Abstract:
PURPOSE:Treatment of atherosclerotic rabbits with intravenous methotrexate or etoposide carried in lipid nanoemulsions (LDE) markedly reduced the lesions in the aorta. Here, the combined treatment with LDE-methotrexate and LDE-etoposide was investigated aiming to increase the anti-atherosclerosis effect. METHODS:Thirty-six male rabbits received a diet with 1 % cholesterol for 2 months. After the first month, the animals received 4 weekly intravenous injections of LDE-methotrexate (4 mg/kg dose), LDE-etoposide (6 mg/kg), or a combination of those two drugs, while the control animals were injected with LDE (n = 9 for each group). RESULTS:LDE-methotrexate+LDE-etoposide reduced aortic lesion areas by 95 % compared with controls and the intima-media ratio was reduced five-fold, whereas LDE-methotrexate reduced the lesions by 81 % and LDE-etoposide by 83 %. Compared to controls, the positive area of macrophages and MMP-9 in the arterial intima was significantly reduced in all treated groups (p < 0.001), but the MMP9 reduction was greater with the combined chemotherapy than the reduction achieved by the isolated treatments. Presence of CD3 positive cells was equal in controls and LDE-methotrexate+LDE-etoposide treated animals. However, FOXP3 positive T lymphocytes in the intima were increased in the LDE-methotrexate+LDE-etoposide rabbits. Weight, food intake evolution and the hematologic parameters suggested that the treatment had very low toxicity. CONCLUSIONS:Compared to the single treatments with LDE-methotrexate and LDE-etoposide, the combined treatment was more effective in reducing the atherosclerotic lesions. Because the toxicity of the novel drug-target combined scheme was low, those results favor the possibility of future clinical studies in patients with cardiovascular disease.
journal_name
Cardiovasc Drugs Therjournal_title
Cardiovascular drugs and therapyauthors
Leite AC Jr,Solano TV,Tavares ER,Maranhão RCdoi
10.1007/s10557-014-6566-1subject
Has Abstractpub_date
2015-02-01 00:00:00pages
15-22issue
1eissn
0920-3206issn
1573-7241journal_volume
29pub_type
杂志文章abstract::There can be no doubt that ACE inhibitors prolong survival in patients with a low ejection fraction. There is no evidence whether or not diuretics have the same effect. The pathophysiology of asymptomatic patients with poor left ventricular function differs from that of patients with the clinical syndrome of heart fai...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877716
更新日期:1993-12-01 00:00:00
abstract:INTRODUCTION:Most circulating fatty acids are contained in lipoprotein triglycerides. For the heart to acquire these lipids, they must be broken down into free fatty acids via the enzyme lipoprotein lipase (LpL). Although it has long been known that hearts primarily use esterified fatty acids as fuel, different sources...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-006-0633-1
更新日期:2006-12-01 00:00:00
abstract::To evaluate cordiodepressive risks of antiarrhythmic treatment with diprafenone, we monitored, in addition to conventional hemodynamic parameters, end-systolic pressure-volume relations to assess potential negative inotropic effects. Thirteen patients underwent hemodynamic analysis with and without the influence of di...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF01883858
更新日期:1989-04-01 00:00:00
abstract::Ouabain, when applied to rings of the left circumflex coronary artery of the dog (which contains both alpha 1-adrenoceptors leading to contraction and beta 1-adrenoceptors leading to relaxation) caused an initial contraction which peaked within 15 minutes and a later secondary increase in tension which peaked within 6...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00051242
更新日期:1988-07-01 00:00:00
abstract::The present study was performed in order to compare the efficacy, safety, and tolerability of lisinopril, a long-acting angiotensin-converting enzyme (ACE) inhibitor, with captopril, the shorter acting ACE inhibitor available, in the treatment of elderly patients (mean age 70 +/- 0.5 years) with congestive heart failu...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1023/a:1007704024393
更新日期:1997-03-01 00:00:00
abstract::The pathogenetic theories and treatment of Raynaud's phenomenon are reviewed. In primary Raynaud's disease, most evidence supports a local defect at the digital artery level, with vasoconstriction or vasospasm of the digital arteries inducing the color changes. Normal sympathetic activity, low transmural arterial dist...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00053426
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF). METHODS:We examined the prevalence and outcomes associated...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-017-6754-x
更新日期:2017-12-01 00:00:00
