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1.
Nature ; 527(7576): 82-5, 2015 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-26536959

RESUMEN

Spontaneous removal of condensed matter from surfaces is exploited in nature and in a broad range of technologies to achieve self-cleaning, anti-icing and condensation control. But despite much progress, our understanding of the phenomena leading to such behaviour remains incomplete, which makes it challenging to rationally design surfaces that benefit from its manifestation. Here we show that water droplets resting on superhydrophobic textured surfaces in a low-pressure environment can self-remove through sudden spontaneous levitation and subsequent trampoline-like bouncing behaviour, in which sequential collisions with the surface accelerate the droplets. These collisions have restitution coefficients (ratios of relative speeds after and before collision) greater than unity despite complete rigidity of the surface, and thus seemingly violate the second law of thermodynamics. However, these restitution coefficients result from an overpressure beneath the droplet produced by fast droplet vaporization while substrate adhesion and surface texture restrict vapour flow. We also show that the high vaporization rates experienced by the droplets and the associated cooling can result in freezing from a supercooled state that triggers a sudden increase in vaporization, which in turn boosts the levitation process. This effect can spontaneously remove surface icing by lifting away icy drops the moment they freeze. Although these observations are relevant only to systems in a low-pressure environment, they show how surface texturing can produce droplet-surface interactions that prohibit liquid and freezing water-droplet retention on surfaces.

2.
Langmuir ; 33(8): 1799-1809, 2017 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-28151671

RESUMEN

Controlled handling of liquids and colloidal suspensions as they interact with surfaces, targeting a broad palette of related functionalities, is of great importance in science, technology, and nature. When small liquid volumes (drops on the order of microliters or nanoliters) need to be processed in microfluidic devices, contamination on the solid/liquid interface and loss of liquid due to adhesion on the transport channels are two very common problems that can significantly alter the process outcome, for example, the chemical reaction efficiency or the purity and the final concentration of a suspension. It is, therefore, no surprise that both levitation and minimal contact transport methods-including nonwetting surfaces-have been developed to minimize the interactions between liquids and surfaces. Here, we demonstrate contactless surface levitation and transport of liquid drops, realized by harnessing and sustaining the natural sublimation of a solid-carbon-dioxide-coated substrate to generate a continuous supporting vapor layer. The capability and limitations of this technique in handling liquids of extreme surface tension and kinematic viscosity values are investigated both experimentally and theoretically. The sublimating coating is capable of repelling many viscous and low-surface-tension liquids, colloidal suspensions, and non-Newtonian fluids as well, displaying outstanding omniphobic properties. Finally, we demonstrate how sublimation can be used for liquid transport, mixing, and drop coalescence, with a sublimating layer coated on an underlying substrate with prefabricated channels, conferring omniphobicity using a simple physical approach (i.e., phase change) rather than a chemical one. The independence of the surface levitation principle from material properties, such as electromagnetic, thermal or optical, surface energy, adhesion, or mechanical properties, renders this method attractive for a wide range of potential applications.

3.
Langmuir ; 33(17): 4250-4259, 2017 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-28388096

RESUMEN

Separating petroleum hydrocarbons from water is an important problem to address in order to mitigate the disastrous effects of hydrocarbons on aquatic ecosystems. A rational approach to address the problem of marine oil-water separation is to disperse the oil with the aid of surfactants in order to minimize the formation of large slicks at the water surface and to maximize the oil-water interfacial area. Here we investigate the fundamental wetting and transport behavior of such surfactant-stabilized droplets and the flow conditions necessary to perform sieving and separation of these stabilized emulsions. We show that, for water-soluble surfactants, such droplets are completely repelled by a range of materials (intrinsically underwater superoleophobic) due to the detergency effect; therefore, there is no need for surface micro-/nanotexturing or chemical treatment to repel the oil and prevent fouling of the filter. We then simulate and experimentally investigate the effect of emulsion flow rate on the transport and impact behavior of such droplets on rigid meshes to identify the minimum pore opening (w) necessary to filter a droplet with a given diameter (d) in order to minimize the pressure drop across the mesh-and therefore maximize the filtering efficiency, which is strongly dependent on w. We define a range of flow conditions and droplet sizes where minimum droplet deformation is to be expected and therefore find that the condition of w ≈ d is sufficient for efficient separation. With this new understanding, we demonstrate the use of a commercially available filter-without any additional surface engineering or functionalization-to separate oil droplets (d < 100 µm) from a surfactant-stabilized emulsion with a flux of ∼11,000 L m-2 h-1 bar-1. We believe these findings can inform the design of future oil separation materials.

