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1.
目的探讨阿利吉仑对单侧输尿管梗阻大鼠肾间质纤维化的作用及机制。方法 24只雌性SD大鼠随机分为3组,Sham组、UUO组及aliskiren组,除Sham组外,UUO组及aliskiren组均行左侧输尿管结扎术。aliskiren组术前1 d开始灌胃给药,阿利吉伦50 mg/(kg·d),每日1次,连续2周。术后第14天处死大鼠,留取梗阻侧肾组织行HE染色和Masson染色,光镜下观察各组大鼠肾组织病理变化,免疫组化和Western印迹检测肾组织TGF-β1、Smad2和Smad7蛋白表达水平。结果阿利吉仑可明显减轻大鼠肾间质炎性细胞浸润、纤维组织增生及肾小管扩张和萎缩。免疫组化和Western印迹结果均显示:与Sham组相比,UUO组TGF-β1、Smad2表达明显上升,而Smad7表达明显下降(均P<0.05);与UUO组相比,aliskiren组TGF-β1、Smad2表达明显下降,Smad7表达明显上升(均P<0.05)。结论 TGF-β1/Smad信号通路与肾间质纤维化有关,阿利吉仑可抑制肾间质纤维化,其机制可能与下调TGF-β1、Smad2的表达和上调Smad7的表达有关。  相似文献   
2.
目的 探讨肾素抑制剂阿利吉仑的抗动脉粥样硬化(As)作用及对As炎症的影响.方法 通过高脂饲养建立兔As模型,24只新西兰大白兔随机分为单纯高脂组(n=8)、阿利吉仑组(n=8)和正常对照组(n=8).单纯高脂组以高脂饲料(1.5%胆固醇+5%猪油)喂养,阿利吉仑组在高脂饲料喂养的基础上加阿利吉仑(25 mg·kg-1 ·d-1)喂养,正常对照组以常规颗粒饲料喂养.分组喂养16周,处死动物取胸主动脉标本行组织形态学检查,免疫组织化学法检测斑块内巨噬细胞和平滑肌细胞标志物(RAM11和α-actin)及植物血凝素样氧化低密度脂蛋白受体1(LOX-1)表达,以阳性面积表达率表示.结果 油红O染色组织学检查显示:阿利吉仑组的脂质斑块面积为( 34.38±2.07)%,明显小于单纯高脂组的(47.12±4.16)%(P<0.01).免疫组织化学检测显示:阿利吉仑组斑块内RAM11和LOX-1蛋白表达阳性细胞百分比分别为(21.13 ±2.10)%和(11.38±1.69)%,均明显小于单纯高脂组的(30.63±2.26)%和(16.75±1.67)%(P<0.01,P<0.05).单纯高脂组和阿利吉仑组斑块内均可见α-actin表达阳性的梭形平滑肌细胞,主要分布于内膜及中膜.结论 阿利吉仑抑制了As的进展,具有抗炎症作用.  相似文献   
3.
郝炎  杨乔岚  陈明 《安徽医学》2013,34(12):1740-1743
目的 选择一肾一夹(1K1C)、二肾一夹(2K1C)肾动脉狭窄性大鼠主动脉弓作为研究对象,比较阿利吉仑与苯磺酸氨氯地平对斑块部位基质金属蛋白酶9(MMP9)表达的影响.方法 将健康雄性SD大鼠随机分为对照组、1K1C组及2K1C组,行平行针灸针缩窄法造模及高脂饲养10周,生理盐水组:0.9% NS 2 ml/d、阿利吉仑组:50 mg/(kg·d)、苯磺酸氨氯地平组:6 mg/(kg·d),4周后游离并切取SD大鼠主动脉弓,采用免疫组织化学法检测斑块部位MMP9的表达,Western-blot检测MMP9的表达.结果 1K1C及2K1C苯磺酸氨氯地平组与生理盐水组比较,其斑块部位MMP9的表达差异无统计学意义(P﹥0.05);但阿利吉仑各组差异有统计学意义(P﹤0.05).结论 苯磺酸氨氯地平对2K1C和1K1C大鼠斑块部位MMP9的表达无明显抑制作用,而阿利吉仑均可抑制各组斑块部位MMP9的表达,提示阿利吉仑稳定动脉粥样硬化斑块的作用可能优于苯磺酸氨氯地平.  相似文献   
4.
ABSTRACT

Background: Aliskiren, an antihypertensive drug approved in the United States and Europe, is the first in a new class known as direct renin inhibitors. Aliskiren has been evaluated for safety and tolerability in more than 6400 patients. It has demonstrated a favorable safety and tolerability profile alone or in combination with other drugs.

Objective: This article reviews the currently available safety and tolerability data for aliskiren.

