A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1β immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.

Study of tissue inflammatory response in different mice strains infected by dematiaceous fungi Fonsecaea pedrosoi

Abstract: Background: Diseases caused by melanized fungi include mycetoma, chromoblastomycosis and phaeohyphomycosis. This broad clinical spectrum depends on the dynamic interactions between etiologic agent and host. The immune status of the host influences on the development of the disease, as, an exemple. phaeohyphomicosis is more frequently observed in immunocompromised patients. Objectives: Examine the histological inflammatory response induced by Fonsecaea pedrosoi in several different strains of mice (BALB/c, C57BL/6, Nude and SCID, and reconstituted Nude). Methods: Fonsecaea pedrosoi was cultivated on agar gel and a fragment of this gel was implanted subcutaneously in the abdominal region of female adult mice. After infection has been obtained, tissue fragment was studied histopathologically. Results: There were significant changes across the strains, with the nodular lesion more persistent in Nude and SCID mice, whereas in immunocompetent mice the lesion progressed to ulceration and healing. The histopathological analysis showed a significant acute inflammatory reaction which consisted mainly of neutrophils in the initial phase that was subsequently followed by a tuberculoid type granuloma in immunocompetent mice. Study limitations: There is no a suitable animal model for chromoblastomycosis. Conclusions: The neutrophilic infiltration had an important role in the containment of infection to prevent fungal spreading, including in immunodeficient mice. The fungal elimination was dependent on T lymphocytes. The re-exposure of C57BL/6 mice to Fonsecaea pedrosoi caused a delay in resolving the infection, and appearance of muriform cells, which may indicate that re-exposure to fungi, might lead to chronicity of infection.

Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation

Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association.

Consumo de bebidas alcoólicas e direção de veículos nas capitais brasileiras e no Distrito Federal, segundo dois inquéritos nacionais de saúde / Alcohol consumption and driving in Brazilian capitals and Federal District according to two national health surveys

RESUMO: Objetivo Apresentar os resultados dos indicadores sobre consumo de álcool e direção para as capitais brasileiras obtidos em dois inquéritos populacionais realizados em 2013 no Brasil. Métodos: Estudo transversal realizado com dados da população adulta (≥ 18 anos) participante da Vigilância de Doenças Crônicas por Inquérito Telefônico (Vigitel) e da Pesquisa Nacional de Saúde (PNS). Foram calculadas as prevalências para os indicadores de consumo de bebida alcoólica e direção veicular. Resultados: A proporção de motoristas adultos de carro ou moto que dirigiram logo depois de beber foi significativamente maior no sexo masculino (29,3% - Vigitel; 24,4% - PNS), entre jovens de 18 a 29 anos (31,6% - Vigitel; 24,1% - PNS) e entre os residentes das capitais da Região Centro-Oeste (33,7% - Vigitel; 28,3% - PNS). A proporção de adultos que referiram beber e dirigir foi maior no sexo masculino (9,4% - Vigitel; 7,4% - PNS), no grupo de 18 a 29 anos (7,1% - Vigitel; 4,5% - PNS) e entre os residentes das capitais da Região Centro-Oeste (7,9% - Vigitel; 6,1% - PNS). Conclusão: O estudo permitiu estimar a prevalência do hábito de dirigir após ingestão de bebida alcoólica entre motoristas e na população em geral e mostrou coerência entre os resultados dos dois inquéritos epidemiológicos de abrangência nacional.

ABSTRACT: Objective: To present the results of indicators of alcohol consumption and driving for Brazilian capitals based on two population surveys performed in Brazil in 2013. Methods: Cross sectional study with data from adults (≥ 18 years) participants of the Telephone Survey on Risk and Protective Factors for Chronic Diseases (Vigitel) and the National Health Survey (NHS). Prevalence for indicators of alcohol consumption and driving was then calculated. Results: The proportion of adult drivers who drove soon after drinking was significantly higher among males (29.3% - Vigitel and 24.4% - NHS), the young aging 18 to 29 years (31.6% - Vigitel and 24.1% - NHS) and among residents of the capitals of the Midwest (33.7% - Vigitel and 28.3% - NHS). The proportion of adults who reported drinking and driving was higher among males (9.4% - Vigitel and 7.4% - NHS) in the 18 to 29 age group (7.1% - Vigitel; 4.5% - NHS), and among residents of the capitals of the Midwest (7.9% - Vigitel and 6.1% - NHS). Conclusion: The study estimated the prevalence of the habit of driving after alcohol consumption among drivers and in the general population. There was consistency between the results from two nationwide surveys.

