Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
1.
Molecules ; 28(4)2023 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-36838939

RESUMO

CO2 electrochemical reduction (CO2 ER) from (bi)carbonate feed presents an opportunity to efficiently couple this process to alkaline-based carbon capture systems. Likewise, while this method of reducing CO2 currently lags behind CO2 gas-fed electrolysers in certain performance metrics, it offers a significant improvement in CO2 utilization which makes the method worth exploring. This paper presents two simple modifications to a bicarbonate-fed CO2 ER system that enhance the selectivity towards CO. Specifically, a modified hydrophilic cathode with Ag catalyst loaded through electrodeposition and the addition of dodecyltrimethylammonium bromide (DTAB), a low-cost surfactant, to the catholyte enabled the system to achieve a FECO of 85% and 73% at 100 and 200 mA·cm-2, respectively. The modifications were tested in 4 h long experiments where DTAB helped maintain FECO stable even when the pH of the catholyte became more alkaline, and it improved the CO2 utilization compared to a system without DTAB.


Assuntos
Dióxido de Carbono , Carbono , Íons , Bicarbonatos
2.
Environ Health ; 21(1): 76, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978396

RESUMO

BACKGROUND: Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain. METHODS: The Di@bet.es study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5µm (PM2.5) and Nitrogen Dioxide (NO2), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). TSH, free thyroxine (FT4), free triiodothyronine (FT3) and TPO Abs concentrations were analyzed using an electrochemiluminescence immunoassay (Modular Analytics E170 Roche). RESULTS: In multivariate linear regression models, there was a highly significant negative correlation between PM2.5 concentrations and both FT4 (p<0.001), and FT3 levels (p<0.001). In multivariate logistic regression, there was a significant association between PM2.5 concentrations and the odds of presenting high TSH [OR 1.24 (1.01-1.52) p=0.043], lower FT4 [OR 1.25 (1.02-1.54) p=0.032] and low FT3 levels [1.48 (1.19-1.84) p=<0.001] per each IQR increase in PM2.5 (4.86 µg/m3). There was no association between NO2 concentrations and thyroid hormone levels. No significant heterogeneity was seen in the results between groups of men, pre-menopausal and post-menopausal women. CONCLUSIONS: Exposures to PM2.5 in the general population were associated with mild alterations in thyroid function.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Adulto , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estudos Transversais , Feminino , Humanos , Masculino , Dióxido de Nitrogênio/análise , Material Particulado/análise , Glândula Tireoide/química , Hormônios Tireóideos , Tireotropina
3.
Angew Chem Int Ed Engl ; 61(48): e202213106, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36184949

RESUMO

High energy demand results in comprehensive research of novel materials for energy sources and storage applications. Covalent organic frameworks (COFs) possess appropriate features such as long-range order, permanent porosity, tunable pore size, and ion diffusion pathways to be competitive electrode materials. Herein, we present a deep electrochemical study of two COF-aerogels shaped into flexible COF-electrodes (ECOFs) by a simple compression method to fabricate an electrochemical double-layer capacitor (EDLC). This energy storage system has considerable interest owing to its high-power density and long cycle life compared with batteries. Our result confirmed the outstanding behavior of ECOFs as EDLC devices with a capacity retention of almost 100 % after 10 000 charge/discharge cycles and, to our knowledge, the highest areal capacitance (9.55 mF cm-2 ) in aqueous electrolytes at higher scan rates (1000 mV s-1 ) for COFs. More importantly, the hierarchical porosity observed in the ECOFs increases ion transport, which permits a fast interface polarization (low τ0 values). The complete sheds light on using ECOFs as novel electrode material to fabricate EDLC devices.