4.
Langmuir ; 31(17): 4807-21, 2015 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-25346213

RESUMEN

Icing of surfaces is commonplace in nature and technology, affecting everyday life and sometimes causing catastrophic events. Understanding (and counteracting) surface icing brings with it significant scientific challenges that requires interdisciplinary knowledge from diverse scientific fields such as nucleation thermodynamics and heat transfer, fluid dynamics, surface chemistry, and surface nanoengineering. Here we discuss key aspects and findings related to the physics of ice formation on surfaces and show how such knowledge could be employed to rationally develop surfaces with extreme resistance to icing (extraordinary icephobicity). Although superhydrophobic surfaces with micro-, nano-, or (often biomimetic) hierarchical roughnesses have shown in laboratory settings (under certain conditions) excellent repellency and low adhesion to water down to temperatures near or below the freezing point, extreme icephobicity necessitates additional important functionalities. Other approaches, such as lubricant-impregnated surfaces, exhibit both advantages and serious limitations with respect to icing. In all, a clear path toward passive surfaces with extreme resistance to ice formation remains a challenge, but it is one well worth undertaking. Equally important to potential applications is scalable surface manufacturing and the ability of icephobic surfaces to perform reliably and sustainably outside the laboratory under adverse conditions. Surfaces should possess mechanical and chemical stability, and they should be thermally resilient. Such issues and related research directions are also addressed in this article.

5.
Proc Natl Acad Sci U S A ; 109(40): 16073-8, 2012 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-23012410

RESUMEN

Water freezing on solid surfaces is ubiquitous in nature. Even though icing/frosting impairs the performance and safety in many processes, its mechanism remains inadequately understood. Changing atmospheric conditions, surface properties, the complexity of icing physics, and the unorthodox behavior of water are the primary factors that make icing and frost formation intriguing and difficult to predict. In addition to its unquestioned scientific and practical importance, unraveling the frosting mechanism under different conditions is a prerequisite to develop "icephobic" surfaces, which may avoid ice formation and contamination. In this work we demonstrate that evaporation from a freezing supercooled sessile droplet, which starts explosively due to the sudden latent heat released upon recalescent freezing, generates a condensation halo around the droplet, which crystallizes and drastically affects the surface behavior. The process involves simultaneous multiple phase transitions and may also spread icing by initiating sequential freezing of neighboring droplets in the form of a domino effect and frost propagation. Experiments under controlled humidity conditions using substrates differing up to three orders of magnitude in thermal conductivity establish that a delicate balance between heat diffusion and vapor transport determines the final expanse of the frozen condensate halo, which, in turn, controls frost formation and propagation.


Asunto(s)
Congelación , Hielo , Modelos Teóricos , Propiedades de Superficie , Agua/química , Física
6.
Nano Lett ; 14(1): 172-82, 2014 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-24320719

RESUMEN

The superhydrophobic behavior of nano- and microtextured surfaces leading to rebound of impacting droplets is of great relevance to nature and technology. It is not clear however, if and under what conditions this behavior is maintained when such surfaces are severely undercooled possibly leading to the formation of frost and icing. Here we elucidate key aspects of this phenomenon and show that the outcome of rebound or impalement on a textured surface is affected by air compression underneath the impacting drop and the time scale allowing this air to escape. Remarkably, drop impalement occurred at identical impact velocities, both at room and at very low temperatures (-30 °C) and featured a ringlike liquid meniscus penetration into the surface texture with an entrapped air bubble in the middle. At low temperatures, the drop contact time and receding dynamics of hierarchical surfaces were profoundly influenced by both an increase in the liquid viscosity due to cooling and a partial meniscus penetration into the texture. For hierarchical surfaces with the same solid fraction in their roughness, minimizing the gap between the asperities (both at micro- and nanoscales) yielded the largest resistance to millimetric drop impalement. The best performing surface impressively showed rebound at -30 °C for drop impact velocity of 2.6 m/s.

