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1.
Purinergic Signal ; 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32808144

RESUMO

We aim to investigate the role of A2A receptor in peritonitis-related sepsis by injection of a fecal solution (FS) as a model of polymicrobial infection. C57/black J6 wild-type (WT) and A2A-deficient mice (A2AKO) were exposed to sepsis induced by intraperitoneal injection of a FS (FS-induced peritonitis) or instead was injected with saline buffer (Sham). Survival rate and sepsis score were measured up to 48 h. The presence of bacteria in tissue homogenates was analyzed. Telemetry and speckle laser Doppler were used for systemic blood pressure and peripheral blood perfusion analysis, respectively. Histological analysis and identification of active caspase 3 were performed in selected organs, including the liver. The survival rate of A2AKO mice exposed to FS-induced peritonitis was significantly higher, and the sepsis score was lower than their respective WT counterpart. Injection of FS increases (50 to 150 folds) the number of colonies forming units in the liver, kidney, blood, and lung in WT mice, while these effects were significantly attenuated in A2AKO mice exposed to FS-induced peritonitis. A significant reduction in both systolic and diastolic blood pressure, as well as in the peripheral perfusion was observed in WT and A2AKO mice exposed to FS-induced peritonitis. Although, these last effects were significantly attenuated in A2AKO mice. Histological analysis showed a large perivascular infiltration of polymorphonuclear in the liver of WT and A2AKO mice exposed to FS-induced peritonitis, but again, this effect was attenuated in A2AKO mice. Finally, high expression of active caspase 3 was found only in the liver of WT mice exposed to FS-induced peritonitis. The absence of the A2A receptor increases the survival rate in mice exposed to polymicrobial sepsis. This outcome was associated with both hemodynamic compensation and enhanced anti-bacterial response.

2.
Syst Biol Reprod Med ; 66(3): 151-169, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32482148

RESUMO

The placenta works as a selective barrier, protecting the fetus from potential infections that may affect the maternal organism during pregnancy. In this review, we will discuss several challenging infections that are common within Latin American countries and that may affect the maternal-fetal interface and pose risks to fetal development. Specifically, we will focus on emerging infectious diseases including the arboviruses, malaria, leishmaniasis, and the bacterial foodborne disease caused by Shiga toxin-producing Escherichia coli. We will also highlight some topics of interest currently being studied by research groups that comprise an international effort aimed at filling the knowledge gaps in this field. These topics address the relationship between exposure to microorganisms and placental abnormalities, congenital anomalies, and complications of pregnancy. ABBREVIATIONS: ADE: antibody-dependent enhancement; CCL2: monocyte chemoattractant protein-1; CCL3: macrophage inflammatory protein-1 α; CCL5: chemokine (C-C motif) ligand 5; CHIKV: chikungunya virus; DCL: diffuse cutaneous leishmaniasis; DENV: dengue virus; Gb3: glycolipid globotriaosylceramyde; HIF: hypoxia-inducible factor; HUS: hemolytic uremic syndrome; IFN: interferon; Ig: immunoglobulins; IL: interleukin; IUGR: intrauterine growth restriction; LCL: localized cutaneous leishmaniasis; LPS: lipopolysaccharid; MCL: mucocutaneous leishmaniasis; NO: nitric oxide; PCR: polymerase chain reaction; PGF: placental growth factor; PM: placental malaria; RIVATREM: Red Iberoamericana de Alteraciones Vasculares em transtornos del Embarazo; sVEGFR: soluble vascular endothelial growth factor receptor; STEC: shiga toxin-producing Escherichia coli; stx: shiga toxin protein; TNF: tumor necrosis factor; TOAS: T cell original antigenic sin; Var2CSA: variant surface antigen 2-CSA; VEGF: vascular endothelial growth factor; VL: visceral leishmaniasis; WHO: world health organization; YFV: yellow fever virus; ZIKV: Zika virus.