abstract::As damage to the pulmonary vascular endothelium may be responsible for the lung toxicity of amiodarone, we evaluated the cytolytic toxicity of the drug in cultures of endothelial cells. Cells were cultured from human umbilical cord veins. Amiodarone caused a vacuolization of the cells with liberation of both lactate d...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00050996
更新日期:1996-11-01 00:00:00
abstract::In order to compare and clarify the effects of various antiarrhythmic drugs when given as monotherapy, we reevaluated our previous data on antiarrhythmic drugs and recalculated antiarrhythmic plasma concentrations of drugs for several canine arrhythmia models. We used three spontaneously occurring arrhythmias: a) digi...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00120829
更新日期:1991-08-01 00:00:00
abstract:AIM:To review whether brain natriuretic peptides (BNP) can be used as a surrogate for the traditional methods of assessing functional status in interventional studies of patients with left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS:The traditional methods for assessing functional status including New...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1023/B:CARD.0000033643.93393.46
更新日期:2004-05-01 00:00:00
abstract::Quality of life in heart failure patients is receiving increased attention as a reflection of a treatment's potential secondary benefit of general well-being and daily functioning. The Metoprolol in Dilated Cardiomyopathy (MDC) trial was conducted as a large, multicenter trial to establish the effects of metoprolol on...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/BF02627961
更新日期:1996-07-01 00:00:00
abstract::Ca2+ channel antagonists are agents that interact with the voltage-dependent Ca2+ channel in a highly specific way. The prototype agents of cardiovascular importance are verapamil, nifedipine, and diltiazem, in historical order of appearance. These agents all have different molecular structures and bind separately wit...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF02209083
更新日期:1987-12-01 00:00:00
abstract::The clinical efficacy and safety of ibopamine and diuretic therapy were compared in a multicenter, multinational, parallel, positive-controlled, randomized, double-blind, 12-week study, involving 103 patients with mild CHF (NYHA Class II). Body weight, NYHA functional class, symptom assessment scores, laboratory blood...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/BF01869579
更新日期:1989-12-01 00:00:00
abstract::Despite continuous advances in myocardial revascularization procedures and intracoronary devices, patients with ischemic heart disease (IHD) still experience worse prognosis and poor quality of life (QoL). Indeed, chronic stable angina (CSA) is a common disease with a large burden on healthcare costs. Traditionally, C...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-016-6677-y
更新日期:2016-08-01 00:00:00
abstract::Excess activity of the sympathetic nervous system (SNS) is linked to human obese hypertension and to salt-sensitive hypertension. Paradoxically, reduced SNS activity has been implicated as a contributor to obesity, particularly in animal models, and salt loading usually inhibits SNS activity. We have investigated the ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00120497
更新日期:1996-06-01 00:00:00
abstract::Encainide is a class 1C antiarrhythmic agent that is indicated for the treatment of life-threatening arrhythmias, such as sustained ventricular tachycardia. Furthermore, encainide possesses a moderate degree of antiserotonin activity, which was quantitated in this present study by determining displacement of [3H]spipe...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF03029752
更新日期:1991-08-01 00:00:00
abstract:BACKGROUND:Although Takotsubo syndrome (TS) was once considered to be rare and largely benign, it is now recognized to represent a major cause of cardiac morbidity and mortality, especially in ageing women. The biochemical precipitant of attacks of TS is an increase in catecholamine concentrations within the myocardium...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-019-06918-5
更新日期:2020-02-01 00:00:00
abstract:PURPOSE:Single- and multiple-dose studies were conducted to assess the pharmacokinetics, pharmacodynamics and safety of tolvaptan in healthy Japanese subjects. METHODS:All studies were single-center, randomized, placebo-controlled, single-blind or double-blind. In an ascending single-dose study, subjects were given a ...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s10557-011-6299-3
更新日期:2011-12-01 00:00:00
abstract::Cardiac reperfusion injury after heart transplantation or cardiopulmonary bypass has been difficult to control due to the variable degree of myocardial damage with respect to the length of ischemia and the complexity of the surgical procedure. Here, we evaluated the myocardial metabolic and functional recovery of hear...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF03029747
