regulated by the enteric nervous system (ENS), we investigated how colonic contractile activity within each rodent species responds to modulation of the ENS inhibitory neuronal network. Here we used Nω-nitro-l-arginine (l-NNA), an inhibitor of nitric oxide synthase (NOS) to assess proximal colon responses to the stimulatory effect of blocking the major inhibitory neurotransmitter, nitric oxide (NO). In rats, the frequency of proximal colonic contractions increased in the presence of l-NNA (vs. control levels) to a greater extent than in mice. This is despite a similar number of NOS-expressing neurons in the myenteric plexus across species. Given this increase in colonic contraction frequency, the rat represents another relevant animal model for investigating how gastrointestinal motility is regulated by the inhibitory neuronal network of the ENS.NEW & NOTEWORTHY Mice and rats are widely used in gastrointestinal research but have fundamental differences that make them important as different models for different questions. We found that mice have a higher villi length-to-width and villi length-to-crypt depth ratio than rat in proximal colon. Using the ex vivo video imaging technique, we observed that rat colon has more prominent response to blockade of major inhibitory neurotransmitter (nitric oxide) in myenteric plexus than mouse colon.


Assuntos
Sistema Nervoso Entérico , Óxido Nítrico , Ratos , Camundongos , Animais , Óxido Nítrico/farmacologia , Ratos Sprague-Dawley , Sistema Nervoso Entérico/fisiologia , Plexo Mientérico , Motilidade Gastrointestinal/fisiologia , Colo , Nitroarginina/farmacologia , Óxido Nítrico Sintase , Modelos Animais de Doenças
16.
World J Gastroenterol ; 28(29): 3854-3868, 2022 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-36157548

RESUMO

BACKGROUND: The mechanisms underlying gastrointestinal (GI) dysmotility with ulcerative colitis (UC) have not been fully elucidated. The enteric nervous system (ENS) plays an essential role in the GI motility. As a vital neurotransmitter in the ENS, the gas neurotransmitter nitric oxide (NO) may impact the colonic motility. In this study, dextran sulfate sodium (DSS)-induced UC rat model was used for investigating the effects of NO by examining the effects of rate-limiting enzyme nitric oxide synthase (NOS) changes on the colonic motility as well as the role of the ENS in the colonic motility during UC. AIM: To reveal the relationship between the effects of NOS expression changes in NOS-containing nitrergic neurons and the colonic motility in a rat UC model. METHODS: Male rats (n = 8/each group) were randomly divided into a control (CG), a UC group (EG1), a UC + thrombin derived polypeptide 508 trifluoroacetic acid (TP508TFA; an NOS agonist) group (EG2), and a UC + NG-monomethyl-L-arginine monoacetate (L-NMMA; an NOS inhibitor) group (EG3). UC was induced by administering 5.5% DSS in drinking water without any other treatment (EG1), while the EG2 and EG3 were gavaged with TP508 TFA and L-NMMA, respectively. The disease activity index (DAI) and histological assessment were recorded for each group, whereas the changes in the proportion of colonic nitrergic neurons were counted using immunofluorescence histochemical staining, Western blot, and enzyme linked immunosorbent assay, respectively. In addition, the contractile tension changes in the circular and longitudinal muscles of the rat colon were investigated in vitro using an organ bath system. RESULTS: The proportion of NOS-positive neurons within the colonic myenteric plexus (MP), the relative expression of NOS, and the NOS concentration in serum and colonic tissues were significantly elevated in EG1, EG2, and EG3 compared with CG rats. In UC rats, stimulation with agonists and inhibitors led to variable degrees of increase or decrease for each indicator in the EG2 and EG3. When the rats in EGs developed UC, the mean contraction tension of the colonic smooth muscle detected in vitro was higher in the EG1, EG2, and EG3 than in the CG group. Compared with the EG1, the contraction amplitude and mean contraction tension of the circular and longitudinal muscles of the colon in the EG2 and EG3 were enhanced and attenuated, respectively. Thus, during UC, regulation of the expression of NOS within the MP improved the intestinal motility, thereby favoring the recovery of intestinal functions. CONCLUSION: In UC rats, an increased number of nitrergic neurons in the colonic MP leads to the attenuation of colonic motor function. To intervene NOS activity might modulate the function of nitrergic neurons in the colonic MP and prevent colonic motor dysfunction. These results might provide clues for a novel approach to alleviate diarrhea symptoms of UC patients.


