Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon™ (AmB-D) and two new different AmB formulations. Methods: three products were studied: Fungizon™, and two Fungizon™ /Lipofundin™ admixtures, which were diluted through two methods: in the first one, Fungizon™ was previously diluted with water for injection and then, in Lipofundin™ (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). Results: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. Conclusion: The Fungizon™- Lipofundin™ admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented

Diagnóstico ecotoxicológico dos efluentes lançados no complexo estuarino do Jundiaí/Potengi, Natal/RN

Untreated effluents that reach surface water affect the aquatic life and humans. This study aimed to evaluate the wastewater s toxicity (municipal, industrial and shrimp pond effluents) released in the Estuarine Complex of Jundiaí- Potengi, Natal/RN, through chronic quantitative e qualitative toxicity tests using the test organism Mysidopsis Juniae, CRUSTACEA, MYSIDACEA (Silva, 1979). For this, a new methodology for viewing chronic effects on organisms of M. juniae was used (only renewal), based on another existing methodology to another testorganism very similar to M. Juniae, the M. Bahia (daily renewal).Toxicity tests 7 days duration were used for detecting effects on the survival and fecundity in M. juniae. Lethal Concentration 50% (LC50%) was determined by the Trimmed Spearman-Karber; Inhibition Concentration 50% (IC50%) in fecundity was determined by Linear Interpolation. ANOVA (One Way) tests (p = 0.05) were used to determinate the No Observed Effect Concentration (NOEC) and Low Observed Effect Concentration (LOEC). Effluents flows were measured and the toxic load of the effluents was estimated. Multivariate analysis - Principal Component Analysis (PCA) and Correspondence Analysis (CA) - identified the physic-chemical parameters better explain the patterns of toxicity found in survival and fecundity of M. juniae. We verified the feasibility of applying the only renewal system in chronic tests with M. Juniae. Most efluentes proved toxic on the survival and fecundity of M. Juniae, except for some shrimp pond effluents. The most toxic effluent was ETE Lagoa Aerada (LC50, 6.24%; IC50, 4.82%), ETE Quintas (LC50, 5.85%), Giselda Trigueiro Hospital (LC50, 2.05%), CLAN (LC50, 2.14%) and COTEMINAS (LC50, IC50 and 38.51%, 6.94%). The greatest toxic load was originated from ETE inefficient high flow effluents, textile effluents and CLAN. The organic load was related to the toxic effects of wastewater and hospital effluents in survival of M. Juniae, as well as heavy metals, total residual chlorine and phenols. In industrial effluents was found relationship between toxicity and organic load, phenols, oils and greases and benzene. The effects on fertility were related, in turn, with chlorine and heavy metals. Toxicity tests using other organisms of different trophic levels, as well as analysis of sediment toxicity are recommended to confirm the patterns found with M. Juniae. However, the results indicate the necessity for implementation and improvement of sewage treatment systems affluent to the Potengi s estuary

Atividade antimalárica de plantas medicinais da biorregião do Araripe-CE em modelo murino - Plasmodium berghei

Malaria, also popularly known as maleita , intermittent fever, paludism, impaludism, third fever or fourth fever, is an acute infectious febrile disease, which, in human beings, is caused by four species: Plasmodium falciparum, P. vivax, P. malariae and P. ovale. Malaria, one of the main infectious diseases in the world, is the most important parasitoses, with 250 million annual cases and more than 1 million deaths per year, mainly in children younger than live years of age. The prophylactic and therapeutic arsenal against malaria is quite restricted, since all the antimalarials currently in use have some limitation. Many plant species belonging to several families have been tested in vivo, using the murine experimental model Plasmodium berghei or in vitro against P. falciparum, and this search has been directed toward plants with antithermal, antimalarial or antiinflammatory properties used in popular Brazilian bolk medicine. Studies assessing the biological activity of medicinal plant essential oils have revealed activities of interest, such as insecticidal, spasmolytic and antiplasmodic action. It has also been scientifically established that around 60% of essential oils have antifungal properties and that 35% exhibit antibacterial properties. In our investigation, essential oils were obtained from the species Vanillosmopsis arborea, Lippia sidoides and Croton zethneri which are found in the bioregion of Araripe-Ceará. The chemical composition of these essential oils was partially characterized and the presence of monoterpenes and sesquiterpenes. The acute toxicity of these oils was assessed in healthy mice at different doses applied on a single day and on four consecutive days, and in vitro cytotoxicity in HeLa and Raw cell lines was determined at different concentrations. The in vivo tests obtained lethal dose values of 7,1 mg/Kg (doses administered on a single day) and 1,8 mg/Kg (doses administered over four days) for 50% of the animals. In the in vitro tests, the inhibitory concentration for 50% of cell growth in Hela cell lines was 588 μg/mL (essential oil from C. zethneri after 48 h), from 340-555 μg/mL (essential oil from L. sidoides, after 24 and 48 h). The essential oil from V. arborea showed no cytotoxicity and none of the essential oils were cytotoxic in Raw cell lines. These data suggest a moderate toxicity in the essential XVIII oils under study, a finding that does not impede their testing in in vivo antimalarial assays. Was shown the antimalarial activity of the essential oils in mice infected with P. berghei was assessed. The three species showed antimalarial activity from 36%-57% for the essential oil from the stem of V. arborea; from 32%-82% for the essential oil from the leaves of L. sidoides and from 40%-70% of reduction for the essential oil from the leaves of C. zethneri. This is the first study showing evidence of antimalarial activity with these species from northeast Brazil. Further studies to isolate the active ingredients of these oils are needed to determine if a single active ingredient accounts for the antimalarial activity or if a complex integration of all the compounds present occurs, a situation reflected in their biological activity