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1.
Neurogastroenterol Motil ; 34(11): e14394, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35531931

RESUMO

BACKGROUND: Gastroparesis (GP) is a gastrointestinal disorder associated with significant morbidity and healthcare costs. GP patients form a heterogeneous population with diverse etiology, and treatment is often challenging due to a poorly understood underlying pathophysiology. The aim of the present study was to assess antroduodenal motility patterns among the different GP etiologies. METHODS: We reviewed antroduodenal manometry (ADM) recordings of patients with confirmed GP between 2009 and 2019. ADM measurements were evaluated for fed period duration, number of phase III contractions and migrating motor complexes (MMCs), motility index (MI), and presence of neuropathic patterns. KEY RESULTS: A total of 167 GP patients (142 women, median age 45 [31-57]) were included. The following etiologies were identified: idiopathic n = 101; post-surgery n = 36; and diabetes n = 30. Fed period duration was significantly longer in idiopathic (p < 0.01) and diabetic GP patients (p < 0.05) compared with post-surgery GP patients. Furthermore, the number and duration of phase III contractions and the number of MMCs were significantly lower in idiopathic and diabetic patients compared with post-surgery GP patients (p < 0.01). Likewise, absence of MMCs during 6-h recording was more often observed in idiopathic and diabetes GP patients compared with post-surgery GP patients (resp. p < 0.01 and p < 0.05). CONCLUSIONS AND INFERENCES: Antroduodenal motility patterns are different among GP etiologies. A dysmotility spectrum was identified with different patterns ranging from post-surgery GP to idiopathic and diabetic GP.


Assuntos
Neuropatias Diabéticas , Gastroparesia , Duodeno/fisiologia , Feminino , Motilidade Gastrointestinal/fisiologia , Gastroparesia/diagnóstico , Gastroparesia/etiologia , Humanos , Manometria , Pessoa de Meia-Idade , Complexo Mioelétrico Migratório/fisiologia
2.
Neurogastroenterol Motil ; 34(8): e14334, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35254724

RESUMO

BACKGROUND/OBJECTIVES: Gastric emptying (GE) requires precise antropyloroduodenal coordination for effective transpyloric flow, the mechanisms of which are still unclear. We aimed to correlate gastric antral function assessed by antroduodenal manometry (ADM) with GE scintigraphy (GES) for liquid feeds in children with suspected gastrointestinal dysmotility. METHODS: Children who underwent both ADM and GES over a five-year period were reviewed. ADM tracings were re-analyzed to assess antral frequency, amplitude, and motility index (MI) pre-prandially and postprandially. Transpyloric propagation (TPP) was defined as antegrade propagated antral activity preceding duodenal phase III of the migrating motor complex (MMC). TPP was defined as "poor" if occurring in <50% of all presented duodenal phases III. For GES, regions of interest over the whole stomach, fundus, and antrum were drawn to calculate GE half-time (GE-T1/2 ) and retention rate (RR) in each region at 1 and 2 h. RESULTS: Forty-seven children (median age: 7.0 years) were included. Twenty-two had PIPO, 14 functional GI disorders, and 11 gastroparesis. Children with poor TPP had longer GE-T1/2 (113.0 vs 66.5 min, p = 0.028), higher RR of the whole stomach and fundus at 1 h (79.5% vs 63.5%, p = 0.038; 60.0% vs 41.0%, p = 0.022, respectively) and 2 h (51.0% vs 10.5%, p = 0.005; 36.0% vs 6.5%, p = 0.004, respectively). The pre-prandial antral amplitude of contractions inversely correlated with GE-T1/2 , RR of the whole stomach, and fundus at 2 h. CONCLUSIONS: TPP during phase III of the MMC correlated with gastric emptying of liquid and its assessment on ADM might predict abnormalities in postprandial gastric function.


Assuntos
Esvaziamento Gástrico , Gastroparesia , Criança , Duodeno , Motilidade Gastrointestinal , Humanos , Manometria , Complexo Mioelétrico Migratório , Antro Pilórico
3.
Am J Physiol Gastrointest Liver Physiol ; 321(6): G656-G667, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34612062

