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BACKGROUND: Blueberry muffin is a descriptive term for a neonate with multiple purpuric skin lesions. Many causes are known, amongst them life-threatening diseases like congenital infections or leukemia. Indeterminate cell histiocytosis (ICH) is an exceptionally rare cause of blueberry muffin rash. ICH is a histiocytic disorder which can be limited to the skin or can present with systemic involvement. A mutation that has been described in histiocytic disorders is a MAP2K1 mutation. In ICH, this mutation has previously been described in merely one case. CASE PRESENTATION: A term male neonate was admitted to the neonatology ward directly after birth because of a blueberry muffin rash. ICH was diagnosed on skin biopsy. The lesions resolved spontaneously. The patient is currently 3 years old and has had no cutaneous lesions or systemic involvement so far. This disease course is similar to that of the Hashimoto-Pritzker variant of LCH. CONCLUSIONS: ICH can manifest in neonates as resolving skin lesions. It is limited to the skin in most cases, but systemic development is possible. Therefore, it is essential to confirm the diagnosis with a biopsy before the lesions resolve and to monitor these patients closely with routine follow-up.
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Exantema , Histiocitose de Células de Langerhans , Púrpura , Dermatopatias , Recém-Nascido , Lactente , Feminino , Humanos , Masculino , Pré-Escolar , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/congênito , Dermatopatias/complicações , Dermatopatias/congênito , Dermatopatias/patologia , Pele , Exantema/etiologiaRESUMO
Different types of biological cells respond differently to mechanical stresses, and these responses are mainly governed by the cytoskeleton. The main components of this biopolymer network are actin filaments, microtubules, and intermediate filaments, whose mechanical and dynamic properties are highly distinct, thus opening up a large mechanical parameter space. Aside from experiments on whole, living cells, "bottom-up" approaches, utilizing purified, reconstituted protein systems, tremendously help to shed light on the complex mechanics of cytoskeletal networks. Such experiments are relevant in at least three aspects: (i) from a fundamental point of view, cytoskeletal networks provide a perfect model system for polymer physics; (ii) in materials science and "synthetic cell" approaches, one goal is to fully understand properties of cellular materials and reconstitute them in synthetic systems; (iii) many diseases are associated with cell mechanics, so a thorough understanding of the underlying phenomena may help solving pressing biomedical questions. In this review, we discuss the work on networks consisting of one, two, or all three types of filaments, entangled or cross-linked, and consider active elements such as molecular motors and dynamically growing filaments. Interestingly, tuning the interactions among the different filament types results in emergent network properties. We discuss current experimental challenges, such as the comparability of different studies, and recent methodological advances concerning the quantification of attractive forces between filaments and their influence on network mechanics.
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INTRODUCTION: In the first wave, thrombotic complications were common in COVID-19 patients. It is unknown whether state-of-the-art treatment has resulted in less thrombotic complications in the second wave. METHODS: We assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients admitted to eight Dutch hospitals between September 1st and November 30th 2020. Follow-up ended at discharge, transfer to another hospital, when they died, or on November 30th 2020, whichever came first. Cumulative incidences were estimated, adjusted for competing risk of death. These were compared to those observed in 579 patients admitted in the first wave, between February 24th and April 26th 2020, by means of Cox regression techniques adjusted for age, sex and weight. RESULTS: In total 947 patients with COVID-19 were included in this analysis, of whom 358 patients were admitted to the ICU; 144 patients died (15%). The adjusted cumulative incidence of all thrombotic complications after 10, 20 and 30 days was 12% (95% confidence interval (CI) 9.8-15%), 16% (13-19%) and 21% (17-25%), respectively. Patient characteristics between the first and second wave were comparable. The adjusted hazard ratio (HR) for overall mortality in the second wave versus the first wave was 0.53 (95%CI 0.41-0.70). The adjusted HR for any thrombotic complication in the second versus the first wave was 0.89 (95%CI 0.65-1.2). CONCLUSIONS: Mortality was reduced by 47% in the second wave, but the thrombotic complication rate remained high, and comparable to the first wave. Careful attention to provision of adequate thromboprophylaxis is invariably warranted.
