text: content CONGESTIVE HEART FAILURE AND CARDIOMYOPATHY (Page 3) Printing? Use This! Abnormal membrane concentrations of 20 and 22-carbon essential fatty acids: a common link between risk factors and coronary and peripheral vascular disease? Differential changes in left and right ventricular adenylyl cyclase activities in congestive heart failure Chronic opiate-receptor inhibition in experimental congestive heart failure in dogs beta-adrenoceptor mediated signal transduction in congestive heart failure in cardiomyopathic (UM-X7.1) hamsters Pharmacology and inotropic potential of forskolin in the human heart. [Effects of forskolin on canine congestive heart failure] Italian multicenter study on the safety and efficacy of Coenzyme Q10 as adjunctive therapy in heart failure. [Coenzyme Q10 (ubiquinone) in the treatment of heart failure. Are any positive effects documented?] Italian multicenter study on the safety and efficacy of Coenzyme Q10 as adjunctive therapy in heart failure (interim analysis). The CoQ10 Drug Surveillance Investigators. Isolated diastolic dysfunction of the myocardium and its response to CoQ10 treatment. Effect of Coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. Role of metabolic therapy in cardiovascular disease. Usefulness of taurine in chronic congestive heart failure and its prospective application. Co-enzyme Q10: a new drug for cardiovascular disease. Coenzyme Q10: a new drug for myocardial ischemia? Cardiac performance and Coenzyme Q10 in thyroid disorders A clinical study of the effect of Coenzyme Q on congestive heart failure. [Magnesium in cardiology] Magnesium therapy in acute myocardial infarction when patients are not candidates for thrombolytic therapy [Oral magnesium supplementation to patients receivingdiuretics -- normalization of magnesium, potassium and sodium, and potassium pumps in the skeletal muscles]. Effects of intravenous magnesium sulfate on arrhythmias in patients with congestive heart failure. Magnesium-potassium interactions in cardiac arrhythmia. Examples of ionic medicine. Clinical clues to magnesium deficiency. Platelet taurine in patients with arterial hypertension, myocardial failure or infarction. Physiological and experimental regulation of taurine content in the heart. A relation between myocardial taurine contest and pulmonary wedge pressure in dogs with heart failure. Adrenergic stimulation of taurine transport by the heart. Effects of L-Carnitine administration on left ventricular remodeling after acute anterior myocardial infarction The myocardial distribution and plasma concentration of Carnitine in patients with mitral valve disease. Myocardial Carnitine metabolism in congestive heart failure induced by incessant tachycardia. [The clinical and hemodynamic effects of propionyl-L-Carnitine in the treatment of congestive heart failure] L-Carnitine treatment for congestive heart failure--experimental and clinical study. The therapeutic potential of Carnitine in cardiovascular disorders. [Dilated cardiomyopathy due to primary Carnitine deficiency] Cardiomiopatia dilatativa da deficit primitivo di carnitina. Characterization of inwardly rectifying K+ channel in human cardiac myocytes. Alterations in channel behavior in myocytes isolated from patients with idiopathic dilated cardiomyopathy. Impaired forearm vasodilation to hyperosmolal stimuli in patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy or to ischemic cardiomyopathy. Usefulness of coenzyme Q10 in clinical cardiology: a long-term study. Bioenergetics in clinical medicine. Studies on coenzyme Q10 and essential hypertension. Can antioxidants prevent ischemic heart disease? Antioxidant therapy in the aging process. Abnormal membrane concentrations of 20 and 22-carbon essential fatty acids: a common link between risk factors and coronary and peripheral vascular disease? Horrobin DF Scotia Research Institute, Kentville, Nova Scotia, Canada. Prostaglandins Leukot Essent Fatty Acids 1995 Dec;53(6):385-96 Although elevated levels of cholesterol are associated with increased risks of coronary and peripheral vascular disease, the association frequently fails to provide a causative explanation at the individual level. New hypotheses are required which, whether or not they are correct, will provide new lines of research. It is proposed here that the causes of vascular disease are abnormal membrane phospholipid concentrations of the 20-carbon and 22-carbon essential fatty acids (EFAs) of the n-6 and n-3 series. These levels become abnormal with ageing, with stress and in resp to smoking, high cholesterol levels and high saturated fat intakes. They are also abnormal in patients with diabetes and hypertension. The effects of these EFAs and their metabolites include lowering of triglycerides, elevation of high-density lipoprotein (HDL)-cholesterol, reduction of blood pressure, vasodilatation, reduction of fibrinogen levels and inhibition of platelet aggregation and of cardiac arrhythmias. Prospective studies have shown that abnormal levels of these fatty acids are predictive of future coronary death. Controlled trials of treatment have demonstrated that provision of the fatty acids reduces both coronary and total mortality. Further experimental and clinical investigations of the roles of appropriate membrane concentrations of these fatty acids are justified. (157 Refs.) Differential changes in left and right ventricular adenylyl cyclase activities in congestive heart failure Sethi R, Dhalla KS, Beamish RE, Dhalla NS Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada. Am J Physiol 1997 Feb;272(2 Pt 2):H884-93 The status of beta-adrenergic receptors and adenylyl cyclase in crude membranes from both left and right ventricles was examined when the left coronary artery in rats was occluded for 4, 8, and 16 wk. The adenylyl cyclase activity in the presence of isoproterenol was decreased in the uninfarcted (viable) left ventricle and increased in the right ventricle subsequent to myocardial infarction. The density of beta1-adrenergic receptors, unlike beta2-receptors, was reduced in the left ventricle, whereas no change in the characteristics of beta1- and beta2-adrenergic receptors was seen in the right ventricle. The catalytic activity of adenylyl cyclase was depressed in the viable left ventricle but was unchanged in the right ventricle. In comparison to sham controls, the basal, as well as NaF-, forskolin-, and 5'-guanylyl imidodiphosphate (Gpp(NH)p)-stimulated adenylyl cyclase activities were decreased in the left ventricle and increased in the right ventricle of the experimental animals. Opposite alterations in the adenylyl cyclase activities in left and right ventricles from infarcted animals were also seen when two types of purified sarcolemmal preparations were employed. These changes in adenylyl cyclase activities in the left and right ventricles were dependent on the degree of heart failure. Furthermore, adenosine 3',5'-cyclic monophosphate contents were higher in the right ventricle and lower in the left ventricle from infarcted animals injected with saline, isoproterenol, or forskolin in comparison to the controls. The results suggest differential changes in the viable left and right ventricles with respect to adenylyl cyclase activities during the development of congestive heart failure due to myocardial infarction. Chronic opiate-receptor inhibition in experimental congestive heart failure in dogs Yatani A, Imai N, Himura Y, Suematsu M, Liang CS Department of Medicine, University of Rochester Medical Center, New York 14642, USA. Am J Physiol 1997 Jan;272(1 Pt 2):H478-84 Acute administration of opiate-receptor antagonists has previously been shown to improve cardiac output, sortie blood pressure, systolic ventricular performance, and the baroreflex function in conscious dogs with right-sided congestive heart failure (RHF). However, whether similar changes occur after chronic opiate-receptor inhibition in congestive heart failure is not known. To determine the chronic effects of opiate-receptor antagonism on RHF, we administered naltrexone (200 mg/day), a long-acting, orally active opiate- receptor blocking agent, to RHF and sham-operated animals for 6 wk. Naltrexone had no effects on resting heart rate, right atrial pressure, aortic pressure, or cardiac output in RHF dogs but increased the first derivative of right and left ventricular pressure with respect to time (dP/dt) at rest and improved the dP/dt responses to isoproterenol. The inotropic responses to isoproterenol and forskolin in isolated right ventricular trabeculate muscle also were improved by chronic naltrexone in RHF. Myocardial beta-receptor density was reduced in the failing right ventricle compared with the control (58 plus or minus 3 vs. 108 plus or minus 6 fmol/mg protein, P < 0.01) but was unaffected by addition of naltrexone. Finally, naltrexone prevented the decline in baroreflex sensitivity that occurred in RHF (-0.2 plus or minus 0.5 vs. -6.0 plus or minus 0.5 ms/mmHg, P < 0.01). These effects of naltrexone did not occur in the sham-operated animals. Chronic opiate-receptor blockade with naltrexone attenuates the development of reduced adrenergic inotropic responsiveness and barereflex subsensitivity that occur in RHF. Because there was a similar improvement in the forskolin response in the absence of significant alterations in myocardial beta-adrenoceptor density after naltrexone treatment, the improvement in adrenergically mediated inotropic effects probably is mediated via a postreceptor mechanism. beta-adrenoceptor mediated signal transduction in congestive heart failure in cardiomyopathic (UM-X7.1) hamsters Kaura D, Takeda N, Sethi R, Wang X, Nagano M, Dhalla NS Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada. Mol Cell Biochem 1996 Apr 12-26;157(1-2):191-6 In view of the lack of information regarding the status of beta-adrenoceptor mediated signal transduction mechanisms at severe stages of congestive heart failure, the status of beta-adrenoceptors, G-proteins and adenylyl cyclase activities was examined in 220-275 day old cardiomyopathic hamster hearts. Although no changes in the Kd values for beta1- and beta2,-adrenoceptors were seen, the number of beta1-adrenoceptors, unlike that of beta2-adrenoceptors, was markedly decreased in cardiac membranes from failing hearts. The activation of adenylyl cyclase in the failing hearts by different concentrations of isoproterenol was also attenuated in comparison to the control preparations. The basal adenylyl cyclase activity in cardiac membranes from the failing hearts was not altered; however, the stimulated enzyme activities, when measured in the presence of forskolin, NaF or Gpp(NH)p were depressed significantly. The functional activity of Gs-proteins (measured by cholera toxin stimulation of adenylyl cyclase) was depressed whereas that of Gi-proteins (measured by pertussis toxin stimulation of adenylyl cyclase) was increased in the failing hearts. Not only were the Gs- and Gi-protein contents (measured by immunoblotting) increased, the bioactivities of these proteins as determined by ADP-ribosylations in the presence of cholera toxin and pertussis toxin, respectively, were also higher in failing hearts in comparison to the control values. Northern blot analysis revealed that the signals for Gs- and Gi-protein mRNAs were augmented at this stage of heart failure. These results indicate that the loss of adrenergic support at severe stages of congestive heart failure in cardiomyopathic hamsters may involve a reduction in the number of beta1-adrenoceptors, and an increase in Gi-protein contents as well as bioactivities in addition to an uncoupling of Gs-proteins from the catalytic site of adenylyl cyclase in cardiac membrane. Pharmacology and inotropic potential of forskolin in the human heart. Bristow MR, Ginsburg R, Strosberg A, Montgomery