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1.
J Gastrointest Surg ; 24(1): 188-197, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31637625

RESUMO

INTRODUCTION: Severe burns lead to marked impairment of gastrointestinal motility, such as delayed gastric emptying and small and large intestinal ileus. However, the cellular mechanism of these pathologic changes remains largely unknown. METHODS: Male Sprague Dawley rats approximately 3 months old and weighing 300-350 g were randomized to either a 60% total body surface area full-thickness scald burn or sham procedure and were sacrificed 24 h after the procedure. Gastric emptying, gastric antrum contractility ileal smooth muscle contractility, and colonic contractility were measured. Muscularis externa was isolated from the ileal segment to prepare smooth muscle protein extracts for Western blot analysis. RESULTS: Compared with sham controls, the baseline rhythmic contractile activities of the antral, ileal, and colonic smooth muscle strips were impaired in the burned rats. Simultaneously, our data showed that ileal muscularis ECM proteins fibronectin and laminin were significantly up-regulated in burned rats compared with sham rats. TGF-ß signaling is an important stimulating factor for ECM protein expression. Our results revealed that TGF-ß signaling was activated in the ileal muscle of burned rats evidenced by the activation of Smad2/3 expression and phosphorylation. In addition, the total and phosphorylated AKT, which is an important downstream factor of ECM signaling in smooth muscle cells, was also up-regulated in burned rats' ileal muscle. Notably, these changes were not seen in the colonic or gastric tissues. CONCLUSION: Deposition of fibrosis-related proteins after severe burn is contributors to decreased small intestinal motility.


Assuntos
Queimaduras/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Íleo/metabolismo , Pseudo-Obstrução Intestinal/metabolismo , Contração Muscular/fisiologia , Músculo Liso/metabolismo , Animais , Queimaduras/complicações , Queimaduras/fisiopatologia , Colo/metabolismo , Colo/fisiopatologia , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/biossíntese , Fibronectinas/biossíntese , Fibronectinas/metabolismo , Fibrose/etiologia , Fibrose/metabolismo , Fibrose/fisiopatologia , Esvaziamento Gástrico/fisiologia , Motilidade Gastrointestinal/fisiologia , Íleo/fisiopatologia , Íleus/metabolismo , Íleus/fisiopatologia , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Pseudo-Obstrução Intestinal/etiologia , Pseudo-Obstrução Intestinal/fisiopatologia , Laminina/biossíntese , Laminina/metabolismo , Masculino , Músculo Liso/fisiopatologia , Fosforilação , Antro Pilórico/metabolismo , Antro Pilórico/fisiopatologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Estômago/fisiopatologia
2.
Neurogastroenterol Motil ; 29(11)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28585346

RESUMO

BACKGROUND: Tacr2 is one of the G protein-coupled receptors(GPCRs) that mediate the biological actions of tachykinins. It is abundantly expressed in the gastrointestinal (GI) system and is thought to play an important role in GI motility, secretion, and visceral sensitivity. Previously, the physiological and pathophysiological functions of Tacr2 were mainly studied using Tacr2 selective agonists or antagonists. Here, we seek to investigate the effect of Tacr2 disruption in mice to provide further insights. METHODS: The Tacr2 knockout mice were generated by homologous recombination and the phenotypic changes of the Tacr2-null mice were analyzed and compared with their wild type (wt) littermates. KEY RESULTS: Increased food retention was detected in Tacr2-/- mice. The stomach of Tacr2-/- mice had thinner muscularis externa and less neurons in the myenteric plexus. The stomach and small intestine exhibited longer duration of electrical field stimulation (EFS)-induced inhibition in the gastric fundus and decreased frequency of migrating motor complex (MMC), respectively. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were significantly up-regulated due to Tarc2 deficiency, contributing to enhanced nitric oxide (NO) signaling in the stomach of Tacr2-/- mice. Intraperitoneal application of 7-nitroindazole (7-NI) to Tacr2-/- mice effectively relieved the gastric emptying disturbance. Moreover, Creb and NF-κB signalings were involved in the regulation of these physiological changes initiated by Tacr2 deficiency. CONCLUSIONS & INFERENCES: Tacr2 negatively regulated the expression of nNOS and VIP both in vivo and in vitro. Its ablation in mice elevated the expression of nNOS and VIP, enhanced NO signaling and changed the Creb and NF-κB signalings, finally leading to the gastric emptying disturbance of Tacr2-/- mice.


