RESUMO
Macrophage migration inhibitory factor (MIF) is involved in eosinophil biology and in type 2 inflammation, contributing to allergic and helminthic diseases. We hypothesized that MIF participates in the pathogenesis of eosinophilic esophagitis (EoE), an allergic condition characterized by esophageal eosinophilic inflammation. MIF is highly expressed in esophageal mucosa of patients with EoE, compared with gastro-esophageal reflux disease and control patients, where it co-localizes predominantly with eosinophils. In vitro, recombinant MIF promotes human eosinophil chemotaxis, while MIF antagonist and CXCR4 antagonist, AMD3100, revert this effect. In a model of EoE induced by ovalbumin, Mif-deficient mice have reduced inflammation and collagen deposition compared with wild-type (WT) mice. Importantly, treatment of WT mice with anti-MIF or with AMD3100 during the challenge phase prevents accumulation of eosinophils and tissue remodeling. Conversely, recombinant MIF promoted tissue eosinophil inflammation in allergic mice. Together, these results implicate MIF in the pathogenesis of esophageal inflammation and suggest that targeting MIF might represent a novel therapy for EoE.
Assuntos
Esofagite Eosinofílica/imunologia , Eosinófilos/imunologia , Oxirredutases Intramoleculares/imunologia , Fatores Inibidores da Migração de Macrófagos/imunologia , Adolescente , Adulto , Animais , Benzilaminas , Ciclamos , Esofagite Eosinofílica/genética , Esofagite Eosinofílica/patologia , Esofagite Eosinofílica/terapia , Eosinófilos/patologia , Feminino , Compostos Heterocíclicos/farmacologia , Humanos , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Mucosa/imunologia , Mucosa/patologia , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/genética , Receptores CXCR4/imunologiaRESUMO
BACKGROUND: To describe clinical, laboratorial, radiological, and histopathological lung findings from necroscopy of aidetic children with pulmonary disease. MATERIAL AND METHODS: Fourteen children admitted at the Hospital Universitário Antônio Pedro - Universidade Federal Fluminense, Niterói, RJ, and Instituto de Puericultura e Pediatria Martagão Gesteira - Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, between 1989 and 1996, were revised in a retrospective survey. RESULTS: Eight were males (57%). The median age was 1.2 years old (from three months to nine years). Nine children (64.4%) were younger than 24 months old. The HIV transmission was vertical in 10 (71%) children. In these cases, five mothers were contaminated from heterosexual relations. Pneumonia (n=8), oral candidiasis (n=8), and diarrhea (n=5) were the most common previous conditions. The most frequent signs and symptoms on admission were fever (n=12), respiratory distress (n=10), cough (n=10), peripheral lymphadenopathy (n=11), hepatomegaly and/or splenomegaly (n=10), and malnutrition (n=9). The chest x-rays findings were condensation (n=5) and diffuse infiltrates (n=6) patterns. The microscopic lung characteristics were compatibles with pneumonia by cytomegalovirus (CMV) (n=9), bacteria (n=8), Pneumocystis carinii (n=3), Toxoplasma gondii (n=1), Hystoplasma capsulatum (n=1) and Lymphocytic interstitial pneumonia (n=1). The association between CMV and bacteria was observed in six cases. CONCLUSIONS: Age less than two years old, vertical transmission, inespecific clinical presentation of pneumonia, and infiltrates and condensation patterns at the x-rays were the predominant characteristics. Cytomegalovirus and bacteria were the most common etiologic agents, being their association frequent. Lymphocytic interstitial pneumonia and pneumonia by P. carinii were not common causes of pulmonary disease.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/patologia , Síndrome da Imunodeficiência Adquirida/patologia , Pneumonia Bacteriana/patologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/transmissão , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pneumonia Bacteriana/microbiologia , Estudos RetrospectivosRESUMO
