1.
Effect of orlistat on weight loss, hormonal and metabolic profiles in women with polycystic ovarian syndrome: a randomized double-blind placebo-controlled trial.
Moini, A, Kanani, M, Kashani, L, Hosseini, R, Hosseini, L
Endocrine. 2015;(1):286-9
2.
In vivo activity of 11β-hydroxysteroid dehydrogenase type 1 in man: effects of prednisolone and chenodesoxycholic acid.
Diederich, S, Quinkler, M, Mai, K, Schöneshöfer, M, Baehr, V, Pfeiffer, A, Oelkers, W, Eigendorff, E
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2011;(1):66-71
Abstract
The 11β-hydroxysteroid dehydrogenases (11β-HSDs) play a pivotal role in glucocorticoid (GC) action. 11β-HSD1 is a predominant reductase, activating GCs from inert metabolites, whereas 11β-HSD2 is a potent dehydrogenase inactivating GCs. Knowing the metabolic effects of GCs, a selective inhibition of 11β-HSD1 represents a potential target for therapy of impaired glucose tolerance, insulin insensitivity and central obesity. In vitro, 11β-HSD1 is selectively inhibited by chenodesoxycholic acid (CDCA) and upregulated under GC exposure. Therefore, we aimed to investigate the effects of CDCA and prednisolone on hepatic 11β-HSD1 activity in vivo by measuring 11-reduction of orally given cortisone (E) acetate to cortisol (F). CDCA or placebo was given to 5 male healthy volunteers within a randomised cross-over trial before and after oral administration of 12.5 mg E acetate at 8:00 h. For measurement of in vivo effects of GCs on 11β-HSD1 activity, hepatic reduction of 25 mg E acetate before and after treatment with prednisolone (30 mg for 6 days) was determined in 7 healthy males. Serum GC levels were determined using a fully automated liquid chromatographic system. CDCA had no effect on the activity of 11β-HSD1 in vivo. Prednisolone therapy leads to a marked rise in serum F concentrations and an elevated F/E serum ratio. This proves GC-induced activation of hepatic 11β-HSD1, which could not be extinguished by a parallel increase of IGF-1 under prednisolone. CDCA does not affect in vivo activity of 11β-HSD1 when given in therapeutic dosages. During GC treatment, increased hepatic activation of E to F may aggravate metabolic side effects of GCs such as seen in the metabolic syndrome.
3.
B-type natriuretic peptide and the effect of ranolazine in patients with non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial.
Morrow, DA, Scirica, BM, Sabatine, MS, de Lemos, JA, Murphy, SA, Jarolim, P, Theroux, P, Bode, C, Braunwald, E
Journal of the American College of Cardiology. 2010;(12):1189-1196
Abstract
OBJECTIVES We designed a prospective evaluation of the interaction between B-type natriuretic peptide (BNP) and the effect of ranolazine in patients with acute coronary syndromes (ACS) as part of a randomized, blinded, placebo-controlled trial. BACKGROUND Ranolazine is believed to exert anti-ischemic effects by reducing myocardial sodium and calcium overload and consequently ventricular wall stress. BNP increases in response to increased wall stress and is a strong risk indicator in ACS. METHODS We measured plasma BNP in all available baseline samples (n = 4,543) among patients with non-ST-segment elevation ACS randomized to ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial and followed them for a mean of 343 days. The primary end point was a composite of cardiovascular death, myocardial infarction, and recurrent ischemia. BNP elevation was defined as >80 pg/ml. RESULTS Patients with elevated BNP (n = 1,935) were at significantly higher risk of the primary trial end point (26.4% vs. 20.4%, p < 0.0001), cardiovascular death (8.0% vs. 2.1%, p < 0.001), and myocardial infarction (10.6% vs. 5.8%, p < 0.001) at 1 year. In patients with BNP >80 pg/ml, ranolazine reduced the primary end point (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.66 to 0.94, p = 0.009). The effect of ranolazine in patients with BNP >80 pg/ml was directionally similar for recurrent ischemia (HR: 0.78; 95% CI: 0.62 to 0.98; p = 0.04) and cardiovascular death or myocardial infarction (HR: 0.83; 95% CI: 0.66 to 1.05, p = 0.12). There was no detectable effect in those with low BNP (p interaction value = 0.05). CONCLUSIONS Our findings indicate that ranolazine may have enhanced efficacy in high-risk patients with ACS identified by increased BNP. The interaction of biomarkers of hemodynamic stress and the effects of ranolazine warrants additional investigation. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes; NCT00099788).
4.
Evaluation of a novel anti-ischemic agent in acute coronary syndromes: design and rationale for the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation acute coronary syndromes (MERLIN)-TIMI 36 trial.
Morrow, DA, Scirica, BM, Karwatowska-Prokopczuk, E, Skene, A, McCabe, CH, Braunwald, E, ,
American heart journal. 2006;(6):1186.e1-9
Abstract
BACKGROUND Despite advances in antithrombotic therapies and invasive technology, the risk of recurrent ischemic complications in patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs) remains substantial. Ranolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload and has been shown to reduce ischemia in patients with chronic stable angina. STUDY DESIGN MERLIN-TIMI 36 is a phase III, randomized, double-blind, parallel-group, placebo-controlled, multinational clinical trial to evaluate the efficacy and safety of ranolazine during long-term treatment of patients with NSTE-ACS receiving standard therapy (N = 6500). Eligible patients are randomized 1:1 to ranolazine or matched placebo, initiated as 200 mg intravenously over 1 hour, followed by an 80-mg/h infusion (40 mg/h for patients with severe renal insufficiency) for up to 96 hours and oral ranolazine ER 1000 mg BID or matched placebo until the end of study. The primary end point is the time to first occurrence of any element of the composite of cardiovascular death, myocardial infarction, or recurrent ischemia. Secondary end points include ischemia on Holter monitoring, hospitalization for new or worsening heart failure, quality of life measures, and exercise performance. The evaluation of long-term safety will include death from any cause and symptomatic documented arrhythmia. Recruitment began in October 2004. The trial will continue until 730 major cardiovascular events and 310 deaths are recorded with expected completion in 24 to 28 months. CONCLUSIONS MERLIN-TIMI 36 will evaluate the role of ranolazine in the acute and chronic management of patients presenting with NSTE-ACS.