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Sample records for renal epo production

  1. Renoprotective capacities of non-erythropoietic EPO derivative, ARA290, following renal ischemia/reperfusion injury

    NARCIS (Netherlands)

    van Rijt, Willem G; Nieuwenhuijs-Moeke, Gertrude J; van Goor, Harry; Ottens, Petra J; Ploeg, Rutger J; Leuvenink, Henri G D

    2013-01-01

    Background: ARA290 is a non-erythropoietic EPO derivative which only binds to the cytoprotective receptor complex (EPOR2-beta cR(2)) consisting of two EPO-receptors (EPOR) and two beta common receptors (beta cR). ARA290 is renoprotective in renal ischemia/reperfusion (I/R). In a renal I/R model we f

  2. Amiodarone-induced Hypothyroidism with EPO-resistant Anemia in a Patient with Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Peter M.S. Chang

    2008-11-01

    Full Text Available The overall incidence of amiodarone-induced thyroid dysfunction ranges from 2% to 24%. One third to half of patients with hypothyroidism have anemia due to some decrease in normal red blood cell mass and erythropoietin (EPO resistance. Therefore, for patients with chronic renal disease under medication with amiodarone, early regular thyroid function test should be checked in order to avoid amiodarone-induced hypothyroidism and EPO-resistant anemia. If amiodarone-induced hypothyroidism and EPO-resistant anemia occur in patients with chronic renal failure, early thyroxine should be given instead of waiting for spontaneous recovery by amiodarone discontinuation only. Here, we report a patient with chronic renal failure who developed EPO-resistant anemia after amiodarone treatment for arrhythmia. The hemoglobin level responded to EPO therapy rapidly after thyroxine administration and amiodarone discontinuation.

  3. Effect and dosage of EPO-βand EPO-αin the treatment of renal anemia%EPO-β与EPO-α治疗肾性贫血的疗效及剂量分析

    Institute of Scientific and Technical Information of China (English)

    李彩凤; 梁萌; 许树根; 沈淑琼; 李娟; 胡玉清

    2015-01-01

    Objective To compare the efficacy and dosage of EPO-βand EPO-αin the treatment of renal ane-mia. Methods 139 maintenance hemodialysis patients were divided into EPO-β group ( n =57 ) and EPO-α group (n=82),the haemoglobin,ferritin,transferrin saturation,parathyroid hormone,epoetin dosage and epoetin index were compared between the two groups. Results The distribution of haemoglobin of the two groups was essentially identi-cal,and there was no significant difference in the ferritin (567 ng/mL vs. 461 ng/mL),transferrin saturation (28. 0%vs. 27. 5%) and parathyroid hormone (713 pg/mL vs. 546 pg/mL) between EPO-β group and EPO-α group ( P >0. 05),but the weekly EPO-β dosage (4 894 U vs. 10 073 U) and epoetin index (15 787 U/% vs. 32 493 U/%) in EPO-β group were much lower than those of EPO-α group ( P0.05),两EPO-β、EPO-α组患者的铁蛋白(567 ng/mL vs.461 ng/mL)、转铁蛋白饱和度(28.0% vs.27.5%)、甲状旁腺激素(713 pg/mL vs.546 pg/mL)水平比较差异无统计学意义(P>0.05)。与EPO-α组比较,EPO-β组的EPO周使用剂量(4894 U vs.10073 U)及EPO指数(15787 U/% vs.32493 U/%)更低(P<0.001)。结论在达到相同的血红蛋白水平的前提下,EPO-β的使用剂量明显小于EPO-α,可能减少大剂量使用EPO所带来的潜在风险。

  4. Amiodarone-induced Hypothyroidism with EPO-resistant Anemia in a Patient with Chronic Renal Failure

    OpenAIRE

    Peter M.S. Chang; Yee-Yung Ng

    2008-01-01

    The overall incidence of amiodarone-induced thyroid dysfunction ranges from 2% to 24%. One third to half of patients with hypothyroidism have anemia due to some decrease in normal red blood cell mass and erythropoietin (EPO) resistance. Therefore, for patients with chronic renal disease under medication with amiodarone, early regular thyroid function test should be checked in order to avoid amiodarone-induced hypothyroidism and EPO-resistant anemia. If amiodarone-induced hypothyroidism and EP...

  5. Huh-7 cell line as an alternative cultural model for the production of human like erythropoietin (EPO

    Directory of Open Access Journals (Sweden)

    Kausar Humera

    2011-11-01

    Full Text Available Abstract Background and Aims Erythropoietin (EPO is a glycoprotein hormone which is required to regulate the production of red blood cells. Deficiency of EPO is known to cause anemia in chronically infected renal patients and they require regular blood transfusion. Availability of recombinant EPO has eliminated the need for blood transfusion and now it is extensively used for the treatment of anemia. Glycosylation of erythropoietin is essential for its secretion, stability, protein conformation and biological activity. However, maintenance of human like glycosylation pattern during manufacturing of EPO is a major challenge in biotechnology. Currently, Chinese hamster ovary (CHO cell line is used for the commercial production of erythropoietin but this cell line does not maintain glycosylation resembling human system. With the trend to eliminate non-human constituent from biopharmaceutical products, as a preliminary approach, we have investigated the potential of human hepatoma cell line (Huh-7 to produce recombinant EPO. Materials and methods Initially, the secretory signal and Kozak sequences was added before the EPO mature protein sequence using overlap extension PCR technique. PCR-amplified cDNA fragments of EPO was inserted into mammalian expression vector under the control of the cytomegalovirus (CMV promoter and transiently expressed in CHO and Huh-7 cell lines. After RT-PCR analysis, ELISA and Western blotting was performed to verify the immunochemical properties of secreted EPO. Results Addition of secretory signal and Kozak sequence facilitated the extra-cellular secretion and enhanced the expression of EPO protein. Significant expression (P Conclusion Huh-7 cell line has a great potential to produce glycosylated EPO, suggesting the use of this cell line to produce glycoproteins of the therapeutic importance resembling to the natural human system.

  6. Tumor biology of non-metastatic stages of clear cell renal cell carcinoma; overexpression of stearoyl desaturase-1, EPO/EPO-R system and hypoxia-related proteins.

    Science.gov (United States)

    Stoyanoff, Tania Romina; Rodríguez, Juan Pablo; Todaro, Juan Santiago; Espada, Joaquín Diego; Colavita, Juan Pablo Melana; Brandan, Nora Cristina; Torres, Adriana Mónica; Aguirre, María Victoria

    2016-10-01

    Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas. There is great interest to know the molecular basis of the tumor biology of ccRCC that might contribute to a better understanding of the aggressive biological behavior of this cancer and to identify early biomarkers of disease. This study describes the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (hypoxia-inducible factor (HIF)-1α, erythropoietin (EPO), vascular endothelial growth factor (VEGF)), their receptors (EPO-R, VEGFR-2), and stearoyl desaturase-1 (SCD-1) in early stages of ccRCC. Tissue samples were obtained at the Urology Unit of the J.R. Vidal Hospital (Corrientes, Argentina), from patients who underwent radical nephrectomy for renal cancer between 2011 and 2014. Four experimental groups according to pathological stage and nuclear grade were organized: T1G1 (n = 6), T2G1 (n = 4), T1G2 (n = 7), and T2G2 (n = 7). The expression of HIF-1α, EPO, EPO-R, VEGF, VEGFR-2, Bcl-xL, and SCD-1 were evaluated by immunohistochemistry, Western blotting, and/or RT-PCR. Apoptosis was assessed by the TUNEL in situ assay, and tumor proliferation was determined by Ki-67 immunohistochemistry. Data revealed that HIF-1α, EPO, EPO-R, VEGF, and VEGF-R2 were overexpressed in most samples. The T1G1 group showed the highest EPO levels, approximately 200 % compared with distal renal tissue. Bcl-xL overexpression was concomitant with the enhancement of proliferative indexes. SCD-1 expression increased with the tumor size and nuclear grade. Moreover, the direct correlations observed between SCD-1/HIF-1α and SCD-1/Ki-67 increments suggest a link among these molecules, which would determine tumor progression in early stages of ccRCC. Our results demonstrate the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (HIF-1α, EPO, VEGF), their

  7. Acute short-term hyperoxia followed by mild hypoxia does not increase EPO production: resolving the "normobaric oxygen paradox".

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    Debevec, Tadej; Keramidas, Michail E; Norman, Barbara; Gustafsson, Thomas; Eiken, Ola; Mekjavic, Igor B

    2012-03-01

    Recent findings suggest that besides renal tissue hypoxia, relative decrements in tissue oxygenation, using a transition of the breathing mixture from hyperoxic to normoxic, can also stimulate erythropoietin (EPO) production. To further clarify the importance of the relative change in tissue oxygenation on plasma EPO concentration [EPO], we investigated the effect of a consecutive hyperoxic and hypoxic breathing intervention. Eighteen healthy male subjects were assigned to either IHH (N = 10) or CON (N = 8) group. The IHH group breathed pure oxygen (F(i)O(2) ~ 1.0) for 1 h, followed by a 1-h period of breathing a hypoxic gas mixture (F(i)O(2) ~ 0.15). The CON group breathed a normoxic gas mixture (F(i)O(2) ~ 0.21) for the same duration (2 h). Blood samples were taken just before, after 60 min, and immediately after the 2-h exposure period. Thereafter, samples were taken at 3, 5, 8, 24, 32, and 48 h after the exposure. During the breathing interventions, subjects remained in supine position. There were significant increases in absolute [EPO] within groups at 8 and 32 h in the CON and at 32 h only in the IHH group. No significant differences in absolute [EPO] were observed between groups following the intervention. Relative (∆[EPO]) levels were significantly lower in the IHH than in the CON group, 5 and 8 h following exposure. The tested protocol of consecutive hyperoxic-hypoxic gas mixture breathing did not induce [EPO] synthesis stimulation. Moreover, the transient attenuation in ∆[EPO] in the IHH group was most likely due to a hyperoxic suppression. Hence, our findings provide further evidence against the "normobaric O(2) paradox" theory.

  8. EPO Program and Product Evaluation Throughout the Development Lifecycle

    Science.gov (United States)

    Kaiser, C.; Butcher, G. J.

    2013-12-01

    Evaluation of successful education and public outreach (EPO) programs and products is becoming increasingly important for the continued development of such efforts. This presentation will detail the tools and techniques used to evaluate two EPO efforts- 1) NASA's REEL Science Communications Contest and Video Production Workshop, and 2) the 'Sensors, Circuits, and Satellites' product. A primary challenge with evaluating any EPO product geared towards children and students is the limitation on collecting information from minors. With regards to the REEL Science Contest, over 120 students participated in producing and entering 48 contest entries but because of the Office of Budget and Management (OBM) regulations that restrict collecting feedback from more than nine individuals, we were only able to collect evaluation data from a small subset of this group. The five winning students who participated in the final workshop took part in the evaluation. The benefit of a small group size is that it allowed for more in-depth one-on-one interviews with each student. The feedback collected from this evaluation offered valuable insight into what worked well along with areas of improvement for futures contests and workshops. The REEL Science video contest had another evaluation opportunity since NASA scientists, communications experts, and producers also participated in the program and worked directly with the students. A survey was administered for this audience in an effort to gauge the perceived value and success of the program from the perspective of the originating institution. We found that if a program is well received, the program is more likely to receive future support. Additionally, this component of the program evaluation provided useful feedback and lessons learned to help optimize the role of the internal audience for similar programs in the future. Implementing formative evaluation is key to developing a successful EPO product development. Collecting data at key

  9. Bone marrow fibrosis and production of anti—rhEPO antibody induced by long—term abministration of rhEPO

    Institute of Scientific and Technical Information of China (English)

    LuQJ; WenLQ

    2002-01-01

    Recombinant human erythropoietin(rhEPO) is used extensively in anemic patients on dialysis and other patients,and is considered as very safety and effective in the correction of anemia in these patients.In a safety evaluation recently done in Beagles dogs,mild or moderate bone marrow fibrosis and neutralizing anti-rhEPO IgG production were found in the high dosage group of 1800 U·kg-1 after 13-week subcutaneous administration of rhEPO.The results suggest that long-term administration of rhEPO may result in the occurrence of bone marrow fibrosis and the development of neutralizing antibodies to rhEPO.In clinical practice,it is important to choose an appropriate dose regimen to reduce the risk of antibody production and adverse effects associated with long-term administration of high dose of rhEPO while achieving target hematocrit hevel.

  10. Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation.

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    Heitrich, Mauro; García, Daiana Maria de Los Ángeles; Stoyanoff, Tania Romina; Rodríguez, Juan Pablo; Todaro, Juan Santiago; Aguirre, María Victoria

    2016-08-01

    Sepsis remains the most important cause of acute kidney injury (AKI) and acute lung injury (ALI) in critically ill patients. The cecal ligation and puncture (CLP) model in experimental mice reproduces most of the clinical features of sepsis. Erythropoietin (EPO) is a well-known cytoprotective multifunctional hormone, which exerts anti-inflammatory, anti-oxidant, anti-apoptotic and pro-angiogenic effects in several tissues. The aim of this study was to evaluate the underlying mechanisms of EPO protection through the expression of the EPO/EPO receptor (EPO-R) and VEGF/VEF-R2 systems in kidneys and lungs of mice undergoing CLP-induced sepsis. Male inbred Balb/c mice were divided in three experimental groups: Sham, CLP, and CLP+EPO (3000IU/kg sc). Assessment of renal functional parameters, survival, histological examination, immunohistochemistry and/or Western blottings of EPO-R, VEGF and VEGF-R2 were performed at 18h post-surgery. Mice demonstrated AKI by elevation of serum creatinine and renal histologic damage. EPO treatment attenuates renal dysfunction and ameliorates kidney histopathologic changes. Additionally, EPO administration attenuates deleterious septic damage in renal cortex through the overexpression of EPO-R in tubular interstitial cells and the overexpression of the pair VEGF/VEGF-R2. Similarly CLP- induced ALI, as evidenced by parenchymal lung histopathologic alterations, was ameliorated through pulmonary EPO-R, VEGF and VEGF-R2 over expression suggesting and improvement in endothelial survival and functionality. This study demonstrates that EPO exerts protective effects in kidneys and lungs in mice with CLP-induced sepsis through the expression of EPO-R and the regulation of the VEGF/VEGF-R2 pair.

  11. Effects of r—HuEPO on the biophysical characteristics of erythrocyte membrane in patients with anemia of chronic renal failure

    Institute of Scientific and Technical Information of China (English)

    SHIHONGLIAN; FAJUNYANG; 等

    1994-01-01

    Using electron spin resonance (ESR) spin labeling technique,we have studied the conformation of sulfhydryl groups(-SH) binding sites in membrane proteins and mem brane fluidity of red blood cells(RBCs) from two groups of patients with anemia of chronic renal failure(ACRF).One of the groups is composed of patients who were untreated with recombinant human erythropoietin(r-HuEPO),and the other is composed of patients who were treated with r-HuEPO.The results indicated:1)the conformation of SH group binding site in RBC membrane proteins from former group was different from those of healty people.2)the fluidity in the region near the surface of RBC membrane from former group was lower than those of healthy people.3)However,the above biophysical properties of RBC membrane from later group were normal.We concluded that RBC membrane in patients with ACRF was abnormal,and the treatment of r-HuEPO may promote the production of normal RBCs,thus ameliorate the biophysical properties of RBCs from the patients with ACRF.

  12. Multi-omic profiling of EPO-producing CHO cell panel reveals metabolic adaptation to heterologous protein production

    DEFF Research Database (Denmark)

    Ley, Daniel; Kazemi Seresht, Ali; Engmark, Mikael

    discovered indications of metabolic adaptation of the amino acid catabolism in favor of heterologous protein production. We established a panel of stably EPO expressing CHO-K1 clones spanning a 25-fold productivity range and characterized the clones in batch and chemostat cultures. For this, we employed......, EPO gene expression, intracellular protein levels and genomewide differential gene expression analysis of genes functionally related to secretory protein processing,respectively. Finally, we generated a network reconstruction of the amino acid catabolism in CHO cells. There construction was utilized...... clone during chemostat culture. The EPO productivity levels were not reflected in EPO gene load,EPO gene expression or intracellular protein retention, indicating that these processes were not limiting EPO productivity. The global gene expression analysis did not identify significant differentially...

  13. EPOS-GNSS - Improving the infrastructure for GNSS data and products in Europe

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    Fernandes, Rui; Bos, Machiel; Bruyninx, Carine; Crocker, Paul; Dousa, Jan; Socquet, Anne; Walpersdorf, Andrea; Avallone, Antonio; Ganas, Athanassios; Gunnar, Benedikt; Ionescu, Constantin; Kenyeres, Ambrus; Ozener, Haluk; Vergnolle, Mathilde; Lidberg, Martin; Liwosz, Tomek; Soehne, Wolfgang

    2017-04-01

    EPOS-IP WP10 - "GNSS Data & Products" is the Working Package 10 of the European Plate Observing System - Implementation Phase project in charge of implementing services for the geo-sciences community to access existing Pan-European Geodetic Infrastructures. WP10 is currently formed by representatives of participating European institutions but in the operational phase contributions will be solicited from the entire geodetic community. In fact, WP10 also includes members from other institutions/countries that formally are not participating in the EPOS-IP but will be key players in the future services to be provided by EPOS. Additionally, several partners are also key partners at EUREF, which is also actively collaborating with EPOS. The geodetic component of EPOS is dealing essentially with implementing an e-infrastructure to store and disseminate the continuous GNSS data from existing Research Infrastructures. Present efforts are on developing geodetic tools to support Solid Earth research by optimizing the existing resources. However, other research and technical applications (e.g., reference frames, meteorology, space weather) can also benefit in the future from the optimization of the geodetic resources in Europe. We present and discuss the status of the implementation of the thematic and core services (TCS) for GNSS data within EPOS and the related business plan. We explain the tools and web-services being developed towards the implementation of the best solutions that will permit to the end-users, and in particular geo-scientists, to access the geodetic data, derived solutions, and associated metadata using a transparent and standardized processes. We also detail the different DDSS (Data, Data-Products, Services, Software) that will be made available for the Operational Phase of EPOS, which will start to be tested and made available during 2017 and 2018.

  14. Production of rhEPO with a serum-free medium in the packed bed bioreactor.

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    Deng, J; Yang, Q; Cheng, X; Li, L; Zhou, J

    1997-01-01

    Recombinant CHO (C2) cells producing human erythropoietin (rhEPO) were cultured with DMEM:F12 media containing 5% FBS for 8-10 days in a packed bed bioreactor, then rhEPO was produced with a serum-free medium (SFM-p) which was prepared in our laboratory. The SFM-p medium can support the growth of C2 cells and the production of rhEPO, and furthermore, it easily separates rhEPO from the culture supernatant. The cell culture in a packed bed bioreactor system using SFM-p was maintained in a stable condition for 20-25 days. The expression level of rhEPO was 12-28.4 mg/L. The bioreactor productivity was 71.0 mg/L.d and increased by 12-14 fold over that of the roller bottle. The glucose consumption rate was 21 g/L.d. At the end of 30 days of perfusion circulation, a final cell density of over 3.0 x 10(7)/ml of culture volume was achieved. Since the cells were entrapped in the polyester disk, the culture supernatant contained only a few detachment cells. Variations in lactate and ammonia production in the reactor were observed, and results showed that the productions of lactate and ammonia by the bioreactor were 3.5 g/L and 5 mmol/L, respectively, and did not affect the expression of interest protein. This experiment demonstrates that SFM-p is suitable for the growth and rhEPO production of recombinant C2 in the packed bed bioreactor.

  15. Multi-omic profiling -of EPO-producing Chinese hamster ovary cell panel reveals metabolic adaptation to heterologous protein production.

    Science.gov (United States)

    Ley, Daniel; Seresht, Ali Kazemi; Engmark, Mikael; Magdenoska, Olivera; Nielsen, Kristian Fog; Kildegaard, Helene Faustrup; Andersen, Mikael Rørdam

    2015-11-01

    Chinese hamster ovary (CHO) cells are the preferred production host for many therapeutic proteins. The production of heterologous proteins in CHO cells imposes a burden on the host cell metabolism and impact cellular physiology on a global scale. In this work, a multi-omics approach was applied to study the production of erythropoietin (EPO) in a panel of CHO-K1 cells under growth-limited and unlimited conditions in batch and chemostat cultures. Physiological characterization of the EPO-producing cells included global transcriptome analysis, targeted metabolome analysis, including intracellular pools of glycolytic intermediates, NAD(P)H/NAD(P)(+) , adenine nucleotide phosphates (ANP), and extracellular concentrations of sugars, organic acids, and amino acids. Potential impact of EPO expression on the protein secretory pathway was assessed at multiple stages using quantitative PCR (qPCR), reverse transcription PCR (qRT-PCR), Western blots (WB), and global gene expression analysis to assess EPO gene copy numbers, EPO gene expression, intracellular EPO retention, and differentially expressed genes functionally related to secretory protein processing, respectively. We found no evidence supporting the existence of production bottlenecks in energy metabolism (i.e., glycolytic metabolites, NAD(P)H/NAD(P)(+) and ANPs) in batch culture or in the secretory protein production pathway (i.e., gene dosage, transcription and post-translational processing of EPO) in chemostat culture at specific productivities up to 5 pg/cell/day. Time-course analysis of high- and low-producing clones in chemostat culture revealed rapid adaptation of transcription levels of amino acid catabolic genes in favor of EPO production within nine generations. Interestingly, the adaptation was followed by an increase in specific EPO productivity.

  16. Paraneoplastic hormones: parathyroid hormone-related protein (PTHrP) and erythropoietin (EPO) are related to vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma.