W, Minobe W J Clin Invest 1984 Jul;74(1):212-23 We evaluated the effects of the diterpene compound forskolin in human myocardial adenylate cyclase preparations, isolated trabeculae and capillary muscles derived from failing human hearts, and acutely instrumented dogs. forskolin was a potent, powerful activator of human myocardial adenylate cyclase and produced maximal effects that were 4.82 (normally functioning left ventricle) and 6.13 (failing left ventricle) fold greater than isoproterenol. In contrast to isoproterenol, forskolin retained full activity in membrane preparations derived from failing hearts. In cyclase preparations, forskolin demonstrated unique substrate and Mg2+ kinetic properties that could be distinguished from hormone receptor-coupled agonists or fluoride ion. The adenylate cyclase stimulatory effect of forskolin was synergistic with isoproterenol, apparently due to the location of forskolin activation being beyond the level of hormone receptor-agonist in the receptor-cyclase complex. Forskolin was a potent positive inotrope in failing human myocardium, producing a stimulation of contraction that was similar to isoproterenol. Finally, in open chest dogs Forskolin was a positive inotropic agent that reduced preload and afterload. We conclude that forskolin belongs to a class of agents that may have therapeutic potential in the treatment of congestive heart failure. [Effects of forskolin on canine congestive heart failure] Sonoki H, Uchida Y, Masuo M, Tomaru T, Katoh A, Sugimoto T Nippon Yakurigaku Zasshi 1986 Nov;88(5):389-94 Forskolin is a diterpene of the labdane family which activates adenylate cyclase. The effects of forskolin were investigated in a congestive heart failure (CHF) model that we newly established using anesthetized dogs. The model was made by the intramural injection of protease into the left ventricular free wall, saline loading, and dextran and methoxamine infusion. By this maneuver, aortic blood flow (AoBF) was decreased; left atrial pressure (LAP), systemic vascular resistance (SVR) and left ventricular endodiastolic pressure (LVEDP) were markedly increased; and systemic blood pressure was unchanged. A bolus injection of 5.0 micrograms/kg forskolin reversed the hemodynamic findings of CHF. It reduced LAP (17.5----7.9 mmHg) (mean, N = 7), SVR (19980----10390 dyne sec/cm5), time constant T (90.7----59.2 msec) and LVEDP (22.8----16.8 mmHg); and it increased Vmax (2.32----2.82 l/sec) and AoBF (0.50----0.72 l/min). Forskolin improved the CHF mainly through its vasodilator and positive inotropic actions. Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Baggio E, Gandini R, Plancher AC, Passeri M, Carmosino G Department of Internal Medicine, V. Buzzi Hospital, Reggio Emilia. Mol Aspects Med 1994;15 Suppl:s287-94 Digitalis, diuretics and vasodilators are considered the standard therapy for patients with congestive heart failure, for which treatment is tailored according to the severity of the syndrome and the patient profile. Apart from the clinical seriousness, heart failure is always characterized by an energy depletion status, as indicated by low intramyocardial ATP and coenzyme Q10 levels. We investigated safety and clinical efficacy of Coenzyme Q10 (CoQ10) adjunctive treatment in congestive heart failure which had been diagnosed at least 6 months previously and treated with standard therapy. A total of 2664 patients in NYHA classes II and III were enrolled in this open noncomparative 3-month postmarketing study in 173 Italian centers. The daily dosage of CoQ10 was 50-150 mg orally, with the majority of patients (78%) receiving 100 mg/day. Clinical and laboratory parameters were evaluated at the entry into the study and on day 90; the assessment of clinical signs and symptoms was made using from two-to seven-point scales. The results show a low incidence of side effects: 38 adverse effects were reported in 36 patients (1.5%) of which 22 events were considered as correlated to the test treatment. After three months of test treatment the proportions of patients with improvement in clinical signs and symptoms were as follows: cyanosis 78.1%, oedema 78.6%, pulmonary rales77.8%, enlargement of liver area 49.3%, jugular reflux 71.81%, dyspnoea 52.7%, palpitations 75.4%, sweating 79.8%, subjective arrhytmia 63.4%, insomnia 662.8%, vertigo 73.1% and nocturia 53.6%. Moreover we observed a contemporary improvement of at least three symptoms in 54% of patients; this could be interpreted as an index of improved quality of life. [Coenzyme Q10 (ubiquinone) in the treatment of heart failure. Are any positive effects documented?] Spigset O Avdelningen for klinisk farmakologi, Norrlands Universitetssjukhus, Umea. Tidsskr Nor Laegeforen 1994 Mar 20;114(8):939-42 Coenzyme Q10 is an endogenous substance which has a well established role as electron carrier in the mitochondrial synthesis of adenosine triphosphate (ATP). In addition, coenzyme Q10 also has antioxidant and membrane stabilizing properties. Based on biopsy samples from patients undergoing cardiac surgery and blood samples from patients with congestive heart failure, the existence of a relative Q10 deficiency in patients with cardiac failure has been suggested. A total number of eight double blind, placebo controlled studies in patients with heart failure have been published. Most of these studies include a small number of patients, and various methodological problems have been attributed to these. The results, judged as improvement in ejection fraction or work capacity, are inconsistent. In one large study, Coenzyme Q10 was found to have a positive effect on morbidity, and in another on quality of life. However, although some of the results appear to be promising, more studies are needed, including studies designed with mortality as a primary end point, before the effect of the substance in patients with heart failure can be established. (30 Refs.) Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure (interim analysis). The CoQ10 Drug Surveillance Investigators. Baggio E, Gandini R, Plancher AC, Passeri M, Carmosino G Department of Internal Medicine, V. Buzzi Hospital, Milan. Clin Investig 1993;71(8 Suppl):S145-9 Digitalis, diuretics, and vasodilators are considered standard therapy for patients with congestive heart failure, for which treatment is tailored according to the severity of the syndrome and the patient profile. Apart from the clinical seriousness, heart failure is always characterized by an energy depletion status, as indicated by low intramyocardial ATP and coenzyme Q10 levels. We investigated safety and clinical efficacy of coenzyme Q10 (CoQ10) adjunctive treatment in congestive heart failure, which had been diagnosed at least 6 months previously and treated with standard therapy. A total of 2500 patients in NYHA classes II and III were enrolled in this open noncomparative 3-month postmarketing drug surveillance study in 173 Italian centers. The daily dose of CoQ10 was 50-150 mg orally, with the majority of patients (78%) receiving 100 mg/day. Clinical and laboratory parameters were evaluated at the entry into the study and on day 90; the assessment of clinical signs and symptoms was made using from two- to seven-point scales. Preliminary results on 1113 patients (mean age 69.5 years) show a low incidence of side effects: 10 adverse reactions were reported in 8 (0.8%) patients, of which only 5 reactions were considered as correlated to the test treatment. After 3 months of test treatment the proportions of patients with improvement in clinical signs and symptoms were as follows: cyanosis 81%, edema 76.9%, pulmonary rales 78.4%, enlargement of the liver area 49.3%, jugular reflux 81.5%, dyspnea 54.2%, palpitations 75.7%, sweating 82.4%, arrhythmia 62%, insomnia 60.2%, vertigo 73%, and nocturia 50.7%. Isolated diastolic dysfunction of the myocardium and its response to CoQ10 treatment. Langsjoen PH, Langsjoen PH, Folkers K Clin Investig 1993;71(8 Suppl):S140-4 Symptoms of fatigue and activity impairment, atypical precordial pain, and cardiac arrhythmia frequently precede by years the development of congestive heart failure. Of 115 patients with these symptoms, 60 were diagnosed as having hypertensive cardiovascular disease, 27 mitral valve prolapse syndrome, and 28 chronic fatigue syndrome. These symptoms are common with diastolic dysfunction, and diastolic function is energy dependent. All patients had blood pressure, clinical status, Coenzyme Q10 (CoQ10) blood levels and echocardiographic measurement of diastolic function, systolic function, and myocardial thickness recorded before and after CoQ10 replacement. At control, 63 patients were functional class III and 54 class II; all showed diastolic dysfunction; the mean CoQ10 blood level was 0.855 micrograms/ml; 65%, 15%, and 7% showed significant myocardial hypertrophy, and 87%, 30%, and 11% had elevated blood pressure readings in hypertensive disease, mitral valve prolapse and chronic fatigue syndrome respectively. Except for higher blood pressure levels and more myocardial thickening in the hypertensive patients, there was little difference between the three groups. CoQ10 administration resulted in improvement in all; reduction in high blood pressure in 80%, and improvement in diastolic function in all patients with follow-up echocardiograms to date; a reduction in myocardial thickness in 53% of hypertensives and 36% of the combined prolapse and fatigue syndrome groups; and a reduced fractional shortening in those high at control and an increase in those initially low. Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. Morisco C, Trimarco B, Condorelli M Facolta di Medicina e Chiruriga, Universita degli Studi di Napoli Federico II. Clin Investig 1993;71(8 Suppl):S134-6 The improved cardiac function in patients with congestive heart failure treated with coenzyme Q10 supports the hypothesis that this condition is characterized by mitochondrial dysfunction and energy starvation, so that it may be ameliorated by Coenzyme Q10 supplementation. However, the main clinical problems in patients with congestive heart failure are the frequent need of hospitalization and the high incidence of life-threatening arrhythmias, pulmonary edema, and other serious complications. Thus, we studied the influence of Coenzyme Q10 long-term treatment on these events in patients with chronic congestive heart failure (New York Heart Association functional class III and IV) receiving conventional treatment for heart failure. They were randomly assigned to receive either placebo (n = 322, mean age 67 years, range 30-88 years) or COENZYME Q10 (n = 319, mean age 67 years, range 26-89 years) at the dosage of 2 mg/kg per day in a 1-year double-blind trial. The number of patients who required hospitalization for worsening heart failure was smaller in the Coenzyme Q10 treated group (n = 73) than in the control group (n = 118, P < 0.001). Similarly, the episodes of pulmonary edema or cardiac asthma were reduced in the control group (20 versus 51 and 97 versus 198, respectively; both P < 0.001) as compared to the placebo group. Our results demonstrate that the addition of coenzyme Q10 to conventional therapy significantly reduces hospitalization for worsening of heart failure and the incidence of serious complications in patients with chronic congestive heart failure. Role of metabolic therapy in cardiovascular disease. Rengo F, Abete P, Landino P, Leosco D, Covelluzzi F, Vitale D, Fedi V, Ferrara N Istituto di Medicina Interna, Cardiologia e Chirurgia Cardiovascolare, Catiedra di Geriatria, Facolta di Medicina, Napoli. Clin Investig 1993;71(8 Suppl):S124-8 The pathophysiological basis for the use of metabolic therapy in the treatment of heart failure is analyzed. Bioenergetical processes related to ATP bioavailability play a central role in regulating myocardial contractility