MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Cardiovascular Toxicology' source. Sat, 20 Mar 2010 13:55:41 +0100 http://www.medworm.com/index.php?rid=3374776&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20229123%26dopt%3DAbstract Authors: Arvapalli RK, Paturi S, Laurino JP, Katta A, Kakarla SK, Gadde MK, Wu M, Rice KM, Walker EM, Wehner P, Blough ER It is thought that aging in rats and humans is associated with increases in iron accumulation and cell apoptosis. Here, we examine the relationship between cardiac iron levels and apoptosis in aged F344XBN rats that had been treated with an oral iron chelator (Deferasirox; 100 mg/kg body weight) on alternate days for 6 months. Compared to adult animals (6 month), cardiac iron (+72%), liver iron (+87%), ferritin light chain (+59%), divalent metal transporter-1 (+56%) and the number of TdT-mediated dUTP nick end labeling (TUNEL) positive cells (4.3 fold increase) were higher in 33-month-old animals (P < 0.05). Deferasirox treatment decreased cardiac iron levels by ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=3374776 Sat, 13 Mar 2010 00:00:00 +0100 3374776 http://www.medworm.com/index.php?rid=3331866&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20195793%26dopt%3DAbstract Authors: Silva JP, Sardão VA, Coutinho OP, Oliveira PJ PMID: 20195793 [PubMed - as supplied by publisher] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=3331866 Tue, 02 Mar 2010 00:00:00 +0100 3331866 http://www.medworm.com/index.php?rid=3316473&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20186580%26dopt%3DAbstract Authors: Makwana O, King NM, Ahles L, Selmin O, Granzier HL, Runyan RB Trichloroethylene is an organic solvent used as an industrial degreasing agent. Due to its widespread use and volatile nature, TCE is a common environmental contaminant. Trichloroethylene exposure has been implicated in the etiology of heart defects in human populations and animal models. Recent data suggest misregulation of Ca(2+) homeostasis in H9c2 cardiomyocyte cell line after TCE exposure. We hypothesized that misregulation of Ca(2+) homeostasis alters myocyte function and leads to changes in embryonic blood flow. In turn, changes in cardiac flow are known to cause cardiac malformations. To investigate this hypothesis, we dosed developing chick embryos in ovo with environmentally relevant doses of TCE (8 and 80... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=3316473 Fri, 26 Feb 2010 00:00:00 +0100 3316473 http://www.medworm.com/index.php?rid=3280478&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20155331%26dopt%3DAbstract Authors: Torres SM, Divi RL, Walker DM, McCash CL, Carter MM, Campen MJ, Einem TL, Chu Y, Seilkop SK, Kang H, Poirier MC, Walker VE To delineate temporal changes in the integrity and function of mitochondria/cardiomyocytes in hearts from mice exposed in utero to commonly used nucleoside analogs (NRTIs), CD-1 mice were exposed in utero to 80 mg AZT/kg, 40 mg 3TC/kg, 80 mg AZT/kg plus 40 mg 3TC/kg, or vehicle alone during days 12-18 of gestation and hearts from female mouse offspring were examined at 13 and 26 weeks postpartum. Alterations in cardiac mitochondrial DNA (mtDNA) content, oxidative phosphorylation (OXPHOS) enzyme activities, mtDNA mutations, and echocardiography of NRTI-exposed mice were assessed and compared with findings in vehicle-exposed control mice. A hybrid capture-ch... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=3280478 Sat, 13 Feb 2010 00:00:00 +0100 3280478 http://www.medworm.com/index.php?rid=3232146&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20119744%26dopt%3DAbstract This study was designed to assess the effects of saffron (Crocus sativus) on rats' heart with isoproterenol-induced myocardial injury. Animals were divided randomly into four groups: vehicle-control group (CTL); ISO group, administrated with Isoproterenol 85 mg/kg s.c.; saffron group; and finally combined Saffron + ISO group. Basal and final serum levels of heart troponin I, heart tissue antioxidants and histopathological indices were assessed in all groups. Isoproterenol administration significantly increased serum level of troponin I when compared to control group (3.46 +/- 0.77 vs. 0.53 +/- 0.35 ml in ng/ml, P < 0.001) and reduced significantly the glutathione peroxidase activity of heart muscle (1.63 +/- 0.21 vs. 4.01 +/- 0.64 nmol/mg protein, P < 0.05). The grade of heart muscle... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=3232146 Sat, 30 Jan 2010 00:00:00 +0100 3232146 http://www.medworm.com/index.php?rid=3232145&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20119745%26dopt%3DAbstract Authors: Silva JP, Sardão VA, Coutinho OP, Olveira PJ Oxidative stress has been connected to various forms of cardiovascular diseases. Previously, we have been investigating the potential of new nitrogen-containing synthetic compounds using a neuronal cell model and different oxidative stress conditions in order to elucidate their potential to ameliorate neurodegenerative diseases. Here, we intended to extend these initial studies and investigate the protective role of four of those new synthetic compounds (FMA4, FMA7, FMA762 and FMA796) against oxidative damage induced to H9c2 cardiomyoblasts by tert-butylhydroperoxide (t-BHP). The data indicates that FMA762 and FMA796 decrease t-BHP-induced cell death, as measured by both sulforhodamine B assay and nuclear chromatin condensation... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=3232145 Sat, 30 Jan 2010 00:00:00 +0100 3232145 http://www.medworm.com/index.php?rid=3213339&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20101476%26dopt%3DAbstract Authors: Torres SM, March TH, Carter MM, McCash CL, Seilkop SK, Poirier MC, Walker DM, Walker VE The current study was designed to delineate temporal changes in cardiomyocytes and mitochondria at the light and electron microscopic levels in hearts of mice exposed transplacentally to commonly used nucleoside analogs (NRTIs). Pregnant CD-1 mice were given 80 mg AZT/kg, 40 mg 3TC/kg, 80 mg AZT/kg plus 40 mg 3TC/kg, or vehicle alone during the last 7 days of gestation, and hearts from female mouse pups were examined at 13 and 26 weeks postpartum for histopathological or ultrastructural changes in cross-sections of both the ventricles and the interventricular septum. Using light microscopy and special staining techniques, transplacental exposure to AZT, 3TC, or AZT/3TC was shown to induce s... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=3213339 Wed, 27 Jan 2010 00:00:00 +0100 3213339 http://www.medworm.com/index.php?rid=3120835&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20033351%26dopt%3DAbstract Authors: Leblanc AJ, Moseley AM, Chen BT, Frazer D, Castranova V, Nurkiewicz TR We have shown that nanoparticle inhalation impairs endothelium-dependent vasodilation in coronary arterioles. It is unknown whether local reactive oxygen species (ROS) contribute to this effect. Rats were exposed to TiO(2) nanoparticles via inhalation to produce a pulmonary deposition of 10 mug. Coronary arterioles were isolated from the left anterior descending artery distribution, and responses to acetylcholine, arachidonic acid, and U46619 were assessed. Contributions of nitric oxide synthase and prostaglandin were assessed via competitive inhibition with N(G)-Monomethyl-L-Arginine (L-NMMA) and indomethacin. Microvascular wall ROS were quantified via dihydroethidium (DHE) fluorescence. Coronary arteriole... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=3120835 Tue, 22 Dec 2009 00:00:00 +0100 3120835 http://www.medworm.com/index.php?rid=3058207&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19957052%26dopt%3DAbstract Authors: Wang CH, Chen CL, Hsiao CK, Chiang FT, Hsu LI, Chiou HY, Hsueh YM, Wu MM, Chen CJ Chronic arsenic poisoning is a major worldwide public health problem. Recently, we had reported chronic arsenic poisoning was dose-dependently associated with ventricular abnormalities quantified by electrocardiographic QT prolongation linking to atherosclerotic diseases. An association of chronic arsenic poisoning with ventricular repolarization inhomogeneity quantified by QT dispersion (QTD) is of particular interest from a theoretical and practical perspective. We aimed to further elucidate (1) the association of chronic arsenic exposure with ventricular abnormalities quantified by QTD, (2) the association of QTD with atherosclerotic diseases and (3) the predictability of QTD for long-term mor... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=3058207 Thu, 03 Dec 2009 00:00:00 +0100 3058207 http://www.medworm.com/index.php?rid=3052539&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19949891%26dopt%3DAbstract This study investigated whether improvement in cardiac function and attenuation of cardiac remodeling by some beta-adrenoceptor (beta-AR) antagonists were associated with a depression in sympathetic activity in congestive heart failure (CHF) due to myocardial infarction (MI). Although cardiac dysfunction, hypertrophy and dilatation as well as increased plasma level of catecholamines are known to occur in CHF, the relationship between these parameters is poorly understood. Three weeks after occlusion of the coronary artery, rats were treated daily with 20 and 75 mg/kg of either atenolol or propranolol for 5 weeks. Sham-operated rats served as controls. Both atenolol and propranolol at 20 and 75 mg/kg doses attenuated the MI-induced cardiac hypertrophy, increases in left ventricular (LV) end... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=3052539 Tue, 01 Dec 2009 00:00:00 +0100 3052539 http://www.medworm.com/index.php?rid=3012906&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19924570%26dopt%3DAbstract Authors: Sethi R, Rehsia NS, Jindal K, Dhalla KS, Elimban V, Dhalla NS PMID: 19924570 [PubMed - as supplied by publisher] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=3012906 Thu, 19 Nov 2009 00:00:00 +0100 3012906 http://www.medworm.com/index.php?rid=3004469&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19915982%26dopt%3DAbstract In conclusion, given the extreme lack of kinase selectivity that sorafenib exhibits, it is likely that inhibition of kinases other than RAF, or combinations of kinases, contributes to the cardiotoxic effects of sorafenib. PMID: 19915982 [PubMed - as supplied by publisher] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=3004469 Sat, 14 Nov 2009 00:00:00 +0100 3004469 http://www.medworm.com/index.php?rid=2935937&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19859831%26dopt%3DAbstract In conclusion, rhEPO doping in rats under chronic exercise promotes not only the expected RBC count increment, suggesting hyperviscosity, but also other serious deleterious cardiovascular and thromboembolic modifications, including mortality risk, which might be known and assumed by all sports authorities, including athletes and their physicians. PMID: 19859831 [PubMed - as supplied by publisher] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2935937 Tue, 27 Oct 2009 00:00:00 +0100 2935937 http://www.medworm.com/index.php?rid=2931302&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19855945%26dopt%3DAbstract Authors: Machado NG, Alves MG, Carvalho RA, Oliveira PJ Myocardial ischemia is the main cause of death in the Western societies. Therapeutic strategies aimed to protect the ischemic myocardium have been extensively studied. Reperfusion is the definitive treatment for acute coronary syndromes, especially acute myocardial infarction; however, reperfusion has the potential to exacerbate tissue injury, a process termed reperfusion injury. Ischemia/reperfusion (I/R) injury may lead to cardiac arrhythmias and contractile dysfunction that involve apoptosis and necrosis in the heart. The present review describes the mitochondrial role on cardiomyocyte death and some potential pharmacological strategies aimed at preventing the opening of the box, i.e., mitochondrial dysfunction and membrane per... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2931302 Sat, 24 Oct 2009 00:00:00 +0100 2931302 http://www.medworm.com/index.php?rid=2848237&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19787300%26dopt%3DAbstract Authors: Balakumar P, Kaur J The incidence of arsenic toxicity has been observed in various countries including Taiwan, Bangladesh, India, Argentina, Australia, Chile, China, Hungary, Peru, Thailand, Mexico and United States of America. Arsenic is a ubiquitous element present in drinking water, and its exposure is associated with various cardiovascular disorders. Arsenic exposure plays a key role in the pathogenesis of vascular endothelial dysfunction as it inactivates endothelial nitric oxide synthase, leading to reduction in the generation and bioavailability of nitric oxide. In addition, the chronic arsenic exposure induces high oxidative stress, which may affect the structure and function of cardiovascular system. Further, the arsenic exposure has been noted to induce atheroscleros... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2848237 Mon, 28 Sep 2009 23:00:00 +0100 2848237 http://www.medworm.com/index.php?rid=2832736&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19777380%26dopt%3DAbstract The objective of this study is to assess the cardiovascular effects consequent to chronic respiratory exposure of carbon soot. A cross-sectional occupational health survey was conducted in all consenting workers who employed in the production wing of diamond-processing industries. Blood pressure, ECGs, height, weight, and blood counts were measured and evaluated. Blood pressure measurements revealed a high prevalence of hypertension in young workers. Left atrial abnormality (LAA) was the major finding in the electrocardiograms. We found a high prevalence of hypertension in young diamond workers. The LASER saw operators had highest prevalence of LAA. White cell count and prevalence of hypertension was highest for the workers in grinder operations. PMID: 19777380 [PubMed - as supplied by... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2832736 Wed, 23 Sep 2009 23:00:00 +0100 2832736 http://www.medworm.com/index.php?rid=2807967&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19757201%26dopt%3DAbstract Authors: Alves MG, Oliveira PJ, Carvalho RA Various stressful conditions such as ischemia in cold cardioplegic solutions and reperfusion occur during heart transplantation. Since ATP production is essential for the maintenance of contractile activity, mitochondrial function may be a mediator of ischemia and ischemia/reperfusion (I/R) injury. We aimed at testing the ability of two distinct cardioplegic solutions, Celsior (Cs) and Histidine Buffer (HBS), to protect rat heart mitochondria (HM) function during ischemia alone or ischemia followed by reperfusion. A standard Krebs-Henseleit solution (KH) was used as "negative" control. Male and Female Wistar rats were divided into control (Ctrl), reperfusion control (Ctrl_R), ischemia and I/R groups. Ischemia and I/R were divided into three s... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2807967 Mon, 14 Sep 2009 23:00:00 +0100 2807967 http://www.medworm.com/index.php?rid=2744360&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19714493%26dopt%3DAbstract Authors: Albayrak F, Bayir Y, Halici Z, Kabalar E, Bayram E, Ozturk C, Suleyman H, Keles MS, Kurt M, Bakan E The ability of amiodarone to prevent pathological changes and oxidative stress after isoproterenol (ISO)-induced myocardial injury was investigated in rats. A better understanding of the processes involved in the pathophysiology of myocardial infarction has led to the search for drugs that can limit the extent of myocardial injury. Amiodarone was administered to groups of rats groups once per day for 30 days. On days 29 and 30, the rats of the ISO control and drug treatment groups were administered 180 mg/kg ISO subcutaneously at an interval of 24 h for two consecutive days. In the control groups, clinical indicators, such as creatine kinase-isoenzymes and troponin-I, were found... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2744360 Thu, 27 Aug 2009 23:00:00 +0100 2744360 http://www.medworm.com/index.php?rid=2661164&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19644660%26dopt%3DAbstract Authors: Berzingi C, Chen F, Finkel MS HIV infection in patients is associated with a surprisingly high frequency of diastolic dysfunction followed by the development of a dilated cardiomyopathy. Potential mechanisms include direct effects of HIV proteins, including gp120. We have previously reported direct inotropic and p38 MAP kinase signaling effects of HIV gp120 on isolated cardiac myocytes in vitro. We now report effects of a single injection of HIV gp120 on cardiac hemodynamics in vivo. HIV gp120 (50 mug/kg) was injected intravenously and hemodynamics assessed at 1, 24, 48 and 72 h in freely ambulatory, awake rats. Rats injected with gp120 demonstrated a blunted diastolic response to increasing intravenous (IV) injections of the beta-adrenergic agonist, isoproterenol (ISO), compa... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2661164 Thu, 30 Jul 2009 23:00:00 +0100 2661164 http://www.medworm.com/index.php?rid=2661165&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19641857%26dopt%3DAbstract Authors: He X, Hong X, Zeng F, Kang F, Li L, Sun Q It has been suggested that zinc may have a protective role against heart defects during fetal development. We investigated the effects of zinc on the development of fetal cardiac malformations induced by homocysteine. Pregnant Sprague-Dawley rats were randomized into one of five groups: control (C), homocysteine (H), homocysteine + zinc (Z), homocysteine + folic acid (F), or homocysteine + zinc + folic acid (ZF) (each n = 8). Homocysteine (8 nmol/day) was administered intraperitoneally in the H, Z, F, and ZF groups on gestation days (GD) 8, 9, and 10. Zinc (30 mg/kg day), folic acid (30 mg/kg day), or both (30 mg/kg day each) were administered intragastrically daily in the Z, F, and ZF groups, respectively, throughout the pregnancy. In... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2661165 Wed, 29 Jul 2009 23:00:00 +0100 2661165 http://www.medworm.com/index.php?rid=2615760&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19609730%26dopt%3DAbstract In conclusion, this study provides evidence for a dose-dependent valvular toxicity of serotonergic drugs, which appears to be reversible after drug withdrawal. PMID: 19609730 [PubMed - as supplied by publisher] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2615760 Wed, 15 Jul 2009 23:00:00 +0100 2615760 http://www.medworm.com/index.php?rid=2573793&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19572114%26dopt%3DAbstract Authors: Stummann TC, Beilmann M, Duker G, Dumotier B, Fredriksson JM, Jones RL, Hasiwa M, Kang YJ, Mandenius CF, Meyer T, Minotti G, Valentin YJ, Zünkler BJ, Bremer S Cardiotoxicity is among the leading reasons for drug attrition and is therefore a core subject in non-clinical and clinical safety testing of new drugs. European Centre for the Validation of Alternative Methods held in March 2008 a workshop on "Alternative Methods for Drug-induced Cardiotoxicity" in order to promote acceptance of alternative methods reducing, refining or replacing the use of laboratory animals in this field. This review reports the outcome of the workshop. The participants identified the major clinical manifestations, which are sensitive to conventional drugs, to be arrhythmias, contractility toxici... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2573793 Wed, 01 Jul 2009 23:00:00 +0100 2573793 http://www.medworm.com/index.php?rid=2530045&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19554478%26dopt%3DAbstract Authors: Cushing DJ, Cooper WD, Gralinski MR, Lipicky RJ, Kudenchuk PJ, Kowey PR Intravenous amiodarone (AIV) must be administered slowly after dilution to avoid hypotension, which is due to the cosolvents polysorbate 80 and benzyl alcohol used in its formulation. PM101 is a formulation of amiodarone devoid of these cosolvents, which enables bolus administration. We evaluated any potential toxicity or exaggerated adverse cardiac electrophysiologic effects of PM101 compared with AIV and control. Beagle dogs were treated with the human-equivalent amiodarone loading dose (2.14 mg/kg) with PM101 (bolus push) or AIV (10 min infusion in the toxicology study and bolus push in the electrophysiology study) followed by maintenance infusion (0.014 mg kg(-1) min(-1) through 6 h followed by 0.007 m... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2530045 Wed, 24 Jun 2009 23:00:00 +0100 2530045 http://www.medworm.com/index.php?rid=2530060&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19381878%26dopt%3DAbstract Authors: Celik A PMID: 19381878 [PubMed - in process] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2530060 Sun, 31 May 2009 23:00:00 +0100 2530060 http://www.medworm.com/index.php?rid=2530059&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19387569%26dopt%3DAbstract This study was designed to examine the effect of infrasound exposure (5 Hz at 130 dB) on whole-cell L-type Ca2+ currents (WLCC) in rat ventricular myocytes and the underlying mechanism(s) involved. Thirty-two adult Sprague-Dawley rats were randomly assigned to infrasound exposure and control groups. [Ca2+](i), WLCC, mRNA expression of the a(1c) subunit of L-type Ca2+ channels (LCC), and SERCA2 protein were examined on day 1, 7, and 14 after initiation of infrasound exposure. Fluo-3/AM fluorescence and the laser scanning confocal microscope techniques were used to measure [Ca2+](i) in freshly isolated ventricular myocytes. The Ca2+ fluorescence intensity (FI), denoting [Ca2+](i) in cardiomyocytes, was significantly elevated in a time-dependent manner in the exposure groups. There was a sign... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2530059 Sun, 31 May 2009 23:00:00 +0100 2530059 http://www.medworm.com/index.php?rid=2530057&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19399644%26dopt%3DAbstract Authors: Taban-Shomal O, Kilter H, Wagner A, Schorr H, Umanskaya N, Hübner U, Böhm M, Herrmann W, Herrmann M In the recent past, hyperhomocysteinemia (HHCY) has been linked to chronic heart failure. Folate and vitamin B12 deficiencies are the common causes of HHCY. The impact of these vitamins on cardiac function and morphology has scarcely been investigated. The aim of this study was to conduct an analysis of the cardiac effect of folate and vitamin B12 deficiency in vivo. Two groups of rats, a control (Co, n = 10) and a vitamin-deficient group (VitDef, n = 10), were fed for 12 weeks with a folate and vitamin B12-free diet or an equicaloric control diet. Plasma and tissue concentrations of HCY, S-adenosyl-homocysteine (SAH), S-adenosyl-methionine (SAM), and brain natriuretic... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2530057 Sun, 31 May 2009 23:00:00 +0100 2530057 http://www.medworm.com/index.php?rid=2530055&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19415530%26dopt%3DAbstract Authors: Ghanizadeh A PMID: 19415530 [PubMed - in process] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2530055 Sun, 31 May 2009 23:00:00 +0100 2530055 http://www.medworm.com/index.php?rid=2530053&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19484390%26dopt%3DAbstract Authors: Joseph J, Handy DE, Loscalzo J Four decades of research on the link between hyperhomocysteinemia and cardiovascular disease has led to a crossroads. Several negative studies on the role of homocysteine-lowering B-vitamin therapy in reducing the risk of atherothrombotic cardiovascular disease have dampened enthusiasm for this important field of research. In this review, we assess the present state of homocysteine research and suggest potential avenues that would help to clarify the purported link between the plasma homocysteine level and cardiovascular risk. We address several questions raised by the findings of various basic, epidemiological and clinical studies and attempt to construct a framework that we believe will allow us to address the fundamental unresolved issues in t... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2530053 Sun, 31 May 2009 23:00:00 +0100 2530053 http://www.medworm.com/index.php?rid=2530051&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19484391%26dopt%3DAbstract Authors: Belhani D, Fanton L, Vaillant F, Descotes J, Manati W, Tabib A, Bui-Xuan B, Timour Q Further to our previous observation of post-mortem cardiac lesions after sudden death in several athletes with a history of anabolic steroid abuse, this study was intended to reproduce these lesions in rabbits administered testosterone oenanthate, a prototypic anabolic steroid abused by athletes, and to provide evidence for the protective effects of trimetazidine and dexrazoxane that are used as antianginal and cardioprotective drugs, respectively. Groups of six rabbits each were administered saline, testosterone, or a combination of testosterone and either trimetazidine or dexrazoxane for 3 months. Histologic cardiac lesions including necrosis, misshapen cell nuclei, interstitial and endocard... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2530051 Sun, 31 May 2009 23:00:00 +0100 2530051 http://www.medworm.com/index.php?rid=2530049&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19484392%26dopt%3DAbstract Authors: Mak IT, Chmielinska JJ, Kramer JH, Weglicki WB Cardiovascular effects of chronic AZT treatment on SD male rats (185 g) fed either a normal Mg diet (0.1% MgO) or a high Mg diet (0.6% MgO) were examined. AZT treatment (1 mg/ml drinking water) for 3 weeks led to a 5.5-fold (0.88 +/- 0.11 nmol/min/10(6) cells, P < 0.05) elevation in neutrophil basal activity of O2(-) production versus controls (0.16 +/- 0.03 nmol/min, assayed ex vivo as SOD-inhibitable cytochrome c reduction). Concomitantly, plasma 8-isoprostane and PGE(2) levels rose 2.1-fold and 3-fold (both P < 0.05), respectively, compared to control; however, RBC GSH decreased 28% (P < 0.02) with GSSG content increased 3-fold, indicative of systemic oxidative stress. High Mg diet substantially attenuated the AZT-indu... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2530049 Sun, 31 May 2009 23:00:00 +0100 2530049 http://www.medworm.com/index.php?rid=2530047&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19517273%26dopt%3DAbstract In conclusion, Zn2+ and Cu2+ increased IL-6 release and MAP-kinase activation in primary cardiac cells, processes known to be involved in cardiac inflammation and hypertrophy. PMID: 19517273 [PubMed - in process] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2530047 Sun, 31 May 2009 23:00:00 +0100 2530047 http://www.medworm.com/index.php?rid=2304364&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19337863%26dopt%3DAbstract Authors: Fang Q, Kan H, Lewis W, Chen F, Sharma P, Finkel MS Mechanisms responsible for HIV cardiomyopathy are unknown, but may include direct effects of HIV proteins on the heart. Transgenic mice (TG) expressing HIV Tat protein targeted to the myocardium, +/- Tat TG, have revealed anatomical and biochemical defects in the heart. The present studies were conducted to clarify the effect of Tat on cardiac function. In vivo hemodynamics was measured in awake mice after inserting a catheter tip in the left ventricle under general anesthesia. Under the age of 3 months, the heart rate (HR) was significantly lower in TG (591 +/- 47 vs. 716 +/- 45 bpm, TG versus FVB control (FVB), respectively (P < 0.05; n = 8-12). Other hemodynamic indexes, including left ventricular systolic pressure (LVS... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2304364 Wed, 01 Apr 2009 04:00:00 +0100 2304364 http://www.medworm.com/index.php?rid=2304370&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19333788%26dopt%3DAbstract In this study, we demonstrated that metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes. Metabolites of MDMA used in this study included alpha-methyl dopamine, N-methyl alpha-methyl dopamine and 2,5-bis(glutathion-S-yl)-alpha-MeDA. Dihydroethidium was used to detect drug-induced increases in reactive oxygen species (ROS) production in ventricular myocytes. Contractile function and changes in intracellular calcium transients were measured in paced (1 Hz), Fura-2 AM loaded, myocytes using the IonOptix system. Production of ROS in ventricular myocytes treated with MDMA was not different from control. In contrast, all three metabolites of MDMA exhibited time- and concentration-dependent increases in ROS that were prevented by N-acetyl-... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2304370 Tue, 31 Mar 2009 04:00:00 +0100 2304370 http://www.medworm.com/index.php?rid=2286654&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19296063%26dopt%3DAbstract We report the case of a 17-year-old male who developed chest pain, elevated cardiac biomarkers, and acute left ventricular dysfunction following a single dose of methylphenidate. The risk of cardiomyopathy in the setting of methylphenidate treatment should prompt further study on the safety of this drug, and lead to ways of identifying those at risk of developing these complications. PMID: 19296063 [PubMed - as supplied by publisher] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2286654 Thu, 19 Mar 2009 04:00:00 +0100 2286654 http://www.medworm.com/index.php?rid=2191761&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19219407%26dopt%3DAbstract We report the case of a 38-year-old woman with a ST elevation myocardial infarction (STEMI) few days after artificially induced abortion by oral prescription of methylergometrine. Coronary angiography performed 2 days after onset of chest pain did not reveal any abnormalities of the coronary arteries but a provocative test using intravenous methylergometrine was positive with reproduction of chest pain, ECG changes and with a significant narrowing localized on the second segment of the left anterior descending artery at the angiogram. Thus, since methylergometrin may clearly induce coronary spasm when prescribed orally, chest pain occurring under oral treatment should require immediate attention even if atypical or in the absence of cardiovascular risk factors. PMID: 19219407 [PubMed -... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2191761 Sat, 14 Feb 2009 05:00:00 +0100 2191761 http://www.medworm.com/index.php?rid=2164297&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19191032%26dopt%3DAbstract In this study, we cloned and sequenced the as yet uncharacterized Nkx2.5 cDNA from normal and cardiac mutant axolotl heart RNA. Comparison of cDNA sequences of Nkx2.5 from normal and mutant axolotl hearts did not show differences suggesting that loss of function mutation in Nkx2.5 is not responsible for the mutant phenotype. However, quantitative studies show higher expression of Nkx2.5 in mutant hearts raising the possibility that increased expression of Nkx2.5 may contribute to the mutant phenotype. We also evaluated quantitative changes in expression of Nkx2.5 in axolotl hearts during embryonic and postembryonic heart development induced by exogenous thyroid hormone. There is an apparent increase in Nkx2.5 transcript levels in metamorphosed hearts. PMID: 19191032 [PubMed - as suppli... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2164297 Wed, 04 Feb 2009 05:00:00 +0100 2164297 http://www.medworm.com/index.php?rid=2028843&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19067249%26dopt%3DAbstract Authors: Kline ER, Bassit L, Hernandez-Santiago BI, Detorio MA, Liang B, Kleinhenz DJ, Walp ER, Dikalov S, Jones DP, Schinazi RF, Sutliff RL Nucleoside reverse transcriptase inhibitors (NRTIs), such as zidovudine (AZT) and stavudine (d4T), cause toxicities to numerous tissues, including the liver and vasculature. While much is known about hepatic NRTI toxicity, the mechanism of toxicity in endothelial cells is incompletely understood. Human aortic endothelial and HepG2 liver cells were exposed to 1 muM AZT or d4T for up to 5 weeks. Markers of oxidative stress, mitochondrial function, NRTI phosphorylation, mitochondrial DNA (mtDNA) levels, and cytotoxicity were monitored over time. In endothelial cells, AZT significantly oxidized glutathione redox potential, increased total cellular and... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=2028843 Tue, 09 Dec 2008 05:00:00 +0100 2028843 http://www.medworm.com/index.php?rid=1912196&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18953671%26dopt%3DAbstract This study ascertains the effects of zinc, a major component of particulate matter, on pulmonary and systemic endpoints using hyperlipidemic rabbits to model diet-induced human atherosclerosis. New Zealand White rabbits were fed a normal or cholesterol-enriched diet and then were intratracheally instilled 1x/week for 4 weeks with saline or 16 microg/kg of zinc, equal parts sulfate and oxide. Physiologic responses, blood after each exposure, and terminal bronchoalveolar lavage (BAL) were assessed. Rabbits fed a cholesterol-rich diet developed hyperlipidemia and had consistently higher circulating leukocyte counts than rabbits fed normal chow. Within minutes after zinc instillation, saturation of peripheral oxygen was decreased in hyperlipidemic rabbits and heart rate was increased in hyperl... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1912196 Sat, 25 Oct 2008 04:00:00 +0100 1912196 http://www.medworm.com/index.php?rid=1873551&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18850075%26dopt%3DAbstract Authors: Kopf PG, Huwe JK, Walker MK The mechanisms by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases the incidence of human cardiovascular disease are not known. We investigated the degree to which cardiovascular disease develops in mice following subchronic TCDD exposure. Adult male C57BL/6 mice were dosed with vehicle or 300 ng TCDD/kg by oral gavage three times per week for 60 days. Blood pressure was recorded by radiotelemetry and aortic endothelial function was assessed by acetylcholine-induced vasorelaxation. Mean arterial pressure of TCDD-exposed mice was increased significantly by day 4 and between days 7-10, 25-35, and 45-60 with two periods of normalization on days 11-24 and days 36-39. Consistent with a prolonged period of systemic hypertension, heart weight was... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1873551 Sat, 11 Oct 2008 04:00:00 +0100 1873551 http://www.medworm.com/index.php?rid=1873550&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18850076%26dopt%3DAbstract Authors: Yuan Y, Kan H, Fang Q, Chen F, Finkel MS The prognosis for patients with human immunodeficiency virus (HIV) infection has improved remarkably as a result of effective antiretroviral therapy. This has resulted in an increased awareness of cardiac complications from HIV infection, including cardiomyopathy and overt heart failure. Mechanisms responsible for HIV cardiomyopathy and heart failure are unknown, but may include direct effects of HIV proteins on the heart. We have previously reported that the HIV envelope glycoprotein, gp120, has a p38 MAP kinase-dependent negative inotropic effect on adult rat ventricular myocytes (ARVM). This signaling pathway presumably results from the binding of gp120 to a specific receptor on the surface of cardiac myocytes. HIV gp120 has been sho... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1873550 Sat, 11 Oct 2008 04:00:00 +0100 1873550 http://www.medworm.com/index.php?rid=1830029&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18813882%26dopt%3DAbstract Authors: Pradhan L, Mondal D, Chandra S, Ali M, Agrawal KC Cocaine remains the most frequently used illicit substance. Although cocaine-induced atherosclerosis is well documented, its mechanism of action on human vascular endothelial cells has not been determined. Nitric oxide (NO) and endothelin-1 (ET-1) are involved in endothelial cell activation and leukocyte recruitment. The present study monitored the effects of cocaine on NO and ET-1 production in human aortic endothelial cells (HAECs) and the effects of sodium nitroprusside (SNP) and BQ-123 on leukocyte adhesion to HAECs. Acute exposure to cocaine (1 and 3 muM) significantly increased ET-1 production (2-fold) and ET-1 receptor type-A (ET(A)R) protein expression, within 6-12 h. Cocaine exposure for a longer duration (24-72 h) sho... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1830029 Wed, 24 Sep 2008 04:00:00 +0100 1830029 http://www.medworm.com/index.php?rid=1776223&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18777166%26dopt%3DAbstract This study was designed to evaluate the epidemiology of type 2 diabetes and hypertension in Uygur and Kazak ethnic populations. A three-step stratified sampling method was used. Questionnaires, blood pressure, anthropometric measurement, and fasting blood glucose were monitored. In total, 1,571 Uygur and 2,913 Kazak subjects were randomly enrolled. The prevalence of type 2 diabetes and glucose intolerance was 5.55- and 1.90-fold higher, respectively, in Uygur than in the Kazak population (8.16 vs. 1.47%, P < 0.001 and 3.29 vs. 1.73%, P < 0.001). However, the prevalence of hypertension and obesity was significantly higher in the Kazak than in the Uygur population (hypertension: 43.52 vs. 31.98%, P < 0.001; obesity: 25.0 vs. 14.5%, P < 0.001, respectively). Our data suggest a sig... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1776223 Sat, 06 Sep 2008 04:00:00 +0100 1776223 http://www.medworm.com/index.php?rid=1743225&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18751928%26dopt%3DAbstract Authors: Barta J, Sanganalmath SK, Kumamoto H, Takeda N, Edes I, Dhalla NS Antiplatelet agents, sarpogrelate (SAR), a 5-hydroxy tryptamine 2A receptor antagonist and cilostazol (CIL), a phosphodiesterase-III inhibitor, were observed to be beneficial in attenuating cardiac remodeling and improving cardiac function in congestive heart failure due to myocardial infarction in rats; however, CIL increased ventricular tachycardia and mortality. In order to study the effects of these antiplatelet agents on arrhythmias, Sprague-Dawley rats were pretreated with either SAR or CIL (5 mg/kg/day) for 2 weeks and were then either injected cumulative doses of epinephrine (Epi) or subjected to coronary occlusion. Saline-treated animals served as controls. Electrocardiographic analysis revealed that SA... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1743225 Wed, 27 Aug 2008 04:00:00 +0100 1743225 http://www.medworm.com/index.php?rid=1689568&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18683081%26dopt%3DAbstract Authors: Booth EA, Lucchesi BR Before menopause, a woman has a relatively low risk for developing cardiovascular disease. After menopause, however, the risk increases nearly twofold and cardiovascular disease remains the number one cause of death among women. Observational trials and studies in animal models of cardiovascular disease suggested that females have reduced injury after myocardial ischemia and reperfusion injury. However, two large clinical trials, the women's health initiative (WHI) and the heart estrogen and progestin replacement study (HERS), found an increase in cardiovascular incidences in women taking hormone replacement therapy. The discrepancy between these data highlights the need for further research on the mechanism of estrogen in the cardiovascular system. Anima... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1689568 Wed, 06 Aug 2008 04:00:00 +0100 1689568 http://www.medworm.com/index.php?rid=1683973&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18679830%26dopt%3DAbstract In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart. PMID: 18679830 [PubMed - as supplied by publisher] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1683973 Tue, 05 Aug 2008 04:00:00 +0100 1683973 http://www.medworm.com/index.php?rid=1675665&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18670907%26dopt%3DAbstract Authors: Aragon AC, Goens MB, Carbett E, Walker MK In utero and lactational exposure of mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to cardiac hypertrophy and hydronephrosis in adulthood. We tested the hypothesis that perinatal TCDD exposure increases the susceptibility to cardiovascular disease when offspring are exposed to a common cardiovascular disease risk factor, angiotensin II (Ang II). Pregnant C57BL/6N mice were exposed to corn oil (control) or 6.0 mug/kg TCDD on gestation day 14.5. Male offspring were then exposed to a subpressor (0.1 mg/kg/day) or pressor (0.7 mg/kg/day) dose of Ang II at 3.5 months and cardiac morphology and blood pressure analyzed, respectively. Perinatal TCDD exposure increased left ventricular cavity dilation during diastole, and wall thickn... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1675665 Fri, 01 Aug 2008 04:00:00 +0100 1675665 http://www.medworm.com/index.php?rid=1626280&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18084726%26dopt%3DAbstract We describe a case of a man, 76 years old, who was admitted to our department for dyspnoea in APL in treatment with arsenic trioxide. Chest radiograph illustrated an enlarged cardiac silhouette and bilateral pleuric effusion and the ECG evidenced QT prolongation. The patient was also submitted to transthoracic echocardiography that revealed moderate pericardial effusion without signs of cardiac tamponade and a normal biventricular function. This condition was considered to be associated with arsenic trioxide polyserosit and the drug therapy was immediately discontinued and steroid drugs started. After 2 weeks of arsenic trioxide therapy suspension there was evidence of complete resolution of pericardial and pleuric effusion and the ECG showed normal QT interval. PMID: 18084726 [PubMed ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626280 Wed, 16 Jul 2008 14:52:47 +0100 1626280 http://www.medworm.com/index.php?rid=1626279&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18172783%26dopt%3DAbstract Authors: Dubé MP, Gorski JC, Shen C Endothelial dysfunction may contribute to increased cardiovascular events among HIV-1-infected patients receiving antiretroviral therapy. The HIV-1 protease inhibitor indinavir causes both vascular dysfunction and insulin resistance, but the relationship between the two disturbances is not established. Endothelium-dependent vasodilation (EDV), insulin-mediated vasodilation (IMV), and whole body and leg glucose uptake during a euglycemic hyperinsulinemic clamp (40 mU/m(2)/min) were measured before and after four weeks of indinavir in nine healthy men. EDV fell from 270 +/- 67% above basal to 124 +/- 30% (P = 0.04) and IMV from 56 +/- 14% above basal to 8 +/- 8% (P = 0.001) with indinavir. During the clamp, arteriovenous glucose difference and leg... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626279 Wed, 16 Jul 2008 14:52:47 +0100 1626279 http://www.medworm.com/index.php?rid=1626278&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18176845%26dopt%3DAbstract Authors: Gillum N, Sarvazyan N Cell-transplantation therapy is a promising treatment option that is being actively explored as a way to repair cardiac muscle. The ultimate goal is to reconstitute the architecture of the cardiac muscle and to reestablish electrical propagation, while avoiding hypertrophy and scar formation. In this review, we focus on recent advances in the field as well as the difficulties encountered when the engraftment of cells into the host tissue is to be confirmed and functionally characterized. This is critical since incomplete or partial engraftment of transplanted cells within the host cardiac network exacerbates the heterogeneity already present in the injured myocardium and increases its propensity to arrhythmia. We conclude with a brief discussion of how th... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626278 Wed, 16 Jul 2008 14:52:47 +0100 1626278 http://www.medworm.com/index.php?rid=1626277&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18273709%26dopt%3DAbstract We present the case of a young man with CO poisoning who had elevated cardiac biomarkers, a regional wall motion abnormality, and was found to have obstructive coronary disease. Evidence of myocardial necrosis in the setting of CO toxicity should prompt consideration of an evaluation for coronary artery disease, particularly among those with risk factors. PMID: 18273709 [PubMed - in process] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626277 Wed, 16 Jul 2008 14:52:47 +0100 1626277 http://www.medworm.com/index.php?rid=1626276&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18317950%26dopt%3DAbstract Authors: Vary TC, Lang CH Acute alcohol intoxication leads to an inhibition of protein synthesis in heart that results in part through altered phosphorylation of protein factors controlling mRNA translation initiation. The purpose of the present set of experiments was designed to examine the effects of inhibitors of ethanol metabolism on the phosphorylation of 4E-binding protein (4EBP1) and S6k1(Thr(389)), two factors regulating mRNA translation initiation. Phosphorylation of 4E-BP1, S6k1(Thr(389)), and Erk 1/2 was reduced 2 h following IP injection of alcohol. Pretreatment with 4-methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase (ADH), did not attenuate the ethanol-induced decrease in phosphorylation of 4EBP1 and S6k1(Thr(389)). In contrast, 4-MP prevented the decrease in E... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626276 Wed, 16 Jul 2008 14:52:47 +0100 1626276 http://www.medworm.com/index.php?rid=1626274&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18437584%26dopt%3DAbstract In this study, we investigated the global changes in gene expression caused by exposure of P19 embryonal carcinoma cells to TCE and TCA, and whether or not TCE and/or TCA influence the expression levels of genes encoding for proteins that regulate calcium fluxes in cardiac cells. We report that TCE and TCA disrupt the expression of genes involved in processes important during embryonic development suggesting that exposure to environmentally significant concentrations of TCE may have deleterious effects on specific stages of cardiac differentiation. PMID: 18437584 [PubMed - in process] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626274 Wed, 16 Jul 2008 14:52:47 +0100 1626274 http://www.medworm.com/index.php?rid=1626273&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18446447%26dopt%3DAbstract Authors: Kohler JJ, Hosseini SH, Green E, Hoying-Brandt A, Cucoranu I, Haase CP, Russ R, Srivastava J, Ivey K, Ludaway T, Kapoor V, Abuin A, Shapoval A, Santoianni R, Saada A, Elpeleg O, Lewis W Mitochondrial (mt) DNA biogenesis is critical to cardiac contractility. DNA polymerase gamma (Pol gamma) replicates mtDNA, whereas thymidine kinase 2 (TK2) monophosphorylates pyrimidines intramitochondrially. Point mutations in POLG and TK2 result in clinical diseases associated with mtDNA depletion and organ dysfunction. Pyrimidine analogs (NRTIs) inhibit Pol gamma and mtDNA replication. Cardiac "dominant negative" murine transgenes (TGs; Pol gamma Y955C, and TK2 H121N or I212N) defined the role of each in the heart. mtDNA abundance, histopathological features, histochemistry, mitochondrial pr... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626273 Wed, 16 Jul 2008 14:52:47 +0100 1626273 http://www.medworm.com/index.php?rid=1626272&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18463988%26dopt%3DAbstract This study was undertaken to investigate if Nrf2 signaling could control the constitutive and inducible expression of antioxidants and phase 2 enzymes in primary cardiomyocytes as well as the susceptibility of these cells to oxidative and electrophilic injury. The basal expression of a series of antioxidants and phase 2 enzymes was significantly lower in cardiomyocytes from Nrf2(-/-) mice than those from wild-type littermates. Incubation of wild-type cardiomyocytes with 3H-1,2-dithiole-3-thione (D3T) led to significant induction of various antioxidants and phase 2 enzymes, including catalase, glutathione, glutathione peroxidase (GPx), glutathione reductase, glutathione S-transferase, NAD(P)H:quinone oxidoreductase 1, and heme oxygenase-1. The inducibility of the above cellular defenses exc... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626272 Wed, 16 Jul 2008 14:52:47 +0100 1626272 http://www.medworm.com/index.php?rid=1626271&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18483876%26dopt%3DAbstract In conclusion, our results indicated that high caloric food intake may trigger hyperlipidemia and subsequently elevated blood pressure, with elevated BMI and cholesterol levels being the major risk factors for hypertension. PMID: 18483876 [PubMed - in process] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626271 Wed, 16 Jul 2008 14:52:47 +0100 1626271 http://www.medworm.com/index.php?rid=1626270&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18584335%26dopt%3DAbstract Authors: Sun H, Chen QM Our recent study has demonstrated that glucocorticoids (GCs) induce cyclooxygenase-1 (COX-1) gene expression in rat cardiomyocytes. While investigating the mechanism underlying corticosterone (CT) induced COX-1, we found that three structurally and mechanistically distinct GSK-3 inhibitors, LiCl, SB216763, and (2'Z,3'E)-6-Bromoindirubin-3'-oxime (BIO), inhibited COX-1 transcription and protein induction. A genetic approach of expressing wild type GSK-3beta increased COX-1 promoter activity, which was abolished by LiCl. LiCl increased inhibitory GSK-3alpha/beta phosphorylation at Ser21/Ser9, while BIO or SB216763 prevented stimulatory phosphorylation at Tyr279/Tyr216 of GSK-3alpha/beta. GSK inhibitors failed to block nuclear translocation of glucocorticoid recept... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626270 Wed, 16 Jul 2008 14:52:47 +0100 1626270 http://www.medworm.com/index.php?rid=1626269&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18607771%26dopt%3DAbstract Authors: Zhu H, Jia Z, Strobl JS, Ehrich M, Misra HP, Li Y Sulforaphane, a cruciferous isothiocyanate compound, upregulates cytoprotective genes in liver, but its effects on antioxidants and phase 2 defenses in vascular cells are unknown. Here we report that incubation of rat aortic smooth muscle A10 cells with sulforaphane (0.25-5 muM) resulted in concentration-dependent induction of a spectrum of important cellular antioxidants and phase 2 enzymes, including superoxide dismutase (SOD), catalase, the reduced form of glutathione (GSH), glutathione peroxidase, glutathione reductase (GR), glutathione S-transferase (GST), and NAD(P)H:quinone oxidoreductase 1 (NQO1). Sulforaphane also increased levels/activities of SOD, catalase, GSH and GST in isolated mitochondria of aortic smooth muscle... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626269 Tue, 08 Jul 2008 04:00:00 +0100 1626269 http://www.medworm.com/index.php?rid=1626275&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18327657%26dopt%3DAbstract Authors: Guéguen Y, Lestaevel P, Grandcolas L, Baudelin C, Grison S, Jourdain JR, Gourmelon P, Souidi M Cardiovascular system impairment has been observed in children and in liquidators exposed to the Chernobyl nuclear power plant accident. No experimental studies of animals have analyzed whether these disorders might be attributed to chronic ingestion of low levels of cesium 137 ((137)Cs). Biochemical, physiological, and molecular markers of the cardiovascular system were analyzed in rats exposed through drinking water to (137)Cs at a dose of 500 Bq kg(-1) (6500 Bq l(-1)). Plasma concentrations of CK and CK-MB were higher (+52%, P < 0.05) in contaminated rats. No histological alteration of the heart was observed, but gene expression was modified in the atria. Specifically, lev... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626275 Sat, 01 Mar 2008 05:00:00 +0100 1626275 http://www.medworm.com/index.php?rid=1626317&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17646677%26dopt%3DAbstract The objective of this study was to determine whether an HMG Co A reductase inhibitor (statin) reduces protein synthesis in cardiomyocytes and whether this action maybe an underlying mechanism for statin-induced cell death. Cardiomyocytes from embryonic chick heart were maintained in culture. Cells exposed to lovastatin for 4 h showed a concentration dependent reduction in protein synthesis as assessed by [3H] leucine incorporation and [35S] methionine incorporation. Compared to control, lovastatin 100 microM, which produced a 25% increase in cell death, induced a three-fold reduction in methionine incorporation. [35S] methionine autoradiography showed little (new) protein synthesis at concentrations of lovastatin of 70 microM or higher; an effect that was not limited to specific proteins. ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626317 Mon, 01 Jan 2007 05:00:00 +0100 1626317 http://www.medworm.com/index.php?rid=1626316&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17646678%26dopt%3DAbstract Authors: Zibadi S, Yu Q, Rohdewald PJ, Larson DF, Watson RR Cardiac remodeling is a determinant of the clinical progression of heart failure and now slowing or reversing remodeling is considered as a potential therapeutic target in heart failure. Pycnogenol has been reported to mediate a number of beneficial effects in the cardiovascular system but its effects on hemodynamic and functional cardiovascular changes following cardiac remodeling have not been elucidated. Therefore, we investigated the influence of Pycnogenol supplementation (30 mg/kg) on left ventricular function and myocardial extracellular matrix composition in old C57BL/6N mice following induction of cardiac remodeling by chronic nitric oxide synthase blockade by NG-nitro-L-arginine methyl ester (L-NAME) administration. ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626316 Mon, 01 Jan 2007 05:00:00 +0100 1626316 http://www.medworm.com/index.php?rid=1626315&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17646679%26dopt%3DAbstract Authors: Hasinoff BB, Patel D, Wu X The cyclooxygenase (COX)-2 inhibitors celecoxib and rofecoxib were studied for their effects on neonatal rat cardiac myocytes as a possible model for the adverse cardiovascular effects that this class of compounds have shown in their clinical use. Celecoxib, but not rofecoxib, as measured by lactate dehydrogenase release was toxic to myocytes in the low micromolar concentration range. This toxicity shown by celecoxib was also associated with a high degree of myofibrillar disruption similar to that caused by doxorubicin. As measured by induction of caspase-3/7 activity and by changes in nuclear morphology, neither celecoxib nor rofecoxib strongly induced apoptosis in myocytes. The stable prostacyclin analog iloprost was unable to reduce celecoxib-indu... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626315 Mon, 01 Jan 2007 05:00:00 +0100 1626315 http://www.medworm.com/index.php?rid=1626314&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17646680%26dopt%3DAbstract Authors: Rowan WH, Campen MJ, Wichers LB, Watkinson WP Heart rate variability (HRV) is a measure of cardiac pacing dynamics that has recently garnered a great deal of interest in environmental health studies. While the use of these measures has become popular, much uncertainty remains in the interpretation of results, both in terms of human and animal research. In humans, HRV endpoints, specifically chronic alterations in baseline HRV patterns, have been reasonably well characterized as prognostic indicators of adverse outcomes for a variety of diseases. However, such information is lacking for reversible HRV changes that may be induced by short-term exposures to environmental toxicants. Furthermore, there are minimal substantive data, either acute or chronic, regarding the pathologica... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626314 Mon, 01 Jan 2007 05:00:00 +0100 1626314 http://www.medworm.com/index.php?rid=1626313&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652803%26dopt%3DAbstract Authors: Minotti G, Sarvazyan N In the era of targeted therapy the anthracyclines, which were discovered almost half-century ago, may appear to be too old to be good. While it is certainly true that the prototypic anthracyclines have been around for many years, there are robust clinical facts to confute that their time is over. These drugs continue to play an undisputed role in the treatment of many forms of cancer, including hematological malignancies and solid tumors. Unfortunately, however, their main side-effect remains: a life-threatening cardiotoxicity which became apparent at the beginning of anthracyclines' clinical use. In addition to this long-standing problem, we are now discovering that new combination therapies often cause a higher than expected incidence of cardiotoxicity... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626313 Mon, 01 Jan 2007 05:00:00 +0100 1626313 http://www.medworm.com/index.php?rid=1626312&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652804%26dopt%3DAbstract Authors: Cortés-Funes H, Coronado C Anthracyclines such as doxorubicin, epirubicin, and daunorubicin are among the most active cytoxic agents for treatment of a wide variety of solid tumors and hematological malignancies. The downside associated with chronic administration of anthracyclines is the induction of cardiomyopathy and congestive heart failure, usually refractory to common treatments. Anthracycline liposomal formulations are currently the best-known alternatives to improve the index and spectrum of anticancer activity of these drugs and decrease their cardiotoxicity. In the current target therapy era in oncology, anthracyclines increase the antitumor effects in more than additive fashion, being excellent partners for other active agents like taxanes and trastuzumab. It i... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626312 Mon, 01 Jan 2007 05:00:00 +0100 1626312 http://www.medworm.com/index.php?rid=1626311&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652805%26dopt%3DAbstract Authors: Zuppinger C, Timolati F, Suter TM The clinical manifestations of anti-cancer drug associated cardiac side effects are diverse and can range from acutely induced cardiac arrhythmias to Q-T interval prolongation, changes in coronary vasomotion with consecutive myocardial ischemia, myocarditis, pericarditis, severe contractile dysfunction, and potentially fatal heart failure. The pathophysiology of these adverse effects is similarly heterogeneous and the identification of potential mechanisms is frequently difficult since the majority of cancer patients is not only treated with a multitude of cancer drugs but might also be exposed to potentially cardiotoxic radiation therapy. Some of the targets inhibited by new anti-cancer drugs also appear to be important for the maintenance of... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626311 Mon, 01 Jan 2007 05:00:00 +0100 1626311 http://www.medworm.com/index.php?rid=1626310&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652806%26dopt%3DAbstract Authors: Gianni L, Salvatorelli E, Minotti G Doxorubicin is known to cause cardiomyopathy and congestive heart failure (CHF) upon chronic administration. A major obstacle to doxorubicin-containing multiagent therapies pertains to the possible development of cardiomyopathy and CHF at lower than expected cumulative doses of doxorubicin. For example, the cardiac toxicity of doxorubicin is aggravated by the anti-HER2 antibody Trastuzumab or by the tubulin-active taxane paclitaxel; however, the mechanisms by which Trastuzumab and paclitaxel aggravate doxorubicin-induced cardiotoxicity are mechanistically distinct: Trastuzumab interferes with cardiac-specific survival factors that help the heart to withstand stressor agents like anthracyclines, while paclitaxel acts by stimulating the format... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626310 Mon, 01 Jan 2007 05:00:00 +0100 1626310 http://www.medworm.com/index.php?rid=1626309&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652807%26dopt%3DAbstract Authors: Batist G Anthracyclines remain amongst the most active therapeutic agents for breast cancer treatment. Rather than being supplanted by novel targeted agents, they are being combined with them in various schedules. Furthermore, anthracyclines themselves are still being studied, with increasing biological understanding of their biological activity and molecular targets. A cardiac safe formulation of doxorubicin opens a number of interesting therapeutic opportunities. Liposomal doxorubicins appear to provide this opportunity. PMID: 17652807 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626309 Mon, 01 Jan 2007 05:00:00 +0100 1626309 http://www.medworm.com/index.php?rid=1626308&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652808%26dopt%3DAbstract Authors: Sessa C, Valota O, Geroni C Many anthracyclines are currently in clinical development with the common aim of improving selectivity. This could be achieved by improving tumor drug delivery through the identification and development of molecules with new structure, prodrugs with low molecular weight for selective release and activation, prodrugs with high molecular weight conjugated to antibody with active targeting or macromolecules with enhanced permeability and retention. There are still interfering factors to be defined, in particular chemical, with degradation steps in tumor tissues, biological, related to tumor proteases, pharmacological, with inter-individual tumor differences in the extent of accumulation. Another way to improve selectivity is to activate the drug at the... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626308 Mon, 01 Jan 2007 05:00:00 +0100 1626308 http://www.medworm.com/index.php?rid=1626307&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652809%26dopt%3DAbstract Authors: Menna P, Recalcati S, Cairo G, Minotti G Antitumor therapy with doxorubicin and other anthracyclines is limited by the possible development of cardiomyopathy upon chronic administration. Several lines of evidence suggest that a close link exists between cardiotoxicity and the amount of anthracycline that accumulates in the heart and then undergoes one- or two- electron reduction to toxic metabolites or by-products. Alternative metabolic pathways lead to an oxidative degradation of anthracyclines, possibly counteracting anthracycline accumulation and reductive bioactivation; unfortunately, however, the actual role of anthracycline oxidation is only partially characterized. Here, we briefly review the biochemical foundations of reductive versus oxidative anthracycline metabolism... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626307 Mon, 01 Jan 2007 05:00:00 +0100 1626307 http://www.medworm.com/index.php?rid=1626306&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652810%26dopt%3DAbstract Authors: Swift L, McHowat J, Sarvazyan N The purpose of this essay is to overview our findings that membrane-associated calcium-independent phospholipase A2 is markedly inhibited by low, clinically relevant concentrations of anthracyclines. Our studies suggest that due to the essential role of this enzyme in membrane homeostasis, its inhibition can be one of the early culprits leading to anthracycline-induced cardiac dysfunction. The clinical importance and potential pharmaceutical use of this new phenomenon await further studies. PMID: 17652810 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626306 Mon, 01 Jan 2007 05:00:00 +0100 1626306 http://www.medworm.com/index.php?rid=1626305&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652811%26dopt%3DAbstract Authors: Kalyanaraman B In this brief essay we discuss the interrelationship between the cellular signaling effects induced by extracellular and intracellular ROS and nitric oxide in the context of doxorubicin (DOX) toxicity. PMID: 17652811 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626305 Mon, 01 Jan 2007 05:00:00 +0100 1626305 http://www.medworm.com/index.php?rid=1626304&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652812%26dopt%3DAbstract Authors: Kang YJ Anthracycline cardiotoxicity is related to oxidative stress generated from the metabolism of anthracyclines in the heart. Studies using transgenic mice with high levels of antioxidants such as catalase or metallothionein (MT) specifically in the heart have demonstrated that elevation of cardiac antioxidant defense leads to intervention of anthracycline cardiotoxicity. MT protection against anthracycline-induced cardiac toxicity is related to its anti-apoptotic effect by inhibiting both p38-MAPK-mediated and mitochondrial cytochrome c-release-mediated apoptotic signaling. The anti-apoptotic effect of MT is closely related to its antioxidant action, which involves regulation of zinc homeostasis by the MT redox cycle. MT interferes with oxidant-mediated detrimental proces... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626304 Mon, 01 Jan 2007 05:00:00 +0100 1626304 http://www.medworm.com/index.php?rid=1626303&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652813%26dopt%3DAbstract Authors: Wallace KB Adriamycin (doxorubicin) is a potent and broad-spectrum antineoplastic agent, the clinical utility of which is limited by the development of a cumulative and irreversible cardiomyopathy. Although the drug affects numerous structures in different cell types, the mitochondrion appears to a principal subcellular target for the development of cardiomyopathy. This review describes evidence demonstrating that adriamycin redox cycles on complex I of the mitochondrial electron transport chain to liberate highly reactive free radical species of molecular oxygen. The primary effect of adriamycin on mitochondrial performance is the interference with oxidative phosphorylation and inhibition of ATP synthesis. Free radicals liberated from adriamycin redox cycling are thought to b... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626303 Mon, 01 Jan 2007 05:00:00 +0100 1626303 http://www.medworm.com/index.php?rid=1626302&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652814%26dopt%3DAbstract Authors: Lebrecht D, Walker UA Doxorubicin (adriamycin) is an effective drug in the treatment of many malignancies. Its prolonged use is, however, limited by an irreversible, dose-dependent and progressive cardiomyopathy, which may become evident even years after completion of therapy. Data from rats and humans show that oxidative phosphorylation is impaired rapidly after acute doxorubicin-exposure. Such respiratory chain dysfunction is known to enhance the production of reactive oxygen species and may lead to quantitative and qualitative injury of mitochondrial DNA (mtDNA) and its encoded respiratory chain subunits. MtDNA depletion, mtDNA mutations and respiratory defects then accumulate with time also in the absence of continued anthracycline exposure. Chronic cardiotoxicity then man... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626302 Mon, 01 Jan 2007 05:00:00 +0100 1626302 http://www.medworm.com/index.php?rid=1626301&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652815%26dopt%3DAbstract Authors: Chen B, Peng X, Pentassuglia L, Lim CC, Sawyer DB The molecular and cellular mechanisms that cause cumulative dose-dependent anthracycline-cardiotoxicity remain controversial and incompletely understood. Studies examining the effects of anthracyclines in cardiac myocytes inA vitro have demonstrated several forms of cellular injury. Cell death in response to anthracyclines can be observed by one of several mechanisms including apoptosis and necrosis. Cell death by apoptosis can be inhibited by dexrazoxane, the iron chelator that is known to prevent clinical development of heart failure at high cumulative anthracycline exposure. Together with clinical evidence for myocyte death after anthracycline exposure, in the form of elevations in serum troponin, make myocyte cell death a p... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626301 Mon, 01 Jan 2007 05:00:00 +0100 1626301 http://www.medworm.com/index.php?rid=1626300&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652816%26dopt%3DAbstract Authors: Scully RE, Lipshultz SE Anthracycline chemotherapy is a widely-used and effective treatment for a wide spectrum of childhood cancers. Its use is limited by associated progressive and clinically significant cardiotoxic effects. Onset can be acute, early, or late. While acute onset is rare, long-term survivors have significantly elevated rates of cardiac morbidity and mortality. Major complications include cardiomyopathy, coronary artery disease, and atherosclerosis. Means of prevention and treatment continue to be explored including limiting cumulative anthracycline dose, controlling the rate of administration, and using liposomal preparations and novel anthracycline analogues. Dexrazoxane prior to anthracycline chemotherapy has been shown to significantly lower rates of elevat... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626300 Mon, 01 Jan 2007 05:00:00 +0100 1626300 http://www.medworm.com/index.php?rid=1626299&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652817%26dopt%3DAbstract Authors: Deng S, Wojnowski L Anthracyclines belong to the most successful antineoplastic drugs, but they are cardiotoxic, which may result in congestive heart failure (CHF). The CHF risk increases with the cumulative anthracycline dose, but it seems also to be modified by individual factors. A role of the individual genetic background is consistent with the altered sensitivity to anthracyclines observed in many transgenic and knockout mouse strains. First clinical data obtained in humans suggest the existence of predisposing variants in genes involved in the oxidative stress, and in the metabolism and transport of anthracyclines. These data will have to be verified in further clinical trials before any attempts of their application in the individual cardiotoxicity prediction can be und... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626299 Mon, 01 Jan 2007 05:00:00 +0100 1626299 http://www.medworm.com/index.php?rid=1626298&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652818%26dopt%3DAbstract Authors: Robert J The clinical importance of the cardiotoxicity of anthracyclines requires the availability of preclinical models able to predict the cardiotoxicity of novel anthracycline analogs in reference to doxorubicin or of cardioprotectors aimed at circumventing the deleterious effects of these drugs. The reference model has been defined long ago and has proven its validity. Weanling rabbits given weekly injections of doxorubicin for 4 months developed a cardiomyopathy, which can be assessed from a clinical and pathological point of view. Models in other animals such as rats or mice were similarly implemented, also with long-term exposures to the drug, resulting in cardiac failure and severe pathological alterations, which could be graded for comparison. Starting from the eviden... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626298 Mon, 01 Jan 2007 05:00:00 +0100 1626298 http://www.medworm.com/index.php?rid=1626297&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652819%26dopt%3DAbstract Authors: Hasinoff BB, Herman EH Dexrazoxane is highly effective in reducing anthracycline-induced cardiotoxicity and extravasation injury and is used clinically for these indications. Dexrazoxane has two biological activities: it is a prodrug that is hydrolyzed to an iron chelating EDTA-type structure and it is also a strong inhibitor of topoisomerase II. Doxorubicin is able to be reductively activated to produce damaging reactive oxygen species. Iron-dependent cellular damage is thought to be responsible for its cardiotoxicity. The available experimental evidence supports the conclusion that dexrazoxane reduces doxorubicin cardiotoxicity by binding free iron and preventing site-specific oxidative stress on cardiac tissue. However, it cannot be ruled out that dexrazoxane may also be pr... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626297 Mon, 01 Jan 2007 05:00:00 +0100 1626297 http://www.medworm.com/index.php?rid=1626296&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652820%26dopt%3DAbstract Authors: Kaiserová H, Simunek T, Sterba M, den Hartog GJ, Schröterová L, Popelová O, Gersl V, Kvasnicková E, Bast A The use of anthracycline anticancer drugs is limited by a cumulative, dose-dependent cardiac toxicity. Iron chelation has long been considered as a promising strategy to limit this unfavorable side effect, either by restoring the disturbed cellular iron homeostasis or by removing redox-active iron, which may promote anthracycline-induced oxidative stress. Aroylhydrazone lipophilic iron chelators have shown promising results in the rabbit model of daunorubicin-induced cardiomyopathy as well as in cellular models. The lack of interference with the antiproliferative effects of the anthracyclines also favors their use in clinical settings. The dose, h... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626296 Mon, 01 Jan 2007 05:00:00 +0100 1626296 http://www.medworm.com/index.php?rid=1626295&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652821%26dopt%3DAbstract Authors: Langer SW, Jensen PB, Sehested M Dexrazoxane has been in clinical use for more than 25 years for prevention of cardiotoxicity in anthracycline based anticancer therapy. However, we discovered another property of the compound, i.e. the ability to prevent the devastating tissue necrosis after accidental extravasation of anthracyclines. The preclinical and clinical studies leading to the clinical implementation of Savene (dexrazoxane) as the first and only proven antidote in anthracycline extravasation are described in short. PMID: 17652821 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626295 Mon, 01 Jan 2007 05:00:00 +0100 1626295 http://www.medworm.com/index.php?rid=1626294&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652822%26dopt%3DAbstract Authors: Bast A, Haenen GR, Bruynzeel AM, Van der Vijgh WJ Cardiotoxic side-effects of doxorubicin limit the clinical use of this anti-cancer agent. Iron chelators have been studied as protectors against doxorubicin-induced cardiotoxicity. These iron chelators do not provide optimal protection and have certain drawbacks. We therefore looked for new protectors and decided that these new compounds should combine iron chelating and antioxidant activity. Flavonoids appeared to possess those combined iron chelating and antioxidant properties. Quantum chemical evaluation of radical stabilization and determination of physico-chemical properties of a series of flavonoids brought our attention to the semi-synthetic flavonoid 7-monohydroxyetylrutoside (monoHER). Both in vitro (using an electrica... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626294 Mon, 01 Jan 2007 05:00:00 +0100 1626294 http://www.medworm.com/index.php?rid=1626293&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17652823%26dopt%3DAbstract Authors: Hideg K, Kálai T It has been suggested nitroxides and their amine precursors prevent incidence of damage caused by superoxide and hydroxyl radicals formed during the oxidative metabolism of doxorubicin (DOX) and daunorubicin (DAU). Both doxorubicin and daunorubicin have been associated with cardiac toxicity in both adults and children. The authors herein suggest that cardioprotective molecules modified by nitroxides and their secondary amine precursors can prevent or diminish the anthracycline-induced cardiomyopathy by accumulating in cardiomiocytes. PMID: 17652823 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626293 Mon, 01 Jan 2007 05:00:00 +0100 1626293 http://www.medworm.com/index.php?rid=1626292&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17901560%26dopt%3DAbstract Authors: Flaherty MP, Brown M, Grupp IL, Schultz JE, Murphree SS, Jones WK Although studies have shown that endothelial nitric oxide synthase (eNOS) homozygous knockout mice (eNOS-/-) develop left ventricular (LV) hypertrophy, well compensated at least to 24 wks, uncertainty still exists as to the cardiac functional and molecular mechanistic consequences of eNOS deficiency at later time-points. To bridge the gap in existent data, we examined whole hearts from eNOS-/- and age-matched wild-type (WT) control mice ranging in age from 18 to 52 wks for macroscopic and microscopic histopathology, LV mRNA and protein expression using RNA Dot blots and Western blots, respectively, and LV function using isolated perfused work-performing heart preparations. Heart weight to body weight (HW/BW in m... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626292 Mon, 01 Jan 2007 05:00:00 +0100 1626292 http://www.medworm.com/index.php?rid=1626291&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17901561%26dopt%3DAbstract In conclusion, this comprehensive transcript profile provides important insights into critical targets and molecular adaptations that characterize the persistent cardiomyopathy associated with long-term exposure to DOX. PMID: 17901561 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626291 Mon, 01 Jan 2007 05:00:00 +0100 1626291 http://www.medworm.com/index.php?rid=1626290&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17901562%26dopt%3DAbstract This study compared the effects of mainstream smoke from Quest, Eclipse, and 2R4F reference cigarettes on the development of atherosclerosis in apolipoprotein E-deficient (apoE -/-) mice. Mice were exposed to smoke from four cigarette types for 12 weeks beginning at age of 12 weeks, and in a separate study for 8 weeks, beginning at age of 8 weeks. In both studies, mice exposed to smoke from high-nicotine, high-tar Quest 1, and 2R4F cigarettes developed greater areas of lipid-rich aortic lesions than did non-smoking controls. Exposure to smoke from the lower-nicotine products, Eclipse, and Quest 3, was associated with smaller lesion areas, but animals exposed to smoke from all of the tested types of cigarette had larger lesions than did control animals not exposed to smoke. Urinary levels o... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626290 Mon, 01 Jan 2007 05:00:00 +0100 1626290 http://www.medworm.com/index.php?rid=1626289&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17901563%26dopt%3DAbstract This study was undertaken to determine if the endogenously expressed NQO1 in cardiovascular cells could scavenge O2(.-). We observed that NQO1 was highly expressed in cardiovascular cells, including rat aortic smooth muscle A10 and cardiac H9c2 cells, as well as normal human aortic smooth muscle and endothelial cells. NQO1, but not SOD in the cardiovascular cells was highly inducible by 3H-1,2-dithiole-3-thione (D3T). Cytosols from H9c2 and human aortic smooth muscle cells (HASMCs) were isolated to determine the O2(.-) scavenging ability of the endogenously expressed NQO1 by using pyrogallol autooxidation assay. We showed that cytosols from the above cells inhibited pyrogallol autooxidation in an NADPH or NADH-dependent manner. The NADH/NADPH-dependent inhibition of pyrogallol autooxidatio... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626289 Mon, 01 Jan 2007 05:00:00 +0100 1626289 http://www.medworm.com/index.php?rid=1626288&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17901564%26dopt%3DAbstract We report myocarditis associated with ingestion of a large dose of camphor. The electrocardiogram revealed prolonged QRS duration and QTc interval. 2D- Echo images revealed features of acute myocarditis. The changes were transient and resolved in a short time while the patient was on supportive therapy. The medicinal uses of camphor are unsupported by evidence and safer, more effective alternatives exist. Its use in household products and edibles should be discouraged. PMID: 17901564 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626288 Mon, 01 Jan 2007 05:00:00 +0100 1626288 http://www.medworm.com/index.php?rid=1626287&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17943461%26dopt%3DAbstract CONCLUSIONS: The expression of Fas ligand in the myocardium, as identified in HIV-positive patients, might increase the susceptibility to HAART-induced cardiomyopathy due to activation of apoptotic pathways, resulting in cardiac dilation and dysfunction. PMID: 17943461 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626287 Mon, 01 Jan 2007 05:00:00 +0100 1626287 http://www.medworm.com/index.php?rid=1626286&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17943462%26dopt%3DAbstract Authors: Lipniacki T, Kimmel M In the article, we discuss the state of art and perspectives in deterministic and stochastic models of NFkappaB regulatory module. The NFkappaB is a transcription factor controlling various immune responses including inflammation and apoptosis. It is tightly regulated by at least two negative feedback loops involving IkappaBalpha and A20. This mode of regulation results in nucleus-to-cytoplasm oscillations in NFkappaB localization, which induce subsequent waves of NFkappaB responsive genes. Single cell experiments carried by several groups provided comprehensive evidence that stochastic effects play an important role in NFkappaB regulation. From modeling point of view, living cells might be considered noisy or stochastic biochemical reactors. In eukaryoti... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626286 Mon, 01 Jan 2007 05:00:00 +0100 1626286 http://www.medworm.com/index.php?rid=1626285&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17955387%26dopt%3DAbstract Authors: Arzuaga X, Reiterer G, Majkova Z, Kilgore MW, Toborek M, Hennig B Exposure to polychlorinated biphenyls (PCBs) can activate inflammatory responses in vascular endothelial cells. Activation of peroxisome proliferator-activated receptors (PPARs) by nutrients or synthetic agonists has been shown to block pro-inflammatory responses both in vitro and in vivo. Here we demonstrate that activation of PPARalpha by synthetic agonists can reduce 3,3'4,4'-tetrachlorobiphenyl (PCB77)-induced endothelial cell activation. Primary vascular endothelial cells were pretreated with the PPARalpha ligands fenofibrate or WY14643 followed by exposure to PCB77. PPARalpha activation protected endothelial cells against PCB77-induced expression of the pro-inflammatory proteins vascular cell adhesion mole... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626285 Mon, 01 Jan 2007 05:00:00 +0100 1626285 http://www.medworm.com/index.php?rid=1626284&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17960499%26dopt%3DAbstract This study was designed to evaluate the effect of IGF-1 on migration, proliferation, and signaling mechanisms in VSMCs from early (3-5) to late (20-22) passages. Migration, proliferation, and cell survival were measured using monolayer wounding, 3[H]-thymidine incorporation and MTT assay, respectively. Akt and ERK, which are critical to proliferation, differentiation and migration, were examined using Western blot analysis. DCF-DA fluorescence was used to quantify Reactive Oxygen Species (ROS) production. Late-passage VSMCs exhibited significantly higher basal cell proliferation and enhanced sensitivity to IGF-1-stimulated migration compared to cells from early-passages. Phosphorylated Akt and ERK levels were significantly higher in late-passage cells compared to early-passage, which was f... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626284 Mon, 01 Jan 2007 05:00:00 +0100 1626284 http://www.medworm.com/index.php?rid=1626283&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17968679%26dopt%3DAbstract In conclusion, constitutive CYP1A1 mRNA expression is dependent on AHR and is reduced by hypoxia via a HIF-2alpha-dependent mechanism, which may be mediated by a HIF-2alpha-dependent reduction of AHR expression. PMID: 17968679 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626283 Mon, 01 Jan 2007 05:00:00 +0100 1626283 http://www.medworm.com/index.php?rid=1626282&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17990128%26dopt%3DAbstract Authors: Zajdel RW, Thurston H, Prayaga S, Dube S, Poiesz BJ, Dube DK The cardiac lethal mutation in Mexican axolotl (Ambystoma mexicanum) results in a lack of contractions in the ventricle of mutant embryos. Previous studies have demonstrated that tropomyosin, a component of thin filaments, is greatly reduced in mutant hearts lacking myofibril organization. Confocal microscopy was used to examine the structure and comparative amount of tropomyosin at heartbeat initiation and at a later stage. The formation of functional sarcomeres coincided with contractions in normal hearts at stage 35. A-bands and I-bands were formed at stage 35 and did not change at stage 39. The widening of Z-bodies into z-lines was the main developmental difference between stage 35 and 39 normal hearts. Relative ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626282 Mon, 01 Jan 2007 05:00:00 +0100 1626282 http://www.medworm.com/index.php?rid=1626281&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17990129%26dopt%3DAbstract In conclusion, similar to male rats long-term ethanol consumption in gonad-intact and OVX female rats is associated with the development of a dilated cardiomyopathy. PMID: 17990129 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626281 Mon, 01 Jan 2007 05:00:00 +0100 1626281 http://www.medworm.com/index.php?rid=1626335&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16845178%26dopt%3DAbstract Authors: Li XA, Everson W, Smart EJ Endothelial nitric oxide synthase (eNOS) is an enzyme that plays a critical role in normal cardiovascular function. Caveolae are structures within the surface membrane of cells in which many signaling and second messenger pathways, including nitric oxide, are regulated. Many interventions in cardiovascular disease act, in part, either by changing factors that directly influence eNOS, or by changing a complex set of proteins that act indirectly on caveolae, to alter eNOS activity. In this review, we will focus on the regulation of eNOS activity by circulating factors which are altered in cardiovascular disease and the effects of pharmacological interventions that act partially through effects on eNOS. PMID: 16845178 [PubMed - indexed for MEDLINE] ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626335 Sun, 01 Jan 2006 05:00:00 +0100 1626335 http://www.medworm.com/index.php?rid=1626334&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16845179%26dopt%3DAbstract Authors: Bunderson M, Pereira F, Schneider MC, Shaw PK, Coffin JD, Beall HD Long-term exposure to arsenic in drinking water has been linked to cancer and other health effects, including cardiovascular disease. Arsenic in the environment is found in combination with a range of metals that could influence its toxicity. Manganese, in particular, is a metal that is typically found in conjunction with arsenic in contaminated groundwater. Peroxynitrite is a powerful oxidant formed from the reaction between nitric oxide and superoxide anion. Arsenic has been shown to increase the formation of peroxynitrite in bovine aortic endothelial cells (BAECs) and promote the formation of 3-nitrotyrosine (3-NY) in the atherosclerotic plaque of ApoE-/-/LDLr-/- mice. Arsenic exposure also increases leukotr... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626334 Sun, 01 Jan 2006 05:00:00 +0100 1626334 http://www.medworm.com/index.php?rid=1626333&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16845180%26dopt%3DAbstract The objective of this study was to characterize acute coronary artery injury evoked by the endothelin A receptor (ETAR) antagonist, CI-1034. Male dogs (n = 5) were intravenously administered CI-1034 at 120 mg/kg for 4 d. Control animals (n = 3) received vehicle. Macroscopically, drug-related hemorrhage was observed in the right coronary groove and atrium. Histologically, drugrelated coronary changes were characterized as medial hemorrhage and necrosis, with mixed inflammatory-cell infiltrates in the adventitia and media. Immunohistochemistry staining indicated increased expression of inducible nitric oxide synthase (iNOS), cleaved caspase-3, and S100A8/A9 (within in monocytes and neutrophils) proteins in coronary arteries of CI-1034-treated animals. However, there were similar expression l... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626333 Sun, 01 Jan 2006 05:00:00 +0100 1626333 http://www.medworm.com/index.php?rid=1626332&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16845181%26dopt%3DAbstract Authors: Ueno H, Pradhan S, Schlessel D, Hirasawa H, Sumpio BE Investigation into the etiology of atherosclerosis has identified cigarette smoking as a major risk factor. Although it has been established that cellular adhesion molecule expression on endothelial cells is stimulated by nicotine, the mechanism by which this occurs is not clear. The aim of this study was to determine the effect of nicotine on the expression of the adhesion molecules, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in endothelial cells and to determine the involvement of important known intermediaries, protein kinase C (PKC), p38 mitogen-activated protein kinase (p38 MAPK), and the transcription factors NF-kappaB and AP-1. Human umbilical vein endothelial cells (HUVEC) ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626332 Sun, 01 Jan 2006 05:00:00 +0100 1626332 http://www.medworm.com/index.php?rid=1626331&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16845182%26dopt%3DAbstract Authors: Soloviev MV, Hamlin RL, Shellhammer LJ, Barrett RM, Wally RA, Birchmeier PA, Schaefer GJ Interpretation of the dynamic cardiovascular parameters on safety pharmacology studies is a challenging process; sometimes, it is difficult to separate normal physiological variations from the effects of the test drug. Data from healthy control Beagle dogs (41 males and 25 females) implanted with telemetry transmitters (DSI, St. Paul, MN) from 34 studies performed from 2003 to 2005 were analyzed. Telemetry data were collected for a 30-s period every 10 min for 24 h after sham dosing. One-hour averages were analyzed. Prior to dosing, heart rate (HR) was 95.6 +/- 26.6 bpm; mean, systolic, and diastolic blood pressure (BP) were 105.3 +/- 12.7, 142.5 +/- 5.3, and 84.7 +/- 11.1 mmHg, respective... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626331 Sun, 01 Jan 2006 05:00:00 +0100 1626331 http://www.medworm.com/index.php?rid=1626330&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16845183%26dopt%3DAbstract In this study, we evaluated the effects of such an association on the cardiovascular parameters in anesthetized dogs. Bupropion, either alone or together with nicotine, had no significant effect on the cardiac index (CI; 4.7 +/- 0.2 vs 4.3 +/- 0.1 and 3.5 +/- 0.3 vs 3.4 +/- 0.3 L x min(-1) x m(2), respectively; mean +/- SEM) and mean arterial pressure (MAP; 134 +/- 5.0 vs 145 +/- 11.0 and 118 +/- 5.0 vs 133 +/- 10.5 mmHg, respectively). There was a slight but significant increase in the systemic vascular resistance index (SVRI; 2,165 +/- 93 vs 2,645 +/- 126 and 2,335 +/- 100 vs 2,737 +/- 200 dyn x cm(-5)m(-2), respectively). However, there was a significant increase in the mean pulmonary artery pressure (MPAP; 20 +/- 0.8 vs 25 +/- 1.6 and 18 +/- 1.3 vs 25 +/- 1.6 mmHg, respectively; p <... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626330 Sun, 01 Jan 2006 05:00:00 +0100 1626330 http://www.medworm.com/index.php?rid=1626329&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16845184%26dopt%3DAbstract This study was designed to examine whether UFPs could exert a direct effect on the cardiovascular system without dependence upon lung-mediated responses. The direct effects of UFPs were determined in normal rats (infused intravenously with UFPs), and in the isolated Langendorff perfused rat heart. UFPs from either ambient air (UFAAs) or diesel engine exhaust (UFDGs) were studied. Infusion of UFDGs prepared in our laboratory caused ventricular premature beats (VPBs) in 2 of 3 rats in vivo. Ejection fraction increased slightly (approximately 4.5%) in rats receiving UFPAA and was unchanged in the UFDG and saline groups in vivo. In the isolated rat heart, perfused according to Langendorff, UFDGs caused a marked increase in left-ventricular end-diastolic pressure (LVEDP; from 12.0 +/- 4.6 mmHg ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626329 Sun, 01 Jan 2006 05:00:00 +0100 1626329 http://www.medworm.com/index.php?rid=1626328&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17303916%26dopt%3DAbstract We report on a 45- yr-old female patient who sustained acute inferior MI 8 h following Cassia italica ingestion. Subsequently, cardiac catheterization revealed patent coronary arteries. We assume that, in this case, MI may partly be related herbal ingestion. Further studies and public awareness of this complication in certain communities are needed. PMID: 17303916 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626328 Sun, 01 Jan 2006 05:00:00 +0100 1626328 http://www.medworm.com/index.php?rid=1626327&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17303917%26dopt%3DAbstract Authors: McLean MD, Zajdel RW, Dube S, Thurston H, Dube DK In the axolotl, Ambystoma mexicanum, a simple, recessive cardiac-lethal mutation in gene "c" results in the hearts of c/c homozygous animals being deficient in sarcomeric tropomyosin (TM) and failing to form mature myofibrils. Subsequently, the mutant hearts do not beat. A three-step model of myofibril assembly recently developed in cell culture prompted a reassessment of the myofibril assembly process in mutant hearts using a relatively new late marker for thin filament assembly, tropomodulin (Tmod). This is, to the best of our knowledge, the first report of tropomodulin in an amphibian system. Tropomodulin antibodies were immunolocalized to the ends of the thin filaments. Tropomodulin was also found in discrete punctate spots... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626327 Sun, 01 Jan 2006 05:00:00 +0100 1626327 http://www.medworm.com/index.php?rid=1626326&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17303918%26dopt%3DAbstract Authors: Xie A, Walker NJ, Wang D The effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on action potential and afterdepolarizations were studied in rat ventricular myocytes using nystatin-perforated whole-cell patch-clamp technique. TCDD treatment, in the concentration range of 1 to 100 nM, significantly prolonged action potential duration measured at 90% of repolarization (APD90). The triggered delayedafterdepolarizations (DADs) were observed in 6 out of 8 cells after exposure of TCDD (10 nM). In the presence of isoproterenol (ISO, 10 nM) or Bay K 8644 (1 microM), TCDD (10 nM) markedly augmented the amplitude and frequency of the arrhythmogenic DADs and triggered sustained spontaneous firings in ventricular myocytes. Voltage-clamp data indicated that TCDD (10 nM) exposure signifi... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626326 Sun, 01 Jan 2006 05:00:00 +0100 1626326 http://www.medworm.com/index.php?rid=1626325&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17303919%26dopt%3DAbstract Authors: Brasier AR Nuclear factor (NF)-kappaB is a family of seven structurally related transcription factors that play a central role in cardiovascular growth, stress response, and inflammation by controlling gene network expression. Although the NF- kappaB subunits are ubiquitously expressed, their actions are regulated in a celltype and stimulus-specific manner, allowing for a diverse spectrum of effects. For example, NF-kappalB is activated by cytokines, reactive oxygen species, bacterial cell wall products, vasopressors, viral infection, and DNA damage. Recent molecular dissection of its mechanisms for activation has shown that NF-kappalB can be induced by the so-called "canonical" and "noncanonical" pathways, leading to distinct patterns in the individual subunits activated and ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626325 Sun, 01 Jan 2006 05:00:00 +0100 1626325 http://www.medworm.com/index.php?rid=1626324&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17303920%26dopt%3DAbstract Authors: Wang L, Yang Y, Dwivedi S, Xu Y, Chu ET, Li J, Fitchett K, Boor PJ Tolerance to clinically important organic nitrates such as nitroglycerin (NTG) has been experimentally related to endothelial dysfunction and vascular oxidative stress. Anti-oxidant enzymes such as the glutathione-S-transferases GSTs) could potentially play a protective role in NTG tolerance. Our previous work showed that an alpha-class glutathione-S-transferase (GSTA4-4) defends against oxidative damage in the vascular wall; therefore, we asked whether overexpression of GSTA4-4 in endothelial cells and smooth muscle cells might alter the development of tolerance to NTG. Stable transfections of mouse pancreatic islet endothelial cells (MS1) with cDNA of mGSTA4-4, and human fetal aortic vascular smooth muscle ce... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626324 Sun, 01 Jan 2006 05:00:00 +0100 1626324 http://www.medworm.com/index.php?rid=1626323&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17303921%26dopt%3DAbstract Authors: Soloviev MV, Hamlin RL, Barrett RM, Chengelis CP, Schaefer GJ The ICH S7B guideline specifically requests the evaluation of the QT interval in in vivo models as an accepted risk factor for fatal tachyarrythmias. While it recommends correcting the QT interval for heart rate (HR), it also concedes that such corrections can yield misleading results. Data acquired from 40 cynomolgus monkeys (CM) and 66 Beagle dogs (BD) on 64 and 166 episodes, respectively, of 25-h ECG data collection in healthy control group animals were analyzed for this publication. The total number of ECGs evaluated was 10,761 (CM) and 24,882 (BD). The two species appear to have some difference in cardiac repolarization regulatory mechanisms. CM are more subject to diurnal fluctuations of autonomic nervous tone... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626323 Sun, 01 Jan 2006 05:00:00 +0100 1626323 http://www.medworm.com/index.php?rid=1626322&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17347527%26dopt%3DAbstract The objective of the present work was to investigate whether heart mitochondria isolated from rats submitted to ET with or without ADR treatment were more or less susceptible to in vitro anoxia-reoxygenation (AR) when compared with control rats. Twenty-four male Wistar rats were assigned into four groups (n = 6 each): control (C), ADR 20 mg-kg-1), 14 wk ET (T), and T+ADR. Respiratory parameters and oxidative damage were determined before and after 1 min anoxia followed by 4 min reoxygenation. Basal heat shock proteins (HSPs)60 and -70 and antioxidant enzymes' activity were measured. ADR by itself decreased state 3 and respiratory control ratio (RCR), as opposed to ET by itself, which improved state 3 and RCR. As expected, AR impaired state 3 and 4, RCR, and ADP/O in the C group (p > 0.0... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626322 Sun, 01 Jan 2006 05:00:00 +0100 1626322 http://www.medworm.com/index.php?rid=1626321&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17347528%26dopt%3DAbstract This study was designed to examine the effect of transgenic overexpression of the free radical scavenger metallothionein on alcohol-induced cardiac contractile dysfunction. Wild-type FVB and metallothionein mice were placed on a 4% alcohol or control diet for 12 wk. Cardiac contractile function was evaluated in cardiomyocytes including peak shortening (PS), time-to-peak shortening, time-to-90% relengthening (TR90), maximal velocity of shortening/relengthening (+/-dL/dt), intracellular Ca2+ rise (change in fura-2 fluorescent intensity [DeltaFFI]) and intracellular Ca2+ decay rate. Intracellular Ca2+ cycling proteins including sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a), Na+-Ca2+ exchanger (NCX) and phospholamban were assessed using Western blot analysis. Alcohol intake depressed PS, ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626321 Sun, 01 Jan 2006 05:00:00 +0100 1626321 http://www.medworm.com/index.php?rid=1626320&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17347529%26dopt%3DAbstract Authors: Khanna D, Kan H, Failinger C, Jain AC, Finkel MS A growing body of clinical and experimental literature supports a strong association between emotional stress and adverse outcomes from CVD. Effects of emotional stress on coronary blood flow and cardiac arrhythmias provide only a partial explanation. A direct impact of emotional stress on myocardial function has recently received attention as a result of reports of patients presenting with new onset of unexplained reversible heart failure following episodes of emotional stress. Potential mechanisms responsible for myocardial dysfunction following emotional stress remain to be elucidated. This review will explore potential pathophysiologic mechanisms linking emotional stress to adverse cardiovascular outcomes beginning with prim... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626320 Sun, 01 Jan 2006 05:00:00 +0100 1626320 http://www.medworm.com/index.php?rid=1626319&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17347530%26dopt%3DAbstract Authors: Campen MJ, McDonald JD, Reed MD, Seagrave J Fresh vehicular emissions potentially represent a ubiquitous environmental concern for cardiovascular health. We compared electrocardiographic effects of fresh gasoline engine emissions with resuspended paved road dust in a mouse model of coronary insufficiency. Apolipoprotein E (ApoE)-/- mice on a high fat diet were exposed by whole-body inhalation to either gasoline emissions at 60 microg/m3 particulate matter (PM), an equivalent atmosphere with particles filtered out of the whole exhaust, or paved road dust at 0.5 and 3.5 mg /m3 for 6 h/d for 3 d. Radiotelemetry recordings of electrocardiogram (ECG) were analyzed for changes in T-wave morphology (QT interval, T-wave amplitude, and T-wave Area). Following exposures, lung lavage and... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626319 Sun, 01 Jan 2006 05:00:00 +0100 1626319 http://www.medworm.com/index.php?rid=1626318&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17347531%26dopt%3DAbstract Authors: Herman E, Zhang J, Knapton A, Lipshultz SE, Rifai N, Sistare F In rats, high doses of isoproterenol (Iso) have caused acute myocardial lesions and increased serum levels of cardiac troponin T (cTnT). We determined whether low doses of Iso also cause cardiac alterations and whether monitoring cTnT levels could detect this injury. Rats received 8 to 500 microg/kg Iso and were followed for 3 to 48 h. Lesion severity was scored from 0 to 5. Within 3 h, mean cTnT was elevated in all 29 rats receiving 8, 16, 32, or 64 microg/kg Iso (0.20 to 0.28 ng/mL ), but minimal lesions occurred in only two animals. However, by 6 h, cardiac lesions and increases in serum cTnT (mean = 0.21 to 0.23 ng/mL) were observed in all 14 rats receiving 32 or 64 microg/kg Iso. Doses of 125, 250, or 500 micr... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626318 Sun, 01 Jan 2006 05:00:00 +0100 1626318 http://www.medworm.com/index.php?rid=1626368&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15738580%26dopt%3DAbstract In this study, we have made an expression construct, pEGFP.TPM4alpha.E-L-FLAG, that, on transfection into normal and mutant axolotl hearts in organ culture, expresses GFP.TPM4alpha.E-L-FLAG fusion protein in which both the N- and C-termini of TPM4alpha are being extended. TPM4alpha is one of the three tropomyosins expressed in normal axolotl hearts. Both confocal and electron microscopic analyses show that this modified sarcomeric tropomyosin can form organized myofibrils in axolotl hearts. PMID: 15738580 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626368 Sat, 01 Jan 2005 05:00:00 +0100 1626368 http://www.medworm.com/index.php?rid=1626367&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15738581%26dopt%3DAbstract Authors: Dong F, Zhang X, Li SY, Zhang Z, Ren Q, Culver B, Ren J Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases, although the mechanism leading to vascular dysfunction is not clear. The aim of this study was to examine the effect of homocysteine (Hcy) on oxi-dative stress and apoptosis in human umbilical vein endothelial cells (HUVECs). HUVECs were challenged for 24 h with Hcy (10 microM-3 mM) in the presence of various stress signaling inhibitors, including the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin (100 microM), the p38 mito-gen-activated protein kinase inhibitor SB203580 (2.5 microM), the extracellular signal-regulated kinase inhibitor U0126 (2.5 microM), the stress-activated protein kinase (SAPK)/c-Jun NH2-term... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626367 Sat, 01 Jan 2005 05:00:00 +0100 1626367 http://www.medworm.com/index.php?rid=1626366&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15738582%26dopt%3DAbstract In conclusion, TCR Vbeta8.1 peptide induced immunoregulation, and inhibited or reduced coxsackievirus B3-induced cardiopathology in aged mice. PMID: 15738582 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626366 Sat, 01 Jan 2005 05:00:00 +0100 1626366 http://www.medworm.com/index.php?rid=1626365&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15738583%26dopt%3DAbstract This study investigated the effects of chronic arsenic exposure on vessel growth and expression of angiogenic and tissue remodeling genes in cardiac tissues. Male mice were exposed to low to moderately high levels of arsenite (AsIII) for 5, 10, or 20 wk in their drinking water. Vessel growth in Matrigel implants was tested during the last 2 wk of each exposure period. Implant vascularization increased in mice exposed to 5-500 ppb AsIII for 5 wk. Similar increases were seen following exposure to 50-250 ppb of AsIII over 20 wk, but the response to 500 ppb decreased with time. RT-PCR analysis of cardiac mRNA revealed differential expression of angiogenic or tissue remodeling genes, such as vascular endothelial cell growth factor (VEGF), VEGF receptors, plasminogen activator inhibitor-1, endot... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626365 Sat, 01 Jan 2005 05:00:00 +0100 1626365 http://www.medworm.com/index.php?rid=1626364&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15738584%26dopt%3DAbstract We report a German shepherd (i.e., dog 1) and a poodle (i.e., dog 2) that were referred to our cardiology unit after receiving pimobendan for 10 and 5 mo, respectively. In both dogs, conventional echo-Doppler examination demonstrated mitral valve regurgitation and myocardial hypertrophy. Tissue Doppler imaging (TDI) was performed in the first case and revealed an abnormal relaxation phase. After the first examination, pimobendan administration was stopped in both cases and dogs were re-examined 3 and 1 mo later, respectively. Mitral valve regurgitation assessed by echocardiography decreased in both dogs, and the systolic heart murmur disappeared in dog 1. Importantly, most echocardiographic and TDI parameters tended to normalize in dog 1, suggesting, at least partial reversal of both myoca... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626364 Sat, 01 Jan 2005 05:00:00 +0100 1626364 http://www.medworm.com/index.php?rid=1626363&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15738585%26dopt%3DAbstract In conclusion, this study suggests that ambasilide has multichannel blocking properties including beta-adrenergic antagonism. PMID: 15738585 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626363 Sat, 01 Jan 2005 05:00:00 +0100 1626363 http://www.medworm.com/index.php?rid=1626362&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15738586%26dopt%3DAbstract The objective of this work was to test the hypothesis that bile acids are toxic to heart mitochondria for concentrations that are relevant for cholestasis. Heart mitochondria were isolated from rat and subjected to incubation with selected bile acids (litocholic acid [LCA], deoxycholic acid [DCA], chenodeoxycholic acid [CDCA], glycochenodeoxycholic acid [GCDC], taurodeoxycholic acid [TDCA], and glycoursodeoxycholic acid [GUDC]). We observed that the most toxic bile acids were also the most lipophilic ones (LCA, DCA, and CDCA), inducing a decrease on state 3 respiration, respiratory control ratio, and membrane potential and causing the induction of the mitochondrial permeability transition. GUDC was the bile acid with lower indexes of toxicity on isolated heart mitochondria.The results of t... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626362 Sat, 01 Jan 2005 05:00:00 +0100 1626362 http://www.medworm.com/index.php?rid=1626361&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D15738587%26dopt%3DAbstract This study examines the predominant embry-onic axolotl TPM-4 type tropomyosin (TPM4alpha), containing a conservative re- placement of glutamic acid for aspartic acid at the clinically important 175 site. In this study, ATmC-3 (TPM4alpha) promoted formation of organized myofibrils in hearts without endogenous tropomyosin. Site-directed mutagenesis of 175 glutamic acid with 175 glutamine or 175 lysine was toxic to the formation of organized myofibrils in mutant hearts in the absence of endogenous tropo-myosin. Cationic liposome co-transfection of both wild-type tropomyosin and Glu175Gln.TPM4alpha cDNA formed organized myofibrils in mutant hearts. A construct with GFP.Glu175Gln.TPM4alpha cDNA was used to confirm expression of the mutant fusion protein. Mutation at the 175 site in TPM4alpha ty... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626361 Sat, 01 Jan 2005 05:00:00 +0100 1626361 http://www.medworm.com/index.php?rid=1626360&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16046786%26dopt%3DAbstract Authors: Mastin JP The last decade has seen a remarkable growth in the evidence establishing exposure to environmental agents as a risk factor for cardiovascular disease (CVD). Most of this has come from research linking exposure to ambient particulate matter with CVD, although more recent evidence suggests that the ozone might also be contributing factor. Research on the cardiovascular toxicity of other pollutants, notably arsenic, has also grown during this period. In addition to their effects in adults, environmental agents, such as dioxin, have also been shown to adversely affect development of the heart in laboratory animals. Taken together, these results suggest that environmental exposure must be considered as an important risk factor for CVD and that further research to determi... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626360 Sat, 01 Jan 2005 05:00:00 +0100 1626360 http://www.medworm.com/index.php?rid=1626359&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16046787%26dopt%3DAbstract Authors: Doris PA, Fornage M Gene expression can be now assessed quantitatively and comprehensively. In addition to reflecting the specialized differentiation of the cell or tissue type from which gene expression is sampled, it also manifests patterns determined by inheritance. Thus gene expression is a phenotypic trait, at least when assessed comprehensively. This trait shows familial aggregation and segregation patterns indicative of an inherited contribution. The molecular evolution of genes includes mutations affecting regulatory sequences in the genome that influence gene expression in cis and in trans. Such mutations may increase in frequency in a population either by genetic drift or by selection. Traits of gene expression, acting alone or in concert with other gene expression t... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626359 Sat, 01 Jan 2005 05:00:00 +0100 1626359 http://www.medworm.com/index.php?rid=1626358&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16046788%26dopt%3DAbstract Authors: Imumorin IG, Dong Y, Zhu H, Poole JC, Harshfield GA, Treiber FA, Snieder H The case for a gene-environment interaction model of stress-induced hypertension is detailed in this paper. We hypothesize that repeated exposure to stress in combination with an environmentally and/or genetically mediated susceptibility may lead to the development of essential hypertension. Previously, we reviewed the evidence for a genetic influence on the two major intermediate phenotypes of our model: cardiovascular reactivity to psychological stress and stress-induced sodium retention, representing the cardiovascular and renal stress response, respectively. Here we first describe how genes underlying the physiological systems mediating the stress response of heart, vasculature, and kidney (i.e., th... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626358 Sat, 01 Jan 2005 05:00:00 +0100 1626358 http://www.medworm.com/index.php?rid=1626357&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16046789%26dopt%3DAbstract Authors: Kurland L, Liljedahl U, Lind L Hypertension is prevalent, affecting approx 20--25% of the adult population in the Western world. Primary hypertension is a multifactorial, complex disorder where many genes and genetic variants are assumed to interact with environmental factors in order to produce the specific blood pressure level for a given individual. Family and twin studies show that between 30 and 60% of blood pressure variation is determined by genetic factors. Monogenic disorders of hypertension are rare and do not explain blood pressure variability in the population at large. Obvious candidate genes for the study of hypertension are those that encode components of a blood pressure regulating system targeted by an antihypertensive drug, or those that are involved in count... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626357 Sat, 01 Jan 2005 05:00:00 +0100 1626357 http://www.medworm.com/index.php?rid=1626356&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16046790%26dopt%3DAbstract Authors: Cambien F, Tiret L It is generally considered that the genetics of atherosclerosis and its complications involves a large number of genes with common alleles having weak effects on disease risk but possibly interacting with each other and with non-genetic factors. In such a complex system, absence of marginal effects (effects of polymorphisms considered one at a time) is insufficient to exclude the implication of a polymorphism on disease risk. Investigating polymorphisms and even genes one by one is no longer appropriate. It is necessary to focus on biological systems and integrate the contribution of genetic as well as non-genetic factors and their interactions. Hopefully, system genetics will ultimately improve our understanding of the genetic architecture of complex traits... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626356 Sat, 01 Jan 2005 05:00:00 +0100 1626356 http://www.medworm.com/index.php?rid=1626355&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16046791%26dopt%3DAbstract Authors: Hennig B, Reiterer G, Majkova Z, Oesterling E, Meerarani P, Toborek M We hypothesize that nutrition can modulate the toxicity of environmental pollutants and thus modulate health and disease outcome associated with chemical insult. There is now increasing evidence that exposure to persistent organic pollutants, such as PCBs, can contribute to the development of inflammatory diseases such as atherosclerosis. Activation, chronic inflammation, and dysfunction of the vascular endothelium are critical events in the initiation and acceleration of atherosclerotic lesion formation. Our studies indicate that an increase in cellular oxidative stress and an imbalance in antioxidant status are critical events in PCB-mediated induction of inflammatory genes and endothelial cell dysfunction... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626355 Sat, 01 Jan 2005 05:00:00 +0100 1626355 http://www.medworm.com/index.php?rid=1626354&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16046792%26dopt%3DAbstract Authors: Ghesquiere SA, Hofker MH, de Winther MP Phospholipases have received wide attention as it has become clear that several isoforms of the phospholipase family play a role in onset and progression of atherosclerosis. The release of free fatty acids (FFA) and lysophospholipids (lysoPL) provide metabolites for various inflammatory pathways, and this has been considered the main mechanism of phospholipase-driven inflammation. However, generation of FFA and lysoPL are only part of the story. The induction of low-density phospholipoprotein (LDL) aggregation and accumulation, receptor binding, co-regulation with cyclooxygenase (COX) and lip-oxygenase (LO) pathways, internalization through heparan sulfate proteoglycan (HSPG) shuttling, and crosstalk between phospholipases all play a rol... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626354 Sat, 01 Jan 2005 05:00:00 +0100 1626354 http://www.medworm.com/index.php?rid=1626353&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16046793%26dopt%3DAbstract Authors: Jones WK, Brown M, Wilhide M, He S, Ren X The transcription factor NF-kappaB regulates a wide variety of biological effects in diverse cell types and organs, particularly stress and adaptive responses. Recently, it has become recognized that NF-kappaB and its upstream regulator tumor necrosis factor (TNF)-alpha regulate specific antithetical effects. For instance, in the heart, NF-kappaB has been found to be required for development of late preconditioning against myocardial infarction and yet is critically involved in mediating cell death after ischemia/reperfusion injury. There remains a bias that NF-kappaB is a "general" transcription factor that is activated by a plethora of stimuli, including neurohormonal, pathophysiological, and stress stimuli, and affects regulation of... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626353 Sat, 01 Jan 2005 05:00:00 +0100 1626353 http://www.medworm.com/index.php?rid=1626352&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16046794%26dopt%3DAbstract Authors: Heideman W, Antkiewicz DS, Carney SA, Peterson RE Model systems are a mainstay in toxicological research. Zebrafish are rapidly becoming an important model organism for studying vertebrate development. The advantages of zebrafish: short reproductive cycle, production of numerous transparent, synchronously developing embryos, low cost, and standardization make zebrafish an attractive model for toxicologists as well. The use of these fish to study heart development has moved forward very rapidly, laying the groundwork for studying the effects of chemicals on cardiac development and function. Here we describe approaches that can be used to study cardiac toxicity in developing zebrafish, focusing on examples where zebrafish embryos have been especially useful in understanding the ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626352 Sat, 01 Jan 2005 05:00:00 +0100 1626352 http://www.medworm.com/index.php?rid=1626351&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16046795%26dopt%3DAbstract Authors: Ivnitski-Steele I, Walker MK The formation of new blood vessels, neovascularization, occurs by two unique processes: vasculogenesis, the de novo assembly of blood vessels from angioblast precursors, and angiogenesis, the formation of new capillary sprouts from preexisting vessels. There are many potential targets by which environmental pollutants may inhibit neovascularization and thus there are many possible phenotypic outcomes. Two examples of environmental pollutants that have been demonstrated to inhibit neovascularization include 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a prototypical halogenated aromatic hydrocarbon, and constituents found in environmental tobacco smoke. Studies have shown that TCDD disrupts neoangiogenesis by inhibiting the expression of angiogenic s... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626351 Sat, 01 Jan 2005 05:00:00 +0100 1626351 http://www.medworm.com/index.php?rid=1626350&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16046796%26dopt%3DAbstract This study was conducted to characterize spontaneous and chemically-induced rodent heart lesions. A retrospective light-microscopic evaluation was performed on the hearts of F344 rats and B6C3F1 mice from National Toxicology Program studies of six chemicals in which chemically-induced myocardial toxicity was present: oxymetholone, monochloroacetic acid, 3,3'-4,4'- tetrachoroazoxybenzene, diethanolamine, urethane, and methyl bromide. Two myocardial lesions were observed: cardiomyopathy (multifocal myofiber degeneration that could occur spontaneously or as a treatment effect) and degeneration (diffuse myofiber degeneration that was clearly related to treatment). Oxymetholone produced cardiotoxicity that was apparent as an increase in the incidence and average severity of cardiomyopathy. The ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626350 Sat, 01 Jan 2005 05:00:00 +0100 1626350 http://www.medworm.com/index.php?rid=1626349&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16244370%26dopt%3DAbstract Authors: Ramos KS, Partridge CR Scientific and medical evidence over the past 30 years has established striking parallels between atherosclerosis and cancer--pathogenetic relationships that cross the boundaries of fiction into the realm of reason. Both diseases in humans are characterized by uncontrolled regulation of cellular growth and differentiation and share many common genomic targets during the course of growth dysregulation. Such parallels can be reconciled if atherosclerotic plaques are viewed as neoplasms of smooth muscle origin. PMID: 16244370 [PubMed - indexed for MEDLINE] (Source: Cardiovascular Toxicology) Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626349 Sat, 01 Jan 2005 05:00:00 +0100 1626349 http://www.medworm.com/index.php?rid=1626348&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16244371%26dopt%3DAbstract Authors: Berthiaume JM, Oliveira PJ, Fariss MW, Wallace KB Doxorubicin (DOX) is a widely prescribed antineoplastic and although the precise mechanism(s) have yet to be identified, DOX-induced oxidative stress to mitochondrial membranes is implicated in the pathogenic process. Previous attempts to protect against DOX-induced cardiotoxicity with alpha-tocopherol (vitamin E) have met with limited success, possibly as a result of inadequate delivery to relevant subcellular targets such as mitochondrial membranes. The present investigation was designed to assess whether enrichment of cardiac membranes with alpha-ocopherol is sufficient to protect against DOX-induced mitochondrial cardiotoxicity. Adult male Sprague-Dawley rats received seven weekly subcutaneous injections of 2 mg/kg DOX and ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626348 Sat, 01 Jan 2005 05:00:00 +0100 1626348 http://www.medworm.com/index.php?rid=1626347&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16244372%26dopt%3DAbstract Authors: Olson RD, Gambliel HA, Vestal RE, Shadle SE, Charlier HA, Cusack BJ Utilizing a model of chronic doxorubicin cardiomyopathy, this study examines the relationship between changes in expression and function of calcium handling proteins and contractile dysfunction. A possible mechanism to account for this relationship is suggested. New Zealand white rabbits were injected with either doxorubicin (1 mg/kg, twice weekly for 8 wk) or 0.9% NaCl. Gene transcript, protein levels, and the function of several proteins from the left ventricle were assessed. Protein levels of sarcoplasmic reticulum (SR) Ca2+ transporting ATPase (SERCA2a and b), Ca2+ release channel (RYR2), calsequestrin, Na/Ca exchanger, mRNA levels of RYR2, and [3H]-ryanodine binding (B(max)) to RYR2 were significantly dec... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626347 Sat, 01 Jan 2005 05:00:00 +0100 1626347 http://www.medworm.com/index.php?rid=1626346&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16244373%26dopt%3DAbstract Authors: Kralik PM, Ye G, Metreveli NS, Shem X, Donthi RV, Epstein PN Cardiomyopathy is a major cause of mortality for both type 1 and 2 diabetic patients. However, experimental analysis of diabetic cardiomyopathy has focused on type 1 diabetes and there are few reports on cardiomyocyte dysfunction in the widely used type 2 diabetic model, db/db. In the current study, we assessed function in isolated ventricular myocytes from type 1 diabetic OVE26 mice and from type 2 diabetic db/db mice. When compared with their respective control strains, both diabetic models showed significant impairment in contractility, as assessed by percent peak shortening, maximal rate of contraction, and maximal rate of relaxation. The calcium decay rate was also significantly reduced in both types of diabetes... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626346 Sat, 01 Jan 2005 05:00:00 +0100 1626346 http://www.medworm.com/index.php?rid=1626345&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16244374%26dopt%3DAbstract This study is designed to assess the ability of hexo-kinase and elevated ATP to protect cardiomyocyte contractility from hypoxia and diabetes. We used cardiomyocytes from the transgenic mouse Mh, which has cardiac specific expression of yeast hexokinase, to investigate the importance of glucose phosphorylation in the myocyte response to hypoxia and diabetes. Cardiomyocytes were isolated from FVB control and Mh hearts to assess the effects of 2 h of hypoxia on myocyte contractility and ATP content. The protective effect of hexokinase on diabetes was assessed in myocytes from the OVE26 Type I diabetic mouse and in OVE26Mh diabetic mice that carry the hexokinase gene. Overexpression of hexokinase had no effect during aerobic culture, but during hypoxia, hexokinase improved ATP content by 44% ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626345 Sat, 01 Jan 2005 05:00:00 +0100 1626345 http://www.medworm.com/index.php?rid=1626344&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16244375%26dopt%3DAbstract Authors: Tiangco DA, Lattanzio FA, Osgood CJ, Beebe SJ, Kerry JA, Hargrave BY 3,4-Methylenedioxymethamphetamine (MDMA) is an illicit psychoactive drug that has gained immense popularity among teenagers and young adults. The cardiovascular toxicological consequences of abusing this compound have not been fully characterized. The present study utilized a transient transfection/dual luciferase genetic reporter assay, fluorescence confocal microscopy, and gene expression macroarray technology to determine nuclear factor-kappaB (NF-kappaB) activity, intracellular calcium balance, mitochondrial depolarization, and gene transcription profiles, respectively, in cultured rat striated cardiac myocytes (H9c2) exposed to MDMA. At concentrations of 1 x 10(-3) M and 1 x 10(-2) M, MDMA significantly ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626344 Sat, 01 Jan 2005 05:00:00 +0100 1626344 http://www.medworm.com/index.php?rid=1626343&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16244376%26dopt%3DAbstract Authors: Melin A, Bonnet P, Eder V, Antier D, Obert P, Fauchier L Pollution is known to particularly affect patients with respiratory insufficiency and right ventricle abnormalities. We therefore hypothesized that carbon monoxide (CO) at low dose could be involved in cardiovascular disorders in patients with chronic hypoxic pulmonary hypertension secondary to chronic hypoxia. Ten-week-old male and female healthy Dark Agouti rats were randomly divided into two series--untrained (U) and trained (T)--of four groups of 18 animals each. Both U and T series were continuously exposed to ambient air (U(AIR), and T(AIR); n = 16) or air plus 50 ppm CO (U(AIR+CO) and T(AIR+CO); n = 18). Similarly, rats initially subjected to right ventricle hypertrophy secondary to chronic hypoxia (H) were contin... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626343 Sat, 01 Jan 2005 05:00:00 +0100 1626343 http://www.medworm.com/index.php?rid=1626342&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16244377%26dopt%3DAbstract In this study, we tested the hypothesis that multiple ALDH enzymes are inhibited by different NBVs. ALDH2, ALDH3A, and ALDH5A were present in aorta with ALDH2 and ALDH3A localized to the smooth muscle layers. GTN (1 microM) inhibited ALDH2 activity (55 +/- 6% of control) and ablated ALDH3 activity. In contrast, isosorbide-2,5-dinitrate (ISDN, 1 microM) inhibited ALDH3 activity (1.1 +/- 0.4% of control) but did not inhibit ALDH2 activity even up to 50 microM ISDN. In homogenates of rat aorta, GTN (1 microM) inhibited the NAD+-dependent (41 +/- 5% of control) and NADP+-dependent (25 +/- 6% of control) detoxification of HNE. The inhibition of ALDH3A, but not ALDH2, could be prevented by the addition of dithiothreitol. These studies demonstrate that GTN and ISDN possess selectivity for ALDH in... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626342 Sat, 01 Jan 2005 05:00:00 +0100 1626342 http://www.medworm.com/index.php?rid=1626341&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16244378%26dopt%3DAbstract Authors: Divi RL, Leonard SL, Kuo MM, Walker BL, Orozco CC, St Claire MC, Nagashima K, Harbaugh SW, Harbaugh JW, Thamire C, Sable CA, Poirier MC Hearts from 1-yr-old Erythrocebus patas monkeys were examined after in utero and 6-wk-postbirth exposure to antiretroviral nucleoside reverse transcriptase inhibitors (NRTIs). Protocols were modeled on those given to human immunodeficiency virus (HIV)-1-infected pregnant women. NRTIs were administered daily to the dams for the last 20% or 50% of gestation, and to the infants for 6 wk after birth. Exposures included: no drug (n = 4); Zidovudine, 3'-azido-3'-deoxythymidine (AZT; n = 4); AZT/Lamivudine, (-)-beta-L-2', 3'-Dideoxy-3'-thiacytidine (Epivir, 3TC) (n = 4); AZT/Didanosine (Videx, ddI) (n = 4); and Stavudine (Zerit, d4T)/3TC (n = 4). Ech... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626341 Sat, 01 Jan 2005 05:00:00 +0100 1626341 http://www.medworm.com/index.php?rid=1626340&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16382172%26dopt%3DAbstract Authors: Jiang Y, Zheng W Manganese (Mn)-induced Parkinsonism has been well documented; however, little attention has been devoted to Mn-induced cardiovascular dysfunction. This review summarizes literature data from both animal and human studies on Mn's effect on cardiovascular function. Clinical and epidemiological evidence suggests that the incidence of abnormal electrocardiogram (ECG) is significantly higher in Mn-exposed workers than that in the control subjects. The main types of abnormal ECG include sinus tachycardia, sinus bradycardia, sinus arrhythmia, sinister megacardia, and ST-T changes. The accelerated heart-beat and shortened P-R interval appear to be more prominent in female exposed workers than in their male counterparts. Mn-exposed workers display a mean diastolic bloo... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626340 Sat, 01 Jan 2005 05:00:00 +0100 1626340 http://www.medworm.com/index.php?rid=1626339&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16382173%26dopt%3DAbstract Authors: Burniston JG, Ellison GM, Clark WA, Goldspink DF, Tan LB We sought to determine the relative myotoxicity of a sample of cardiotonic (catecholaminergic and PDE Inhibitory) agents currently available for clinical use. Male Wistar rats (292 +/- 24 g) were administered single subcutaneous injections of 20 mmol kg(-1) of each agent. Myocyte apoptosis (caspase-3 and annexin-V) and necrosis (anti-myosin antibody) were detected immunohistochemically on cryosections of the heart and soleus muscle. All of the cardiotonic agents except dopamine produced significant amounts of cardiomyocyte death compared with the vehicle controls, with necrosis (range 2-8%, p < 0.01) approximately one order of magnitude greater in extent than apoptosis (range 0.06-0.5%, p < 0.05). The incidence of ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626339 Sat, 01 Jan 2005 05:00:00 +0100 1626339 http://www.medworm.com/index.php?rid=1626338&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16382174%26dopt%3DAbstract Authors: Slupe A, Williams B, Larson C, Lee LM, Primbs T, Bruesch AJ, Bjorklund C, Warner DL, Peloquin J, Shadle SE, Gambliel HA, Cusack BJ, Olson RD, Charlier HA Carbonyl reductase (CR) catalyzes the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of several carbonyls. Anthracyclines used to treat cancer are reduced by CR at the C13 carbonyl and the resulting metabolites are implicated in the cardiotoxicity associated with anthracycline therapy. CR also is believed to have a role in detoxifying quinones, raising the question whether CR catalyzes reduction of anthracycline quinones. Steady-state kinetic studies were done with several anthraquinone-containing compounds, including 13-deoxydoxorubicin and daunorubicinol, which lack the C13 carbonyl, thus unmasking ... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626338 Sat, 01 Jan 2005 05:00:00 +0100 1626338 http://www.medworm.com/index.php?rid=1626337&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16382175%26dopt%3DAbstract Authors: Lattanzio FA, Tiangco D, Osgood C, Beebe S, Kerry J, Hargrave BY To determine the cardiovascular molecular events associated with acute exposure to cocaine, the present study utilized in vivo analysis of left-ventricular heart function in adult rabbits, fluorescence confocal microscopy of fluo-2, rhod-2, (5-(and-6) carboxy 2',7' dichlorodihydrofluores-cein diacetate (carboxy-H2DCFDA), and JC-1 in H9C2 cells and gene expression microarray technology for analysis of gene activation in both rabbit ventricular tissue and H9C2 cells. In the rabbit, acute cocaine exposure (2 mg/kg) caused left-ventricular dysfunction and 0.1-10 mM cocaine increased cytosolic and mitochondrial calcium activity and mitochondrial membrane depolarization in H9C2 cells. A 3-min pretreatment of H9C2 cells... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626337 Sat, 01 Jan 2005 05:00:00 +0100 1626337 http://www.medworm.com/index.php?rid=1626336&cid=s_37758_7_f&fid=37758&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16382176%26dopt%3DAbstract The objective of this study was to investigate the role of vagal activity and atropine blockage on the bradycardic and hypotensive effects of CAPE in rats. The rats were divided into five groups (n = 8). Saline and vehicle (10% ethanol) of CAPE were given to the first and second groups, respectively. Group 3 was treated with 5 mg/kg CAPE. Group 4 bivagotomized and treated with 5 mg/kg CAPE. Group 5 treated with atropine (5 microg/microL/min) continuously and treated with CAPE. The electrophysiological monitoring was done for each experiment under urethane anesthetize. As a result, CAPE caused intense and transient bradycardia and hypotension. Vagotomy completely abolished bradycardia occurred via CAPE injection; however atropine attenuated bradycardic effects of CAPE. On the other hand, hy... Cardiovascular Toxicology journals http://www.medworm.com/rss/comments.php?id=1626336 Sat, 01 Jan 2005 05:00:00 +0100 1626336