RESUMO
BACKGROUND: Loss of response (LOR) to infliximab (IFX) has become an important clinical issue for patients with Crohn's disease (CD). Elemental diet (ED) therapy has been established as a nutrition therapy for CD in Japan. ED therapy can reduce antigen exposure and is both efficacious and safe. AIM: To evaluate the efficacy of concomitant ED therapy in maintaining regular IFX infusion in patients with CD. METHODS: We retrospectively studied 125 patients with luminal CD treated with scheduled IFX maintenance therapy with a regular dosage. Patients were classified into two groups: the ED group with intake ≥ 900 kcal/day and the non-ED group with intake <900 kcal/day. When clinical LOR was detected on the basis of disease activity, laboratory parameters, or endoscopic findings, the physician discontinued the infusion schedule of IFX. We investigated the efficacy of ED therapy for sustaining the scheduled IFX maintenance therapy. RESULTS: With the exception of ED intake, no significant differences were found in patient characteristics between the ED group and the non-ED group. The ED group was significantly superior to the non-ED group (p = 0.049) in sustaining scheduled IFX maintenance therapy. It is well known that ED therapy is more effective for small bowel lesions than colonic lesions in CD. When comparing ileitis and ileocolitis patients with CD, the ED group was significantly superior to the non-ED group (p = 0.015). CONCLUSIONS: Concomitant ED therapy is effective in maintaining scheduled IFX maintenance therapy in patients with luminal CD in order to prevent LOR.
Assuntos
Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Doença de Crohn/dietoterapia , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Adulto , Terapia Combinada , Doença de Crohn/diagnóstico , Tolerância a Medicamentos , Feminino , Humanos , Infliximab , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Small intestinal tuberculosis is a rare disorder of the small intestine. We report the development of deep small bowel tuberculosis in a rheumatoid arthritis patient who was taking methotrexate. The diagnosis of small bowel tuberculosis was ascertained by typical endoscopic findings and production of interferon gamma in the peripheral blood. The patient was successfully treated with antituberculous chemotherapy combined with an antifibrotic agent, tranilast, to suppress the progression of intestinal stenosis toward symptomatic stricture.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Obstrução Intestinal/microbiologia , Obstrução Intestinal/prevenção & controle , Tuberculose Gastrointestinal/complicações , Tuberculose Gastrointestinal/diagnóstico , ortoaminobenzoatos/uso terapêutico , Antituberculosos/uso terapêutico , Progressão da Doença , Endoscopia Gastrointestinal , Feminino , Humanos , Intestino Delgado , Pessoa de Meia-Idade , Tuberculose Gastrointestinal/tratamento farmacológicoRESUMO
Introduction. An on-going coronavirus disease 2019 (COVID-19) has become a challenge all over the world. Since an endoscopy unit and its staff are at potentially high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we conducted a survey for the management of the gastrointestinal endoscopic practice, personal protective equipment (PPE), and risk assessment for COVID-19 during the pandemic at multiple facilities.Methods. The 11-item survey questionnaire was sent to representative respondent of Department of Gastroenterology, Osaka City University Hospital, and its 19 related facilities.Results. A total of 18 facilities submitted valid responses and a total of 373 health care professionals (HCPs) participated. All facilities (18/18: 100%) were screening patients at risk for SARS-CoV-2 infection before endoscopy. During the pandemic, we found that the total volume of endoscopic procedures decreased by 44%. Eleven facilities (11/18: 61%) followed recommendations of the Japan Gastroenterological Endoscopy Society (JGES); consequently, about 35%-50% of esophagogastroduodenoscopy and colonoscopy were canceled. Mask (surgical mask or N95 mask), face shield/goggle, gloves (one or two sets), and gown (with long or short sleeves) were being used by endoscopists, nurses, endoscopy technicians, and endoscope cleaning staff in all the facilities (18/18: 100%). SARS-CoV-2 infection risk assessment of HCPs was conducted daily in all the facilities (18/18: 100%), resulting in no subsequent SARS-CoV-2 infection in HCPs.Conclusion. COVID-19 has had a dramatic impact on the gastrointestinal endoscopic practice. The recommendations of the JGES were appropriate as preventive measures for the SARSCoV-2 infection in the endoscopy unit and its staff.