Assuntos
Colite Ulcerativa , Água Potável , Neurônios Nitrérgicos , Animais , Colite Ulcerativa/patologia , Colo/patologia , Sulfato de Dextrana/toxicidade , Motilidade Gastrointestinal , Masculino , Neurônios Nitrérgicos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Ratos , Trombina/metabolismo , Ácido Trifluoracético/metabolismo , Ácido Trifluoracético/farmacologia , ômega-N-Metilarginina/metabolismo , ômega-N-Metilarginina/farmacologia
17.
Headache ; 62(9): 1164-1176, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36111429

RESUMO

OBJECTIVE: To compare effects of an initial dose of calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) antagonists on gastrointestinal (GI) motility in patients with migraine and to explore if the mechanistic difference contributes to GI adverse events (AEs). BACKGROUND: Different frequencies of constipation have been observed between CGRP mAbs that target the ligand (galcanezumab [GMB]) or receptor (erenumab [ERE]). METHODS: Patients (n = 65) with migraine without significant GI symptoms were enrolled in a multi-center, single-blind phase IV clinical trial (NCT04294147) and randomized 1:1 to receive GMB (240 mg; n = 33) or ERE (140 mg; n = 32). GI whole and regional transit times were assessed using a wireless motility capsule 1 week before and 2 weeks after mAb administration. The primary endpoint was change from baseline in colonic transit time (CTT) within each treatment group. Other measures included GI Symptom Rating Scale (GSRS), Bristol Stool Form Scale (BSFS), and spontaneous bowel movement (SBM) evaluation. AEs were monitored throughout the study. RESULTS: Baseline characteristics indicated significant GI transit time variability with minimal GI reported symptoms. While not statistically significant, a numerical mean increase in CTT was observed in ERE patients (n = 28, mean [SD] at baseline: 33.8 [29.4] h; least square [LS] mean [SE] change: 5.8 [5.7] h, 95% confidence interval [CI] -5.7 to 17.2, p = 0.320), while GMB decreased CTT (n = 31, mean [SD] at baseline: 29.3 [24.5] h; LS mean [SE] change: -5.4 [5.4] h, 95% CI -16.2 to 5.5, p = 0.328) compared to baseline. No meaningful changes were observed in other regional transit times. ERE significantly reduced BSFS (LS mean [SE] score -0.5 [0.2], p = 0.004) and SBM (LS mean [SE] -1.2 [0.5], p = 0.0120), and increased GSRS-constipation compared to baseline (LS mean [SE] score 0.3 [0.1], p = 0.016). GMB increased GSRS-constipation (LS mean [SE] score 0.4 [0.1], p = 0.002). There were no discontinuations due to or serious AEs. A higher percentage of treatment-emergent AEs were reported with ERE than GMB (ERE: nine of 32 [28.1%] versus GMB: three of 33 [9.1%]), with constipation the most frequently reported (ERE: five of 32 [15.6%] versus GMB one of 33 [3.0%]). CONCLUSION: While the primary endpoint of this study was not met, secondary and tertiary endpoints support a within- and between-treatment change in GI effects suggesting possible mechanistic differences between ligand (GMB) and receptor (ERE) antagonism.


Assuntos
Anticorpos Monoclonais Humanizados , Constipação Intestinal , Motilidade Gastrointestinal , Transtornos de Enxaqueca , Adulto , Humanos , Peptídeo Relacionado com Gene de Calcitonina , Constipação Intestinal/induzido quimicamente , Método Duplo-Cego , Ligantes , Transtornos de Enxaqueca/tratamento farmacológico , Método Simples-Cego , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/efeitos adversos , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico
18.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 2224-2227, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-36086523

RESUMO

Gastric pacing is an attractive therapeutic approach for correcting abnormal bioelectrical activity. While high-resolution (HR) electrical mapping techniques have largely contributed to the current understanding of the effect of pacing on the electrophysiological function, these mapping techniques are restricted to surface contact electrodes and the signal quality can be corrupted by pacing artifacts. Optical mapping of voltage sensitive dyes is an alternative approach used in cardiac research, and the signal quality is not affected by pacing artifacts. In this study, we simultaneously applied HR optical and electrical mapping techniques to evaluate the bioelectrical slow wave response to gastric pacing. The studies were conducted in vivo on porcine stomachs ( n=3) where the gastric electrical activity was entrained using high-energy pacing. The pacing response was optically tracked using voltage-sensitive fluorescent dyes and electrically tracked using surface contact electrodes positioned on adjacent regions. Slow waves were captured optically and electrically and were concordant in time and direction of propagation with comparable mean velocities ([Formula: see text]) and periods ([Formula: see text]). Importantly, the optical signals were free from pacing artifacts otherwise induced in electrical recordings highlighting an advantage of optical mapping. Clinical Relevance- Entrainment mapping of gastric pacing using optical techniques is a major advance for improving the preclinical understanding of the therapy. The findings can thereby inform the efficacy of gastric pacing in treating functional motility disorders.