Evaluation of Nosocomial Infection Control Programs in health services / Avaliação dos Programas de Controle de Infecção Hospitalar em serviços de saúde / Evaluación de los Programas de Control de Infección Hospitalaria en servicios de salud

OBJECTIVES: to evaluate the Nosocomial Infection Control Programs in hospital institutions regarding structure and process indicators. METHOD: this is a descriptive, exploratory and quantitative study conducted in 2013. The study population comprised 13 Nosocomial Infection Control Programs of health services in a Brazilian city of the state of São Paulo. Public domain instruments available in the Manual of Evaluation Indicators of Nosocomial Infection Control Practices were used. RESULTS: The indicators with the highest average compliance were "Evaluation of the Structure of the Nosocomial Infection Control Programs" (75%) and "Evaluation of the Epidemiological Surveillance System of Nosocomial Infection" (82%) and those with the lowest mean compliance scores were "Evaluation of Operational Guidelines" (58.97%) and "Evaluation of Activities of Control and Prevention of Nosocomial Infection" (60.29%). CONCLUSION: The use of indicators identified that, despite having produced knowledge about prevention and control of nosocomial infections, there is still a large gap between the practice and the recommendations. .

OBJETIVOS: avaliar os Programas de Controle de Infecção Hospitalar nas instituições hospitalares, quanto aos indicadores de estrutura e processo. MÉTODO: trata-se de um estudo descritivo, exploratório e quantitativo, realizado em 2013. A população foi composta por 13 Programas de Controle de Infecção Hospitalar de serviços de saúde, de uma cidade brasileira do interior paulista. Foram utilizados instrumentos de domínio público, disponibilizados no Manual de Indicadores de Avaliação de Práticas de Controle de Infecção Hospitalar. RESULTADOS: os indicadores com maior média de conformidade foram "Avaliação da Estrutura dos Programas de Controle de Infecção Hospitalar" (75%) e "Avaliação do Sistema de Vigilância Epidemiológica de Infecção Hospitalar" (82%) e os com menores médias foram "Avaliação das Diretrizes Operacionais" (58,97%) e "Avaliação das Atividades de Controle e Prevenção de Infecção Hospitalar" (60,29%). CONCLUSÃO: o uso de indicadores identificou que, apesar do conhecimento produzido sobre ações de prevenção e controle de infecções hospitalares, ainda existe um grande hiato entre prática e recomendações. .

OBJETIVOS: evaluar los Programas de Control de Infección Hospitalaria en las instituciones hospitalarias respecto a los indicadores de estructura y proceso. MÉTODO: se trata de un estudio descriptivo, exploratorio y cuantitativo, desarrollado en 2013. La población fue compuesta por 13 Programas de Control de Infección Hospitalaria de servicios de salud de una ciudad brasileña del interior paulista. Fueron utilizados instrumentos de dominio público, disponibles en el Manual de Indicadores de Evaluación de Prácticas de Control de Infección Hospitalaria. RESULTADOS: los indicadores con mayor promedio de conformidad fueron "Evaluación de la Estructura de los Programas de Control de Infección Hospitalaria" (75%) y "Evaluación del Sistema de Vigilancia Epidemiológica de Infección Hospitalaria" (82%) y aquellos con menores promedios "Evaluación de las Directivas Operacionales" (58,97%) y "Evaluación de las Actividades de Control y Prevención de Infección Hospitalaria" (60,29%). CONCLUSIÓN: el uso de indicadores posibilitó identificar que, a pesar del conocimiento producido sobre acciones de prevención y control de infecciones hospitalarias, todavía existe un gran hiato entre la práctica y las recomendaciones. .

Percepção dos idosos jovens e longevos gaúchos quanto aos espaços públicos em que vivem / The perception of the young and long-lived elderly ‘Gauchos’ (from the State of Rio Grande do Sul, Brazil) about the public spaces they live in Resumo

Em 2050, o número de brasileiros residindo em áreas urbanas passará dos 200 milhões e 29% da população será composta por idosos. Os idosos longevos possuem 80 anos ou mais, os idosos jovens são aqueles que apresentam idade entre 60 e 79 anos. O objetivo foi verificar a diferença da percepção de idosos jovens e longevos do Rio Grande do Sul quanto ao ambiente urbano em que vivem. Estudo de base populacional, observacional, descritivo, retrospectivo, com paradigma de análise quantitativa, analisou dados da pesquisa Perfil dos Idosos do RS, realizado pelo Instituto de Geriatria e Gerontologia da PUCRS em parceria com a Escola de Saúde Pública do RS. A amostra foi composta por 6913 questionários respondidos por idosos de 59 cidades. A análise dos dados foi realizada com cada um dos grupos etários e as variáveis independentes foram testadas pelo Qui-Quadrado, sendo o nível de significância menor que 0,05. Como resultado, a percepção de dificuldades, como poucos bancos, falta de faixas de segurança, tempo de sinal muito curto para pedestres, degraus muito altos e mau cheiro dos banheiros públicos, foi maior entre os idosos jovens. Os idosos longevos perceberam menos esses fatores, porém, referiram que frequentam menos os ambientes comunitários.