RESUMO

Gastric distension is known to affect normal slow-wave activity and gastric function, but links between slow-wave dysrhythmias and stomach function are poorly understood. Low-resolution mapping is unable to capture complex spatial properties of gastric dysrhythmias, necessitating the use of high-resolution mapping techniques. Characterizing the nature of these dysrhythmias has implications in the understanding of postprandial function and the development of new mapping devices. In this two-phase study, we developed and implemented a protocol for measuring electrophysiological responses to gastric distension in porcine experiments. In vivo, serosal high-resolution electrical mapping (256 electrodes; 36 cm2) was performed in anaesthetized pigs (n = 11), and slow-wave pattern, velocity, frequency, and amplitude were quantified before, during, and after intragastric distension. Phase I experiments (n = 6) focused on developing and refining the distension mapping methods using a surgically inserted intragastric balloon, with a variety of balloon types and distension protocols. Phase II experiments (n = 5) used barostat-controlled 500-mL isovolumetric distensions of an endoscopically introduced intragastric balloon. Dysrhythmias were consistently induced in all five gastric distensions, using refined distension protocols. Dysrhythmias appeared 23 s (SD = 5 s) after the distension and lasted 129 s (SD = 72 s), which consisted of ectopic propagation originating from the greater curvature in the region of distension. In summary, our results suggest that distension disrupts gastric entrainment, inducing temporary ectopic slow-wave propagation. These results may influence the understanding of the postprandial stomach and electrophysiological effects of gastric interventions.NEW & NOTEWORTHY This study presents the discovery of temporary dysrhythmic ectopic pacemakers in the distal stomach caused by localized gastric distension. Distension-induced dysrhythmias are an interesting physiological phenomenon that can inform the design of new interventional and electrophysiological protocols for both research and the clinic. The observation of distension-induced dysrhythmias also contributes to our understanding of stretch-sensitivity in the gut and may play an important role in normal and abnormal postprandial physiology.


Assuntos
Relógios Biológicos , Células Intersticiais de Cajal/fisiologia , Complexo Mioelétrico Migratório , Estômago/fisiologia , Animais , Feminino , Balão Gástrico , Sus scrofa , Fatores de Tempo
4.
Neurogastroenterol Motil ; 33(12): e14240, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34378830

RESUMO

BACKGROUND: The manometric diagnosis of severe intestinal dysmotility is performed at most institutions using catheters with 2-8 sensors 5-10 cm apart. The recent application of high-resolution manometry catheters with closely spaced sensors to other gut segments has been highly successful. The objective of the present study was to determine the feasibility of a jejunal high-resolution manometry method and to carry out a descriptive analysis of normal jejunal motor function. METHODS: A 36-channel high-resolution water-perfused manometry catheter (MMS-Laborie, Enschede, The Netherlands) was orally placed in the jejunum of 18 healthy subjects (10 men, eight women; 21-38 age range). Intestinal motility was recorded during 5 h, 3 during fasting, and 2 after a 450 kcal solid-liquid meal. Analysis of motility patterns was supported by computerized tools. KEY RESULTS: All healthy subjects except one showed at least one complete migrating motor complex during the 3 h fasting period. Phase III activity lasted 5 ± 1 min and migrated aborally at a velocity of 7 ± 3 cm/min. High-resolution spatial analysis showed that during phase III each individual contraction propagated rapidly (75 ± 37 cm/min) over a 32 ± 10 cm segment of the jejunum. During phase II, most contractile activity corresponded to propagated contractile events which increased in frequency from early to late phase II (0.5 ± 0.9 vs 2.5 ± 1.3 events/10 min, respectively; p < 0.001). After meal ingestion, non-propagated activity increased, whereas propagated events were less frequent than during late phase II. CONCLUSIONS & INFERENCES: Jejunal motility analysis with high-resolution manometry identifies propagated contractile patterns which are not apparent with conventional manometric catheters.


Assuntos
Ingestão de Alimentos/fisiologia , Jejuno/fisiologia , Complexo Mioelétrico Migratório/fisiologia , Adulto , Jejum/fisiologia , Feminino , Humanos , Masculino , Manometria , Estudos Prospectivos , Água , Adulto Jovem
5.
J Physiol ; 599(20): 4561-4579, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34418078

RESUMO

Soft faecal material is transformed into discrete, pellet-shaped faeces at the colonic flexure. Here, analysis of water content in natural faecal material revealed a decline from cecum to rectum without significant changes at the flexure. Thus, pellet formation is not explained by changes in viscosity alone. We then used video imaging of colonic wall movements with electromyography in isolated preparations containing guinea-pig proximal colon, colonic flexure and distal colon. To investigate the pellet formation process, the colonic segments were infused with artificial contents (Krebs solution and 4-6% methylcellulose) to simulate physiological faecal content flow. Remarkably, pellet formation took place in vitro, without extrinsic neural inputs. Infusion evoked slowly propagating neurogenic contractions, the proximal colon migrating motor complexes (∼0.6 cpm), which initiated pellet formation at the flexure. Lesion of the flexure, but not the proximal colon, disrupted the formation of normal individual pellets. In addition, a distinct myogenic mechanism was identified, whereby slow phasic contractions (∼1.9 cpm) initiated at the flexure and propagated short distances retrogradely into the proximal colon and antegradely into the distal colon. There were no detectable changes in the density or distribution of pacemaker-type interstitial cells of Cajal across the flexure. The findings provide new insights into how solid faecal content is generated, suggesting the major mechanisms underlying faecal pellet formation involve the unique interaction at the colonic flexure between antegrade proximal colon migrating motor complexes, organized by enteric neurons, and retrograde myogenic slow phasic contractions. Additional, as yet unidentified extrinsic and/or humoral influences appear to contribute to processing of faecal content in vivo. KEY POINTS: In herbivores, including guinea-pigs, clearly defined faecal pellets are formed at a distinct location along the large intestine (colonic flexure). The mechanism underlying the formation of these faecal pellets at this region has remained unknown. We reveal a progressive and gradual reduction in water content of faecal content along the bowel. Hence, the distinct transition from amorphous to pellet shaped faecal content could not be explained by a dramatic increase in water reabsorption from a specific site. We discovered patterns of anterograde neurogenic and retrograde myogenic motor activity that facilitate the formation of faecal pellets. The formation of 'pellet-like' boluses at the colonic flexure involves interaction of an antegrade migrating motor complex in the proximal colon and retrograde myogenic slow phasic contractions that emerge from the colonic flexure. The findings uncover intrinsic mechanisms responsible for the formation of discrete faecal scybala in the large intestine of a vertebrate.


