福辛普利—新的血管紧张素转换酶抑制剂

福辛普利为含有磷酸的新一类血管紧张素转换酶抑制剂，口服吸收后迅速在体内水解成福辛普利拉，从而抑制血管紧张素转换酶的活性，其效力相当于恩纳普利，为卡托普利的４倍，赖诺普利的１／２。本品经肝、肾双向清除，降压安全、可靠，而且能改善左室舒张功能，长期服用无严重副作用。     

血管紧张素转换酶抑制剂对高血压胰岛素抗性的影响

采用血管紧张素转换酶抑制剂（卡托普利、依那普利、赖诺普利）治疗原发性高血压患者30例。剂量分别为12．5～37．5，5～15，10～30mg／　d，疗程4周，血压从治疗前171／106mmHg降到143／88mmHg。治疗后的血胰岛素水平、血胰岛素／葡萄糖比值均较治疗前明显降低（P＜0．05），显示有明显的改善胰岛素抗性效应。     

福辛普利和依那普利治疗老年人轻中度原发性高血压的比较

目的比较福辛普利和依那普利治疗老年人原发性高血压的疗效和安全性。方法经２周安慰剂导入期，６２例患者服用福辛普利１０ｍｇ１／ｄ或依那普利５ｍｇ１／ｄ，２周后无效则剂量加倍，４周后如仍无效则加服双氢克尿噻２５ｍｇ１／ｄ。结果两组药物均能明显降压（Ｐ＜０．００１），福辛普利降压谷峰值比率７３．９％，依那普利为４１．３％，不良反应发生率相似，依那普利有２例因不良反应退出试验。结论对老年患者福辛普利是一种有效、安全且易耐受的降压药，每日一次能维持２４小时降压效应。     

赖诺普利治疗收缩性心力衰竭疗效观察

赖诺普利是长效血管紧张素转换酶抑制剂，我们选用赖诺普利治疗收缩性心力衰竭40例，观察临床疗效满意，现报告如下。     

血管紧张素转换酶抑制剂与心脏保护

左心室结构和功能的显著改变与全身血管阻力的增加及伴随的血压升高密切相关,因而降低血管阻力有重要意义。利用首过放射性核素血管造影比较血管紧张素转换酶抑制剂(ACEI)卡托普利、赖诺普利和福辛普利的血流动力学效应,福辛普利较相同剂量的卡托普利和赖诺普利降低全身血管阻力更显著。     

血管紧张素转换酶抑制剂与心脏保护

左心室结构和功能的显著改变与全身血管阻力的增加及伴随的血压升高密切相关,因而降低血管阻力有重要意义.利用首过放射性核素血管造影比较血管紧张素转换酶抑制剂(ACEI)卡托普利、赖诺普利和福辛普利的血流动力学效应,福辛普利较相同剂量的卡托普利和赖诺普利降低全身血管阻力更显著.     

非洛地平与赖诺普利的降压效应及对左室肥厚逆转作用的对比

目的：评价并比较非洛地平及赖诺普利治疗轻、中度原发性高血压（ＥＨ）的降压疗效及对左心室肥厚的逆转作用。方法：选择１２８例轻、中度ＥＨ患者,入选前服用安慰剂２周,随机分为非洛地平组６６例和赖诺普利组６２例。非洛地平组服用非洛地平５～１０ｍｇ／ｄ,赖诺普利组服用赖诺普利１０～２０ｍｇ／ｄ,每日１次,疗程２４周。两组均在治疗前及治疗后的２、１２、２４周分别进行偶测血压、２４ｈ动态血压及超声心动图检查。结果：非洛地平和赖诺普利均能显著降低血压,两药对偶测血压的下降幅度差异无显著性（Ｐ＞０．０５）。非洛地平能有效控制清晨高峰期血压。收缩压、舒张压的谷／峰比值分别是７２％、６７％。非洛地平降低２４ｈ平均血压和白昼血压的幅度大于赖诺普利,而夜间血压降低的幅度显著低于白昼。两药治疗２４周后,室间隔厚度、左心室后壁厚度、左室心肌重量及左室重量指数较治疗前显著改善（Ｐ＜０．００１）。两组药物副反应均较轻。结论：非洛地平能有效降低ＥＨ患者的血压,降低靶器官损害的危险性。     

