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1.
Int J Mol Sci ; 25(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38256192

RESUMO

The retina is the sensory tissue responsible for the first stages of visual processing, with a conserved anatomy and functional architecture among vertebrates. To date, retinal eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and others, affect nearly 170 million people worldwide, resulting in vision loss and blindness. To tackle retinal disorders, the developing retina has been explored as a versatile model to study intercellular signaling, as it presents a broad neurochemical repertoire that has been approached in the last decades in terms of signaling and diseases. Retina, dissociated and arranged as typical cultures, as mixed or neuron- and glia-enriched, and/or organized as neurospheres and/or as organoids, are valuable to understand both neuronal and glial compartments, which have contributed to revealing roles and mechanisms between transmitter systems as well as antioxidants, trophic factors, and extracellular matrix proteins. Overall, contributions in understanding neurogenesis, tissue development, differentiation, connectivity, plasticity, and cell death are widely described. A complete access to the genome of several vertebrates, as well as the recent transcriptome at the single cell level at different stages of development, also anticipates future advances in providing cues to target blinding diseases or retinal dysfunctions.


Assuntos
Doenças Retinianas , Animais , Humanos , Cegueira , Nível de Saúde , Neuroglia , Neurônios , Retina
2.
Preprint em Português | SciELO Preprints | ID: pps-3389

RESUMO

Data analysis is a fundamental step in the development of scientific projects. Before starting a project, the researcher needs to plan their experiments and analyzes clearly, ensuring a robust approach, protected from the most elementary biases. This document reports the creation of the "heRcules" repository, which will provide public access to script models in R language for the analysis of scientific data, with an emphasis on disciplines of the Biological and Health Sciences. The model presented here provides scripts for essential tasks in planning, analysis, visualization, and hypothesis testing procedures, including sample size calculation, statistical power calculation, spreadsheet import, vector and data frame creation, descriptive statistics, file export, plot creation (base R and ggplot2), outlier tests, normality tests, hypothesis tests and notebook creation with R markdown. The "heRcules" repository is deposited on GitHub, which will ensure efficient, free, and collaborative access to these resources.


El análisis de datos es un paso fundamental en el desarrollo de proyectos científicos. Antes de iniciar un proyecto, el investigador debe planificar sus experimentos y análisis con claridad, asegurando un enfoque robusto, protegido de los sesgos más elementales. Este documento reporta la creación del repositorio "Hércules", que brindará acceso público a modelos de script en lenguaje R para el análisis de datos científicos, con énfasis en disciplinas de las Ciencias Biológicas y de la Salud. El modelo que se presenta aquí proporciona scripts para tareas esenciales en la planificación, análisis, visualización y procedimientos de prueba de hipótesis, incluido el cálculo del tamaño de la muestra, el cálculo de la potencia estadística, la importación de hojas de cálculo, la creación de vectores y marcos de datos, estadísticas descriptivas, exportación de archivos, creación de gráficos (base R y ggplot2), pruebas de valores atípicos, pruebas de normalidad, pruebas de hipótesis y creación de libretas con R markdown. El repositorio "heRcules" se deposita en GitHub, lo que garantizará un acceso eficiente, gratuito y colaborativo a estos recursos.


A análise de dados é uma etapa fundamental do desenvolvimento de projetos científicos. Antes mesmo de iniciar o trabalho, o pesquisador precisa planejar seus experimentos e análises de forma clara, garantindo uma abordagem robusta e protegida dos vieses mais elementares. O presente documento reporta a criação do repositório "heRcules," que dará acesso público a modelos de scripts em linguagem R para a análise de dados científicos, com ênfase nas disciplinas das Ciências Biológicas e da Saúde. Nesse primeiro modelo, reportado aqui, estão inclusos scripts para tarefas essenciais no planejamento, análise, visualização e teste de hipóteses, incluindo cálculo de tamanho amostral, cálculo de poder estatístico, importação de planilhas, criação de vetores e data frames, estatística descritiva, exportação de arquivos, criação de gráficos (base R e ggplot2), testes de outliers,testes de normalidade, testes de hipóteses e criação de notebooks com o R markdown. O repositório está depositado na plataforma GitHub1, o que garantirá acesso aos recursos de forma eficiente, gratuita e colaborativa.