Assuntos
Motilidade Gastrointestinal , Complexo Mioelétrico Migratório , Animais , Colo , Fezes , Cobaias , Intestino Grosso
6.
J Pediatr Gastroenterol Nutr ; 73(4): 507-512, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34224491

RESUMO

OBJECTIVES: Antroduodenal manometry (ADM) is used to evaluate antral and small intestinal motility, with the presence of phase III migrating motor complexes (MMCs) indicating an intact enteric neuromuscular system. The lack of evidence-based or consensus-driven established norms for MMC in fasting phase and after provocative testing marks a major limitation in the interpretation of ADM studies. We aimed to determine the characteristics of MMC in fasting and post-provocative phase in children. METHODS: Data from subjects ages <20 years with ADM results evaluated at neuro-gastroenterology and Motility Disorders Center, Cincinnati Children's Hospital Medical Center from January 2018 to March 2019 were analyzed. RESULTS: Forty-eight ADM tracings that did not demonstrate abnormal patterns were included; the mean age was 10.00 ±â€Š5.72 years and 50% were male. Indications for ADM included: vomiting (27.1%), feeding intolerance (27.1%), abdominal pain (16.6%), nausea (14.6%), and abdominal distension (14.6%). Thirty-seven percent of subjects had enteral access for feeds. During fasting, one-third of all MMC originated in the antrum. Azithromycin-induced MMC occurred in 28% of subjects and two-thirds of these originated in the antrum with antral contractions of significantly higher frequency and amplitude compared to fasting. Octreotide significantly increased frequency, amplitude, and duration of MMC compared to fasting, with 76% originating in the antrum. Both azithromycin and octreotide induced more than one MMC in a third of subjects. CONCLUSIONS: We describe the characteristics of antral and small intestinal motility during fasting and after provocative testing in children. These values will help standardize our interpretation of pediatric ADM studies.


Assuntos
Motilidade Gastrointestinal , Complexo Mioelétrico Migratório , Adolescente , Adulto , Criança , Pré-Escolar , Duodeno , Jejum , Humanos , Intestino Delgado , Masculino , Manometria , Adulto Jovem
7.
United European Gastroenterol J ; 9(6): 727-734, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34153172

RESUMO

BACKGROUND: Different peripheral pathways are implicated in the regulation of the food ingestion-digestion cycle. METHODS: Narrative review on gastrointestinal mechanisms involved in satiety and hunger signalling. RESULTS: Combined mechano- and chemoreceptors, peripherally released peptide hormones and neural pathways provide feedback to the brain to determine sensations of hunger (increase energy intake) or satiation (cessation of energy intake) and regulate the human metabolism. The gastric accommodation reflex, which consists of a transient relaxation of the proximal stomach during food intake, has been identified as a major determinant of meal volume, through activation of tension-sensitive gastric mechanoreceptors. Motilin, whose release is the trigger of gastric Phase 3, has been identified as the major determinant of return of hunger after a meal. In addition, the release of several peptide hormones such as glucagon-like peptide 1 (GLP-1), cholecystokinin as well as motilin and ghrelin contributes to gut-brain signalling with relevance to control of hunger and satiety. A number of nutrients, such as bitter tastants, as well as pharmacological agents, such as endocannabinoid receptor antagonists and GLP-1 analogues act on these pathways to influence hunger, satiation and food intake. CONCLUSION: Gastrointestinal mechanisms such as gastric accommodation and motilin release are key determinants of satiety and hunger.


Assuntos
Trato Gastrointestinal/fisiologia , Fome/fisiologia , Saciação/fisiologia , Animais , Colecistocinina/sangue , Grelina/sangue , Peptídeo 1 Semelhante ao Glucagon , Humanos , Motilina/sangue , Complexo Mioelétrico Migratório , Paladar
8.
Gastroenterology ; 161(2): 608-622.e7, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33895170