药物逆转左心室肥厚研究进展

高血压引起的左心室肥厚(LVH)已被公认为是心血管并发症的独立危险因素[1],引起高血压LVH的主要原因是血流动力学和神经内分泌激活两方面。高血压LVH时心脏的组织结构发生的改变,包括心肌细胞肥大和心肌间质纤维化。下面就药物逆转左心室肥厚研究进展简单综述如下。1血管紧张素转换酶抑制剂现已证实多种血管紧张素转换酶抑制剂如苯那普利、依那普利、赖诺普利,均能有效逆转高血压LVH。一项多研究分析表明,血管紧张素转换酶抑制剂是逆转高血压LVH的最有效药物[2]。以往认为血管紧张素转换酶抑制剂主要通过抑制AngⅡ形成来防止LVH,但…     

福辛普利对有转换酶抑制剂相关咳嗽的高血压病人咳嗽？…

目的：观察福辛普利对有转换酶抑制剂相关咳嗽高血压病人的影响，方法：２１例有上述咳嗽的高血压患者改服福辛普利１０ｍｇ／ｄ，或２０ｍｇ／ｄ，连续４周，密切观察咳嗽情况，结果：福辛普利治疗４周后，咳嗽频率，程度，对睡眠的影响等明显改善，临床疗效相同，结论：福辛普利能明显减少转换酶抑制剂的相关咳嗽，提示不同的转换酶抑制剂引起的咳嗽情况不同。     

培哚普利在心血管临床中的应用

培哚普利是新一代的血管紧张素转换酶抑制剂，系非硫氢基化合物，较依那普利具有更强和更长的抑制作用，每日给药一次即可维持２４小时疗效。适用于高血压病和心力衰竭，是很有前途的药物。     

血管紧张素Ⅱ对人单核细胞CD40信号系统的作用研究

目的：以体外培养的单核细胞系为研究对象,从细胞水平探讨血管紧张素Ⅱ对CD40信号系统的影响。方法：用1640培养液进行单核细胞的培养,并用佛波醇肉豆蔻乙酸酯（PMA）诱导其分化为巨噬细胞。将培养的细胞置于不同浓度的血管紧张素Ⅱ（10-10~10-5mol/L）及拮抗剂氯沙坦、PD123319中培养24 h,用实时聚合酶链反应（PCR）的技术检测细胞CD40mRNA的变化;同时酶联免疫法测定细胞上清分泌的CD40蛋白水平。结果：给予PMA（50ng/ml）刺激4 h后,单核细胞贴壁分化为巨噬细胞,与不同浓度血管紧张素Ⅱ（10-10~10-5mol/L）共培养24 h后,与对照组相比较,血管紧张素Ⅱ的10-6mol/L组与10-5mol/L组CD40 mRNA的表达均明显增加（P均〈0.05）;受体AT1拮抗剂氯沙坦（25μg/ml）抑制了CD40 mRNA的表达,另一受体AT2拮抗剂PD123319（25μg/ml）显示了明显的相反作用（P〈0.05）。含单核细胞分化成的巨噬细胞上清液中CD40蛋白水平在血管紧张素Ⅱ及其受体拮抗剂的刺激下显示与CD40 mRNA水平一致的结果。结论：血管紧张素Ⅱ对于单核细胞转化生成的巨噬细胞CD40-CD40L系统的表达具有上调作用。血管紧张素Ⅱ两种受体拮抗剂对CD40系统的作用不同,提示肾素-血管紧张素系统与CD40信号系统之间具有一定相互作用。     

冠心病患者可溶性OX40配体与白细胞介素10的相关性分析

目的观察冠心病稳定型心绞痛患者及高危因素患者和健康人血浆可溶性OX40配体(sOX40L)和白细胞介素10(IL-10)水平及两者之间的相关性,探讨sOX40L在冠心病中的作用及其相关因素。方法采用酶联免疫吸附法测定35例稳定型心绞痛患者、30例高危因素患者以及20名健康人血浆中sOX40L及IL-10的水平。结果稳定型心绞痛患者血浆OX40L水平[(24.95±15.60)ng/L]高于健康对照组[(16.44±11.31)ng/L],差异有统计学意义(P<0.05),略高于高危因素组[(19.99±9.35)ng/L],但差异无统计学意义(P>0.05)。与健康对照组相比,稳定型心绞痛组IL-10水平显著降低[(27.3±9.9)ng/L比(20.5±8.9)ng/L,P<0.05]。血浆sOX40L与IL-10呈显著负相关(r=-0.394,P=0.000)。结论本研究首次观察到血浆可溶性OX40L水平与抗炎细胞因子IL-10的水平呈显著负相关,提示sOX40L可能通过影响IL-10的水平而影响冠心病的危险程度。     