4.
Chemistry ; 25(53): 12394-12404, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31265184

RESUMO

Lithium-sulfur batteries stands out as a promising technology for energy storage owing to a combination of favorable characteristics including a high theoretical gravimetric capacity, energy density, inexpensive character, and environmental benignity. Covalent organic frameworks (COFs) are a rapidly developing family of functional nanostructures which combine porosity and crystallinity, and which have been already used in these kinds of batteries to build sulfur electrodes, by embedding sulfur into porous COFs in order to enhance cycle lifetimes. In this contribution, this is taken one step forward and a COF endowed with vinyl groups is used, in order to graft sulfur to the COF skeleton through inverse vulcanization. The main aim of the article is to show the synergistic effect of covalent bonding and physical encapsulation of sulfur in the pores of the COF in order to alleviate the fatal redox shuttling process, to improve the cycling performance, and to provide faster ion diffusion pathways. In addition, it is shown how the material with covalently-bound S provides better electrochemical performance under demanding and/or changeable charge conditions than a parent analogue material with sulfur physically confined, but without covalent linkage.

5.
Int J Mol Sci ; 19(7)2018 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-30041458

RESUMO

In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade's experiments with lithium and the beginning of the so-called "Psychopharmacological Revolution" in the 1950s. We also describe the clinical studies and development processes, enabling the therapeutic introduction of pharmacological agents currently available for the treatment of bipolar disorder in its different phases and manifestations. Those drugs include lithium salts, valproic acid, carbamazepine, new antiepileptic drugs, basically lamotrigine and atypical antipsychotic agents (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, asenapine, cariprazine and lurasidone). Finally, the socio-sanitary implications derived from the clinical introduction of these drugs are also discussed.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Psicofarmacologia/história , Tranquilizantes/uso terapêutico , Animais , Transtorno Bipolar/história , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Lítio/história , Lítio/uso terapêutico , Tranquilizantes/história
6.
J Am Chem Soc ; 139(29): 10079-10086, 2017 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-28669183

RESUMO

We present the novel potential application of imine-based covalent organic frameworks (COFs), formed by the direct Schiff reaction between 1,3,5-tris(4-aminophenyl)benzene and 1,3,5-benzenetricarbaldehyde building blocks in m-cresol or acetic acid, named RT-COF-1 or RT-COF-1Ac/RT-COF-1AcB. The post-synthetic treatment of RT-COF-1 with LiCl leads to the formation of LiCl@RT-COF-1. The ionic conductivity of this series of polyimine COFs has been characterized at variable temperature and humidity, using electrochemical impedance spectroscopy. LiCl@RT-COF-1 exhibits a conductivity value of 6.45 × 10-3 S cm-1 (at 313 K and 100% relative humidity) which is among the highest values so far reported in proton conduction for COFs. The mechanism of conduction has been determined using 1H and 7Li solid-state nuclear magnetic resonance spectroscopy. Interestingly, these materials, in the presence of controlled amounts of acetic acid and under pressure, show a remarkable processability that gives rise to quasi-transparent and flexible films showing in-plane structural order as confirmed by X-ray crystallography. Finally, we prove that these films are useful for the construction of proton exchange membrane fuel cells (PEMFC) reaching values up to 12.95 mW cm-2 and 53.1 mA cm-2 for maximum power and current density at 323 K, respectively.

7.
Chemistry ; 22(5): 1646-51, 2016 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-26643144

RESUMO

The ionic conductivity properties of the face-centered cubic [Ni8 (OH)4 (H2O)2 (BDP_X)6] (H2 BDP_X=1,4-bis(pyrazol-4-yl)benzene-4-X with X=H (1), OH (2), NH2 (3)) metal-organic framework (MOF) systems as well as their post-synthetically modified materials K[Ni8 (OH)5 (EtO)(BDP_X)5.5] (1@KOH, 3@KOH) and K3 [Ni8 (OH)3 (EtO)(BDP_O)5] (2@KOH), which contain missing-linker defects, have been studied by variable temperature AC impedance spectroscopy. It should be noted that these modified materials exhibit up to four orders of magnitude increase in conductivity (-) values in comparison to pristine 1-3 systems. As an example, the conductivity value of 5.86 × 10(-9) S cm(-1) (activation energy Ea of 0.60 eV) for 2 at 313 K and 22% relative humidity (RH) increases up to 2.75 × 10(-5) S cm(-1) (Ea of 0.40 eV) for 2@KOH. Moreover, a further increase of conductivity values up to 1.16 × 10(-2) S cm(-1) and diminution of Ea down to 0.20 eV is achieved at 100% RH for 2@KOH. The increased porosity, basicity and hydrophilicity of the 1@KOH-3@KOH materials compared to the pristine 1-3 systems should explain the better performance of the KOH-modified materials.