Assuntos
COVID-19 , Endoscopia Gastrointestinal , Controle de Infecções , Exposição Ocupacional/prevenção & controle , Medição de Risco , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/transmissão , Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/normas , Pesquisas sobre Atenção à Saúde , Humanos , Controle de Infecções/instrumentação , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Japão/epidemiologia , Equipamento de Proteção Individual/classificação , Equipamento de Proteção Individual/normas , Equipamento de Proteção Individual/provisão & distribuição , SARS-CoV-2 , Gestão da Segurança/tendênciasRESUMO
Prostaglandin (PG) E(2) promotes gastrointestinal carcinogenesis and tumor progression. We determined the correlations between pattern of expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a catabolic enzyme for biological inactivation of PGE(2), in gastric adenocarcinoma and various clinicopathological factors and patient outcome in an attempt to elucidate its biological significance. In 35 of 71 cases of gastric adenocarcinoma, expression of 15-PGDH protein was reduced in tumor tissues. Multivariate analysis revealed reduction of 15-PGDH expression to be an independent predictor of poor survival. The proportion of Ki67-positive cells in 15-PGDH-negative adenocarcinoma was higher than that in 15-PGDH-positive adenocarcinoma. No differences were found in clinicopathological parameters between patients with cyclooxygenase-2 (COX-2)-positive tumors and those with COX-2 negative tumors. In an in vitro study, use of specific siRNA to silence 15-PGDH or a specific inhibitor of 15-PGDH enhanced cell proliferation in the gastric cancer cell line AGS, which expresses 15-PGDH. These findings suggest that reduction of 15-PGDH is an independent predictor of poor survival associated with enhancement of cell proliferation in gastric adenocarcinoma.
Assuntos
Adenocarcinoma/enzimologia , Hidroxiprostaglandina Desidrogenases/análise , Neoplasias Gástricas/enzimologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Ciclo-Oxigenase 2/análise , Dinoprostona/metabolismo , Feminino , Humanos , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND AND AIM: Leptin, a key hormone in regulation of food intake and energy expenditure, exerts pleiotropic cytokine-like biological effects. Its role in gastric ulcer healing is unclear. In this study, we investigated the role of leptin in gastric ulcer healing. METHODS: Experimental gastric ulcer was induced by focal serosal application of acetic acid in leptin-deficient ob/ob mice and wild-type mice. Healing of gastric ulcer and angiogenesis in the ulcer tissue was evaluated. RESULTS: Gastric ulcer healing was delayed in ob/ob mice compared with that in wild-type mice. The impairment of ulcer healing observed in ob/ob mice was characterized by reduced expression of vascular endothelial growth factor (VEGF) and impairment of angiogenesis. Systemic administration of leptin to ob/ob mice reversed the impairment of gastric ulcer healing; this reversal was accompanied by an increase in VEGF expression and angiogenesis. Although mRNA for leptin was not expressed in normal gastric mucosa and not induced in ulcerous tissue, leptin receptor expression was markedly upregulated in gastric epithelial cells at ulcer margins, and was colocalized with VEGF. CONCLUSION: These findings suggest that leptin promotes gastric ulcer healing by induction of angiogenesis in the granular tissue of ulcers via upregulation of VEGF expression.
Assuntos
Leptina/farmacologia , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Neovascularização Fisiológica/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Regulação para Cima , Cicatrização/efeitos dos fármacosRESUMO
AIM: Various different clinical indices (CI) and endoscopic indices (El) have been used to evaluate the clinical disease activity of ulcerative colitis (UC). However, no standardized CI or El of UC has been established. The aim of the present study was to determine whether or not any of the CI and/or EI for assessing the disease activity of UC could be established as a standard. METHODS: The most frequently used CI and EI were identified from 100 published clinical trials dealing with UC, and representative CI and El were selected. Seventy-four patients were enrolled in this study and their CI and El were assessed prior to treatment and at 2, 4 and 8 weeks after treatment. Furthermore, changes over time and relationships among the indices were analyzed. In this study, the clinical activity index (CAI), the disease activity index (DAI), the Lichtiger index (LI) and the Seo index were selected as the representative CI, and the Baron score and the Rachmilewitz endoscopic index (REI) were selected as the representative EI. RESULTS: A significant decrease in all the CI and El was observed after treatment, as compared with the baseline values. Moreover, there were positive relationships among the CI and between the CI and El. CONCLUSION: Our results demonstrated that all the CI and El examined were almost equally useful for evaluating disease activity in UC patients. Further studies may help to determine which of the indices is the most suitable for use in UC clinical trials.
