A lipidic nanoemulsion termed LDE concentrates in neoplastic cells after injection into the bloodstream and thus can be used as a drug carrier to tumour sites. The chemotherapeutic agent daunorubicin associates poorly with LDE; the aim of this study was to clarify whether the derivatization of daunorubicin by the attachment of an oleyl group increases the association with LDE, and to test the cytotoxicity and animal toxicity of the new preparation. The association of oleyl-daunorubicin (oDNR) to LDE showed high yield (93 +/- 2% and 84 +/- 4% at 1:10 and 1:5 drug:lipid mass, respectively) and was stable for at least 20 days. Association with oDNR increased the LDE particle diameter from 42 +/- 4 nm to 75 +/- 6 nm. Cytotoxicity of LDE-oDNR was reduced two-fold in HL-60 and K-562 cell lines, fourteen-fold in B16 cells and nine-fold in L1210 cells when compared with commercial daunorubicin. When tested in mice, LDE-oDNR showed remarkable reduced toxicity (maximum tolerated dose > 253 micromol kg(-1), compared with <3 micromol kg(-1) for commercial daunorubicin). At high doses, the cardiac tissue of LDE-oDNR-treated animals had much smaller structural lesions than with commercial daunorubicin. LDE-oDNR is therefore a promising new preparation that may offer superior tolerability compared with commercial daunorubicin.

No abstract

A cholesterol-rich microemulsion that binds to low-density lipoprotein (LDL) receptors (LDE), after injection into the bloodstream, concentrates in neoplastic tissues that over-express those receptors. LDE can thus serve as a vehicle for drug targeting. It was shown that carmustine side effects are pronouncedly reduced when the drug is associated with LDE in cancer patients. In this study, the therapeutic action of LDE associated with carmustine was compared with that of the non-associated drug in rats implanted with Walker 256 tumour. The toxicity and anti-tumour activity in rats treated with either free carmustine or carmustine associated with LDE and in control rats treated with saline solution were determined after a single intraperitoneal injection. The LD90 (90% lethal dose) of LDE-carmustine was 77 mg kg(-1) and of free carmustine was 44 mg kg(-1), indicating that LDE decreases toxicity. LDE-carmustine was able to decrease tumour mass at a lower dose level than free carmustine. Tumour regression time was shorter in LDE-carmustine- than in free carmustine-treated animals. Therefore, this study shows that the association of carmustine with LDE increases the therapeutic index of carmustine.

Resumo: Pretende neste trabalho avaliar a influência do teor de umidade, da porosidade e do intervalo de tempo até a aplicação, sobre a resistência à compressão simples (RCS) de misturas de solo-cimento. Foram realizadas três baterias de ensaios, usando misturas de solo-cimento compactadas, com 6 e 7 % de cimento. Na primeira bateria foi utilizada a umidade ótima (ótima) e energia Normal de Proctor, na segunda usou-se ótima + 1 % e energia Normal de Proctor e na terceira foi utilizada a ótima + 1 % e energia de compactação alterada, a fim de verificar a influência do teor de umidade. Para cada dosagem as compactações ocorreram em 10 intervalos de tempo até a aplicação, variando de 0 min a 6 h, com o intuito de verificar, no desempenho mecânico, a influência do intervalo de tempo até a aplicação do solo-cimento. Os resultados apontaram que o aumento no intervalo de tempo até a aplicação diminui a RCS e este tempo é limitado para atingir a RCS mínima requerida de 21 kg/cm², variando conforme o teor de cimento, teor de umidade e energia de compactação. Quando a compactação se deu com ótima + 1 % foram obtidos maiores valores de RCS, para os mesmos tempos de aplicação. Em todas as dosagens verificou-se que quanto mais baixa a porosidade da mistura solo-cimento melhor foi o desempenho mecânico.Palavras-chave: resistência à compressão simples, desempenho mecânico, solo-cimento. Abstract:In this paper it intends to evaluate the moisture content, porosity and time lapse until the application influences over their unconfined strength of soil-cement mixtures. They were made three groups of laboratorial tests, over compacted soil-cement mixtures, using 6 and 7 % Portland cement. In the first group, the dosage mixture was made under the optimum humidity (optimun) and Proctor normal energy. In the second group, the dosage mixture was made under the optimun + 1 % and Proctor normal energy. In the third group, the dosage mixture was made under the optimun + 1% and altered Proctor energy. These conditions were adopted for moisture content influence verifications. Over each dosage mixture, the compaction was made after 10 time lapses between the until application works, varying for 0 min to 6 h, to verify in the mechanical performance, the influence of the time lapse until the application influences. The results appointed to the unconfined strength decreasing for the increasing time lapse until the mixture application and this time lapse was limited for the 21 kg/cm² minimum unconfined strength required, varying according to the cement content, moisture content and compaction energy.When the compaction was made with the optimun + 1 %, the unconfined strength obtained was higher, for the same time lapse until application. For all dosage mixtures was verified that the better mechanical performance occurred to the lower mixture porosity.

No abstract

The contamination of soils by metals issuing from municipal solid waste (MSW) disposal in tropical environments has hardly been studied with regard to the particular problems associated with them, i.e., generally a high permeability of soils despite the abundance of clay, and the role of reactive Fe compounds. From a previous geotechnical and chemical survey, three latosol profiles differently affected by MSW leachates in the region of Londrina (Paraná, Brazil) were selected. The aims were to evaluate the extent of their contamination, to better understand the fate of potentially harmful metals in tropical soils and rank the determining factors. Samples between 0.5 and 7 m depth were analyzed for their physical, mineralogical and chemical properties, and their micro-morphology was described by optical and transmission electron microscopy. Two steps of a sequential extraction procedure helped to assess the mobility of elements and to better discriminate between metals originating from pedogenesis and issued from MSW. These combined approaches showed that exposed soil profiles have been impacted at various depths, down to 7 m, through increased metal content, especially enhanced mobility of Zn, Co, Mn, Cu and Fe, and through increased salinity and organic matter. The mobility of potentially harmful metals should decrease with pH, which significantly increased in some impacted horizons, but other factors can reverse this trend.

No abstract

A lipidic nanoemulsion termed LDE concentrates in neoplastic cells after injection into the bloodstream and thus can be used as a drug carrier to tumour sites. The chemotherapeutic agent daunorubicin associates poorly with LDE; the aim of this study was to clarify whether the derivatization of daunorubicin by the attachment of an oleyl group increases the association with LDE, and to test the cytotoxicity and animal toxicity of the new preparation. The association of oleyl-daunorubicin (oDNR) to LDE showed high yield (93 +/- 2% and 84 +/- 4% at 1:10 and 1:5 drug:lipid mass, respectively) and was stable for at least 20 days. Association with oDNR increased the LDE particle diameter from 42 +/- 4 nm to 75 +/- 6 nm. Cytotoxicity of LDE-oDNR was reduced two-fold in HL-60 and K-562 cell lines, fourteen-fold in B16 cells and nine-fold in L1210 cells when compared with commercial daunorubicin. When tested in mice, LDE-oDNR showed remarkable reduced toxicity (maximum tolerated dose > 253 micromol kg(-1), compared with <3 micromol kg(-1) for commercial daunorubicin). At high doses, the cardiac tissue of LDE-oDNR-treated animals had much smaller structural lesions than with commercial daunorubicin. LDE-oDNR is therefore a promising new preparation that may offer superior tolerability compared with commercial daunorubicin.