The incidence of hypotension developed in the 1.0-l HES group was significantly lower than that in the LR and 0.5-l HES groups, showing that greater volume expansion results in less hypotension. This result indicates that the augmentation of blood volume with preloading, regardless of the fluid used, must be large enough to result in a significant increase in cardiac output for effective prevention of hypotension.
KeywordsCYP2C9, CYP4F2, Chinese, mechanical heart valve replacement, VKORC1, warfarin
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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Genetic polymorphisms of VKORC1 and CYP2C9 are known to influence warfarin dosage.• Recent studies among Caucasians showed that polymorphisms of CYP4F2 also play a role in warfarin pharmacogenetics.• The contribution of CYP4F2 variants to the variability inwarfarin dose requirement in Chinese subjects remains to be investigated.
WHAT THIS STUDY ADDS• This research was to study the effect of CYP4F2 variants on warfarin requirements in the Han Chinese population.• This study developed a multiple regression model including CYP2C9, VKORC1 3673G>A, CYP4F2 genotypes and age, weight, combination use of amiodarone which could explain 56.1% of the individual variability in warfarin dose CYP4F2 could explain 4% of the variance in warfarin dose.• We found that one novel genotypic polymorphism 5417G>T for Asp36Tyr, which was identified as an important marker of warfarin resistance, was absent in the Han Chinese population in our study.
AIMSThe objective of this study was to assess the effect of the CYP4F2 on the daily stable warfarin dose requirement in Han Chinese patients with mechanical heart valve replacement (MHVR).
METHODS
From March 2007 to November 2008, 222Han Chinese MHVR patients were recruited in our study. VKORC1 3673G>A, 5417G>T, CYP2C9 *3 and CYP4F2 rs2108622 were genotyped by using the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). Polymorphisms of VKORC1 9041G>A were detected by direct sequencing. Multiple linear regression analysis was used to investigate the contribution of CYP4F2.
RESULTSThe CYP4F2 rs2108622 CT/TT group took a significantly higher stable warfarin dose (3.2 mg day
CONCLUSIONCYP4F2 is a minor significant factor of individual variability in the stable warfarin dose in Han Chinese patients with MHVR. The effect of CYP2C9 and VKORC1 genotypes on variability in the stable warfarin dose had also been confirmed.
The BV estimation with a bolus injection of ICG and pulse-spectrophotometry is reliable, as reflected by the reproducible BVs estimated in the same subject. The integrated pulse-spectrophotometry monitoring system offers a less invasive and useful tool for bedside estimation of BV.
Reactive oxygen species (ROS) is a normal metabolic product of cellular respiration, but too much ROS can induce cell apoptosis. Here, we used N-acetylcysteine (NAC) to inhibit ROS activity to explore the effects of NAC on silica-induced pulmonary fibrosis in rats and provide evidence for study on the mechanism of silicosis. 24 adult male Sprague-Dawley rats weighing 180-220 g were randomly divided into three groups with eight rats in each group. Silicosis model group and NAC group were adopted non-tracheal exposure method of disposable intrapulmonary injection of 50 g/L, silica suspension 1 mL to establish animal silicosis model, NAC group treated with 600 mg/kg NAC by gavage from the right day of modeling, all animals were sacrificed after 28 days. The level of ROS contents and mitochondrial transmembrane potential changes of AM, the mRNA expression level of type I and type III procollagen, cytochrome C, cysteinyl aspartate specific protease-9 and caspase-3 were detected. The severity of pathological changes and pulmonary fibrosis were observed by pathologic specimens. It was showed that ROS contents and MTP changes were lower in the NAC group compared with the silicosis model group, other indexes were lower in the NAC group than the model group, but higher than those of the control group, the degree of lung fibrotic lesions observed from the pathological slices showed the same trend. These data indicated that NAC can reduce ROS content of AM in silica exposure rats, the mitochondrial apoptosis pathway can also be inhibited, the severity of pulmonary fibrosis alleviated as a result.
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