Altered calcium signaling in platelets from nitric oxide-deficient hypertensive rats

BACKGROUND: In the present study we have analyzed the mechanisms of calcium entry and mobilization in platelets obtained from rats chronically treated with the nitric oxide synthesis inhibitor, N-nitro L-arginine methyl ester [L-NAME, 40 mg/kg/day, 5 days). The platelets were obtained the day of the experiment, washed and loaded with fura-2. The intracellular calcium levels were determined in suspension of cells by means of fluorescence spectroscopy. RESULTS: Basal calcium levels were always elevated in the platelets of the L-NAME-treated rats, both in the presence and in the absence of extracellular calcium. The administration of thrombin in the absence and in the presence of extracellular calcium induced important elevations in calcium levels that were always of greater magnitude in the platelets of the L-NAME-treated rats than in those of the controls. The addition of calcium to thapsigargin-treated platelets produced a massive elevation in calcium levels in both groups that was significantly greater in the platelets obtained from the hypertensive rats than in those of the controls. CONCLUSIONS: It is concluded that the arterial hypertension induced by the reduction of nitric oxide alters the regulation of platelet calcium levels so that elevated baseline levels and calcium entry and mobilization are enhanced. This could be the result of direct or indirect effects of the lack of nitric oxide synthesis in platelets or in other tissues

One year follow-up of a randomized trial with a dilemma-focused intervention for depression: Exploring an alternative to problem-oriented strategies

© 2018 Feixas et al.Cognitive behavioural therapy (CBT) is aimed to counteract cognitions and behaviours that are considered as dysfunctional. The aim of the study is to test whether the inclusion of a non-counteractive approach (dilemma-focused intervention, DFI) in combination with CBT group therapy will yield better short- and long-term outcomes than an intervention conducted entirely using CBT.Peer reviewedFinal Published versio

El oficio de defender los derechos humanos

Son pocas las personas que se dedican a velar por el respeto a las garantías individuales y la defensa los derechos humanos. Este solo hecho ya las hace excepcionales. Por esta misma razón, merecen un mayor reconocimiento debido a las dificultades, el alto costo personal e incluso los peligros que implica este oficio en una cultura donde la actuación del gobierno y otros actores involucrados en este tema es controversial, como es el caso de México. En este libro se presentan los testimonios de 18 personas que han dedicado su vida a defender a escala local, regional, nacional e internacional, los derechos de los demás. Son mujeres y hombres que comparten los motivos que les llevaron a ejercer esta actividad como una opción y estilo de vida, así como su particular forma de llevar a cabo su lucha y el recuento de sus logros y vicisitudes. A partir de estos testimonios, se analizan las características fundamentales de la génesis y práctica del oficio de ombudsman, en aras de entender su peculiar habitus, con la esperanza de impulsar a más hombres y mujeres a adoptar sin temor esta profesión de un gran impacto social que, sí, puede ser de alto riesgo, aunque se olvida ante la gran satisfacción personal que brinda a quien la desempeña.ITESO, A.C

Bacterial behavior on coated porous titanium substrates for biomedical applications

In this work, bacterial behavior on dense and porous titanium substrates is discussed. Porous titanium was fabricated by a space holder technique (using 50 vol%, NH4HCO3 with particle sizes between 250 and 355 μm). These substrates were coated by sulfonated PEEK (termed SPEEK). Characterization of the porous substrate was carried out using the Archimedes Method, Image Analysis, and three-dimensional X-ray Micro-Computed Tomography (including total and interconnected porosity, equivalent diameter, and pore shape factor), as well as mechanical characterization (specifically stiffness and yield strength). A detailed study was performed here to investigate the influence of substrate porosity on the adhesion and proliferation of E. coli, MRSA, and P. aeruginosa (common causes of orthopedic device-associated infections). Bacterial colonization was examined in terms of the initial bacterial concentration, as well as bacterial adherence to and growth on the surface and inside the pores. Results suggest that fully dense titanium supported the least bacterial colonization, while the porous titanium promoted bacterial growth in the medium and inside the cavities. Furthermore, the SPEEK coating deposited onto the samples inhibited bacteria growth inside the porous materials. In this manner, this study showed for the first time that SPEEK could have potential antibacterial properties to offset the increase in bacteria growth commonly observed in porous materials.Junta de Andalucía-FEDER (Spain) Ref. P12-TEP-1401Ministry of Economy and Competitiveness of Spain, MAT2015-71284-

Beneficial Effects of Different Flavonoids on Vascular and Renal Function in L-NAME Hypertensive Rats

Background: we have evaluated the antihypertensive effect of several flavonoid extracts in a rat model of arterial hypertension caused by chronic administration (6 weeks) of the nitric oxide synthesis inhibitor, L-NAME. Methods: Sprague Dawley rats received L-NAME alone or L-NAME plus flavonoid-rich vegetal extracts (Lemon, Grapefruit + Bitter Orange, and Cocoa) or purified flavonoids (Apigenin and Diosmin) for 6 weeks. Results: L-NAME treatment resulted in a marked elevation of blood pressure, and treatment with Apigenin, Lemon Extract, and Grapefruit + Bitter Orange extracts significantly reduced the elevated blood pressure of these animals. Apigenin and some of these flavonoids also ameliorated nitric oxide-dependent and -independent aortic vasodilation and elevated nitrite urinary excretion. End-organ abnormalities such as cardiac infarcts, hyaline arteriopathy and fibrinoid necrosis in coronary arteries and aorta were improved by these treatments, reducing the end-organ vascular damage. Conclusions: the flavonoids included in this study, specially apigenin, may be used as functional food ingredients with potential therapeutic benefit in arterial hypertension.This report was supported by a grant from the National Spanish R&D Program CENIT of the Spanish Ministry of Science and Technology denominated “Industrial research diets and food with specific features for the elderly”, CEN-20091006; Acronym: SENIFOOD.We have not received funds for covering the costs to publish in open access. We acknowledge the assistance of Justin Davis with the English language

