249 research outputs found

    MOTION OF A LARGE OBJECT IN A 2D BUBBLING FLUIDIZED BED

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    The motion of a large object in a bubbling fluidized bed is experimentally studied using digital image analysis. A wide range of fluidized bed applications involves the motion of large objects within the bed, such objects being reactants, catalysts, agglomerates, etc. The experiments were run in a 2D bubbling fluidized bed with glass spheres as bed material. The object motion is measured using tracking techniques, while independent measurements of the dense phase velocity (using PIV) and bubble velocity were carried out. The effect of the excess gas velocity on the object motion was also analyzed. It is generally accepted that objects with densities in a range around the bed density will describe sinking-rising cycles throughout the whole bed, where the sinking motion is similar to that of the dense phase, and the rising motion is composed of a number of sudden jerks or jumps, as a result of the raising effect of passing bubbles. This work characterized the circulation patterns of an object with a density similar to that of the bed material, but much larger in size. A comparison between the object rising motion and the local bubble motion provided evidence for the study of the bubble ability to raise the object, depending on the bubble velocity and size. A comparison between the object sinking motion and the dense phase motion served to analyze the minor effect of buoyancy forces over the object sinking motion. Finally, the combined effects of the maximum attained depth and the number of jerks in the circulation time is studied, with some insight in the multiple-jerks phenomenon

    Combined application of polyacrylate scaffold and lipoic acid treatment promotes neural tissue reparation after brain injury