Assuntos
Esvaziamento Gástrico , Mucosa Gástrica/metabolismo , Receptores da Neurocinina-2/fisiologia , Estômago/fisiopatologia , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Feminino , Fundo Gástrico/fisiopatologia , Regulação da Expressão Gênica , Intestino Delgado/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Fenótipo , Antro Pilórico/fisiopatologia , Receptores da Neurocinina-2/genética , Receptores da Neurocinina-2/metabolismo , Transdução de Sinais , Estômago/patologia , Peptídeo Intestinal Vasoativo/metabolismo
3.
Postgrad Med ; 129(3): 312-317, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28299959

RESUMO

OBJECTIVES: Although a common cause of intestinal blood loss, the pathophysiology of gastric antral vascular ectasia (GAVE) is not well understood. We aimed to evaluate gastric antral and body mucosal flow in GAVE patients compared to a control population using laser Doppler flowmetry. METHODS: 27 patients with GAVE and 11 control patients without GAVE were evaluated using an endoscopic LDF probe. The probe was placed in the gastric antrum and body in order to calculate standardized mucosal flow rates recorded as perfusion units (PU). RESULTS: Despite its hyperemic appearance and propensity to bleed, antral blood flow was not increased in GAVE: 115.5 PU (IQR: [94.4, 135.9 PU]) in GAVE versus 123.7 PU (IQR: [109.7, 186.5 PU]) in controls. There was a significant gradient between the gastric body and antral blood flow in GAVE (p < 0.001) that was not evident in controls. CONCLUSION: These results indicate that antral mucosal blood flow is not increased in GAVE despite its grossly hyperemic appearance. A mild but statistically significant gradient was noted between the gastric antrum and body in patients with GAVE compared to controls. The pathophysiological significance of this finding is uncertain.


Assuntos
Ectasia Vascular Gástrica Antral/fisiopatologia , Mucosa Gástrica/fisiopatologia , Idoso , Complicações do Diabetes , Feminino , Fibrose/complicações , Ectasia Vascular Gástrica Antral/tratamento farmacológico , Mucosa Gástrica/efeitos dos fármacos , Gastroscopia , Humanos , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Bomba de Prótons/farmacologia , Antro Pilórico/efeitos dos fármacos , Antro Pilórico/fisiopatologia , Estômago/fisiopatologia
4.
Gut ; 65(7): 1110-8, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-25986945

RESUMO

OBJECTIVE: Motilin-induced phase III contractions of the migrating motor complex (MMC) signal hunger in healthy volunteers. The current aim was to study the role of motilin as a hunger-inducing factor in obese patients and to evaluate the effect of Roux-en-Y gastric bypass (RYGB) surgery on plasma motilin levels and hunger scores. DESIGN: Motilin and ghrelin plasma levels were determined during a complete MMC cycle in controls and obese patients selected for RYGB before, 6 months and 1 year after surgery. 20 min after the end of the second phase III, obese patients received an intravenous infusion of 40 mg erythromycin. Hunger was scored every 5 min. Hedonic hunger was assessed in obese patients with the Power of Food Scale questionnaire. RESULTS: Obesity caused a switch in the origin of phase III from antrum to duodenum. Obese patients had significantly higher motilin levels compared with controls during the MMC but tended to lack the motilin peak prior to phase III necessary to trigger hunger. Hunger scores during phase III were significantly lower in obese patients, but could be restored to control levels through the administration of a low dose of the motilin agonist, erythromycin. After RYGB surgery motilin, but not ghrelin, levels decreased in parallel with hedonic hunger scores. CONCLUSIONS: Motilin may be an important regulator involved in the pathogenesis of obesity.


Assuntos
Fome/fisiologia , Motilina/sangue , Complexo Mioelétrico Migratório , Obesidade/sangue , Obesidade/cirurgia , Adulto , Estudos de Casos e Controles , Duodeno/fisiopatologia , Eritromicina/farmacologia , Feminino , Derivação Gástrica , Fármacos Gastrointestinais/farmacologia , Grelina/sangue , Humanos , Fome/efeitos dos fármacos , Masculino , Período Pós-Operatório , Período Pré-Operatório , Antro Pilórico/fisiopatologia , Inquéritos e Questionários
5.
Am J Clin Nutr ; 102(6): 1323-31, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26561615

