Successful Dendrimer and Liposome-Based Strategies to Solubilize an Antiproliferative Pyrazole Otherwise Not Clinically Applicable

Water-soluble formulations of the pyrazole derivative 3-(4-chlorophenyl)-5-(4-nitrophenylamino)-1H-pyrazole-4-carbonitrile (CR232), which were proven to have in vitro antiproliferative effects on different cancer cell lines, were prepared by two diverse nanotechnological approaches. Importantly, without using harmful organic solvents or additives potentially toxic to humans, CR232 was firstly entrapped in a biodegradable fifth-generation dendrimer containing lysine (G5K). CR232-G5K nanoparticles (CR232-G5K NPs) were obtained with high loading (DL%) and encapsulation efficiency (EE%), which showed a complex but quantitative release profile governed by Weibull kinetics. Secondly, starting from hydrogenated soy phosphatidylcholine and cholesterol, we prepared biocompatible CR232-loaded liposomes (CR232-SUVs), which displayed DL% and EE% values increasing with the increase in the lipids/CR232 ratio initially adopted and showed a constant prolonged release profile ruled by zero-order kinetics. When relevant, attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR) and nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM) and dynamic light scattering (DLS) experiments, as well as potentiometric titrations completed the characterization of the prepared NPs. CR232-G5K NPs were 2311-fold more water-soluble than the pristine CR232, and the CR232-SUVs with the highest DL% were 1764-fold more soluble than the untreated CR232, thus establishing the success of both our strategies

Poly(Vinylalcohol-Co-Vinyloleate) for the Preparation of Micelles Enhancing Retinyl Palmitate Transcutaneous Permeation

The amphiphilic properties of poly(vinylalcohol) substituted with oleic acid was evaluated to assess the possibility to prepare polymeric micelles in an aqueous phase containing a hydrophobic core able to host lipophilic drugs such as retinyl palmitate and thereby enhance its transcutaneous absorption in the stratum corneum. The effect of the increased drug absorption suggests the possibility of interaction between the substituted polymer and the components present in the intercorneocyte spaces. Correlations between the drug concentration in the preparative mixture, micelle size, and drug permeation were evaluated to establish the best functional properties of the micellar systems enhancing retinyl palmitate absorption. Transcutaneous absorption increased with decreasing micelle size, and micelle size decreased on decreasing the drug concentration in the preparative mixture

Avaliacao do desempenho reprodutivo e estabelecimento da estacao de monta de equinos em regime de monta natural a campo no Pantanal.

O cavalo Pantaneiro caracteriza-se pela sua rusticidade e adaptacao as condicoes ecologicas do Pantanal, fruto de selecao natural por mais de dois seculos. Como animal de trabalho, constitui fator de importancia economica e social auxiliando nas producao pecuaria, alem de contribuir para a fixacao do homem na regiao. A partir de 1900, cruzamentos indiscriminados com outras racas, alem da disseminacao de enfermidades, como o "mal-de-cadeiras" (tripanosomose) e mais recentemente a anemia infecciosa equina (AIE), contribuiram para a diminuicao do seu efetivo. A AIE, enfermidade endemica para a regiao, apresenta incidencia media de 42,7% (SILVA, et al. 1995), sendo considerada, atualmente o principal fator limitante para a expansao da criacao de equino no Pantanal. O presente trabalho teve como objetivo avaliar o desempenho reprodutivo do plantel, submetido ao metodo de acasalamento direcionado a campo e estabelecer a epoca mais adequada para a estacao de monta de equinos no Pantanal Mato-Grossense.bitstream/item/79384/1/COT15.pd

A 3D Printing Scaffold Using Alginate/Hydroxyapatite for Application in Bone Regeneration