Assuntos
Colite Ulcerativa/diagnóstico , Endoscopia Gastrointestinal , Colite Ulcerativa/patologia , Colite Ulcerativa/terapia , Feminino , Humanos , Masculino , Índice de Gravidade de DoençaRESUMO
Inflammatory responses triggered by activation of the lipopolysaccharide (LPS)/Toll-like receptor (TLR) 4 signaling pathway are a key mechanism in nonsteroidal anti-inflammatory drug-induced enteropathy. The aim of this study was to investigate the probiotic effect of Lactobacillus casei strain Shirota (LcS) on indomethacin-induced small intestinal injury. Rats pretreated with viable LcS or heat-killed LcS once or once daily for a week were administered indomethacin by gavage to induce injury. Anti-inflammatory effects of L-lactic acid (1-15 mM) were evaluated in vitro by use of THP-1 cells. One-week treatment with viable LcS prevented indomethacin-induced intestinal injury with increase in the concentration of lactic acid in small intestinal content and inhibited increases in myeloperoxidase activity and expression of mRNA for tumor necrosis factor-alpha (TNF-alpha) while affecting neither TLR4 expression nor the number of gram-negative bacteria in intestinal content, whereas neither heat-killed LcS nor a single dose of viable LcS inhibited intestinal injury. Prevention of this injury was also observed in rats given l-lactic acid in drinking water. Both L-lactic acid and LcS culture supernatant containing 10 mM lactic acid inhibited NF-kappaB activation and increases in TNF-alpha mRNA expression and TNF-alpha protein secretion in THP-1 cells treated with LPS. Western blot analyses showed that both L-lactic acid and LcS culture supernatants suppressed phosphorylation and degradation of I-kappaB-alpha induced by LPS without affecting expression of TLR4. These findings suggest that LcS exhibits a prophylactic effect on indomethacin-induced enteropathy by suppressing the LPS/TLR4 signaling pathway and that this probiotic effect of LcS may be mediated by L-lactic acid.
Assuntos
Enteropatias/prevenção & controle , Intestino Delgado/microbiologia , Ácido Láctico/metabolismo , Lacticaseibacillus casei/metabolismo , Probióticos , Animais , Linhagem Celular , Modelos Animais de Doenças , Humanos , Proteínas I-kappa B/metabolismo , Indometacina , Enteropatias/induzido quimicamente , Enteropatias/metabolismo , Enteropatias/microbiologia , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Ácido Láctico/administração & dosagem , Lacticaseibacillus casei/isolamento & purificação , Masculino , Monócitos/metabolismo , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Peroxidase/metabolismo , Fosforilação , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Helicobacter pylori-induced immune responses are skewed toward a T helper (Th) 1 phenotype. IL-17-producing Th17 cells have recently been discovered, and we examined the role of IL-17A in H. pylori-induced gastritis. Six months after inoculation with H. pylori, the mice received an intraperitoneal injection of recombinant IL-17A, anti-IL-17A antibody or irrelevant IgG(2a) for 3days. H. pylori infection markedly increased mRNA for IL-17A. Double immunofluorescence studies showed that IL-17A proteins were expressed on CD4(+) T cells, macrophages, and dendritic cells. H. pylori infection elevated mRNAs for IL-12, IFN-gamma, and TNF-alpha with increase in myeloperoxidase activity, whereas it did not affect mRNAs for IL-4 and IL-5. Neutralization of IL-17A elevated mRNAs for IFN-gamma and TNF-alpha, and myeloperoxidase activity, whereas recombinant IL-17A had a tendency to reduce these parameters. In conclusion, IL-17A exerts anti-inflammatory effects on H. pylori-induced gastritis through suppression of Th1 differentiation.
