RESUMO
The Paneth cells reside in the small intestine at the bottom of the crypts of Lieberkühn, intermingled with stem cells, and provide a niche for their neighbors by secreting growth and Wnt-factors as well as different antimicrobial peptides including defensins, lysozyme and others. The most abundant are the human Paneth cell α-defensin 5 and 6 that keep the crypt sterile and control the local microbiome. In ileal Crohn's disease various mechanisms including established genetic risk factors contribute to defects in the production and ordered secretion of these peptides. In addition, life-style risk factors for Crohn's disease like tobacco smoking also impact on Paneth cell function. Taken together, current evidence suggest that defective Paneth cells may play the key role in initiating inflammation in ileal, and maybe ileocecal, Crohn's disease by allowing bacterial attachment and invasion.
Assuntos
Células-Tronco Adultas/fisiologia , Doença de Crohn/patologia , Microbioma Gastrointestinal/fisiologia , Doenças do Íleo/patologia , Inflamação/patologia , Celulas de Paneth/fisiologia , alfa-Defensinas/metabolismo , Animais , Autofagia , Doença de Crohn/imunologia , Humanos , Doenças do Íleo/imunologia , Inflamação/imunologia , Necroptose , Nicho de Células-TroncoRESUMO
BACKGROUND: Gastrointestinal acute graft-versus-host disease (GVHD) occurring after allogeneic hematopoietic cell transplant is an allo-reactive T cell and inflammatory cytokine driven organ injury with epithelial apoptosis as 1 of its hallmark findings and is associated with significant mortality. Tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8 or TIPE) acts as a negative mediator of apoptosis via inhibition of caspase-3 activation, promotes cell proliferation and Tipe deficiency is associated with increased inflammation. METHODS: To evaluate the role of TIPE in acute GVHD, naive C57BL/6 and Tipe C57BL/6 mice were conditioned with 1000 cGy single dose total body irradiation, followed by transplantation of 10 million bone marrow cells and 20 million splenocytes from either syngeneic C57BL/6 or allogeneic BALB/c donors. RESULTS: Allo TIPE-deficient mice developed exacerbated gut GVHD compared with allo controls and had significantly decreased survival (6 wk overall survival: 85% versus 37%; P < 0.05), higher clinical GVHD scores, more profound weight loss, increased serum proinflammatory cytokines (interleukin-17A, TNF, interleukin-6, and interferon-γ). T-cell infiltration into the ileum was increased; epithelial proliferation was decreased along with significantly higher levels of chemokines KC and monokine induced by gamma interferon. Using bone marrow chimeric experiments, TIPE was found to have a role in both hematopoietic and nonhematopoietic cells. CONCLUSIONS: Absence of TIPE results in excessive inflammation and tissue injury after allo-HCT, supporting that TIPE confers immune homeostasis and has tissue-protective function during the development of gut GVHD and may be a potential future target to prevent or treat this complication after allogeneic HCT.
Assuntos
Proteínas Reguladoras de Apoptose/deficiência , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças do Íleo/imunologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/imunologia , Transplante de Medula Óssea , Modelos Animais de Doenças , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Doenças do Íleo/patologia , Íleo/imunologia , Íleo/patologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Quimeras de Transplante/imunologia , Transplante Homólogo/efeitos adversosRESUMO
AIM: To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies (Ab) level and time to surgical recurrence after initial surgery for Crohn's disease (CD). METHODS: We reviewed 412 charts from a clinical database at tertiary academic hospital. Patients included in the study had ileal or ileocolonic CD and surgical resection of small bowel or ileocecal region for management of disease. Serum samples were analyzed for serological assays including GM-CSF cytokine, GM-CSF Ab, ASCA IgG and IgA, and genetic markers including SNPs rs2066843, rs2066844, rs2066845, rs2076756 and rs2066847 in NOD2, rs2241880 in ATG16L1, and rs13361189 in IRGM. Cox proportional-hazards models were used to assess the predictors of surgical recurrence. RESULTS: Ninety six percent of patients underwent initial ileocecal resection (ICR) or ileal resection (IR) and subsequently 40% of patients required a second ICR/IR for CD. GM-CSF Ab level was elevated at a median of 3.81 mcg/mL. Factors predicting faster time to a second surgery included elevated GM-CSF Ab [hazard ratio (HR) 3.52, 95%CI: 1.45-8.53, P = 0.005] and elevated GM-CSF cytokine (HR = 2.48, 95%CI: 1.31-4.70, P = 0.005). Factors predicting longer duration between first and second surgery included use of Immunomodulators (HR = 0.49, 95%CI: 0.31-0.77, P = 0.002), the interaction effect of low GM-CSF Ab levels and smoking (HR = 0.60, 95%CI: 0.45-0.81, P = 0.001) and the interaction effect of low GM-CSF cytokine levels and ATG16L1 (HR = 0.65, 95%CI: 0.49-0.88, P = 0.006). CONCLUSION: GM-CSF bioavailability plays a critical role in maintaining intestinal homeostasis. Decreased bioavailability coupled with the genetic risk markers and/or smoking results in aggressive CD behavior.
