Protein from Hevea brasiliensis "Hev b 13" latex attenuates systemic inflammatory response and lung lesions in rats with sepsis / Proteína do latex de Hevea brasiliensis "Hev b 13" atenua resposta inflamatória sistêmica e lesão pulmonar de ratos com sepse

Abstract Sepsis induces a severe systemic inflammatory response that may result in multiple organ dysfunction and death. Studies using a protein derived from natural Hevea brasiliensis (rubber tree) latex, denominated Hev b 13, have demonstrated important anti-inflammatory effects, but no data have been published regarding its effects on sepsis. The aim of this study was to investigate the effects of Hev b 13 on the inflammatory response and lung lesions of septal rats. Male Wistar rats were submitted to cecal ligation and puncture (CLP), randomized into groups and treated with subcutaneously administered doses of 0.5/2.0/3.0 mg/Kg of Hev b 13. Next, animals were subdivided into three different points in time (1, 6 and 24 hours after treatments) for collection of blood samples and euthanasia accompanied by organ removal. Total and differential leukocyte counts, cytokine dosage and histological assessment were analyzed. Treatment with Hev b 13 resulted in a significant decline in total and differential leukocytes as well as suppression of TNF-α and IL-6 production, associated with the increase in IL-10 and IL-4 in plasma and lung tissue. Moreover, it reduced morphological and pathological changes found in the lungs, including neutrophil infiltration, edema and alveolar thickening. The present study concluded that Hev b 13 exerts anti-inflammatory effects and attenuates lung lesions in septal rats, showing potential for clinical application.

Resumo Sepse induz uma resposta inflamatória sistêmica grave podendo resultar em disfunção de múltiplos órgãos e morte. Pesquisas utilizando uma proteína derivada do látex natural de Hevea brasiliensis (seringueira), denominada Hev b 13 tem demonstrado importantes efeitos anti-inflamatórios, mas nenhum dado foi publicado dos seus efeitos na sepse. O objetivo deste estudo foi investigar os efeitos da Hev b 13 na resposta inflamatória e na lesão pulmonar de ratos com sepse. Ratos machos da linhagem Wistar foram submetidos a ligação e perfuração do ceco (LPC), randomizados em grupos e tratados com as doses 0,5/2,0/3,0 mg/Kg de Hev b 13 subcutâneo. Após subdividiu-se os animais em três pontos diferentes de tempo (1, 6 e 24 horas após os tratamentos) para coleta de amostras sanguíneas e eutanásia com remoção dos órgãos. Contagem total e diferencial de leucócitos, dosagem de citocinas e avaliação histológica foram analisadas. O tratamento com a Hev b 13 resultou em diminuição significativa de leucócitos totais e diferenciais bem como suprimiu a produção de TNF-α e IL-6, associado ao aumento de IL-10 e IL-4 no plasma e tecido pulmonar. Além disso, reduziu as alterações morfológicas e patológicas encontradas nos pulmões, incluindo infiltrado de neutrófilos, edema e espessamento alveolar. Este estudo concluiu que a Hev b 13 tem efeitos anti-inflamatórios e atenua lesões pulmonares em ratos com sepse, apresentando potencialidades para aplicabilidade clínica.

Myositis-specific and myositis-associated autoantibody profiles and their clinical associations in a large series of patients with polymyositis and dermatomyositis