OX40 ligand shuts down IL-10-producing regulatory T cells

IL-10-producing CD4(+) type 1 regulatory T (Tr1) cells play a critical role in the maintenance of peripheral tolerance. Although immunosuppressive drugs, cytokines, costimulatory molecules, and immature dendritic cells are implicated in the induction of Tr1 cells, the signals that negatively regulate the generation and function of Tr1 cells have been elusive. We report that OX40 ligand (OX40L) completely inhibited the generation of IL-10-producing Tr1 cells from na?ve and memory CD4(+) T cells induced by the immunosuppressive drugs dexamethasone and vitamin D3. This unique function of OX40L was not shared by two costimulatory TNF family members, GITR ligand and 4-1BB ligand. OX40L strongly inhibited the generation of IL-10-producing Tr1 cells induced by two physiologic stimuli, the inducible costimulatory ligand and immature dendritic cells. In addition, OX40L strongly inhibited IL-10 production and suppressive function of differentiated IL-10-producing Tr1 cells. These two novel functions of OX40L shed light on the mechanism by which OX40/OX40L regulates immunity and tolerance.     

The effect of inhaled verapamil on resting bronchial tone and airway contractions induced by histamine and acetylcholine in normal and asthmatic subjects

In man, the influence of calcium entry blockers (CEB) on nonspecific bronchial sensitivity and resting bronchial tone is controversial. In 10 asthmatic and 8 normal subjects we recorded specific airway conductance (Gaw/VL) and flow volume loops before, 30, 60, and 90 min after the inhalation of saline, 10 (V10) and 20 mg (V20) of verapamil. The dose of inhaled histamine and acetylcholine producing Gaw/VL of -40% (PD40H and PD40ACH, respectively) with and without pretreatment with saline, V10, and, in 15 subjects, V20 was also determined. We measured plasma verapamil concentrations immediately after the end of nebulization of V10 and V20, and 30 and 60 min later. In normal subjects, V10 and V20 produced a maximal % delta Gaw/VL of 22.30 (+/- 19.50) and 33.00 (+/- 15.82), respectively (p less than 0.05). In asthmatics, V10 and V20 produced comparable % delta Gaw/VL of 22.00 (+/- 22.50) and 38.60 (+/- 38.60), respectively. This bronchodilating effect involved predominantly the large airways, persisted for 60 to 90 min, was reproducible, affected only some subjects (11 of 18), and was independent of the resting Gaw/VL, degree of bronchial sensitivity to H and ACH, and the time course of plasma verapamil concentration. The latter reached a maximum of 24.3 +/- 7.1 ng/ml after V20. In both normal and asthmatic subjects, saline or V10 did not significantly alter PD40H and PD40ACH. In normal subjects, pretreatment with V20 increased PD40H 5.3 times and PD40ACH 3.22 times (p less than 0.05). Except in 2 asthmatics, in whom V20 decreased PD40 and PD40ACH, it increased significantly PD40ACH (dose ratio: 3.15, p less than 0.05) but not PD40H.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of ezetimibe/simvastatin 10/20 and 10/40 mg compared with atorvastatin 20 mg in patients with type 2 diabetes mellitus

