ABSTRACT
Fructose 1, 6 diphosphate (FDP), a metabolic intermediate, provides an alternative mechanism to circumvent the rate-limiting step in the Kreb's cycle. This agent has been observed to prevent the effects of ischemia on heart tissue and kidney function and the effects of endotoxic shock. It has been shown conclusively to minimize the adverse effects of ischemia-reperfusion injury in experimental pedicled skin flaps in animals. The present study was done to evaluate the effect of intra-arterial administration of FDP on salvage of ischemic microvascular transfer of gracilis muscle flaps in rats, with the premise that it might prolong the ischemia time of muscle flaps at room temperature, thus increasing chances of flap survival. Irrigation with FDP did not change the quantitative survival of the flaps, but there was qualitative improvement on histologic evaluation and DNA analysis. Decreased inflammatory damage and DNA fragmentation were seen at the 2.5-hr period. Histologic staining for mitochondrial oxygenation in gracilis muscle also showed increased uptake in the FDP-treated group vs. control at the 2.5-hr ischemia period. Further experiments with different modes of FDP administration should be carried out to identify more effective means of amelioration of flap ischemia.
Subject(s)
Cardiovascular Agents/therapeutic use , Fructosediphosphates/therapeutic use , Ischemia/drug therapy , Surgical Flaps/blood supply , Animals , Cardiovascular Agents/pharmacology , Fructosediphosphates/pharmacology , Graft Survival/drug effects , Male , Models, Animal , Muscle, Skeletal/blood supply , Rats , Rats, Sprague-DawleyABSTRACT
We describe several families of African origin with SCA3/Machado-Joseph disease gene expansions. In these cases, the phenotype ranges from ataxia with parkinsonian signs to a syndrome clinically almost indistinguishable from idiopathic, L-dopa-responsive Parkinson's disease. In contrast, these parkinsonian phenotypes are rare in those of European descent. Haplotype analysis shows that these African families do not share a common founder, thus a cis-acting element in the promoter is unlikely to be responsible these unusual presentations. We suggest that trans-acting factors are responsible for the variable phenotype and discuss the implications of diseases showing racially different expressivities.