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Titolo:
TUCARESOL INCREASES OXYGEN-AFFINITY AND REDUCES HEMOLYSIS IN SUBJECTSWITH SICKLE-CELL-ANEMIA
Autore:
ARYA R; ROLAN PE; WOOTTON R; POSNER J; BELLINGHAM AJ;
Indirizzi:
UNIV LONDON KINGS COLL,SCH MED & DENT,DEPT HAEMATOL MED,DENMARK HILL LONDON SE5 9RS ENGLAND UNIV LONDON KINGS COLL HOSP,DEPT HAEMATOL MED LONDON ENGLAND WELLCOME RES LABS,DEPT CLIN PHARMACOL BECKENHAM BR3 3BS KENT ENGLAND
Titolo Testata:
British Journal of Haematology
fascicolo: 4, volume: 93, anno: 1996,
pagine: 817 - 821
SICI:
0007-1048(1996)93:4<817:TIOARH>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEMOGLOBIN; DISEASE; GELATION; BW12C; DEFORMABILITY; ERYTHROCYTES; INHIBIT; ANEMIA; BASES;
Keywords:
SICKLE CELL ANEMIA; TUCARESOL; SUBSTITUTED BENZALDEHYDE; OXYGEN AFFINITY; ANTI-SICKLING AGENT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
20
Recensione:
Indirizzi per estratti:
Citazione:
R. Arya et al., "TUCARESOL INCREASES OXYGEN-AFFINITY AND REDUCES HEMOLYSIS IN SUBJECTSWITH SICKLE-CELL-ANEMIA", British Journal of Haematology, 93(4), 1996, pp. 817-821

Abstract

The primary pathophysiological event in sickling is the intracellularpolymerization of deoxygenated haemoglobin S. Tucaresol (589C80;4[2-formyl-3-hydroxyphenoxymethyl] benzoic acid), a substituted benzaldehyde, was designed to interact with haemoglobin to increase oxygen affinity and has been shown to inhibit sickling in vitro. We administered tucaresol to sickle cell patients in the steady state to examine the anti-sickling effect in vivo. Oral doses of tucaresol or placebo were given to nine stable sickle cell patients (aged 17-39 years; tucaresol, six; placebo, three) for 10 d. The first two patients on tucaresol werescheduled to receive a loading dose of 800 mg or 1200 mg (depending on bodyweight) for the first 4 d, followed by maintenance doses of 200 or 300 mg for the next 6 d. Due to concerns over the sharp rise in haematocrit in one patient, subsequent cohorts received 300 mg tucaresol daily throughout the dosing period. The oxygen affinity of haemoglobinS was increased in all patients receiving tucaresol, with between 10%and 24% of the haemoglobin modified, dependent on dose. In all patients on tucaresol, haemolysis was reduced with rises in haemoglobin of 0.9 - 3.7 g/dl (mean 2.2 g/dl), falls in lactate dehydrogenase of 16-52%, and a halving of the irreversibly sickled cell counts. These effects were apparent within a few days and persisted for 1-2 weeks following discontinuation of the drug. Three of the six patients on tucaresol developed fever and cervical lymphadenopathy, with onset between days 7 and 11 from start of drug. Further evaluation of the tolerability and efficacy of tucaresol in sickle cell patients is necessary.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 01:08:08