Assuntos
Motilidade Gastrointestinal , Estômago , Animais , Eletricidade , Eletrodos , Fenômenos Eletrofisiológicos , Motilidade Gastrointestinal/fisiologia , Estômago/diagnóstico por imagem , Estômago/fisiologia , Suínos
19.
Biomed Pharmacother ; 154: 113627, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36058152

RESUMO

Constipation has become an epidemic enteric medical problem, accompanied with increasing long-term sequelae. Gut microbiota and serotonin (5-HT) have been believed as predominant player in the treatment of constipation. In clinical practices, Shouhui Tongbian Capsule (SHTB) was found to effectively improve constipation symptoms and promote gastrointestinal motility. However, the specific mechanism of SHTB is not clearly elucidated. Our current study aims to explore the therapeutic effects of SHTB against the development of constipation and the underlying mechanisms related to gut bacterial and 5-HT. We established loperamide hydrochloride (LH)-induced experimental constipation mouse model to evaluate the effect of SHTB. 16S RNA sequencing, fecal microbiota transplants (FMT), high performance liquid chromatograph, and molecular biological analysis were performed to investigate the potential mechanisms of SHTB. Our data demonstrated that SHTB significantly ameliorated LH-induced experimental constipation and accelerated enteric motility via promoting 5-HT biosynthesis in enterochromaffin cells and enteric neuron growth of the enteric nervous system (ENS) in both the small intestine and colon. Additionally, SHTB significantly modulated gut microbiota dysbiosis and potentially altered microbiota metabolites to enhance intestinal 5-HT production. Finally, FMT study confirmed that the effects of SHTB on 5-HT production and constipation are dependent on modulating intestinal microbiota dysbiosis. In conclusion, our current study deciphered therapeutic mechanism of SHTB in the treatment of experimental constipation from perspectives of gut microbiota-5-HT-intetinal motility axis and provides novel insights into the appropriate and safe application of SHTB in the clinic.


Assuntos
Microbioma Gastrointestinal , Animais , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Disbiose , Motilidade Gastrointestinal/fisiologia , Loperamida/uso terapêutico , Camundongos , Serotonina/metabolismo
20.
Aliment Pharmacol Ther ; 56(9): 1337-1348, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36082475

RESUMO

BACKGROUND: Accurate definition of the gastroduodenal and ileocaecal junctions (GDJ, ICJ) is essential for the measurement of regional transit times. AIMS: To compare the assessment of these landmarks using the novel gas-sensing capsule and validated wireless motility capsule (WMC), and to evaluate intra-subject variance in transit times METHODS: Healthy subjects ingested the gas-sensing capsule and WMC tandemly in random order. Inter-observer agreement was evaluated by intra-class correlation coefficient (ICC). Agreement between the paired devices' transit times was assessed using Bland-Altman analysis; coefficient of variation was performed to express intra-individual variance in transit times. Similar analyses were completed with tandemly ingested gas-sensing capsules. RESULTS: The inter-observer agreement for landmarks for both capsules was excellent (mean ICC ≥0.97) in 50 studies. The GDJ was identifiable in 92% of the gas-sensing capsule studies versus 82% of the WMC studies (p = 0.27); the ICJ in 96% versus 84%, respectively (p = 0.11). In the primary cohort (n = 26), median regional transit times differed by less than 6 min between paired capsules. Bland-Altman revealed a bias of -0.12 (95% limits of agreement, -0.94 to 0.70) hours for GDJ and - 0.446 (-2.86 to 2.0) hours for ICJ. Similar results were found in a demographically distinct validation cohort (n = 24). For tandemly ingested gas-sensing capsules, coefficients of variation of transit times were 11%-35%, which were similar to variance between the paired gas-sensing capsule and WMC, as were the biases. The capsules were well tolerated. CONCLUSIONS: Key anatomical landmarks are accurately identified with the gas-sensing capsule in healthy individuals. Intra-individual differences in transit times between capsules are probably due to physiological factors. Studies in populations with gastrointestinal diseases are now required.


Assuntos
Endoscopia por Cápsula , Gastroenteropatias , Endoscopia por Cápsula/métodos , Cápsulas , Motilidade Gastrointestinal/fisiologia , Trânsito Gastrointestinal/fisiologia , Voluntários Saudáveis , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...