Potassium channels are involved in testosterone-induced vasorelaxation of human umbilical artery

Recent studies have shown that testosterone induces relaxation of different arteries, although the mechanism of this action is still under debate. We investigated the involvement of potassium channels in this mechanism. Using standard organ bath techniques, rings of human umbilical arteries (HUA) without endothelium were contracted by serotonin (5-HT, 1 μM), histamine (10 μM) and potassium chloride (KCl, 30 and 60 mM), and the vasorelaxant effect of testosterone was analysed. Testosterone (100 μM) relaxed human umbilical arteries contracted with 5-HT (30.1±3.2%), histamine (55.1±2.6%), KCl 30 mM (52.9±8.3%) and KCl 60 mM (54.8±6.3%). Flutamide (10 μM), an inhibitor of classical intracellular testosterone receptor, and glibenclamide, an ATP-sensitive potassium-channels (KATP) inhibitor, did not influence the testosterone relaxant effect. 4-aminopyridine, a voltagesensitive potassium-channels (Kv) inhibitor, decreased the effect of testosterone on histamine- and 5-HT-contracted arteries. Tetraethylammonium (TEA), which inhibits Kv channels and large-conductance Ca2+-activated potassium channels (BKCa), decreased the effect of testosterone on KCl (60 mM)-contracted and 5-HT-contracted HUA. In conclusion, testosterone induces relaxation of HUA, and this effect does not appear to be mediated via a classic intracellular testosterone receptor-dependent mechanism. Our results suggest that this relaxation is partially mediated by activation of BKCa and KV channels. The involvement of these two channels in testosterone-relaxant mechanism is dependent on the pathways activated by the contractile agent used

Effects of trans- and cis-resveratrol on Ca2+ handling in A7r5 vascular myocytes

Although the natural polyphenol resveratrol posses a direct vasorelaxant effect, its effects on cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) in vascular cells remain still unclear. Here, we have investigated the effects of the isomers trans- and cis-resveratrol on agonist- and high-K(+)-induced [Ca(2+)](i) increases and on voltage-activated transmembrane Ca(2+) fluxes using imaging and patch-clamp techniques in vascular A7r5 myocytes. Arginine vasopressin (AVP) or angiotensin II caused a biphasic increase in [Ca(2+)](i) that was reduced by preincubation with trans-resveratrol and cis-resveratrol. Both isomers also reduced the agonist-induced increase in [Ca(2+)](i) in absence of extracellular Ca(2+). In high-K(+) Ca(2+)-free solution, reintroduction of Ca(2+) caused a sustained rise in [Ca(2+)](i) that was reduced by preincubation with trans-resveratrol or cis-resveratrol. When the isomers were applied during the plateau phase of the agonist- or the high-K(+)-induced response, a biphasic change in [Ca(2+)](i) was observed: a transient reduction of the plateau (10 min). Finally, trans-resveratrol and cis-resveratrol inhibited voltage-dependent L-type Ca(2+) currents (I(Ca(L))). In conclusion, resveratrol isomers exert a dual effect on [Ca(2+)](i) handling in A7r5 myocytes: 1) a blockade of I(Ca(L)) and 2) an increase in [Ca(2+)](i) by depletion of intracellular Ca(2+) stores (which interferes with the agonist-induced release of intracellular Ca(2+)) and influx of Ca(2+), mainly due to activation of capacitative Ca(2+) entry, although other Ca(2+)-permeable channels are also involved. Taken together, these effects may explain, in part, the endothelium-independent vasorelaxant effects of resveratrol in rat aorta

PDE4 and PDE5 regulate cyclic nucleotides relaxing effects in human umbilical arteries

