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Biomedical subjects

R T Mehta

Publications and source records attributed to R T Mehta.

13 recordsLinked to original sources
PubMed1995

Determination of MICs for Mycobacterium avium-M. intracellulare complex in liquid medium by a colorimetric method.

We investigated the potential of a rapid colorimetric microassay based on the reduction of dimethylthiazol-diphenyltetrazolium bromide (MTT) for determining the growth of Mycobacterium avium-M. intracellulare complex (MAC) and MICs of clofazimine, resorcinomycin A, and the quinolone PD 127391 against MAC. The reduction of MTT was directly proportional to the number of viable bacteria. A comparison of the MTT reduction test with the [3H]glycerol uptake assay showed the former to possess higher analytical sensitivity for detecting MAC growth in microtiter plates. The MIT reduction test avoids the use of radioisotopes and costly material and equipment; it is reliable, reproducible, and convenient for rapid routine susceptibility testing of MAC.

Anti-Bacterial Agents↗
PubMed1993

In vitro activities of free and liposomal drugs against Mycobacterium avium-M. intracellulare complex and M. tuberculosis.

We compared MICs and MBCs of various free- and liposome-incorporated antimicrobial agents against several patient isolates of Mycobacterium avium-M. intracellulare complex and certain American Type Culture Collection strains of M. avium, M. intracellulare, and Mycobacterium tuberculosis. Seven of 19 agents were selected for incorporation into liposomes. The MICs of these agents for 50 and 90% of isolates tested (MIC50s and MIC90s, respectively) ranged from 0.5 to 62 micrograms/ml. Members of the M. avium-M. intracellulare complex were resistant to killing by most of the other agents tested in the free form. However, clofazimine, resorcinomycin A, and PD 117558 showed complete killing of bacteria at concentrations ranging from 8 to 31 micrograms/ml, represented as MBC90s. Among the liposome-incorporated agents, clofazimine and resorcinomycin A had the highest killing effects (MBC90s, 8 and 16 micrograms/ml, respectively). Furthermore, both free and liposome-incorporated clofazimine had equivalent growth-inhibitory and killing effects on all American Type Culture Collection strains of M. avium, M. intracellulare, and M. tuberculosis tested. These results show that the antibacterial activities of certain drugs, particularly those of clofazimine and resorcinomycin, were maintained after the drugs were incorporated into liposomes.

Anti-Bacterial Agents↗
PubMed1991

Liposomal hamycin: reduced toxicity and improved antifungal efficacy in vitro and in vivo.

Hamycin has been used to treat a variety of yeast and other fungal infections by oral, topical, and intraperitoneal routes. However, its parenteral use has been reported to be associated with high toxicity. Multilamellar liposomes composed of dimyristoyl phosphatidyl choline, dimyristoyl phosphatidyl glycerol, and various amounts of cholesterol were used as drug carriers for hamycin. The antifungal activity of hamycin was maintained after liposome encapsulation (MIC range, 0.6-1.2 micrograms/ml), and toxicity was reduced in vitro and in vivo as the concentration of cholesterol was increased to an appropriate ratio. Mice were treated with various doses of free or liposomal hamycin 2 days after infection. Although free drug did not significantly improve survival, liposomal hamycin at an equivalent dose (0.6 mg/kg) increased the survival from 18 to 38 days. Higher doses (1.2 and 1.8 mg/kg) showed further improvement in survival and reduction in numbers of colony-forming units in the kidneys. Liposome encapsulation resulted in improved therapeutic index of hamycin.

Animals↗
PubMed1989

A comparison of in vitro toxicity and antifungal efficacy of membrane-active drugs after liposome encapsulation.

The membrane-active ionophores were observed to possess antifungal activity against Candida albicans 336 and were toxic to human erythrocytes. Liposome encapsulation of these drugs significantly reduced their toxicity to erythrocytes but resulted in the loss of their antifungal potency. These results are compared with membrane-active polyenes which maintained their antifungal activity after encapsulation into liposomes. Liposomal-ionophores, however, showed antifungal activity along with low concentrations of Amphotericin B indicating the presence of synergism between these drugs.

Antifungal Agents↗
PubMed1989

Effects of free and liposomal amphotericin B and gramicidin S alone and in combination on potassium leakage from human erythrocytes and Candida albicans.

We studied the toxic effects of amphotericin B and gramicidin S, alone and in combination, using free and liposome-encapsulated drugs. In vitro toxic effects of the drugs on human erythrocytes and Candida albicans were determined by measuring leakage of intracellular potassium ions (K+). Liposomal formulations of both drugs greatly reduced K+ leakage from human erythrocytes, whereas liposomal gramicidin S, but not liposomal amphotericin B, prevented K+ leakage from C. albicans. In both free and liposomal forms, the combinations of drugs produced decreased toxicity to erythrocytes compared with the drugs alone. This protective effect was more apparent with liposomal combinations than with free drug combinations. A significant increase in fungal cell toxicity was observed, however, when free and liposomal drug combinations were tested against C. albicans. The results suggest that optimal concentrations of liposomal drug combinations (amphotericin B and gramicidin S) may provide increased toxicity against fungal cells and simultaneously protect mammalian cells.

Amphotericin B↗
PubMed1987

Formulation, toxicity, and antifungal activity in vitro of liposome-encapsulated nystatin as therapeutic agent for systemic candidiasis.

