Paradoxical effects of adenovirus-mediated blockade of TNF activity in murine collagen-induced arthritis.

Collagen-induced arthritis (CIA) is an experimental model of arthritis widely used to dissect the pathogenesis of human rheumatoid arthritis and to identify potential therapeutic targets. Among these, TNF-alpha has been recognized to play an important role. Here we investigate the feasibility and therapeutic efficacy of prolonged blockade of TNF-alpha activity through the adenovirus-mediated gene delivery of a dimeric chimeric human p55 TNFR-IgG fusion protein and compare it to protein therapy in established CIA. A single i.v. administration of the replication-deficient adenovirus yielded microgram serum levels of the chimeric fusion protein and ameliorated CIA for 10 days. Subsequently, benefit was lost and a rebound to greater inflammatory activity was observed despite the continual presence of bioactive TNFR fusion protein. A similar trend was also observed in mice injected directly with comparable amounts of a human TNFR-IgG fusion protein, whereas the administration of a control adenovirus-encoding beta-galactosidase or of a control human IgG1 protein did not significantly affect the disease course. The mechanisms of the rebound of CIA were investigated, and augmented Ab response to collagen type II and TNFR were identified as potential causes. Our results confirm the feasibility of adenovirus-mediated gene delivery of cytokine inhibitors in animal models of autoimmune diseases for investigational purposes and highlight the importance of prolonged studies. Further investigations are needed to optimize ways of exploiting the potential of adenoviral gene therapy in RA

Beneficiamento de sementes de café e efeitos na qualidade fisiológica Coffee seed processing and effects on physiological seed quality

Considerando-se a escassez de informações sobre o beneficiamento mecanizado de sementes de café, realizou-se este trabalho para estudar seus efeitos na qualidade fisiológica das sementes de café arábica. Um lote de sementes de 'Catuaí Amarelo IAC 62' foi submetido à ação de máquina de pré-limpeza, máquina de ventiladores e peneiras e mesa densimétrica, em diversas combinações, e as sementes foram avaliadas quanto à germinação e ao vigor (envelhecimento acelerado, emergência de plântulas, altura e massa de matéria seca de plântulas e mudas). O teor de água das sementes também foi determinado. Utilizou-se o delineamento estatístico de blocos ao acaso, com quatro repetições, e o teste de Tukey a 5% para comparação de médias. Concluiu-se que: a) a qualidade fisiológica das sementes foi aprimorada à medida que o lote passou por equipamentos específicos no beneficiamento, culminando com a melhor qualidade na seqüência operacional em que o lote foi submetido à ação da máquina de ventiladores e peneiras e mesa densimétrica; b) a mesa densimétrica, associada à máquina de ventiladores e peneiras, foi o equipamento que proporcionou a melhor separação de materiais que interferem negativamente na qualidade fisiológica das sementes; c) as sementes maiores e/ou mais pesadas tiveram qualidade fisiológica superior, e as sementes mocas graúdas, qualidade fisiológica similar à das sementes chatas graúdas; d) o descarte das frações do lote constituídas por sementes pequenas ou de menor densidade possibilitou a obtenção de lotes homogêneos e com alta qualidade fisiológica, favorecendo a obtenção de mudas mais vigorosas.<br>The objective of this research was to obtain more suitable information concerning coffee seed processing in the air-screen machines and gravity table, studying their effects on the physiological seed quality. One coffee seed lot of the Yellow Catuaí IAC 62 cultivar was processed in a precleaner machine, in an air-screen cleaner and in a gravity table, working in several sequences and combinations, according to technical recommendations for seed processing. The seeds were evaluated as to their physiological quality by the germination test, accelerated aging test, seedling emergence, height and weight of dry matter of seedlings and young plants. The seed moisture was determined at the beginning of the evaluations. The statistical design was randomized blocks with four replications. Mean comparisons were done by the Tukey test at 5 % of probability. It was concluded that: a) physiological seed quality was improved by specific equipments in the several phases of processing, with the best seed quality, obtained with complete operational sequence, where the lot was submitted to the action of the air-screen cleaner and gravity table; b) the gravity table, associated with air-screen cleaner, was effective in removing debris from the seed lot, improving the physiological seed quality; c) larger or denser seeds had superior physiological performance than small sizeor lowdensity seeds, and the large pea berry seeds presented physiological quality similar to the large flat seeds; d) discart of smallest or lightest seeds to improved the physiological seed quality, resulting in homogeneous, and high quality seed lots, and more vigorous young plants