Linked Life Data

10547152

Source:http://linkedlifedata.com/resource/pubmed/id/10547152

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1999-12-8
pubmed:abstractText
CNI-1493, a newly developed, water-soluble tetravalent guanylhydrazone, is a powerful inhibitor of tumor necrosis factor (TNF) and interleukin-1 (IL-1) synthesis. Microencapsulation of drugs into microcapsules that target macrophages has improved the effectiveness of both TNF and IL-1 neutralizing antibodies in experimental models of septic shock. It is the purpose of this study to determine if microencapsulation of CNI-1493 will improve cytokine inhibition. CNI-1493 was microencapsulated using albumin into 1 microm spheres. Comparable amounts of CNI-1493 in solution and in microencapsulated form were added to 1 ml aliquots of whole blood along with 100 ng of endotoxin. TNF and IL-1 were measured by ELISA. Microencapsulated CNI-1493 was also given to rats with endotoxic shock (15 mg/kg Escherichia coli endotoxin) and rats with peritonitis induced by peritoneally injecting 10(10) CFU E. coli. Equivalent amounts of encapsulated and solution CN I-493 were given intravenously. Endotoxin 15 mg/kg was also given to rats 6 and 24 h after a dose of encapsulated CNI-1493 to determine the duration of action of encapsulated drug. The microencapsulated CNI-1493 produced significantly greater inhibition of TNF and IL-1 at all doses in the whole blood model. There was significantly improved survival and cytokine inhibition in the endotoxic shock model as well as the peritonitis model in rats treated with microencapsulated CNI-1493. There was also 83% survival in rats given endotoxin 24 h after a dose of encapsulated CNI-1493. From these data, we conclude that CNI-1493 is a potent inhibitor of cytokine production and is greatly potentiated by microencapsulation, which transports the drug to macrophages.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1079-9907
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1125-33
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Prevention of lethality and suppression of proinflammatory cytokines in experimental septic shock by microencapsulated CNI-1493.
pubmed:affiliation
Department of Pharmaceutical Sciences, Southern College of Pharmacy, Mercer University, Atlanta, GA 30341, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't