Linked Life Data

9790308

Source:http://linkedlifedata.com/resource/pubmed/id/9790308

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-11-13
pubmed:abstractText
A77 1726 is a malononitrilamide (MNA) and the active metabolite of leflunomide, which has been extensively investigated and shown to be a potent immunosuppressive drug. However, the half-life of A77 1726 is about 15-18 days in humans and leflunomide is therefore currently being developed for the treatment of autoimmune disease and not for transplantation. Search for analogues has led to the discovery of MNA 715 and 279, derivatives of A77 1726. Previous experimental experience of these compounds is still limited. The aim of the present study was to verify the efficacy of these MNAs concerning prevention and reversal of rejection, inhibition of antibody production and interaction with cyclosporin A (CsA). Heterotopic cardiac transplantation in DA to PVG rats was used. Subgroups of rats were given either CsA, MNA 715 or MNA 279 for 10 days, starting at either day 0 or day 4, or received no treatment. Titres of allospecific immunoglobulin M (IgM) and immunoglobulin G (IgG) were quantified by flow cytometry. Ten days of induction with MNA 715 or 279 produced significantly longer graft survival than in controls. Treatment from day 4 onwards, when acute rejection was established, rescued all grafts. Allospecific production of IgM or IgG was absent during MNA induction and was suppressed in animals receiving a rescue course of MNA. The transplant model was potentiated by addition of the immunomodulator quinolone-3-carboxamide (Linomide), which eliminates the effect of CsA and other immunosuppressants. The combined treatment with MNA and CsA was successful in overcoming the challenge of Linomide, demonstrating the additive effects of the two drugs. In conclusion, MNA 715 and 279 were shown to be potent immunosuppressants, preventing and reversing acute allograft rejection, inhibiting and suppressing allospecific antibody production, and the drugs interacted positively with CsA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0300-9475
pubmed:author
pubmed:issnType
Print
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
379-88
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Malononitrilamides 715 and 279 prolong rat cardiac allograft survival, reverse ongoing rejection, inhibit allospecific antibody production and interact positively with cyclosporin.
pubmed:affiliation
Department of Experimental Research, Lund University, University Hospital, Malmö, Sweden.
pubmed:publicationType
Journal Article