RESUMO

BACKGROUND: In lean individuals, intraduodenal protein and lipid modulate gastrointestinal motor and hormone functions and reduce energy intake in a load-dependent manner; protein also stimulates insulin, with modest effects on reducing blood glucose. The effect of intraduodenal lipid on gastrointestinal motor and hormone responses is diminished in obesity; whether the effects of protein are also attenuated remains unclear. OBJECTIVES: The objectives of this study were to characterize the load-dependent effects of intraduodenal whey protein hydrolysate on antropyloroduodenal pressures, gut hormones, glycemia, appetite, and energy intake in obese subjects and to compare the responses to the higher protein load with those in lean subjects. DESIGN: We measured antropyloroduodenal pressures, plasma cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, insulin, blood glucose, appetite, and energy intake in 12 nondiabetic obese men on 3 separate occasions, in a double-blind, randomized order, during 60-min intraduodenal infusions of hydrolyzed whey protein at either 0 (saline control), 1.5, or 3 kcal/min. Twelve age-matched lean individuals received a 3-kcal/min infusion only. Immediately after the infusions, energy intake from a buffet lunch was quantified. RESULTS: In obese subjects, protein suppressed antral and duodenal pressures; stimulated plasma CCK, GLP-1, GIP, insulin, and glucagon (all r > 0.57, P < 0.01); and tended to reduce energy intake (r = -10.38, P = 0.057) in a dose-dependent manner. In response to the 3-kcal/min protein load, antropyloroduodenal pressures, CCK, GLP-1, and glucagon did not differ between lean and obese subjects. Insulin release was greater, and GIP release less, in obese than in lean subjects (both P < 0.05), whereas the reduction in glucose was comparable. Energy intake tended to be higher in obese subjects (P = 0.08). CONCLUSIONS: The gastrointestinal effects of hydrolyzed whey protein remain relatively intact in obesity; however, the observed changes in insulin and GIP suggest early disturbances in the insulin-incretin axis. This study was registered at www.anzctr.org.au as ACTRN 12612000203853.


Assuntos
Duodeno/fisiopatologia , Nutrição Enteral , Intubação Gastrointestinal , Obesidade/terapia , Hidrolisados de Proteína/uso terapêutico , Antro Pilórico/fisiopatologia , Proteínas do Soro do Leite/uso terapêutico , Adolescente , Adulto , Regulação do Apetite , Índice de Massa Corporal , Método Duplo-Cego , Duodeno/metabolismo , Ingestão de Energia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/fisiopatologia , Hormônios Gastrointestinais/sangue , Hormônios Gastrointestinais/metabolismo , Motilidade Gastrointestinal , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/fisiopatologia , Almoço , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/metabolismo , Obesidade/fisiopatologia , Hidrolisados de Proteína/administração & dosagem , Antro Pilórico/metabolismo , Proteínas do Soro do Leite/administração & dosagem , Adulto Jovem
7.
Ann Thorac Surg ; 96(5): 1833-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23998403

RESUMO

BACKGROUND: Reflux esophagitis is a significant problem in patients after an esophagectomy with gastric tube reconstruction. The pathogenesis of reflux esophagitis is not fully understood. The aim of the present study was to evaluate whether gastropyloric motility influences the pathogenesis of reflux esophagitis after an esophagectomy. METHODS: Thirty esophagectomized patients were assessed by endoscopy and manometry. The patients were classified into 3 groups according to the postoperative period as follows: Group 1 (less than 12 months), group 2 (12 to 24 months), and group 3 (more than 24 months). Gastropyloric motor activity was quantified by calculating the motility index, which is equivalent to the area under the contractile waves. RESULTS: Reflux esophagitis was observed in 80% of group 1, 80% of group 2, and 30% of group 3. The severity of reflux esophagitis decreased with time. Contractions of the gastric body were not observed in any of the patients. The antral motility index in group 3 was significantly greater than that in groups 1 and 2. The pyloric motility index progressively increased. The severity of reflux esophagitis is significantly associated with gastropyloric motor activity. CONCLUSIONS: The severity of reflux esophagitis decreases with time, coupled with recovery of antropyloric motor activity. Gastropyloric motor activity plays an important role in the genesis of reflux esophagitis after an esophagectomy.


Assuntos
Esofagectomia/efeitos adversos , Esofagectomia/métodos , Esofagite Péptica/etiologia , Motilidade Gastrointestinal , Antro Pilórico/fisiopatologia , Estômago/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Obes Surg ; 23(4): 567-73, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23306796

RESUMO

BACKGROUND: The surgical technique of laparoscopic sleeve gastrectomy (LSG) has not been fully standardized yet and there is the unresolved question of what is the optimum size of retained pyloric antrum. The aim of our research was to prove that even after a radical resection of the pyloric antrum the physiological stomach evacuation function can still be preserved. METHODS: Our study was based on 12 patients, who were randomly divided into two groups. Patients undergoing radical antrum resection (RA group) underwent gastric emptying scintigraphy to determine the evacuation half-time (T1/2) and food retention in the 90th minute of the test (%GE) both before the operation and 3 months afterward. Patients in whom the antrum was preserved (PA group) served as a control group for comparison of postoperative weight loss (in kilogram), decrease in body mass index (BMI), and decline in excess weight (%EWL). The resulting changes were statistically processed. RESULTS: In the RA group, the average time T1/2 declined from 57.5 to 32.25 min (p = 0.016) and average retention %GE dropped from 20.5 to 9.5% (p = 0.073). Differences in the average values of weight, BMI, or %EWL between both groups were of no statistical significance (p > 0.8). CONCLUSIONS: In the RA group, an increase in gastric emptying postoperatively was noted. Complications such as failure of stomach evacuation were not observed in the RA group. Our results suggest that even more radical resection of the pyloric antrum performed by LSG is possible without concerns of postoperative disorder of the stomach evacuation function.


