An in Vitro Micromethod for Drug Sensitivity Testing of Leishmania

Jackson, Joan E.; Tally, John D.; Tang, Douglas B.

doi:10.4269/ajtmh.1989.41.318

Cited by 18 publications

(12 citation statements)

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“…The availability of a drug that is effective alone would be preferable for helping to control this disease. Also, leishmaniasis clinically refractory to SbV has been reported (3,7), and resistance is frequently considered to be due to Sbv-resistant parasites (15) by a mechanism(s) not clearly defined. Therefore, a continued search for new chemotherapeutic strategies is warranted.…”

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confidence: 99%

Suppression of Leishmania donovani by oral administration of a bis(benzyl)polyamine analog

Baumann¹,

McCann²,

Bitonti³

1991

Antimicrob Agents Chemother

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We reported previously that intraperitoneal administration of a bis(benzyl)polyamine analog, MDL 27,695, suppressed both pentavalent antimony (Sbv)-susceptible and -resistant Leishmania donovani in vivo. The present studies were performed to optimize parasite suppression by parenteral administration and to evaluate the efficacy of oral treatment with MDL 27,695. L. donovani infections in BALB/c mice were suppressed >99% after intraperitoneal dosing for 20 days with a total dose of 150 mg of MDL 27,695 per kg of body weight or 560 mg of SbV per kg. Suppression was not increased by a total dose of 400 mg of MDL 27,695 per kg given for 20 days. In mice treated for 2, 4, or 7 days with either MDL 27,695 or Sb" (total doses of 60, 120, and 210 mg/kg, respectively), more liver parasites were killed with MDL 27,695 than with Sb". Assessment of livers posttreatment showed that parasite killing continued for at least 3 days in MDL 27,695-treated mice but not for longer than 1 day in SbW-treated mice. Intramuscular administration of drugs resulted in 92% parasite suppression by MDL 27,695 (15 mg/kg three times per day for 5 days) and 64% suppression by Sbv (60 mg/kg once per day for 5 days). Dosing of mice by oral gavage with 100 mg of MDL 27,695 per kg twice per day for 14 days resulted in 99.7% parasite suppression, and the 50% effective dose was approximately 11 mg of MDL 27,695 per kg. MDL 27,695 represents an effective new drug potentially useful for oral or parenteral treatment of visceral leishmaniasis.

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mentioning

confidence: 99%

Suppression of Leishmania donovani by oral administration of a bis(benzyl)polyamine analog

Baumann¹,

McCann²,

Bitonti³

1991

Antimicrob Agents Chemother

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“…24 Media developed for serum-free growth of mammalian cells were adapted for the serial cultivation of different Leishmania species. These media were enriched with large concentrations of certain amino acids, vitamins, bovine albumin, hormones, peptide supplements, [25][26][27][28][29][30][31] or more recently, with human urine. 32,33 In the present paper, we report a completely chemically defined culture medium free of serum, macromolecules, proteins, and peptides that readily supports the growth and maintenance of promastigote forms of various Leishmania species without compromising parasite growth rates.…”

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confidence: 99%

Leishmania spp: completely defined medium without serum and macromolecules (CDM/LP) for the continuous in vitro cultivation of infective promastigote forms.

Merlen

Sereno²,

Brajon³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. The elimination of serum or of serum-derived macromolecules that supplant the fetal calf serum requirement from Leishmania culture media could decrease costs and improve the feasibility of large-scale production of well-defined parasite material. We report a completely defined medium, without serum-derived protein and/or macromolecules as a serum substitute, of common, available, and inexpensive constituents that can be used in place of serum-supplemented media for the continuous in vitro cultivation of promastigote forms of various Leishmania species. Typical promastigote morphology was observed in Giemsa-stained smears, regardless of the strain analyzed. Electrophoretic analysis showed that the proteinase patterns of aserically grown promastigote forms were similar to those obtained in serum-supplemented RPMI 1640 medium for all Leishmania studied. Similar antigenic profiles were recognized in immunoblots by sera from hosts with visceral or cutaneous leishmaniasis after growing promastigotes in the two different culture media. For parasites causing both cutaneous and visceral leishmaniasis, the absence of serum and macromolecules in the culture medium did not markedly change their in vitro infectivity for resident mouse macrophages and their virulence in animals compared with parasites cultivated in nondefined medium. Serum-free technology will be increasingly important in providing stability and reproducibility as research using promastigote moves closer to therapeutic applications.Parasites from the genus Leishmania cause a variety of disease states in humans and other mammals in tropical and subtropical areas, which include cutaneous, mucocutaneous, and visceral leishmaniasis. The parasite undergoes a digenic life cycle between a nonmotile intracellular amastigote stage parasitizing the mammalian phagocytic cells and a flagellated, motile promastigote stage in the midgut of its sandfly vector. 1 A similar promastigote form develops when parasites are cultured in cell-free medium. 2

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“…2a), had been developed earlier in our laboratories. The RAM relies on drug inhibition of parasite production of 14C02 from a battery of 14C-substrates to detect drugmediated parasite damage at low drug concentration within a short time (Jackson et al, 1989(Jackson et al, , 1990.…”

Section: Saponins Used In Traditional and Modern Medicinementioning

confidence: 99%