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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1996-6-13
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pubmed:databankReference | |
pubmed:abstractText |
Tricyclic antidepressant overdose can be reversed in rats by drug-specific antibody Fab fragments, but the required Fab dose may itself by toxic. We studied the potential use of a smaller, recombinant desipramine (DMI)-specific single chain Fv fragment (B9-sFv) for this purpose. Anesthetized rats received a tracer (subtoxic) dose of [3H]-DMI followed in 15 min by B9-IgG, B9-Fab, B9-sFv (0.1 mumol of binding sites) or BSA. Each of the active treatments produced a rapid and substantial increase in the serum radiolabel concentration, whereas BSA did not (P < 0.001). The increase in serum radiolabel concentration 1 min after treatment was 13.3-fold with B9-IgG, 10.0-fold with B9-Fab and 7.3-fold with B9-sFv. Serum antibody concentrations were also highest after B9-IgG and lower with B9-Fab or B9-sFv. The 24-hr urinary excretion of radiolabel did not differ among groups, but was extensive even in the BSA group and probably represented the excretion of DMI metabolites. B9-sFv concentrations in urine or buffer at 37 degrees declined by >90% over 24 hr, but this fragment was much more stable in serum, retaining 70% of its activity after 96 hr. These data demonstrate that B9-sFv can alter markedly the distribution of [3H]-DMI in vivo. The rapidity of this effect, and its magnitude in comparison with Fab fragment or IgG, suggest that further study of B9-sFv as a treatment of DMI overdose is warranted.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antidepressive Agents, Tricyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Desipramine,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fab Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Variable Region,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/immunoglobulin Fv
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
531-7
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8619899-Analysis of Variance,
pubmed-meshheading:8619899-Animals,
pubmed-meshheading:8619899-Antidepressive Agents, Tricyclic,
pubmed-meshheading:8619899-Binding Sites,
pubmed-meshheading:8619899-Desipramine,
pubmed-meshheading:8619899-Immunoglobulin Fab Fragments,
pubmed-meshheading:8619899-Immunoglobulin Fragments,
pubmed-meshheading:8619899-Immunoglobulin Variable Region,
pubmed-meshheading:8619899-Male,
pubmed-meshheading:8619899-Metabolic Clearance Rate,
pubmed-meshheading:8619899-Radioisotope Dilution Technique,
pubmed-meshheading:8619899-Rats,
pubmed-meshheading:8619899-Recombinant Proteins,
pubmed-meshheading:8619899-Tritium
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pubmed:year |
1996
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pubmed:articleTitle |
Effects of recombinant drug-specific single chain antibody Fv fragment on [3H]-desipramine distribution in rats.
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pubmed:affiliation |
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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