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Abstract Background Patients with reduced responsiveness to clopidogrel often have diminished platelet inhibition, a factor associated with increased rates of major adverse cardiovascular events. Clinical trials that have focused on reducing high on-treatment platelet reactivity (HPR) with an additional loading dose of clopidogrel have reported varying effects. Prasugrel, a newer thienopyridine, exhibits a more consistent antiplatelet effect and more rapid onset time when compared to clopidogrel. We hypothesize that prasugrel reloading would be more effective than clopidogrel reloading in patients with HPR after an initial loading dose of clopidogrel. Method/Design Comparison of Prasugrel and Clopidogrel Reloading on High Platelet Reactivity in Clopidogrel-loaded Patients Undergoing Percutaneous Coronary Intervention (PRAISE-HPR) is a prospective, randomized, open-label, active controlled study. A total of 76 patients undergoing percutaneous coronary intervention (PCI), with HPR after administration of a loading dose of clopidogrel will be randomly assigned to either prasugrel or clopidogrel groups, and patients in each group will be reloaded with 20 mg of prasugrel or 300 mg of clopidogrel. The primary endpoint will be HPR at 24 hours after PCI, as determined by the VerifyNow assay during the study period. The rate of sustained high platelet reactivity and 30-day clinical outcomes will also be measured. Discussion PRAISE-HPR is a randomized controlled clinical trial to investigate the efficacy and safety of reloading prasugrel and clopidogrel in suppressing residual high platelet reactivity. The results will be made publicly available in the year 2013. Trial registration NCT01609647

Published data suggests that the presence of CYP2C19*2 or *3 loss of function ( LOF) alleles is indicative of increased platelet aggregation and a higher risk of adverse cardiovascular events after clopidogrel administration. We sought to determine cut-off values using three different assays for prediction of the CYP2C19 phenotype in Korean percutaneous coronary intervention (PCI) patients. We enrolled 244 patients with drug-eluting stent implantation who were receiving clopidogrel and aspirin maintenance therapy for one month or more. Platelet reactivity was assessed with light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA) and the VerifyNow P2Y12 assay (VN). The CYP2C19 genotype was analyzed by polymerase chain reaction (PCR) and snapshot method. The frequency of CYP2C19 LOF allele carriers was 58.6%. The cut-off values from LTA, MEA and VerifyNow for the identification of LOF allele carriers were as follows: 10 µM ADP-induced LTA ≥ 48 %, VN > 242 PRU and MEA ≥ 37 U. Between the three tests, correlation was higher between LTA vs. VN assays ( r = 0.69) and LTA vs. MEA ( r = 0.56), with moderate agreement ( κ = 0.46 and κ = 0.46), but between VN assay and MEA, both devices using whole blood showed a lower correlation ( r = 0.42) and agreement ( κ = 0.3). Our results provide guidance regarding cut-off levels for LTA, VerifyNow and MEA assays to detect the CYP2C19 LOF allele in patients during dual antiplatelet maintenance therapy. [ABSTRACT FROM AUTHOR]

An accumulating number of studies are revealing that platelet reactivity above specific cut-off scores leads to exponentially increased rates of post-percutaneous coronary intervention (PCI) ischemic events. To evaluate the optimal predictive values for three different platelet function measurement assays of platelet reactivity on early clinical outcomes in Korean patients undergoing PCI, we enrolled 228 patients receiving clopidogrel prior to PCI. Platelet reactivity was measured by light transmittance aggregometry (LTA), VerifyNow P2Y12 assay, and multiple electrode platelet aggregometry (MEA). The primary endpoint was the 30-day occurrence of ischemic events after PCI. MACE occurred in 36 patients (15.8%), including 35 patients (15.4%) with periprocedural MI and the death of one patient (0.4%). ADP-induced LTA and VerifyNow values (pre- and post-PCI) were significantly higher in patients with the subsequent occurrence of periprocedural MI, but the MEA assay data (PCI and post-PCI) displayed no significant differences (pre-PCI p = 0.25 and post-PCI p = 0.33). ROC curve analysis demonstrated HPR values for LTA (pre-PCI, >66% and post-PCI, >53 %, all p < 0.001), VerifyNow (pre-PCI, >347 PRU and post-PCI >272 PRU, all p < 0.001) and MEA (pre-PCI, >50 U and post-PCI >39 U, all p > 0.05). The platelet reactivity measurements by LTA and the VerifyNow assay can discriminate the risk of 30-day ischemic events after PCI. The predictive cut-off values for adverse events are dependent on sampling time. [ABSTRACT FROM AUTHOR]