更新日期:1991-08-01 00:00:00
abstract::When severely ischemic myocardium is reperfused, prolonged myocardial dysfunction--a phenomenon named myocardial stunning--frequently occurs. Stunning also occurs in a variety of other situations. These include myocardium located adjacent to infarcted tissue, transient increase in myocardial O2 demands in the presence...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00053546
更新日期:1991-10-01 00:00:00
abstract:PURPOSE:To investigate the protective effects of hydrogen sulfide (H(2)S) against chronic alcohol intake-induced left ventricular remodeling and explore the potential mechanisms involved. METHODS:Rats were randomly divided into 4 groups: alcohol group, NaHS group, alcohol + NaHS group, and control group. The echocardi...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-013-6441-5
更新日期:2013-06-01 00:00:00
abstract::The aim of this study was to compare the pharmacokinetics and antiarrhythmic activity of dihydroquinidine and quinidine in 14 patients (11 men, 3 women, aged 28 to 67 years) with heart disease and chronic, stable, high-frequency premature ventricular beats (PVB) (greater than 100/hr). A randomized, double-blind, cross...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00054209
更新日期:1988-12-01 00:00:00
abstract:AIM:To study the relationship between Daxx expression and the antiapoptotic effects of probucol in THP-1 macrophage. MATERIALS AND METHODS:Apoptosis of THP-1 derived macrophages was induced by exposure to oxidized low density lipoprotein (oxLDL). The development of apoptosis was determined by flow cytometry analysis a...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-007-6002-x
更新日期:2007-02-01 00:00:00
abstract:PURPOSE:Protein kinase C alpha (gene: PRKCA) is a key regulator of cardiac contractility. Two genetic variants have recently been discovered to regulate PRKCA expression in failing human heart tissue (rs9909004 [T → C] and rs9303504 [C → G]). The association of those variants with clinical outcomes in patients with hea...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-019-06909-6
更新日期:2019-12-01 00:00:00
abstract::A survey of the pharmacokinetic properties of the three prototypical calcium antagonist agents shows that they have in common a very high rate of hepatic first-pass metabolism with, in the case of verapamil and diltiazem, the formation of an active metabolite that affects the dose during chronic therapy. Therefore, th...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF01865507
更新日期:1989-08-01 00:00:00
abstract:PURPOSE:Epidemiologic and clinical research suggests important gender-related differences in the prevalence, presentation, associated conventional and non-conventional risk factors, management and outcomes of coronary heart disease (CHD) patients. Adequate data is not available for Indian population where prevalence of...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-015-6594-5
更新日期:2015-08-01 00:00:00
abstract::Cilazapril, an angiotensin-converting enzyme inhibitor, and mibefradil, a selective T-type voltage-operated calcium channel blocker, have been shown to prevent neointima formation after vascular injury. The goal of the present study was to evaluate the mechanism of action of both drugs. For this purpose, the influence...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00823586
更新日期:1996-05-01 00:00:00
abstract::Nicorandil (N) and isosorbide dinitrate (ISDN) are vasodilator drugs used in patients with angina. In 24 healthy male volunteers (18-32 years), the acute effect of a single oral dose (20 mg) of N and ISDN on arterial diameter (D), distensibility, and compliance of the elastic common carotid artery (CCA) and the muscul...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00878678
更新日期:1995-04-01 00:00:00
abstract::Calcium channel blockers are a group of drugs used for the treatment of hypertension. Carbonic anhydrase (CA) I detected in vascular smooth muscle and in other cells in the organism has a major role in the acid-base balance and in vascular processes. Our previous work has proven that verapamil inhibits CA activity by ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1007893207279
更新日期:2000-10-01 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate the efficacy and safety of intravenous infusion of low-dose flecainide (50 mg) followed by oral pilsicainide (50 mg t.i.d.)in patients with paroxysmal atrial fibrillation (AF). METHODS:Thirty-one patients with symptomatic and hemodynamically stable AF lasting less than 48 ...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,信件
doi:10.1023/a:1024368111557
更新日期:2003-01-01 00:00:00