Assuntos
Gastrite/imunologia , Infecções por Helicobacter/complicações , Helicobacter pylori/imunologia , Interleucina-17/biossíntese , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Gastrite/microbiologia , Tolerância Imunológica , Interleucina-17/administração & dosagem , Interleucina-17/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Células Th1/efeitos dos fármacos , Células Th1/imunologiaRESUMO
OBJECTIVES: Although balloon-occluded retrograde transvenous obliteration (B-RTO) is useful for management of gastric varices, worsening of esophageal varices (EV) is the most important complication of B-RTO. The predictive factors of worsening of EV have not been evaluated in detail. This study was designed to evaluate the role of endoscopic color Doppler ultrasonography (ECDUS) in the detection of possible risk factors for worsening of EV after B-RTO. METHODS: A total of 39 cirrhotic patients with high-risk gastric varices successfully treated by B-RTO were included in this study. All patients underwent ECDUS before B-RTO to measure hemodynamic parameters of gastric varices and regular endoscopic follow-up after B-RTO to detect worsening of EV. The risk factors were analyzed by Cox's proportional hazards regression. RESULTS: Worsening of EV was found in 24 (61.5%) patients. The presence of esophageal varices before B-RTO and a lower degree of liver dysfunction (Child-Pugh class B) were statistically independent risk factors for worsening of EV after B-RTO (hazard ratio, HR, 5.81, 95% confidence interval, CI, 1.71-19.77 and HR 2.92, 95% CI: 1.21-7, respectively). High resistance index (> or =0.24), measured by ECDUS, is also an independent risk factor for worsening of EV after B-RTO (HR 4.06, 95% CI: 1.14-14.38) and increase in resistance index is associated with worsening of EV (P for trend=0.028). CONCLUSIONS: The presence of EV, higher Child-Pugh class, and higher resistance index assessed by ECDUS before B-RTO were significant risk factors for worsening of EV after B-RTO.
Assuntos
Cateterismo/efeitos adversos , Varizes Esofágicas e Gástricas/terapia , Adulto , Idoso , Progressão da Doença , Endossonografia , Doenças do Esôfago/diagnóstico por imagem , Doenças do Esôfago/etiologia , Varizes Esofágicas e Gástricas/etiologia , Feminino , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Ultrassonografia Doppler em CoresRESUMO
BACKGROUND: Helicobacter pylori (H. pylori) is associated with chronic gastritis and gastric carcinogenesis. The effects of nonsteroidal anti-inflammatory drugs (NSAIDs), which exert chemopreventive effects on several cancers, on H. pylori-induced gastritis remain unknown. We investigated the effects of NSAIDs on gastric inflammation and the kinetics of gastric epithelial cells in H. pylori-induced gastritis. METHODS: Patients with rheumatoid arthritis or osteoarthritis who took NSAIDs for more than 1 month and complained of dyspeptic symptoms were recruited for this study. Patients not on any NSAIDs were included as non-NSAID user controls. All patients underwent diagnostic testing for H. pylori infection, esophagogastroduodenoscopy, and gastric biopsies. Neutrophil infiltration into gastric mucosa, expression of inducible nitric oxide synthase (iNOS), and apoptosis and proliferation of gastric epithelial cells were evaluated by immunohistochemistry. In an in vitro study, the effects of NSAIDs on production of interleukin (IL)-8 induced by H. pylori in a gastric epithelial cell line (AGS) were determined. RESULTS: Numbers of neutrophils infiltrating the gastric mucosa, iNOS-expressing inflammatory cells and apoptotic cells, and proliferating cells in gastric epithelium were higher in H. pylori-positive groups than H. pylori-negative groups. Among H. pyloripositive groups, these parameters were lower in NSAID users than in non-NSAID users. NSAIDs inhibited the production of IL-8 induced by H. pylori in AGS cells. CONCLUSIONS: These findings suggest that long-term use of NSAIDs normalizes the kinetics of gastric epithelial cells in patients with H. pylori infection by attenuating gastric mucosal inflammation, which may result in prevention of the gastric carcinogenesis associated with H. pylori infection.