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1.
Artigo em Inglês | MEDLINE | ID: mdl-38438188

RESUMO

Astrocytic metabolism has taken center stage. Interposed between the neuron and the vasculature, astrocytes exert control over the fluxes of energy and building blocks required for neuronal activity and plasticity. They are also key to local detoxification and waste recycling. Whereas neurons are metabolically rigid, astrocytes can switch between different metabolic profiles according to local demand and the nutritional state of the organism. Their metabolic state even seems to be instructive for peripheral nutrient mobilization and has been implicated in information processing and behavior. Here, we summarize recent progress in our understanding of astrocytic metabolism and its effects on metabolic homeostasis and cognition.

2.
Nat Neurosci ; 27(3): 433-448, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38267524

RESUMO

The integrity of myelinated axons relies on homeostatic support from oligodendrocytes (OLs). To determine how OLs detect axonal spiking and how rapid axon-OL metabolic coupling is regulated in the white matter, we studied activity-dependent calcium (Ca2+) and metabolite fluxes in the mouse optic nerve. We show that fast axonal spiking triggers Ca2+ signaling and glycolysis in OLs. OLs detect axonal activity through increases in extracellular potassium (K+) concentrations and activation of Kir4.1 channels, thereby regulating metabolite supply to axons. Both pharmacological inhibition and OL-specific inactivation of Kir4.1 reduce the activity-induced axonal lactate surge. Mice lacking oligodendroglial Kir4.1 exhibit lower resting lactate levels and altered glucose metabolism in axons. These early deficits in axonal energy metabolism are associated with late-onset axonopathy. Our findings reveal that OLs detect fast axonal spiking through K+ signaling, making acute metabolic coupling possible and adjusting the axon-OL metabolic unit to promote axonal health.


Assuntos
Axônios , Substância Branca , Camundongos , Animais , Axônios/fisiologia , Oligodendroglia/metabolismo , Substância Branca/metabolismo , Homeostase , Lactatos/metabolismo
3.
Nat Metab ; 5(11): 1852-1853, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37932429
4.
Oper Dent ; 48(6): 720-731, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37881067

RESUMO

OBJECTIVE: To evaluate the effects of commercial mouth rinses on color, roughness, sorption (SR), and solubility (SL) of resin composites. METHODS AND MATERIALS: Disc-shaped specimens (stage I: 6 mm × 2 mm; stage II: 10 mm × 1.5 mm) were made from the following resin composites (n=10): conventional nanofilled (Filtek Z350XT, 3M Oral Care), conventional nanohybrid (Luna, SDI), bulk-fill nanofilled (Filtek One Bulk-Fill, 3M Oral Care), and bulk-fill nanohybrid (Aura Bulk-Fill, SDI) exposed to distilled water (control), blue mouth rinse without alcohol (Colgate Total 12 Clean Mint, Colgate-Palmolive), or blue mouth rinse with alcohol and essential oil (Listerine Tartar Control, Johnson & Johnson). In stage I, tests were performed at the baseline, and after the immersion in solution time points to evaluate coordinates of the CIEL*a*b* system (ΔL*, Δa*, Δb*), general color change (ΔEab, ΔE00, and ΔSGU), and surface roughness (Ra). In stage II, SR and SL were evaluated (ISO 4049:2019) after immersion in the solutions for 7 days. The results were evaluated by generalized linear models (Ra, SR), Kruskal-Wallis, and Dunn tests (color, SL), with α = 0.05. RESULTS: There were no significative differences for Ra between the solutions. Both mouth rinses promoted significantly negative ΔL* (Luna), Δa* (Filtek One Bulk-fill), and Δb* (all materials except conventional nanofilled resin composite). Mouth rinse without alcohol promoted significantly negative Δa* on all resin composites tested. Both mouth rinses promoted higher ΔEab and ΔE00 for bulk-fill resin composites compared to control. Mouth rinse with alcohol caused higher ΔSGU for bulk-fill nanofilled resin composite. It also promoted greater SR in all the resin composites compared with mouth rinse without alcohol and higher SR in nanohybrid resin composites compared with control. Both mouth rinses promoted higher SL values in Luna and differed significantly from control. CONCLUSIONS: The physical properties were manufacturer dependent and mediated by mouth rinses. The mouth rinses promoted color changes in the resin composites, pointing out that bulk-fill resin composites were more affected by these effects, especially when the mouth rinse contained essential oil and alcohol.


