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.

Age and length composition of Columbia Basin chinook, sockeye, and coho salmon at Bonneville Dam in 2002

In 2002, representative samples of migrating Columbia Basin chinook (Oncorhynchus tshawytscha), sockeye (O. nerka), and coho salmon (O. kisutch) adult populations were collected at Bonneville Dam. Fish were trapped, anesthetized, sampled for scales and biological data, revived, and then released. Scales were examined to estimate age composition; the results contributed to an ongoing database for age class structure of Columbia Basin salmon populations. Based on scale analysis of chinook salmon, four-year-old fish (from brood year [BY] 1998) comprised 86% of the spring chinook, 51% of the summer chinook, and 51% of the bright fall chinook salmon population. Five-year-old fish (BY 1997) comprised 13% of the spring chinook, 43% of the summer chinook, and 11% of the bright fall chinook salmon population. The sockeye salmon population at Bonneville was predominantly five-year-old fish (55%), with 40% returning as four-year-olds in 2002. For the coho salmon population, 88% of the population was three-year-old fish of age class 1.1, while 12% were age class 1.0. Length analysis of the 2002 returns indicated that chinook salmon with a stream-type life history are larger (mean length) at age than the chinook salmon with an ocean-type life history. Trends in mean length over the sampling period for returning 2002 chinook salmon were analyzed. Chinook salmon of age classes 1.2 and 1.3 show a significant increase in mean length over the duration of the migration. A year class regression over the past 14 years of data was used to predict spring, summer, and bright fall chinook salmon population sizes for 2003. Based on three-year-old returns, the relationship predicts four-year-old returns of 54,200 (± 66,600, 90% predictive interval [PI]) spring chinook, 23,800 (± 19,100, 90% PI) summer, and 169,100 (± 139,500, 90% PI) bright fall chinook salmon for the 2003 runs. Based on four-year-old returns, the relationship predicts five-year-old returns of 36,300 (± 35,400, 90% PI) spring, 63,800 (± 10,300, 90% PI) summer, and 91,100 (± 69,400, 90% PI) bright fall chinook salmon for the 2003 runs. The 2003 run size predictions should be used with caution; some of these predictions are well beyond the range of previously observed data.

冬小麦春化过程中蛋白质、氨基酸的代谢变化

本实验以北京冬小麦“农大139”、春小麦“中80-22”为材料，研究了不同时间低温处理对其蛋白质、氨基酸代谢及随后生长发育的影响。主要实验结果如下： 1. 冬小麦“农大139”只有经40天以上的春化处理之后才能迅速而整齐地抽穗，但经14-21天低温处理之后，已经具有在夏季抽穗的可能，虽然抽穗延迟且极不整齐，所以在整个春化处理过程中低温对发育的作用可分为两种不同的性质，前期低温是诱发生理状态的转变，后期低温则只具有加速作用。表明春化过程中有两个性质不同的过程存在，这两个过程的转变时期是在春化的中期。 2. 蛋白质合成抑制剂乙基硫氨酸和对--氟苯丙氨酸能抑制冬小麦的春化，抑制时期也是在春化过程的中期。 3. 不同时间的低温处理后冬小麦幼芽中可溶性蛋白质含量及组成发生变化，春化过程中期（低温处理14天之后）不仅含量比对照增加了一倍，而且有新的蛋白质谱带出现，21KD的新带在春化7天后开始出现;51KD和17KD的新带在春化14天后开始出现;21KD和17KD的新带其相对含量随着低温处理时间的延长而增加。春麦中无类似现象出现，未经低温处理的对照与冬麦经35天春化处理的蛋白质谱带相似。 4. 春化处理35天后紧接着给予35 ℃高温脱春化处理5天，其电泳谱带与未经低温处理的对照相同，植株亦不能拔节、抽穗;春化处理56天后再进行脱春化处理，其电泳谱带更接近于低温处理35天的幼芽，植株亦可正常抽穗。说明春化过程中新出现的蛋白质带的有无是决定播种后植株能否抽穗的关键。 5. 低温下两种小麦中游离氨基酸含量都随低温处理时间而增加，但冬麦的高峰是春化过程的中期，而春麦呈直线上升。冬麦的这种变化趋势可能是为同期蛋白质的大量合成准备原料。 6. 醇不溶性蛋白质的结合氨基酸含量变化趋势与可溶性蛋白质含量的变化一致;春中随着低温处理时间的延长含量逐渐减少;冬麦中则有所增加，高峰在春化过程的中期。说明春化过程中期是冬小麦中与发育有关的蛋白质合成的关键时期。

Change in Pacific Northwest coastal ecosystems. Proceedings of the Pacific Northwest Coastal Ecosystems Regional Study Workshop, August 73-14, 1996, Troutdale, Oregon

Over the past one hundred and fifty years, the landscape and ecosystems of the Pacific Northwest coastal region, already subject to many variable natural forces, have been profoundly affected by human activities. In virtually every coastal watershed from the Strait of Juan de Fuca to Cape Mendocino, settlement, exploitation and development of resou?-ces have altered natural ecosystems. Vast, complex forests that once covered the region have been largely replaced by tree plantations or converted to non-forest conditions. Narrow coastal valleys, once filled with wetlands and braided streams that tempered storm runoff and provided salmon habitat, were drained, filled, or have otherwise been altered to create land for agriculture and other uses. Tideflats and saltmarshes in both large and small estuaries were filled for industrial, commercial, and other urban uses. Many estuaries, including that of the Columbia River, have been channeled, deepened, and jettied to provide for safe, reliable navigation. The prodigious rainfall in the region, once buffered by dense vegetation and complex river and stream habitat, now surges down sirfiplified stream channels laden with increased burdens of sediment and debris. Although these and many other changes have occurred incrementally over time and in widely separated areas, their sum can now be seen to have significantly affected the natural productivity of the region and, as a consequence, changed the economic structure of its human communities. This activity has taken place in a region already shaped by many interacting and dynamic natural forces. Large-scale ocean circulation patterns, which vary over long time periods, determine the strength and location of currents along the coast, and thus affect conditions in the nearshore ocean and estuaries throughout the region. Periodic seasonal differences in the weather and ocean act on shorter time scales; winters are typically wet with storms from the southwest while summers tend to be dry with winds from the northwest. Some phenomena are episodic, such as El Nifio events, which alter weather, marine habitats, and the distribution and survival of marine organisms. Other oceanic and atmospheric changes operate more slowly; over time scales of decades, centuries, and longer. Episodic geologic events also punctuate the region, such as volcanic eruptions that discharge widespread blankets of ash, frequent minor earthquakes, and major subduction zone earthquakes each 300 to 500 years that release accumulated tectonic strain, dropping stretches of ocean shoreline, inundating estuaries and coastal valleys, and triggering landslides that reshape stream profiles. While these many natural processes have altered, sometimes dramatically, the Pacific Northwest coastal region, these same processes have formed productive marine and coastal ecosystems, and many of the species in these systems have adapted to the variable environmental conditions of the region to ensure their long-term survival.