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Biomedical subjects

A M Dhople

Publications and source records attributed to A M Dhople.

66 records · Page 4Linked to original sources
PubMedDate not supplied

In vitro and in vivo interactions of drugs used in multidrug therapy in leprosy.

Interactions of different drugs commonly used in multiple drug therapy were evaluated using both in vitro culture (cell-free as well as macrophage) system and mouse footpad. No additive effects were obtained in the in vitro system when dapsone was combined with either rifampicin or clofazimine, while a strong antagonism was observed when clofazimine was combined with rifampicin but not with rifabutin. In the mouse footpad system, a strong synergism was obtained when clofazimine was combined with either rifampicin or rifabutin, but significant antagonism was observed with the combination of clofazimine and dapsone.

Animals↗
PubMedDate not supplied

An in vitro culture method for screening new drugs against Mycobacterium leprae.

An in vitro culture system has been devised for the maintenance and growth of M. leprae in a cell-free medium. Cells from four-week old cultures could be transferred to fresh medium and normal growth was observed in subcultures. Using this system, the M.I.Cs of dapsone and rifampicin were determined. Dapsone at 25 ng/ml and rifampicin at 300 ng/ml completely inhibited the growth of host-grown as well as in vitro-adapted M. leprae. It was further shown that the effects of both the drugs were bactericidal; this observation was subsequently confirmed using mouse foot-pad technique.

Animals↗
PubMedDate not supplied

Effect of brodimoprim on Mycobacterium leprae in vitro and in mouse foot-pads.

The new in vitro screening system reported earlier was adopted to determine anti-M. leprae activity of a dihydrofolate reductase inhibitor, brodimoprim, and the results were compared with those obtained using mouse foot-pad technique. Even though the MIC of brodimoprim against M. leprae was very high compared to other commonly used anti-leprosy drugs, in combination with dapsone it showed a remarkable synergistic activity in inhibiting the growth of M. leprae at concentrations much lower than the MICs of each of the drugs used singly. Similar effects were also demonstrated in mouse foot-pad experiments.

Animals↗
PubMedDate not supplied

Serum angiotensin-converting enzyme in leprosy.

Serum angiotensin-converting enzyme activity was measured in 91 adult healthy and lepromatous armadillos before inoculation with M. leprae and at necropsises. Mean ACE values were significantly elevated in armadillos with leprosy and the degree of elevation was roughly proportional to the extent of infection. There was also significant difference in the serum ACE levels between Florida and Louisiana armadillos. The dapsone treatment resulted in bringing these levels to normal. Serial assays of serum, ACE provided information on the response of armadillos to dapsone therapy.

Animals↗
PubMedDate not supplied

Presence of "difficult to isolate" mycobacteria in armadillos.

Contrary to the findings with armadillos from Louisiana and Texas, armadillos from Florida are free of natural leprosy-like infection. Examination of ear clip, nasal, blood buffy coat, liver and spleen of inoculated armadillos from Florida did not reveal the presence of any acid fast bacteria. However, using massive inocula, 6 out of 77 armadillo tissues were found to contain very negligible proportions of cultivable mycobacteria. The significance of these isolates in relation to M. leprae and also to leprosy research is discussed.

Animals↗
PubMedDate not supplied

Armadillo as a model for studying chemotherapy of leprosy: preliminary studies.

In order to determine the suitability of the armadillos as a model of human leprosy for chemotherapeutic studies, especially in evaluating newer anti-leprosy drugs, uninfected Armadillos were used to study the metabolic disposition of DDS. Serum DDS levels ranged from 500 ng/ml at 3 hours to 13 ng/ml at 96 hours after intravenous administration of DDS (1 mg/kg). In an ad libitum feeding trial of DDS it was found that the level of serum DDS varied according to the dose of DDS, and even at a dose of 0.0001%, the animals maintained MIC of DDS against M. leprae. Finally, it was demonstrated that armadillos acetylate DDS to MADDS and 7-9% of DDS is acetylated by armadillos.

Animals↗
PubMedDate not supplied

In vivo activities of novel benzoxazinorifamycins against Mycobacterium leprae.

Among the four newly synthesized benzoxazinorifamycin derivatives, KRM-1648 and KRM-2312 completely inhibited the multiplication of rifampicin-sensitive as well as rifampicin-resistant strains of M. leprae in the foot-pads of mice. Both were found to be more potent than rifampicin and were bactericidal. In combination with ofloxacin, another potent bactericidal drug against M. leprae, both KRM-1648 and KRM-2312 exhibited synergism. Thus, combination of one of these benzoxazinorifamycin derivatives and ofloxacin in multidrug regimens is worth evaluating in clinical trials.

Animals↗
PubMedDate not supplied

Comparative in vitro activities of rifamycin analogues against Mycobacterium leprae.

Comparative activities of various rifamycin analogues against leprosy were studied by evaluating their effects on in vitro growth of Mycobacterium leprae in DH medium as described earlier. Among the seven analogues studied, KRM-1648 was found to be the most potent in inhibiting the growth of rifampicin-sensitive strains of M. leprae, MIC being 0.05 microgram/ml. This was followed by KRM-2312 and T9 (MIC of each being 0.1 microgram/ml) and rifabutin (MIC, 0.2 microgram/ml). Rifampicin, along with KRM-1657 and KRM-1668, were least effective, with MIC for each being 0.4 microgram/ml. The effects of each at their respective MICs were bactericidal. The results were similar for rifampicin-resistant strains of M. leprae, but the MICs were higher than those obtained with rifampicin-sensitive strains of M. leprae. Thus, even though rifampicin has been the first-line drug in the treatment of leprosy, the results in present studies suggest that other rifamycin analogues are available that are more potent than rifampicin against both rifampicin-sensitive as well as rifampicin-restraint strains of M. leprae.

Drug Resistance, Microbial↗