Diet rich in high glucoraphanin broccoli reduces plasma LDL cholesterol: evidence from randomised controlled trials

Cruciferous-rich diets have been associated with reduction in plasma LDL-cholesterol (LDL-C), which may be due to the action of isothiocyanates derived from glucosinolates that accumulate in these vegetables. This study tests the hypothesis that a diet rich in high glucoraphanin (HG) broccoli will reduce plasma LDL-C. METHODS AND RESULTS: One hundred and thirty volunteers were recruited to two independent double-blind, randomly allocated parallel dietary intervention studies, and were assigned to consume either 400 g standard broccoli or 400 g HG broccoli per week for 12 weeks. Plasma lipids were quantified before and after the intervention. In study 1 (37 volunteers), the HG broccoli diet reduced plasma LDL-C by 7.1% (95% CI: -1.8%, -12.3%, p = 0.011), whereas standard broccoli reduced LDL-C by 1.8% (95% CI +3.9%, -7.5%, ns). In study 2 (93 volunteers), the HG broccoli diet resulted in a reduction of 5.1% (95% CI: -2.1%, -8.1%, p = 0.001), whereas standard broccoli reduced LDL-C by 2.5% (95% CI: +0.8%, -5.7%, ns). When data from the two studies were combined the reduction in LDL-C by the HG broccoli was significantly greater than standard broccoli (p = 0.031). CONCLUSION: Evidence from two independent human studies indicates that consumption of high glucoraphanin broccoli significantly reduces plasma LDL-C

Pharmacological actions of nobiletin in the modulation of platelet function

Background and Purpose The discovery that flavonoids are capable of inhibiting platelet function has led to their investigation as potential antithrombotic agents. However, despite the range of studies on the antiplatelet properties of flavonoids, little is known about the mechanisms by which flavonoids inhibit platelet function. In this study, we aimed to explore the pharmacological effects of a polymethoxy flavonoid, nobiletin in the modulation of platelet function. Experimental Approach The ability of nobiletin to modulate platelet function was explored by using a range of in vitro and in vivo experimental approaches. Aggregation, dense granule secretion and spreading assays were performed using washed platelets. The fibrinogen binding, α-granule secretion and calcium mobilisation assays were performed using platelet-rich plasma and whole blood was used in impedance aggregometry and thrombus formation experiments. The effect of nobiletin in vivo was assessed by measuring tail bleeding time using C57BL/6 mice. Key Results Nobiletin was shown to supress a range of well-established activatory mechanisms, including platelet aggregation, granule secretion, integrin modulation, calcium mobilisation and thrombus formation. Nobiletin was shown to extend bleeding time in mice and reduce the phosphorylation of Akt and PLCγ2 within the collagen receptor (GPVI) - stimulated pathway, in addition to increasing the levels of cGMP and phosphorylation of VASP, a protein whose activity is associated with inhibitory cyclic nucleotide signalling. Conclusions and Implications This study provides insight into the underlying molecular mechanisms through which nobiletin modulates haemostasis and thrombus formation. Therefore nobiletin may represent a potential antithrombotic agent of dietary origins.

In vitro cytotoxicity of dental alloys and cpTi obtained by casting

Background: This study aimed to compare the cytotoxicity of base-metal dental alloys and to evaluate if the casting method could influence their cytotoxicity. Methods: Disks of base-metal dental alloys were cast by two methods: plasma, under argon atmosphere, injected by vacuum-pressure; and oxygen-gas flame, injected by centrifugation, except Ti-6Al-4V and commercially pure titanium (cpTi), cast only by plasma. SCC9 cells were cultured in culture media D-MEM/Ham`s F12 supplemented, at 37 degrees C in a humidified atmosphere of 5% carbon dioxide and 95% air, on the previously prepared disks. At subconfluence in wells without disks (control), cell number and viability were evaluated. Results: In plasma method, cpTi and Ti-6Al-4V were similar to control and presented higher number of cells than all other alloys, followed by Ni-Cr. In oxygen-gas name method, all alloys presented fewer cells than control. Ni-Cr presented more cells than any other alloy, followed by Co-Cr-Mo-W which presented more cells than Ni-Cr-Ti, Co-Cr-Mo, and Ni-Cr-Be. There were no significant differences between casting methods related to cell number. Cell viability was not affected by either chemical composition or casting methods. Conclusion: cpTi and Ti-6Al-4V were not cytotoxic while Ni-Cr-Be was the most cytotoxic among tested alloys. The casting method did not affect cytotoxicity of the alloys. (c) 2007 Wiley Periodicals, Inc.