Assuntos
Doença de Crohn/cirurgia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Doenças do Íleo/cirurgia , Íleo/imunologia , Adulto , Autoanticorpos/sangue , Proteínas Relacionadas à Autofagia/genética , Biomarcadores/análise , Doença de Crohn/sangue , Doença de Crohn/genética , Doença de Crohn/imunologia , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Doenças do Íleo/sangue , Doenças do Íleo/genética , Doenças do Íleo/imunologia , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de TempoRESUMO
We describe a young female patient who had refractory intestinal Behçet's disease that responded to tocilizumab, a humanised anti-interleukin-6 receptor antibody. The patient had suffered from long disease activity courses and was treated with multiple medications, and the disease became refractory when immunosuppressants (e.g., thalidomide, sulfasalazine and azathioprine) were limited for poor remission, methylprednisolone pulse therapy, cyclophosphamide, and biological agents (e.g., adalimumab or infliximab) were restricted due to side effects after administration. Therefore, tocilizumab was considered as a therapeutic option and the symptoms resolved during 9 months of administration. Tocilizumab may be a good choice for intestinal Behçet's disease refractory to conventional treatment.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Doenças do Íleo/tratamento farmacológico , Imunossupressores/uso terapêutico , Receptores de Interleucina-6/antagonistas & inibidores , Úlcera/tratamento farmacológico , Adulto , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/imunologia , Resistência a Medicamentos , Substituição de Medicamentos , Feminino , Humanos , Doenças do Íleo/diagnóstico , Doenças do Íleo/imunologia , Receptores de Interleucina-6/imunologia , Resultado do Tratamento , Úlcera/diagnóstico , Úlcera/imunologiaRESUMO
Johne's disease is a chronic infection of the small intestine caused by Mycobacterium avium subspecies paratuberculosis (MAP), an intracellular bacterium. The events of pathogen survival within the host cell(s), chronic inflammation and the progression from asymptomatic subclinical stage to an advanced clinical stage of infection, are poorly understood. This study examines gene expression in the ileocecal valve (ICV) of Holstein dairy cows at different stages of MAP infection. The ICV is known to be a primary site of MAP colonization and provides an ideal location to identify genes that are relevant to the progression of this disease. RNA was prepared from ICV tissues and RNA-Seq was used to compare gene transcription between clinical, subclinical, and uninfected control animals. Interpretation of the gene expression data was performed using pathway analysis and gene ontology categories containing multiple differentially expressed genes. Results demonstrated that many of the pathways that had strong differential gene expression between uninfected control and clinical cows were related to the immune system, such as the T- and B-cell receptor signaling, apoptosis, NOD-like receptor signaling, and leukocyte transendothelial migration pathways. In contrast, the comparison of gene transcription between control and subclinical cows identified pathways that were primarily involved in metabolism. The results from the comparison between clinical and subclinical animals indicate recruitment of neutrophils, up regulation of lysosomal peptidases, increase in immune cell transendothelial migration, and modifications of the extracelluar matrix. This study provides important insight into how cattle respond to a natural MAP infection at the gene transcription level within a key target tissue for infection.
