Acidosis tubular renal como presentación clínica de Síndrome de Sjögren: reporte de caso

Presentamos el caso clínico de una mujer en la quinta década de la vida, de nacionalidad argentina, que acudió a la guardia de clínica médica de un hospital de tercer nivel por cuadro de mialgias y paresia en las cuatro extremidades, de inicio agudo, progresivo, con dificultad para la movilización de miembros superiores, bipedestación y marcha. Se constató hipocalemia severa, acidosis metabólica, pH urinario alcalino, brecha aniónica urinaria positiva (excreción de amonio), hipocitraturia e hipercalciuria, por lo que se diagnosticó Acidosis Tubular Renal (ATR) tipo I; además se evidenció elevación de creatinkinasa (CK) e insuficiencia renal aguda que corrigió con la reposición de líquidos. Al interrogatorio dirigido, la paciente refirió síndrome seco asociado a artralgias, de varios años de evolución, por lo que se realizaron estudios complementarios que apoyaron el diagnóstico de Síndrome de Sjögren

The presence of a social stimulus reduces cocaine seeking in a place preference conditioning paradigm.

BACKGROUND: One challenge in the treatment of substance use disorders is to re-engage the interest toward non-drug-related activities. Among these activities, social interaction has had a prominent role due to its positive influence on treatment outcome. AIMS AND METHODS: Our aim was to study whether the presence of a social stimulus during the cocaine-induced conditioned place preference test was able to reduce the time spent in the drug-paired compartment. For that purpose, mice were trained for four days on a conditioned place preference task with one compartment paired with cocaine and the opposite with saline. On the test day, we introduced an unfamiliar juvenile male mouse into the saline-conditioned compartment (inside a pencil cup) to analyse the animal preference towards the two rewarding stimuli (cocaine vs mouse). Additionally, to discard the possible effect of novelty, as well as the housing condition (social isolation) on social preference, we decided to include a novel object during the test session, as well as perform the same conditioned place preference protocol with a group of animals in social housing conditions. RESULTS: The social stimulus was able to reduce the preference for cocaine and enhance the active interaction with the juvenile mouse (sniffing) compared to the empty pencil cup paired with the drug. The introduction of a novel object during the test session did not reduce the preference for the cocaine-paired compartment, and interestingly, the preference for the social stimulus was independent of the housing condition. c-Fos immunohistochemistry revealed a different pattern of activation based on cocaine-paired conditioning or the presence of social stimulus. CONCLUSIONS: These results suggest that social interaction could constitute a valuable component in the treatment of substance use disorders by reducing the salience of the drug.Plan Propio 2017 – ‘Ayudas para proyectos dirigidos por jóvenes investigadores’, PPIT.UMA.B1.2017/38. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Analysis of metals and phosphorus in biodiesel B100 from different feedstock using a Flow Blurring® multinebulizer in inductively coupled plasma-optical emission spectrometry

A simple and fast method for determining the content of Na, K, Ca, Mg, P, and 20 heavy metals in biodiesel samples with inductively coupled plasma optical emission spectrometry (ICP OES) using a two-nozzle Flow Blurring® multinebulizer prototype and on-line internal standard calibration, are proposed. The biodiesel samples were produced from different feedstock such as sunflower, corn, soybean and grape seed oils, via a base catalyst transesterification. The analysis was carried out without any sample pretreatment. The standards and samples were introduced through one of the multinebulizer nozzles, while the aqueous solution containing yttrium as an internal standard was introduced through the second nozzle. Thus, the spectral interferences were compensated and the formation of carbon deposits on the ICP torch was prevented. The determination coefficients (R2) were greater than 0.99 for the studied analytes, in the range 0.21–14.75 mg kg−1. Short-term and long-term precisions were estimated as relative standard deviation. These were acceptable, their values being lower than 10%. The LOQ for major components such as Ca, K, Mg, Na, and P, were within a range between 4.9 ng g−1 for Mg (279.553 nm) and 531.1 ng g−1 for Na (588.995 nm), and for the other 20 minor components they were within a range between 1.1 ng g−1 for Ba (455.403 nm) and 2913.9 ng g−1 for Pb (220.353 nm). Recovery values ranged between 95% and 106%.The authors gratefully acknowledge Universidad Nacional del Sur (UNS) and Instituto de Química del Sur – Universidad Nacional del Sur – Consejo Nacional de Investigaciones Científicas y Técnicas (INQUISUR-UNS-CONICET) from Argentina for the financial support. FDAO acknowledges Universidad de Alicante (UA) for his short visit fellowship. Ministerio de Asuntos Exteriores y de Cooperación (MAEC) and Dirección de Relaciones Culturales y Científicas (AECID) from Spain for the financial support. The authors wish to thank the Spanish Government (CTQ2011-23968) for the financial support

