University of Valencia
Repositori d'Objectes Digitals per a l'Ensenyament la Recerca i la CulturaNot a member yet
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β2- and β1-Adrenoceptor Expression Exhibits a Common Regulatory Pattern With GRK2 and GRK5 in Human and Animal Models of Cardiovascular Diseases
No full textTo explore if genic expression of β1- or β2-adrenoceptors (ARs) exhibits a common regulatory pattern with G protein-coupled receptor kinase (GRK) 2, GRK3, or GRK5 expression, we determined messenger RNA levels for these genes in different tissues from human and animal models of cardiovascular disease. We measured genic expression by qRT polymerase chain reaction in the left and right ventricles or peripheral blood mononuclear cells from healthy (n = 21), hypertensive (n = 20), heart failure (n = 24), and heart transplanted patients (n = 17) or in left ventricle, peripheral blood mononuclear cells, and kidney from spontaneously hypertensive rats or L-N-methyl-arginine-induced hypertensive rats and their respective controls (n = 4-5). In diseased versus healthy subjects and rats, parallel changes in messenger RNA levels of GRK2 and β2-AR or GRK5 and β1-AR were observed in each territory. Therefore, without excluding other regulatory mechanisms, the parallelism observed suggests a common regulatory pattern for the β1-AR/GRK5 and β2-AR/GRK2 genes, which is independent of cellular type or pathology. This highlights the need to focus not only on GRKs but also on β1- or β2-AR changes to completely understand the involvement of β-AR/GRK pathways in cardiovascular diseases
Dose-response of talus mobilizations in weight bearing ankle dorsiflexion ROM of the older adults with limited ankle mobility: A randomized clinical trial
No full textBackground: Although manual therapy is an effective technique for increasing ankle range of motion, the doseresponse required is unclear.Objective: To find out what number of sessions of talus mobilizations will induce a detectable change in weight bearing ankle dorsiflexion range of motion of older adults with limited ankle mobility.Design: Four-arm randomized clinical trial.Setting: Community-dwelling.Methods: 62 older adults; aged over 60; with ankle dorsiflexion ROM below 35 degrees. Four groups received from one to four treatment sessions. Each session consisted of 3 mobilizations of 30 s, with of the talus in anteroposterior glide, with a rest of 30 s. Grade IV mobilizations were applied to target the accessory movement of the ankle up to the resistance offered by periarticular tissues. The Lunge test was used to measure weight bearing ankle dorsiflexion.Results: The four groups increased their ankle mobility after one session, but two sessions were needed to overcome the established 4.7 degrees' threshold, regardless of group. Only those participants who received four sessions maintained the improvements for 8 weeks. Conclusions: Two sessions of talus mobilizations are effective in improving weight bearing ankle dorsiflexion ROM. It will be necessary to deliver four sessions of treatment if these improvements are to be maintained for at least 8 weeks.Clinical trial registration number: NCT04563663
Vías de protección del crédito y clases de acreedores en las modificaciones estructurales transfronterizas intracomunitarias
No full textEl presente trabajo aborda las diferentes vías para la protección de los créditos en la Directiva (UE) 2017/1132, tras las modificaciones introducidas en la Directiva (UE) 2019/2121 del Parlamento Europeo y del Consejo de 27 de noviembre de 2019 en lo que atañe a las transformaciones, fusiones y escisiones transfronterizas intracomunitarias. La necesidad de respetar el derecho primario de las sociedades a su libre establecimiento dentro del mercado interior de la Unión Europea contrasta con la necesidad de garantizar adecuadamente los derechos de los acreedores dignos de protección. A su vez, las distintas clases de acreedores y su distinta posición jurídica, especialmente cuando se trate de aquellos públicos, merecen ser objeto de consideración en este ámbito, en orden a la emisión de los certificados previos de la operación transfronteriza por la autoridad nacional competente. Igualmente, otras vías de protección del crédito, a través de la acción pauliana o del levantamiento del velo de la personalidad jurídica, no obstante su carácter excepcional, son objeto de atención a estos efecto
La sucesión de empresas en las contratas y subcontratas:una propuesta de reforma normativa
No full textEl objeto de este trabajo es revisar críticamente la institución laboral de la sucesión de empresa aplicada en el ámbito de las contratas y concesiones de obras y servicios, detectando las principales distorsiones y problemas aplicativos que existen. Tras este diagnóstico previo, se formula una propuesta de lege ferenda que, al menos, se espera que pueda aportar nuevos elementos de valoración para el debate científico. Se propone una revisión del marco normativo interno compatible con los objetivos y finalidades de la Directiva 2001/23/CE, en tanto que es más pragmático y factible que revisar la disposición europea
The Intricate Role of Non-Coding RNAs in Sepsis-Associated Disseminated Intravascular Coagulation
