多区域性高血压与血管紧张素转化酶基因的插入/缺失多态性的关系

目的 :观察肾素血管紧张素系统 (RAS)的关键酶——血管紧张素转化酶 (ACE)基因水平在高血压发病机制中的作用 ,探讨 ACE基因多态性与不同区域高血压之间是否存在相互关系。方法 :选择西藏高原区域(2 9例 )、武汉地区 (2 3例 )、福州沿海地区高血压患者 (36例 )及正常对照组 (各 2 0例 )。对影响 ACE基因表达水平的第 16内含子存在的插入 (I)和缺失 (D)的多态性进行分析。提取患者血清 DNA,采用聚合酶链反应(PCR)技术扩增 ACE基因第 16内含子 ,反应产物在质量分数为 1.5 %的琼脂凝胶上电泳分析 ,检测各地区组血清 ACE基因多态性。对 ACE等位基因频率和各基因型频率进行统计学分析。结果 :高血压组 DD、ID和 II基因型的频率分别为 :福州 :0 .36、0 .5 6和 0 .0 8;武汉 :0 .6 5、0 .30和 0 .0 4;西藏 :0 .34、0 .5 9和 0 .0 7。高血压组等位基因 D和 I的频率分别为 :福州 :0 .6 4和 0 .36 ;武汉 :0 .80和 0 .2 0 ;西藏 :0 .6 4和 0 .36。正常对照组 DD、ID和II基因型的频率分别为 :福州 :0 .2 0、0 .5 0和 0 .30 ;武汉 :0 .2 5、0 .40和 0 .35 ;西藏 :0 .30、0 .45和 0 .2 5。正常对照组等位基因 D和 I的频率分别为福州 :0 .45和 0 .5 5 ;武汉 :0 .45和 0 .5 5 ;西藏 :0 .5 3和 0 .47。结果 ,除武汉地区高?

血管紧张素转化酶抑制剂在心血管病中的应用

随着我国人民生活水平的提高,高血压、脑卒中、冠心病等心血管病的发病率急剧上升,心血管病防治形势逼人,既要综合预防,又要突出重点。以降压药物为主的综合治疗对降低血压及预防高血压严重并发症的发生极为重要。血管紧张素转化酶抑制剂(ACEI)作为一种新型降压药物,被认为是高血压治疗史上的一大飞跃。随着对ACEI研究的不断深入和各种ACEI制剂的广泛应用,其优势也日益显现。尤其是长效制剂赖诺普利(Lisinopril:利压定)。

血管紧张素转换酶抑制剂常见不良反应与防治

1 咳嗽是ACEI(血管紧张素转换抑制剂)最常见的不良反应,各种ACEI的咳嗽发生率为1.5%～4.3%,停药率为0.36%～1.2%,咳嗽一般出现在用药后7～30d,可延迟到停药20d后方消失.

替米沙坦及培垛普利治疗老年原发性高血压患者的效果观察

目的探讨替米沙坦及培垛普利对老年原发性高血压患者的治疗效果。方法本研究入选老年原发性高血压患者139例,随机分配(1:1)到替米沙坦(口服80mg～160mg/d)组或培垛普利(口服4～8mg/d)组,治疗8个月,分别进行治疗前、后两组之间降压幅度比较。结果替米沙坦组治疗老年原发性高血压与培垛普利组比较,2组间收缩压及舒张压比较差异均无统计学意义(p>0.05);但2组药物的安全性比较,替米沙坦的安全性优于培垛普利组,差异有统计学意义(p<0.05)。结论与培垛普利相比较,老年原发性高血压患者在替米沙坦治疗8个月后同样可使患者的收缩压及舒张压明显下降,且不良反应明显减少。

缬沙坦、苯那普利及卡托普利对老年高血压效果的观察及护理

目的:观察缬沙坦、苯那普利及卡托普利对老年高血压的作用。方法:选择120例2～3级老年原发性高血压患者,分为三组,缬沙坦组(n=40)、苯那普利组(n=40)、卡托普利组(n=40),分别进行治疗前、后三组之间降压幅度比较。结果:缬沙坦治疗老年原发性高血压与苯那普利、卡托普利一样有效;但缬沙坦组未见干咳现象,而苯那普利组、卡托普利组干咳发生率分别为2.7%、13.7%。结论:高血压虽然是一种慢性病,但并不可怕,如果能在医生指导下进行治疗和休养,仍能够长寿。