    Science.gov (United States)

    Feng, Chen-chen; Ding, Guan-xiong; Song, Ning-hong; Li, Xuan; Wu, Zhong; Jiang, Hao-wen; Ding, Qiang

    2013-12-01

    To investigate the correlation between parathyroid hormone-related protein (PTHrP), erythropoietin (EPO), and vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma (ccRCC). Immunohistochemical studies on PTHrP, EPO and VEGF were performed in 249 patients with ccRCC. Serum calcium level and haematocrit were analyzed. The expression of the factors and clinicopathological parameters were studied statistically for possible correlations. The incidence for hypercalcaemia and polycythaemia were 15.3% and 2.0% respectively. Expression of PTHrP, EPO, and VEGF were respectively related to advanced stage (P PTHrP was not related to tumour grade. Expressions of EPO and VEGF were correlated to tumour grade significantly. All factors were expressed higher in hypercalcaemic patients. PTHrP, EPO, and VEGF were positively correlated with each other in non-hypercalcaemic patients yet not in hypercalcaemic ones. PTHrP and EPO are related to VEGF expression and to the progression of ccRCC. This finding offers us new insight on the behaviour of ccRCC and offers possible targets in RCC treatment.

  17. Cbl ubiquitination of p85 is essential for Epo-induced EpoR endocytosis.

    Science.gov (United States)

    Bulut, Gamze B; Sulahian, Rita; Yao, Huiyu; Huang, Lily Jun-shen

    2013-12-05

    Erythropoietin (Epo) binding to the Epo receptor (EpoR) elicits downstream signaling that is essential for red blood cell production. One important negative regulatory mechanism to terminate Epo signaling is Epo-induced EpoR endocytosis and degradation. Defects in this mechanism play a key role in the overproduction of erythrocytes in primary familial and congenital polycythemia (PFCP). Here we have identified a novel mechanism mediating Epo-dependent EpoR internalization. Epo induces Cbl-dependent ubiquitination of the p85 regulatory subunit of PI3K, which binds to phosphotyrosines on EpoR. Ubiquitination allows p85 to interact with the endocytic protein epsin-1, thereby driving EpoR endocytosis. Knockdown of Cbl, expression of its dominant negative forms, or expression of an epsin-1 mutant devoid of ubiquitin-interacting motifs all compromise Epo-induced EpoR internalization. Mutated EpoRs mimicking those from PFCP patients cannot bind p85, co-localize with epsin-1, or internalize on Epo stimulation and exhibit Epo hypersensitivity. Similarly, knockdown of Cbl also causes Epo hypersensitivity in primary erythroid progenitors. Restoring p85 binding to PFCP receptors rescues Epo-induced epsin-1 co-localization and EpoR internalization and normalizes Epo hypersensitivity. Our results uncover a novel Cbl/p85/epsin-1 pathway in EpoR endocytosis and show that defects in this pathway contribute to excessive Epo signaling and erythroid hyperproliferation in PFCP.

  18. Multi-omic profiling of EPO-producing Chinese hamster ovary cell panel reveals metabolic adaptation to heterologous protein production

    DEFF Research Database (Denmark)

    Ley, Daniel; Kazemi Seresht, Ali; Engmark, Mikael

    2015-01-01

    the existence of production bottlenecks in energy metabolism (i.e., glycolytic metabolites, NAD(P)H/NAD(P)+ and ANPs) in batch culture or in the secretory protein production pathway (i.e., gene dosage, transcription and post-translational processing of EPO) in chemostat culture at specific productivities up...... to 5 pg/cell/day. Time-course analysis of high- and low-producing clones in chemostat culture revealed rapid adaptation of transcription levels of amino acid catabolic genes in favor of EPO production within nine generations. Interestingly, the adaptation was followed by an increase in specific EPO......Chinese hamster ovary (CHO) cells are the preferred production host for many therapeutic proteins. The production of heterologous proteins in CHO cells imposes a burden on the host cell metabolism and impact cellular physiology on a global scale. In this work, a multi-omics approach was applied...

  19. Latest results from EPOS3 on the production of stable and unstable hadrons

    Directory of Open Access Journals (Sweden)

    Werner K.

    2015-01-01

    Full Text Available Evidence for hydrodynamical flow in AA or in pA collisons is to a large extent obtained from the observation of identified hadrons, such as pions, kaons, and protons. But much more information in particular about the late stage can be obtained by also considering unstable particles, which decay during the lifetime of the expanding hadronic matter. We therefore started to use EPOS3, a unified approach for pp, pA, and AA scattering, to investigate the production of stable and unstable particles.

  20. Effect of EPO erythropoietin combined with iron sucrose treatment on serum indexes and micro inflammation state of renal anemia patients who received hemodialysis

    Institute of Scientific and Technical Information of China (English)

    Yuan-Yuan Guan

    2015-01-01

    Objective:To study the effect of EPO erythropoietin combined with iron sucrose treatment on serum indexes and micro inflammation state of renal anemia patients who received hemodialysis.Methods: 90 cases of renal anemia patients who received hemodialysis in our hospital from May 2013 to September 2014 were enrolled and randomly divided into two groups. Observation group received recombinant human erythropoietin combined with iron supplementation treatment; control group only received recombinant human erythropoietin treatment. Then serum index, oxidative stress index and micro inflammation state were compared.Results: (1) serum index: after treatment, hemoglobin, hematocrit, serum ferritin, transferrin saturation of observation group were higher than those of control group; (2) oxidative stress index: serum NOX2, AOPP, MDA contents of observation group were lower than those of control group; CAT, SOD and GSH-Px were higher than those of control group;(3) micro inflammatory state: serum NF-毷B, AGEs, IL-6, IL-8, IL-17, IL-23 contents of observation group were lower than those of control group.Conclusion:EPO erythropoietin combined with iron sucrose treatment is helpful to improve anemia, alleviate oxidative stress and micro inflammatory state; it’s an ideal method of treating renal anemia with hemodialysis.

  1. EPOSAR: an innovative service to provide EPOS community with advanced DInSAR products

    Science.gov (United States)

    Manunta, Michele; De Luca, Claudio; Elefante, Stefano; Lanari, Riccardo; Pepe, Antonio; Zinno, Ivana; Casu, Francesco

    2015-04-01

    The quantitative evaluation of ground deformation is traditionally based on in-situ surveying techniques that, through the intensive use of GPS stations, automatic total stations and levelling benchmarks, can measure up to sub-centimetre displacements. In the last decades, the extensive use of satellite remote sensing data, such as Synthetic Aperture Radar (SAR) images, has represented an important breakthrough in the context of non-invasive ground deformation analyses over large areas, thanks to their large spatial coverage and relatively short revisit time, as well as to their medium-high ground resolution. In such a context, the well-known Differential SAR Interferometry (DInSAR) technique allows us to map and measure deformation phenomena due to both natural and man-made causes with centimetre to millimetre accuracy. The Earth Science community has a wide interest in the use of DInSAR displacement maps both for crisis management and risk mitigation activities, and for surveillance, monitoring and analysis of geophysical phenomena. In areas characterized by high level of hazards the availability of routinely generated advanced DInSAR products would allow a fast analysis of their current status, providing a near real time monitoring. Similarly, an on-demand service would allow the customization of the products by selecting the area of interest, the SAR data to be processed, and other processing parameters to be set by the users to edit/correct/improve the final products. In this work we discuss the Satellite Data Thematic Core Service of EPOS and we present the EPOSAR service. In particular, the EPOSAR service, based on the well-known DInSAR approach referred to as Small Baseline Subset (SBAS), accomplishes a shared and synergic Earth Observation (EO) service aimed at designing, implementing and harmonizing efficient satellite data processing chains capable of ingesting the significantly increased data stream expected from the ESA Sentinel-1 satellites. EPOSAR

  2. Emerging EPO and EPO receptor regulators and signal transducers.

    Science.gov (United States)

    Kuhrt, David; Wojchowski, Don M

    2015-06-04

    As essential mediators of red cell production, erythropoietin (EPO) and its cell surface receptor (EPO receptor [EPOR]) have been intensely studied. Early investigations defined basic mechanisms for hypoxia-inducible factor induction of EPO expression, and within erythroid progenitors EPOR engagement of canonical Janus kinase 2/signal transducer and activator of transcription 5 (JAK2/STAT5), rat sarcoma/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAS/MEK/ERK), and phosphatidylinositol 3-kinase (PI3K) pathways. Contemporary genetic, bioinformatic, and proteomic approaches continue to uncover new clinically relevant modulators of EPO and EPOR expression, and EPO's biological effects. This Spotlight review highlights such factors and their emerging roles during erythropoiesis and anemia.

  3. Enhancement of recombinant human EPO production and glycosylation in serum-free suspension culture of CHO cells through expression and supplementation of 30Kc19.

    Science.gov (United States)

    Park, Ju Hyun; Wang, Zesong; Jeong, Hee-Jin; Park, Hee Ho; Kim, Byung-Gee; Tan, Wen-Song; Choi, Shin Sik; Park, Tai Hyun

    2012-11-01

    We previously reported that the expression of Bombyx mori 30Kc19 gene in CHO cells significantly improved both the production and sialylation of recombinant human EPO (rHuEPO) in adhesion culture mode. In this study, the effects of 30Kc19 expression and supplementation of 30Kc19 recombinant protein on the productivity and glycosylation pattern of rHuEPO were investigated in the serum-free suspension culture mode. Especially, glycosylation pattern was examined in detail using a quantitative MALDI-TOF MS method. The expression of 30Kc19 increased the EPO production by 2.5-folds and the host cells produced rHuEPO with more complex glycan structures and a larger content of sialic acid and fucose. The glycan structures of rHuEPO in the 30Kc19-expressing cell consisted of bi-, tri-, tetra-, and penta-antennary branching (35, 18, 33, and 14 %, respectively), while the control cells produced predominantly bi-antennary branching (70 %). About 53 % of the glycans from rHuEPO in the 30Kc19-expressing cell was terminally sialylated, while no obvious sialylated glycan was found in the control cells. The percentage of fucosylated glycans from the 30Kc19-expressing cell culture was 77 %, whereas only 61 % of the glycans from the control cell were fucosylated glycans. We also examined whether these effects were observed when the recombinant 30Kc19 protein produced from Escherichia coli was supplemented into the culture medium for CHO cells. In the control cell line without the 30Kc19 gene, EPO production increased by 41.6 % after the addition of 0.2 mg/mL of the recombinant 30Kc19 protein to the culture medium. By the Western blot analysis after two-dimensional electrophoresis (2-DE) of isoforms of EPO, we confirmed that 30Kc19 enhanced the sialylation of EPO glycans. These results demonstrated that both 30Kc19 gene expression and the recombinant 30Kc19 protein addition enhanced rHuEPO productivity and glycosylation in suspension culture. In conclusion, the utilization of

  4. Cadmium and cisplatin damage erythropoietin-producing proximal renal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Hyogo; Oguma, Etsuko; Kayama, Fujio [Jichi Medical School, Division of Environmental Medicine, Center for Community Medicine, Tochigi (Japan); Core Research for Evolutional Science and Technology, Japan Science Technology Corporation (CREST-JST), Saitama (Japan)

    2006-10-15

    The concomitant manifestations of proximal renal tubular dysfunction and anemia with erythropoietin (Epo) deficiency observed in chronic cadmium (Cd) intoxication, such as Itai-itai disease, suggest a close local correlation between the Cd-targeted tubular cells and Epo-producing cells in the kidney. Therefore, we investigated the local relationship between hypoxia-induced Epo production and renal tubular injury in rats injected with Cd at 2 mg/kg twice a week for 8 months. Anemia due to insufficient production of Epo was observed in Cd-intoxicated rats. In situ hybridization detected Epo mRNA expression in the proximal renal tubular cells of hypoxic rats without Cd intoxication, and the Cd-intoxicated rats showed atrophy of Epo-expressing renal tubules and replacement of them with fibrotic tissue. A single dose of cisplatin at 8 mg/kg, which can induce clinical manifestations similar to those of Cd including renal tubular damage along with Epo-deficient anemia, resulted in Epo-expressing renal tubule destruction on day 4. These data indicate that Cd and cisplatin would induce anemia through the direct injury of the proximal renal tubular cells that are responsible for Epo production. (orig.)

  5. Renal erythropoietin-producing cells in health and disease

    Directory of Open Access Journals (Sweden)

    Tomokazu eSouma

    2015-06-01

    Full Text Available Erythropoietin (Epo is an indispensable erythropoietic hormone primarily produced from renal Epo-producing cells (REPs. Epo production in REPs is tightly regulated in a hypoxia-inducible manner to maintain tissue oxygen homeostasis. Insufficient Epo production by REPs causes renal anemia and anemia associated with chronic disorders. Recent studies have broadened our understanding of REPs from prototypic hypoxia-responsive cells to dynamic fibrogenic cells. In chronic kidney disease, REPs are the major source of scar-forming myofibroblasts and actively produce fibrogenic molecules, including inflammatory cytokines. Notably, myofibroblast-transformed REPs recover their original physiological properties after resolution of the disease insults, suggesting that renal anemia and fibrosis could be reversible to some extent. Therefore, understanding the plasticity of REPs will lead to the development of novel targeted therapeutics for both renal fibrosis and anemia. This review summarizes the regulatory mechanisms how hypoxia-inducible Epo gene expression is attained in health and disease conditions.

  6. Sustainable access to data, products, services and software from the European seismological Research Infrastructures: the EPOS TCS Seismology

    Science.gov (United States)

    Haslinger, Florian; Dupont, Aurelien; Michelini, Alberto; Rietbrock, Andreas; Sleeman, Reinoud; Wiemer, Stefan; Basili, Roberto; Bossu, Rémy; Cakti, Eser; Cotton, Fabrice; Crawford, Wayne; Diaz, Jordi; Garth, Tom; Locati, Mario; Luzi, Lucia; Pinho, Rui; Pitilakis, Kyriazis; Strollo, Angelo

    2016-04-01

    Easy, efficient and comprehensive access to data, data products, scientific services and scientific software is a key ingredient in enabling research at the frontiers of science. Organizing this access across the European Research Infrastructures in the field of seismology, so that it best serves user needs, takes advantage of state-of-the-art ICT solutions, provides cross-domain interoperability, and is organizationally and financially sustainable in the long term, is the core challenge of the implementation phase of the Thematic Core Service (TCS) Seismology within the EPOS-IP project. Building upon the existing European-level infrastructures ORFEUS for seismological waveforms, EMSC for seismological products, and EFEHR for seismological hazard and risk information, and implementing a pilot Computational Earth Science service starting from the results of the VERCE project, the work within the EPOS-IP project focuses on improving and extending the existing services, aligning them with global developments, to at the end produce a well coordinated framework that is technically, organizationally, and financially integrated with the EPOS architecture. This framework needs to respect the roles and responsibilities of the underlying national research infrastructures that are the data owners and main providers of data and products, and allow for active input and feedback from the (scientific) user community. At the same time, it needs to remain flexible enough to cope with unavoidable challenges in the availability of resources and dynamics of contributors. The technical work during the next years is organized in four areas: - constructing the next generation software architecture for the European Integrated (waveform) Data Archive EIDA, developing advanced metadata and station information services, fully integrate strong motion waveforms and derived parametric engineering-domain data, and advancing the integration of mobile (temporary) networks and OBS deployments in

  7. Erythropoietin-mediated protection in kidney transplantation : Nonerythropoietic EPO derivatives improve function without increasing risk of cardiovascular events

    NARCIS (Netherlands)

    van Rijt, Willem G; van Goor, Harry; Ploeg, Rutger J; Leuvenink, Henri G D

    2014-01-01

    The protective, nonerythropoietic effects of erythropoietin (EPO) have become evident in preclinical models in renal ischaemia/reperfusion injury and kidney transplantation. However, four recently published clinical trials using high-dose EPO treatment following renal transplantation did not reveal

  8. Erythropoietin (EPO) in acute kidney injury.

    Science.gov (United States)

    Moore, Elizabeth; Bellomo, Rinaldo

    2011-03-21

    Erythropoietin (EPO) is a 30.4 kDa glycoprotein produced by the kidney, and is mostly well-known for its physiological function in regulating red blood cell production in the bone marrow. Accumulating evidence, however, suggests that EPO has additional organ protective effects, which may be useful in the prevention or treatment of acute kidney injury. These protective mechanisms are multifactorial in nature and include inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways, and promotion of recovery.In this article, we review the physiology of EPO, assess previous work that supports the role of EPO as a general tissue protective agent, and explain the mechanisms by which it may achieve this tissue protective effect. We then focus on experimental and clinical data that suggest that EPO has a kidney protective effect.

  9. Hard probes and the event generator EPOS

    CERN Document Server

    Guiot, Benjamin

    2014-01-01

    After a short presentation of the event generator EPOS, we discuss the production of heavy quarks and prompt photons which has been recently implemented. Whereas we have satisfying results for the charm, work on photons is still in progress.

  10. Impact of increased erythropoietin receptor expression and elevated serum erythropoietin levels on clinicopathological features and prognosis in renal cell carcinoma

    OpenAIRE

    ITO, KEIICHI; YOSHII, HIDEHIKO; ASANO, TAKAKO; HORIGUCHI, AKIO; Sumitomo, Makoto; Hayakawa, Masamichi; ASANO, TOMOHIKO

    2012-01-01

    Erythropoietin (EPO) expression and EPO receptor (EpoR) expression have been demonstrated in various malignant tumors. EPO-EpoR signaling can activate several downstream signal transduction pathways that enhance tumor aggressiveness. The present study was undertaken to evaluate the impact of overexpression of EpoR and elevated serum EPO (sEPO) levels on the clinicopathological features and prognosis of patients with renal cell carcinoma (RCC). EpoR expression was evaluated immunohistochemical...

  11. The EPOS e-Infrastructure: metadata driven integration of data products and services in solid Earth Science

    Science.gov (United States)

    Bailo, Daniele; Jeffery, Keith

    2015-04-01

    The European Plate Observing System (EPOS) is an ambitious long term integration plan addressing the major solid-earth research infrastructures in Europe. For its large scale and extent it is an unique initiative which will foster new scientific discoveries and enable scientists to investigate the solid earth system with unprecedented ways. A key aspect of EPOS is to provide end-users with homogeneous access to services and multidisciplinary data collected by monitoring infrastructures and experimental facilities as well as access to software, processing and visualization tools. Such a complex system requires a solid, scalable and reliable architecture in order to accommodate innovative features and to meet the evolving expectations of the heterogeneous communities involved.

  12. Erythropoietin (EPO) in acute kidney injury

    OpenAIRE

    Moore, Elizabeth; Bellomo, Rinaldo

    2011-01-01

    Erythropoietin (EPO) is a 30.4 kDa glycoprotein produced by the kidney, and is mostly well-known for its physiological function in regulating red blood cell production in the bone marrow. Accumulating evidence, however, suggests that EPO has additional organ protective effects, which may be useful in the prevention or treatment of acute kidney injury. These protective mechanisms are multifactorial in nature and include inhibition of apoptotic cell death, stimulation of cellular regeneration, ...

  13. Erythropoietin-mediated protection in kidney transplantation: nonerythropoietic EPO derivatives improve function without increasing risk of cardiovascular events.

    Science.gov (United States)

    van Rijt, Willem G; van Goor, Harry; Ploeg, Rutger J; Leuvenink, Henri G D

    2014-03-01

    The protective, nonerythropoietic effects of erythropoietin (EPO) have become evident in preclinical models in renal ischaemia/reperfusion injury and kidney transplantation. However, four recently published clinical trials using high-dose EPO treatment following renal transplantation did not reveal any protective effect for short-term renal function and even reported an increased risk of thrombosis. This review focusses on the current status of protective pathways mediated by EPO, the safety concerns using high EPO dosage and discusses the discrepancies between pre-clinical and clinical studies. The protective effects are mediated by binding of EPO to a heteromeric receptor complex consisting of two β-common receptors and two EPO receptors. An important role for the activation of endothelial nitric oxide synthase is proposed. EPO-mediated cytoprotection still has enormous potential. However, only nonerythropoietic EPO derivatives may induce protection without increasing the risk of cardiovascular events. In preclinical models, nonerythropoietic EPO derivatives, such as carbamoylated EPO and ARA290, have been tested. These EPO derivatives improve renal function and do not affect erythropoiesis. Therefore, nonerythropoietic EPO derivatives may be able to render EPO-mediated cytoprotection useful and beneficial for clinical transplantation.

  14. Progress of erythropoietin for patients with renal anemia%促红细胞生成素治疗肾性贫血研究进展

    Institute of Scientific and Technical Information of China (English)

    俞岗; 汪年松

    2011-01-01

    Erythropoietin (EPO) produced by the kidney in adults is a kind of glycoprotein hormone, which regulates red cell production. Lacking of EPO anemia. Treatment with recombinant human EPO (rHuEPO) is an effective and safe approach to improve anemia associated with chronic renal failure (CRF). This review summarizes the physiological function, clinical application and development of EPO.%促红细胞生成素(EPO)主要由肾脏产生,其作用为调节红细胞生成.EPO缺乏可致贫血,重组促红细胞生成素(rHuEPO)治疗慢性肾衰引起的贫血疗效确切且不良反应小.本文综述EPO的生理功能、临床应用及新品种开发.