No full textAbstract: Disseminated Intravascular Coagulation (DIC) is a type of tissue and organ dysregulation in sepsis, due mainly to the effect of the inflammation on the coagulation system. Unfortunately, the underlying molecular mechanisms that lead to this disorder are not fully understood. Moreover, current biomarkers for DIC, including biological and clinical parameters, generally provide a poor diagnosis and prognosis. In recent years, non-coding RNAs have been studied as promising and robust biomarkers for a variety of diseases. Thus, their potential in the diagnosis and prognosis of DIC should be further studied. Specifically, the relationship between the coagulation cascade and non-coding RNAs should be established. In this review, microRNAs, long non-coding RNAs, and circular RNAs are studied in relation to DIC. Specifically, the axis between these non-coding RNAs and the corresponding affected pathway has been identified, including inflammation, alteration of the coagulation cascade, and endothelial damage. The main affected pathway identified is PI3K/AKT/mTOR axis, where several ncRNAs participate in its regulation, including miR-122-5p which is sponged by circ_0005963, ciRS-122, and circPTN, and miR-19a-3p which is modulated by circ_0000096 and circ_0063425. Additionally, both miR-223 and miR-24 were found to affect the PI3K/AKT pathway and were regulated by lncGAS5 and lncKCNQ1OT1, respectively. Thus, this work provides a useful pipeline of inter-connected ncRNAs that future research on their impact on DIC can further explore
Kinetics and spatial distribution of OTA in Aspergillus carbonarius cultures
No full textThe aim of this study was to characterize Ochratoxin A (OTA) production by Aspergillus carbonarius under different environmental conditions, and to elucidate the diffusion capacity of OTA throughout synthetic medium. One strain belonging to the species A. carbonarius isolated from vine dried fruit was single-point inoculated onto triplicate synthetic nutrient medium plates at two water activities (0.92 and 0.97) and two temperatures (20 and 30 1C). Daily radii were measured and OTA production was tested after 4, 7, 10, 14 and 18 days of incubation at four distances from the centre of colony (1-4 cm). OTA production was detected mainly at 0.97aw. Earlier production was detected at 30 1C (optimum for growth), whereas maximum OTA concentrations were found at 20 1C. OTA production was detected from mycelium that was only a few days old and attained its optimum when mycelium was 4-7 days old at 0.97aw. OTA diffusion was observed at 0.92aw and 20 1C. Thus OTA production is discernable in young A. carbonarius mycelium and diffusion of the toxin has been shown to occur in a solid substrate
A Surgical Model for Isolating the Pig Liver in vivo for Gene Therapy
No full textSeveral studies report results that suggest the need of vascularization blocking for efficient gene transfer to the liver, especially in nonviral gene therapy. In this study, we describe a surgical strategy for in vivo isolation of the pig liver, resulting in a vascular watertight organ that allows the evaluation of several gene injection conditions. The hepatic artery and portal, suprahepatic and infrahepatic cava veins were dissected. Then, liver vascularization was excluded for 5-7 min. In that time, we first injected 200 ml saline solution containing the p3c-eGFP plasmid (20 µg/ml) simultaneously through two different catheters placed in the portal and cava veins, respectively. Vital constants were monitored during the surgery to assess the safety of the procedure. Basal systolic/diastolic blood pressures were 92.8/63.2 mm Hg and dropped to 40.7/31.3 mm Hg at the end of vascular exclusion; the mean basal heart rate was 58 bpm, reaching 95 bpm when the blood pressure was low. Oxygen saturation was maintained above 98% during the intervention, and no relevant changes were observed in the ECG tracing. Peak plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) levels were observed after 24 h (151 and 57 IU, respectively). These values were higher, but not relevant, in 60 ml/s injection than in 20 ml/s injection. Efficiency of gene transfer was studied with simultaneous (cava and portal veins) injection of eGFP gene at flow rates of 20 and 60 ml/s. Liver tissue samples were collected 24 h after injection and qPCR was carried out on each lobe sample. The results confirmed the efficiency of the procedure. Gene delivery differed between 20 ml/s (9.9-31.0 eGFP DNA copies/100 pg of total DNA) and 60 ml/s injections (0.6-1.1 eGFP DNA copies/100 pg of total DNA). Gene transcription showed no significant differences between 20 ml/s (15,701.8-21,475.8 eGFP RNA copies/100 ng of total RNA) and 60 ml/s (12,014-36,371 eGFP RNA copies/100 ng of total RNA). The procedure is not harmful for animals and it offers a wide range of gene delivery options because it allows different perfusion ways (anterograde and retrograde) and different flow rates to determine the optimal conditions of gene transfer. This strategy permits the use of cell therapy and viral or non-viral liver gene therapy, especially appropriated to a wide variety of inherited or acquired diseases because of the liver's ability to produce and deliver proteins to the bloodstream
Nasal immunization of mice with a rotavirus DNA vaccine that induces protective intestinal IgA antibodies
