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

Sodium Ascorbate induces apoptosis in neuroblastoma cell lines by interfering with iron uptake

<p>Abstract</p> <p>Background</p> <p>Neuroblastoma (NB) is an extra-cranial solid tumour of childhood. In spite of the good clinical response to first-line therapy, complete eradication of NB cells is rarely achieved. Thus, new therapeutic strategies are needed to eradicate surviving NB cells and prevent relapse. Sodium ascorbate has been recently reported to induce apoptosis of B16 melanoma cells through down-regulation of the transferrin receptor, CD71. Since NB and melanoma share the same embryologic neuroectodermal origin, we used different human NB cell lines to assess whether the same findings occurred.</p> <p>Results</p> <p>We could observe dose- and time-dependent induction of apoptosis in all NB cell lines. Sodium ascorbate decreased the expression of CD71 and caused cell death within 24 h. An increase in the global and specific caspase activity took place, as well as an early loss of the mitochondrial transmembrane potential. Moreover, intracellular iron was significantly decreased after exposure to sodium ascorbate. Apoptotic markers were reverted when the cells were pretreated with the iron donor ferric ammonium citrate (FAC), further confirming that iron depletion is responsible for the ascorbate-induced cell death in NB cells.</p> <p>Conclusion</p> <p>Sodium ascorbate is highly toxic to neuroblastoma cell lines and the specific mechanism of vitamin C-induced apoptosis is due to a perturbation of intracellular iron levels ensuing TfR-downregulation.</p

energy consumption of a last generation full hybrid vehicle compared with a conventional vehicle in real drive conditions

Abstract Hybrid vehicles are one of the most important choices to improve efficiency and reduce CO2 production of vehicles. Benefits in using hybrid powertrains are generally found in urban environment where lower average speeds, higher accelerations make the internal combustion engine run at lower efficiency points. The originality of the present paper consists in the data elaboration and analysis collected in a measurement campaign on road in real driving conditions, on an ad hoc path planned according to the average national daily mileage in metropolitan urban context, which thus acquires a significance generalizable in that specific context, which led to the consumption quantification and an analysis of the main factors that determine the reduction in consumption of full-hybrid vs conventional vehicles. Another important and original aspect of this paper is the analysis of the operating times in ZEV mode of hybrid vehicles, which shows how this solution leads to a significant reduction of pollutant emissions in urban contest. An on-road experimental campaign has been done by comparing two different versions of the same model (Toyota Yaris Hybrid and a conventional one, Toyota Yaris 1.5 gasoline) and a hybrid vehicle with different characteristics (the hybrid born - Toyota Prius), like size, traction battery capacity, generator/motor electric power. Thirty drivers on a fixed path have done this experimental campaign and in this paper, the results are reported. The results show that a strong influence on consumption is due not only to the type of vehicle, but also to driving style and speed. The comparison between the two versions of Yaris, shows a strong reduction in consumption using hybrid vehicle for low and medium speeds (for 20 km/h about 50%), such benefit decreases with the increasing speed and for values higher than 90 km/h both the vehicles have the same consumption. The reduced consumption of the hybrid vehicle at low speeds is due, on the one hand, to the greater efficiency of the hybrid vehicle engine compared to the conventional one and on the other hand to the high functioning in ZEV mode, with the engine off, (63% of time) thanks to the use of the electric motor. The comparison between the two hybrid vehicles with different characteristics (YarisHy and Prius) shows that the consumption trend vs. speeds is similar but the Prius has lower consumption due above all to the high efficiency of the braking energy recovery system, despite the greatest mass. This lead then to significant consumption reduction, but also lower emissions in places where such parameters have an important role: the urban environment

Forming and preserving aragonite in shear zones: First report of blueschist facies metamorphism in the Jabal Akhdar Dome, Oman Mountains

