Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthetic ovine corticotropin-releasing factor (CRF) was administered to normal male volunteer subjects as an intravenous bolus or 30-s infusion. Doses of CRF ranging from 0.001 to 30 micrograms/kg body wt were administered, and plasma immunoreactive (IR)-ACTH and IR-cortisol concentrations were measured. The threshold dose appeared to be 0.01-0.03 micrograms/kg, the half-maximal dose 0.3-1 micrograms/kg, and the maximally effective dose 3-10 micrograms/kg. Basal concentrations of IR-ACTH and IR-cortisol were 14 +/- 7.6 pg/ml (mean +/- SD) and 5.6 +/- 2.2 micrograms/dl, respectively. IR-ACTH rose as early as 2 min after CRF injection, reached peak levels in 10-15 min, and declined slowly thereafter. IR-cortisol rose at 10 min or later and reached peak levels in 30-60 min. At a dose of 30 micrograms/kg, neither IR-ACTH nor IR-cortisol fell from peak levels of 82 +/- 21 pg/ml (mean +/- SE) and 23 +/- 1.4 micrograms/dl, respectively, during the 2-h course of the experiment, indicating that CRF has a sustained effect on ACTH release and/or a prolonged circulating plasma half-life. There was little or no increase in the levels of other anterior pituitary hormones. At doses of 1 microgram/kg and higher, facial flushing, tachycardia, and, in some subjects, a 15-29-mmHg decline in systemic arterial blood pressure were observed, even though blood volume was replaced and the subjects remained supine. These data indicate that synthetic ovine CRF is a very potent and specific ACTH secretagogue in man. Administered with caution until its vasomotor effects are more fully defined, CRF promises to be a safe and very useful investigative, diagnostic, and, possibly, therapeutic agent in man.
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PMID:Effect of synthetic ovine corticotropin-releasing factor. Dose response of plasma adrenocorticotropin and cortisol. 629 80

Corticorelin is a synthetic analog of the naturally occurring human peptide corticotropin-releasing factor (CRF). Several studies have indicated the ability of CRF to reduce the brain edema caused by brain tumors. Peritumoral brain edema (PBE), caused by an intracerebral tumor, manifests several features of vasogenic edema, which is a type of edema characterized by disruption of the blood-brain barrier. Traditionally, PBE has been treated using corticosteroids, primarily dexamethasone. Introduced more than four decades ago, dexamethasone revolutionized the treatment of PBE, but the side effects and withdrawal symptoms associated with corticosteroids propelled the investigation of other drugs. Clinical trials with the synthetic human CRF (hCRF) corticorelin (Xerecept, NEU-3002; Celtic Pharmaceutical Holdings) have indicated that this drug has a distinct advantage over classical corticosteroids in the treatment of PBE. Fewer and/or milder side effects have been reported for corticorelin compared with dexamethasone, although at higher doses of corticorelin several side effects, including hypotension and transient flushing, have been reported. Nevertheless, corticorelin was reasonably well tolerated in patients and healthy volunteers, and may be a good candidate for reducing PBE and associated neural damage, as well as improving neurological symptoms.
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PMID:Corticorelin, a synthetic human corticotropin-releasing factor analog, for the treatment of peritumoral brain edema. 2115 69