Cisplatin is a highly effective chemotherapeutic agent but displays significant ototoxic side effects. The most prominent change seen in the cochlea after cisplatin administration consists of loss of outer hair cells. Several mechanisms are believed to mediate cisplatin-induced apoptosis: binding of cisplatin to guanine bases on DNA and the formation of inter- and intra-strand chain cross-linking, generation of reactive oxygen species (ROS) with increased lipid peroxidation and Ca(2+) influx and, finally, inflammation mediated by cisplatin. The aim of the present review is to analyze the role of ROS in the mechanisms causing cisplatin-mediated apoptosis in the inner ear and the contribution of the different pathways involved, emphasizing the main strategies to blockade events leading to apoptosis of cochlear cells.

In this study, we asked whether the serum acute-phase protein C-reactive protein (CRP) increased in large surfactant aggregates after lung transplantation and analyzed the changes in composition and interfacial adsorption activity of those aggregates. Single left lung transplantation was performed in weight-matched pairs of dogs. A double-lung block from the donor animal was flushed with either modified Euro-Collins solution (EC) (n = 6) or University of Wisconsin solution (UW) (n = 6) at 4 degrees C followed by immersion in cold EC or UW for 22 h. The left donor lung was transplanted. The recipient dog was then reperfused for 4.5 h. Irrespective of the preservation fluid, gas exchanged was impaired in the transplanted lung after 4.5 h of reperfusion. Large surfactant aggregates obtained from this lung showed reduced ability to rapidly adsorb to an air-liquid interface. Phospholipid (PL) content and PL composition of surfactant from lung transplants was similar to that of the control lungs. However, the content of surfactant protein A decreased after reperfusion. In addition, Western blot analyses showed that levels of CRP increased in surfactant from transplanted but not from donor lungs. The addition of human CRP to control surfactant (CRP:PL weight ratio, 0.01:1) caused a decrease of surfactant adsorption. We conclude that the impairment of adsorption facilities of surfactant from transplanted lungs may be correlated with decreased levels of surfactant protein A and increased levels of CRP. The presence of elevated levels of CRP in bronchoalveolar lavage could be a very sensitive marker of lung injury.

The ventral approach to the rat middle ear is a rapid and simple technique that makes the rat the animal of choice for many otologic investigations.

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