La Directiva 2004/38/CE y la jurisprudencia del TJCE sobre el disfrute de las prestaciones sociales: ¿freno al avance en materia social o adecuación a los intereses de los Estados?

El artículo tiene como objetivo analizar el modelo social incorporado en la Directiva 2004/38/CE en el marco de la jurisprudencia del Tribunal de Justicia. El artículo está dividido en dos partes. En la primera se describe la evolución del modelo de coordinación social de la Unión Europea y los avances propuestos por el TJCE a partir de la ciudadanía europea sobre el acceso a las prestaciones sociales (Martínez Sala, Grzelczyk y Collins). La segunda parte del artículo describe el modelo social incorporado en la Directiva 2004/38/ CE y los cambios que éste supuso para la jurisprudencia que venía dictando el TJCE. El artículo concluye que la Directiva 2004/38/CE tuvo un papel de contención frente los pasos dados por el Tribunal para incluir los derechos sociales en la ciudadanía de la Unión; además, la Directiva fragmentó la interpretación del principio de no discriminación para los ciudadanos no económicamente activos.

Determinação indireta de N-acetil-L-cisteína por injeção em fluxo empregando Ce(IV) e ferroína

An indirect flow injection spectrophotometric procedure is proposed for the determination of N-acetyl-L-cysteine in pharmaceutical formulations. In this system, ferroin ([Fe(II)-(fen)2]2+) in excess, with a strong absorption at 500 nm, is oxidized by cerium(IV) yielding cerium(III) and [Fe(III)-(fen)2]3+ (colorless), thus producing a baseline. When N-acetyl-L-cysteine solution is introduced into the flow injection system, it reacts with cerium(IV) increasing the analytical signal in proportion to the drug concentration. Under optimal experimental conditions, the linearity of the analytical curve for N-acetyl-L-cysteine ranged from 6.5x10-6 to 1.3x10-4 mol L-1. The detection limit was 5.0x10-6 mol L-1and recoveries between 98.0 and 106% were obtained. The sampling frequency was 60 determinations per hour and the RSD was smaller than 1.4% for 2.2x10-5 mol L-1 N-acetyl-L-cysteine.

Cu and Co exchanged ZSM-5 zeolites: activity towards no reduction and hydrocarbon oxidation

|Cu x|[Si yAl]-MFI and |Co x|[Si yAl]-MFI catalysts were prepared by ion exchange from |Na|[Si yAl]-MFI zeolites (y = 12, 25 and 45). The activity of the catalysts was evaluated in the reduction of NO to N2 in an oxidative atmosphere using propane or methane as reducing agents. The Cu catalysts were only active with propane and they presented higher activity than the Co-based catalysts, the latter being active with both hydrocarbons. H2-TPR and DRS-UV/Vis data allowed correlation between the activity towards NO reduction and the presence of cationic charge-compensating species in the zeolite. It was also verified that the hydrocarbons are preferentially oxidised by O2, a reaction that occurs simultaneously with their oxidation with NO.

Influence of EfOM on the oxidation of micropollutants by Ozone and UV/H2O2 in secondary effluents

The aim of this work was to study the influence of effluent organic matter (EfOM) on micropollutants removal by ozone and UV/H2O2. To perform the experiments, deionized water and municipal secondary effluents (SE) were artificially contaminated with atrazine (ATZ) and treated by the two proposed methods. ATZ concentration, COD and TOC were recorded along the reaction time and used to evaluate EfOM effect on the system efficiency. Results demonstrate that the presence of EfOM can significantly reduce the micropollutant removal rate due to competition of EfOM components to react with radicals and/or molecular ozone. The hydroxyl radical scavenging caused by EfOM was quantified as well as the contribution of molecular ozone and �OH radicals during the ozonation of SE. EfOM components promoted higher inhibition of ATZ oxidation by hydroxyl radicals than by molecular ozone.

Myoglobins: the link between discoloration and lipid oxidation in muscle and meat

Aerobic metabolism changes rapidly to glycolysis post-mortem resulting in a pH-decrease during the transformation of muscle in to meat affecting ligand binding and redox potential of the heme iron in myoglobin, the meat pigment. The "inorganic chemistry" of meat involves (i) redox-cycling between iron(II), iron(III), and iron(IV)/protein radicals; (ii) ligand exchange processes; and (iii) spin-equilibra with a change in coordination number for the heme iron. In addition to the function of myoglobin for oxygen storage, new physiological roles of myoglobin are currently being discovered, which notably find close parallels in the processes in fresh meat and nitrite-cured meat products. Myoglobin may be characterized as a bioreactor for small molecules like O2, NO, CO, CO2, H2O, and HNO with importance in bio-regulation and in protection against oxidative stress in vivo otherwise affecting lipids in membranes. Many of these processes may be recognised as colour changes in fresh meat and cured meat products under different atmospheric conditions, and could also be instructive for teaching purposes.