  15. The EPOS ICT Architecture

    Science.gov (United States)

    Jeffery, Keith; Harrison, Matt; Bailo, Daniele

    2016-04-01

    The EPOS-PP Project 2010-2014 proposed an architecture and demonstrated feasibility with a prototype. Requirements based on use cases were collected and an inventory of assets (e.g. datasets, software, users, computing resources, equipment/detectors, laboratory services) (RIDE) was developed. The architecture evolved through three stages of refinement with much consultation both with the EPOS community representing EPOS users and participants in geoscience and with the overall ICT community especially those working on research such as the RDA (Research Data Alliance) community. The architecture consists of a central ICS (Integrated Core Services) consisting of a portal and catalog, the latter providing to end-users a 'map' of all EPOS resources (datasets, software, users, computing, equipment/detectors etc.). ICS is extended to ICS-d (distributed ICS) for certain services (such as visualisation software services or Cloud computing resources) and CES (Computational Earth Science) for specific simulation or analytical processing. ICS also communicates with TCS (Thematic Core Services) which represent European-wide portals to national and local assets, resources and services in the various specific domains (e.g. seismology, volcanology, geodesy) of EPOS. The EPOS-IP project 2015-2019 started October 2015. Two work-packages cover the ICT aspects; WP6 involves interaction with the TCS while WP7 concentrates on ICS including interoperation with ICS-d and CES offerings: in short the ICT architecture. Based on the experience and results of EPOS-PP the ICT team held a pre-meeting in July 2015 and set out a project plan. The first major activity involved requirements (re-)collection with use cases and also updating the inventory of assets held by the various TCS in EPOS. The RIDE database of assets is currently being converted to CERIF (Common European Research Information Format - an EU Recommendation to Member States) to provide the basis for the EPOS-IP ICS Catalog. In

  16. EPOS Data and Service Provision

    Science.gov (United States)

    Bailo, Daniele; Jeffery, Keith G.; Atakan, Kuvvet; Harrison, Matt

    2017-04-01

    EPOS is now in IP (implementation phase) after a successful PP (preparatory phase). EPOS consists of essentially two components, one ICS (Integrated Core Services) representing the integrating ICT (Information and Communication Technology) and many TCS (Thematic Core Services) representing the scientific domains. The architecture developed, demonstrated and agreed within the project during the PP is now being developed utilising co-design with the TCS teams and agile, spiral methods within the ICS team. The 'heart' of EPOS is the metadata catalog. This provides for the ICS a digital representation of the TCS assets (services, data, software, equipment, expertise…) thus facilitating access, interoperation and (re-)use. A major part of the work has been interactions with the TCS. The original intention to harvest information from the TCS required (and still requires) discussions to understand fully the TCS organisational structures linked with rights, security and privacy; their (meta)data syntax (structure) and semantics (meaning); their workflows and methods of working and the services offered. To complicate matters further the TCS are each at varying stages of development and the ICS design has to accommodate pre-existing, developing and expected future standards for metadata, data, software and processes. Through information documents, questionnaires and interviews/meetings the EPOS ICS team has collected DDSS (Data, Data Products, Software and Services) information from the TCS. The ICS team developed a simplified metadata model for presentation to the TCS and the ICS team will perform the mapping and conversion from this model to the internal detailed technical metadata model using (CERIF: a EU recommendation to Member States maintained, developed and promoted by euroCRIS www.eurocris.org ). At the time of writing the final modifications of the EPOS metadata model are being made, and the mappings to CERIF designed, prior to the main phase of (meta

  17. Isolation and characterization of renal erythropoietin-producing cells from genetically produced anemia mice.

    Directory of Open Access Journals (Sweden)

    Xiaoqing Pan

    Full Text Available Understanding the nature of renal erythropoietin-producing cells (REPs remains a central challenge for elucidating the mechanisms involved in hypoxia and/or anemia-induced erythropoietin (Epo production in adult mammals. Previous studies have shown that REPs are renal peritubular cells, but further details are lacking. Here, we describe an approach to isolate and characterize REPs. We bred mice bearing an Epo gene allele to which green fluorescent protein (GFP reporter cDNA was knocked-in (Epo(GFP with mice bearing an Epo gene allele lacking the 3' enhancer (Epo(Δ3'E. Mice harboring the mutant Epo(GFP/Δ3'E gene exhibited anemia (average Hematocrit 18% at 4 to 6 days after birth, and this perinatal anemia enabled us to identify and purify REPs based on GFP expression from the kidney. Light and confocal microscopy revealed that GFP immunostaining was confined to fibroblastic cells that reside in the peritubular interstitial space, confirming our previous observation in Epo-GFP transgenic reporter assays. Flow cytometry analyses revealed that the GFP fraction constitutes approximately 0.2% of the whole kidney cells and 63% of GFP-positive cells co-express CD73 (a marker for cortical fibroblasts and Epo-expressing cells in the kidney. Quantitative RT-PCR analyses confirmed that Epo expression was increased by approximately 100-fold in the purified population of REPs compared with that of the unsorted cells or CD73-positive fraction. Gene expression analyses showed enrichment of Hif2α and Hif3α mRNA in the purified population of REPs. The genetic approach described here provides a means to isolate a pure population of REPs, allowing the analysis of gene expression of a defined population of cells essential for Epo production in the kidney. This has provided evidence that positive regulation by HIF2α and negative regulation by HIF3α might be necessary for correct renal Epo induction.

  18. Optimization of growth of reconstructed CHO cells and expression of its product EPO%pH对重组CHO细胞生长及产物EPO表达的优化

    Institute of Scientific and Technical Information of China (English)

    吴园园; 盛光阳; 张涤平; 吴建祥; 黎雄辉; 黄俊龙

    2012-01-01

    目的 探索唾液酸化程度高且EPO表达量高的最优pH.方法 考察不同pH对细胞生长、EPO产量和EPO唾液酸含量的影响.结果 pH7.10~ 7.25 EPO表达量可达10 388 IU/ml,唾液酸可达11.5 mol/mol EPO,纯化收率达17.9%.结论 综合细胞维持时间、EPO表达量、纯化收率、唾液酸含量等因素,选择pH 7.10 ~7.25为CHO细胞表达EPO的最优pH,为优化工业化生产EPO提供基础.%Objective To explore the optimal pH value for over-expression of erythropoietin with high level of sialic acidification.Methods The effects of different pH values on cell growth,yield of EPO,and content of EPO sialic acid were obserred.Results Level of EPO expression could reach 10 388 IU/ml,sialic acid up to 11.5 mol/molEPO,and purification yield up to 17.9% as the pH value was between 7.10 to 7.25.Conclusions 7.10 to 7.25 can be the optimal pH value by a comprehensive assessment of the factors of level of cell maintenance,expression of EPO,purification yield,and sialic acid content,which provides a basis for optimization of the industrial production of EPO.

  19. Mystery Story about Erythropoietin (Epo) and Erythropoietin Receptor (EpoR) are Disguised?

    Science.gov (United States)

    Cubranić, Aleksandar; Redzovic, Arnela; Dobrila-Dintinjana, Renata; Vukelić, Jelena; Dintinjana, Marijan

    2015-05-01

    In this review we would like to focus our attention upon very controversial reports on Erythropoietin (Epo) and Erythropoietin Receptor (EpoR) expression in cancer patients. The effects of Epo on cancerous tissues are poorly understood. Hypoxia results in an increase in the level of the production of both Epo and EpoR via activation of the hypoxia-inducible factor 1 (HIF-1) pathway. HIF-1α, promotes the expression of vascular endothelial growth factor (VEGF). The signaling through VEGF in both a paracrine and an autocrine manner is required for the homeostasis of adult vessels. Macrophages stimulate vessel sprouting via a soluble factor other than VEGF, rather than through direct contact with endothelial cells. The intriguing questions are set about many researches to link Epo/EpoR expression and function in order to establish one of the mechanisms of tumor growth, disease progression of cancer patient. However, it is uncertain role in tumour angiogenesis as promoter and stimulator of tumour growth which should need to be furtherly validated.

  20. Enzymatic assembly of epothilones: the EpoC subunit and reconstitution of the EpoA-ACP/B/C polyketide and nonribosomal peptide interfaces.

    Science.gov (United States)

    O'Connor, Sarah E; Chen, Huawei; Walsh, Christopher T

    2002-04-30

    The biosynthesis of epothilones, a family of hybrid polyketide (PK)/nonribosomal peptide (NRP) antitumor agents, provides an ideal system to study a hybrid PK/NRP natural product with significant biomedical value. Here the third enzyme involved in epothilone production, the five domain 195 kDa polyketide synthase (PKS) EpoC protein, has been expressed and purified from Escherichia coli. EpoC was combined with the first two enzymes of the epothilone biosynthesis pathway, the acyl carrier protein (ACP) domain of EpoA and EpoB, to reconstitute the early steps in epothilone biosynthesis. The acyltransferase (AT) domain of EpoC transfers the methylmalonyl moiety from methylmalonyl-CoA to the holo HS-acyl carrier protein (ACP) in an autoacylation reaction. The ketosynthase (KS) domain of EpoC decarboxylates the methylmalonyl-S-EpoC acyl enzyme to generate the carbon nucleophile that reacts with methylthiazolylcarboxyl-S-EpoB. The resulting condensation product can be reduced in the presence of NADPH by the ketoreductase (KR) domain of EpoC and then dehydrated by the dehydratase (DH) domain to produce the methylthiazolylmethylacrylyl-S-EpoC acyl enzyme intermediate that serves as the acyl donor for subsequent elongation of the epothilone chain. The acetyl-CoA donor can be replaced with propionyl-CoA, isobutyryl-CoA, and benzoyl-CoA and the acyl chains accepted by both EpoB and EpoC subunits to produce ethyl-, isopropyl-, and phenylthiazolylmethylacrylyl-S-EpoC acyl enzyme intermediates, suggesting that future combinatorial biosynthetic variations in epothilone assembly may be feasible. These results demonstrate in vitro reconstitution of both the PKS/NRPS interface (EpoA-ACP/B) and the NRPS/PKS interface (EpoB/C) in the assembly line for this antitumor natural product.

  1. Schwann cells express erythropoietin receptor and represent a major target for Epo in peripheral nerve injury.

    Science.gov (United States)

    Li, Xiaoqing; Gonias, Steven L; Campana, W Marie

    2005-09-01

    Erythropoietin (Epo) expresses potent neuroprotective activity in the peripheral nervous system; however, the underlying mechanism remains incompletely understood. In this study, we demonstrate that Epo is upregulated in sciatic nerve after chronic constriction injury (CCI) and crush injury in rats, largely due to local Schwann cell production. In uninjured and injured nerves, Schwann cells also express Epo receptor (EpoR), and its expression is increased during Wallerian degeneration. CCI increased the number of Schwann cells at the injury site and the number was further increased by exogenously administered recombinant human Epo (rhEpo). To explore the activity of Epo in Schwann cells, primary cultures were established. These cells expressed cell-surface Epo receptors, with masses of 71 and 62 kDa, as determined by surface protein biotinylation and affinity precipitation. The 71-kDa species was rapidly but transiently tyrosine-phosphorylated in response to rhEpo. ERK/MAP kinase was also activated in rhEpo-treated Schwann cells; this response was blocked by pharmacologic antagonism of JAK-2. RhEpo promoted Schwann cell proliferation, as determined by BrdU incorporation. Cell proliferation was ERK/MAP kinase-dependent. These results support a model in which Schwann cells are a major target for Epo in injured peripheral nerves, perhaps within the context of an autocrine signaling pathway. EpoR-induced cell signaling and Schwann cell proliferation may protect injured peripheral nerves and promote regeneration.

  2. Cbl ubiquitination of p85 is essential for Epo-induced EpoR endocytosis

    OpenAIRE

    Bulut, Gamze B.; Sulahian, Rita; Yao, Huiyu; Huang, Lily Jun-shen

    2013-01-01

    Epo-induced EpoR internalization is mediated through a novel Cbl/p85/epsin-1 pathway.Mutated EpoR in primary familial and congenital polycythemia patients cannot activate this pathway, exhibiting excessive Epo signaling.

  3. The Core Services of the European Plate Observing System (EPOS)

    Science.gov (United States)

    Hoffmann, T. L.; Euteneuer, F. H.; Lauterjung, J.

    2013-12-01

    from different EPOS Thematic Core Services and from the National RIs & Data Centers, 2) provide access to data products, synthetic data from simulations, data processing and data visualization tools, 3) serve science, industry, education, government, legal and other stakeholders in an integrated fashion through the EPOS User Interface, and 4) provide a variety of ICT technological services including (but not being limited) to discovery functions, data mining, access to modeling tools and high performance computing, and training & tutorials.

  4. Mechanism of Protective Effect of High Dosage Erythropoietin (EPO) on Renal Anemia Treated with Combination of Chinese and Western Medicine%中西医结合治疗肾性贫血的红细胞保护机理研究

    Institute of Scientific and Technical Information of China (English)

    张熙; 王怡

    2013-01-01

    Objective: To study the effect of combination of yangxueyin Recipe and high dosage erythropoietin ( EPO ) in the treatment of renal anemia and the influence on change of CD55, CD59 and ROS, so as to explore the possible mechanism of inte-grative Chinese and Western medicine (ICWM) in treating renal anemia. Methods :60 patients with renal anemia were randomly divided into two groups:the ICWM group and the control group with 30 in each group. The symptomatic and supporting treatment, such as dialysis supplementing of ferrous .foliac acid and vitamin B12,was given to both groups. 3 months later,blood levels of hemoglobin (Hb) , hematocrit ( Hct) ,CD55,CD59 and ROS were measured and the therapeutic effect was observed. Results: After treatment, levels of HB and HCT in two groups were obviously increased (P <0. 01) ,but there was on difference between the two groups. CD55 and CD59 in two groups had no difference before and after treatment and there was also no difference between the two groups. ROS level in two groups was obviously higher than that in normal group and after treatment it was decreased more significantly (P <0. 01) ,but there was no difference between the two groups. Conclusion: The control and ICWM groups both could significantly inhibit the production of ROS, and this may be an important factor for ICWM and control group in effectively improving renal anemia.%目的:评价养血饮联合促红细胞生成素(EPO)对肾性贫血患者临床症状及其对红细胞膜的保护作用.方法:60例肾性贫血患者随机分为养血饮合益比奥治疗组30例(中西组),西药益比奥组30例(对照组),治疗3个月后用流式细胞仪检测CD55、CD59、ROS,并检测和评估血常规的变化.结果:实验前后.结果:对照组和中西组治疗后HB,HCT均较前明显上升(P<0.01),两组之间无明显差异.红细胞膜上CD55、CD59治疗前后无明显差异,两组间比较也无明显差异.红细胞膜上ROS均明显高于正常组;治

  5. Soluble erythropoietin receptor contributes to erythropoietin resistance in end-stage renal disease.

    Directory of Open Access Journals (Sweden)

    Eliyahu V Khankin

    Full Text Available BACKGROUND: Erythropoietin is a growth factor commonly used to manage anemia in patients with chronic kidney disease. A significant clinical challenge is relative resistance to erythropoietin, which leads to use of successively higher erythropoietin doses, failure to achieve target hemoglobin levels, and increased risk of adverse outcomes. Erythropoietin acts through the erythropoietin receptor (EpoR present in erythroblasts. Alternative mRNA splicing produces a soluble form of EpoR (sEpoR found in human blood, however its role in anemia is not known. METHODS AND FINDINGS: Using archived serum samples obtained from subjects with end stage kidney disease we show that sEpoR is detectable as a 27kDa protein in the serum of dialysis patients, and that higher serum sEpoR levels correlate with increased erythropoietin requirements. Soluble EpoR inhibits erythropoietin mediated signal transducer and activator of transcription 5 (Stat5 phosphorylation in cell lines expressing EpoR. Importantly, we demonstrate that serum from patients with elevated sEpoR levels blocks this phosphorylation in ex vivo studies. Finally, we show that sEpoR is increased in the supernatant of a human erythroleukaemia cell line when stimulated by inflammatory mediators such as interleukin-6 and tumor necrosis factor alpha implying a link between inflammation and erythropoietin resistance. CONCLUSIONS: These observations suggest that sEpoR levels may contribute to erythropoietin resistance in end stage renal disease, and that sEpoR production may be mediated by pro-inflammatory cytokines.

  6. Near Fault Observatories: multidisciplinary research infrastructures, high resolution data and scientific products available through dedicated services implemented within the EPOS-IP project

    Science.gov (United States)

    Festa, Gaetano; Chiaraluce, Lauro; Ergintav, Semih; Bernard, Pascal; Clinton, John; Marmureanu, Alexandru; Tataru, Dragos; Vogfjord, Kristin

    2017-04-01

    Near Fault Observatories (NFOs) are innovative research infrastructures based on dense, state of the art networks of multi-parametric sensors that continuously monitor the underlying Earth instability processes over a broad time interval. They aim at understanding the physical/chemical processes responsible for earthquakes and faulting and tracking their evolution over time by enabling advancements in ground shaking prediction. EPOS-IP is aimed at contributing in creating and harmonizing data and products distributors from seven NFOs, operating on different tectonic regimes and different areas of Europe. They include plate boundary systems at South Iceland Seismic Zone, the Marmara Sea and the Corinth rift. In mountain settings, NFOs monitor the Alto Tiberina and Irpinia faults in the Apennine mountain range, the Valais region in the Alps, and the Vrancea fault in the Carpathian Mountains. They monitor diverse faulting mechanisms (strike-slip, normal and thrust), high to low angle faults, shallow and deep faults, as well as regions with fast and slow strain rate accumulation. The focus of the observatories varies, ranging from small- to large-scale seismicity and includes the role of different parameters such as fluid playing in fault initiation, the internal structure of fault systems, site effects and derived processes such as earthquake generated landslides and tsunamis. In response to their specific objectives, the NFOs operate a diverse set of monitoring instrumentation using seismic, deformation, strain, geochemical and electromagnetic equipment. Since NFO methodological approach is based on extremely dense networks and less common instruments deserving multi-parameter data description, a main goal of this group is to build inclusive and harmonised services supporting the installation over the next decade of tens of near-fault observatories monitoring active faults in different tectonic environments in Europe. The NFO Thematic Core Service (TCS) relies on

  7. Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of l-DOPA.

    Science.gov (United States)

    Jiang, Xiaoliang; Zhang, Yanrong; Yang, Yu; Yang, Jian; Asico, Laureano D; Chen, Wei; Felder, Robin A; Armando, Ines; Jose, Pedro A; Yang, Zhiwei

    2017-01-01

    Gastrin is a peptide hormone that is involved in the regulation of sodium balance and blood pressure. Dopamine, which is also involved in the regulation of sodium balance and blood pressure, directly or indirectly interacts with other blood pressure-regulating hormones, including gastrin. This study aimed to determine the mechanisms of the interaction between gastrin and dopamine and tested the hypothesis that gastrin produced in the kidney increases renal dopamine production to keep blood pressure within the normal range. We show that in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively), gastrin stimulates renal dopamine production by increasing the cellular uptake of l-DOPA via the l-type amino acid transporter (LAT) at the plasma membrane. The uptake of l-DOPA in RPTCs from C57Bl/6J mice is lower than in RPTCs from normotensive humans. l-DOPA uptake in renal cortical slices is also lower in salt-sensitive C57Bl/6J than in salt-resistant BALB/c mice. The deficient renal cortical uptake of l-DOPA in C57Bl/6J mice may be due to decreased LAT-1 activity that is related to its decreased expression at the plasma membrane, relative to BALB/c mice. We also show that renal-selective silencing of Gast by the renal subcapsular injection of Gast siRNA in BALB/c mice decreases renal dopamine production and increases blood pressure. These results highlight the importance of renal gastrin in stimulating renal dopamine production, which may give a new perspective in the prevention and treatment of hypertension. Copyright © 2017 the American Physiological Society.

  8. Liver iron is a major regulator of hepcidin gene expression via BMP/SMAD pathway in a rat model of chronic renal failure under treatment with high rHuEPO doses.

    Science.gov (United States)

    Ribeiro, Sandra; Garrido, Patrícia; Fernandes, João; Rocha-Pereira, Petronila; Costa, Elísio; Belo, Luís; Reis, Flávio; Santos-Silva, Alice

    2016-05-01

    Hepcidin is the major central regulator of iron metabolism, controlling iron absorption and mobilization. Considering its interaction with several factors that are altered in chronic kidney disease (CKD), particularly in hyporesponsive CKD patients under therapy with high recombinant human erythropoietin (rHuEPO) doses, it was aimed to study the impact of increasing rHuEPO doses on the regulation of iron-hepcidin metabolism. The blood, cellular, and tissue studies, using the remnant kidney rat model of CKD induced by 5/6 nephrectomy, under rHuEPO (100, 200, 400, and 600 IU/Kg body weight [BW]/week) treatment during 3 weeks were performed. It was found that the rHuEPO stimulus triggered a first wave to achieve correction of anemia, by inhibiting hepcidin synthesis, favoring erythropoiesis and iron absorption; this continuous stimulus enhanced iron absorption leading to iron overload, as showed by the hepatic iron deposits found in rats treated with higher rHuEPO dose that seems to trigger the upregulation of hepcidin synthesis through the activation of the BMP6/SMAD pathway. The data suggested that liver iron overload was an important stimuli for hepcidin synthesis, stronger than the inhibitory effect of high rHuEPO doses; moreover, the findings raised the hypothesis that when high inflammation (triggering hepcidin expression) was associated with increased iron stores in hemodialysis patients, hepcidin expression was also upregulated via BMP6, enhancing hepcidin synthesis, leading, therefore, to worsening of anemia and, eventually, to a hyporesponse/resistance to rHuEPO therapy. © 2016 BioFactors, 42(3):296-306, 2016.