RESUMO

BACKGROUND & AIMS: Constipation is commonly associated with diabetes. Serotonin (5-HT), produced predominantly by enterochromaffin (EC) cells via tryptophan hydroxylase 1 (TPH1), is a key modulator of gastrointestinal (GI) motility. However, the role of serotonergic signaling in constipation associated with diabetes is unknown. METHODS: We generated EC cell reporter Tph1-tdTom, EC cell-depleted Tph1-DTA, combined Tph1-tdTom-DTA, and interstitial cell of Cajal (ICC)-specific Kit-GCaMP6 mice. Male mice and surgically ovariectomized female mice were fed a high-fat high-sucrose diet to induce diabetes. The effect of serotonergic signaling on GI motility was studied by examining 5-HT receptor expression in the colon and in vivo GI transit, colonic migrating motor complexes (CMMCs), and calcium imaging in mice treated with either a 5-HT2B receptor (HTR2B) antagonist or agonist. RESULTS: Colonic transit was delayed in males with diabetes, although colonic Tph1+ cell density and 5-HT levels were increased. Colonic transit was not further reduced in diabetic mice by EC cell depletion. The HTR2B protein, predominantly expressed by colonic ICCs, was markedly decreased in the colonic muscles of males and ovariectomized females with diabetes. Ca2+ activity in colonic ICCs was decreased in diabetic males. Treatment with an HTR2B antagonist impaired CMMCs and colonic motility in healthy males, whereas treatment with an HTR2B agonist improved CMMCs and colonic motility in males with diabetes. Colonic transit in ovariectomized females with diabetes was also improved significantly by the HTR2B agonist treatment. CONCLUSIONS: Impaired colonic motility in mice with diabetes was improved by enhancing HTR2B signaling. The HTR2B agonist may provide therapeutic benefits for constipation associated with diabetes.


Assuntos
Colo/efeitos dos fármacos , Constipação Intestinal/prevenção & controle , Complicações do Diabetes/prevenção & controle , Motilidade Gastrointestinal/efeitos dos fármacos , Indóis/farmacologia , Células Intersticiais de Cajal/efeitos dos fármacos , Complexo Mioelétrico Migratório/efeitos dos fármacos , Receptor 5-HT2B de Serotonina/efeitos dos fármacos , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Tiofenos/farmacologia , Animais , Sinalização do Cálcio , Colo/metabolismo , Colo/fisiopatologia , Constipação Intestinal/etiologia , Constipação Intestinal/metabolismo , Constipação Intestinal/fisiopatologia , Complicações do Diabetes/metabolismo , Complicações do Diabetes/fisiopatologia , Modelos Animais de Doenças , Feminino , Genes Reporter , Células Intersticiais de Cajal/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Ovariectomia , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptor 5-HT2B de Serotonina/metabolismo , Serotonina/metabolismo , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismo
9.
Molecules ; 26(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918638

RESUMO

Gastrointestinal side effects of donepezil, including dyspepsia, nausea, vomiting or diarrhea, occur in 20-30% of patients. The pathogenesis of these dysmotility associated disorders has not been fully clarified yet. Pharmacokinetic parameters of donepezil and its active metabolite 6-O-desmethyldonepezil were investigated in experimental pigs with and without small intestinal injury induced by dextran sodium sulfate (DSS). Morphological features of this injury were evaluated by a video capsule endoscopy. The effect of a single and repeated doses of donepezil on gastric myoelectric activity was assessed. Both DSS-induced small intestinal injury and prolonged small intestinal transit time caused higher plasma concentrations of donepezil in experimental pigs. This has an important implication for clinical practice in humans, with a need to reduce doses of the drug if an underlying gastrointestinal disease is present. Donepezil had an undesirable impact on porcine myoelectric activity. This effect was further aggravated by DSS-induced small intestinal injury. These findings can explain donepezil-associated dyspepsia in humans.


Assuntos
Donepezila/farmacocinética , Trato Gastrointestinal/patologia , Trato Gastrointestinal/fisiopatologia , Indanos/metabolismo , Metaboloma , Complexo Mioelétrico Migratório , Piperidinas/metabolismo , Estômago/fisiopatologia , Animais , Endoscopia por Cápsula , Sulfato de Dextrana , Donepezila/química , Donepezila/farmacologia , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Complexo Mioelétrico Migratório/efeitos dos fármacos , Estômago/efeitos dos fármacos , Suínos
10.
Am J Physiol Gastrointest Liver Physiol ; 320(4): G675-G687, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33624530

RESUMO

Electrical stimulation of the enteric nervous system (ENS) is an attractive approach to modify gastrointestinal transit. Colonic motor complexes (CMCs) occur with a periodic rhythm, but the ability to elicit a premature CMC depends, at least in part, upon the intrinsic refractory properties of the ENS, which are presently unknown. The objectives of this study were to record myoelectric complexes (MCs, the electrical correlates of CMCs) in the smooth muscle and 1) determine the refractory periods of MCs, 2) inform and evaluate closed-loop stimulation to repetitively evoke MCs, and 3) identify stimulation methods to suppress MC propagation. We dissected the colon from male and female C57BL/6 mice, preserving the integrity of intrinsic circuitry while removing the extrinsic nerves, and measured properties of spontaneous and evoked MCs in vitro. Hexamethonium abolished spontaneous and evoked MCs, confirming the necessary involvement of the ENS for electrically evoked MCs. Electrical stimulation reduced the mean interval between evoked and spontaneous CMCs (24.6 ± 3.5 vs. 70.6 ± 15.7 s, P = 0.0002, n = 7). The absolute refractory period was 4.3 s (95% confidence interval (CI) = 2.8-5.7 s, R2 = 0.7315, n = 8). Electrical stimulation applied during fluid distention-evoked MCs led to an arrest of MC propagation, and following stimulation, MC propagation resumed at an increased velocity (n = 9). The timing parameters of electrical stimulation increased the rate of evoked MCs and the duration of entrainment of MCs, and the refractory period provides insight into timing considerations for designing neuromodulation strategies to treat colonic dysmotility.NEW & NOTEWORTHY Maintained physiological distension of the isolated mouse colon induces rhythmic cyclic myoelectric complexes (MCs). MCs evoked repeatedly by closed-loop electrical stimulation entrain MCs more frequently than spontaneously occurring MCs. Electrical stimulation delivered at the onset of a contraction temporarily suppresses the propagation of MC contractions. Controlled electrical stimulation can either evoke MCs or temporarily delay MCs in the isolated mouse colon, depending on timing relative to ongoing activity.