We report the first occurrence of high-pressure metamorphic aragonite in Precambrian carbonates of the Jabal Akhdar Dome in the Oman Mountains (northern Oman). We propose a model for both its formation at blueschist facies conditions and its subsequent preservation to the surface within the tectonic framework of the Late Cretaceous obduction of the Semail Ophiolite. Aragonite formed at temperature ∼350 °C and pressure ≥0.9 GPa and is preserved within mylonitic shear zones and in stretched-fiber dilational veins where the necessary conditions for its formation and preservation, such as plastic strain accommodation, fluid-enhanced mineralogical reactions, and an anisotropic permeability structure, were preferentially met with respect to the surrounding rock. High-strain structural domains are ideal sites to look for and study prograde and retrograde high-pressure metamorphic histories in deeply subducted and exhumed terrains

Stream water quality in the context of payments for environmental services in Southeastern Brazil.

Public policy of payment for environmental services (PES) was established in 2007 to face the challenge of recuperatingwater resources at one of the headwater areas of the Jaguari River Basin, which supplies an important reservoir for the metropolitan region of São Paulo, Brazil. Such effort consists of reforestation of riparian zones and spring lands at the hills of selected catchments, including the Ribeirão das Posses (RP) catchment. Since 2012 the University of São Paulo has developed research at RP to monitor the benefits of these practices on stream water quality, and identified a few parameters as good indicators to follow up the results of this PES program. The present study has the objective to show results of the monthly monitoring in 2015,including 13 sampling stations at RP catchment distributed as follows: one in a spring forested area, three in spring areas of different ages of reforestation (3, 5 and 8 years), and nine at reaches of RP streamlocated in a way to contemplate the effects of the first order streams that comes from the studied spring areas entering RP. We established two additional stations at the Jaguari River, upstream and downstream of RP outlet. In situ measurements include temperature, pH, electric conductivity (EC) and dissolved oxygen (DO), and collect water samples to bring to the laboratory for analyses of dissolved organic and inorganic carbon (DOC and DIC), total nitrogen (TN) and alkalinity. Also, sediments (fine fraction: >0.45 ?m; and coarse fraction: >63 ?m) are collected for isotopic carbon analyses. Preliminary results show pH values ranging from 5.5 to 7.8, while DO ranges from 5.8 to 8.9 mg L . As for EC, the mean at the spring forested station was 34.6 ?S cm , while at spring areas of 3, 6 and 8 years of reforestation they were 53.3, 73.8 and 34.8 ?S cm , respectively. We expected that by the end of this annual monitoring the benefits of reforestation will be affirmed

Influence of land use on the hydrobiogeochemistry of the Camanducaia and Jaguari watersheds, Brazil.

Two medium-sized watersheds of the Piracicaba river basin, the Camanducaia and Jaguari subbasins,are being studied to evaluate the effects of land use change on the basin?s hydrobiogeochemistry. The Jaguari basin is an important provider the Cantareira reservoir system that supplies around six million inhabitants of the Metropolitan Region of São Paulo, Brazil. A one-year hydrological study began on January 2015 to monitor some water quality parameters such as pH, electric conductivity (EC), dissolved oxygen (DO), dissolved organic and inorganic carbon (DOC and DIC), nitrate (NO ), ammonium (NH ) and total nitrogen (TN). For that purpose we established 19 sampling stations along the Camanducaia (8 stations) and Jaguari (11 stations) river channels; two stations at their main tributaries Mosquito and Camanducaia Mineiro, respectively; and another two stations at small streams in headwater areas of the Jaguari and Camanducaia watersheds. Preliminary results show that DOC concentrations are correlated DIC (r=0.81 at Jaguari; r=0.70 at Camanducaia; p <0.05). We observe that DOC tends to increase by multiples of 2.5 and 3.5 times from forested headwater areas to the most downstream stations of Jaguari and Camanducaia, respectively. Regarding DIC these multiples are 4.4 and 1.9 times greater. The four most downstream stations at Jaguari show urban area effects with higher DIC monthly values ranging from 28.7 to 33 mg L . Also DIC correlated with EC values (means around 160 ?S) at two of these stations. We expect that at the end of this monitoring year results will show stronger relations between hydrobiogeochemical parameters and land use change

Land use effects on quality and quantity aspects of water resources in headwater areas of the Jaguari River Basin.

