998 resultados para Sarpi, Paolo , 1552-1623


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Pasolini es poesía. La vida de Pasolini es poesía. Su obra, y especialmente su cine, es poesía. Todo, poesía. Palabra poética. Y teatro de la palabra. De un poeta que sueña un sueño dentro de otro sueño. Y de un poeta que sueña muchos sueños. Por eso sabe qué es verdad. Verdad-mito, porque es realidad. Y realidad-mito, porque es realidad verdadera. Sueño soñado despierto. Y cómo voy a hablar de un poeta que sueña ‘la razón de su sueño’, sin que utilice (prestada) la poesía de sus palabras? Espero poderlo conseguir.

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George Keith, fourth Earl Marischal is a case study of long-term, quietly successful and stable lordship through the reign of James VI. Marischal’s life provides a wholly underrepresented perspective on this era, where the study of rebellious and notorious characters has dominated. He is also a counter-example to the notion of a general crisis among the European nobility, at least in the Scottish context, as well as to the notion of a ‘conservative’ or ‘Catholic’ north east. In 1580 George inherited the richest earldom in Scotland, with a geographical extent stretching along the east coast from Caithness to East Lothian. His family came to be this wealthy as a long term consequence of the Battle of Flodden (1513) where a branch of the family, the Inverugie Keiths had been killed. The heiress of this branch was married to the third earl and this had concentrated a large number of lands, and consequently wealth, in the hands of the earls. This had, however, also significantly decreased the number of members and hence power of the Keith kindred. The third earl’s conversion to Protestantism in 1544 and later his adherence to the King’s Party during the Marian Civil War forced the Keiths into direct confrontation with their neighbours in the north east, the Gordons (led by the Earls of Huntly), a Catholic family and supporters of the Queen’s Party. Although this feud was settled for a time at the end of the war, the political turmoil caused by a succession of short-lived factional regimes in the early part of the personal reign of James VI (c.1578-1585) led the new (fourth) Earl Marischal into direct confrontation with the new (sixth) Earl of Huntly. Marischal was outclassed, outmanoeuvred and outgunned at both court and in the locality in this feud, suffering considerably. However, Huntly’s over-ambition in wider court politics meant that Marischal was able to join various coalitions against his rival, until Huntly was exiled in 1595. Marischal also came into conflict briefly with Chancellor John Maitland of Thirlestane as a consequence of Marischal’s diplomatic mission to Denmark in 1589-1590, but was again outmatched politically and briefly imprisoned. Both of these feuds reveal Marischal to be relatively cautious and reactionary, and both reveal the limitations of his power. Elsewhere, the study of Marischal’s activities in the centre of Scottish politics reveal him to be unambitious. He was ready to serve King James, the two men having a healthy working relationship, but Marischal showed no ambition as a courtier, to woo the king’s favour or patronage, instead delegating interaction with the monarch to his kinsmen. Likewise, in government, Marischal rarely attended any of the committees he was entitled to attend, such as the Privy Council, although he did keep a keen eye on the land market and the business conducted under the Great Seal. Although personally devout and a committed Protestant, the study of Marischal’s interaction with the national Kirk and the parishes of which he was patron reveal that he was at times a negligent patron and exercised his right of ministerial presentation as lordly, not godly patronage. The notion of a ‘conservative North East’ is, however, rejected. Where Marischal was politically weak at court and weak in terms of force in the locality, we see him pursuing sideways approaches to dealing with this. Thus he was keen to build up his general influence in the north and in particular with the burgh of Aberdeen (one result of this being the creation of Marischal College in 1593), pursued disputes through increasing use of legal methods rather than bloodfeud (thus exploiting his wealth and compensating for his relative lack of force) and developed a sophisticated system of maritime infrastructure, ultimately expressed through the creating of the burghs of Peterhead and Stonehaven. Although his close family caused him a number of problems over his lifetime, he was able to pass on a stable and enlarged lordship to his son in 1623.