8.
J Cardiovasc Pharmacol ; 68(3): 230-40, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27631438

RESUMO

The sprouting of new vessels is greatly influenced by the procedure chosen. We sought to optimize the experimental conditions of the angiogenic growth of fresh and cryopreserved vessels cultured in Matrigel with the aim to use this system to analyze the pharmacological modulation of the process. Segments of second-order branches of rat mesenteric resistance arteries, thoracic aorta of rat or mouse, and cryopreserved rat aorta and human femoral arteries were cultured in Matrigel for 7-21 days in different mediums, as well as in the absence of endothelial or adventitia layer. Quantification of the angiogenic growth was performed by either direct measurement of the mean length of the neovessels or by calcein AM staining and determination of fluorescence intensity and area. Fresh and cryopreserved arterial rings incubated in Matrigel exhibited a spontaneous angiogenic response that was strongly accelerated by fetal calf serum. Addition of vascular endothelial growth factor, fibroblast growth factor, endothelial growth factor, or recombinant insulin-like growth factor failed to increase aortic sprouting, unless all were added together. Removal of adventitia, but not the endothelial layer, abrogated the angiogenic response of aortic rings. Determination of the mean neovessel length is an easy and accurate method to quantify the angiogenic growth devoid of confounding factors, such as inclusion of other cellular types surrounding the neovessels. Activity of a α1-adrenoceptor agonist (phenylephrine) and its inhibition by a selective antagonist (prazosin) were analyzed to prove the usefulness of the Matrigel system to evaluate the pharmacological modulation of the angiogenic growth.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Criopreservação/métodos , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/fisiologia , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Colágeno/farmacologia , Combinação de Medicamentos , Humanos , Laminina/farmacologia , Masculino , Camundongos , Técnicas de Cultura de Órgãos/métodos , Proteoglicanas/farmacologia , Ratos , Ratos Wistar
9.
J Cardiovasc Pharmacol ; 66(5): 478-86, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26248277

RESUMO

To explore if genic expression of ß(1)- or ß(2)-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 ß(2)-AR or GRK5 and ß(1)-AR were observed in each territory. Therefore, without excluding other regulatory mechanisms, the parallelism observed suggests a common regulatory pattern for the ß(1)-AR/GRK5 and ß(2)-AR/GRK2 genes, which is independent of cellular type or pathology. This highlights the need to focus not only on GRKs but also on ß(1)- or ß(2)-AR changes to completely understand the involvement of ß-AR/GRK pathways in cardiovascular diseases.


Assuntos
Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Quinase 5 de Receptor Acoplado a Proteína G/metabolismo , Cardiopatias/metabolismo , Hipertensão/metabolismo , Receptores Adrenérgicos beta 1/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Quinase 2 de Receptor Acoplado a Proteína G/genética , Quinase 5 de Receptor Acoplado a Proteína G/genética , Regulação da Expressão Gênica , Cardiopatias/genética , Humanos , Hipertensão/induzido quimicamente , Hipertensão/genética , NG-Nitroarginina Metil Éster , Especificidade de Órgãos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética
10.
Nitric Oxide ; 37: 17-27, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24365975