Outcomes of platelet function tests are highly dependent on the type of blood anticoagulant used. The primary objective of this study was to clinically evaluate the platelet function after dual antiplatelet therapy using two different types of anticoagulant (citrate and hirudin). We compared data obtained from multiple electrode platelet aggregometry (MEA) with reference to light transmission aggregometry (LTA) and VerifyNow (VN) assays. Blood samples were obtained from 119 patients on dual antiplatelet therapy at the time of PCI (PCI) and the following morning (post-PCI). The platelet function tests were performed using two anticoagulated (citrate or hirudin) blood types for MEA as well as citrated blood for LTA and VerifyNow assays. ADP-induced MEA values at PCI for citrated and hirudinated anticoagulants were 36.5 ± 14.3 AUC and 41.4 ± 18.2 AUC ( p = 0.021) and post-PCI values were 28.2 ± 11.9 AUC and 28.3 ± 12.8 AUC ( p = 0.95). Additionally, AA-induced MEA values at PCI by citrated and hirudinated blood was 13.4 ± 7.3 AUC and 17.6 ± 13.4 AUC ( p < 0.01). Post-PCI AA-induced MEA values were 12.0 ± 6.7 AUC and 13.5 ± 8.5 AUC ( p = 0.12), respectively. Significant correlations were observed between the two anticoagulants used for MEA and LTA or VN values under ADP-induced platelet stimulation. Citrate tubes are clinically adequate for MEA assays and provide a more economical alternative to hirudin for early and/or delayed phases after clopidogrel-loading doses. [ABSTRACT FROM AUTHOR]

Previously, we reported the angio-vasculogenic properties of human stromal vascular fraction (SVF) and adipose tissue-derived mesenchymal stem cells (ASCs). In this study, we investigated whether the combination of ASCs and SVF cells exhibited synergistic angiogenic properties. We conducted quantitative (q)RT-PCR, Matrigel plug, tube formation assays, and in vivo therapeutic assays using an ischemic hind limb mouse model. Immunohistochemical analysis was also conducted. qRT-PCR results revealed that FGF-2 was highly upregulated in ASCs compared with SVF, while PDGF-b and VEGF-A were highly upregulated in SVF. Conditioned medium from mixed cultures of ASCs and SVF (A+S) cells showed higher Matrigel tube formation and endothelial cell proliferation in vitro. A+S cell transplantation into ischemic mouse hind limbs strongly prevented limb loss and augmented blood perfusion compared with SVF cell transplantation. Transplanted A+S cells also showed high capillary density, cell proliferation, angiogenic cytokines, and anti-apoptotic potential in vivo compared with transplanted SVF. Our data indicate that A+S cell transplantation results in synergistic angiogenic therapeutic effects. Accordingly, A+S cell injection could be an alternative therapeutic strategy for treating ischemic diseases. [ABSTRACT FROM AUTHOR]

Objective: Research continued measures to reduce the cesarean section rates under the premise of ensuring medical safety. Methods: Statistically analyzed all the delivery data from Maternal Health Care Management System of five midwifery organizations in Tanggu, Binhai New Area, Tianjin, from 2001 to 2013. Results: Cesarean section rate increased from 40.09% in 2001 to 53.81% (peak rate) in 2008, which was an increasing trend year by year. Undergoing health care, control weight gain during pregnancy and good technique training, cesarean section rate decreased to 37.74 % in 2013. Cesarean section rate decreased year by year between 2008 -2013 . Social factors ranked 6th in cesarean section indications, and gradually increased until 2008 ranked second, uterine scar ranked first in 2013. Conclusions: Processing pregnancy care and control weight gain, improving skills is the effective methods to decrease the rate of cesarean section. In the future, vaginal delivery after cesarean section will be effective prevention methods. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recently, we showed the angio-vasculogenic potential of uncultured human peripheral blood (hPB)-derived CD31+ cells. However, thus far, the angiogenic property of the cultured hPB-derived CD31+ (C-31+) cells is unknown. Thus, this study aimed to assess the angiogenic potency of C-31+ cells on experimental ischemia. Methods: CD31+ and CD31− cells were isolated by magnetic bead separation technique, and cultured in EBM-2 complete medium for 6days. The expression of multiple angiogenic genes in these cells was measured using qRT-PCR. In addition, endothelial progenitor cell culture and matrigel network formation assays were performed. A mouse model of hindlimb ischemia induced by surgical resection of the right femoral artery was used, and the C-31+ cells were intramuscularly transplanted into the ischemic area. Immunohistochemical analysis was also performed. Results: C-31+ cells exclusively showed higher colony-forming activity, and gave rise to EPCs. C-31+ cells also induced higher endothelial network formation, and exhibited higher pro-angiogenic and lower inflammatory gene expression. In our ischemic hindlimb model, transplantation of C-31+ cells induced increased blood perfusion (0.652±0.03 vs. 0.47±0.04; P<0.01) and increased capillary density (85±5.5 vs. 57±4.1; P<0.01) as compared to C-31− cells. In addition, angiogenic factors were markedly upregulated after the transplantation of C-31+ cells, indicating that C-31+ cells contributed to the neovascularization. Conclusions: The high angiogenic and therapeutic potential of C-31+ cells observed in our ischemic animal model suggests a novel role of hPB-derived cultured CD31+ cells in the treatment of ischemic cardiovascular diseases. [Copyright &y& Elsevier]