Assuntos
Doenças do Íleo/microbiologia , Valva Ileocecal/microbiologia , Mycobacterium avium subsp. paratuberculosis/imunologia , Transcrição Gênica/genética , Animais , Apoptose/imunologia , Linfócitos B/imunologia , Linfócitos B/microbiologia , Bovinos , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/microbiologia , Movimento Celular/imunologia , Células Endoteliais/imunologia , Células Endoteliais/microbiologia , Matriz Extracelular/imunologia , Matriz Extracelular/microbiologia , Expressão Gênica/genética , Expressão Gênica/imunologia , Perfilação da Expressão Gênica/métodos , Doenças do Íleo/imunologia , Valva Ileocecal/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/microbiologia , Paratuberculose/imunologia , Paratuberculose/microbiologia , Transdução de Sinais/imunologia , Linfócitos T/imunologia , Linfócitos T/microbiologia , Transcrição Gênica/imunologiaAssuntos
Doenças do Íleo/diagnóstico , Valva Ileocecal/patologia , Mucosa Intestinal/patologia , Tecido Linfoide/patologia , Idoso , Biópsia , Colonoscopia , Humanos , Hiperplasia , Doenças do Íleo/imunologia , Doenças do Íleo/patologia , Valva Ileocecal/imunologia , Mucosa Intestinal/imunologia , Tecido Linfoide/imunologia , MasculinoAssuntos
Doenças do Íleo/diagnóstico , Hospedeiro Imunocomprometido , Obstrução Intestinal/diagnóstico , Perfuração Intestinal/diagnóstico , Transplante de Rim , Tuberculose Gastrointestinal/diagnóstico , Diagnóstico Diferencial , Humanos , Doenças do Íleo/imunologia , Doenças do Íleo/microbiologia , Obstrução Intestinal/imunologia , Obstrução Intestinal/microbiologia , Perfuração Intestinal/imunologia , Perfuração Intestinal/microbiologia , Masculino , Pessoa de Meia-Idade , Tuberculose Gastrointestinal/imunologiaRESUMO
AIM: To investigate the phasic alteration of intestinal homeostasis in an experimental model of intestinal obstruction. METHODS: A rabbit model of intestinal obstruction was established by transforming parts of an infusion set into an in vivo pulled-type locking clamp and creating a uniform controllable loop obstruction in the mesenteric non-avascular zone 8 cm from the distal end of the ileum. The phasic alteration of intestinal homeostasis was studied after intestinal obstruction. The changes in goblet cells, intraepithelial lymphocytes, lamina propria lymphocytes, and intestinal epithelium were quantified from periodic acid-Schiff-stained sections. Ornithine decarboxylase (ODC) activity and serum citrulline levels were measured by high-performance liquid chromatography. Claudin 1 mRNA expression was examined by real-time polymerase chain reaction analysis. Intestinal microorganisms, wet/dry weight ratios, pH values, and endotoxin levels were determined at multiple points after intestinal obstruction. Furthermore, the number and ratio of CD3(+), CD4(+) and CD8(+) T cells were determined by flow cytometry, and secretory IgA levels were measured with an enzyme-linked immunosorbent assay. RESULTS: A suitable controllable rabbit model of intestinal obstruction was established. Intestinal obstruction induced goblet cell damage and reduced cell number. Further indicators of epithelial cell damage were observed as reduced serum citrulline levels and claudin 1 gene expression, and a transient increase in ODC activity. In addition, the wet/dry weight ratio and pH of the intestinal lumen were also dramatically altered. The ratio of Bacillus bifidus and enterobacteria was reversed following intestinal obstruction. The number and area of Peyer's patches first increased then sharply decreased after the intestinal obstruction, along with an alteration in the ratio of CD4/CD8(+) T cells, driven by an increase in CD3(+) and CD8(+) T cells and a decrease in CD4(+) T cells. The number of lamina propria lymphocytes also gradually decreased with prolonged obstruction. CONCLUSION: Intestinal obstruction can induce disruption of intestinal homeostasis.