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A atenção à saúde das crianças tem como objetivo garantir um adequado desenvolvimento nesse período da vida a partir de um estudo adequado nas diferentes faixas etárias para conseguir um desenvolvimento e crescimento ótimo, abordando aspectos ambientais, biopsicossociais, promoção a saúde e prevenção de agravos como estratégia fundamental. O acompanhamento das crianças na atenção primária é de fundamental relevância, pois pode atuar de forma preventiva na diminuição das taxas de mortalidade infantil com a garantia de um acompanhamento de qualidade. Objetivando qualificar a atenção das crianças pertencentes à Unidade de Saúde Agenor Paolo da Silva do município de Alto Alegre/RR foi realizada uma intervenção em saúde entre os meses de fevereiro e junho de 2015 direcionada à população anteriormente citada. Inicialmente, foi organizado um projeto com os seguintes objetivos: ampliar a cobertura, melhorar a adesão e qualidade dos atendimentos às crianças, melhorar o registro das informações, mapear as crianças de risco e promover saúde. A relevância da intervenção encontra-se na garantia da saúde por meio de um acompanhamento efetivo e humanizado incluindo ações de prevenção e promoção à saúde, além de diagnóstico e tratamento precoce das patologias que podem ocorrer nesse período. Para alcançar os objetivos foram realizadas ações nos quatro eixos pedagógicos do curso, a saber: monitoramento e avaliação, organização e gestão do serviço, engajamento público e qualificação da prática clínica. Utilizamos a Planilha de coleta de dados e ficha espelho disponibilizada pela Universidade Federal de Pelotas. Antes da intervenção, das 162 crianças estimadas para a área, a equipe acompanhava 6% (11) das crianças menores de 1 ano. Diante disso, a equipe propôs a intervenção para realizar uma ampliação e qualificação da atenção a saúde das crianças. Desta forma, após a intervenção alcançamos como principais resultados o acompanhamento na puericultura de 79 crianças até 72 meses (48%) estimadas para a área. A maioria dos indicadores de qualidade foi alcançada em sua totalidade, tais como, monitoramento de crianças com excesso de peso, monitoramento do desenvolvimento, realização do teste do pezinho e triagem auditiva. Os resultados que não tiveram êxito foram vacinação em dia para 73 crianças (92,4%), suplementação de ferro para 20 crianças (87%) e primeira consulta odontológica para 55 crianças (77,5%). As ações desenvolvidas na unidade durante a intervenção podem ser consideradas como ações simples, mas de grande relevância para a qualificação da assistência as crianças, pois contribuíram para a melhoria dos atendimentos dispensados.

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Leg ulcers represent a particularly disabling complication in patients with sickle cell disease (SCD). Platelet gel (PG) is a novel therapeutic strategy used for accelerating wound healing of a wide range of tissues through the continuous release of platelet growth factors. Here, we describe the use of PG preparation according to Anitua's PRGF (preparations rich in growth factors) protocol for treating chronic nonhealing ulcers in patients with SCD. A positive response occurred in 3 patients with an area reduction of 85.7% to 100%, which occurred within 7 to 10 weeks, and a 35.2% and 20.5% of area reduction in 2 other patients, who however, had large ulcers. After calcium chloride addition, the platelet-rich plasmas demonstrated enhanced platelet-derived growth factors-BB (P < .001), transforming growth factor-β1 (P = .015), vascular endothelial growth factors (P = .03), and hepatocyte growth factors (nonsignificant) secretion. Furthermore, calcium chloride addition induced a significant decrease in platelet number (P = .0134) and there was no leukocyte detection in the PG product. These results demonstrate that PG treatment might impact the healing of leg ulcers in sickle cell disease, especially in patients with small ulcers.