Targeting proteases involved in the viral replication of SARS-CoV-2 by sesquiterpene lactones from chicory (Cichorium intybus L.)

Funding Information: This research has been supported by the EU Horizon 2020 research & innovation programme (H2020-NMBP-BIO-2017, project CHIC grant agreement no. 760891). Publisher Copyright: © 2022 The Royal Society of Chemistry.SARS-CoV-2 is a highly transmissible and pathogenic coronavirus causing a respiratory disease that emerged in 2019, leading to a public health emergency situation which continues to date. The treatment options are still very limited and vaccines available are less effective against new variants. SARS-CoV-2 enzymes, namely main protease (Mpro) and papain-like protease (PLpro), play a pivotal role in the viral life cycle, making them a putative drug target. Here, we described for the first time the potential inhibitory activity of chicory extract against both proteases. Besides, we have identified that the four most abundant sesquiterpene lactones in chicory inhibited these proteases, showing an effective binding in the active sites of Mpro and PLpro. This paper provides new insight for further drug development or food-based strategies for the prevention of SARS-CoV-2 by targeting viral proteases.publishersversionepub_ahead_of_prin

Potential Operating Models, Harvest Control Rules and Performance Statistics for the NAFO 3M Cod MSE.

This document presents a proposal of possible Operating Models (OMs), Harvest Control Rules (HCR) and Performance Statistics (PS) to carry out the Management Strategies Evaluation (MSE) for the 3M cod of NAFO. This proposal will have to be reviewed by the NAFO SC to decide the first set of OMs to test with the possible HCRs in the 3M Cod MSE

Apoptotic cells subjected to cold/warming exposure disorganize apoptotic microtubule network and undergo secondary necrosis

Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath the plasma membrane which plays a critical role in preserving cell morphology and plasma membrane integrity. The aim of this study was to examine the effect of cold/warming exposure on apoptotic microtubules and plasma membrane integrity during the execution phase of apoptosis. We demonstrated in camptothecin-induced apoptotic H460 cells that cold/warming exposure disorganized apoptotic microtubules and allowed the access of active caspases to the cellular cortex and the cleavage of essential proteins in the preservation of plasma membrane permeability. Cleavage of cellular cortex and plasma membrane proteins, such as ¿-spectrin, paxilin, focal adhesion kinase and calcium ATPase pump (PMCA-4) involved in cell calcium extrusion resulted in increased plasma permeability and calcium overload leading apoptotic cells to secondary necrosis. The essential role of caspase-mediated cleavage in this process was demonstrated because the addition of the pan-caspase inhibitor z-VAD during cold/warming exposure that induces AMN depolymerization avoided the cleavage of cortical and plasma membrane proteins and prevented apoptotic cells to undergo secondary necrosis. Likewise, apoptotic microtubules stabilization by taxol during cold/warming exposure also prevented cellular cortex and plasma membrane protein cleavage and secondary necrosis. Furthermore, microtubules stabilization or caspase inhibition during cold/warming exposure was also critical for proper phosphatidylserine externalization and apoptotic cell clearance by macrophages. These results indicate that cold/warming exposure of apoptotic cells induces secondary necrosis which can be prevented by both, microtubule stabilization or caspase inhibition.This work was supported by FIS PI10/00543 Grant, FIS EC08/00076 Grant, Ministerio de Sanidad, Spain and Fondo Europeo de Desarrollo Regional (FEDER-Unión Europea), SAS 111242 Grant, Servicio Andaluz de Salud-Junta de Andalucía, Proyecto de Investigación de Excelencia de la Junta de Andalucía CTS-5725, and by Asociación de Enfermos de Patología Mitocondrial (AEPMI).Peer Reviewe