This work aimed to manufacture scaffolds from a hydrogel composed of a sodium alginate matrix with hydroxyapatite reinforcements using a 3D bioprinter, aiming at application in bone tissue regeneration. The alginate solution was prepared by dissolving sodium alginate at a concentration of 10% (w/v). Hydroxyapatite (HAp) was added to the solution at 2.5% and 5.0% (w/v) concentrations, followed by placing the samples in a container with a 1.0% (w/v) calcium chloride solution. The scaffolds were analyzed for HAp concentration and morphological characteristics, physicochemical properties, and biological response. The scaffolds show reproducibility and spectroscopic analyses confirm hydrogel formation and hydroxyapatite incorporation in the alginate matrix. The hydrophilic properties are compatible with scaffolds obtained through 3D printing made from polysaccharides, and the thermal analysis showed the expected behavior of these same materials. Preliminary findings indicated that scaffolds containing 2.5% (w/v) hydroxyapatite are inside cytotoxicity limit (66.4 ± 7.0%) towards canine E20 lineage cells. In contrast, scaffolds with 0% and 5.0% (w/v) hydroxyapatite were non-cytotoxic. Notably, the latter scaffold demonstrated enhanced cell proliferation, as anticipated, owing to the hydrophilic properties of alginate that enable easy and swift cell seeding, facilitating nutrient transport and cellular growth within the scaffold

Efecto del tamaño de picado del forraje sobre el consumo voluntario y la produccion en vacas lecheras y ovejas

The objectives of the present study were: 1) to measure the chop length produced by different forage harvesters on maize, and 2) to evaluate the effect of chopping on voluntary dry matter intake and performance. The experiment was carried out with lactating cows and dry ewes during 20 days, being the first 6 days for adaptation of the experimental animals to the dieto The whole plant of maize CV. colorado La Holandesa was used as animal feed, cut by four different ways, the four treatments: 1) PE: cutting of the whole plant by sickle; 2) PS: cutting and chopping by a hammermill machine; 3) PO: cutting and chopping by a hammermill, transporter and fan, and 4) PF: cutting and chopping by a two ways mili with knives. The feed was offered ad libitum to 16 Holstein- Freisian lactating cows and to 16 dry, non-pregnant Corriedale ewes into two experiment within a randomized blocks design each. The three chopping machines produced particles of different chop length: PS: tassel: 91.3 mm ± 7.63; leaf: 100.3 mm ± 10.47; stem: 114.8 mm ± 7.05; PO: tassel: 60.1 mm ± 9.86; leaf: 58.0 ± 4.74; stem: 90.8 ± 9.10; PF: tassel: 13.0 mm ± 1.21; leaf: 45.3 mm ± 3,62; stem: 23.8 mm ± 2.17. Within each plant part, all comparisons among chop length produced by the three machines were highly significant (P<0.01). The voluntary intake of the lactating cows was not different between treatments (P> 0.05). The lowest value was obtained in PS (80.3 g/kg LWO.75) and the highest in PF (91,2 g) (PE: 88.1 g; PO: 85.2 g). The voluntary intake of ewes was significantly lower in PE (21.6 g/kg LWO.75) than in PS (36.2 g) and in PO (36.0 g). AII other comparisons between treatments were not significant (P>0.05). The particle size did not significantly affect mil k production of the lactating cows (PE: 13.02 liters/cow.day; PS: 10.24 liters; PO: 10.24 liters; PF: 11.78 liters) and liweweight loss of ewes (PE: 217 g/day; PS: 51 g/day; PO: 35 g/day; PF: 133 g/day). The results show that, under these experimental conditions, chop length of forage does not affect voluntary intake and performance of lactating cows or dry ewes; the voluntary intake of maize by the dry ewes, however, was very low, especially when the whole plant was offered as feed.Los objetivos de este trabajo fueron: 1) medir el tamaño de partícula obtenido con distintas máquinas picadoras de forraje disponibles en el mercado, sobre maíz para pastoreo, y 2) evaluar el efecto del picado sobre el consumo voluntario y la performance productiva. El ensayo se realizó utilizando vacas lecheras y ovejas como animales experimentales durante 20 días, de los cuales los primeros 6 fueron de acostumbramiento a la dieta. Se utilizó como alimento plantas enteras de maíz colorado la Holandesa en estado de grano pastoso, cortado por cuatro medios distintos, correspondientes a cuatro tratamientos: 1) PE: corte manual de plantas enteras; 2) PS: máquina de corte por martillos; 3)PO: máquina con rotor de martillos, sinfin transportador y rotor-ventilador y 4) PF: máquina que posee rotor de cuchilla y contracuchilla. El alimento fue ofrecido ad libitum a 16 vacas lecheras Holando-Argentino en lactación y a 16 ovejas Corriedale vacias y secas en dos ensayos paralelos, ambos con un diseño de bloques al azar. Las distintas máquinas produjeron partículas de diferente tamaño: PS: espiga: 91,3 mm ± ,63; hoja: 100,3 mm ± 10,47; tallo: 114,8 mm ± 7,05; PO: espiga: 60,1 mm ± 9,86; hoja: 58,0 ± 4,74; tallo: 90,8 ± 9,10; PF: espiga: 13,0 mm ± 1,21; hoja: 45,3 mm ± 3,62; tallo: 23,8 mm ± 2,17. Se encontraron diferencias significativas al 1%, dentro de cada fracción analizada, al comparar las medias de tamaño de picado correspondientes a los distintos tratamientos. El consumo voluntario de las vacas lecheras, expresado en g M.S./ kg PV 0,75 no fue significativamente distinto entre tratamientos (P>0,05). El valor más bajo fue para PS (80,3 g/Kg PV 0,75) Y el más alto para PF (91,2 g) (PE: 88,1 g; P0: 85,2 g). El consumo voluntario de las ovejas fue significativamente más bajo en PE (21,6 g/kg PV 0,75) que en PS (36,2 g) y en P0 (36,0 g). Todas las restantes comparaciones entre medias fueron no significativas al nivel del 5 %. No se encontraron diferencias significativas en la producción de leche de las vacas (PE: 13,02 litros/vaca.día; PS: 10,24 litros; PO: 10,24 litros; PF: 11,78 litros) ni en la pérdida de peso vivo de las ovejas (PE: 217 g/día; PS: 51 g/día; PO: 35 g/día; PF: 133 g/día). Se concluye que, para las condiciones en que se .realizó el ensayo, el tamaño de partícula del forraje utilizado no tiene influencia sobre el consumo voluntario ni la performance productiva de vacas lecheras y ovejas; el consumo de maíz por parte de las ovejas, sin embargo, fue muy bajo, cuando la planta entera fue ofrecida como alimento