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Viscosupplements, used for treating joint and cartilage diseases, restore the rheological properties of synovial fluid, regulate joint homeostasis and act as scaffolds for cell growth and tissue regeneration. Most viscosupplements are hydrogels composed of hyaluronic acid (HA) microparticles suspended in fluid HA. These microparticles are crosslinked with chemicals to assure their stability against enzyme degradation and to prolong the action of the viscosupplement. However, the crosslinking also modifies the mechanical, swelling and rheological properties of the HA microparticle hydrogels, with consequences on the effectiveness of the application. The aim of this study is to correlate the crosslinking degree (CD) with these properties to achieve modulation of HA/DVS microparticles through CD control. Because divinyl sulfone (DVS) is the usual crosslinker of HA in viscosupplements, we examined the effects of CD by preparing HA microparticles at 1:1, 2:1, 3:1, and 5:1 HA/DVS mass ratios. The CD was calculated from inductively coupled plasma spectrometry data. HA microparticles were previously sized to a mean diameter of 87.5 µm. Higher CD increased the viscoelasticity and the extrusion force and reduced the swelling of the HA microparticle hydrogels, which also showed Newtonian pseudoplastic behavior and were classified as covalent weak. The hydrogels were not cytotoxic to fibroblasts according to an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014.

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The metabolic enzyme fatty acid synthase (FASN) is responsible for the endogenous synthesis of palmitate, a saturated long-chain fatty acid. In contrast to most normal tissues, a variety of human cancers overexpress FASN. One such cancer is cutaneous melanoma, in which the level of FASN expression is associated with tumor invasion and poor prognosis. We previously reported that two FASN inhibitors, cerulenin and orlistat, induce apoptosis in B16-F10 mouse melanoma cells via the intrinsic apoptosis pathway. Here, we investigated the effects of these inhibitors on non-tumorigenic melan-a cells. Cerulenin and orlistat treatments were found to induce apoptosis and decrease cell proliferation, in addition to inducing the release of mitochondrial cytochrome c and activating caspases-9 and -3. Transfection with FASN siRNA did not result in apoptosis. Mass spectrometry analysis demonstrated that treatment with the FASN inhibitors did not alter either the mitochondrial free fatty acid content or composition. This result suggests that cerulenin- and orlistat-induced apoptosis events are independent of FASN inhibition. Analysis of the energy-linked functions of melan-a mitochondria demonstrated the inhibition of respiration, followed by a significant decrease in mitochondrial membrane potential (ΔΨm) and the stimulation of superoxide anion generation. The inhibition of NADH-linked substrate oxidation was approximately 40% and 61% for cerulenin and orlistat treatments, respectively, and the inhibition of succinate oxidation was approximately 46% and 52%, respectively. In contrast, no significant inhibition occurred when respiration was supported by the complex IV substrate N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD). The protection conferred by the free radical scavenger N-acetyl-cysteine indicates that the FASN inhibitors induced apoptosis through an oxidative stress-associated mechanism. In combination, the present results demonstrate that cerulenin and orlistat induce apoptosis in non-tumorigenic cells via mitochondrial dysfunction, independent of FASN inhibition.

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Retinal pigment epithelium cells, along with tight junction (TJ) proteins, constitute the outer blood retinal barrier (BRB). Contradictory findings suggest a role for the outer BRB in the pathogenesis of diabetic retinopathy (DR). The aim of this study was to investigate whether the mechanisms involved in these alterations are sensitive to nitrosative stress, and if cocoa or epicatechin (EC) protects from this damage under diabetic (DM) milieu conditions. Cells of a human RPE line (ARPE-19) were exposed to high-glucose (HG) conditions for 24 hours in the presence or absence of cocoa powder containing 0.5% or 60.5% polyphenol (low-polyphenol cocoa [LPC] and high-polyphenol cocoa [HPC], respectively). Exposure to HG decreased claudin-1 and occludin TJ expressions and increased extracellular matrix accumulation (ECM), whereas levels of TNF-α and inducible nitric oxide synthase (iNOS) were upregulated, accompanied by increased nitric oxide levels. This nitrosative stress resulted in S-nitrosylation of caveolin-1 (CAV-1), which in turn increased CAV-1 traffic and its interactions with claudin-1 and occludin. This cascade was inhibited by treatment with HPC or EC through δ-opioid receptor (DOR) binding and stimulation, thereby decreasing TNF-α-induced iNOS upregulation and CAV-1 endocytosis. The TJ functions were restored, leading to prevention of paracellular permeability, restoration of resistance of the ARPE-19 monolayer, and decreased ECM accumulation. The detrimental effects on TJs in ARPE-19 cells exposed to DM milieu occur through a CAV-1 S-nitrosylation-dependent endocytosis mechanism. High-polyphenol cocoa or EC exerts protective effects through DOR stimulation.