Assuntos
Antissépticos Bucais , Óleos Voláteis , Antissépticos Bucais/farmacologia , Resinas Compostas , Etanol , Solubilidade , Teste de Materiais , Propriedades de Superfície
5.
Oper Dent ; 48(6): 677-688, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37881103

RESUMO

OBJECTIVE: To evaluate the flexural strength of two types of high-viscosity resin composites (conventional or bulk-fill) that were repaired with either high-viscosity composites (conventional or bulk-fill) or low-viscosity composites (conventional or bulk-fill) of the same manufacturer (3M Oral Care, St Paul, MN, USA). METHODS AND MATERIALS: Specimens (25 mm × 2 mm × 2 mm) of both conventional nanofilled resin (Filtek Z350XT), and bulk-fill nanofilled resin (Filtek One Bulk Fill) were prepared. After fracture of the specimens in the 3-point bending test (initial), half of the specimens were repaired immediately afterwards (24 hours), and the other half were repaired after 6 months of storage in distilled water. Repairs were performed with (n=15) high-viscosity resin composites (Filtek Z350XT, Filtek One Bulk Fill), or their low-viscosity versions (Filtek Supreme XT Flow, Filtek Bulk Fill Flowable Restorative). The repair was performed by roughening the surface and applying phosphoric acid, silane, and adhesive. The bending test (results reported in MPa) was performed in a universal testing machine, and the fracture pattern was determined. Data were evaluated by generalized linear models, chi-square test and the Fisher exact test (α=0.05). RESULTS: There was no significant difference between the former pair of high-viscosity resins in terms of initial flexural strength (p=0.42). The repairs performed with low-viscosity resin composites after 24 hours or 6 months obtained higher MPa values compared with those using high-viscosity composites (p=0.0006). There was a significant decrease in MPa values when the repair was performed after 24 hours and an increase after 6 months, regardless of the material (p<0.0001). After 6 months, fractures involving the old (conventional) resin were more frequent in the repair performed with bulk-fill resin composites compared with the conventional composites (p=0.02). CONCLUSIONS: Considering the tested products, the material to be repaired did not influence the flexural strength of the repair composite; however, the use of the low-viscosity resin composites resulted in greater flexural strength of the repaired material. The repair of the aged composite resulted in an increase in its flexural strength, regardless of the material repaired or used to perform the repair.


Assuntos
Materiais Dentários , Resistência à Flexão , Viscosidade , Teste de Materiais , Resinas Compostas/uso terapêutico
6.
Environ Toxicol Pharmacol ; 102: 104241, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37562547

RESUMO

The use of in vivo models to assess nephrotoxicity has faced ethical limitations. A viable alternative is the ex vivo model that combines the 3 R principles with the preservation of tissue histology. Here, we established a gentamicin nephrotoxicity model using pigs` kidney explants and investigated the effect of phytic acid (IP6) against gentamicin- induced nephrotoxicity. A total of 360 kidney explants were divided into control, gentamicin (10 mM), IP6 (5 mM), and gentamicin+IP6 groups. The activity of gammaglutamyltransferase (GGT), creatinine levels, histological assessment, oxidative stress, and inflammatory cytokine expression were analyzed. Exposure to gentamicin induced an increase in GGT activity, creatinine levels, lesion score, lipoperoxidation and IL-8 expression. Explants exposed to IP6 remained like the control. The addition of IP6 to gentamicin prevented tissue damage, increasing the antioxidant status and gene expression of IL-10. This model proved to be an adequate experimental approach for identifying nephrotoxins and potential products to modulate the toxicity.


Assuntos
Nefropatias , Insuficiência Renal , Animais , Suínos , Ácido Fítico/farmacologia , Ácido Fítico/uso terapêutico , Ácido Fítico/metabolismo , Creatinina , Rim , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Gentamicinas/toxicidade , Estresse Oxidativo , Nefropatias/patologia
7.
Neurobiol Dis ; 184: 106211, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37352985

RESUMO

Brain tissue metabolism is distributed across several cell types and subcellular compartments, which activate at different times and with different temporal patterns. The introduction of genetically-encoded fluorescent indicators that are imaged using time-lapse microscopy has opened the possibility of studying brain metabolism at cellular and sub-cellular levels. There are indicators for sugars, monocarboxylates, Krebs cycle intermediates, amino acids, cofactors, and energy nucleotides, which inform about relative levels, concentrations and fluxes. This review offers a brief survey of the metabolic indicators that have been validated in brain cells, with some illustrative examples from the literature. Whereas only a small fraction of the metabolome is currently accessible to fluorescent probes, there are grounds to be optimistic about coming developments and the application of these tools to the study of brain disease.


Assuntos
Encéfalo , Corantes Fluorescentes , Corantes Fluorescentes/metabolismo , Encéfalo/metabolismo , Metaboloma , Metabolismo Energético
8.
Aging (Albany NY) ; 15(19): 9896-9912, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37074814

RESUMO

Dysregulated central-energy metabolism is a hallmark of brain aging. Supplying enough energy for neurotransmission relies on the neuron-astrocyte metabolic network. To identify genes contributing to age-associated brain functional decline, we formulated an approach to analyze the metabolic network by integrating flux, network structure and transcriptomic databases of neurotransmission and aging. Our findings support that during brain aging: (1) The astrocyte undergoes a metabolic switch from aerobic glycolysis to oxidative phosphorylation, decreasing lactate supply to the neuron, while the neuron suffers intrinsic energetic deficit by downregulation of Krebs cycle genes, including mdh1 and mdh2 (Malate-Aspartate Shuttle); (2) Branched-chain amino acid degradation genes were downregulated, identifying dld as a central regulator; (3) Ketone body synthesis increases in the neuron, while the astrocyte increases their utilization, in line with neuronal energy deficit in favor of astrocytes. We identified candidates for preclinical studies targeting energy metabolism to prevent age-associated cognitive decline.


Assuntos
Astrócitos , Metabolismo Energético , Astrócitos/metabolismo , Metabolismo Energético/genética , Transmissão Sináptica , Perfilação da Expressão Gênica , Glucose/metabolismo
9.
Mol Neurodegener ; 18(1): 15, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36882871

RESUMO

BACKGROUND: Major retinal degenerative diseases, including age-related macular degeneration, diabetic retinopathy and retinal detachment, are associated with a local decrease in oxygen availability causing the formation of hypoxic areas affecting the photoreceptor (PR) cells. Here, we addressed the underlying pathological mechanisms of PR degeneration by focusing on energy metabolism during chronic activation of hypoxia-inducible factors (HIFs) in rod PR. METHODS: We used two-photon laser scanning microscopy (TPLSM) of genetically encoded biosensors delivered by adeno-associated viruses (AAV) to determine lactate and glucose dynamics in PR and inner retinal cells. Retinal layer-specific proteomics, in situ enzymatic assays and immunofluorescence studies were used to analyse mitochondrial metabolism in rod PRs during chronic HIF activation. RESULTS: PRs exhibited remarkably higher glycolytic flux through the hexokinases than neurons of the inner retina. Chronic HIF activation in rods did not cause overt change in glucose dynamics but an increase in lactate production nonetheless. Furthermore, dysregulation of the oxidative phosphorylation pathway (OXPHOS) and tricarboxylic acid (TCA) cycle in rods with an activated hypoxic response decelerated cellular anabolism causing shortening of rod photoreceptor outer segments (OS) before onset of cell degeneration. Interestingly, rods with deficient OXPHOS but an intact TCA cycle did not exhibit these early signs of anabolic dysregulation and showed a slower course of degeneration. CONCLUSION: Together, these data indicate an exceeding high glycolytic flux in rods and highlight the importance of mitochondrial metabolism and especially of the TCA cycle for PR survival in conditions of increased HIF activity.


Assuntos
Fosforilação Oxidativa , Degeneração Retiniana , Humanos , Glucose , Hipóxia , Ácido Láctico , Células Fotorreceptoras Retinianas Bastonetes
10.
Annu Rev Physiol ; 85: 115-135, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36270291

RESUMO

Information processing imposes urgent metabolic demands on neurons, which have negligible energy stores and restricted access to fuel. Here, we discuss metabolic recruitment, the tissue-level phenomenon whereby active neurons harvest resources from their surroundings. The primary event is the neuronal release of K+ that mirrors workload. Astrocytes sense K+ in exquisite fashion thanks to their unique coexpression of NBCe1 and α2ß2 Na+/K+ ATPase, and within seconds switch to Crabtree metabolism, involving GLUT1, aerobic glycolysis, transient suppression of mitochondrial respiration, and lactate export. The lactate surge serves as a secondary recruiter by inhibiting glucose consumption in distant cells. Additional recruiters are glutamate, nitric oxide, and ammonium, which signal over different spatiotemporal domains. The net outcome of these events is that more glucose, lactate, and oxygen are made available. Metabolic recruitment works alongside neurovascular coupling and various averaging strategies to support the inordinate dynamic range of individual neurons.


