RESUMEN
The aim of the present studies was to examine mechanisms by which the rectally administered combination of N-acetylcysteine (NAC) plus mesalamine (5-ASA) affects inducers of inflammation to promote mucosal healing and reduce tissue inflammation in chemically (trinitrobenzene sulfonic acid, TNBS) induced colitis in rats. Experimental findings demonstrate that dual therapy with NAC plus 5-ASA was superior to individual agents in reducing histological measures of colitis. NAC alone and in combination with 5-ASA suppressed COX2 gene expression and prostaglandin E(2) (PGE(2)) levels to control values. Furthermore, NAC plus 5-ASA reduced nitrate generation, an expression of inducible nitric oxide synthase (iNOS) activity, to basal levels and these results were significantly lower than those observed with either NAC or 5-ASA alone. In conclusion, these results indicate that NAC plus 5-ASA exerts therapeutic benefit, in part by countering the actions of PGE(2) and the deleterious effects of oxidative and nitrosative stress induced by TNBS colitis.
Asunto(s)
Acetilcisteína/uso terapéutico , Colitis/tratamiento farmacológico , Dinoprostona/biosíntesis , Mesalamina/uso terapéutico , Óxido Nítrico/biosíntesis , Acetilcisteína/farmacología , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/patología , Colon/enzimología , Colon/patología , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Quimioterapia Combinada , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/uso terapéutico , Mucosa Intestinal/patología , Masculino , Proteínas de la Membrana/metabolismo , Mesalamina/farmacología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Ácido TrinitrobencenosulfónicoRESUMEN
UNLABELLED: Previous experiments in rats with chemically induced colitis have shown that the antioxidant N-acetylcysteine plus mesalamine (5-ASA) exerted a significantly greater therapeutic effect in promoting mucosal healing when compared to either agent alone. The aims of the present study were to compare the effects of three antioxidants plus mesalamine vs. 5-ASA alone in treatment of colitis induced by trinitrobenzene sulfonic acid (TNBS) in rats. METHODS: Three days following induction of TNBS colitis, rats received 8 days of rectal therapy with 5-ASA, or 5-ASA plus vitamin C (ascorbic acid), 5-ASA plus phenyl butylnitrone (PBN) and 5-ASA plus vitamin E (alpha-tocopherol). Distal colonic tissues were examined for microscopic colitis and myeloperoxidase (MPO) activity. RESULTS: Global assessments of microscopic colitis induced by TNBS indicated that 5-ASA alone significantly changed colonic injury by -31%. Combination therapy with ascorbic acid plus 5-ASA or alpha-tocopherol plus 5-ASA caused further significant change in TNBS colitis by -65 and -82%, respectively. Each of these values was significantly below scores observed with 5-ASA as monotherapy. Reduction in colitis with PBN plus 5-ASA was not different from 5-ASA alone. MPO activity was decreased significantly in response to monotherapy with 5-ASA and each of the antioxidants plus 5-ASA when compared to TNBS. alpha-Tocopherol plus 5-ASA, however, was the only treatment strategy that reduced significantly MPO activity below that recorded for 5-ASA alone. In conclusion, our results indicate that antioxidants other than N-acetylcysteine significantly enhance the therapeutic effectiveness of 5-ASA in the treatment of TNBS colitis. alpha-Tocopherol plus 5-ASA exerted profound anti-inflammatory and reparative effects upon colitis induced by TNBS.
Asunto(s)
Antioxidantes/uso terapéutico , Colitis/tratamiento farmacológico , Colitis/patología , Mesalamina/uso terapéutico , Animales , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Colitis/inducido químicamente , Óxidos N-Cíclicos/farmacología , Óxidos N-Cíclicos/uso terapéutico , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Masculino , Mesalamina/farmacología , Ratas , Ratas Sprague-Dawley , Ácido Trinitrobencenosulfónico , Vitamina E/farmacología , Vitamina E/uso terapéuticoRESUMEN
The pathogenesis of Brunner gland hamartoma of the duodenum is unknown. This case report describes the chronology of the development of Brunner gland hamartoma from Brunner gland hyperplasia over a 12-year interval. The study subject, a 64-year-old man with chronic iron deficiency anemia, underwent serial upper endoscopies during this period. Repeated endoscopies demonstrated the evolution of Brunner gland hyperplasia, as manifest endoscopically by a submucosal mass, to a pedunculated polyp with histologic features of Brunner gland hamartoma. The duodenal polypoid mass was removed by snare polypectomy. The patient also had a chronic Helicobacter pylori infection of the stomach. This report details the time-dependent evolution of Brunner gland hyperplasia to hamartoma in association with chronic gastric H. pylori infection.
Asunto(s)
Glándulas Duodenales/patología , Enfermedades Duodenales/patología , Duodenitis/patología , Hamartoma/patología , Infecciones por Helicobacter/patología , Helicobacter pylori , Biopsia , Progresión de la Enfermedad , Endoscopía del Sistema Digestivo , Estudios de Seguimiento , Humanos , Pólipos Intestinales/patología , Masculino , Persona de Mediana EdadRESUMEN
Gastrointestinal stromal tumor (GIST) is a submucosal tumor which is most commonly found in the stomach and less commonly in small bowel. Small bowel GIST can be difficult to diagnose by conventional imaging and endoscopy techniques. We report a case of obscure GI bleeding due to a stromal tumor (GIST) of the jejunum diagnosed by video capsule endoscopy.
Asunto(s)
Endoscopía Capsular , Hemorragia Gastrointestinal/etiología , Tumores del Estroma Gastrointestinal/diagnóstico , Neoplasias del Yeyuno/diagnóstico , Anciano de 80 o más Años , Hemorragia Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/complicaciones , Tumores del Estroma Gastrointestinal/fisiopatología , Humanos , Neoplasias del Yeyuno/complicaciones , Neoplasias del Yeyuno/fisiopatología , MasculinoRESUMEN
BACKGROUND AND AIMS: GPCR stimulation by various ligands including histamine has been shown to transactivate the epidermal growth factor receptor (EGFR). This study examines the functional interactions between the H2 receptor and the EGFR in the regulation of matrix metalloproteinase-1 (MMP-1) secretion and gene expressions in cultured gastric epithelial cells. METHODS: AGS cells were incubated for up to 24 h with either histamine or heparin binding-epidermal growth factor (HB-EGF) and MMP-1 release was determined by immunoassay. MMP-1 responses to histamine and HB-EGF were further tested by the use of H2 receptor antagonist, EGFR inhibitor and mitogen activator protein kinase (MAPK) inhibitor. The role of EGFR in MMP-1 release was further tested in cells transfected with specific EGFR siRNA. EGFR and ERK1/2 phosphorylation was determined by Western blot analysis. MMP-1 gene expression was determined by RNase protection assay (RPA). RESULTS: Histamine and HB-EGF caused a dose-dependent release of MMP-1 with maximal responses that were 2.7- and 4.5-fold greater, respectively, than control, P<0.001. Famotidine prevented histamine-mediated MMP-1 release and AG1478 and EGFR siRNA completely inhibited MMP-1 secretion stimulated by both histamine and HB-EGF. Both histamine and HB-EGF stimulation of MMP-1 release was associated with activation of ERK1/2. MAPK inhibition also prevented histamine-and HB-EGF-induced MMP-1 secretion. Results of MMP-1 gene expression, either stimulatory or inhibitory, paralleled responses to MMP-1 secretion. CONCLUSION: Histamine stimulation of the H2 receptor on AGS cells evoked MMP-1 secretion and gene up regulation that was dependent on transactivation of the EGFR and downstream activation of MAPK.