Abstract
A cell-impermeable diffusion chamber technique has been developed that lends itself to growth studies of Mycobacterium lepraemurium. This technique, in which the organism grows within macrophage cultures inside the chambers that are maintained on monolayer cultures of macrophages, provides a method for a strict in vitro evaluation of antileprosy drugs without the influence of a multiplicity of host factors. This system was used to compare the effect of three sulfone derivatives and rifampin on the growth of M. lepraemurium within these diffusion chamber cultures. Two sulfones, 4,4'-diaminodiphenyl sulfone and 4,4'-diacetamidodiphenyl sulfone, as well as rifampin, suppressed the growth of M. lepraemurium, but monoacetyl sulfone 4-amino-4'acetamidodiphenyl sulfone had no effect. The results indicate that the diffusion chamber technique can be used to evaluate the inhibitory effect of antileprosy drugs on the growth of M. lepraemurium. Also, the method provides for the first time a relatively rapid in vitro method for directly comparing the effects of drugs or their analogs when outside the metabolic influence of an animal host. This technique may be a useful tool for chemotherapy studies with other antileprosy compounds.
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Selected References
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- Argyris B. F. Role of macrophages in immunological maturation. J Exp Med. 1968 Sep 1;128(3):459–467. doi: 10.1084/jem.128.3.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chang Y. T. Suppressive activity of streptomycin on the growth of Mycobacterium lepraemurium in macrophage cultures. Appl Microbiol. 1969 May;17(5):750–754. doi: 10.1128/am.17.5.750-754.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gelber R., Peters J. H., Gordon G. R., Glazko A. J., Levy L. The polymorphic acetylation of dapsone in man. Clin Pharmacol Ther. 1971 Mar-Apr;12(2):225–238. doi: 10.1002/cpt1971122part1225. [DOI] [PubMed] [Google Scholar]
- Gordon G. R., Peters J. H., Ghoul D. C., Murray J. F., Jr, Levy L., Biggs J. T., Jr Disposition of dapsone and monoacetyldapsone in rats. Proc Soc Exp Biol Med. 1975 Nov;150(2):485–492. doi: 10.3181/00379727-150-39062. [DOI] [PubMed] [Google Scholar]
- Levy L., Biggs J. T., Jr, Gordon G. R., Peters J. H. Disposition of the antileprosy drug, dapsone, in the mouse. Proc Soc Exp Biol Med. 1972 Jul;140(3):937–943. doi: 10.3181/00379727-140-36584. [DOI] [PubMed] [Google Scholar]
- Murray J. F., Jr, Gordon G. R., Peters J. H. A chromatographic-fluorometric procedure for the determination of nanogram quantities of antileprotic sulfones. J Lab Clin Med. 1971 Sep;78(3):464–471. [PubMed] [Google Scholar]
- Peters J. H., Murray J. F., Jr, Gordon G. R., Levy L., Russell D. A., Scott G. C., Vincin D. R., Shepard C. C. Acedapsone treatment of leprosy patients: response versus drug disposition. Am J Trop Med Hyg. 1977 Jan;26(1):127–136. doi: 10.4269/ajtmh.1977.26.127. [DOI] [PubMed] [Google Scholar]
- REES R. J., WONG P. C. Limited multiplication of M. lepraemurium in tissue culture. Nature. 1958 Feb 1;181(4605):359–360. doi: 10.1038/181359b0. [DOI] [PubMed] [Google Scholar]
- Rees R. J., Pearson J. M., Waters M. F. Experimental and clinical studies on rifampicin in treatment of leprosy. Br Med J. 1970 Jan 10;1(5688):89–92. doi: 10.1136/bmj.1.5688.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rightsel W. A., Wiygul W. C. Growth of Mycobacterium lepraemurium in Cell-Impermeable Diffusion Chambers. Infect Immun. 1971 Jan;3(1):127–132. doi: 10.1128/iai.3.1.127-132.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shepard C. C. Chemotherapy of leprosy. Annu Rev Pharmacol. 1969;9:37–50. doi: 10.1146/annurev.pa.09.040169.000345. [DOI] [PubMed] [Google Scholar]
- Shepard C. C., Levy L., Fasal P. The death rate of Mycobacterium leprae during treatment of lepromatous leprosy with acedapsone (DADDS). Am J Trop Med Hyg. 1972 Jul;21(4):440–445. doi: 10.4269/ajtmh.1972.21.440. [DOI] [PubMed] [Google Scholar]
- Shepard C. C., McRae D. H. A method for counting acid-fast bacteria. Int J Lepr Other Mycobact Dis. 1968 Jan-Mar;36(1):78–82. [PubMed] [Google Scholar]
- Shepard C. C., Tolentino J. G., McRae D. H. The therapeutic effect of 4,4'-diacetyldiamino-diphenylsulfone (DADDS) in leprosy. Am J Trop Med Hyg. 1968 Mar;17(2):192–201. doi: 10.4269/ajtmh.1968.17.192. [DOI] [PubMed] [Google Scholar]