3.
Front Neurosci ; 15: 747229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776851

RESUMO

The endocannabinoid system (ECS) is an important brain modulatory network. ECS regulates brain homeostasis throughout development, from progenitor fate decision to neuro- and gliogenesis, synaptogenesis, brain plasticity and circuit repair, up to learning, memory, fear, protection, and death. It is a major player in the hypothalamic-peripheral system-adipose tissue in the regulation of food intake, energy storage, nutritional status, and adipose tissue mass, consequently affecting obesity. Loss of ECS control might affect mood disorders (anxiety, hyperactivity, psychosis, and depression), lead to drug abuse, and impact neurodegenerative (Alzheimer's, Parkinson, Huntington, Multiple, and Amyotrophic Lateral Sclerosis) and neurodevelopmental (autism spectrum) disorders. Practice of regular physical and/or mind-body mindfulness and meditative activities have been shown to modulate endocannabinoid (eCB) levels, in addition to other players as brain-derived neurotrophic factor (BDNF). ECS is involved in pain, inflammation, metabolic and cardiovascular dysfunctions, general immune responses (asthma, allergy, and arthritis) and tumor expansion, both/either in the brain and/or in the periphery. The reason for such a vast impact is the fact that arachidonic acid, a precursor of eCBs, is present in every membrane cell of the body and on demand eCBs synthesis is regulated by electrical activity and calcium shifts. Novel lipid (lipoxins and resolvins) or peptide (hemopressin) players of the ECS also operate as regulators of physiological allostasis. Indeed, the presence of cannabinoid receptors in intracellular organelles as mitochondria or lysosomes, or in nuclear targets as PPARγ might impact energy consumption, metabolism and cell death. To live a better life implies in a vigilant ECS, through healthy diet selection (based on a balanced omega-3 and -6 polyunsaturated fatty acids), weekly exercises and meditation therapy, all of which regulating eCBs levels, surrounded by a constructive social network. Cannabidiol, a diet supplement has been a major player with anti-inflammatory, anxiolytic, antidepressant, and antioxidant activities. Cognitive challenges and emotional intelligence might strengthen the ECS, which is built on a variety of synapses that modify human behavior. As therapeutically concerned, the ECS is essential for maintaining homeostasis and cannabinoids are promising tools to control innumerous targets.

4.
Light Sci Appl ; 10(1): 145, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262015

RESUMO

In vivo, minimally invasive microscopy in deep cortical and sub-cortical regions of the mouse brain has been challenging. To address this challenge, we present an in vivo high numerical aperture optical coherence microscopy (OCM) approach that fully utilizes the water absorption window around 1700 nm, where ballistic attenuation in the brain is minimized. Key issues, including detector noise, excess light source noise, chromatic dispersion, and the resolution-speckle tradeoff, are analyzed and optimized. Imaging through a thinned-skull preparation that preserves intracranial space, we present volumetric imaging of cytoarchitecture and myeloarchitecture across the entire depth of the mouse neocortex, and some sub-cortical regions. In an Alzheimer's disease model, we report that findings in superficial and deep cortical layers diverge, highlighting the importance of deep optical biopsy. Compared to other microscopic techniques, our 1700 nm OCM approach achieves a unique combination of intrinsic contrast, minimal invasiveness, and high resolution for deep brain imaging.

