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Effect of Amphotericin B Nanodisks on Leishmania major Infected Mice.

Cole P, Bishop J, Beckstead J, Titus R, Ryan R - Pharm Anal Acta (2014)

Bottom Line: Balb/c and CH3 mice infected with Leishmania major on Day 0 were administered vehicle alone, empty ND or AMB-ND on Day 1 and day 7, via the tail vein.Mice were sacrificed 25 or 50 days post inoculation and tissue histology evaluated.It may be inferred that AMB-ND may be useful for prophylactic and/or treatment of early stage Leishmania spp. infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Microbiology, Immunology, and Pathology Department, Colorado State University, Fort Collins, CO 80523-1619.

ABSTRACT

Objective: To assess the efficacy of a novel formulation of the polyene antibiotic, amphotericin B (AMB), as therapy for cutaneous leishmaniasis in different mouse strains.

Methods: (AMB), was formulated into water-soluble transport particles, termed nanodisks (ND). Balb/c and CH3 mice infected with Leishmania major on Day 0 were administered vehicle alone, empty ND or AMB-ND on Day 1 and day 7, via the tail vein. Mice were sacrificed 25 or 50 days post inoculation and tissue histology evaluated. Balb/c mice treated with vehicle or empty ND showed signs of severe infection while CH3 mice had less inflammation and fewer parasites. AMB-ND treatment (2 mg/kg) had a marked therapeutic effect on L. major infected Balb/c mice and a discernable therapeutic benefit on CH3 mice.

Conclusions: AMB-ND is efficacious in the treatment of cutaneous leishmaniasis in both susceptible and resistant mouse strains. It may be inferred that AMB-ND may be useful for prophylactic and/or treatment of early stage Leishmania spp. infection.

No MeSH data available.


Related in: MedlinePlus

Photomicrographs of a sagittally sectioned foot of a representative Balb/c mouse sacrificed 25 days PI with L. major and treatment with PBS. Panel A) The footpad epithelium is ulcerated and the surface has a thick crust of cellular debris, inflammatory cells and fibrin. The subcutaneous tissue has severe chronic inflammation. The central area of the metatarsal bone (*) has undergone lysis due to osteomyelitis. H&E, bar=500µm. Panel B) The subcutis has solid sheets of densely packed mixed mononuclear inflammatory cells. H&E, bar=50µm. Panel C) Note that macrophages have Leishmania sp. amastigotes in the cytoplasm. The cell near the center of the photograph has 8 organisms in its cytoplasm (arrows). H&E, bar=10 µm.
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Figure 1: Photomicrographs of a sagittally sectioned foot of a representative Balb/c mouse sacrificed 25 days PI with L. major and treatment with PBS. Panel A) The footpad epithelium is ulcerated and the surface has a thick crust of cellular debris, inflammatory cells and fibrin. The subcutaneous tissue has severe chronic inflammation. The central area of the metatarsal bone (*) has undergone lysis due to osteomyelitis. H&E, bar=500µm. Panel B) The subcutis has solid sheets of densely packed mixed mononuclear inflammatory cells. H&E, bar=50µm. Panel C) Note that macrophages have Leishmania sp. amastigotes in the cytoplasm. The cell near the center of the photograph has 8 organisms in its cytoplasm (arrows). H&E, bar=10 µm.

Mentions: Over the time course of the experiment, the infected left foot of both treatment groups became progressively thicker than the uninfected rightfoot, with severe thickening present by day 50. Extensive ulceration of the footpad was grossly evident by day 25. Histologic examination of infected foot tissue collected at day 25 revealed epidermal ulceration, severe pyogranulomatous inflammation in the soft tissues, and osteomyelitis of metatarsal bones. A photomicrograph of the sagittal section of a typical infected foot (Figure 1A and 1B) illustrates a large epidermal ulcer with a thick surface crust of cellular debris, inflammatory cells, and fibrin. In addition, the subcutaneous tissue has extensive inflammation with neutrophils, macrophages, lymphocytes and plasma cells present. The central area (*) of the metatarsal bone has undergone lysis. The haired skin of the dorsum of the foot is intact. Large numbers of L. major were present within macrophages located in the soft tissues. Higher magnification of the subcutis of this sagittal section of the foot reveals sheets of closely packed mixed mononuclear inflammatory cells with L. major amastigotes present in many macrophages (Figure 1C). The extent of tissue damage at day 50 (not shown) was similar to that at day 25 in these mice, whether treated with PBS or empty ND. The left popliteal lymph nodes were severely reactive at days 25 and 50 in both treatment groups. The number of L. major present in the left popliteal lymph nodes varied among mice in the PBS treatment group and was highest in the empty ND treatment group. Nodes with high numbers of parasites also had high numbers of neutrophils. Furthermore, spleens of infected Balb/c mice treated with PBS or empty ND had moderately reactive lymphoid follicles and moderate numbers of neutrophils in red pulp at day 25 and milder changes of a similar nature at day 50. Livers had mild, moderate or severe randomly located accumulations of mixed mononuclear inflammatory cells. No differences in liver inflammation were detected between these treatment groups or between day 25 and day 50.