Assuntos
Esvaziamento Gástrico , Gastroplastia/métodos , Laparoscopia , Obesidade Mórbida/cirurgia , Antro Pilórico/diagnóstico por imagem , Antro Pilórico/cirurgia , Adulto , Análise de Variância , Índice de Massa Corporal , Peso Corporal , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/fisiopatologia , Projetos Piloto , Antro Pilórico/fisiopatologia , Cintilografia , Resultado do Tratamento , Redução de Peso
9.
World J Surg ; 35(8): 1879-86, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21559999

RESUMO

Gastric carcinoid tumors comprise 7% of all gastrointestinal carcinoids and have significantly increased in incidence over the past few decades. Seventy to 80% of gastric carcinoids are type I, which usually are clinically asymptomatic and found incidentally at endoscopic evaluation for abdominal pain or anemia. In this review, advances in understanding the pathophysiology of type I gastric carcinoid are highlighted. In addition, various current diagnostic and treatment options are discussed. Although type I carcinoids generally hold a benign course, rigorous investigation is needed to ensure accurate diagnosis and optimal treatment. This includes appropriate diagnostic procedures and imaging and accurate staging of tumor. Tumor size, depth of invasion, presence of metastasis, and the tumor's gastrin dependency dictate treatment options. Appropriate treatments can consist of endoscopic resection, antrectomy, medical management, or frequent follow-up. This article provides a systematic method of evaluating and treating type I gastric carcinoid.


Assuntos
Tumor Carcinoide/diagnóstico , Tumor Carcinoide/fisiopatologia , Gastrectomia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/fisiopatologia , Tumor Carcinoide/patologia , Tumor Carcinoide/cirurgia , Células Enterocromafins/patologia , Células Enterocromafins/fisiologia , Determinação da Acidez Gástrica , Fundo Gástrico/patologia , Fundo Gástrico/fisiopatologia , Fundo Gástrico/cirurgia , Mucosa Gástrica/patologia , Mucosa Gástrica/fisiopatologia , Gastrinas/sangue , Gastrite Atrófica/complicações , Gastrite Atrófica/patologia , Gastrite Atrófica/fisiopatologia , Gastrite Atrófica/cirurgia , Gastroscopia , Humanos , Estadiamento de Neoplasias , Pólipos/diagnóstico , Pólipos/patologia , Pólipos/fisiopatologia , Pólipos/cirurgia , Prognóstico , Antro Pilórico/patologia , Antro Pilórico/fisiopatologia , Antro Pilórico/cirurgia , Cintilografia , Fatores de Risco , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
10.
Surg Today ; 41(5): 680-7, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21533941

RESUMO

PURPOSE: To investigate the phenomenon of remnant gastric motility and emptying after local resection. METHODS: Fifteen dogs were divided into three groups: a control (CONT) group, a group that underwent local resection of the greater (GREAT) curvature, and a group that underwent resection of the lesser (LESS) curvature. We conducted a strain gauge force transducer study, a [(13)C]octanoic acid breath test ((13)C-OBT), and a mosapride citrate effect test. Based on these results, we worked out the receptive relaxation (RR), motility index (MI), and postprandial period (PP) in the postprandial state, and the frequency, duration, and MI of phase III in the fasted state. The half emptying time (T (1/2)) of (13)C-OBT was also calculated. The MI was compared according to the mosapride effect test results. RESULTS: Postprandial RR, antro-pyloro-duodenal coordination, and fasting contractions were maintained in all three groups. Receptive relaxation was significantly shorter in the LESS group than in the other groups. Motility index was significantly lower in both treatment groups than in the CONT group. The PP was significantly longer in the GREAT group than in the other two groups. The (13)CO(2) excretion curves did not differ significantly among the groups. The duration of phase III was remarkably less in the treatment groups than in the CONT group, and MI was significantly lower in the LESS group than in the other groups in the fasted state. The MI increased remarkably after mosapride administration in the CONT group, showing no differences in other objective groups. CONCLUSION: Gastric function was maintained after gastric local resection, although its motility decreased.