7.
Nano Lett ; 11(11): 4846-51, 2011 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-21985612

RESUMEN

We present a new fully conjugated diblock copolymer, P3HT-b-PFTBTT, containing donor and acceptor blocks with suitably positioned energy levels for use in a solar cell. This is the first block copolymer to be based on an existing high-performance polymer:polymer blend. We observe phase separation of the blocks and self-assembly behavior. In ternary blends with the respective homopolymers the diblock copolymer introduces lateral nanostructure without restricting P3HT crystallization in the charge transport direction, resulting in standing lamellae. By adding the diblock to the homopolymer blend as a compatibilizer, we prevent phase separation at elevated temperatures and benefit from a dramatic increase in P3HT ordering, allowing us to demonstrate polymer blend photovoltaics where the nanostructure is thermodynamically, rather than kinetically, controlled.


Asunto(s)
Suministros de Energía Eléctrica , Nanoestructuras/química , Nanotecnología/instrumentación , Compuestos de Organoselenio/química , Energía Solar , Transporte de Electrón , Diseño de Equipo , Análisis de Falla de Equipo , Luz , Ensayo de Materiales , Nanoestructuras/efectos de la radiación , Compuestos de Organoselenio/efectos de la radiación , Tamaño de la Partícula
8.
Langmuir ; 27(6): 3059-66, 2011 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-21319778

RESUMEN

Ice formation can have catastrophic consequences for human activity on the ground and in the air. Here we investigate water freezing delays on untreated and coated surfaces ranging from hydrophilic to superhydrophobic and use these delays to evaluate icephobicity. Supercooled water microdroplets are inkjet-deposited and coalesce until spontaneous freezing of the accumulated mass occurs. Surfaces with nanometer-scale roughness and higher wettability display unexpectedly long freezing delays, at least 1 order of magnitude longer than typical superhydrophobic surfaces with larger hierarchical roughness and low wettability. Directly related to the main focus on heterogeneous nucleation and freezing delay of supercooled water droplets, the observed ensuing crystallization process consisted of two distinct phases: one very rapid recalescent partial solidification phase and a subsequent slower phase. Observations of the droplet collision process employed for the continuous liquid mass accumulation up to the point of ice formation reveal a previously unseen atmospheric-pressure, subfreezing-temperature regime for liquid-on-liquid bounce. On the basis of the entropy reduction of water near a solid surface, we formulate a modification to the classical heterogeneous nucleation theory, which predicts the observed freezing delay trends. Our results bring to question recent emphasis on super water-repellent surface formulations for ice formation retardation and suggest that anti-icing design must optimize the competing influences of both wettability and roughness.

9.
J Neurotrauma ; 38(5): 604-615, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33191851

RESUMEN

Hemorrhage volume is an important variable in emergently assessing traumatic brain injury (TBI). The most widely used method for rapid volume estimation is ABC/2, a simple algorithm that approximates lesion geometry as perfectly ellipsoid. The relative prognostic value of volume measurement based on more precise hematoma topology remains unknown. In this study, we compare volume measurements obtained using ABC/2 versus computer-assisted volumetry (CAV) for both intra- and extra-axial traumatic hemorrhages, and then quantify the association of measurements using both methods with patient outcome following moderate to severe TBI. A total of 517 computer tomography (CT) scans acquired during the Progesterone for Traumatic Brain Injury Experimental Clinical Treatment Phase-III (ProTECTIII) multi-center trial were retrospectively reviewed. Lesion volumes were measured using ABC/2 and CAV. Agreement between methods was tested using Bland-Altman analysis. Relationship of volume measurements with 6-month mortality, Extended Glasgow Outcome Scale (GOS-E), and Disability Rating Scale (DRS) were assessed using linear regression and area under the curve (AUC) analysis. In subdural hematoma (SDH) >50cm3, ABC/2 and CAV produce significantly different volume measurements (p < 0.0001), although the difference was not significant for smaller SDH or intra-axial lesions. The disparity between ABC/2 and CAV measurements varied significantly with hematoma size for both intra- and extra-axial lesions (p < 0.0001). Across all lesions, volume was significantly associated with outcome using either method (p < 0.001), but CAV measurement was a significantly better predictor of outcome than ABC/2 estimation for SDH. Among large traumatic SDH, ABC/2 significantly overestimates lesion volume compared with measurement based on precise bleed topology. CAV also offers significantly better prediction of patient functional outcofme and mortality.


