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Biomedical subjects

A M Dhople

Publications and source records attributed to A M Dhople.

At least 37 records · Page 2Linked to original sources
PubMed1994

In vivo susceptibility of Mycobacterium leprae to ofloxacin either singly or in combination with rifampicin and rifabutin. Anti-leprosy activity of ofloxacin and ansamycins in mice.

The antimicrobial effects of ofloxacin against Mycobacterium leprae, either alone or in combination with rifampicin and rifabutin, were studied using mouse foot pad assay technique. When used singly, the minimum concentrations of the drugs needed to completely inhibit the growth of Mycobacterium leprae in foot pads of mice were 50 mg/kg body weight for ofloxacin and 0.003% and 0.0001%, respectively, for rifampicin and rifabutin. However, excellent synergistic effects were observed when mice were fed with 25 mg/kg body weight of ofloxacin along with 0.00003% rifabutin, but not rifampicin. Thus, incorporation of ofloxacin and rifabutin in the multiple drug therapy of leprosy patients is suggested.

Animals↗
PubMed1993

In-vitro activity of three new fluoroquinolones and synergy with ansamycins against Mycobacterium leprae.

The efficacy of three fluorinated quinolones, clinafloxacin (PD 127391), sparfloxacin (PD 131501) and PD 131628, either alone or in combination with rifampicin/rifabutin, against Mycobacterium leprae was evaluated in vitro using two biochemical parameters to measure the metabolic activity of the organism. Clinafloxacin was found to be most effective with an MIC of 0.75 mg/L, followed by sparfloxacin (MIC 1.5 mg/L) and PD131628 (MIC 3.0 mg/L). When combined with rifampicin each of the three quinolones were additive to the activity. However, when combined with rifabutin, both clinafloxacin and sparfloxacin demonstrated pronounced synergic activity. Incorporation of clinafloxacin and rifabutin in a multi-drug therapy regimen is suggested.

Anti-Bacterial Agents↗
PubMed1993

In vitro synergistic activity between ofloxacin and ansamycins against Mycobacterium leprae.

The antimicrobial effects of ofloxacin, alone and in combination with either rifampicin or rifabutin, were evaluated against M. leprae, using in vitro cell-free culture system. The minimum inhibitory concentration (MIC) of ofloxacin against M. leprae was 1.5 micrograms/ml, while MICs of rifampicin and rifabutin were 0.4 and 0.2 microgram/ml, respectively. Combination of 0.375 microgram/ml ofloxacin and 0.05 microgram/ml of rifabutin exhibited synergistic bactericidal activity while the effect of combination of 0.75 microgram/ml ofloxacin and 0.2 microgram/ml rifampicin was additive bactericidal. Thus, combination of ofloxacin and rifabutin deserves further attention in multi-drug therapy of leprosy.

Animals↗
PubMed1992

Isolation of cultivable mycobacteria from feces and lungs of armadillos infected with Mycobacterium leprae.

In the past, no cultivable mycobacteria were isolated from armadillos captured in the state of Florida, U.S.A. But recent findings of acid-fast bacilli (AFB) in the lungs of armadillos infected with Mycobacterium leprae prompted us to undertake this study to determine the correlation between systemic leprosy infection and the occurrence of cultivable mycobacteria in the lungs and stools of these animals. No AFB could be isolated from noninfected animals. Seventy percent of the infected animals developed disseminated infection, but no cultivable mycobacteria were isolated from their livers and spleens. However, cultivable mycobacteria were isolated from the lungs and stools of a large number of armadillos showing disseminated infection. The most common among these were M. gordonae, M. fortuitum, and M. avium. There was a close correlation between the development of disseminated leprosy infection and the occurrence of cultivable mycobacteria in their lungs and stools, perhaps due to the decline in the immune system in these animals in the later stages of infection.

Animals↗
PubMed1991

Factors influencing the in vitro growth of Mycobacterium leprae: effect of sulfhydryl compounds.

In an attempt to determine the factors that influence the in vitro growth of Mycobacterium leprae in DH medium, the effects of sulfhydryl compounds were studied. Growth of M. leprae was monitored using two biochemical indicators. Only the sulfhydryl compounds, in reduced form, containing carboxyl group could support the growth of M. leprae. Higher cell yields were obtained when these sulfhydryl compounds were supplemented with dithiothreitol, presumable to keep the monothiols in reduced state during long incubation periods. Ascorbic acid could not replace dithiothreitol for this purpose. It is suggested that these carboxylated sulfhydryl compounds play a role in the metabolic activity of M. leprae along with maintaining low redox potential of the medium.

