Animal models for diabetes insipidus

The hormone arginine vasopressin (AVP) is a nonapeptide synthesized by hypothalamic magnocellular nuclei and secreted from the posterior pituitary into the bloodstream. It binds to AVP receptor 2 in the kidney to promote the insertion of aquaporin channels (AQP2) and antidiuretic responses. AVP secretion deficits produce central diabetes insipidus (CDI), while renal insensitivity to the antidiuretic effect of AVP causes nephrogenic diabetes insipidus (NDI). Hereditary and acquired forms of CDI and NDI generate hypotonic polyuria, polydipsia, hyperosmolality, and hypernatremia. The AVP mutant (Brattleboro) rat is the principal animal model of hereditary CDI, while neurohypophysectomy, pituitary stalk compression, hypophysectomy, and mediobasal hypothalamic lesions produce acquired CDI. In animals, hereditary NDI is mainly caused by mutations in AVP2R or AQP2 genes, while acquired NDI is most frequently induced by lithium. We report here on the determinants of the intake and excretion of water and mineral salts and on the different types of DI in humans. We then describe the hydromineral characteristics of these animal models and the responses observed after administration of hypertonic NaCl or when they are fed with low-sodium diets. Finally, we report on the effects of drugs such as AVP analogues and/or oxytocin, another neuropeptide that increases sodium excretion in animal models and humans with CDI, and silden- afil, a compound that increases the expression and function of AQP2 channels in animal models and humans with NDI.Spanish Ministry of Science, Innovation and Universities (Ref. PSI2017-89324-C2-1-P)

Electrophysiological correlates of an alcohol-cued Go/NoGo task: A dual-process approach to binge drinking in university students.

Binge drinking is a common pattern of alcohol consumption in adolescence and youth. Neurocognitive dual-process models attribute substance use disorders and risk behaviours during adolescence to an imbalance between an overactivated a ective-automatic system (involved in motivational and affective processing) and a reflective system (involved in cognitive inhibitory control). The aim of the present study was to investigate at the electrophysiological level the degree to which the motivational value of alcohol-related stimuli modulates the inhibition of a prepotent response in binge drinkers. First-year university students (n = 151, 54 % females) classified as binge drinkers (n = 71, 6 or more binge drinking episodes, defined as 5/7 standard drinks per occasion in the last 180 days) and controls (n = 80, <6 binge drinking episodes in the last 180 days) performed a beverage Go/NoGo task (pictures of alcoholic and nonalcoholic drinks were presented according to the condition as Go or NoGo stimuli; Go probability = 0.75) during event-related potential recording. In binge drinkers but not controls, the amplitude of the anterior N2-NoGo was larger in response to nonalcohol than in response to alcohol pictures. No behavioural difference in task performance was observed. In terms of dual-process models, binge drinkers may require increased activation to monitor conflict in order to compensate for overactivation of the affective-automatic system caused by alcohol-related biasFunding for this research was provided by the Plan Nacional Sobre Drogas (PNSD 2015/034) and Ministerio de Economía, Industria y Competitividad together with European Regional Development Fund (PSI2015-70525-P) and Xunta de Galicia (ED431C 2917/06). J.B-R was supported by the FPU program (FPU2015-03591) of the Spanish Ministry of Education, Culture, and SportsS

Study of Temporal Variations of Equivalent Black Carbon in a Coastal City in Northwest Spain Using an Atmospheric Aerosol Data Management Software

[Abstract] Light-absorbing carbonaceous aerosols (including black carbon (BC)) pose serious health issues and play significant roles in atmospheric radiative properties. Two-year measurements (2015–2016) of aerosol light absorption, combined with measurements of sub-micrometric particles, were continuously conducted in A Coruña (northwest (NW) Spain) to determine their light absorption properties: absorption coefficients (σabs) and the absorption Ångström exponent (AAE). The mean and standard deviation of equivalent black carbon (eBC) during the period of study were 0.85 ± 0.83 µg m−3, which are lower than other values measured in urban areas of Spain and Europe. High eBC concentrations found in winter are associated with an increase in emissions from anthropogenic sources in combination with lower mixing layer heights and frequent stagnant conditions. The pronounced diurnal variability suggests a strong influence from local sources. AAE had an average value of 1.26 ± 0.22 which implies that both fossil fuel combustion and biomass burning influenced optical aerosol properties. This also highlights biomass combustion in suburban areas, where the use of wood for domestic heating is encouraged, as an important source of eBC. All data treatment was gathered using SCALA© as atmospheric aerosol data management support software program.This research was funded by the Spanish R&D Plan (PROACLIM project: CGL2014-52877-R and CRISOL project: CGL2017-85344-R) and by the Xunta de Galicia (GRC2013-047 and ED431C 2017/28).Xunta de Galicia; GRC2013-047Xunta de Galicia; ED431C 2017/2

Web Application for Atmospheric Aerosol Data Management: Software and Case Study in the Spanish Network on Environmental Differential Mobility Analysers