Assuntos
Doenças do Íleo , Íleo , Mucosa Intestinal , Obstrução Intestinal , Animais , Bacillus/crescimento & desenvolvimento , Biomarcadores/metabolismo , Modelos Animais de Doenças , Enterobacteriaceae/crescimento & desenvolvimento , Homeostase , Doenças do Íleo/diagnóstico , Doenças do Íleo/imunologia , Doenças do Íleo/metabolismo , Doenças do Íleo/microbiologia , Íleo/imunologia , Íleo/metabolismo , Íleo/microbiologia , Íleo/patologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/imunologia , Obstrução Intestinal/metabolismo , Obstrução Intestinal/microbiologia , Coelhos , Subpopulações de Linfócitos T/imunologia , Fatores de TempoRESUMO
Small endoscopic biopsies of the terminal ileum may be difficult to assess for early involvement by lymphoma. Immunophenotypic and genotypic analyses are often utilized, but the performance of these studies in this setting is not well defined. Terminal ileal biopsies from 66 patients with prominent lymphoid hyperplasia and abnormal "lymphoma-like" morphology were evaluated by immunohistochemistry (IHC) for CD3, CD5, CD43, CD20, CD21, and CD10 expression and for IGH@ gene rearrangement by polymerase chain reaction using BIOMED-2 primers. Patients ranged in age from 3 to 80 years. Indications for endoscopy included inflammatory bowel disease (29), diarrhea and/or abdominal pain (28), history of lymphoma (13), and others (4). Four biopsies with abnormal morphology had abnormal IHC and a clonal IGH@ peak; all were obtained from patients with a history of lymphoma and determined to be recurrent lymphoma. Three biopsies with abnormal morphology and abnormal IHC but no clonal IGH@ peak were obtained from patients with a history of lymphoma (2) and chronic diarrhea (1); all showed symptom resolution or remission of disease (mean follow-up, 37 mo). Eight biopsies with abnormal morphology but no abnormal IHC expression also had abnormal IGH@ results (4 clonal and 4 borderline). IGH@ evaluation of follow-up biopsies for these cases were nonclonal (7) or clonal, but with a different clone from the prior biopsy (1); follow-up of the 8 patients showed no evidence of lymphoma (mean, 37.8 mo). Abnormal IHC expression pattern or clonal IGH@ rearrangement in endoscopic biopsies of the lymphoid-rich terminal ileum do not necessarily warrant a diagnosis of lymphoma. To prevent misdiagnosis, B-cell clonality studies should only be performed when there is strong clinical suspicion for lymphoma and compelling IHC data; the absence of a reproducible clone in repeat biopsy specimens may be useful in patients that do not have other clinical evidence of lymphoma.
Assuntos
Rearranjo Gênico , Doenças do Íleo/imunologia , Cadeias Pesadas de Imunoglobulinas/genética , Pseudolinfoma/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/imunologia , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Doenças do Íleo/genética , Imunofenotipagem , Lactente , Masculino , Pessoa de Meia-Idade , Pseudolinfoma/genética , Adulto JovemRESUMO
It has been previously shown that acetylcholine (ACh) may affect pro-inflammatory and anti-inflammatory cytokines. The role of the cholinergic system in radiation-induced inflammatory responses and tissue damage remains unclear. Therefore, the present study was designed to determine the radio-protective properties of the cholinergic system in the ileum and the liver of rats. Rats were exposed to 8-Gy single-fraction whole-abdominal irradiation and were then decapitated at either 36 h or 10 d post-irradiation. The rats were treated either with intraperitoneal physiological saline (1 ml/kg), physostigmine (80 µg/kg) or atropine (50 µg/kg) twice daily for 36 h or 10 d. Cardiac blood samples and liver and ileal tissues were obtained in which TNF-α, IL-1ß and IL-10 levels were assayed using ELISA. In the liver and ileal homogenates, caspase-3 immunoblots were performed and myeloperoxidase (MPO) activity was analyzed. Plasma levels of IL-1ß and TNF-α increased significantly following radiation (P < 0.01 and P < 0.001, respectively) as compared with non-irradiated controls, and physostigmine treatment prevented the increase in the pro-inflammatory cytokines (P < 0.01 and P < 0.001, respectively). Plasma IL-10 levels were not found to be significantly changed following radiation, whereas physostigmine augmented IL-10 levels during the late phase (P < 0.01). In the liver and ileum homogenates, IL-1ß and TNF-α levels were also elevated following radiation, and this effect was inhibited by physostigmine treatment but not by atropine. Similarly, physostigmine also reversed the changes in MPO activity and in the caspase-3 levels in the liver and ileum. Histological examination revealed related changes. Physostigmine experiments suggested that ACh has a radio-protective effect not involving the muscarinic receptors.