Asunto(s)
Hemorragia Encefálica Traumática/diagnóstico por imagen , Hemorragia Encefálica Traumática/mortalidad , Análisis de Datos , Procesamiento de Imagen Asistido por Computador/métodos , Progesterona , Tomografía Computarizada por Rayos X/métodos , Hemorragia Encefálica Traumática/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/mortalidad , Femenino , Humanos , Masculino , Mortalidad/tendencias , Progesterona/uso terapéutico , Pronóstico , Estudios Prospectivos , Método Simple Ciego , Resultado del Tratamiento
10.
Neurol Res Pract ; 3(1): 31, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34059132

RESUMEN

BACKGROUND: The prehospital identification of stroke patients with large-vessel occlusion (LVO), that should be immediately transported to a thrombectomy capable centre is an unsolved problem. Our aim was to determine whether implementation of a state-wide standard operating procedure (SOP) using the Los Angeles Motor Scale (LAMS) is feasible and enables correct triage of stroke patients to hospitals offering (comprehensive stroke centres, CSCs) or not offering (primary stroke centres, PSCs) thrombectomy. METHODS: Prospective study involving all patients with suspected acute stroke treated in a 4-month period in a state-wide network of all stroke-treating hospitals (eight PSCs and two CSCs). Primary endpoint was accuracy of the triage SOP in correctly transferring patients to CSCs or PSCs. Additional endpoints included the number of secondary transfers, the accuracy of the LAMS for detection of LVO, apart from stroke management metrics. RESULTS: In 1123 patients, use of a triage SOP based on the LAMS allowed triage decisions according to LVO status with a sensitivity of 69.2% (95% confidence interval (95%-CI): 59.0-79.5%) and a specificity of 84.9% (95%-CI: 82.6-87.3%). This was more favourable than the conventional approach of transferring every patient to the nearest stroke-treating hospital, as determined by geocoding for each patient (sensitivity, 17.9% (95%-CI: 9.4-26.5%); specificity, 100% (95%-CI: 100-100%)). Secondary transfers were required for 14 of the 78 (17.9%) LVO patients. Regarding the score itself, LAMS detected LVO with a sensitivity of 67.5% (95%-CI: 57.1-78.0%) and a specificity of 83.5% (95%-CI: 81.0-86.0%). CONCLUSIONS: State-wide implementation of a triage SOP requesting use of the LAMS tool is feasible and improves triage decision-making in acute stroke regarding the most appropriate target hospital.

11.
Clin Chem Lab Med ; 47(10): 1271-6, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19743953

RESUMEN

BACKGROUND: Analysis of cerebrospinal fluid (CSF) to discriminate between benign and malignant conditions is of fundamental importance for the physician and the patient because of the differential therapeutic options and resulting morbidity and mortality. Most human tumours demonstrate increased telomerase activity (TA). Recent technical advances in the detection of TA allow for sensitive and specific detection within 4 h. Thus, the detection of TA is suitable for routine clinical testing. METHODS: This study examines TA in cellular proteins in CSF from 111 patients compared to cytomorphological and laboratory examination. RESULTS: A positive result for TA in cellular proteins of CSF was correlated significantly with Meningeosis neoplastica, but not with non-malignant conditions. Telomerase was not detected in CSF supernatant, despite positive results in cellular proteins from identical patients. Furthermore, a 48-h time delay during the pre-analytic processing is not critical for detection of TA detection in native CSF when stored at room temperature. CONCLUSIONS: We conclude that TA is a promising marker for the detection of Meningeosis neoplastica and warrants further study.


Asunto(s)
Meningitis/diagnóstico , Meningitis/enzimología , Telomerasa/metabolismo , Animales , Línea Celular , Niño , Estudios de Factibilidad , Femenino , Humanos , Masculino , Meningitis/líquido cefalorraquídeo , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Telomerasa/genética , Factores de Tiempo
12.
Personal Disord ; 9(6): 530-542, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29999393

RESUMEN

Individuals with borderline personality disorder (BPD) have difficulties regulating emotions, which may be a consequence of using less effective emotion regulation (ER) strategies to lessen the intensity of their negative emotions. It is not yet known whether people with BPD utilize particular ER strategies to modulate specific mood states and if these strategies are different from those used by individuals with depressive and anxiety disorders. In the present study, 90 participants (30 BPD, 30 anxiety and/or depressive disorders, and 30 healthy controls) underwent a mood induction procedure and specified which ER strategies they used and their perceived difficulty regulating mood following induction. Compared with healthy controls, BPD endorsed higher negative mood prior to, immediately following, and 4 min after neutral and negative mood inductions; more maladaptive ER strategies (e.g., rumination); and more perceived difficulty regulating negative mood. Compared with anxiety and/or depressive disorders, BPD endorsed similar ER strategies and subjective difficulty during mood inductions, endorsed higher negative mood following a neutral video and 1 negative video, and recorded higher RSA reactivity during and following 2 negative videos. Results suggest that individuals with BPD use a higher number of maladaptive ER strategies compared with healthy controls, which may lead to less effective modulation of negative mood and higher reports of difficulty regulating emotions. In addition, physiological measurements indicated that individuals with BPD may have higher RSA reactivity in response to negative mood induction compared with other mental disorders, which may reflect inefficient or disorganized attempts to regulate emotional arousal. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Asunto(s)
Afecto/fisiología , Trastornos de Ansiedad/psicología , Trastorno de Personalidad Limítrofe/psicología , Trastorno Depresivo/psicología , Rumiación Cognitiva/fisiología , Adolescente , Adulto , Trastornos de Ansiedad/complicaciones , Nivel de Alerta/fisiología , Trastorno de Personalidad Limítrofe/complicaciones , Trastorno Depresivo/complicaciones , Emociones/fisiología , Femenino , Humanos , Adulto Joven
13.
FASEB J ; 19(13): 1878-80, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16123171

RESUMEN

Glutamate excitotoxicity is increasingly being recognized as a pathogenic mechanism in autoimmune inflammatory disorders of the central nervous system (CNS). Astrocytes are the predominant players in clearing the extracellular space from glutamate and normally have extensive spare capacities in terms of glutamate uptake. We asked what might be the basis of glutamate accumulation in T cell triggered autoimmune inflammation. In vitro, coculture of primary rat astrocytes with activated myelin basic protein (MBP)-specific T cells resulted in a decrease of astrocytic glutamate uptake rates (Vmax). In parallel, the amount of the Na+-dependent glutamate transporter GLAST was reduced within 48-60 h. Significant decreases of GLAST protein were observed in astrocytes harvested after incubation with T cells activated by MBP during coculture or after incubation with T cell blasts preactivated in the presence of splenocytes beforehand. Since exposure of astrocytes to cell-free supernatant of MBP-activated T cells also resulted in reduced expression of GLAST, a humoral factor appeared to be the driving agent. In blocking experiments using neutralizing antibodies and by incubation of astrocytes with recombinant cytokines, tumor necrosis factor-alpha (TNF-alpha) was identified as being responsible for the down-modulation of GLAST. GLAST was also down-regulated in the CNS of autoimmune encephalomyelitic rats but not in animals suffering from systemic inflammation. Since the loss of GLAST was not confined to inflammatory infiltrates, here too, a humoral factor seemed to be causative. In conclusion, T cell derived TNF-alpha impairs glutamate clearance capacity of astrocytes in vitro and probably also in vivo providing a pathogenic link to glutamate excitotoxicity that may contribute to early axonal dysfunction remote from active autoimmune inflammatory demyelination.


Asunto(s)
Sistema de Transporte de Aminoácidos X-AG/fisiología , Astrocitos/metabolismo , Autoantígenos/química , Glutamatos/farmacocinética , Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/fisiología , Sistema de Transporte de Aminoácidos X-AG/metabolismo , Animales , Astrocitos/citología , Sitios de Unión , Sistema Nervioso Central/embriología , Técnicas de Cocultivo , Citocinas/metabolismo , Enfermedades Desmielinizantes/patología , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Encefalomielitis Autoinmune Experimental/metabolismo , Citometría de Flujo , Immunoblotting , Inflamación , Cinética , Modelos Biológicos , Proteína Básica de Mielina/metabolismo , Ratas , Sodio/metabolismo , Linfocitos T/química , Linfocitos T/metabolismo , Factores de Tiempo , Factor de Necrosis Tumoral alfa/metabolismo
14.
Neurosci Lett ; 381(1-2): 175-8, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15882812

