Trigger and Target of Renal Functions

This work was supported by “Fundação para a Ciência e a Tecnologia” – FCT to AP (PD/BD/136887/2018); MJM (PD/BD/114256/2016), MPM (PTDC/DTP-EPI/0207/2012), DOB e MPM (PTDC/BIM-MET/2115/2014); iNOVA4Health (UIDB/Multi/04462/2020), by the European Commission Marie Skłodowska -Curie Actions H2020 (grant agreements nos. 722619 and 734719), and by the Sociedade Portuguesa de Diabetologia.Kidney function in metabolism is often underestimated. Although the word “clearance” is associated to “degradation”, at nephron level, proper balance between what is truly degraded and what is redirected to de novo utilization is crucial for the maintenance of electrolytic and acid–basic balance and energy conservation. Insulin is probably one of the best examples of how diverse and heterogeneous kidney response can be. Kidney has a primary role in the degradation of insulin released in the bloodstream, but it is also incredibly susceptible to insulin action throughout the nephron. Fluctuations in insulin levels during fast and fed state add another layer of complexity in the understanding of kidney fine-tuning. This review aims at revisiting renal insulin actions and clearance and to address the association of kidney dysmetabolism with hyperinsulinemia and insulin resistance, both highly prevalent phenomena in modern society.publishersversionpublishe

Wearable Sensor for Real-time Monitoring of Hydrogen Peroxide in Simulated Exhaled Air

In this work, an innovative and cheap electrochemical sensor for hydrogen peroxide quantification in exhaled breath was developed. H2O2 is the most used biomarker among the Reactive Oxygen Species (ROS) for monitoring the level of oxidative stress in the respiratory system. This is due to its stability and ability to cross biological membranes and also because it is detectable in extracellular space. The electrochemical sensor was obtained using the silver layer of wasted compact discs (CDs). All three electrodes, working (WE), counter (CE), and pseudo-reference electrode (RE), were fabricated using a laser cutter. The working electrode was used directly, while an Ag/AgCl paste and a graphite paste were applied respectively on the RE and the CE. In addition, a chitosan layer was deposited by Electro-Phoretic Deposition (EPD) on the surface of the sensor. This biopolymer improves the wettability of the sensor in presence of a humid atmosphere such as that given by exhaled air. The sensor was tested in both liquid and nebulized solutions containing different concentrations of hydrogen peroxide. The detection of H2O2 was evaluated using Linear Sweep Voltammetry (LSV) as electrochemical technique. The results show that the peak current increases linearly with hydrogen peroxide concentration from 100 to 500 μM with a sensitivity of 0.068 µA µM−1 cm−2 and 0.108 µA µM−1 cm−2, a Limit Of Detection (LOD) of 60 μM and 30 μM respectively for liquid and nebulized solutions. Therefore, the use of the electrochemical sensor can allow the monitoring of hydrogen peroxide in real time with good results

Monitoring Risk Factors and Improving Adherence to Therapy in Patients With Chronic Kidney Disease (Smit-CKD Project): Pilot Observational Study

Background: Chronic kidney disease is a major public health issue, with about 13% of the general adult population and 30% of the elderly affected. Patients in the last stage of this disease have an almost uniquely high risk of death and cardiovascular events, with reduced adherence to therapy representing an additional risk factor for cardiovascular morbidity and mortality. Considering the increased penetration of mobile phones, a mobile app could educate patients to autonomously monitor cardiorenal risk factors. Objective: With this background in mind, we developed an integrated system of a server and app with the aim of improving self-monitoring of cardiovascular and renal risk factors and adherence to therapy. Methods: The software infrastructure for both the Smit-CKD server and Smit-CKD app was developed using standard web-oriented development methodologies preferring open source tools when available. To make the Smit-CKD app suitable for Android and iOS, platforms that allow the development of a multiplatform app starting from a single source code were used. The integrated system was field tested with the help of 22 participants. User satisfaction and adherence to therapy were measured by questionnaires specifically designed for this study; regular use of the app was measured using the daily reports available on the platform. Results: The Smit-CKD app allows the monitoring of cardiorenal risk factors, such as blood pressure, weight, and blood glucose. Collected data are transmitted in real time to the referring general practitioner. In addition, special reminders improve adherence to the medication regimen. Via the Smit-CKD server, general practitioners can monitor the clinical status of their patients and their adherence to therapy. During the test phase, 73% (16/22) of subjects entered all the required data regularly and sent feedback on drug intake. After 6 months of use, the percentage of regular intake of medications rose from 64% (14/22) to 82% (18/22). Analysis of the evaluation questionnaires showed that both the app and server components were well accepted by the users. Conclusions: Our study demonstrated that a simple mobile app, created to self-monitor modifiable cardiorenal risk factors and adherence to therapy, is well tolerated by patients affected by chronic kidney disease. Further studies are required to clarify if the use of this integrated system will have long-term effects on therapy adherence and if self-monitoring of risk factors will improve clinical outcomes in this population

Effect of Vitamin D Receptor Activation on the AGE/RAGE System and Myeloperoxidase in Chronic Kidney Disease Patients