5.
Front Neurosci ; 14: 569361, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33122991

RESUMO

Complex dynamic cellular networks have been studied in physiological and pathological processes under the light of single-cell calcium imaging (SCCI), a method that correlates functional data based on calcium shifts operated by different intracellular and extracellular mechanisms integrated with their cell phenotypes. From the classic synaptic structure to tripartite astrocytic model or the recent quadripartite microglia added ensemble, as well as other physiological tissues, it is possible to follow how cells signal spatiotemporally to cellular patterns. This methodology has been used broadly due to the universal properties of calcium as a second messenger. In general, at least two types of receptor operate through calcium permeation: a fast-acting ionotropic receptor channel and a slow-activating metabotropic receptor, added to exchangers/transporters/pumps and intracellular Ca2+ release activated by messengers. These prototypes have gained an enormous amount of information in dynamic signaling circuits. SCCI has also been used as a method to associate phenotypic markers during development and stage transitions in progenitors, stem, vascular cells, neuro- and glioblasts, neurons, astrocytes, oligodendrocytes, and microglia that operate through ion channels, transporters, and receptors. Also, cancer cells or inducible cell lines from human organoids characterized by transition stages are currently being used to model diseases or reconfigure healthy cells in terms of the expression of calcium-binding/permeable molecules and shed light on therapy.

6.
Front Cell Dev Biol ; 7: 303, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850342

RESUMO

The limited access to functional human brain tissue has led to the development of stem cell-based alternative models. The differentiation of human pluripotent stem cells into cerebral organoids with self-organized architecture has created novel opportunities to study the early stages of the human cerebral formation. Here we applied state-of-the-art label-free shotgun proteomics to compare the proteome of stem cell-derived cerebral organoids to the human fetal brain. We identified 3,073 proteins associated with different developmental stages, from neural progenitors to neurons, astrocytes, or oligodendrocytes. The major protein groups are associated with neurogenesis, axon guidance, synaptogenesis, and cortical brain development. Glial cell proteins related to cell growth and maintenance, energy metabolism, cell communication, and signaling were also described. Our data support the variety of cells and neural network functional pathways observed within cell-derived cerebral organoids, confirming their usefulness as an alternative model. The characterization of brain organoid proteome is key to explore, in a dish, atypical and disrupted processes during brain development or neurodevelopmental, neurodegenerative, and neuropsychiatric diseases.

7.
Cell Mol Neurobiol ; 39(7): 1039-1049, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31197744

RESUMO

Serotonin (5-HT) has been recognized as a neurotransmitter in the vertebrate retina, restricted mainly to amacrine and bipolar cells. It is involved with synaptic processing and possibly as a mitogenic factor. We confirm that chick retina amacrine and bipolar cells are, respectively, heavily and faintly immunolabeled for 5-HT. Amacrine serotonergic cells also co-express tyrosine hydroxylase (TH), a marker of dopaminergic cells in the retina. Previous reports demonstrated that serotonin transport can be modulated by neurotransmitter receptor activation. As 5-HT is diffusely released as a neuromodulator and co-localized with other transmitters, we evaluated if 5-HT uptake or release is modulated by several mediators in the avian retina. The role of different glutamate receptors on serotonin transport and release in vitro and in vivo was also studied. We show that L-glutamate induces an inhibitory effect on [3H]5-HT uptake and this effect was specific to kainate receptor activation. Kainate-induced decrease in [3H]5-HT uptake was blocked by CNQX, an AMPA/kainate receptor antagonist, but not by MK-801, a NMDA receptor antagonist. [3H]5-HT uptake was not observed in the presence of AMPA, thus suggesting that the decrease in serotonin uptake is mediated by kainate. 5-HT (10-50 µM) had no intrinsic activity in raising intracellular Ca2+, but addition of 10 µM 5-HT decreased Ca2+ shifts induced by KCl in retinal neurons. Moreover, kainate decreased the number of bipolar and amacrine cells labeled to serotonin in chick retina. In conclusion, our data suggest a highly selective effect of kainate receptors in the regulation of serotonin functions in the retinal cells.