Multilamellar vesicles containing nystatin (NYS) were compared with vesicles containing the free drug for toxicity to erythrocytes and for antifungal activity in vitro. Liposomal nystatin was as active as free NYS was against a wide variety of yeasts and fungi. The antifungal activity against Candida albicans was maintained with different liposome compositions and without sterols. Liposome encapsulation also protected the erythrocytes from the toxicity of free NYS.

Candida↗
PubMed1987

Toxicity and therapeutic effects in mice of liposome-encapsulated nystatin for systemic fungal infections.

The therapeutic activity of nystatin (NYS) incorporated in multilamellar liposomes (L-NYS) was studied in vivo. Hale-Stoner mice injected intravenously with various doses of L-NYS and free NYS showed a significant reduction in toxicity of NYS after the NYS was incorporated into liposomes (maximal tolerated doses, 16 and 4 mg/kg of body weight, respectively). The maximal tolerated dose of free NYS had no effect in the treatment of mice infected with Candida albicans, whereas L-NYS at an equivalent dose improved the survival of mice. A marked increase in survival was observed when L-NYS was administered in higher and multiple doses (total doses up to 80 mg/kg). Liposome encapsulation thus provided a means for intravenous administration of NYS, reducing its toxicity and making it an active systemic antifungal agent.

Animals↗
PubMed1985

Prophylaxis of murine candidiasis via application of liposome-encapsulated amphotericin B and a muramyl dipeptide analog, alone and in combination.

The present study was conducted to examine the effect of a lipophilic analog of muramyl dipeptide, 6-O-stearoyl-N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine (6-O-S-Abu-MDP), a macrophage activator, on the prophylactic activity of liposomal amphotericin B (L-AmpB) against disseminated candidiasis in mice. Multilamellar vesicles containing AmpB and (6-O-S-Abu)-MDP were prepared by using dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (7:3 molar ratio). Hale-Stoner mice (6 to 8 weeks old) were injected with 7 X 10(5) CFU of Candida albicans 336 isolated from a patient. Groups of mice were injected intravenously with different doses of L-AmpB and L-(6-O-S-Abu)-MDP, individually or in combination, 2 days before challenge with C. albicans. The mice were injected with a fixed dose of L-AmpB (1.2 mg/kg in 400 mg of lipid per kg) and various doses of L-(6-O-S-Abu)-MDP (0.6, 1.2, 2, and 4 mg/kg in 400 mg of lipid per kg) or vice versa. Other control groups included untreated mice and those receiving empty liposomes (400 mg of lipid per kg), free AmpB (0.6 mg/kg), or free (6-O-S-Abu)-MDP (4 mg/kg). The mice receiving L-AmpB (1.2 mg/kg) plus L-(6-O-S-Abu)-MDP (0.6 to 4.0 mg/kg) survived up to 25 to 30 days as compared with those injected with L-AmpB alone (15 days) or with L-(6-O-S-Abu)-MDP alone (10 to 15 days). All the mice in other control groups died within 7 to 11 days. The kidney cultures of the mice that received L-AmpB (4 mg/kg) plus L-(6-O-S-Abu)-MDP (1.2 mg/kg) were free of C. albicans infection, unlike those injected with L-AmpB. Variance analysis of these findings indicates a synergistic activity between L-AmpB and L-(6-O-S-Abu)-MDP in the prophylaxis of candidiasis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Effect of liposomal amphotericin B on murine macrophages and lymphocytes.

The effect of liposome-encapsulated amphotericin B on mouse macrophages and on T- and B-lymphocyte functions in vitro was compared with that of free amphotericin B. Liposomal amphotericin B was generally less toxic than the free form of the drug. Low concentrations of free amphotericin B completely inhibited the serum-dependent induction of transglutaminase, a marker for macrophage differentiation, and production of superoxide anion by macrophages, whereas encapsulation of the drug within liposomes protected the cells from these adverse effects. Liposomal amphotericin B did not affect the blastogenic response of T cells compared with the free drug, which was inhibitory at high concentrations. Antibody production in vivo was inhibited partially by both free and liposomal amphotericin B. These results thus suggest that encapsulation of amphotericin B in liposomes reduces the immunosuppressive effects exerted by free amphotericin B. This provides further justification for therapeutic use of liposomal amphotericin B in systemic fungal infections (G. Lopez-Berestein, R. Mehta, R. L. Hopfer, K. Mills, L. Kasi, K. Mehta, V. Fainstein, M. Luna, E. M. Hersh, and R. L. Juliano, J. Infect. Dis. 147:939-945, 1983).

Acyltransferases↗
PubMedDate not supplied

Phagocyte transport as mechanism for enhanced therapeutic activity of liposomal amphotericin B.

Liposomal amphotericin B (L-AmB) is emerging as one of the most attractive new antifungal agents. We have attempted to show that phagocytic cells circulating in blood play an important role in transport and accumulation of L-AmB at inflammatory sites in vivo. Free AmB or L-AmB was injected intravenously to mice, and the amount of AmB in peritoneal exudate cells was quantitated by high-performance liquid chromatography. Higher levels of AmB were detected in a higher number of mice injected with L-AmB. The presence of L-AmB in inflammatory peritoneal cells after intravenous administration of fluorescence-labeled L-AmB also suggested that macrophages play an important role in the transport of intravenously administered L-AmB to inflammatory sites.

Amphotericin B↗