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COVID-19/complicações , Embolia Pulmonar/etiologia , Trombose/etiologia , Tromboembolia Venosa/etiologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , Estudos de Coortes , Estado Terminal/mortalidade , Feminino , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Modelos de Riscos Proporcionais , SARS-CoV-2/isolamento & purificaçãoRESUMO
BACKGROUND: It has been proposed that two main phenotypes of hidradenitis suppurativa (HS) exist. This proposal is based upon different elementary structures detected in the skin, namely follicular subtypes and inflammatory subtypes. Having an accurate definition of these two variants could help us to better identify patients who may require an early intervention with currently approved targeted immunomodulatory therapies. OBJECTIVE: To define and distinguish between the epidemiological, clinical and analytic characteristics of these two HS phenotypes. METHODS: An observational, descriptive, non-randomized and prospective study was conducted. Patients diagnosed with HS between May 2012 and April 2017 by a specialized unit were included. Ultrasound evaluation was performed in all cases. RESULTS: About 197 patients were included, 100 women and 97 men, aged between 25 and 47 years. The mean age of onset was significantly different between phenotypes, ranging between 26.69 ± 9.05 in the inflammatory subtype and 17.62 ± 6.42 in the follicular subtype. Follicular subtype patients exhibited a significantly higher number of nodules combined with the presence of multiple commedons (5.65 ± 3.38 versus 0.89 ± 2.72). This contrasted with the higher count of abscesses and fistulas detected in the inflammatory subtype (respectively, 4 ± 2.74 and 3.11 ± 2.56 versus 0.56 ± 1.02 and 0.26 ± 0.56). IgA levels were significantly higher in the inflammatory subtype (497.71 ± 262.26 versus 232.38 ± 84.06). Mean IHS4 score evaluation was higher in the inflammatory subtype (21.04 ± 11.9) compared with the follicular phenotype (7.54 ± 4.66). The inflammatory subtype was found to be an independent risk factor for disease aggressiveness in the multivariate analysis (OR 0.034 [95% CI 0.015-0.072]). LIMITATIONS: Small sample size. CONCLUSION: Preliminary data suggest the existence of an inflammatory HS phenotype that is associated with higher aggressiveness and major risk of progression during natural history of the disease.
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Hidradenite Supurativa , Abscesso , Adulto , Feminino , Hidradenite Supurativa/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
We present a correlative microscopy approach for biology based on holographic X-ray imaging, X-ray scanning diffraction, and stimulated emission depletion (STED) microscopy. All modalities are combined into the same synchrotron endstation. In this way, labeled and unlabeled structures in cells are visualized in a complementary manner. We map out the fluorescently labeled actin cytoskeleton in heart tissue cells and superimpose the data with phase maps from X-ray holography. Furthermore, an array of local far-field diffraction patterns is recorded in the regime of small-angle X-ray scattering (scanning SAXS), which can be interpreted in terms of biomolecular shape and spatial correlations of all contributing scattering constituents. We find that principal directions of anisotropic diffraction patterns coincide to a certain degree with the actin fiber directions and that actin stands out in the phase maps from holographic recordings. In situ STED recordings are proposed to formulate models for diffraction data based on co-localization constraints.
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Holografia/métodos , Microscopia/métodos , Radiografia/métodos , Citoesqueleto de Actina , Animais , Animais Recém-Nascidos , Corantes Fluorescentes , Miócitos Cardíacos , Ratos WistarRESUMO
Mn has been found to self-assemble into atomic chains running perpendicular to the surface dimer reconstruction on Si(001). They differ from other atomic chains by a striking asymmetric appearance in filled state scanning tunneling microscopy (STM) images. This has prompted complicated structural models involving up to three Mn atoms per chain unit. Combining STM, atomic force microscopy, and density functional theory we find that a simple necklacelike chain of single Mn atoms reproduces all their prominent features, including their asymmetry not captured by current models. The upshot is a remarkably simpler structure for modeling the electronic and magnetic properties of Mn atom chains on Si(001).