Next Generation Sequencing of Pooled Samples Reveals New SNRNP200 Mutations Associated with Retinitis Pigmentosa

The gene SNRNP200 is composed of 45 exons and encodes a protein essential for pre-mRNA splicing, the 200 kDa helicase hBrr2. Two mutations in SNRNP200 have recently been associated with autosomal dominant retinitis pigmentosa (adRP), a retinal degenerative disease, in two families from China. In this work we analyzed the entire 35-Kb SNRNP200 genomic region in a cohort of 96 unrelated North American patients with adRP. To complete this large-scale sequencing project, we performed ultra high-throughput sequencing of pooled, untagged PCR products. We then validated the detected DNA changes by Sanger sequencing of individual samples from this cohort and from an additional one of 95 patients. One of the two previously known mutations (p.S1087L) was identified in 3 patients, while 4 new missense changes (p.R681C, p.R681H, p.V683L, p.Y689C) affecting highly conserved codons were identified in 6 unrelated individuals, indicating that the prevalence of SNRNP200-associated adRP is relatively high. We also took advantage of this research to evaluate the pool-and-sequence method, especially with respect to the generation of false positive and negative results. We conclude that, although this strategy can be adopted for rapid discovery of new disease-associated variants, it still requires extensive validation to be used in routine DNA screenings. (C) 2011 Wiley-Liss, Inc.

Continuous and High-Level In Vivo Delivery of Endostatin From Recombinant Cells Encapsulated in TheraCyte (R) Immunoisolation Devices

Endostatin (ES) is a potent inhibitor of angiogenesis and tumor growth. Continuous ES delivery of ES improves the efficacy and potency of the antitumoral therapy. The TheraCyte (R) system is a polytetrafluoroethylene (PTFE) semipermeable membrane macroencapsulation system for implantation of genetically engineered cells specially designed for the in vivo delivery of therapeutic proteins, such as ES, which circumvents the problem of limited half-life and variation in circulating levels. In order to enable neovascularization at the tissues adjacent to the devices prior to ES secretion by the cells inside them, we designed a scheme in which empty TheraCyte (R) devices were preimplanted SC into immunodeficient mice. Only after healing (17 days later) were Chinese hamster ovary cells expressing ES injected into the preimplanted devices. In another model for device implantation, the cells expressing ES where loaded into the immunoisolation devices prior to implantation into the animals, and the TheraCyte (R) were then immediately implanted SC into the mice. Throughout the 2-month study, constant high ES levels of up to 3.7 mu g/ml were detected in the plasma of the mice preimplanted with the devices, while lower but also constant levels of ES (up to 2.1 mu g/ml plasma) were detected in the mice that had received devices preloaded with the ES-expressing cells. Immunohistochemistry using anti-ES antibody showed reaction within the device and outside it, demonstrating that ES, secreted by the confined recombinant cells, permeated through the membrane and reached the surrounding tissues.

Exercise Training Reduces Insulin Resistance and Upregulates the mTOR/p70S6k Pathway in Cardiac Muscle of Diet-Induced Obesity Rats

Obesity and insulin resistance are rapidly expanding public health problems. These disturbances are related to many diseases, including heart pathology. Acting through the Akt/mTOR pathway, insulin has numerous and important physiological functions, such as the induction of growth and survival of many cell types and cardiac hypertrophy. However, obesity and insulin resistance can alter mTOR/p70S6k. Exercise training is known to induce this pathway, but never in the heart of diet-induced obesity subjects. To evaluate the effect of exercise training on mTOR/p70S6k in the heart of obese Wistar rats, we analyzed the effects of 12 weeks of swimming on obese rats, induced by a high-fat diet. Exercise training reduced epididymal fat, fasting serum insulin and plasma glucose disappearance. Western blot analyses showed that exercise training increased the ability of insulin to phosphorylate intracellular molecules such as Akt (2.3-fold) and Foxo1 (1.7-fold). Moreover, reduced activities and expressions of proteins, induced by the high-fat diet in rats, such as phospho-JNK (1.9-fold), NF-kB (1.6-fold) and PTP-1B (1.5-fold), were observed. Finally, exercise training increased the activities of the transduction pathways of insulin-dependent protein synthesis, as shown by increases in Raptor phosphorylation (1.7-fold), p70S6k phosphorylation (1.9-fold), and 4E-BP1 phosphorylation (1.4-fold) and a reduction in atrogin-1 expression (2.1-fold). Results demonstrate a pivotal regulatory role of exercise training on the Akt/ mTOR pathway, in turn, promoting protein synthesis and antagonizing protein degradation. J. Cell. Physiol. 226: 666-674, 2011. (C) 2010 Wiley-Liss, Inc.

Ideal internal kink modes in a differentially rotating cylindrical plasma

The Velikhov effect leading to magnetorotational instability (MRI) is incorporated into the theory of ideal internal kink modes in a differentially rotating cylindrical plasma column. It is shown that this effect can play a stabilizing role for suitably organized plasma rotation profiles, leading to suppression of MHD (magnetohydrodynamic) instabilities in magnetic confinement systems. The role of this effect in the problem of the Suydam and the m = 1 internal kink modes is elucidated, where m is the poloidal mode number.

BREAKING WAVES IN AN IDEAL QUARK GLUON PLASMA

We study the propagation of perturbations in the energy density in a quark gluon plasma. Expanding the Euler and continuity equations of relativistic hydrodynamics around equilibrium configurations we obtain a nonlinear differential equation called the breaking wave equation. We solve it numerically and follow the time-evolution of initially localized pulses. We find that, quite unexpectedly, these pulses live for a very long time (compared to the reaction time-scales) before breaking. In practice, they mimick the Korteweg-de Vries solitons. Their existence may have some observable consequences.

Investigation of the Europium Emission Spectra of the Europium-Oxytetracycline Complex in the Presence of Human Low-Density Lipoproteins

Low-Density Lipoprotein (LDL), often known as ""bad cholesterol"" is one of the responsible to increase the risk of coronary arterial diseases. For this reason, the cholesterol present in the LDL particle has become one of the main parameters to be quantified in routine clinical diagnosis. A number of tools are available to assess LDL particles and estimate the cholesterol concentration in the blood. The most common methods to quantify the LDL in the plasma are the density gradient ultracentrifugation and nuclear magnetic resonance (NMR). However, these techniques require special equipments and can take a long time to provide the results. In this paper, we report on the increase of the Europium emission in Europium-oxytetracycline complex aqueous solutions in the presence of LDL. This increase is proportional to the LDL concentration in the solution. This phenomenum can be used to develop a method to quantify the number of LDL particles in a sample. A comparison between the performances of the oxytetracycline and the tetracycline in the complexes is also made.

