目的:分析高胆固醇血症患者服用他汀类调脂药前后血清触珠蛋白(haptoglobin,Hp)水平的变化,探讨其与他汀类药物治疗的关系和临床意义。方法:入组原发性高胆固醇血症患者32例,分别服用洛伐他汀/烟酸缓释片(10 mg/500 mg.d-1)和匹伐他汀(2 mg.d-1),治疗8周后,观察药前、药后血清Hp水平的变化。结果:高胆固醇血症患者分别服用2种他汀类调脂药物后,两组Hp水平均高于治疗前(P<0.05)。其中,服用洛伐他汀/烟酸缓释片的患者,Hp增加了17.87%;服用匹伐他汀的患者,Hp增加了19%。结论:服用他汀药物后,高胆固醇血症患者的血清Hp水平增加。

Combination drugs of new mechanisms are constantly emerging,and the development and clinical application of these drugs have been significantly increased.New combination antihypertensive drugs can markedly improve compliance and antihypertensive efficacy as well as reduce adverse events.Therefore,new-mechanism antihypertensive drug combinations are becoming a mainstream of the combination therapies.This article described trends in the development of new-mechanism antihypertensive drug combinations in China.More large-scale clinical trials will enrich the medicine evidence of combination therapies.With the transformation of therapy conception,it is probable that optimized initial combination therapies may become a new prevalence.

This article is to introduce the CHMP guideline on the clinical investigations of medical products for the treatment of pulmonary arterial hypertension newly released by European Medicines Agency,hoping to give some reference to design and evaluation of clinical trials for pulmonary arterial hypertension agents in China.

Objective: To investigate the acute effects of rosuvastatin on lipids profile and gene expression of peripheral leukocytes following a single dose of rosuvastatin therapy.Methods: Thirty healthy Chinese male volunteers were enrolled.The serum lipids,high-sensitivity C-reactive protein,and plasma fibrinogen were determined before and 72 h after a single dose of 20 mg rosuvastatin.The differentially expressed genes of peripheral leukocytes after rosuvastatin administration were screened by human oligonucleotide microarray expression chips.Then the mRNA levels of four differentially expressed genes of ATM,CASP8,IL8RB and S100B were identified by RT-PCR.Results: Rosuvastatin decreased both serum total cholesterol and low density lipoprotein cholesterol significantly at 72 h following a single dose of 20 mg rosuvastatin administration.However,no significant changes occurred in blood high-density lipoprotein cholesterol,triglycerides,C-reactive protein and fibrinogen after treatment.A total of 24 genes were differentially expressed after treatment.Their function involved important cell biological processes such as cytokine-cytokine receptor interaction,and apoptosis signaling pathway.The expression levels of ATM,CASP8,IL8RB and S100B measured by RT-PCR agreed with those by microarray,thus confirmed that the expression of these genes were changed by rosuvastatin.Conclusion: Rosuvastatin rapidly decreased the serum cholesterol as well as affected the gene expression of peripheral leukocytes in healthy volunteers.It may provide us some new clues for further studies on its potential pleitropic effects.

Background Statins are potent lipid-lowering agents widely used in medical practice. There has been growing evidence suggesting the pleiotropic effects of statins in addition to the lipid-lowering effect. However, it is still unclear how rapidly the beneficial effects of statins occur. The transcriptome of peripheral blood cells can be used as a sensor to drug therapy. The purpose of the study was to investigate the acute effects of rosuvastatin both on lipids profile and gene expression of peripheral leukocytes following therapy with a single dose of rosuvastatin. Methods Thirty healthy Chinese male volunteers were enrolled. The serum lipids, high-sensitivity C-reactive protein, and plasma fibrinogen were determined before and 72 hours after administration of 20 mg of rosuvastatin. The differentially expressed genes of peripheral leukocytes after administration of rosuvastatin were screened using human oligonucleotide microarray gene expression chips. Then four of the differentially expressed genes including ATM, CASP8, IL8RB and S100B were verified by real-time polymerase chain reaction (PCR). Results Rosuvastatin decreased both serum total cholesterol and low-density lipoprotein cholesterol significantly 72 hours after administration of a single dose of 20 mg rosuvastatin. However, no significant changes occurred in blood high-density lipoprotein cholesterol, triglycerides, C-reactive protein and fibrinogen after the treatment. A total of 24 genes were differentially expressed after the treatment. They were involved in important cell biological processes such as cytokine-cytokine receptor interaction, apoptosis signaling, etc. Conclusions Rosuvastatin rapidly modulates the serum lipids and affects the gene expression of peripheral leukocytes in healthy volunteers. This finding provides some new clues for further studies on its potential pleiotropic effects.