  9. EPOS Seismology services and their users

    Science.gov (United States)

    Haslinger, Florian; Dupont, Aurelien; Michelini, Alberto; Rietbrock, Andreas; Sleeman, Reinoud; Wiemer, Stefan; Basili, Roberto; Bossu, Rémy; Cakti, Eser; Cotton, Fabrice; Crawford, Wayne; Crowley, Helen; Danciu, Laurentiu; Diaz, Jordi; Garth, Tom; Locati, Mario; Luzi, Lucia; Pitilakis, Kyriazis; Roumelioti, Zafeiria; Strollo, Angelo

    2017-04-01

    The construction of seismological community services for the European Plate Observing System Research Infrastructure (EPOS) is by now well under way. A significant number of services are already operational, largely based on those existing at established institutions or collaborations like ORFEUS, EMSC, AHEAD and EFEHR, and more are being added to be ready for internal validation by late 2017. In this presentation we focus on a number of issues related to the interaction of the community of users with the services provided by the seismological part of the EPOS research infrastructure. How users interact with a service (and how satisfied they are with this interaction) is viewed as one important component of the validation of a service within EPOS, and certainly is key to the uptake of a service and from that also it's attributed value. Within EPOS Seismology, the following aspects of user interaction have already surfaced: - user identification (and potential tracking) versus ease-of-access and openness Requesting users to identify themselves when accessing a service provides various advantages to providers and users (e.g. quantifying & qualifying the service use, customization of services and interfaces, handling access rights and quotas), but may impact the ease of access and also shy away users who don't wish to be identified for whatever reason. - service availability versus cost There is a clear and prominent connection between the availability of a service, both regarding uptime and capacity, and its operational cost (IT systems and personnel), and it is often not clear where to draw the line (and based on which considerations). In connection to that, how to best utilize third-party IT infrastructures (either commercial or public), and what the long-term cost implications of that might be, is equally open. - licensing and attribution The issue of intellectual property and associated licensing policies for data, products and services is only recently gaining

  10. Renal-Adenocarcinoma-Associated Erythrocytosis in a Cat

    Directory of Open Access Journals (Sweden)

    Sungjun Noh, Ji-Houn Kang*, Gonhyung Kim, Dongwoo Chang, Byeongwoo Ahn, Ki-Jeong Na and Mhan-Pyo Yang

    2013-01-01

    Full Text Available A 9-year-old spayed female domestic shorthair cat was referred for erythrocytosis. Even after the correction of dehydration, blood analyses showed that there had been no improvement. An abdominal ultrasonography and computed tomography identified the presence of a mass on the left kidney. Measurement of serum erythropoietin (EPO showed higher concentration than the reference interval. These findings suggested a direct association of the erythrocytosis with excessive EPO production. The cat underwent nephrectomy of the affected (left kidney. Subsequent histopathology was consistent with a diagnosis of renal adenocarcinoma. Following the nephrectomy, serum EPO concentrations decreased gradually, and the erythrocytosis resolved 15 days postoperatively. This case describes the diagnosis and treatment of secondary inappropriate erythrocytosis in a cat with renal adenocarcinoma.

  11. New Developments of EPOS 2

    CERN Document Server

    Pierog, T; Porteboeuf, S; Werner, K

    2010-01-01

    Since 2006, EPOS hadronic interaction model is being used for very high energy cosmic ray analysis. Designed for minimum bias particle physics and used for having a precise description of SPS and RHIC heavy ion collisions, EPOS brought more detailed description of hadronic interactions in air shower development. Thanks to this model it was possible to understand why there were less muons in air shower simulations than observed in real data. With the start of the LHC era, a better description of hard processes and collective effects is needed to deeply understand the incoming data. We will describe the basic physics in EPOS and the new developments and constraints which are taken into account in EPOS 2.

  12. EPO modulation in a 14-days undersea scuba dive.

    Science.gov (United States)

    Revelli, L; Vagnoni, S; D'Amore, A; Di Stasio, E; Lombardi, C P; Storti, G; Proietti, R; Balestra, C; Ricerca, B M

    2013-10-01

    Erythropoiesis is affected during deep saturation dives. The mechanism should be related to a downregulation of serum Erythropoietin (s-EPO) concentration or to a toxic effect of the hyperbaric hyperoxia. We evaluated s-EPO and other haematological parameters in 6 scuba divers before, during and after a 14-days guinness saturation dive (8-10 m). Athletes were breathing air at 1.8-2 ATA, under the control of a team of physicians. Serum parameters were measured before diving (T0) and: 7 days (T1), 14 days (T2) after the beginning of the dive and 2 h (T3) and 24 h (T4) after resurfacing. Hgb, and many other haematological parameters did not change whereas Ht, s-EPO, the ratio between s-EPO predicted and that observed and reticulocytes (absolute, percent) declined progressively from T0 to T3. At T4 a significant rise in s-EPO was observed. Hgb did not vary but erythropoiesis seemed to be affected as s-EPO and reticulocyte counts showed. All these changes were statistically significant. The experiment, conducted in realistic conditions of dive length, oxygen concentration and pressure, allows us to formulate some hypotheses about the role of prolonged hyperbarism on erythropoiesis. The s-EPO rise, 24 h after resurfacing, is clearly documented and related to the "Normobaric Oxygen Paradox". This evidence suggests interesting hypotheses for new clinical applications such as modulation of s-EPO production and Hgb content triggered by appropriate O₂ administration in pre-surgical patients or in some anemic disease.

  13. Kidney EPO expression during chronic hypoxia in aged mice.

    Science.gov (United States)

    Benderro, Girriso F; LaManna, Joseph C

    2013-01-01

    In order to maintain normal cellular function, mammalian tissue oxygen concentrations must be tightly regulated within a narrow physiological range. The hormone erythropoietin (EPO) is essential for maintenance of tissue oxygen supply by stimulating red blood cell production and promoting their survival. In this study we compared the effects of 290 Torr atmospheric pressure on the kidney EPO protein levels in young (4-month-old) and aged (24-month-old) C57BL/6 mice. The mice were sacrificed after being anesthetized, and kidney samples were collected and processed by Western blot analysis. Relatively low basal expression of EPO during normoxia in young mice showed significant upregulation in hypoxia and stayed upregulated throughout the hypoxic period (threefold compared to normoxic control), showing a slight decline toward the third week. Whereas, a relatively higher normoxic basal EPO protein level in aged mice did not show significant increase until seventh day of hypoxia, but showed significant upregulation in prolonged hypoxia. Hence, we confirmed that there is a progressively increased accumulation of EPO during chronic hypoxia in young and aged mouse kidney, and the EPO upregulation during hypoxia showed a similarity with the pattern of increase in hematocrit, which we have reported previously.

  14. Effects of L-Carnitine Added to Erythropoietin in Anemic Chronic Renal Failure Patients on Hemodialysis.

    Directory of Open Access Journals (Sweden)

    N Taheri

    2006-10-01

    Full Text Available Introduction: Chronic renal disease (C.R.D is a pathophysiological process due to progressive and irreversible decrease in number and function of nephrons in the kidney. Anemia is one of the most important complications in CRD patients. Anemia is caused mainly due to diminished production of erythropoietin (EPO, which is treated by weekly injection of the EPO. L-carnitine added to EPO can increase the efficacy of EPO. Methods: Present study, from March 2003 until September 2004 (18 months, evaluates the effects of L-carnitine added to EPO in 30 patients at Shaheed Rahnemon hemodialysis center of Yazd. Each patient was administered one oral table (250 mg of L-carnitine, twice a day along with EPO for 90 days. EPO was in the form of injection 2000 iu/sc after dialysis.(three times per week. One questionnaire was completed for each patient, which included demographic characteristics, type of disease, duration of the hemodialysis, Hb and Hct levels, transferrin saturation and ferritin levels. Hb ,Hct and transferrin saturations were measured on days 1, 45 and 90. Results were analyzed by paired t test and analysis of variance. Results: Results of this study showed that the mean Hb levels and Hct were significantly raised up to 1.1 mg/dl (P.value<0.001 and 2.7% (P.Value<0.001, respectively. In addition, significant decrease of 5.75% in transferrin (P.Value< 0.001 and 121ng/ml in ferritin levels (P.Value< 0.001 was observed. Efficacy of EPO plus L-carnitine was affected only by duration of hemodialysis and not by age, sex or causes of CRD. Conclusion: L-carnitine added to EPO increases the efficacy of EPO after 3 months.

  15. Clinical efficacy and safety of recombinant canine erythropoietin in dogs with anemia of chronic renal failure and dogs with recombinant human erythropoietin-induced red cell aplasia.

    Science.gov (United States)

    Randolph, John E; Scarlett, Janet; Stokol, Tracy; MacLeod, James N

    2004-01-01

    The efficacy and safety of recombinant canine erythropoietin (rcEPO) therapy was evaluated in 19 dogs with anemia of chronic renal failure (group 1) and 6 dogs with chronic renal failure and recombinant human erythropoietin (rhEPO)-induced red cell aplasia (group 2). Hematocrit (Hct) and absolute reticulocyte count (ARC) were monitored weekly for the first 8 weeks, CBC (including ARC) and serum iron profiles were evaluated monthly, and serum biochemical analyses were performed every 2 months for 6 (group 2) to 12 (group 1) months. For group 1 dogs, median Hct and ARC increased significantly during the 1st week of rcEPO treatment, and median Hct was sustained at >35% after week 5. In contrast, median Hct and ARC for group 2 did not change significantly with rcEPO treatment, even with doses greater than those used in group 1. Nevertheless, 2 (33%) of the 6 dogs in group 2 developed erythroid hyperplasia, reticulocytosis, and increases in Hct with rcEPO treatment. Although median systolic blood pressure did not change significantly in either group, 5 dogs developed systolic blood pressures > or = 180 mm Hg during the study. Appetite and energy level improved in most group 1 dogs with increases in Hct. Recombinant cEPO stimulated erythrocyte production in dogs with nonregenerative anemia secondary to chronic renal failure without causing the profound erythroid hypoplasia that can occur in rhEPO-treated dogs. Unfortunately, rcEPO was not as effective in restoring erythrocyte production in dogs that had previously developed rhEPO-induced red cell aplasia.

  16. Setting the stage for the EPOS ERIC: Integration of the legal, governance and financial framework

    Science.gov (United States)

    Atakan, Kuvvet; Bazin, Pierre-Louis; Bozzoli, Sabrina; Freda, Carmela; Giardini, Domenico; Hoffmann, Thomas; Kohler, Elisabeth; Kontkanen, Pirjo; Lauterjung, Jörn; Pedersen, Helle; Saleh, Kauzar; Sangianantoni, Agata

    2017-04-01

    EPOS - the European Plate Observing System - is the ESFRI infrastructure serving the need of the solid Earth science community at large. The EPOS mission is to create a single sustainable, and distributed infrastructure that integrates the diverse European Research Infrastructures for solid Earth science under a common framework. Thematic Core Services (TCS) and Integrated Core Services (Central Hub, ICS-C and Distributed, ICS-D) are key elements, together with NRIs (National Research Infrastructures), in the EPOS architecture. Following the preparatory phase, EPOS has initiated formal steps to adopt an ERIC legal framework (European Research Infrastructure Consortium). The statutory seat of EPOS will be in Rome, Italy, while the ICS-C will be jointly operated by France, UK and Denmark. The TCS planned so far cover: seismology, near-fault observatories, GNSS data and products, volcano observations, satellite data, geomagnetic observations, anthropogenic hazards, geological information modelling, multiscale laboratories and geo-energy test beds for low carbon energy. In the ERIC process, EPOS and all its services must achieve sustainability from a legal, governance, financial, and technical point of view, as well as full harmonization with national infrastructure roadmaps. As EPOS is a distributed infrastructure, the TCSs have to be linked to the future EPOS ERIC from legal and governance perspectives. For this purpose the TCSs have started to organize themselves as consortia and negotiate agreements to define the roles of the different actors in the consortium as well as their commitment to contribute to the EPOS activities. The link to the EPOS ERIC shall be made by service agreements of dedicated Service Providers. A common EPOS data policy has also been developed, based on the general principles of Open Access and paying careful attention to licensing issues, quality control, and intellectual property rights, which shall apply to the data, data products

  17. Subchronic safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis stimulating agent, after 5-week subcutaneous injection in Cynomolgus monkeys and Sprague-Dawley rats.

    Science.gov (United States)

    Gong, Xue-Lian; Zhang, Xiao-Dong; Li, Juan; Zhang, Xiao-Fang; Zong, Ying; Lu, Guo-Cai; Yuan, Bo-Jun

    2013-10-01

    EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is coupled to polyethylene glycol (PEG) and designed to specifically bind and activate the erythropoietin (EPO) receptor to result in production of red blood cells. This study was designed to evaluate the potential subchronic toxicity of EPO-018B for Cynomolgus monkeys and Sprague-Dawley rats both at 0, 0.5, 5 and 50 mg/kg every week for 5 weeks, followed by 6-week recovery for rats and 12-week recovery for monkeys. The No Observed Adverse Effect Level (NOAEL) for rats and monkeys were both considered to be at least 0.5 mg/kg/day, the minimum toxic dose to be 5.0 mg/kg/day and the severe toxic dose to be more than 50.0 mg/kg/day. The toxicological effects included the exaggerated pharmacology and secondary sequelae that resulted from an erythropoiesis-stimulating agent treatment to healthy animals. Most treatment induced effects were reversible or showed ongoing recovery upon discontinuation of treatment. The anticipated patient population for EPO-018B treatment is targeted to be the anemia patients caused by chronic renal failure or chemotherapy against to cancer and is expected to have an ideal clinical application prospect.

  18. Mimicking hypoxia to treat anemia: HIF-stabilizer BAY 85-3934 (Molidustat stimulates erythropoietin production without hypertensive effects.

    Directory of Open Access Journals (Sweden)

    Ingo Flamme

    Full Text Available Oxygen sensing by hypoxia-inducible factor prolyl hydroxylases (HIF-PHs is the dominant regulatory mechanism of erythropoietin (EPO expression. In chronic kidney disease (CKD, impaired EPO expression causes anemia, which can be treated by supplementation with recombinant human EPO (rhEPO. However, treatment can result in rhEPO levels greatly exceeding the normal physiological range for endogenous EPO, and there is evidence that this contributes to hypertension in patients with CKD. Mimicking hypoxia by inhibiting HIF-PHs, thereby stabilizing HIF, is a novel treatment concept for restoring endogenous EPO production. HIF stabilization by oral administration of the HIF-PH inhibitor BAY 85-3934 (molidustat resulted in dose-dependent production of EPO in healthy Wistar rats and cynomolgus monkeys. In repeat oral dosing of BAY 85-3934, hemoglobin levels were increased compared with animals that received vehicle, while endogenous EPO remained within the normal physiological range. BAY 85-3934 therapy was also effective in the treatment of renal anemia in rats with impaired kidney function and, unlike treatment with rhEPO, resulted in normalization of hypertensive blood pressure in a rat model of CKD. Notably, unlike treatment with the antihypertensive enalapril, the blood pressure normalization was achieved without a compensatory activation of the renin-angiotensin system. Thus, BAY 85-3934 may provide an approach to the treatment of anemia in patients with CKD, without the increased risk of adverse cardiovascular effects seen for patients treated with rhEPO. Clinical studies are ongoing to investigate the effects of BAY 85-3934 therapy in patients with renal anemia.

  19. The EPOS Legal and Governance Framework : tailoring the infrastructure to fit the needs of the EPOS services

    Science.gov (United States)

    Kohler, Elisabeth; Pedersen, Helle; Kontkanen, Pirjo; Korja, Annakaisa; Lauterjung, Jörn; Haslinger, Florian; Sangianantoni, Agata; Bartolini, Alessandro; Consortium, Epos

    2016-04-01

    One of the most important issues regarding a pan-European distributed large scale research infrastructure is the setting up of its legal and governance structure as this will shape the very operation of the undertaking, i.e. the decision-making process, the allocation of tasks and resources as well as the relationship between the different bodies. Ensuring long-term operational services requires a robust, coherent and transparent legal and governance framework across all of the EPOS TCS (Thematic Core Services) and ICS (Integrated Core Services) that is well aligned to the EPOS global architecture. The chosen model for the EPOS legal entity is the ERIC (European Research Infrastructure Consortium). While the statutory seat of EPOS-ERIC will be in Rome, Italy, most of the services will be hosted in other countries. Specific agreements between EPOS-ERIC and the legal bodies hosting EPOS services will be implemented to allow proper coordination of activities. The objective is to avoid multiple agreements and, where possible, to standardize them in order to reach a harmonized situation across all services. For the governance careful attention will be paid to the decision-making process, the type of decisions and the voting rights, the definition of responsibilities, rights and duties, the reporting mechanisms, as well as other issues like who within a TCS represents the service to the 'outside' world or who advices the TCS on which subjects. Data policy is another crucial issue as EPOS aims to provide interdisciplinary services to researchers interested in geoscience, including access to data, metadata, data products, software and IT tools. EPOS also provides access to computational resources for visualization and processing. Beyond the general principles of Open Access and Open Source the following questions have to be addressed: scope and nature of data that will be accepted; intellectual property rights in data and terms under which data will be shared; openness and

  20. Advanced glycation end products in renal failure: an overview.

    Science.gov (United States)

    Noordzij, M J; Lefrandt, J D; Smit, A J

    2008-12-01

    The article aims to present an overview of the existing knowledge on advanced glycation end products (AGE). They are moieties that bind to proteins, but also lipids and nuclear acids. AGE are formed during glycation and oxidative stress. Accumulation of AGE occurs especially in diabetes and chronic renal failure and plays a major pathogenetic role. The deleterious effects of AGE result from cross-linking of proteins and activation of the receptor for advanced glycation end products. AGE accumulation can be noninvasively assessed by the skin autofluorescence reader. In diabetics, the skin autofluorescence predicts cardiac mortality and the occurrence of macro- and microvascular complications. In patients on haemodialysis, skin autofluorescence is highly elevated and predicts mortality. After renal transplantation AGE accumulation is lower than during haemodialysis, but still remains elevated and is a strong risk factor for chronic renal transplant dysfunction. Some of the potential methods to intervene with AGE accumulation are discussed in this article.

  1. Iron-hepcidin dysmetabolism, anemia and renal hypoxia, inflammation and fibrosis in the remnant kidney rat model.

    Directory of Open Access Journals (Sweden)

    Patrícia Garrido

    Full Text Available Anemia is a common complication of chronic kidney disease (CKD that develops early and its severity increases as renal function declines. It is mainly due to a reduced production of erythropoietin (EPO by the kidneys; however, there are evidences that iron metabolism disturbances increase as CKD progresses. Our aim was to study the mechanisms underlying the development of anemia of CKD, as well as renal damage, in the remnant kidney rat model of CKD induced by 5/6 nephrectomy. This model of CKD presented a sustained degree of renal dysfunction, with mild and advanced glomerular and tubulointerstitial lesions. Anemia developed 3 weeks after nephrectomy and persisted throughout the protocol. The remnant kidney was still able to produce EPO and the liver showed an increased EPO gene expression. In spite of the increased EPO blood levels, anemia persisted and was linked to low serum iron and transferrin levels, while serum interleukin (IL-6 and high sensitivity C-reactive protein (hs-CRP levels showed the absence of systemic inflammation. The increased expression of duodenal ferroportin favours iron absorption; however, serum iron is reduced which might be due to iron leakage through advanced kidney lesions, as showed by tubular iron accumulation. Our data suggest that the persistence of anemia may result from disturbances in iron metabolism and by an altered activity/function of EPO as a result of kidney cell damage and a local inflammatory milieu, as showed by the increased gene expression of different inflammatory proteins in the remnant kidney. In addition, this anemia and the associated kidney hypoxia favour the development of fibrosis, angiogenesis and inflammation that may underlie a resistance to EPO stimuli and reduced iron availability. These findings might contribute to open new windows to identify putative therapeutic targets for this condition, as well as for recombinant human EPO (rHuEPO resistance, which occurs in a considerable

  2. A lentiviral gene therapy strategy for the in vitro production of feline erythropoietin.

    Directory of Open Access Journals (Sweden)

    Natalia Vapniarsky

    Full Text Available Nonregenerative anemia due to chronic renal failure is a common problem in domestic cats. Unfortunately, administration of recombinant human erythropoietin often only improves anemia temporarily due to antibody development. In this in vitro study, feline erythropoietin cDNA was cloned from feline renal tissue and utilized in the construction of a replication-defective lentiviral vector. The native recombinant feline erythropoietin (rfEPO sequence was confirmed by sequencing. Upon viral vector infection of human 293H cells, Crandall Renal Feline Kidney cell line and primary feline peripheral blood mononuclear cells, bioactive rfEPO protein was produced. The presence of cellular rfEPO cDNA was confirmed by standard PCR, production of abundant rfEPO mRNA was confirmed by real-time PCR, and secretion of rfEPO protein was demonstrated by Western blot analyses, while rfEPO protein bioactivity was confirmed via an MTT proliferation bioassay. This in vitro study demonstrates the feasibility of a replication-defective lentiviral vector delivery system for the in vitro production of biologically active feline erythropoietin. Anemic cats with chronic renal failure represent a potential in vivo application of a lentiviral gene therapy system.