4.
Expert Rev Clin Pharmacol ; 13(3): 247-263, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32129110

RESUMO

Introduction: The placenta is a temporary and unique organ that allows for the physical connection between a mother and fetus; this organ regulates the transport of gases and nutrients mediating the elimination of waste products contained in the fetal circulation. The placenta performs metabolic and excretion functions, on the basis of multiple enzymatic systems responsible for the oxidation, reduction, hydrolysis, and conjugation of xenobiotics. These mechanisms give the placenta a protective role that limits the fetal exposure to harmful compounds. During pregnancy, some diseases require uninterrupted treatment even if it is detrimental to the fetus. Drugs and other xenobiotics alter gene expression in the placenta with repercussions for the fetus and mother's well-being.Areas covered: This review provides a brief description of the human placental structure and function, the main drug and xenobiotic transporters and metabolizing enzymes, placenta-metabolized substrates, and alterations in gene expression that the exposure to xenobiotics may cause.Expert opinion: Research should be focused on the identification and validation of biological markers for the assessment of the harmful effects of some drugs in pregnancy, including the evaluation of polymorphisms and methylation patterns in chorionic villous samples and/or amniotic fluid.

5.
Nitric Oxide ; 99: 7-16, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32165314

RESUMO

Insulin regulates the l-arginine/nitric oxide (NO) pathway in human umbilical vein endothelial cells (HUVECs), increasing the plasma membrane expression of the l-arginine transporter hCAT-1 and inducing vasodilation in umbilical and placental veins. Placental vascular relaxation induced by insulin is dependent of large conductance calcium-activated potassium channels (BKCa), but the role of KCa channels on l-arginine transport and NO synthesis is still unknown. The aim of this study was to determine the contribution of KCa channels in both insulin-induced l-arginine transport and NO synthesis, and its relationship with placental vascular relaxation. HUVECs, human placental vein endothelial cells (HPVECs) and placental veins were freshly isolated from umbilical cords and placenta from normal pregnancies. Cells or tissue were incubated in absence or presence of insulin and/or tetraethylammonium, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole, iberiotoxin or NG-nitro-l-arginine methyl ester. l-Arginine uptake, plasma membrane polarity, NO levels, hCAT-1 expression and placenta vascular reactivity were analyzed. The inhibition of intermediate-conductance KCa (IKCa) and BKCa increases l-arginine uptake, which was related with protein abundance of hCAT-1 in HUVECs. IKCa and BKCa activities contribute to NO-synthesis induced by insulin but are not directly involved in insulin-stimulated l-arginine uptake. Long term incubation (8 h) with insulin increases the plasma membrane hyperpolarization and hCAT-1 expression in HUVECs and HPVECs. Insulin-induced relaxation in placental vasculature was reversed by KCa inhibition. The results show that the activity of IKCa and BKCa channels are relevant for both physiological regulations of NO synthesis and vascular tone regulation in the human placenta, acting as a part of negative feedback mechanism for autoregulation of l-arginine transport in HUVECs.

6.
Br J Pharmacol ; 177(12): 2666-2682, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32201941

RESUMO

Since their discovery, the orphan nuclear receptors constitutive androstane receptor (CAR;NR1I3) and pregnane X receptor (PXR;NR1I2) have been regarded as master regulators of drug disposition and detoxification mechanisms. They regulate the metabolism and transport of endogenous mediators and xenobiotics in organs including the liver, intestine and brain. However, with proposals of new physiological functions for NR1I3 and NR1I2, there is increasing interest in the role of these receptors in influencing brain function. This review will summarise key findings regarding the expression and function of NR1I3 and NR1I2 in the brain, hereby highlighting the need for further research in this field.

8.
J Biosci Bioeng ; 129(4): 435-440, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31757606

RESUMO

Detection of bioactive peptides in complex ecosystems like intestinal environment is a difficult task. In this study, we developed two new bioreporters for nisin based on Lactococcus lactis NZ9000 transformed with the vector pNZ:Nis-aFP or pNZ:Nis-mCherry, that encoded for the anaerobic fluorescent protein evoglow-Pp1 (aFP) or the fluorescent protein mCherry, respectively. The biosensors were used to study nisin A production by L. lactis INIA 650 in milk and in a colonic model. The use of L. lactis NZ9000 pNZ:Nis-aFP as a biosensor allowed the detection of nisin produced by L. lactis INIA 650 in milk, but not in the in vitro colonic model. In milk, this reporter was induced by direct addition of 10 ng/ml nisin while, in the colonic model, nisin concentrations of 50 ng/ml were necessary. However, the reporter system based on pNZ:Nis-mCherry showed a higher sensibility, detecting nisin concentrations of 1 ng/ml produced by L. lactis INIA 650 in colonic media using agar diffusion or cross streak bioassays.