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Silk fibroin has been widely explored for many biomedical applications, due to its biocompatibility and biodegradability. Sterilization is a fundamental step in biomaterials processing and it must not jeopardize the functionality of medical devices. The aim of this study was to analyze the influence of different sterilization methods in the physical, chemical, and biological characteristics of dense and porous silk fibroin membranes. Silk fibroin membranes were treated by several procedures: immersion in 70% ethanol solution, ultraviolet radiation, autoclave, ethylene oxide, and gamma radiation, and were analyzed by scanning electron microscopy, Fourier-transformed infrared spectroscopy (FTIR), X-ray diffraction, tensile strength and in vitro cytotoxicity to Chinese hamster ovary cells. The results indicated that the sterilization methods did not cause perceivable morphological changes in the membranes and the membranes were not toxic to cells. The sterilization methods that used organic solvent or an increased humidity and/or temperature (70% ethanol, autoclave, and ethylene oxide) increased the silk II content in the membranes: the dense membranes became more brittle, while the porous membranes showed increased strength at break. Membranes that underwent sterilization by UV and gamma radiation presented properties similar to the nonsterilized membranes, mainly for tensile strength and FTIR results.

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Skin-wound healing is a complex and dynamic biological process involving inflammation, proliferation, and remodeling. Recent studies have shown that statins are new therapeutical options because of their actions, such as anti-inflammatory and antioxidant activity, on vasodilation, endothelial dysfunction and neoangiogenesis, which are independent of their lipid-lowering action. Our aim was to investigate the effect of atorvastatin on tissue repair after acute injury in healthy animals. Rats were divided into four groups: placebo-treated (P), topical atorvastatin-treated (AT), oral atorvastatin-treated (AO), topical and oral atorvastatin-treated (ATO). Under anesthesia, rats were wounded with an 8-mm punch in the dorsal region. Lesions were photographed on Days 0, 1, 3, 7, 10, 12, and 14 post-injury and samples taken on Days 1, 3, 7, and 14 for protein-expression analysis of insulin receptor substrate (IRS)-1, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase (GSK)-3, endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), extracellular signal-regulated kinase (ERK), interleukin (IL)-10, IL-1β, IL-6, and tumor necrosis factor (TNF)-α. Upon macroscopic examination, we observed significant reductions of lesion areas in groups AT, AO, and ATO compared to the P group. Additionally, AT and AO groups showed increased expression of IRS-1, PI3K, Akt, GSK-3, and IL-10 on Days 1 and 3 when compared with the P group. All atorvastatin-treated groups showed higher expression of IRS-1, PI3K, Akt, GSK-3, IL-10, eNOS, VEGF, and ERK on Day 7. On Days 1, 3, and 7, all atorvastatin-treated groups showed lower expression of IL-6 and TNF-α when compared with the P group. We conclude that atorvastatin accelerated tissue repair of acute lesions in rats and modulated expressions of proteins and cytokines associated with cell-growth pathways.