RESUMEN

Campylobacter jejuni-induced enteritis is the most common infection preceding Guillain-Barre syndrome (GBS), an immune-mediated polyradiculoneuritis. The acute autoimmune attack is thought to be based on C. jejuni antigens which may mimick antigens of the peripheral nervous system. Additional pathomechanisms, like disturbance of natural T cell immunoregulation by C. jejuni, have not been evaluated so far. In experimental autoimmune neuritis (EAN), a T lymphocyte-mediated animal model of human GBS, tolerance to myelin-derived autoantigens can be induced by oral feeding of the respective antigen. Here we investigated whether the lipooligosaccharide (LOS) fraction of C. jejuni may directly alter immunologic tolerance through gastrointestinal pathways. While EAN, actively induced by immunization with bovine peripheral nerve myelin could be ameliorated by precedent feeding of myelin, feeding of C. jejuni LOS along with the myelin antigen not only prevented the tolerizing effects of oral myelin but even accelerated the onset of overt EAN and augmented the myelin-specific B cell response. These findings provide evidence that LOS of C. jejuni, as produced in the gut during C. jejuni-induced enteritis, can disturb natural tolerance to definite proteins which may be or may mimic peripheral nerve antigens. In human patients this may be one of the potential mechanisms to explain why C. jejuni enteritis is a common trigger of GBS.


Asunto(s)
Campylobacter jejuni/metabolismo , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/inmunología , Síndrome de Guillain-Barré/inmunología , Lipopolisacáridos/administración & dosificación , Vaina de Mielina/inmunología , Neuritis Autoinmune Experimental/inmunología , Animales , Femenino , Tracto Gastrointestinal/microbiología , Síndrome de Guillain-Barré/inducido químicamente , Síndrome de Guillain-Barré/microbiología , Inmunidad Innata/efectos de los fármacos , Neuritis Autoinmune Experimental/inducido químicamente , Neuritis Autoinmune Experimental/microbiología , Ratas , Ratas Endogámicas Lew
15.
J Leukoc Biol ; 76(5): 950-60, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15328336

RESUMEN

Leflunomide inhibits de novo pyrimidine synthesis and is a novel, immunosuppressive agent that has been successfully used to treat rheumatoid arthritis. Here, we investigated the efficacy of leflunomide and its mode of action in experimental autoimmune encephalomyelitis (EAE), which is a T helper cell type 1 cell-borne disease model to simulate inflammatory aspects of multiple sclerosis and was induced in Lewis rats by adoptive transfer of myelin basic protein (MBP)-specific T line cells. Given in vivo for 7 days after cell transfer, leflunomide suppressed clinical signs of disease even in uridine-substituted animals. MBP-specific T line cells that had been antigen-activated in vitro in the presence of A77 1726 (active metabolite of leflunomide) produced less interferon-gamma, whereas interleukin (IL)-10 secretion had a tendency to be increased without changes in signal transducer and activator of transcription 6 trafficking. Furthermore, these T cells exhibited reduced chemotaxis and induced a significantly mitigated disease course upon transfer into naive rats. The effects of leflunomide on MBP-specific memory type T line cells in vitro may not be mediated by pyrimidine depletion, as they were not reversible by exogenous uridine. Moreover, A77 1726 led to increased expression of CD86 (B7-2) and secretion of IL-10 in cultured microglial cells in vitro, strengthening their down-modulatory impact on activated, autoantigen-specific T cells. In conclusion, our observations underline that the immunomodulatory potential of leflunomide in effector cells of EAE is clinically relevant and is not exclusively dependent on the depletion of cellular pyrimidine pools.


Asunto(s)
Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/inmunología , Isoxazoles/farmacología , Pirimidinas/metabolismo , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Linfocitos T Colaboradores-Inductores/inmunología , Traslado Adoptivo , Animales , Animales Recién Nacidos , Antígenos CD/metabolismo , Antígeno B7-2 , Células Cultivadas , Quimiotaxis de Leucocito/genética , Quimiotaxis de Leucocito/inmunología , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/metabolismo , Cobayas , Inmunosupresores/farmacología , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-2/inmunología , Interleucina-2/farmacología , Leflunamida , Glicoproteínas de Membrana/metabolismo , Microglía/efectos de los fármacos , Microglía/inmunología , Microglía/metabolismo , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/metabolismo , Proteína Básica de Mielina/genética , Proteína Básica de Mielina/inmunología , Ratas , Ratas Endogámicas Lew , Factor de Transcripción STAT6 , Transactivadores/metabolismo , Uridina/metabolismo , Uridina/farmacología
16.
Lab Chip ; 15(8): 1923-33, 2015 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-25737365

