N-acetylcysteine reduces amphotericin B deoxycholate nephrotoxicity and improves the outcome of murine cryptococcosis.

Cryptococcosis is a life-threatening fungal infection, and its current treatment is toxic and subject to resistance. Drug repurposing represents an interesting approach to find drugs to reduce the toxicity of antifungals. In this study, we evaluated the combination of N-acetylcysteine (NAC) with amphotericin B (AMB) for the treatment of cryptococcosis. We examined the effects of NAC on fungal morphophysiology and on the macrophage fungicidal activity 3 and 24 hours post inoculation. The therapeutic effects of NAC combination with AMB were investigated in a murine model with daily treatments regimens. NAC alone reduced the oxidative burst generated by AMB in yeast cells, but did not inhibit fungal growth. The combination NAC + AMB decreased capsule size, zeta potential, superoxide dismutase activity and lipid peroxidation. In macrophage assays, NAC + AMB did not influence the phagocytosis, but induced fungal killing with different levels of oxidative bursts when compared to AMB alone: there was an increased reactive oxygen species (ROS) after 3 hours and reduced levels after 24 hours. By contrast, ROS remained elevated when AMB was tested alone, demonstrating that NAC reduced AMB oxidative effects without influencing its antifungal activity. Uninfected mice treated with NAC + AMB had lower concentrations of serum creatinine and glutamate-pyruvate transaminase in comparison to AMB. The combination of NAC + AMB was far better than AMB alone in increasing survival and reducing morbidity in murine-induced cryptococcosis, leading to reduced fungal burden in lungs and brain and also lower concentrations of pro-inflammatory cytokines in the lungs. In conclusion, NAC + AMB may represent an alternative adjuvant for the treatment of cryptococcosis.

Host range and susceptibility to Toxoplasma gondii infection in captive neotropical and Old-world primates.

BACKGROUND: Toxoplasmosis is an important disease affecting captive non-human primates. The goal of this study was to assess the seroprevalence and pathological findings of toxoplasmosis in different species of captive primates. METHODS: Six captive neotropical primates died naturally due to Toxoplasma gondii infection and were necropsied. Tissue samples were evaluated by histopathology and immunohistochemistry. Serum samples from 57 captive neotropical and Old-world primates housed at the Belo Horizonte zoological garden were analyzed by indirect fluorescent antibody test (IFAT), enzyme-linked immunosorbent assay (ELISA), and indirect hemagglutination assay (IHA). RESULTS: Neotropical primates had lesions compatible with toxoplasmosis with immunolabeled intralesional T gondii. All Old-World primates (10/10), but only three neotropical primates (3/47), all belonging to the Sapajus apella species (3/6), were serologically positive. CONCLUSIONS: Our results suggest a higher susceptibility of neotropical primates to toxoplasmosis. However, this study also supports the hypothesis that Sapajus apella may be naturally resistant.

Necrotizing placentitis in a cow caused by Bacillus cereus / Placentite necrotizante em uma vaca por Bacillus cereus

ABSTRACT: This report described a case of necrotizing placentitis caused by Bacillus cereus in a cow associated with abortion and maternal lethality. The etiological diagnosis of placentitis by B. cereus was based on histopathology of placenta, cytology and bacterial isolation from intrauterine aminiotic fluid in retained placenta and further characterization of the pathogen by the MALDI-TOF. Although, B. cereus abortions are sporadic, the bacterium has the ability to release necrotizing toxins that can lead to placentitis, fetal death and abortion.

RESUMO: Este relato descreve a placentite necrotizante causada por Bacillus cereus em uma vaca associada a aborto e mortalidade materna. O diagnóstico etiológico de placentite por B. cereus foi baseado na histopatologia da placenta, citologia e isolamento bacteriano partir do líquido aminiótico em placenta retida e identificação do patógeno pela técnica de MALDI-TOF. Embora abortos por B. cereus sejam esporádicos, a bactéria tem a capacidade de liberar toxinas necrotizantes que podem levar a placentite e aborto.