Assuntos
Acetilcolina/imunologia , Doenças do Íleo/imunologia , Doenças do Íleo/prevenção & controle , Hepatopatias/imunologia , Hepatopatias/prevenção & controle , Lesões por Radiação/imunologia , Lesões por Radiação/prevenção & controle , Animais , Colinérgicos/administração & dosagem , Citocinas/imunologia , Doenças do Íleo/patologia , Hepatopatias/patologia , Doses de Radiação , Lesões por Radiação/patologia , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
OBJECTIVES: Ischaemia-reperfusion (I/R) injury is encountered in conditions that diminish intestinal blood flow. There is no clinically feasible technique available for mucosal preservation. METHODS: One hundred Wistar rats were subjected to intestinal ischaemia for 15 and 60 min (I15', I60'), followed by 1 and 7 days of reperfusion (R1d, R7d). Rats were subjected to ischaemia by clamping the superior mesenteric artery. Prostaglandin E1 (PGE1) (2.500 ng/kg intra-arterial bolus or 20 ng/kg intravenous infusion) was administered immediately prior to the commencement of the experimental period. Animals were divided into 20 groups: sham (laparotomy alone), sacrificed at 1 or 7 days; saline administration, 15 or 60 min of ischaemia, 1 or 7 days of reperfusion; prostaglandin E1 administration, 15 or 60 min of ischaemia, 1 or 7 days of reperfusion, each one for intra-arterial or intravenous administration. Ileal segments were excised and assessed for histopathological score, polymorphonuclear (PMN) leucocytes encountered and myeloperoxidase (MPO) activity measurement. RESULTS: I/R caused deterioration of histological characteristics. Prophylactic administration of PGE1 resulted in a significant decrease in the histological score compared with the respective saline group (analysis of variance, P < 0.005). In groups treated with PGE1, PMN leucocyte infiltration was lower for the 60 min of ischaemia group (I60'/R1d *P = 0.026; I60'/R7d P = 0.015). I15'/R7d did not lead to a significant reduction in PMN infiltration (P = 0.061). Pretreatment with PGE1 attenuates MPO levels after intestinal I/R injury (P < 0.05). No differences were encountered between types of administration. CONCLUSIONS: Results of this study showed that administration of prostaglandin E1 prevents I/R injury by diminishing histological damage parameters, inhibiting PMN leucocyte infiltration and attenuating MPO activity.
Assuntos
Alprostadil/administração & dosagem , Doenças do Íleo/prevenção & controle , Íleo/irrigação sanguínea , Íleo/efeitos dos fármacos , Oclusão Vascular Mesentérica/tratamento farmacológico , Substâncias Protetoras/administração & dosagem , Traumatismo por Reperfusão/prevenção & controle , Animais , Citoproteção , Modelos Animais de Doenças , Doenças do Íleo/imunologia , Doenças do Íleo/patologia , Íleo/imunologia , Íleo/patologia , Infusões Intravenosas , Injeções Intra-Arteriais , Oclusão Vascular Mesentérica/imunologia , Oclusão Vascular Mesentérica/patologia , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Peroxidase/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Fatores de TempoRESUMO
BACKGROUND: Glycoprotein 2 (GP2) was discovered as the major autoantigen of Crohn's disease (CD)-specific pancreatic autoantibodies (PAB). We investigated anti-GP2 IgA and IgG antibodies as novel serological parameters in CD and assessed their association with distinct disease phenotypes. METHODS: Anti-GP2 and anti-Saccharomyces cerevisiae (ASCA) IgA and IgG were detected by ELISA employing recombinant human GP2 and phosphopeptidomannan, respectively and PAB by indirect immunofluorescence (IIF) in 271 sera, 169 with CD and 102 with ulcerative colitis (UC). As healthy controls 160 adult blood donors and 65 children were included. RESULTS: Anti-GP2 IgG and/or IgA were more prevalent in CD (51/169, 30.2%) than in UC (9/102, 8.9%) patients and in controls (9/225, 4%) (p < 0.001 respectively). ASCA IgG and/or IgA were present in 60/169 (35.5%) in CD and in 7/102 (6.9%) in UC patients (p < 0.001). CD patients with ileocolonic location (L3) showed a significantly higher prevalence of anti-GP2 and ASCA IgA and/or IgG (40/113 and 48/113, respectively; p < 0.05 for both comparisons), whereas CD patients with colonic location (L2) revealed a significantly diminished prevalence for these autoantibody specificities (2/32 and 5/32, respectively, p < 0.05 for both). Anti-GP2 IgG were significantly more prevalent in CD patients with stricturing