Effect of Amphotericin B Nanodisks on Leishmania major Infected Mice.

Cole P, Bishop J, Beckstead J, Titus R, Ryan R - Pharm Anal Acta (2014)

Photomicrographs of a sagittally sectioned foot of a representative Balb/c mouse sacrificed 25 days PI with L. major and treatment with PBS. Panel A) The footpad epithelium is ulcerated and the surface has a thick crust of cellular debris, inflammatory cells and fibrin. The subcutaneous tissue has severe chronic inflammation. The central area of the metatarsal bone (*) has undergone lysis due to osteomyelitis. H&E, bar=500µm. Panel B) The subcutis has solid sheets of densely packed mixed mononuclear inflammatory cells. H&E, bar=50µm. Panel C) Note that macrophages have Leishmania sp. amastigotes in the cytoplasm. The cell near the center of the photograph has 8 organisms in its cytoplasm (arrows). H&E, bar=10 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4288788&req=5

Figure 1: Photomicrographs of a sagittally sectioned foot of a representative Balb/c mouse sacrificed 25 days PI with L. major and treatment with PBS. Panel A) The footpad epithelium is ulcerated and the surface has a thick crust of cellular debris, inflammatory cells and fibrin. The subcutaneous tissue has severe chronic inflammation. The central area of the metatarsal bone (*) has undergone lysis due to osteomyelitis. H&E, bar=500µm. Panel B) The subcutis has solid sheets of densely packed mixed mononuclear inflammatory cells. H&E, bar=50µm. Panel C) Note that macrophages have Leishmania sp. amastigotes in the cytoplasm. The cell near the center of the photograph has 8 organisms in its cytoplasm (arrows). H&E, bar=10 µm.
Mentions: Over the time course of the experiment, the infected left foot of both treatment groups became progressively thicker than the uninfected rightfoot, with severe thickening present by day 50. Extensive ulceration of the footpad was grossly evident by day 25. Histologic examination of infected foot tissue collected at day 25 revealed epidermal ulceration, severe pyogranulomatous inflammation in the soft tissues, and osteomyelitis of metatarsal bones. A photomicrograph of the sagittal section of a typical infected foot (Figure 1A and 1B) illustrates a large epidermal ulcer with a thick surface crust of cellular debris, inflammatory cells, and fibrin. In addition, the subcutaneous tissue has extensive inflammation with neutrophils, macrophages, lymphocytes and plasma cells present. The central area (*) of the metatarsal bone has undergone lysis. The haired skin of the dorsum of the foot is intact. Large numbers of L. major were present within macrophages located in the soft tissues. Higher magnification of the subcutis of this sagittal section of the foot reveals sheets of closely packed mixed mononuclear inflammatory cells with L. major amastigotes present in many macrophages (Figure 1C). The extent of tissue damage at day 50 (not shown) was similar to that at day 25 in these mice, whether treated with PBS or empty ND. The left popliteal lymph nodes were severely reactive at days 25 and 50 in both treatment groups. The number of L. major present in the left popliteal lymph nodes varied among mice in the PBS treatment group and was highest in the empty ND treatment group. Nodes with high numbers of parasites also had high numbers of neutrophils. Furthermore, spleens of infected Balb/c mice treated with PBS or empty ND had moderately reactive lymphoid follicles and moderate numbers of neutrophils in red pulp at day 25 and milder changes of a similar nature at day 50. Livers had mild, moderate or severe randomly located accumulations of mixed mononuclear inflammatory cells. No differences in liver inflammation were detected between these treatment groups or between day 25 and day 50.

Bottom Line: Balb/c and CH3 mice infected with Leishmania major on Day 0 were administered vehicle alone, empty ND or AMB-ND on Day 1 and day 7, via the tail vein.Mice were sacrificed 25 or 50 days post inoculation and tissue histology evaluated.It may be inferred that AMB-ND may be useful for prophylactic and/or treatment of early stage Leishmania spp. infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Microbiology, Immunology, and Pathology Department, Colorado State University, Fort Collins, CO 80523-1619.

ABSTRACT

Objective: To assess the efficacy of a novel formulation of the polyene antibiotic, amphotericin B (AMB), as therapy for cutaneous leishmaniasis in different mouse strains.

Methods: (AMB), was formulated into water-soluble transport particles, termed nanodisks (ND). Balb/c and CH3 mice infected with Leishmania major on Day 0 were administered vehicle alone, empty ND or AMB-ND on Day 1 and day 7, via the tail vein. Mice were sacrificed 25 or 50 days post inoculation and tissue histology evaluated. Balb/c mice treated with vehicle or empty ND showed signs of severe infection while CH3 mice had less inflammation and fewer parasites. AMB-ND treatment (2 mg/kg) had a marked therapeutic effect on L. major infected Balb/c mice and a discernable therapeutic benefit on CH3 mice.

Conclusions: AMB-ND is efficacious in the treatment of cutaneous leishmaniasis in both susceptible and resistant mouse strains. It may be inferred that AMB-ND may be useful for prophylactic and/or treatment of early stage Leishmania spp. infection.

No MeSH data available.


Related in: MedlinePlus