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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

A novel inhibitor of Rho-associated protein kinase, Y-27632, ameliorates hepatic ischemia and reperfusion injury in rats.

BACKGROUND: A Rho-ROCK signal system induces vascular contraction and neutrophil migration, both of which are characteristic features found with ischemia and reperfusion injury of the liver. We tested our hypothesis that a novel ROCK I inhibitor, Y-27632, attenuates hepatic ischemia and reperfusion injury. METHODS: Rats underwent 70% partial hepatic ischemia for 120 minutes and subsequent reperfusion. Y-27632 of 10mg/kg was given orally 1 hour before ischemia, while distilled water was given to the control animals. One week animal survival, systemic hemodynamics, hepatic tissue blood flow, liver function tests, plasma endothelin-1, serum hyaluronic acid levels, myeloperoxidase activity and malondialdehyde level in liver tissue, membrane attack complex-1 and intracellular adhesion molecule-1 staining, and histological architecture were analyzed. RESULTS: Y-27632 prolonged 1-week animal survival from 25% of untreated animals to 75% accompanied with significant amelioration of hepatic tissue blood flow, liver function tests and histological architecture without any adverse effects on systemic hemodynamics. In addition, plasma endothelin-1 and serum hyaluronic acid levels decreased markedly compared to the control, concomitant with remarkable suppression of membrane attack complex-1 stain positive neutrophils infiltration, myeloperoxidase activity and malondialdehyde level. CONCLUSION: Present study suggests that activation of a Rho-ROCK signal system is associated with ischemia and reperfusion injury of the liver, and that Y-27632 may be an attractive agent for application in major liver resection using temporary inflow occlusion and hepatic preservation.[1]

References

  1. A novel inhibitor of Rho-associated protein kinase, Y-27632, ameliorates hepatic ischemia and reperfusion injury in rats. Takeda, K., Jin, M.B., Fujita, M., Fukai, M., Sakurai, T., Nakayama, M., Taniguchi, M., Suzuki, T., Shimamura, T., Furukawa, H., Todo, S. Surgery (2003) [Pubmed]
 
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