血管紧张素转换酶与肺源性心脏病的相关性分析

目的　探讨血管紧张素转换酶(ACE)与肺源性心脏病(肺心病)的关系。方法　选取肺心病病人6 0例,正常对照组4 0例。采用多聚酶链反应(PCR)检测两组人群ACE基因的I/D多态性,同时检测血清ACE水平(SACE)。结果　两组人群检测到ACE基因的DD ,ID及Ⅱ3种基因型,两组比较3种基因型的频率差异无显著性(X2 =2 .191,P >0 .0 5 ) ;两组I/D等位基因频率分别为0 .5 8,0 .4 2和0 .6 9,0 .31,差异无显著性(X2 =2 .2 15 ,P >0 .0 5 )。女性组ACE基因型中DD型占2 5 .9% ,ID型2 5 .9% ,Ⅱ型4 8.2 % ;男性组分别为15 .1%、2 7.3%和5 7.6 % ,统计学分析表明两组间基因型构成有明显差异,I/D等位基因频率无明显差别,DD型与非DD型基因型构成无明显差别。肺心病病人血清ACE水平明显低于正常人群。结论　ACE基因I/D多态性与肺心病发生无明显相关性,血清ACE活性降低可能参与肺心病进程     

Effects of the angiotensin-converting enzyme inhibitor enalapril on blood haematopoietic progenitors and Acetyl-N-Ser-Asp-Lys-Pro concentrations

Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) is a physiological inhibitor of the proliferation of haematopoietic stem cells. In 12 healthy volunteers treated with the angiotensin-converting enzyme (ACE) inhibitor enalapril (20 mg day⁻¹ for 15 days), we studied plasma and urinary AcSDKP levels, the in vitro degradation of AcSDKP by plasma ACE and the numbers of circulating haematopoietic progenitors (granulocyte-monocytic colony forming unit: CFU-GM; burst forming unit-erythroid: BFU-E; and mixed colony forming unit: CFU-mixed). During treatment, plasma and urinary AcSDKP concentrations increased 2- to 5-fold, degradation of AcSDKP was reduced, and CFU-mixed significantly increased by 100% while BFU-E and CFU-GM significantly decreased by 16% and 26%, respectively. These results indicate that ACE inhibitors may be of value during chemotherapy or radiotherapy, warranting further study.     

血管紧张素转化酶(ACE)试剂盒的性能评价

目的自建血管紧张素转化酶检测系统的性能评价。方法依据临床和实验室标准化协会(CLSI)标准中EP5-A2,EP9-A文件的要求,采用全自动生化分析仪对九强公司的ACE试剂盒的精密度、线性、与比对试剂的相关性以及可报告范围等一些性能进行评价。结果自建系统血清ACE高低值的批内CV分别为6.87%和2.39%,批间CV分别为6.09%和1.81%,日间CV分别为8.00%和2.8%均在厂家提供的小于10%的范围内;线性结果R2=0.99;与比对试剂相关系数r=0.990 56,且平均偏倚为8.55%有良好的相关性;血清ACE检测试剂盒可报告范围为9.0U/L-600U/L。结论自建ACE检测系统各项性能可以满足临床应用的要求。     

Pharmacokinetics of perindopril and its metabolites in healthy volunteers

Perindopril, an angiotensin converting enzyme (ACE) inhibitor, is converted in vivo to its active diacid metabolite, perindoprilat and to a perindoprilat glucuronide. The pharmacokinetic parameters of perindopril, perindoprilat and perindoprilat glucuronide were evaluated after single administration to healthy volunteers (N = 12) of 8 mg of perindopril tert-butylamine salt by oral route (treatment A), by intravenous route (bolus in 5 min, treatment B) and of an equimolar dose of perindoprilat (6.1 mg) by intravenous route (infusion over 2 h, treatment C). The treatments were administered as a randomised 3-way cross-over design. Plasma samples were collected up to 96 h and urines up to 120 h. Perindopril is rapidly absorbed with an oral bioavailability of 95% and is mainly eliminated by metabolic processes. The formation of perindoprilat is slow and about 20% of the available parent drug is transformed into this metabolite. Elimination profile of perindoprilat is biphasic, with a rapid renal excretion of the free fraction and a long terminal half-life of the fraction bound to ACE. Perindoprilat glucuronide is mainly obtained from perindopril by a pre-systemic first pass metabolism.     

