Biomedical subjects
Publications and source records attributed to P R Gangadharam.
A case of ulcerative keratitis has been followed by ophthalmological, bacteriological and histopathological examinations. Mycobacterium chelonei has been repeatedly isolated from the lesion before and after surgical interventions.
Fourteen compounds were tested in vitro for activity against Mycobacterium intracellulare and other pathogenic mycobacteria. Only clofazimine and chaulmoogric acid showed significant activity against M. intracellulare. In view of known minimal side effects of clofazimine further studies are warranted for this drug in chemotherapy of M. intracellulare infections.
The value of RVA, N-1, 7H10, 7H11 and Sauton's media for studies on mycobacteriophage infeciton and lysis of mycobacteria was assessed. Experiments were made with mycobacteriophages BGI, BKI, CRI-3, G37, and LG, all of which lyse Mycobacterium smegmatis strain 607B, and with mycobacteriophage DS6A which lyses Mycobacterium tuberculosis strain H37Rv. The methods involved "direct lysis", the measurement of "routine test dilutions" and counts of plaque-forming units. It was found that N-1, 7H10 and 7H11 media gave better overall results than RVA medium for M. smegmatis strain 607B and its phages, and that RVA medium was generally the most useful for M. tuberculositems employed.
The suitability of phage-impregnated paper discs for the phage typing of mycobacteria was studied. The relevance of the routine test dilution, the volume of the phage used, the mode of incubation, and the effect of prolonged storage of phage-impregnated paper discs were considered. By using paper discs, each impregnated with one of 5 different mycobacteriophages (BG1, BK1, G37, CRI-3 and LG) that lyse Mycobacterium smegmatis 607B, it was determined that 100 x the routine test dilution in a volume of at least 20 microliter was required for phage lysis. Soaked and dried paper discs produced larger areas of lysis than those with 20-microliter volumes. Soaked discs were found to be stable even after storage for 8 weeks at 4 degrees C.
Because vitamin K is present in several species of mycobacteria, and because coenzyme Q has been found to stimulate the growth of Mycobacterium tuberculosis and atypical mycobacteria, 8 quinones that can be considered to be dual analogues of vitamin K and coenzyme Q were tested for their activity against Mycobacterium intracellulare. One compound, 6-cyclo-octylamino-5,8-quinolinequinone (CQQ) exhibited considerable activity in vitro against several strains of Mycobacterium intracellulare at a concentration of 8 micrograms per ml. It has also shown evidence of bactericidal activity against growing cultures of Mycobacterium intracellulare. Time exposure studies indicated that a minimal contact period of 24 hours with a concentration of 8 micrograms of CQQ per ml is necessary for permanent inhibitory action against Mycobacterium intracellulare. At a concentration of 1 microgram per ml, CQQ inhibited Mycobacterium tuberculosis, including the rifampin-resistant strains. The drug has no activity against rapidly growing mycobacteria or organisms that are not acid-fast.
Four new aminoglycoside antibiotics, namely gentamycin, amikacin, tobramycin and sisiomycin were tested against several pathogenic strains of so-called 'typical' and 'atypical' mycobacteria. Only amikacin exhibited considerable in vitro anti-mycobacterial activity against Mycobacterium tuberculosis and not against other mycobacterial pathogens. None of the other three antibiotics exhibited activity against any of the mycobacteria at low concentrations.
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A series of 12 compounds, consisting of 3 known antileprosy drugs (dapsone, B663, and Ciba 1906) and 9 structural derivatives of dapsone, were tested for their antimycobacterial activity against 50 strains of Mycobacterium intracellulare. Detailed investigations of B663, the only compound showing considerable in vitro activity, were carried out. All of the strains of M. intracellulare were inhibited by a B663 concentration of 1.6 mug per ml, and 88% were inhibited by a drug concentration of 0.8 microng per ml. The rate of emergence of in vitro resistance was similar to that of M. tuberculosis against streptomycin and isoniazid. Preliminary experiments indicated that the action of the drug on M. intracellulare may be bacteriocidal in nature.
Mycobacterium tuberculosis H37Rv demonstrates a loss of acid-fastness following exposure to specific mycobacteriophage DS6A. No effect was seen with another mycobacteriophage GS7 which does not lyse this organism.