Adenosine Triphosphate↗
PubMed1991

Factors influencing the in vitro growth of Mycobacterium leprae: effect of oxygen.

In our efforts to evaluate factors responsible for in vitro growth of Mycobacterium leprae in DH medium and also to improve the system, effects of oxygen tension on in vitro growth of M. leprae were determined. This was achieved by varying the ratio between DH medium and free air space above the medium in the culture tubes. Growth-competent M. phlei (ATCC 11758) could tolerate all the oxygen it can get in the medium. On the other hand, M. leprae seemed to be of microaerophilic nature. In vivo-grown M. leprae cells were more sensitive than their counterparts that were adapted to in vitro environment. In vivo-grown cells grew better when 70% of the space in culture tube was occupied by DH medium. These in vitro-adapted cells gave optimum growth in subcultures when the air spaces in the culture tubes were 40-50%. The role of oxygen tensions in the development of lesions in leprosy patients and armadillos has been discussed.

Adenosine Triphosphate↗
PubMed1991

Intrabacterial sodium-to-potassium ratios and ATP contents of Mycobacterium leprae from ofloxacin-treated patients.

In a clinical trial including 17 multibacillary leprosy patients the in vivo effectiveness of ofloxacin on Mycobacterium leprae was tested via mass spectrometric determination of intrabacterial ratios of the concentrations of the sodium and potassium ions of individual organisms and of the ATP content per 10(6) bacteria isolated from skin biopsies. After 3 months of treatment, the in vivo drug effect could be determined with at least one of the two methods in 14 cases. Both methods revealed that in two cases the bacteria definitely did not respond to a 3-month ofloxacin monotherapy (200 mg twice daily). In three further cases a nonresponse of the M. leprae organisms was suspected from the mass spectrometric measurements. In the responder cases, the M. leprae were severely impaired. From the intrabacterial cation ratios the percentage of viable organisms averaged over all untreated biopsies was determined to be 58% and the percentage-killing during the first 3 months of treatment was 72%.

Adenosine Triphosphate↗
PubMed1991

Changes in hydrolytic enzyme activities in armadillos infected with Mycobacterium leprae.

The activities of hydrolytic enzymes in various organs of armadillos infected with Mycobacterium leprae were compared with those in normal armadillos. Except for aspartate aminopeptidase and esterase, the levels of the other enzymes in liver, spleen and inguinal lymph nodes were significantly higher in armadillos infected with M. leprae compared with those in non-infected ones. These enzymes levels were at a maximum when the animals were sacrificed 22 to 30 months post-inoculation, a period when the bacterial load in the animals had also reached a maximum. Animals infected with M. leprae but not showing any signs of disseminated infection behaved similar to those in the non-infected group. The observed changes in enzymatic activities were not due to bacterial enzymes and so can be related to tissue damage caused by M. leprae.

Animals↗
PubMed1991

In vitro and in vivo effects of N-methyl-3,5-dichloro-benzylamine hydrochloride on Mycobacterium leprae.

The antimicrobial effects of a new benzylamine, ME-93 (N-methyl-3,5-dichloro-benzylamine hydrochloride), alone and in combination with dapsone and rifampicin, have been evaluated in vitro in cell-free culture system and in vivo in mouse foot pad system. Even at 50 micrograms/ml, ME-93 did not completely inhibit the in vitro growth of M. leprae, and the effects were bacteriostatic. However, there was a synergism when ME-93 was combined with rifampicin, and the effects were bactericidal. Similar findings were also obtained in the mouse foot pad system. Thus, there is a new drug that needs further attention in the chemotherapy of leprosy.

Animals↗
PubMed1990

The pathology of the eye in armadillos experimentally infected with Mycobacterium leprae.

