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Titolo:
Immunohematotoxicity studies with combinations of dapsone and zidovudine
Autore:
Freund, YR; Dousman, L; Riccio, ES; Sato, B; MacGregor, JT; Mohagheghpour, N;
Indirizzi:
SRI Int, Menlo Pk, CA 94025 USA SRI Int Menlo Pk CA USA 94025SRI Int, Menlo Pk, CA 94025 USA
Titolo Testata:
INTERNATIONAL IMMUNOPHARMACOLOGY
fascicolo: 12, volume: 1, anno: 2001,
pagine: 2131 - 2141
SICI:
1567-5769(200111)1:12<2131:ISWCOD>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; PNEUMOCYSTIS-CARINII PNEUMONIA; PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; 3'-AZIDO-3'-DEOXYTHYMIDINE AZT; INDUCED METHEMOGLOBINEMIA; AZIDOTHYMIDINE AZT; HEMOLYTIC-ANEMIA; DOUBLE-BLIND; TOXICITY;
Keywords:
dapsone; DDS; zidovudine; ZDV; AZT; combination therapy; hematotoxicity; Pneumocystis carinii;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Freund, YR SRI Int, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA SRI Int 333Ravenswood Ave Menlo Pk CA USA 94025 , CA 94025 USA
Citazione:
Y.R. Freund et al., "Immunohematotoxicity studies with combinations of dapsone and zidovudine", INT IMMUNO, 1(12), 2001, pp. 2131-2141

Abstract

We investigated the immunohematoxicities of the antiparasitic drug dapsone(DDS) and the antiretroviral drug zidovudine (ZDV, AZT) given alone or in combination in BALB/c mice. DDS is used for prophylaxis and treatment of Pneumocystis carinii infection in AIDS patients. We examined the impact of concurrent administration of these drugs on the immune and hematopoietic systems because DDS causes hematotoxicity and ZDV therapy results in bone marrow toxicity. Daily oral administration of DDS at 25 and 50 mg/kg for 28 dayscaused a slight anemia, marked methemoglobinemia, reticulocytosis, and a moderate leukopenia (P < 0.01 for all parameters) but had no discernible effect on platelet count. In DDS-treated mice, the proliferative response of splenic T cells to concanavalin A was greater than or equal to 35% higher than that manifested by splenocytes from vehicle-treated control mice. ZDV at240 and 480 mg/kg was not immunosuppressive but caused low-grade macrocytic anemia, thrombocytosis, and neutropenia; these effects were drug dose-dependent and statistically significant (P < 0.01). Concurrent administration of DDS and ZDV augmented the severity of ZDV-mediated macrocytic anemia, and 7 of 12 (58%) mice did not survive treatment with the high doses of DDS and ZDV (50 and 480 mg/kg, respectively). On the other hand, co-administration of ZDV mitigated DDS-induced methemoglobinemia and the DDS-associated elevation in lymphoproliferative response. These data suggest interaction between DDS and ZDV in mice and indicate a need for caution in using DDS as long-term therapy in AIDS patients receiving ZDV. (C) 2001 Elsevier Science B. V. All rights reserved.

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Documento generato il 17/01/20 alle ore 20:13:20