Comparative Model for Immobility Osteopenia
The mechanism of immobility osteopenia is a complex phenomenon of both biochemical and mechanical etiology. This study is designed to investigate the hypothesis that changes in patterns of both known and unknown small molecular weight compounds (e. g., tyrosine and tryptophan metabolites, neurotransmitters, cofactors, peptides and purines). This study can predict and precede or trigger changes in the balance of anabolic and catabolic processes ultimately resulting in osteopenia. The work will examine the osteopenia inducing human bedrest model as compared with seasonal bear metabolism as a model where osteopenia does not occur. Coulometric Electrode Array Systems (CEAS) will be used to isolate patterns of 4-500 compounds at the picogram level from plasma. Developmental software will be employed for complete pattern matching and data base transfer of 40-60 known and 200-300 unknown compounds. Existing plasma samples from 200-250 seasonal bear, 100-150 human bedrest study subjects, and 30-40 rats will be analyzed. Initial CEAS analysis of summer and winter bear plasma corroborates the theory that, fueled by the bear's winter lipid metabolism, protein synthesis proceeds at higher rates in winter than during summer. There were significant differences in serotonergic, kynurenic, dopaminergic, purine and peptide profiles. Pattern changes in small molecular weight nitrogen cycle metabolites may represent evolutionary adaptation coping with environmental factors and offering osteoregulatory mechanisms mitigating torpor's immobility effects. The data will be analyzed for inter and intraspecies differences in metabolic profiles that may be potential triggers or suppressors of osteopenia. Particular attention will be paid to acquiring information regarding the timing and pattern changes in anabolic metabolism. The data will guide design of a Phase II effort to investigate potential endogenous pharmaceuticals for suppression of osteopenia.
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Principal Investigator:Paul E. Milbury
45 Wiggins Avenue Bedford, MA 01730
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