Assuntos
Colo/inervação , Terapia por Estimulação Elétrica , Sistema Nervoso Entérico/fisiologia , Trânsito Gastrointestinal , Músculo Liso/inervação , Complexo Mioelétrico Migratório , Animais , Feminino , Masculino , Mecanotransdução Celular , Camundongos Endogâmicos C57BL , Pressão , Período Refratário Eletrofisiológico , Fatores de Tempo
11.
Neurogastroenterol Motil ; 33(5): e14052, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33452855

RESUMO

BACKGROUND: Age-associated changes alter calcium-activated potassium channel (BKCa ) expression of colon. Sphingolipids (SLs) are important cell membrane structural components; altered composition of SLs may affect BKCa expression. This study investigated the mechanism by which sphingosine-1-phosphate (S1P) contributes to age-associated contractile dysfunction. METHODS: Fifty male Sprague Dawley rats of different ages were randomly assigned to five age-groups, namely 3, 6, 12, 18, and 24 months. BKCa expression, S1P levels, and phosphorylated myosin light chain (p-MLC) levels were tested in colonic tissues. In the absence and presence of S1P treatment, BKCa expression, p-MLC levels, and intracellular calcium mobilization were tested in vitro. BKCa small interfering RNA (siRNA) was used to investigate whether p-MLC expression and calcium mobilization were affected by BKCa in colonic smooth muscle cells (SMCs). The expressions of phosphorylated protein kinase B, c-Jun N-terminal kinases (JNKs), extracellular-regulated protein kinases, nuclear factor kappa-B (NF-κB), and protein kinase Cζ (PKCζ ) were examined to investigate the correlation between S1P and BKCa . KEY RESULTS: Sphingosine-1-phosphate levels and sphingosine-1-phosphate receptor 2 (S1PR2) and BKCa expressions were upregulated and p-MLC expression was downregulated in the colonic tissues, age dependently. In the cultured SMCs, S1P treatment increased BKCa expression and reduced calcium concentration and p-MLC was observed. BKCa siRNA increased calcium concentration, and p-MLC levels significantly compared with control. We also showed that S1P upregulated BKCa through PKCζ , JNK, and NF-κB pathways. CONCLUSIONS AND INFERENCES: In conclusion, S1P and S1PR2 participate in age-associated contractile dysfunction via BKCa upregulation through PKCζ , JNK, and NF-κB pathways.


Assuntos
Envelhecimento/metabolismo , Colo/metabolismo , Motilidade Gastrointestinal/fisiologia , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Lisofosfolipídeos/metabolismo , Miócitos de Músculo Liso/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Esfingosina/análogos & derivados , Envelhecimento/fisiologia , Animais , Colo/fisiopatologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Técnicas de Silenciamento de Genes , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Contração Muscular/fisiologia , Miócitos de Músculo Liso/fisiologia , Complexo Mioelétrico Migratório/fisiologia , Cadeias Leves de Miosina/metabolismo , NF-kappa B/metabolismo , Proteína Quinase C/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno , Ratos , Esfingosina/metabolismo , Regulação para Cima
12.
Am J Physiol Gastrointest Liver Physiol ; 320(1): G12-G29, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33085903

RESUMO

The primary functions of the gastrointestinal (GI) tract are to absorb nutrients, water, and electrolytes that are essential for life. This is accompanied by the capability of the GI tract to mix ingested content to maximize absorption and effectively excrete waste material. There have been major advances in understanding intrinsic neural mechanisms involved in GI motility. This review highlights major advances over the past few decades in our understanding of colonic motor complexes (CMCs), the major intrinsic neural patterns that control GI motility. CMCs are generated by rhythmic coordinated firing of large populations of myenteric neurons. Initially, it was thought that serotonin release from the mucosa was required for CMC generation. However, careful experiments have now shown that neither the mucosa nor endogenous serotonin are required, although, evidence suggests enteroendocrine (EC) cells modulate CMCs. The frequency and extent of propagation of CMCs are highly dependent on mechanical stimuli (circumferential stretch). In summary, the isolated mouse colon emerges as a good model to investigate intrinsic mechanisms underlying colonic motility and provides an excellent preparation to explore potential therapeutic agents on colonic motility, in a highly controlled in vitro environment. In addition, during CMCs, the mouse colon facilitates investigations into the emergence of dynamic assemblies of extensive neural networks, applicable to the nervous system of different organisms.