behaviour (B2) and perianal disease (7/11, p < 0.02) and less prevalent in those with penetrating behaviour (B3) and perianal disease (4/31, p < 0.05). The occurrence of anti-GP2 IgA and/or IgG was significantly more prevalent in CD patients with age at diagnosis of ≤16 years (16/31, p < 0.009). Prevalence of one or more anti-GP2 or ASCA IgA and/or IgG was significantly higher in L3, B2, and A1 and lower in L2 (68/113, 27/41, 23/31, 6/32; p < 0.04, respectively). CONCLUSIONS: Anti-GP2 IgG and IgA, constituting novel CD specific autoantibodies, appear to be associated with distinct disease phenotypes identifying patients at a younger age, with ileocolonic location, and stricturing behaviour with perianal disease.
Assuntos
Autoanticorpos/imunologia , Doença de Crohn/imunologia , Proteínas Ligadas por GPI/imunologia , Pâncreas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Criança , Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/imunologia , Doenças do Colo/sangue , Doenças do Colo/diagnóstico , Doenças do Colo/imunologia , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Feminino , Humanos , Doenças do Íleo/sangue , Doenças do Íleo/diagnóstico , Doenças do Íleo/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Saccharomyces cerevisiae/imunologia , Adulto JovemRESUMO
We report three cases of ileocolic mucormycosis in adult immunocompromised patients presenting as acute abdomen. All patients underwent laparotomy but two of them died from multiorgan failure before the diagnoses were confirmed. The diagnosis of gastrointestinal mucormycosis is rarely suspected, and antemortem diagnosis is made in only 25%-50% of cases. These cases illustrate the difficulty encountered by surgeons in managing acute abdomen in neutropenic patients with hematological malignancy. The management of colonic mucormycosis in the published literature is also reviewed.
Assuntos
Antineoplásicos/efeitos adversos , Doenças do Colo/diagnóstico , Neoplasias Hematológicas/terapia , Doenças do Íleo/diagnóstico , Hospedeiro Imunocomprometido , Mucormicose/diagnóstico , Abdome Agudo/imunologia , Abdome Agudo/microbiologia , Adulto , Idoso , Antifúngicos/uso terapêutico , Doenças do Colo/imunologia , Doenças do Colo/microbiologia , Doenças do Colo/terapia , Evolução Fatal , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/imunologia , Humanos , Doenças do Íleo/imunologia , Doenças do Íleo/microbiologia , Doenças do Íleo/terapia , Laparotomia , Masculino , Pessoa de Meia-Idade , Mucormicose/imunologia , Mucormicose/microbiologia , Mucormicose/terapia , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/microbiologia , Neutropenia/imunologia , Radioterapia Adjuvante/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The role of polymorphonuclear neutrophil granulocytes (PMNs) and the PMN-derived protease, which is called matrix metalloproteinase-9 (MMP-9), for the gut barrier dysfunction in severe acute pancreatitis (SAP) has not yet been clarified. The aim of this study was to evaluate the effects of PMNs and MMP-9 on gut barrier dysfunction in rat SAP. METHODS: SAP was induced by the injection of 5% sodium taurocholate, and anti-rat PMN serum or BB-94 were administered 48 h and 24 h, respectively, before the induction of acute pancreatitis. Twenty-four hours after the induction of acute pancreatitis, the gut barrier dysfunction and the incidence of bacterial translocation (BT) and PMN transmigration were investigated by bacterial, histologic, and biochemical (MPO) analysis. Inhibition of MMP-9 was achieved by depletion of PMNs or inhibition of MMP-activity by a broad-spectrum MMP inhibitor and confirmed by zymography. In addition, reactive oxygen species were evaluated by spin trap assay. RESULTS: The mucosal injury and the infiltration of PMNs into the gut tissue of rats with SAP were significantly increased in comparison with rats treated with anti-rat PMN serum or BB-94. The levels of MMP-9 and reactive oxygen species in the gut of rats with SAP were significantly higher than those of the rats treated with anti-rat PMN serum or BB-94. Pretreatment with anti-rat PMN serum or BB-94 reduced the incidence of BT in SAP. CONCLUSION: The incidence of BT in SAP was prevented by the depletion of PMNs or less pronounced by the injection of the MMP inhibitor BB-94. PMNs play an important pathophysiologic role in the occurrence of BT, and MMP-9 is involved in both BT and PMN transmigration in rat SAP.
