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.
An ex vivo shunt, established in dogs between both femoral arteries and right atrium, has been used to quantify the platelet deposition on six prosthetic materials used in the construction of cardiovascular prostheses: highly porous knitted Dacron (intervascular HP 800, 1400 mL/cm2/min/120 mm Hg), low-porosity woven Dacron (intervascular LP 200, 200 mL/cm2/min/120 mm Hg), double velour knitted Dacron, Avcothane 51 elastomere, and the mesothelial and epipericardial surfaces of bovine pericardium. In the search for a method to prevent platelet thrombi formation on these materials, we studied four groups of dogs: group 1 (control), group 2 (5 mg/kg body weight (BW)/day acetylsalicylic acid), group 3 (20 mg/kg BW/day acetylsalicylic acid), and group 4 (5 mg/kg BW/day acetylsalicylic acid plus 5 mg/kg BW/day dipyridamole). Platelets were labeled with 111In-oxine. The least thrombogenic material was Avcothane 51 elastomere. The only effective treatment for reduction of platelet deposition on the six materials was 5 mg/kg BW/day of acetylsalicylic acid. The dose used in group 3 only decreased the deposition of platelets on three of the six materials studied. The treatment employed in group 4 did not significantly reduce the deposition of platelets on any of the materials when compared with the control group.
Metabolic syndrome (MS) individuals have a higher risk of developing chronic kidney disease through unclear pathogenic mechanisms. MS has been also related with higher nephrolithiasis prevalence. To establish the influence of MS on renal function, we designed a murine model of combined metabolic syndrome and hyperoxaluria. Four groups of male Sprague-Dawley rats were established: (1) control group (n = 10) fed with standard chow; (2) stone former group (SF) (n = 10) fed with standard chow plus 0.75% ethylene glycol administered in the drinking water; (3) metabolic syndrome group (MS) (n = 10), fed with 60% fructose diet; (4) metabolic syndrome + stone former group (MS + SF) (n = 10), 60% fructose diet and 0.75% EG in the drinking water. MS group showed a significant injury to renal function when hyperoxaluria was induced. It was demonstrated by a significant decrease of creatinine clearance (p < 0.001), with higher tubular damage (34.3%, CI 95% 23.9-44.7, p < 0.001), produced by deposition of crystals, and increased tubular synthesis of osteopontin as a response to tubular damage. Induction of hyperoxaluria in rats with MS causes severe morphological alterations with a significant impairment of renal function. This impairment is not produced in rats without MS. Therefore, this model can be useful for the study of the influence of MS in stone formation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.