Assuntos
Gastrectomia , Coto Gástrico/fisiopatologia , Motilidade Gastrointestinal , Animais , Testes Respiratórios , Caprilatos/metabolismo , Digestão , Cães , Duodeno/fisiopatologia , Jejum/fisiologia , Esvaziamento Gástrico , Jejuno/fisiopatologia , Período Pós-Prandial , Antro Pilórico/fisiopatologia , Piloro/fisiopatologia , Transdutores
11.
Eksp Klin Gastroenterol ; (12): 54-9, 2010.
Artigo em Russo | MEDLINE | ID: mdl-21560622

RESUMO

OBJECTIVE: To determine the frequency of duodenogastric reflux (DGR), and to assess the changes in the gastric mucosa in the presence of bile reflux. MATERIALS AND METHODS: Our study includes the results of 1371 gastroduodenoscopies carried out in 2008, for patients between 65 and 92 years old, the study includes both kind of patients who were admitted to hospital and those who were investigated on an outpatient basis. The main group includes 695 patients with various level of DGR severity, and the control group consists of 676 patients without DGR. RESULTS: DGR was diagnosed in 14.8% more in women. In case of the presence of DGR we have found changes in the antrum mucosa as congestion, and minor erosion, hyperplasia, metaplasia of gastric and esophageal mucosa, and stomach polyps. And we have not noticed such changes when DGR was absent. We have found that the high frequency of antral hyperplasia is correlated to the DGR severity. CONCLUSION: DGR is diagnosed in more than 10% of patients who undergo gastroduodenoscopy. DGR is an indicator of conditions often associated with various morphological changes in gastric mucosa; therefore this finding has to be taken in consideration in the further investigations and management of such patients.


Assuntos
Envelhecimento , Refluxo Duodenogástrico/diagnóstico , Refluxo Duodenogástrico/patologia , Mucosa Gástrica/patologia , Antro Pilórico/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Refluxo Duodenogástrico/fisiopatologia , Endoscopia Gastrointestinal/métodos , Feminino , Mucosa Gástrica/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Antro Pilórico/fisiopatologia , Fatores Sexuais
12.
Obes Surg ; 19(9): 1270-3, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19495893

RESUMO

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) has been popularized as an effective, safe, minimally invasive surgical technique for the treatment of morbid obesity. We performed a pilot study to evaluate gastric emptying of semisolid meals and antral motility following LAGB. METHODS: Gastric emptying half-time was compared in normal volunteers and morbidly obese patients before and 6-12 months after LAGB using sulfur colloid-labeled semisolid meals. RESULTS: There was no difference in mean age between groups. Women were prevalent in the group of obese patients. BMI was higher in patients before surgery (p < 0.001). Patients following LAGB demonstrated prolonged gastric pouch emptying (T1/2 = 36.6 +/- 9.8 min) compared to subjects without surgery (23.8 +/- 4.7 min) and healthy volunteers (22.8 +/- 6.8 min; p < 0.001). Similar gastric contractility was found all groups (3.3 +/- 0.4; p = 0.968). No cases of band slippage or pouch dilatation were observed during mean follow-up of 11.4 months. CONCLUSIONS: A standard normal gastric pouch emptying rate of semisolids in asymptomatic patients after LAGB was established. Postoperative prolongation of gastric emptying is a matter of mechanical delay without gastric pouch denervation. This study provides a first step of future functional evaluation of complications following this type of bariatric surgery.


Assuntos
Esvaziamento Gástrico/fisiologia , Gastroplastia , Laparoscopia , Obesidade/fisiopatologia , Obesidade/cirurgia , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complexo Mioelétrico Migratório/fisiologia , Obesidade/diagnóstico por imagem , Antro Pilórico/fisiopatologia , Cintilografia
13.
Gastroenterology ; 136(2): 630-9, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19032955

RESUMO

BACKGROUND & AIMS: Gastrointestinal stromal tumors (GISTs) express the receptor tyrosine kinase c-kit. Approximately 90% of GISTs have gain-of-function mutations in the Kit gene, which leads to its constitutive activation and drives malignant behavior of GISTs. Interstitial cells of Cajal (ICC) express c-kit; however, it is unknown whether uncontrolled hyperplasia of ICC is responsible for GISTs. Here, we sought to determine whether gain-of-function mutations in Kit lead to hyperplasia of all classes of ICC, whether ICC hyperplasia begins before birth, and whether functional defects occur in ICC hyperplasia or the development of GISTs. METHODS: Heterozygous mutant Kit(V558Delta)/+ mice that develop symptoms of human familial GISTs and prematurely die from pathology of the gastrointestinal tract were utilized and compared with wild-type controls. C-kit-immunohistochemistry and intracellular electrical recording of spontaneous and nerve-evoked activity were applied to examine the density and functionality of ICC in these mutants. RESULTS: There was considerable hyperplasia in all classes of ICC throughout the GI tract of Kit(V558Delta)/+ mice, except for ICC in the deep muscular plexus of the intestine. Spontaneous electrical activity and postjunctional neural responses in hyperplastic ICC tissues appeared normal but were up-regulated in the cecum, where GISTs were commonly found. CONCLUSIONS: Kit gain-of-function leads to hyperplasia of most classes of ICC throughout the GI tract. ICC retain normal pacemaker function and enteric neural responses well after development of hyperplasia.