9.
Sensors (Basel) ; 19(24)2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31835498

RESUMO

Indoor positioning systems based on radio frequency inherently present multipath-related phenomena. This causes ranging systems such as ultra-wideband (UWB) to lose accuracy when detecting secondary propagation paths between two devices. If a positioning algorithm uses ranging measurements without considering these phenomena, it will face critical errors in estimating the position. This work analyzes the performance obtained in a localization system when combining location algorithms with machine learning techniques applied to a previous classification and mitigation of the propagation effects. For this purpose, real-world cross-scenarios are considered, where the data extracted from low-cost UWB devices for training the algorithms come from a scenario different from that considered for the test. The experimental results reveal that machine learning (ML) techniques are suitable for detecting non-line-of-sight (NLOS) ranging values in this situation.

10.
J Am Chem Soc ; 141(49): 19304-19311, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31774282

RESUMO

Ruthenium nanoparticles with a core-shell structure formed by a core of metallic ruthenium and a shell of ruthenium carbide have been synthesized by a mild and easy hydrothermal treatment. The dual structure and composition of the nanoparticles have been determined by synchrotron X-ray photoelectron spectroscopy (XPS), near-edge X-ray absorption fine structure (NEXAFS) analysis, and transmission electron microscopy (TEM) imaging. According to depth profile synchrotron XPS and X-ray diffraction (XRD) analysis, metallic ruthenium species predominate in the inner layers of the material, ruthenium carbide species being located on the upper surface layers. The ruthenium carbon catalysts presented herein are able to activate both CO2 and H2, exhibiting exceptional high activity for CO2 hydrogenation at low temperatures (160-200 °C) with 100% selectivity to methane, surpassing by far the most active Ru catalysts reported up to now. On the basis of catalytic studies and isotopic 13CO/12CO2/H2 experiments, the active sites responsible for this unprecedented activity can be associated with surface ruthenium carbide (RuC) species, which enable CO2 activation and transformation to methane via a direct CO2 hydrogenation mechanism. Both the high activity and the absence of CO in the gas effluent confer relevance to these catalysts for the Sabatier reaction, a chemical process with renewed interest for storing surplus renewable energy in the form of methane.

11.
Nanoscale ; 11(38): 17920-17930, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31553338

RESUMO

The combination of scanning probe microscopy and ambient pressure X-ray photoelectron spectroscopy opens up new perspectives for the study of combined surface chemical, electrochemical and electromechanical properties at the nanoscale, providing both nanoscale resolution of physical information and the chemical sensitivity required to identify surface species and bulk ionic composition. In this work, we determine the nature and evolution over time of surface chemical species obtained after water-mediated redox reactions on Pb(Zr0.2,Ti0.8)O3 thin films with opposite as-grown polarization states. Starting with intrinsically different surface chemical composition on the oppositely polarized films (as a result of their ferroelectric-dominated interaction with environmental water), we identify the reversible and irreversible electrochemical reactions under an external electric field, distinguishing switching and charging events. We find that while reversible ionic displacements upon polarization switching dominate screening in the bulk of the sample, polarization dependent irreversible redox reactions determine surface chemical composition, which reveals itself as a characteristic fingerprint of the ferroelectric polarization switching history.

12.
Curr Hypertens Rep ; 21(9): 72, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375930

RESUMO

PURPOSE OF REVIEW: To provide insight into the mechanisms underlying cerebral pathophysiology and to highlight possible methods for evaluation, screening, and surveillance of cerebral complications in preeclampsia. RECENT FINDINGS: The pathophysiology of eclampsia remains enigmatic. Animal studies show that the cerebral circulation in pregnancy and preeclampsia might be affected with increased permeability over the blood-brain barrier and altered cerebral blood flow due to impaired cerebral autoregulation. The increased blood pressure cannot be the only underlying cause of eclampsia and cerebral edema, since some cases of eclampsia arise without simultaneous hypertension. Findings from animal studies need to be confirmed in human tissues. Evaluation of brain alterations in preeclampsia and eclampsia is challenging and demands a multidisciplinary collaboration, since no single method can accurately and fully describe how preeclampsia affects the brain. Cerebral complications of preeclampsia are significant factors in maternal morbidity and mortality worldwide. No single method can accurately describe the full picture of how preeclampsia affects the brain vasculature and parenchyma. We recommend an international and multidisciplinary effort not only to overcome the issue of limited sample availability but also to optimize the quality of research.

14.
Appl Physiol Nutr Metab ; 44(9): 944-951, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31389713

RESUMO

The objective was to assess if there was any relationship between the amount of skeletal muscle mass (SMM) in children aged 6-8 years and their nutritional intake. The Valencian Anthropometry and Child Nutrition (ANIVA) study is a cross-sectional study with children aged between 6-8 years (n = 1988) from schools in Valencia. Children were distributed into 4 groups for comparison: normal and high SMM and by sex. Anthropometric data were obtained following World Health Organization protocols. Nutritional intake was measured using a prospective 3-day food journal and the KIDMED questionnaire. Of the whole child sample, 63.9% had high SMM values. No differences were found in adherence to a Mediterranean diet or absolute energy intake. Significant differences were found in the proportion of energy intake in relation to estimated energy requirements and between nutritional intake of certain macro or micronutrients with SMM. This study provides values of SMM for children. Children's adherence to a Mediterranean diet was not related to total SMM. At the same time, the consumption of excess calories or overeating is associated with SMM, with those children overeating more having lower SMM values. The differences in the intake of the other macro- and micronutrients were not associated with children's SMM.


Assuntos
Composição Corporal/fisiologia , Fenômenos Fisiológicos da Nutrição Infantil , Dieta Mediterrânea , Músculo Esquelético/fisiologia , Criança , Exercício Físico , Feminino , Humanos , Masculino
15.
Sensors (Basel) ; 19(16)2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398892

RESUMO

Indoor location systems based on ultra-wideband (UWB) technology have become very popular in recent years following the introduction of a number of low-cost devices on the market capable of providing accurate distance measurements. Although promising, UWB devices also suffer from the classic problems found when working in indoor scenarios, especially when there is no a clear line-of-sight (LOS) between the emitter and the receiver, causing the estimation error to increase up to several meters. In this work, machine learning (ML) techniques are employed to analyze several sets of real UWB measurements, captured in different scenarios, to try to identify the measurements facing non-line-of-sight (NLOS) propagation condition. Additionally, an ulterior process is carried out to mitigate the deviation of these measurements from the actual distance value between the devices. The results show that ML techniques are suitable to identify NLOS propagation conditions and also to mitigate the error of the estimates when there is LOS between the emitter and the receiver.

16.
J Synchrotron Radiat ; 26(Pt 4): 1288-1293, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31274456

RESUMO

Platinum thin films activated ex situ by oxygen plasma become reduced by the combined effect of an intense soft X-ray photon beam and condensed water. The evolution of the electronic structure of the surface has been characterized by near-ambient-pressure photoemission and mimics the inverse two-step sequence observed in the electro-oxidation of platinum, i.e. the surface-oxidized platinum species are reduced first and then the adsorbed species desorb in a second step leading to a surface dominated by metallic platinum. The comparison with measurements performed under high-vacuum conditions suggests that the reduction process is mainly induced by the reactive species generated by the radiolysis of water. When the photon flux is decreased, then the reduction process becomes slower.

17.
Pregnancy Hypertens ; 16: 139-144, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31056149

RESUMO

The goals of the United Nation's Millennium Summit for reducing maternal mortality have proven difficult to achieve. In Bolivia, where maternal mortality is twice the South American average, improving the diagnosis, treatment and ultimately prevention of preeclampsia is key for achieving targeted reductions. We held a workshop in La Paz, Bolivia to review recent revisions in the diagnosis and treatment of preeclampsia, barriers for their implementation, and means for overcoming them. While physicians are generally aware of current recommendations, substantial barriers exist for their implementation due to geographic factors increasing disease prevalence and limiting health-care access, cultural and economic factors affecting the care provided, and infrastructure deficits impeding diagnosis and treatment. Means for overcoming such barriers include changes in the culture of health care, use of standardized diagnostic protocols, the adoption of low-cost technologies for improving the diagnosis and referral of preeclamptic cases to specialized treatment centers, training programs to foster multidisciplinary team approaches, and efforts to enhance local research capacity. While challenging, the synergistic nature of current barriers for preeclampsia diagnosis and treatment also affords opportunities for making far-reaching improvements in maternal, infant and lifelong health.


Assuntos
Acesso aos Serviços de Saúde/organização & administração , Serviços de Saúde Materna/organização & administração , Pré-Eclâmpsia/epidemiologia , Bolívia/epidemiologia , Feminino , Humanos , Pré-Eclâmpsia/mortalidade , Pré-Eclâmpsia/prevenção & controle , Gravidez
18.
J Phys Chem C Nanomater Interfaces ; 123(13): 8421-8428, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30976377

RESUMO

Surface segregation and restructuring in size-selected CuNi nanoparticles were investigated via near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) at various temperatures in different gas environments. Particularly in focus were structural and morphological changes occurring under CO2 hydrogenation conditions in the presence of carbon monoxide (CO) in the reactant gas mixture. Nickel surface segregation was observed when only CO was present as adsorbate. The segregation trend is inverted in a reaction gas mixture consisting of CO2, H2, and CO, resulting in an increase of copper concentration on the surface. Density functional theory calculations attributed the inversion of the segregation trend to the formation of a stable intermediate on the nanocatalyst surface (CH3O) in the CO-containing reactant mixture, which modifies the nickel segregation energy, thus driving copper to the surface. The promoting role of CO for the synthesis of methanol was demonstrated by catalytic characterization measurements of silica-supported CuNi NPs in a fixed-bed reactor, revealing high methanol selectivity (over 85%) at moderate pressures (20 bar). The results underline the important role of intermediate reaction species in determining the surface composition of bimetallic nanocatalysts and help understand the effect of CO cofeed on the properties of CO2 hydrogenation catalysts.

19.
Phys Chem Chem Phys ; 21(9): 4920-4930, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30758026

RESUMO

Water dissociation on oxides is of great interest because its fundamental aspects are still not well understood and it has implications in many processes, from ferroelectric polarization screening phenomena to surface catalysis and surface chemistry on oxides. In situ water dissociation and redox processes on metal oxide perovskites which easily expose TiO2-terminated surfaces, such as SrTiO3, BaTiO3 or Pb(Zr,Ti)O3, are studied by ambient pressure XPS, as a function of water vapour pressure. From the analysis of the O1s spectrum, we determine the presence of different types of oxygen based species, from hydroxyl groups, either bound to Ti4+ and metal sites or lattice oxygen, to different peroxide compounds, and propose a model for the adsorbate layer composition, valid for environmental conditions. From the XPS analysis, we describe the existing surface redox reactions for metal oxide perovskites, occurring at different water vapour pressures. Among them, peroxide species resulting from surface oxidative reactions are correlated with the presence of Ti4+ ions, which are observed to specifically promote surface oxidation and water dissociation as compared to other metals. Finally, surface peroxidation is enhanced by X-ray beam irradiation, leading to a higher coverage of peroxide species after beam overexposure and by ferroelectric polarization, demonstrating the enhancement of the reactivity of the surfaces of ferroelectric materials due to the effect of internal electric fields.

20.
Front Physiol ; 9: 1502, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30459636

RESUMO

Transport of drugs across biological barriers has been a subject of study for decades. The discovery and characterization of proteins that confer the barrier properties of endothelia and epithelia, including tight junction proteins and membrane transporters belonging to the ATP-binding cassette (ABC) and Solute Carrier (SLC) families, represented a significant step forward into understanding the mechanisms that govern drug disposition. Subsequently, numerous studies, including both pre-clinical approaches and clinical investigations, have been carried out to determine the influence of physiological and pathological states on drug disposition. Importantly, there has been increasing interest in gaining a better understanding of drug disposition during pregnancy, since epidemiological and clinical studies have demonstrated that the use of medications by pregnant women is significant and this condition embodies a series of significant anatomical and physiological modifications, particularly at excretory organs and barrier sites (e.g., placenta, breast) expressing transporter proteins which influence pharmacokinetics. Currently, most of the research in this field has focused on the expression profiling of transporter proteins in trophoblasts and endothelial cells of the placenta, regulation of drug-resistance mechanisms in disease states and pharmacokinetic studies. However, little attention has been placed on the influence that the cerebrovascular dysfunction present in pregnancy-related disorders, such as preeclampsia, might exert on drug disposition in the mother's brain. This issue is particularly important since recent findings have demonstrated that preeclamptic women suffer from long-term alterations in the integrity of the blood-brain barrier (BBB). In this review we aim to analyze the available evidence regarding the influence of pregnancy on the expression of transporters and TJ proteins in brain endothelial cells, as well the mechanisms that govern the pathophysiological alterations in the BBB of women who experience preeclampsia. Future research efforts should be focused not only on achieving a better understanding of the influence of preeclampsia-associated endothelial dysfunction on drug disposition, but also in optimizing the pharmacological treatments of women suffering pregnancy-related disorders, its comorbidities and to develop new therapies aiming to restore the integrity of the BBB.

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