ABSTRACT
Coronary artery disease (CAD)is a major cause of death and disability worldwide, and consumes a considerable amount of medical resources every year.Clopidogrel is a first-line antiplate-let therapy for CHD, butit is associated with substantial variability in PK and pharmacodynamics re-sponse. To date, gene variants explain only a smallproportion of the variability.The study aimed to identify new genetic loci-modifying antiplatelet response to clopidogrel in Chinese patients with CAD by a systematic analysis combining antiplatelet effects and PK, and further to investigate the PON1 gene promoter DNA methylation and genetic variations possibly influencing clinical outcomes in pa-tients undergoing PCI. We identified novel variants in two transporter genes (SLC14A2rs12456693, ATP-binding cassette [ABC]A1 rs2487032) and in N6AMT1 (rs2254638) associated with P2Y12 reac-tion unit (PRU) and plasma active metabolite (H4) concentration. These new variants dramatically im-proved the predictability of PRU variability to 37.7％. The associations between these loci and PK pa-rameters of clopidogrel and H4 were observed in additional patients, and its function on the activation of clopidogrel was validated in liver S9 fractions (P<0.05). Rs2254638 was further identified to exert a marginal risk effect formajor adverse cardiac events in an independent cohort.Multivariate logistic regression analysis indicated that PON1methylation level at CpG site-161 (OR=0.95; 95％ CI=0.92–0.98;P<0.01)and the use of angiotensin converting enzyme inhibitors(OR=0.48;95％ CI=0.26–0.89;P<0.01) were associated with decreased risk of bleeding events. In conclusion, new genetic variants were systematically identified as risk factors for the reduced efficacy of clopidogrel treatment.The ab-normal expression of DNA methylation-regulating key genes in the pharmacokinetic and pharmacody-namics pathways of clopidogrel and aspirin may modify clinical outcomes in dual antiplatelet-treated pa-tients undergoing PCI.
ABSTRACT
The purpose of this study is to systematically investigate the characteristics of absorption and metabolism of oxymatrine (OMT) using rat intestinal perfusion model. Ultra performance liquid chromatography (UPLC) and high performance liquid chromatography-electrospray ionization-quadrupole-time of flight mass spectrometry (HPLC-ESI(+)-Q-TOF-MS) were used to test absorption of OMT in intestine at 100, 200 and 400 µmol · L(-1). The absorption rate and permeability of OMT is not dependent on concentration, but through passive absorption in intestine (P > 0.05). In the rat intestine, the absorbed amount of OMT was significantly different in four sections of the intestine in an order of duodenum > jejunum > ileum > colon (P < 0.05). OMT is metabolized into two metabolites in duodenum and jejunum, and matrine (MT) is the major one.
Subject(s)
Animals , Rats , Alkaloids , Metabolism , Chromatography, High Pressure Liquid , Intestinal Absorption , Intestines , Metabolism , Quinolizines , Metabolism , Spectrometry, Mass, Electrospray IonizationABSTRACT
ZnO nanopowders were prepared by the sol-gel techniques with two kinds of solvent. Microstructure of powder samples was examined by XRD and TEM. The results indicate that the two ZnO samples have the same crystal and energy band structure. Their photoluminescence (PL) spectra in ultraviolet region are analogous, but their photoluminescence (PL) spectra in visible region are different. The reason is that the two kinds of solvent with different polarity result in the difference in configuration and distribution of the sample surface states in the two systems.
Subject(s)
Luminescence , Nanoparticles/chemistry , Zinc Oxide/chemistry , Algorithms , Gels , Microscopy, Electron, Transmission , Models, Chemical , Nanoparticles/ultrastructure , Polymethyl Methacrylate , Powders , Spectrometry, Fluorescence , X-Ray DiffractionABSTRACT
CeOx/ZnO nanocomposite powders were prepared by sol-gel process. The powder samples were examined by XRD, TEM, XPS and photoluminescence (PL). PL enhancement of nanocomposite powder at 502 nm compared to pure ZnO was observed when Ce3+ were present in samples. New peak at 603 nm was observed when Ce4+ were present. PL enhancement of nanocomposite powder was correlated with more oxygen vacancies which were caused by Ce3+. The new peak at 603 nm is attributed to new energy transition in the interface of CeO2/ZnO.
Subject(s)
Cerium/chemistry , Luminescence , Nanocomposites/chemistry , Zinc Oxide/chemistry , Luminescent Measurements/methods , Microscopy, Electron, Transmission , Nanocomposites/ultrastructure , Photoelectron Spectroscopy , Powders , Spectrometry, Fluorescence , X-Ray DiffractionABSTRACT
ZnO nanopowders were prepared by the sol-gel techniques with two kinds of solvent. Microstructure of the powdersamples was examined by XRD and TEM. The results indicate that two ZnO samples have the same crystal and energy band structure. Their photolurminescence (PL) spectra in the ultraviolet region are analogous, but their photoluminescence (PL) spectra in the visible region are different. The reason is that two kinds of solvent with different polarity result in the difference in configuration and distribution of the sample surface states in the two systems.