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Infecções por Helicobacter/patologia , Helicobacter pylori/imunologia , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Linhagem Celular Tumoral , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Regulação Enzimológica da Expressão Gênica , Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Humanos , Interleucina-8/efeitos dos fármacos , Interleucina-8/metabolismo , Masculino , Pessoa de Meia-Idade , Infiltração de Neutrófilos , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoartrite/complicações , Osteoartrite/tratamento farmacológico , Fatores de TempoRESUMO
BACKGROUND: Video capsule endoscopy (VCE) and double-balloon enteroscopy (DBE) enable the detection of small intestinal lesions. AIM: To examine causes of acute overt gastrointestinal (GI) bleeding and the prevalence of mid-GI bleeding, defined as small intestinal bleeding from the ampulla of Vater to the terminal ileum, in a multi-center experience in Japan in the VCE/DBE era. METHODS: Data were collected retrospectively from consecutive patients with acute overt GI bleeding in ten participating hospitals. All patients were examined by esophagogastroduodenoscopy and/or colonoscopy. When the source of bleeding was not identified after these procedures, patients suspected to have mid-GI bleeding were referred to our hospital and VCE/DBE was performed to determine the source of bleeding. RESULTS: Of the 1044 patients with acute overt GI bleeding, 524 (50.2%) patients were diagnosed with upper GI bleeding, 442 (42.3%) with lower GI bleeding, and 13 (1.2%) with mid-GI bleeding. Gastric ulcer was the most common cause of bleeding (20.4%). Among cases of mid-GI bleeding, ulcers were found in 4 (30.8%) patients, erosions in 3 (23.1%), angiodysplasia in 3 (23.1%), submucosal tumor in 2 (15.4%), and hemangioma in one (7.7%). Seven lesions were located in the jejunum, 5 in the ileum, and one in both the jejunum and ileum. Analysis of age-related cause showed that the prevalence of mid-GI bleeding among younger patients under 40 years of age was higher (5%) than in other age groups (1-2%). CONCLUSION: mid-GI bleeding is rare among Japanese patients with acute overt GI bleeding.
Assuntos
Endoscopia Gastrointestinal/métodos , Hemorragia Gastrointestinal/epidemiologia , Adulto , Idoso , Endoscopia por Cápsula , Doenças do Colo/diagnóstico , Doenças do Colo/epidemiologia , Doenças do Esôfago/diagnóstico , Doenças do Esôfago/epidemiologia , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Doenças Retais/diagnóstico , Doenças Retais/epidemiologia , Estudos Retrospectivos , Gastropatias/diagnóstico , Gastropatias/epidemiologiaRESUMO
Pathogenic bacterial components play critical roles in initiation of gastrointestinal inflammation via activation of intracellular signaling pathways which induce proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Lansoprazole (LANSO), a proton pump inhibitor, has been widely used for the treatment of peptic ulcers and reflux esophagitis due to its potent acid-suppressive effect. It has also been reported to have anti-inflammatory effects. In this study we investigated the effects of LANSO on the production of TNF-alpha and IL-1beta induced by lipopolysaccharide (LPS) and Helicobacter pylori water-soluble extract (HpWE) in the human monocytic cell line (THP-1). LANSO (100 microM) significantly reduced mRNA expression and production of TNF-alpha and IL-1beta by THP-1 cells stimulated by LPS and HpWE. LANSO inhibited phosphorylation and degradation of inhibitory factor kappaB-alpha (IkappaB-alpha) and phosphorylation of extracellular signal-regulated kinase (ERK) induced by LPS and HpWE in THP-1 cells. These findings suggest that LANSO exerts anti-inflammatory effects by suppressing induction of TNF-alpha and IL-1beta via inhibition of nuclear factor (NF)-kappaB and ERK activation.
