IGF-II promotes neuroprotection and neuroplasticity recovery in a long-lasting model of oxidative damage induced by glucocorticoids

Insulin-like growth factor-II (IGF-II) is a naturally occurring hormone that exerts neurotrophic and neuroprotective properties in a wide range of neurodegenerative diseases and ageing. Accumulating evidence suggests that the effects of IGF-II in the brain may be explained by its binding to the specific transmembrane receptor, IGFII/M6P receptor (IGF-IIR). However, relatively little is known regarding the role of IGF-II through IGF-IIR in neuroprotection. Here, using adult cortical neuronal cultures, we investigated whether IGF-II exhibits long-term antioxidant effects and neuroprotection at the synaptic level after oxidative damage induced by high and transient levels of corticosterone (CORT). Furthermore, the involvement of the IGF-IIR was also studied to elucidate its role in the neuroprotective actions of IGF-II. We found that neurons treated with IGF-II after CORT incubation showed reduced oxidative stress damage and recovered antioxidant status (normalized total antioxidant status, lipid hydroperoxides and NAD(P) H:quinone oxidoreductase activity). Similar results were obtained when mitochondria function was analysed (cytochrome c oxidase activity, mitochondrial membrane potential and subcellular mitochondrial distribution). Furthermore, neuronal impairment and degeneration were also assessed (synaptophysin and PSD-95 expression, presynaptic function and FluoroJade B® stain). IGF-II was also able to recover the long-lasting neuronal cell damage. Finally, the effects of IGF-II were not blocked by an IGF-IR antagonist, suggesting the involvement of IGF-IIR. Altogether these results suggest that, in or model, IGF-II through IGF-IIR is able to revert the oxidative damage induced by CORT. In accordance with the neuroprotective role of the IGF-II/IGF-IIR reported in our study, pharmacotherapy approaches targeting this pathway may be useful for the treatment of diseases associated with cognitive deficits (i.e., neurodegenerative disorders, depression, etc.)

Influence of environmental factors in the in vitro dehydration of hydrogel and silicone hydrogel contact lenses

Purpose: To analyze in vitro the influence of different environmental conditions on the dehydration pattern of seven currently marketed hydrogel (Hy) and silicone hydrogel (Si-Hy) contact lenses (CL). Methods: Three Hy and four Si-Hy CLs were evaluated. CLs were exposed to four different relative humidity (RH) conditions (5%, 30%, 50%, and 70%) and two air flow (AF) rates (0 and 2.75 m/seg) within an environmental chamber. Dehydration was assessed using the gravimetric method. Data were taken at baseline, 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes of exposure. Dehydration rate (DR), valid dehydration (VD) and stabilization time were calculated. Results: The interaction between RH, AF and the type of the CL material had a significant effect (p 0.03) on DR up to 60 minutes. The maximum differences in VD values among CL occurred around 15 minutes exposure varying from 25.16% to 42.75%. Stabilization time was quicker under the 5%RH with AF condition than under 70% RH without AF one for most CLs. Conclusions: Lower RH seems to increase CL dehydration being further accelerated with the AF presence. The dehydration pattern is material dependent, thus current marketed CLs behave differently under several controlled environmental conditions. Future in vivo studies should confirm these outcomes.The present study was partially supported by Junta Castilla y Leon (GR217 and VA145A11-2); by Junta de Castilla y Leon and European Social Fund (VA317-11); by Junta de Castilla y Leon and European Regional Development Fund (O22/12/VA/0112) and by Ministerio de Economia y Competitividad through Centro para el Desarrollo Tecnologico Industrial (IDI-2006-0676)

The influence of the carrier molecule on amoxicillin recognition by specific IgE in patients with immediate hypersensitivity reactions to betalactams

