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Biotech / Medical : Indications -- cardiovascular -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (63)	10/16/2003 12:20:37 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 214

>> Titan Pharmaceuticals.... acquired ....... product in development, 3,5-diiodothyropropionic acid << some background....... Am J Physiol Heart Circ Physiol. 2003 Feb;284(2):H613-8. Epub 2002 Oct 31. DITPA stimulates bFGF, VEGF, angiopoietin, and Tie-2 and facilitates coronary arteriolar growth. Wang X, Zheng W, Christensen LP, Tomanek RJ. Department of Anatomy and Cell Biology and The Cardiovascular Center, University of Iowa, Iowa City 52242, USA. Previous studies from our laboratory and those of others have shown thyroxine to be a stimulator of coronary microvascular growth. The present study tested the hypothesis that 3,5-diiodothyropropionic acid (DITPA), a thyroid hormone analog with inotropic but not chronotopic characteristics, is angiogenic in the nonischemic heart. Daily injections (3.75 mg/kg sc) of DITPA to Sprague-Dawley rats affected protein increases in vascular endothelial growth factor (VEGF)(164), VEGF(188,) basic fibroblast growth factor (bFGF) (FGF-2), angiopoietin-1, and Tie-2 during the first few days of treatment. After 3 wk of treatment, arteriolar length density and the relative number of terminal arterioles (<10 microm diameter) increased in the left ventricle as determined by image analysis of perfuse-fixed hearts. These findings occurred in hearts that did not undergo changes in mass nor in increases in capillary length density. We conclude that DITPA, which is known to improve ventricular function after infarction, is angiogenic in normal nonischemic hearts. Thyroid. 2002 Jun;12(6):527-33. Clinical and experimental studies on the use of 3,5-diiodothyropropionic acid, a thyroid hormone analogue, in heart failure. Morkin E, Pennock GD, Spooner PH, Bahl JJ, Goldman S. Department of Medicine, University of Arizona, Tucson, Arizona 85724, USA. Thyroid hormone has unique actions that make it a novel and possibly useful agent for treatment of heart failure. Because of potential adverse effects of thyroid hormone, however, there has been interest in developing analogues with fewer undesirable side effects. Screening of compounds structurally related to levothyroxine identified 3,5-diiodothyropropionic acid (DITPA) as an analogue with inotropic selectivity and low metabolic activity in hypothyroid rats. When DITPA was administered alone or in combination with captopril in rat and rabbit postinfarction models of heart failure, cardiac output was increased and left ventricular end-diastolic pressure (LV EDP) was decreased without increasing heart rate. A pilot clinical study was undertaken to evaluate the safety and efficacy of DITPA. In a dose-ranging study in 7 normal volunteers the drug was well tolerated. A double-blind comparison then was made of DITPA versus placebo in a group of 19 patients with moderately severe heart failure. Patients were randomly assigned to receive either 1.875 mg/kg of DITPA or placebo daily. After 2 weeks the drug was increased to 3.75 mg/kg daily for an additional 2 weeks. In heart failure patients receiving the drug for 4 weeks, cardiac index was increased (p = 0.04) and systemic vascular resistance index was decreased (p = 0.02). Total serum cholesterol (p = 0.013) and triglycerides (p = 0.005) also were decreased significantly. These results indicate that DITPA is well tolerated and could represent a useful new agent for treatment of congestive heart failure.