Oxidative stress is one of the factors involved in age-related impairment of cardiac function. In the present study, we investigated the role of the catecholamine-degrading enzyme monoamine oxidase (MAO) in H(2)O(2) production in the hearts of young, adult, and old rats. MAO-dependent H(2)O(2) production, measured by a chemiluminescence-based assay, increased with age, reaching the maximum in 24-mo-old rats (7.5-fold increase vs. 1-mo-old rats). The following observations indicate that the age-dependent increase in H(2)O(2) generation was fully related to the MAO-A isoform: 1) at all the ages tested, chemiluminescence production was inhibited by the MAO-A inhibitor clorgyline but not by the MAO-B inhibitor RO-19 6327; 2) enzyme assay, Western blot, and semiquantitative RT-PCR analysis showed an age-dependent increase in cardiac MAO-A activity, immunodetection, and mRNA expression, respectively; and 3) the MAO-B isoform was undetectable by enzyme assay and Western blot analysis. These results suggest that MAO-A could be a major source of H(2)O(2) in the aging heart.

Induction of angiogenesis is an effective means of potentiating the functional benefits of myoblast transplantation, and hypoxia-inducible factor 1alpha can successfully achieve this goal.

Aims Fluid retention is a phenomenon associated with taxoids. The principal objective of this study was to investigate the pathophysiological mechanism of docetaxel-induced fluid retention in advanced cancer patients. Methods Docetaxel was administered as a 1 h intravenous infusion every 3 weeks, for at least 4-6 consecutive cycles, to patients with advanced breast (n=21) or ovarian (n=3) carcinoma, who had received previous chemotherapy, 21 for advanced disease. Phase II clinical trials have shown that 5 day corticosteroid comedication, starting 1 day before docetaxel infusion, significantly reduces the incidence and severity of fluid retention. This prophylactic corticosteroid regimen is currently recommended for patients receiving docetaxel but was not permitted in this study because of its possible interference with the underlying pathophysiology of the fluid retention. Results Fluid retention occurred in 21 of the 24 patients but was mainly mild to moderate, with only five patients experiencing severe fluid retention. Eighteen patients received symptomatic flavonoid treatment, commonly prescribed after the last cycle. Specific investigations for fluid retention confirmed a relationship between cumulative docetaxel dose and development of fluid retention. Capillary filtration test analysis showed a two-step process for fluid retention generation, with progressive congestion of the interstitial space by proteins and water starting between the second and the fourth cycle, followed by insufficient lymphatic drainage. Conclusions A vascular protector such as micronized diosmine hesperidine with recommended corticosteroid premedication and benzopyrones may be useful in preventing and treating docetaxel-induced fluid retention.