Assuntos
Ácido Caínico/farmacologia , Retina/metabolismo , Serotonina/metabolismo , Animais , Cálcio/metabolismo , Células Cultivadas , Embrião de Galinha , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Neurotransmissores/metabolismo , Receptores de Glutamato/metabolismo , Receptores de Ácido Caínico/metabolismo , Retina/citologia , Retina/efeitos dos fármacos , Retina/embriologia , Neurônios Retinianos/efeitos dos fármacos , Neurônios Retinianos/metabolismo , Trítio/metabolismo
8.
Mol Neurobiol ; 56(9): 6472-6486, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30838518

RESUMO

Development of progenitors in the embryonic retina is modulated by signaling molecules, and cannabinoid receptors are highly expressed in the early developing retina. Here, we investigated whether the CB1/CB2 receptor agonist WIN 5212-2 (WIN) modulated the proliferation, viability, and calcium responses in chick embryo retinal progenitors in culture. A decline in [3H]-thymidine incorporation was observed when cultures were incubated with 0.5-1.0 µM WIN, an effect that was mimicked by URB602 and URB597, inhibitors of the monoacylglycerol lipase and fatty acid amide hydrolase, respectively. A reduction in the number of proliferating cell nuclear antigen-positive nuclei was also noticed in WIN-treated cultures, suggesting that activation of cannabinoid receptors decreases the proliferation of cultured retinal progenitors. WIN (0.5-5.0 µM), but not capsaicin, decreased retinal cell viability, an effect that was blocked by CB1 and CB2 receptor antagonists and by the P2X7 receptor antagonist A438079, implicating this nucleotide receptor in the cannabinoid-mediated cell death. Treatment with WIN also induced an increase in mitochondrial superoxide and P2X7 receptor-mediated uptake of sulforhodamine B in the cultured cells. While a high proportion of cultured cells responded to glutamate, GABA, and 50 mM KCl with intracellular calcium shifts, very few cells responded to the activation of P2X7 receptors by ATP. Noteworthy, while decreasing the number of cells responding to glutamate, GABA, and KCl, treatment of the cultures with WIN induced a significant increase in the number of cells responding to 1 mM ATP, suggesting that activation of cannabinoid receptors primes P2X7 receptor calcium signaling in retinal progenitors in culture.


Assuntos
Apoptose/efeitos dos fármacos , Canabinoides/farmacologia , Neuroglia/citologia , Receptores Purinérgicos P2X7/metabolismo , Retina/citologia , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/metabolismo , Animais , Benzoxazinas/farmacologia , Cálcio/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Embrião de Galinha , Corantes Fluorescentes/metabolismo , Morfolinas/farmacologia , Naftalenos/farmacologia , Nestina/metabolismo , Fenótipo , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Células-Tronco/efeitos dos fármacos
9.
Neurochem Int ; 120: 182-190, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30170018

RESUMO

GABA transporters regulate synaptic GABA levels and dysfunctions in this system might result in psychiatric disorders. The endocannabinoid system (ECS) is the main circuit breaker in the nervous system and may alter noradrenaline (NA) communication, which in turn modulates the release of GABA. However, a close relationship between these systems has not been recognized. We asked whether NA and ECS might control extracellular GABA levels in slices of frontal cortex (FC) of adolescent Swiss mice with 40 days after birth (PN40). Here we show that NA and isoproterenol (ISO), a beta-adrenergic agonist, increased [3H]-GABA uptake in mice FC, while alpha1-adrenergic agonist phenylephrine had no effect. As GAT-1 is expressed and fully functional at the FC, addition of NO-711, a GAT-1 inhibitor, dose dependently blocked [3H]-GABA uptake. The increase of [3H]-GABA uptake induced by ISO was also blocked by NO-711. [3H]-GABA release induced by 80 mM KCl was reduced by NO-711, but not by removal of Ca2+. ISO also increased cyclic AMP (cAMP) levels and addition of WIN 55,212-2, a mixed CB1/CB2 receptor agonist, inhibited the effect of ISO in GABA uptake increase, GAT-1 expression and cAMP levels compared to control. Our data show that GABA transport increased by NA and ISO is negatively regulated by cannabinoid receptor agonist WIN55,212-2.


