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1.
Am J Physiol Gastrointest Liver Physiol ; 321(5): G552-G575, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34612070

RESUMO

Our understanding of human colonic motility, and autonomic reflexes that generate motor patterns, has increased markedly through high-resolution manometry. Details of the motor patterns are emerging related to frequency and propagation characteristics that allow linkage to interstitial cells of Cajal (ICC) networks. In studies on colonic motor dysfunction requiring surgery, ICC are almost always abnormal or significantly reduced. However, there are still gaps in our knowledge about the role of ICC in the control of colonic motility and there is little understanding of a mechanistic link between ICC abnormalities and colonic motor dysfunction. This review will outline the various ICC networks in the human colon and their proven and likely associations with the enteric and extrinsic autonomic nervous systems. Based on our extensive knowledge of the role of ICC in the control of gastrointestinal motility of animal models and the human stomach and small intestine, we propose how ICC networks are underlying the motor patterns of the human colon. The role of ICC will be reviewed in the autonomic neural reflexes that evoke essential motor patterns for transit and defecation. Mechanisms underlying ICC injury, maintenance, and repair will be discussed. Hypotheses are formulated as to how ICC dysfunction can lead to motor abnormalities in slow transit constipation, chronic idiopathic pseudo-obstruction, Hirschsprung's disease, fecal incontinence, diverticular disease, and inflammatory conditions. Recent studies on ICC repair after injury hold promise for future therapies.


Assuntos
Colo/patologia , Doenças do Colo/patologia , Defecação , Motilidade Gastrointestinal , Células Intersticiais de Cajal/patologia , Animais , Sistema Nervoso Autônomo/fisiopatologia , Colo/inervação , Colo/metabolismo , Doenças do Colo/metabolismo , Doenças do Colo/fisiopatologia , Pseudo-Obstrução do Colo/metabolismo , Pseudo-Obstrução do Colo/patologia , Pseudo-Obstrução do Colo/fisiopatologia , Constipação Intestinal/metabolismo , Constipação Intestinal/patologia , Constipação Intestinal/fisiopatologia , Sistema Nervoso Entérico/fisiopatologia , Incontinência Fecal/metabolismo , Incontinência Fecal/patologia , Incontinência Fecal/fisiopatologia , Doença de Hirschsprung/metabolismo , Doença de Hirschsprung/patologia , Doença de Hirschsprung/fisiopatologia , Humanos , Células Intersticiais de Cajal/metabolismo , Manometria
2.
World J Gastroenterol ; 23(30): 5634-5644, 2017 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-28852322

RESUMO

AIM: To critically review the literature addressing the definition, epidemiology, aetiology and pathophysiology of acute colonic pseudo-obstruction (ACPO). METHODS: A systematic search was performed to identify articles investigating the aetiology and pathophysiology of ACPO. A narrative synthesis of the evidence was undertaken. RESULTS: No consistent approach to the definition or reporting of ACPO has been developed, which has led to overlapping investigation with other conditions. A vast array of risk factors has been identified, supporting a multifactorial aetiology. The pathophysiological mechanisms remain unclear, but are likely related to altered autonomic regulation of colonic motility, in the setting of other predisposing factors. CONCLUSION: Future research should aim to establish a clear and consistent definition of ACPO, and elucidate the pathophysiological mechanisms leading to altered colonic function. An improved understanding of the aetiology of ACPO may facilitate the development of targeted strategies for its prevention and treatment.


Assuntos
Cesárea/efeitos adversos , Colo/fisiopatologia , Pseudo-Obstrução do Colo/epidemiologia , Pseudo-Obstrução do Colo/etiologia , Viroses/complicações , Doença Aguda , Colo/inervação , Pseudo-Obstrução do Colo/metabolismo , Pseudo-Obstrução do Colo/fisiopatologia , Feminino , Humanos , Incidência , Fatores de Risco
3.
Gastroenterology ; 143(3): 687-697.e9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22683258