One hundred and twenty-seven eyes from 66 Mycobacterium leprae inoculated armadillos were studied histologically and some ultrastructurally. Inflammatory reactions were found in the following extraocular tissues: the eyelid, including the orbicularis muscle and the third eyelid, extraocular muscles, tear gland and Harder's gland. The early and slight changes of the intraocular tissues, small amounts of lymphocytes, plasma cells and macrophage infiltrations were confined to the area around the anterior angle specifically within the trabeculae and the adjacent ciliary body, the root of the iris and the limbus region of the cornea. But in the cases with severe lesions the whole uvea was densely infiltrated with large, foamy macrophages intermingled with small amounts of lymphocytes, plasma cells and frequently, neutrophils. No specific necrosis of the granulomas was seen. No explanation for the neutrophil infiltrations was given. The lesions in the cornea were significantly less severe than those in the uvea. Retinal lesions comprised of macrophage infiltrations were all obvious extensions of the adjacent uvea lesions. Acid-fast bacilla (AFB) were found within all tissues. The infection of the intraocular tissues in the armadillo eyes seemed to be mainly, if not solely, haematogenous.

Animals↗
PubMed1990

In vitro and in vivo experiments with the new inhibitor of mycobacterium leprae brodimoprim alone and in combination with dapsone.

The antibacterial effect of brodimoprim alone and in combination with dapsone has been studied in vitro in cell-free systems and in whole mycobacterial cells as well as in vivo in mice and humans. The obtained inhibitory effects in vitro and in vivo against model mycobacterial strains and M. leprae, the pharmacokinetic properties in human and its synergistic effect with the most used drug in the chemotherapy of leprosy, dapsone, make brodimoprim a promising candidate in the therapy of leprosy.

Adenosine Triphosphate↗
PubMed1988

Presence of mycobactin-like substance in Mycobacterium leprae.

Chloroform extracts of M. leprae suspensions--crude, partially purified and purified--were prepared by standard methods. Similar extracts were also prepared from the livers of normal armadillos using the same methods that were used to prepare crude and partially purified M. leprae suspensions. The only chloroform extract that supported the growth of M. paratuberculosis was the one prepared from Percoll gradient-purified M. leprae. Other four extracts not only did not support the growth of mycobactin-dependent M. paratuberculosis, but also inhibited the growth of mycobactin-independent strain of M. paratuberculosis. These results suggest the presence of mycobactin-like substance in M. leprae, and also, the presence of other unknown substance(s) in the crude suspensions of armadillo livers that inhibits the growth of M. paratuberculosis.

Animals↗
PubMed1985

Intrinsic energy potential of Mycobacterium lepraemurium essential for growth in NC-5 medium.

The intrinsic energy potential of the fastidious mycobacterium, Mycobacterium lepraemurium, essential for growth in axenic liquid medium was determined by ultraviolet irradiation of the inoculum. The growth potential in NC-5 medium of irradiated inocula was measured by an ultrasensitive method of adenosine triphosphate (ATP) using a luciferin-luciferase acceptor system. The results indicate that growth of bacilli ceased when more than one third of the ATP pool in 7 X 10(6) cells was lost. The residual level of ATP is roughly equivalent to that found in 10(5) non-irradiated cells.

Adenosine Triphosphate↗
PubMed1985

Results from cation and mass fingerprint analysis of single cells and from ATP measurements of M. leprae for drug sensitivity testing: a comparison.

The physiologic states of Mycobacterium leprae isolated from patient biopsies were studied using single cell mass spectrometry by laser microprobe mass analysis (LAM-MA) and ATP bioluminescence assay. The changes in the physiologic state of M. leprae after the patients had been treated with dapsone (DDS) monotherapy were also studied. The shift of the low intracellular Na+, K+-ratio of untreated M. leprae cells to higher values under DDS therapy, as measured from a limited number of single bacteria, correlates with a decrease in the ATP content. Further information on the influence of the drug could be drawn from the multivariate analysis of mass fingerprints of the organic matrix of the cells. Evidence is provided that the combination of the measurement of the intracellular cation ratios and of the mass fingerprint analysis could give fast answers to the question of drug resistance and to the persister hypothesis. The ATP bioluminescence assay and the single cell mass analysis should be alternatives to the mouse foot pad test.

Animals↗
PubMed1984

Adenosine triphosphate content of Mycobacterium leprae from leprosy patients.

Mycobacterium leprae obtained from randomly selected lepromatous leprosy patients were used to evaluate the ATP assay technique for detecting viability of these cells. The findings were further confirmed by the standard mouse foot pad technique. While the latter takes about 8-12 months to obtain any valid information on the status of M. leprae, the ATP data can be generated within hours and at much lower cost. It is hoped that the ATP data could also instantaneously identify viable bacilli from patients taking dapsone and thereby identify dapsone-resistant patients so that alternative treatment could be given. The advantages of this method over other currently available methods are discussed.

Adenosine Triphosphate↗