RESUMEN

Enhancing mixing is of uttermost importance in many laminar microfluidic devices, aiming at overcoming the severe performance limitation of species transport by diffusion alone. Here we focus on the significant category of microscale co-laminar flows encountered in membraneless redox flow cells for power delivery. The grand challenge is to achieve simultaneously convective mixing within each individual reactant, to thin the reaction depletion boundary layers, while maintaining separation of the co-flowing reactants, despite the absence of a membrane. The concept presented here achieves this goal with the help of optimized herringbone flow promoting microstructures with an integrated separation zone. Our electrochemical experiments using a model redox couple show that symmetric flow promoter designs exhibit laminar to turbulent flow behavior, the latter at elevated flow rates. This change in flow regime is accompanied by a significant change in scaling of the Sherwood number with respect to the Reynolds number from Sh ~ Re(0.29) to Sh ~ Re(0.58). The stabilized continuous laminar flow zone along the centerline of the channel allows operation in a co-laminar flow regime up to Re ~325 as we demonstrate by micro laser-induced fluorescence (µLIF) measurements. Micro particle image velocimetry (µPIV) proves the maintenance of a stratified flow along the centerline, mitigating reactant cross-over effectively. The present work paves the way toward improved performance in membraneless microfluidic flow cells for electrochemical energy conversion.

17.
J Neuroimmunol ; 155(1-2): 64-72, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15342197

RESUMEN

In an autoimmune inflammatory setting, ingestion of apoptotic T cells leads to a down-regulation of microglial immune functions. Recent studies have indicated that microglia can be matured by exposure to GM-CSF. GM-CSF stimulation led to a differentiated microglial phenotype and enhanced antigen-presenting capabilities. The secretion of TNF-alpha was significantly decreased by the uptake of apoptotic cells in unstimulated microglia, but not in GM-CSF-differentiated microglia. IL-10 secretion was unaffected. After ingestion of apoptotic cells, only previously unstimulated, but not GM-CSF-differentiated microglial cells decreased their T cell-activating potential as measured by IFN-gamma secretion in antigen-activated MBP-specific T cells. Thus, GM-CSF stimulation reduces the immunomodulatory functions of microglial cells.


Asunto(s)
Apoptosis/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Encefalitis/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Microglía/inmunología , Fagocitosis/inmunología , Adyuvantes Inmunológicos/farmacología , Animales , Células Presentadoras de Antígenos/efectos de los fármacos , Células Presentadoras de Antígenos/inmunología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/inmunología , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Interferón gamma/efectos de los fármacos , Interferón gamma/inmunología , Interleucina-1/inmunología , Interleucina-1/metabolismo , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Microglía/efectos de los fármacos , Microglía/metabolismo , Ratas , Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/inmunología
18.
J Neuroimmunol ; 148(1-2): 63-73, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14975587

RESUMEN

Glatiramer acetate (GLAT) is a mixture of basic polypeptides that have been shown to suppress experimental autoimmune encephalomyelitis (EAE). As Copaxone, GLAT is approved for the treatment of relapsing-remitting multiple sclerosis (MS). Different immunomechanisms have been suggested to contribute to the beneficial effects of GLAT which rely on blockade of MHC class II molecules or cross-recognition with myelin basic protein (MBP). Because GLAT could also inhibit experimental autoimmunity not related to myelin proteins, we searched for additional, less-restricted immunomodulatory actions of GLAT. Using freshly isolated resident peritoneal macrophages from naive Lewis rats, it is shown that GLAT profoundly modulates cytokine secretion of the cells. In unseparated macrophages (MPhi) and MPhi of low density, GLAT enhanced constitutive and LPS-induced production of interleukin 10 (IL-10) while LPS-induced synthesis of tumor necrosis factor-alpha (TNF-alpha) was dose-dependently suppressed by GLAT. Although both basic proteins GLAT and MBP facilitated adherence of MPhi, MBP had opposite effects on cytokine production suggesting unique properties of GLAT. In contrast to MPhi, peritoneal mast cells produced only little amounts of cytokines. The inductive effect of GLAT on IL-10 production by antigen-presenting cells was also observed in bone marrow-derived rat dendritic cells (DCs) which, unlike MPhi, were not suppressed in their production of TNF-alpha. Induction of IL-10 in different antigen-presenting cells is a new immunomodulatory mechanism of GLAT. In part, it goes along with the inhibition of TNF-alpha and may be a common basis for the known beneficial effects of GLAT on various cellular autoimmune responses including MS.


