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1.
Int J Biol Sci ; 20(7): 2476-2490, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725863

RESUMO

Peristaltic movements in gut are essential to propel ingested materials through the gastrointestinal tract. Intestinal resident macrophages play an important role in this physiological function through protecting enteric neurons. However, it is incompletely clear how individuals maintain the homeostasis of gut motility. Here we found that NLRP3 is a critical factor in controlling loss of muscularis resident macrophages (MMs), and demonstrate that MMs are involved in the homeostasis of excitatory neurons such as choline acetyltransferase (ChAT)+ and vesicular glutamate transporter 2 (VGLUT2)+ but not inhibitory neuronal nitric oxide synthase (nNOS)+ neurons. NLRP3 knockout (KO) mice had enhanced gut motility and increased neurons, especially excitatory ChAT+ and VGLUT2+ neurons. Single cell analyses showed that there had increased resident macrophages, especially MMs in NLRP3 KO mice. The MM proportion in the resident macrophages was markedly higher than those in wild-type (WT) or caspase 1/11 KO mice. Deletion of the MMs and transplantation of the NLRP3 KO bone marrow cells showed that survival of the gut excitatory ChAT+ and VGLUT2+ neurons was dependent on the MMs. Gut microbiota metabolites ß-hydroxybutyrate (BHB) could promote gut motility through protecting MMs from pyroptosis. Thus, our data suggest that MMs regulated by NLRP3 maintain the homeostasis of excitatory neurons.


Assuntos
Homeostase , Macrófagos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Neurônios , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Camundongos , Macrófagos/metabolismo , Neurônios/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Colina O-Acetiltransferase/metabolismo , Colina O-Acetiltransferase/genética , Motilidade Gastrointestinal/fisiologia , Microbioma Gastrointestinal/fisiologia
2.
J Dig Dis ; 25(3): 176-190, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38697922

RESUMO

OBJECTIVES: Functional constipation (FC), a common functional gastrointestinal disorder, is usually overlapping with upper gastrointestinal symptoms (UGS). We aimed to explore the clinical characteristics of patients with FC overlapping UGS along with the related risk factors. METHODS: The differences in the severity of constipation symptoms, psychological state, quality of life (QoL), anorectal motility and perception function, autonomic function, and the effect of biofeedback therapy (BFT) among patients with FC in different groups were analyzed, along with the risk factors of overlapping UGS. RESULTS: Compared with patients with FC alone, those with FC overlapping UGS had higher scores in the Patient Assessment of Constipation Symptoms and Self-Rating Anxiety Scale and lower scores in the Short Form-36 health survey (P < 0.05). Patients with FC overlapping UGS also had lower rectal propulsion, more negative autonomic nervous function, and worse BFT efficacy (P < 0.05). Overlapping UGS, especially overlapping functional dyspepsia, considerably affected the severity of FC. Logistic regression model showed that age, body mass index (BMI), anxiety, exercise, and sleep quality were independent factors influencing overlapping UGS in patients with FC. CONCLUSIONS: Overlapping UGS reduces the physical and mental health and the QoL of patients with FC. It also increases the difficulty in the treatment of FC. Patient's age, BMI, anxiety, physical exercise, and sleep quality might be predictors for FC overlapping UGS.


Assuntos
Constipação Intestinal , Qualidade de Vida , Humanos , Constipação Intestinal/fisiopatologia , Constipação Intestinal/psicologia , Constipação Intestinal/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto , Índice de Gravidade de Doença , Biorretroalimentação Psicológica , Ansiedade , Gastroenteropatias/psicologia , Gastroenteropatias/fisiopatologia , Gastroenteropatias/etiologia , Idoso , Motilidade Gastrointestinal/fisiologia
4.
World J Gastroenterol ; 30(14): 1963-1967, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38681124

RESUMO

Digestion and intestinal absorption allow the body to sustain itself and are the emblematic functions of the bowel. On the flip side, functions also arise from its role as an interface with the environment. Indeed, the gut houses microorganisms, collectively known as the gut microbiota, which interact with the host, and is the site of complex immune activities. Its role in human pathology is complex and scientific evidence is progressively elucidating the functions of the gut, especially regarding the pathogenesis of chronic intestinal diseases and inflammatory conditions affecting various organs and systems. This editorial aims to highlight and relate the factors involved in the pathogenesis of intestinal and systemic inflammation.


