Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-4-28
pubmed:abstractText
Diethylcarbamazine (DEC) was discovered in 1947 as a potent therapeutic agent in lymphatic filariasis and has been a mainstay of antifilarial therapy over the past five decades (R. I. Hewitt, et al., 1947, Journal of Laboratory and Clinical Medicine 32, 1304-1313). Several hundred million doses of this drug have been administered to people. Despite its widespread and successful use over this prolonged time scale, its mechanism of action remains obscure (R. M. Maizels and D. A. Denham, 1992, Parasitology 105 Suppl. 549-560). Numerous studies suggest that DEC has no direct effect on the parasite (F. Hawking and W. Laurie, 1949, Lancet 2, 146-147) and that it exerts its action by stimulating host immune defense mechanisms (F. Hawking et al., 1948, Lancet 2, 730-731), or by activating host platelets to become microfilaricidal (J. Y. Cesbron et al., 1987, Nature 325(6104) 533-536). Recent data from two different laboratories suggest that NO may be involved in host defense against filarial parasites (T. V. Rajan et al., 1996, Infection and Immunity 64(8), 3351-3353; M. J. Taylor et al., 1996, Parasitology 112, 315-322). We investigated whether DEC stimulates the production of NO from murine macrophages or rat endothelial cells. DEC did not stimulate the synthesis or secretion of NO from either, nor did it synergize with interferon-gamma or tumor necrosis factor-alpha in the induction of inducible NO synthase (iNOS). In addition, there was no consistent increase in the output of inorganic nitrate, the end product of NO metabolism, in the urines of rats treated with DEC. These data suggest that DEC does not achieve its therapeutic efficacy through the induction of host iNOS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0014-4894
pubmed:author
pubmed:issnType
Print
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
217-22
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9562425-Animals, pubmed-meshheading:9562425-Cells, Cultured, pubmed-meshheading:9562425-Diethylcarbamazine, pubmed-meshheading:9562425-Dose-Response Relationship, Drug, pubmed-meshheading:9562425-Drug Synergism, pubmed-meshheading:9562425-Endothelium, Vascular, pubmed-meshheading:9562425-Filaricides, pubmed-meshheading:9562425-Interferon-gamma, pubmed-meshheading:9562425-Macrophages, Peritoneal, pubmed-meshheading:9562425-Mice, pubmed-meshheading:9562425-Nitrates, pubmed-meshheading:9562425-Nitric Oxide, pubmed-meshheading:9562425-Nitric Oxide Synthase, pubmed-meshheading:9562425-Nitric Oxide Synthase Type II, pubmed-meshheading:9562425-Rats, pubmed-meshheading:9562425-Rats, Nude, pubmed-meshheading:9562425-Thioglycolates, pubmed-meshheading:9562425-Tumor Necrosis Factor-alpha, pubmed-meshheading:9562425-Up-Regulation
pubmed:year
1998
pubmed:articleTitle
Diethylcarbamazine (DEC) does not induce nitric oxide (NO) synthesis.
pubmed:affiliation
Department of Pathology, University of Connecticut Health Center, Farmington 06030-3105, USA.
pubmed:publicationType
Journal Article