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Enzyme
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Target Concepts:
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Query: UMLS:C0018133 (
graft-versus-host disease
)
18,032
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Thalidomide is in clinical use for the treatment of
graft-versus-host disease
in leukemia patients after bone marrow transplant. Low levels of the drug in plasma after oral administration have made an intravenous thalidomide formulation desirable. Thalidomide, however, is sparingly soluble in aqueous solution (50 micrograms/mL) and unstable. Complexation with hydroxypropyl-beta-cyclodextrin has significantly improved the aqueous solubility and stability of thalidomide. Results obtained with HPLC and 1H
NMR
spectrometry have demonstrated that the solubility is increased to 1.7 mg/mL and the half-life of a diluted solution is extended from 2.1 to 4.1 h. Hence, an intravenous thalidomide-hydroxypropyl- beta-cyclodextrin solution has the potential to significantly improve current therapy for
graft-versus-host disease
by providing sustained high levels of drug in the plasma.
...
PMID:Improvements in solubility and stability of thalidomide upon complexation with hydroxypropyl-beta-cyclodextrin. 140 4
The liver is a major target organ of
graft-versus-host disease
. We have induced graded intensities of acute
GVHD
to minor histocompatibility antigens in a well-characterized murine bone marrow transplant model and analyzed hepatic pathology one month after BMT. Nuclear-magnetic-resonance relaxation times and proton spectra were compared to systemic clinical disease, serum biochemistries, and histologic findings. T2 relaxation times correlated directly with the intensity of histologic abnormalities, but the hepatic histology remained mild even in animals with moderate
GVHD
. In contrast,
NMR
proton spectra of hepatic tissue showed large decreases in metabolite levels (acetate and glycogen) in animals with moderate systemic disease despite mild hepatic histology. We conclude that
NMR
of the liver can be used to differentiate hepatic from systemic
GVHD
in this model and may help to elucidate the differential effects of
GVHD
in various target organs.
...
PMID:Nuclear magnetic resonance of hepatic graft-versus-host disease in mice. 225 43