Assuntos
Microbioma Gastrointestinal , Motilidade Gastrointestinal , Intestinos , Humanos , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Motilidade Gastrointestinal/fisiologia , Intestinos/microbiologia , Intestinos/imunologia , Intestinos/fisiopatologia , Inflamação/imunologia , Inflamação/fisiopatologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Animais
5.
J Physiol Sci ; 74(1): 26, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654149

RESUMO

Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an organ bath, and mechanical responses were recorded using a force transducer. Exogenous application of ATP (10-100 µM) evoked relaxation of the esophageal smooth muscle in a longitudinal direction under the condition of carbachol (1 µM) -induced precontraction. Pretreatment with a non-selective P2 receptor antagonist, suramin (500 µM), and a P2Y receptor antagonist, cibacron blue F3GA (200 µM), inhibited the ATP (100 µM) -induced relaxation, but a P2X receptor antagonist, pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (50 µM), did not affect it. A blocker of ATP-dependent potassium channels (KATP channels), glibenclamide (200 µM), inhibited the ATP-induced relaxation and application of an opener of KATP channels, nicorandil (50 µM), produced relaxation. The findings suggest that ATP is involved in inhibitory regulation of the longitudinal smooth muscle in the muscularis mucosae of the rat esophagus via activation of P2Y receptors and then opening of KATP channels.


Assuntos
Trifosfato de Adenosina , Esôfago , Canais KATP , Músculo Liso , Receptores Purinérgicos P2Y , Animais , Ratos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Músculo Liso/metabolismo , Masculino , Receptores Purinérgicos P2Y/metabolismo , Esôfago/efeitos dos fármacos , Esôfago/fisiologia , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Canais KATP/metabolismo , Relaxamento Muscular/efeitos dos fármacos , Relaxamento Muscular/fisiologia , Ratos Wistar , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Ratos Sprague-Dawley
6.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(2): 288-294, 2024 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-38686409

RESUMO

Monitoring of bowel sounds is an important method to assess bowel motility during sleep, but it is seriously affected by snoring noise. In this paper, the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) method was applied to remove snoring noise from bowel sounds during sleep. Specifically, the noisy bowel sounds were first band-pass filtered, then decomposed by the CEEMDAN method, and finally the appropriate components were selected to reconstruct the pure bowel sounds. The results of semi-simulated and real data showed that the CEEMDAN method was better than empirical mode decomposition and wavelet denoising method. The CEEMDAN method is used to remove snoring noise from bowel sounds during sleep, which lays an important foundation for using bowel sounds to assess the intestinal motility during sleep.


Assuntos
Sono , Ronco , Humanos , Sono/fisiologia , Ronco/fisiopatologia , Processamento de Sinais Assistido por Computador , Motilidade Gastrointestinal/fisiologia , Som , Algoritmos , Ruído
7.
Curr Opin Endocrinol Diabetes Obes ; 31(3): 131-137, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38533785

RESUMO

PURPOSE OF REVIEW: Metabolic and bariatric surgery (MBS) and endoscopic bariatric therapies (EBT) are being increasingly utilized for the management of obesity. They work through multiple mechanisms, including restriction, malabsorption, and changes in the gastrointestinal hormonal and motility. RECENT FINDINGS: Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) cause decrease in leptin, increase in GLP-1 and PYY, and variable changes in ghrelin (generally thought to decrease). RYGB and LSG lead to rapid gastric emptying, increase in small bowel motility, and possible decrease in colonic motility. Endoscopic sleeve gastroplasty (ESG) causes decrease in leptin and increase in GLP-1, ghrelin, and PYY; and delayed gastric motility. SUMMARY: Understanding mechanisms of action for MBS and EBT is critical for optimal care of patients and will help in further refinement of these interventions.


