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Articles by Patrick L. Gentry
Total Records ( 1 ) for Patrick L. Gentry
  Patrick L. Gentry and Stephen A. Kempson
  There has been recent interest in the role of the kidney in the regulation of metabolic byproducts thought to be involved in the induction of endothelial dysfunction. The symptoms include increased blood pressure, decreased kidney function, increase in serum markers such as transforming growth factor beta, reactive oxygen species, asymmetric dimethylated arginine and an increase in the prothrombic and inflammatory state of the vasculature. Pathologies that exhibit this unique set of physiological findings include such diseases as diabetes, hypertension and other types of cardiovascular disease. Interestingly, the side effects of cyclosporine (CsA) treatment or more specifically, CsA induced nephropathy, exhibit many of the same type of symptoms. CsA was introduced as a way to inhibit the immune system for the purposes of increasing the long-term success of organ transplantations. However, as the CsA doses were increased to gain a higher level of immune system suppression, the greater the incidence of CsA induced side effects. When these are examined, there is a strong resemblance to the group of physiological findings in endothelial dysfunction. In what was supposed to be an immune system suppressant, CsA appears to have the ability, in high doses, to initiate an inflammatory response. This response seems to implicate a mechanism with its roots in the calcineurin/nuclear factor of activated T-cells (NFAT) pathway. Kidney dysfunction and hypertension are precursors to endothelial dysfunction and the calcineurin/NFAT pathway, which is disrupted by CsA, is strongly implicated in the process and may be a key to understanding the pathophysiology.
 
 
 
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