Current therapies to treat opportunistic infections associated with the Acquired Immunedeficiency Syndrome (AIDS) are either highly toxic, extremely expensive or marginally effective. In addition, there is no therapy recognized as effective for certain of the pathogens. Because present therapies produce toxic reactions in a large percentage of patients, the availability of alternative therapeutics is of upmost importance. Since these infections produce significant morbidity and mortality in patients with AIDS, the National Institute of Allergy and Infectious Diseases (NIAID) has funded several programs to facilitate drug development efforts against opportunistic infections by providing contract resources for efficacy evaluations in animals, a critical component in new drug approval. The availability of animal model testing systems will provide the NIAID with testing capabilities to evaluate therapies for treatment against Mycobacterium avium, both singly and in combination as well as determine the pharmacokinetics and toxicities of the experimental therapies. This will permit the submission of the resulting data in support of an IND application for the new therapy. The contractor will have the capability to evaluate therapeutic agents in small animal (in vivo) and culture (in vitro) model test systems, develop alternative protocols to accommodate special characteristics of individual therapies or model test systems, measure general toxicity, determine pharmacokinetic parameters, etc, to assist the sponsor in the development of new therapies against M. avium.

Project Start
1992-07-23
Project End
1997-07-22
Budget Start
1993-03-31
Budget End
1994-07-23
Support Year
Fiscal Year
1993
Total Cost
Indirect Cost
Name
California Pacific Medical Center Research Institute
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94107
Wagner, Dirk; Sangari, Felix J; Parker, Amy et al. (2005) fecB, a gene potentially involved in iron transport in Mycobacterium avium, is not induced within macrophages. FEMS Microbiol Lett 247:185-91
Bermudez, Luiz E; Reynolds, Robert; Kolonoski, Peter et al. (2003) Thiosemicarbazole (thiacetazone-like) compound with activity against Mycobacterium avium in mice. Antimicrob Agents Chemother 47:2685-7
Nash, K A (2001) Effect of drug concentration on emergence of macrolide resistance in Mycobacterium avium. Antimicrob Agents Chemother 45:1607-14
Bermudez, L E; Wagner, D; Sosnowska, D (2000) Mechanisms of Mycobacterium avium pathogenesis. Arch Immunol Ther Exp (Warsz) 48:521-7
Sangari, F J; Goodman, J; Bermudez, L E (2000) Mycobacterium avium enters intestinal epithelial cells through the apical membrane, but not by the basolateral surface, activates small GTPase Rho and, once within epithelial cells, expresses an invasive phenotype. Cell Microbiol 2:561-8
Sangari, F J; Bachli, M; Bermudez, L E et al. (2000) Characterization of IS666, a newly described insertion element of Mycobacterium avium. Microb Comp Genomics 5:181-8
Bermudez, L E; Kolonoski, P; Wu, M et al. (1999) Mefloquine is active in vitro and in vivo against Mycobacterium avium complex. Antimicrob Agents Chemother 43:1870-4
Petrofsky, M; Bermudez, L E (1999) Neutrophils from Mycobacterium avium-infected mice produce TNF-alpha, IL-12, and IL-1 beta and have a putative role in early host response. Clin Immunol 91:354-8
Sangari, F J; Petrofsky, M; Bermudez, L E (1999) Mycobacterium avium infection of epithelial cells results in inhibition or delay in the release of interleukin-8 and RANTES. Infect Immun 67:5069-75
Bermudez, L E; Goodman, J; Petrofsky, M (1999) Role of complement receptors in uptake of Mycobacterium avium by macrophages in vivo: evidence from studies using CD18-deficient mice. Infect Immun 67:4912-6

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