M.A.T. Marques

NEOPTERIN IN TUBERCULOUS AND NEOPLASTIC PLEURAL FLUIDS

Neopterin is derived from guanosine-triphosphate, produced by stimulated macrophages under the influence of gamma interferon of lymphocyte origin. It has been suggested as an excellent marker for activation of the monocyte/macrophage axis in some clinical situations. We evaluated its concentration in the pleural effusions of 25 individuals (10 tuberculous and 15 neoplastic) as well as in the blood of 22 of them (8 tuberculous and 14 neoplastic), comparing these levels with those of a control group in 99 normal individuals. The concentration of neopterin was determined by radioimmunologic assay. This showed a significant increase (p < 0.001) of neopterin levels in the tuberculous pleural fluid, compared to the neoplastic group (42 ± 23/17 ± nmol/L).In the blood, values were nearly identical to the pleural fluid (41.3 ±25/15.8 ± 6.9 nmol/L), although with significant differences between them and in relation to the control group (p < 0.001), which had a normal serum value (5.11 ± 1.92 nmol/L).We emphasize the influence of the neopterin levels in the pleural fluid on the diagnosis of causes of pleurisy and its importance as a marker of immunologic cellular activity.

Nanoradioliposomes molecularly modulated to study the lung deep lymphatic drainage

Abstract Lung deep lymphatic drainage (LDLD) plays an important role in the removal of foreign materials from lungs being alveolar macrophages the first line of phagocytic defence with high affinity for pathogenic microorganisms. Bacillus subtilis is a well-known genome- decoded saprophyte of the human respiratory tract used in research and in the biotechnology industry. Lung deep lymphatic chains (LDLC) constitute one of the first sites of lung tumours’ dissemination. In this work we intended to develop and validate a non-invasive method for assessing LDLC by nanoradioliposomes aerosolised modulated on the Bacillus subtilis spore wall. The final goal was to produce a nanoradioliposome formulation that can mimics the dynamics of preferential removal of spores by LDLD and present the ideal properties as a tracer for molecular imaging studies. Seven different liposomal formulations were tested, and the formulation-F demonstrated physicochemical and radiopharmaceutical properties that make it an ideal candidate as an in vivo probe for molecular imaging studies of the LDLC. Nanoradioliposomes of the formulation-F after labelling with 99mTc-HMPAO were administered as aerosols to 20 Sus scrofa. Hilar and interpulmonary communications were visualized in first 5 minutes post-inhalation, infradiaphragmatic chains between 10 and 20 minutes, the ganglia of the aortic chain at 20 minutes and those of the renal hilar region at 30 minutes. Conclusion the proposed method enables visualization of deep lymphatic lung network and lymph nodes. Besides, this technique involving the modulation of nanoradioliposomes targeting specific organs or tissues may be an important tool for diagnostic or even for therapeutic purposes.

Nanorradiolipossomas modulados molecularmente para estudar a drenagem linfática pulmonar profunda

Resumo A drenagem linfatica pulmonar profunda (DLPP) desempenha um papel importante na remocao de materiais estranhos, constituindo os macrofagos alveolares a primeira linha de defesa fagocitaria, dada a grande afinidade para microrganismos patogenicos. Os Bacillus subtilis sao saprofitas do tracto respiratorio humano com ampla utilizacao em investigacao e em biotecnologia. As cadeias linfaticas pulmonares profundas (CLPP) constituem um dos primeiros locais de disseminacao de tumores pulmonares. Neste trabalho pretendeu-se desenvolver e validar um metodo nao invasivo para avaliar as CLPP atraves de nanorradiolipossomas aerosolisados e modulados pela parede do esporo do Bacillus subtilis . O objectivo final foi produzir uma formulacao de nanorradiolipossomas capaz de imitar a dinâmica da remocao de esporos pelas CLPP e simultaneamente ter propriedades ideais como tracador para imagiologia molecular. Testamos sete diferentes formulacoes lipossomicas, tendo a formulacao F demonstrado possuir propriedades fisicoquimicas e radiofarmaceuticas que a tornam o tracador ideal para imagiologia molecular in vivo das CLPP. Os nanorradiolipossomas da formulacao F apos marcacao com 99m Tc-HMPAO foram administrados sob a forma de aerossois a 20 Sus scrofa . Visualizaram-se comunicacoes hilares e interpulmonares nos primeiros 5 minutos apos a inalacao, as cadeias infradiafragmaticas entre os 10 e os 20 minutos, os gânglios da cadeia aortica aos 20 minutos e os da regiao hilar renal aos 30 minutos. Em conclusao, o metodo proposto visualiza os gânglios linfaticos e a rede linfatica pulmonar profunda. A modulacao dos nanorradiolipossomas permite que eles atinjam orgaos ou tecidos especificos, conferindo-lhes importantes potencialidades no âmbito do diagnostico e/ou da terapeutica. Rev Port Pneumol 2009; XV (2): 261-293