Emergency Department Management of Patients with ACE-inhibitor Angioedema

Background

Angiotensin-converting-enzyme inhibitors (ACEI) are one of the most prescribed medications worldwide. Angioedema is a well-recognized adverse effect of this class of medications, with a reported incidence of ACEI angioedema of up to 1.0%. Of importance to note, ACEI angioedema is a class effect and is not dose dependent. The primary goal of this literature search was to determine the appropriate Emergency Department management of patients with ACEI angioedema.

Methods

A MEDLINE literature search from January 1990 to August 2012 and limited to human studies written in English for articles with keywords of ACEI angioedema. Guideline statements and non-systematic reviews were excluded. Studies identified then underwent a structured review from which results could be evaluated.

Results

Five hundred sixty-two papers on ACEI angioedema were screened and 27 appropriate articles were rigorously reviewed in detail and recommendations given.

Conclusion

The literature search did not support any specific treatment protocol with a high level of evidence due to the limited—and limitations of the—available studies.     

Specific immunotherapy for allergic rhinitis to grass and tree pollens in daily medical practice—symptom load with sublingual immunotherapy compared to subcutaneous immunotherapy

The renin-angiotensin-aldosterone system is known to play an essential role in controlling sodium balance and body fluid volumes, and thus blood pressure. In addition to the circulating system which regulates urgent cardiovascular responses, a tissue-localized renin-angiotensin system (RAS) regulates long-term changes in various organs. Many recognized RAS components have also been identified in the human eye. The highly vasoconstrictive angiotensin II (Ang II) is considered the key peptide in the circulatory RAS. However, the ultimate effect of RAS activation at tissue level is more complex, being based not only on the biological activity of Ang II but also on the activities of other products of angiotensinogen metabolism, often exerting opposite effects to Ang II action. In recent studies, orally administered angiotensin II type 1 receptor blockers and angiotensin-converting enzyme inhibitors lower intra-ocular pressure (IOP), likewise topical application of these compounds, the effect being more prominent in ocular hypertensive eyes. Based on previous findings and our own experimental data, it can strongly be suggested that the RAS not only regulates blood pressure but is also involved in the regulation of IOP.     

Combined effects of ACE and MMP-3 polymorphisms on migraine development

Migraine is a primary headache disorder which involves both genetic and environmental components. Since angiotensin-converting enzyme (ACE) and matrix metalloproteinase (MMP) share the same homology, we investigated whether the MMP-3 and ACE I/D gene variants are involved in migraine risk and whether the ACE variant might act in combination with the MMP-3 genetic variant in patients with migraine. This is the first study to evaluate the association between MMP-3 and ACE polymorphisms, and migraine. Genotypes were determined by polymerase chain reaction. The frequencies of 5A5A genotypes of the MMP-3 and D allele of ACE were significantly elevated, but II genotypes of the ACE and 6A allele of MMP-3 significantly decreased in all patients. The combined DD/5A5A and ID/5A5A genotypes increased the risk of migraine. Individuals who were homozygous for the deletion (D) allele showed increased ACE activity. Subjects with the 5A5A genotype and/or D allele or with the combined DD/5A5A or ID/5A5A might be more susceptible to migraine development. In contrast, subjects with the II and/or 6A6A genotypes may be protected from migraine development. The greater activity of the 5A5A and DD genotypes might result in vascular reactivity that is more pronounced in migraine. Taken together, our data suggest that numerous genes may influence ACE activity. Discovery of new genes might better clarify the pathogenesis of migraine and open an avenue to therapeutic strategies against migraine.     

温州地区汉族人群血管紧张素转换酶(ACE)基因多态性分析

目的研究温州地区汉族人群血管紧张素转换酶（ACE）基因插入/缺失多态性分布情况.方法采用聚合酶链反应（PCR）分别检测204例温州地区汉族正常人群样本的ACE I/D基因型,分类计数进行统计学分析.结果温州地区汉族正常人的ACE基因三种基因型频率分别为：DD型13.73%,DI型41.18%,Ⅱ型45.09%.D和I等位基因频率分别为34.5%和65.5%.结论 ACE基因多态性的分布与性别无关,温州地区汉族人群ACE基因频率分布与日本人相近,但DD型及D等位基因频率低于欧美人群.     

No relation between angiotensin‐converting enzyme gene polymorphism and smoking dependence

Background: Smoking as a major risk factor for development of cancer and cardiovascular disease is thought to be partially genetically determined. The aim of this study was to investigate whether there is an association between insertion/deletion (I/D) polymorphism in angiotensin‐converting enzyme (ACE) and smoking status and the number of cigarettes smoked per week. Methods: Using polymerase chain reaction, I/D polymorphism was evaluated in the ACE gene in 1204 male and 1375 female representative Caucasians. Information about smoking status and number of cigarettes smoked per week was collected via a questionnaire. Results: Frequencies of the alleles and genotypes of ACE I/D polymorphism did not differ between smokers, past smokers and individuals who had never smoked. No association was found between ACE I/D polymorphism and the number of cigarettes smoked per week, either in males or in females. Conclusion: I/D polymorphism in the ACE gene does not play any role in genetic determination of predisposition to smoking.     