RESUMO

UNLABELLED: Our aim was to investigate the role played by endothelial nitric oxide (NO) during acute vascular response to hypoxia, as a modulator of both vascular tone (through guanylate cyclase (sGC) activation) and mitochondrial O2 consumption (through competitive inhibition of cytochrome-c-oxydase (CcO)). Organ bath experiments were performed and O2 consumption (Clark electrode) was determined in isolated aorta, mesenteric and pulmonary arteries of rats and eNOS-knockout mice. All pre-contracted vessels exhibited a triphasic hypoxic response consisting of an initial transient contraction (not observed in vessels from eNOS-knockout mice) followed by relaxation and subsequent sustained contraction. Removal of the endothelium, inhibition of eNOS (by L-NNA) and inhibition of sGC (by ODQ) abolished the initial contraction without altering the other two phases. The initial hypoxic contraction was observed in the presence of L-NNA+NO-donors. L-NNA and ODQ increases O2 consumption in hypoxic vessels and increases the arterial tone in normoxia but not in hypoxia. When L-NNA+mitochondrial inhibitors (cyanide, rotenone or myxothiazol) were added, the increase in tone was similar in normoxic and hypoxic vessels, which suggests that inhibition of the binding of NO to reduced CcO restored the action of NO on sGC. CONCLUSION: A complex equilibrium is established between NO, sGC and CcO in vessels in function of the concentration of O2: as O2 falls, NO inhibition of mitochondrial O2 consumption increases and activation of sGC decreases, thus promoting a rapid increase in tone in both pulmonary and systemic vessels, which is followed by the triggering of NO-independent vasodilator/vasoconstrictor mechanisms.


Assuntos
Aorta/metabolismo , Células Endoteliais/metabolismo , Hipóxia/metabolismo , Artérias Mesentéricas/metabolismo , Óxido Nítrico/metabolismo , Artéria Pulmonar/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo III/deficiência , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Ratos Sprague-Dawley
11.
Life Sci ; 336: 122286, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38007144

RESUMO

AIMS: Transient receptor potential vanilloid 2 (TRPV2) channels are expressed in both smooth muscle and endothelial cells and participate in vascular mechanotransduction and sensing of high temperatures and lipids. Nevertheless, the impact of TRPV2 channel activation by agonists on the coordinated and cell-type specific modulation of vasoreactivity is unknown. MAIN METHODS: Aorta from 2- to 4-months-old male Oncins France 1 mice was dissected and mounted in tissue baths for isometric tension measurements. TRPV2 channel expression was assessed by immunofluorescence and western blot in mice aortas and in cultured A7r5 rat aortic smooth muscle cells. KEY FINDINGS: TRPV2 channels were expressed in all three mouse aorta layers. Activation of TRPV2 channels with probenecid evoked endothelium-dependent relaxations through a mechanism that involved activation of smooth muscle Kir and Kv channels. In addition, TRPV2 channel inhibition with tranilast increased endothelium-independent relaxations to probenecid and this effect was abrogated by the KATP channel blocker glibenclamide, revealing that smooth muscle TRPV2 channels induce negative feedback on probenecid relaxations mediated via KATP channel inhibition. Exposure to the NO donor sodium nitroprusside increased TRPV2 channel translocation to the plasma membrane in cultured smooth muscle cells and enhanced negative feedback on probenecid relaxations. SIGNIFICANCE: In conclusion, we present the first evidence that TRPV2 channels may modulate vascular tone through a balance of opposed inputs from the endothelium and the smooth muscle leading to net vasodilation. The fact that TRPV2 channel-induced activity can be amplified by NO emphasizes the pathophysiological relevance of these findings.


Assuntos
Células Endoteliais , Probenecid , Camundongos , Ratos , Masculino , Animais , Probenecid/farmacologia , Mecanotransdução Celular , Aorta/metabolismo , Vasodilatação , Trifosfato de Adenosina/metabolismo , Endotélio Vascular/fisiologia
12.
Sci Rep ; 14(1): 3729, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355737