10 p.-4 fig.-1 tab.The optimal recognition of penicillin determinants, including amoxicillin (AX), by specific IgE antibodies is widely believed to require covalent binding to a carrier molecule. The nature of the carrier and its contribution to the antigenic determinant is not well known. Here we aimed to evaluate the specific-IgE recognition of different AX-derived structures. We studied patients with immediate hypersensitivity reactions to AX, classified as selective or cross-reactors to penicillins. Competitive immunoassays were performed using AX itself, amoxicilloic acid, AX bound to butylamine (AXO-BA) or to human serum albumin (AXO-HSA) in the fluid phase, as inhibitors, and amoxicilloyl-poli-L-lysine (AXO-PLL) in the solid-phase. Two distinct patterns of AX recognition by IgE were found: Group A showed a higher recognition of AX itself and AX-modified components of low molecular weights, whilst Group B showed similar recognition of both unconjugated and conjugated AX. Amoxicilloic acid was poorly recognized in both groups, which reinforces the need for AX conjugation to a carrier for optimal recognition. Remarkably, IgE recognition in Group A (selective responders to AX) is influenced by the mode of binding and/or the nature of the carrier; whereas IgE in Group B (cross-responders to penicillins) recognizes AX independently of the nature of the carrier.The present study has been supported by Institute of Health “Carlos III” of the Ministry of Economy and Competitiveness (grants cofunded by European Regional Development Fund (ERDF): PI12/02529, PI15/01206, CP15/00103,Red de Reacciones Adversas a Alergenos y Farmacos RD12/0013/0001, RD12/0013/0003 and RD12/0013/0008,RD09/0076/00112 for the Biobank network and PT13/0010/0006 for the Biobank platform) and by State Secretariat for Research, Development and Innovation of the Ministry of Economy and Competitiveness (grants cofunded by European Regional Development Fund (ERDF): MINECO SAF2012-36519, SAF2015-68590-R/FEDER and CTQ2013-41339-P). Andalusian Regional Ministry of Economy and Knowledge (grants cofunded by European Regional Development Fund (ERDF): CTS-06603); Andalusian Regional Ministry Health (grants:PI-0699-2011, PI-0159-2013 and PI-0179-2014) and Merck-Serono Research Grant from Fundación Salud 2000. CM holds a ‘Nicolas Monardes’ research contract by Andalusian Regional Ministry Health: C-0044-2012 SAS 2013. MIM holds a ‘Miguel Servet I’ research contract by Institute of Health “Carlos III” of the Ministry of Economy and Competitiveness (grants cofunded by European Social Fund (ESF)): CP15/00103. AA thanks “pFIS fellowship” (FI08/00385) from ISCIII and Andalucia “Talent Hub Fellowship” (TAHUB/II-004) cofunded by the Junta de Andalucia and the European Union, VII Framework Programme of the European Commission (grant agreement No. 291780).Peer reviewe

Clinical and Molecular Inflammatory Response in Sjögren Syndrome–Associated Dry Eye Patients Under Desiccating Stress

Producción CientíficaTo evaluate the response of the lacrimal function unit in Sjogren syndrome (SS)-associated dry eye patients exposed to 2 simulated daily life environ-mental conditions. Fourteen female SS dry eye patients were exposed for 2 hours to a controlled normal condition (23 C, 45% relative humidity, and air flow 0.10 m/s) and a controlled adverse condition that simulates desic- cating stress (23 C, 5% relative humidity, and air flow 0.10 m/s). The following dry eye tests were performed before and after the exposure: tear osmolarity, phenol red thread test, conjunctival hyperemia, fluorescein tear break-up time, corneal fluorescein staining, conjunctival lissamine green staining, and Schirmer test. Levels of 16 molecules were analyzed in tears by multiplex immu- nobead analysis.Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA174U14

7th Drug hypersensitivity meeting: part two

No abstract availabl

Hierro intravenoso perioperatorio; una opción terapéutica para el tratamiento de la anemia y la reducción de los requerimientos de transfusión

Perioperative anaemia, with iron deficiency being its leading cause, is a frequent condition among surgical patients, and has been linked to increased postoperative morbidity and mortality, and decreased quality of life. Postoperative anaemia is even more frequent and is mainly caused by perioperative blood loss, aggravated by inflammation-induced blunting of erythropoiesis. Allogenic transfusion is commonly used for treating acute perioperative anaemia, but it also increases the rate of morbidity and mortality in surgical and critically ill patients. Thus, overall concerns about adverse effects of both preoperative anaemia and allogeneic transfusion have prompted the review of transfusion practice and the search for safer and more biologically rational treatment options. In this paper, the role of intravenous iron therapy (mostly with iron sucrose and ferric carboxymaltose), as a safe and efficacious tool for treating anaemia and reducing transfusion requirements in surgical patients, as well as in other medical areas, has been reviewed. From the analysis of published data and despite the lack of high quality evidence in some areas, it seems fair to conclude that perioperative intravenous iron administration, with or without erythropoiesis stimulating agents, is safe, results in lower transfusion requirements and hastens recovery from postoperative anaemia. In addition, some studies have reported decreased rates of postoperative infection and mortality, and shorter length of hospital stay in surgical patients receiving intravenous iron.YesLa anemia perioperatoria, cuya principal causa es la deficiencia de hierro, es frecuente entre pacientes quirúrgicos y se asocia a un aumento de la morbimortalidad postoperatoria y a una disminución de la calidad de vida. La anemia postoperatoria es aún más frecuente y está causada principalmente por la pérdida perioperatoria de sangre, agravada por la reducción de la actividad eritropóyetica inducida por la inflamación. La transfusión alogénica es el tratamiento habitual de la anemia aguda perioperatoria, pero también aumenta la tasas de morbimortalidad en pacientes quirúrgicos y críticos. La preocupación por los efectos adversos de la anemia preoperatoria y la transfusión alogénica han impulsado la revisión de la práctica transfusional y la búsqueda de opciones de tratamiento más seguras y biológicamente más racionales. En este artículo se revisa el papel de la terapia con hierro intravenoso (mayoritariamente hierro sacarosa y carboxymaltosa de hierro), como herramienta segura y eficaz para el tratamiento de la anemia y la reducción de los requerimientos transfusionales en el paciente quirúrgico, así como en otras áreas médicas. Del análisis de los datos publicados y a pesar de la falta de evidencia de alta calidad en algunas áreas, parece razonable concluir que la administración perioperatoria de hierro intravenoso, con o sin agentes estimuladores de la eritropoyesis, es segura, reduce las necesidades de transfusión y acelera la recuperación de la anemia postoperatoria. Además, algunos estudios han encontrado una reducción de las tasas de infección postoperatoria y de mortalidad, así como de la duración de la estancia hospitalaria, en pacientes quirúrgicos tratados con hierro intravenoso

