New perspectives on the cardioprotective phosphonate effect of the spin trap 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide: an hemodynamic and 31P NMR study in rat hearts.

The spin trap 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO) is an improved ESR probe to assess superoxide (O2*-) formation in the postischemic heart. We recently found that DEPMPO pretreatment improves recovery of cardiac function with the concomitant inhibition of postischemic O2*- production. By perfusing diethyl methylphosphonate MeP(O)(OEt)2 to ischemic-reperfused isolated rat hearts, we provide hemodynamic evidence that this preservation, which exerts during ischemia, is in fact specific to the phosphonate group. Using 31P NMR on intact rat hearts, it was also found that the "phosphonate effect" of DEPMPO is related to the preservation of ATP levels during ischemia, when compared to 5,5-dimethyl-1-pyrroline N-oxide. This mechanism may be a means of reducing the potency of cardiac tissue to produce O2*- during reperfusion.

Cardioprotective and anti-oxidant effects of the terpenoid constituents of Ginkgo biloba extract (EGb 761).

Hemodynamic and electron spin resonance analyses were used to assess the in vivo and in vitro cardioprotective and antioxidant effects of therapeutically relevant doses of Ginkgo biloba extract (EGb 761) and its terpenoid constituents (ginkgolides A and B, bilobalide) in the rat. Significant anti-ischemic effects, indicating improved myocardial functional recovery, were observed after repeated (15-day) oral treatments with both EGb 761 (60 mg/kg/day) and ginkgolide A (4 mg/kg/day), as compared to placebo. In vitro pre- and post-ischemic perfusion of hearts in the presence of the ginkgolides A and B (both at 0.05 microgram/ml) or bilobalide (0.15 microgram/ml), but not EGb 761 (5 micrograms/ml), significantly improved all hemodynamic parameters. Post-ischemic levels of the 5,5-dimethyl-1-pyrroline N-oxide (DMPO)/hydroxyl radical spin-adduct (DMPO-OH) in coronary effluents were significantly decreased after in vivo oral treatments or after in vitro perfusion with EGb 761 or the terpenes, the most effective compound being ginkgolide A. As the presence of the terpenes did not influence the formation of the superoxide/DMPO adduct or DMPO-OH in acellular tests with superoxide and hydroxyl radical generators, their cardioprotective effects appear to involve an inhibition of free radical formation rather than direct free radical scavenging.

Research project on the treatment of anorexia and bulimia: an integrative, multidimensional approach.

This research project tries to test a therapeutic strategy that could improve the prognosis of anorexic and bulimic syndrome, by reducing their tendency to chronicity. The hypothesis is that, whenever we deal with complex, multifactoral syndromes, such as anorexia and bulimia, a therapy based upon the association of different kinds of treatments (medical-biological-nutritional treatments plus family therapy) helps to obtain better results than one type of treatment only (medical-biological-nutritional alone). The selection of the samples (experimental and control samples), the materials and methods of the research project, and the follow-up series are described.