Accession Number : ADA254943


Title :   Augmented Oxygen-Dependent Killing of Leishmania.


Descriptive Note : Final technical rept. Jul 90-Jul 92,


Corporate Author : ARMED FORCES INST OF PATHOLOGY WASHINGTON DC


Personal Author(s) : Muhvich, K H ; Criswell, D W ; Anderson, L H ; Wilson, B ; Howard, R T


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a254943.pdf


Report Date : 30 Jun 1992


Pagination or Media Count : 53


Abstract : This study examined the role of oxygen in amphotericin B-induced killing of Leishmania braziliensis panamensis promastigotes and Candida albicans. In the first phase of the study, we explored the effects of high oxygen tensions on the lethal effects of three reduction-oxidation cycling drugs: amphotericin B, menadione, and phenazine methosulfate. Promastigotes were exposed to the above drugs under normoxic, hyperoxic (100% 02 at 101.3 kPa), ot hyperbaric hyperoxic (100% 02 at 253.3 kPa) conditions. After 24 h incubation at 27 deg C, viable promastigotes stained with fluorescein diacetate and were counted using epifluorescence microscopy. Hyperbaric hyperoxia alone (PO2 = 229 kPa) was as effective as AmB alone (0.2 uM); both killed 80% of the original inoculum. AmB killed more promastigotes in a hyperbaric hyperoxic environment than in normoxic (PO2 = 21.1 kPa) or hyperoxic conditions (PO2 = 91.7 kPa). High oxygen tensions did not alter the lethal effects of either menadione or phenazine methosulfate. In the second phase of the study, the effects of hypoxia on AmB killing in Leishmania and yeast cells were investigated. Leishmania promastigotes were exposed to AmB (0.1 and 1.0 uM) in media with dissolved PO2s of 22 mmHg (hypoxia) and 150 mmHg (normoxia) for two h at 27 deg C. Following incubation, promastigotes were stained as above and viable organisms counted. Promustigote, hyperoxia, hyperbaric hyperoxia, amphotericin B, Leishmania.


Descriptors :   *OXYGEN , *LEISHMANIA , *AMPHOTERICIN , ENVIRONMENTS , CELLS , STRESS(PHYSIOLOGY) , IN VITRO ANALYSIS , TENSION , INCUBATION , YEASTS , DRUGS , HYPEROXIA , CANDIDA , MACROPHAGES , ENVIRONMENTAL TESTS , MEDIA , HYPOXIA , OXIDATION , PHASE , MICROSCOPY , REDUCTION


Subject Categories : Microbiology
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE