Abstract: The present invention provides methods for preventing the accumulation of cholesterol/triglycerides within mammalian cells. The present methods are based upon the surprising discovery that ER stress in a cell leads to cholesterol/triglyceride accumulation within the cell, which cholesterol/triglyceride accumulation is often a causative factor in the development of any of a number of conditions or diseases, such as atherosclerosis. The ER stress can be the result of any of a variety of causes, including homocysteine, viral infection, and hypoxia. Accordingly, counteracting the progression or the severity of ER stress can be used to inhibit the accumulation of cholesterol/triglycerides in said cell, thereby preventing or lessening the severity of any of a number of cholesterol-related diseases or conditions, e.g., atherosclerosis. In addition, the presence of ER stress in a cell can be used to diagnose a cholesterol associated disease, or to predict the propensity of a mammal to develop a disease.

Abstract: Novel conjugates of glycosaminoglycans, particularly heparin and dermatan sulfate, and amine containing species and therapeutic uses thereof are described. In particular, mild methods of conjugating heparins to proteins, such as antithrombin III and heparin cofactor II, which provide covalent conjugates which retain maximal biological activity are described. Uses of these conjugates to prevent thrombogenesis, in particular in lung airways, such as found in infant and adult respiratory distress syndrome, and on surfaces in contact with blood are also described.

Abstract: Novel conjugates of glycosaminoglycans, particularly heparin and dermatan sulfate, and amine containing species and therapeutic uses thereof are described. In particular, mild methods of conjugating heparins to proteins, such as antithrombin III and heparin cofactor II, which provide covalent conjugates which retain maximal biological activity are described. Uses of these conjugates to prevent thrombogenesis, in particular in lung airways, such as found in infant and adult respiratory distress syndrome are also described.

Abstract: Novel conjugates of glycosaminoglycans, particularly heparin and dermatan sulfate, and amine containing species and therapeutic uses thereof are described. In particular, mild methods of conjugating heparins to proteins, such as antithrombin III and heparin cofactor II, which provide covalent conjugates which retain maximal biological activity are described. Uses of these conjugates to prevent thrombogenesis, in particular in lung airways, such as found in infant and adult respiratory distress syndrome, and on surfaces in contact with blood are also described.

Abstract: A method for diagnosing hyperhomocysteinemia by molecular genetic means is disclosed.

Abstract: The present invention provides compositions and methods for the treatment of cardiovascular diseases. More particularly, the present invention relates to modifying thrombus formation by administering an agent which, inter alia, is capable of (1) inactivating fluid-phase thrombin and thrombin which is bound either to fibrin in a clot or to some other surface by catalyzing antithrombin; and (2) inhibiting thrombin generation by catalyzing factor Xa inactivation by antithrombin III (ATIII). The compositions and methods of the present invention are particularly usefull for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc.

Abstract: The present invention provides compositions and methods for the treatment of cardiovascular diseases. More particularly, the present invention relates to modifying thrombus formation by administering an agent which, inter alia, is capable of (1) selectively inactivating thrombin which is bound either to fibrin in a clot or to some other surface, but which has only minimal inhibitory activity against free thrombin, i.e., fluid-phase thrombin; (2) inhibiting the assembly of the intrinsic tenase complex, thereby inhibiting the activation of Factor X by Factor IXa; and (3) inhibiting the activation of Factor IX by Factor XIa.

Abstract: A method for diagnosing hyperhomocysteinemia by molecular genetic means is disclosed.

Abstract: The present invention generally relates to a processes for preparing low affinity, low molecular weight heparins (LA-LWM-heparins) which are endowed with pharmacological and therapeutic properties that are surprisingly advantageous. In one embodiment, the process comprises: (1) nitrous acid depolymerization of unfractionated heparin to yield low molecular weight heparin (LMWH); (2) oxidation of the resulting LMWH to open the ring structures the nonsulfated uronic acid moieties using, for example, sodium periodate; and (3) reduction of the oxidized LMWH to reduce the aldehydes (to alcohols) formed during the depolymerization and oxidation steps using, for example, sodium borohydride. The resulting LA-LMW-heparins are capable of inactivating thrombin bound to fibrin within a thrombus or clot, whereby the ability of clot-bound thrombin to catalytically promote further clot accretion is substantially diminished or eliminated.

Abstract: The present invention provides compositions and methods for inactivating thrombin bound to fibrin within a thrombus or clot, whereby the ability of clot-bound thrombin to catalytically promote further clot accretion is substantially diminished or eliminated. The compositions and methods of the present invention are particularly useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc.

Abstract: The present invention provides compositions and methods for inactivating thrombin bound to fibrin within a thrombus or clot, whereby the ability of clot-bound thrombin to catalytically promote further clot accretion is substantially diminished or eliminated. The compositions and methods of the present invention are particularly useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc.

Abstract: Thrombus or clot formation and accretion are inhibited by administering thrombin-displacing substances to a patient. The thrombin-displacing substances comprise either thrombin analogs which bind to the thrombin-binding site on fibrin or fibrin analogs which bind to a fibrin-binding site on thrombin. By displacing the thrombin from clot or thrombus, the thrombin is released into circulation where it is inactivated by endogenous anti-proteinases. The fibrin analogs which bind to the fibrin-binding site on thrombin may be linked to a second binding moiety which binds to and/or inactivates the catalytic site on thrombin to further inhibit thrombosis.

Abstract: A fibrin glue includes a fibrinogen component and a thrombin component, both prepared from single donor plasma. The plasma is precipitated to produce a precipitate containing fibrinogen and a supernatant containing the thrombin. The precipitate may be resuspended in a small volume of supernatant and used as the fibrinogen component. The supernatant is further treated by clotting to convert residual fibrinogen to fibrin and filtration to remove the fibrin. The resulting serum can be used as the thrombin component.