Telomere Length Shows No Association with BRCA1 and BRCA2 Mutation Status

This study aimed to determine whether telomere length (TL) is a marker of cancer risk or genetic status amongst two cohorts of BRCA1 and BRCA2 mutation carriers and controls. The first group was a prospective set of 665 male BRCA1/2 mutation carriers and controls (mean age 53 years), all healthy at time of enrolment and blood donation, 21 of whom have developed prostate cancer whilst on study. The second group consisted of 283 female BRCA1/2 mutation carriers and controls (mean age 48 years), half of whom had been diagnosed with breast cancer prior to enrolment. TL was quantified by qPCR from DNA extracted from peripheral blood lymphocytes. Weighted and unweighted Cox regressions and linear regression analyses were used to assess whether TL was associated with BRCA1/2 mutation status or cancer risk. We found no evidence for association between developing cancer or being a BRCA1 or BRCA2 mutation carrier and telomere length. It is the first study investigating TL in a cohort of genetically predisposed males and although TL and BRCA status was previously studied in females our results don't support the previous finding of association between hereditary breast cancer and shorter TL

Moderate Effect of Flavonoids on Vascular and Renal Function in Spontaneously Hypertensive Rats

Many studies have shown that flavonoids are effective as antihypertensive drugs in arterial hypertension. In the present work, we have analyzed the effects of some flavonoid extracts in the spontaneous hypertensive rat model (SHR). An important feature of this study is that we have used a low dose, far from those that are usually applied in human therapy or experimental animals, a dose that responded to the criterion of a potential future commercial use in human subjects. Treatments were carried out for 6 and 12 weeks in two groups of SHR rats, which received apigenin, lemon extract, grapefruit + bitter orange (GBO) extracts, and cocoa extract. Captopril was used as a positive control in the SHR group treated for 6 weeks (SHR6) and Diosmin was used as the industry reference in the SHR group treated for 12 weeks (SHR12). Captopril and GBO extracts lowered the high arterial pressure of the SHR6 animals, but none of the extracts were effective in the SHR12 group. Apigenin, lemon extract (LE), GBO, and captopril also improved aortic vascular relaxation and increased plasma and urinary excretion of nitrites, but only in the SHR6 group. Kidney and urinary thiobarbituric acid reactive substances (TBARS) were also significantly reduced by GBO in the SHR6 rats. Apigenin also improved vascular relaxation in the SHR12 group and all the flavonoids studied reduced urinary thiobarbituric acid reactive substances (TBARS) excretion and proteinuria. Vascular abnormalities, such as lumen/wall ratio in heart arteries and thoracic aorta, were moderately improved by these treatments in the SHR6 group. In conclusion, the flavonoid-rich extracts included in this study, especially apigenin, LE and GBO improved vascular vasodilatory function of young adult SHRs but only the GBO-treated rats benefited from a reduction in blood pressure. These extracts may be used as functional food ingredients with a moderate therapeutic benefit, especially in the early phases of arterial hypertension.This report was supported by a grant from the National Spanish R & D Program CENIT of the Spanish Ministry of Science and Technology denominated “Industrial research diets and food with specific features for the elderly”, CEN-20091006; Acronym: SENIFOOD

La humanización del “oficio de defender los Derechos Humanos” desde la práctica de las defensoras

El presente artículo analiza la problemática en torno al género y al debate sobre los principios masculinos y femeninos como fuentes de construcción de lo humano. Examina también las alianzas y oposiciones entre los diferentes feminismos y masculinidades. Finalmente expone, desde una perspectiva de género, la cuestión de la vulnerabilidad de los/as defensores de derechos humanos. La tesis principal versa sobre la posibilidad de humanizar la defensa de los derechos humanos al incorporar los principios masculinos y femeninos en la práctica del oficio

Preparation and in vitro evaluation of 177Lu-iPSMA-RGD as a new heterobivalent radiopharmaceutical

This study aimed to synthesize a new 177Lu-iPSMA-RGD heterobivalent radiopharmaceutical, as well as to assess the in vitro radiopharmaceutical potential to target cancer cells overexpressing PSMA and a(v) b(3) integrins. The radiotracer prepared with a radiochemical purity of 98.8 ± 1.0% showed stability in human serum, specific recognition with suitable affinity to PSMA and a(v)b(3) integrins, and capability to inhibit cancer cell proliferation and VEGF signaling (antiangiogenic effect). Results warrant further preclinical studies to establish the 177Lu-iPSMA-RGD potential as a dual therapeutic radiopharmaceutical.CONACyT-CB-2016-01-28152