at rest and on effort. Furthermore, a significant correlation has been demonstrated in diseased heart between ATP content, revealed at endomyocardial biopsy, and systolic and diastolic left ventricular indexes evaluated with invasive and noninvasive methods. Several international investigations demonstrate the beneficial effects of ubiquinone (Coenzyme Q10) in the treatment of heart failure. Here the results of a study are reported that was conducted on patients with heart failure treated with ubiquinone. After 7 months of oral drug administration (100 mg/day), a significant improvement was observed in echocardiographic indexes of systolic function, cardiothoracic ratio, and clinical signs and symptoms of congestive heart failure. In conclusion, the introduction of metabolic drugs, such as ubiquinone, in the treatment of heart failure opens new horizons in the therapeutic approach to an ailment that entails substantial human and social costs. Usefulness of taurine in chronic congestive heart failure and its prospective application. Azuma J, Sawamura A, Awata N Third Department of Internal Medicine, Osaka University Medical School, Japan. Jpn Circ J 1992 Jan;56(1):95-9 We compared the effect of oral administration of taurine (3 g/day) and coenzyme Q10 (CoQ10) (30 mg/day) in 17 patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy, whose ejection fraction assessed by echocardiography was less than 50%. The changes in echocardiographic parameters produced by 6 weeks of treatment were evaluated in a double-blind fashion. In the taurine-treated group significant treatment effect was observed on systolic left ventricular function after 6 weeks. Such an effect was not observed in the CoQ10-treated group. Co-enzyme Q10: a new drug for cardiovascular disease. Greenberg S, Frishman WH Department of Medicine, Mt. Sinai Hospital and Medical Center, New York, New York. J Clin Pharmacol 1990 Jul;30(7):596-608 Co-enzyme Q10 (ubiquinone) is a naturally occurring substance which has properties potentially beneficial for preventing cellular damage during myocardial ischemia and reperfusion. It plays a role in oxidative phosphorylation and has membrane stabilizing activity. The substance has been used in oral form to treat various cardiovascular disorders including angina pectoris, hypertension, and congestive heart failure. Its clinical importance is now being established in clinical trails worldwide. (133 Refs.) Coenzyme Q10: a new drug for myocardial ischemia? Greenberg SM, Frishman WH Department of Medicine, Mt. Sinai Hospital and Medical School, New York, New York Med Clin North Am 1988 Jan;72(1):243-58 A biochemical rationale for using CoQ in treating certain cardiovascular diseases has been established. CoQ subserves an endogenous function as an essential cofactor in several metabolic pathways, particularly oxidative respiration. As an exogenous source in supraphysiologic doses, CoQ may have pharmacologic effects that are beneficial to tissues rendered ischemic and then reperfused. Its mechanism of action appears to be that of a free radical scavenger and/or direct membrane stabilizer. Initial clinical studies performed abroad and in the United States indicate that CoQ may be effective in treating certain patients with ischemic heart disease, congestive heart failure, toxin-induced cardiotoxicity, and possibly hypertension. The most intriguing property of CoQ is its potential to protect and preserve ischemic myocardium during surgery. Currently, CoQ is still considered an experimental agent and only further studies will determine whether it will be useful therapy for human cardiovascular disease states. (105 Refs.) Cardiac performance and Coenzyme Q10 in thyroid disorders Suzuki H, Naitoh T, Kuniyoshi S, Banba N, Kuroda H, Suzuki Y, Hiraiwa M, Yamazaki N, Ishikawa M, Hashigami Y, et al Endocrinol Jpn 1984 Dec;31(6):755-61 To investigate the relationship between serum levels of Coenzyme Q10 and cardiac performance in thyroid disorders, we studied the cardiac performance and assessed serum levels of thyroid hormones and Coenzyme Q10 in 20 patients with hyperthyroidism, 5 patients with hypothyroidism and 10 normal subjects. A significant inverse correlation between thyroid hormones and Coenzyme Q10 levels was found by performing partial correlation analysis. Because low serum levels of Coenzyme Q10 were found in thyrotoxic patients and congestive heart failure may occur as a result of severe hyperthyroidism, 120 mg of Coenzyme Q10 was administered daily for one week to 12 hyperthyroid patients and the change in cardiac performance was assessed. Further augmentation of cardiac performance was found in hyperthyroid hearts, which were already augmented, after the administration of Coenzyme Q10. It appears, therefore, that the Coenzyme Q10 dose actually has a therapeutic value for congestive heart failure induced by severe thyrotoxicosis. A clinical study of the effect of Coenzyme Q on congestive heart failure. Ishiyama T, Morita Y, Toyama S, Yamagami T, Tsukamoto N Jpn Heart J 1976 Jan;17(1):32-42 Expecting activation of myocardial energy liberation, COENZYME Q was applied as a treatment to 55 patients suffering from congestive heart failure. Daily doses of 50 to 100 mg of coenzyme Q7 were injected intravenously in 21 cases for 3 to 35 days. Daily doses of 60 mg of coenzyme Q7 were administered perorally in 17 cases for 14 to 196 days. Daily doses of 30 mg of Coenzyme Q10 were administered perorally in 17 cases for 7 to 182 days. Clinical effects were evaluated within 4 weeks by the criteria using a scoring method of severity of congestive heart failure which was devised by the authors. In summary a certain effect was found in 20 cases and a mild effect was observed in 29 cases. No significant changes were observed in heart rate and blood pressure. Exanthema appeared in 2 patients of the group of COENZYME Q7 intravenous injection. In conclusion the therapeutic effect of COENZYME Q was thought to be mild but stable in supplement to digitalis therapy in cases of congestive heart failure. [Magnesium in cardiology] Weiss M Medizinische Abteilung, Inselspital Bern. Schweiz Rundsch Med Prax 1995 May 2;84(18):526-32 Magnesium acts as a cofactor of numerous enzymes and is important for the maintenance of a high intracellular potassium concentration and the transmembrane action potential. Of the total magnesium content of about 1000 mmol, only 0.3% are located in plasma. Hypomagnesemia and probable magnesium deficiency are found in 7 to 11% of hospitalized patients but are only rarely accompanied by relevant clinical symptoms. Prolonged diuretic therapy and secondary aldosteronism are frequent causes of hypomagnesemia in cardiology. Intravenous magnesium is a vasodilatator and prolongs the AH interval. In animal studies magnesium has been shown to have cardioprotective and platelet-inhibiting properties. The only verified indication for intravenous magnesium is the initial treatment of torsade de pointes. Magnesium may suppress digitalis-induced tachyarrhythmias and convert paroxysmal supraventricular tachycardia and monomorphic ventricular tachycardia to sinus rhythm. Its role in the treatment of acute myocardial infarction and of ventricular arrhythmias in congestive heart failure is unclear. (81 Refs.) Magnesium therapy in acute myocardial infarction when patients are not candidates for thrombolytic therapy Shechter M, Hod H, Chouraqui P, Kaplinsky E, Rabinowitz B Heart Institute, Sheba Medical Center, Tel-Hashomer, Israel. Am J Cardiol 1995 Feb 15;75(5):321-3 Thrombolytic therapy reduces in-hospital mortality. However, 70% to 80% of patients do not receive thrombolysis and their in-hospital mortality is high. During the last decade some clinical trials demonstrated that magnesium sulfate reduced in-hospital mortality. The aim of this study was to evaluate the effects of magnesium sulfate in patients with acute myocardial infarction (AMI) who were considered unsuitable for thrombolytic therapy. Intravenous magnesium sulfate was evaluated in 194 patients with AMI ineligible for thrombolytic therapy in a randomized, double-blind, placebo-controlled study. Group I consisted of 96 patients who received 48-hour intravenous magnesium. Group II consisted of 98 patients who received isotonic glucose as a placebo. Magnesium reduced the incidence of arrhythmias, congestive heart failure, and conduction disturbances compared with placebo (27% vs 40%, p = 0.04; 18% vs 23%, p = 0.27; 10% vs 15%, p = 0.21, respectively). Left ventricular ejection fraction 72 hours and 1 to 2 months after admission was higher in patients who received magnesium sulfate than in those taking placebo (49% vs 43% and 52% vs 45%; p = 0.01, respectively). In-hospital mortality was significantly reduced in patients receiving magnesium sulfate than in those receiving placebo (4% vs 17%; p < 0.01), and also in the subgroup of elderly patients (> 70 years) (9% vs 23%; p = 0.09). In conclusion, magnesium sulfate should be considered as an alternative therapy to thrombolysis in patients with AMI. [Oral magnesium supplementation to patients receiving diuretics--normalization of magnesium, potassium and sodium, and potassium pumps in the skeletal muscles] Dorup I, Skajaa K, Thybo NK Aarhus Universitet, Fysiologisk Institut. Ugeskr Laeger 1994 Jul 4;156(27):4007-10, 4013 In 76 consecutive patients who had received diuretics for 1-17 years for arterial hypertension or congestive heart failure, muscle concentrations of magnesium, potassium, and sodium-potassium pumps were significantly reduced compared to 31 age- and sex-matched controls. Thirty-six patients with muscle magnesium and/or potassium below the control level received oral magnesium hydroxide supplement for 2-12 weeks (N = 20) or 26 weeks (N = 16). After short term (2-12 weeks) magnesium supplementation muscle parameters were increased, but far from normalized. After magnesium supplementation for 26 weeks, the muscle concentrations of magnesium, potassium and sodium-potassium pumps were normalized in most cases. Oral magnesium supplementation may restore diuretic-induced disturbances in the concentrations of magnesium, potassium and sodium-potassium pumps in skeletal muscle. A supplemental period of at least six months seems required before complete normalization can be expected. Effects of intravenous magnesium sulfate on arrhythmias in patients with congestive heart failure. Gottlieb SS, Fisher ML, Pressel MD, Patten RD, Weinberg M, Greenberg N Division of Cardiology, University of Maryland School of Medicine, Baltimore 21201. Am Heart J 1993 Jun;125(6):1645-50 Intravenous magnesium is an effective treatment for ventricular tachycardia of some etiologies, and in patients with congestive heart failure low serum magnesium concentrations are associated with frequent arrhythmias and high mortality. This suggests that magnesium administration may decrease the frequency of ventricular arrhythmias in patients with heart failure. We therefore assessed the impact of an intravenous magnesium infusion upon the frequency of ventricular premature depolarizations in 40 patients with New York Heart Association (NYHA) class II to IV heart failure and serum magnesium < or = 2.0 mg/dl. Within 1 week of a baseline 6-hour ambulatory electrocardiographic recording, an infusion of 0.2 mEq/kg of MgSO4 was given over 1 hour and a repeat 6-hour recording was obtained. There was an inverse relationship between the change in magnesium concentration and the change in frequency of premature ventricular depolarizations; premature ventricular depolarizations declined by 134 +/207 hr-1 in patients in whom serum magnesium concentration increased > or = 0.75 mg/dl, but increased by 72 +/- 393 hr-1 in patients with a change < 0.75 mg/dl (p < 0.05). For all patients, the frequency of premature ventricular depolarizations was 283 +/- 