Perioperative intravenous iron: an upfront therapy for treating anaemia and reducing transfusion requirements Hierro intravenoso perioperatorio: una opción terapéutica para el tratamiento de la anemia y la reducción de los requerimientos de transfusión

Perioperative anaemia, with iron deficiency being its leading cause, is a frequent condition among surgical patients, and has been linked to increased postoperative morbidity and mortality, and decreased quality of life. Postoperative anaemia is even more frequent and is mainly caused by perioperative blood loss, aggravated by inflammation-induced blunting of erythropoiesis. Allogenic transfusion is commonly used for treating acute perioperative anaemia, but it also increases the rate of morbidity and mortality in surgical and critically ill patients. Thus, overall concerns about adverse effects of both preoperative anaemia and allogeneic transfusion have prompted the review of transfusion practice and the search for safer and more biologically rational treatment options. In this paper, the role of intravenous iron therapy (mostly with iron sucrose and ferric carboxymaltose), as a safe and efficacious tool for treating anaemia and reducing transfusion requirements in surgical patients, as well as in other medical areas, has been reviewed. From the analysis of published data and despite the lack of high quality evidence in some areas, it seems fair to conclude that perioperative intravenous iron administration, with or without erythropoiesis stimulating agents, is safe, results in lower transfusion requirements and hastens recovery from postoperative anaemia. In addition, some studies have reported decreased rates of postoperative infection and mortality, and shorter length of hospital stay in surgical patients receiving intravenous iron.La anemia perioperatoria, cuya principal causa es la deficiencia de hierro, es frecuente entre pacientes quirúrgicos y se asocia a un aumento de la morbimortalidad postoperatoria y a una disminución de la calidad de vida. La anemia postoperatoria es aún más frecuente y está causada principalmente por la pérdida perioperatoria de sangre, agravada por la reducción de la actividad eritropóyetica inducida por la inflamación. La transfusión alogénica es el tratamiento habitual de la anemia aguda perioperatoria, pero también aumenta la tasas de morbimortalidad en pacientes quirúrgicos y críticos. La preocupación por los efectos adversos de la anemia preoperatoria y la transfusión alogénica han impulsado la revisión de la práctica transfusional y la búsqueda de opciones de tratamiento más seguras y biológicamente más racionales. En este artículo se revisa el papel de la terapia con hierro intravenoso (mayoritariamente hierro sacarosa y carboxymaltosa de hierro), como herramienta segura y eficaz para el tratamiento de la anemia y la reducción de los requerimientos transfusionales en el paciente quirúrgico, así como en otras áreas médicas. Del análisis de los datos publicados y a pesar de la falta de evidencia de alta calidad en algunas áreas, parece razonable concluir que la administración perioperatoria de hierro intravenoso, con o sin agentes estimuladores de la eritropoyesis, es segura, reduce las necesidades de transfusión y acelera la recuperación de la anemia postoperatoria. Además, algunos estudios han encontrado una reducción de las tasas de infección postoperatoria y de mortalidad, así como de la duración de la estancia hospitalaria, en pacientes quirúrgicos tratados con hierro intravenoso

The S1P mimetic fingolimod phosphate regulates mitochondrial oxidative stress in neuronal cells.

Fingolimod is one of the few oral drugs available for the treatment of multiple sclerosis (MS), a chronic, inflammatory, demyelinating and neurodegenerative disease. The mechanism of action proposed for this drug is based in the phosphorylation of the molecule to produce its active metabolite fingolimod phosphate (FP) which, in turns, through its interaction with S1P receptors, triggers the functional sequestration of T lymphocytes in lymphoid nodes. On the other hand, part if not most of the damage produced in MS and other neurological disorders seem to be mediated by reactive oxygen species (ROS), and mitochondria is one of the main sources of ROS. In the present work, we have evaluated the anti-oxidant profile of FP in a model of mitochondrial oxidative damage induced by menadione (Vitk3) on neuronal cultures. We provide evidence that incubation of neuronal cells with FP alleviates the Vitk3-induced toxicity, due to a decrease in mitochondrial ROS production. It also decreases regulated cell death triggered by imbalance in oxidative stress (restore values of advanced oxidation protein products and total thiol levels). Also restores mitochondrial function (cytochrome c oxidase activity, mitochondrial membrane potential and oxygen consumption rate) and morphology. Furthermore, increases the expression and activity of protective factors (increases Nrf2, HO1 and Trx2 expression and GST and NQO1 activity), being some of these effects modulated by its interaction with the S1P receptor. FP seems to increase mitochondrial stability and restore mitochondrial dynamics under conditions of oxidative stress, making this drug a potential candidate for the treatment of neurodegenerative diseases other than MS