Assuntos
Cirurgia Bariátrica , Hormônios Gastrointestinais , Motilidade Gastrointestinal , Humanos , Motilidade Gastrointestinal/fisiologia , Cirurgia Bariátrica/métodos , Hormônios Gastrointestinais/metabolismo , Grelina/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Obesidade/cirurgia , Obesidade/metabolismo , Obesidade/fisiopatologia , Leptina/metabolismo , Obesidade Mórbida/cirurgia , Obesidade Mórbida/metabolismo , Derivação Gástrica/métodos , Derivação Gástrica/efeitos adversos , Peptídeo YY/metabolismo
8.
Neurogastroenterol Motil ; 36(5): e14776, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38454312

RESUMO

Functional constipation (FC) is a common condition in childhood in the United Kingdom and worldwide. Various radiological approaches have been established for diagnostic purposes. The radiopaque marker study (ROMS) is universally accepted and used to assess colonic transit time (CTT) in children with FC. Despite being widely used, there is a lack of standardization with various technical protocols, reproducibility of different populations, the purpose for using investigation, variance in the number of markers used, the amount of study days and calculations, the need to empty the colon before performing the test, and whether to perform on medication or off, or the use of specific diets. As part of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) motility working group (MWG), we decided to explore further into the evidence, in order to provide guidance regarding the use of ROMS in dealing with FC in the pediatric population.


Assuntos
Colo , Constipação Intestinal , Trânsito Gastrointestinal , Criança , Humanos , Colo/diagnóstico por imagem , Consenso , Constipação Intestinal/diagnóstico por imagem , Constipação Intestinal/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Trânsito Gastrointestinal/fisiologia
9.
Sci Rep ; 14(1): 6038, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38472365

RESUMO

Pacing has been proposed as a therapy to restore function in motility disorders associated with electrical dysrhythmias. The spatial response of bioelectrical activity in the small intestine to pacing is poorly understood due to a lack of high-resolution investigations. This study systematically varied pacing parameters to determine the optimal settings for the spatial entrainment of slow wave activity in the jejunum. An electrode array was developed to allow simultaneous pacing and high-resolution mapping of the small intestine. Pacing parameters including pulse-width (50, 100 ms), pulse-amplitude (2, 4, 8 mA) and pacing electrode orientation (antegrade, retrograde, circumferential) were systematically varied and applied to the jejunum (n = 15 pigs). Pulse-amplitudes of 4 mA (p = 0.012) and 8 mA (p = 0.002) were more effective than 2 mA in achieving spatial entrainment while pulse-widths of 50 ms and 100 ms had comparable effects (p = 0.125). A pulse-width of 100 ms and a pulse-amplitude of 4 mA were determined to be most effective for slow wave entrainment when paced in the antegrade or circumferential direction with a success rate of greater than 75%. These settings can be applied in chronic studies to evaluate the long-term efficacy of pacing, a critical aspect in determining its therapeutic potential.


Assuntos
Motilidade Gastrointestinal , Jejuno , Animais , Suínos , Jejuno/fisiologia , Motilidade Gastrointestinal/fisiologia , Estimulação Elétrica , Eletrodos
10.
Neurogastroenterol Motil ; 36(5): e14779, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38488234

