Abstract: A method of using an estrogen receptor agonist and antagonist to reduce a toxic effect of a cytostatic drug on bone marrow derived cells in a biological system. The methods comprise contacting the cells with a therapeutically effective amount of an estrogen receptor agonist or antagonist, and contacting the cells with a cytostatic agent, whereby the toxic effect of the cytostatic drug on bone marrow derived cells is reduced. Agonists disclosed include 17-beta-estradiol. Antagonists disclosed include antisense nucleic acids and selective estrogen receptor modulators (SERMs). Furthermore, uses and medicaments comprising estrogen receptor agonists and antagonists are provided, as are screening methods for identifying therapeutic candidates for reducing the effect of cytostatic agents, and methods of using estrogen receptor agonists for increasing the proliferation of CD117+ cells in a biological system.

Abstract: An implantable device for the controlled delivery of an estrogen receptor agonist to an injured site in the lumen of a mammalian blood vessel, wherein the estrogen receptor agonist is present in an amount of at least about 16.7 ?g/mm implantable device length. Methods of use thereof.

Abstract: The present invention relates to the upregulation of estrogen receptors (ER) alpha (ER?) and/or beta (ER?) in endothelial cells and/or smooth muscle cells to prevent or treat heart disease. The upregulation is achieved through the use of recombinant DNA technology and, depending on therapeutic needs, may be performed with a simultaneous or subsquent downregulation, as with antisense technology. Oligonucleotides coding for ER? and/or ER? are introduced into the targeted cells through the use of adenoviruses, for example. With an increase in receptors, the cells should be more responsive to such agonists as 17-beta-estradiol (17?E) and related compounds (genistein, estradiol derivatives . . . ) to improve plaque stabilization, vascular healing and endothelial recovery after vascular injury. Such oligonucleotides may be used to modulate the beneficial effects mediated by the ER on vascular healing, for example, restenosis or plaque stabilisation, in mammals.

Abstract: The present invention relates to the use of the dye methylene blue (MB) or a related compound to prevent or reverse an exaggerated hemodynamic reaction in animals in need thereof, including humans. More specifically, the present invention concerns the use of MB or a related compound to prevent or reverse hypotension, unstable angina, myocardial infarction or shock caused by the concomitant ingestion of a phosphodiesterase inhibitor, such as sildenafil citrate, and a NO-donor, such as L-arginine, or an organic nitrate, such as nitroglycerin.

Abstract: The present invention provides novel antisense oligonucleotides that target the genes and mRNAs encoding mammalian Estrogen Receptors (ER) alpha and/or beta and modulate the receptors' responses. These antisense oligonucleotides may be used alone or in combination with 17 Beta estradiol or a related compound (genistein, estradiol derivatives . . . ) to improve plaque stabilization, vascular healing and endothelial recovery after vascular injury. Also provided are methods for designing and testing the antisense oligonucleotides. Such oligonucleotides may be used to modulate the beneficial effects mediated by the ER on vascular healing, for example, restenosis or plaque stabilisation, in mammals.

Abstract: A device for local intracoronary delivery comprising 17-? estradiol or a derivative thereof in a dosage of 1 to 5000 ?g/Kg of patient's body weight, and a pharmaceutically acceptable parenteral vehicle

Abstract: The present invention relates to the upregulation of estrogen receptors (ER) alpha (ER?) and/or beta (ER?) in endothelial cells and/or smooth muscle cells to prevent or treat heart disease. The upregulation is achieved through the use of recombinant DNA technology and, depending on therapeutic needs, may be performed with a simultaneous or subsquent downregulation, as with antisense technology. Oligonucleotides coding for ER? and/or ER? are introduced into the targeted cells through the use of adenoviruses, for example. With an increase in receptors, the cells should be more responsive to such agonists as 17-beta-estradiol (17?E) and related compounds (genistein, estradiol derivatives . . . ) to improve plaque stabilization, vascular healing and endothelial recovery after vascular injury. Such oligonucleotides may be used to modulate the beneficial effects mediated by the ER on vascular healing, for example, restenosis or plaque stabilisation, in mammals.

Abstract: The cardioprotective effects of estrogen are well recognized. In in vitro experiments, and upon systemic administration, 17-beta estradiol has shown to inhibit vascular smooth muscle cell proliferation and intima hyperplasia and to improve vascular endothelium function, after vascular injury. We hypothesized that locally delivered 17-beta estradiol could prevent restenosis. Compositions are use of 17-beta estradiol for in-situ administration at a vascular injured site are objects of the present invention.

Abstract: The present invention relates to methods and compositions for the modulation of restenosis and stenosis characterized by constrictive vascular remodeling and neointimal formation, in a subject, by administering a P-selectin antagonist. The invention further provides methods for modulating leukocyte recruitment, cell to cell adhesion, and cell adhesion to blood vessels in a subject by administering soluble P-selectin ligand, an anti-P-selectin ligand antibody, or an anti-P-selectin antibody. The invention also provides methods for identifying compounds capable of modulating restenosis.

Abstract: The present invention relates to the use of the dye methylene blue (MB) or a related compound to prevent or reverse an exaggerated hemodynamic reaction in animals in need thereof, including humans. More specifically, the present invention concerns the use of MB or a related compound to prevent or reverse hypotension, unstable angina, myocardial infarction or shock caused by the concomitant ingestion of a phosphodiesterase inhibitor, such as sildenafil citrate, and a NO-donor, such as L-arginine, or an organic nitrate, such as nitroglycerin.

Abstract: The present invention provides novel antisense oligonucleotides that target the genes and mRNAs encoding mammalian Estrogen Receptors (ER) alpha and/or beta and modulate the receptors' responses. These antisense oligonucleotides may be used alone or in combination with 17 Beta estradiol or a related compound (genistein, estradiol derivatives . . . ) to improve plaque stabilization, vascular healing and endothelial recovery after vascular injury. Also provided are methods for designing and testing the antisense oligonucleotides. Such oligonucleotides may be used to modulate the beneficial effects mediated by the ER on vascular healing, for example, restenosis or plaque stabilisation, in mammals.

Abstract: A method for inhibiting restenosis includes applying cryogenic energy to a treatment site for a predetermined amount of time. In one embodiment, the treatment site, e.g., a region of an artery dilated by means of a balloon catheter, is cooled to a temperature of about minus fifty degrees Celsius for about two minutes. The application of cryogenic energy inhibits restenosis of the dilated region of the vessel.