卡托普利与硝苯吡啶治疗老年高血压病的临床观察比较

目的 比较卡托普利与硝苯吡啶对老年高血压病的疗效。方法 选择符合WHO诊断标准的老年高血压病患者38例,男28例,女16例,年龄60—82岁。随机分成两组,每组均为19例,单独服用降压药硝苯吡啶或卡托普例,观察治疗前后血压、心率、血胆固醇、甘油三酯、血糖及胰岛素的变化。结果 卡托普列降压作用与硝苯吡啶比较无显著差异(P>0.05)。结论 卡托普利与硝苯吡啶均能显著降低老年高血压,疗效显著。

Meta-analysis of the Use of ACEI for Inhibiting Albuminuria in Diabetic Patients

Aim To examine whether AER(albumin excretion rate) in normotensive diabeticpatients can be effectively inhibited by ACEI. Methods Literature on randomized controlled trials ofACEI for inhibiting AER in normotensive diabetic patients was searched. The electronic databasesretrieved were Medline (1980 ― 2003), Embase database (1980 ― 2000), Cochrane Library, CL( 1980 ―2004), CBMdisc( 1980 ― 2002), and IPA( 1980 ― 2002). Seven studies were chosen. Data werecombined by Revman 4.2. Results: The pooled effect of change in AER is - 56.31 μg·min^(-1)) [ -81.96, -30.66] (P<0.0001). According to the analysis of subgroups, the pooled effects of 1 - 5 yearsare - 11.97 μg·min^(-1)[-22.04, -1.89] (P = 0.02), -28.01 μg·min^(-1)[-34.50, -21.52](P<0.00001), -43.24 μg·min^(-1) [ -57.15, -29.32] (P< 0.00001), -61.65 μg·min^(-1)[77.77,-45.54] (P< 0.00001), and -98.41 μg·min^(-1)[-162.02,-34.79] (P = 0.002). Regarding progression toclinincal proteinuria as end-point, the pooled Peto OR =0.27 [0.18,0.40] (95% CI), P < 0.00001.According to the analysis of subgroups, the pooled effects of 2 and 5 years are Peto OR = 0.30[0.18,0.51] (P<0.00001) and Peto OR=0.25 [0.13, 0.50](P<0.0001). Publication bias is small.Conclusion In normotensive diabetic patients, ACEI inhibits AER effectively and reduces theprobability of progression of microalbuminuria to clinical proteinuria.

Effect of L158,809 and Cilazapril on the Expression of TGF-β_1 and Secretion of Extracellular Matrix Proteins in Cultured Human Mesangial Cells

Objective: To explore the effect of L158, 809 (angiatensin Ⅱ receptorMockers, ARBs) and Cilazapril (Angiotensin converting enzyme inhibitor, ACEI) on the expression oftransforming growth factor-β_1 (TGF-β_1) and secretion of fibronectin, laminin and type Ⅳcollagen from the cultured human mesangial cells . Methods: Human mesangial cells were cultured indifferent glucose (5.6 mmol/L and 30 mmol/L) and agents (1, 10, 100 and 500 μmol/L) concentrations. The proliferation of mesangial cells were detected at 24, 48 and 72 h . Then the mesangial cellsare divided into four groups, low glucose (5.6 mmol/L) control group, high glucose (30 mmol/L)control group , L158, 809 (10 μmol/L) group and cilazapril (10 μmol/L) group. Forty- eight hourslater, the expression of TGF-β_1 were detected by RT-PCR. Concentrations of TGF-β_1 ,fibronection, laminin and type Ⅳ collagen in the su-pematants of the, mesangial cells weredetermined by EUSA and radioimmunoassay methods. Results: Compared with low glucose control group,the mesangial cells under high glucose medium show excessive proliferation and more TGF-β_1,fibronectin, laminin and type Ⅳ collagen in the supernatant. The expression of TGF-β_1 mRNA wasalso significantly increased under high glucose. The levels of TGF-β_1 and ECM (extracellularmatrix) proteins in the L158, 809 group and cilazapril group are obviously lower than that of thehigh glucose control group. The expression of TGF-β_1 mRNA was markedly decreased in the L158, 809group and cilazapril group compared with that of high glucose control group . Conclusion: Highglucose stimulated the cultured human mesangial cells to excessively proliferate, express TGF-β_1and secrete ECM proteins, and the high glucose-indeced changes were suppressed by either L158, 809and cilazapril.

近代高血压诊治原则

近代高血压诊治原则福建省莆田市医院黄德龙，林振伟高血压病是临床上最常见的心血管疾病，又是人类死亡主要疾病如冠心病、脑血管疾病等的最重要危险因素，我国居民死因以脑血管意外占第一位，心脏病患居第三位，这些都与高血压有密切关系。要在心血管病中贯彻预防为主的...

SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway

While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- and receptor-dependent endocytosis. Treatment of cells with either SARS-COV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 （ACE2）, the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic path- way inhibitors and dominant-negative Epsl5 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.

Cardiovascular and cerebrovascular outcomes in elderly hypertensive patients treated with either ARB or ACEI

Background Although angiotensin converting enzyme inhibitors （ACEI） and angiotensin receptor blockers （ARB） are equally important in the treatment of hypertension, there is less evidence whether they have equal cardiovascular and cerebrovascular protective effects, especially in elder hypertensive patients. This study aims to clarify this unresolved issue. Methods This cross-sectional study included clinical data on 933 aged male patients with hypertension who received either an ARB or ACEI for more than two months between January 2007 and May 2011. The primary outcome was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary endpoints were unstable angina, new atrial fibrillation, and transient ischemic attack. Results The median follow-up time was 24 months. Age, drug types, cerebral infarction history, renal dysfunction history were the independent predictors of the primary endpoint. The risk of an occurrence of a primary endpoint event was higher in the ARB group than the ACEI group [P = 0.037, hazard ratios （HR）： 2.124, 95% confidence interval （95% CI）： 1.048-4.306]. The Kaplan-Meier method also suggests that the rate of primary endpoint occurrence was higher in the ARB group than the ACEI group （P = 0.04）. In regard to the secondary endpoints, there were no significant differences between the two treatment arms （P = 0.137, HR： 1.454, 95% CI： 0.888-2.380）. Patient age and coronary heart disease history were independent predictors of the secondary endpoint. Conclusion ACEI were more effective than ARB in reducing cardiovascular and cerebrovascular morbidity and mortality in aged patients with hypertension.

ASSOCIATION ANALYSIS OF POLYMORPHISMS OF ACE GENE AND AGT GENE WITH ESSENTIAL HYPERTENSION IN CHINESE HAN'S POPULATION

Objective. To investigate whether the polymorphisms in the angiotensin converting enzyme (ACE) gene and angiotensinogen (AGT) gene are associated with essential hypertension. Methods. A case-control study was carried out using 103 hypertensive (HT) and 131 normotensive (NT) subjects. The insertion/deletion(I / D ) polymorphism of the ACE gene and the methionine→threo- nine variant at position 235 (M235T) of the AGT gene were determined by the polymerase chain reaction (PCR) technique and PCR/restriction fragment length polymorphism (PCR/RFLP) analysis, respective- ly. Results. The differences of D allele frequency and genotype distribution of the ACE gene between NT and HT groups were statistically significant (X^2=18.12, P<0. 005 ). The T235 allele frequency of the AGT gene was 69% in NT Chinese group (approximately 1. 38 to l. 64 fold that in Caucasians), and was greater in female HT than in NT (0. 82 vs 0. 72, X^2= 8. l, P<0. 025). A correlation between M235T molecular variant of the AGT gene and I/D molecular variant of ACE gene to hypertension was found. Cbeclusions. The possession of D allele of the ACE gene might be a marker for predisposition to hyper- tension. The T235 allele of the AGT gene was more common in Chinese than in Caucasians, and might contribute to the risk for hypertension in female Chinese.

Inappropriate use of digoxin in patients presenting with digoxin toxicity

Background Digoxin remains widely used today despite its narrow therapeutic index and toxicity. The objective of this study was to investigate the percentage of inappropriate use of digoxin and long-term outcomes of elderly patients hospitalized for digoxin toxicity. Methods The study included 99 consecutive patients hospitalized for digoxin toxicity. The other study criteria for the inappropriate use of digoxin was regarded if participants having depressed left ventricular systolic function （ejection fraction 〈 45%） who were not on optimal medical therapy including beta-blocker and angiotensin-converting-enzyme inhibitor therapy or if participants having permanent AF who were not on optimal beta-blocker therapy. Results Appropriate digoxin usage was confirmed in 33 of patients in spite of its narrow therapeutic index. A total of 16 of 99 patients died, with a mean follow-up time of 22.1 ± 10.3 months. Conclusions Contrary to popular belief, the rate of inappropriate digoxin usage remains high. On account of its narrow therapeutic index and toxicity, digoxin should be used more carefully according to the current evidence and guidelines.

Purification and Characterization of Angiotensin I Converting Enzyme Inhibition Peptides from Sandworm Sipunculus nudus

Three angiotensin I converting enzyme(ACE) inhibition peptides were isolated from sandworm Sipunculus nudus protein hydrolysate prepared using protamex. Consecutive purification methods, including size exclusion chromatography and reverse-phase high performance liquid chromatography(RP-HPLC), were used to isolate the ACE inhibition peptides. The amino acid sequences of the peptides were identified as Ile-Asn-Asp, Val-Glu-Pro-Gly and Leu-Ala-Asp-Glu-Phe. The IC_(50) values of the purified peptides for ACE inhibition activity were 34.72 μmol L^(-1), 20.55 μmol L^(-1) and 22.77 μmol L^(-1), respectively. These results suggested that S. nudus proteins contain specific peptides that can be released by enzymatic hydrolysis. This study may provide an experimental basis for further systematic research, rational development and clinical utilization of sandworm resources.

The impact of optimal medical therapy at discharge on mortality in patients with coronary artery disease

Objective To analyze the current usage of optimal medical therapy （OMT）, influencing factors, and the predictive value of OMT for all-cause mortality in coronary artery disease （CAD） patients with different subgroups. Methods A total of 3176 CAD patients confirmed by coronary angiography were included. OMT was defined as the combination of anti-platelet drugs, statins, beta blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Factors for OMT and its prognostic value were analyzed in CAD patients across different subgroups. Results Out of 3176 patients, only 39.8% （n = 1265） were on OMT at discharge. Factors associated with OMT at discharge were pre-admission OMT and discharge department. All-cause mortality occurred in 6.8% （n = 217） of patients. Multivariate analyses indicated that OMT was significantly associated with reduced all-cause mortality （HR： 0.65, 95% CI： 0.45~0.95; P = 0.025）. Sub-group analyses indicate that male acute coronary syndrome （ACS） patients were more likely to receive survival benefits with OMT at discharge. The positive impact of OMT at discharge was more apparent after 24 months, regardless of revascularization therapy. Four-drug combination of OMT was superior to 3-drug combination therapy in ACS patients but not in stable patients. Conclusions OMT was asso- ciated with significant improvement in survival in patients with CAD. The positive impact of OMT was distinct in the CAD patients with different characteristics.

Pharmarcogenetic Mechanism of ACE liD Polymorphism Adversely Responding to ACE Inhibitors in Regulating the ACE Promoter Activity in Neurons

The ACE （angiotensin converting enzyme） inhibitors are not only drugs widely prescribed drugs in cardiovascular diseases, but also potentially therapeutic agents in dementia. Based on the findings that the ACE inhibitors could activate the c-Jun N-terminal kinase signal to increase the ACE gene expression and that the Alu element of the human ACE gene involved in regulating ACE promoter activity, we aimed to investigate whether there are different pharmacogenetic responses of ACE I/D polymorphism to the ACE inhibitors in neurons. The three reporter vectors, pACEpro（0-SEAP, p-I-ACEpro-SEAP, and p-D-ACEpro-SEAP were used to examine the transcriptional activity of the vectors responding to the lisinopril treatment using a transient-transfection method in SH-SY5Y cells. Our results showed that lisinopril increased the promoter activity of an ACE gene by 16.7%. Additionally, we found the lisinopril enhanced the ACE promoter activity of the I-form vector by 17.2%, but adversely reduced that of the D-form vector by 16.8%, as compared with the respective control without the lisinopril treatment. Firstly, our findings had proved that the UD polymorphism of ACE gene contrarily responds to the ACE inhibitors in regulating the ACE expression in neurons, which provide a novel insight suggesting genetic testing to tailor the treatment regimens in AD （Alzheimer＇s disease） patients.

Left ventricular hypertrophy in relation to systolic blood pressure and the angiotensin converting enzyme I/D polymorphism in Chinese