Assuntos
Benzoxazinas/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Lobo Frontal/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de GABA/efeitos dos fármacos , Morfolinas/farmacologia , Naftalenos/farmacologia , Animais , Endocanabinoides/metabolismo , Lobo Frontal/metabolismo , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Camundongos , Receptor CB1 de Canabinoide/efeitos dos fármacos , Receptor CB1 de Canabinoide/metabolismo , Receptores Adrenérgicos beta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Ácido gama-Aminobutírico/efeitos dos fármacos
10.
Neurochem Int ; 112: 27-37, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29108864

RESUMO

Endocannabinoids are endogenous lipids that activate selective G protein coupled receptors (CB1 and CB2), mostly found at neuronal presynaptic sites in the nervous system. One of the main consequences of the activation of CB receptors is a decrease in GABA or glutamate release, controlling cell excitability. Here we studied the expression of CB1 and CB2 receptors in E8C8 cultured retina cells (embryonic day 8 and 8 days in vitro) using immunocytochemistry and western blot analysis. We also evaluated their functions in terms of cyclic AMP (cAMP) production, single cell calcium imaging (SCCI) and GABA release induced in basal conditions or activated by l-Aspartate (L-ASP) in cell cultures or under ischemia in young chick retina. We show that both cannabinoid receptors are expressed in retinal neurons and glial cells. WIN 55,212-2 (WIN, a CB1/CB2 agonist) decreased cAMP production in cultured avian embryonic retinal cells in basal conditions. WIN also led to a decrease in the number of glial cells that increased Ca2+ levels evoked by ATP, but had no effect in Ca2+ shifts in neuronal cells activated by KCl. Finally, WIN inhibited [3H]-GABA release induced by KCl or L-ASP, accumulated in amacrine cells, but had no effect in the amount of GABA released in an oxygen glucose deprivation (OGD) condition. Altogether, our data indicate that cannabinoid receptors function as regulators of avian retina signaling at critical embryonic stages during synapse formation.


Assuntos
Neuroglia/metabolismo , Neurônios/metabolismo , Receptor CB1 de Canabinoide/fisiologia , Receptor CB2 de Canabinoide/fisiologia , Retina/embriologia , Retina/metabolismo , Analgésicos/farmacologia , Animais , Benzoxazinas/farmacologia , Embrião de Galinha , Técnicas de Cocultura , Morfolinas/farmacologia , Naftalenos/farmacologia , Neuroglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Retina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
11.
Nutr Neurosci ; 21(10): 695-714, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28686542

RESUMO

Polyunsaturated fatty acids (PUFAs) are lipid derivatives of omega-3 (docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA) or of omega-6 (arachidonic acid, ARA) synthesized from membrane phospholipids and used as a precursor for endocannabinoids (ECs). They mediate significant effects in the fine-tune adjustment of body homeostasis. Phyto- and synthetic cannabinoids also rule the daily life of billions worldwide, as they are involved in obesity, depression and drug addiction. Consequently, there is growing interest to reveal novel active compounds in this field. Cloning of cannabinoid receptors in the 90s and the identification of the endogenous mediators arachidonylethanolamide (anandamide, AEA) and 2-arachidonyglycerol (2-AG), led to the characterization of the endocannabinoid system (ECS), together with their metabolizing enzymes and membrane transporters. Today, the ECS is known to be involved in diverse functions such as appetite control, food intake, energy balance, neuroprotection, neurodegenerative diseases, stroke, mood disorders, emesis, modulation of pain, inflammatory responses, as well as in cancer therapy. Western diet as well as restriction of micronutrients and fatty acids, such as DHA, could be related to altered production of pro-inflammatory mediators (e.g. eicosanoids) and ECs, contributing to the progression of cardiovascular diseases, diabetes, obesity, depression or impairing conditions, such as Alzheimer' s disease. Here we review how diets based in PUFAs might be linked to ECS and to the maintenance of central and peripheral metabolism, brain plasticity, memory and learning, blood flow, and genesis of neural cells.