Purpose: To evaluate the clinical performance of at-home bleaching and its application in combination with cold-light bleaching for esthetic management of fluorosed teeth，providing guidance for clinicians to choose the right treatment regimen and communicate with patients successfully., Methods: We divided 43 cases with stained dental fluorosis into 2 groups, with 22 cases in the at-home bleaching group and 21 in the combination therapy group. Stained spots were chosen and colorimetric assay was performed using CMYK colorimetric table before treatment. According to the color of the splash, the light and shade were divided into light grade, medium grade and heavy grade. The CMYK data of the selected point and complete decolorization ratio (stain decolorization rate) were recorded after cold-light bleaching, every 2 weeks and half a year later. Meanwhile, tooth sensitivity was recorded using visual analogue scale (VAS). Statistical analysis was performed using SPSS 17.0 software package., Results: In the combination therapy group, the decolorization rates of light, medium and heavy stains were 73.44%, 8.70% and 0% immediately after cold-light bleaching respectively. At 2 weeks, in the at-home group, the postoperative decoloring rate was 64.17% in the light grade group and 4.44% in the medium grade group, respectively. In the combination therapy group, the postoperative decoloring rate was 100% in the light grade group and 63.04% in the medium grade group, respectively (P＜0.01). The postoperative decoloring rate in the heavy grade group was 0%. At 4 weeks, in the at-home group, the postoperative decoloring rate was 100% in the light grade group, 73.33% in the medium grade group and 11.40% in the heavy grade group, respectively. In the combination therapy group, the postoperative decoloring rate was 100% in the medium grade group and 53.00% in the heavy grade group, respectively (P＜0.01). At 6 weeks, in the at-home group, the postoperative decoloring rate was 100% in the medium grade group and 76.32% in the heavy grade group. In the combination therapy group, the postoperative decoloring rate was 94.00% in the heavy grade group (P＜0.01). At 8 weeks, the postoperative decoloring rate was 95.61% in the heavy grade group of at-home group. Half a year after treatment, bleaching decoloration rate had no significant difference compared with that at the end of treatment (P＞0.05). Tooth sensitivity was 45.45% in the at-home group and 80.95% in the combination therapy group (P＜0.05)., Conclusions: Fluorosed teeth show significantly better esthetic appearance after both the at-home bleaching and the combination therapy at 6-8 weeks, and can maintain stable for a long time. Cold-bleaching has faster decoloration speed, with the final decolorization rate of the stains unchanged. In addition, it increases the incidence of postoperative sensitivity of teeth.

Background: Previous studies involving a loading dose (LD) of 60 mg prasugrel have suggested that active metabolite exposure and pharmacodynamic responses may be higher in persons of Asian ethnicity than in Caucasian subjects. The aim of this study was to determine the pharmacodynamic effect of an LD of 30 mg prasugrel and 600 mg clopidogrel in healthy Korean volunteers., Methods and Results: Twelve volunteers were randomly assigned to a prasugrel or a clopidogrel group. Following a 2-week washout period, group designations and treatments were switched (6 per group). Platelet function was serially measured via light transmission aggregometry (LTA), VerifyNow and multiple electrode platelet aggregometry (MEA) assays at baseline and 0.5, 2, 6, and 24h after LD. Inhibition of platelet aggregation (IPA) at 0.5-24 h after prasugrel was significantly higher (P<0.001) than that achieved by clopidogrel. The prasugrel peak IPA at 2 h after LD was 93.7% (±6.2%) compared to the clopidogrel peak IPA at 6h after LD at 65.8% (±17.2%). The VerifyNow and MEA assay yielded results similar to those obtained by LTA., Conclusions: In healthy Korean subjects, a 30-mg LD of prasugrel yields a more rapid, potent and consistent inhibition of platelet function than a 600-mg LD of clopidogrel.