Objective: To evaluate the diuretic and electrolyte effects of 4 different doses of tolvaptan in healthy male Chinese volunteers.Methods: Thirty-nine healthy men were randomly divided to four groups,and orally administered with tolvaptan at single dose of 15 mg(n=9),30 mg(n=10),60 mg(n=10),or 120 mg(n=10).The changes in urine volumes,serum concentrations of electrolytes and water drink volumes were observed;the body weight(BW) and adverse events were also observed during 48 h.Results: The average BW did not change significantly(P0.05).The urine volumes(mL) during 0~6 h,6~12 h,12~24 h and 24~48 h were(1 921±496),(2 977±389),(3 680±724),(3 948±398) after taking 15 mg;(1 361±500),(2 631±661),(3 492±1 094),(4 518±802) after taking 30 mg;(1 268±868),(2 167±1 074),(2 267±1 088),(3 981±1 667) after taking 60 mg;(1 302±624),(2 643±1 100),(2 460±660),(4 394±1 132) after taking 120 mg,respectively.The serum chloride and sodium concentrations were significantly increased at 24 h but recovered at 48 h after administration;especially the serum chloride was over the normal range(110 mmol ·L-1) but did not need to treat.The serum concentration of sodium was increased and that of potassium was decreased slightly,but they were within the normal ranges without clinical significance.Blood pressure and heart rate did not change significantly.Mild and moderate dry mouth and/or thirsty occurred in 13/39 volunteers(33.3%),but the symptoms were well tolerated.No severe adverse events were observed.Conclusion: Single doses of tolvaptan(15 mg,30 mg,60 mg or 120 mg) exert a strong diuretic effect that lasts for 24 h and is dose-dependent in healthy male Chinese volunteers;it also increases serum chloride concentration significantly but is well tolerated.

AIM: To investigate the effects of polymorphisms of aldehyde dehydrogenase 2 gene(ALDH2)at positions Glu504Lys on pharmacokinetic(PK) characteristics of isosorbide-5-mononitrate (IS-5-MN) in Chinese healthy volunteers. METHODS:Among 45 persons, twenty-two healthy male volunteers were selected and orally taken 60 mg IS-5-MN.An HPLC-MS method was applied to analyze IS-5-MN plasma concentration.ALDH2 genotype was determined by PCR-RFLP. Pharmacokinetic analysis was performed to assess the effects of the genotype on IS-5-MN pharmacokinetics. RESULTS: In these 22 volunteers,13 homozygous GG and 9 heterozygous GA genotypes for ALDH2 at positions of Glu504Lys were detected by PCR-RFLP. IS-5-MN plasma concentration, AUC0-t, Cmax and tmax did not show significant statistical difference (P0.05) in the two groups. CONCLUSION: The polymorphisms of ALDH2 gene at positions of Glu504Lys could not influence the pharmacokinetics of IS-5-MN in the research.

OBJECTIVE:To provide references for clinicians in the choice of antihypertensive drugs.METHODS:The antihypertensive efficacy 6 classes(or 15 kinds) of antihypertensive drugs in a monotherapy in the treatment of 370 patients with essential hypertension(EH) were compared.RESULTS:The blood pressure was effectively lowered by all of the antihypertensive drugs except doxazosin,and doxazosin and torasemide showed inferior efficacy in the reduction of diastolic blood pressure(DBP).CONCLUSION:Calcium antagonists with prolonged action,angiotensin converting enzyme inhibitor(ACEI),angiotens-in receptor antagonist,and the monotherapy of Terazosin or Indapamide can all effectively bring down the blood pressure.It is suggested that low-dose doxazosin and torasemide should not be used alone in treating essential hypertension.