Análise da presença de comunidades de macroinvertebrados como bioindicadores de qualidade de água em córregos de cabeceira da bacia do rio Jaguari em Minas Gerais.

A bacia do rio Jaguari tem grande importância sócio-econômica para o estado de São Paulo, que recentemente passou por uma crise hídrica sem precedentes. Neste estudo, foram monitorados três riachos de baixa ordem em áreas de cabeceira nesta bacia, a fim de se relacionar a qualidade da água com o grau de conservação das áreas de preservação permanente (APPs). Para tanto, foram coletadas amostras de sedimento para identificação da comunidade de macroinvertebrados bentônicos e amostras de água para monitoramento de variáveis físico-químicas. Os resultados indicaram um gradiente de qualidade ambiental, sendo que o trecho de rio que apresentava maior conservação da APP em sua microbacia teve maiores concentrações de oxigênio dissolvido, menores temperatura e condutividade elétrica e maior presença de famílias de macroinvertebrados sensíveis à degradação ambiental, além de ausência de táxons considerados resistentes, como Hirudinea e Oligochaeta. Existem também indicações de que as práticas de recuperação estão colaborando para a melhoria da qualidade da água fluvial em uma das microbacias. The Jaguari River basin has great socioeconomic importance for the São Paulo state, that recently faced a water crisis without precedents. In this study, three low order streams were monitored at the headwater areas of this basin, in order to relate the water quality to the degree of conservation of the permanent preservation areas (APPs). For this purpose, sediment samples were collected to identify the community of benthic macroinvertebrates and water samples to monitor physico-chemical variables. The results indicated a gradient of environmental quality, and the river section that presented greater conservation of the APP at its catchment had higher concentrations of dissolved oxygen, lower water temperature and electrical conductivity and greater presence of macroinvertebrate families sensitive to environmental degradation, besides the absence of taxa considered resistant, such as Hirudinea and Oligochaeta. There is also some indications that recovery practices are collaborating to improve river water quality in one of the watersheds

Relação do uso e cobertura das terras e a qualidade da água na bacia hidrográfica do rio Camanducaia, MG e SP.