Assuntos
Metabolismo Energético , Glicólise , Humanos , Metabolismo Energético/fisiologia , Glicólise/fisiologia , Glucose/metabolismo , Ácido Láctico/metabolismo , Encéfalo/metabolismo
11.
Cell Mol Neurobiol ; 43(4): 1595-1618, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35953741

RESUMO

Fiber intake is associated with a lower risk for Alzheimer´s disease (AD) in older adults. Intake of plant-based diets rich in soluble fiber promotes the production of short-chain fatty acids (SCFAs: butyrate, acetate, propionate) by gut bacteria. Butyrate administration has antiinflammatory actions, but propionate promotes neuroinflammation. In AD patients, gut microbiota dysbiosis is a common feature even in the prodromal stages of the disease. It is unclear whether the neuroprotective effects of fiber intake rely on gut microbiota modifications and specific actions of SCFAs in brain cells. Here, we show that restoration of the gut microbiota dysbiosis through the intake of soluble fiber resulted in lower propionate and higher butyrate production, reduced astrocyte activation and improved cognitive function in 6-month-old male APP/PS1 mice. The neuroprotective effects were lost in antibiotic-treated mice. Moreover, propionate promoted higher glycolysis and mitochondrial respiration in astrocytes, while butyrate induced a more quiescent metabolism. Therefore, fiber intake neuroprotective action depends on the modulation of butyrate/propionate production by gut bacteria. Our data further support and provide a mechanism to explain the beneficial effects of dietary interventions rich in soluble fiber to prevent dementia and AD. Fiber intake restored the concentration of propionate and butyrate by modulating the composition of gut microbiota in male transgenic (Tg) mice with Alzheimer´s disease. Gut dysbiosis was associated with intestinal damage and high propionate levels in control diet fed-Tg mice. Fiber-rich diet restored intestinal integrity and promoted the abundance of butyrate-producing bacteria. Butyrate concentration was associated with better cognitive performance in fiber-fed Tg mice. A fiber-rich diet may prevent the development of a dysbiotic microbiome and the related cognitive dysfunction in people at risk of developing Alzheimer´s disease.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Microbioma Gastrointestinal , Fármacos Neuroprotetores , Camundongos , Animais , Propionatos/farmacologia , Doença de Alzheimer/metabolismo , Microbioma Gastrointestinal/fisiologia , Disbiose , Fármacos Neuroprotetores/farmacologia , Butiratos/farmacologia , Butiratos/metabolismo , Fibras na Dieta/farmacologia , Camundongos Transgênicos , Disfunção Cognitiva/prevenção & controle
12.
Orphanet J Rare Dis ; 17(1): 398, 2022 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-36309700

RESUMO

BACKGROUND: Congenital disorders of glycosylation (CDG) are a growing group of rare genetic disorders. The most common CDG is phosphomannomutase 2 (PMM2)-CDG which often has a severe clinical presentation and life-limiting consequences. There are no approved therapies for this condition. Also, there are no validated disease-specific quality of life (QoL) scales to assess the heterogeneous clinical burden of PMM2-CDG which presents a challenge for the assessment of the disease severity and the impact of a certain treatment on the course of the disease. AIM AND METHODS: This study aimed to identify the most impactful clinical signs and symptoms of PMM2-CDG, and specific patient and observer reported outcome measures (PROMs and ObsROMs, respectively) that can adequately measure such impact on patients' QoL. The most burdensome signs and symptoms were identified through input from the CDG community using a survey targeting PMM2-CDG families and experts, followed by family interviews to understand the real burden of these symptoms in daily life. The list of signs and symptoms was then verified and refined by patient representatives and medical experts in the field. Finally, a literature search for PROMs and ObsROMs used in other rare or common diseases with similar signs and symptoms to those of PMM2-CDG was performed. RESULTS: Twenty-four signs/symptoms were identified as the most impactful throughout PMM2-CDG patients' lifetime. We found 239 articles that included tools to measure those community-selected PMM2-CDG symptoms. Among them, we identified 80 QoL scales that address those signs and symptoms and, subsequently, their psychometric quality was analysed. These scales could be applied directly to the PMM2-CDG population or adapted to create the first PMM2-CDG-specific QoL questionnaire. CONCLUSION: Identifying the impactful clinical manifestations of PMM2-CDG, along with the collection of PROMs/ObsROMs assessing QoL using a creative and community-centric methodology are the first step towards the development of a new, tailored, and specific PMM2-CDG QoL questionnaire. These findings can be used to fill a gap in PMM2-CDG clinical development. Importantly, this methodology is transferable to other CDG and rare diseases with multiple signs and symptoms.


Assuntos
Defeitos Congênitos da Glicosilação , Fosfotransferases (Fosfomutases) , Humanos , Defeitos Congênitos da Glicosilação/tratamento farmacológico , Qualidade de Vida , Glicosilação , Fosfotransferases (Fosfomutases)/genética , Medidas de Resultados Relatados pelo Paciente
13.
Proc Natl Acad Sci U S A ; 119(33): e2204619119, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35939682

RESUMO

Brain activity is constrained by local availability of chemical energy, which is generated through compartmentalized metabolic processes. By analyzing data of whole human brain gene expression, we characterize the spatial distribution of seven glucose and monocarboxylate membrane transporters that mediate astrocyte-neuron lactate shuttle transfer of energy. We found that the gene coding for neuronal MCT2 is the only gene enriched in cerebral cortex where its abundance is inversely correlated with cortical thickness. Coexpression network analysis revealed that MCT2 was the only gene participating in an organized gene cluster enriched in K[Formula: see text] dynamics. Indeed, the expression of K[Formula: see text] subunits, which mediate lactate increases with spiking activity, is spatially coupled to MCT2 distribution. Notably, MCT2 expression correlated with fluorodeoxyglucose positron emission tomography task-dependent glucose utilization. Finally, the MCT2 messenger RNA gradient closely overlaps with functional MRI brain regions associated with attention, arousal, and stress. Our results highlight neuronal MCT2 lactate transporter as a key component of the cross-talk between astrocytes and neurons and a link between metabolism, cortical structure, and state-dependent brain function.


Assuntos
Nível de Alerta , Atenção , Córtex Cerebral , Ácido Láctico , Transportadores de Ácidos Monocarboxílicos , Neurônios , Angústia Psicológica , Transporte Biológico , Córtex Cerebral/metabolismo , Córtex Cerebral/ultraestrutura , Glucose/metabolismo , Humanos , Ácido Láctico/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Neurônios/metabolismo , Tomografia por Emissão de Pósitrons
14.
Nat Commun ; 13(1): 2125, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440557

RESUMO

Neurovascular coupling is a fundamental brain mechanism that regulates local cerebral blood flow (CBF) in response to changes in neuronal activity. Functional imaging techniques are commonly used to record these changes in CBF as a proxy of neuronal activity to study the human brain. However, the mechanisms of neurovascular coupling remain incompletely understood. Here we show in experimental animal models (laboratory rats and mice) that the neuronal activity-dependent increases in local CBF in the somatosensory cortex are prevented by saturation of the CO2-sensitive vasodilatory brain mechanism with surplus of exogenous CO2 or disruption of brain CO2/HCO3- transport by genetic knockdown of electrogenic sodium-bicarbonate cotransporter 1 (NBCe1) expression in astrocytes. A systematic review of the literature data shows that CO2 and increased neuronal activity recruit the same vasodilatory signaling pathways. These results and analysis suggest that CO2 mediates signaling between neurons and the cerebral vasculature to regulate brain blood flow in accord with changes in the neuronal activity.


Assuntos
Acoplamento Neurovascular , Animais , Dióxido de Carbono/metabolismo , Córtex Cerebral/metabolismo , Circulação Cerebrovascular , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Simportadores de Sódio-Bicarbonato/genética
15.
Appl Radiat Isot ; 184: 110122, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35272231

RESUMO

This work consists of an experimental determination of k0 and Q0 for 121Sb, 123Sb and 130Ba targets. Covariance analysis has been introduced to supply not only the overall uncertainties in these parameters but also their correlations. The irradiations were performed near the core of the IEA-R1 4.5 MW swimming-pool nuclear research reactor of the Nuclear and Energy Research Institute (IPEN-CNEN/SP), in São Paulo, Brazil. The epithermal neutron flux shape parameter, alpha, at the irradiation position is very close to zero, which favors to obtain Q0 values more accurately. Two irradiations were carried out in sequence, using two sets of samples: the first with bare samples and the second inside a Cd cover. The activity measurements were carried out in a previously calibrated HPGe gamma-ray spectrometer. The measurements were corrected for: saturation, decay time, cascade summing, geometry, self-attenuation, measuring time and mass. Standard sources of 152Eu, 133Ba, 60Co and 137Cs traceable to a 4πß-γ primary system were used to obtain the HPGe gamma-ray peak efficiency as a function of the energy. The experimental efficiency curve was performed by a fourth-degree polynomial fit, in the energy range of the standard sources, 121-1408 keV, it contains all correlations between points. For energies above 1408 keV, the efficiencies were obtained by the Monte Carlo Method. The covariance matrix methodology was applied to all uncertainties involved. The final values for k0 and Q0 were compared with the literature.


Assuntos
Método de Monte Carlo , Brasil
16.
Food Chem ; 383: 132450, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35182861

RESUMO

Dehydration of the edible seaweed Chondrus crispus was performed by freeze-drying, conventional oven-drying and emerging microwave hydrodiffusion and gravity (MHG). In this work, the drying kinetics and modelling, estimating specific energy consumption and environmental impact of distinct processes were tested. Color and microstructural features of the dried macroalgae were also evaluated, as well as their nutritive characterization, chemical profile and bioactive potential (antioxidant and antimicrobial activities). Moreover, collected liquid phases from both the defrosted and MHG treated samples were also characterized. All methodologies provided solid phases with an adequate final moisture content. MHG significantly reduced the needed time, specific energy consumption and environmental impact, providing C. crispus with intermediate color and histological structure characteristics. Overall, this trend was also defined to tested chemical parameters and bioactivities. MHG provided aqueous extracts with potential bioactive compounds from this red alga, increasing the efficiency of this drying method.


Assuntos
Chondrus , Alga Marinha , Antioxidantes/química , Chondrus/química , Dessecação , Liofilização , Alga Marinha/química , Verduras
17.
Free Radic Biol Med ; 182: 34-58, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35183660

RESUMO

The study of metabolism is undergoing a renaissance. Since the year 2002, over 50 genetically-encoded fluorescent indicators (GEFIs) have been introduced, capable of monitoring metabolites with high spatial/temporal resolution using fluorescence microscopy. Indicators are fusion proteins that change their fluorescence upon binding a specific metabolite. There are indicators for sugars, monocarboxylates, Krebs cycle intermediates, amino acids, cofactors, and energy nucleotides. They permit monitoring relative levels, concentrations, and fluxes in living systems. At a minimum they report relative levels and, in some cases, absolute concentrations may be obtained by performing ad hoc calibration protocols. Proper data collection, processing, and interpretation are critical to take full advantage of these new tools. This review offers a survey of the metabolic indicators that have been validated in mammalian systems. Minimally invasive, these indicators have been instrumental for the purposes of confirmation, rebuttal and discovery. We envision that this powerful technology will foster metabolic physiology.


Assuntos
Técnicas Biossensoriais , Transferência Ressonante de Energia de Fluorescência , Aminoácidos , Animais , Técnicas Biossensoriais/métodos , Transferência Ressonante de Energia de Fluorescência/métodos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Mamíferos/metabolismo , Microscopia de Fluorescência/métodos
18.
J Hosp Infect ; 123: 23-26, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35176413