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    [EN] Primary objective: The aim of this study was to investigate the reparative potential of a polymeric scaffold designed for brain tissue repair in combination with lipoic acid. Research design: Histological, cytological and structural analysis of a combined treatment after a brain cryo-injury model in rats. Methods and procedures: Adult Wistar rats were subjected to cryogenic brain injury. A channelled-porous scaffold of ethyl acrylate and hydroxyethylacrylate, p(EA-co-HEA) was grafted into cerebral penumbra alone or combined with intraperitoneal LA administration. Histological and cytological evaluation was performed after 15 and 60 days and structural magnetic resonance (MRI) assessment was performed at 2 and 6 months after the surgery. Main outcomes and results: The scaffold was suitable for the establishment of different cellular types. The results obtained suggest that this strategy promotes blood vessels formation, decreased microglial response and neuron migration, particularly when LA was administrated. Conclusions: These evidences demonstrated that the combination of a channelled polymer scaffold with LA administration may represent a potential treatment for neural tissue repair after brain injury.The authors report no conflicts of interest. JMSL acknowledges funding through Programa de Ayudas a la InvestigaciĂłn CientĂ­fica Universidad CEU-Cardenal Herrera (PRCEU-UCH 34/12), PRCEU-UCH 38/10 and programa ayudas a grupos consolidados 2014-15). CMR and MMP acknowledge financing through projects MAT2011-28791-C03-02 and ERA-NET NEURON project PRI-PIMNEU-2011-1372.Rocamonde, B.; Paradells, S.; Garcia Esparza, MA.; Sanchez Vives, M.; Sauro, S.; MartĂ­nez-Ramos, C.; MonleĂłn Pradas, M.... (2016). Combined application of polyacrylate scaffold and lipoic acid treatment promotes neural tissue reparation after brain injury. Brain Injury. 30(2):208-216. https://doi.org/10.3109/02699052.2015.1091505S208216302Das, M., Mohapatra, S., & Mohapatra, S. S. (2012). New perspectives on central and peripheral immune responses to acute traumatic brain injury. Journal of Neuroinflammation, 9(1). doi:10.1186/1742-2094-9-236Jennett, B. (1972). Prognosis after Severe Head Injury. Neurosurgery, 19(CN_suppl_1), 200-207. doi:10.1093/neurosurgery/19.cn_suppl_1.200Kumar, S., Rao, S. L., Chandramouli, B. A., & Pillai, S. (2013). Reduced contribution of executive functions in impaired working memory performance in mild traumatic brain injury patients. Clinical Neurology and Neurosurgery, 115(8), 1326-1332. doi:10.1016/j.clineuro.2012.12.038Muehlschlegel, S., Carandang, R., Ouillette, C., Hall, W., Anderson, F., & Goldberg, R. (2013). Frequency and Impact of Intensive Care Unit Complications on Moderate-Severe Traumatic Brain Injury: Early Results of the Outcome Prognostication in Traumatic Brain Injury (OPTIMISM) Study. Neurocritical Care, 18(3), 318-331. doi:10.1007/s12028-013-9817-2Kaur, C., & Ling, E.-A. (2008). Antioxidants and Neuroprotection in the Adult and Developing Central Nervous System. Current Medicinal Chemistry, 15(29), 3068-3080. doi:10.2174/092986708786848640Helfaer MA, Kirsch JR, Traystman RJ. Radical scavenegers: penetration into brain following the ischemia and reperfusion. In: Krieglstein J O-S H, editor. Pharmacology of cerebral ischemia. Stuggart: Medpharma Scientific Publishers; 1994. p 297–309.Xia, W., Han, J., Huang, G., & Ying, W. (2010). Inflammation in ischaemic brain injury: Current advances and future perspectives. Clinical and Experimental Pharmacology and Physiology, 37(2), 253-258. doi:10.1111/j.1440-1681.2009.05279.xRocamonde, B., Paradells, S., Barcia, C., Garcia Esparza, A., & Soria, J. M. (2013). Lipoic Acid Treatment after Brain Injury: Study of the Glial Reaction. Clinical and Developmental Immunology, 2013, 1-8. doi:10.1155/2013/521939Rocamonde, B., Paradells, S., Barcia, J. M., Barcia, C., GarcĂ­a Verdugo, J. M., Miranda, M., 
 Soria, J. M. (2012). Neuroprotection of lipoic acid treatment promotes angiogenesis and reduces the glial scar formation after brain injury. Neuroscience, 224, 102-115. doi:10.1016/j.neuroscience.2012.08.028Bokara, K. K., Kim, J. Y., Lee, Y. I., Yun, K., Webster, T. J., & Lee, J. E. (2013). Biocompatability of carbon nanotubes with stem cells to treat CNS injuries. Anatomy & Cell Biology, 46(2), 85. doi:10.5115/acb.2013.46.2.85Walker, P. A., Aroom, K. R., Jimenez, F., Shah, S. K., Harting, M. T., Gill, B. S., & Cox, C. S. (2009). Advances in Progenitor Cell Therapy Using Scaffolding Constructs for Central Nervous System Injury. Stem Cell Reviews and Reports, 5(3), 283-300. doi:10.1007/s12015-009-9081-1Ito, Y., Hasuda, H., Kamitakahara, M., Ohtsuki, C., Tanihara, M., Kang, I.