Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new dilatrate research articles will be listed here shortly after becoming available to us.
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Medical research on dilatrate
Pharmacotherapy. 2008 Jul; 28(7): 920-31
Norgard NB, Stark JE
Abstract Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers make up the cornerstone of therapy for patients with heart failure involving left ventricular dysfunction. These drug classes have been proven to decrease morbidity and mortality in patients with heart failure. Unfortunately, many patients remain symptomatic and experience disease progression despite taking both an ACE inhibitor and a beta-blocker. Others may be unable to tolerate one or both of these agents. In recent years, several other drug classes have been shown to provide additional morbidity and mortality benefits in patients with heart failure. These include angiotensin II receptor blockers (ARBs), aldosterone antagonists, and the combination of isosorbide dinitrate plus hydralazine. To select the most appropriate drug therapy for patients with heart failure, clinicians should consider results from clinical trials in specific patient populations, adverse-event profiles, tolerability, cost, and dosing regimens.
[PETN: long acting nitrate with tolerance devoiding properties and innovative potential]
MMW Fortschr Med. 2008 Apr 10; 150 Suppl 1: 43-7
Richartz BM, Schneider HT, Silber S
Fiziol Cheloveka. 2008 Mar-Apr; 34(2): 136-8
Zinchuk VV, Dobrodeĭ MA, Lis MA
Vascul Pharmacol. 2008 Mar 27;
Baluchnejadmojarad T, Roghani M
Diabetes mellitus is associated with major cardiovascular risk factors which are responsible for excess morbidity and mortality. Soy isoflavones like genistein are beneficial for correcting the hyperglycemia and preventing some diabetic complications. Thus, the effect of chronic administration of genistein was studied on aortic reactivity of streptozotocin (STZ)-diabetic rats. Male diabetic rats received genistein 1 mg/kg/day (i.p.) for 4 weeks 3 days after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation responses to acetylcholine (ACh) and isosorbide dinitrate (ISD) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to KCL and PE was significantly lower in genistein-treated diabetic rats relative to untreated diabetic ones. Endothelium removal abolished the significant difference between genistein-treated and untreated diabetic groups regarding contractile response to KCl and PE. Meanwhile, endothelium-dependent relaxation to ACh was significantly higher in genistein-treated diabetic rats as compared to diabetic ones. Pretreatment of rings with N(omega)-l-arginine methyl ester (l-NAME) and indomethacin (INDO) significantly attenuated the observed responses. Meanwhile, one-month diabetes resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity in aortic tissue and genistein treatment attenuated the increased MDA content and reduced activity of SOD. Therefore, chronic treatment of diabetic rats with genistein could prevent the abnormal functional changes in vascular reactivity in diabetic rats through nitric oxide- and prostaglandin-dependent pathways and via attenuating oxidative stress in the wall of aortic tissue.
Clin Sci (Lond). 2008 Apr 28;
Webb CM, Hayward CS, Mason MJ, Ilsley CD, Collins P
Animal data suggest favourable coronary vasomotor actions of isoflavones however the effects of isoflavones on the human coronary circulation are undetermined. We therefore investigated the effects of short-term isoflavone-intact soy protein ingestion on basal coronary arterial tone and stimulated vasoreactivity and blood flow in patients with coronary heart disease (CHD) or risk factors for CHD. Seventy-one subjects were randomised, double-blind, to isoflavone-intact soy protein (active; n=33, mean+/-SD, aged 58+/-8 years) or isoflavone-free placebo (n=38, aged 61+/-8 years) for 5 days prior to coronary angiography. In 25 of these subjects stimulated coronary blood flow was calculated from flow velocity, measured using intracoronary Doppler, and coronary luminal diameter before and after intracoronary adenosine, acetylcholine (ACh) and isosorbide dinitrate (ISDN) infusions. Basal and stimulated coronary artery luminal diameters were measured using quantitative coronary angiography. Serum concentrations of isoflavones genistein, daidzein and equol were increased by active treatment (p
Pharmacologic management of heart failure caused by systolic dysfunction.