  3. EPOS data and service provision to scientists and other stakeholders

    Science.gov (United States)

    Cocco, Massimo; EPOS Team

    2017-04-01

    EPOS brings together European nations and combines solid Earth science infrastructures and their associated data and services together with the scientific expertise into one integrated delivery system for solid Earth science. By improving and facilitating the integration, access, use, and re-use of solid Earth science data, data products, services and facilities EPOS is developing a holistic, sustainable, multidisciplinary research platform to provide coordinated access to harmonized and quality controlled data from diverse Earth science disciplines, together with tools for their use in analysis and modelling. EPOS has been designed with the vision of creating a single distributed pan-European infrastructure for solid Earth science to support a safe and sustainable society. In accordance with this scientific vision, the EPOS mission is to integrate the diverse and advanced European Research Infrastructures for solid Earth relying on new e-science opportunities to monitor and unravel the dynamic and complex Earth System. EPOS is presently in its implementation phase, which consists of the EPOS IP project and the legal establishment of EPOS-ERIC. The EPOS Implementation Phase builds on the achievements of the successful EPOS Preparatory Phase project. The EPOS implementation phase will last from 2015 to 2019. The key objectives of the project are: implementing Thematic Core Services (TCS), the domain-specific service hubs for coordinating and harmonizing national resources/plans with the European dimension of EPOS; building the Integrated Core Services (ICS) to provide a novel research platform to different stakeholders; designing the access to distributed computational resources (ICS-D); ensuring sustainability and governance of TCS and EPOS-ERIC. Here we present the activities planned for the implementation phase focusing on the TCS, the ICS and on their interoperability. We will present and discuss the data and service provision focusing on the data, data-products

  4. The EPOS e-Infrastructure

    Science.gov (United States)

    Jeffery, Keith; Bailo, Daniele

    2014-05-01

    The European Plate Observing System (EPOS) is integrating geoscientific information concerning earth movements in Europe. We are approaching the end of the PP (Preparatory Project) phase and in October 2014 expect to continue with the full project within ESFRI (European Strategic Framework for Research Infrastructures). The key aspects of EPOS concern providing services to allow homogeneous access by end-users over heterogeneous data, software, facilities, equipment and services. The e-infrastructure of EPOS is the heart of the project since it integrates the work on organisational, legal, economic and scientific aspects. Following the creation of an inventory of relevant organisations, persons, facilities, equipment, services, datasets and software (RIDE) the scale of integration required became apparent. The EPOS e-infrastructure architecture has been developed systematically based on recorded primary (user) requirements and secondary (interoperation with other systems) requirements through Strawman, Woodman and Ironman phases with the specification - and developed confirmatory prototypes - becoming more precise and progressively moving from paper to implemented system. The EPOS architecture is based on global core services (Integrated Core Services - ICS) which access thematic nodes (domain-specific European-wide collections, called thematic Core Services - TCS), national nodes and specific institutional nodes. The key aspect is the metadata catalog. In one dimension this is described in 3 levels: (1) discovery metadata using well-known and commonly used standards such as DC (Dublin Core) to enable users (via an intelligent user interface) to search for objects within the EPOS environment relevant to their needs; (2) contextual metadata providing the context of the object described in the catalog to enable a user or the system to determine the relevance of the discovered object(s) to their requirement - the context includes projects, funding, organisations

  5. The EPOS Implementation Phase: building thematic and integrated services for solid Earth sciences

    Science.gov (United States)

    Cocco, Massimo; Epos Consortium, the

    2015-04-01

    The European Plate Observing System (EPOS) has a scientific vision and approach aimed at creating a pan-European infrastructure for Earth sciences to support a safe and sustainable society. To follow this vision, the EPOS mission is integrating a suite of diverse and advanced Research Infrastructures (RIs) in Europe relying on new e-science opportunities to monitor and understand the dynamic and complex Earth system. To this goal, the EPOS Preparatory Phase has designed a long-term plan to facilitate integrated use of data and products as well as access to facilities from mainly distributed existing and new research infrastructures for solid Earth Science. EPOS will enable innovative multidisciplinary research for a better understanding of the Earth's physical processes that control earthquakes, volcanic eruptions, ground instability and tsunami as well as the processes driving tectonics and Earth surface dynamics. Through integration of data, models and facilities EPOS will allow the Earth Science community to make a step change in developing new concepts and tools for key answers to scientific and socio-economic questions concerning geo-hazards and geo-resources as well as Earth sciences applications to the environment and to human welfare. Since its conception EPOS has been built as "a single, Pan-European, sustainable and distributed infrastructure". EPOS is, indeed, the sole infrastructure for solid Earth Science in ESFRI and its pan-European dimension is demonstrated by the participation of 23 countries in its preparatory phase. EPOS is presently moving into its implementation phase further extending its pan-European dimension. The EPOS Implementation Phase project (EPOS IP) builds on the achievements of the successful EPOS preparatory phase project. The EPOS IP objectives are synergetic and coherent with the establishment of the new legal subject (the EPOS-ERIC in Italy). EPOS coordinates the existing and new solid Earth RIs within Europe and builds the

  6. EPO's alter ego: erythropoietin has multiple actions.

    Science.gov (United States)

    Lappin, Terence R; Maxwell, A Peter; Johnston, Patrick G

    2002-01-01

    Many cancer patients suffer from anemia, which has a major detrimental effect on their quality of life. Recombinant human erythropoietin (rHuEPO) is now widely used in cancer patients, as it improves hematocrit, lowers blood transfusion requirements, and improves quality of life. Recent research indicates that EPO has pleiotropic effects on the body well beyond the maintenance of red cell mass, but the mechanisms involved in relieving fatigue and improving quality of life in cancer patients are poorly understood. EPO receptors (EPO-Rs) have been detected in many different cells and tissues, providing evidence for autocrine, paracrine, and endocrine functions of EPO. Apart from its endocrine function, EPO may have a generalized role as an antiapoptotic agent that is associated with enhancement of muscle tone, mucosal status, and gonadal and cognitive function. The recent discovery of EPO-Rs in breast tumor vasculature, while raising important questions about the possible effects of pharmacological doses of rHuEPO on tumor cells, also suggests that the receptors could provide a useful target for drugs attached to EPO.

  7. Accumulation of advanced glycation end products, measured as skin autofluorescence, in renal disease

    NARCIS (Netherlands)

    Hartog, JWL; De Vries, APJ; Lutgers, HL; Meerwaldt, R; Huisman, RM; Van Son, WJ; De Jong, PE; Smit, AJ; Baynes, JW; Monnier, VM; Ames, JM; Thorpe,

    2005-01-01

    Advanced glycation end products (AGEs) accumulate during renal failure and dialysis. Kidney transplantation is thought to reverse this accumulation by restoring renal function. Using a noninvasive and validated autofluorescence reader, we evaluated AGE levels in 285 transplant recipients (mean age,

  8. Accumulation of advanced glycation end products, measured as skin autofluorescence, in renal disease

    NARCIS (Netherlands)

    Hartog, JWL; De Vries, APJ; Lutgers, HL; Meerwaldt, R; Huisman, RM; Van Son, WJ; De Jong, PE; Smit, AJ; Baynes, JW; Monnier, VM; Ames, JM; Thorpe,

    2005-01-01

    Advanced glycation end products (AGEs) accumulate during renal failure and dialysis. Kidney transplantation is thought to reverse this accumulation by restoring renal function. Using a noninvasive and validated autofluorescence reader, we evaluated AGE levels in 285 transplant recipients (mean age,

  9. Erythropoietin (EPO) increases myelin gene expression in CG4 oligodendrocyte cells through the classical EPO receptor.

    Science.gov (United States)

    Cervellini, Ilaria; Annenkov, Alexander; Brenton, Thomas; Chernajovsky, Yuti; Ghezzi, Pietro; Mengozzi, Manuela

    2013-08-28

    Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in nonhematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein [MOG] and myelin basic protein [MBP]). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by Western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects.

  10. Epo is relevant neither for microvascular formation nor for the new formation and maintenance of mice skeletal muscle fibres in both normoxia and hypoxia.

    Science.gov (United States)

    Hagström, Luciana; Agbulut, Onnik; El-Hasnaoui-Saadani, Raja; Marchant, Dominique; Favret, Fabrice; Richalet, Jean-Paul; Beaudry, Michèle; Launay, Thierry

    2010-01-01

    Erythropoietin (Epo) and vascular growth factor (VEGF) are known to be involved in the regulation of cellular activity when oxygen transport is reduced as in anaemia or hypoxic conditions. Because it has been suggested that Epo could play a role in skeletal muscle development, regeneration, and angiogenesis, we aimed to assess Epo deficiency in both normoxia and hypoxia by using an Epo-deficient transgenic mouse model (Epo-TAg(h)). Histoimmunology, ELISA and real time RT-PCR did not show any muscle fiber atrophy or accumulation of active HIF-1alpha but an improvement of microvessel network and an upregulation of VEGFR2 mRNA in Epo-deficient gastrocnemius compared with Wild-Type one. In hypoxia, both models exhibit an upregulation of VEGF120 and VEGFR2 mRNA but no accumulation of Epo protein. EpoR mRNA is not up-regulated in both Epo-deficient and hypoxic gastrocnemius. These results suggest that muscle deconditioning observed in patients suffering from renal failure is not due to Epo deficiency.

  11. Epo Is Relevant Neither for Microvascular Formation Nor for the New Formation and Maintenance of Mice Skeletal Muscle Fibres in Both Normoxia and Hypoxia

    Directory of Open Access Journals (Sweden)

    Luciana Hagström

    2010-01-01

    Full Text Available Erythropoietin (Epo and vascular growth factor (VEGF are known to be involved in the regulation of cellular activity when oxygen transport is reduced as in anaemia or hypoxic conditions. Because it has been suggested that Epo could play a role in skeletal muscle development, regeneration, and angiogenesis, we aimed to assess Epo deficiency in both normoxia and hypoxia by using an Epo-deficient transgenic mouse model (Epo-TAgh. Histoimmunology, ELISA and real time RT-PCR did not show any muscle fiber atrophy or accumulation of active HIF-1 but an improvement of microvessel network and an upregulation of VEGFR2 mRNA in Epo-deficient gastrocnemius compared with Wild-Type one. In hypoxia, both models exhibit an upregulation of VEGF120 and VEGFR2 mRNA but no accumulation of Epo protein. EpoR mRNA is not up-regulated in both Epo-deficient and hypoxic gastrocnemius. These results suggest that muscle deconditioning observed in patients suffering from renal failure is not due to Epo deficiency.

  12. Building thematic and integrated services for solid Earth sciences: the EPOS integrated approach

    Science.gov (United States)

    Cocco, Massimo; Consortium, Epos

    2016-04-01

    Services (ICS) to provide a novel research platform to different stakeholders; designing the access to distributed computational resources (ICS-d); ensuring sustainability and governance of TCS and EPOS-ERIC. The research infrastructures (RIs) that EPOS is coordinating include: i) distributed geophysical observing systems (seismological and geodetic networks); ii) local observatories (including geomagnetic, near-fault and volcano observatories); iii) analytical and experimental laboratories; iv) integrated satellite data and geological information services; v) new services for natural and anthropogenic hazards; vi) access to geo-energy test beds. Here we present the activities planned for the implementation phase focusing on the TCS, the ICS and on their interoperability. We will discuss the data, data-products, software and services (DDSS) presently under implementation, which will be validated and tested during the project lifetime. Particular attention will be given to showing the progress toward the establishment of EPOS-ERIC Headquarter, to coordinate and harmonize national RIs and EPOS services, and the ICS central hub as a key contribution for providing multidisciplinary services for solid Earth science as well as the glue to keep ICT aspects integrated and rationalized across EPOS. It will be an important and timely opportunity to discuss the EPOS roadmap toward the operation of the novel multidisciplinary platform for discoveries to foster scientific excellence in solid Earth science.

  13. EPOS Thematic Core Service Anthropogenic Hazards: Implementation Plan

    Science.gov (United States)

    Orlecka-Sikora, Beata; Lasocki, Stanislaw; Grasso, Jean Robert; Schmittbuhl, Jean; Styles, Peter; Kwiatek, Grzegorz; Sterzel, Mariusz; Garcia, Alexander

    2015-04-01

    EPOS Thematic Core Service ANTHROPOGENIC HAZARDS (TCS AH) aims to integrate distributed research infrastructures (RI) to facilitate and stimulate research on anthropogenic hazards (AH) especially those associated with the exploration and exploitation of geo-resources. The innovative element is the uniqueness of the integrated RI which comprises two main deliverables: (1) Exceptional datasets, called "episodes", which comprehensively describe a geophysical process; induced or triggered by human technological activity, posing hazard for populations, infrastructure and the environment, (2) Problem-oriented, bespoke services uniquely designed for the discrimination and analysis of correlations between technology, geophysical response and resulting hazard. These objectives will be achieved through the Science-Industry Synergy (SIS) built by EPOS WG10, ensuring bi-directional information exchange, including unique and previously unavailable data furnished by industrial partners. The Episodes and services to be integrated have been selected using strict criteria during the EPOS PP. The data are related to a wide spectrum of inducing technologies, with seismic/aseismic deformation and production history as a minimum data set requirement and the quality of software services is confirmed and referenced in literature. Implementation of TCS AH is planned for four years and requires five major activities: (1) Strategic Activities and Governance: will define and establish the governance structure to ensure the long-term sustainability of these research infrastructures for data provision through EPOS. (2) Coordination and Interaction with the Community: will establish robust communication channels within the whole TCS AH community while supporting global EPOS communication strategy. (3) Interoperability with EPOS Integrated Core Service (ICS) and Testing Activities: will coordinate and ensure interoperability between the RIs and the ICS. Within this modality a functional e

  14. NASA's Planetary Science E/PO Forum: Reflections on Five Years of Effort to Support an E/PO Community

    Science.gov (United States)

    Shipp, S. S.; Shebby, S.; Buxner, S.; Boonstra, D.; Cobabe-Ammann, E. A.; Cobb, W. H.; Dalton, H.; Grier, J.; Klug Boonstra, S. L.; LaConte, K.; Ristvey, J.; Shupla, C. B.; Weeks, S.; Wessen, A. S.; Zimmerman-Brachman, R.

    2014-12-01

    Over the past decade, NASA's Science Mission Directorate (SMD) has funded four education and public outreach (E/PO) forums, aligned with each of its science divisions, including Astrophysics, Earth Science, Heliophysics, and Planetary Science. Together, these forums help organize individual division E/PO programs into a coordinated, effective, efficient, nationwide effort that shares the scientific discoveries of NASA across a broad array of audiences. In the past four-and-a-half years, the Planetary Science Division's Forum - in collaboration with the other three Forums - has worked to support its community of education professionals and scientists involved in E/PO to communicate, collaborate, and strengthen their efforts. The Forum's work encompasses identification of best practices based on educational research, increasing understanding of needs through audience-based working groups, the development of strategic collaborations and partnerships to increase programmatic reach, and the creation of strategic resources to support community members in their E/PO work (e.g., an online workspace for the community to communicate, collaborate, and share practices; recommendations to scientists for increasing impact in educational settings; a one-stop shop for NASA SMD classroom and informal education products, http://nasawavelength.org). Drawing on evaluation data, the presentation will explore what resources and support mechanisms are valued by the community, ways the community uses the available resources, and the outcomes of the effort to date.

  15. Current status of the EPOS WG4 - GNSS and Other Geodetic Data

    Science.gov (United States)

    Fernandes, Rui; Bastos, Luísa; Bruyninx, Carine; D'Agostino, Nicola; Dousa, Jan; Ganas, Athanassios; Lidberg, Martin; Nocquet, Jean-Mathieu

    2013-04-01

    WG4 - "EPOS Geodetic Data and Other Geodetic Data" is the Working Group of the EPOS project in charge of defining and preparing the integration of the existing Pan-European Geodetic Infrastructures that will support the European Geosciences, which is the ultimate goal of the EPOS project. The WG4 is formed by representatives of the participating EPOS countries (23) but it is also open to the entire geodetic community. In fact, WG4 also includes members from countries that formally are not part of the current phase of EPOS. In an ongoing effort, the majority of existing GNSS Research Infrastructures in Europe were identified. The current database, available at http://epos-couch.cloudant.com/epos-couch/_design/epos-couch/, lists a total of 50 Research Infrastructures managing a total of 1534 GNSS CORS sites. This presentation intends to detail the work being produced within the working group WG4 related with the definition of strategies towards the implementation of the best solutions that will permit to the end-users, and in particular geo-scientists, to access the geodetic data, derived solutions, and associated metadata using transparent and uniform processes. The first step toward the design of an implementation and business plan is the definition of the core services for geodetic data within EPOS. In this talk, we will present the current status of the discussion about the content of core services. Three levels of core services could be distinguished, for which their content need to be defined. The 3 levels are: (1) the core services associated to data (diffusion, archive, long-term preservation, quality check, rapid analysis) (2) core services associated to geodetic products (analysis, products definition like position time series, velocity field and Zenithal Total Delay) (3) User oriented services (reference frames, real-time solutions for early warning systems, strain rate maps, meteorology, space weather, …). Current propositions and remaining open

  16. The Demonstrator for the European Plate Observing System (EPOS)

    Science.gov (United States)

    Hoffmann, T. L.; Euteneuer, F.; Ulbricht, D.; Lauterjung, J.; Bailo, D.; Jeffery, K. G.

    2014-12-01

    An important outcome of the 4-year Preparatory Phase of the ESFRI project European Plate Observing System (EPOS) was the development and first implementation of the EPOS Demonstrator by the project's ICT Working Group 7. The Demonstrator implements the vertical integration of the three-layer architectural scheme for EPOS, connecting the Integrated Core Services (ICS), Thematic Core Services (TCS) and the National Research Infrastructures (NRI). The demonstrator provides a single GUI with central key discovery and query functionalities, based on already existing services by the seismic, geologic and geodetic communities. More specifically the seismic services of the Demonstrator utilize webservices and APIs for data and discovery of raw seismic data (FDSN webservices by the EIDA Network), events (Geoportal by EMSC) and analytical data products (e.g., hazard maps by EFEHR via OGC WMS). For geologic services, the EPOS Demonstrator accesses OneGeology Europe which serves the community with geologic maps and point information via OGC webservices. The Demonstrator also provides access to raw geodetic data via a newly developed universal tool called GSAC. The Demonstrator itself resembles the future Integrated Core Service (ICS) and provides direct access to the end user. Its core functionality lies in a metadata catalogue, which serves as the central information hub and stores information about all RIs, related persons, projects, financial background and technical access information. The database schema of the catalogue is based on CERIF, which has been slightly adapted. Currently, the portal provides basic query functions as well as cross domain search. [www.epos.cineca.it

  17. Methylation impact analysis of erythropoietin (EPO) Gene to hypoxia inducible factor-1α (HIF-1α) activity.

    Science.gov (United States)

    Dewi, Firli Rahmah Primula; Fatchiyah, Fatchiyah

    2013-01-01

    Erythropoietin (EPO) is a glycoprotein hormone that play a role as key regulator in the production of red blood cells. The promoter region of EPO is methylated in normoxic (non-hypoxia) condition, but not in hypoxic condition. Methylation of the EPO enhancer region decline the transcription activity of EPO gene. The aim of this study is to investigate how different methylation percentage affected on the regulation and transcriptional activity of EPO gene. The DNA sequence of erythropoietin gene and protein sequence was retrieved from the sequence database of NCBI. DNA structure was constructed using 3D-DART web server and modeling structure of HIF1 predicted using SWISS-MODEL web server. Methylated DNA sequence of EPO gene using performed with YASARA View software and docking of EPO gene and transcription factor HIF1 analyzed by using HADDOCK webserver. Our result showed that binding energy in 46% methylated DNA was higher (-161,45 kcal/mol) than in unmethylated DNA (-194,16 kcal/mol) and 8% methylated DNA (-175,94 kcal/mol). So, we presume that a silencing mechanism of the Epo gene by methylation is correlated with the binding energy, which is required for interaction. A higher methylation percentage correlates with a higher binding energy which can cause an unstable interaction between DNA and transcription factor. In conclution, methylation of promoter and enhancer region of Epo gene leads to silencing.

  18. 左旋卡尼汀联合应用EPO治疗肾性贫血临床观察%The clinic treatment effect of L-carnitine and EPO on renal anemia in hemodialysis patien

    Institute of Scientific and Technical Information of China (English)

    苏华丰; 梁宇

    2009-01-01

    目的:观察左旋卡尼汀联合应用促红细胞生成素(EPO)治疗肾性贫血的疗效观察.方法:30例维持性血液透析患者随机分为两组,A组给予EPO及左旋卡尼汀治疗,B组给予EPO及等容积生理盐水作为对照,治疗前、后第4,8周测定血红蛋白及血细胞比容.结果:A组患者的血红蛋白及血细胞比容水平显著高于B组(P<0.05),且A组的EPO平均用量明显少于B组(P<0.05).结论:左旋卡尼汀联合应用EPO可以改善肾性贫血.提高EPO疗效,可以减少EPO的用量.

  19. A dominant negative erythropoietin (EPO) receptor inhibits EPO-dependent growth and blocks F-gp55-dependent transformation.

    OpenAIRE

    Barber, D L; DeMartino, J C; Showers, M O; D'Andrea, A D

    1994-01-01

    The erythropoietin receptor (EPO-R), a member of the cytokine receptor superfamily, can be activated to signal cell growth by binding either EPO or F-gp55, the Friend spleen focus-forming virus glycoprotein. Activation by F-gp55 results in constitutive EPO-R signalling and the first stage of Friend virus-induced erythroleukemia. We have generated a truncated form of the EPO-R polypeptide [EPO-R(T)] which lacks the critical cytoplasmic signal-transducing domain of the EPO-R required for EPO- o...

  20. RIDE: the Research Infrastructure Database for EPOS

    Science.gov (United States)

    Bailo, Daniele; Bartoloni, Alessandro; Jeffery, Keith G.; Clemenceau, Alice; Hoffmann, Thomas L.

    2013-04-01

    The European Plate Observing System (EPOS) is a European initiative which aims to promote and make possible innovative approaches for a better understanding of the physical processes laying behind natural events and geo-science phenomena (earthquakes, volcanic eruptions, unrest episodes and tsunamis etc.) by integrating existing national and trans-national Research Infrastructures (RIs). Such integration will increase access and use of the multidisciplinary data recorded by solid Earth monitoring networks, acquired in laboratory experiments and/or produced by computational simulations. Here we present the Research Infrastructures Database for EPOS (RIDE), a database containing technical information about the different RIs declared by EPOS partners and EPOS associate partners, which will eventually compose the EPOS distributed Research Infrastructure. The main goals of RIDE are (i) to allow the EPOS RI to be organized, with interactive access and information mining available to a broad community of users and stakeholders, (ii) to have a first set of information to be stored in the EPOS catalogue, which will be used as a basis for the development of EPOS Core Services, (iii) to enable EPOS partners to revise and update the current RI information, (iv) to show the contents of the EPOS integration plan to all stakeholders, (v) to facilitate the dissemination of existing data infrastructures to different communities and to promote a discussion within the community to implement the present data infrastructures. RIDE - whose driving technology is Apache CouchDB - contains at the current status detailed information on more than 200 Research Infrastructures. It enables any user to visualize RIs and sensors on a map, to carry out statistics on the stored data and to browse through the details of any RI. Based on the content of RIDE it is now possible to estimate the potential size of the new EPOS distributed RI: EPOS is going to integrate more than 7000 sensors (seismic

  1. EPOS-S: Integrated access to seismological waveforms

    Science.gov (United States)

    Sleeman, Reinoud; Strollo, Angelo; Michelini, Alberto; Clinton, John; Gueguen, Philippe; Luzi, Lucia; Pinar, Ali; Diaz, Jordi; Ceken, Ulubey; Evangelidis, Christos; Haslinger, Florian

    2016-04-01

    The main challenges of the EPOS TCS Seismology are to improve and to extend existing services to access earthquake waveforms (ORFEUS), parameters (EMSC) and hazard data and products (EFEHR), and producing a single framework that is technically integrated within the EPOS architecture. Technical developments in the services for seismological waveforms and associated data, including the compilation of station metadata and installing common data archival and sharing policies are within ORFEUS and its Working Groups. The focus is on 1) the development of the next generation software architecture for the European Integrated (seismological) Data Archive EIDA based on standardized webservices, the implementation of a data quality service and the realisation of a mediator service; 2) the development of EIDA-compliant services for strong motion data and acceleration data and the extension of the station metadata model; 3) the integration of data from mobile networks and OBS waveforms into EIDA by implementing mechanisms for coordination of transnational access and multinational experiments at available pools of OBS and mobile seismic stations; 4) achieve close integration with other EPOS TCS and the ICS with regard to interoperability and common use of tools & services, common and coordinated data models and metadata formats, and common computational platforms and IT solution implementations. This presentation will present the status of and current developments towards the above objectives.