No full textDNA vaccination using a plasmid encoding the rotavirus inner capsid VP6 has been explored in the mouse model of rotavirus infection. BALB/c mice were immunized with a VP6 DNA vaccine by the intramuscular, nasal and oral routes. VP6 DNA vaccination by the nasal and oral routes induced the production of anti-VP6 IgA antibodies by intestinal lymphoid cells. Intramuscular DNA injection stimulated the production of serum anti-VP6 IgG but not serum anti-VP6 IgA antibodies. Protection against shedding of rotaviruses in stools after oral challenge with the murine EDIM rotavirus strain was investigated in the immunized mice. A significant reduction in the level of rotavirus antigen shedding was demonstrated in those mice immunized at mucosal surfaces, both orally and nasally, with the VP6 DNA vaccine. Intramuscular DNA immunization, which elicited serum anti-VP6 IgG responses but not virus-specific intestinal IgA antibodies, did not provide significant protection against rotavirus challenge. ©2004 Elsevier Ltd. All rights reserved
Potentially harmful elements pollute soil and vegetation around the Atrevida mine (Tarragona, NE Spain)
No full textMining activity is one of the main sources to pollute soil, water and plants. An analysis of soil and plant samples around the Atrevida mining area in Catalonia (NE Spain) was preformed to determine potentially harmful elements (PHEs). Soil and plant samples were taken at eight locations around the mining area. The topsoil (0-15 cm) samples were analysed for physico-chemical properties by standard methods, by ICP-MS for Cd, Co, Cr, Cu, Fe, Ni, Pb and Zn, and were microwave-digested. Plant, root and shoot samples were digested separately, and heavy metals were analysed by AAS. Translocation factor (TF), biological concentration factor (BCF) and biological accumulation factor (BAF) were determined to assess the tolerance strategies developed by native species and to evaluate their potential for phytoremediation purposes. Soil pH was generally acid (5.48-6.72), with high soil organic matter (SOM) content and a sandy loamy or loamy texture. According to the agricultural soil values in southern Europe, our PHEs concentrations exceeded the toxicity thresholds. The highest root content of the most studied PHEs appeared in Thymus vulgaris L. and Festuca ovina L., while Biscutella laevigata L. accumulated more PHEs in shoots. The TF values were > 1 in B. laevigata L., but BAF obtained < 1, except Pb. B. laevigata L., and can be considered potentially useful for phytoremediation for having the capacity to restrict the accumulation of large PHEs amounts in roots and Pb translocation to shoots
Influence of Demographic and Lifestyle Variables on Plasma Magnesium Concentrations and Their Associations with Cardiovascular Risk Factors in a Mediterranean Population.
No full textSeveral studies have shown that a low magnesium (Mg) intake in the diet is associated with greater cardiovascular risk and greater risk of diabetes. However, the results are not consistent in all populations. To minimize the biases derived from diet measurement, more objective biomarkers of magnesium status have been proposed. Although there is still no ideal biomarker for Mg, several studies have shown that plasma Mg concentrations could be a relatively acceptable biomarker for cardiovascular risk assessment. However, further studies are required to better characterize this marker in different populations. Our aim was to analyze the association between plasma Mg concentrations (measured through inductively coupled plasma mass spectrometry (ICP-MS)) methods, and cardiovascular risk factors in individuals from a general Mediterranean population (aged 18-80 years). The influence of demographic and lifestyle variables, including adherence to the Mediterranean diet, on plasma Mg concentrations was analyzed. The mean Mg level of the population studied was 0.77 ± 0.08 mmol/L, the prevalence of hypomagnesemia ( 0.05). We found a statistically significant association between plasma Mg concentrations and the prevalence of type-2 diabetes (0.77 ± 0.08 mmol/L in non-diabetics versus 0.73 ± 0.13 mmol/L in diabetics; p = 0.009). Despite the low prevalence of type-2 diabetes in this population (11.24% in subjects with hypomagnesemia versus 3.91%, in normomagnesemia; p = 0.005), hypomagnesemia was associated with greater odds of being diabetic in comparison with normomagnesemia (OR = 3.36; p = 0.016, even after adjustment for sex, age, obesity, and medications). On the other hand, no statistically significant association of plasma Mg concentrations with obesity, hypertension, fasting triglycerides, HDL-cholesterol or uric acid was found. However, in contrast to what was initially expected, a statistically significant association was found between plasma Mg concentrations (basically in the highest quartile) and greater total cholesterol (p < 0.05) and LDL-cholesterol concentrations (p < 0.05). In conclusion, our results contribute to increasing the evidence gathered by numerous studies on the inverse association between hypomagnesemia and type-2 diabetes, as well as to the observation, previously reported in some studies, of a direct association with hypercholesterolemia. This paradoxical link should be deeply investigated in further studies