Occupational airborne contamination in south Brazil: 1. Oxidative stress detected in the blood of coal miners

Reactive oxygen species and nitrogen species have been implicated in the pathogenesis of coal dust-induced toxicity. The present study investigated several oxidative stress biomarkers (Contents of lipoperoxidation = TBARS, reduced = GSH, oxidized = GSSG and total glutathione = TG, alpha-tocopherol, and the activities of glutathione S-transferase = GST, glutathione reductase = GR, glutathione peroxidase = GPx, catalase = CAT and superoxide dismutase = SOD), in the blood of three different groups (n = 20 each) exposed to airborne contamination associated with coal mining activities: underground workers directly exposed, surface workers indirectly exposed, residents indirectly exposed (subjects living near the mines), and controls (non-exposed subjects). Plasma TBARS were increased and whole blood TG and GSH levels were decreased in all groups compared to controls. Plasma alpha-tocopherol contents showed approximately half the values in underground workers compared to controls. GST activity was induced in workers and also in residents at the vicinity of the mining plant, whilst CAT activity was induced only in mine workers. SOD activity was decreased in all groups examined, while GPx activity showed decreased values only in underground miners, and GR did not show any differences among the groups. The results showed that subjects directly and indirectly exposed to coal dusts face an oxidative stress condition. They also indicate that people living in the vicinity of the mine plant are in health risk regarding coal mining-related diseases.

A method for Ca, Fe, Ga, Na, Si and Zn determination in alumina by inductively coupled plasma optical emission spectrometry after aluminum precipitation

In this present work a method for the determination of Ca, Fe, Ga, Na, Si and Zn in alumina (Al(2)O(3)) by inductively coupled plasma optical emission spectrometry (ICP OES) with axial viewing is presented. Preliminary studies revealed intense aluminum spectral interference over the majority of elements and reaction between aluminum and quartz to form aluminosilicate, reducing drastically the lifetime of the torch. To overcome these problems alumina samples (250 mg) were dissolved with 5 mL HCl + 1.5 mLH(2)SO(4) + 1.5 mL H(2)O in a microwave oven. After complete dissolution the volume was completed to 20 mL and aluminum was precipitated as Al(OH)(3) with NH(3) (by bubbling NH(3) into the solution up to a pH similar to 8, for 10 min). The use of internal standards (Fe/Be, Ga/Dy, Zn/In and Na/Sc) was essential to obtain precise and accurate results. The reliability of the proposed method was checked by analysis of alumina certified reference material (Alumina Reduction Grade-699, NIST). The found concentrations (0.037%w(-1) CaO, 0.013% w w(-1) Fe(2)O(3), 0.012%w w(-1)Ga(2)O(3), 0.49% w w(-1) Na(2)O, 0.014% w w(-1) SiO(2) and 0.013% w w(-1) ZnO) presented no statistical differences compared to the certified values at a 95% confidence level. (C) 2011 Elsevier B.V. All rights reserved.

The kidney in different stages of the cardiovascular continuum

Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. The complex, interaction between the kidney and the cardiovascular system is incompletely understood, particularly at the early stages of the cardiovascular continuum. The overall aim of this thesis was to clarify novel aspects of the interplay between the kidney and the cardiovascular system at different stages of the cardiovascular continuum; from risk factors such as insulin resistance, inflammation and oxidative stress, via sub-clinical cardiovascular damage such as endothelial dysfunction and left ventricular dysfunction, to overt cardiovascular death. This thesis is based on two community-based cohorts of elderly, Uppsala Longitudinal Study of Adult Men (ULSAM) and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The first study, show that higher insulin sensitivity, measured with euglycemic-hyperinsulinemic clamp technique was associated to improve estimated glomerular filtration rate (eGFR) in participants with normal fasting plasma glucose, normal glucose tolerance and normal eGFR. In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function during follow-up. In the second study, eGFR was inversely associated with different inflammatory markers (C-reactive protein, interleukin-6, serum amyloid A) and positively associated with a marker of oxidative stress (urinary F2-isoprostanes). In line with this, the urinary albumin/creatinine ratio was positively associated with these inflammatory markers, and negatively associated with oxidative stress. In study three, higher eGFR was associated with better endothelial function as assessed by the invasive forearm model. Further, in study four, higher eGFR was significantly associated with higher left ventricular systolic function (ejection fraction). The 5th study of the thesis shows that higher urinary albumin excretion rate (UAER) and lower eGFR was independently associated with an increased risk for cardiovascular mortality. Analyses of global model fit, discrimination, calibration, and reclassification suggest that UAER and eGFR add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent cardiovascular disease. Conclusion: this thesis show that the interaction between the kidney and the cardiovascular system plays an important role in the development of cardiovascular disease and that this interplay begins at an early asymptomatic stage of the disease process.