By 2050, the number of Brazilians living in urban areas will be over 200 million and 29% of the population will be elderly. The long-lived elderly are 80 or more years old and the young elderly are between 60 and 79 years of age. The scope of this article was to verify the difference in perception between the young elderly and the long-lived elderly from Rio Grande do Sul (RS) about the urban environment they live in. This is a population-based, observational, descriptive, retrospective study with a quantitative analysis paradigm. Data was analyzed from Elderly Profile research in RS conducted by the Geriatric and Gerontological Institute of PUCRS in partnership with the RS School of Public Health. The sample consisted of 6913 questionnaires answered by the elderly from 59 cities. Data analysis was performed for each age group and independent variables were processed using the Chi-square test, with p under 0.05. Results showed that the perception of difficulties such as a lack of park benches and safety strips, short traffic light times for pedestrians, high steps and bad-smelling public toilets was greater among the young elderly. The long-lived elderly noticed these facts less, though they admitted that they frequent community environments less often.

Marcadores inflamatórios e perfusionais como preditores e fatores de risco para readmissão de pacientes gravemente enfermos / Inflammatory and perfusion markers as risk factors and predictors of critically ill patient readmission

Objetivo: Avaliar o desempenho da saturação venosa central, lactato, défice de bases, níveis de proteína C-reativa, escore SOFA e SWIFT do dia da alta da unidade de terapia intensiva como preditores para readmissão de pacientes na unidade de terapia intensiva. Métodos: Estudo prospectivo observacional com dados coletados de 1.360 pacientes internados consecutivamente no período de agosto de 2011 a agosto de 2012 em uma unidade de terapia intensiva clínico-cirúrgica. Foram comparadas as características clínicas e os dados laboratoriais dos pacientes readmitidos e dos pacientes não readmitidos após a alta da unidade de terapia intensiva. Por meio de análise multivariada, foram identificados os fatores de risco independentemente associados à readmissão. Resultados: A proteína C-reativa, a saturação venosa central, o défice de bases, o lactato, os escores SOFA e o SWIFT não foram associados à readmissão de pacientes graves. Pacientes mais idosos e a necessidade de isolamento de contato devido a germes multirresistentes foram identificados como fatores de risco independentemente associados à readmissão na população estudada. Conclusão: Os parâmetros inflamatórios e perfusionais não foram associados à readmissão. Idade e necessidade de isolamento de contato devido a germes multirresistentes foram identificados como preditores para readmissão na unidade de terapia intensiva. .

Objective: To assess the performance of central venous oxygen saturation, lactate, base deficit, and C-reactive protein levels and SOFA and SWIFT scores on the day of discharge from the intensive care unit as predictors of patient readmission to the intensive care unit. Methods: This prospective and observational study collected data from 1,360 patients who were admitted consecutively to a clinical-surgical intensive care unit from August 2011 to August 2012. The clinical characteristics and laboratory data of readmitted and non-readmitted patients after discharge from the intensive care unit were compared. Using a multivariate analysis, the risk factors independently associated with readmission were identified. Results: The C-reactive protein, central venous oxygen saturation, base deficit, and lactate levels and the SWIFT and SOFA scores did not correlate with the readmission of critically ill patients. Increased age and contact isolation because of multidrug-resistant organisms were identified as risk factors that were independently associated with readmission in this study group. Conclusion: Inflammatory and perfusion parameters were not associated with patient readmission. Increased age and contact isolation because of multidrug-resistant organisms were identified as predictors of readmission to the intensive care unit. .

Alterações anatomopatológicas de corações de pacientes chagásicos portadores de marcapasso definitivo endocárdico / Anatomopathological changes in hearts of Chagas disease patients with permanent endocardial pacemakers

OBJETIVO: Descrever as lesões morfológicas, macro e microscópicas, associadas ao marcapasso definitivo (MP) em corações de pacientes falecidos com cardiopatia chagásica crônica e compará-las com as descritas em outras cardiopatias. MÉTODO: Foram estudados 22 corações de pacientes chagásicos crônicos (16 homens e seis mulheres) de 26 a 86 anos de idade (média de 54 anos) portadores de MP definitivo endocárdico. Foram retirados fragmentos das paredes das quatro câmaras, do septo interventricular e da ponta cardíaca, bem como de tecidos que envolviam os cabos-eletrodos e de áreas de aderências para processamento histológico. As características do exsudato leucocitário nos sítios de implante e no miocárdio ventricular foram analisadas por meio da técnica de imuno-histoquímica. RESULTADOS: Inflamação e trombose nos sítios de implante resultaram em encapsulamento fibroso das pontas dos cabos-eletrodos que permaneceram firmemente aderidos ao endocárdio adjacente. Nos sítios de implante, linfócitos B e T ocorreram em proporções semelhantes, diferentemente dos focos da miocardite chagásica ventricular, na qual foi observado marcante predomínio de linfócitos T. CONCLUSÃO: Os cabos-eletrodos não são estruturas biologicamente inertes; sua permanência produz constante estímulo trombogênico, assim como processo inflamatório e fibrogênico nos sítios dos implantes. A organização de trombos vermelhos e/ou de fibrina que se formam em torno dos cabos-eletrodos parece responsável por seu encapsulamento e por frequentes aderências às estruturas adjacentes. As lesões cardíacas associadas aos MP na cardiopatia chagásica crônica dos casos estudados foram semelhantes às descritas em outras cardiopatias.