Assuntos
Translocação Bacteriana , Doenças do Íleo/imunologia , Metaloproteinase 9 da Matriz/metabolismo , Neutrófilos/enzimologia , Pancreatite Necrosante Aguda/complicações , Animais , Doenças do Íleo/enzimologia , Doenças do Íleo/patologia , Doenças do Íleo/prevenção & controle , Íleo/imunologia , Íleo/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz , Naftol AS D Esterase , Infiltração de Neutrófilos , Pâncreas/patologia , Pancreatite Necrosante Aguda/enzimologia , Pancreatite Necrosante Aguda/imunologia , Pancreatite Necrosante Aguda/patologia , Peroxidase/análise , Fenilalanina/análogos & derivados , Fenilalanina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Ácido Taurocólico , Tiofenos/uso terapêuticoRESUMO
BACKGROUND: The serum markers ASCA and pANCA can help the clinician in certain difficult situations of colites in IBD. The aim of this study was to determine the sensitivity and the specificity of each one of these markers and to establish the characteristics of the positive patients for each one. METHODS: We included patients having a Crohn's disease (CD) or an ulcerative colitis (UC). These patients was compared to a control group. RESULTS: 80 CD patients with an average age of 35.62 years, 25 UC cases with an average age of 34.92 years and 79 healthy subjects with an average age of 34.2 years were included. The ASCA were detected in 33.8% of CD cases , 8% of UC cases of RCH and 2.5% of contro group (p < 000.1). The pANCA were detected in 48% of UC cases, 27.5% of CD patients and 1.3% of controls (p < 000.1). The sensitivity and the specificity of the ASCA and the pANCA for the diagnosis respectively of CD and UC were 33.8%, 97.5% and of 48%, 97.8%. During the CD, the positivity of the ASCA was significantly associated with ileal location (p = 0.001), with the sténosant and/or fistulisant phenotyp of the disease (p = 0.006), the young age at the time of the diagnosis of the CD (p = 0.067) and at a greater frequency of surgical treatment (p = 00.7). The pANCA were more frequently found in colic location of CD (p = 0.09). During UC, the positivity of the pANCA was not associated with the sex, age, loca tion of the disease, medical treatment nor chiurgical treatment. CONCLUSION: The ASCA and pANCA are useful during some clinical situations such as differentiation between IBD otherss colitis and to distinguish CD from UC.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Antifúngicos/sangue , Colite Ulcerativa/sangue , Doença de Crohn/sangue , Fatores Imunológicos/sangue , Mananas/imunologia , Saccharomyces cerevisiae/imunologia , Adulto , Fatores Etários , Biomarcadores/sangue , Colite Ulcerativa/classificação , Colite Ulcerativa/imunologia , Colite Ulcerativa/cirurgia , Constrição Patológica/sangue , Constrição Patológica/imunologia , Doença de Crohn/classificação , Doença de Crohn/imunologia , Doença de Crohn/cirurgia , Feminino , Humanos , Doenças do Íleo/sangue , Doenças do Íleo/imunologia , Fístula Intestinal/sangue , Fístula Intestinal/imunologia , Masculino , Mananas/sangue , Valor Preditivo dos Testes , Proctocolite/sangue , Sensibilidade e EspecificidadeAssuntos
Dor Abdominal/parasitologia , Anisaquíase/complicações , Anisakis/isolamento & purificação , Dor Abdominal/sangue , Dor Abdominal/terapia , Idoso , Animais , Anisaquíase/imunologia , Anisaquíase/terapia , Anisakis/imunologia , Anticorpos Anti-Helmínticos/sangue , Humanos , Doenças do Íleo/imunologia , Doenças do Íleo/parasitologia , Doenças do Íleo/terapia , Masculino , Recidiva , Gastropatias/imunologia , Gastropatias/parasitologia , Gastropatias/terapia , Resultado do TratamentoAssuntos