Análise da desverticalização e das condições favoráveis à produção "in house"

Este trabalho procura compreender um ambiente de negócios bastante específico. As empresas, diante dos fenômenos da globalização e do crescimento das exigências impostas pelos consumidores (produtos melhores a preços mais baixos), buscarão diversas soluções para enfrentar estes desafios. Soluções para otimizar as suas redes de suprimentos serão uma das possíveis respostas para este problema. As redes de suprimentos, quanto mais eficazes, estarão agregando mais valor ao produto final causando um impacto mínimo nos custos do produto, e terão uma papel importante na estratégia da empresa para vencer este desafio. Ao longo dessa dissertação serão avaliadas as relações existentes entre cliente e fornecedor e focadas algumas variáveis que influenciam este relacionamento. Através da análise das estratégias de verticalização, estaremos avaliando outras possibilidades de fornecimento que possam ser mais atraentes para as empresas, no que diz respeito à gerência de sua rede de fornecedores. O trabalho está centrado na análise da estratégia de verticalização e como são criadas as condições que favorecem a desverticalização, conduzindo a empresa para a solução de fornecimento através de uma produção "in house". O setor industrial será tomado como exemplo deste tipo de relacionamento, mais especificamente, o segmento de produção de embalagens plásticas. A produção "in house" , como será descrito mais detalhadamente adiante, se estabelece da seguinte forma: uma unidade produtiva de um fornecedor estratégico é construída dentro do ambiente físico do cliente. Desse local, o fornecedor supre as necessidades do cliente de um ou diversos itens necessários para a realização da sua atividade industrial. Diversas questões serão exploradas neste trabalho, dentre elas, em que situações vale a pena manter uma operação integrada verticalmente ou optar pela terceirização desta operação, que um dia foi verticalizada? Sob que condições esta seria uma boa solução para o fornecimento de insumos básicos para a produção? Este trabalho se desenvolverá a partir de uma pesquisa bibliográfica assim como de um trabalho de campo, envolvendo a análise de diversas situações reais. vi Como identificar se a verticalização de um segmento oferecerá as vantagens esperadas? Quais são os principais fatores que devemos levar em conta para esta análise? Que tipo de modelo de desverticalização pode ser o mais adequado para a empresa cliente? Que medidas podem ser promovidas para se incrementar uma relação com o fornecedor "in house" ? Este estudo apresenta algumas propostas para responder às questões acima.

General (in-house) counsels in Brazil: career, professional profile and a new role

This paper discusses who the legal directors are in private companies in Brazil, emphasizing their profile, career, and performance, focusing on the period of 2008- 2013, investigating changes which have occurred to legal departments in those companies, and to legal directors’ careers. Our argument is that since the expansion of legal departments in Brazil in the 1990s, with expanding privatizing of companies and further opening of the Brazilian market to foreign capital, the profiles and careers of legal directors have undergone several transformations, culminating in more value and prestige being given to those professionals inside companies. This paper explores these transformations and the a series of implications generated for the corporate legal market in the country, ranging from changing the criteria for hiring professionals, to creating new demands for more sophisticated legal services.

Nitriding in cathodic cage of stainless steel AISI 316: influence of sample position

R.R.M. de Sousa et al. Nitriding in cathodic cage of stainless steel AISI 316: Influence of sample position. Vacuum, [s.l.], n.83, 2009. Disponivel em: plasma.ct.ufrn.br/index.php?id=5>. Acesso em: 04 out.2010.