BACKGROUND:Beta-blockers exert complex effects on plasma N-terminal-pro-B-type natriuretic peptide (NT-proBNP) level.HYPOTHESIS:We aimed to investigate whether NT-proBNP was still able to mirror the severity of chronic heart failure and predict the prognosis of the disease after administration of a beta-blocker.METHODS:Forty-four patients with chronic congestive heart failure were enrolled in the study to randomly receive carvedilol or bisoprolol in addition to background therapy. These patients underwent clinical measurement and blood sampling for NT-proBNP measurement at baseline and 3 or 7 months after the addition of the beta-blocker. The patients were followed-up for 3 years in order to register the occurrence of all-cause death.RESULTS:NT-proBNP level showed a positive correlation with the severity of heart failure as evaluated by New York Heart Association (NYHA) classification both before and after administration of either beta-blocker. The relationship between NT-proBNP and NYHA class was not weakened with the duration of therapy. Furthermore, NT-proBNP was the only independent predictor of all-cause mortality both before and after administration of either beta-blocker. Left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), age, NYHA class and treatment group were not independently predictive of mortality in this study.CONCLUSIONS:The ability of NT-proBNP to reflect the severity and to predict the endpoint in chronic heart failure is not undermined after administration of a beta-blocker, suggesting that NT-proBNP remains a sensitive biomarker for chronic heart failure both before and after administration of a beta-blocker.

OBJECTIVE:To evaluate the efficacy of the monotherapy of 15 agents in treating essential hypertension.METHODS:After 2-week wash-out, a total of 370 patients with seated diastolic blood pressure 95-114 mmHg and seated systolic blood pressure < 180 mmHg were randomized to different therapeutic groups. 24-hour ambulatory blood pressure monitoring was performed before medication and at the end of 8 weeks.RESULT:All the agents significantly reduced the 24 hour mean blood pressures after treatment except doxazosin, terazosin, and torasemide.CONCLUSION:The result suggested that the angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers and long-acting calcium antagonists were effective in treating essential hypertension, while the low-dose doxazosin, terazosin and torasemide can be used for combination therapy but not for monotherapy.

For investigating the harmfulness in blood glucose and lipids in obese children. Height, body weight, fasting blood glucose (FBG), total cholesterol (TC) and triglyceride (TG) were examined in 672 children aged 7∼12 years in Beijing Primary School. With increasing age, the plasma TC, TG and FBG level increased in children. There were positive correlations between Rohrer index, BMI and TG levels (P< 0.001), and between BMI and FBG, TC levels (P<0.05, 0.001). Positive correlation between Rohrer index, BMI and TG were adjusted by age (P< 0.001). The obese children had greater TG and TC levels than healthy children that were independent of age (P < 0.001). Obese children had higher plasma TG and TC level than healthy children. Obesity and TG had strong positive correlation that was independent of age.

为了解6～12岁儿童血脂和血糖代谢的状况及其与单纯肥胖症的相关性,选择北京市长椿街地区在校小学生672名,均测定血清总胆固醇(TC)、三酰甘油(TG)、空腹血糖(FBG)、身高和体质量.应用SPSS软件包进行统计学处理.发现:672例6～12岁儿童的TC、TG和FBG浓度分别为(4.66±0.52) mmol/L、(1.97±0.22) mmol/L、(4.25±0.96) mmol/L.其中TC 4.68～5.17 mmol/L占30.3%,5.20～5.69 mmol/L占21.9%,≥5.72 mmol/L占17.3%;TG≥1.65 mmol/L占10.0%;FBG≥6.05 mmol/L占7.8%.男女学生的TG、TC、FBG比较无统计学差别.TC、TG、FBG与儿童的年龄呈正相关.超重和肥胖儿童的TG、TC平均水平显著高于正常儿童.TG、TC与FBG之间存在两两正相关的关系.提示:超重和肥胖者在学龄儿童期即可出现脂类代谢异常.