Assuntos
Colo/fisiologia , Sistema Nervoso Entérico/fisiologia , Motilidade Gastrointestinal/fisiologia , Músculo Liso/fisiologia , Animais , Células Enteroendócrinas/fisiologia , Trato Gastrointestinal/fisiologia , Camundongos , Complexo Mioelétrico Migratório/fisiologia , Neurônios/fisiologia
13.
Z Gastroenterol ; 59(6): 540-550, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32512591

RESUMO

INTRODUCTION: Altered small intestinal motility has been observed in various manometry studies in patients with cirrhosis. Since small bowel manometry is available only in a few centers, interpretation of dysmotility in cirrhosis is controversial. PATIENTS AND METHODS: In this study, both fasting and postprandial manometric tracings of 24-hour antroduodenojejunal manometries were analyzed using both visual analysis and computer-aided analysis. RESULTS: In 34 patients (83 %), the mean migrating motor complex (MMC) cycle length was different compared with healthy controls. Phase II was prolonged in 27 patients (66 %), while phase I showed a reduced duration in 23 (56 %) and in phase III in 13 individuals (32 %). We also observed special motor patterns, e. g., migrating clustered contractions (MCCs) or retrograde clustered contractions (RCCs), which were present during fasting (69 %) and postprandial (92 %) motility, while none of the healthy controls showed any special motor patterns. Special motor patterns showed a significant correlation with the severity of cirrhosis (Child-Score; p > 0.05) and the existence of ascites (p < 0.05). DISCUSSION: This study in a large cohort of patients with cirrhosis by using 24-hour, solid state portable manometry showed in most individuals disturbances of cyclic fasting motility. Special motor patterns like RCCs during fasting and postprandial motility could be observed exclusively in the cirrhosis group, showing a significant correlation with severity of cirrhosis and the occurence of associated complications.


Assuntos
Motilidade Gastrointestinal , Complexo Mioelétrico Migratório , Criança , Humanos , Intestino Delgado , Cirrose Hepática/diagnóstico , Manometria
14.
Neurogastroenterol Motil ; 33(1): e13967, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32812313

RESUMO

BACKGROUND: Toxoplasma gondii infection causes intestinal inflammation and diarrhea indicating possible intestinal motor dysfunction. Anatomical studies have shown alterations in the colonic myenteric plexus, but it is unknown whether this impacts motility and therefore whether motility is a target for treatment. We determined whether colonic coordinated movements are compromised by toxoplasmic infection and how it is associated with anatomical changes. METHODS: Male Wistar rats were evaluated at 6, 12, 24, 48, and 72 hours and 30 days postinfection (dpi) and controls. Infected rats received orally 5 × 103 sporulated oocysts of strain ME-49 (genotype II) of T gondii. The colon was collected for anatomical analysis (including the myenteric plexus immunolabeled with HuC/D, nNOS, and ChAT) and motility analysis in vitro (conventional manometry). Fecal output was measured daily. KEY RESULTS: At 12 hours postinfection, T gondii caused hypertrophy of the muscularis externa layer of the distal colon. There was loss of total, nitrergic, and cholinergic myenteric neurons in the proximal colon at 30 day postinfection (dpi); however, only loss of cholinergic neurons was found in the distal colon. Contractile complexes in the middle and distal colon were longer in duration in infected animals, which was associated with slower migration of the colonic motor complex. However, gastrointestinal transit time and fecal pellet output remained unchanged during the T gondii infection. CONCLUSIONS AND INFERENCES: Toxoplasma gondii caused myenteric neuronal loss in the proximal and distal colon and altered the motility pattern in the middle and distal colon to a more propulsive phenotype.


Assuntos
Colo/inervação , Motilidade Gastrointestinal/fisiologia , Músculo Liso/inervação , Neurônios/patologia , Toxoplasmose/fisiopatologia , Animais , Colo/fisiopatologia , Músculo Liso/fisiopatologia , Plexo Mientérico , Complexo Mioelétrico Migratório/fisiologia , Ratos , Toxoplasmose/patologia
15.
Neurosci Lett ; 743: 135583, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33352279

RESUMO

There are isolated instances in the literature that suggest the 'onion skin' phenomenon is not always present. That is, newly recruited high threshold motor units (MU) have higher discharge rates than previously recruited low threshold MUs. Therefore, the purpose of this paper was to investigate the presence of the 'onion skin' phenomenon in a large sample of intramuscular myoelectric recordings from low to maximal force outputs. Forty-eight participants performed rapid isometric dorsiflexion contractions at 20, 40, 60, 80 and 100 % MVC while intramuscular electrical activity was recorded. A bivariate frequency-distribution of the motor unit discharge rate and motor unit action potential peak-to-peak (P-P) amplitude was assessed. There was a significant difference in bivariate frequency-distribution across force levels (D's = 0.1083-0.3094, p's < 0.001). Newly recruited high threshold MUs did have lower discharge rates, but there was an increase in the presence of high threshold, large P-P amplitude MUs with higher discharge rates than lower threshold MUs (reverse onion skin) during the stable portion of the force output. The recruitment of high threshold MUs with higher discharge rates decreased the level of common drive from the cross-correlation (Rxy) = 0.79 at 20 % MVC to Rxy = 0.68 at 100 % MVC (p < 0.01), but it remained high. As the interference pattern becomes more complex with the recruitment of more motor units at higher force outputs, intramuscular electrodes may be more discriminating while recording motor unit activity leading to the identification of both the 'reverse onion skin' and 'onion skin' phenomenon being present.


