Linked Life Data

16206083

Source:http://linkedlifedata.com/resource/pubmed/id/16206083

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-10-5
pubmed:abstractText
There is an urgent need to discontinue the use of highly toxic compounds still in use for treatment of the encephalitic stage of human African trypanosomiasis (HAT). We show here that intraperitoneal injection of the adenosine analogue cordycepin (3'-deoxyadenosine), together with an adenosine deaminase (ADA) inhibitor (coformycin or deoxycoformycin), cures Trypanosoma brucei brucei infection in mice. Treatment was also effective at a stage when the trypanosomes had penetrated into the brain parenchyma, as determined by double immunolabeling of parasites and cerebral vessel endothelial cells in brain sections. At this stage, the parasites were eliminated not only from the blood but also from the brain parenchyma. In parallel with the elimination of parasites, in treated mice, the number of CD45+ inflammatory cells in the brain parenchyma was reduced. Treatment was not immunosuppressive. In vitro incubation with cordycepin reduced the growth of T. brucei brucei and T. cruzi, as well as Leishmania major and L. amazonensis. Administration of cordycepin plus deoxycofomycin to T. cruzi-infected mice also significantly reduced parasitemia. Accordingly, we propose nucleoside analogues resistant to ADA as candidates for treatment of late-stage HAT.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1899
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
192
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1658-65
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16206083-Adenosine Deaminase, pubmed-meshheading:16206083-Adenosine Deaminase Inhibitors, pubmed-meshheading:16206083-Animals, pubmed-meshheading:16206083-Antiprotozoal Agents, pubmed-meshheading:16206083-Deoxyadenosines, pubmed-meshheading:16206083-Disease Models, Animal, pubmed-meshheading:16206083-Dose-Response Relationship, Drug, pubmed-meshheading:16206083-Drug Evaluation, Preclinical, pubmed-meshheading:16206083-Drug Therapy, Combination, pubmed-meshheading:16206083-Injections, Intraperitoneal, pubmed-meshheading:16206083-Leishmania, pubmed-meshheading:16206083-Mice, pubmed-meshheading:16206083-Mice, Inbred BALB C, pubmed-meshheading:16206083-Mice, Inbred C57BL, pubmed-meshheading:16206083-Trypanosoma brucei brucei, pubmed-meshheading:16206083-Trypanosoma cruzi, pubmed-meshheading:16206083-Trypanosomiasis, African
pubmed:year
2005
pubmed:articleTitle
Treatment of African trypanosomiasis with cordycepin and adenosine deaminase inhibitors in a mouse model.
pubmed:affiliation
Microbiology and Tumorbiology Center, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. martin.rottenberg@mtc.ki.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't