Purinergic receptors in ocular inflammation

Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly 'tuned,' can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P(1),P(4)-diadenosine tetraphosphate (Ap4A), and P(1),P(5)-diadenosine pentaphosphate (Ap5A) are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (CF101) have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases) can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation.

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants.

One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. We used data from 751 studies including 4,372,000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-7.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. Wellcome Trust.

Proyecto de construcción y puesta en marcha de nueva explotación de cebo porcino para 4.000 plazas en el término municipal de La Puebla de Castro (Huesca)

Aquest treball intenta explicar, de forma detallada, tots els materials, obres i processos que s’han de dur a terme per a la construcción d’una nova explotació d’engreix porcí. L’explotació que es projecta tindrà capacitat per a 4.000 places, i s’ubicarà al terme municipal de La Puebla de Castro, província d’Osca. Es tracta d’un projecte d’enginyeria on es descriu el disseny i el càlcul de les diferents edificacions i instal·lacions que formaran part de la futura explotació. Alhora, es realitzen diversos estudis com el de l’impacte ambiental o el de protecció contra incendis, per a complir el que estableix el Codi Tècnic de l’Edificació; i poder sol·licitar la llicència d’activitat per posar en funcionament l’explotació.

Ager Tarraconensis 4. Els Antigons, una vil·la senyorial del Camp de Tarragona = Els Antigons, a High Status Villa in the Camp de Tarragona

La vil·la romana dels Antigons (Reus, tocant amb la Canonja) fou una de les més riques de l’ager Tarraconensis, raó per la qual ha merescut un tractament monogràfic. El nom ja indica la rellevància de les restes que s’hi han trobat des del segle XIX. És un jaciment dissortat, però: la construcció d’un complex industrial els anys 70 el va destruir en gran part i avui no en queda cap resta visible. En les excavacions d’urgència entre el 1976 i el 1979 es va recollir una importantíssima documentació. Destaca un forn del segle I dC on es produïen materials constructius i àmfores vineres. La vil·la experimentà un moment de gran riquesa la primera meitat del segle III, com ho indica el luxós nimfeu decorat amb estàtues, així com l’important abocador del mateix moment, que ha permès estudiar un abundantíssim conjunt de ceràmiques romanes. La vil·la perdurà almenys fins al segle V, i hi ha traces de freqüentació i ús en època visigòtica.

Tastets d'economia número 4:el paradigma dels diamants i l'aigua

Peer-reviewed

Tastets d'economia número 4:el paradigma dels diamants i l'aigua

Article tastets d'economia número 4, que explica el paradigma dels diamants i l'aigua, adreçat al target de les ciències socials.

Editorial del número 4 de la Revista Observar

sabel Ruíz Pujadas regala al lector una imagen con trampa y cartón. A primera vista, casi podría haberse extraído de aquellas épocas en las que dibujantes intrépidos ponían su maña al servicio de la ciencia, del apoderamiento de los territorios inexplorados y de la fantasía europea. De estar en lo cierto, su regalo respira vendetta: llegó un momento en que el acta notarial de la realidad comenzó a sellarse con cristales de plata; hasta que alguien cayó en la cuenta de que la fotografía llevaba lentes y se acabó la discusión. Tal vez la imagen sea un homenaje a aquellos álbumes de plantas y bichos hechos con mucho esmero y no menos ojo. Pero, Isabel Ruíz la acompaña de un título, Mirada de gallina Leghorn, y el asunto se complica. Porque el título le da la vuelta al dibujo, desplaza su sentido y lo trae a la actualidad. Es una muestra de esas interferencias lingüísticas que apuntalan en no pocas ocasiones el efecto estético contemporáneo. Ni el rótulo ni la imagen; es su simbiosis lo que esclarece una intención hasta traerla al coto artístico.