OBJETIVOS: Descrever os aspectos clínicos, laboratoriais, radiológicos e anatomopatológicos encontrados em tecidos pulmonares de necrópsias de crianças com Aids e acometimento pulmonar. MÉTODOS: Foram revisados, retrospectivamente, prontuários, radiografias simples de tórax e laudos de necrópsias de 14 crianças com Aids e acometimento pulmonar. RESULTADOS: Oito casos eram do sexo masculino e seis do feminino. As idades variaram de três meses a nove anos, mediana de 1,2, sendo nove deles menores de dois anos. A transmissäo foi vertical em 10 pacientes, dos quais cinco mäes tinham história de contaminaçäo por relaçäo heterossexual; três, por hemotransfusäo e em duas, ignorada. Pneumonia (n=8), candidíase oral (n=8) e diarréia (n=5) foram as doenças prévias mais referidas. Os sinais e sintomas observados à internaçäo foram febre (n=12), dispnéia (n=10), tosse (n=11), linfoadenomegalia (n=11), hepato e/ou esplenomegalia (n=10), desnutriçäo (n=9), palidez (n=8), cianose (n=5) e baqueteamento digital (n=2). Os achados radiológicos mais comuns foram infiltrados difusos (n=6) e condensaçöes (n=5). As alteraçöes histológicas pulmonares foram compatíveis com pneumonia pelo citomegalovírus (n=9), por bactérias (n=8), por Pneumocystis carinii (n=3), por Hystoplasma capsulatum (n=1), por Toxoplasma gondii (n=1) e pneumonia intersticial linfocítica (n=1). A associaçäo CMV e bactéria foi observada em seis casos. CONCLUSÖES: Houve predomínio de menores de dois anos, de transmissäo vertical, de quadro clínico inespecífico de doença pulmonar e de infiltrados e condensaçöes à radiografia. Citomegalovírus e bactérias foram os agentes mais comuns, sendo freqüente a sua associaçäo. Pneumonia Intersticial Linfocítica e Pneumonia pelo P. carinii näo foram causas freqüentes de doenças pulmonares
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Infecções Oportunistas Relacionadas com a AIDS , Pneumonia Bacteriana , Síndrome da Imunodeficiência Adquirida/patologia , Estudos Retrospectivos , Pneumonia Bacteriana , Síndrome da Imunodeficiência Adquirida/transmissãoRESUMO
Formerly considered rare, adenocarcinoma has become the commonest form of primary lung cancer in developed countries. Its clinical presentation has changed, with central tumors becoming more frequent. We reviewed all biopsies with a diagnosis of primary lung cancer obtained from October 1988 to April 1997 in a tertiary care hospital in Rio de Janeiro. Medical records from adenocarcinomas were analysed. Adenocarcinoma was the commonest form of lung cancer (168/409, 41%). Central tumors were observed in 43% according to radiological criteria and 47% according to bronchoscopic criteria. The frequency and clinical presentation of adenocarcinoma have evolved lately in Rio de Janeiro.
Assuntos
Adenocarcinoma/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Broncoscopia , Carcinoma de Células Grandes/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Fumar/epidemiologia , População UrbanaRESUMO
Forty-five patients with systemic lupus erythematosus (SLE) underwent a cross-sectional study to evaluate intestinal secretory immunity. Peroral jejunal biopsy with histologic and immunohistochemical assessment of the mucosa were carried out in the patients and in 12 healthy volunteers. It was observed that an altered pattern of immunoglobulin-bearing plasma cells distributed in the lamina propria and complementary components were invariably present, mainly in the patients with active disease. The basement membrane of the intestinal crypt epithelium exhibited immunoglobulin and complementary deposits, similar to the lupus band test. None of the immunologic findings correlated with the medical treatment and with the peripheral blood analysis. The local changes in humoral immunity in patients with SLE did not correlate with gastrointestinal symptoms and may reflect the systemic effects of the disease.