RESUMO

Electrodes with nanostructured surface have emerged as promising low-impedance neural interfaces that can avoid the charge-injection restrictions typically associated to microelectrodes. In this work, we propose a novel approximation, based on a two-step template assisted electrodeposition technique, to obtain flexible nanostructured electrodes coated with core-shell Ni-Au vertical nanowires. These nanowires benefit from biocompatibility of the Au shell exposed to the environment and the mechanical properties of Ni that allow for nanowires longer and more homogeneous in length than their only-Au counterparts. The nanostructured electrodes show impedance values, measured by electrochemical impedance spectroscopy (EIS), at least 9 times lower than those of flat reference electrodes. This ratio is in good accordance with the increased effective surface area determined both from SEM images and cyclic voltammetry measurements, evidencing that only Au is exposed to the medium. The observed EIS profile evolution of Ni-Au electrodes over 7 days were very close to those of Au electrodes and differently from Ni ones. Finally, the morphology, viability and neuronal differentiation of rat embryonic cortical cells cultured on Ni-Au NW electrodes were found to be similar to those on control (glass) substrates and Au NW electrodes, accompanied by a lower glial cell differentiation. This positive in-vitro neural cell behavior encourages further investigation to explore the tissue responses that the implantation of these nanostructured electrodes might elicit in healthy (damaged) neural tissues in vivo, with special emphasis on eventual tissue encapsulation.


Assuntos
Nanoestruturas , Nanofios , Ratos , Animais , Eletrodos , Microeletrodos , Neurônios/fisiologia , Impedância Elétrica
13.
Materials (Basel) ; 16(9)2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37176407

RESUMO

Biomass-derived products, such as lignin, are interesting resources for energetic purposes. Lignin is a natural polymer that, when added to the anode of an alkaline exchange membrane water electrolyser, enhances H2 production rates and efficiencies due to the substitution of the oxygen evolution reaction. Higher efficiencies are reported when different catalytic materials are employed for constructing the lignin anolyte, demonstrating that lower catalytic loadings for the anode improves the H2 production when compared to higher loadings. Furthermore, when a potential of -1.8 V is applied, higher gains are obtained than when -2.3 V is applied. An increase of 200% of H2 flow rates with respect to water electrolysis is reported when commercial lignin is used coupled with Pt-Ru at 0.09 mg cm-2 and E = -1.8 V is applied at the cathode. This article provides deep information about the oxidation process, as well as an optimisation of the method of the lignin electro-oxidation in a flow-reactor as a pre-step for an industrial implementation.

14.
ACS Appl Mater Interfaces ; 15(30): 36242-36249, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37489711

RESUMO

A new highly soluble triazine derivative (SPr)34TpyTz showing three reversible redox processes with fast kinetics and high diffusion coefficients has been synthesized using an efficient, low-cost, and straightforward synthetic route. Concentrated single cell tests and DFT studies reveal a tendency of the reduced triazine species to form aggregates which could be avoided by tuning the supporting electrolyte concentration. Under the right conditions, (SPr)34TpyTz shows no capacity decay and good Coulombic, voltage, and energy efficiencies for the storage of two electrons. The storage of further electrons leads to a higher capacity decay and an increase of the electrolyte pH, suggesting the irreversible protonation of the generated species. So, a plausible mechanism has been proposed. A higher concentration of (SPr)34TpyTz shows slightly higher capacity decay and lower efficiencies due to the aggregate formation.

15.
Am J Physiol Heart Circ Physiol ; 303(3): H368-76, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22685168

RESUMO

Downregulation of ß(1)- adrenergic receptors (ß(1)-ARs) and increased expression/function of G-protein-coupled receptor kinase 2 (GRK2) have been observed in human heart failure, but changes in expression of other ARs and GRKs have not been established. Another unresolved question is the incidence of these compensatory mechanisms depending on heart failure etiology and treatment. To analyze these questions, we quantified the mRNA/protein expressions of six ARs (α(1A), α(1B), α(1D), ß(1), ß(2), and ß(3)) and three GRKs (GRK2, GRK3, and GRK5) in left (LV) and right ventricle (RV) from four donors, 10 patients with ischemic cardiomyopathy (IC), 14 patients with dilated cardiomyopathy (DC), and 10 patients with nonischemic, nondilated cardiopathies (NINDC). We correlated the changes in the expressions of ARs and GRKs with clinical variables such as left ventricular ejection fraction (LVEF) and left ventricular end-systolic and left ventricular end-diastolic diameter (LVESD and LVEDD, respectively). The main findings were 1) the expression of the α(1A)-AR in the LV positively correlates with LVEF; 2) the expression of GRK3 and GRK5 inversely correlates with LVESD and LVEDD, supporting previous observations about a protective role for both kinases in failing hearts; and 3) ß(1)-AR expression is downregulated in the LV and RV of IC, in the LV of DC, and in the RV of NINDC. This difference, better than an increased expression of GRK2 (not observed in IC), determines the lower LVEF in IC and DC vs. NINDC.