RESUMO

BACKGROUND: Gastric motility disorder is an increasingly common problem among people with diabetes. Neurotransmitters have been recognized as critical regulators in the process of gastric motility. Previous study has shown that herb pair huanglian-banxia (HL-BX) can improve gastric motility, but the underlying mechanism is still unclear. The aim of this study was to further investigate the role of HL-BX in modulating brain-gut neurotransmission to promote gastric motility in diabetic rats, and to explore its possible mechanism. METHODS: The diabetic rats were divided into five groups. Gastric emptying rate, intestinal propulsion rate, body weight, and average food intake were determined. Substance P (SP), 5- hydroxytryptamine (5-HT), and glucagon-like peptide -1 (GLP-1) in the serum were measured by enzyme-linked immunosorbent assay. Dopamine (DA) and norepinephrine (NE) in the brain were analyzed by high-pressure liquid chromatography with a fluorescence detector. Protein expression of the tissues in the stomach and brain was determined by Western blot. KEY RESULTS: HL-BX reduced average food intake significantly, increased body weight, and improved gastric emptying rate and intestinal propulsion rate. HL-BX administration caused a significant increase in SP, GLP-1, and 5-HT, but a significant decrease in DA and NE. Interestingly, HL-BX regulated simultaneously the different expressions of MAPK and its downstream p70S6K/S6 signaling pathway in the stomach and brain. Moreover, berberine exhibited a similar effect to HL-BX. CONCLUSIONS: These results indicated that HL-BX promoted gastric motility by regulating brain-gut neurotransmitters through the MAPK signaling pathway. HL-BX and MAPK provide a potential therapeutic option for the treatment of gastroparesis.


Assuntos
Diabetes Mellitus Experimental , Medicamentos de Ervas Chinesas , Motilidade Gastrointestinal , Sistema de Sinalização das MAP Quinases , Animais , Masculino , Ratos , Encéfalo/metabolismo , Eixo Encéfalo-Intestino/fisiologia , Diabetes Mellitus Experimental/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Motilidade Gastrointestinal/fisiologia , Motilidade Gastrointestinal/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Neurotransmissores/metabolismo
11.
Neurogastroenterol Motil ; 36(4): e14758, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342973

RESUMO

BACKGROUND AND PURPOSE: The pathophysiology of obesity has been the product of extensive research, revealing multiple interconnected mechanisms contributing to body weight regulation. The regulation of energy balance involves an intricate network, including the gut-neuroendocrine interplay. As a consequence, research on the gut-brain-microbiota axis in obesity has grown extensively. The physiology of the gastrointestinal tract, far from being underexplored, has significant implications for the development of specific complications in people living with obesity across the fields of gastroenterology, nutrition, and pharmacology. Clinical research indicates higher fasting bile acids serum levels, and blunted postprandial increases in bilious secretions in people living with obesity. Findings are less straightforward for the impact of obesity on gastric emptying with various studies reporting accelerated, normal, or delayed gastric emptying rates. Conversely, the effect of obesity on gastrointestinal pH, gastrointestinal transit, and gastric and pancreatic enzyme secretion is largely unknown. In this review, we explore the current evidence on the gastrointestinal physiology of obesity.


Assuntos
Trânsito Gastrointestinal , Obesidade , Humanos , Obesidade/complicações , Trânsito Gastrointestinal/fisiologia , Peso Corporal , Jejum , Estômago , Motilidade Gastrointestinal/fisiologia , Esvaziamento Gástrico , Trato Gastrointestinal
12.
Neurogastroenterol Motil ; 36(5): e14759, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38361112