Methodology: Using the search term aliskiren, MEDLINE (no timeframe set) and major cardiovascular congresses (2005–2008) were searched. Articles and abstracts with safety and drug interaction data were included.

Findings: Aliskiren may share common adverse effects observed with angiotensin-converting enzyme (ACE)-inhibitor and angiotensin receptor blocker (ARB) therapy. In placebo-controlled trials, those commonly reported for aliskiren at the approved dosage were headache, diarrhea, and fatigue, with incidences similar to those of placebo. Aliskiren has been well tolerated in black, geriatric, diabetic, or obese patients and patients with renal or hepatic impairment. Aliskiren neither inhibits nor induces the cytochrome P450 system; it does not inhibit P-glycoprotein, but is a substrate for this drug transporter. Adding a direct renin inhibitor to another renin–angiotensin–aldosterone system (RAAS) inhibitor may further improve cardiovascular outcomes, renal outcomes, or both, without increasing the incidence of adverse effects.

Conclusions: Aliskiren is well tolerated, has an adverse effect profile comparable to that of placebo, and has a low potential for drug interactions. Data from ongoing trials evaluating the effects of aliskiren on surrogate markers, morbidity, and mortality will further define the role of direct renin inhibition in the antihypertensive armamentarium.  相似文献   
5.
Abstract

Objective:

We aimed to investigate whether the single pill combination (SPC) of aliskiren 300?mg and amlodipine 10?mg (ALIS 300/AMLO 10) improves blood pressure (BP) reduction in hypertensive patients not adequately controlled by the SPC olmesartan 40?mg and amlodipine 10?mg (OLM 40/AMLO 10).  相似文献   
6.
7.
Introduction  Surrogate markers represent a significant contribution to early diagnosis, longitudinal prognoses, and outcome prediction in cases of hypertension. They often enable detection of disease and disease potential when the disease is still subclinical and are useful noninvasive tools for designing and evaluating therapeutic programs. Surrogate markers are increasingly employed as predictive endpoints for treatment. Methods  Key studies supporting the importance of surrogate markers as diagnostic and prognostic predictors of cardiovascular and renal clinical outcomes in hypertension, as well as what is known about the effects of renin-angiotensin-aldosterone system-blocking agents on these biomarkers were reviewed. Results  Clinical data supporting the use of surrogate markers for heart failure, such as brain natriuretic peptide (BNP) and N-terminal prohormone BNP; markers for renal function, such as urinary albumin to creatinine ratio (UACR), urinary albumin excretion rates (UAER), and creatinine, reflecting glomerular filtration; and markers of cardiac remodeling, such as left ventricular hypertrophy and calculations of left ventricular mass index (LVMI), were reviewed for their utility in improving prognosis and treatment efficacy. Finally, hypertension treatment with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and potentially direct renin inhibitors can significantly improve outcomes predicted by surrogate markers. Conclusions  BNP, UACR, UAER, and LVMI, among others, have been increasingly established as valid surrogate markers with significant value for hypertension prognosis and therapy. The benefits of using surrogate markers to gauge the effectiveness of hypertension therapy in reducing renal and cardiac complications can be seen in improved morbidity and mortality.  相似文献   
8.

Objectives

Aliskiren, the first in a new class of orally active renin inhibitors, is licensed for the treatment of hypertension. It inhibits plasma renin activity directly, thereby reducing generation of angiotensin II. In this study, we have explored the anti-Candida properties of aliskiren.

Methods

Candida albicans was cultured in the presence or absence of aliskiren for various time periods. Subsequently, inhibition of growth, germtube formation, adhesion, early/matured biofilm development and secreted aspartic protease (SAP) activity were studied.

Results

When cultured in the presence of aliskiren, Candida showed significant reduction in the activity of aspartic proteases. Aliskiren impaired in vitro growth of C. albicans. It also affected two other virulence factors, germtube and adhesion. There is reduction in early and matured biofilm when treated with aliskiren.

Conclusions

Aliskiren could be considered as a candidate for antifungal drug development.  相似文献   
9.
Abstract

Objective:

To assess the long-term safety and antihypertensive efficacy of aliskiren/valsartan 300/320?mg combination.  相似文献   
10.
目的观察脑缺血-再灌注损伤后PI3-K/Akt通路的活性变化,并探讨阿利吉仑的调控机制。方法采用改良线栓法制备大脑中动脉缺血-再灌注模型。实验采用Western blot和qR-T PCR观察PI3-K、Akt基因和蛋白变化,比较各组脑梗死体积、患侧脑水肿和神经功能。结果缺血-再灌注后PI3-K、Akt表达明显减少。阿利吉仑通过激活PI3-K/Akt通路,明显改善神经功能缺失,减轻脑水肿,减小梗死体积。结论 PI3-K/Akt通路参与了阿利吉仑的脑保护作用,为其临床应用提供了理论基础。  相似文献   
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