Assuntos
Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Quinases de Receptores Acoplados a Proteína G/genética , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Isquemia Miocárdica/complicações , Miocárdio/química , Receptores Adrenérgicos/análise , Adulto , Análise de Variância , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/genética , Cardiomiopatias/fisiopatologia , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/fisiopatologia , Feminino , Genótipo , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia , Fenótipo , RNA Mensageiro/análise , Receptores Adrenérgicos/genética , Espanha , Volume Sistólico , Função Ventricular Esquerda
16.
J Card Fail ; 18(1): 53-61, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22196842

RESUMO

BACKGROUND: In heart failure (HF), sympathetic hyperactivation induces deleterious effects in myocardial ß-adrenergic signaling, with receptor down-regulation and desensitization mediated by G protein receptor-coupled kinases (GRKs). We hypothesised that changes in GRK isoforms may be associated with clinical status in advanced HF, using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scale. METHODS: We included 31 patients with advanced HF undergoing transplantation. According to INTERMACS profiles, mRNA and protein levels of GRK isoforms in left ventricular (LV) myocardium were analyzed and compared with nonfailing LV samples. RESULTS: In failing LV myocardium, GRK2 and GRK5 (but not GRK3) protein was up-regulated compared with control samples. Among HF patients, an increase in GRK2 and GRK5 mRNA and protein abundance was observed in ß-agonist-treated patients (vs ß-blockers: P < .05) and in higher-risk INTERMACS status (profiles 2 and 3 vs 4 and 5: P < .05). A significant negative correlation of GRK2 expression with LV stroke volume supported these findings. CONCLUSIONS: Increased GRK2 correlates with clinical severity using the INTERMACS scale and LV stroke volume, supporting it as a potential target in advanced HF. These changes are paralleled by GRK5 expression in the failing myocardium, suggesting a relevant role in human HF.


Assuntos
Quinases de Receptores Acoplados a Proteína G/genética , Insuficiência Cardíaca/enzimologia , Miocárdio/enzimologia , Regulação para Baixo , Feminino , Quinase 2 de Receptor Acoplado a Proteína G/genética , Quinase 5 de Receptor Acoplado a Proteína G/genética , Quinases de Receptores Acoplados a Proteína G/química , Quinases de Receptores Acoplados a Proteína G/metabolismo , Regulação Enzimológica da Expressão Gênica , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , Coração Auxiliar , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Sistema de Registros , Índice de Gravidade de Doença , Espanha
17.
Nanomaterials (Basel) ; 12(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364534

RESUMO

The exfoliation of tridimensional crystal structures has recently been considered a new source of bidimensional materials. The new approach offers the possibility of dramatically enlarging the library of bidimensional materials, but the number of nanolayers produced so far is still limited. Here, we report for the first time the use of a new type of material, α-germanium nanolayers (2D α-Ge). The 2D α-Ge is obtained by exfoliating crystals of α-germanium in a simple one-step procedure assisted by wet ball-milling (gram-scale fabrication). The α-germanium nanolayers have been tested as anode material for high-performance LIBs. The results show excellent performance in semi-cell configuration with a high specific capacity of 1630 mAh g-1 for mass loading of 1 mg cm-2 at 0.1 C. The semi-cell was characterized by a constant current rate of 0.5 C during 400 cycles and different scan rates (0.1 C, 0.5 C, and 1 C). Interestingly, the structural characterization, including Raman spectroscopy, XRPD, and XPS, concludes that 2D α-Ge largely retains its crystallinity after continuous cycling. These results can be used to potentially apply these novel 2D germanium nanolayers to high-performance Li-ion batteries.