  2. The role of renal adenosine 3',5'-monophosphate in the control of erythropoietin production.

    Science.gov (United States)

    Rodgers, G M; Fisher, J W; George, W J

    1975-01-01

    A regulatory role for adenosine 3',5'-monophosphate (cyclic AMP) in the production of the renal hormone rythropoietin following erythropoietic stimulation with cobaltous chloride hexahydrate is proposed. Studies in rates reveal a temporal relationship between renal cyclic AMP levels and plasma titers of erythropoietin. In addition, cobalt increases the activity of an erythropoietin-generating enzyme (renal erythropoietic factor) with maximal enzyme activity occurring after the rise in cyclic AMP levels but before the increase in erythropoietin titers. This increase in renal cyclic AMP is localized to the renal cortex. Cobalt stimulates renal cortical adenylate cyclase but has no effect on renal cyclic nucleotide phosphodiesterase. The addition of cyclic AMP (3 time 10-6 M) and a partially purified cyclic AMP-dependent protein kinase from rat kidney to an inactive preparation of renal erythropoietic factor increases the ability of renal erythropoietic factor to generate erythropoietin. Data from the polycythemic mouse assay, a bioassay used to quantitate erythropoietic activity of test substances, indicate that dibutyryl cyclic AMP is erythropoietically active with respect to its ability to increase radioactive-labelled iron (59Fe) incorporation into heme of newly formed red blood cells. Theophylline, which by itself is erythropoietically inactive, potentiated the erythropoietic effect of cobalt in polycythemic mice. These results suggest that cyclic AMP plays a significant role in the renal production of erythropoietin following cobalt administration. It is postulated that cobalt stimulates renal cortical adenyoate cyclase, thus increasing renal cyclic AMP levels. Cyclic AMP then activates a protein kinase which subsequently stimulates renal erythropoietic factor to generate erythropoietin. A similar cyclic AMP mechanism may be operative after erythropoietic stimulation by exposure to hypoxia or prostaglandin treatment.

  3. NASA Astrophysics EPO Community: Enhancing STEM Instruction

    Science.gov (United States)

    Bartolone, L.; Manning, J.; Lawton, B.; Meinke, B. K.; Smith, D. A.; Schultz, G.; NASA Astrophysics EPO community

    2015-11-01

    The NASA Science Mission Directorate (SMD) Astrophysics Education and Public Outreach (EPO) community and Forum work together to capitalize on the cutting-edge discoveries of NASA Astrophysics missions to enhance Science, Technology, Engineering, and Math (STEM) instruction. In 2010, the Astrophysics EPO community identified online professional development for classroom educators and multiwavelength resources as a common interest and priority for collaborative efforts. The result is NASA's Multiwavelength Universe, a 2-3 week online professional development experience for classroom educators. The course uses a mix of synchronous sessions (live WebEx teleconferences) and asynchronous activities (readings and activities that educators complete on their own on the Moodle, and moderated by course facilitators). The NASA SMD Astrophysics EPO community has proven expertise in providing both professional development and resources to K-12 Educators. These mission- and grant-based EPO programs are uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise. We present examples of how the NASA Astrophysics EPO community and Forum engage the K-12 education community in these ways, including associated metrics and evaluation findings.

  4. Substrate specificity of the acyl transferase domains of EpoC from the epothilone polyketide synthase.

    Science.gov (United States)

    Petković, Hrvoje; Sandmann, Axel; Challis, Iain R; Hecht, Hans-Jürgen; Silakowski, Barbara; Low, Lindsey; Beeston, Nicola; Kuscer, Enej; Garcia-Bernardo, Jose; Leadlay, Peter F; Kendrew, Steven G; Wilkinson, Barrie; Müller, Rolf

    2008-02-07

    The production of epothilone mixtures is a direct consequence of the substrate tolerance of the module 3 acyltransferase (AT) domain of the epothilone polyketide synthase (PKS) which utilises both malonyl- and methylmalonyl-CoA extender units. Particular amino acid motifs in the active site of AT domains influence substrate selection for methylmalonyl-CoA (YASH) or malonyl-CoA (HAFH). This motif appears in hybrid form (HASH) in epoAT3 and may represent the molecular basis for the relaxed specificity of the domain. To investigate this possibility the AT domains from modules 2 and 3 of the epothilone PKS were examined in the heterologous DEBS1-TE model PKS. Substitution of AT1 of DEBS1-TE by epoAT2 and epoAT3 both resulted in functional PKSs, although lower yields of total products were observed when compared to DEBS1-TE (2% and 11.5% respectively). As expected, epoAT3 was significantly more promiscuous in keeping with its nature during epothilone biosynthesis. When the mixed motif (HASH) of epoAT3 within the hybrid PKS was mutated to HAFH (indicative of malonyl-CoA selection) it resulted in a non-productive PKS. When this mixed motif was converted to YASH (indicative of methylmalonyl-CoA selection) the selectivity of the hybrid PKS for methylmalonyl-CoA showed no statistically significant increase, and was associated with a loss of productivity.

  5. Urinary collagen degradation products as early markers of progressive renal fibrosis

    DEFF Research Database (Denmark)

    Hijmans, Ryanne S.; Rasmussen, Daniel Guldager Kring; Yazdani, Saleh

    2017-01-01

    Background: Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrot...

  6. The EPOS Automated Selective Chemistry Analyzer evaluated.

    Science.gov (United States)

    Moses, G C; Lightle, G O; Tuckerman, J F; Henderson, A R

    1986-01-01

    We evaluated the analytical performance of the EPOS (Eppendorf Patient Oriented System) Automated Selective Chemistry Analyzer, using the following tests for serum analytes: alanine and aspartate aminotransferases, lactate dehydrogenase, creatine kinase, gamma-glutamyltransferase, alkaline phosphatase, and glucose. Results from the EPOS correlated well with those from comparison instruments (r greater than or equal to 0.990). Precision and linearity limits were excellent for all tests; linearity of the optical and pipetting systems was satisfactory. Reagent carryover was negligible. Sample-to-sample carryover was less than 1% for all tests, but only lactate dehydrogenase was less than the manufacturer's specified 0.5%. Volumes aspirated and dispensed by the sample and reagent II pipetting systems differed significantly from preset values, especially at lower settings; the reagent I system was satisfactory at all volumes tested. Minimal daily maintenance and an external data-reduction system make the EPOS a practical alternative to other bench-top chemistry analyzers.

  7. Reflecting and Strategizing about Measuring EPO Impact

    Science.gov (United States)

    Bartolone, L.; Nichols-Yehling, M.; Peticolas, L.; Schultz, G.; Smith, D.; Schwerin, T.; Shipp, S.

    2014-07-01

    This paper is a result of a Special Interest Group workshop held at the Astronomical Society of the Pacific Annual Meeting on July 23, 2013. Members of the NASA Science Mission Directorate Education and Public Outreach (EPO) community and other EPO professionals reflected on program impacts across the spectrum of EPO. Questions considered during the workshop included the following: What have we learned from our work? How have we measured program impacts? How can we collaborate to determine next best steps for collectively measuring impact? How can our individual programs and projects contribute towards a better understanding of the impact we are able to have as a community across a range of federal and non-federal funding sources? This paper is a summary of the discussion.

  8. Erythropoietin (EPO): EPO-receptor signaling improves early endochondral ossification and mechanical strength in fracture healing.

    Science.gov (United States)

    Holstein, Joerg H; Menger, Michael D; Scheuer, Claudia; Meier, Christoph; Culemann, Ulf; Wirbel, Rainer J; Garcia, Patric; Pohlemann, Tim

    2007-02-13

    Beyond its role in the regulation of red blood cell proliferation, the glycoprotein erythropoietin (EPO) has been shown to promote cell regeneration and angiogenesis in a variety of different tissues. In addition, EPO has been indicated to share significant functional and structural homologies with the vascular endothelial growth factor (VEGF), a cytokine essential in the process of fracture healing. However, there is complete lack of information on the action of EPO in bone repair and fracture healing. Therefore, we investigated the effect of EPO treatment on bone healing in a murine closed femur fracture model using radiological, histomorphometric, immunohistochemical, biomechanical and protein biochemical analysis. Thirty-six SKH1-hr mice were treated with daily i.p. injections of 5000 U/kg EPO from day 1 before fracture until day 4 after fracture. Controls received equivalent amounts of the vehicle. After 2 weeks of fracture healing, we could demonstrate expression of the EPO-receptor (EPOR) in terminally differentiating chondrocytes within the callus. At this time point EPO-treated animals showed a higher torsional stiffness (biomechanical analysis: 39.6+/-19.4% of the contralateral unfractured femur) and an increased callus density (X-ray analysis (callus density/spongiosa density): 110.5+/-7.1%) when compared to vehicle-treated controls (14.3+/-8.2% and 105.9+/-6.6%; pEPO treatment had vanished at 5 weeks after fracture. We conclude that EPO-EPOR signaling is involved in the process of early endochondral ossification, enhancing the transition of soft callus to hard callus.

  9. Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

    Science.gov (United States)

    Cakiroglu, Figen; Enders-Comberg, Sora Maria; Pagel, Horst; Rohwedel, Jürgen; Lehnert, Hendrik; Kramer, Jan

    2016-03-01

    Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham-operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non-significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133- and CD34-positive EPC both in the peripheral blood and renal vessels.

  10. FIN-EPOS - Finnish national initiative of the European Plate Observing System: Bringing Finnish solid Earth infrastructures into EPOS

    Science.gov (United States)

    Vuorinen, Tommi; Korja, Annakaisa

    2017-04-01

    FIN-EPOS consortium is a joint community of Finnish national research institutes tasked with operating and maintaining solid-earth geophysical and geological observatories and laboratories in Finland. These national research infrastructures (NRIs) seek to join EPOS research infrastructure (EPOS RI) and further pursue Finland's participation as a founding member in EPOS ERIC (European Research Infrastructure Consortium). Current partners of FIN-EPOS are the University of Helsinki (UH), the University of and Oulu (UO), Finnish Geospatial Research Institute (FGI) of the National Land Survey (NLS), Finnish Meteorological Institute (FMI), Geological Survey of Finland (GTK), CSC - IT Center for Science and MIKES Metrology at VTT Technical Research Centre of Finland Ltd. The consortium is hosted by the Institute of Seismology, UH (ISUH). The primary purpose of the consortium is to act as a coordinating body between various NRIs and the EPOS RI. FIN-EPOS engages in planning and development of the national EPOS RI and will provide support in EPOS implementation phase (IP) for the partner NRIs. FIN-EPOS also promotes the awareness of EPOS in Finland and is open to new partner NRIs that would benefit from participating in EPOS. The consortium additionally seeks to advance solid Earth science education, technologies and innovations in Finland and is actively engaging in Nordic co-operation and collaboration of solid Earth RIs. The main short term objective of FIN-EPOS is to make Finnish geoscientific data provided by NRIs interoperable with the Thematic Core Services (TCS) in the EPOS IP. Consortium partners commit into applying and following metadata and data format standards provided by EPOS. FIN-EPOS will also provide a national Finnish language web portal where users are identified and their user rights for EPOS resources are defined.

  11. Oxidative stress induces the decline of brain EPO expression in aging rats.

    Science.gov (United States)

    Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

    2016-10-01

    Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of β-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (pEPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (pEPO (r=-0.701, pEPO in the hippocampus and oxidative stress might be the main reason for the decline of brain EPO in aging rats, involved with the decrease of HIF-2α stability.

  12. 抗重组人红细胞生成素(rhEPO)多克隆抗体的制备及其亲合常数(Kaff)的测定%PRODUCTION OF ANTI-RECOMBINANT HUMAN ERYTHROPOIETIN (rhEPO) POLYCOLONAL ANTIBODY AND DETERMINATION OF CONSTANT OF AFFINITY (Kaff)

    Institute of Scientific and Technical Information of China (English)

    闫瑾; 宓捷波; 郭振泉; 常文保

    2003-01-01

    @@ 人促红细胞生成素(EPO)是由肾脏分泌的一种单链酸性糖蛋白.相对分子质量为34 000D.蛋白质部分由165个氨基酸组成,糖部分由三条天门冬氨酸N末端糖链和一条丝氨酸O末端糖链构成其主要生理功能是刺激骨髓红细胞的生成与释放,促进血液中红细胞数量增多,提高血液的载氧能力.目前,通过基因重组技术获得的rhEPO已作为生物药品被广泛应用于临床治疗中同时由于其"兴奋剂"的作用,也被国际奥委会列为禁用药物抗重组人促红细胞生成素(rhEPO)多克隆抗体(pAb)的制备对EPO作用机制的研究和临床应用有重要的意义,是实现对其定量检测的物质基础我们采用rhEPO抗原直接免疫家兔的方法获得了含有rhEPO多克隆抗体的动物血清.经测定抗血清效价为10-5.抗血清经纯化后,采用系列稀释固定化抗原与抗体的酶联免疫吸附分析(ELISA)方法测定了抗体与固定化抗原作用的亲合常数(Kaff).

  13. Epo is involved in angiogenesis in human glioma.

    Science.gov (United States)

    Nico, Beatrice; Annese, Tiziana; Guidolin, Diego; Finato, Nicoletta; Crivellato, Enrico; Ribatti, Domenico

    2011-03-01

    In this study, the extent of angiogenesis, evaluated as microvascular density, and the immunoreactivity of tumor cells to erythropoietin (Epo) and of endothelial cells to Epo receptor (EpoR) have been correlated in human glioma specimens, and the effect of anti-Epo antibody on glioma-induced angiogenesis in vivo in the chick embryo chorioallantoic membrane (CAM) has been investigated. Results show that: (1) Epo/EpoR expression correlates with angiogenesis, (2) in the CAM assay, tumor bioptic specimens induce a strong angiogenic response, comparable to that induced by VEGF, and (3) an anti-Epo antibody co-administered with tumor bioptic specimens significantly inhibits the angiogenic response. These findings suggest the presence of a loop in the Epo/EpoR system, i.e. Epo is secreted by glioma tumor cells and it affects glioma vascular endothelial cells via its receptor and promotes angiogenesis in a paracrine manner. Moreover, as demonstrated by in vivo experiments, Epo is responsible for the strong angiogenic response induced by human glioma bioptic specimens, because an anti-Epo antibody is able to significantly inhibit this response.

  14. Potential of Novel EPO Derivatives in Limb Ischemia

    Directory of Open Access Journals (Sweden)

    Dhiraj Joshi

    2012-01-01

    Full Text Available Erythropoietin (EPO has tissue-protective properties, but it increases the risk of thromboembolism by raising the haemoglobin concentration. New generation of EPO derivatives is tissue protective without the haematopoietic side effects. Preclinical studies have demonstrated their effectiveness and safety. This paper summarizes the development in EPO derivatives with emphasis on their potential use in critical limb ischaemia.

  15. Efficient breathing at neonatal ages: A sex and Epo-dependent issue.

    Science.gov (United States)

    Iturri, Pablo; Bairam, Aida; Soliz, Jorge

    2016-12-29

    During postnatal life, the respiratory control system undergoes intense development and is highly responsive to stimuli emerging from the environment. In fact, interruption of breathing prevents gas exchange and results in systemic hypoxia that, if prolonged, can lead to cardio-respiratory failure or sudden infant death. Moreover, in newborns and infants, respiratory disorders related to neural control dysfunction show significant sexual dimorphism with a higher prevalence in males. To this day, the therapeutic tools available to alleviate these respiratory disorders remain limited. Furthermore, the factors explaining the sexual dimorphism in newborns and during infancy remain unknown. Erythropoietin (Epo) was originally discovered as a cytokine able to increase the production of red blood cells upon conditions of reduced oxygen availability. We now know that Epo is a cytokine also secreted by neurons and astrocytes that protects the brain during trauma or hypoxic stress in a sex dependent manner. In this novel line of research, our previous studies demonstrated at adult ages that cerebral Epo acts as a respiratory stimulant in rodents and humans. These results provided a strong rationale for exploring the role of cerebral Epo in neuronal respiratory control during postnatal development. The objective of this review is to summarize our recent findings showing that cerebral Epo is a potent sex-specific respiratory stimulant at neonatal ages. Keeping in mind that Epo is routinely and safely administrated in newborn humans for anemia and neonatal asphyxia, we predict that our research provides the basis necessary to promote the clinical use of Epo against neonatal respiratory disorders related to neural control dysfunction.

  16. Effect of mild-thiol reducing agents and alpha2,3-sialyltransferase expression on secretion and sialylation of recombinant EPO in CHO cells.

    Science.gov (United States)

    Chang, Kern Hee; Jeong, Yeon Tae; Kwak, Chan Yeong; Choi, One; Kim, Jung Hoe

    2013-05-01

    We have previously reported that N-acetylcysteine (NAC) not only delayed apoptosis but also enhanced the production of recombinant erythropoietin (EPO) in Chinese hamster ovary (CHO) cell culture. To investigate the production enhancement mechanism, the effects of similar thiolreducing agents were studied. Intriguingly, all mild reducing agents examined including mercaptoethanesulfonic acid (MESNA), thiolactic acid (TLA), and thioglycolate (TG) were shown to block apoptosis and increase EPO production. A pulse-chase study of EPO secretion revealed that all four thiol-reducing agents increased the EPO secretion rate; among them TLA showed the highest rate. In terms of product quality, the sialic acid content of the glycoprotein is one of the most important factors. It was reported that a number of glycoproteins produced by CHO cells often have incomplete sialylation, particularly under high-producing conditions. Human alpha2,3-sialyltransferase (alpha2,3-ST) was introduced into EPO-producing CHO cells in order to compensate for the reduced sialylation during supplementation with NAC. When alpha2,3-ST was expressed in the presence of NAC, reduced sialylation was restored and an even more sialylated EPO was produced. Thus, our study is significant in that it offers increased EPO production while still allowing the prevention of decreased sialylation of EPO.

  17. Synergistic upregulation of erythropoietin receptor (EPO-R) expression by sense and antisense EPO-R transcripts in the canine lung

    OpenAIRE

    Zhang, Quiyang; Zhang, Jianning; Moe, Orson W.; Hsia, Connie C. W.

    2008-01-01

    We previously found increased erythropoietin receptor (EPO-R) protein levels in vigorously growing canine lungs after pneumonectomy (PNX), suggesting a role for paracrine EPO signaling in lung growth and remodeling. Now we find that sense and antisense EPO-R transcripts (sEPO-R and asEPO-R, respectively) are concordantly up-regulated in the post-PNX remaining lung, leading to the hypothesis that sEPO-R and asEPO-R interactions enhance EPO signaling during lung growth. We cloned a canine asEPO...

  18. Endogenous fructose production and fructokinase activation mediate renal injury in diabetic nephropathy.

    Science.gov (United States)

    Lanaspa, Miguel A; Ishimoto, Takuji; Cicerchi, Christina; Tamura, Yoshifuru; Roncal-Jimenez, Carlos A; Chen, Wei; Tanabe, Katsuyuki; Andres-Hernando, Ana; Orlicky, David J; Finol, Esteban; Inaba, Shinichiro; Li, Nanxing; Rivard, Christopher J; Kosugi, Tomoki; Sanchez-Lozada, Laura G; Petrash, J Mark; Sautin, Yuri Y; Ejaz, A Ahsan; Kitagawa, Wataru; Garcia, Gabriela E; Bonthron, David T; Asipu, Aruna; Diggle, Christine P; Rodriguez-Iturbe, Bernardo; Nakagawa, Takahiko; Johnson, Richard J

    2014-11-01

    Diabetes is associated with activation of the polyol pathway, in which glucose is converted to sorbitol by aldose reductase. Previous studies focused on the role of sorbitol in mediating diabetic complications. However, in the proximal tubule, sorbitol can be converted to fructose, which is then metabolized largely by fructokinase, also known as ketohexokinase, leading to ATP depletion, proinflammatory cytokine expression, and oxidative stress. We and others recently identified a potential deleterious role of dietary fructose in the generation of tubulointerstitial injury and the acceleration of CKD. In this study, we investigated the potential role of endogenous fructose production, as opposed to dietary fructose, and its metabolism through fructokinase in the development of diabetic nephropathy. Wild-type mice with streptozotocin-induced diabetes developed proteinuria, reduced GFR, and renal glomerular and proximal tubular injury. Increased renal expression of aldose reductase; elevated levels of renal sorbitol, fructose, and uric acid; and low levels of ATP confirmed activation of the fructokinase pathway. Furthermore, renal expression of inflammatory cytokines with macrophage infiltration was prominent. In contrast, diabetic fructokinase-deficient mice demonstrated significantly less proteinuria, renal dysfunction, renal injury, and inflammation. These studies identify fructokinase as a novel mediator of diabetic nephropathy and document a novel role for endogenous fructose production, or fructoneogenesis, in driving renal disease.

  19. Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure.

