Triglycerides and risk of atherosclerotic cardiovascular disease: An update.
- 作者列表："Farnier M","Zeller M","Masson D","Cottin Y
:Low-density lipoprotein cholesterol is a well-known causal factor for atherosclerotic cardiovascular disease, and is the primary target of lipid-lowering therapy. There is, however, still a substantial risk of atherosclerotic cardiovascular disease events despite intensive statin therapy, and data from clinical trials suggest that an elevated concentration of triglycerides is a marker of residual cardiovascular risk on low-density lipoprotein-lowering therapy. Serum triglycerides are a biomarker for triglyceride-rich lipoproteins, and several lines of evidence indicate that triglyceride-rich lipoproteins and their cholesterol-enriched remnant particles are associated with atherogenesis. Moreover, genetic data in humans strongly suggest that the remnants of triglyceride-rich lipoproteins are a causal cardiovascular risk factor. Although lifestyle changes remain the cornerstone of management of hypertriglyceridaemia, a recent trial with high doses of the omega-3 fatty acid icosapent ethyl showed a significant reduction in cardiovascular events that was not explained by the reduction in triglycerides alone. In patients with elevated triglycerides, several novel drugs are in development to reduce the residual risk on statin therapy linked to an excess of atherogenic triglyceride-rich lipoproteins. In this review, we provide an update on the biology, epidemiology and genetics of triglycerides, and the risk of atherosclerotic cardiovascular disease.
: 低密度脂蛋白胆固醇是众所周知的动脉粥样硬化性心血管疾病的致病因素，是降脂治疗的首要靶点。然而，尽管强化他汀类药物治疗，仍存在动脉粥样硬化性心血管疾病事件的显著风险，临床试验数据表明，甘油三酯浓度升高是低密度脂蛋白降低治疗的残余心血管风险的标志物。血清甘油三酯是富含甘油三酯的脂蛋白的生物标志物，并且几行证据表明富含甘油三酯的脂蛋白及其富含胆固醇的残余颗粒与动脉粥样硬化有关。此外，人类的遗传数据强烈表明，富含甘油三酯的脂蛋白的残余物是心血管危险因素。尽管生活方式的改变仍然是治疗高甘油三酯血症的基石，但最近一项使用高剂量omega -3脂肪酸二十碳四烯酸乙酯的试验显示，心血管事件显著减少，这并不能单独用甘油三酯的减少来解释.在甘油三酯升高的患者中，几种新型药物正在开发中，以降低他汀类药物治疗的残余风险，这些风险与致动脉粥样硬化的富含甘油三酯的脂蛋白过量有关。在这篇综述中，我们提供了关于甘油三酯的生物学流行病学和遗传学以及动脉粥样硬化性心血管疾病风险的最新进展。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.