Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,...
Patent
1995-11-27
1999-01-05
Huff, Sheela
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
4241391, 4241581, 514 12, 514 13, 514 14, 514 15, 514 16, 514 17, 514 18, 514 19, 53038824, 5303892, A61K 39395, A61K 3800
Patent
active
058558845
ABSTRACT:
Non-traumatic immobilization (restrain) stress causes rapid degranulation of rat dura mast cells, as shown both by light and electron microscopy. These morphologic findings were accompanied by elevation of rat mast cell protease cerebrospinal fluid. Mast cell activation due to stress was abolished in animals that had been treated neonatally with capsaicin, indicating that neuropeptides in sensory nerve endings are involved in this response. Complete inhibition was also achieved by pretreating the animals intraperitoneally with antiserum to corticotropin releasing hormone (CRH). Mast cells in the dura were localized close to nerve processes containing substance P, but no CRH-fibers were identified even though these were found close to mast cells elsewhere in the brain, i.e., in the median eminence. This is the first time that stress is shown to activate intracranial mast cells, apparently through the sequential actions of CRH and one or more sensory neuropeptides such as Substance P. These findings suggest that therapy of neuroinflammatory disorders such as stress-induced migraine headaches, can be achieved with blockers of the physiological actions of CRH or inhibitors of CRH production or secretion.
REFERENCES:
patent: 5250529 (1993-10-01), Theoharides
W. Boucher et al., "Corticotropin Releasing Hormone (CRH) Induces Rat Mast Cell (MC) Secretion", Tufts University Experimental Biology 95 Abstract Form, May 1995.
E. Webster et al., "The Mast Cell as a Target of Peripheral Immune Corticotrophin-Releasing Hormone (CRH) and Mediator of its Proinflammatory Properties: Clinical Implications", The Endocrine Society Abstract Form, Jun. 1995.
T. Theoharides, "Tufts Researcher Uncovers Link Between Stress and Migraines", Tufts University, Nov. 28, 1995, pp. 1-4.
T. Theoharides et al., "Stress-Induced Inracranial Mast Cell Degranulation: A Corticotrophin-Releasing Hormone-Mediated Effect", Endocrinology, vol. 136, No. 12, Dec. 1, 1995, pp. 5745-5750.
Huff Sheela
KOS Pharmaceuticals, Inc.
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