ACE I allele and eNOS G allele crosstalk may have a role in chronic obstructive pulmonary disease

BACKGROUND: Pulmonary hypertension, a characteristic of chronic obstructive pulmonary disease (COPD) has led us to investigate polymorphisms in angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) genes. DESIGN AND METHODS: Sixty-six normal and 27 patients, all of whom were smokers, were screened for ACE Insertion/Deletion (I/D) and eNOS G894T and CA-repeat polymorphisms and for plasma ACE and NO levels. RESULTS: Elevated ACE and decreased NO levels were obtained with the pattern of II to ID to DD and GG to GT to TT conversion, respectively. Furthermore, the genotype combination of II and GG was significantly greater in controls as compared to patients (P = 0.01; OR = 2.43; 95% CI: 1.21-4.87; RR = 2.00, 1.15-3.48). The CA-repeat multialleles showed a trimodal pattern in both the groups with a frequency range of 0.0057-0.103 and 0.0208-0.1875 in the controls and patients, respectively. CONCLUSIONS: The lower ACE and higher NO levels by virtue of the interchromosomal interaction between the I and G alleles appear to cause less vasoconstriction and increase vasodilatation that may be advantageous in the improvement of the disease.     

Enalapril‐induced angioedema: A forgotten adverse event

Angioedema is an edema of skin, mucosa, respiratory, and gastrointestinal tract, due to vascular permeability increase, resulting in plasma extravasation, which has been associated with multiple causes. We describe a case of a patient who was prescribed with enalapril and presented with symptoms suggestive of angioedema.     

血管紧张素转换酶和内皮型一氧化氮合酶基因多态性与高血压的相关性

目的探讨血管紧张素转换酶(ACE)基因I/D、内皮型一氧化氮合酶 (eNOS)基因G894T多态性与原发性高血压(EH)的关系.方法采用基因芯片技术检测 224例(124例高血压患者和100例健康人)ACE和eNOS基因多态性.结果 EH组ACE DD基因型携带者频率显著高于对照组 (30.65% vs16.00%,P<0.05 ),eNOS- GT TT基因型频率与对照组相比无显著性差异( 12.90% vs 15.00%,P＞0.0 5).结论 ACE-DD基因多态性可能是高血压病的独立危险因素,eNOS基因G894T多态性可能不是高血压病的独立危险因素.基因芯片技术为研究多种易感基因与高血压病的相关性提供了一项高效、敏感的方法.     

血管紧张素Ⅰ转换酶基因对脑卒中发病分子机理探讨

目的从分子生物学的角度探讨血管紧张素Ｉ转换酶（ＡＣＥ）基因型变化及高血压参与临床急性脑血管病（ＡＣＶＤ）的分子生物学机理的可能性。方法对２０３例ＡＣＶＤ患者和５１例对照组的外显子１６片段进行ＰＣＲ扩增,检测扩增的ＤＮＡ条带,进行统计分析。结果有高血压史伴ＡＣＥ基因的脑梗死（ＡＩ）发生率显著高于ＡＣＥ基因阴性的患者。结论ＡＣＥ基因多态性与ＡＣＶＤ无关,但高血压史伴ＡＣＥ基因多态性是ＡＩ发生的致危因素之一,ＤＤ型ＡＣＥ基因的患者中高血压的有无之比为１０：２。     

ACE Inhibitors for Prophylaxis of Migraine Headaches

Seventeen patients with migraine headaches, occurring at least twice a month, were successfully treated with an ACE inhibitor for prophylaxis. Most were given enalapril, some used lisinopril. Duration of treatment ranged from 3 months to 3 years. Side effects were generally not noted. Cough occurred in four patients. The mechanism of action is unknown. The lack of side effects and the presence of clearly sustained benefit in this small group of migraineurs should prompt further study and use of this class of drugs for prophylaxis.     