    Science.gov (United States)

    Johnson, D W; Pat, B; Vesey, D A; Guan, Z; Endre, Z; Gobe, G C

    2006-05-01

    Administration of human recombinant erythropoietin (EPO) at time of acute ischemic renal injury (IRI) inhibits apoptosis, enhances tubular epithelial regeneration, and promotes renal functional recovery. The present study aimed to determine whether darbepoetin-alfa (DPO) exhibits comparable renoprotection to that afforded by EPO, whether pro or antiapoptotic Bcl-2 proteins are involved, and whether delayed administration of EPO or DPO 6 h following IRI ameliorates renal dysfunction. The model of IRI involved bilateral renal artery occlusion for 45 min in rats (N = 4 per group), followed by reperfusion for 1-7 days. Controls were sham-operated. Rats were treated at time of ischemia or sham operation (T0), or post-treated (6 h after the onset of reperfusion, T6) with EPO (5000 IU/kg), DPO (25 mug/kg), or appropriate vehicle by intraperitoneal injection. Renal function, structure, and immunohistochemistry for Bcl-2, Bcl-XL, and Bax were analyzed. DPO or EPO at T0 significantly abrogated renal dysfunction in IRI animals (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.08 +/- 0.03 mmol/l vs EPO-IRI 0.04 +/- 0.01 mmol/l, P = 0.01). Delayed administration of DPO or EPO (T6) also significantly abrogated subsequent renal dysfunction (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.06 +/- 0.01 mmol/l vs EPO-IRI 0.03 +/- 0.03 mmol/l, P = 0.01). There was also significantly decreased tissue injury (apoptosis, P EPO at T0 or T6. These results reaffirm the potential clinical application of DPO and EPO as novel renoprotective agents for patients at risk of ischemic acute renal failure or after having sustained an ischemic renal insult.

  20. Intranasal formulation of erythropoietin (EPO) showed potent protective activity against amyloid toxicity in the Aβ₂₅₋₃₅ non-transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Maurice, Tangui; Mustafa, Muhammad-Hariri; Desrumaux, Catherine; Keller, Emeline; Naert, Gaëlle; de la C García-Barceló, María; Rodríguez Cruz, Yamila; Garcia Rodríguez, Julío César

    2013-11-01

    Erythropoietin (EPO) promotes neurogenesis and neuroprotection. We here compared the protection induced by two EPO formulations in a rodent model of Alzheimer's disease (AD): rHu-EPO and a low sialic form, Neuro-EPO. We used the intracerebroventricular administration of aggregated Aβ₂₅₋₃₅ peptide, a non-transgenic AD model. rHu-EPO was tested at 125-500 µg/kg intraperitoneally and Neuro-EPO at 62-250 µg/kg intranasally (IN). Behavioural procedures included spontaneous alternation, passive avoidance, water-maze and object recognition, to address spatial and non-spatial, short- and long-term memories. Biochemical markers of Aβ₂₅₋₃₅ toxicity in the mouse hippocampus were examined and cell loss in the CA1 layer was determined. rHu-EPO and Neuro-EPO led to a significant prevention of Aβ₂₅₋₃₅-induced learning deficits. Both EPO formulations prevented the induction of lipid peroxidation in the hippocampus, showing an antioxidant activity. rHu-EPO (250 µg/kg) or Neuro-EPO (125 µg/kg) prevented the Aβ₂₅₋₃₅-induced increase in Bax level, TNFα and IL-1β production and decrease in Akt activation. A significant prevention of the Aβ₂₅₋₃₅-induced cell loss in CA1 was also observed. EPO is neuroprotective in the Aβ₂₅₋₃₅ AD model, confirming its potential as an endogenous neuroprotection system that could be boosted for therapeutic efficacy. We here identified a new IN formulation of EPO showing high neuroprotective activity. Considering its efficacy, ease and safety, IN Neuro-EPO is a new promising therapeutic agent in AD.

  1. The expression of EPOR in renal cortex during postnatal development.

    Directory of Open Access Journals (Sweden)

    Lu Xiao

    Full Text Available Erythropoietin (EPO, known for its role in erythroid differentiation, has been shown to be an important growth factor for brain and heart. EPO is synthesized by fibroblast-like cells in the renal cortex. Prompted by this anatomical relationship and its significant impact on the maturation process of brain and heart, we asked whether EPO could play a role during the development of renal cortex. The relationship between the development of renal cortex and the change of EPO receptor (EPOR, through which EPO could act as a renotropic cytokine, became interesting to us. In this study, the day of birth was recorded as postnatal day 0(P0. P7, P14, P21, P28, P35, P42 and mature mice (postnatal days>56 were used as the animal model of different developmental stages. Immunohistochemistry and Western blotting were used to detect the expression of EPOR in mouse renal cortex. Results showed that expression of EPOR decreased with the development of renal cortex and became stable when kidney became mature. The expression of EPOR was detected at the renal tubule of all developmental stages and a relatively higher expression was observed at P14. However, at the renal corpuscle the expression was only observed at P7 and quickly became undetectable after that. All these suggested that a translocation of EPOR from renal corpuscle to renal tubule may take place during the developmental process of renal cortex. Also, EPO may be an essential element for the maturation of renal cortex, and the requirement for EPO was changed during postnatal development process.

  2. [Treatment of renal anemia with erythropoietin].

    Science.gov (United States)

    Spustova, V; Kovac, A

    1999-08-01

    During the last decade, a considerable amount of new information has accumulated regarding therapy optimalization of renal anaemia with recombinant human erythropoietin (EPO). Key question involved is EPO hyporesponsiveness caused by absolute or functional iron deficiency. Most controversial issue in the treatment of renal anaemia in patients with chronic renal insufficiency is the definition of optimal target haemoglobin. Many questions about optimizing EPO therapy were considered at the 2nd European Epoetin Symposium which was held in April 1998 on Crete. Discussion was devoted also to revision of a draft version of the European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure. The presented review is on summary of new insights presented at the symposium. (Ref. 85.)

  3. EPOS-IP WP10: services and data provision for the GNSS community

    Science.gov (United States)

    Fernandes, Rui

    2016-04-01

    The EPOS-IP WP10 - "GNSS Data & Products" is the Working Package of the EPOS-IP project in charge of implementing the necessary services in order that the geo-sciences community can access the existing Pan-European Geodetic Infrastructures. The WP10 is formed by representatives of the participating institutions (10) but it is also open to the entire geodetic community. In fact, WP10 also includes members from other institutions/countries that formally are not participating in the EPOS-IP. During the EPOS-IP project, the geodetic component of EPOS (WP10) is dealing essentially with Research Infrastructures focused on continuous operating GNSS (cGNSS). The option of concentrating the efforts on the presently most generalized geodetic tool supporting research on Solid Earth was decided in order to optimize the existing resources. Furthermore, although the focus is on Solid Earth applications, other research and technical applications (e.g., reference frames, meteorology, space weather) can also benefit from the efforts of WP10 towards the optimization of the geodetic resources in Europe. We will present and discuss the plans for the implementation of the thematic and core services (TCS) for GNSS data within EPOS and the related business plan. We will focus on strategies towards the implementation of the best solutions that will permit to the end-users, and in particular geo-scientists, to access the geodetic data, derived solutions, and associated metadata using transparent and uniform processes. The collaboration with EUREF is also an essential component of the implementation plan.

  4. The European Plate Observing System (EPOS) Services for Solid Earth Science

    Science.gov (United States)

    Cocco, Massimo; Atakan, Kuvvet; Pedersen, Helle; Consortium, Epos

    2016-04-01

    The European Plate Observing System (EPOS) aims to create a pan-European infrastructure for solid Earth science to support a safe and sustainable society. The main vision of the European Plate Observing System (EPOS) is to address the three basic challenges in Earth Sciences: (i) unravelling the Earth's deformational processes which are part of the Earth system evolution in time, (ii) understanding the geo-hazards and their implications to society, and (iii) contributing to the safe and sustainable use of geo-resources. The mission of EPOS is to monitor and understand the dynamic and complex Earth system by relying on new e-science opportunities and integrating diverse and advanced Research Infrastructures in Europe for solid Earth Science. EPOS will enable innovative multidisciplinary research for a better understanding of the Earth's physical and chemical processes that control earthquakes, volcanic eruptions, ground instability and tsunami as well as the processes driving tectonics and Earth's surface dynamics. EPOS will improve our ability to better manage the use of the subsurface of the Earth. Through integration of data, models and facilities EPOS will allow the Earth Science community to make a step change in developing new concepts and tools for key answers to scientific and socio-economic questions concerning geo-hazards and geo-resources as well as Earth sciences applications to the environment and to human welfare. EPOS has now started its Implementation Phase (EPOS-IP). One of the main challenges during the implementation phase is the integration of multidisciplinary data into a single e-infrastructure. Multidisciplinary data are organized and governed by the Thematic Core Services (TCS) and are driven by various scientific communities encompassing a wide spectrum of Earth science disciplines. These include Data, Data-products, Services and Software (DDSS), from seismology, near fault observatories, geodetic observations, volcano observations

  5. Comparison of two recombinant erythropoietin formulations in patients with anemia due to end-stage renal disease on hemodialysis: A parallel, randomized, double blind study

    Directory of Open Access Journals (Sweden)

    Ávila-Albuerne Yisel

    2005-05-01

    Full Text Available Abstract Background Recombinant human erythropoietin (EPO is used for the treatment of last stage renal anemia. A new EPO preparation was obtained in Cuba in order to make this treatment fully nationally available. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety properties of two recombinant EPO formulations in patients with anemia due to end-stage renal disease on hemodialysis. Methods A parallel, randomized, double blind study was performed. A single 100 IU/Kg EPO dose was administered subcutaneously. Heberitro (Heber Biotec, Havana, formulation A, a newly developed product and Eprex (CILAG AG, Switzerland, formulation B, as reference treatment were compared. Thirty-four patients with anemia due to end-stage renal disease on hemodialysis were included. Patients had not received EPO previously. Serum EPO level was measured by enzyme immunoassay (EIA during 120 hours after administration. Clinical and laboratory variables were determined as pharmacodynamic and safety criteria until 216 hours. Results Both groups of patients were similar regarding all demographic and baseline characteristics. EPO kinetics profiles were similar for both formulations; the pharmacokinetic parameters were very close (i.e., AUC: 4667 vs. 4918 mIU.h/mL; Cmax: 119.1 vs. 119.7 mIU/mL; Tmax: 13.9 vs. 18.1 h; half-life, 20.0 vs. 22.5 h for formulations A and B, respectively. The 90% confidence intervals for the ratio between both products regarding these metrics were close to the 0.8 – 1.25 range, considered necessary for bioequivalence. Differences did not reach 20% in any case and were not determined by a formulation effect, but probably by a patients' variability effect. Concerning pharmacodynamic features, a high similitude in reticulocyte counts increments until 216 hours and the percentage decrease in serum iron until 120 hours was observed. There were no differences between formulations regarding the adverse events and their

  6. Comparison of two recombinant erythropoietin formulations in patients with anemia due to end-stage renal disease on hemodialysis: A parallel, randomized, double blind study

    Science.gov (United States)

    Pérez-Oliva, Jorge F; Casanova-González, Martha; García-García, Idrian; Porrero-Martín, Pedro J; Valenzuela-Silva, Carmen M; Hernández-Montero, Tairí; Lagarde-Ampudia, Marcia; Casanova-Kutsareva, Yuri; Ávila-Albuerne, Yisel; Vargas-Batista, Alicia; Bobillo-López, Hailen; Herrera-Valdés, Raúl; López-Saura, Pedro A

    2005-01-01

    Background Recombinant human erythropoietin (EPO) is used for the treatment of last stage renal anemia. A new EPO preparation was obtained in Cuba in order to make this treatment fully nationally available. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety properties of two recombinant EPO formulations in patients with anemia due to end-stage renal disease on hemodialysis. Methods A parallel, randomized, double blind study was performed. A single 100 IU/Kg EPO dose was administered subcutaneously. Heberitro (Heber Biotec, Havana, formulation A), a newly developed product and Eprex (CILAG AG, Switzerland, formulation B), as reference treatment were compared. Thirty-four patients with anemia due to end-stage renal disease on hemodialysis were included. Patients had not received EPO previously. Serum EPO level was measured by enzyme immunoassay (EIA) during 120 hours after administration. Clinical and laboratory variables were determined as pharmacodynamic and safety criteria until 216 hours. Results Both groups of patients were similar regarding all demographic and baseline characteristics. EPO kinetics profiles were similar for both formulations; the pharmacokinetic parameters were very close (i.e., AUC: 4667 vs. 4918 mIU.h/mL; Cmax: 119.1 vs. 119.7 mIU/mL; Tmax: 13.9 vs. 18.1 h; half-life, 20.0 vs. 22.5 h for formulations A and B, respectively). The 90% confidence intervals for the ratio between both products regarding these metrics were close to the 0.8 – 1.25 range, considered necessary for bioequivalence. Differences did not reach 20% in any case and were not determined by a formulation effect, but probably by a patients' variability effect. Concerning pharmacodynamic features, a high similitude in reticulocyte counts increments until 216 hours and the percentage decrease in serum iron until 120 hours was observed. There were no differences between formulations regarding the adverse events and their intensity. The more

  7. Epo deficiency alters cardiac adaptation to chronic hypoxia.

    Science.gov (United States)

    El Hasnaoui-Saadani, Raja; Marchant, Dominique; Pichon, Aurélien; Escoubet, Brigitte; Pezet, Mylène; Hilfiker-Kleiner, Denise; Hoch, Melanie; Pham, Isabelle; Quidu, Patricia; Voituron, Nicolas; Journé, Clément; Richalet, Jean-Paul; Favret, Fabrice

    2013-04-01

    The involvement of erythropoietin in cardiac adaptation to acute and chronic (CHx) hypoxia was investigated in erythropoietin deficient transgenic (Epo-TAg(h)) and wild-type (WT) mice. Left (LV) and right ventricular functions were assessed by echocardiography and hemodynamics. HIF-1α, VEGF and Epo pathways were explored through RT-PCR, ELISA, Western blot and immunocytochemistry. Epo gene and protein were expressed in cardiomyocytes of WT mice in normoxia and hypoxia. Increase in blood hemoglobin, angiogenesis and functional cardiac adaptation occurred in CHx in WT mice, allowing a normal oxygen delivery (O2T). Epo deficiency induced LV hypertrophy, increased cardiac output (CO) and angiogenesis, but O2T remained lower than in WT mice. In CHx Epo-TAg(h) mice, LV hypertrophy, CO and O2T decreased. HIF-1α and Epo receptor pathways were depressed, suggesting that Epo-TAg(h) mice could not adapt to CHx despite activation of cardioprotective pathways (increased P-STAT-5/STAT-5). HIF/Epo pathway is activated in the heart of WT mice in hypoxia. Chronic hypoxia induced cardiac adaptive responses that were altered with Epo deficiency, failing to maintain oxygen delivery to tissues.

  8. [Neuroprotection of herbs promoting EPO on cerebral ischemia].

    Science.gov (United States)

    Li, Xu; Bai, Zhen-ya; Zhang, Fei-yan; Xu, Xiao-yu

    2015-06-01

    Amounts of researches show that EPO is characterized with neurotrophic and neuroprotective manner, especially in brain stroke, which attracts a large numbers of researchers to study it. With the accumulating researches on its neuroprotection, many related mechanisms were revealed, such as antioxidant, anti-apoptosis, angiogenesis, anti-inflammatory, which suggests a multiple targets role of EPO on brain stroke. However, because of the high risk of thromboembolism in clinical administration of rhEPO and its analogs, the herbs are potential to be a replacer for its less side effects. Many researchers suggested that a larger of herbs were founded having the action of increasing the endogenous EPO in the model of anemia and cerebral ischemia. At the same time, there herbs were also proved that they had the action of against cerebral ischemia while some without considering the role of EPO in the reports. Considering of the action of promoting EPO of these herbs and the neural protection of EPO, this essay mainly summarizes the studies of herbs promoting EPO in the cerebral ischemia and discusses the mechanism of regulating the EPO of these herbs, for the aim of finding the potential drugs against cerebral ischemia.

  9. Lessons learned from IRIS EPO program evaluations

    Science.gov (United States)

    Taber, J.; Hubenthal, M.

    2012-12-01

    Evaluating the overall impact of EPO programs that include activities ranging from formal education through broad public outreach, is a complex issue. The impact of education activities targeted at narrowly defined audiences is generally easier to quantify than the national impact of outreach activities conducted by a relatively small program. For educational activities, our approach has been to leverage the best-practices identified through research and to continuously assess the individual elements internally with the intention of making improvements based on the data generated and the existing research. By constructing our elements on the best practices identified by the research community we feel that internal formative evaluation is a valid means to determine if an activity is effective, particularly when the results are compared to similar programs. For example, effective practices of professional development are well documented in the literature. As a result, this allows us to shape our programs and our evaluations to monitor elements that have been identified as key by the educational research community. Further, such actions allow us to avoid allocating significant resources with the intention of pinning down direct causal relationships between our programs and consumers, when similar interventions (conducted by others) have already shown such relationships. Ongoing review by an EPO advisory committee also provides regular oversight of program impact. While we find internal and external formative evaluation extremely useful in shaping the program and documenting its impact, we also recognize the value of a summative evaluation process. For example, an external summative evaluation of the IRIS EPO program was conducted in 2009, followed by an external panel review, as part of the regular review of IRIS programs. We found that the most valuable part of the external evaluation was our preparation, including clarifying the goals of each of the elements of the

  10. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke

    2012-01-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic...

  11. The Contribution of OLG Data and Analysis Centre to EPOS

    Science.gov (United States)

    Stangl, Günter; Krauss, Sandro

    2013-04-01

    OLG (Observatory Lustbuehel Graz) as a joint venture of the Austrian Academy of Sciences and the Federal Office of Metrology and Surveying works as a GNSS data centre and analyses GNSS data for reference maintenance, geokinematics and ionosphere research. Due to the change from epoch to permanent sites regions in Africa, Asia and Europe are investigated since 1995. Presently, observations from about 300 GNSS stations are used for analysis. Most of the stations are public and are retrieved from different global, regional and local data centres. In addition some institutions provide their private data to the OLG. After presenting the main regions Austria, Central Europe, the Eastern Mediterranean and the Western Indian Ocean the question will be how these data and products could be included into EPOS.

  12. Re-establishment of erythropoietin responsiveness in end-stage renal failure following renal transplantation.

    Science.gov (United States)

    Jeffrey, R F; Kendall, R G; Prabhu, P; Norfolk, D R; Will, E J; Davison, A M

    1995-10-01

    Re-establishment of erythropoietin (EPO) secretion following renal transplantation is poorly understood. The development of sensitive EPO radioimmunoassay has enabled further study of this phenomenon. Forty-one adult patients were studied during the first 16 weeks following renal transplantation. Twenty six received cyclosporin monotherapy and 15 also received prednisolone and azathioprine. Serum creatinine, haemoglobin (Hb), ferritin and EPO were assayed pre-operatively, daily for 1 week, weekly for 1 month, and fortnightly to 16 weeks. An expected EPO value, for any Hb level, was derived by linear regression analysis in 144 patients with iron deficiency anemia. An observed to expected ratio (O/E) was calculated, a value of 1.0 implying appropriate responsiveness. Hb increased from 8.6 +/- 2.0 (SD) to 12.3 +/- 2.1 g/dl (p weeks, an increase unaffected by ferritin status. Mean EPO concentration increased during the first week with a peak at day 4 (22.1 +/- 13.3 to 44.6 +/- 40.0 mu/ml, p week 16 (r = -0.404, p weeks (p weeks when mean serum creatinine was 142 +/- 48 mumol/l. Patients with poor ongoing renal function (9 cases, serum creatinine > 250 mumol/l at 16 weeks) had impaired Hb recovery (10.1 +/- 1.6 vs 12.7 +/- 2.0 g/dl at 16 weeks, p < 0.05). EPO values were not different in those patients but median O/E ratios were significantly depressed (p < 0.05) throughout, the maximum O/E ratio being 0.75. Recovery of renal function is accompanied by a beneficial Hb response driven by EPO synthesis in the transplant. The O/E ratio provides a useful index to assess EPO responsiveness. Appropriate secretion was achieved during the first 4 months and optimized by immediate and satisfactory graft function.

  13. The relationships between hypoxia-dependent markers: HIF-1alpha, EPO and EPOR in colorectal cancer.

    Science.gov (United States)

    Baltaziak, Marek; Wincewicz, Andrzej; Kanczuga-Koda, Luiza; Lotowska, Joanna M; Koda, Mariusz; Sulkowska, Urszula; Baltaziak, Marcin; Podbielski, Monika; Sobaniec-Lotowska, Maria E; Sulkowski, Stanislaw

    2013-01-01

    Hypoxia triggers production of several cytoprotective proteins. Hypoxia-inducible factor 1alpha (HIF-1α) is a powerful stimulator of transcription of many genes, including erythropoietin (EPO) in hypoxia-affected cells. Recent data have also implicated signaling by EPO receptor (EPOR) as a new factor influencing tumor progression. The aim of the study was to detect by immunohistochemistry the presence of HIF-1α, EPO and EPOR in colorectal cancer (CRC) in reference to clinicopathological variables. We found the presence of the studied proteins in specimens of all 125 CRC patients which is suggestive of the occurrence of hypoxia in colorectal cancer tissues. The expression of HIF-1α correlated significantly with the presence of EPO and EPOR in all samples (P < 0.001, r = 0.549 and P < 0.001, r = 0.536, respectively). Significant correlations (from P < 0.024 to P < 0.001) were found in the analyses of CRC subgroups such as histopathological type tumor, tumor grade, tumor stage and patients with lymph nodes metastases. The same high significant correlations (P < 0.001) were observed in group of sex, age and tumor location. However, the values of the correlation coefficients (r) which usually ranged from 0.5 to 0.6 suggest the existence of independent or concurrent mechanism stimulating generation of these proteins in colorectal cancer.