Doenças do Íleo/imunologia , Linfopenia/imunologia , Tuberculose Gastrointestinal/imunologia , Idoso , Linfócitos T CD4-Positivos , Criptococose/complicações , Feminino , Humanos , Doenças do Íleo/complicações , Pneumopatias Fúngicas/complicações , Linfopenia/complicações , Infecções Oportunistas/complicações , Tuberculose Gastrointestinal/complicações , Tuberculose Pulmonar/complicaçõesRESUMO
We investigated whether a lack of IL-10 production or responsiveness could be involved in Crohn's disease pathogenesis. Lamina propria mononuclear cells, isolated from the ilea of Crohn's disease patients (n = 16) and controls (n = 13), were activated with anti-CD3 mAb in the presence of CD80 transfectants or LPS +/- IFN-gamma. No evidence for deficient IL-10 production by either T cells or macrophages in Crohn's disease was found. However, the efficacy of rhIL-10 to down-regulate IFN-gamma and especially TNF production in cell cultures from the involved tissues of Crohn's disease patients was poor, and the use of an anti-IL-10R mAb even provided evidence for proinflammatory effects of IL-10. This lack of IL-10 effect possibly results from IL-12 activity. We conclude that IL-10 exhibits poor anti- and even potential proinflammatory effects on ileal Crohn's disease lamina propria. These data might explain the lack of therapeutic efficacy when IL-10 is given to Crohn's disease patients.
Assuntos
Anti-Inflamatórios não Esteroides/metabolismo , Doença de Crohn/imunologia , Doenças do Íleo/imunologia , Interleucina-10/metabolismo , Células Cultivadas , Doença de Crohn/etiologia , Interações Medicamentosas , Humanos , Doenças do Íleo/etiologia , Interferon gama/metabolismo , Interleucina-12/metabolismo , Interleucina-12/farmacologia , Interleucina-2/farmacologia , Interleucina-4/farmacologia , Macrófagos/imunologia , Receptores de Interleucina/metabolismo , Receptores de Interleucina-10 , Linfócitos T/citologia , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: Selected mechanisms of the immune system participate in the development of inflammatory bowel disease. Recently, overexpression of the ligand for CD40 (CD40L), a lymphocyte costimulatory molecule, was shown to induce severe inflammatory bowel disease in transgenic mice. In the present study, we examined the expression of CD40 and CD40L on surgical specimens of ileum from 12 patients with Crohn's disease and 10 patients with diverticulitis. METHODS: Several CD40L+ cells were present in the affected tissue of patients with Crohn's disease, whereas few scattered CD40L+ cells were detected in sections of histologically normal ileum, resected distantly from the affected tissue, in patients with diverticulitis and in normal ileum portions obtained from colorectal cancer undergoing extensive surgery. The phenotype of CD40L+ cells was mainly CD4+. RESULTS: In patients with Crohn's disease, several CD40+ cells were detectable in the same areas of lymphocytes expressing CD40L, whereas in patients with diverticulitis, the number of CD40+ cells was significantly lower. Most of the CD40+ cells costained with CD20, thus showing to be B-lymphocytes, and only a few were CD14+ macrophages. Several von Willebrand-positive vessels were also positive for CD40. In addition, several infiltrating macrophages were found to express B7-1 and B7-2 molecules, the ligands of CD28 and CTLA-4, which cooperate with the CD40-CD40L pathway in lymphocyte activation. Staining of ileal lesions with anti-CTLA-4 antibodies resulted in detection of none or very few positive cells. In contrast, in patients with diverticulitis, an enhanced number of B7-1 and B7-2 and CTLA-4 was observed. CONCLUSION: The local accumulation of CD40L+ together with CD40+ cells within intestinal lesions of Crohn's disease suggests the involvement of this co-stimulatory pathway.