24 research outputs found

    Grip strength in mice with joint inflammation: A rheumatology function test sensitive to pain and analgesia

    Get PDF
    Grip strength deficit is a measure of pain-induced functional disability in rheumatic disease. We tested whether this parameter and tactile allodynia, the standard pain measure in preclinical studies, show parallels in their response to analgesics and basic mechanisms. Mice with periarticular injections of complete Freund's adjuvant (CFA) in the ankles showed periarticular immune infiltration and synovial membrane alterations, together with pronounced grip strength deficits and tactile allodynia measured with von Frey hairs. However, inflammation-induced tactile allodynia lasted longer than grip strength alterations, and therefore did not drive the functional deficits. Oral administration of the opioid drugs oxycodone (1–8 mg/kg) and tramadol (10–80 mg/kg) induced a better recovery of grip strength than acetaminophen (40–320 mg/kg) or the nonsteroidal antiinflammatory drugs ibuprofen (10–80 mg/kg) or celecoxib (40–160 mg/kg); these results are consistent with their analgesic efficacy in humans. Functional impairment was generally a more sensitive indicator of drug-induced analgesia than tactile allodynia, as drug doses that attenuated grip strength deficits showed little or no effect on von Frey thresholds. Finally, ruthenium red (a nonselective TRP antagonist) or the in vivo ablation of TRPV1-expressing neurons with resiniferatoxin abolished tactile allodynia without altering grip strength deficits, indicating that the neurobiology of tactile allodynia and grip strength deficits differ. In conclusion, grip strength deficits are due to a distinct type of pain that reflects an important aspect of the human pain experience, and therefore merits further exploration in preclinical studies to improve the translation of new analgesics from bench to bedside.This study was partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO, grant SAF2013-47481P), the Junta de Andalucía (grant CTS 109), and funding from Esteve and the European Regional Development Fund (FEDER)

    Ferrimagnetic clusters as the origin of anomalous Curie-Weiss behavior in ZnFe_2O_4 antiferromagnetic susceptibility

    Get PDF
    Different studies carried out in the last three decades on the magnetic susceptibility of the spinel ZnFe_2O_4 ferrite have revealed the positive character of its Curie-Weiss temperature, contradicting its observed antiferromagnetic behavior which is characterized by a well-defined susceptibility peak centered around the Neel temperature (10 K). Some approaches based on ab initio calculations and mixture of interactions have been attempted to explain this anomaly. This work shows how for very low values of the inversion parameter, the small percentage of Fe atoms located in tetrahedral sites gives rise to the appearance of ferrimagnetic clusters around them. Superparamagnetism of these clusters is the main cause of the anomalous Curie-Weiss behavior. This finding is supported experimentally from the thermal dependence of the inverse susceptibility and its evolution with the degree of inversion

    Unveiling the hidden entropy in ZnFe_2O_4

    Get PDF
    The antiferromagnetic (AFM) transition of the normal ZnFe_2O_4 has been intensively investigated with results showing a lack of long-range order, spin frustrations, and a "hidden" entropy in the calorimetric properties for inversion degrees delta approximate to 0 or delta = 0. As delta drastically impacts the magnetic properties, it is logical to question how a delta value slightly different from zero can affect the magnetic properties. In this work, (Zn_(1-delta)Fe_delta)[Zn_delta Fe_(2-delta)]O_4 with delta = 0.05 and delta = 0.27 have been investigated with calorimetry at different applied fields. It is shown that a delta value as small as 0.05 may affect 40% of the unit cells, which become locally ferrimagnetic (FiM) and coexists with AFM and spin disordered regions. The spin disorder disappears under an applied field of 1 T. Mossbauer spectroscopy confirms the presence of a volume fraction with a low hyperfine field that can be ascribed to these spin disordered regions. The volume fractions of the three magnetic phases estimated from entropy and hyperfine measurements are roughly coincident and correspond to approximately 1/3 for each of them. The "hidden" entropy is the zero point entropy different from 0. Consequently, the so-called "hidden" entropy can be ascribed to the frustrations of the spins at the interphase between the AFM-FiM phases due to having delta approximate to 0 instead of ideal delta = 0

    Recursos didácticos de formación en el área de magnetismo y electromagnetismo para profesores y estudiantes de ESO y Bachillerato

    Get PDF
    Este proyecto persigue un doble objetivo. Por un lado, por medio de acciones formativas específicas, facilitar al personal docente de secundaria y bachillerato los medios para el montaje y realización de experimentos sencillos de bajo coste, que no requieran un equipamiento especial para su ejecución, y que sirvan como introducción a la explicación de conceptos científicos, tales como campo magnético, inducción electromagnética, etc. Por otro, abrir el Instituto de Magnetismo Aplicado (IMA) de la Universidad Complutense de Madrid a la comunidad educativa en las modalidades ya desarrolladas en el IMA, como charlas, prácticas experimentales, prácticas de empresa, etc. y ofrecer la posibilidad de realizar en un entorno controlado diversos tipos de ensayos, experimentos y prácticas de laboratorio

