Other

Bette S Pollard

Harvey B Pollard

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.

Cardiac glycosides to treat cystic fibrosis and other IL-8 dependent disorders

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.

Amphiphilic pyridinum compounds to treat epilepsy and other disorders of the nervous system

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.

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Potomac, MD, United States of America

Bette S Pollard