AIM: This randomized, double-blind study evaluated the efficacy of switching from atorvastatin (ATV) 10 mg to ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg, EZE/SIMVA 10/40 mg or doubling the dose of ATV from 10 to 20 mg in patients with type 2 diabetes (T2D). METHODS: Eligible patients had haemoglobin A(1C)< or =10%, were aged > or =18 years and were on ATV 10 mg for > or =6 weeks before study entry. After a 4-week open-label ATV 10 mg run-in, patients were randomized to EZE/SIMVA 10/20 mg (n = 220), EZE/SIMVA 10/40 mg (n = 222) or ATV 20 g (n = 219) daily for 6 weeks. RESULTS: Greater (p < or = 0.001) reductions in low-density lipoprotein cholesterol (LDL-C) (the primary end-point) were achieved by switching to EZE/SIMVA 10/20 mg (26.2%) or 10/40 mg (30.1%) than by doubling the dose of ATV to 20 mg (8.5%). EZE/SIMVA 10/20 mg and 10/40 mg produced greater (p < or = 0.001) reductions in total cholesterol, non-high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B relative to ATV 20 mg. A reduction (p < or = 0.050) in C-reactive protein was observed with EZE/SIMVA 10/40 mg vs. ATV 20 mg. Similar reductions in triglycerides were observed across the three groups, and none of the treatments produced a significant change in HDL-C. A greater (p < or = 0.001) proportion of patients achieved LDL-C <2.5 mmol/l with EZE/SIMVA 10/20 mg (90.5%) and 10/40 mg (87.0%) than with ATV 20 mg (70.4%). Both EZE/SIMVA doses were generally well tolerated, with an overall safety profile similar to ATV 20 mg. CONCLUSIONS: EZE/SIMVA 10/20 and 10/40 mg provided greater lipid-altering efficacy than doubling the dose of ATV from 10 to 20 mg and were well tolerated in patients with T2D.     

Variable region framework differences result in decreased or increased affinity of variant anti-digoxin antibodies.

Rare spontaneous variants of the anti-digoxin antibody-producing hybridoma 40-150 (Ko = 5.4 x 10(9) M-1) were selected for altered antigen binding by two-color fluorescence-activated cell sorting. The parent antibody binds digoxin 890-fold greater than digitoxin. The variant 40-150 A2.4 has reduced affinity for digoxin (Ko = 9.2 x 10(6) M-1) and binds digoxin 33-fold greater than digitoxin. A second-order variant, derived from 40-150 A2.4 (designated 40-150 A2.4 P.10), demonstrated partial regain of digoxin binding (Ko = 4.4 x 10(8) M-1). The altered binding of the variant 40-150 A2.4 was accounted for by a point mutation resulting in substitution of arginine for serine at position 94 in the heavy chain variable region. Antibody 40-150 A2.4 P.10 also contains this arginine but owes its enhanced antigen binding to deletion of two amino acids from the heavy chain amino terminus. This unusual sequence alteration in an immunoglobulin framework region confers increased affinity for antigen.     

Annealing Effect on the Characteristics of Co40Fe40W10B10 Thin Films on Si(100) Substrate

This research explores the behavior of Co₄₀Fe₄₀W₁₀B₁₀ when it is sputtered onto Si(100) substrates with a thickness (t_f) ranging from 10 nm to 100 nm, and then altered by an annealing process at temperatures of 200 °C, 250 °C, 300 °C, and 350 °C, respectively. The crystal structure and grain size of Co₄₀Fe₄₀W₁₀B₁₀ films with different thicknesses and annealing temperatures are observed and estimated by an X-ray diffractometer pattern (XRD) and full-width at half maximum (FWHM). The XRD of annealing Co₄₀Fe₄₀W₁₀B₁₀ films at 200 °C exhibited an amorphous status due to insufficient heating drive force. Moreover, the thicknesses and annealing temperatures of body-centered cubic (BCC) CoFe (110) peaks were detected when annealing at 250 °C with thicknesses ranging from 80 nm to 100 nm, annealing at 300 °C with thicknesses ranging from 50 nm to 100 nm, and annealing at 350 °C with thicknesses ranging from 10 nm to 100 nm. The FWHM of CoFe (110) decreased and the grain size increased when the thickness and annealing temperature increased. The CoFe (110) peak revealed magnetocrystalline anisotropy, which was related to strong low-frequency alternative-current magnetic susceptibility (χ_ac) and induced an increasing trend in saturation magnetization (Ms) as the thickness and annealing temperature increased. The contact angles of all Co₄₀Fe₄₀W₁₀B₁₀ films were less than 90°, indicating the hydrophilic nature of Co₄₀Fe₄₀W₁₀B₁₀ films. Furthermore, the surface energy of Co₄₀Fe₄₀W₁₀B₁₀ presented an increased trend as the thickness and annealing temperature increased. According to the results, the optimal conditions are a thickness of 100 nm and an annealing temperature of 350 °C, owing to high χ_ac, large Ms, and strong adhesion; this indicates that annealing Co₄₀Fe₄₀W₁₀B₁₀ at 350 °C and with a thickness of 100 nm exhibits good thermal stability and can become a free or pinned layer in a magnetic tunneling junction (MTJ) application.     

