Abstract: A small molecule inhibitor for treating a disorder in mammals, wherein the disorder is characterized by high levels of inflammatory components. In a preferred embodiment, the inhibitor comprises cardiac glycosides, also known as cardiac cardenolides. In one example, the drug digitoxin is used to treat the disorder cystic fibrosis. The compounds and methods of the invention are particularly effective for treating cystic fibrosis, a disorder or condition characterized by high levels of inflammation and IL-8.

Abstract: Disclosed is the use of a cardiac glycoside to decrease or inhibit the secretion of proinflammatory mediators in the treatment of disease conditions characterized by elevated levels of the proinflammatory mediator. The cardiac glycoside is administered to a mammalian subject in need of such treatment, and dosage is adjusted to the mass of the recipient and the need of the recipient to reduce or inhibit the level of the proinflammatory mediator. The proinflammatory mediators suppressed by the invention include IL-8, IL-6, TNFalpha, ICAM-1, IFNgamma, IL-1-beta, MCP-1, MIP-2, and/or epithelial-mesenchymal-transition (EMT). The cardiac glycoside, digitoxin or oleandrin, can be formulated for administration by injection or as an aerosol administered to the respiratory tract or by being ingested, or as nose drops or nasal spray. According to one use, the digitoxin controls microRNA expression in castration-resistant prostate cancer. The microRNA suppresses IL-8 and IL-6 expression in these cells.

Abstract: A pharmaceutical composition including an amphiphilic pyridinium compound for treating neurological disorders or seizure disorders, in particular epilepsy, and other disorders of the nervous system. The pharmaceutical composition may be used as a primary treatment or as an adjuvant treatment. Administration of the amphiphilic pyridinium compound(s) may occur prior to the manifestation of symptoms characteristic of epilepsy, such that epilepsy is prevented, or alternatively, delayed in its progression.

Abstract: A pharmaceutical composition including an amphiphilic pyridinium compound for treating neurological disorders or seizure disorders, in particular epilepsy, and other disorders of the nervous system. The pharmaceutical composition may be used as a primary treatment or as an adjuvant treatment. Administration of the amphiphilic pyridinium compound(s) may occur prior to the manifestation of symptoms characteristic of epilepsy, such that epilepsy is prevented, or alternatively, delayed in its progression.

Abstract: Disclosed is the use of a cardiac glycoside to decrease or inhibit the secretion of proinflammatory mediators in the treatment of disease conditions characterized by elevated levels of the proinflammatory mediator. The cardiac glycoside is administered to a mammalian subject in need of such treatment, and dosage is adjusted to the mass of the recipient and the need of the recipient to reduce or inhibit the level of the proinflammatory mediator. The proinflammatory mediators suppressed by the invention include IL-8, IL-6, TNFalpha, ICAM-1, IFNgamma, IL-1-beta, MCP-1, MIP-2, and/or epithelial-mesenchymal-transition (EMT). The cardiac glycoside, digitoxin or oleandrin, can be formulated for administration by injection or as an aerosol administered to the respiratory tract or by being ingested, or as nose drops or nasal spray. According to one use, the digitoxin controls microRNA expression in castration-resistant prostate cancer. The microRNA suppresses IL-8 and IL-6 expression in these cells.

Abstract: A method of inhibiting the secretion of IL-8 and other pro-inflammatory cytokines from cells secreting elevated levels of these compounds is provided. The method includes contacting the cell with a composition comprising a cardiac glycoside such as oleandrin. The cardiac glycoside can be used to treat cystic fibrosis and other IL-8 dependent disorders by lowering levels of spontaneously secreted IL-8 and other pro-inflammatory cytokines. Oleandrin was found to suppress the secretion of IL-8 from cultured CF lung epithelial cells in the nanomolar concentration range. Structure-activity relationships (SARs) for cardiac glycosides are also elucidated.

Abstract: A method of inhibiting the secretion of IL-8 and other pro-inflammatory cytokines from cells secreting elevated levels of these compounds is provided. The method includes contacting the cell with a composition comprising a cardiac glycoside such as oleandrin. The cardiac glycoside can be used to treat cystic fibrosis and other IL-8 dependent disorders by lowering levels of spontaneously secreted IL-8 and other pro-inflammatory cytokines. Oleandrin was found to suppress the secretion of IL-8 from cultured CF lung epithelial cells in the nanomolar concentration range. Structure-activity relationships (SARs) for cardiac glycosides are also elucidated.

Abstract: A method of inhibiting the secretion of IL-8 and other pro-inflammatory cytokines from cells secreting elevated levels of these compounds is provided. The method includes contacting the cell with a composition comprising a cardiac glycoside such as oleandrin. The cardiac glycoside can be used to treat cystic fibrosis and other IL-8 dependent disorders by lowering levels of spontaneously secreted IL-8 and other pro-inflammatory cytokines. Oleandrin was found to suppress the secretion of IL-8 from cultured CF lung epithelial cells in the nanomolar concentration range. Structure-activity relationships (SARs) for cardiac glycosides are also elucidated.

Abstract: The present invention is directed to a Factor XIIa-coated solid support comprising a recombinant Factor XIIa polypeptide or a Factor XIIa-expressing cell comprising an expression vector construct containing a gene encoding a Factor XII polypeptide. The invention is also directed to methods of treating a subject with a coagulation protein. Additionally, the invention is directed to methods of treating or preventing bleeding. The present invention is also directed towards a kit.

Abstract: Bypass activity for hemophilia A and B can be generated by natural or recombinant Factor VIIa. Factor XIIa when implanted into a guinea pig or monkey also facilitates the conversion of endogenous factor VII to VIIa, thereby providing bypass activity. Additionally, certain modified versions of Factor XII are known to be intrinsically active, with properties like Factor XIIa. Administration of unencapsulated Factor XIIa to a guinea pig causes a transient increase in plasma bypass activity. A continuous source of Factor XIIa, as provided by a gene therapy, is therapeutic for both Hemophilia A and B. There are three ways to provide for gene therapy. In each case, the gene for Factor XII (or Factor XIIa) can be introduced into the cell by the usual means, including, but not limited to, as naked DNA, as a DNA/lipid mixture, or as part of a viral vector system.