The administration of alpha-melanocyte-stimulating hormone protects the ischemic/reperfused myocardium

The contribution of alpha-melanocyte-stimulating hormone (alpha-MSH) treatment, an active fragment of adrenocorticotropic hormone (ACTH), to the recovery of postischemic cardiac function, infarct size, the incidence of reperfusion-induced ventricular fibrillation and apoptotic cell death was studied in ischemic/reperfused isolated rat hearts. Rats were subcutaneously injected with 40, 200 and 400 microg/kg of alpha-MSH, and 12 h later, hearts were isolated, perfused and subjected to 30 min of ischemia followed by 120 min of reperfusion. Thus, after 120 min of reperfusion, with the concentration of 200 microg/kg alpha-MSH, coronary flow, aortic flow and left ventricular developed pressure were significantly improved from their control values of 14.6+/-0.6 ml/min, 7.5+/-0.5 ml/min and 9.1+/-0.4 kPa to 20.2+/-0.4 ml/min (p<0.05), 31.5+/-0.9 ml/min (p<0.05) and 15.9+/-0.6 (p<0.05) kPa, respectively. With the doses of 40, 200 and 400 microg/kg of alpha-MSH, infarct size was reduced from its control value of 38+/-5% to 33+/-6% (NS), 17+/-3% (p<0.05) and 19+/-4% (p<0.05), respectively. The reduction in the incidence of reperfusion-induced ventricular fibrillation followed the same pattern. It is reasonable to assume that a reduction in infarct size, in the alpha-MSH-treated myocardium, resulted in a reduction as well in apoptotic cell death. Although we did not specifically study the exact mechanism(s) of alpha-MSH-afforded postischemic protection, we assume that this protection may be related to alpha-MSH-induced corticosterone release and corticosterone-induced de novo protein synthesis, which reflected in the recovery of postischemic cardiac function in isolated hearts. Thus, interventions that are able to increase plasma corticosterone or glucocorticoid release may prevent the development of ischemia/reperfusion-induced damage.     

Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy.

PURPOSE: To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. PATIENTS AND METHODS: Eligible patients had a performance status 0 to 2, previous treatment with one prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Patients received pemetrexed 500 mg/m(2) intravenously (i.v.) day 1 with vitamin B(12), folic acid, and dexamethasone or docetaxel 75 mg/m(2) i.v. day 1 with dexamethasone every 21 days. The primary end point was overall survival. RESULTS: Five hundred seventy-one patients were randomly assigned. Overall response rates were 9.1% and 8.8% (analysis of variance P =.105) for pemetrexed and docetaxel, respectively. Median progression-free survival was 2.9 months for each arm, and median survival time was 8.3 versus 7.9 months (P = not significant) for pemetrexed and docetaxel, respectively. The 1-year survival rate for each arm was 29.7%. Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia (40.2% v 5.3%; P <.001), febrile neutropenia (12.7% v 1.9%; P <.001), neutropenia with infections (3.3% v 0.0%; P =.004), hospitalizations for neutropenic fever (13.4% v 1.5%; P <.001), hospitalizations due to other drug related adverse events (10.5% v 6.4%; P =.092), use of granulocyte colony-stimulating factor support (19.2% v 2.6%, P <.001) and all grade alopecia (37.7% v 6.4%; P <.001) compared with patients receiving pemetrexed. CONCLUSION: Treatment with pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a standard treatment option for second-line NSCLC when available.