Asunto(s)
Antígenos CD , Antígenos de Neoplasias , Antígenos de Superficie , Proteínas Aviares , Proteínas Sanguíneas , Células Dendríticas/efectos de los fármacos , Interleucina-10/metabolismo , Macrófagos Peritoneales/efectos de los fármacos , Péptidos/farmacología , Animales , Antígenos de Diferenciación/metabolismo , Basigina , Células Cultivadas , Células Dendríticas/metabolismo , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Ensayo de Inmunoadsorción Enzimática/métodos , Citometría de Flujo/métodos , Acetato de Glatiramer , Proteínas del Grupo de Alta Movilidad/farmacología , Inmunosupresores/farmacología , Lipopolisacáridos/farmacología , Macrófagos Peritoneales/metabolismo , Mastocitos/efectos de los fármacos , Glicoproteínas de Membrana/metabolismo , Proteína Básica de Mielina/metabolismo , Ratas , Ratas Endogámicas Lew , Factor de Necrosis Tumoral alfa/metabolismo
19.
J Neuroimmunol ; 139(1-2): 17-26, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12799016

RESUMEN

Mice that lack the guanine nucleotide exchange factor (GEF) Vav1 exhibit particular defects in antigen-triggered T cell activation but may have an autoreactive T cell repertoire due to impaired intra-thymic negative selection. MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE) was used to test the susceptibility of Vav1(-/-) mice to organ-specific autoimmunity. Vav1(-/-) animals were found to be resistant to MOG(35-55)-EAE since the priming and in vivo expansion of myelin oligodendrocyte glycoprotein (MOG)-specific T cells was inefficient despite fully functional antigen presentation. Protection from cell-mediated autoimmunity was not due to a Th2 bias, to the lack of IL-2 or a failure of Vav1(-/-) T cells in terms of chemotactic mobility.


Asunto(s)
Presentación de Antígeno/genética , Proteínas de Ciclo Celular , Encefalomielitis Autoinmune Experimental/genética , Predisposición Genética a la Enfermedad/genética , Inmunidad Innata/genética , Glicoproteína Asociada a Mielina/farmacología , Proteínas Proto-Oncogénicas/deficiencia , Animales , Presentación de Antígeno/efectos de los fármacos , Quimiotaxis de Leucocito/efectos de los fármacos , Quimiotaxis de Leucocito/genética , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/metabolismo , Femenino , Inmunidad Celular/efectos de los fármacos , Inmunidad Celular/genética , Inmunidad Innata/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/genética , Masculino , Ratones , Ratones Noqueados , Proteínas de la Mielina , Glicoproteína Asociada a Mielina/inmunología , Glicoproteína Asociada a Mielina/metabolismo , Glicoproteína Mielina-Oligodendrócito , Fragmentos de Péptidos/farmacología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-vav , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Células Th2/efectos de los fármacos , Células Th2/inmunología
20.
J Neurol ; 249(8): 1001-3, 2002 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12195444

RESUMEN

In multiple sclerosis (MS), serum levels of ICAM-1 were elevated during acute exacerbations and were therefore proposed as a marker of disease activity, but the potential of this molecule as an indicator of long-term activity, i. e. the progression of the disease outside acute exacerbations, is not known. We therefore measured sICAM-1 levels by an enzyme-linked immunosorbent assay in 26 patients with active relapsing-remitting (RR) MS (at least two relapses in the preceding 2 years, but not within the last 30 days), in 10 patients with active secondary-progressive MS (progression of at least one point on the EDSS and/or two relapses in the preceding 2 years, but not within the last 30 days), in 8 patients with stable RR MS (no relapse and no progression during the last two years), and in 16 healthy controls. There was no significant difference between the different MS subtypes and healthy controls, nor within the different MS subtypes. Thus, while sICAM-1 may be useful to indicate short-term activity of MS in terms of relapses and MRI activity, this does not hold true for the long-term activity of MS outside acute exacerbations.


Asunto(s)
Molécula 1 de Adhesión Intercelular/sangre , Esclerosis Múltiple/sangre , Adulto , Biomarcadores , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/sangre , Esclerosis Múltiple Recurrente-Remitente/sangre , Proyectos Piloto
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