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Expression of cytokines, particularly chemokines, after application of acyclic nucleoside phosphonates
Potměšil, Petr ; Zídek, Zdeněk (advisor) ; Otová, Berta (referee) ; Farghali, Hassan (referee)
Acyclic nucleoside phosphonates (ANPs) are novel class of virostatics, that inhibit replication of both DNA viruses and retroviruses. ANP approved for the treatment of viral diseases are: tenofovir (Viread®) for the therapy of AIDS, adefovir (Hepsera®) for the treatment of hepatitis B and cidofovir (Vistide®), that is used in HIV-1 positive patients suffering from retinitis caused by cytomegalovirus [23, 24]. Some ANPs, such as tenofovir, are endowed by immunomodulatory properties that can non specifically influence replication of viruses. Tenofovir has been shown previously to increase gene expression of nitric oxide, cytokines TNF- , IL-10 and chemokines RANTES, MIP-1 [6, 22, 30]. In present experiments we investigated possible immunobiological properties of newly synthesized derivatives of ANPs in vitro using mouse macrophages and lymphocytes (or human leukocytes, respectively). N6-substituted derivatives of adenine or 2,6-diaminopurine, that possess phosphonomethoxyethyl or phosphonomethoxypropyl moiety at the position N9 of the heterocyclic base were included in the study. Some of these compounds were found to activate production of nitric oxide, cytokines TNF- , IL-10 and chemokines RANTES, MIP- 1 [21]. Various hydroxylated derivatives of ANPs were also screened for their immunobiological potential....
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Expression of cytokines, particularly chemokines, after application of acyclic nucleoside phosphonates
Potměšil, Petr ; Zídek, Zdeněk (advisor) ; Otová, Berta (referee) ; Farghali, Hassan (referee)
Acyclic nucleoside phosphonates (ANPs) are novel class of virostatics, that inhibit replication of both DNA viruses and retroviruses. ANP approved for the treatment of viral diseases are: tenofovir (Viread®) for the therapy of AIDS, adefovir (Hepsera®) for the treatment of hepatitis B and cidofovir (Vistide®), that is used in HIV-1 positive patients suffering from retinitis caused by cytomegalovirus [23, 24]. Some ANPs, such as tenofovir, are endowed by immunomodulatory properties that can non specifically influence replication of viruses. Tenofovir has been shown previously to increase gene expression of nitric oxide, cytokines TNF- , IL-10 and chemokines RANTES, MIP-1 [6, 22, 30]. In present experiments we investigated possible immunobiological properties of newly synthesized derivatives of ANPs in vitro using mouse macrophages and lymphocytes (or human leukocytes, respectively). N6-substituted derivatives of adenine or 2,6-diaminopurine, that possess phosphonomethoxyethyl or phosphonomethoxypropyl moiety at the position N9 of the heterocyclic base were included in the study. Some of these compounds were found to activate production of nitric oxide, cytokines TNF- , IL-10 and chemokines RANTES, MIP- 1 [21]. Various hydroxylated derivatives of ANPs were also screened for their immunobiological potential....
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