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The olfactory signal transduction cascade transforms odor information into electrical signals by a cAMP-based amplification mechanism. The mechanisms underlying the very precise temporal and spatial organization of the relevant signaling components remains poorly understood. Here, we identify, using co-immunoprecipitation experiments, a macromolecular assembly of signal transduction components in mouse olfactory neurons, organized through MUPP1. Disruption of the PDZ signaling complex, through use of an inhibitory peptide, strongly impaired odor responses and changed the activation kinetics of olfactory sensory neurons. In addition, our experiments demonstrate that termination of the response is dependent on PDZ-based scaffolding. These findings provide new insights into the functional organization, and regulation, of olfactory signal transduction.
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Proteínas de Transporte/metabolismo , Complexos Multiproteicos/metabolismo , Mucosa Olfatória/fisiologia , Animais , Proteínas de Transporte/genética , AMP Cíclico/metabolismo , Células HEK293 , Humanos , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Neurônios Receptores Olfatórios/metabolismo , Domínios PDZ/genética , Fragmentos de Peptídeos/metabolismo , Ligação Proteica , Receptores Odorantes/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Segmental dose reduction with increasing age after thoracic epidural anaesthesia (TEA) has been documented. We hypothesised that after a fixed loading dose of ropivacaine at the T3-T4 level, increasing age would result in more extended analgesic spread. In addition, other aspects of neural blockade and haemodynamic changes were studied. METHODS: Thirty-five lung surgery patients were included in three age groups. Thirty-one patients received an epidural catheter at the T3-T4 interspace followed by an injection of 8-ml ropivacaine 0.75%. Analgesia was assessed with pinprick and temperature discrimination. Motor block was tested using the Bromage and epidural scoring scale for arm movements score. An arterial line was inserted for invasive measurement of blood pressure, cardiac index (CI) and stroke volume (SV). RESULTS: There was no influence of age on quality of TEA except for the caudal border of analgesia being somewhat lower in the middle and older age group compared with the young age group. Heart rate (6.0 ± 5.9, P < 0.001), mean arterial pressure (16.1 ± 15.6, P < 0.001), CI (0.55 ± 0.49, P < 0.001) and SV (9.6 ± 14.6, P = 0.001) decreased after TEA for the total group. Maximal reduction in heart rate after TEA was more extensive in the young age group compared with the other age groups. There was no effect of age on other cardiovascular parameters. CONCLUSION: We were unable to demonstrate an effect of age on the maximal number of spinal segments blocked after TEA; however, the caudad spread of analgesia increased with advancing age. In addition, reduction of heart rate was greater in the youngest group.
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Envelhecimento/fisiologia , Amidas/farmacocinética , Anestesia Epidural/métodos , Anestésicos Locais/farmacocinética , Frequência Cardíaca/efeitos dos fármacos , Bloqueio Nervoso , Condução Nervosa/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amidas/administração & dosagem , Amidas/farmacologia , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Difusão , Humanos , Pessoa de Meia-Idade , Pleurodese , Ropivacaina , Volume Sistólico/efeitos dos fármacos , Cirurgia Torácica Vídeoassistida , Vértebras Torácicas , Toracotomia , Distribuição Tecidual , Adulto JovemRESUMO
Membrane bioreactor (MBR) technology is a very reliable and extensively tested solution for biological wastewater treatment. Nowadays, separate treatment of highly polluted wastewater streams especially from hospitals and other health care facilities is currently under investigation worldwide. In this context, the MBR technology will play a decisive role because an effluent widely cleaned up from solids and nutrients is absolutely mandatory for a subsequent further elimination of organic trace pollutants. Taking hospital wastewater as an example, the aim of this study was to investigate to what extent MBR technology is an adequate 'pre-treatment' solution for further elimination of trace pollutants. Therefore, we investigated - within a 2-year period - the performance of a full-scale hospital wastewater treatment plant (WWTP) equipped with a MBR by referring to conventional chemical and microbiological standard parameters. Furthermore, we measured the energy consumption and tested different operating conditions. According to our findings the MBR treatment of the hospital wastewater was highly efficient in terms of the removal of solids and nutrients. Finally, we did not observe any major adverse effects on the operation and performance of the MBR system which potentially could derive from the composition of the hospital wastewater. In total, the present study proved that MBR technology is a very efficient and reliable treatment approach for the treatment of highly polluted wastewater from hospitals and can be recommended as a suitable pre-treatment solution for further trace pollutant removal.
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Reatores Biológicos , Filtração/instrumentação , Hospitais , Eliminação de Resíduos de Serviços de Saúde/métodos , Eliminação de Resíduos Líquidos/métodos , Alemanha , Esgotos , Poluentes da Água , Poluição da Água/prevenção & controle , Purificação da Água/métodosRESUMO
Membrane Bioreactors (MBR) are a very attractive option for the treatment of hospital wastewater and elimination of pharmaceuticals in high density urban areas. The present investigation showed that, depending on the substance, between 19% and 94% of the level of antibiotics found in the environment originate from hospitals. Because of their ecotoxic potential, hospital wastewaters can have a significant impact on the environment. The segregation of these wastewaters and their separate treatment at the source can reduce the entry of drugs in waterways and enable water reuse after adequate polishing treatment processes.
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Reatores Biológicos , Hospitais , Resíduos Industriais , Membranas Artificiais , Urbanização , Poluentes Químicos da Água/isolamento & purificaçãoRESUMO
A variety of melaware articles were tested for the migration of melamine into the food simulant 3% w/v acetic acid as a benchmark, and into other food simulants, beverages and foods for comparison. The results indicate that the acidity of the food simulant plays a role in promoting migration, but not by as much as might have been anticipated, since 3% acetic acid gave migration values about double those obtained using water under the same time and temperature test conditions. In contrast, migration into the fatty food simulant olive oil was not detectable and at least 20-fold lower than with the aqueous food simulants. This was expected given the solubility properties of melamine and the characteristics of the melaware plastic. Migration levels into hot acidic beverages (apple juice, tomato juice, red-fruit tea and black coffee) were rather similar to the acetic acid simulant when the same time and temperature test conditions are used, e.g. 2 h at 70°C. However, migration levels into foods that were placed hot into melaware articles and then allowed to cool on standing were much lower (6-14 times lower) than if pre-heated food was placed into the articles and then maintained (artificially) at that high temperature in the same way that a controlled time-temperature test using simulants would be conducted. This very strong influence of time and especially temperature was manifest in the effects seen of microwave heating of food or beverage in the melaware articles. Here, despite the short duration of hot contact, migration levels were similar to simulants used for longer periods, e.g. 70°C for 2 h. This is rationalized in terms of the peak temperature achieved on microwave heating, which may exceed 70°C, counterbalancing the shorter time period held hot. There was also evidence that when using melaware utensils in boiling liquids, as for stovetop use of spatulas, the boiling action of circulating food/simulant can have an additional effect in promoting surface erosion, increasing the plastic decomposition and so elevating the melamine release.
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Análise de Alimentos , Contaminação de Alimentos , Plásticos/química , Triazinas/análise , Bebidas/análise , Bebidas/efeitos da radiação , Qualidade de Produtos para o Consumidor , Culinária , Utensílios de Alimentação e Culinária , Alimentos/efeitos da radiação , Manipulação de Alimentos/métodos , Embalagem de Alimentos , Formaldeído/química , Concentração de Íons de Hidrogênio , Micro-Ondas/efeitos adversos , Modelos Químicos , Plásticos/efeitos adversos , Plásticos/efeitos da radiação , Temperatura , Fatores de Tempo , Triazinas/químicaRESUMO
Considerable concern exists regarding the appearance and effects of trace and ultra trace pollutants in the aquatic environment. In this context, it is necessary to identify relevant hot spot wastewater - such as hospital wastewater - and to implement specific wastewater treatment solutions. Membrane bioreactor (MBR) technology seems to be a suitable pre-treatment approach for the subsequent advanced treatment by high pressure membrane systems such as nanofiltration (NF) and reverse osmosis (RO). This paper is based upon investigations on the first full scale MBR for separate treatment of hospital wastewater in Germany. In this study an NF as well as an RO module for further treatment of the MBR filtrate were tested. The removal efficiencies were assessed using the following target compounds: bezafibrate, bisoprolol, carbamazepine, clarithromycin, ciprofloxacin, diclofenac, ibuprofen, metronidazole, moxifloxacin, telmisartan and tramadol. In summary, the results of this study confirmed that MBR technology followed by an advanced treatment for trace pollutant removal is an adequate approach for specific treatment of hot spot wastewater such as hospital wastewater. In particular, it was shown that - comparing the tested NF and RO - only (a two stage) RO is appropriate to remove pharmaceutical residues from hospital wastewater entirely. The recommended yield of the 2-stage RO is 70% which results in a retentate sidestream of 9%. Our investigations proved that RO is a very efficient treatment approach for elimination of trace pollutants.
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Filtração/instrumentação , Hospitais , Eliminação de Resíduos de Serviços de Saúde/métodos , Nanotecnologia/instrumentação , Nanotecnologia/métodos , Eliminação de Resíduos Líquidos/métodos , Filtração/métodos , Osmose , Projetos Piloto , Poluentes da Água , Poluição da Água/prevenção & controle , Purificação da Água/métodosRESUMO
Dravet syndrome or severe myoclonic epilepsy in infancy (SMEI) is an epileptic syndrome characterised by refractory epilepsy and intellectual disability, typically presenting with febrile and afebrile generalised and unilateral clonic/tonic-clonic seizures in the first year of life and other types of seizures appearing later in the course of the disease. Five adult patients with SMEI and SCN1A mutations are reported, in which motor and behavioural abnormalities were outstanding symptoms. Bradykinesia, responding with latency, slow speaking with a thin voice, midface hypomimia and perseveration were distinctive features in all cases. These symptoms may be fit to define the adult phenotype of SMEI beyond seizure/epilepsy criteria. The motor and behavioural symptoms are discussed in the context of a possibly underlying frontal lobe/mesofrontal and cerebellar dysfunction.
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The scope of the Cu(I)-catalyzed [2 + 3] azide/alkyne cycloaddition (CuAAC, click chemistry) as a key reaction for the conjugation of ferrocene derivatives to N-terminal functionalized PNA oligomers is explored herein (PNA: peptide nucleic acid). The facile solid-phase synthesis of N-terminal azide or alkyne-functionalized PNA oligomer precursors and their cycloaddition with azidoferrocene, ethynylferrocene, and N-(3-ethylpent-1-yn-3-yl)ferrocene-carboxamide (DEPA-ferrocene) on the solid phase are presented. While the click reaction with azidomethylferrocene worked equally well, the ferrocenylmethyl group is lost from the conjugate upon acid cleavage. However, the desired product was obtained via a post-SPPS conversion of the alkyne-PNA oligomer with azidomethylferrocene in solution. The synthesis of all ferrocene-PNA conjugates (trimer t(3)-PNA, 3, 4, 5, 6; 12mer PNA, 10 - t c t a c a a g a c t c, 11 - t c t a c c g t a c t c) succeeded with excellent yields and purities, as determined by mass spectrometry and HPLC. Electrochemical studies of the trimer Fc-PNA conjugates 3, 4, 5, and 6 with four different ferrocene moieties revealed quasi-reversible redox processes of the ferrocenyl redox couple Fc(0/+) and electrochemical half-wave potentials in a range of E(1/2) = -20 mV to +270 mV vs FcH(0/+) (Fc: ferrocenyl, C(10)H(9)Fe). The observed potential differences ΔE(1/2)(min) are always greater than 60 mV for any given pair of Fc-PNA conjugates, thus allowing a reliable differentiation with sensitive electrochemical methods like e.g. square wave voltammetry (SWV). This is the electrochemical equivalent of "four-color" detection and is hence denoted "four-potential" labeling. Preparation and electrochemical investigation of the set of four structurally different and electrochemically distinguishable ferrocenyl groups conjugated to PNA oligomers, as exemplified by the conjugates 3, 4, 5, and 6, demonstrates the scope of the azide/alkyne cycloaddition for the labeling of PNA with electrochemically active ferrocenyl groups. Furthermore, it provides a PNA-based system for the electrochemical detection of single-nucleotide polymorphism (SNP) in DNA/RNA.