Assuntos
Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/fisiopatologia , Trato Gastrointestinal/patologia , Trato Gastrointestinal/fisiopatologia , Músculo Liso/patologia , Músculo Liso/fisiopatologia , Animais , Ceco/metabolismo , Ceco/patologia , Ceco/fisiopatologia , Colo/metabolismo , Colo/patologia , Colo/fisiopatologia , Modelos Animais de Doenças , Fenômenos Eletrofisiológicos , Sistema Nervoso Entérico/fisiopatologia , Feto/metabolismo , Feto/patologia , Feto/fisiopatologia , Fundo Gástrico/metabolismo , Fundo Gástrico/patologia , Fundo Gástrico/fisiopatologia , Tumores do Estroma Gastrointestinal/metabolismo , Trato Gastrointestinal/metabolismo , Hiperplasia/metabolismo , Hiperplasia/patologia , Hiperplasia/fisiopatologia , Íleo/metabolismo , Íleo/patologia , Íleo/fisiopatologia , Jejuno/metabolismo , Jejuno/patologia , Jejuno/fisiopatologia , Masculino , Camundongos , Camundongos Mutantes , Músculo Liso/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Antro Pilórico/metabolismo , Antro Pilórico/patologia , Antro Pilórico/fisiopatologia
14.
J Gastroenterol Hepatol ; 23(7 Pt 2): e23-8, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18702684

RESUMO

BACKGROUND AND AIM: Patients with celiac disease may present with abnormal upper gut motor activity. However, it is not known if these abnormalities persist after the introduction of a gluten-free diet. The present study aimed to compare antroduodenojejunal motor variables recorded in untreated celiac patients with those of celiac patients given a gluten-free diet and healthy volunteers. METHODS: Eleven untreated celiac disease patients, 12 age- and sex-matched celiac patients on a gluten-free diet (at least 12 months), and 33 controls entered the study. Antroduodenojejunal motility was recorded for 6 h during fasting and for 3 h after a standard meal by means of a perfused, multiple lumen catheter. RESULTS: More than 80% of untreated celiac patients had discrete motor abnormalities of the upper gut, in both fasting and fed recordings, compared to the other subjects. Patients on a gluten-free diet also showed motor abnormalities, albeit to a lesser extent. In these patients histological evaluation showed the persistence of mild mucosal abnormalities. CONCLUSIONS: Upper gut motor abnormalities are frequent in patients with celiac disease, even in those on a gluten-free diet. In the latter group, these abnormalities may suggest an incomplete adherence to the dietary regimen.


Assuntos
Doença Celíaca/dietoterapia , Dieta com Restrição de Proteínas , Duodeno/fisiopatologia , Motilidade Gastrointestinal , Jejuno/fisiopatologia , Antro Pilórico/fisiopatologia , Adulto , Idoso , Doença Celíaca/patologia , Doença Celíaca/fisiopatologia , Duodenoscopia , Duodeno/patologia , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Período Pós-Prandial , Pressão , Inquéritos e Questionários
16.
Pathol Res Pract ; 203(6): 433-44, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17509776

RESUMO

Helicobacter pylori infection is related to the development of diverse gastric pathologies, possibly by affecting epithelial junctional complexes that define cell polarity and play an essential role in transepithelial transport and cell-cell adhesion. Using primary gastric epithelial cell cultures, effects of H. pylori on the expression and localization of tight/adherence junction proteins and the resulting morphological changes and migratory capabilities were studied under in vivo-like conditions. Gastric epithelial cells were isolated from biopsies or gastrectomies and maintained in Quantum286 on collagen I-coated culture dishes or cover-slips. Cell cultures were characterized and further analyzed by western blot and immunofluorescent staining for ZO-1, p120ctn, and H. pylori CagA. Morphological changes and migratory response were monitored by time-lapse digital image microscopy. ZO-1 and p120ctn protein expression levels remain unaffected by H. pylori infection. Immunocytochemistry on H. pylori-infected primary cell monolayers focally showed disruption of intercellular ZO-1 staining and accumulation of ZO-1 in small vesicles. H. pylori infection recruited non-phosphorylated p120ctn to perinuclear vesicles. The fraction of phosphorylated p120ctn increased and could be detected in the nucleus, at the cell membrane, and at the leading edge of migrating cells. These alterations, triggered by H. pylori infection, are associated with an elongation phenotype and increased migration.