A bacia hidrográfica do rio Camanducaia, que integra as bacias PCJ, possui nascentes no sul do Estado de Minas Gerais e foz no município de Jaguariúna, SP, e recentemente foi alvo de estiagem que causou grande crise hídrica na região. Dada a crescente pressão antrópica sobre essas bacias foi realizado estudo sobre o efeito do uso da terra sobre a biogeoquímica do rio Camanducaia. Durante um ano foram monitorados oito pontos de amostragem ao longo do rio principal, distribuídos desde a área das nascentes até a foz, e de um ponto na foz do seu principal tributário, o rio do Mosquito. As variáveis estudadas foram Oxigênio Dissolvido, Saturação do Oxigênio Dissolvido, Demanda Bioquímica de Oxigênio, Temperatura da água, pH e Condutividade Elétrica. Para relacionar a qualidade da água com o uso da terra foi produzido mapa de uso e cobertura das terras com a utilização de imagens Landsat 8. Os resultados mostraram que a qualidade da água do rio na maior parte das estações ainda se mantém em equilíbrio entre os processos de produção de oxigênio e degradação aeróbica da matéria orgânica, mas em três das estações já acontecem flutuações no O2, DBO e condutividade elétrica sugerindo aporte pontual de substâncias de áreas urbanas e também em menor proporção uma poluição difusa advinda da agricultura. --- The Camanducaia River Basin, which is part of the PCJ basins, has its headwaters in the south of the State of Minas Gerais and its outlet located in the municipality of Jaguariúna, State of São Paulo, and recently suffered a drought that caused the major water crisis in the region. Given the increasing anthropogenic pressure on these basins, a study was carried out to evaluate the effects of land use on the biogeochemistry of the Camanducaia River. During one year eight in-place sampling stations were selected along the main river, from its headwater areas to its mouth, and another station at the outlet of its main tributary, the Mosquito river. The studied variables were Dissolved Oxygen Concentration, Dissolved Oxygen Saturation, Biochemical Oxygen Demand, Water Temperature, pH and Electrical Conductivity. In order to relate water quality with land use, a land use and land cover map was produced using Landsat 8 images. The results showed that the water quality of the river in most of the stations is still in balance between the processes of oxygen production and aerobic degradation of organic matter, but in three of the stations there are already fluctuations in O2, BOD and electrical conductivity suggesting punctual contribution of substances from urban areas and also to lesser extention a diffuse pollution from agriculture

Efeitos do uso da terra sobre a hidrobiogeoquímica de microbacias de cabeceira na bacia do rio Jaguari - Minas Gerais.

Resumo: A caracterização da hidrobiogeoquímica de três cursos d?água foi realizada em microbacias de cabeceira de baixa ordem, relacionando-se com as mudanças de uso da terra, para apoiar a gestão e uso sustentável dos recursos hídricos da bacia do rio Jaguari, no sul do estado de Minas Gerais. A avaliação realizada constatou impactos nas águas fluviais decorrentes da mudança da cobertura florestal original. As pastagens ocasionaram aumento nas concentrações de íons maiores, carbono dissolvido e sedimentos, enquanto a agricultura, e em menor escala a silvicultura, promoveram aumento de nutrientes como o nitrogênio. A recuperação florestal iniciada ainda não reflete, de forma clara, melhoria nas águas fluviais, uma vez que os pastos predominam na paisagem. A floresta original, no entanto, exerceu papel importante na dinâmica de carbono. Por fim, constatou-se que a floresta ripária se apresenta como fator decisivo para a qualidade ambiental das microbacias estudadas e, em extensão, para seus setores mais a jusante. -- Abstract: The hydrobiogeochemical characterization of three small streams was carried out in low-order headwater catchments, relating it to land use change, to support the sustainable management and use of water resources in the Jaguari river basin, in the south of the state of Minas Gerais. In this evaluation there were impacts in the river water resulted from the change of the original forest cover. Pastures caused an increase in the concentration of mayor ions, dissolved carbon and sediments, while agriculture, and to forestry at a lesser extent, promoted an increase in nutrients such as nitrogen. The initiation of the recovery of the native forest, still does not clearly reflect any improvement in river waters, since pastures predominate in the landscape. On the other hand, forest played an important role in carbon dynamics. Finally, it was found that the riparian forest presents itself as a decisive factor for the environmental quality of the studied catchments and, by extension, to the downstream sectors of these ones.bitstream/item/217878/1/Figueiredo-Efeitos-uso-terra-2020.pd

Metodologia para a sistematização dos dados sobre recursos hídricos em bacias experimentais de diferentes biomas brasileiros.

bitstream/item/173455/1/DOC-216.pd