Assuntos
Eletromiografia/métodos , Contração Isométrica/fisiologia , Neurônios Motores/fisiologia , Músculo Esquelético/fisiologia , Complexo Mioelétrico Migratório/fisiologia , Recrutamento Neurofisiológico/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
16.
Neurogastroenterol Motil ; 33(5): e14047, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33252184

RESUMO

BACKGROUND: Colonic motor complexes (CMCs) have been widely recorded in the large intestine of vertebrates. We have investigated whether in the smooth muscle, a single unified pattern of electrical activity, or different patterns of electrical activity give rise to the different neurogenic patterns of motility underlying CMCs in vitro. METHODS: To study differences of the CMCs between proximal and distal colon, we used a novel combination of techniques to simultaneously record muscle diameter and force at multiple sites along the whole mouse colon ex vivo. In addition, electrical activity of smooth muscle was recorded by suction electrodes. KEY RESULTS: Two distinct types of CMCs were distinguished; CMCs that propagated along the entire colon (complete CMC) and CMCs which were restricted to the proximal colon (incomplete CMC). The two types of CMC often occurred in the same preparations. Incomplete CMCs had longer bursts of smooth muscle action potentials than complete CMCs and propagated more slowly. Interestingly, both types of CMC were associated with similar frequency bursts of smooth muscle action potentials at ~2.4 Hz. In the most proximal colon, an additional firing frequency was detected close to ~7 Hz generating multiple peaks within each CMC. CONCLUSIONS & INFERENCES: We report distinct characteristics underlying complete and incomplete CMCs in isolated mouse colon. Recognizing these distinct patterns of motility will be important for future interpretation of analysis of murine colonic motility recordings. The identification of alternating patterns of motor activity in proximal colon, but not distal colon may reflect specific neural mechanisms for fecal pellet formation.


Assuntos
Potenciais de Ação/fisiologia , Colo/fisiologia , Músculo Liso/fisiologia , Complexo Mioelétrico Migratório/fisiologia , Animais , Motilidade Gastrointestinal/fisiologia , Camundongos
17.
Gan To Kagaku Ryoho ; 48(13): 1954-1956, 2021 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-35045458

RESUMO

The demerit of pylorus-preserving gastrectomy(PPG)is the postprandial abdominal fullness(PAF)with gastric stasis in the remnant stomach(GSRS). We investigated the relationship between clinical findings and GSRS, and between GSRS and interdigestive migrating motor complex(IMMC)in PPG patients. A total of 30 patients(17 men and 13 women, mean age of 62.3 years)after PPG for early gastric cancer(Billroth Ⅰ)were divided into 2 groups(group A; 18 patients with GSRS, group B; 12 patients without GSRS). The relationship between GSRS including clinical findings and IMMC was studied from 1.5 to 3 years after operation. A catheter equipped with a micro-tip force transducer was inserted transnassally into the remnant stomach and duodenum in a supine position, and the IMMC was studied. All patients were Stage ⅠA(mucosal cancer, no lymph node metastasis, no distant metastasis). The remnant stomach was 1/3 compared with stomach size before operation. The length of the antral cuff in group A(1.5±0.2 cm)was significantly shorter than group B(3.2±0.3 cm)(p =0.0004). Appetite was significantly recognized in group B compared with group A(p=0.0067). PAF was significantly recognized in group A compared with group B(p=0.0001). Reflux esophagitis was found in group A more than group B. Early dumping syndroms did not found significant differences in both groups. In endoscopic esophagogastric finding of the remnant stomch, gastritis with GSRS was significantly found in group A compared with group B(p=0.0001). The IMMC was significantly recognized in group B compared with group A(p<0.0001). The occurrence of the PAF due to the GSRS may be caused by abscens of the IMMC.