Vitamin D receptor (VDR) activation has been reported to increase circulating levels of the advanced glycation end products (AGE) and their decoy receptor (RAGE). However, until now, the effect of VDR activation on AGE and RAGE has not been tested in the setting of a randomized, double-blind clinical trial. We have therefore analyzed the effect of VDR activation by paricalcitol on pentosidine, S100A12/ENRAGE, and RAGE and on established biomarkers of oxidative stress like myeloperoxidase in CKD patients in the PENNY trial. At baseline, human S100A12/ENRAGE, RAGE, and myeloperoxidase, but not pentosidine, were intercorrelated, and the association between S100A12/ENRAGE and myeloperoxidase (r=0.71, P<0.001) was the strongest among these correlations. Paricalcitol failed to modify biomarkers of the AGE/RAGE system and myeloperoxidase in unadjusted and adjusted analyses by the generalized linear model (GLM). No effect modification by other risk factors was registered. Paricalcitol does not modify biomarkers of the AGE/RAGE system and myeloperoxidase in CKD patients. The apparent increase in RAGE levels by VDR activation reported in previous uncontrolled studies is most likely due to confounding factors rather than to VDR activation per se. This trial is registered with NCT01680198

Flexible electrode based on gold nanoparticles and reduced graphene oxide for uric acid detection using linear sweep voltammetry

In this work, an electrochemical sensor for uric acid determination is shown with a preliminary study for its validation in real samples (milk and urine). Uric acid can be electrochemically oxidized in aqueous solutions and thus it is possible to obtain electrochemical sensors for this chemical by means of this electrooxidation reaction. Indium tin oxide coated on flexible polyethylene terephthalate substrate, modified with reduced graphene oxide and gold nanoparticles by co-electrodeposition, was used. Electrodeposition was performed at -0.8V vs SCE for 200 s. All samples were characterized by electron scan microscopy and electron diffraction spectroscopy. A careful investigation on the effect of pH was performed to understand its influence on uric acid oxidation. The detection of uric acid was using the linear sweep voltammetry. Results show that the peak current increases linearly with uric acid concentration from 10 to 1000 μM with a limit of detection of about 7.1 μM. The sensor shows high selectivity towards different interferents that can be found in the milk and urine matrix, such as chloride, calcium, sodium and ammonium ions. To prove the applicability of the proposed sensor, uric acid was quantified in real milk and urine samples with excellent results comparable to those of conventional techniques

Experimental determination of the Ta-Ge phase diagram

International audienceIn the present work, the Ta-Ge phase diagram has been experimentally studied, considering the inexistence of a Ta-Ge phase diagram in the literature. The samples were prepared via arc melting and characterized by Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS) and X-ray Diffraction (XRD). The intermetallics phases beta Ta3Ge, alpha Ta3Ge, beta Ta5Ge3 and TaGe2 where confirmed in this system. Three eutectics reactions where determined with the liquid compositions at 20.5; 28.0; 97.0 at.% Ge. The phases beta Ta3Ge and beta Ta5Ge3 solidifies congruently while TaGe2 is formed through a peritectic transformation. The temperature of the Ta-rich eutectic (L Ta-ss + beta Ta3Ge) was measured by the Pirani-Alterthum method at 2440 degrees C and the Ge-rich eutectic (L TaGe2 + Ge-ss) by DTA at 937 degrees C

FLEXIBLE ELECTRODE BASED ON GOLD NANOPARTICLES AND REDUCED GRAPHENE OXIDE FOR URIC ACID DETECTION USING LINEAR SWEEP VOLTAMMETRY

Uric acid (UA) can be electrochemically oxidized in aqueous solutions and thus it is detectable through the use of electrochemical sensors. As electrode, a flexible polyethylene terephthalate substrate coated indium with tin oxide (ITO-PET) was used. The electrode was modified by co-electrodeposition with reduced graphene oxide (rGO) and gold nanoparticles (AuNPs). All samples were characterized by scanning electron microscope and electron diffraction spectroscopy. A careful investigation on the effect of pH was performed to understand its influence on uric acid oxidation. The detection of uric acid was performed by linear sweep voltammetry. Results show that the peak current increases linearly with uric acid concentration from 10 to 1000 μM with a limit of detection (LOD) of about 7.1 μM. The sensor shows high selectivity towards different interferents that can be found in the milk and urine matrix, such as chloride, calcium, sodium and ammonium ions. To prove the applicability of the proposed sensor, uric acid was quantified in real milk and urine samples with excellent results comparable to those of conventional techniques

Curcumin-Like Compounds as Neuroprotective Agents: Interactions with HSP60 and Amyloid Beta Peptide

Alzheimer’s Disease (AD) represents a fundamental challenge for public health in the 21st century. Current AD therapies largely focus on symptomatic aspects of the clinical pathology, but they have yet to demonstrate any major impact on the disease progression [1]. The most important role of the research aimed at fighting the AD is the development of neuro-protective agents, able to interfere with the protein aggregation process whose clinical signature is represented by the plaques deposition. An important role in AD’s framework could be played by Heat shock proteins (HSPs), highly regulated proteins that mediate the proteins proper folding and promote recovery of their native conformations lost due to stress [2]. Recently, it was shown that HSP60 mediates translocation of Amyloid Precursor Protein (APP) and Amyloid Beta peptide (Aβ) to the mitochondria, leading to dysfunction of the organelle [3]. In the field of potential therapeutic approaches, curcumin, a non-toxic component of the curry spice turmeric, with anti-inflammatory, antioxidant and anti-aggregation properties, is emerging as a lead-compound for the development of neuro-protective drugs [4]. Here we present our recent findings on Curcumin and Curcumin-like drugs obtained by a combination of cellular and in-vitro experiments, such as Thioflavine T fluorescence spectroscopy and Small Angle X-ray Scattering [5]. In particular, together with the synthesis of some curcumin-like compounds, we present the results about their effect on a neuronal cell model, concerning the cytotoxicity and ability to affect Hsp60 expression, as well as their influence on Aβ aggregation, provided by in vitro experiments