Hypocalcemic toxicity and atypical reactions in therapeutic plasma exchange

Hypocalcemic toxicity accounts for the most common adverse effects of therapeutic plasma exchange. The symptoms can be related to a fall in plasma ionized calcium. Citrate-based anticoagulants, notably sodium citrate and ACD formula A, have been indicated as the major cause of hypocalcemic toxicity, but colloid replacement fluids containing human serum albumin are also at fault. Recognition of the signs and symptoms of hypocalcemic toxicity is important because several clinical measures are available to deal with them and to ensure patient comfort. A typical reactions, characterized by flushing and hypotension during plasma exchange, have been attributed to the effects of angiotensin converting enzyme inhibitors. Both exchange and adsorption apheresis procedures can result in atypical reactions in patients who have been taking this class of drugs within 48 to 72 hours of an apheresis procedure. These reactions are less common than hypocalcemic toxicity, but can be prevented by paying attention to detail.     

丁咯地尔与川芎嗪治疗急性脑梗死疗效及对血液流变学影响的比较

目的 比较丁咯地尔与川芎嗪治疗急性脑梗死的临床疗效及其对血液流变学的影响.方法 62例急性脑梗死患者随机分为两组,每组31例,一组在常规治疗基础上给予川芎嗪注射液治疗,另一组在常规治疗基础上给予地尔注射液治疗,观察两组患者的临床疗效、血液流变学指标.结果 治疗组的显效率和总有效率均明显高于对照组(P<0.01或P<0.05);两组患者治疗后的血液流变学参数均比治疗前有所改善(P<0.05),且治疗组患者各项血液流变学参数的改善均优于对照组(P<0.05).结论 丁咯地尔治疗急性脑梗死比川芎嗪的疗效更佳,且无严重的毒副反应.     

血管紧张素-1转换酶基因多态性与急性心肌梗死的相关性研究

目的　研究血管紧张素 - 1转换酶 (ACE)基因多态性与急性心肌梗死 (AMI)的相关性。方法　本研究选择了1999～ 2 0 0 0年间在我院住院的 14 0例AMI患者 ,连续地挑选 5 7例非心肌梗死患者作为对照组 ,进行相应的临床观察及实验室检查 ;并从外周血中提取基因组DNA ,利用聚合酶链式反应的方法对ACE基因进行分型。结果　 14 0例AMI患者中ACEDD型百分比明显高于ID、II的患者 (P <0 0 0 0 5 ) ;D等位基因频率显著增高。结论　ACEDD型的AMI患者与Ⅱ、ID型的患者相比 ,有较高的AMI发生率 ;且D等位基因与AMI的发生有显著的相关性     

A 13-year review of lisinopril ingestions in children less than 6 years of age

Abstract

Background. Lisinopril is an angiotensin converting enzyme inhibitor used for treatment of hypertension, congestive heart failure, and acute myocardial infarction. Reports of clinical experience with pediatric ingestions are minimal. Method. A 13-year retrospective study of lisinopril ingestions in children reported to the California Poison Control System was analyzed and case notes were reviewed. Institutional Review Board approval was obtained and cases were blinded. Inclusion criteria were lisinopril as a single ingestant, age less than 6 years, treatment in a health care facility, case followed to a known outcome. Results. Inclusion criteria were met in 296 cases. Demographics include 51% of male patients and the mean age was 1.97 years (range: 9 months–5 years). Of the 296 patients, 8 patients (2.7%) developed hypotension (ranges: 55–74 mm Hg systolic and 22–48 mm Hg diastolic). The lowest blood pressure of 55/22 mm Hg was recorded in a 22-month old male who ingested an estimated 120-mg lisinopril (13.3 mg/kg). The lowest dose of lisinopril causing hypotension was with an estimated dose of approximately 50 mg or 3.9 mg/kg in a 2-year old. Two hundred and eighty-two patients (95.3%) were treated and released from the emergency department and 14 patients (4.7%) were admitted. The dose ingested was reported in 189 cases and an exact-dose of lisinopril was reported in 61 patients (20.6%); mean amount ingested was 3.0 mg/kg, median amount ingested was 2.1 mg/kg (range: 0.1–10.9 mg/kg, N = 38); and mean total dose was 33.4 mg, median total dose was 20 mg (range: 2.5–160 mg, N = 61). None of the patients with exact-dose lisinopril ingestions developed hypotension, received intravenous fluids, or were admitted. Conclusion. The lowest estimated dose of lisinopril to cause hypotension was 50 mg or 3.9 mg/kg. Although continued evaluation of pediatric lisinopril ingestions is essential to determine more specific thresholds of toxicity, the lack of effect on blood pressure in children with exact-dose ingestions indicate that pediatric lisinopril ingestions (for ages > 9 months) ≤ 4 mg/kg up to 40 mg total may be safely managed at home.