RESUMO
Human neutrophil migratory responses to Toll-like receptor (TLR) agonists were studied using videomicroscopy. When challenged with lipopolysaccharide (LPS, TLR4 agonist) or N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-seryl-(lysyl)(3)-lysine (P3CSK4, TLR2 agonist), neutrophils displayed enhanced motility, which was found to reflect increased random migration but not directed migration (chemotaxis). Enhanced neutrophil motility was detected within 10 min after stimulation with LPS or P3CSK4, and was sustained for more than 80 min. Stimulation of neutrophils with LPS or P3CSK4 resulted in the activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), which preceded neutrophil migration. TLR-mediated neutrophil migration was strongly suppressed by pretreatment of cells with U0126 (MAPK/ERK kinase inhibitor) but not with U0124 (an inactive analogue of U0126) or SB203580 (a p38 MAPK inhibitor), and was almost completely abolished by pretreatment of cells with U0126 and SB203580 in combination. Randomly migrating neutrophils in response to LPS or P3CSK4 displayed directed migration when further challenged with gradient concentrations of N-formyl-methionyl-leucyl-phenylalanine (FMLP) or platelet-activating factor (PAF). These findings indicate that TLR agonists stimulate human neutrophil migration via the activation of ERK and p38 MAPK, and FMLP- or PAF-induced neutrophil chemotaxis is not affected by the pre-exposure of cells to TLR agonists.
Assuntos
Quimiotaxia de Leucócito/imunologia , Proteínas Quinases Ativadas por Mitógeno/imunologia , Neutrófilos/imunologia , Receptores Toll-Like/agonistas , Butadienos/imunologia , Relação Dose-Resposta Imunológica , Ativação Enzimática/imunologia , Inibidores Enzimáticos/imunologia , MAP Quinases Reguladas por Sinal Extracelular/imunologia , Humanos , Imidazóis/imunologia , Lipopolissacarídeos/imunologia , Lipoproteínas/imunologia , N-Formilmetionina Leucil-Fenilalanina/imunologia , Nitrilas/imunologia , Fosforilação , Fator de Ativação de Plaquetas/imunologia , Piridinas/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologiaRESUMO
We studied the role of c-Jun N-terminal kinase (JNK) in human neutrophils stimulated by tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Stimulation of neutrophils with TNF-alpha and GM-CSF caused phosphorylation of p54 or p46 JNK or both. The phosphorylated p46 JNK band in TNF-alpha-stimulated neutrophils mobilized faster than that in GM-CSF-stimulated cells. The JNK isoform transcripts expressed in neutrophils were JNK1beta1, JNK1beta2, JNK2alpha1, and JNK2alpha2. The JNK isoforms phosphorylated by TNF-alpha and GM-CSF stimulation were found to be JNK1 and JNK2, respectively, on the basis of the molecular mass and the capture assay. TNF-alpha-induced JNK phosphorylation was sustained in the presence of cycloheximide, which was accompanied by accelerated neutrophil apoptosis. The JNK inhibitors (SP600125 and TAT-TI-JIP(153163)) suppressed neutrophil apoptosis induced by TNF-alpha plus cycloheximide, whereas they attenuated the GM-CSF-mediated antiapoptotic effect on neutrophils. The JNK inhibitor did not affect the levels of Mcl-1 and XIAP (antiapoptotic molecules), which were regulated by TNF-alpha plus cycloheximide and GM-CSF. The JNK inhibitor markedly suppressed TNF-alpha-induced and GM-CSF-induced superoxide release. These findings suggest that JNK1 and JNK2 are involved in TNF-alpha-induced neutrophil apoptosis and GM-CSF-mediated antiapoptotic effect on neutrophils, respectively, and both JNK isoforms are involved in TNF-alpha-induced and GM-CSF-induced superoxide release.
Assuntos
Apoptose/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neutrófilos/citologia , Neutrófilos/enzimologia , Fator de Necrose Tumoral alfa/farmacologia , Adulto , Antracenos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Proteína 11 Semelhante a Bcl-2 , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Isoenzimas/metabolismo , Proteínas de Membrana/metabolismo , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides , Neutrófilos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Recombinantes , Superóxidos/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismoRESUMO
BACKGROUND & AIMS: With capsule endoscopy, the ulcerogenic effect of low-dose enteric-coated aspirin on the small bowel and the therapeutic effect of misoprostol on intestinal injury were evaluated. METHODS: Eleven patients who developed gastric ulcers while undergoing low-dose enteric-coated aspirin therapy were enrolled. They continued aspirin therapy while taking proton pump inhibitors (PPIs) for 8 weeks to heal the gastric ulcers. Then misoprostol 200 microg 4 times a day was administered instead of PPIs for 8 weeks. When the patients could not tolerate misoprostol as a result of side effects, they received another 8 weeks of PPI therapy. RESULTS: Capsule endoscopy performed after 8 weeks of PPI treatment identified red spots and mucosal breaks in 100% (11/11) and 90.9% (10/11) of patients, respectively. In 7 patients who completed the study protocol, misoprostol significantly decreased the median number of red spots and mucosal breaks, with complete disappearance of mucosal breaks in 4 patients. Intestinal lesions tended not to heal in 3 patients who discontinued misoprostol. CONCLUSIONS: Low-dose enteric-coated aspirin frequently damages the small intestine, and misoprostol is effective in the treatment of aspirin-induced enteropathy.