Cyclic nucleotides (cAMP and cGMP) are the main second messengers linked to vasodilatation. They are synthesized by cyclases and degraded by different types of phosphodiesterases (PDE). The effect of PDE inhibition and cyclases stimulation on 5-hydroxytryptamine (5-HT; 1 microM) and histamine (10 microM) contracted arteries was analysed. Stimulation of guanylate cyclase or adenylate cyclase relaxed the histamine- and 5-HT-induced contractions indicating that intracellular increase of cyclic nucleotides leads to vasodilatation of the human umbilical artery. We investigated the role of different PDE families in the regulation of this effect. The presence of the different PDE types in human umbilical artery smooth muscle was analysed by RT-PCR and the expression of PDE1B, PDE3A, PDE3B, PDE4C, PDE4D and PDE5A was detected. The unspecific PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX; 50 microM) relaxed histamine-contracted human umbilical artery on 47.4+/-7.2%. This effect seems to be due to PDE4 and PDE5 inhibition because among the selective PDE inhibitors used only the PDE4 inhibitor (rolipram; 1 microM) and the PDE5 inhibitors (dipyridamole and T0156; 3 microM and 1 microM respectively) induced significant relaxation (39.0+/-8.7, 30.4+/-6.0 and 36.3+/-2.8 respectively). IBMX, dipyridamole and T0156 produced similar relaxation on 5-HT-induced contraction. After forskolin, the addition of IBMX or rolipram increased the effect of the adenylate cyclase stimulator and almost completely relaxed the human umbilical artery contracted by histamine (92.5+/-4.9 and 90.9+/-4.7 respectively), suggesting a main role of PDE4. The data obtained with 5-HT contracted arteries confirmed this, because only rolipram and IBMX significantly increased the forskolin vasodilator effect. The administration of dipyridamole and T0156 after sodium nitroprusside (SNP) induced a significant increase of the SNP relaxant effect on histamine-contracted arteries, but PDE1 and PDE3 inhibition did not increase the effect of the guanylate cyclase stimulator. Similar effects were obtained in 5-HT contracted arteries, the SNP induced relaxation was increased by the PDE5 inhibition, but not by PDE1 or PDE3 inhibition. In summary, our results demonstrate that: 1) the increase of cAMP and/or cGMP levels induces relaxation of the human umbilical vascular smooth muscle; 2) four families of PDE are expressed in this smooth muscle: PDE1, PDE3, PDE4 and PDE5; 3) between these families, PDE4 and PDE5 are the key enzymes involved in the regulation of the relaxation associated to cAMP and cGMP, respectively

Inhibidores de las Janus Kinasas en el tratamiento de las dermatitis caninas

Las dermatitis alérgicas constituyen uno de los grupos de enfermedades inflamatorias de la piel de mayor relevancia clínica en la especie canina. Las tres más significativas son la Dermatitis atópica canina (DAC), la Dermatitis por hipersensibilidad alimentaria y la Dermatitis por picadura de pulga.La DAC es una enfermedad inflamatoria crónica de la piel que afecta a muchos perros en todo el mundo. Los síntomas incluyen prurito, enrojecimiento, inflamación y lesiones cutáneas, y pueden tener un impacto significativo en la calidad de vida del perro y su propietario.Aunque existen varias opciones de tratamiento disponibles para la DAC, todavía hay mucho por hacer para mejorar la eficacia y la seguridad de estos tratamientos.Hasta hace algo más de veinte años, los fármacos de acción más rápida y eficaz frente a las DAC eran los corticosteroides, pero los efectos secundarios de estas drogas son un problema que se trata de evitar buscando otras alternativas.Los inhibidores de Janus Kinasas constituyen unas nuevas moléculas que inhiben la activación de diversas interleucinas proinflamatorias y que han dejado atrás otros tratamientos convencionales, como los corticosteroides o los inhibidores de calcineurina. Estos son capaces de inhibir selectivamente las citoquinas dependientes de las JAK1 y, en menor grado, de las JAK2, lo que puede reducir los efectos de las citoquinas proinflamatorias y proalergénicas. Además, los inhibidores de Janus Kinasas han demostrado su eficacia en el tratamiento de enfermedades inflamatorias pruriginosas, la rinitis alérgica y el asma.<br /

A Survey on IEEE 1588 Implementation for RISC-V Low-Power Embedded Devices

IEEE 1588, also known as the Precision Time Protocol (PTP), is a standard protocol for clock synchronization in distributed systems. While it is not architecture-specific, implementing IEEE 1588 on Reduced Instruction Set Computer-V (RISC-V) low-power embedded devices demands considering the system requirements and available resources. This paper explores various approaches and techniques to achieve accurate time synchronization in such instruments. The analysis covers software and hardware implementations, discussing each method’s challenges, benefits, and trade-offs. By examining the state-of-the-art in this field, this paper provides valuable insights and guidance for researchers and engineers working on time-critical applications in RISC-V-based embedded systems, aiding in selecting the most-suitable stack for their designs.This work was partially supported by the ECSEL Joint Undertaking in the H2020 project IMOCO4.E, grant agreement No.10100731, and by the Basque Government within the fund for research groups of the Basque University System IT1440-22 and KK-2023/00015

Primer registro del nido de abeja fósil Elipsoideichnus meyeri de Argentina (Colón, provincia de Entre Ríos)

Se presenta el primer registro de la traza fósil Elipsoideichnus meyeri Roselli, 1987, de afloramientos de la cantera Prefectura Naval Argentina, Parque Nacional El Palmar, Colón (provincia de Entre Ríos), Argentina. E. meyeri consiste en un nido de abeja fósil helicoidal, hasta la fecha solo registrado en la Formación Asencio (Cuenca Norte) del suroeste de Uruguay. El nuevo espécimen fue encontrado en rocas tradicionalmente asignadas a la Formación Puerto Yeruá (Cuenca Chaco Paraná), consideradas del Cretácico Superior sobre la base del contenido paleontológico de estratos correlativos en el área, conformado por restos de dinosaurios y plantas. Sin embargo, el marco estratigráfico más confiable para la localidad de estudio debería mantener los nombres litoestratigráficos de la Cuenca Norte de Uruguay, siendo el principal argumento para la presencia de una discordancia regional entre las formaciones Guichón y Mercedes, lo que imposibilita la asignación de este nuevo registro a la Formación Puerto Yeruá. Las facies observadas y este nuevo registro en sí permitieron la asignación preliminar de los estratos portadores de E. meyeri de la Prefectura Naval Argentina a la Formación Asencio, reforzado por el registro que aquí se presenta ya que no existe evidencia tafonómica que apoye un transporte significativo horizontal o vertical del mismo. Sobre la asignación cronoestratigráfica de este registro, no existen elementos concluyentes para ubicarlo dentro del Cretácico Superior o Eoceno, siendo un hecho aún en análisis. Este registro amplía la distribución geográfica de este icnotaxón, permitiendo el desarrollo de nuevas investigaciones en el área, reabriendo interrogantes relacionados con la paleobiología y la cronoestratigrafía de abejas antiguas en esta zona del sur de América del Sur.We present the first record of the trace fossil Elipsoideichnus meyeri Roselli, 1987, from outcrops of the Prefectura Naval Argentina quarry, Parque Nacional El Palmar, Colón (Entre Ríos province), Argentina. E. meyeri consists of a singular helicoidal fossil bee nest, to date only recorded from the Asencio Formation (Norte Basin) of southwestern Uruguay. The new specimen came from rocks traditionally assigned to the Puerto Yeruá Formation (Chaco Paraná Basin), considered Upper Cretaceous in age based on paleontological content of correlative strata in the area, composed of dinosaur and plant remains. However, the most reliable stratigraphic framework for the studied locality should keep the lithostratigraphic names of the Norte Basin of Uruguay, being the main argument for the presence of a regional unconformity between Guichón and Mercedes formations, which precludes the assignment of this new record to the Puerto Yeruá Formation. Observed facies and this new record itself allowed the preliminary assignation of Prefectura Naval Argentina E. meyeri-hosting strata to the Asencio Formation, which is reinforced by the record presented here itself due to there are no taphonomic evidence supporting significant transport horizontally or vertically. About the chronostratigraphic assignment of this record, there are no concluding elements to locate it within the Upper Cretaceous or Eocene, being a matter of fact and still in flux. This record expands the geographical distribution of this ichnotaxon, allowing the development of further research in this area and, re-opening questions related to the palaeobiology and chronostratigraphy of ancient bees in this area of southern South America.Fil: Cónsole Gonella, Carlos Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Correlación Geológica. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Departamento de Geología. Cátedra Geología Estructural. Instituto Superior de Correlación Geológica; ArgentinaFil: Verde, Mariano. Universidad de la República; UruguayFil: de Valais, Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Apesteguía, Sebastián. Fundación de Historia Natural Félix de Azara; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Díaz Martínez, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Gallina, Pablo Ariel. Universidad Maimónides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gianechini, Federico Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Citton, Paolo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Aceñolaza, Florencio Gilberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Correlación Geológica. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Departamento de Geología. Cátedra Geología Estructural. Instituto Superior de Correlación Geológica; Argentin