    “Ver, tocar, hacer”: una propuesta para acercar la ciencia a la sociedad

    Get PDF
    Este proyecto persigue un doble objetivo. Por un lado, por medio de acciones formativas específicas, facilitar al personal docente de institutos de secundaria y bachillera los medios para el montaje y realización de experimentos sencillos de bajo coste, que no requieran un equipamiento especial para su ejecución, y que sirvan como introducción a la explicación de conceptos científicos que suelen ser complejos, tales como campo magnético, inducción electromagnética, etc. Por otro, abrir el laboratorio a la comunidad educativa en las modalidades ya desarrolladas en el Instituto de Magnetismo Aplicado (UCM), como charlas, prácticas experimentales, prácticas de empresa, etc. y ofrecer la posibilidad de realizar en un entorno controlado diversos tipos de ensayos, experimentos y prácticas de laboratorio. Dado el carácter eminentemente práctico y experimental de los contenidos de las acciones formativas, nos centraremos en el diseño de experimentos bajo la consigna “Do it yourself”, de modo que puedan ser fácilmente realizados por los estudiantes con un mínimo de requisitos técnicos. Este método de “ver, tocar, hacer” no sólo ayuda a internalizar conceptos teóricos, sino que sirve también como vehículo motivador de la práctica científica. Este tipo de actividad resulta más atractiva, cercana y eficaz a la hora de despertar vocaciones científicas desde edades temprana

    Tetrodotoxin (TTX) as a Therapeutic Agent for Pain

    Get PDF
    Tetrodotoxin (TTX) is a potent neurotoxin that blocks voltage-gated sodium channels (VGSCs). VGSCs play a critical role in neuronal function under both physiological and pathological conditions. TTX has been extensively used to functionally characterize VGSCs, which can be classified as TTX-sensitive or TTX-resistant channels according to their sensitivity to this toxin. Alterations in the expression and/or function of some specific TTX-sensitive VGSCs have been implicated in a number of chronic pain conditions. The administration of TTX at doses below those that interfere with the generation and conduction of action potentials in normal (non-injured) nerves has been used in humans and experimental animals under different pain conditions. These data indicate a role for TTX as a potential therapeutic agent for pain. This review focuses on the preclinical and clinical evidence supporting a potential analgesic role for TTX. In addition, the contribution of specific TTX-sensitive VGSCs to pain is reviewed

    Anafilaxia en niños y adultos: prevención, diagnóstico y tratamiento

    Get PDF
    La anafilaxia es una condición que requiere asistencia inmediata para su resolución, se puede presentar en diferentes entornos: consultorio, hospital, escuela, hogar o en algún otro espacio público. La información aquí contenida forma parte de lineamientos conocidos sobre prevención, diagnóstico y tratamiento. Se abordan aspectos epidemiológicos, desencadenantes, factores de riesgo y cofactores; se explican de una manera didáctica los mecanismos fisiopatológicos que se traducen en fenotipos de presentación. Se enfatiza el diagnóstico clínico con base en criterios ya establecidos, se mencionan clasificaciones para evaluar la gravedad de la reacción, así como el rol de las pruebas clínicas o de laboratorio. Como aspectos de relevancia, se abordan el tratamiento de primera elección con adrenalina, instrucciones sobre autoinyectores y diferentes elementos para el tratamiento complementario y de segunda elección. También se refieren aspectos a considerar al dar de alta a un paciente y medidas de seguimiento, con un énfasis preventivo en la comunidad. Finalmente, se menciona el abordaje en el consultorio de alergia para decidir sobre opciones de inmunomodulación. ABSTRACT Anaphylaxis is a condition that requires immediate assistance for its resolution, it can occur in different settings: office, hospital, school, home or some other public space. The information contained herein forms part of known guidelines on prevention, diagnosis and treatment. Epidemiological aspects, triggers, risk factors and co-factors are addressed; physiopathological mechanisms that are translated into presentation phenotypes are explained in a didactic way. Clinical diagnosis is emphasized based on established criteria, classifications are mentioned to evaluate the severity of the reaction, as well as the role of clinical or laboratory tests. As relevant aspects, the first choice treatment with adrenaline, instructions on auto-injectors and different elements for the complementary and second choice treatment are dealt with. They also refer to aspects to consider when discharging a patient and followup measures, with a preventive emphasis on the community. Finally, the allergy clinic approach to deciding on immunomodulation options is mentione

    Role of age and comorbidities in mortality of patients with infective endocarditis

    Get PDF
    [Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group
    corecore