Therapeutic azulenyl nitrone antioxidants

The reactions of nitrones with free radicals have been widely studied both in vitro and in vivo. In comparison to classical chain-breaking phenolic antioxidants (such as Vitamin E and butylated hydroxytoluene [BHT]), conventional phenyl-substituted nitrones have much higher oxidation potentials. Azulenyl-substituted nitrones have lower oxidation potentials than conventional nitrones and react efficiently with free radicals in vitro and in vivo. The design and synthesis of novel azulenyl nitrones with yet lower oxidation potentials, prepared from commercially available guaiazulene, has produced several 1,2-trans -bis-azulenyl ethene compounds with enhanced antioxidant activity. A convenient 1H NMR-based assay for assessing the potency of chain-breaking antioxidants has shown these novel nitrones to be more than 300 times more potent in inhibiting the free radical-mediated aerobic peroxidation of cumene than α-phenyl-N-tert-butyl nitrone (PBN) and the experimental stroke drug NXY-059. The low oxidation potential of these novel nitrones and the stability of the corresponding radical cation have been implicated in the explanation of the increased antioxidant potency of these second generation azulenyl nitrones. Based on the results of these in vitro studies, the first of these novel compounds, stilbazulenyl nitrone (STAZN), was investigated in animal models of disease known to involve free radical-mediated pathology. In view of STAZN's marked lipophilicity and anticipated blood brain barrier permeability, neurodegenerative conditions were investigated. All animal experiments were performed at the University of Miami by members of the Ginsberg research group. STAZN was neuroprotective in traumatic brain injury in rats. It also provided exceptional neuroprotection in an animal model of stroke. The concentration of STAZN required for neuroprotection was 300–600 times less than doses of PBN or NXY-059 required for similar effect. Thus, the benefits of greater antioxidant potency sought by lowering the oxidation potential of nitrones appear to have been reaped both in vitro and in vivo. In spite of the challenges and difficulties in understanding free radical-mediated pathology, this work establishes that considerations such as redox potential and lipophilicity can provide a very fruitful rationale for the design of therapeutic azulenyl nitrone antioxidants. ^

The role of group activity participation in depression among institutionalized elderly

The role of group activity participation in depression among a group of residents (N=65), age 80 and older, in a nursing home was examined using the framework of Roy's Adaptation Theory and Nolen-Hoeksema's Response Style Theory of Depression. Roy views depression as a maladaptation. Nolen-Hoeksema views group activity participation as a therapeutic distraction to break depressed moods and thus allow for positive adaptation. This study utilized data from medical records, group activity attendance, and self-report questionnaires. Demographic distributions were computed and correlational statistics were performed between subjects' participation and their degree of depression, pain experience, functional status, presence of social support, and perception of benefits. Results show a negative correlation between frequency of participation and Geriatric Depression Scale score (GDS). The wide range of measured frequencies among low GDS-scored subjects suggests that less depressed individuals exercise more freedom of choice to participate than those who are more depressed. Significant finding show a positive correlation of group activity participation with functional status in terms of ambulation. Data shows that the experience of pain was not a significant deterrent to participation. The presence of social support from the staff and family did not increase participation. However there is a lesser GDS score among subjects who had recent family/friends visit suggesting a positive role of family in decreasing depression. These results are significant not only for optimizing group therapeutic effects but also for understanding basic human and environmental correlates of depression. Study limitations are pointed out and recommendations are presented.