Am Fam Physician. 2008 Apr 1; 77(7): 957-64
Chavey WE, Bleske BE, Van Harrison R, Hogikyan RV, Kesterson SK, Nicklas JM
Heart failure caused by systolic dysfunction affects more than 5 million adults in the United States and is a common source of outpatient visits to primary care physicians. Mortality rates are high, yet a number of pharmacologic interventions may improve outcomes. Other interventions, including patient education, counseling, and regular self-monitoring, are critical, but are beyond the scope of this article. Angiotensin-converting enzyme inhibitors and beta blockers reduce mortality and should be administered to all patients unless contraindicated. Diuretics are indicated for symptomatic patients as needed for volume overload. Aldosterone antagonists and direct-acting vasodilators, such as isosorbide dinitrate and hydralazine, may improve mortality in selected patients. Angiotensin receptor blockers can be used as an alternative therapy for patients intolerant of angiotensin-converting enzyme inhibitors and in some patients who are persistently symptomatic. Digoxin may improve symptoms and is helpful for persons with concomitant atrial fibrillation, but it does not reduce cardiovascular or all-cause mortality. Serum digoxin levels should not exceed 1.0 ng per mL (1.3 nmol per L), especially in women.
Am Heart J. 2008 May; 155(5): 848-54
Meisel SR, Dagan Y, Blondheim DS, Dacca S, Shochat M, Kazatsker M, Asif A, Frimerman A, Shotan A
Patients presenting with ST-elevation myocardial infarction (STEMI), whose symptoms and electrocardiographic changes completely resolve upon admission and before the administration of reperfusion therapy, pose a therapeutic dilemma. The optimal management of this syndrome, termed here as transient STEMI (TSTEMI), has not yet been fully determined. We describe 69 prospectively recorded patients with TSTEMI, of which 63 patients (56.7 +/- 11 years, 48 men) were available for long-term follow-up out of 1244 consecutive patients with acute myocardial infarction (5%). Patients with TSTEMI treated with intravenous isosorbide dinitrate, aspirin, and clopidogrel, and/or with glycoprotein IIb/IIIa inhibitors were compared with a control group of matched patients with STEMI without resolution, who were treated conventionally. The time interval from symptom onset to presentation at the emergency department of patients with TSTEMI was 1.7 +/- 1.3 hours, and to first recording of ST elevations, 1.5 +/- 1.4 hours. Symptoms and electrocardiographic changes fully resolved 1.2 +/- 0.8 hours later, 1 hour after aspirin and nitrate administration. Coronary angiography, performed 36 +/- 39 hours (median, 24 hours) from admission, demonstrated no obstructive lesion or single-vessel obstructive disease in 43 patients (70%). Primary coronary intervention was performed in 48 patients (77%), and 8 patients (13%) were referred to surgery. Left ventricular ejection fraction was within normal limits, and peak creatine kinase was mildly elevated. Patients with TSTEMI had less extensive coronary artery disease (P < .038), better thrombolysis in myocardial infarction flow on angiography (P < .01), lower peak creatine kinase level (P < .001), higher left ventricular ejection fraction (P < .0001), and lower likelihood to sustain a second additional coronary event after index admission (P = .024) than patients with STEMI. Transient STEMI was associated with less myocardial damage, less extensive coronary artery disease, higher thrombolysis in myocardial infarction flow grade in culprit artery, and better cardiac function. These data suggest that immediate intense medical therapy with an early invasive approach is an appropriate therapy in patients with TSTEMI.
Hdm2 and nitric oxide radicals contribute to the p53-dependent radioadaptive response.
Int J Radiat Oncol Biol Phys. 2008 Jun 1; 71(2): 550-8
Takahashi A, Matsumoto H, Ohnishi T
PURPOSE: The aim of this work was to characterize the radioadaptive response at the molecular level. METHODS AND MATERIALS: We used wild-type (wt) p53 and mutated (m) p53-containing cells derived from the human lung cancer H1299 cell line, which is p53-null. Cellular radiation sensitivities were determined with a colony-forming assay. The accumulations of p53, the human homolog of endogenous murine double minute 2 (Hdm2), and inducible nitric oxide synthase were analyzed with Western blotting. Quantification of chromosomal aberrations was estimated by scoring dicentrics per cell. RESULTS: In wtp53 cells, it was demonstrated that the lack of p53 accumulation was coupled with the activation of Hdm2 after low-dose irradiation (0.02 Gy). Although NO radicals were only minimally induced in wtp53 cells irradiated with a challenging irradiation (6 Gy) alone, NO radicals were seen to increase about two- to fourfold after challenging irradiation subsequent to a priming irradiation (0.02 Gy). Under similar irradiation conditions with a priming and challenging irradiation in wtp53 cells, induction of radioresistance and a depression of chromosomal aberrations were observed only in the absence of 5, 5'-(2, 5-Furanidiyl)bis-2-thiophenemethanol (RITA) or Nutlin-3 (p53-Hdm2 interaction inhibitors), aminoguanidine (an inducible nitric oxide synthase inhibitor), and c-PTIO (an NO radical scavenger). On the other hand, in p53 dysfunctional cells, a radioadaptive response was not observed in the presence or absence of those inhibitors. Moreover radioresistance developed when wtp53 cells were treated with isosorbide dinitrate (an NO-generating agent) alone. CONCLUSIONS: These findings suggest that NO radicals are initiators of the radioadaptive response, acting through the activation of Hdm2 and the depression of p53 accumulations.