RESUMO

BACKGROUND & AIMS: Gastrointestinal development requires regulated differentiation of visceral smooth muscle cells (SMCs) and their contractile activities; alterations in these processes might lead to gastrointestinal neuromuscular disorders. Gastrointestinal SMC development and remodeling involves post-transcriptional modification of messenger RNA. We investigated the function of the RNA-binding protein for multiple splicing 2 (RBPMS2) during normal development of visceral smooth muscle in chicken and expression of its transcript in human pathophysiological conditions. METHODS: We used avian replication-competent retroviral misexpression approaches to analyze the function of RBPMS2 in vivo and in primary cultures of chicken SMCs. We analyzed levels of RBPMS2 transcripts in colon samples from pediatric patients with Hirschsprung's disease and patients with chronic pseudo obstruction syndrome (CIPO) with megacystis. RESULTS: RBPMS2 was expressed strongly during the early stage of visceral SMC development and quickly down-regulated in differentiated and mature SMCs. Misexpression of RBPMS2 in differentiated visceral SMCs induced their dedifferentiation and reduced their contractility by up-regulating expression of Noggin, which reduced activity of bone morphogenetic protein. Visceral smooth muscles from pediatric patients with CIPO expressed high levels of RBPMS2 transcripts, compared with smooth muscle from patients without this disorder. CONCLUSIONS: Expression of RBPMS2 is present in visceral SMC precursors. Sustained expression of RBPMS2 inhibits the expression of markers of SMC differentiation by inhibiting bone morphogenetic protein activity, and stimulates SMC proliferation. RBPMS2 transcripts are up-regulated in patients with CIPO; alterations in RBPMS2 function might be involved in digestive motility disorders, particularly those characterized by the presence of muscular lesions (visceral myopathies).


Assuntos
Colo/metabolismo , Pseudo-Obstrução do Colo/metabolismo , Motilidade Gastrointestinal , Moela das Aves/metabolismo , Doença de Hirschsprung/metabolismo , Contração Muscular , Músculo Liso/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Embrião de Galinha , Colo/fisiopatologia , Pseudo-Obstrução do Colo/genética , Pseudo-Obstrução do Colo/fisiopatologia , Regulação da Expressão Gênica no Desenvolvimento , Moela das Aves/embriologia , Doença de Hirschsprung/genética , Doença de Hirschsprung/fisiopatologia , Humanos , Lactente , Músculo Liso/embriologia , Músculo Liso/fisiopatologia , Miócitos de Músculo Liso/metabolismo , Proteínas de Ligação a RNA/genética , Fatores de Tempo , Transcrição Gênica , Transfecção
4.
Am Surg ; 77(6): 736-42, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21679643

RESUMO

There are subsets of chronic constipation patients showing features of colonic pseudo-obstruction (CPO) with distinct transitional zone (TZ). We intended to analyze the clinicopathologic characteristics and surgical outcomes of these patients. Twenty-five consecutive patients who underwent surgery for constipation over the 9-year period were analyzed. TZ (+) group was defined as patients showing symptoms or signs of large bowel obstruction with dilated proximal and collapsed distal colon around the TZ at the time of operation, but without any evidence of mechanical causes of obstruction. Nineteen (76%) patients had features of CPO with TZ. All TZs were located in the left colon. Pathologically, segmental hypoganglionosis was identified at the TZ in all TZ (+) patients. On the other hand, pathologic diagnosis was intestinal neuronal dysplasia type B in the remaining six (24%) patients having a uniform colon diameter without demonstrable dilatations (TZ (-) group). Among TZ (+) patients, 17 (90%) underwent total colectomy with ileorectal anastomosis and two (10%) underwent enterostomy. Long-term follow-up (median 56 months) showed no recurrence of constipation in this group of patients. All six TZ (-) patients underwent total colectomy with ileorectal anastomosis and two (33%) of them had persistent symptoms of constipation on long-term follow-up (median 60 months). In a subset of adult constipation patients presenting with features of CPO with TZ, segmental hypoganglionosis was the final pathologic diagnosis. Constipation patients with features of CPO with distinct TZ in the left colon are expected to benefit from surgical intervention.