RESUMO

BACKGROUND: Although the risk of SARS-CoV-2 transmission within hospitals has been well recognized, there is a paucity of data on its occurrence. Our aim was to report the incidence of hospital-acquired (HA) COVID-19 at Brazilian hospitals. METHODS: We investigated the incidence of HA COVID-19 in Brazilian hospitals using data from a national surveillance system, from August 2020 through September 2021. Definitions of HA COVID-19 were: (1) symptom onset >14 days after hospital admission plus a positive SARS-CoV-2 RNA or antigen test; (2) symptom onset on days 8-14 after admission, plus a positive SARS-CoV-2 RNA or antigen test positive, plus documented high-risk exposure. We performed descriptive analyses and reported HA COVID-19 rates using pooled mean and percentile distribution. RESULTS: A total of 48,634 cases of HA COVID-19 were reported from 1428 hospitals. Incidence ranged from 0.16/1000 patient-days at neonatal intensive care units (ICUs) to 5.8/1000 patient-days at adult ICUs. The highest incidence of HA COVID-19 was during the months March to July 2021, similar to that which was observed for community-acquired COVID-19. CONCLUSIONS: This report provides a national view of the burden of HA COVID-19. The highest incidence of HA COVID-19 similar that which was observed for community-acquired COVID-19. We believe that this reflects the difficulty of implementing preventive measures. Further studies evaluating risk factors for the hospital transmission of SARS-Cov-2 should clarify strategies to minimize the risk of HA COVID-19 and may be applicable to other respiratory diseases. Furthermore, the implementation of a national system to evaluate HA COVID-19 has the potential to shine a light on this problem and lead to interventions in each hospital.


Assuntos
COVID-19 , Adulto , Brasil/epidemiologia , COVID-19/epidemiologia , Hospitais , Humanos , Recém-Nascido , RNA Viral , SARS-CoV-2
19.
J Cereb Blood Flow Metab ; 42(5): 738-745, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35080185

RESUMO

The energy cost of information processing is thought to be chiefly neuronal, with a minor fraction attributed to glial cells. However, there is compelling evidence that astrocytes capture synaptic K+ using their Na+/K+ ATPase, and not solely through Kir4.1 channels as was once thought. When this active buffering is taken into account, the cost of astrocytes rises by >200%. Gram-per-gram, astrocytes turn out to be as expensive as neurons. This conclusion is supported by 3D reconstruction of the neuropil showing similar mitochondrial densities in neurons and astrocytes, by cell-specific transcriptomics and proteomics, and by the rates of the tricarboxylic acid cycle. Possible consequences for reactive astrogliosis and brain disease are discussed.


Assuntos
Astrócitos , Encefalopatias , Astrócitos/metabolismo , Humanos , Neuroglia , Neurônios/metabolismo , Sódio/metabolismo
20.
Arq. bras. med. vet. zootec. (Online) ; 73(4): 984-988, Jul.-Aug. 2021. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1285258

RESUMO

O Parque Nacional da Serra da Canastra (PNSC), localizado no estado de Minas Gerais, é um importante habitat de inúmeras espécies de animais ameaçados de extinção, como o lobo-guará (Chrysocyon brachyurus). Parasitos de animais selvagens podem representar um problema para os programas de manejo e recuperação de espécies ameaçadas, pois atuam como causa primária ou agravante de inúmeras doenças. Dependendo da época do ano, a suscetibilidade ao parasitismo pode ser maior devido à facilidade de infecção. Com o objetivo de avaliar a frequência de endoparasitos e a sazonalidade dessas parasitoses em diferentes épocas do ano, foram examinadas 103 amostras fecais de lobos-guarás, coletadas no PNSC, durante o período de março de 2017 a agosto de 2019. O número de amostras positivas para pelo menos uma espécie de parasito foi de 47 amostras (45,63%), sendo o outono a estação em que foi encontrada a maior frequência de formas parasitárias, com 60,86% (14/23) de amostras positivas, seguido do inverno, com 52,38% (11/21), verão com 37,5% (15/40), e primavera com 36,84% (7/19). Dentre os parasitos encontrados, Capillaria sp. apresentou a maior frequência, sendo encontrado em 23 amostras (22,33%), seguido de trematódeos, em 15 amostras (14,56%), acantocéfalos, ascarídeos, Trichuris sp. e Ancylostoma sp., em cinco amostras (4,85%), nematoides da superfamília Strongyloidea, Lynxacarus sp., em duas amostras (1,94%), e pentastomídeos em uma amostra (0,97%).(AU)


Assuntos
Animais , Doenças Parasitárias em Animais/diagnóstico , Doenças Parasitárias em Animais/epidemiologia , Canidae/parasitologia , Contagem de Ovos de Parasitas/veterinária , Brasil , Animais Selvagens/parasitologia
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