Assuntos
Mucosa Intestinal/patologia , Jejuno/patologia , Lúpus Eritematoso Sistêmico/imunologia , Adolescente , Adulto , Formação de Anticorpos , Membrana Basal/patologia , Estudos Transversais , Feminino , Imunofluorescência , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Mucosa Intestinal/metabolismo , Jejuno/metabolismo , Pessoa de Meia-IdadeRESUMO
PURPOSE: To develop a stereological comparison between right (RV) and left ventricle (LV) myocardium during the third human gestational trimester. METHODS: Five human fetal hearts of the third trimester provided representative samples of 5 RV myocardium and 4 LV myocardium. The material was fixed in 10% buffered formaldehyde, and processed through routine methods. Fifteen microscopic fields were randomly chosen and counted in each ventricular myocardium using an "M-42" test system. The following stereological parameters were assessed: Vv (%), Lv (micron 2), Sv (micron 2/micron 3), Vp (micron 3), Nv (1/mm3) and total N. RESULTS: No significant difference between the stereological parameters of the myocardial structures assessed was evidenced, when comparing RV and LV. CONCLUSION: Right and left human ventricular myocardium are very similar during the fetal period at least in regard to their structural aspects.
Assuntos
Coração Fetal/embriologia , Feminino , Coração Fetal/anatomia & histologia , Ventrículos do Coração/embriologia , Humanos , Gravidez , Terceiro Trimestre da GravidezRESUMO
beta-Myrcene (MYR) is a monoterpene found in the oils of a variety of aromatic plants including lemongrass, verbena, hop, bay, and others. MYR and essential oils containing this terpenoid compound are used in cosmetics, household products, and as flavoring food additives. This study was undertaken on investigate the effects of MYR on fertility and general reproductive performance in the rat. MYR (0, 100, 300 and 500 mg/kg) in peanut oil was given by gavage to male Wistar rats (15 per dose group) for 91 days prior to mating and during the mating period, as well as to females (45 per dose group) continuously for 21 days before mating, during mating and pregnancy, and throughout the period of lactation up to postnatal day 21. On day 21 of pregnancy one-third of the females of each group were submitted to cesarean section. Resorption, implantation, as well as dead and live fetuses were counted. All fetuses were examined for external malformations, weighed, and cleared and stained with Alizarin Red S for skeleton evaluation. The remaining dams were allowed to give birth to their offspring. The progeny was examined at birth and subsequently up to postnatal day 21. Mortality, weight gain and physical signs of postnatal development were evaluated. Except for an increase in liver and kidney weights, no other sign of toxicity was noted in male and female rats exposed to MYR. MYR did not affect the mating index (proportion of females impregnated by males) or the pregnancy index (ratio of pregnant to sperm-positive females). No sign of maternal toxicity and no increase in externally visible malformations were observed at any dose level. Only at the highest dose tested (500 mg/kg) did MYR induce an increase in the resorption rate and a higher frequency of fetal skeleton anomalies. No adverse effect of MYR on postnatal weight gain was noted but days of appearance of primary coat, incisor eruption and eye opening were slightly delayed in the exposed offspring. On the basis of the data presented in this paper the no-observed-adverse-effect level (NOAEL) for toxic effects on fertility and general reproductive performance can be set at 300 mg of beta-myrcene/kg body weight by the oral route.