RESUMO

BACKGROUND: Colonic manometry (CM) is a diagnostic procedure utilized in the evaluation of intractable constipation and involves endoscopic insertion of a manometry catheter with the tip placed in the cecum. Difficulty in advancing the colonic manometry catheter to the right colon and/or distal displacement of the catheter after appropriate placement can result in partial evaluation of the colon. Our study aimed to assess the value of limited left CM in identifying motility disorders. METHODS: We evaluated CM studies conducted at a tertiary pediatric center (2019-2022). Abnormal CM studies with catheter tips located in the cecum or ascending colon were included. KEY RESULTS: Of 161 CM studied, 68 with abnormal CM studies met inclusion criteria (29 [42.7%] females, median age 10.3 years). Pan-colonic dysmotility was noted in 29 (42.7%) studies and segmental dysmotility in 39 (57.4%) studies. Dysmotility of the descending and/or sigmoid colon was the most common segmental dysmotility (30, 76.9%). Isolated dysmotility of the ascending colon was noted only in patients with a cecostomy (6/13, 46.2%). The diagnostic sensitivity for dysmotility by left CM was 91.2%, which increased to 100% when excluding patients with cecostomy. CONCLUSIONS AND INFERENCES: Left CM is a valuable and sensitive diagnostic tool for identifying abnormal colonic motility in most pediatric patients with constipation without cecostomy. Our study results provide reassurance when the manometry catheter becomes dislodged from the cecum and moves distally. Those with cecostomy have a high prevalence of dysmotility in the ascending colon and need a complete CM to identify it.


Assuntos
Constipação Intestinal , Motilidade Gastrointestinal , Manometria , Humanos , Manometria/métodos , Feminino , Criança , Masculino , Adolescente , Motilidade Gastrointestinal/fisiologia , Constipação Intestinal/diagnóstico , Constipação Intestinal/fisiopatologia , Colo/fisiopatologia , Pré-Escolar
13.
Sci Robot ; 9(87): eadh8170, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38416855

RESUMO

Postoperative ileus (POI) is the leading cause of prolonged hospital stay after abdominal surgery and is characterized by a functional paralysis of the digestive tract, leading to symptoms such as constipation, vomiting, and functional obstruction. Current treatments are mainly supportive and inefficacious and yield acute side effects. Although electrical stimulation studies have demonstrated encouraging pacing and entraining of the intestinal slow waves, no devices exist today to enable targeted intestinal reanimation. Here, we developed an ingestible self-propelling device for intestinal reanimation (INSPIRE) capable of restoring peristalsis through luminal electrical stimulation. Optimizing mechanical, material, and electrical design parameters, we validated optimal deployment, intestinal electrical luminal contact, self-propelling capability, safety, and degradation of the device in ex vivo and in vivo swine models. We compared the INSPIRE's effect on motility in models of normal and depressed motility and chemically induced ileus. Intestinal contraction improved by 44% in anesthetized animals and up to 140% in chemically induced ileus cases. In addition, passage time decreased from, on average, 8.6 days in controls to 2.5 days with the INSPIRE device, demonstrating significant improvement in motility. Luminal electrical stimulation of the intestine via the INSPIRE efficaciously restored peristaltic activity. This noninvasive option offers a promising solution for the treatment of ileus and other motility disorders.


Assuntos
Íleus , Robótica , Animais , Suínos , Motilidade Gastrointestinal/fisiologia , Íleus/terapia , Íleus/etiologia , Intestinos , Complicações Pós-Operatórias
14.
Sci Rep ; 14(1): 4842, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418514

RESUMO

Abnormal cyclic motor pattern (CMP) activity is implicated in colonic dysfunction, but the only tool to evaluate CMP activity, high-resolution colonic manometry (HRCM), remains expensive and not widely accessible. This study aimed to validate body surface colonic mapping (BSCM) through direct correlation with HRCM. Synchronous meal-test recordings were performed in asymptomatic participants with intact colons. A signal processing method for BSCM was developed to detect CMPs. Quantitative temporal analysis was performed comparing the meal responses and motility indices (MI). Spatial heat maps were also compared. Post-study questionnaires evaluated participants' preference and comfort/distress experienced from either test. 11 participants were recruited and 7 had successful synchronous recordings (5 females/2 males; median age: 50 years [range 38-63]). The best-correlating MI temporal analyses achieved a high degree of agreement (median Pearson correlation coefficient (Rp) value: 0.69; range 0.47-0.77). HRCM and BSCM meal response start and end times (Rp = 0.998 and 0.83; both p < 0.05) and durations (Rp = 0.85; p = 0.03) were similar. Heat maps demonstrated good spatial agreement. BSCM is the first non-invasive method to be validated by demonstrating a direct spatio-temporal correlation to manometry in evaluating colonic motility.