[Abstract] SCALA© (Sampling Campaigns for Aerosols in the Low Atmosphere) is a web-based software system that was developed in a multidisciplinary manner to integrally support the documentation and the management and analysis of atmospheric aerosol data from sampling campaigns. The software development process applied considered the prototyping and the evolutionary approaches. The software product (SCALA©) allows for the comprehensive management of the sampling campaigns’ life cycle (management of the profiles and processes involved in the start-up, development and closure of a campaign) and provides support for both intra- and inter-campaigns data analysis. The pilot deployment of SCALA© considers the Spanish Network on Environmental Differential Mobility Analysers (DMAs) (REDMAAS) and the PROACLIM project. This research project involves, among other objectives, the study of temporal and spatial variations of the atmospheric aerosol through a set of microphysical properties (size distribution, optical properties, hygroscopicity, etc.) measured in several locations in Spain. The main conclusions regarding size distribution are presented in this work. These have been have been extracted through SCALA© from the data collected in the REDMAAS 2015 and 2019 intercomparison campaigns and two years (2015 and 2016) of measurements with two Scanning Mobility Particle Sizers (SMPS) at CIEMAT (Madrid, central Spain) and UDC (A Coruña, NW of Spain) sites.Ministerio de Economía y Competitividad; CGL2014-52877-RMinisterio de Economía y Competitividad; CGL2017-85344-RXunta de Galicia; GRC2013-047Xunta de Galicia; ED431C 2017/28Gobierno Regional de Madrid; Y2018/EMT-517

La región tuberomamilar del hipotálamo en la regulación hidromineral y nutritiva: características diferenciales en relación con la diabetes insípida neurológica

Tesis Univ. Granada. Departamento de Psicología Experimental y Fisiología del Comportamiento

Opposite effects of oxytocin on water intake induced by hypertonic NaCl or polyethylene glycol administration

Oxytocin (OT), a neurohormone, has been related to natriuretic and diuretic effects and also to water intake and sodium appetite. The objective of the present study was to determine the effect of subcutaneous OT administration on water intake and urine-related measures induced by the administration of hypertonic NaCl (experiment 1) or polyethylene glycol (PEG) (experiment 2). Experiment 1 showed that OT administration increases the urine volume, urinary sodium concentration, and natriuresis and reduces the water intake, water and sodium balances, and estimated plasma sodium concentration induced by hypertonic NaCl administration. Conversely, experiment 2 showed that OT administration increases the water intake and the antidiuretic response induced by PEG administration. These results show that the opposite effects of OT on the water intake induced by hypertonic NaCl or PEG administration are accompanied by differential regulatory effects, enhancing a natriuretic response in the first experiment and generating an antidiuretic reaction in the second experiment. This study suggests a differential regulatory effect of OT during states of intra- and extracellular thirst

Effects of persistent binge drinking on brain structure in emerging adults: a longitudinal study

Previous cross-sectional research has largely associated binge drinking (BD) with changes in volume and thickness during adolescence and early adulthood. Nevertheless, the long-term alcohol-related effects on gray matter features in youths who had maintained a BD pattern over time have not yet been sufficiently explored. The present study aimed to assess group differences both cross-sectionally and longitudinally [using symmetric percent change (SPC)] on several structural measures (i.e., thickness, surface area, volume). For this purpose, magnetic resonance imaging was recorded twice within a 2-year interval; at baseline (18–19 years) and a follow-up (20–21 years). The sample included 44 university students who were classified as 16 stable binge drinkers (8 females) and 28 stable controls (13 females). Whole-brain analysis showed larger insular surface area in binge drinkers relative to controls at follow-up (cluster-wise p = 0.045). On the other hand, region of interest (ROI) analyses on thickness also revealed a group by sex interaction at follow-up (p = 0.005), indicating that BD males had smaller right rostral middle frontal gyrus thickness than both control males (p = 0.011) and BD females (p = 0.029). Similarly, ROI-based analysis on longitudinal data showed a group by sex interaction in the right nucleus accumbens (p = 0.009) which revealed a decreased volume across time in BD males than in control males (p = 0.007). Overall, continued BD pattern during emerging adulthood appears to lead to gray matter abnormalities in regions intimately involved in reward processing, emotional regulation and executive functions. Notably, some anomalies varied significantly depending on sex, suggesting a sex-specific impact of BD on typical neurodevelopment processesThis work was supported by grants from the Spanish Ministerio de Sanidad, Servicios Sociales e Igualdad, Plan Nacional sobre Drogas (PNSD 2015/034), Ministerio de Economìa y Competitividad (PSI2015-70525-P) co-funded for European Regional Development Fund, MCIN/ AEI/10.13039/501100011033 (grant PID2020-113487RB-I00), and Xunta de Galicia (GRC ED431C 2017/06; ED431C 2021/08). JP-G was supported by the FPU program from the Spanish Ministerio de Educacion, Cultura y Deporte (FPU16/01573). EC-R was supported by the Swiss National Science Foundation (SNSF, Ambizione grant PZ00P2 185814).S