Identidad y nuevas ecologías de aprendizaje: análisis de cuatro casos de 4º de la ESO

Este trabajo pretende, en primer lugar, ilustrar empíricamente las características de las nuevas ecologías de aprendizaje de los estudiantes mediante el análisis pormenorizado de cuatro alumnos de cuarto de la ESO durante una semana de sus vidas. En segundo lugar, analizar los perfiles personales de dichos alumnos desde el análisis de su identidad aprendiz; cómo integran su yo de estudiante en su vida cotidiana y qué posturas sostienen en relación a la escuela y al papel que juega tanto en su vida presente como en su proyecto de vida futura

Spectrophotometric and spectrofluorimetric determination of some drugs containing secondary amino group in bulk drug and dosage forms via derivatization with 7-Chloro-4-Nitrobenzofurazon

Sensitive and selective spectrophotometric and spectrofluorimetric methods have been developed for determination of some drugs such as Pramipexole, Nebivolol, Carvedilol, and Eletriptan, which commonly contain secondary amino group. The subject methods were developed via derivatization of the secondary amino groups with 7-Chloro-4-Nitrobenzofurazon in borate buffer where a yellow colored reaction product was obtained and measured spectrophotometrically or spectrofluorimetrically. Concentration ranges were found as 2.0 to 250 μg mL-1 and 0.1 to 3.0 μg mL-1, for spectrophotometric and spectrofluorimetric study, respectively. The described methods can be easily applied by the quality control laboratories in routine analyses of these drugs in pharmaceutical preparations.

Determinação da constante de velocidade absoluta para a reação de abstração de hidrogênio fenólico pelo estado excitado triplete de xantona em acetonitrila e no líquido iônico hexafluorfosfato de 1-butil-3-metil-imidazólio [bmim.PF6]

The triplet excited state of xanthone was generated and characterized by laser flash photolysis in acetonitrile (λmax=620 nm; t=1.8 ms) and in ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate [bmim.PF6] (λmax=620 nm; t=3.0 ms). It reacts with phenols yielding the corresponding xanthone ketyl radical. Stern-Volmer plots for the reaction of triplet xanthone with phenols led to the determination of absolute rate constants for phenolic hydrogen abstraction in the order of ~10(9) Lmol-1s-1 in acetonitrile and ~10(8) Lmol-1s-1 in [bmim.PF6]. The lower diffusioncontrolled rate constant for [bmim.PF6] is responsible for the difference in the phenolic hydrogen abstraction rate constants in this solvent.

Tolerância do milheto (Pennisetum americanum) ao 2, 4-D

Objetivou-se com este trabalho avaliar os efeitos do 2,4-D sobre o crescimento das plantas, a produção de massa seca e verde e a produtividade de grãos do milheto. O experimento foi realizado no período de março a junho de 2006, em Rio Verde-GO, em um Latossolo Vermelho eutroférrico. O milheto (cultivar ADR 500) foi semeado manualmente em área cultivada sob sistema de plantio direto, em espaçamento de 0,45 m, distribuindo-se 12 sementes por metro. Utilizou-se o delineamento de blocos casualizados, em esquema fatorial 4 x 4, sendo avaliadas quatro doses de 2,4-D (0, 335, 670 e 1.005 g ha-1) aplicadas em quatro épocas [10 dias após a emergência das plantas de milheto (DAE) (3 folhas); 20 DAE (5 a 6 folhas expandidas); 30 DAE (início de emissão da inflorescência); e 40 DAE (florescimento pleno)]. Para evitar a interferência das plantas daninhas na cultura, esta foi capinada manualmente, sempre que necessário. Não se observou nenhum sinal de intoxicação das plantas de milheto pelo 2,4-D aos 15 dias após a aplicação, independentemente da dose ou época de aplicação do herbicida. Todavia, as maiores doses de 2,4-D, em qualquer época de aplicação, provocaram menor acúmulo de massa verde e seca das plantas de milheto, quando se avaliaram os resultados no ponto de rolagem da cultura. O 2,4-D, independentemente da dose utilizada ou época de aplicação, não influenciou a produtividade de grãos do milheto.

Linear competitive inhibition of human tissue kallikrein by 4-aminobenzamidine and benzamidine and linear mixed inhibition by 4-nitroaniline and aniline