Apoptotic microtubules delimit an active caspase free area in the cellular cortex during the execution phase of apoptosis

This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License.Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath plasma membrane, which has an important role in preserving cell morphology and plasma membrane permeability. The aim of this study was to examine the role of AMN in maintaining plasma membrane integrity during the execution phase of apoptosis. We demonstrated in camptothecin-induced apoptosis in H460 cells that AMN delimits an active caspase free area beneath plasma membrane that permits the preservation of cellular cortex and transmembrane proteins. AMN depolymerization in apoptotic cells by a short exposure to colchicine allowed active caspases to reach the cellular cortex and cleave many key proteins involved in plasma membrane structural support, cell adhesion and ionic homeostasis. Cleavage of cellular cortex and plasma membrane proteins, such as α-spectrin, paxilin, focal adhesion kinase (FAK), E-cadherin and integrin subunit β4 was associated with cell collapse and cell detachment. Otherwise, cleavage-mediated inactivation of calcium ATPase pump (PMCA-4) and Na(+)/Ca(2+) exchanger (NCX) involved in cell calcium extrusion resulted in calcium overload. Furthermore, cleavage of Na(+)/K(+) pump subunit β was associated with altered sodium homeostasis. Cleavage of cell cortex and plasma membrane proteins in apoptotic cells after AMN depolymerization increased plasma permeability, ionic imbalance and bioenergetic collapse, leading apoptotic cells to secondary necrosis. The essential role of caspase-mediated cleavage in this process was demonstrated because the concomitant addition of colchicine that induces AMN depolymerization and the pan-caspase inhibitor z-VAD avoided the cleavage of cortical and plasma membrane proteins and prevented apoptotic cells to undergo secondary necrosis. Furthermore, the presence of AMN was also critical for proper phosphatidylserine externalization and apoptotic cell clearance by macrophages. These results indicate that AMN is essential to preserve an active caspase free area in the cellular cortex of apoptotic cells that allows plasma membrane integrity during the execution phase of apoptosis.This work was supported by FIS PI10/00543 grant, FIS EC08/00076 grant, Ministerio de Sanidad, Spain and Fondo Europeo de Desarrollo Regional (FEDER-Unión Europea), SAS 111242 grant, Servicio Andaluz de Salud Junta de Andalucía, Proyecto de Investigación de Excelencia de la Junta de Andalucía CTS-5725, and by AEPMI (Asociación de Enfermos de Patología Mitocondrial).Peer reviewe

Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics

Heteroplasmy, multiple variants of mitochondrial DNA (mtDNA) in the same cytoplasm, may be naturally generated by mutations but is counteracted by a genetic mtDNA bottleneck during oocyte development. Engineered heteroplasmic mice with nonpathological mtDNA variants reveal a nonrandom tissue-specific mtDNA segregation pattern, with few tissues that do not show segregation. The driving force for this dynamic complex pattern has remained unexplained for decades, challenging our understanding of this fundamental biological problem and hindering clinical planning for inherited diseases. Here, we demonstrate that the nonrandom mtDNA segregation is an intracellular process based on organelle selection. This cell type-specific decision arises jointly from the impact of mtDNA haplotypes on the oxidative phosphorylation (OXPHOS) system and the cell metabolic requirements and is strongly sensitive to the nuclear context and to environmental cues