Objective: Describe morphologic, macro and microscopic lesions associated with permanentpacemaker (PM) in hearts of patients who died with chronic Chagas disease and compare them with those reportedin other heart diseases. Methods: Twenty-two hearts of chronic chagasic patients (16 mean and six women) from26 to 86 years of age (mean 54 years) with a permanent endocardial PM were studied. Fragments representing thewalls of four the chambers, the ventricular septum and the tip of the heart as well as tissue involving the leads and areas of adhesions were obtained for histological processing. The characteristics of leukocyte exudates leukocyte inimplant sites and the ventricular myocardium were analyzed by immunohistochemistry. Results: Inflammationand thrombosis at the site of implantation resulted in fibrous encapsulation of the tips of the electrode leadsthat remained firmly adhered to the adjacent endocardium. At the site of implantation, B and T lymphocytesoccurred in similar proportions, unlike ventricular chagasic myocarditis areas, where a large predominance ofT lymphocytes was observed. Conclusion: The leads are not biologically inert structures, their permanenceproduces constant thrombogenic stimulation, as well as thrombogenic and fibrogenic inflammatory process in thesites of the implants. The organization of red thrombi and/or fibrin formed around the electrode leads seems to beresponsible for the encapsulation and frequent adhesions to adjacent structures. Cardiac lesions associated PM inchronic Chagas disease in the studied cases were similar to those described in other heart diseases.

Objetivo: Describir las lesiones morfológicas, macro y microscópicas, asociadas con marcapasosdefinitivo (MP) en corazones de pacientes fallecidos con cardiopatía chagásica crónica y compararlas con lasdescritas en otras cardiopatías. Métodos: Fueron estudiados 22 corazones de pacientes chagásicos crónicos (16hombres y seis mujeres) de 26 a 86 años de edad (promedio de 54 años) portadores de MP definitivo endocárdico.Fueron retirados fragmentos de las paredes de las cuatro cámaras, del tabique interventricular y la punta cardiaca,así como de tejidos que envolvían los cables-electrodos y de áreas de adherencias para procesamiento histológico.Las características del exudado leucocitario en los sitios de implante y el miocardio ventricular fueron analizadaspor medio de la técnica de inmunohistoquímica. Resultados: Inflamación y trombosis en los sitios de implanteresultaron en encapsulamiento fibroso de las puntas de los cables-electrodos que permanecieron firmementeadheridos al endocardio adyacente. En los sitios de implante, linfocitos B y T ocurrieron en proporcionessemejantes, diferentemente de los focos de la miocarditis chagásica ventricular en la que se observó distintivopredominio de linfocitos T. Conclusión: Los cables-electrodos no son estructuras biológicamente inertes; supermanencia produce constante estímulo trombogénico, así como proceso inflamatorio y fibrogénico en los sitiosde los implantes. La organización de trombos rojos y/o fibrina que se forman alrededor de los cables-electrodosparece responsable de su encapsulamiento y las frecuentes adherencias a las estructuras adyacentes. Las lesionescardiacas asociadas con los MP en la cardiopatía chagásica crónica de los casos estudiados fueron semejantes a lasdescritas en otras cardiopatías.

Inflammation in disseminated lesions: an analysis of CD4+, CD20+, CD68+, CD31+ and vW+ cells in non-ulcerated lesions of disseminated leishmaniasis

Disseminated leishmaniasis (DL) differs from other clinical forms of the disease due to the presence of many non-ulcerated lesions (papules and nodules) in non-contiguous areas of the body. We describe the histopathology of DL non-ulcerated lesions and the presence of CD4-, CD20-, CD68-, CD31- and von Willebrand factor (vW)-positive cells in the inflamed area. We analysed eighteen biopsies from non-ulcerated lesions and quantified the inflamed areas and the expression of CD4, CD20, CD68, CD31 and vW using Image-Pro software (Media Cybernetics). Diffuse lymphoplasmacytic perivascular infiltrates were found in dermal skin. Inflammation was observed in 3-73% of the total biopsy area and showed a significant linear correlation with the number of vW+ vessels. The most common cells were CD68+ macrophages, CD20+ B-cells and CD4+ T-cells. A significant linear correlation between CD4+ and CD20+ cells and the size of the inflamed area was also found. Our findings show chronic inflammation in all DL non-ulcerated lesions predominantly formed by macrophages, plasmacytes and T and B-cells. As the inflamed area expanded, the number of granulomas and extent of the vascular framework increased. Thus, we demonstrate that vessels may have an important role in the clinical evolution of DL lesions.

