Avaliação do efeito anti-inflamatório e antiasmático da 15-deoxy-delta-12,14-prostaglandina J2 em modelos murinos de asma

A asma é um distúrbio crônico pulmonar caracterizado por inflamação, obstrução e remodelamento brônquico, levando a sintomas como sibilo, tosse e falta de ar. A terapia antiasmática consiste em corticosteroides inalados e agonistas β2 de curta ou longa duração. O tratamento é limitado por efeitos colaterais e refratariedade de alguns pacientes, justificando a necessidade de novas terapias. Estudos demonstram que a 15-deoxy-delta- 12,14-prostaglandina J2 (15d-PGJ2), um ligante endógeno de receptores ativados por proliferadores de peroxissomos do tipo gama (PPAR-γ), é capaz de reduzir a expressão de citocinas pró-inflamatórias, o que pode resultar em benefícios no tratamento de doenças com esse perfil. O objetivo deste estudo foi avaliar o potencial anti-inflamatório e antiasmático da 15d-PGJ2 em modelos experimentais de asma. Camundongos A/J machos foram sensibilizados nos dias 0 e 7 através de injeção subcutânea (s.c.), contendo ovoalbumina (OVA) e Al(OH)3, e desafiados com 4 instilações intranasais (i.n.) de OVA em intervalos semanais. O tratamento com 15d-PGJ2 (30 e 100 g/Kg, s.c.) foi realizado 30 min antes dos desafios a partir da terceira provocação antigênica. Em outro modelo, camundongos A/J foram desafiados intranasalmente com extrato de ácaro 3 vezes por semana durante 3 semanas. As administrações de 15d-PGJ2 (30, 70 e 100 g/Kg, s.c. e 0,65; 1,5 e 2,3 g/animal, i.n.) foram realizadas a partir da 3 semana, 30 min antes dos desafios. As análises ocorreram 24 h após o último desafio. Nossos resultados mostraram que, em camundongos previamente sensibilizados e desafiados com OVA, a administração de 15d-PGJ2 limitou significativamente o influxo peribrônquico de eosinófilos e neutrófilos, bem como a produção de muco por células caliciformes e fibrose sub-epitelial, além da hiperreatividade das vias aéreas e produção de IL-5. A redução do epitélio brônquico e das citocinas IL-13 e TNF-α foram observadas somente na maior dose administrada. No modelo HDM a inflamação e o remodelamento foram atenuados em todas as doses administradas do composto, enquanto que a hiperresponssividade brônquica foi inibida apenas nas doses de 70 e 100 μg/Kg (via sistêmica) e na dose intermediária dada topicamente (1,5 μg/animal, i.n.). Os níveis de citocinas foram atenuados pelo tratamento subcutâneo, porém somente os níveis de IL-17, eotaxina-1 e TNF-α foram inibidos com a dose intranasal de 0,65 g/animal. O aumento da expressão de NF-κB, induzido por provocação com HDM também foi reduzido significativamente pela administração de 15d-PGJ2. Em conjunto, nossos dados indicam que o tratamento com 15d-PGJ2 inibe alterações cruciais associadas à patogênese da asma, em modelos experimentais distintos da doença, demonstrando possuir grande potencial para controlar e reverter inflamação, hiperreatividade e remodelamento pulmonar desencadeados por provocação alérgica.

Climatic factors associated with phytoplankton community succession during and after the 1977 drought for the San Francisco Bay-Delta Estuary [abstract]

Principal coordinates analysis and multiple regression analysis were used to determine the environmental factors associated with the decline in phytoplankton production during and after the 1977 drought for the San Francisco Bay-Delta Estuary. Physical, chemical and biological data were collected semimonthly or monthly during the spring-summer between 1973 and 1982 from 15 sampling sites located throughout the Bay-Delta. A decline in phytoplankton community diversity and density during the 1977 drought and subsequent years (1978 through 1981) was described using principal coordinates analysis. The best multiple regression which described the changes in phytoplankton community succession contained the variables water temperature, wind velocity and ortho-phosphate concentration. Together these variables accounted for 61 percent of the variation in the phytoplankton community among years described by principal coordinates analysis. An increase in water temperature, wind velocity and ortho-phosphate concentration within the Bay-Delta, beginning in June 1976 and continuing through 1981, was demonstrated using weighted moving averages. From the strong association between phytoplankton community succession and climatic variables it was hypothesized that the decline in phytoplankton production during and after the 1977 drought was associated with climatic changes within the northeast Pacific.

Associations among chlorophyll concentration and climatic variables for Suisun Bay and the Sacramento-San Joaquin Delta [abstract]

EXTRACT (SEE PDF FOR FULL ABSTRACT): The recent changes in phytoplankton production and community composition within the Suisun Bay and Sacramento-San Joaquin Delta may be related to climate. Chlorophyll a concentration, decreased by 42% (spring-summer) and 29% (fall) between 1972 through 1976 and 1977 through 1981. The decrease in biomass was characterized by a shift in phytoplankton community dominance from Skeletonema spp., Cyclotella spp. and Coscinodiscus spp. to Melosira granulata. The possible influence of climate on phytoplankton abundance was suggested by multivariate statistical analyses that demonstrated an association between changes in phytoplankton community composition and abundance between 1975 and 1982 and the climate related variables wind velocity, precipitation, river flow and water temperature.

Influence of climate on environmental factors associated with long-term changes in chlorophyll production for the Sacramento-San Joaquin delta and Suisun Bay, California

Long-term changes in chlorophyll production were predicted from environmental variables for the Sacramento and San Joaquin rivers and Suisun Bay using Box-Jenkins transfer function models. Data used for the analyses were collected semimonthly or monthly between 1971 and 1987. Transfer function models developed to describe changes in chlorophyll production over time as a function of environmental variables were characterized by lagged responses and described between 39 and 51 percent of the data variation. Significant correlations between environmental variables and the California climate index (CA SLP) were used to develop a conceptual model of the link between regional climate and estuarine production.

Distribution of surface sediments off Indus delta on the continental shelf of Pakistan

Surface sediments from the continental shelf area off Indus delta were analysed for their textural characteristics and carbonate content. The sediments are largely silt, silty clay and clayey silty sand. Sandy fraction is dominant in the outer region with relatively high carbonate content. The study shows that distribution of carbonate in sediments off Indus delta continental shelf is controlled by the dilution of terrigenous material and its distance from source area.