antimony-sodium-gluconate and allopurinol-riboside

Pentavalent antimony has been considered to be the standard treatment for leishmaniasis, but more recently, the orally administrable agent allopurinol ribonucleoside has been the subject of several clinical trials. In this study, these two agents were evaluated in patients with Ecuadorian cutaneous leishmaniasis. Patients were randomly assigned to the two treatment groups. The mean reduction in lesion size for the 28 patients treated with Pentostam (20 mg Sb/kg/day intramuscularly for 20 days) was 61%, 23%, and 11% after one, two, and three weeks, respectively. There was a wide range in the individual values, and some lesions markedly enlarged in the first week of therapy. An initially healed lesion was defined as one that had greater than 80% re-epithelialized by the 1.5-month post-treatment followup. All Pentostam patients demonstrated this degree of lesion resolution (100% initial healing rate), but one patient showed evidence of relapse at the three month followup resulting in a 96% complete healing rate for the 12 month observation period. Patients in the untreated control group demonstrated a strikingly high rate of healing with 9 of 12 patients having re-epithelialized all lesions after 1.5 months observation (75% initial healing rate). The mean reduction in lesion size for the untreated patients was 56%, 29%, and 25% after one, two, and three weeks, respectively. Twenty-one patients received allopurinol ribonucleoside (1,500 mg QID) plus probenecid (500 mg QID) for 28 days. Lesions in nine of these patients were healed at the time of the 1.5 month followup (41% healing rate).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Allopurinol; Antimony Sodium Gluconate; Antiprotozoal Agents; Ecuador; Humans; Leishmaniasis; Ribonucleosides

We have developed a simple in vitro method of infecting a continuous human macrophage cell line (U937) with promastigotes of several species of Leishmania. These include L. braziliensis braziliensis, L. b. panamensis, L. donovani, L. mexicana mexicana, L. m. pifanoi, L. tropica, and L. major. The growth kinetics of these species are presented as well as drug sensitivity data. The U937 cell system can be used to determine drug efficacy and eliminates the need to use amastigotes from animal tissues to infect the tissue culture.

Topics: Allopurinol; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Cell Line; Humans; Leishmania; Leishmania braziliensis; Leishmania donovani; Leishmania mexicana; Leishmania tropica; Ribonucleosides

Pyrazolopyrimidines, particularly allopurinol, allopurinol riboside, and other purine analogues, show promise as experimental therapeutic compounds for the treatment of leishmaniasis. The combination of these agents with pentostam may produce an improved therapeutic effect. We report here on strong synergistic activity between pyrazolopyrimidines and pentavalent antimonials in a human macrophage tissue culture system infected with Leishmania donovani and L. braziliensis.

Topics: Allopurinol; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Cell Line; Drug Synergism; Gluconates; Humans; Leishmania; Leishmania braziliensis; Leishmania donovani; Macrophages; Ribonucleosides

Topics: Allopurinol; Allylamine; Amines; Antifungal Agents; Antimony Sodium Gluconate; Antiprotozoal Agents; Drug Combinations; Humans; Ketoconazole; Leishmania; Naphthalenes; Ribonucleosides; Terbinafine

We have developed a simple and reproducible system for infecting a human macrophage cell line (U937) with stationary-phase Leishmania donovani promastigotes. Four days after infection, greater than 90% of the promastigotes had transformed to amastigotes. The antileishmanial agents allopurinol riboside, formycin B, 9-deazainosine, and sodium stibogluconate effectively inhibited the growth of L. donovani amastigotes in this cell line. To study the capability of amastigotes in the U937 cell line to carry out biochemical reactions that could be monitored experimentally, we incubated the cells with radiolabeled 9-deazainosine. This purine analogue underwent metabolism in the amastigote phase similar to that occurring in the promastigote phase. This cell line should be useful for studies of parasite maturation and differentiation, parasite-human interactions, and antiparasitic drugs.

Topics: Allopurinol; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Cell Line; Formycins; Humans; Inosine; Leishmania donovani; Macrophages; Ribonucleosides