Safety and efficacy of ezetimibe/simvastatin combination versus atorvastatin alone in adults ≥65 years of age with hypercholesterolemia and with or at moderately high/high risk for coronary heart disease (the VYTELD study)

Higher than 80% of coronary heart disease-related mortality occurs in patients ≥65 years of age. Guidelines recommend low-density lipoprotein (LDL) cholesterol targets for these at-risk patients; however, few clinical studies have evaluated lipid-lowering strategies specifically in older adults. This multicenter, 12-week, randomized, double-blind, parallel-group trial evaluated the efficacy and safety of the usual starting dose of ezetimibe/simvastatin (10/20 mg) versus atorvastatin 10 or 20 mg and the next higher dose of ezetimibe/simvastatin (10/40 mg) versus atorvastatin 40 mg in 1,289 hypercholesterolemic patients ≥65 years of age with or without cardiovascular disease. Patients randomized to ezetimibe/simvastatin had greater percent decreases in LDL cholesterol (-54.2% for 10/20 mg vs -39.5% and -46.6% for atorvastatin 10 and 20 mg, respectively; -59.1% for 10/40 mg vs -50.8% for atorvastatin 40 mg; p <0.001 for all comparisons) and the number attaining LDL cholesterol <70 mg/dl (51.3% for 10/20 mg, 68.2% for 10/40 mg) and <100 mg/dl (83.6% for 10/20 mg; 90.3% for 10/40 mg) was significantly larger compared to those receiving atorvastatin for all prespecified dose comparisons (p <0.05 to <0.001). A significantly larger percentage of high-risk patients achieved LDL cholesterol <70 mg/dl on ezetimibe/simvastatin 10/20 mg (54.3%) versus atorvastatin 10 mg (10.9%, p <0.001) or 20 mg (28.9%, p <0.001) and ezetimibe/simvastatin 10/40 mg (69.2%) versus atorvastatin 40 mg (38.2%, p <0.001), and a significantly larger percentage of intermediate-risk patients achieved LDL cholesterol <100 mg/dl on ezetimibe/simvastatin 10/20 mg (82.1%) versus atorvastatin 10 mg (59.3%, p <0.05). Improvements in non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and lipoprotein ratios were significantly greater with ezetimibe/simvastatin than atorvastatin for all comparisons (p <0.01 to <0.001). High-density lipoprotein cholesterol and triglyceride results were variable. All treatments were generally well tolerated. In conclusion, ezetimibe/simvastatin provided significantly greater improvements in key lipid parameters and higher attainment of LDL cholesterol targets than atorvastatin, with comparable tolerability.     

Interactions between three common subunits of yeast RNA polymerases I and III.

The AC40 and AC19 subunits (encoded by RPC40 and RPC19) are shared by yeast RNA polymerases I and III and have a local sequence similarity to prokaryotic alpha subunits. Mutational analysis of the corresponding "alpha motif" indicated that its integrity is essential on AC40 subunit but is not essential on AC19 subunit. By applying the two-hybrid method, these two polypeptides were shown to associate in vivo. Extragenic suppression of rpc19 and rpc40 mutations confirmed that AC19 and AC40 subunits interact with each other in vivo and revealed an interaction with ABC10 beta subunit [encoded by RPB10; Woychick, N. A. & Young, R.A. (1990) J. Biol. Chem. 265, 17816-17819], one of the five polypeptides common to all three nuclear RNA polymerases. A correction of the RPB10 sequence showed that ABC10 beta subunit is a 70-amino acid polypeptide, as confirmed by peptide microsequencing. These results suggest that the assembly of RNA polymerase I and III requires the association of ABC10 beta subunit with an AC19/AC40 heterodimer.