-K., & Kwon, O. H. (2005). A composite of hydroxyapatite with electrospun biodegradable nanofibers as a tissue engineering material. Journal of Bioscience and Bioengineering, 100(1), 43-49. doi:10.1263/jbb.100.43Saracino, G. A. A., Cigognini, D., Silva, D., Caprini, A., & Gelain, F. (2013). Nanomaterials design and tests for neural tissue engineering. Chem. Soc. Rev., 42(1), 225-262. doi:10.1039/c2cs35065cBROWN, R., BLUNN, G., & EJIM, O. (1994). Preparation of orientated fibrous mats from fibronectin: composition and stability. Biomaterials, 15(6), 457-464. doi:10.1016/0142-9612(94)90225-9Ejim, O. S., Blunn, G. W., & Brown, R. A. (1993). Production of artificial-orientated mats and strands from plasma fibronectin: a morphological study. Biomaterials, 14(10), 743-748. doi:10.1016/0142-9612(93)90038-4Keilhoff, G., Stang, F., Wolf, G., & Fansa, H. (2003). Bio-compatibility of type I/III collagen matrix for peripheral nerve reconstruction. Biomaterials, 24(16), 2779-2787. doi:10.1016/s0142-9612(03)00084-xZhang, W., Chen, J., Tao, J., Jiang, Y., Hu, C., Huang, L., 
 Ouyang, H. W. (2013). The use of type 1 collagen scaffold containing stromal cell-derived factor-1 to create a matrix environment conducive to partial-thickness cartilage defects repair. Biomaterials, 34(3), 713-723. doi:10.1016/j.biomaterials.2012.10.027MartĂ­nez-Ramos, C., Lainez, S., Sancho, F., GarcĂ­a Esparza, M. A., Planells-Cases, R., GarcĂ­a Verdugo, J. M., 
 Soria, J. M. (2008). Differentiation of Postnatal Neural Stem Cells into Glia and Functional Neurons on Laminin-Coated Polymeric Substrates. Tissue Engineering Part A, 14(8), 1365-1375. doi:10.1089/ten.tea.2007.0295Soria, J. M., MartĂ­nez Ramos, C., SalmerĂłn SĂĄnchez, M., Benavent, V., Campillo FernĂĄndez, A., GĂłmez Ribelles, J. L., 
 Barcia, J. A. (2006). Survival and differentiation of embryonic neural explants on different biomaterials. Journal of Biomedical Materials Research Part A, 79A(3), 495-502. doi:10.1002/jbm.a.30803Xie, J., Willerth, S. M., Li, X., Macewan, M. R., Rader, A., Sakiyama-Elbert, S. E., & Xia, Y. (2009). The differentiation of embryonic stem cells seeded on electrospun nanofibers into neural lineages. Biomaterials, 30(3), 354-362. doi:10.1016/j.biomaterials.2008.09.046Wong, D. Y., Hollister, S. J., Krebsbach, P. H., & Nosrat, C. (2007). Poly(ɛ-Caprolactone) and Poly (L-Lactic-Co-Glycolic Acid) Degradable Polymer Sponges Attenuate Astrocyte Response and Lesion Growth in Acute Traumatic Brain Injury. Tissue Engineering, 13(10), 2515-2523. doi:10.1089/ten.2006.0440MartĂ­nez‐Ramos, C., VallĂ©s‐Lluch, A., Verdugo, J. M. G., Ribelles, J. L. G., Barcia Albacar, J. A., Orts, A. B., 
 Pradas, M. M. (2012). Channeled scaffolds implanted in adult rat brain. Journal of Biomedical Materials Research Part A, 100A(12), 3276-3286. doi:10.1002/jbm.a.34273RodrĂ­guez HernĂĄndez, J. C., Serrano Aroca, Á., GĂłmez Ribelles, J. L., & Pradas, M. M. (2008). Three-dimensional nanocomposite scaffolds with ordered cylindrical orthogonal pores. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 84B(2), 541-549. doi:10.1002/jbm.b.30902Paxinos G, Watson C. The rat brain in stereotaxic coordinates. San Diego, CA: Academic Press; 1986.Harting, M. T., Sloan, L. E., Jimenez, F., Baumgartner, J., & Cox, C. S. (2009). Subacute Neural Stem Cell Therapy for Traumatic Brain Injury. Journal of Surgical Research, 153(2), 188-194. doi:10.1016/j.jss.2008.03.037Wallenquist, U., BrĂ€nnvall, K., Clausen, F., LewĂ©n, A., Hillered, L., & Forsberg-Nilsson, K. (2009). Grafted neural progenitors migrate and form neurons after experimental traumatic brain injury. Restorative Neurology and Neuroscience, 27(4), 323-334. doi:10.3233/rnn-2009-0481Sun, D., Gugliotta, M., Rolfe, A., Reid, W., McQuiston, A. R., Hu, W., & Young, H. (2011). Sustained Survival and Maturation of Adult Neural Stem/Progenitor Cells after Transplantation into the Injured Brain. Journal of Neurotrauma, 28(6), 961-972. doi:10.1089/neu.2010.1697Doetsch, F., CaillĂ©, I., Lim, D. A., GarcĂ­a-Verdugo, J. M., & Alvarez-Buylla, A. (1999). Subventricular Zone Astrocytes Are Neural Stem Cells in the Adult Mammalian Brain. Cell, 97(6), 703-716. doi:10.1016/s0092-8674(00)80783-7Fuentealba, L. C., Obernier, K., & Alvarez-Buylla, A. (2012). Adult Neural Stem Cells Bridge Their Niche. Cell Stem Cell, 10(6), 698-708. doi:10.1016/j.stem.2012.05.012Rice, A. (2003). Proliferation and neuronal differentiation of mitotically active cells following traumatic brain injury. Experimental Neurology, 183(2), 406-417. doi:10.1016/s0014-4886(03)00241-3Lee, C., & Agoston, D. V. (2010). Vascular Endothelial Growth Factor Is Involved in Mediating Increased De Novo Hippocampal Neurogenesis in Response to Traumatic Brain Injury. Journal of Neurotrauma, 27(3), 541-553. doi:10.1089/neu.2009.0905Sun, D., Bullock, M. R., Altememi, N., Zhou, Z., Hagood, S., Rolfe, A., 
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 Snyder, E. Y. (2002). Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proceedings of the National Academy of Sciences, 99(5), 3024-3029. doi:10.1073/pnas.05267889