Assuntos
Moléculas de Adesão Celular/metabolismo , Células Epiteliais/metabolismo , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori/isolamento & purificação , Proteínas de Membrana/metabolismo , Fosfoproteínas/metabolismo , Antro Pilórico/metabolismo , Junções Íntimas/metabolismo , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Cateninas , Movimento Celular , Forma Celular , Células Cultivadas , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Mucosa Gástrica/fisiopatologia , Expressão Gênica , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/metabolismo , Humanos , Imuno-Histoquímica , Microscopia de Vídeo , Permeabilidade , Fosforilação , Antro Pilórico/microbiologia , Antro Pilórico/patologia , Antro Pilórico/fisiopatologia , Junções Íntimas/patologia , Fatores de Tempo , Cicatrização , Proteína da Zônula de Oclusão-1 , delta Catenina
17.
Hepatogastroenterology ; 54(74): 639-42, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17523340

RESUMO

BACKGROUND/AIMS: Gastric emptying after PPG is directly associated with postoperative QOL. Few studies have investigated gastric emptying after a gastrectomy for stomach cancer using carbon-labeled acetic acid breath test. METHODOLOGY: We analyzed gastric emptying in 28 patients who underwent a gastrectomy for gastric carcinoma. Among the patients, 14 underwent pylorus-preserving gastrectomy and 14 underwent distal gastrectomy. We recruited 15 healthy subjects as controls. Gastric emptying was evaluated with the 13C-Acetic acid breath test was performed. Postprandial breath samples were collected at a 15-min interval for 2 hours and at a 30-min interval thereafter. We calculated the ratio of (13)CO2 expired per hour and determined the time required to reach peak (13)CO2 expiration level. RESULTS: The time required to reach peak (13)C02 expiration level were 1.78 hours for the patients who underwent pylorus-preserving gastrectomy, 1.19 hours for the control group and 0.70 hours for the patients who underwent distal gastrectomy. CONCLUSIONS: Our 13C-Acetic acid breath test following an intake of solid foods showed that gastric retention can be preserved after a pylorus-preserving gastrectomy.


Assuntos
Testes Respiratórios , Síndrome de Esvaziamento Rápido/prevenção & controle , Gastrectomia/métodos , Esvaziamento Gástrico/fisiologia , Antro Pilórico/fisiopatologia , Neoplasias Gástricas/cirurgia , Ácido Acético , Radioisótopos de Carbono , Síndrome de Esvaziamento Rápido/fisiopatologia , Seguimentos , Trânsito Gastrointestinal/fisiologia , Humanos
18.
J Med Invest ; 53(3-4): 277-84, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16953065

RESUMO

Although Crohn's disease is associated with various digestive symptoms, there have been few reports on gastric motility. In this study, we conducted a study of gastric motility in Crohn's disease using 20 healthy subjects (N group) and 15 patients with Crohn's disease (C group) by electrogastrography (EGG) using a Nipro electrogastrograph. An EGG was recorded for 30 minutes in a fasting state and after ingestion of 300 ml of a liquid meal. As an index of gastric emptying, the rate of change in the cross-sectional area of the gastric antrum was measured 1 and 15 minutes after ingestion of the liquid meal by external ultrasonography. In an EGG frequency analysis, waveforms with a peak of 3 cycles/minute (cpm) were noted in the N group, and the peak amplitude increased significantly after the ingestion of food. In the C group, division of the normal-gastria component was noted after the ingestion of food in 5 patients (33.3%). In a comparison of the peak amplitudes of fasting brady-gastria, normal-gastria, and tachy-gastria between the N and C groups, the peak amplitude was significantly increased in normal-gastria in the N group, and in brady-gastria and tachy-gastria in the C group. In a comparison of the rates of food ingestion-induced changes in the peak amplitudes for brady-gastria, normal-gastria, and tachy-gastria between the N and C groups, the peak amplitudes were significantly increased in normal-gastria in the N group, but not in the C group. In the case of gastric emptying investigated by external ultrasonography, the rate of food ingestion-induced change in the cross-sectional antrum area was significantly lower in the C group (50.5+/-9.2%) than in the N group (65.0+/-8.5%). For gastrointestinal motility, a 3 cpm normal-gastria represents efficient gastric motility. In the C group, the peak amplitudes of brady-gastria and tachy-gastria were significantly increased, but were low in normal-gastria in the fasting EGG, postprandial division of the normal-gastria component was noted, and the rate of food ingestion-induced increase in the normal-gastria peak amplitude was significantly lower than that in the N group, suggesting that patients with Crohn's disease have a functional abnormality in, not only the small and large intestine, but also the stomach.