Assuntos
Endocanabinoides/farmacologia , Ácidos Graxos Insaturados/farmacologia , Envelhecimento/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Humanos , Inflamação/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico
12.
Nutrients ; 9(11)2017 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-29156608

RESUMO

Polyunsaturated fatty acids and antioxidants are important mediators in the central nervous system. Lipid derivatives may control the production of proinflammatory agents and regulate NF-κB activity, microglial activation, and fatty acid oxidation; on the other hand, antioxidants, such as glutathione and ascorbate, have been shown to signal through transmitter receptors and protect against acute and chronic oxidative stress, modulating the activity of different signaling pathways. Several authors have investigated the role of these nutrients in the brains of the young and the aged in degenerative diseases such as Alzheimer's and Parkinson's, and during brain aging due to adiposity- and physical inactivity-mediated metabolic disturbances, chronic inflammation, and oxidative stress. Through a literature review, we aimed to highlight recent data on the role of adiposity, fatty acids, antioxidants, and physical inactivity in the pathophysiology of the brain and in the molecular mechanisms of senescence. Data indicate the complexity and necessity of endogenous/dietary antioxidants for the maintenance of redox status and the control of neuroglial signaling under stress. Recent studies also indicate that omega-3 and -6 fatty acids act in a competitive manner to generate mediators for energy metabolism, influencing feeding behavior, neural plasticity, and memory during aging. Finding pharmacological or dietary resources that mitigate or prevent neurodegenerative affections continues to be a great challenge and requires additional effort from researchers, clinicians, and nutritionists in the field.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Exercício Físico , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Adiposidade/efeitos dos fármacos , Animais , Encéfalo/fisiologia , Dieta , Humanos , Inflamação/prevenção & controle , Modelos Animais , Sistema Nervoso/efeitos dos fármacos , Doenças Neurodegenerativas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos
13.
Acta sci., Biol. sci ; 39(4): 475-479, Oct. - Dec. 2017. tab
Artigo em Inglês | LILACS | ID: biblio-877600

RESUMO

Hemodialysis water and dialysates are fundamental in the treatment of kidney disease. During just one hemodialysis session, 120 liters of dialysate are consumed. Thus, it is essential that the parameters of chemical and microbiological quality of the fluids used in dialysis systems are carefully observed. In this study, water samples were collected at 12 hospitals in the state of Rio de Janeiro. The samples were obtained at three points of fluid reservoirs: pre-, post-osmosis and dialysis solution. After collection, colony forming units (CFU), total coliforms and Escherichia coli 100 mL-1 were quantified. Later, isolated colonies and endotoxin content were identified by biochemical assays. Data about total aluminum levels per sample (mg L-1) were also obtained. Samples of all mobile dialysis services and points of collection were contaminated above the levels set out by national laws, in particular by Pseudomonas aeruginosa. Endotoxin levels were also above the recommended by current legislation (> 0.25 EU mL-1). Only three samples contained detectable levels of aluminum, which were found to be above the recommended values for the corresponding resolution (0.01 mg L-1). Finally, there were no observable amounts of total coliforms and E. coli 100 mL-1 sample. The data from this study are an important step forward in the standardization and control of chemical/microbiological quality of mobile dialysis services.


Águas de hemodiálise e dialisatos são peças fundamentais na terapêutica da doença renal. Durante apenas uma sessão de hemodiálise, são consumidos aproximadamente 120 litros de dialisato. Desta forma, é essencial que os parâmetros de qualidade microbiológica e química dos fluidos utilizados em sistemas de diálise sejam cuidadosamente observados. Neste trabalho, foram coletadas amostras de água em 12 hospitais do Estado do Rio de Janeiro. Amostras foram obtidas em pontos pré-osmose, pós-osmose e solução de diálise. Após coleção, quantificaram-se unidades formadoras de colônias (UFC), coliformes totais e Escherichia coli 100 mL-1. Posteriormente, colônias isoladas e teor de endotoxinas foram identificados por ensaios bioquímicos. Dados acerca dos níveis totais de alumínio por amostra (mg L-1) também foram obtidos. Amostras de todos os serviços de diálise móvel e pontos de coleção apresentaram contaminação acima dos níveis previstos em legislação nacional, em especial por Pseudomonas aeruginosa. Teores de endotoxinas também se mostraram acima da legislação vigente (> 0,25 EU mL-1). Apenas três amostras continham níveis detectáveis e acima dos valores preconizados por resolução correspondente (0,01 mg L-1). Por fim, não foram encontradas quantidades observáveis de coliformes totais e E. coli 100 mL-1 de amostra. Dados de nosso estudo são importante avanço na padronização e controle de qualidade química/microbiológica em serviços de diálise móvel.


