In the past two years pneumocystis pneumonia has become the major opportunistic disease in patients with acquired immunodeficiency syndrome (AIDS). The disease is rapidly progressive with a mortality rate over 40% despite treatment, whereas the mortality rate approaches 100% in untreated cases. Pentamidine is an effective chemotherapeutic agent but is highly toxic. Various combinations and analogs of pyrimethamine and sulfadiazine have been used with varying degrees of success. However, AIDS patients with pneumocystis pneumonia have not responded well to such treatment. The objective of this contract is to identify new drugs which have potential for use in the treatment of pneumocystis pneumonia in AIDS patients, utilizing animal models and/or in vitro techniques. Evaluation of such promising drugs in AIDS patients will then be carried out under a separate project.

Project Start
1987-07-10
Project End
1992-07-09
Budget Start
1990-03-26
Budget End
1991-07-09
Support Year
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Pathology
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Bartlett, M S; Queener, S F; Shaw, M M et al. (1997) In vitro and in vivo models of Pneumocystis carinii. J Eukaryot Microbiol 44:51S
Bartlett, M S; Current, W L; Goheen, M P et al. (1996) Semisynthetic echinocandins affect cell wall deposition of Pneumocystis carinii in vitro and in vivo. Antimicrob Agents Chemother 40:1811-6
Bartlett, M S; Shaw, M; Navaran, P et al. (1995) Evaluation of potent inhibitors of dihydrofolate reductase in a culture model for growth of Pneumocystis carinii. Antimicrob Agents Chemother 39:2436-41
Ittarat, I; Asawamahasakda, W; Bartlett, M S et al. (1995) Effects of atovaquone and other inhibitors on Pneumocystis carinii dihydroorotate dehydrogenase. Antimicrob Agents Chemother 39:325-8
Queener, S F (1995) New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii. J Med Chem 38:4739-59
Hong, Y L; Bartlett, M S; Queener, S et al. (1995) Pteroylpolyglutamate synthesis by lung- and culture-derived Pneumocystis carinii. FEMS Microbiol Lett 134:251-4
Bartlett, M S; Lee, C H; Lu, J J et al. (1994) Pneumocystis carinii detected in air. J Eukaryot Microbiol 41:75S
Bartlett, M S; Goheen, M P; Lee, C H et al. (1994) Close association of Pneumocystis carinii from infected rat lung with culture cells as shown by light and electron microscopy. Parasitol Res 80:208-15
Lu, J J; Bartlett, M S; Shaw, M M et al. (1994) Typing of Pneumocystis carinii strains that infect humans based on nucleotide sequence variations of internal transcribed spacers of rRNA genes. J Eukaryot Microbiol 41:102S
Shaw, M M; Kleyman, T R; Bartlett, M S et al. (1994) Sodium transport inhibitors decrease proliferation of Pneumocystis carinii in short-term culture. J Eukaryot Microbiol 41:110S

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