Caspases are believed to play a key role in the delayed neuronal cell death observed in the rat brain after hypoxicischemic (HI) insult. Caspase inhibitors have been developed as antiapoptotic agents. Hippocampal damage after HI insult is strongly related to tissue temperature, and systemic hypothermia has been introduced clinically for brain protection. In this study, we examined the effects of a caspase inhibitor and systemic hypothermia on neuronal protection in the developing rat brain. Postnatal d 7 rat pups were subjected to the Rice model of hypoxia for 1 h. Systemic hypothermia was induced with a water bath at 29°C. Before HI insult, a pan-caspase inhibitor, bocaspartyl-(OMe)-fluoromethyl-ketone (BAF), was injected into the cerebral ventricle. The ipsilateral hippocampus was subjected to caspase assays and histologic assessment. The HI group at 37°C (HI-37°C) showed a peak of caspase-3 activity 16 h after insult. This activity was significantly reduced in the presence of BAF or hypothermia (HI-29°C group, p Ͻ 0.05) or by the combination of HI-29°C ϩ BAF (p Ͻ 0.01 versus HI-37°C). The number of neuronal cells in the ipsilateral hippocampal CA1 region in the HI-37°C group was significantly decreased (62.9% versus control). The number of neuronal cells was maintained in the HI-37°C ϩ BAF group (82.7%), the HI-29°C group (78.7%), and the combination group (95.2%) (p Ͻ 0.05 versus HI-37°C). A combination of systemic hypothermia and BAF produced a strong protective effect against neuronal damage in the developing rat brain, along with a reduction in caspase-3 activity. Investigators have recently reported that transient HI induces not only acute brain damage but also DNCD in selected regions such as the hippocampus, striatum, and pons in human and animal brains (1, 2). DNCD is characteristically observed 3-5 d after insult. Others have reported that DNCD displays characteristics of PCD (3, 4). Some of the morphologic features observed in PCD, such as condensation of nuclear chromatin, cytoplasmic shrinkage without inflammatory reaction, dilated endoplasmic reticulum, membrane blebbing, and formation of apoptotic bodies, are characteristic of apoptosis (3, 5). Apoptotic PCD plays an important role in animal and human models of various diseases, such as ischemic brain damage (3, 5, 6), traumatic brain injury (7,8), neurodegenerative diseases (9 -12), CNS infection (13), and epilepsy (14 -16). Many reports have also revealed biochemical and genetic events that accompany apoptotic cell death. One of these events is the activation of a specific family of cysteine proteases, caspases, that precede the occurrence of DNA fragmentation, which also occurs in apoptosis (17, 18). In brief, caspases are synthesized in most cells as inactive precursors (pro-caspases) and are activated to form active caspases. Caspase-3, a terminal player in the caspase family, activates an endonuclease (caspase-activated DNAse, or CAD) to induce the fragmentation of DNA (4).Recently, various caspase inhibitors have been developed. Some inve...
International surveys have demonstrated that asthma is still underdiagnosed and undertreated in many parts of the world. Despite improvements in the standard of asthma care delivered in many areas, as evidenced by improved global asthma mortality data, much information on projects and programmes undertaken in resource-limited regions of the world is not in the public domain. The aim of this report is to review projects and programmes in diverse regions around the world so that health care providers, planners and consumers may draw on the successes, failures and lessons learnt. Such real world experiences may contribute to achieving Global Initiative for Asthma goals of asthma control. Asthma projects and programmes in Argentina, Australia, Brazil, China, Japan, Mexico, Philippines, Russia, South Africa and Turkey were discussed by a group of experts in asthma care, the Advancing Asthma Care Network, from their respective countries, over a course of three satellite meetings in 2010. Collective analyses consistently identified low rates of dissemination and implementation of national and international treatment guidelines, low levels of continuing medical education and training of primary health care professionals and access and distribution of inhaled corticosteroids to be major barriers that are critical to the overall success of a national asthma management programme. In the less developed asthma programmes, under-recognition and undertreatment further limited the success of the programmes. Evidence from well-established national asthma management programmes suggests that establishment of a successful programme entails a logical progression through specific developmental stages, starting with political/stakeholder endorsement and commitment, followed by epidemiological evaluation, evaluation of disease burden, evaluation of access to care and best therapy, and finally optimisation and maintenance therapy for individual patients.
Preterm WS patients responded well to treatment. Distinguishing WS patients on the basis of different etiologies is important for evaluating the effectiveness of treatment.
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