Assuntos
Diálise , Soluções para Diálise , Unidades Hospitalares de Hemodiálise
14.
Eur J Med Chem ; 139: 698-717, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28858765

RESUMO

Fifty-one 1,2,3-triazole derivatives were synthesized and evaluated with respect to P2X7 receptor (P2X7R) activity and its associated pore. These triazoles were screened in vitro for dye uptake assay and its cytotoxicity against mammalian cell types. Seven 1,2,3-triazole derivatives (5e, 6e, 8h, 9d, 9i, 11, and 12) potently blocked P2X7 receptor pore formation in vitro (J774.G8 cells and peritoneal macrophages). All blockers displayed IC50 value inferior to 500 nM, and they have low toxicity in either cell types. These seven selected triazoles inhibited P2X7R mediated interleukin-1 (IL-1ß) release. In particular, compound 9d was the most potent P2X7R blocker. Additionally, in mouse acute models of inflammatory responses induced by ATP or carrageenan administration in the paw, compound 9d promoted a potent blocking response. Similarly, 9d also reduced mouse LPS-induced pleurisy cellularity. In silico predictions indicate this molecule appropriate to develop an anti-inflammatory agent when it was compared to commercial analogs. Electrophysiological studies suggest a competitive mechanism of action of 9d to block P2X7 receptor. Molecular docking was performed on the ATP binding site in order to observe the preferential interaction pose, indicating that binding mode of the 9d is by interacting its 1,2,3-triazole and ether moiety with positively charged residues and with its chlorobenzene moiety orientated toward the apolar end of the ATP binding site which are mainly composed by the Ile170, Trp167 and Leu309 residues from α subunit. These results highlight 9d derivative as a drug candidate with potential therapeutic application based on P2X7 receptor blockade.


Assuntos
Inflamação/tratamento farmacológico , Pleurisia/tratamento farmacológico , Receptores Purinérgicos P2X7/metabolismo , Triazóis/farmacologia , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Inflamação/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
15.
Neurogenesis (Austin) ; 4(1): e1283188, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28229088

RESUMO

The retinal tissue of warm-blooded vertebrates performs surprisingly complex and accurate transduction of visual information. To achieve precision, a multilayered neuroglia structure is established throughout the embryonic development, and the presence of radial Müller (glial) cells ensure differentiation, growth and survival for the neuronal elements within retinal environment. It is assumed that Müller cells serve as a dynamic reservoir of progenitors, capable of expressing transcription factors, differentiating and proliferating as either neuronal or glial cells depending on extrinsic cues. In the postnatal period, Müller glia may re-enter cell cycle and produce new retinal neurons in response to acute damage. In this context, glutathione (GSH), a virtually ubiquitous tripeptide antioxidant, which is found at milimolar concentrations in central glial cells, plays a vital role as a reducing agent, buffering radical oxygen species (ROS) and preventing cell death in severely injured retinal tissues. Despite its antioxidant role, data also point to GSH as a signaling agent, suggesting that GABA release and P2X7R-mediated calcium inwards occur in Müller cells in a GSH-enriched environment. These phenomena indicate a novel mechanistic response to damage in the vertebrate retinal tissue, particularly in neuron-glia networks.

