液相色谱法测定吗氯贝胺及其多剂量口服后在人体的药动学(英文)

目的 :建立人血浆中吗氯贝胺的反相高效液相色谱检测方法 ,并研究中国健康男性志愿者多剂量口服吗氯贝胺后的药动学特征。方法 :采用反相高效液相色谱法测定人血浆中吗氯贝胺含量。血浆样品在碱性条件下 (pH 11)用二氯甲烷提取处理。色谱柱为 μ BondapakTM C18(12 5 ,10 μm ,3.9mm× 15 0mm)。流动相为乙腈 :0 .0 6 7mol·L- 1磷酸二氢钾溶液 (1∶5 ,V/V ,pH 2 .6 ) ,2 4 0nm检测。内标为甲氧氯普胺。应用 3P97程序拟合药动学参数。结果 :吗氯贝胺在 4 0～ 4 0 0 0 μg·L- 1范围内线性关系良好 (r =0 .9999) ,方法回收率在 99%～10 3%之间 ,日内日间RSD小于 8.14 %。吗氯贝胺血药浓度 时间曲线符合一室模型 ,主要稳态药动学参数Cmax为 (3911± 14 2 ) μg·L- 1;Tmax为 (1.4 2± 0 .2 0 )h ;T1/2 (kel) 为 (2 .6± 0 .3)h ;AUC0 2 4 为(2 2 5 83± 182 1) μg·h·L- 1;MRT为 (4.76± 0 .2 5 )h ;CL/F(s) 为 (2 1.2± 1.2 )L·h- 1。结论 :该方法快速、准确、灵敏度高、专属性强 ,可应用于吗氯贝胺的血药浓度测定     

Effect of pregnancy, menopause and hormone substitution therapy on disseminated systemic lupus erythematosus

EXACERBATIONS DURING PREGNANCY: Clinical and experimental data have clearly evidenced the influence of hormones on the course of systemic lupus erythematosus. In prospective studies of pregnant women, an exacerbation is observed in 57% to 60% of the cases. It can be severe in 10% of the cases and occur in the post partum in 7%. For most patients, the exacerbation is moderate and has no unfavorable effect on the outcome of pregnancy. In case of renal involvement, it is difficult to differentiate an intricated HELPP syndrome. MARKERS AND RISK FACTORS: Low complement and elevated anti-DNA levels are distinctive markers. Earlier renal involvement and hypertension are important prognostic factors, particularly when the lupus begins during pregnancy. However, when serum creatinine is lower than 100 mumol/l at pregnancy onset in patients in remission, pregnancy does not alter renal function. An association with antiphospholipid antibodies increases the risk for the fetus and the kidney function. TREATMENT: Optimal treatment remains to be defined. Commonly, patients are given aspirin, heparin in case of a history of thromboembolism, or both. The rate of success currently exceeds 70%. The risk of thromboembolism in the peri or post partum period requires anticoagulant treatment. Outside pregnancy: Ovulation induction raises two risks: triggering a lupus flare-up and thrombosis, particularly for patients with antiphospholipid antibodies. The influence of menopause and hormone replacement therapy remains poorly understood.     

Predictors of men's acceptance of modern contraceptive practice: study in rural Vietnam.

Studies have shown family planning adoption is likely to be more effective for women when men are actively involved. The transtheoretical model of behavior change was used to examine men's involvement in general contraception and intrauterine device (IUD) use by their wives. The study was carried out in rural Vietnam with 651 eligible participants. Cons of IUD use for men in precontemplation and contemplation/preparation were significantly higher than those in the action/maintenance stages, whereas the reverse was true for pros of IUD. The self-efficacy for convincing wife to have IUD in precontemplation was significantly lower than for those in higher stages. Women's education and ages, spontaneous recall of modern contraceptive method, cons for IUD, and self-efficacy for contraception and for convincing wives to get IUD inserted (or continue use) were significant predictors of men's readiness to accept IUD. Interventions are targeted to reduce cons and increase self-efficacy for IUD use.     

