Effects of peroxisome proliferator-activated receptor- activation in endothelin-dependent hypertension

Aims We analysed the chronic effects of the peroxisome proliferator-activated receptor β/δ (PPAR-β) agonist GW0742 on the renin-independent hypertension induced by deoxycorticosterone acetate (DOCA)-salt. Methods and results Rats were treated for 5 weeks with: control-vehicle, control-GW0742 (5 or 20 mg kg−1 day−1), DOCA-vehicle, DOCA-GW0742 (5 or 20 mg kg−1 day−1), DOCA-GSK0660 (1 mg kg−1 day−1), and DOCA-GSK0660-GW0742. Rats receiving DOCA-vehicle showed increased systolic blood pressure, left ventricular and kidney weight indices, endothelin-1 (ET-1), and malondialdehyde plasma levels, urinary iso-PGF2α excretion, impaired endothelium-dependent relaxation to acetylcholine, and contraction to ET-1 when compared with controls. Aortic reactive oxygen species content, NADPH oxidase activity, and p47phox, p22phox, NOX-4, glutathione peroxidase 1, hemeoxygenase-1, and preproET-1 expression were increased, whereas catalase and regulators of G protein-coupled signalling proteins (RGS)5 expression were decreased in the DOCA-vehicle group. GW0742 prevented the development of hypertension in a dose-dependent manner but the reduction of renal and cardiac hypertrophy, systemic and vascular oxidative stress markers, and improvement of endothelial dysfunction were only observed after the higher dose. GW0742, at 20 mg kg−1 day−1, attenuated ET-1 contraction by increasing RGS5 expression and restored the intracellular redox balance by reducing NADPH-oxidase activity, and by increasing the antioxidant genes expression. The PPAR-β antagonist GSK0660 prevented all vascular changes induced by GW0742 but not its antihypertensive effects. Conclusion Vascular protective effects of GW0742 operate via PPAR-β by interference with the ET-1 signalling as a result of increased expression of RGS5 and up-regulation of antioxidant genes and via PPAR-β-independent mechanisms to decrease blood pressure

Aplicación y evaluación de una metodología de programación visual para el desarrollo de competencias matemáticas

El uso de la programación visual en metodología docente es un aspecto novedoso de especial interés en el ámbito educativo actual. Más concretamente, pensamos que la utilización del lenguaje de programación Scratch puede contribuir positivamente, entre otros aspectos, al desarrollo de competencias matemáticas. Por este motivo se ha procedido, en el trabajo que aquí se presenta, al diseño, aplicación y evaluación de una metodología docente de programación visual mediante lenguaje Scratch. Ello se ha desarrollado en el contexto de la formación de maestros de educación primaria, buscando, además de la adquisición de competencias matemáticas, el conocimiento de nuevas metodologías para su futuro como docentes

Peroxisome proliferator-activated receptor-β activation restores the high glucose-induced impairment of insulin signaling in endothelial cells

BACKGROUND AND PURPOSE: PPARβ enhances insulin sensitivity in adipocytes and skeletal muscle cells, but its effects on insulin signalling in endothelial cells are not known. We analysed the effects of the PPARβ/δ (PPARβ) agonists, GW0742 and L165041, on impaired insulin signalling induced by high glucose in HUVECs and aortic and mesenteric arteries from diabetic rats. EXPERIMENTAL APPROACH: Insulin-stimulated NO production, Akt-Ser(473) and eNOS-Ser(1177) phosphorylation, and reactive oxygen species (ROS) production were studied in HUVECs incubated in low- or high-glucose medium. Insulin-stimulated relaxations and protein phosphorylation in vessels from streptozotocin (STZ)-induced diabetic rats were also analysed. KEY RESULTS: HUVECs incubated in high-glucose medium showed a significant reduction in insulin-stimulated production of NO. High glucose also reduced insulin-induced Akt-Ser(473) and eNOS-Ser(1177) phosphorylation, increased IRS-1-Ser(636) and ERK1/2-Thr(183)-Tyr(185) phosphorylation and increased ROS production. The co-incubation with the PPARβ agonists GW0742 or L165041 prevented all these effects induced by high glucose. In turn, the effects induced by the agonists were suppressed when HUVEC were also incubated with the PPARβ antagonist GSK0660, the pyruvate dehydrogenase kinase (PDK)4 inhibitor dichloroacetate or after knockdown of both PPARβ and PDK4 with siRNA. The ERK1/2 inhibitor PD98059, ROS scavenger catalase, inhibitor of complex II thenoyltrifluoroacetone or uncoupler of oxidative phosphorylation, carbonyl cyanide m-chlorophenylhydrazone, also prevented glucose-induced insulin resistance. In STZ diabetic rats, oral GW0742 also improved insulin signalling and the impaired NO-mediated vascular relaxation. CONCLUSION AND IMPLICATIONS: PPARβ activation in vitro and in vivo restores the endothelial function, preserving the insulin-Akt-eNOS pathway impaired by high glucose, at least in part, through PDK4 activation