    Mesenchymal Stromal Cell-Based Therapies as Promising Treatments for Muscle Regeneration After Snakebite Envenoming

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    Snakebite envenoming is a global neglected disease with an incidence of up to 2.7 million new cases every year. Although antivenoms are so-far the most effective treatment to reverse the acute systemic effects induced by snakebite envenoming, they have a limited therapeutic potential, being unable to completely neutralize the local venom effects. Local damage, such as dermonecrosis and myonecrosis, can lead to permanent sequelae with physical, social, and psychological implications. The strong inflammatory process induced by snake venoms is associated with poor tissue regeneration, in particular the lack of or reduced skeletal muscle regeneration. Mesenchymal stromal cells (MSCs)-based therapies have shown both anti-inflammatory and pro-regenerative properties. We postulate that using allogeneic MSCs or their cell-free products can induce skeletal muscle regeneration in snakebite victims, improving all the three steps of the skeletal muscle regeneration process, mainly by anti-inflammatory activity, paracrine effects, neovascularization induction, and inhibition of tissue damage, instrumental for microenvironment remodeling and regeneration. Since snakebite envenoming occurs mainly in areas with poor healthcare, we enlist the principles and potential of MSCs-based therapies and discuss regulatory issues, good manufacturing practices, transportation, storage, and related-procedures that could allow the administration of these therapies, looking forward to a safe and cost-effective treatment for a so far unsolved and neglected health problem.The authors are supported by the University Pablo de Olavide (Sevilla), the University Miguel Hernåndez (Elche, Alicante), National University Toribio Rodriguez de Mendoza (Chachapoyas, Peru) Grants: Contrato N° 09-2019-FONDECYT-BM-INC.INV to JRT, JDRF 2-SRA-2019-837-S-B and AVI-GVA COVID-19-68 to BS, Fundación Andaluza de I+D and Al-Andalus Biopharma Project (FAID-2018-1). The authors CC-O, CG-D, and TCSA were supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq) (Process: 406163/2018-9), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil - CAPES (Program COFECUB Process: 88881.191812/2018-01) and by Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Brazil (FAPEMIG)

    Herschel/HIFI observations of molecular emission in protoplanetary nebulae and young planetary nebulae

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    We performed Herschel/HIFI observations of intermediate-excitation molecular lines in the far-infrared/submillimeter range in a sample of ten protoplanetary nebulae and young planetary nebulae. The high spectral resolution provided by HIFI yields accurate measurements of the line profiles. The observation of these high-energy transitions allows an accurate study of the excitation conditions, particularly in the warm gas, which cannot be properly studied from the low-energy lines. We have detected FIR/sub-mm lines of several molecules, in particular of 12CO, 13CO, and H2O. Emission from other species, like NH3, OH, H2^{18}O, HCN, SiO, etc, has been also detected. Wide profiles showing sometimes spectacular line wings have been found. We have mainly studied the excitation properties of the high-velocity emission, which is known to come from fast bipolar outflows. From comparison with general theoretical predictions, we find that CRL 618 shows a particularly warm fast wind, with characteristic kinetic temperature Tk >~ 200 K. In contrast, the fast winds in OH 231.8+4.2 and NGC 6302 are cold, Tk ~ 30 K. Other nebulae, like CRL 2688, show intermediate temperatures, with characteristic values around 100 K. We also discuss how the complex structure of the nebulae can affect our estimates, considering two-component models. We argue that the differences in temperature in the different nebulae can be due to cooling after the gas acceleration (that is probably due to shocks); for instance, CRL 618 is a case of very recent acceleration, less than ~ 100 yr ago, while the fast gas in OH 231.8+4.2 was accelerated ~ 1000 yr ago. We also find indications that the densest gas tends to be cooler, which may be explained by the expected increase of the radiative cooling efficiency with the density.Comment: 24 pages, 31 figure

    Strontium hexaferrite platelets: a comprehensive soft X-ray absorption and Mössbauer spectroscopy study