Assuntos
Colo/patologia , Pseudo-Obstrução do Colo/patologia , Constipação Intestinal/patologia , Adolescente , Adulto , Idoso , Doença Crônica , Colectomia , Colo/metabolismo , Pseudo-Obstrução do Colo/metabolismo , Constipação Intestinal/metabolismo , Dilatação Patológica , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Plexo Mientérico/patologia , Terapêutica , Adulto Jovem
5.
Gastroenterol Clin Biol ; 32(4): 401-4, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18394839

RESUMO

OBJECTIVE: To report the mechanism of diarrhoea in patients with subacute colonic pseudo-obstruction, profuse secretory diarrhoea and hypokalemia. PATIENTS: Five consecutive patients who developed colonic pseudo-obstruction, profuse watery diarrhoea and severe hypokalemia. Investigations excluded mechanical intestinal obstruction. Usual cause of diarrhoea were ruled out. Abdominal distension and diarrhoea improved simultaneously in all cases after colonoscopic decompression or intravenous neostigmine. RESULTS: Faecal ionograms showed a low osmotic gap and high faecal potassium concentration explaining the hypokalemia: 100 to 180 mEq/kg (usually inferior than 50 mEq/l in case of secretory diarrhoea) and low faecal sodium concentrations. Potassium salts were the only factor identified as the driving osmotic force for the diarrhoea. CONCLUSION: Secretory diarrhoea is classically due to chloride active secretion with passive sodium secretion or to inhibition of sodium absorption. In five cases of Ogilvie's syndrome we evidenced an original mechanism of secretory diarrhoea due to active potassium secretion responsible of a profound hypokalemia. This novel type of diarrhoea may be a hallmark of colonic pseudo-obstruction due to colonic distension.


Assuntos
Pseudo-Obstrução do Colo/complicações , Pseudo-Obstrução do Colo/metabolismo , Diarreia/metabolismo , Fezes/química , Hipopotassemia/etiologia , Potássio/análise , Potássio/metabolismo , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino
6.
Leuk Lymphoma ; 45(9): 1943-5, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15223660

RESUMO

Involvement of the gastrointestinal (GI) tract by multiple myeloma (MM) is extremely rare. The small intestine and stomach are the most frequent sites of spread. We report 1 case of a 61-year-old woman who presented with clinical and radiographic features of an acute large bowel pseudo-obstruction. An abdominal computerized tomography (CT) showed a large tumor of the rectum. On morphological and immunohistochemical examination the tumor fulfilled the criteria of MM. The patient received combined chemotherapy and radiotherapy which led to the disappearance of the tumor. A review of the literature revealed that this is the first reported case of MM presented as acute large bowel pseudo-obstruction due to a rectal myeloma tumor.


Assuntos
Pseudo-Obstrução do Colo/etiologia , Pseudo-Obstrução do Colo/patologia , Mieloma Múltiplo/complicações , Pseudo-Obstrução do Colo/metabolismo , Pseudo-Obstrução do Colo/terapia , Colonoscopia , Feminino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Proteoglicanas/metabolismo , Sindecanas
7.
J Pediatr Surg ; 24(12): 1264-6, 1989 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2593057

RESUMO

A typical case of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is reported. The patient, an infant girl, was fed only by total intravenous nutrition and is now 3 years old. The distribution of several gut peptides was examined in the resected small intestine using an immunohistochemical method. Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM)-containing nerve fibers were decreased; however, substance P- and leucine enkephalin (Leu-ENK)-containing fibers were increased. The imbalance between several kinds of gut peptides might be one the causes of aperistalsis in MMIHS. This is the first report about the gut peptides of MMIHS.


Assuntos
Sistema Nervoso Autônomo/análise , Colo/anormalidades , Pseudo-Obstrução do Colo/metabolismo , Cistite/patologia , Pseudo-Obstrução Intestinal/metabolismo , Intestino Delgado/inervação , Cistite/metabolismo , Feminino , Seguimentos , Humanos , Hipertrofia , Recém-Nascido , Intestino Delgado/metabolismo , Peristaltismo , Síndrome , Peptídeo Intestinal Vasoativo/análise
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