Primer registro del nido de abeja fósil Elipsoideichnus meyeri de Argentina (Colón, provincia de Entre Ríos)

Se presenta el primer registro de la traza fósil Elipsoideichnus meyeri Roselli, 1987, de afloramientos de la cantera Prefectura Naval Argentina, Parque Nacional El Palmar, Colón (provincia de Entre Ríos), Argentina. E. meyeri consiste en un nido de abeja fósil helicoidal, hasta la fecha solo registrado en la Formación Asencio (Cuenca Norte) del suroeste de Uruguay. El nuevo espécimen fue encontrado en rocas tradicionalmente asignadas a la Formación Puerto Yeruá (Cuenca Chaco Paraná), consideradas del Cretácico Superior sobre la base del contenido paleontológico de estratos correlativos en el área, conformado por restos de dinosaurios y plantas. Sin embargo, el marco estratigráfico más confiable para la localidad de estudio debería mantener los nombres litoestratigráficos de la Cuenca Norte de Uruguay, siendo el principal argumento para la presencia de una discordancia regional entre las formaciones Guichón y Mercedes, lo que imposibilita la asignación de este nuevo registro a la Formación Puerto Yeruá. Las facies observadas y este nuevo registro en sí permitieron la asignación preliminar de los estratos portadores de E. meyeri de la Prefectura Naval Argentina a la Formación Asencio, reforzado por el registro que aquí se presenta ya que no existe evidencia tafonómica que apoye un transporte significativo horizontal o vertical del mismo. Sobre la asignación cronoestratigráfica de este registro, no existen elementos concluyentes para ubicarlo dentro del Cretácico Superior o Eoceno, siendo un hecho aún en análisis. Este registro amplía la distribución geográfica de este icnotaxón, permitiendo el desarrollo de nuevas investigaciones en el área, reabriendo interrogantes relacionados con la paleobiología y la cronoestratigrafía de abejas antiguas en esta zona del sur de América del Sur.We present the first record of the trace fossil Elipsoideichnus meyeri Roselli, 1987, from outcrops of the Prefectura Naval Argentina quarry, Parque Nacional El Palmar, Colón (Entre Ríos province), Argentina. E. meyeri consists of a singular helicoidal fossil bee nest, to date only recorded from the Asencio Formation (Norte Basin) of southwestern Uruguay. The new specimen came from rocks traditionally assigned to the Puerto Yeruá Formation (Chaco Paraná Basin), considered Upper Cretaceous in age based on paleontological content of correlative strata in the area, composed of dinosaur and plant remains. However, the most reliable stratigraphic framework for the studied locality should keep the lithostratigraphic names of the Norte Basin of Uruguay, being the main argument for the presence of a regional unconformity between Guichón and Mercedes formations, which precludes the assignment of this new record to the Puerto Yeruá Formation. Observed facies and this new record itself allowed the preliminary assignation of Prefectura Naval Argentina E. meyeri-hosting strata to the Asencio Formation, which is reinforced by the record presented here itself due to there are no taphonomic evidence supporting significant transport horizontally or vertically. About the chronostratigraphic assignment of this record, there are no concluding elements to locate it within the Upper Cretaceous or Eocene, being a matter of fact and still in flux. This record expands the geographical distribution of this ichnotaxon, allowing the development of further research in this area and, re-opening questions related to the palaeobiology and chronostratigraphy of ancient bees in this area of southern South America.Fil: Cónsole Gonella, Carlos Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Correlación Geológica. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Departamento de Geología. Cátedra Geología Estructural. Instituto Superior de Correlación Geológica; ArgentinaFil: Verde, Mariano. Universidad de la República; UruguayFil: de Valais, Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Apesteguía, Sebastián. Fundación de Historia Natural Félix de Azara; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Díaz Martínez, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Gallina, Pablo Ariel. Universidad Maimónides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gianechini, Federico Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Citton, Paolo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Aceñolaza, Florencio Gilberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Correlación Geológica. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Departamento de Geología. Cátedra Geología Estructural. Instituto Superior de Correlación Geológica; Argentin

CD45RA, CD8β, and IFNγ Are Potential Immune Biomarkers of Human Cognitive Function