Assuntos
Doença de Crohn/diagnóstico por imagem , Doença de Crohn/fisiopatologia , Esvaziamento Gástrico/fisiologia , Motilidade Gastrointestinal/fisiologia , Antro Pilórico/fisiopatologia , Adulto , Ingestão de Alimentos/fisiologia , Eletrofisiologia , Jejum/fisiologia , Feminino , Humanos , Masculino , Período Pós-Prandial/fisiologia , Antro Pilórico/diagnóstico por imagem , Ultrassonografia
19.
Digestion ; 73(4): 249-58, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16954694

RESUMO

AIM: To investigate the functional and molecular mechanisms by which sulfated cholecystokinin octapeptide (CCK-8S) regulates calcium mobilization in gastric antral smooth muscle cells (SMCs) of rats. METHODS: Isotonic contraction of antral strips was recorded using a polyphysiograph. Immunoprecipitation was used to determine the regulatory effect of protein kinase C (PKC) on regulating the phosphorylation of the type III inositol 1,4,5-triphosphate receptor (InsP(3)R3) in gastric SMCs. Alterations in the intracellular calcium ([Ca(2+)](i)) concentration were assayed using fura-2/AM-loaded microspectrofluorometry, and the L-type calcium current (I(Ca-L)) was recorded by patch-clamp techniques. RESULTS: CCK-8S (5 x 10(-8) mol/l) significantly increased the mean contractile amplitude of circular muscle by 61.85 +/- 12.67% and the frequency of longitudinal muscle by 57.91 +/- 15.70% in gastric antral strips, which were suppressed by dexloxiglumide or thapsigargin (TG) and BAPTA-AM (BA). Treatment with chelerythrine (5 x 10(-8) mmol/l) significantly inhibited the CCK-8S-increased phosphorylation of InsP(3)R3 in SMCs. The amplitudes of the CCK-8S-triggered [Ca(2+)](i) concentration oscillations were reduced in a dose-dependent manner when the SMCs were pretreated with increasing concentrations of PMA (from 10(-8) to 10(-5) mol/l). On removal of extracellular calcium or blocking I(Ca-L) by nifedipine, a smaller but significant rise in the [Ca(2+)](i) concentration was still elicited by CCK-8S. When [Ca(2+)](i) was depleted by the administration of 10(-5) mol/l TG and 10(-5) mol/l BA or blocked by the calcium-dependent chloride current (I(Cl-Ca)) by giving 5 x 10(-6) mol/l niflumic acid, the CCK-8S-intensified I(Ca-L) (from -56.42 +/- 6.57 to -88.54 +/- 5.71 pA) was apparently inhibited by 90.34 +/- 4.71% and 82.59 +/- 4.24%. CONCLUSIONS: These results demonstrate that the CCK-8S-evoked [Ca(2+)](i) concentration increase in gastric antral SMCs depends on the release of [Ca(2+)](i) stores which are negatively regulated by PKC-mediated phosphorylation of InsP(3)R3. Released calcium in turn activates I(Ca-L) through the activation of I(Cl-Ca), ultimately resulting in the contraction of the gastric smooth muscle.


Assuntos
Esvaziamento Gástrico/fisiologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiopatologia , Antro Pilórico , Receptores da Colecistocinina/agonistas , Transdução de Sinais/efeitos dos fármacos , Sincalida/análogos & derivados , Animais , Canais de Cálcio Tipo L/efeitos dos fármacos , Canais de Cálcio Tipo L/metabolismo , Feminino , Masculino , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Antro Pilórico/efeitos dos fármacos , Antro Pilórico/metabolismo , Antro Pilórico/fisiopatologia , Ratos , Ratos Sprague-Dawley , Sincalida/farmacologia
20.
Folia Med Cracov ; 47(1-4): 61-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-18038613

RESUMO

The aim of the study was to evaluate the influence of pancreatic carcinoma on gastric motility and autonomic system activity in patients before surgery. Patients with histologically confirmed pancreatic cancer were studied. Our results show that gastric dysrrhythmias are continuously present in patients with pancreatic cancer both with and without gastric emptying delay. Antral distribution of meal suggests the presence of impaired proximal gastric response to meal due to diminished autonomic nervous system function and impaired myoelectric gastric activity in patients with pancreatic cancer.


Assuntos
Neoplasias Pancreáticas/complicações , Antro Pilórico/fisiopatologia , Gastropatias/etiologia , Idoso , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Hormônios Pancreáticos/metabolismo , Hormônios Pancreáticos/farmacologia , Neoplasias Pancreáticas/fisiopatologia , Neoplasias Pancreáticas/cirurgia , Projetos Piloto , Cuidados Pré-Operatórios , Antro Pilórico/inervação , Gastropatias/fisiopatologia
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