Assuntos
Antiulcerosos/uso terapêutico , Aspirina/efeitos adversos , Intestino Delgado/efeitos dos fármacos , Misoprostol/uso terapêutico , Comprimidos com Revestimento Entérico/efeitos adversos , Úlcera/induzido quimicamente , Idoso , Antiulcerosos/administração & dosagem , Endoscopia por Cápsula , Feminino , Humanos , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Misoprostol/administração & dosagem , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Úlcera/patologiaRESUMO
BACKGROUND & AIMS: Double-balloon endoscopy (DBE) enables endoscopic and histopathologic diagnosis of malignant small-bowel tumors (MSBT). This study examined the clinical features of patients with MSBT and evaluated the usefulness of DBE in the diagnosis of MSBT. METHODS: We retrospectively examined consecutive DBE studies of 358 patients who underwent DBE in our hospital between December 2003 and October 2007 because of suspected or established small-bowel disease. RESULTS: Fourteen patients with MSBT were diagnosed by DBE. The most common type was primary adenocarcinoma (8 patients), followed by metastatic carcinoma (3 patients) and malignant lymphoma (3 patients). Half of these patients presented with obscure gastrointestinal bleeding (OGIB). Histopathologic diagnosis was obtained in 11 of 14 patients. CONCLUSIONS: Of 180 patients with OGIB, MSBT accounted for only 3.9%, however, 50% of patients with MSBT presented with OGIB. OGIB is an important clinical feature of small-bowel malignancy, which can be diagnosed by DBE.
Assuntos
Adenocarcinoma/diagnóstico , Endoscopia Gastrointestinal/métodos , Neoplasias Intestinais/diagnóstico , Intestino Delgado/patologia , Linfoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Intestinais/patologia , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVES: Anal fistulas are common in individuals with Crohn's disease (CD). We sought to evaluate the efficacy of oral spherical adsorptive carbon (AST-120) (Kremezin; Kureha Corporation, Tokyo, Japan) for the treatment of intractable anal fistulas in patients with CD. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, patients with CD and at least one active anal fistula under treatment were assigned to receive either AST-120 or placebo for 8 wk. Improvement was defined as a reduction of 50% or more from baseline in the number of draining fistulas observed at both 4 and 8 wk. Remission was defined by closure of all draining fistulas at both 4 and 8 wk. The Perianal Disease Activity Index (PDAI) and Crohn's Disease Activity Index (CDAI) were also assessed. RESULTS: In total, 62 patients were randomized, of whom 57 received AST-120 (N = 27) or placebo (N = 30). The improvement rate in the AST-120 group (37.0%) was significantly greater than that in the placebo group (10.0%) (P= 0.025). The corresponding remission rates were 29.6% and 6.7%, respectively (P= 0.035). PDAI significantly improved at both 4 and 8 wk with AST-120, compared to placebo (P= 0.004 and P= 0.005, respectively). CDAI was also significantly improved at both 4 and 8 wk in the AST-120 group, compared to the placebo group (P= 0.007 and P= 0.001, respectively). AST-120 treatment was well tolerated and no life-threatening adverse events were observed. CONCLUSION: AST-120 is useful for the control of intractable anal fistulas in CD patients.