16.
RBM rev. bras. med ; 72(11)nov. 2015.
Artigo em Português | LILACS | ID: lil-778625

RESUMO

Apesar de estabilizar o equilíbrio hidroeletrolítico, pacientes com insuficiência renal crônica (IRC) submetidos à hemodiálise apresentam risco aumentado de desenvolver doenças cardiovasculares, cuja susceptibilidade pode não ser amenizada pela terapia eletrolítica, além de não substituir funções endócrinas em estado fisiológico. A explicação para complicações cardiovasculares e outras comorbidades relacionadas à hemodiálise talvez seja a presença de contaminantes microbianos e tóxicos nas águas utilizadas para o processo. Esta revisão utilizou-se de bases de dados indexadas e bibliotecas universitárias para a busca bibliográfica. A busca foi limitada aos artigos publicados até Março de 2014. Estudos atuais demonstram que o controle de qualidade em águas de hemodiálise é um processo negligenciado e torna imperativo que o profissional da saúde e pesquisadores trabalhem em conjunto para tornar mais eficiente a purificação, fornecimento e armazenamento de águas para o processo, reduzindo índices de mortalidade apresentados pelos pacientes.

17.
Nutrire Rev. Soc. Bras. Aliment. Nutr ; 40(2): 246-260, 2015. tab
Artigo em Português | LILACS | ID: biblio-881948

RESUMO

OBJECTIVE: This study aims to evaluate the betaine supplementation and its possible ergogenic potential in physically active adults. Data source: In the present review, articles were searched using indexed databases (SciELO and NCBI) and the following keywords were selected for the search: "supplement", "betaine", "performance" and "adults", including terms of lexical proximity, limited to articles in English, published between 2000 and the present date. Inclusion criteria: adults, physically active individuals or individuals under physical test and betaine supplementation. Data synthesis: According to the applied search criteria, 20,750 articles were found, from which only seven obeyed to inclusion parameters after judicious reading of the texts. In these, betaine supplementation was capable to increase anaerobic potency, muscular and isometric endurance, and stimulate an anabolic environment. In contrast, no increase was observed in the plasmatic levels of nitrate/nitrite and, when compared to creatine, betaine supplementation was not able to raise the levels of phosphorylcreatine or strength in sedentary individuals. CONCLUSIONS: The present work showed that betaine supplementation plays an important role as an ergogenic resource, mainly in biomarkers and muscular strength and power; nevertheless, it is apparently ineffective when given to sedentary individuals


OBJETIVO: Este estudo teve como objetivo avaliar a suplementação de betaína e seu possível potencial ergogênico em adultos fisicamente ativos. Fonte de dados: Na presente revisão, artigos foram pesquisados usando bancos de dados indexados (e.g., SciELO e NCBI) e as seguintes palavras-chave foram selecionados para a procura: "suplemento", "betaína", "desempenho" e "adultos", incluindo termos de proximidade léxica, limitado-se a artigos em inglês e português publicados entre 2000 e a presente data. Critérios de inclusão: referirem-se a adultos, indivíduos fisicamente ativos ou sob teste físico e suplementação de betaína. Síntese dos dados: De acordo com os critérios de pesquisa aplicada, 20.750 artigos foram encontrados, dos quais apenas sete obedeceram aos parâmetros de inclusão após leitura criteriosa do texto. Nesses estudos, a suplementação de betaína foi capaz de elevar potência anaeróbica, resistência muscular e isométrica e estimular um ambiente anabólico. Em contraste, não foram encontradas elevações nos níveis plasmáticos de nitrato/nitrito e, quando comparada à suplementação de creatina, não foi capaz de elevar níveis de fosforilcreatina ou força em indivíduos sedentários. CONCLUSÕES: O presente trabalho mostrou que a suplementação de betaína desempenha um papel importante como ergogênico, principalmente em níveis de marcadores biológicos e sobre força e potência muscular, embora aparentemente seja inefetiva quando fornecida a indivíduos sedentários


Assuntos
Humanos , Masculino , Feminino , Betaína/análise , Betaína/metabolismo , Ciências da Nutrição e do Esporte/métodos , Ciências da Nutrição e do Esporte/estatística & dados numéricos
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