Inflamação esclerosante idiopática da órbita: estudo clinico-patológico / Idiopathic sclerosing orbital inflammation: clinicopathologic study

OBJETIVO: Descrever oito casos de inflamação esclerosante idiopática da órbita, incluindo a análise clínica e histopatológica. MÉTODOS: Estudo retrospectivo através do livro de registros do Laboratório de Patologia Ocular (LPO) do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, no período de 1974 a 2010. Além de revisão de lâminas de todos os casos e das imagens clínicas e de exames complementares recuperadas dos arquivos pessoais dos autores. RESULTADOS: Dentre o total de espécimes submetidos ao LPO (7546) apenas 8 casos receberam diagnóstico final de inflamação esclerosante idiopática da órbita. Em todos os casos houve piora ou deterioração da acuidade visual à despeito do tratamento, com exceção de um, que permaneceu com a mesma visão (percepção luminosa). Em nosso estudo, observamos envolvimento orbitário predominantemente apical. Todos os nossos pacientes foram submetidos à biópsia incisional com finalidade diagnóstica. Também submeteram-se à corticoterapia e em um caso foi associada à radioterapia anti-inflamatória; em dois destes casos, foi utilizado também ciclofosfamida. Dois pacientes com acuidade final sem percepção luminosa tiveram que ser submetidos à exenteração parcial da órbita para tratamento de dor incontrolável. CONCLUSÃO: A inflamação esclerosante orbitária idiopática permanece como uma doença pouco conhecida, de péssimo prognóstico visual.

PURPOSE: To describe the clinical and histopathologic findings of eight cases of idiophatic sclerosing orbital inflammation. METHODS: A retrospective study from the file of the Ophthalmic Pathology Laboratory of the Hospital Universitário Professor Edgard Santos, Federal University of Bahia, during the period from 1974 to 2010. The clinical data, computed tomography and histopathologic sections obtained by biopsy of all cases were reviewed. RESULTS: From 10312 specimens submitted to the Ophthalmic Pathology Laboratory, eight (0,08%) had a final diagnosis of idiopathic sclerosing orbital inflammation. All cases were unilateral and in all of them vision acuity decreased or was lost despite of treatment, except for one case that remained with light perception as in the first examination. A predominance of diffuse orbital involvement was observed by computed tomography. Histopathologic evaluation disclosed dense fibrosis and collagen deposition with paucicellular inflammation in all cases. All patients were treated by immunosupression with steroids and one case had an association of anti-inflammatory radiotherapy. Two patients were also treated with ciclophosphamide. Partial orbital exenteration was necessary in two cases due to uncontrollable pain. CONCLUSION: Idiopathic sclerosing orbital inflammation remains as a disease with poor response to treatment ans a very bad visual prognosis.

Imunopatogênese da leishmaniose cutânea humana: correlação entre extensão da inflamação, células e vasos em lesões fechadas causadas por leishmania Viannia braziliensis na forma disseminada (LD) / Immunopathogenesis of human cutaneous leishmaniasis: correlation between extent of inflammation, cells and vessels in closed lesions caused by Leishmania Viannia braziliensis in disseminated form (LD

Leishmania (Viannia) braziliensis causa várias formas de doença clinica cutânea, entre elas a forma cutânea disseminada (LD) com uma úlcera cutânea e lesões secundárias disseminadas por mais de duas regiões do corpo. Esta forma além da úlcera inicial apresenta manifestação clínica de múltiplas pápulas e lesões não ulceradas. Neste estudo, descrevemos a histopatologia das lesões não ulceradas da LD, correlacionando-a com a extensão da área inflamada com células CD4, CD20, CD68, CD31 e células de fator de von Willebrand (vW). Metodologia: Dezoito biópsias de lesões de pacientes diagnosticados com LD por critérios clínicos, teste cutâneo de Montenegro positivo e cultivo positivo para L. braziliensis dos aspirados locais das lesões. A análise histopatológica foi feita a partir dos fragmentos de tecidos corados com Hematoxilina e Eosina (HE). A quantificação da área inflamada e células positivas para CD4, CD20, CD68, CD31 e vW foi avaliada com o auxílio do programa Image-Pro Plus (Media Cibernetics). Resultados: Infiltrado inflamatório linfoplasmocitário perivascular e formação de granulomas são achados comuns nas lesões papulares causadas por L. braziliensis. A extensão da área de inflamação variou de 3% a 73%. Houve uma correlação linear significativa entre a extensão da inflamação e a presença de vasos vW+. As células mais frequentes no infiltrado inflamatório foram os macrófagos CD68+, seguido por células B CD20+ e células T CD4+. Houve uma correlação linear significante entre células CD4+ e CD20+ e a área inflamada. Amastigotas foram detectadas por HE e imunohistoquímica em nove biópsias, todos os dezoito aspirados foram positivos para L. (Viannia) braziliensis nos cultivos in vitro. Conclusão: Pela análise histopatológica e imunohistoquímica em lesões fechadas causadas por L. braziliensis, observamos a presença de inflamação crônica variável qualitativa e quantitativamente. Com a expansão da área de inflamação, células CD4+ aumentam proporcionalmente ao número de vasos encontrados e células CD20+.