OBJECTIVE: To analyze the prevalence of myositis-specific and myositis-associated autoantibodies and their clinical correlations in a large series of patients with dermatomyositis/polymyositis. METHOD: This cross-sectional study enrolled 127 dermatomyositis cases and 95 polymyositis cases. The disease-related autoantibody profiles were determined using a commercially available blood testing kit. RESULTS: The prevalence of myositis-specific autoantibodies in all 222 patients was 34.4%, whereas myositis-associated autoantibodies were found in 41.4% of the patients. The most frequently found autoantibody was anti-Ro-52 (36.9%), followed by anti-Jo-1 (18.9%), anti-Mi-2 (8.1%), anti-Ku (4.1%), anti-SRP (3.2%), anti-PL-7 (3.2%), anti-PL-12 (2.7%), anti-PM/Scl75 (2.7%), and anti-PM/Scl100 (2.7%). The distributions of these autoantibodies were comparable between polymyositis and dermatomyositis, except for a higher prevalence of anti-Jo-1 in polymyositis. Anti-Mi-2 was more prevalent in dermatomyositis. Notably, in the multivariate analysis, anti-Mi-2 and anti-Ro-52 were associated with photosensitivity and pulmonary disorders, respectively, in dermatomyositis. Anti-Jo-1 was significantly correlated with pulmonary disorders in polymyositis. Moreover, anti-Ro-52 was associated with anti-Jo-1 in both diseases. No significant correlation was observed between the remaining autoantibodies and the clinical and/or laboratory findings. CONCLUSIONS: Our data are consistent with those from other published studies involving other populations, although certain findings warrant consideration. Anti-Ro-52 and anti-Jo-1 were strongly associated with one another. Anti-Ro-52 was correlated with pulmonary disorders in dermatomyositis, whereas anti-Jo-1 was correlated with pulmonary alterations in polymyositis. .

Hallazgos tomográficos pulmonares y su asociación con niveles de linfocitos T CD4+ en pacientes portadores del virus de inmunodeficiencia humana / CT pulmonary findings and their association with CD4+ T lymphocytes levels in human immunodeficiency virus carriers

Respiratory diseases are frequent complications in HIV infection. High Resolution Computed Tomography (HRCT) has proven superior to conventional imaging techniques to establish a pulmonary disease diagnosis. A study was conducted in order to establish the association between tomographic pulmonary patterns and immune status of HIV-infected patients. We evaluated 35 patients with respiratory symptoms and / or abnormal chest radiograph. An association was observed between the presence of ground glass pattern and P jirovecii infection. Likewise, a correlation between pulmonary histoplasmosis diagnosis and honeycomb pattern, lung cysts and nodules was established. Few correlation between tomographic patterns and CD4 + T lymphocyte counts was observed. In summary, HRCT findings can predict certain types of infection; nevertheless, further studies are required to extrapolate this association to other noninfectious lung diseases in HIV-infected patients.

Las enfermedades respiratorias constituyen complicaciones frecuentes en la infección por VIH. La Tomografía Axial Computarizada de Alta Resolución (TACAR) ha demostrado ser superior a las técnicas de imagen convencionales para establecer diagnóstico de enfermedad pulmonar. Se realizó un estudio con la finalidad de establecer la asociación entre patrones tomográficos pulmonares y el estado inmunológico de pacientes VIH+. Se evaluaron 35 pacientes sintomáticos respiratorios y/o con radiografía torácica patológica. Se observó una asociación entre la presencia de patrón en vidrio esmerilado e infección por P jirovecii. Asimismo, se observó una asociación entre diagnóstico de histoplasmosis pulmonar y patrón de panal de abejas, quistes pulmonares y nódulos. Se demostraron pocas correlaciones entre patrones tomográficos y conteo de linfocitos T CD4+. En conclusión, los hallazgos en la TACAR pueden predecir determinados tipos de infección requiriendo de más estudios para extrapolar esta asociación a otras enfermedades pulmonares no infecciosas en el paciente VIH+.

[Pulmonary manifestations of pediatric hyper IgE syndrome]

Hyper IgE syndrome is a rare primary immune deficiency disorder characterized by pulmonary and cutaneous infection, eczema, and elevated serum IgE levels. In this article, 4 patients with hyper IgE syndrome and recurrent pulmonary infection were reported. Four girls with history of recurrent pulmonary infections were worked up and hyper IgE syndrome was diagnosed for them. All patients had recurrent pulmonary infections including pneumonia, bronchiectasis, pulmonary abscess, hydropneumothorax. Serum IgE levels were greater than 2000 Iu/ml in all cases. Microbial cultures showed staphylococcus aureas and pseudomans aeroginosa in two cases. All patients respond well to the wide spectrum intravenous antibiotics. Extra-pulmonary manifestations including purulent lymphadenitis, and skin and brain abcesses were observed. Hyper IgE syndrome causes recurrent pulmonary and extra-pulmonary infections which response fairly well to wide spectrum antibiotic therapy

Pulmonary manifestations of primary sjögren’s syndrome.

