Objective To investigate the association between CYP2C19 polymorphisms and efficacy of clopidogrel in Chinese Han patients with coronary atherosclerotic heart disease.Methods A total of 176 Chinese Han patients who underwent percutaneous coronary intervention and were treated with dual antiplatelet therapy with aspirin and clopidogrel were enrolled.Polymorphisms of CYP2C19 * 2,* 3 were measured by PCR-restriction fragment length polymorphism (PCR RFLP).The correlation between the genetic variants and cardiovascular events was analyzed.Results In the 176 patients,the allele frequencies of CYP2C19 * 2 and * 3 were 34.38％ and 5.97％ respectively,the percent of patients with poor metabolizer genotypes (* 2/* 2,* 2/* 3,* 3/* 3) was 14.20％.Among the 176 patients,11 patients reoccured acute coronary syndrome,1 patient suffered from stroke,and 4 patients had stent thrombosis.The incidence of cardiovascular events was 9.09 ％.Thecumulative incidence of cardiovascular events had no significant differences between poor metabolizer genotype carriers and extensive and intermediate metabolizer genotype carriers (16.00％ vs.7.95％,x2 =1.683,P=0.195).Conclusions The frequencies of CYP2C19 poor metabolizer genotypes are higher in Chinese Han population than in Caucasians,but the incidence of cardiovascular events in Chinese Han population is not increased.

The formulations of pramipexole hydrochloride sustained-release tablets were screened by single factor test and optimized by Box-Behnken design. The effects of the viscosity and content of hydroxypropyl methyl cellulose, as well as the insoluble sustained-release material combined with HPMC K100M on the in vitro release behavior were investigated. After single factor screening, a three-factor, three-level Box-Behnken design was used for optimization using the contents of HPMC K100, Eudragit RSPO and Eudragit L100 as independent variables, and the cumulative release at different time as responses. The optimal range of the three-factor optimized by Box-Behnken design, one of the optimized formulations was achieved with HPMC K100M of 101. 5 mg, Eudragit RSPO of 98 mg, and Eudragit L100 of 13. 7 mg, and the observed responses of the optimized formulation were very close to the predicted values. The in vitro drug release mechanism of the tablet was studied by drug released model fitted with different equations. The results explained that Eudragit RSPO promoted the release of the pramipexole hydrochloride, while Eudragit L100 blocked the release, and there was an antagonism between them. In conclusion, the drug release behavior of optimized formulations prepared by Eudragit RSPO/L100 was stable, less pH-dependent, which improved the drug bioavailability in vivo.

Dental pulp can initiate its damage repair after an injury of the pulp-dentin complex by rearrangement of odontoblasts and formation of newly differentiated odontoblast-like cells. Connexin 43 (Cx43) is one of the gap junction proteins that participates in multiple tissue repair processes. However, the role of Cx43 in the repair of the dental pulp remains unclear. This study aimed to determine the function of Cx43 in the odontoblast arrangement patterns and odontoblastic differentiation. Human teeth for in vitro experiments were acquired, and a pulp injury model in Sprague-Dawley rats was used for in vivo analysis. The odontoblast arrangement pattern and the expression of Cx43 and dentin sialophosphoprotein (DSPP) were assessed. To investigate the function of Cx43 in odontoblastic differentiation, we overexpressed or inhibited Cx43. The results indicated that polarized odontoblasts were arranged along the pulp-dentin interface and had high levels of Cx43 expression in the healthy teeth; however, the odontoblast arrangement pattern was slightly changed concomitant to an increase in the Cx43 expression in the carious teeth. Regularly arranged odontoblast-like cells had high levels of the Cx43 expression during the formation of mature dentin, but the odontoblast-like cells were not regularly arranged beneath immature osteodentin in the pulp injury models. Subsequent in vitro experiments demonstrated that Cx43 is upregulated during odontoblastic differentiation of the dental pulp cells, and inhibition or overexpression of Cx43 influence the odontoblastic differentiation. Thus, Cx43 may be involved in the maintenance of odontoblast arrangement patterns, and influence the pulp repair outcomes by the regulation of odontoblastic differentiation.
Animals ; Cell Differentiation ; Connexin 43 ; Dental Pulp ; Extracellular Matrix Proteins ; Odontoblasts ; Phosphoproteins ; Rats ; Rats, Sprague-Dawley