Objective There is little population-based data on the prevalence and the environmental or genetic determinants of left ventricular hypertrophy （LVH） in China. The purpose of this paper is to study LVH in relation to systolic blood pressure and the angiotensin converting enzyme （ACE） insertion/deletion（I/D） polymorphism in Chinese. Methods We recorded 12- lead ECG （CardioSoft, v4.2） in 1365 residents in the Jingning County, Zhejiang Province, China. LVH was defined according to the gender-specific Sokolow-Lyon and Cornell product ECG criteria. Results Regardless of whether the Sokolow-Lyon or Cornell product ECG criteria was used, the prevalence of LVH （20.7% and 4.8%, respectively） significantly （P〈0.0001） increased with male gender （odds ratio [OR] 2.33 and 7.15） and systolic blood pressure （per 10 mm Hg increase, OR 1.46 and 1.33）. If the Sokolow-Lyon criteria was used, the prevalence of LVH was also influenced by alcohol intake （OR 1.44, P=-0.03） and body mass index （OR 0.83, P=0.0005）. The association between the Sokolow-Lyon voltage amplitude and the ACE I/D polymorphism was dependent on antihypertensive therapy （P=0.01）. In 1262 untreated subjects, but not 103 patients on antihypertensive medication, the ACE DD compared with II subjects had significantly higher Sokolow-Lyon voltage amplitudes （29.8：-0.6 vs. 28.0-3：0.5 mV, P=-0.02） and higher risk of LVH （OR 1.74, 95% CI： 1.12-2.69, P=-0.01）. Conclusion LVH is prevalent in Chinese, and is associated with systolic blood pressure and the ACE D allele. The genetic association might be modulated by antihypertensive therapy（J Geriatr Cardio12009; 6：131-136）.

Nursing care in old patients with heart failure： current status and future perspectives

The prognosis of heart failure （HF） patients has significantly improved in the last 20 years, given the advent of therapies such as angiotensin-converting enzyme （ACE） inhibitors/angiotensin receptor blockers （ARBs）, beta-block- ers, and implantable cardioverter-defibrillator （ICD）/cardiac resynchronization therapy devices （CRT）. In addition to these promising therapies, proper nursing-care is also important. Here we summarize recent progress of nursing-care strategies in older HF patients, including routine nursing care, transitional care model, self-care, and role of exercise training in old patients with HF.

A population-based case-crossover study of polyethylene glycol use and acute renal failure risk in the elderly

AIM:To evaluate the possibility of an association between polyethylene glycol(PEG) and acute renal failure(ARF) in elderly patients using a health insurance claims database.METHODS:We conducted a population-based casecrossover study using information obtained from Korean Health Insurance Review and Assessment Service(HIRA) claims from January 1,2005 to December 31,2005(Seoul,Korea).The study population consisted of elderly patients who received PEG prior to experiencing their first ARF-related hospitalization from April 1,2005 to December 31,2005.For each patient,one case and two control periods were matched.PEG use in a 2-or 4-wk window period prior to hospitalization for ARF was compared with PEG use in two earlier 2-or 4-wk control window periods.Conditional logistic regression analysis was used to estimate odds ratios(ORs) and 95% CI,adjusting for concomitant uses of diuretics,angiotensin converting enzyme inhibitors,non-steroidal anti-inflammatory drugs,antibiotics,anti-cancer drugs,and contrast media.RESULTS:Within the HIRA database which contained 1 093 262 elderly patients,1156 hospitalized ARF cases were identified.Among these cases,PEG was prescribed to 17(1.5%) patients before hospitalization.The adjusted ORs when applying the 2-and 4-wk window periods were 0.4(95% CI:0.03-5.24) and 2.1(95% CI:0.16-27.78),respectively.CONCLUSION:No increased risk of ARF was found in elderly PEG users.However,based on the limited number of study subjects,further analysis should be performed to confirm these results.

Effect of captopril or verapamil on intracellular sodium in cultured vascular smooth muscle cells

The effects of captopril (Cap) and verapamil (Ver)alone and in combination on intracellular Na+ concentration ([Na+]i) in cultured aortic smooth muscle cells (ASMC) of rabbits was evaluated by a direct measurement of [Na+]i with fluorescent dye sodium-binding benzofuran isophthalate (SBFI) combined with digital image. [Na+]i in resting cells was found to be 11.9 ± 0. 7 mmol/L. Angiotensin II (Ang-II, 0.1-10μmol/L) induced an increase of [Na+]i in concentration-dependent manner. Ver (0.1-10μmol/L) inhibited Ang-II (1 μmol/L)-induced increase in [Na+]i, while Cap enhanced Ang-II-induced increase in [Na+]i at 10μmol/L but not at 0.1-1μmol/L. Ver (0.1-1μmol/L)abolished enhancement of Ang-II-induced increase in [Na+]i by Cap. Thus, the inhibition of Capenhanced [Na+]i by Ver may provide a new hypothesis for the underlying molecular mechanism of synergistic effect of the combination of Ca2+ antagonists and angiotensinconverting enzyme inhibitors in controlling blood pressure.