Methods Find Exp Clin Pharmacol. 2008 Jan-Feb; 30(1): 67-99
Bayés M, Rabasseda X
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prouse Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 3F8; Abatacept, ABT-263, Adalimumab, AG-7352, Agatolimod sodium, Alfimeprase, Aliskiren fumarate, Alvimopan hydrate, Aminolevulinic acid hexyl ester, Ammonium tetrathiomolybdate, Anakinra, Aripiprazole, AS-1404, AT-9283, Atomoxetine hydrochloride, AVE-1642, AVE-9633, Axitinib, AZD-0530; Becocalcidiol, Belotecan hydrochloride, Bevacizumab, BG-9928, BIBF-1120, BMS-275183, Bortezomib, Bosentan; Catumaxomab, Cetuximab, CHR-2797, Ciclesonide, Clevidipine, Cypher, Cytarabine/daunorubicin; Darifenacin hydrobromide, Darunavir, Denosumab, Desvenlafaxine succinate, Disufenton sodium, Duloxetine hydrochloride, Dutasteride; Eculizumab, Efalizumab, Eicosapentaenoic acid/docosahexaenoic acid, Eplerenone, Epratuzumab, Erlotinib hydrochloride, Escitalopram oxalate, Ethynylcytidine, Etravirine, Everolimus, Ezetimibe; Fulvestrant; Garenoxacin mesilate, Gefitinib, Gestodene; HI-164, Hydralazine hydrochloride/isosorbide dinitrate; Icatibant acetate, ICX-RHY, Idraparinux sodium, Indacaterol, Ispronicline, Ivabradine hydrochloride, Ixabepilone; KB-2115, KW-2449; L-791515, Lapatinib ditosylate, LGD-4665, Licofelone, Liposomal doxorubicin, Lisdexamfetamine mesilate, Lumiracoxib; Methoxy polyethylene glycol-epoetin-beta, Miglustat, Mipomersen sodium, Mitumprotimut-T, MK-0822A, MK-0974; Nelarabine; Obatoclax mesylate, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paliperidone, Palonosetron hydrochloride, Panitumumab, Pegfilgrastim, Peginterferon alfa-2a, Pemetrexed disodium, Perospirone hydrochloride, Pertuzumab, Pimecrolimus, Pitrakinra, Pixantrone maleate, Posaconazole, Pregabalin; Quercetin; RALGA, Raltegravir potassium, Ranelic acid distrontium salt, rhHistone 1.3, Rimonabant, Rivaroxaban, Rosuvastatin calcium, RTS,S/SBAS2; Satraplatin, SNDX-275, Sodium butyrate, Solifenacin succinate, Sorafenib, SU-14813, Sunitinib malate; Tadalafil, Tafenoquine succinate, Tamatinib fosdium, Taxus, Telbivudine, Telmisartan/hydrochlorothiazide, Temsirolimus, Tiotropium bromide, Tipranavir, Tocilizumab, Trabectedin, Tramadol hydrochloride/acetaminophen; Ulipristal acetate, Uracil, Ursodeoxycholyltaurine; Valdecoxib, Vardenafil hydrochloride hydrate, Varenicline tartrate, Vildagliptin, Vinflunine, Vitespen, Vorinostat; ZK-EPO, Zoledronic acid monohydrate.
Angiology. 2008 Jun-Jul; 59(3): 379-81
Yamashita K, Tasaki H
Nitroglycerin is one of the most widely used drugs in the treatment of angina. However, nitroglycerin fails to relieve angina in patients with syndrome X who have microvessel dysfunction. Microvessel function is impaired in several diseases. In this article, the authors report that despite normal coronary angiograms at control, intracoronary administration of isosorbide dinitrate induced severe coronary slow flow and transient ST-segment elevation with mild chest pain in a patient with congestive heart failure. The authors speculated that functional stenosis and a delay in the dilatation of microvessels less than 100 microm in diameter because of their dysfunction resulted in a severely slow flow after intracoronary administration of isosorbide dinitrate.