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To examine the influence of l-arginine supplementation in combination with physical training on mitochondrial biomarkers from gastrocnemius muscle and its relationship with physical performance. Male Wistar rats were divided into four groups: control sedentary (SD), sedentary supplemented with l-arginine (SDLA), trained (TR) and trained supplemented with l-arginine (TRLA). Supplementation of l-arginine was administered by gavage (62.5mg/ml/day/rat). Physical training consisted of 60min/day, 5days/week, 0% grade, speed of 1.2km/h. The study lasted 8weeks. Skeletal muscle mitochondrial enriched fraction as well as cytoplasmic fractions were obtained for Western blotting and biochemical analyses. Protein expressions of transcriptor coactivator (PGC-1α), transcriptor factors (mtTFA), ATP synthase subunit c, cytochrome oxidase (COXIV), constitutive nitric oxide synthases (eNOS and nNOS), Cu/Zn-superoxide dismutase (SOD) and manganese-SOD (Mn-SOD) were evaluated. We also assessed in plasma: lipid profile, glycemia and malondialdehyde (MDA) levels. The nitrite/nitrate (NOx(-)) levels were measured in both plasma and cytosol fraction of the gastrocnemius muscle. 8-week l-arginine supplementation associated with physical training was effective in promoting greater tolerance to exercise that was accompanied by up-regulation of the protein expressions of mtTFA, PGC-1α, ATP synthase subunit c, COXIV, Cu/Zn-SOD and Mn-SOD. The upstream pathway was associated with improvement of NO bioavailability, but not in NO production since no changes in nNOS or eNOS protein expressions were observed. This combination would be an alternative approach for preventing cardiometabolic diseases given that in overt diseases a profound impairment in the physical performance of the patients is observed.

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Mitochondria are involved in energy supply, signaling, cell death and cellular differentiation and have been implicated in several human diseases. Neks (NIMA-related kinases) represent a family of mammal protein kinases that play essential roles in cell-cycle progression, but other functions have recently been related. A yeast two-hybrid (Y2H) screen was performed to identify and characterize Nek5 interaction partners and the mitochondrial proteins Cox11, MTX-2 and BCLAF1 were retrieved. Apoptosis assay showed protective effects of stable hNek5 expression from Hek293-T's cell death after thapsigargin treatment (2μM). Nek5 silenced cells as well as cells expressing a kinase dead version of Nek5, displayed an increase in ROS formation after 4h of thapsigargin treatment. Mitochondrial respiratory chain activity was found decreased upon stable hNek5expression. Cells silenced for hNek5 on the other hand presented 1.7 fold increased basal rates of respiration, especially at the electrons transfer steps from TMPD to cytochrome c and at the complex II. In conclusion, our data suggest for the first time mitochondrial localization and functions for Nek5 and its participation in cell death and cell respiration regulation. Stable expression of hNek5 in Hek293T cells resulted in enhanced cell viability, decreased cell death and drug resistance, while depletion of hNek5by shRNA overcame cancer cell drug resistance and induced apoptosis in vitro. Stable expression of hNek5 also inhibits thapsigargin promoted apoptosis and the respiratory chain complex IV in HEK293T cells.

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The 22q11 chromosomal region contains low copy repeats (LCRs) sequences that mediate non-allelic homologous recombination, which predisposes to copy number variations (CNVs) at this locus. Hemizygous deletions of the proximal 22q11.2 region result in the 22q11.2 deletion syndrome (22q11.2 DS). In addition, 22q11.2 duplications involving the distal LCR22s have been reported. This article describes a patient presenting a 2.5-Mb de novo deletion at proximal 22q11.21 region (between LCRs A-D), combined with a 1.3-Mb maternally inherited duplication at distal 22q11.23 region (between LCRs F-H). The presence of concomitant chromosomal imbalances found in this patient has not been reported previously. Clinical and molecular data were compared with literature, in order to contribute to genotype-phenotype correlation. These findings exemplify the complexity and genetic heterogeneity observed in 22q11.2 deletion syndrome and highlights the difficulty to make genetic counseling and predict phenotypic consequences in these situations.