Hydrolysis of D-valyl-L-leucyl-L-arginine p-nitroanilide (7.5-90.0 µM) by human tissue kallikrein (hK1) (4.58-5.27 nM) at pH 9.0 and 37ºC was studied in the absence and in the presence of increasing concentrations of 4-aminobenzamidine (96-576 µM), benzamidine (1.27-7.62 mM), 4-nitroaniline (16.5-66 µM) and aniline (20-50 mM). The kinetic parameters determined in the absence of inhibitors were: Km = 12.0 ± 0.8 µM and k cat = 48.4 ± 1.0 min-1. The data indicate that the inhibition of hK1 by 4-aminobenzamidine and benzamidine is linear competitive, while the inhibition by 4-nitroaniline and aniline is linear mixed, with the inhibitor being able to bind both to the free enzyme with a dissociation constant Ki yielding an EI complex, and to the ES complex with a dissociation constant Ki', yielding an ESI complex. The calculated Ki values for 4-aminobenzamidine, benzamidine, 4-nitroaniline and aniline were 146 ± 10, 1,098 ± 91, 38.6 ± 5.2 and 37,340 ± 5,400 µM, respectively. The calculated Ki' values for 4-nitroaniline and aniline were 289.3 ± 92.8 and 310,500 ± 38,600 µM, respectively. The fact that Ki'>Ki indicates that 4-nitroaniline and aniline bind to a second binding site in the enzyme with lower affinity than they bind to the active site. The data about the inhibition of hK1 by 4-aminobenzamidine and benzamidine help to explain previous observations that esters, anilides or chloromethyl ketone derivatives of Nalpha-substituted arginine are more sensitive substrates or inhibitors of hK1 than the corresponding lysine compounds.

Limited-sampling strategy models for estimating the pharmacokinetic parameters of 4-methylaminoantipyrine, an active metabolite of dipyrone

Bioanalytical data from a bioequivalence study were used to develop limited-sampling strategy (LSS) models for estimating the area under the plasma concentration versus time curve (AUC) and the peak plasma concentration (Cmax) of 4-methylaminoantipyrine (MAA), an active metabolite of dipyrone. Twelve healthy adult male volunteers received single 600 mg oral doses of dipyrone in two formulations at a 7-day interval in a randomized, crossover protocol. Plasma concentrations of MAA (N = 336), measured by HPLC, were used to develop LSS models. Linear regression analysis and a "jack-knife" validation procedure revealed that the AUC0-¥ and the Cmax of MAA can be accurately predicted (R²>0.95, bias <1.5%, precision between 3.1 and 8.3%) by LSS models based on two sampling times. Validation tests indicate that the most informative 2-point LSS models developed for one formulation provide good estimates (R²>0.85) of the AUC0-¥ or Cmax for the other formulation. LSS models based on three sampling points (1.5, 4 and 24 h), but using different coefficients for AUC0-¥ and Cmax, predicted the individual values of both parameters for the enrolled volunteers (R²>0.88, bias = -0.65 and -0.37%, precision = 4.3 and 7.4%) as well as for plasma concentration data sets generated by simulation (R²>0.88, bias = -1.9 and 8.5%, precision = 5.2 and 8.7%). Bioequivalence assessment of the dipyrone formulations based on the 90% confidence interval of log-transformed AUC0-¥ and Cmax provided similar results when either the best-estimated or the LSS-derived metrics were used.

In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4+CD25+ T cells of patients with human T-lymphotropic virus type 1-associated myelopathy

HTLV-1 Tax expression exerts an inhibitory effect on the Foxp3 transcription factor in CD4+CD25+ T-regulatory cells (Treg). For a better understanding of the role of Tax mRNA in the gene expression of cellular markers we measured Tax, Foxp3, CTLA-4, GITR, TGF-β, and IL-10 mRNA in Treg cells of 50 patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP; 27 women and 23 men; mean age: 56.7 years). The control group consisted of 23 non-infected subjects (12 women and 11 men) with a mean age of 51.3 years. Real-time PCR was used to measure mRNA of Tax proteins and several cellular markers of Treg function. Determinations revealed a high level of Tax mRNA in HAM/TSP (124.35 copies/100 CD4+CD25+ T cells). Foxp3, GITR, and CTLA-4 mRNA levels were lower in HAM/TSP patients (mean ± SD, 22.07 ± 0.78, 9.63 ± 0.36, and 4.54 ± 0.39, respectively) than in non-infected controls (47.15 ± 12.94, 22.14 ± 1.91, and 21.07 ± 2.31). Both groups had similar levels of TGF-β and IL-10. An inverse relationship was found between Tax levels and Foxp3, CTLA-4, and GITR levels. Conversely, there was a direct correlation between levels of Foxp3, GITR, and CTLA-4. Disease severity and evolution time did not correlate with Tax or Foxp3 levels. The present results suggest that Tax and Foxp3 mRNA vary with the same degree of disease severity in HAM/TSP patients. Tax fluctuations may affect CTLA-4 and GITR expression via the Foxp3 pathway, causing virus-induced dysfunction of CD4+CD25+ T cells in HAM/TSP patients.