340 hr-1 pretreatment and 220 +/269 hr-1 following magnesium infusion (p = 0.21). Patients with > or = 300 premature ventricular depolarizations hr-1 demonstrated a decrease from 794 +/- 309 to 369 +/- 223 hr-1 (p < 0.001). Intravenous magnesium administration decreased the frequency of couplets from 233 +/- 505 to 84 +/- 140 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) Magnesium-potassium interactions in cardiac arrhythmia. Examples of ionic medicine. Iseri LT, Ginkel ML, Allen BJ, Brodsky MA College of Medicine University of California, Irvine. Magnes Trace Elem 1991-92;10(2-4):193-204 Ionic biology involving Ca2+, Na+, K+ and Mg2+ across the cell membrane and in the development of the action potential is reviewed with reference to cardiac arrhythmia. K+ and Mg2+ deficiency which frequently occur together lead to abnormal ionic transfer of Na+, K+ and Ca2+ with development of automaticity, triggered impulses and reentrant tachycardia. Tachycardia occurring in acute myocardial ischemia, congestive heart failure, hypertensives on diuretics and digitalis toxicity is examined according to the concept of ionic imbalance. A protocol for prevention and treatment of cardiac tachyarrhythmia is proposed with this concept in mind. Clinical clues to magnesium deficiency. Cohen L, Kitzes R Department of Medicine B, Lady Davis Carmel Hospital, Haifa, Israel. Isr J Med Sci 1987 Dec;23(12):1238-41 Two cases of congestive heart failure with coexistent magnesium and potassium depletion are described. The prolonged QTc intervals and ventricular premature beats of the first patient and the idionodal tachycardia of the second patient disappeared only after magnesium repletion, which normalized both extra- and intracellular potassium and magnesium levels. The third patient had a case of urosepsis while on total parenteral nutrition. He developed diarrhea, hypocalcemia, hypokalemia, hypomagnesemia, weakness, muscular fasciculations and athetoid movements. The neurological manifestations were relieved and the biochemical abnormalities normalized only after magnesium repletion. Platelet taurine in patients with arterial hypertension, myocardial failure or infarction. Paasonen MK, Penttila O, Himberg JJ, Solatunturi E Acta Med Scand Suppl 1980;642:79-84 The content of taurine in the hypertrophied left ventricle is increased in congestive heart failure an in spontaneously hypertensive (SH) rats. In SH rats the taurine content of and taurine uptake by the platelets are also increased. The present results indicate that, as in the heart, the taurine content may also increase in the platelets of those patients with congestive heart failure. The taurine content and uptake are not increased in the platelets of hypertensive patients as they are in the platelets of SH rats. It is likely that in acute myocardial infarction, a considerable amount of taurine is released from the heart into the plasma. However, there is no simultaneous increase in the platelet taurine content. From this work on can only conclude that platelets may reflect taurine changes in the heart in some pathological states, e.g. congestive heart failure. Physiological and experimental regulation of taurine content in the heart. Huxtable RJ, Chubb J, Azari J Fed Proc 1980 Jul;39(9):2685-90 High concentrations of taurine are found in the heart and these are increased still further in congestive heart failure. It appears that taurine is largely derived by influx from the circulation, and this influx is stimulated by cyclic AMP, whereas influx of alpha-amino acids is unaffected. Influx occurs via a saturable transport system that has strict requirements for ligands. Other substances are transported by this system, including beta-alanine, hypotaurine, guanidoethyl sulfonate, and, to a lesser extent, guanidinopropionate; and these are competitive antagonists for taurine transport. Guanidinoethyl sulfonate, in vivo, markedly lowers taurine concentrations over the course of a few days in all tissues examined in the rat and mouse (but not in the guinea pig). The concentrations of other amino acids are unaffected. Guanidinoethyl sulfonate may prove to be a useful substance in the study of the biological role of taurine, in view of its ability to regulate taurine content in a number of species. Despite the numerous pharmacological actions of taurine, its physiological function in the heart remains problematic. One function appears to be the modulation of calcium movements. The inotropic actions of taurine and beta-adrenergic activation may be linked via the cyclic AMP-dependent regulation of taurine influx. A relation between myocardial taurine contest and pulmonary wedge pressure in dogs with heart failure. Newman WH, Frangakis CJ, Grosso DS, Bressler R Physiol Chem Phys 1977;9(3):259-63 Myocardial taurine levels were correlated with pulmonary wedge pressure (PWP) in dogs with congestive heart failure (CHF). Heart failure was induced by creating an infrarenal aortocaval fistula. PWP ranged from 6.6 to 28 mm Hg, suggesting a wide range in severity of heart failure in those dogs. Compared to taurine levels of normal dogs, levels of the CHF group were significantly elevated in both left and right ventricles. Linear regression analysis of ventricular taurine content yielded a highly significant direct relation to PWP. The results suggest that myocardial taurine content increases as heart failure becomes more severe. Adrenergic stimulation of taurine transport by the heart. Huxtable R, Chubb J Science 1977 Oct 28;198(4315):409-11 A high-affinity transport system that is specific for beta-amino acids has been delineated in rat hearts. This system transports the cardiotonic sulfonic amino acid taurine. beta-Adrenergic stimulation increases the transport capacity without effect on alpha-amino acid uptake, as does stimulation with adenosine 3',5'-monophosphate or theophylline. The existence of such an uptake system for taurine in the heart accounts for the high intra- to extracellular concentration gradient that is maintained, and suggests that cardiac stress is associated with increased taurine uptake. This may explain why taurine is the only amino acid to be markedly elevated in congestive heart failure. taurine is a modifier of calcium fluxes in the heart, as are beta-adrenergic agonists. The presence of this uptake system suggests a link between beta-adrenergic stimulation of calcium and taurine fluxes. Effects of L-Carnitine administration on left ventricular remodeling after acute anterior myocardial infarction Iliceto S, Scrutinio D, Bruzzi P, D'Ambrosio G, Boni L, Di Biase M, Biasco G, Hugenholtz PG, Rizzon P Institute of Cardiology, University of Bari, Italy. J Am Coll Cardiol 1995 Aug;26(2):380-7 OBJECTIVES. This study was performed to evaluate the effects of L-Carnitine administration on long-term left ventricular dilation in patients with acute anterior myocardial infarction. BACKGROUND. Carnitine is a physiologic compound that performs an essential role in myocardial energy production at the mitochondrial level. Myocardial Carnitine deprivation occurs during ischemia, acute myocardial infarction and cardiac failure. Experimental studies have suggested that exogenous Carnitine administration during these events has a beneficial effect on function. METHODS. The L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial was a randomized, double-blind, placebo-controlled, multicenter trial in which 472 patients with a first acute myocardial infarction and high quality two-dimensional echocardiograms received either placebo (239 patients) or L-Carnitine (233 patients) within 24 h of onset of chest pain. Placebo or L-Carnitine was given at a dose of 9 g/day intravenously for the first 5 days and then 6 g/day orally for the next 12 months. Left ventricular volumes and ejection fraction were evaluated on admission, at discharge from hospital and at 3, 6 and 12 months after acute myocardial infarction. RESULTS. A significant attenuation of left ventricular dilation in the first year after acute myocardial infarction was observed in patients treated with L-Carnitine compared with those receiving placebo. The percent increase in both end-diastolic and end-systolic volumes from admission to 3-, 6- and 12-month evaluation was significantly reduced in the L-Carnitine group. No significant differences were observed in left ventricular ejection fraction changes over time in the two groups. Although not designed to demonstrate differences in clinical end points, the combined incidence of death and congestive heart failure after discharge was 14 (6%) in the L-Carnitine treatment group versus 23 (9.6%) in the placebo group (p = NS). Incidence of ischemic events during follow-up was similar in the two groups of patients. CONCLUSIONS. L-Carnitine treatment initiated early after acute myocardial infarction and continued for 12 months can attenuate left ventricular dilation during the first year after an acute myocardial infarction, resulting in smaller left ventricular volumes at 3, 6 and 12 months after the emergent event. The myocardial distribution and plasma concentration of Carnitine in patients with mitral valve disease. Nakagawa T, Sunamori M, Suzuki A Department of Thoracic-Cardiovascular Surgery, Tokyo Medical University, School of Medicine, Japan. Surg Today 1994;24(4):313-7 The myocardial distribution and concentration of Carnitine and its fractions was studied in 11 patients with mitral valve disease not associated with congestive heart failure (CHF). The plasma concentration of Carnitine was found to be identical to the normal values documented in the literature. The left ventricular papillary muscle had the highest concentrations of total, short-acyl, long-acyl, and free Carnitine, being significantly higher than those of the right ventricle, while the right atrial appendage had the lowest values of all fractions of Carnitine. The proportion of long-acyl Carnitine to total Carnitine was significantly greater in the left ventricle than in either the right atrium or the atrial septum, and other Carnitine fractions were identical in all cardiac chambers. Our results suggest that in the compensated heart with mitral valve disease, Carnitine and its fractions are greatest in the left ventricle in the muscles of all cardiac chambers, and that long-acyl Carnitine is most likely to be linked to the cardiac muscle demanding a higher cardiac performance. Myocardial Carnitine metabolism in congestive heart failure induced by incessant tachycardia. Pierpont ME, Foker JE, Pierpont GL Department of Pediatrics, University of Minnesota, School of Medicine, Minneapolis. Basic Res Cardiol 1993 Jul-Aug;88(4):362-70 Persistent tachycardia induces congestive heart failure (CHF), but the mechanism(s) of progressive ventricular dysfunction is (are) unclear. This study was designed to define possible metabolic causes of myocardial dysfunction in rapid ventricular pacing induced CHF. Twelve adult mongrel dogs were paced to 250 beats/min for 19 days. Plasma Carnitine, norepinephrine and renin were measured at 0, 1, 2, and 3 weeks. Myocardial high energy phosphates, Carnitine, glycogen, glucose, non-collagenous protein and collagen were measured at 19 days. Cardiac output, arterial pressure and pulmonary wedge pressure, measured at baseline and with CHF, showed a decrease in cardiac output and increase in pulmonary wedge pressure. Neurohumoral activation was evident by progressively increasing plasma norepinephrine and renin activity and depletion of myocardial norepinephrine. Plasma free Carnitine rose significantly from 12.6 +/- 2.0 control to 28.3 +/- 3.8 nmol/ml at 19 days (p < 0.001), whereas myocardial total Carnitine was lower in paced than in control dogs (6.0 +/- 1.9 vs. 14.1 +/- 3.5 nmol/mg non-collagenous protein, p < 0.001). Myocardial ATP ATP and ADP were unchanged, while AMP decreased 22%, and creatine phosphate decreased 30% compared to control animals. Myocardial glucose was normal but glycogen was decreased 54% (p < 0.005). The low myocardial Carnitine and elevated plasma Carnitine in pacing induced CHF suggests altered Carnitine transport or membrane integrity. [The clinical and hemodynamic effects of propionyl-L-Carnitine in the treatment of congestive heart failure] Pucciarelli G, Mastursi M, Latte S, Sacra C, Setaro A, Lizzadro A, Nolfe G Servizio di Cardiologia, USL n. 42, Ospedale Elena D'Aosta, Napoli. Clin Ter 1992 Nov;141(11):379-84 In order to evaluate the clinical and hemodynamic effects of propionyl-L-Carnitine (PLC) a randomized, double-blind study versus placebo was performed in 50 patients of both sexes, between 48 and 69 years of age, affected by mild-moderate congestive heart failure. All patients participating in said study were on digitalis and diuretic treatment. 