Assuntos
Colo , Constipação Intestinal , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Motilidade Gastrointestinal/fisiologia , Manometria/métodos , Refeições
15.
Neurogastroenterol Motil ; 36(2): e14716, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38031349

RESUMO

BACKGROUND: Colonic motility is regulated by various factors along the gut-brain axis; however, detailed mechanisms are unknown. This study aimed to examine the involvement of the autonomic nervous system in colonic motility. Suncus murinus (suncus) is a small laboratory mammal suitable for gastrointestinal motility studies. METHODS: Colonic motility and concomitant feeding and defecation behaviors in vagotomized and reserpine-administered suncus were recorded simultaneously for 24 h. Furthermore, we performed immunohistochemistry on tyrosine hydroxylase (TH) and in situ hybridization on corticotropin-releasing hormone (CRH) in suncus brain. Additionally, we examined c-Fos expression in the brain using immunohistochemistry in conscious suncus with colorectal distension. KEY RESULTS: In vagotomized suncus, clustered giant migrating contractions (GMCs), consisting of strong contractions occurring in a short time, were observed, and the percentage of GMCs without defecation increased. The frequency of GMCs in the reserpine-administered suncus increased during a light period (ZT0-4, 4-8) and decreased during a dark period (ZT16-20, 20-24) compared to a vehicle group. Additionally, the percentage of GMCs without defecation in the reserpine-administered suncus increased. Suncus TH-immunopositive neurons were found in the locus coeruleus (LC), as shown in rodents. In contrast, CRH mRNA-expressing cells were not observed in a region assumed to be the Barrington's nucleus (Bar). Furthermore, colorectal distension in conscious suncus induced c-Fos expression in LC TH neurons. CONCLUSIONS & INFERENCES: Our results suggest that the vagus and sympathetic nerves are not required for induction of GMCs in vivo. However, they are likely to exert a modulatory role in control of GMC frequency in Suncus murinus.


Assuntos
Neoplasias Colorretais , Reserpina , Animais , Nervo Vago/fisiologia , Motilidade Gastrointestinal/fisiologia , Estado de Consciência , Hormônio Liberador da Corticotropina , Mamíferos
16.
Neurogastroenterol Motil ; 36(2): e14723, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38062544

RESUMO

BACKGROUND: Despite evidence that slow-wave dysrhythmia in the stomach is associated with clinical conditions such as gastroparesis and functional dyspepsia, there is still no widely available device for long-term monitoring of gastric electrical signals. Actionable biomarkers of gastrointestinal health are critically needed, and an implantable slow-wave monitoring device could aid in the establishment of causal relationships between symptoms and gastric electrophysiology. Recent developments in the area of wireless implantable gastric monitors demonstrate potential, but additional work and validation are required before this potential can be realized. METHODS: We hypothesized that translating an existing implantable cardiac monitoring device, the Reveal LINQ™ (Medtronic), would present a more immediate solution. Following ethical approval and laparotomy in anesthetized pigs (n = 7), a Reveal LINQ was placed on the serosal surface of the stomach, immediately adjacent to a validated flexible-printed-circuit (FPC) electrical mapping array. Data were recorded for periods of 7.5 min, and the resultant signal characteristics from the FPC array and Reveal LINQ were compared. KEY RESULTS: The Reveal LINQ device recorded slow waves in 6/7 subjects with a comparable period (p = 0.69), signal-to-noise ratio (p = 0.58), and downstroke width (p = 0.98) to the FPC, but with reduced amplitude (p = 0.024). Qualitatively, the Reveal LINQ slow-wave signal lacked the prolonged repolarization phase present in the FPC signals. CONCLUSIONS & INFERENCES: These findings suggest that existing cardiac monitors may offer an efficient solution for the long-term monitoring of slow waves. Translation toward implantation now awaits.