Cyclin-dependent kinases 4 and 6 control tumor progression and direct glucose oxidation in the pentose cycle

Cyclin-dependent kinases CDK4 and CDK6 are essential for the control of the cell cycle through the G1 phase. Aberrant expression of CDK4 and CDK6 is a hall- mark of cancer, which would suggest that CDK4 and CDK6 are attractive targets for cancer therapy. Herein, we report that calcein AM is a potent specific inhibitor of CDK4 and CDK6 in HCT116 human colon adenocarcinoma cells, inhibiting retinoblastoma protein (pRb) phosphorylation and inducing cell cycle arrest in the G1 phase. The metabolic effects of calcein AM (the calcein acetoxymethyl-ester) on HCT116 cells were also evaluated and the flux between the oxidative and non-oxidative branches of the pentose phos-phate pathway was significantly altered. To elucidate whe-ther these metabolic changes were due to the inhibition of CDK4 and CDK6, we also characterized the metabolic profile of a CDK4, CDK6 and CDK2 triple knockout of mouse embryonic fibroblasts. The results show that the metabolic profile associated with the depletion of CDK4, CDK6 and CDK2 coincides with the metabolic changes induced by calcein AM on HCT116 cells, thus confirming that the inhibition of CDK4 and CDK6 disrupts the balance between the oxidative and non-oxidative branches of the pentose phosphate pathway. Taken together, these results indicate that low doses of calcein can halt cell division and kill tumor cells. Thus, selective inhibition of CDK4 and CDK6 may be of greater pharmacological interest, since inhibitors of these kinases affect both cell cycle progression and the robust metabolic profile of tumors.

Phase diagram and complex patterns in the modeling of the bromate-oxalic acid-Ce-acetone oscillating reaction

Simulations have been carried out on the bromate - oxalic acid - Ce(IV) - acetone oscillating reaction, under flow conditions, using Field and Boyd's model (J. Phys. Chem. 1985, 89, 3707). Many different complex dynamic behaviors were found, including simple periodic oscillations, complex periodic oscillations, quasiperiodicity and chaos. Some of these complex oscillations can be understood as belonging to a Farey sequence. The many different behaviors were systematized in a phase diagram which shows that some regions of complex patterns were nested with one inside the other. The existence of almost all known dynamic behavior for this system allows the suggestion that it can be used as a model for some very complex phenomena that occur in biological systems.

Mitochondrial fatty acid oxidation in obesity

Significance: Current lifestyles with high-energy diets and little exercise are triggering an alarming growth in obesity. Excess of adiposity is leading to severe increases in associated pathologies, such as insulin resistance, type 2 diabetes, atherosclerosis, cancer, arthritis, asthma, and hypertension. This, together with the lack of efficient obesity drugs, is the driving force behind much research. Recent Advances: Traditional anti-obesity strategies focused on reducing food intake and increasing physical activity. However, recent results suggest that enhancing cellular energy expenditure may be an attractive alternative therapy. Critical Issues: This review evaluates recent discoveries regarding mitochondrial fatty acid oxidation (FAO) and its potential as a therapy for obesity. We focus on the still controversial beneficial effects of increased FAO in liver and muscle, recent studies on how to potentiate adipose tissue energy expenditure, and the different hypotheses involving FAO and the reactive oxygen species production in the hypothalamic control of food intake. Future Directions: The present review aims to provide an overview of novel anti-obesity strategies that target mitochondrial FAO and that will definitively be of high interest in the future research to fight against obesity-related disorders.

Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation

Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CARΔ1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes.

Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation

Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CARΔ1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes.