Trypanosoma cruzi: blood parasitism kinetics and their correlation with heart parasitism intensity during long-term infection of Beagle dogs

The goals of the present study were to evaluate the kinetics of blood parasitism by examination of fresh blood, blood culture (BC) and PCR assays and their correlation with heart parasitism during two years of infection in Beagle dogs inoculated with the Be-78, Y and ABC Trypanosoma cruzi strains. Our results showed that the parasite or its kDNA is easily detected during the acute phase in all infected animals. On the other hand, a reduced number of positive tests were verified during the chronic phase of the infection. The frequency of positive tests was correlated with T. cruzi strain. The percentage of positive BC and blood PCR performed in samples from animals inoculated with Be-78 and ABC strains were similar and significantly larger in relation to animals infected with the Y strain.Comparison of the positivity of PCR tests performed using blood and heart tissue samples obtained two years after infection showed two different patterns associated with the inoculated T. cruzi strain: (1) high PCR positivity for both blood and tissue was observed in animals infected with Be-78 or ABC strains; (2) lower and higher PCR positivity for the blood and tissue, respectively, was detected in animals infected with Y strains. These data suggest that the sensitivity of BC and blood PCR was T. cruzi strain dependent and, in contrast, the heart tissue PCR revealed higher sensitivity regardless of the parasite stock.

Espectro clinicopatológico de las tiroiditis

El espectro clinicopatológico de las tiroiditis abarca, desde la rara tiroiditis aguda o supurativa hasta la más rara tiroiditis de Riedel. Las tiroiditis subaguda y silente (y su variante postpartum) también son enfermedades no comunes, mientras que la tiroiditis crónica autoinmune o enfermedad de Hashimoto resulta la tiroiditis y la enfermedad autoinmune órgano específica más frecuente, responsable de la mayor parte de los casos de hipotiroidismo. Efectivamente, en las áreas geográficas no deficientes en yodo, la mayor parte de los desórdenes tiroideos se deben a enfermedad autoinmune. La autoinmunidad como fenómeno primario juega un papel trascendente en la etiopatogenia de la tiroiditis crónica autoinmune, la tiroiditis silente-postpartum y la tiroiditis de Riedel y, sólo un rol secundario en la tiroiditis subaguda. Posiblemente, las infecciones virales causan la tiroiditis subaguda, mientras que los gérmenes piógenos y hongos son responsables de la tiroiditis supurativa. Las tiroiditis autoinmunes y la tiroiditis subaguda se acompañan comúnmente de disfunción tiroidea. Se conoce como “tiroiditis destructiva” al proceso inflamatorio tiroideo acompañado de destrucción y tirotoxicosis transitoria.

En estos casos, la disfunción tiroidea adopta usualmente el patrón de “tiroiditis bifásica”, en la que secuencialmente, la tirotoxicosis pasajera va seguida de hipotiroidismo transitorio y recuperación. Desórdenes con diferente etiopatogenia, como la tiroiditis subaguda, la tiroiditis silente y la enfermedad de Hashimoto, son responsables de los fenómenos fisiopatológicos similares que dan origen a la tiroiditis bifásica. El dolor en la tiroides adquiere relevancia en la tiroiditis subaguda y en la tiroiditis supurativa y, sólo raramente, está presente en la tiroiditis silente o en la exacerbación aguda de la enfermedad de Hashimoto. En la mayor parte de los casos, es posible establecer el diagnóstico de la tiroiditis mediante la historia clínica, las pruebas de función tiroidea y los estudios isotópicos y ecosonográficos. La biopsia tiroidea por aspiración con aguja fina permite resolver los casos dudosos. Esta revisión del “Espectro clínico-patológico de las tiroiditis”, resulta una síntesis de la información bibliográfica y la experiencia lograda con las tiroiditis a través de un enfoque clínico integral.