Assuntos
Motilidade Gastrointestinal , Gastroparesia , Suínos , Humanos , Animais , Motilidade Gastrointestinal/fisiologia , Estômago/fisiologia , Fenômenos Eletrofisiológicos
17.
Ann Biomed Eng ; 52(3): 588-599, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37962674

RESUMO

Intestinal motility is governed in part by bioelectrical slow-waves and spike-bursts. Mesenteric ischemia is a substantial clinical challenge, but its electrophysiological and contractile mechanisms are not well understood. Simultaneous high-resolution bioelectrical and video mapping techniques were used to capture the changes in slow-waves, spike-bursts, and contractile activity during baseline, ischemia, and reperfusion periods. Experiments were performed on anesthetized pigs where intestinal contractions were quantified using surface strain and diameter measurements, while slow-wave and spike-bursts were quantified using frequency and amplitude. Slow-waves entrainment within the ischemic region diminished during ischemia, resulting in irregular slow-wave activity and a reduction in the frequency from 12.4 ± 3.0 cycles-per-minute (cpm) to 2.5 ± 2.7 cpm (p = 0.0006). At the end of the reperfusion period, normal slow-wave entrainment was observed at a frequency of 11.5 ± 2.9 cpm. There was an increase in spike-burst activity between the baseline and ischemia periods (1.1 ± 1.4 cpm to 8.7 ± 3.3 cpm, p = 0.0003) along with a spasm of circumferential contractions. At the end of the reperfusion period, the frequency of spike-bursts decreased to 2.7 ± 1.4 cpm, and contractions subsided. The intestine underwent tonal contraction during ischemia, with the diameter decreasing from 29.3 ± 2.6 mm to 21.2 ± 6.2 mm (p = 0.0020). At the end of the reperfusion period, the intestinal diameter increased to 27.3 ± 3.9 mm. The decrease in slow-wave activity, increase in spike-bursts, and tonal contractions can objectively identify ischemic segments in the intestine. It is anticipated that the use of electrophysiological slow-wave and spike-burst biomarkers, along with contractile measures, could identify mesenteric ischemia in surgical settings and allow an objective biomarker for successful revascularization.


Assuntos
Isquemia Mesentérica , Animais , Suínos , Intestinos , Motilidade Gastrointestinal/fisiologia , Isquemia , Contração Muscular
18.
Cell Mol Gastroenterol Hepatol ; 17(3): 383-398, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38061549

RESUMO

BACKGROUND & AIMS: Although chronic diarrhea and constipation are common, the treatment is symptomatic because their pathophysiology is poorly understood. Accumulating evidence suggests that the microbiota modulates gut function, but the underlying mechanisms are unknown. We therefore investigated the pathways by which microbiota modulates gastrointestinal motility in different sections of the alimentary tract. METHODS: Gastric emptying, intestinal transit, muscle contractility, acetylcholine release, gene expression, and vasoactive intestinal polypeptide (VIP) immunoreactivity were assessed in wild-type and Myd88-/-Trif-/- mice in germ-free, gnotobiotic, and specific pathogen-free conditions. Effects of transient colonization and antimicrobials as well as immune cell blockade were investigated. VIP levels were assessed in human full-thickness biopsies by Western blot. RESULTS: Germ-free mice had similar gastric emptying but slower intestinal transit compared with specific pathogen-free mice or mice monocolonized with Lactobacillus rhamnosus or Escherichia coli, the latter having stronger effects. Although muscle contractility was unaffected, its neural control was modulated by microbiota by up-regulating jejunal VIP, which co-localized with and controlled cholinergic nerve function. This process was responsive to changes in the microbial composition and load and mediated through toll-like receptor signaling, with enteric glia cells playing a key role. Jejunal VIP was lower in patients with chronic intestinal pseudo-obstruction compared with control subjects. CONCLUSIONS: Microbial control of gastrointestinal motility is both region- and bacteria-specific; it reacts to environmental changes and is mediated by innate immunity-neural system interactions. By regulating cholinergic nerves, small intestinal VIP plays a key role in this process, thus providing a new therapeutic target for patients with motility disorders.