Kapillaarielektroforeesin soveltaminen uuttofaasin koostumuksen analysointiin

Työn tarkoituksena oli löytää kapillaarielektroforeesimenetelmä (CE), joka soveltuisi metallien neste-nesteuutossa käytettävien orgaanisten uuttofaasien koostumuksen analysointiin. Kapillaarielektroforeesissa käytetyn elektrolyyttiliuoksen analyytti-kohtaista optimointia ei tässä työssä tehty, vaan liikkeelle lähdettiin fenoleille tarkoitetulla menetelmällä. Tarkasteltavia uuttoreagenssiryhmiä olivat hydroksi-oksiimit sekä fosfiinihappo- ja fosforihappopohjaiset reagenssit. Tutkittavia kaupallisia laimentimia olivat Orfom SX 11 ja Shellsol D70. Lisäksi tutkittiin kahta modifiointiainetta, TOPOa (tri-n-oktyylifosfiinioksidi) ja TXIB:tä (2,2,4-trimetyyli-1,3-pentaanidiolidi-isobutyraatti). Työssä tavoiteltiin kapillaarielektroforeesin hyötyjä erityisesti hydrometallurgisessa teollisuudessa. Suurimpana hyötynä ennakoitiin mahdollisuus analysoida suuria molekyylejä, kuten uuttoreagenssi-metallikomplekseja, joita ei pystytä analysoimaan kaasukromatografilla (GC). Näytteet voidaan myös analysoida ilman hidasta ja usein ei-kvantitatiivista derivatisointia. Kirjallisuudesta ei löytynyt aiempia artikkeleita CE:n soveltamisesta kyseisille aiheille. Kapillaarielektroforeesianalyyseissa pystyttiin esimerkiksi havaitsemaan hydroksi-oksiimin kuparikompleksi orgaanisessa faasissa. Seulonta-ajoissa yleisenä ongelmana oli kuitenkin tulosten heikko toistettavuus. Kapillaari-elektro-foreesi-menetelmä tarjoaa selvästi mahdollisuuksia tulevaisuudessa, mutta vielä sillä ei päästy luotettavaan toistoon sähkökentän häiriöiden ja elektrolyyttiliuoksen riittämättömän optimoinnin vuoksi. Lisäksi teollisissa olosuhteissa käytetyille autenttisille hydroksioksiimi- ja fosfiinihapponäytteille tehtiin perinteisiä kaasukromatografia-analyysejä, joiden perusteella voitiin nähdä uuttofaasin koostumuksen muuttuneen prosessissa. Hapettuminen sekä eri hydrolyysireaktiot ovat tärkeimmät syyt reagenssien ja laimentimien muuttumiselle. Näitä hajoamistuotteita ei tässä työssä onnistuttu analysoimaan kapillaarielektroforeesilla.

Eletroforese capilar acoplada à espectrometria de massas (CE-MS): vinte anos de desenvolvimento

CE-MS has been increasingly used for analysis of a vast array of compounds. This article reviews the different electrophoretic modes, interfaces and mass analyzers that are commonly used in the CE-MS coupling, as well as the technique advantages and performance characteristics. A large compilation of CE-MS applications is also presented. Therefore, this review is both a guide for beginners and a collection of key references for people who are familiar to the technique. Furthermore, this is the first CE-MS review published in a Brazilian journal and marks the installation of the first two commercial CE-MS units in Sao Paulo State.

Estratégias de pré-concentração em eletroforese capilar (CE): parte 1. Manipulação da velocidade eletroforética do analito

Capillary electrophoresis has become a well-established and routine-based separation technique. It is based on the differences between charged analyte mobility in aqueous or organic electrolytes. Its major limitation is the sensitivity due to small sample injection volumes and the narrow diameter of the capillaries, especially when UV detection is used. There are a number of ways to increase the concentration sensitivity. This report shows some on-line preconcentration strategies to perform it in free solution capillary electrophoresis that are based on manipulation of the analyte electrophoretic velocity during the sample introduction (stacking, field amplification and transient isotachophoresis).

Determination of cetirizine in tablets and compounded capsules: comparative study between CE and HPLC

A capillary electrophoresis (CE) method was developed and validated for determination of cetirizine dihydrochloride in tablets and compounded capsules. The electrophoretic separation was performed in an uncoated fused-silica capillary (40 cm x 50 μm i.d.) using 20 mmol L-1 sodium tetraborate buffer (pH 9.3) as background electrolyte, a hydrodinamic sample injection at 50 mBar for 5 s, 20 KV applied voltage at 25 °C, and detection at 232 nm. The proposed method was compared with the high performance liquid chromatographic (HPLC) method previously validated for this drug, and statistical analysis showed no significant difference between the techniques.

Electrocatalytic oxidation of methanol by the [Ru3O(OAc)6(py)2(CH3OH)]3+cluster: improving the metal-ligand electron transfer by accessing the higher oxidation states of a multicentered system

The [Ru3O(Ac)6(py)2(CH3OH)]+ cluster provides an effective electrocatalytic species for the oxidation of methanol under mild conditions. This complex exhibits characteristic electrochemical waves at -1.02, 0.15 and 1.18 V, associated with the Ru3III,II,II/Ru3III,III,II/Ru 3III,III,III /Ru3IV,III,III successive redox couples, respectively. Above 1.7 V, formation of two RuIV centers enhances the 2-electron oxidation of the methanol ligand yielding formaldehyde, in agreement with the theoretical evolution of the HOMO levels as a function of the oxidation states. This work illustrates an important strategy to improve the efficiency of the oxidation catalysis, by using a multicentered redox catalyst and accessing its multiple higher oxidation states.