Sjögren's syndrome (SS) is a complex autoimmune exocrinopathy with multifactorial pathogenesis and multisystem manifestation. It is called primary Sjögren's syndrome (PSS) when the manifestations are seen without any other co-existent rheumatic diseases. The incidence of respiratory system involvement varies widely in the reported medical literature, partly due to lack of a universal agreement over the diagnostic criteria of the disease and the type of study methods employed. Respiratory system manifestations are protean; upper airway symptoms are very common and so is the complaint of dry cough. The PSS patients may develop interstitial lung diseases (ILDs) such as usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), lymphocytic interstitial pneumonia (LIP), bronchiolitis obliterans and organising pneumonia (BOOP), etc. They may also develop the whole spectrum of lymphoproliferative disorders of the lung ranging from LIP to follicular bronchiolitis, nodular lymphoid hyperplasia and low-grade lymphomas. Therapeutic options include symptomatic and supportive measures and corticosteroids as the mainstay of the treatment for ILDs occurring in these patients. In recent years, rituximab (anti-CD20) has emerged as a promising treatment for this disease, though data from controlled trials are still lacking. Pulmonary involvement may be a source of significant morbidity in these patients, though only rarely, it is the cause of death.

Nódulos pulmonares cavitados y vasculitis ANCA asociada: secundarios a infección por zigomicetos / Cavitated pulmonary nodules and associated ANCA vasculitis: secondary to zygomycetes infection

La presencia de nódulos pulmonares cavitados nos obliga a plantear varios diagnósticos diferenciales. El diagnóstico definitivo hay que definirlo en base a lo que nos aportan los exámenes serológicos, imagenológicos e histológicos, y correlacionar con la forma de presentación clínica. Un diagnóstico importante que debe ser considerado es la Granulomatosis de Wegener (GW) que corresponde a una vasculitis, en la mayoría de los casos sistémica y en la que encontramos anticuerpos anticitoplasma de neutrófilos de histología compatible con vasculitis. Las patologías infecciosas son otra causa importante de lesiones nodulares en pulmón. Si estamos ante pacientes con algún grado de inmunosupresión, no debemos olvidar la etiología micótica y dentro de esta la infección causada por hongos del grupo Zigomicetes (mucormicosis), sobre todo por la urgencia de realizar tratamiento agresivo y su alta mortalidad.

The presence of cavitated pulmonary nodules obliges one to pose various differential diagnoses. A definite diagnosis must be defined based on serological, imagenological and histological exams, and contrast these with the clinical manifestation. An important diagnosis that must be considered is Wegener’s granulomatosis, which corresponds to a Vasculitis, usually systemic, in which we find antineutrophil cytoplasmic antibodies and histology compatible with Vasculitis. Infectious pathologies are an important cause of pulmonary nodular lesions. If faced with a patient with a degree of immunosuppression, we must not forget the mycotic etiology, and within this the infection caused by fungi from the Zygomycetes group (mucomycosis), above all due to the urgency of aggressive treatment and its high mortality rate.

Concomitancia de anticuerpos antimembrana basal y ANCA en el síndrome riñón-pulmón / Concomitance of glomerular basement membrane antibodies and ANCA in pulmonary - renal syndrome

La enfermedad antimembrana basal glomerular (anti-MBG) es una condición que se manifiesta clínicamente como glomerulonefritis rápidamente progresiva y hemorragia alveolar, también llamada Síndrome Riñón- Pulmón. Se asocia a la presencia de autoanticuerpos dirigidos contra el colágeno tipo IV de la membrana basal glomerular. Las vasculitis sistémicas asociadas a ANCA también pueden manifestarse como Síndrome Riñón-Pulmón, cuadro clínico a veces indistinguible de la enfermedad anti-MBG. La concomitancia de ANCA y anticuerpos anti-MBG en el Síndrome Riñón-Pulmón es del orden de un 30 por ciento, según distintos reportes de la literatura. El perfil clínico, el pronóstico y el rol fisiopatológico de cada anticuerpo en este grupo de pacientes todavía son materia de investigación. El mecanismo patogénico inicial parece ser el daño mediado por ANCA, que puede inducir la aparición de anticuerpos anti-MBG, los que perpetúan el daño en el glomérulo.

