Fixed‐dose combination of amlodipine and atorvastatin improves clinical outcomes in patients with concomitant hypertension and dyslipidemia

Hypertension and dyslipidemia are important risk factors for cardiovascular disease. However, the clinical outcomes of fixed‐dose combination (FDC) versus free‐equivalent combination (FEC) of amlodipine and atorvastatin in the treatment of concurrent hypertension and dyslipidemia remain unknown. In this study, we included patients with newly diagnosed hypertension and dyslipidemia, without previously established cardiovascular disease, and treated with either FDC or FEC of amlodipine and atorvastatin were identified from the National Health Insurance Research Database of Taiwan and follow‐up for 5 years. By using 1:1 propensity score matching, a total of 1756 patients were enrolled in this study. The composite of major adverse cardiovascular events, including all‐cause mortality, myocardial infarction (MI), stroke, and coronary revascularization, occurred more frequently in the FEC group than in the FDC group (hazard ratio, 1.88; 95% confidence interval [CI], 1.42 to 2.5). Although the all‐cause mortality did not differ (hazard ratio, 0.46; 95% CI, 0.36 to 1.59), the FEC group developed increased MI, stroke, and coronary revascularization (hazard ratio, 2.87; 95% CI, 1.07 to 7.68; hazard ratio, 1.97; 95% CI, 1.41 to 2.74; and hazard ratio, 2.44; 95% CI, 1.26 to 4.69, respectively). Furthermore, as an unexpected result, a higher risk to develop new‐onset diabetes mellitus was observed with FEC regimens (hazard ratio, 2.19; 95% CI, 1.6 to 3.0). In conclusion, although the all‐cause mortality did not differ between the two groups, the FDC regimen of amlodipine and atorvastatin improved clinical outcomes when compared to FEC in patients with newly diagnosed hypertension and dyslipidemia.     

Developmental enamel defects in the primary dentition: aetiology and clinical management

Developmental enamel defects, presenting as enamel hypoplasia or opacities are caused by damage or disruption to the developing enamel organ as a result of inherited and acquired systemic conditions. The high prevalence of these defects in the primary dentition demonstrates the vulnerability of the teeth to changes in the pre‐ and postnatal environment. The presence of enamel hypoplasia increases the risk of primary teeth to early childhood caries and tooth wear as the defective enamel is thinner, more plaque retentive and less resistant to dissolution in acid compared to normal enamel. The purpose of this paper was to critically review the aetiology and clinical complications of developmental enamel defects in the primary dentition and propose recommendations for the clinical management of affected teeth.     

α2β1 integrin and RhoA mediates electric field‐induced ligament fibroblast migration directionality

Guided cell migration is important in tissue development, repair, and engineering. We have previously demonstrated that applied electric fields (EFs) enhanced and directed ligament fibroblast migration and collagen production, depending on EF parameters. Electrical stimulation is widely used for the treatment of pain and to promote wound healing. In orthopaedic practices, applied EFs promote bone healing and ligament repair in vivo. In the current study, stimulation waveforms used in physical therapy for promoting tissue repair were adapted to examine their effects on ACL fibroblast migration. Using different waveform and field strengths, we discovered a decoupling of cell motility and directionality, which suggests disparate mechanisms. Integrin, a major extracellular matrix receptor, polarized in response to applied EFs and controlled cell directionality and signaling. Furthermore, we demonstrated that RhoA is a mediator between integrin aggregation and directed cell migration. Polarization is essential in directed cell migration and our study establishes an outside‐in signaling mechanism for EF‐induced cell directionality. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 322–327, 2013     

Coronarin D induces apoptotic cell death through the JNK pathway in human hepatocellular carcinoma

Coronarin D, a diterpene derived from the rhizomes of Hedychium coronarium, has been used to treat inflammatory diseases. Coronarin D can exert strong anticancer effects through cell growth prevention and cell cycle arrest in many cancer cells. In this study, we investigated the molecular mechanism through which coronarin D suppresses cell proliferation and triggers cell death in human hepatocellular carcinoma (HCC) cells. Treatment of Huh7 and Sk‐hep‐1 cells with coronarin D resulted in a significantly increased loss of mitochondrial membrane potential, leading to the cleavage and activation of caspase‐9, caspase‐8, and caspase‐3 and changes in Bax, Bcl‐2, and Bcl‐xL protein levels. Coronarin D significantly induced autophagy by increasing the expression of Beclin‐1 and LC3‐II and reducing the expression of p62. Moreover, Huh7 and Sk‐hep‐1 cells exposed to coronarin D had decreased expression of phosphorylated AKT, p38, and ERK and increased expression of phosphorylated JNK. Exposure of cells to the JNK‐specific inhibitor SP600125 attenuated the apoptotic effects of coronarin D. Taken together, this is the first study to report that coronarin D may effectively inhibit cell growth through apoptosis. We have provided evidence indicating that coronarin D induces cell death through the upregulation of JNK mitogen‐activated protein kinases in human HCC cells.