25 of these belonged to the control group, while the other 25 were treated with an oral dose of 1 g b.i.d of propionyl-L-Carnitine. At the end of six months of treatment maximum exercise time on the treadmill increased 11.1% after 90 days and 16.4% after 180 in the group treated with PLC. From a hemodynamic standpoint, after 30, 90 and 180 days the ejection fraction increased by 7.3%, 10.7% and 12.1%. At the same time, moreover, the systemic vascular resistances were reduced by 14.9%, 20% and 20.6%. In the patients treated with placebo, however, the above-mentioned parameters showed no significant variation. Finally, no unexpected events or toxic effects were observed in any of the patients in either group. As a consequence of these results it is possible to affirm that propionyl-L-Carnitine, due to its clinical and hemodynamic effects, represents a drug of notable therapeutic interest in patients with congestive heart failure, in whom it may be usefully combined with the usual pharmacological therapy. L-Carnitine treatment for congestive heart failure--experimental and clinical study. Kobayashi A, Masumura Y, Yamazaki N Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan Jpn Circ J 1992 Jan;56(1):86-94 To evaluate the therapeutic efficacy of l-Carnitine in heart failure, the myocardial Carnitine levels and the therapeutic efficacy of l-Carnitine were studied in cardiomyopathic BIO 14.6 hamsters and in patients with chronic congestive heart failure and ischemic heart disease. BIO 14.6 hamsters and patients with heart failure were found to have reduced myocardial free Carnitine levels (BIO 14.6 vs FI, 287 +/- 26.0 vs 384.8 +/83.8 nmol/g wet weight, p less than 0.05; patients with heart failure vs without heart failure, 412 +/- 142 vs 769 +/- 267 nmol/g p less than 0.01). On the other hand, long-chain acylCarnitine level was significantly higher in the patients with heart failure (532 +/- 169 vs 317 +/- 72 nmol/g, p less than 0.01). Significant myocardial damage in BIO 14.6 hamsters was prevented by the intraperitoneal administration of l-Carnitine in the early stage of cardiomyopathy. Similarly, oral administration of l-Carnitine for 12 weeks significantly improved the exercise tolerance of patients with effort angina. In 9 patients with chronic congestive heart failure, 5 patients (55%) moved to a lower NYHA class and the overall condition was improved in 6 patients (66%) after treatment with l-Carnitine. L-Carnitine is capable of reversing the inhibition of adenine nucleotide translocase and thus can restore the fatty acid oxidation mechanism which constitutes the main energy source for the myocardium. Therefore, these results indicate that l-Carnitine is a useful therapeutic agent for the treatment of congestive heart failure in combination with traditional pharmacological therapy. The therapeutic potential of Carnitine in cardiovascular disorders. Pepine CJ Division of Cardiology, University of Florida, Gainesville. Clin Ther 1991 Jan-Feb;13(1):2-21; discussion 1 The naturally occurring compound L-Carnitine plays an essential role in fatty acid metabolism. It is only by combining with Carnitine that the activated long-chain fatty acyl coenzyme A esters in the cytosol are able to be transported to the mitochondrial matrix where beta-oxidation occurs. Carnitine also functions in the removal of compounds that are toxic to metabolic pathways. Clinical evidence indicates that Carnitine may have a role in the management of a number of cardiovascular disorders. Supplemental administration of Carnitine has been shown to reverse cardiomyopathy in patients with systemic Carnitine deficiency. Experimental evidence obtained in laboratory animals and the initial clinical experience in man indicate that Carnitine may also have potential in the management of both chronic and acute ischemic syndromes. Peripheral vascular disease, congestive heart failure, cardiac arrhythmias, and anthracycline-induced cardiotoxicity are other cardiovascular conditions that may benefit from Carnitine administration, although at this time data on the use of Carnitine for these indications are very preliminary. (53 Refs.) [Dilated cardiomyopathy due to primary Carnitine deficiency] Squarcia U, Agnetti A, Caffarra A, Cavalli C, Marbini A Pediatr Med Chir 1986 Mar-Apr;8(2):157-61 A case of a 3 and a half years old girl with severe congestive heart failure, and typical picture of dilated cardiomyopathy is presented. The serum level of Carnitine (17.2 micromoles/l, versus 44.1 +/- 12.2 micromoles/l, normal value for age) and the histologic and biochemical evaluation of quadriceps muscle tissue confirmed the diagnosis of primary deficit of Carnitine. L-Carnitine (2 gr. three times a day p.o.) was added to anti-congestive therapy. After 8 weeks of therapy, the general and cardiocirculatory conditions are much improved. The physiopathology of dilated cardiomyopathy due to deficit of Carnitine are discussed. An early diagnosis, and an early substitutive therapy with L-Carnitine dramatically improve the outcome of the disease. Characterization of inwardly rectifying K+ channel in human cardiac myocytes. Alterations in channel behavior in myocytes isolated from patients with idiopathic dilated cardiomyopathy. Koumi S, Backer CL, Arentzen CE Department of Medicine, Northwestern University School of Medicine, Chicago, Ill., USA. Circulation 1995 Jul 15;92(2):164-74 BACKGROUND: Little is known about the characteristics of the inwardly rectifying K+ channel (IK1) and the influence of preexisting heart disease on the channel properties in the human heart. METHODS AND RESULTS: We studied the characteristics of cardiac IK1 in freshly isolated adult human atrial and ventricular myocytes by using the patch-clamp technique. Specimens were obtained from the atria and ventricles of 48 patients undergoing cardiac surgery or transplantation and from four explanted donor hearts. The action potential in ventricular myocytes exhibited a longer duration (391.4 +/-30.2 milliseconds at 90% repolarization, n = 10) than in atrium (289.4 +/- 23.0 milliseconds, n = 18, P < .001) and had a fast late repolarization phase (phase 3). The final phase of repolarization in ventricle was frequency independent. Whole-cell IK1 in ventricle exhibited greater slope conductance (84.0 +/- 7.9 nS at the reversal potential, EK; n = 27) than in atrium (9.7 +/-1.2 nS at EK; n = 8, P < .001). The steady-state current-voltage (I-V) relation in ventricular IK1 demonstrated inward rectification with a region of negative slope. This negative slope region was not prominent in atrial IK1. The macroscopic currents were blocked by Ba2+ and Cs+. The channel characteristics in ventricular myocytes from patients with congestive heart failure after idiopathic dilated cardiomyopathy (DCM) exhibited distinct properties compared with those from patients with ischemic cardiomyopathy (ICM). The action potential in ventricular myocytes from patients with DCM had a longer duration (490.8 +/- 24.5 milliseconds, n = 11) compared with that for ICM (420.6 +/- 29.6 milliseconds, n = 11, P < .01) and had a slow repolarization phase (phase 3) with a low resting membrane potential. The whole-cell current slope conductance for DCM was smaller (41.2 +/- 9.0 nS at EK, n = 7) than that for ICM (80.7 +/- 17.0 nS, n = 6, P < .05). In single-channel recordings from cell-attached patches, ventricular IK1 channels had characteristics similar to those of atrial IK1; channel openings occurred in long-lasting bursts with similar conductance and gating kinetics. In contrast, the percent of patches in which IK1 channels were found was 34.7% (25 of 72) of patches in atrium and 88.6% (31 of 35) of patches in ventricle. Single IK1 channel activity for DCM exhibited frequent long-lasting bursts separated by brief interburst intervals at every holding voltage with the open probability displaying little voltage sensitivity (approximately 0.6). Channel activity was observed in 56.2% (18 of 32) of patches for DCM and 77.4% (24 of 31) of patches for ICM. Similar results were obtained from atrial IK1 channels for DCM. In addition, channel characteristics were not significantly different between ICM and explanted donor hearts (donors). IK1 channels in cat and guinea pig had characteristics virtually similar to those of humans, with the exception of lower open probability than that in humans. CONCLUSIONS: These results suggest that the electrophysiological characteristics of human atrial and ventricular IK1 channels were similar to those of other mammalian hearts, with the possible exception that the channel open probability in humans may be higher, that the whole-cell IK1 density is higher in human ventricle than in atrium, and that IK1 channels in patients with DCM exhibited electrophysiological properties distinct from IK1 channels found in patients with ICM and in donors. Impaired forearm vasodilation to hyperosmolal stimuli in patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy or to ischemic cardiomyopathy. Bank AJ, Rector TS, Burke MN, Tschumperlin LK, Kubo SH Cardiovascular Division, University of Minnesota Medical School, Minneapolis 55455. Am J Cardiol 1992 Nov 15;70(15):1315-9 Patients with congestive heart failure (CHF) have impaired peripheral vasodilation during exercise. Hyperosmolality is one local stimulus that produces vasodilation during exercise in normal subjects. This study addressed the hypothesis that vasodilation to hyperosmolal stimuli is impaired in patients with CHF. Forearm blood flow responses to intrabrachial artery infusions of isoosmolar (280 mosm/kg) and hyperosmolal (480 and 660 mosm/kg) solutions of saline and glucose were compared in 9 patients with CHF and 13 normal subjects. Forearm blood flow was measured by strain gauge plethysmography. In the normal subjects, hyperosmolal infusions of 480 and 660 mosm/kg increased forearm blood flow by 3.12 +/0.40 and 6.80 +/- 0.67 ml/min/100 ml forearm volume, respectively (both p< 0.001 compared with isoosmolal infusions). In contrast, in the patients with CHF, these infusions increased forearm blood flow by 2.19 +/- 0.44 and 4.06 +/- 0.92 ml/min/100 ml forearm volume (p < 0.05 normal vs CHF). The impaired forearm blood flow responses in heart failure occurred despite significantly greater (p < 0.05, normal vs CHF) increases in venous osmolality (17.3 +/- 6.5 vs 9.6 +/- 1.3 mosm/kg for the 660 mosm/kg infusion). There were no differences between groups in forearm venous hematocrit, calcium, and sodium or potassium changes during hyperosmolal infusions. It is concluded that peripheral vasodilation to hyperosmolal stimuli is impaired in patients with CHF. Usefulness of coenzyme Q10 in clinical cardiology: a long-term study. Langsjoen H, Langsjoen P, Langsjoen P, Willis R, Folkers K University of Texas Medical Branch, Galveston 77551, USA. Mol Aspects Med 1994;15 Suppl:s165-75 Over an eight year period (1985-1993), we treated 424 