University of Wolverhampton
Browse
Collection All
bullet
bullet
bullet
bullet
Listed communities
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet

Wolverhampton Intellectual Repository and E-Theses > Research Institutes > Research Institute in Healthcare Science > Diabetes, Physiology and Molecular Medicine Research Group > Combination of inhibitors of lymphocyte activation (hydroxyurea, trimidox, and didox) and reverse transcriptase (didanosine) suppresses development of murine retrovirus-induced lymphoproliferative disease.

Please use this identifier to cite or link to this item: http://hdl.handle.net/2436/29451
    Del.icio.us     LinkedIn     Citeulike     Connotea     Facebook     Stumble it!



Title: Combination of inhibitors of lymphocyte activation (hydroxyurea, trimidox, and didox) and reverse transcriptase (didanosine) suppresses development of murine retrovirus-induced lymphoproliferative disease.
Authors: Mayhew, Christopher N.
Sumpter, Ryan
Inayat, Mohammed
Cibull, Michael
Phillips, Jonathan D.
Elford, Howard L.
Gallicchio, Vincent S.
Citation: Antiviral Research, 65(1): 13-22
Publisher: Elsevier Science Direct
Journal: Antiviral Research
Issue Date: 2005
URI: http://hdl.handle.net/2436/29451
DOI: 10.1016/j.antiviral.2004.09.003
PubMed ID: 15652967
Additional Links: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2H-4DS7NWT-2&_user=1644469&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000054077&_version=1&_urlVersion=0&_userid=1644469&md5=3a5c40ddbe951fb57d602aa5fdfd6316
Abstract: The ribonucleotide reductase inhibitor hydroxyurea (HU) has demonstrated some benefit as a component of drug cocktails for the treatment of HIV-1 infection. However, HU is notoriously myelosuppressive and often administered only as salvage therapy to patients with late-stage disease, potentially exacerbating the bone marrow toxicity of HU. In this report we have compared the antiviral effects of HU and two novel RR inhibitors trimidox (3,4,5-trihydroxybenzamidoxime) and didox (3,4-dihydroxybenzohydroxamic acid) in combination with didanosine (2,3-didoxyinosine; ddI) in the LPBM5 MuLV retrovirus model (murine AIDS). We also evaluated the effects of these drug combinations on the hematopoietic tissues of LPBM5 MuLV-infected animals. The combination of RR inhibitors and ddI was extremely effective (DX>TX>HU) in inhibiting development of retrovirus-induced disease (splenomegaly, hypergammaglobulinemia, activated B-splenocytes and loss of splenic architecture). In addition, relative levels of proviral DNA were significantly lower in combination drug-treated animals compared to infected controls. Evaluation of femur cellularity, numbers of marrow-derived myeloid progenitor cells (CFU-GM and BFU-E) and peripheral blood indices revealed that TX and DX in combination with ddI were well-tolerated. However, treatment with HU and ddI induced moderate myelosuppression. These data demonstrate that RR inhibitors in combination with ddI provide significant protection against retroviral disease in murine AIDS. Moreover, the novel RR inhibitors TX and DX appear to be more effective and less myelosuppressive than HU when administered with ddI in this model.
Type: Article
Language: en
Keywords: Lymphoproliferative disease
MeSH: Animals
Antiviral Agents
B-Lymphocytes
Benzamidines
Didanosine
Drug Therapy, Combination
Enzyme Inhibitors
Female
Hydroxamic Acids
Hydroxyurea
Leukemia Virus, Murine
Leukemia, Experimental
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Murine Acquired Immunodeficiency Syndrome
Retroviridae Infections
Reverse Transcriptase Inhibitors
Ribonucleotide Reductases
Treatment Outcome
Tumor Virus Infections
ISSN: 0166-3542
Appears in Collections: Diabetes, Physiology and Molecular Medicine Research Group

Files in This Item:

There are no files associated with this item.



Related articles on PubMed
bullet
bullet
bullet
bullet
bullet
See all 332 articles

All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Fairtrade - Guarantees a better deal for Third World Producers

University of Wolverhampton, Wulfruna Street, Wolverhampton, WV1 1LY

Course enquiries: 0800 953 3222, General enquiries: 01902 321000,
Email: enquiries@wlv.ac.uk | Freedom of Information | Disclaimer and copyright | Website feedback | The University as a charity

OR Logo Powered by Open Repository | Cookies