Assuntos
Carbono/uso terapêutico , Doença de Crohn/complicações , Óxidos/uso terapêutico , Fístula Retal/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Retal/etiologia , Resultado do TratamentoRESUMO
Clinical and epidemiological studies have revealed that the incidence of colorectal cancer associated with ulcerative colitis increases with long-term chronic inflammation. Careful endoscopic observation and histological studies to check for dysplasia in the colon are important in detecting neoplasia. Current surveillance protocols mainly involve frequent step biopsies to yield a reasonable rate of dysplasia detection. However, recent studies using chromoendoscopy or magnifying endoscopy have proposed that neoplastic changes may be detected efficiently. Therefore, it is very important to understand the typical endoscopic findings found in neoplastic changes in patients proven to have long-standing ulcerative colitis. In this review, we demonstrate the typical endoscopic findings by conventional endoscopy and chromoendoscopy.
Assuntos
Colite Ulcerativa/patologia , Neoplasias do Colo/patologia , Colonoscopia/métodos , Corantes , Programas de Rastreamento/métodos , Lesões Pré-Cancerosas/patologia , Atlas como Assunto , Neoplasias do Colo/prevenção & controle , Humanos , Lesões Pré-Cancerosas/prevenção & controleRESUMO
BACKGROUND: Wireless capsule endoscopy (CE) and double-balloon enteroscopy (DBE) are new methods enabling diagnostic endoscopy of the entire small intestine. However, which of the two is superior is unclear. We therefore prospectively compared the clinical efficacy of CE and DBE. METHODS: We prospectively examined 32 patients with obscure gastrointestinal bleeding. CE preceded DBE by 1-7 days, and all patients underwent DBE twice, by antegrade and retrograde approaches, to evaluate the entire small intestine. Physicians evaluating the results of CE and DBE were blind to the results of the other method. We evaluated diagnosis, diagnostic yield of the two methods, and clinical outcomes. RESULTS: CE revealed abnormal findings in 29 (90.6%) of 32 patients. CE definitively or probably detected the sources of bleeding in 23 (71.9%) of the 32 patients, including angioectasias (eight), erosions (seven), ulcers (five), tumor (one), and hemorrhagic polyps (two). DBE definitely or probably detected the sources of bleeding in 21 (65.6%) of the 32 patients, including angioectasias (seven), erosions (four), ulcers (five), tumor (one), hemorrhagic polyps (two) and diverticula (two). CE yielded more abnormal findings than DBE (CE 90.6%, DBE 65.6%) (P = 0.032), although there were no significant differences in diagnostic yield between the methods. We were able to perform additional treatment or biopsy with DBE in 13 patients, including coagulation therapy (ten), endoscopic mucosal resection (one), biopsy (seven), and extraction of retained CE (two). CONCLUSIONS: Our results demonstrate the superiority of CE in detecting abnormal lesions, and the superiority of DBE in endoscopic management.
Assuntos
Endoscopia por Cápsula , Endoscopia Gastrointestinal , Hemorragia Gastrointestinal/diagnóstico , Idoso , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Intestino Delgado , Masculino , Pessoa de Meia-Idade , Método Simples-CegoRESUMO
BACKGROUND: Early satiety, bloating, and postprandial distress are common symptoms in patients with functional dyspepsia (FD) and anorexia nervosa (AN). Perfectionism is known to be associated with AN, accompanied by abnormal eating behavior. We analyzed perfectionism in FD as compared with that in AN, and investigated the correlation of perfectionism with abdominal symptoms. METHODS: The study group comprised 168 patients with FD according to the Rome II criteria (65% females, mean age 47.7 years) and 101 with AN according to the DSM-IV criteria (100% females, mean age 23 years). As control, 130 healthy subjects (81% females, mean age 26.2 years) were studied. Frost's Multidimensional Perfectionism Scale (FMPS) was used to evaluate perfectionism. Abdominal symptoms were evaluated on the Gastrointestinal Symptoms Rating Scale (GSRS). RESULTS: All subscale scores except for organization were significantly higher in patients with AN than in controls. The parental criticism (PC) score in patients with FD was also significantly higher than that in controls, but lower than that in patients with AN. PC was significantly correlated with the total GSRS, particularly indigestion scores of FD patients (P = 0.0476 and P = 0.0294). CONCLUSIONS: Perfectionism such as PC underlying the psychological background of FD patients may be correlated with their abdominal symptoms.