Assuntos
Motilidade Gastrointestinal , Peptídeo Intestinal Vasoativo , Humanos , Camundongos , Animais , Peptídeo Intestinal Vasoativo/metabolismo , Motilidade Gastrointestinal/fisiologia , Neuroglia/metabolismo , Colinérgicos
19.
Curr Gastroenterol Rep ; 26(1): 9-19, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38057499

RESUMO

PURPOSE OF REVIEW: To discuss all the various motility disorders impacting people with Cystic Fibrosis (PwCF) and provide diagnostic and management approaches from a group of pediatric and adult CF and motility experts and physiologists with experience in the management of this disease. RECENT FINDINGS: Gastrointestinal (GI) symptoms coexist with pulmonary symptoms in PwCF regardless of age and sex. The GI manifestations include gastroesophageal reflux disease, esophageal dysmotility gastroparesis, small bowel dysmotility, small intestinal bacterial overgrowth syndrome, distal idiopathic obstruction syndrome, constipation, and pelvic floor disorders. They are quite debilitating, limiting the patients' quality of life and affecting their nutrition and ability to socialize. This genetic disorder affects many organ systems and is chronic, potentially impacting fertility and future family planning, requiring a multidisciplinary approach. Our review discusses the treatments of motility disorders in CF, their prevalence and pathophysiology. We have provided a framework for clinicians who care for these patients that can help to guide their clinical management.


Assuntos
Fibrose Cística , Refluxo Gastroesofágico , Gastroenteropatias , Adulto , Humanos , Criança , Fibrose Cística/complicações , Fibrose Cística/terapia , Qualidade de Vida , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Refluxo Gastroesofágico/complicações , Trato Gastrointestinal , Motilidade Gastrointestinal/fisiologia
20.
Neurogastroenterol Motil ; 36(1): e14704, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37964110

RESUMO

BACKGROUND: Chemotherapy-induced adverse effects are an unresolved nightmare. In preclinical studies in rats, the food additive monosodium glutamate (MSG) improved some of the side effects caused by cisplatin, but its effects in other models of chemotherapy-treated animals are not well known. The aim of this study was to test if MSG may improve some of the adverse effects induced by vincristine in rats. METHODS: Young male Wistar rats were exposed or not to MSG (4 g L-1 ) in drinking water from week 0 till 1 week after treatment (week 3). Rats received two cycles of five daily intraperitoneal (ip) injections (Monday to Friday, weeks 1 and 2) of either saline (2 mL kg-1 ) or vincristine (0.1 mg kg-1 ). Gastrointestinal motility was measured in vivo by radiological methods after the first and tenth ip administrations. On week 3, the threshold for mechanical somatic and colorectal sensitivity was recorded using Von Frey filaments applied to the paws and an intracolonic balloon, respectively. Finally, samples of the terminal ileum and distal colon were histologically evaluated in sections. KEY RESULTS: Vincristine reduced body weight gain, food intake, and upper gastrointestinal transit, caused somatic (but not visceral) hypersensitivity and increased the thickness of the submucosal and muscle layers of the small intestine. In vincristine-treated animals, MSG partially prevented gastrointestinal dysmotility and reduced visceral sensitivity but did not improve structural alterations of the small intestine. CONCLUSIONS & INFERENCES: MSG could be used as an adjuvant to conventional treatments to improve some gastrointestinal dysfunctions caused by chemotherapy.


Assuntos
Motilidade Gastrointestinal , Glutamato de Sódio , Ratos , Masculino , Animais , Vincristina/farmacologia , Glutamato de Sódio/farmacologia , Ratos Wistar , Motilidade Gastrointestinal/fisiologia , Cisplatino/farmacologia
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