Assuntos
Coto Gástrico , Gastroparesia , Neoplasias Gástricas , Feminino , Gastrectomia , Coto Gástrico/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Complexo Mioelétrico Migratório , Piloro/cirurgia , Neoplasias Gástricas/cirurgia
18.
Am J Physiol Regul Integr Comp Physiol ; 318(5): R997-R1003, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32320266

RESUMO

The purpose of this study was to characterize intestinal myoelectrical activity along the small intestine and investigate its responses to test meals with different glycemic index at different locations. Sixteen rats were implanted with electrodes in the serosal surface of the duodenum, jejunum, and ileum. Intestinal myoelectrical activities were recorded from these electrodes for 30 min in the fasting state and 3 h after four kinds of meals with different glycemic index, together with the assessment of blood glucose. The results were as follows: 1) in the fasting state, the percentage of normal intestinal slow waves (%NISW) showed no difference; however, the dominant frequency (DF), power (DP), and percentage of spike activity superimposed on the intestinal slow wave (NS/M) were progressively decreased along the entire small intestine; 2) regular solid meal and Ensure solicited no changes in any parameters of intestinal myoelectrical activity; whereas glucose and glucose + glucagon significantly altered the %NISW, DF, DP, and NS/M, and the effects on the proximal intestine were opposite to those in the distal intestine; and 3) postprandial blood glucose level was significantly correlated with %NISW along the entire small intestine. We found that that, in addition to the well-known frequency gradient, there is also a gradual decrease in the DP and spikes along the small intestine in the fasting state. Glucose and hyperglycemic meals inhibit myoelectrical activities in the proximal small intestine but result in enhanced but more dysrhythmic intestinal myoelectrical activities. There is a significant negative correlation between the normality of intestinal slow waves and blood glucose.


Assuntos
Glicemia/metabolismo , Dieta , Índice Glicêmico , Intestino Delgado/fisiologia , Complexo Mioelétrico Migratório , Ração Animal , Animais , Biomarcadores/sangue , Jejum/sangue , Masculino , Período Pós-Prandial , Ratos Sprague-Dawley , Fatores de Tempo
19.
Nat Rev Gastroenterol Hepatol ; 17(6): 338-351, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32152479

RESUMO

The gastrointestinal tract is the only internal organ to have evolved with its own independent nervous system, known as the enteric nervous system (ENS). This Review provides an update on advances that have been made in our understanding of how neurons within the ENS coordinate sensory and motor functions. Understanding this function is critical for determining how deficits in neurogenic motor patterns arise. Knowledge of how distension or chemical stimulation of the bowel evokes sensory responses in the ENS and central nervous system have progressed, including critical elements that underlie the mechanotransduction of distension-evoked colonic peristalsis. Contrary to original thought, evidence suggests that mucosal serotonin is not required for peristalsis or colonic migrating motor complexes, although it can modulate their characteristics. Chemosensory stimuli applied to the lumen can release substances from enteroendocrine cells, which could subsequently modulate ENS activity. Advances have been made in optogenetic technologies, such that specific neurochemical classes of enteric neurons can be stimulated. A major focus of this Review will be the latest advances in our understanding of how intrinsic sensory neurons in the ENS detect and respond to sensory stimuli and how these mechanisms differ from extrinsic sensory nerve endings in the gut that underlie the gut-brain axis.


Assuntos
Sistema Nervoso Entérico/fisiologia , Motilidade Gastrointestinal/fisiologia , Sensação/fisiologia , Células Receptoras Sensoriais/fisiologia , Vias Aferentes/fisiologia , Fibras Autônomas Pré-Ganglionares/fisiologia , Vias Eferentes/fisiologia , Sistema Nervoso Entérico/metabolismo , Células Enteroendócrinas/metabolismo , Células Enteroendócrinas/fisiologia , Humanos , Mecanotransdução Celular/fisiologia , Complexo Mioelétrico Migratório/fisiologia , Vias Neurais/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Neurotransmissores/metabolismo , Células Receptoras Sensoriais/metabolismo , Serotonina/metabolismo
20.
Expert Rev Gastroenterol Hepatol ; 14(2): 103-111, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31996050

RESUMO

Introduction: Motilin was first alluded to nearly a century ago. But it remains a rather abstruse peptide, in the shadow of its younger but more lucid 'cousin' ghrelin.Areas covered: The review aimed to bring to the fore multifarious aspects of motilin research with a view to aiding prioritization of future studies on this gastrointestinal peptide.Expert opinion: Growing evidence indicates that rodents (mice, rats, guinea pigs) do not have functional motilin system and, hence, studies in these species are likely to have a minimal translational impact. Both the active peptide and motilin receptor were initially localized to the upper gastrointestinal tract only but more recently - also to the brain (in both humans and other mammals with functional motilin system). Motilin is now indisputably implicated in interdigestive contractile activity of the gastrointestinal tract (in particular, gastric phase III of the migrating motor complex). Beyond this role, evidence is building that there is a cross-talk between motilin system and the brain-pancreas axis, suggesting that motilin exerts not only contractile but also orexigenic and insulin secretagogue actions.


Assuntos
Encéfalo/fisiologia , Trato Gastrointestinal/fisiologia , Motilina/fisiologia , Pâncreas/fisiologia , Animais , Motilidade Gastrointestinal/fisiologia , Grelina/fisiologia , Humanos , Fome/fisiologia , Insulina/fisiologia , Complexo Mioelétrico Migratório/fisiologia , Receptor Cross-Talk/fisiologia , Receptores dos Hormônios Gastrointestinais/fisiologia , Receptores de Neuropeptídeos/fisiologia , Transdução de Sinais/fisiologia
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