Relevance of subclinical right ventricular dysfunction measured by feature-tracking cardiac magnetic resonance in non-ischemic dilated cardiomyopathy

Right ventricular (RV) dysfunction in patients with non-ischemic dilated cardiomyopathy (NICM) is associated with cardiovascular events. To analyze the feasibility of assessing RV myocardial deformation by feature tracking (FT)-cardiac magnetic resonance (CMR), and its usefulness as a prognostic marker. Retrospective study of NICM patients undergoing CMR. Longitudinal FT-RV free wall (LFT-RVFW) and fractional area change (FAC) were obtained. Correlation with standard RV parameters was studied. An association with combined event (heart failure (HF), ICD implantation or cardiovascular death) was assessed using a logistic regression model. Results 98 patients (64±13 years) were included. Left ventricular (LV) systolic function (LVEF 29.5±9.6%, 47% with LVEF≥30%) and RV (RVEF 52.2±14.6%, 72% with RVEF≥45%). Follow-up of 38±17 months, 26.5% presented at least one admission for HF. An excellent correlation of LFT-RVFW (r=0.82) and FAC (r=0.83) with RVEF was evident. No association of RV-FT parameters with prognosis entire study population was found. However, in patients with LVEF≥30%, admissions for HF were associated with lower LFT-RVFW (−21.6 ± 6.6% vs −31.3 ± 10%; p = 0.006) and FAC (36.6 ± 9.6% vs 50.5 ± 13.4%; p < 0.001) values. Similar diferences were observed when only patients with RVEF≥45% were considered. An LFT-RVFW cut-of point of -19.5% and FAC of 36.5% showed good prognostic performance. Decreased LFT-RVFW or FAC represented an independent predictor of combined event in patients with LVEF≥30%. Conclusions In NICM patients without severe LV dysfunction, decreased values of LFT-RVFW and/or FAC were associated with HF admissions, independently of RVEF.Sin financiación2.174 Q4 JCR 20210.675 Q2 SJR 2021No data IDR 2021UE

Non-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value.

Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. This study reports mechanistic insights into the electromechanical remodeling process associated with AF progression and further demonstrates its prognostic value in the clinic. In pigs, sequential electromechanical assessment during AF progression shows a progressive decrease in mechanical activity and early dissociation from its electrical counterpart. Atrial tissue samples from animals with AF reveal an abnormal increase in cardiomyocytes death and alterations in calcium handling proteins. High-throughput quantitative proteomics and immunoblotting analyses at different stages of AF progression identify downregulation of contractile proteins and progressive increase in atrial fibrosis. Moreover, advanced optical mapping techniques, applied to whole heart preparations during AF, demonstrate that AF-related remodeling decreases the frequency threshold for dissociation between transmembrane voltage signals and intracellular calcium transients compared to healthy controls. Single cell simulations of human atrial cardiomyocytes also confirm the experimental results. In patients, non-invasive assessment of the atrial electromechanical relationship further demonstrate that atrial electromechanical dissociation is an early prognostic indicator for acute and long-term rhythm control.This work was supported by the European Union Horizon 2020 research and innovation program under Grant Agreement#965286. The study was also supported by the Ministry of Science and Innovation (MCIN) (PID2019- 109329RB-I00 and PGC2018-097019-B-I00) funded by MCIN / AEI / 10.13039/501100011033, the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria grant PRB3) (PT17/0019/0003- ISCIII-SGEFI / ERDF, ProteoRed), the Fundación Interhospitalaria para la Investigación Cardiovascular, the Fundación Salud 2000 and by “la Caixa” Banking Foundation (project code HR17-00247). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (CEX2020- 001041-S funded by MICIN/AEI/10.13039/501100011033). We also thank Asunción Conde and Sergey Mironov for their support on monitoring database quality and advice in ECG signal processing, respectively.S

Non-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value

Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. This study reports mechanistic insights into the electromechanical remodeling process associated with AF progression and further demonstrates its prognostic value in the clinic. In pigs, sequential electromechanical assessment during AF progression shows a progressive decrease in mechanical activity and early dissociation from its electrical counterpart. Atrial tissue samples from animals with AF reveal an abnormal increase in cardiomyocytes death and alterations in calcium handling proteins. High-throughput quantitative proteomics and immunoblotting analyses at different stages of AF progression identify downregulation of contractile proteins and progressive increase in atrial fibrosis. Moreover, advanced optical mapping techniques, applied to whole heart preparations during AF, demonstrate that AF-related remodeling decreases the frequency threshold for dissociation between transmembrane voltage signals and intracellular calcium transients compared to healthy controls. Single cell simulations of human atrial cardiomyocytes also confirm the experimental results. In patients, non-invasive assessment of the atrial electromechanical relationship further demonstrate that atrial electromechanical dissociation is an early prognostic indicator for acute and long-term rhythm control. Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. Here, the authors use non-invasive atrial electromechanical assessment during AF to identify early remodeling changes associated with underlying myopathy, which in the clinic decrease the probability of acute and mid-term successful rhythm control