DOUGLAS VAUGHAN, MD
Osteopathic Medicine in Nashville, TN

2002014, Oct 3, 2002

Oct 10, 2001

09/974703

Douglas Vaughan - Nashville TN, US

A61K038/05, A61K031/403

514/019000, 514/412000

A method for preventing or reducing a risk of cardiovascular disease in a healthy subject via administration of an ACE inhibitor. Also provided is a method for reducing a plasma level of PAI-1 in a healthy subject via administration of an ACE inhibitor. The methods can be combined with hormone replacement therapy for improved effectiveness. Representative healthy subjects include post-menopausal women.

2006005, Mar 16, 2006

Jun 29, 2005

11/171083

Douglas Vaughan - Nashville TN, US
Mesut Eren - Nashville TN, US

A61K 31/404

514416000

A method of treating a warm-blooded vertebrate animal having a medical condition in need of treatment with a composition that exhibits PAI-1 inhibition activity is disclosed. The method includes the steps of administering a treatment effective amount of the composition to a warm-blooded vertebrate animal having a medical condition selected from the group consisting of alopecia, undesired weight loss, Alzheimer's Disease, systemic amyloidosis, myelofibrosis, male pattern baldness, glomerulosclerosis, veno-occlusive disease (VOD), pulmonary fibrosis, obesity, non-alcoholic steatohepatitis (NASH), osteoporosis, osteopenia, polycystic ovarian syndrome (PCOS), and combinations thereof; and observing an improvement in the medical condition in the warm-blooded vertebrate animal having the medical condition. A method of testing a candidate composition for PAI-1 inhibition activity is also disclosed. The method includes the steps of obtaining a transgenic non-human warm blooded vertebrate animal having incorporated into its genome a PAI-1 gene encoding a biologically active PAI-1 polypeptide, the PAI-1 gene being present in the genome in a copy number effective to confer overexpression in the transgenic non-human animal of the PAI-1 polypeptide; administering the composition to the transgenic non-human animal; and observing the transgenic non-human animal for determination of a change in the transgenic non-human animal indicative of inhibition of the activity of PAI-1. A transgenic non-human animal useful is such a method is also disclosed, as is a PAI-1 transgene construct encoding a biologically active PAI-1 polypeptide useful for preparing the transgenic non-human animal.

7057086, Jun 6, 2006

Feb 19, 2003

10/368995

Douglas E. Vaughan - Nashville TN, US
Mesut Eren - Nashville TN, US
Paul J. Declerck - Leuven, BE

Vanderbilt University - Nashville TN

A01K 67/027, G01N 33/00, C07H 21/04, C12N 15/00

800 18, 800 3, 536 241, 4353201

A method of testing a candidate composition for PAI-1 inhibition activity is disclosed. The method includes the steps of obtaining a transgenic non-human warm blooded vertebrate animal having incorporated into its genome a PAI-1 gene encoding a biologically active PAI-1 polypeptide, the PAI-1 gene being present in the genome in a copy number effective to confer over-expression in the transgenic non-human animal of the PAI-1 polypeptide; administering the composition to the transgenic non-human animal; and observing the transgenic non-human animal for determination of a change in the transgenic non-human animal indicative of inhibition of the activity of PAI-1. A transgenic non-human animal useful in such a method is also disclosed, as is a PAI-1 transgene construct encoding a biologically active PAI-1 polypeptide useful for preparing the transgenic non-human animal.

5599663, Feb 4, 1997

Aug 27, 1993

8/113292

Douglas E. Vaughan - Nashville TN

Brighan & Women's Hospital - Boston MA

C12Q 168, G01N 33567, G01N 3353

435 6

Angiotensin IV (VAL-TYR-ILE-HIS-PRO-PHE), a degradation product of angiotensin II previously thought to be inactive, interacts directly with endothelial cells to induce expression of PAI-1 and thereby to inhibit clot lysis attributable to endogenous t-PA. Moreover, angiotensin IV does not effect substantial physiological changes (vasoconstriction, increased blood pressure, etc. ) characteristic of angiotensin II. Fibrinolysis is promoted by reducing the amount or the effect of angiotensin IV. Fibrinolysis is inhibited by providing enhanced angiotensin IV. Methods of screening candidates for antagonizing angiotensin IV are also disclosed.