patients with various forms of cardiovascular disease by adding coenzyme Q10 (CoQ10) to their medical regimens. Doses of CoQ10 ranged from 75 to 600 mg/day by mouth (average 242 mg). Treatment was primarily guided by the patient's clinical response. In many instances, CoQ10 levels were employed with the aim of producing a whole blood level greater than or equal to 2.10 micrograms/ml (average 2.92 micrograms/ml, n = 297). Patients were followed for an average of 17.8 months, with a total accumulation of 632 patient years. Eleven patients were omitted from this study: 10 due to non-compliance and one who experienced nausea. Eighteen deaths occurred during the study period with 10 attributable to cardiac causes. Patients were divided into six diagnostic categories: ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM), primary diastolic dysfunction (PDD), hypertension (HTN), mitral valve prolapse (MVP) and valvular heart disease (VHD). For the entire group and for each diagnostic category, we evaluated clinical response according to the New York Heart Association (NYHA) functional scale, and found significant improvement. Of 424 patients, 58 per cent improved by one NYHA class, 28% by two classes and 1.2% by three classes. A statistically significant improvement in myocardial function was documented using the following echocardiographic parameters: left ventricular wall thickness, mitral valve inflow slope and fractional shortening. Before treatment with CoQ10, most patients were taking from one to five cardiac medications. During this study, overall medication requirements dropped considerably: 43% stopped between one and three drugs. Only 6% of the patients required the addition of one drug. No apparent side effects from CoQ10 treatment were noted other than a single case of transient nausea. In conclusion, CoQ10 is a safe and effective adjunctive treatment for a broad range of cardiovascular diseases, producing gratifying clinical responses while easing the medical and financial burden of multidrug therapy. Bioenergetics in clinical medicine. Studies on coenzyme Q10 and essential hypertension. Yamagami T, Shibata N, Folkers K Res Commun Chem Pathol Pharmacol 1975 Jun;11(2):273-88 The specific activities (S.A.) of the succinate dehydrogenase-coenzyme Q10 (CoQ10) reductase of a control group of 65 Japanese adults and 59 patients having essential hypertension were determined. The mean S.A. of the hypertensive group was significantly lower (p less than 0.001) and the mean % deficiency of enzyme activity was significantly higher (p less than 0.001) than the values for the control group. These data on Japanese in Osaka agree with data on Americans in Dallas. Some patients showed no CoQ10-deficiency, and others showed definite deficiencies. Emphasizing the CoQ10-enzyme for patient selection, CoQ10 was administered to hypertensive patients. Four individuals showed significant but partial reductions of blood pressure. Monitoring the CoQ10-enzyme before, during, and after administration of CoQ10 indicated responses. The maintenance of high blood pressure could be primarily due to contraction of the arterial wall. Contraction or relaxation of an arterial wall is dependent upon bioenergetics, which also provide the energy for biosynthesis of angiotensin II, renin, aldosterone, and the energy for sodium and potassium transport. A clinical benefit from administration of CoQ10 to patients with essential hypertension could be based upon correcting a deficiency in bioenergetics, and point to possible combination treatments with a form of CoQ and anti-hypertensive drugs. Can antioxidants prevent ischemic heart disease? Maxwell SR Queen Elizabeth Hospital, Edgbaston, Birmingham, U.K. J Clin Pharm Ther 1993 Apr;18(2):85-95 Ischemic heart disease remains a major cause of mortality in developed countries. A number of important risk factors for the development of coronary atherosclerosis have been identified including hypertension, hypercholesterolaemia, insulin resistance and smoking. However, these factors can only partly explain variations in the incidence of ischaemic heart disease either between populations or within populations over time. In addition, population interventions based upon these factors have had little impact in the primary prevention of heart disease. Recent evidence suggests that one of the important mechanisms predisposing to the development of atherosclerosis is oxidation of the cholesterol-rich low-density lipoprotein particle. This modification accelerates its uptake into macrophages, thereby leading to the formation of the cholesterol-laden 'foam cell'. In vitro, low-density lipoprotein oxidation can be prevented by naturally occurring antioxidants such as vitamin C, vitamin E and beta-carotene. This article explores the evidence that these dietary anti-oxidants may influence the rate of progression of coronary atherosclerosis in vivo and discusses the need for formal clinical trials of antioxidant therapy. Antioxidant therapy in the aging process. Deucher GP Clinica Guilherme Paulo Deucher, Sao Paulo, Brazil. EXS 1992;62:428-37 A total of 1,265 patients with age-related diseases such as diabetes, arthritis, vascular disease and hypertension as well as 1,100 persons in diminished health without apparent disease, were treated with the metal chelator EDTA and antioxidants such as vitamin C, E, beta-carotene, selenium, zinc and chromium. Good results were observed in the majority of patients. This is encouraging for the initiation of controlled clinical trials. Page123


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Model & Styling: Alphie LaFray
Make up: Amy Kelly Makeup Artistry
Photography & Post edits: Giggle-Monster
You know you've made it when Weird Al parodies you :P LMAO!!
One of my favourite quotes from the Telephone video. That and, "When you kill a cow, you gotta make a burger."
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What other readers are saying about this title:
khadra ibrahim said:
This is the 2nd book. I thing uglies was the best one but this one is even better. BE SURE to check out the 3rd book 'Specials'. I
posted Apr 23, 2011 at 4:56PM
bookme said:
tally youngblod finds out whi she is pretties and how because she left a note for herself and she and zane split the pills that were with the note then latter ran away but got cought
posted Dec 30, 2010 at 11:42AM
Chan said:
The second book in the Uglies series continues off where the first book does, with Tally, now a Pretty, alerted about her past promise to herself. Will she choose to remain a brain-less Pretty or a rebel Pretty? Recommended for fans of future fiction.
posted Aug 1, 2010 at 7:04PM
Gracie2111 said:
This is the second book. the book after uglies. This is my favorite in the series I think.
posted Jul 13, 2009 at 2:40PM
kb4444 said:
This was a very good sequel to "Uglies" where Tally undergoes the 'pretty' operation and has to fight to not be sucked in to the pretty lifestyle. The ending was sad but it made me really want to read another sequel!
posted Mar 27, 2009 at 4:03PM
bookworm283 said:
The second book in the series. If you liked Uglies, be sure to check out Pretties
posted Dec 6, 2008 at 12:06PM
chocoholic said:
Book Two.
posted Jul 10, 2008 at 1:41PM
Books You Have To Read said:
Perfect and living a carefree, shallow life, Tally still has the feeling that something isn't right. Soon, a note arrives from her past telling her just what- and she and her boyfriend make a descision that could cost them their lives.
posted May 25, 2008 at 9:49AM
Camrie said:
Now this is really messed up. Confusing, love square, and a lot of plastic surgery. But i did love the first book. Uglies; good
posted May 7, 2008 at 5:06PM
gIrLgOeSsHoPpInG said:
The second book in the Uglies Series and my favorite.
posted Feb 18, 2008 at 10:28AM
jessi_face said:
One of my favorite summer reads! Even though I am 27, hardly a teen, I loved this sci-fi story about a culture obsessed with body image. Westerfeld delivers a fantastic adventure! I can't wait to read the next one.
posted Feb 19, 2007 at 7:16PM
Christina said:
This book is awsome. Now before i get you all siked to read it make sure you read the first on or else you might as well be reading in a different language, because i will NOT make any sence. KK. good. Now this book is UNBELIEVIABLE. I t is a bout a girl named Tally. She lives in a town that (is in the future) is obsesed with beuty and BRAINWAsHING. But when Croy returns from smoke with her letter. SHe tells her boyfriend and they take the pills to become better. Not knowing one of them will become braindead. Uh-huh. Awsome book, though it is not a quick read in any way,
posted Dec 11, 2005
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EXTENDED DEADLINE: Call for Papers for Special Food Systems and Social Justice Issue
Call for Papers for Special Food Systems and Social Justice Issue
EXTENDED DEADLINE: December 15, 2013
The editorial board of the Journal of Critical Thought and Praxis (JCTP) invites you to submit your work for inclusion in our Spring 2014 Special Issue on food systems and social justice. JCTP is a peer-reviewed on-line journal committed to providing a space for critical and progressive scholarship, practice, and activism. Our mission is to create an accessible and inter/transdisciplinary journal that supports awareness and challenges individuals to move towards advocacy. The journal brings together emerging scholars, educators, and activists with the intention of providing recognition to the work of the social justice community. JCTP explores, challenges, and pushes the boundaries among multiple disciplines, while providing all authors with developmental feedback.
The Spring JCTP issue is devoted to topics related to food and agriculture as a way to explore how social justice intersects with the production of food, fiber, and fuel locally, nationally, and internationally. Additionally, there are many food system problems such as pesticide poisoning, the impacts of polluted wells, the treatment of farm and food processing employees, the rising cost of food, and health concerns linked to hunger and obesity. Ecological decline also affects communities all over the world and can be a consequence of, or a contributor to, food system failures.
We want to hear from scholars, practitioners, and activists in the U.S. and abroad and encourage new scholars in and across multiple disciplines to develop theoretical or empirical work relating back to social justice themes in the realm of food and agricultural systems. We are looking for pieces to cover a broad base of approaches including:
• Accounts from activists
• Arts-based research
• Book reviews
• Critical inquiry and methodology
• Empirical research
• Policy analysis
• Social justice practitioner reflections
• Theoretical essays
Specific Guidelines:
Submission Deadline: December 15, 2013
Submissions must include an abstract and should be no more than 30 pages double-spaced (not including abstract, figures, photos, tables, appendices, notes, and references). Manuscripts should follow APA 6th Edition guidelines (if applicable to manuscript). Please include a cover letter with your submission explaining how your work contributes to the mission and scope of JCTP.
For more detailed author guidelines and submission procedures, please see the journal's website. To submit a manuscript or to ask for more information, please contact JCTP Editor, Cameron Beatty, at firstname.lastname@example.com. For specific questions regarding this special issue contact Managing Editor: Gabrielle Roesch, at email@example.com.


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Blue Book® Suggested Retail Value
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Amazing value! by pauliri from Chicago on 03/08/2012. Trim: 2012 Hyundai Genesis 4.6L, Owned 1 year.