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    Platelets of strontium hexaferrite (SrFe12O19, SFO), up to several micrometers in width, and tens of nanometers thick have been synthesized by a hydrothermal method. They have been studied by a combination of structural and magnetic techniques, with emphasis on Mössbauer spectroscopy and X-ray absorption based-measurements including spectroscopy and microscopy on the iron-L edges and the oxygen-K edge, allowing us to establish the differences and similarities between our synthesized nanostructures and commercial powders. The Mössbauer spectra reveal a greater contribution of iron tetrahedral sites in platelets in comparison to pure bulk material. For reference, high-resolution absorption and dichroic spectra have also been measured both from the platelets and from pure bulk material. The O-K edge has been reproduced by density functional theory calculations. Out-of-plane domains were observed with 180° domain walls less than 20 nm width, in good agreement with micromagnetic simulationsThis work is supported by the Spanish Ministry of Economy and Competitiveness through Projects MAT2015-64110-C2-1-P, MAT2015-64110-C2-2-P, MAT2015-66888-C3-1-R and by the European Commission through Project H2020 No. 720853 (Amphibian). These experiments were performed at the CIRCE, MISTRAL and BOREAS beamlines of the ALBA Synchrotron Light Facility. G.D.S. acknowledges the European Youth Employement Initiative and the Autonomous Community of Madrid for a one-year fellowship. Slovenian Research Agency is acknowledged for funding the research program Ceramics and complementary materials for advanced engineering and biomedical applications (P2-0087), CEMM, JSI for the use of TE

    Prevention of diet-induced obesity by apple polyphenols in Wistar rats through regulation of adipocyte gene expression and DNA methylation patterns

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    This study was conducted to determine the mechanisms implicated in the beneficial effects of apple polyphenols (APs) against diet-induced obesity in Wistar rats, described in a previous study from our group. Supplementation of high-fat sucrose diet with AP prevented adiposity increase by inhibition of adipocyte hypertrophy. Rats supplemented with AP exhibited improved glucose tolerance while adipocytes isolated from these rats showed an enhanced lipolytic response to isoproterenol. AP intake led to reduced Lep, Plin, and sterol regulatory element binding transcription factor 1 (Srebf1) mRNA levels and increased aquaporin 7 (Aqp7), adipocyte enhancer binding protein 1 (Aebp1), and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (Ppargc1a) mRNA levels in epididymal adipocytes. In addition, we found different methylation patterns of Aqp7, Lep, Ppargc1a, and Srebf1 promoters in adipocytes from apple-supplemented rats compared to high-fat sucrose fed rats. The administration of AP protects against body weight gain and fat deposition and improves glucose tolerance in rats. We propose that AP exerts the antiobesity effects through the regulation of genes involved in adipogenesis, lipolysis, and fatty acid oxidation, in a process that could be mediated in part by epigenetic mechanisms

    MiTF links Erk1/2 kinase and p21CIP1/WAF1 activation after UVC radiation in normal human melanocytes and melanoma cells

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    As a survival factor for melanocytes lineage cells, MiTF plays multiple roles in development and melanomagenesis. What role MiTF plays in the DNA damage response is currently unknown. In this report we observed that MiTF was phosphorylated at serine 73 after UVC radiation, which was followed by proteasome-mediated degradation. Unlike after c-Kit stimulation, inhibiting p90RSK-1 did not abolish the band shift of MiTF protein, nor did it abolish the UVC-mediated MiTF degradation, suggesting that phosphorylation on serine 73 by Erk1/2 is a key event after UVC. Furthermore, the MiTF-S73A mutant (Serine 73 changed to Alanine via site-directed mutagenesis) was unable to degrade and was continuously expressed after UVC exposure. Compared to A375 melanoma cells expressing wild-type MiTF (MiTF-WT), cells expressing MiTF-S73A mutant showed less p21WAF1/CIP1 accumulation and a delayed p21WAF1/CIP1 recovery after UVC. Consequently, cells expressing MiTF-WT showed a temporary G1 arrest after UVC, but cells expressing MiTF-S73A mutant or lack of MiTF expression did not. Finally, cell lines with high levels of MiTF expression showed higher resistance to UVC-induced cell death than those with low-level MiTF. These data suggest that MiTF mediates a survival signal linking Erk1/2 activation and p21WAF1/CIP1 regulation via phosphorylation on serine 73, which facilitates cell cycle arrest. In addition, our data also showed that exposure to different wavelengths of UV light elicited different signal pathways involving MiTF

    The 1998 outburst of XTE J1550-564: a model based on multiwavelength observations