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Química Click/métodos , Compostos Ferrosos/química , Ácidos Nucleicos Peptídicos/química , Coloração e Rotulagem/métodos , Catálise , Cobre/química , Ciclização , Eletroquímica , Metalocenos , Estrutura Molecular , EstereoisomerismoRESUMO
A new microfluidic approach for charge-based particle separation using combined hydrodynamic and electrokinetic effects is presented. A recirculating flow pattern is employed, generated through application of bi-directional flow in a narrow glass microchannel incorporating diverging or converging segments at both ends. The bi-directional flow in turn is a result of opposing pressure-driven flow and electro-osmotic flow in the device. Trapping and preconcentration of charged particles is observed in the recirculating flow, under conditions where the average net velocity of the particles themselves approaches zero. This phenomenon is termed flow-induced electrokinetic trapping (FIET). Importantly, the electrophoretic mobility (zeta potential) of the particles determines the flow conditions required for trapping. In this paper, we exploit FIET for the first time to perform particle separations. Using a non-uniform channel, one type of particle can be trapped according to its zeta-potential, while particles with higher or lower zeta-potentials are flushed away with the pressure-driven or electro-osmotic components, respectively, of the flow. This was demonstrated using simple mixtures of two polystyrene bead types having approximately the same size (3 microm) but different zeta potentials (differences were in the order of 25 to 40 mV). To gain more insight into the separation mechanism, particle separations in straight, 3 cm-long microchannels with uniform cross-section were also studied under conditions of bi-directional flow without trapping. A thorough theoretical analysis confirmed that trapping occurs when electrokinetic and pressure-driven particle velocities are equal and opposite throughout the diverging segment. This makes it possible to predict the pressure and electric field conditions required to separate particles having defined zeta potentials.
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Eletroforese em Microchip/instrumentação , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Microesferas , Eletricidade Estática , Eletroforese em Microchip/métodos , Desenho de Equipamento , Tamanho da Partícula , Poliestirenos/química , Propriedades de SuperfícieRESUMO
BACKGROUND AND PURPOSE: Glutamate is the main excitatory neurotransmitter in the vertebrate CNS. Removal of the transmitter from the synaptic cleft by glial and neuronal glutamate transporters (GLTs) has an important function in terminating glutamatergic neurotransmission and neurological disorders. Five distinct excitatory amino-acid transporters have been characterized, among which the glial transporters excitatory amino-acid transporter 1 (EAAT1) (glutamate aspartate transporter) and EAAT2 (GLT1) are most important for the removal of extracellular glutamate. The purpose of this study was to describe the effect of the commonly used anaesthetic etomidate on glutamate uptake in cultures of glial cells. EXPERIMENTAL APPROACH: The activity of the transporters was determined electrophysiologically using the whole cell configuration of the patch-clamp recording technique. KEY RESULTS: Glutamate uptake was suppressed by etomidate (3-100 microM) in a time- and concentration-dependent manner with a half-maximum effect occurring at 2.4+/-0.6 microM. Maximum inhibition was approximately 50% with respect to the control. Etomidate led to a significant decrease of V(max) whereas the K(m) of the transporter was unaffected. In all cases, suppression of glutamate uptake was reversible within a few minutes upon washout. Furthermore, both GF 109203X, a nonselective inhibitor of PKs, and H89, a selective blocker of PKA, completely abolished the inhibitory effect of etomidate. CONCLUSION AND IMPLICATIONS: Inhibition of glutamate uptake by etomidate at clinically relevant concentrations may affect glutamatergic neurotransmission by increasing the glutamate concentration in the synaptic cleft and may compromise patients suffering from acute or chronic neurological disorders such as CNS trauma or epilepsy.
