ABSTRACT
Tubercidin (TUB) is an adenosine analog with potent antiparasite action, unfortunately associated with severe host toxicity. Prevention of TUB toxicity can be reached associating nitrobenzylthioinosine (NBMPR), an inhibitor of the purine nucleoside transport, specifically target to the mammal cells. It was demonstrated that this nucleoside transport inhibitor has no significant effect in the in vitro uptake of TUB by Schistosoma mansoni and Trypanosoma gambiense. Seeking to evaluate if the association of these compounds is also effective against leishmania, we analyzed the TUB-NBMPR combined treatment in in vitro cultures of promastigote forms of Leishmania (L.) amazonensis, Leishmania (L.) chagasi, Leishmania (L.) major, and Leishmania (V.) braziliensis as well as in cultures of amastigote forms of L. (L.) amazonensis, mice macrophages infected with L. (L.) amazonensis, and in vivo tests in BALB/c mice infected with L. (L.) amazonensis. We demonstrated that TUB-NBMPR combined treatment can be effective against leishmania cells protecting mammalian cells from TUB toxicity.
Subject(s)
Antiparasitic Agents/therapeutic use , Enzyme Inhibitors/therapeutic use , Leishmania/drug effects , Leishmaniasis/drug therapy , Thioinosine/analogs & derivatives , Thionucleotides/therapeutic use , Tubercidin/therapeutic use , Animals , Antiparasitic Agents/pharmacology , Antiparasitic Agents/toxicity , Cells, Cultured , Drug Therapy, Combination , Enzyme Inhibitors/pharmacology , Macrophages/drug effects , Macrophages/parasitology , Mice , Mice, Inbred BALB C , Schistosoma mansoni/drug effects , Thioinosine/pharmacology , Thioinosine/therapeutic use , Thionucleotides/pharmacology , Trypanosoma brucei gambiense/drug effects , Tubercidin/pharmacology , Tubercidin/toxicityABSTRACT
Microbial-related dysplastic and neoplastic angiomatous proliferative processes are seen with increased frequency, particularly in the acquired immunodeficiency syndrome (AIDS). The microbial-encoded or -induced mediators of angiopathogenesis in AIDS-associated Kaposi's sarcoma and bacillary angiomatosis are actively being sought. The present review addresses the historical, epidemiologic, clinical, etio- and histopathogenic aspects of the verruga peruana (VP). VP is a disease thus far endemic to high Andean valleys and characterized by dermal angioblastic proliferation in association with reactivation of latent Bartonella bacilliformis organisms. VP closely resembles AIDS-associated angiopathogenic manifestations at the clinical, histopathologic, and etiologic levels and therefore has been proposed as a model for the study of angiogenesis and endothelial cell dysplasia and neoplasia. Moreover, the recent epidemic outbreaks in endemic areas, the increased frequency of international travel to the region, the variable incubation period, and the possibility of not recognizing VP due to its rarity further underscore the relevance of studying this rare disorder and of including it in the differential diagnosis of angiomatous-proliferative disorders.