Assuntos
Fertilidade/efeitos dos fármacos , Aditivos Alimentares/farmacologia , Monoterpenos , Prenhez/efeitos dos fármacos , Terpenos/farmacologia , Monoterpenos Acíclicos , Análise de Variância , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Feminino , Feto/efeitos dos fármacos , Masculino , Óleos Voláteis/farmacologia , Gravidez , Ratos , Ratos Wistar , Reprodução/efeitos dos fármacos , Espermatozoides/efeitos dos fármacosRESUMO
Beta-Myrcene (MYR) is a monoterpene found in the oils of a variety of aromatic plants including lemongrass, verbena, hop, bay, and others. MYR and essential oils containing this terpenoid compound are used in cosmetics, household products, and as flavoring food additives. This study was undertaken to investigate the effects of MYR on fertility and general reproductive performance in the rat. MYR (0, 100, 300 and 500 mg/kg) in peanut oil was given by gavage to male Wistar rats (15 per dose group) for 91 days prior to mating and during the mating period, as well ass to females (45 per dose group) continuously for 21 days before mating, during mating and pregnancy, and throughout the period of lactatiomn up to postnatal day 21. On day 21 of pregnancy one-third of the females of each group were submitted to cesarean section. Resorption, implantation, as well as dead and live fetuses were counted. All fetuses were examined for external malformation, weighed, and cleared and stained with Alizarin Red S for skeleton evaluation. The remaining dams were allowed to give birth to their offspring. The progeny was examined at birth and subsequently up to postnatal day 21. Mortality, weight gain and physical signs of postnatal development were evaluated. Except for an increase in liver and kidney weights, no other sign of toxicity was noted in male and female rats exposed to MYR. MYR did not affect the mating index (proportion of females impregnated by males) or the pregnancy index (ratio of pregnant to sperm-positive females). No sign of maternal toxicity and no increase in externally visible malformations were observed at any dose level. Only at the highest dose tested (500 mg/kg) did MYR induce an increase in the resorption rate and a higher frequency of fetal skeleton anomalies. No adverse effect of MYR on postnatal weight gain was noted but days of appearance of primary coat, incisor eruption and eye opening were slightly delayed in the exposed offspring. On the basis of the data presented in this paper the no-observed-adverse-effect level (NOAEL) for toxic effects on fertility and general reproductive performance can be set at 300 mg of Beta-myrcene/kg body weight by the oral route.
Assuntos
Animais , Feminino , Gravidez , Fertilidade/efeitos dos fármacos , Aditivos Alimentares/farmacologia , Prenhez/efeitos dos fármacos , Terpenos/farmacologia , Análise de Variância , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Desenvolvimento Fetal/efeitos dos fármacos , Feto/efeitos dos fármacos , Óleos Voláteis/farmacologia , Ligação do Par , Ratos Wistar , Reprodução/efeitos dos fármacos , Espermatozoides/efeitos dos fármacosRESUMO
Bronchial biopsies of 21 patients with lung cancer were analyzed by Western blot for stress protein HSP70 and p53 proteins. Squamous carcinoma was the most common type found. The p53 protein was detectable in 14 cases. The HSP70 was detectable in 17 and overexpressed in 9 patients. Eleven patients showed positivity for both protein expressions, however no statistical significance was found (Kappa's test, p>0.05). Specific associations were not observed for HSP70 overexpression and p53 detection that could be related to clinical finds or tabagism. Our results indicate that the stress protein HSP70 is detectable and may be involved in the tumor development.
RESUMO
OBJECTIVE: The objective of this study was to examine mononuclear cell subpopulations and evidence of cellular activation in unaffected jejunal mucosa in Crohn's disease. DESIGN: A cross-sectional study was performed in patients with Crohn's disease from the ambulatory unity of the University Hospital, UFRJ. METHODS: Mucosal samples from 20 patients with Crohn's colitis or ileitis were obtained by peroral jejunal biopsy. Patients with jejunal involvement or pregnant women were excluded from the study. Specimens were analysed histologically and by indirect immunoperoxidase method using anti-monoclonal antibodies to CD2, CD4, CD8, CD25, CD45RO, RFDR1, RFD1 and RFD7 by two 'blind' observers. Seven patients with non-inflammatory bowel disorders and two healthy volunteers were studied as controls. RESULTS: Lamina propria CD2-positive (CD2+) cells were reduced in Crohn's disease (P < 0.004) whether clinically active (P < 0.02) or clinically inactive (P < 0.008). CD4+ and CD8+ cells were also reduced in Crohn's disease (P < 0.003), whereas the CD4:CD8 ratio did not differ from that in controls. CD25+, CD45RO+ and HLA-DR+ cells were not significantly increased in patients with Crohn's disease. RFD7+ cells were decreased in Crohn's disease (P < 0.02), whereas RFD1+ cells were not significantly different from the control group. CONCLUSION: No evidence of cellular activation was found in the unaffected mucosa of Crohn's disease. The reduction in T-cell and macrophage-like cell numbers may result from cell migration to inflamed areas. It is also possible that this finding represents a primary defect which may have a role in the pathogenesis of Crohn's disease.