home
***
CD-ROM
|
disk
|
FTP
|
other
***
search
/
Collection of Education
/
collectionofeducationcarat1997.iso
/
HEALTH
/
MED9602.ZIP
/
M9620305.TXT
< prev
next >
Wrap
Text File
|
1996-02-26
|
3KB
|
48 lines
Document 0305
DOCN M9620305
TI Influence of human granulocyte-macrophage colony stimulating
factor/interleukin-3 fusion protein (PIXY321) on the hematopoietic
toxicity associated with anti-viral drugs (zidovudine and didanosine) in
vitro using normal human marrow cells.
DT 9602
AU Gallicchio VS; Hughes NK; Division of Hematology/Oncology, Markey Cancer
Center, University; of Kentucky, Lexington 40536-0084, USA.
SO Life Sci. 1995 Sep 22;57(18):PL265-73. Unique Identifier : AIDSLINE
MED/96035980
AB The antiviral drugs didanosine (ddI) and zidovudine (AZT), synthetic
nucleoside analogs, have been used in the treatment of acquired
immunodeficiency syndrome (AIDS). Although clinical use of zidovudine
(AZT) is still widely used, it is associated with the development of
virus disease resistance and toxicity to the hematopoietic system.
Alternative nucleoside reverse transcriptase derivatives such as
didanosine (ddI) have been developed in order to reduce the incidence of
virus disease resistance and hematological toxicity. We report here
studies designed to ev evaluate the toxicity profile comparing
didanosine (ddI) with zidovudine (AZT) when used alone or in combination
with normal non-adherent, T-cell depleted human marrow cells plated in
the presence or absence of the human cytokine fusion protein of
granulocyte-macrophage colony stimulating factor and interleukin-3
(PIXY321). As expected, didanosine (ddI) was less toxic for human
hematopoietic progenitor cells, i.e., CFU-GEMM, CFU-GM, CFU-Meg, and
BFU-E than zidovudine. Toxicity was additive when didanosine (ddI) and
zidovudine (AZT) were combined. In the absence of drugs PIXY321 colony
formation was increased for all progenitor cells cultured. In the
presence of didanosine (ddI) or zidovudine (AZT), either as
single-agents or combined, PIXY321 reduced toxicity significantly. These
results demonstrate PIXY321 is an effective cytokine capable of
reversing the toxicity associated with anti-viral drugs when used in
vitro where didanosine (ddI) is less toxic than zidovudine (AZT);
however their suppression of hematopoietic progenitors is additive when
combined.
DE Antiviral Agents/PHARMACOLOGY Bone Marrow/*DRUG EFFECTS Cells,
Cultured Didanosine/*PHARMACOLOGY/*TOXICITY Dose-Response
Relationship, Drug Granulocyte-Macrophage Colony-Stimulating
Factor/*PHARMACOLOGY Growth Substances Hematopoietic Stem Cells/*DRUG
EFFECTS Human In Vitro Interleukin-3/*PHARMACOLOGY Recombinant
Fusion Proteins/*PHARMACOLOGY Support, U.S. Gov't, Non-P.H.S. Support,
U.S. Gov't, P.H.S. Zidovudine/*PHARMACOLOGY/*TOXICITY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).