Pulmão profundo – Reacção celular ao VIH

The course of HIV infection is accompanied by a wide individual variability. The complex and large interplay between host and viral factors is crucial in the disease’s evolution. The lung has been recognised from the beginning of the disease as one of the main targets of infectious and non-infectious complications of AIDS. In this setting both anatomic and immunologic particularities of this organ play an important role. The hallmark of HIV is progressive immune dysfunction. Despite the intensive research into the pathogenesis, several questions remain to be answered on the dynamic effects of HIV on pulmonary cells. Previous studies in which we have participated showed the early presence of lymphocytic alveolitis from the asymptomatic phase of infection. Since then, many collected data has brought new insights into the immune and biochemical mechanisms involving HIV cell entry, as well as target cells, cytokines and other cellular mediators.

Predictors of talc slurry pleurodesis success in patients with malignant pleural effusions

INTRODUCTION Malignant pleural effusions are an important burden of malignant disease. Slurry talc pleurodesis remains one of the most common and effective therapeutic options. AIM Investigate the predictive factors related with the efficacy of this technique in malignant pleural effusions. METHODS Retrospective analysis of all pleurodesis performed during a 10-year period in a Pulmonology Unit. All demographic and clinical data were collected, including the histologic tumoral type and the biochemical, microbiological and cytological fluid features. Efficacy was defined as the lack of recurrence of pleural effusion. It was used Kaplan-Meyer analysis to estimate overall survival. RESULTS From a total of 202 patients submitted to pleurodesis (47% men; mean age 66.9±12.02 years). Lights criteria identified 86.6% as exudates. We found 85.1% survival at 30-day post-pleurodesis, which means the therapy used has significant success. A logistic regression model applied explained that variance in post-pleurodesis events was mostly due to age and gender rather than pleural biochemical factors (X2(5)=44.648, p<0.001, R2 28.3%). CONCLUSION This study suggests that clinical evaluation of biochemical values, bacteriological results and malignant tumor diagnosis may not be enough to predict post-pleurodesis relapse with high accuracy. Furthermore, we observed, in ten years of pleurodesis performed in our Hospital, that pleurodesis is an effective life prolonging therapy for patients that fit the criteria for this intervention.

Estratégia diagnóstica do nódulo pulmonar solitário

RESUMO Na sequencia da definicao de Nodulo Pulmonar Solitario (NPS) os autores analisam a sua etiologia, salientando neste contexto os condicionalismos epidemiologicos que a influenciam, assim como a importância assumida pelas lesoes tumorais infecciosas, micoticas e parasitarias nas diferentes series publicadas. Seguidamente, abordam a estrategia diagnostica desta situacao clinica, com especial destaque para os exames clinico-radiologico, tomodensitometrico, broncofibroscopico e cito-histopatologico. Em relacao as semiologias clinico-radiologica e tomodensitometrica, salientam os criterios utilizados na determinacao da natureza benigna ou maligna das lesoes. Quanto ao estudo cito-histopatologico, chamam a ateocao para a importância do material recolhido por broncofibroscopia e para a elevada rendabilidade foroecida pela puncao aspirativa transtoracica. No decurso da exposicao sao pontualmente apresentados os resultados de um estudo retrospectivo efectuado com os elementos recolhidos dos processos clinicos, hospitalares e extra-hospitalares, de 72 individuos operados por NPS. No âmbito desta avaliacao deram um especial relevo aos resultados fornecidos pela tomodensitometria (nas suas vertentes qualitativa e quantitativa) e pela puncao aspirativa transtoracica e, ainda, a relacao de alguns parâmetros (habitos tabagicos, idade, dimensoes, estabilidade lesional e calcificacao) com a natureza benigna ou maligna das respectivas formacoes nodulares. Finalmente, tecem algumas consideracoes sobre as opcoes terapeuticas destas lesoes, as quais, para alem das situacoes que apenas requerem tratamento medico, oscilam entre uma cuidadosa vigilância e a intervencao cirurgica mais ou menos alargada.