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Anestésicos Intravenosos/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Etomidato/farmacologia , Ácido Glutâmico/metabolismo , Neuroglia/metabolismo , Animais , Animais Recém-Nascidos , Encéfalo/citologia , Células Cultivadas , Relação Dose-Resposta a Droga , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Drops of water-in-fluorocarbon emulsions have great potential for compartmentalizing both in vitro and in vivo biological systems; however, surfactants to stabilize such emulsions are scarce. Here we present a novel class of fluorosurfactants that we synthesize by coupling oligomeric perfluorinated polyethers (PFPE) with polyethyleneglycol (PEG). We demonstrate that these block copolymer surfactants stabilize water-in-fluorocarbon oil emulsions during all necessary steps of a drop-based experiment including drop formation, incubation, and reinjection into a second microfluidic device. Furthermore, we show that aqueous drops stabilized with these surfactants can be used for in vitro translation (IVT), as well as encapsulation and incubation of single cells. The compatability of this emulsion system with both biological systems and polydimethylsiloxane (PDMS) microfluidic devices makes these surfactants ideal for a broad range of high-throughput, drop-based applications.
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Materiais Biocompatíveis , Emulsões , Fluorocarbonos/química , Tensoativos/química , Água/química , Polietilenoglicóis/químicaRESUMO
The facile side-specific insertion, on the solid phase, of one or two ferrocene moieties into peptide nucleic acid (PNA) oligomers by click chemistry is presented.
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Compostos Ferrosos/química , Compostos Organometálicos/química , Ácidos Nucleicos Peptídicos/química , Sequência de Bases , Metalocenos , Compostos Organometálicos/síntese química , Ácidos Nucleicos Peptídicos/síntese químicaRESUMO
Confinement effects on single semiflexible macromolecules are of central importance for a fundamental understanding of cellular processes involving biomacromolecules. To analyze the influence of confinement on the fluctuations of semiflexible macromolecules we study individual actin filaments in straight and curved microchannels. We experimentally characterize the segment distributions for fluctuating semiflexible filaments in microchannels as a function of the channel width. Moreover, the effect of channel curvature on the filament fluctuations is investigated. We find quantitative agreement between experimental results, Monte Carlo simulations, and the analytical description. This allows for determination of the persistence length of actin filaments, the deflection length, which characterizes the confinement effects, and the scaling exponents for the segment distribution of semiflexible macromolecules.
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Citoesqueleto de Actina/química , Actinas/química , Algoritmos , Elasticidade , Modelos Moleculares , Estresse MecânicoRESUMO
Epitaxial La(3/4)Ca(1/4)MnO3/MgO(100) (LCMO) thin film shows an unusual rhombohedral (R-3c) structure with a new perovskite superstructure at room temperature due to the CE-type ordering of La and Ca with modulation vector q=1/4[011]. A-site ordered film was found to be electronically homogeneous down to the 1 nm scale as revealed by scanning tunnelling microscopy/spectroscopy. In contrast, orthorhombic and A-site disordered LCMO demonstrate a mesoscopic phase separation far below the Curie temperature (TC). Unique La/Ca ordering compensates the cation mismatch stress within one supercell, a(S) approximately 1.55 nm, and enhances the electronic homogeneity. The phase separation does not seem to be a unique mechanism for the colossal magnetoresistance (CMR) as very large CMR approximately 500% was also observed in A-site ordered films.