甲醇合成过程中基于MAS的故障诊断方法

针对甲醇合成生产过程的特点和故障产生机制,将多智能体系统(MA S)技术引入到生产过程的故障诊断中,把生产过程划分为一些相对独立的组件,分派特定的诊断智能体对其进行故障诊断,通过智能体之间的协作,充分利用过程中的局部信息而给出整个过程的故障诊断结果。通过仿真实验,得到了满意的结果。     

Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants

Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV–specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2^neg γδ T cells in controlling CMV infection. Here, we assessed if Vδ2^neg γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high–risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R−) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2^neg γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2^neg γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2^neg γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P<0.001). At 49 days of antiviral treatment, Vδ2^neg γδ T cell expansion onset was associated with recovery, whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral–resistant mutant CMV strains was associated with delayed Vδ2^neg γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2^neg γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.     

Theoretical basis of a beneficial role for vitamin D in viral hepatitis

Abnormal bone metabolism and dysfunction of the calcium-parathyroid hormone-vitamin D axis have been reported in patients with viral hepatitis. Some studies suggested a relationship between vitamin D and viral hepatitis. Genetic studies have provided an opportunity to identify the proteins that link vitamin D to the pathology of viral hepatitis (i.e., the major histocompatibility complex class Ⅱ molecules, the vitamin D receptor, cytochrome P 450 , the renin-angiotensin system, apolipoprotein E, liver X receptor, toll-like receptor, and the proteins regulated by the Sp1 promoter gene). Vitamin D also exerts its effects on viral hepatitis via non-genomic factors, i.e., matrix metalloproteinase, endothelial vascular growth factor, prostaglandins, cyclooxygenase-2, and oxidative stress. In conclusion, vitamin D could have a beneficial role in viral hepatitis. Calcitriol is best used for viral hepatitis because it is the active form of the vitamin D 3 metabolite.     

Imaging of Vulnerable Plaques Using Near-Infrared Spectroscopy for Risk Stratification of Atherosclerosis

Large randomized trials have shown that lowering the concentration of LDL cholesterol with statins reduces vascular morbidity and mortality rapidly, with further benefit emerging during each year of treatment allocation. But, limited evidence is available about the long-term efficacy and safety of statin treatment. Long-term follow-up of surviving trial participants allows direct assessment of the benefits (and any hazards) of a sustained reduction in LDL cholesterol concentration during the post-trial period. Post-trial follow-up of several large statin trials (of which the Heart Protection Study was the largest) confirms that the substantial absolute benefits and cost-effectiveness of statin therapy were, in fact, underestimated in previous analyses restricted to the “in-trial” periods of randomized studies. Reassuringly, no adverse effects on cancer incidence or non-vascular mortality emerged during the extended follow-up of the Heart Protection Study. These findings support the prompt initiation and long-term continuation of statin therapy in individuals at increased vascular risk.     

Presentation of floating mass transducer and Vibroplasty Couplers on CT and Cone Beam CT

Various titanium coupling elements, Vibroplasty Couplers, maintaining the attachment of the Floating Mass Transducer (FMT) of the active middle ear implant Vibrant Soundbridge (VSB) to the round window, the stapes suprastructure or the stapes footplate are in use to optimally transfer energy from the FMT to the inner ear fluids. In certain cases it is of interest to radiologically verify the correct position of the FMT coupler assembly. The imaging appearance of FMT connected to these couplers, however, is not well known. The aim of this study was to present the radiological appearance of correctly positioned Vibroplasty Couplers together with the FMT using two different imaging techniques. Vibroplasty Couplers were attached to the FMT of a Vibrant Soundbridge and implanted in formalin fixed human temporal bones. Five FMT coupler assemblies were implanted in different positions: conventionally to the incus, a Bell-Coupler, a CliP-Coupler, a Round Window-Coupler and an Oval Window-Coupler. High spatial resolution imaging with Multi-Detector CT (MDCT) and Cone Beam CT (CBCT) was performed in each specimen. Images were blind evaluated by two radiologists on a visual basis. Middle ear details, identification of FMT and coupler, position of FMT coupler assembly and artefacts were assessed. CBCT showed a better spatial resolution and a higher visual image quality than MDCT, but there was no significant advantage over MDCT in delineating the structures or the temporal bone of the FMT Coupler assemblies. The FMT with its coupler element could be clearly identified in the two imaging techniques. The correct positioning of the FMT and all types of couplers could be demonstrated. Both methods, MDCT and CBCT, are appropriate methods for postoperative localization of FMT in combination with Vibroplasty Couplers and for verifying their correct position. If CBCT is available, this method is recommended due to the better spatial resolution and less metal artifacts.