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    The 1998 September outburst of the black-hole X-ray binary XTE J1550-564 was monitored at X-ray, optical and radio wavelengths. We divide the outburst sequence into five phases and discuss their multiwavelength properties. The outburst starts with a hard X-ray spike, while the soft X-ray flux rises with a longer timescale. We suggest that the onset of the outburst is determined by an increased mass transfer rate from the companion star, but the outburst morphology is determined by the distribution of specific angular momentum in the accreting matter. The companion in XTE J1550-564 is likely to be an active magnetic star, with a surface field strong enough to influence the dynamics of mass transfer. We suggest that its magnetic field can create a magnetic bag capable of confining gas inside the Roche lobe of the primary. The impulsive rise in the hard X-rays is explained by the inflow of material with low angular momentum onto the black hole, on a free-fall timescale, when the magnetic confinement breaks down. At the same time, high angular momentum matter, transferred via ordinary Roche-lobe overflow, is responsible for the formation of a disk.Comment: to appear in ApJ, vol 564, January 10, 200

    Glycation does not modify bovine serum albumin (BSA)-induced reduction of rat aortic relaxation: The response to glycated and nonglycated BSA is lost in metabolic syndrome

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    The effects of nonglycated bovine serum albumin (BSA) and advanced glycosylation end products of BSA (AGE-BSA) on vascular responses of control and metabolic syndrome (MS) rats characterized by hypertriglyceridemia, hypertension, hyperinsulinemia, and insulin resistance were studied. Albumin and in vitro prepared AGE-BSA have vascular effects; however, recent studies indicate that some effects of in vitro prepared AGEs are due to the conditions in which they were generated. We produced AGEs by incubating glucose with BSA for 60 days under sterile conditions in darkness and at 37°C. To develop MS rats, male Wistar animals were given 30% sucrose in drinking water since weanling. Six month old animals were used. Blood pressure, insulin, triglycerides, and serum albumin were increased in MS rats. Contraction of aortic rings elicited with norepinephrine was stronger. There were no effects of nonglycated BSA or AGE-BSA on contractions in control or MS rats; however, both groups responded to L-NAME, an inhibitor of nitric oxide synthesis. Arterial relaxation induced using acetylcholine was smaller in MS rats. Nonglycated BSA and AGE-BSA significantly diminished relaxation in a 35% in the control group but the decrease was similar when using nonglycated BSA and AGE-BSA. This decrease was not present in the MS rats and was not due to increased RAGEs or altered biochemical characteristics of BSA. In conclusion, both BSA and AGE-BSA inhibit vascular relaxation in control artic rings. In MS rats the effect is lost possibly due to alterations in endothelial cells that are a consequence of the illness

    Activation of EGFR/ERBB2 via Pathways Involving ERK1/2, P38 MAPK, AKT and FOXO Enhances Recovery of Diabetic Hearts from Ischemia-Reperfusion Injury

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    This study characterized the effects of diabetes and/or ischemia on epidermal growth factor receptor, EGFR, and/or erbB2 signaling pathways on cardiac function. Isolated heart perfusion model of global ischemia was used to study the effect of chronic inhibition or acute activation of EGFR/erbB2 signaling on cardiac function in a rat model of type-1 diabetes. Induction of diabetes with streptozotocin impaired recovery of cardiac function (cardiac contractility and hemodynamics) following 40 minutes of global ischemia in isolated hearts. Chronic treatment with AG825 or AG1478, selective inhibitors of erbB2 and EGFR respectively, did not affect hyperglycemia but led to an exacerbation whereas acute administration of the EGFR ligand, epidermal growth factor (EGF), led to an improvement in cardiac recovery in diabetic hearts. Diabetes led to attenuated dimerization and phosphorylation of cardiac erbB2 and EGFR receptors that was associated with reduced signaling via extracellular-signal-regulated kinase 1/2 (ERK1/2), p38 mitogen activated protein (MAP) kinase and AKT (protein kinase B). Ischemia was also associated with reduced cardiac signaling via these molecules whereas EGF-treatment opposed diabetes and/or ischemia induced changes in ERK1/2, p38 MAP kinase, and AKT-FOXO signaling. Losartan treatment improved cardiac function in diabetes but also impaired EGFR phosphorylation in diabetic heart. Co-administration of EGF rescued Losartan-mediated reduction in EGFR phosphorylation and significantly improved cardiac recovery more than with either agent alone. EGFR/erbB2 signaling is an important cardiac survival pathway whose activation, particularly in diabetes, ischemia or following treatment with drugs that inhibit this cascade, significantly improves cardiac function. These findings may have clinical relevance particularly in the treatment of diabetes-induced cardiac dysfunction
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