Clinical-pathological spectrum of thyroiditis comprises from the rare acute o suppurative thyroiditis as far as the rarest Rieldel's thyroiditis. Also, subacute and silent thyroiditis (and it postpartum variant) are non common diseases, while autoimmune chronic thyroiditis or Hashimoto's disease results the most frequent thyroiditis and organ-specific autoimmune disorder, that is responsible for most part of hypothyroidism cases. Effectively, in iodine-replete geographic areas, most persons with thyroid disorders have autoimmune disease. Autoimmunity as primary phenomenon plays a transcendent role in etiopathogeny of chronic autoimmune thyroiditis, silent-postpartum thyroiditis and Riedel's thyroiditis and only a secondary role in subacute thyroiditis. Probably, viral infections cause subacute thyroiditis, while pyogenic germs and fungus are responsible for suppurative thyroiditis. Commonly, autoimmune and subacute thyroiditis are associated with thyroid dysfunction. It is known as “destructive thyroiditis”, the thyroidal inflammatory process that is joined to destruction and transient thyrotoxicosis.

Usually, thyroid dysfunction in these cases adopt “biphasic thyroiditis” pattern, in which sequentially, transient thyrotoxicosis is followed by transient hypothyroidism and recovery. Disorders with different etiopathogeny as subacute thyroiditis, silent thyroiditis and Hashimoto's thyroiditis are responsible of similarly physiopathologic phenomenons that originated biphasic thyroiditis. Pain in the thyroidal gland is relevant in subacute and suppurative thyroiditis and, rarely is present in silent thyroiditis or in acute exacerbation of Hashimoto's thyroiditis. In most of the cases, it is possible to establish the diagnosis of thyroiditis through clinical history, thyroidal function tests, isotopic studies and ecosonography. Thyroid fine needle biopsy resolves doubtful cases. This review about “Clinical-pathological spectrum of thyroiditis”, results from the synthesis of bibliographic information and the experience obtained with thyroiditis through and integral clinic focus.

Trypanosoma cruzi high infectivity in vitro is related to cardiac lesions during long-term infection in Beagledogs

Trypanosoma cruzi is a hemoflagelate parasite associated with heart dysfunctions causing serious problems in Central and South America. Beagle dogs develop the symptoms of Chagas disease in humans, and could be an important experimental model for better understanding the immunopathogenic mechanisms involved in the chagasic infection. In the present study we investigated the relation among biological factors inherent to the parasite (trypomastigote polymorphism and in vitro infectivity) and immunoglobulin production, inflammation, and fibrosis in the heart of Beagle dogs infected with either T. cruzi Y or Berenice-78 strains. In vitro infectivity of Vero cells as well as the extension of cardiac lesions in infected Beagle was higher for Y strain when compared to Berenice-78 strain. These data suggested that in vitro infectivity assays may correlate with pathogenicity in vivo. In fact, animals infected with Y strain, which shows prevalence of slender forms and high infectivity in vitro, presented cardiomegaly, inflammation, and fibrosis in heart area. Concerning the immunoglobulin production, no statistically significant difference was observed for IgA, IgM or IgG levels among T. cruzi infected animals. However, IgA together IgM levels have shown to be a good marker for the acute phase of Chagas disease.

Bases celulares e bioquímicas da doença pulmonar obstrutiva crônica / Cellular and biochemical bases of chronic obstructive pulmonary disease

A doença pulmonar obstrutiva crônica é uma doença inflamatória com participação ativa de macrófagos, neutrófilos e linfócitos CD8+ em sua patogênese, associada a estímulos oxidantes diretos das estruturas pulmonares, que desencadeiam reações bioquímicas, levando a progressiva desorganização das pequenas vias aéreas e ao remodelamento estrutural não reversível. A liberação de substâncias provenientes das células recrutadas e do estresse oxidativo leva ao desequilíbrio inicialmente temporário dos mecanismos de defesa pulmonar. A permanência desse desequilíbrio é uma das chaves da fisiopatogenia atual. Os autores descrevem as alterações celulares e bioquímicas da doença pulmonar obstrutiva crônica.

Chronic obstructive pulmonary disease is an inflammatory disease. Together with oxidant stimuli, which directly affect lung structures, macrophages, neutrophils and CD8+ lymphocytes actively participate in the pathogenesis of the disease and promote biochemical reactions that result in progressive alteration of the upper airways and irreversible lung remodeling. The release of substances promoted by inflammatory cell recruitment and by oxidative stress lead to a temporary imbalance in the pulmonary defense mechanisms. Understanding the long-term maintenance of this imbalance is key to understanding the current physiopathology of the disease. The present study explores the cellular and molecular alterations seen in chronic obstructive pulmonary disease.

Macrophage elastase (MMP-12): a pro-inflammatory mediator?

As many metalloproteinases (MMPs), macrophage elastase (MMP-12) is able to degrade extracellular matrix components such as elastin and is involved in tissue remodeling processes. Studies using animal models of acute and chronic pulmonary inflammatory diseases, such as pulmonary fibrosis and chronic obstrutive pulmonary disease (COPD), have given evidences that MMP-12 is an important mediator of the pathogenesis of these diseases. However, as very few data regarding the direct involvement of MMP-12 in inflammatory process in the airways were available, we have instilled a recombinant form of human MMP-12 (rhMMP-12) in mouse airways. Hence, we have demonstrated that this instillation induced a severe inflammatory cell recruitment characterized by an early accumulation of neutrophils correlated with an increase in proinflammatory cytokines and in gelatinases and then by a relatively stable recruitment of macrophages in the lungs over a period of ten days. Another recent study suggests that resident alveolar macrophages and recruited neutrophils are not involved in the delayed macrophage recruitment. However, epithelial cells could be one of the main targets of rhMMP-12 in our model. We have also reported that a corticoid, dexamethasone, phosphodiesterase 4 inhibitor, rolipram and a non-selective MMP inhibitor, marimastat could reverse some of these inflammatory events. These data indicate that our rhMMP-12 model could mimic some of the inflammatory features observed in COPD patients and could be used for the pharmacological evaluation of new anti-inflammatory treatment. In this review, data demonstrating the involvement of MMP-12 in the pathogenesis of pulmonary fibrosis and COPD as well as our data showing a pro-inflammatory role for MMP-12 in mouse airways will be summarized.

Inflamação como processo patogenético comum em diabetes melito tipo 2 e doenças cardiovasculares / Inflamation in the common pathogenesis of type 2 diabetes mellitus and cardiovascular diseases

Diabetes melito tipo 2 e doença cardiovascular apresentam um "solo comum" de causalidade composto de fatores de risco comuns com freqüência coexistindo no mesmo indivíduo, a chamada síndrome plurimetabólica. Apresentamos evidências epidemiológicas do estudo "Atherosclerosis Risk in Communities" (ARIC), mostrando que, da mesma forma que o observado na última década para a doença cardiovascular, marcadores de inflamação e disfunção endotelial também predizem o desenvolvimento de diabetes em adultos. Apresentamos uma descrição do sistema imune inato e a proposição de que a hiperativação crônica desse sistema poderia representar uma razão para a coincidência de fatores de risco (síndrome plurimetabólica), causando tanto a doença cardiovascular como o diabetes melito tipo 2. É dada ênfase ao tecido adiposo como agente central nesse processo patogenético.

Incidência da doença fibrocística em 516 mamoplastias reparadoras / Incidence of fibrocystic disease in 516 repairing mamaplasties

Os autores descrevem a incidência da doença fibrocística em 516 mamoplastias reparadoras em pacientes sem história prévia de doença de mama. A idade das pacientes variou de 14 a 91 anos com um pico ao redor da terceira e quarta décadas de vida. Em 347 pacientes (67,25 por cento) havia evidências de alteraçoes fibrocísticas nao proliferativas como fibrose estromal, cistos, inflamaçao crônica, metaplasia apócrina e alteraçoes fibroadenomatóides. Porém, em 13,26 por cento dos casos havia alteraçoes proliferativas como hiperplasia epitelial típica (n=34), adenose esclerosante (n=6) e hiperplasia epitelial atípica (n=6). Um caso de carcinoma ductal in situ também foi precocemente diagnosticado pela análise deste material. As pacientes com história familiar de câncer de mama e doença fibrocística com alteraçoes proliferativas podem ter risco de desenvolvimento de carcinoma até dez vezes maior que a populaçao em geral. Nossos achados enfatizam que todos os espécimes provenientes de mamoplastias devem ser submetidos a exame histopatológico para que as pacientes do grupo de risco de desenvolvimento de carcinoma sejam diagnosticadas e observadas clinicamente.

Inflamación hiperreactividad y controversin terapéutica del asma crónica / Hyperreactivity inflammation and therapeutic controversy of chronic astma

Se analiza la importancia de la inflamación, que cuando es a corto plazo y controlada es una respuesta útil al huésped, cuando se hace crónica puede ser perjudicial y dañar al huésped. Se revisa su relación íntima con la hiperreactividad bronquial, se valoran las células que intervienen en esta patología, los mediadores de la misma y los mecanismos antinflamatorios que modifican también la hiperrespuesta bronquial. Estos conocimientos básicos van a ayudar al médico a mejorar las posibilidades terapéuticas sobre todo en el asmático crónico. Por último se resumen algunas controversias actuales en el uso de broncodilatadores, cromoglicato y corticoesteroides