Anti-glomerular basement membrane (anti-MBG) disease is a condition that is manifested clinically as rapidly progressive glomerulonephritis and alveolar hemorrhage, also known as Pulmonary-Renal Syndrome. It is associated with the presence of autoantibodies directed against type IV collagen of the glomerular basement membrane. Systemic vasculitis associated with ANCA may also manifest as Pulmonary-Renal Syndrome, sometimes clinically indistinguishable from the anti-MBG disease.The concomitance of ANCA and anti-MBG antibodies in the Pulmonary-Renal Syndrome is about 30 percent, according to various reports in literature. The clinical profile, prognosis and physiopathologic roles of each antibody in this group of patients is still under investigation. The pathogenic mechanism appears to be the initial damage mediated by ANCA, which may induce the appearance of anti-MBG, those who perpetuate the glomerulus damage.

Efecto inmunomodulador de los macrólidos en las enfermedades pulmonares / Immunomodulating effect of macrolides in lung disease

Introducción: A lo largo de tres décadas el interés por los macrólidos se ha incrementado considerablemente. Objetivo: Realizar una actualización en torno a los mecanismos inmunomoduladores de estas drogas sobre la cascada inflamatoria, la función del neutrófilo, el broncoespasmo y el biofilm de la Pseudomona aeruginosa. Material y Métodos: Se realizó una búsqueda bibliográfica considerando revisiones o artículos originales indexados en el National Library of Medicine (MEDLINE/Pubmed) empleando las palabras: macrolides, azithromycin, clarithromycin, immunomodulating, antiinflammatory, airway, cystic fibrosis, asthma sinusitis y children. Resultados: Las dosis bajas de macrólidos han producido un incremento dramático en la sobrevida de pacientes con panbronquiolitis difusa. Existe un desarrollo de investigaciones en otras enfermedades pulmonares crónicas con un componente inflamatorio como asma, fibrosis quística y bronquiectasias. No existe evidencia que guíe el correcto uso de estas drogas, sino más bien recomendaciones de ensayo. Conclusiones: Existen beneficios y posibles efectos adversos reconocidos que deben ser determinados de forma clara antes de ser indicados en otras condiciones pulmonares.

Nontuberculous Mycobacterial Pulmonary Diseases in Immunocompetent Patients

Nontuberculous mycobacterial (NTM) infections are an increasingly recognized cause of chronic lung disease in immunocompetent adults, and the M. avium complex, M. kansasii, and a rapidly growing mycobacteria such as M. abscessus, M. fortuitum, and M. chelonae account for most of the pathogens involved. Because the clinical features of NTM disease are not distinguishable from those of tuberculosis, and NTM are ubiquitous in the environment, diagnosis requires that the bacilli are isolated and identified. NTM diseases have been difficult to treat, though since the introduction of new macrolides, the outcome for patients with some NTM diseases has improved significantly. For correct diagnosis and the successful treatment of NTM pulmonary disease, a knowledge of the full spectrum of clinical and radiological findings is important.

HLA association with sarcoidosis and diffuse interstitial pulmonary fibrosis.

HLA typing was performed on 18 patients suffering from sarcoidosis and 30 patients suffering from diffuse interstitial pulmonary fibrosis. One hundred normal healthy people ethnically matched served as the controls. On statistical analysis, the corrected 'p' value of all the HLA antigens for both the patient groups was non significant. The results therefore suggest that there is no particular HLA antigen associated with sarcoidosis and diffuse interstitial pulmonary fibrosis.