Pros: Love the finish, design, materials. Everything is 1st rate. I get a lot of comments about how pretty the car is. The value for the money is 1st class. Can't beat this car.
Cons: The radio knob driven control is too complex. The knob with a touch screen would be a lot better. Also the ride could be better. It feels like the tires have too much air on them. Heard from many that if you change the tires it improves. Also the outside mirrows need some improvement. On the exterior border on both looks like the glass is beveled so you get a reflection of light that can be disconcerting at 1st. Besides this the car is perfect
Overall review: I will buy another one
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American Studies and English professors collaborate to explore difficulties facing new immigrants and the inequalities they face in the 21st century.
A career dedicated to student-teacher relationships, cutting edge research, and campus and community service earns Rita Colon-Urban a place among the "best of the best" in SUNY.
The 2013-2014 academic year was a memorable one. From special campus guests to Commencement, here's a review of 14 key moments of the past academic year.


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17 celebrity-inspired hair and makeup ideas to steal for the holiday party season
Holiday party hair and makeup idea: Kerry Washington's big bun and bold eye
Get Kerry's classic hairstyle with Conair's easy-to-use bun-maker kit, $5. For a dark, intense eye, try Stila's Kajal eyeliner, $18, which glides on smoothly, is easy to blend and smudge, and stays put.
Holiday party hair and makeup idea: Sofia Vergara's long, soft waves and brown lipstick
Prep your hair with mousse (like this TRESemmé Climate Protection mousse, $5) or a lightweight styling lotion (like Bumble & Bumble's styling lotion, from $8), depending on how well your hair usually holds curl. Then—instead of clamping and winding—grab two-inch sections of hair, hold by their ends and wrap them around the barrel of a two-inch curling iron, like this one from Hot Tools, from $26. Get Sofia's brown-lipped look with a '90s classic shade, Revlon's Toast of New York, $8—making sure to blot for a matte finish.
Holiday party hair and makeup idea: Selena Gomez's super-sleek waves and coral cheeks
Dab some protective smoothing serum on your hair (like Alterna's Bamboo Smooth Anti-Break Thermal Protectant, $24) and set your locks with hot rollers (try Jillbere's Ceramic 20 Roller Setter, $50). Remove the rollers after they (and your hair) have cooled; part, comb and tease the hair at the crown for added volume before securing with a lightweight hairspray. For glowing coral cheeks and lips, we love Tarte's Amazonian 12-Hour Blush, $25, in Blissful, and Estée Lauder lipstick, $28, in Curvaceous Coral.
Holiday party hair and makeup idea: Kimberly Perry's soft tousled layers and baby pink lips
For finger-tousled glossy waves like The Band Perry's front woman, start by applying mousse (like John Frieda's Frizz-Ease Curl-Reviver Styling Mousse, $6) or spray gel (try Frédéric Fekkai Coiff Bouffant Lifting and Texturizing Spray Gel, $25) depending on how much control you need. Diffuse-dry your hair—we're fans of T3's Featherweight Luxe Hair Dryer with Finger Diffuser, $250—and finish with a frizz-control hairspray, like Living Proof's No-Frizz Wave/Curl Styling Spray, from $15.
Holiday party hair and makeup idea: Felicity Jones' 1960s-inspired blunt bangs and lush lashes
"Like Crazy" star Felicity's look here is so soft, pretty and retro. Leave the haircut to the pros—bring Felicity's photo or one of Jean Shrimpton, Jane Birkin or Marianne Faithfull with you. For a lush eye, look for false eyelashes that crisscross—like these Shu Uemura Luxe Black lashes, $23—because they look more natural.
Holiday party hair and makeup idea: Natasha Henstridge's loose waves and mauve lips
Spray damp hair with a setting spray (try Ouidad's Styling Mist Setting and Holding Spray, $15) and roll two-inch sections in medium Velcro rollers (you can't go wrong with Velcro Classic Stylers, $4). Blow-dry or air-dry—or try this Conair Pro Soft Bonnet Attachment, $10, that affixes to your hair dryer and fits over your head. For a glossy mauve mouth, check out Rimmel's selection of colors, $6.50 each—we're big fans of Crystal Mauve and Berry Queen.
Holiday party hair and makeup idea: Emma Stone's casual pulled-back updo and smoky gray eye
To get Emma's messy-chic texture, try a sea-salt spray—we like Davines' Sea Salt Primer, $20, which imbues even the straightest of hair with volume and just the right amount of controlled muss. For a smoky, iridescent eye, look for a gray shadow palette—like this NP Set Eye Palette, $20, in the gray-navy colorway.
Holiday party hair and makeup idea: Amanda Seyfried's curled-under locks and smudged liner
Blow-dry your hair with a large round brush, making sure to flick the ends inward and tease the hair at the crown for added volume. For Amanda's super-sultry eye makeup look, try Nars' Arabian Nights eyeshadow trio, $45—the deep purples are stunning—smudged upward and outward. Line the upper and lower lash starting from the inner edge of your iris (that's the colored part of your eyeball—lining from here instead of from all the way in the inside corner makes your eyes look bigger) with a purple-black eyeliner (try Smashbox's Limitless Eyeliner, $19, in Black Violet).
Holiday party hair and makeup idea: Michelle Williams' pixie cut and rich chocolate eyeshadow
Don't try this pixie cut at home! Bring Michelle's photo—and Mia Farrow's, Carey Mulligan's and Natalie Portman's, too—with you to show your stylist. Find a rich chocolate-brown eyeshadow that will complement your eye color and suit your skin tone—we like MAC's Swiss Chocolate, $15.
Holiday party hair idea: Taylor Swift's casual side ponytail
To replicate Taylor's easygoing hairstyle, slick a tiny dab of smoothing potion through your strands (try Phyto's Phytolisse Ultra-Shine Smoothing Serum, $30), choose your part—and blow-dry your part for a quick second to set it—tease the hair on and around the crown for a little oomph, and secure your hair loosely on one side, twisting the front few pieces away from your face as you fasten it.


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EcoGeek is Hiring!
There is honestly too much good news for us to handle! EcoGeek is currently looking for dedicated, informed and http://www.aldentheatre.org/generic-levitra-usa experienced writers to be part of our team. And yes, it pays.
We are currently looking to fill part-time writing positions (min 5 hrs / wk), and part-time writing, editing postions (minimum 10 hrs / wk.)
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**THIS IS NOT EPISODE 2! THIS IS A NON-CANON SHORT. There's gonna be a bunch of these to tide you over between full episodes.**
Happy Halloween from Jeff and I! Given that Halloween is the night of darkness and evil (...er something) I threw this together real quick (read: I wanted to kill myself it was so much work) for all of you to enjoy!
This features Chronomonator as his secret identity, Jacob Snow... in case you're wondering where his bright blue spandex went to.
Rated 5 / 5 stars April 20, 2014
that was to funny.
Rated 5 / 5 stars February 10, 2014
Love it! Had to call the whole family around the soft glow of the PC to share in this gem.
Have you considered putting this short on vhs tapes with bloody pentagrams on them and leaving them scattered about your city? Would you mind if other people did? Seems like an appropriate way to advertise your stuff.
Rated 5 / 5 stars November 8, 2013
So THAT'S why people that use VHS don't exist anymore.... they died because of that darn outdated but evil tape!
(Just kidding don't get mad I used to have a VCR too...)
Rated 5 / 5 stars November 3, 2013
LOL. The first thing I thought when I saw the tape, ended up being the punchline. Awesome.
Rated 5 / 5 stars August 25, 2013
Very funny, man


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140816-N-IY142-290 MEDITERRANEAN SEA (Aug. 16, 2014) Boatswain's Mate 3rd Class Jennifer Sahley directs a helicopter to land during flight quarters aboard the Arleigh Burke-class guided-missile destroyer USS Ross (DDG 71). Ross, forward deployed to Rota, Spain, is conducting naval operations in the U.S. 6th Fleet area of responsibility in support of U.S. national security interests in Europe. (U.S. Navy photo by Mass Communication Specialist 2nd Class John Herman/Released)
Boatswain'sMate3rdclassJenniferSahleydirectshelicopterlandduringflightquartersaboardtheArleighBurkeguidedmissiledestroyerUSSRossDDGMultiple-Exposures-Media, from


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Input an inline six block, single-turbo pressurization and four-digit horsepower figures, and your cerebral cortex conjures up images of a Supra 2JZ-GTE engine with a stand-by default of a Skyline RB26ETT. Imagine the surreal rampant misfiring synapses when an S52 call sign is revealed. The S52 engine code identifies a BMW powerplant, in this case the engine from an E36 M3. The E36 M3 debuted in 1995 with a 3.0-liter variant of the S52. In 1996 displacement jumped to 3.2 liters, where it stayed until the end of the E36's run in 1999.
The E36 M3 is known for its handling prowess and smooth application of thrust - not so much as a platform for four-digit power. Enter George Kakalentris and ICS Performance of Stamford, Connecticut. Their mission: to prove that the S52 is indeed strong enough to handle big boost. The car is a 1995 Dakar Yellow coupe, the engine is a later 3.2-liter S52. The amazing thing is that the Bumble Bee represents Plan B.
"Many moons ago European Car magazine laid down a challenge of a 1000-whp BMW, and we were about to answer the call with a black M3 already making 800+whp," says ICS' Brian Rosenberg. "This was a customer's car that we had been using as a showpiece. We had several major manufacturers in our corner on this project, where they supplied the new technology that was going to take it to the next level. Long story short, the owner of the car said he was going to have it repainted about one week before a major BMW show. He picked up the car and we never saw it again! We also never saw the $28,000 in parts that was owed on the build, and that hurt! But what hurt more was that this client was considered family."
"George and I were standing there wondering how in the world were we going to find 1000whp when we didn't even have a car. It was at that very second that our beat-down stock E36 M3 parts hauler pulled in from a parts run. We looked at each other and said, 'there she is.' After that, it was all hands on deck tearing the stock car apart. I had called all the vendors that were involved in the original project and told them the story behind the black car's betrayal. The universal answer from all parties was, 'What do you need? We'll get it out today. And don't worry about the money, just get her done for the magazine.' With all of our suppliers behind us, we created the fully built 'Bumble Bee' in two weeks of night-and-day wrenching. It made 1025 whp."
"So when we were on our 1000whp mission we hit up ICS and found they were in the middle of revamping the turbo, cams and other tidbits, and retuning the Bee for more power. A sense of deja vu set in as the ICS crew was once again racing the clock."
The original project started with heavy machinery as M&B Machine honed the cylinders and prepped the block of battle. ICS assembled the short block using the stock crank and forged CP pistons and Pauter rods.
