amphotericin-b and Rodent-Diseases

Amphotericin B (AmB) is used to treat cryptococcal meningoencephalitis. However, the mortality rate remains high. Higher doses of AmB in deoxycholate buffer (AmBd) are toxic to human red blood cells (hRBC) and have no effect on brain organism load in mice. Here we show that while AmBd lysed 96% of hRBC, AmB complexed with gold nanoparticles (AuNP-SA-AmB) lysed only 27% of hRBC. In vitro growth of C. neoformans was inhibited by 0.25 μg/ml AmBd and 0.04 μg/ml of AuNP-SA-AmB. In mice infected with C. neoformans, five daily treatments with AuNP-SA-AmB containing 0.25 mg/kg AmB significantly lowered the fungal burden in the brain tissue compared to either untreated or treatment with 0.25 mg/kg of AmBd. When a single dose of AmBd was injected intravenously into BALB/c mice, 81.61% of AmB cleared in the α-phase and 18.39% cleared in the β-phase at a rate of 0.34% per hour. In contrast, when AuNP-SA-AmB was injected, 49.19% of AmB cleared in the α-phase and 50.81% of AmB cleared in the β-phase at a rate of 0.27% per hour. These results suggest that AmB complexed with gold nanoparticles is less toxic to hRBC, is more effective against C. neoformans and persists longer in blood when injected into mice resulting in more effective clearing of C. neoformans from the brain tissue.. Amphotericin B (AmB) was complexed with gold nanoparticles (AuNP-SA-AmB) to improve brain delivery. AuNP-SA-AmB was more effective than AmB alone in clearing of Cryptococcus neoformans from the brain tissue of infected mice. This may be due to longer plasma half-life of AmB as AuNP-SA-AmB.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain Diseases; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Erythrocytes; Gold; Humans; Mice; Rodent Diseases

The therapeutic efficacy of amphotericin B and voriconazole alone and in combination with one another were evaluated in immunodeficient mice (BALB/c-SCID) infected with a fluconazole-resistant strain of Cryptococcus neoformans var. grubii. The animals were infected intravenously with 3 × 10(5) cells and intraperitoneally treated with amphotericin B (1.5 mg/kg/day) in combination with voriconazole (40 mg/kg/days). Treatment began 1 day after inoculation and continued for 7 and 15 days post-inoculation. The treatments were evaluated by survival curves and yeast quantification (CFUs) in brain and lung tissues. Treatments for 15 days significantly promoted the survival of the animals compared to the control groups. Our results indicated that amphotericin B was effective in assuring longest-term survival of infected animals, but these animals still harbored the highest CFU of C. neoformans in lungs and brain at the end of the experiment. Voriconazole was not as effective alone, but in combination with amphotericin B, it prolonged survival for the second-longest time period and provided the lowest colonization of target organs by the fungus. None of the treatments were effective in complete eradication of the fungus in mice lungs and brain at the end of the experiment.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Colony Count, Microbial; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Drug Resistance, Fungal; Drug Therapy, Combination; Fluconazole; Lung; Mice; Mice, Inbred BALB C; Mice, SCID; Pyrimidines; Rodent Diseases; Survival Analysis; Treatment Outcome; Triazoles; Voriconazole; Yeasts

Chagas disease is one of the most important public health problems and a leading cause of cardiac failure in Latin America. The currently available drugs to treat T. cruzi infection (benznidazole and nifurtimox) are effective in humans when administered during months. AmBisome (liposomal amphotericin B), already shown efficient after administration for some days in human and experimental infection with Leishmania, has been scarcely studied in T. cruzi infection.. This work investigates the effect of AmBisome treatment, administered in 6 intraperitoneal injections at various times during acute and/or chronic phases of mouse T. cruzi infection, comparing survival rates and parasitic loads in several tissues.. Quantitative PCR was used to determine parasitic DNA amounts in tissues. Immunosuppressive treatment with cyclophosphamide was used to investigate residual infection in tissues.. Administration of AmBisome during the acute phase of infection prevented mice from fatal issue. Parasitaemias (microscopic examination) were reduced in acute phase and undetectable in chronic infection. Quantitative PCR analyses showed significant parasite load reductions in heart, liver, spleen, skeletal muscle and adipose tissues in acute as well as in chronic infection. An earlier administration of AmBisome (one day after parasite inoculation) had a better effect in reducing parasite loads in spleen and liver, whereas repetition of treatment in chronic phase enhanced the parasite load reduction in heart and liver. However, whatever the treatment schedule, cyclophosphamide injections boosted infection to parasite amounts comparable to those observed in acutely infected and untreated mice.. Though AmBisome treatment fails to completely cure mice from T. cruzi infection, it impedes mortality and reduces significantly the parasitic loads in most tissues. Such a beneficial effect, obtained by administrating it over a short time, should stimulate studies on using AmBisome in association with other drugs in order to shorten recovery from T. cruzi infection.

Topics: Amphotericin B; Animal Structures; Animals; Antiprotozoal Agents; Chagas Disease; Disease Models, Animal; DNA, Protozoan; Humans; Injections, Intraperitoneal; Mice; Mice, Inbred BALB C; Polymerase Chain Reaction; Rodent Diseases; Survival Analysis; Trypanosoma cruzi

Topics: Adult; Amphotericin B; Animal Husbandry; Animals; Animals, Wild; Antifungal Agents; Argentina; Chrysosporium; Coccidioidomycosis; Diagnosis, Differential; Granuloma; Humans; Lung Diseases, Fungal; Male; Radiography; Respiratory Distress Syndrome; Rodent Diseases

Topics: Amphotericin B; Animals; Lung Diseases, Fungal; Mice; Mitosporic Fungi; Rodent Diseases