In the context of the recent drought conditions in southeastern Brazil, EMBRAPA (Brazilian Agricultural Research Corporation) in partnership with two Brazilian universities (USP/CENA and UNIFAL) planned a research project, called BaCaJa, to understand the hydrobiogeochemistry processes that occur in small catchments (<1,000 ha) at the upper portions of the Jaguari River Basin situated on both states of Sao Paulo and Minas Gerais. The approach of this study is based on the fact that the evaluation of stream water quality and quantity is an efficient tool to characterize the sustainability of the agriculture production at a catchment level. Its goal is, therefore, to survey the land use effects on the hydrobiogeochemistry in headwaters areas of the Jaguari River Basin to support sustainable management of water resources in this region. Sampling stations were established on rivers and streams ranging from one to five order channels as well as selected small catchments to conduct studies on overland flow, soil solution, soil quality, aquatic biota and pesticide dynamic. The research team is huge and their goals are specific, diverse and complementary, being summed up as: characterize land use, topography and soils; evaluate erosive potential in agriculture areas; measure soil carbon and nitrogen contents; characterize hydrogeochemistry fluxes; apply hydrological modeling and simulate different land use and management scenarios; monitor possible pesticides contamination; and survey macro invertebrates as indicators of water quality. Based on a synthesis of the results, the project team intends to point out the environmental impacts and contribute recommendations of management for the focused region to conserve water resources in terms of quality and quantity

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&lt;0.01). The voluntary intake of the lactating cows was not different between treatments (P&gt; 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&gt;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&gt;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

Evapotranspiração da bacia do Camanducaia-Jaguari obtida através do modelo agrometeorológico-espectral SAFER.

No contexto do Macroprograma 1 da Rede AgroHidro, as informações quantitativas da evapotranspiração são de grande importância para a avaliação relações entre a agricultura e as mudanças de uso da terra. Este estudo tem o objetivo de estimar a evapotranspiração na área da Bacia do Camanducaia e Jaguari aplicando o modelo agrometeorológico-espectral SAFER (Simple Algorithm For Evapotranspiration Retrieving) e utilizando imagens de satélite e dados de estações meteorológicas. Foram utilizadas imagens do satélite MODIS (Moderate Resolution Imaging Spectroradiometer), produto MOD13Q1, referente à reflectância das bandas 1 (?1) e 2 (?1), com resolução espacial de 250 m e temporal de 16 dias, referentes ao período chuvoso (representado pela imagem de janeiro de 2011) e seco (imagem de julho de 2011). Os dados meteorológicos (temperatura do ar, e radiação solar global) disponibilizados pelo INMET foram agrupados em 16 dias para coincidir com a resolução temporal das imagens. Foram realizados trabalhos de campo para coleta de pontos amostrais ao longo da bacia hidrográfica. Analisando a distribuição espacial da evapotranspiração estimada (ET) via modelo agrometeorológico-espectral SAFER na Bacia do Camanducaia-Jaguari, observa-se que conforme as classes de uso e cobertura da terra, foram obtidos diferentes valores de evapotranspiração. No período chuvoso (dia juliano (DJ) 001), a ET média diária para a área da Bacia do Camanducaia-Jaguari foi de 1,52 ± 0,58 mm d-1. No período seco (DJ 209), a ET média diária apresentou valores de 1,39 ± 0,57 mm d-1. O modelo SAFER se mostrou eficaz para a estimativa da ET em larga escala, tanto para o período chuvoso quanto para o seco, sendo sensível às variações observadas entre as classes de uso e cobertura das terras. Os resultados podem auxiliar no monitoramento das condições hídricas a partir de imagens de satélite, auxiliando nos estudos de qualidade de água da Bacia do Camanducaia-Jaguari. Para estudos futuros, sugere-se utilizar imagens com maior resolução espacial e maior quantidade de dados de estações meteorológicas, possibilitando a operacionalidade do modelo para fins de monitoramento hidrometeorológico da Bacia do Camanducaia

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