Head flow is a key component of making power on a forced induction or naturally aspirated application. Headway Performance handled the big machinery porting and polishing the head. The head was filled with proprietary ICS gear, stainless steel and coated 1mm-over valves, stainless double-spring valvesprings and ICS keepers. The cams are a key player in the BMW's high-boost aspirations. The 'second generation' Bumble Bee runs VAC Motorsports Turbo Profile billet cams. A turbo cam is far different than a cam designed for a naturally aspirated engine because the turbo cam has pressure on its side. An all-motor cam has valve overlap designed into it to promote exhaust gas scavenging and quick cylinder fill up. There is no need to trick exhaust gasses or inspire the next intake charge because the turbo is pressurizing the system.


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Clear skies ahead for United Continental
By cutting costs and investing in an upgraded fleet, this company is set to prosper in an improving airline industry.
The airline industry was one we largely ignored in years past given its long history of boom-and-bust cycles; but there has been a profound change in the way most airlines now operate, and the industry has figured out how to make money on a consistent basis.
Our top pick for 2014 is United Continental (UAL). Consolidation has been the biggest driver of the industry's newfound embrace of rational business practices.
United and Continental merged in 2010 and the new United is a case study of how the industry has refocused its business.
United is upgrading its fleet to newer, more fuel-efficient aircraft; it is intent on using its mileage and amenity programs to drive loyalty and raise revenue; it has poured money into enhanced IT systems, which are helping it to better manage available seats to maximize revenue and lower costs; and the company is much more disciplined in the management of its capital.
Cost reduction will be one of the drivers for United's performance going forward, but the company is also making sensible investments in its product.
The company benefits from being one of the largest carriers in the New York City market and that has helped it to secure a number of corporate travel partnerships that help funnel business travelers onto its planes.
The risks for United include the potential for one of its competitors to veer from the current focus on disciplined pricing and start cutting fares to boost loads.
There is also always the potential for another entrepreneur to try to start up another airline to compete with the majors, though the zeal for such ventures appears to have waned. But with the economy getting stronger, United is well positioned if the industry remains disciplined.
United's enterprise value is currently 4.8x its anticipated 2014 EBIDTA. Its P/E is 9.3x the Street's 2014 EPS consensus of $3.98. Delta (DAL), by comparison, trades at a 5.2x EV/EBITDA multiple and a nearly 10x forward P/E. While United's stock gained about 50 percent this past year, it has lagged the roughly 120 percent return for Delta.
Operationally, United underperformed this year, but with the integration of Continental now largely behind it, we think United's post-merger operational performance should take a similar trajectory to that of Delta -- the top airline performer in 2013 -- as its cost cutting program and investments begin to bear fruit.
An improved economy and pick-up in business travel only add to its allure. This in turn should put the stock in position to outperform in an industry that has regained investor interest.
More from MoneyShow.com
My wife & I do not fly a lot...but my experiences are that United has horrible customer service. Unfortunately where we live United (IAH) is the only option without driving an extra 45 minutes to
Houston Hobby for Southwest or Jet Blue. How can they justify $460 to Missouri versus $238 to New York City?. Maybe I'm still a little bit ticked off because they lost my luggage last time I flew on United.
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30 U.S. Code § 1230a - Strategic Resources Generic Mineral Technology Center
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(a) Establishment
The Secretary of [1] Interior is authorized and directed to establish a Strategic Resources Mineral Technology Center (hereinafter referred to as the "center") for the purpose of improving existing, and developing new, technologies that will decrease the dependence of the United States on supplies of strategic and critical minerals.
(b) Functions
The center shall—
(1) provide for studies and technology development in the areas of mineral extraction and refining processes, product substitution and conservation of mineral resources through recycling and advanced processing and fabrication methods;
(c) Criteria
The Secretary shall establish the center referred to in subsection (a) of this section at a university that—
(2) has established advanced degree programs in geology and geological engineering, and metallurgical and mining engineering;
(d) Authorization of appropriations
There is authorized to be appropriated such sums as may be necessary to carry out this section.
[1] So in original. Probably should be "of the".
Source(Pub. L. 98–409, § 12, as added Pub. L. 101–498, § 2,Nov. 2, 1990, 104 Stat. 1207.)
Section was enacted as part of the Mining and Mineral Resources Research Institute Act of 1984, and not as part of the Surface Mining Control and Reclamation Act of 1977 which comprises this chapter.
The table below lists the classification updates, since Jan. 3, 2012, for this section. Updates to a broader range of sections may be found at the update page for containing chapter, title, etc.
The most recent Classification Table update that we have noticed was Tuesday, August 13, 2013
An empty table indicates that we see no relevant changes listed in the classification tables. If you suspect that our system may be missing something, please double-check with the Office of the Law Revision Counsel.
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Planning to live on campus next year? Housing Selection is going on NOW!!! Your housing deposit is due by MARCH 31st. Squatters must select their rooms by April 4th, Displaced students can choose their rooms on April 5th and the housing lottery will be...
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Due in large part to rising energy costs, you will not be permitted to bring your own refrigerator. The suite is equipped with a microfridge. Students with a medical reason that requires a personal refrigerator must complete a "Special Housing...
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Come visit me, rally and lacie, poncho botd 24/3/14, Jack, thank you all for BOTD, Angel Sassy, Till I see you again,, Casper, you fought a good fight l'il man, amando, sky, Angel Lupe', I will see you again!, l'il angel adler, dixie's wife-bird, broken wings, broken promises, casey, the l'il angel & dixie wedding album, JESSE, VOTE FOR ME BOTM IN OCTOBER, flynn, QUEEN ANGEL, thanks for BOTM my friends, sarah little bird, zeke, thank you friends for BOTD, zeena, thanks for august botm & sweetie, thank you friends for BOTD.
Come visit me, Angel Bertie's Rainbow Gym: Thanks for BOTD!, Angel Bertie: Happy New Year!, Chirps: Happy New Year!!!, The Happy Couple!!!, Spot::vote Angel Girl 224627 BOTM!!! & Lemon Le'BonBon,.
Come visit me, **Scooter--RIP 12/3/2008, **Quincy--RIP 2008, **Minegu--RIP 10/7/2009, Hazel, **Ivy--RIP 8/7/2012, Dino, **Linus--RIP 6/8/2010, **Franklin--RIP 10/24/2013, Julius, Sebastian, Tiberius, Phoenix, **DQ--RIP 10/11/2009, **Ella--RIP 11/28/12, Mabel, **Michelangelo--RIP 2007, **Scout--RIP 12/12/2011 & **Nunzio--RIP 10/21/12.
Come visit me, tucker, blue berry, tater, murdock. im in the front!, snowman, bandit, Blue, Jasper & baby.
Come visit me, Rosie & Jim.
Come visit me, Kookoo, Sassy, Koopa & Winky.
Come visit me, Genghis the Small.
Come visit me, Gizmo, I miss you, sweet boy, Willie, Kaji, TiPaul, and Sky for 10k!, Peppino, Divo & Falco.
Come visit me, Carter-Justice For Ozzi-TY 4 BOTD 8/28/14, Doo Diligence-Justice for Ozzi, Cookie-Justice For Ozzi-thank you for BOTD 7/31/14, Charlie-Thank you for making me BOTD 10-29-13, Tricky D- RIP 12/12/12-Thank you BOTD 12/12/13, Teal'c-Thank you for BOTD 10-14-13, Elvis Thank you for BOTD 2/16/13, Joshua Chico Justice for Ozzi, Blue-Justice for Ozzi-TY 4 BOTD 9/7/14, Moggie -Justice for Ozzi, George (Gen George Hammond)RIP Gen 12/13/08, Cu-Bird -Justice for Ozzi, Nanday Security Services, LLC, Miranda -Justice for Ozzi, Captain Darling-RIP 5/19/2014 ty 4 BOTD 9/19/14 & Baldrick Thank you for BOTD 3/20/14.
Come visit me, DJ LUIGI- It's my bday! Thank you everyone! & Calypso- Happy bday Luigi!.
Come visit me, DITTO, SKITTLES, BOO For Now, RIO I'm not touching your IPad, MOCHA My new swing I love it & LITTLE PEEP.
*Content generated by our loyal visitors, which includes comments and club postings, is free of constraints from our editors' red pens, and therefore not governed by I-5 Publishing, LLC's Gold Standard Quality Content, but instead allowed to follow the free form expression necessary for quick, inspired and spontaneous communication.
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By Howard Pousner
Chamber schedule begins Sept. 16
The Emory Chamber Music Society of Atlanta, the city's largest chamber music organization, has announced its 2011-2012 season. Highlights include:
Multiple appearances of the Vega String Quartet, the artists-in-residence who return with newly appointed first violinist Domenic Salerni. Along with works by Mozart, Brahms and Beethoven, the quartet will perform several new pieces, including a world premiere by Emory music professor Steve Everett for string quartet, electronics and video. Vega String Quartet launches the chamber society season at noon Sept. 16 with a concert in the Michael C. Carlos Museum Reception Hall.
A celebration of Franz Liszt's birthday bicentennial continues with guest pianists Philip Thomson and Victor Asuncion performing with ECMSA artistic director William Ransom and Emory organist Timothy Albrecht on Oct. 23.
All performances are on the Emory University campus. Details: www.arts.emory.edu/ecmsa. HOWARD POUSNER
Season of classical appreciation begins
Pro-Mozart Atlanta, a group that since 1964 has presented classical music events and nurtured the talents of young musicians, has announced its 2011-12 season of concerts, parties, lectures and a scholarship competition.
Kicking things off will be a members and prospective members party, 4-6 p.m. Sept. 18 at Brandon Hall School, 1701 Brandon Hall Drive, Atlanta. The casual event will feature music, food, fun and beverages. Free and open to anyone interested in classical music, but an RSVP is required to incoming president Herbert Buffington: email@example.com or 678-488-3591.
The society's first concert will be held at 5 p.m. Nov. 5, featuring a trio of Sara Shaffer, soprano; D. Ray McClellan, clarinet; and Timothy Shafer, piano. The free performance will be at the Dorothy C. Benson Senior Multi-Purpose Complex, 6500 Vernon Woods Drive, Sandy Springs.
Full season details: www.mozartatlanta.com.
Georgia Festival Chorus seeks voices
The 110-voice Georgia Festival Chorus has announced plans to give its 21st Christmas concert on Dec. 1, but first things first: The chorus will hold auditions at 7:30 p.m. Sept. 6 at Piedmont Church in Marietta. All sections are welcome, with basses and tenors especially encouraged to try out for this experienced group of eight-part harmony singers.
Under founding director Frank Boggs, the chorus will begin rehearsing for its free "Carols by Candlelight" concert, which will be presented with full orchestra at 7:30 p.m. Dec. 1 at Johnson Ferry Baptist Church in Marietta. Audition and performance details: 404-234-3581, www.tgafc.org.