18.
World J Psychiatry ; 12(4): 588-602, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35582332

RESUMO

The role played by serendipity in the origin of modern psychopharmacology has proven to be controversial in scientific literature. In its original meaning (Walpole), serendipity refers to discoveries made through a combination of accidents and sagacity. We have implemented an operational definition of serendipity based on finding something unexpected or unintended, regardless of the systematic process that led to the accidental observation, and we have established four different patterns of serendipitous attributability. In this paper, we have analyzed the role of serendipity in the discovery and development of classical antidepressant drugs, tricyclic antidepressants and monoamine oxidase inhibitors as well as heterocyclic, "atypical" or "second generation" antidepressants. The discovery of the antidepressant properties of imipramine and iproniazid, the prototypes of tricyclic antidepressants and monoamine oxidase inhibitors, respectively, fits the mixed type II pattern; initial serendipitous discoveries (imipramine was an antipsychotic and iproniazid was an anti-tuberculosis agent) led secondarily to non-serendipitous discoveries. But the other components of these two families of drugs were developed specifically as antidepressants, modifying the chemical structure of the series leaders, thereby allowing all of them to be included in the type IV pattern, characterized by the complete absence of serendipity. Among the heterocyclic drugs, mianserin (originally developed as an antihistamine) also falls into the type II pattern.

19.
Front Pharmacol ; 13: 826837, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35645795

RESUMO

Imidazoline receptors (IR) are classified into three receptor subtypes (I1R, I2R, and I3R) and previous studies showed that regulation of I2R signaling has neuroprotective potential. In order to know if I2R has a role in modulating vascular tone in health and disease, we evaluated the putative vasoactive effects of two recently synthesized I2R ligands, diethyl (1RS,3aSR,6aSR)-5-(3-chloro-4-fluorophenyl)-4,6-dioxo-1-phenyl-1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c]pyrrole -1-phosphonate (B06) and diethyl [(1-(3-chloro-4-fluorobenzyl)-5,5-dimethyl-4-phenyl-4,5-dihydro-1H-imidazol-4-yl]phosphonate] (MCR5). Thoracic aortas from Oncins France 1 (3- to 4-months-old) and C57BL/6 (3- to 4- and 16- to 17-months-old mice) were mounted in tissue baths to measure isometric tension. In young mice of both strains, MCR5 induced greater relaxations than either B06 or the high-affinity I2R selective ligand 2-(2-benzofuranyl)-2-imidazoline (2-BFI), which evoked marginal responses. MCR5 relaxations were independent of I2R, as IR ligands did not significantly affect them, involved activation of smooth muscle KATP channels and inhibition of L-type voltage-gated Ca2+ channels, and were only slightly modulated by endothelium-derived nitric oxide (negatively) and prostacyclin (positively). Notably, despite the presence of endothelial dysfunction in old mice, MCR5 relaxations were preserved. In conclusion, the present study provides evidence against a functional contribution of I2R in the modulation of vascular tone in the mouse aorta. Moreover, the I2R ligand MCR5 is an endothelium-independent vasodilator that acts largely via I2R-independent pathways and is resistant to aging. We propose MCR5 as a candidate drug for the management of vascular disease in the elderly.

20.
Langmuir ; 27(15): 9621-9, 2011 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-21739936

RESUMO

Functionalized carbon nanotubes were used as a support for PtCo nanoparticles. Their performance as electrocatalysts for the electrooxidation of methanol was evaluated by cyclic voltammetry and in situ FTIR reflectance spectroscopy. The onset potentials for both the electrooxidation of methanol and the production of CO(2) shifted to less positive values for catalysts prepared with more oxygen groups on the support. Furthermore, the production of CO(2) was higher on catalysts prepared with functionalized carbon nanotubes. The functional groups play two different but complementary roles. On the one hand, they help to stabilize smaller PtCo particles of ca. 3 nm. On the other hand, they provide the -OH groups necessary for the total oxidation of methanol to CO(2) at potentials less positive than on nonfunctionalized supports. Remarkably, the consumption of carboxylic acid groups along with the production of water is observed in the infrared spectra of the functionalized supports recorded during the electrooxidation of methanol. This observation suggests that the -OH groups of the support can also react with methanol, forming water and an ester.

SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa