Concurred with a recently published article with significantly en

Concurred with a recently published article with significantly enhanced angiogenesis and number of EPCs in the scientific assay ischemic zone in a rat CLI model after com bination therapy, remarkably elevation of the circulat ing level of EPCs was found in our patients after similar treatment for 90 days. Second, studies have previously re ported that proliferation of neo intimal growth of vascular smooth Inhibitors,Modulators,Libraries muscle cells plays a key role in the progression of restenosis and PAD as well as restenosis after PAD intervention. Additionally, as described in many studies clopidogrel and cilostazol harbor anti platelet and anti thrombotic effects while cilostazol can inhibit smooth muscle cell proliferation. Ac cording to the results of these studies, we believe that such effects may also contribute to the delight ful outcome of among our patients.

Third, as revealed by our results, clopidogrel and cilostazol combination therapy elicit potent anti inflammatory Inhibitors,Modulators,Libraries effect which is helpful in limiting the exacerbation of ulcers and aug menting would healing. The proposed Inhibitors,Modulators,Libraries mechanisms Inhibitors,Modulators,Libraries of clopidogrel and cilosta zol combination therapy in improving clinical outcome of CLI patients have been summarized in Figure 5 and described as the followings based on the findings of the current study and the previous reportsPlatelet activation in setting of CLI stimulated the acti vation and migration of peripheral leukocytes. Both activated macrophages and T cells then produced the galactin 3 which, in turn, promoted the focal adhesion turnover, cell migration, and RhoA activation.

Additionally, Lp PLA2 enhanced the generation of inflammatory cytokines and up regulated the inflammatory process. Finally, galactin 3, Lp PLA2 and RhoAROCK synergistically promoted the inflammation and ultimately Inhibitors,Modulators,Libraries worsened the wound ulcerations and pain ful sensation. On the other hand, combine ther apy with clopidogrel and cilostazol enhanced angiogenesis neovascularization which, in tern, improve blood flow in the ischemia zone, and finally, improved the wound healing. Study limitations This study has limitations. First, the sample size of the present study was relatively small. However, the prelimin ary results clopidogrel and cilostazol combination therapy in CLI patients who are not amendable by surgical or endovascular methods are promising. Second, the 90 day study period in this initial trial was relatively short. The clinical benefits or drawbacks after long term combination therapy are not known. Third, in addition to clopidogrel and cilostazol combination therapy, patients were also sub jected to statin and ACIARB treatment during the study period and thus the effects or interaction of these drugs could hardly be validated.

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