Bargaining with independence of higher or irrelevant claims

This paper studies independence of higher claims and independence of irrelevant claims on the domain of bargaining problems with claims. Independence of higher claims requires that the payoff of an agent does not depend on the higher claim of another agent. Independence of irrelevant claims states that the payoffs should not change when the claims decrease but remain higher than the payoffs. Interestingly, in conjunction with standard axioms from bargaining theory, these properties characterize a new constrained Nash solution, a constrained Kalai–Smorodinsky solution, and a constrained Kalai solution

Updating claims in bankruptcy problems

We re-examine the consistency axiom in bankruptcy problems and propose arguments in favor of an alternative definition of a reduced problem. The classical definition updates the size of the estate while keeping agents' claims unaffected. Instead, we suggest updating agents' claims along with the estate. The resulting consistency axiom characterizes the well-known Random Arrival rule as the unique bilateral consistent extension of the Contested Garment rule to many agents.Bankruptcy problems Consistency Cooperative games

Solutions for cooperative games with r alternatives

We consider games with n players and r alternatives. In these games each player must choose one and only one alternative, reaching an ordered partition of the set of players. An extension of the Shapley value to this framework is studied.Shapley value, cooperative games with alternatives

Community pharmacy is the key to improving vitamin D levels

Introduction: Vitamin D is an essential micronutrient that participates in the body's fundamental physiological processes. The pharmacist should involve the patient in his medication adherence, leading to a change in the patient's attitude towards his medication and towards his health problem, in order to achieve the pharmacological objective set. Methods: Quasi-experimental multicenter study design with non-probabilistic convenience sampling. A pharmacist-led intervention in health education was carried out, divided in two groups, face-to-face interview and on-line survey, and the results were evaluated 3 months later to observe if there was any change in the patient's health status or in their vitamin D levels. Results: The study was conducted in four pharmacies through face-to-face interviews (n = 49 patients) and online surveys (n = 23). Pharmaceutical intervention improved habits of exercise (0.81 ± 1.44 days/week face-to-face interviews vs −0.09 ± 2.35 days/week online surveys (p = 0.048)). In face-to-face interviews, consumption of vitamin D-rich foods was increased (0.55 unit of tuna/week; p = 0.035 and 0.56 unit of avocado/week; p = 0.001) and was improved correct intake of vitamin D supplements (32.5% baseline to 69.8% at 3 months). The increase in 25-hydroxyvitamin D levels (11.5 ng/mL after 3 months (p = 0.021)) was correlated to salmon consumption (0.951; p = 0.013) and the improvement of quality of life was correlated to avocado consumption (1; p < 0.001). Conclusion: There are habits that improve vitamin D production such as increased physical activity, the correct use of vitamin D supplements and the consumption of foods with high vitamin D levels. The role of the pharmacist is crucial, involving the patient in the treatment making aware of the benefits for his/her health status of increasing vitamin D levels

Coalitional values for cooperative games withr alternatives

Cooperative games withr alternative, coalitional values, 90D12, 90D40,

Sun burn: photoprotection and treatment

La radiación ultravioleta es la principal responsable de los efectos nocivos de la radiación solar sobre el organismo. Las quemaduras solares, reacción aguda y visible de la exposición de la piel a dicha radiación, pueden cursar con lesiones cutáneas graves, destrucción celular y afectación de tejidos anexos, pudiéndose acompañar de edemas y pérdida de líquidos. La revisión tiene por objeto describir y valorar los efectos de la reactividad cutánea frente a la exposición a la radiación ultravioleta y clarifi car las distintas estrategias de prevención y/ o tratamiento de las quemaduras solares. Parece recomendable incidir en la necesidad de adoptar hábitos saludables frente a la exposición a la radiación ultravioleta, especialmente en los primeros 18 años de vida, así como realizar campañas educativas con el objetivo de prevenir la aparición y/ o agravamiento de enfermedades derivadas de dicha exposición.The harmful effects of solar radiation on the organism originate mainly from Ultraviolet rays. Sun burn, an acute and visible reaction arising from skin exposure to such radiation, can cause serious coetaneous lesions, cellular destruction and harmful effects on connective tissue, and may even be accompanied by oedema and loss of liquids. The aims of this work have been to describe and assess the effects of skin reactions to exposure to ultraviolet radiation, to elucidate on different prevention strategies and/or treatment of the sunburn. In general, it seems to be necessary to stress the importance of adopting healthy habits with regard to ultraviolet radiation exposure, especially important in fi rst eighteen y cars of live, and to carry out educational campaigns to prevent the appearance and/or worsening of conditions arising from such