Drugs online research references
Antimicrob Agents Chemother. 1987 Jan;31(1):111-3.
Activity of purine analogs against Leishmania donovani in vivo.
Berman JD, Hanson WL, Lovelace JK, Waits VB, Jackson JE, Chapman WL Jr, Klein RS.
The dose of orally administered 9-deazainosine calculated to suppress 50% of Leishmania donovani amastigotes in hamster livers was 19 mg/kg (body weight) per day; 96 to 99% of Leishmania organisms were eliminated from the liver and spleen of squirrel monkeys by 50 mg/kg per day. Because these activities were greater than that of the experimental clinical agent allopurinol and comparable to that of the classical agent parenteral pentavalent antimony, 9-deazainosine should be considered for clinical development for visceral leishmaniasis.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3566235&dopt=Abstract
Clin Sci (Lond). 1985 May;68(5):561-5.
Superoxide radicals, immunodeficiency and xanthine oxidase activity: man is not a mouse!
Simmonds HA, Goday A, Morris GS.
The importance of intact adenosine deaminase (ADA) activity in the generation of superoxide anion by xanthine oxidase has been disputed in studies using human neutrophils or mouse macrophages. The latter demonstrated a positive correlation between ADA activity and superoxide production during phagocytosis. The immunodeficiency in inherited ADA deficiency was related to a defect in this process. Since there is considerable interspecies variation in the tissue distribution of xanthine oxidase, the metabolism of [8-14C]deoxyadenosine (dAR), the toxic metabolite which accumulates in inherited ADA deficiency, was investigated in human peritoneal macrophages. Evaluation of the distribution of radiolabel in both cell and medium demonstrated that human macrophages with intact ADA metabolize dAR under physiological conditions to deoxyinosine and hypoxanthine exclusively. The hypoxanthine is further metabolized within the cell to ATP and GTP, via IMP. No xanthine or uric acid could be detected, confirming that in human macrophages xanthine oxidase activity is insignificant, as it is in most other human cells and tissues, except liver and intestinal mucosa. Thus production of superoxide radicals in such cells via this route would be impossible, and consequently unaffected either by ADA deficiency or the xanthine oxidase inhibitor allopurinol.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2983925&dopt=Abstract
Am J Trop Med Hyg. 1983 Mar;32(2):286-95.
Efficacy of combined immunostimulation and chemotherapy in experimental visceral Leishmaniasis.
Haidaris CG, Bonventre PF.
A regimen of combined immunostimulation and chemotherapy for the elimination of Leishmania donovani amastigotes was evaluated. An in vitro experimental model utilized cultured peritoneal macrophages from C57B1/6 mice infected with L. donovani tissue forms. Partial or complete activation of macrophages as judged by killing of tumor cells significantly enhanced the efficacy of sodium antimony gluconate (Pentostam). The quantity of drug required for elimination of parasites from immunostimulated cells was considerably lower than that required to achieve comparable amastigote killing in thioglycolate-elicited macrophages. In contrast, amphotericin B cleared infected cells of amastigotes at comparable drug levels when tested with immunostimulated and unstimulated macrophages. Several drugs tested inhibited the conversion of amastigotes to promastigotes in vitro but were ineffective in killing of intracellular tissue forms. Allopurinol and difluoromethylornithine (DMFO) blocked amastigote conversion significantly. These drugs at high concentrations, however, exerted only minimal toxicity for amastigotes residing within macrophages. Efficacy of combined therapy was also demonstrated in vivo. Immunoenhancement of L. donovani-infected mice with Corynebacterium parvum vaccine combined with a regimen of sodium antimony gluconate was significantly more effective than was immunotherapy or drug therapy alone.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6301300&dopt=Abstract
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