There is increasing evidence that in humans the adaptive immunological system can influence cognitive functions of the brain. We have undertaken a comprehensive immunological analysis of lymphocyte and monocyte populations as well as of HLA molecules expression in a cohort of elderly volunteers (age range, 64-101) differing in their cognitive status. Hereby, we report on the identification of a novel signature in cognitively impaired elderly characterized by: (1) elevated percentages of CD8+ T effector-memory cells expressing high levels of the CD45RA phosphate receptor (Temra hi); (2) high percentages of CD8+ T cells expressing high levels of the CD8β chain (CD8βhi); (3) augmented production of IFNγ by in vitro activated CD4+ T cells. Noteworthy, CD3+CD8+ Temra hi and CD3+CD8βhi cells were associated with impaired cognition. Cytomegalovirus seroprevalence showed that all volunteers studied but one were CMV positive. Finally, we show that some of these phenotypic and functional features are associated with an increased frequency of the HLA-B8 serotype, which belongs to the ancestral haplotype HLA-A1, Cw7, B8, DR3, DQ2, among cognitively impaired volunteers. To our knowledge, this is the first proof in humans linking the amount of cell surface CD45RA and CD8β chain expressed by CD8+ Temra cells, and the amount of IFNγ produced by in vitro activated CD4+ T cells, with impaired cognitive function in the elderly.info:eu-repo/semantics/publishedVersio

HLA‐A23/HLA‐A24 serotypes and dementia interaction in the elderly: Association with increased soluble HLA class I molecules in plasma

MHC class I molecules regulate brain development and plasticity in mice and HLA class I molecules are associated with brain disorders in humans. We investigated the relationship between plasma-derived soluble human HLA class I molecules (sHLA class I), HLA class I serotypes and dementia. A cohort of HLA class I serotyped elderly subjects with no dementia/predementia (NpD, n = 28), or with dementia (D, n = 28) was studied. Multivariate analysis was used to examine the influence of dementia and HLA class I serotype on sHLA class I levels, and to compare sHLA class I within four groups according to the presence or absence of HLA-A23/A24 and dementia. HLA-A23/A24 and dementia, but not age, significantly influenced the level of sHLA class I. Importantly, the concurrent presence of HLA-A23/A24 and dementia was associated with higher levels of sHLA class I (p < 0.001). This study has shown that the simultaneous presence of HLA-A23/HLA-A24 and dementia is associated with high levels of serum sHLA class I molecules. Thus, sHLA class I could be considered a biomarker of neurodegeneration in certain HLA class I carriers.info:eu-repo/semantics/publishedVersio

HIF-1alpha-pathway activation in cholangiocytes of patients with biliary atresia : an immunohistochemical/molecular exploratory study

Background: Biliary atresia is a neonatal disease characterized by choledochal obstruction and progressive cholangiopathy requiring liver transplantation in most patients. Hypoxia-ischemia affecting the biliary epithelium may lead to biliary obstruction. We hypothesized that ischemic cholangiopathy involving disruption of the peribiliary vascular plexus could act as a triggering event in biliary atresia pathogenesis. Methods: Liver and porta hepatis paraffin-embedded samples of patients with biliary atresia or intrahepatic neonatal cholestasis (controls) were immunohistochemically evaluated for HIF-1alpha-nuclear signals. Frozen histological samples were analyzed for gene expression in molecular profiles associated with hypoxia-ischemia. Prospective clinical-laboratory and histopathological data of biliary atresia patients and controls were reviewed. Results: Immunohistochemical HIF-1alpha signals localized to cholangiocytes were detected exclusively in liver specimens from biliary atresia patients. In 37.5% of liver specimens, HIF-1alpha signals were observed in biliary structures involving progenitor cell niches and peribiliary vascular plexus. HIF-1alpha signals were also detected in biliary remnants of 81.8% of porta hepatis specimens. Increased gene expression of molecules linked to REDOX status, biliary proliferation, and angiogenesis was identified in biliary atresia liver specimens. In addition, there was a trend towards decreased GSR expression levels in the HIF-1alpha-positive group compared to the HIF-1alpha-negative group. Conclusion: Activation of the HIF-1alpha pathway may be associated with the pathogenesis of biliary atresia, and additional studies are necessary to confirm the significance of this finding. Ischemic cholangiopathy and REDOX status disturbance are putative explanations for HIF-1alpha activation. These findings may give rise to novel lines of clinical and therapeutic investigation in the BA field