Evaluation of enzyme linked immunosorbent-assay and Western blot for diagnosis of histoplasmosis / Evaluation of enzyme linked immunosorbent-assay and Western blot for diagnosis of histoplasmosis

En este estudio se evalúa el ensayo inmunoenzimático (ELISA) para el diagnóstico serológico de histoplasmosis. Esta técnica se compara con los resultados obtenidos por el método de fijación de complemento. Los resultados de este estudio demuestran que el método de ELISA, detectando IgG, tiene una sensibilidad de 88 por ciento para el diagnóstico de histoplasmosis pulmonar aguda, con una especificidad de 91 por ciento. La detección de IgM tiene una sensibilidad de 66 por ciento con una especificidad de 100 por ciento. En este estudio existió una buena correlación entre la técnica de fijación de complemento y la de ELISA. Ninguno de los métodos fue útil para el diagnóstico serológico de histoplasmosis en pacientes inmunosuprimidos. La técnica de inmunoelectrotransferencia identificó, en suero de pacientes con histoplasmosis, anticuerpos dirigidos contra cuatro antígenos dominantes de histoplasma (91, 83, 70 y 38 KD). Estos antígenos también fueron identificados en pacientes inmunosuprimidos. Las conclusiones de este estudio son que la detección de anticuerpos por ELISA es un procedimiento útil para el diagnóstico de histoplasmosis, y que la técnica de inmunoelectrotransferencia puede ser útil para pacientes inmunosuprimidos.

Inmunoglobulina A y antígenos del tabaco en pacientes neumópatas / Inmunoglobulin A and tobacco antigen in pheumophatic patients

El tabaquismo es una adicción relacionada con diversas enfermedades cardiopulmonares. Algunos compuestos derivados de la combustión del tabaco son capaces de inducir una reacción del sistema inmune secretor, ya que su entrada al organismo es a través del epitelio de la vía respiratoria por lo que se propone la formación de complejos inmunes tabaco antitabaco (CI) en la circulación con la participación de IgA. Los anticuerpos antitabaco se demostraron en el suero de 44 porciento de sujetos "sanos" fumadores y en 71 porciento de los no fumadores. Se encontraron CI séricos en 56 porciento de fumadores y en 38 porciento de no fumadores, los cuales mostraron en promedio 0.19 y 0.15 mg/ml de IgA respectivamente. Los pesos moleculares de los constituyentes de los CI oscilaron entre 12 y 80 Kd. No se observaron antígenos de tabaco libre en los sueros probados. Los pacientes neumópatas tuvieron anticuerpos antitabaco en 100 porciento de los casos y los CI fueron positivos en 72 porciento de fumadores y 65 porciento de no fumadores. La IgA fue de 1.41 y 1.26 mg/ml respectivamente. Los compuestos de los CI tuvieron de 14 a 90 Kd. El antígeno del tabaco libre en el suero fue observado en 44 porciento de fumadores y 41 porciento de los no fumadores. Se concluye que los pacientes neumópatas tuvieron mayor frecuencia de anticuerpos antitabaco y de CI; fue mayor y en más casos se demostró antígeno de tabaco libre en el suero de neumópatas que en los sujetos sanos. Es posible que los CI-IgA participen en los procesos inflamatorios pulmonares que se encuentran relacionados con el tabaquismo.

Pulmonary infections in immunocompromised hosts.

Between February 1985 and January 1987, sixty cases of pulmonary infection in immunocompromised host were seen at the Department of Medicine, Ramathibodi hospital. The underlying causes were: thirty-four cases with hematologic malignancies, nine with autoimmune diseases, seven with aplastic anemia, three with non-hematologic malignancies, and seven following corticosteroid therapy. Infectious agents were identified in thirty-two cases; nineteen bacterial, three fungal, four nocardial, three strongyloidiasis and three tuberculosis. In nineteen cases, the infectious agents were classified as "probable", and in nine cases, "unknown" etiology. Eleven of the twenty hospital infected patients and ten of the forty community infected patients died. Mortality appeared to be related to the underlying diseases, infection acquired in hospital and the infectious agent.