  14. Some Empirical Notes on the Epo Epidemic in Professional Cycling

    Science.gov (United States)

    Lodewijkx, Hein F. M.; Brouwer, Bram

    2011-01-01

    The 1990-2010 period in professional cycling is labeled by some as the epo epidemic. Surprisingly, performance enhancement by epo and blood doping is not that clear-cut for endurance athletes, leading to the question whether doping indeed strongly influenced cyclists' performances from the 1990s onwards. We examined the records (1947-2008) of the…

  15. Some Empirical Notes on the Epo Epidemic in Professional Cycling

    Science.gov (United States)

    Lodewijkx, Hein F. M.; Brouwer, Bram

    2011-01-01

    The 1990-2010 period in professional cycling is labeled by some as the epo epidemic. Surprisingly, performance enhancement by epo and blood doping is not that clear-cut for endurance athletes, leading to the question whether doping indeed strongly influenced cyclists' performances from the 1990s onwards. We examined the records (1947-2008) of the…

  16. Metformin Prevents Renal Fibrosis in Mice with Unilateral Ureteral Obstruction and Inhibits Ang II-Induced ECM Production in Renal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Yang Shen

    2016-01-01

    Full Text Available Renal fibrosis is the final common pathway of chronic kidney disease (CKD, and no effective medication is available clinically for managing its progression. Metformin was initially developed as an anti-diabetic drug and recently gained attention for its potential in the treatment of other diseases. In this study, we investigated its effects on renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO in vivo and in angiotensin II (Ang II–treated renal fibroblast NRK-49F cells in vitro. Our data showed that UUO induced renal fibrosis and combined with the activation of ERK signaling, the upregulation of fibronectin, collagen I, and transforming growth factor-β (TGF-β. The administration of metformin inhibited the activation of ERK signaling and attenuated the production of extracellular matrix (ECM proteins and collagen deposition in the obstructed kidneys. In cultured renal fibroblasts, Ang II increased the expression of fibronectin and collagen I and also activated ERK signaling and TGF-β in a time-dependent manner. Pretreatment of the cells with metformin blocked Ang II–induced ERK signaling activation and ECM overproduction. Our results show that metformin prevents renal fibrosis, possibly through the inhibition of ERK signaling, and may be a novel strategy for the treatment of renal fibrosis.

  17. Metformin Prevents Renal Fibrosis in Mice with Unilateral Ureteral Obstruction and Inhibits Ang II-Induced ECM Production in Renal Fibroblasts.

    Science.gov (United States)

    Shen, Yang; Miao, Naijun; Xu, Jinlan; Gan, Xinxin; Xu, Dan; Zhou, Li; Xue, Hong; Zhang, Wei; Lu, Limin

    2016-01-22

    Renal fibrosis is the final common pathway of chronic kidney disease (CKD), and no effective medication is available clinically for managing its progression. Metformin was initially developed as an anti-diabetic drug and recently gained attention for its potential in the treatment of other diseases. In this study, we investigated its effects on renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) in vivo and in angiotensin II (Ang II)-treated renal fibroblast NRK-49F cells in vitro. Our data showed that UUO induced renal fibrosis and combined with the activation of ERK signaling, the upregulation of fibronectin, collagen I, and transforming growth factor-β (TGF-β). The administration of metformin inhibited the activation of ERK signaling and attenuated the production of extracellular matrix (ECM) proteins and collagen deposition in the obstructed kidneys. In cultured renal fibroblasts, Ang II increased the expression of fibronectin and collagen I and also activated ERK signaling and TGF-β in a time-dependent manner. Pretreatment of the cells with metformin blocked Ang II-induced ERK signaling activation and ECM overproduction. Our results show that metformin prevents renal fibrosis, possibly through the inhibition of ERK signaling, and may be a novel strategy for the treatment of renal fibrosis.

  18. Inhibitory effects of tetradecanoylphorbol acetate and diacylglycerol on erythropoietin production in human renal carcinoma cell cultures

    Energy Technology Data Exchange (ETDEWEB)

    Hagiwara, Masamichi; Nagakura, Kazuhiko; Ueno, Munehisa; Fisher, J.W. (Tulane Univ., New Orleans, LA (United States))

    1987-11-01

    A human renal carcinoma from a patient with an erythrocytosis, serially transplanted into athymic nude mice, was grown in primary monolayer cell cultures. After reaching confluency the cultured cells formed multicellular hemicysts (domes) which became more abundant as the cultures approached saturation density. Erythropoietin (Ep) production by this renal carcinoma in culture was only slightly increased at the time of semiconfluency but showed a marked increase in Ep levels in the culture medium after the cultures reached confluency, in parallel with an increase in dome formation. The phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) showed a significant dose-related inhibitory effect on Ep production and dome formation in the renal carcinoma cell cultures, suggesting an important role of protein kinase C, the only known receptor for TPA, in inhibiting the expression of differentiated phenotypes in the renal carcinoma cells. These studies suggest a role of the inositol-lipid second messenger path and protein kinase C in the regulation of Ep production.

  19. Klotho expression in long bones regulates FGF23 production during renal failure.

    Science.gov (United States)

    Kaludjerovic, Jovana; Komaba, Hirotaka; Sato, Tadatoshi; Erben, Reinhold G; Baron, Roland; Olauson, Hannes; Larsson, Tobias E; Lanske, Beate

    2017-02-09

    Circulating levels of bone-derived fibroblast growth factor 23 (FGF23) increase early during acute and chronic kidney disease and are associated with adverse outcomes. Membrane-bound Klotho acts as a permissive coreceptor for FGF23, and its expression was recently found in osteoblasts/osteocytes. We hypothesized that Klotho in bone cells is part of an autocrine feedback loop that regulates FGF23 expression during renal failure. Thus, we induced renal failure in mice with targeted deletion of Klotho in long bones. Uremic wild-type (KL(fl/fl) ) and knockout (Prx1-Cre;KL(fl/fl) ) mice both responded with reduced body weight, kidney atrophy, hyperphosphatemia, and increased bone turnover. Importantly, long bones of Prx1-Cre;KL(fl/fl) mice but not their axial skeleton failed to increase FGF23 expression as observed in uremic KL(fl/fl) mice. Consequently, Prx1-Cre;KL(fl/fl) mice had significantly lower serum FGF23 and parathyroid hormone levels, and higher renal 1-α-hydroxylase expression, serum 1,25-dihydroxyvitamin D, and calcium levels than KL(fl/fl) mice. These results were confirmed in two independent models of renal failure, adenine diet induced and 5/6 nephrectomy. Moreover, FGF23-treated bone cells required Klotho to increase FGF23 mRNA and ERK phosphorylation. In summary, our novel findings show that Klotho in bone is crucial for inducing FGF23 production upon renal failure. We propose the presence of an autocrine feedback loop in which Klotho senses the need for FGF23.-Kaludjerovic, J., Komaba, H., Sato, T., Erben, R. G., Baron, R., Olauson, H., Larsson, T. E., Lanske, B. Klotho expression in long bones regulates FGF23 production during renal failure.

  20. IS-EPOS - a prototype of EPOS Thematic Core Service for seismic processes induced by human operations

    Science.gov (United States)

    Orlecka-Sikora, Beata; Lasocki, Stanislaw; Leptokaropoulos, Konstantinos

    2014-05-01

    The community focused on seismic processes induced by human operations has been organized within EPOS Integration Program as Working Group 10 Infrastructure for Georesources. This group has brought together representatives from the scientific community and industry from 13 European countries. WG10 aims to integrate the research infrastructure (RI) in the area of seismicity induced (IS) by human activity: tremors and rockbursts in underground mines, seismicity associated with conventional and unconventional oil and gas production, induced by geothermal energy extraction and by underground reposition and storage of liquids (e.g. water disposal associated with energy extraction) and gases (CO2 sequestration, inter alia) and triggered by filling surface water reservoirs, etc. WG10 priority is to create new research opportunities in the field responding to global challenges connected with exploitation of georesources. WG10 has prepared the model of integration fulfilling the scientific mission and raising the visibility of stakeholders. The end-state Induced Seismicity Thematic Core Service (IS TCS) has been designed together with key metrics for TCS benefits in four areas: scientific, societal, economic and capacity building. IS-EPOS project, funded by National Centre for Research and Development, Poland within the program "Innovative Economy Operational Program Priority Axis 2 - R&D Infrastructure", aims at building a prototype of IS TCS. The prototype will implement fully the designed logic of IS TCS. Research infrastructure integrated within the prototype will comprise altogether seven comprehensive data cases of seismicity linked to deep mining related, associating geothermal production and triggered by reservoir impoundment. The implemented thematic services will enable studies within the use-case "Clustering of induced earthquakes". The IS TCS prototype is expected to reach full functionality by the end of 2014.

  1. Release of intracellular Calcium increase production of mitochondrial reactive oxygen species in renal distal epithelial cells

    DEFF Research Database (Denmark)

    Bjerregaard, Henning F.

    Release of intracellular Calcium increase production of mitochondrial reactive oxygen species in renal distal epithelial cells. Henning F. Bjerregaard, Roskilde University, Department of Science, Systems and Models , 4000 Roskilde, Denmark. HFB@ RUC.DK Reactive oxygen species (ROS) like, hydrogen...... to G-protein stimulation of phospholipase C and release of inositol -3 phosphate. Cd (0.4 mM) treatment of A6 cells enhanced the ROS production after one minutes incubation. The production rate was constant for at least 10 to 20 min. Experiments showed that the Cd induced increase in ROS production...

  2. Recombinant human erythropoietin in humans down-regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Aachmann-Andersen, Niels Jacob; Oturai, Peter;

    2010-01-01

    rHuEPO elevates hemoglobin concentration both by increasing red blood cell volume and by a decrease in plasma volume. This study delineates the association of rHuEPO-induced changes in blood volumes with changes in the renin-aldosterone system and renal function. 16 healthy males were given rHuEPO...... tubular outflow and to assess segmental renal tubular handling of sodium and water. rHuEPO-induced increases in hematocrit occurred from day 10 onwards and was caused by both an increase in red cell volume and a fall in plasma volume. Well before that (from day 2 and throughout the treatment time), rHuEPO...... decreased plasma levels of renin and aldosterone (N = 8) by 21 - 33 % (P EPO values returned to baseline. On days 11 and 29 C(Li) increased (P

  3. Epo and non-hematopoietic cells: what do we know?

    Science.gov (United States)

    Ogunshola, Omolara O; Bogdanova, Anna Yu

    2013-01-01

    The hematopoietic growth factor erythropoietin (Epo) circulates in plasma and controls the oxygen carrying capacity of the blood (Fisher. Exp Biol Med (Maywood) 228:1-14, 2003). Epo is produced primarily in the adult kidney and fetal liver and was originally believed to play a role restricted to stimulation of early erythroid precursor proliferation, inhibition of apoptosis, and differentiation of the erythroid lineage. Early studies showed that mice with targeted deletion of Epo or the Epo receptor (EpoR) show impaired erythropoiesis, lack mature erythrocytes, and die in utero around embryonic day 13.5 (Wu et al. Cell 83:59-67, 1995; Lin et al. Genes Dev. 10:154-164, 1996). These animals also exhibited heart defects, abnormal vascular development as well as increased apoptosis in the brain suggesting additional functions for Epo signaling in normal development of the central nervous system and heart. Now, in addition to its well-known role in erythropoiesis, a diverse array of cells have been identified that produce Epo and/or express the Epo-R including endothelial cells, smooth muscle cells, and cells of the central nervous system (Masuda et al. J Biol Chem. 269:19488-19493, 1994; Marti et al. Eur J Neurosci. 8:666-676, 1996; Bernaudin et al. J Cereb Blood Flow Metab. 19:643-651, 1999; Li et al. Neurochem Res. 32:2132-2141, 2007). Endogenously produced Epo and/or expression of the EpoR gives rise to autocrine and paracrine signaling in different organs particularly during hypoxia, toxicity, and injury conditions. Epo has been shown to regulate a variety of cell functions such as calcium flux (Korbel et al. J Comp Physiol B. 174:121-128, 2004) neurotransmitter synthesis and cell survival (Velly et al. Pharmacol Ther. 128:445-459, 2010; Vogel et al. Blood. 102:2278-2284, 2003). Furthermore Epo has neurotrophic effects (Grimm et al. Nat Med. 8:718-724, 2002; Junk et al. Proc Natl Acad Sci U S A. 99:10659-10664, 2002), can induce an angiogenic phenotype in cultured

  4. Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure

    DEFF Research Database (Denmark)

    Gülberg, V; Møller, S; Henriksen, Jens Henrik Sahl

    2000-01-01

    .05; mean (SEM)). In contrast, urinary CNP was higher in patients with impaired renal function compared with those with normal renal function and healthy controls (47.2 (7.4) v. 20.8 (1.9) and 17.0 (3.0) ng CNP/g creatinine, respectively; pUrinary CNP was found to be inversely related to urinary...... homeostasis. Therefore, the aim of the present study was to investigate the possible role of CNP in renal function disturbances in patients with cirrhosis of the liver. METHODS: Peripheral venous and urinary concentrations of CNP were determined in samples from 11 healthy controls, 20 cirrhotic patients...... with normal renal function (creatinine clearance 117 (8) ml/min), and 20 cirrhotic patients with impaired renal function (creatinine clearance 35 (4) ml/min). In a second protocol, arterial and renal venous plasma concentrations of CNP were determined in 37 patients with cirrhosis of the liver to estimate...

  5. Studies on Epo/Epo-receptor in the Functions of Nervous System%Epo/Epo-receptor系统在神经系统作用的研究

    Institute of Scientific and Technical Information of China (English)

    彭波; 项辉

    2004-01-01

    促红细胞生成素(Epo)不仅影响红系细胞,而且是一种多功能的营养因子.在神经发育过程中Epo及其受体的表达显著改变.脑缺血时,Epo的生成量成倍增加,发挥抗炎、增强NO扩血管的作用,并促进血管新生,在缺血部位建立侧枝循环,有助于改善局部缺血状况,对神经元起保护作用.此外Epo还能促进神经元增生.

  6. Aging is Associated with Impaired Renal Function, INF-gamma Induced Inflammation and with Alterations in Iron Regulatory Proteins Gene Expression

    Science.gov (United States)

    Costa, Elísio; Fernandes, João; Ribeiro, Sandra; Sereno, José; Garrido, Patrícia; Rocha-Pereira, Petronila; Coimbra, Susana; Catarino, Cristina; Belo, Luís; Bronze-da-Rocha, Elsa; Vala, Helena; Alves, Rui; Reis, Flávio; Santos-Silva, Alice

    2014-01-01

    Our aim was to contribute to a better understanding of the pathophysiology of anemia in elderly, by studying how aging affects renal function, iron metabolism, erythropoiesis and the inflammatory response, using an experimental animal model. The study was performed in male Wistar, a group of young rats with 2 months age and an old one with 18 months age. Old rats presented a significant higher urea, creatinine, interferon (INF)-gamma, ferritin and soluble transferrin receptor serum levels, as well as increased counts of reticulocytes and RDW. In addition, these rats showed significant lower erythropoietin (EPO) and iron serum levels. Concerning gene expression of iron regulatory proteins, old rats presented significantly higher mRNA levels of hepcidin (Hamp), transferrin (TF), transferrin receptor 2 (TfR2) and hemojuvelin (HJV); divalent metal transporter 1 (DMT1) mRNA levels were significantly higher in duodenal tissue; EPO gene expression was significantly higher in liver and lower in kidney, and the expression of the EPOR was significantly higher in both liver and kidney. Our results showed that aging is associated with impaired renal function, which could be in turn related with the inflammatory process and with a decline in EPO renal production. Moreover, we also propose that aging may be associated with INF-gamma-induced inflammation and with alterations upon iron regulatory proteins gene expression. PMID:25489488

  7. The EPOS Architecture: Integrated Services for solid Earth Science

    Science.gov (United States)

    Cocco, Massimo; Consortium, Epos

    2013-04-01

    The European Plate Observing System (EPOS) represents a scientific vision and an IT approach in which innovative multidisciplinary research is made possible for a better understanding of the physical processes controlling earthquakes, volcanic eruptions, unrest episodes and tsunamis as well as those driving tectonics and Earth surface dynamics. EPOS has a long-term plan to facilitate integrated use of data, models and facilities from existing (but also new) distributed research infrastructures, for solid Earth science. One primary purpose of EPOS is to take full advantage of the new e-science opportunities coming available. The aim is to obtain an efficient and comprehensive multidisciplinary research platform for the Earth sciences in Europe. The EPOS preparatory phase (EPOS PP), funded by the European Commission within the Capacities program, started on November 1st 2010 and it has completed its first two years of activity. EPOS is presently mid-way through its preparatory phase and to date it has achieved all the objectives, milestones and deliverables planned in its roadmap towards construction. The EPOS mission is to integrate the existing research infrastructures (RIs) in solid Earth science warranting increased accessibility and usability of multidisciplinary data from monitoring networks, laboratory experiments and computational simulations. This is expected to enhance worldwide interoperability in the Earth Sciences and establish a leading, integrated European infrastructure offering services to researchers and other stakeholders. The Preparatory Phase aims at leveraging the project to the level of maturity required to implement the EPOS construction phase, with a defined legal structure, detailed technical planning and financial plan. We will present the EPOS architecture, which relies on the integration of the main outcomes from legal, governance and financial work following the strategic EPOS roadmap and according to the technical work done during the

  8. The EPOS implementation of thematic services for solid Earth sciences

    Science.gov (United States)

    Cocco, Massimo; Consortium, Epos

    2014-05-01

    The mission of EPOS is to build an efficient and comprehensive multidisciplinary research platform for the solid Earth sciences in Europe. In particular, EPOS is a long-term plan to facilitate integrated use of data, models and facilities from mainly distributed existing, but also new, research infrastructures for Earth Science. EPOS will enable innovative multidisciplinary research for a better understanding of the physical processes controlling earthquakes, volcanic eruptions, unrest episodes, ground stability, and tsunamis as well as those processes driving tectonics and Earth surface dynamics. EPOS will allow the Earth Science community to make a significant step forward by developing new concepts and tools for accurate, durable, and sustainable answers to societal questions concerning geo-hazards and those geodynamic phenomena relevant to the environment and human welfare. EPOS coordinates the existing and new solid Earth RIs within Europe and is building the integrating RI elements. This integration requires a significant coordination between, among others, disciplinary (thematic) communities, national RIs policies and initiatives, as well as geo- and IT-scientists. The RIs that EPOS coordinates include: i) Regionally-distributed geophysical observing systems (seismological and geodetic networks); ii) Local observatories (including geomagnetic, near-fault and volcano observatories); iii) Analytical and experimental laboratories; iv) Integrated satellite data and geological information services. We present the results achieved during the EPOS Preparatory Phase (which will end on October 2014) and the progress towards construction in terms of both the design of the integrated core services (ICS) and the development of thematic core services (TCS) for the different communities participating to the integration plan. We will focus on discussing the strategies adopted to foster the necessary implementation of TCS, clarifying their crucial role as domain

  9. Role of ATP-dependent K channels in the effects of erythropoietin in renal ischaemia injury

    Directory of Open Access Journals (Sweden)

    Tonguç Utku Yilmaz

    2015-01-01

    Interpretation & conclusions: Our results showed that the cell proliferative, cytoprotective and anti-apoptotic effects of EPO were associated with KATP channels in the renal tubular cell culture model under hypoxic/normal conditions.

  10. EPO-receptor is present in mouse C2C12 and human primary skeletal muscle cells but EPO does not influence myogenesis.

    Science.gov (United States)

    Lamon, Séverine; Zacharewicz, Evelyn; Stephens, Andrew N; Russell, Aaron P

    2014-01-01

    Abstract The role and regulation of the pleiotropic cytokine erythropoietin (EPO) in skeletal muscle are controversial. EPO exerts its effects by binding its specific receptor (EPO-R), which activates intracellular signaling and gene transcription in response to internal and external stress signals. EPO is suggested to play a direct role in myogenesis via the EPO-R, but several studies have questioned the effect of EPO treatment in muscle in vitro and in vivo. The lack of certainty surrounding the use of nonspecific EPO-R antibodies contributes to the ambiguity of the field. Our study demonstrates that the EPO-R gene and protein are expressed at each stage of mouse C2C12 and human skeletal muscle cell proliferation and differentiation and validates a specific antibody for the detection of the EPO-R protein. However, in our experimental conditions, EPO treatment had no effect on mouse C2C12 and human muscle cell proliferation, differentiation, protein synthesis or EPO-R expression. While an increase in Akt and MAPK phosphorylation was observed, we demonstrate that this effect resulted from the stress caused by changing medium and not from EPO treatment. We therefore suggest that skeletal muscle EPO-R might be present in a nonfunctional form, or too lowly expressed to play a role in muscle cell function.

  11. NASA Astrophysics EPO Community: Enhancing STEM Experience of Undergraduates

    Science.gov (United States)

    Manning, J.; Meinke, B. K.; Lawton, B.; Smith, D. A.; Bartolone, L.; Schultz, G.; NASA Astrophysics EPO Community

    2015-11-01

    The NASA Science Mission Directorate (SMD) Astrophysics Education and Public Outreach (EPO) community and Forum work together to capitalize on the cutting-edge discoveries of NASA Astrophysics missions to enhance the Science, Technology, Engineering, and Math (STEM) experience of undergraduates. The NASA SMD Astrophysics EPO community has proven expertise in providing both professional development and resources to faculty at two- and four-year institutions and in offering internships and student collaboration opportunities. These mission- and grant-based EPO programs are uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise. We present examples of how the NASA Astrophysics EPO community and Forum engage the higher education community in these ways, including associated metrics and evaluation findings.

  12. EPOS Model and Ultra High Energy Cosmic Rays

    CERN Document Server

    Pierog, T

    2009-01-01

    Interpretation of extensive air showers (EAS) experiments results is strongly based on air shower simulations. The latter being based on hadronic interaction models, any new model can help for the understanding of the nature of cosmic rays. The EPOS model reproducing all major results of existing accelerator data (including detailed data of RHIC experiments) has been introduced in air shower simulation programs CORSIKA and CONEX few years ago. The new EPOS 1.99 has recently been updated taking into account the problem seen in EAS development using EPOS 1.61. We will show in details the relationship between some EPOS hadronic properties and EAS development, as well as the consequences on the model and finally on cosmic ray analysis.

  13. The Doppler paradigm and the APEX-EPOS-ORANGE quandary

    CERN Document Server

    Griffin, J J

    1996-01-01

    The experimental detection of the sharp lines of the \\ee Puzzle is viewed as a struggle against Doppler broadening. Gedanken experiments which are realistic in zeroth order of detail are analyzed to show that the ORANGE and EPOS/I geometries select narrower slices of a Doppler broadened line than spherically inclusive (APEX and EPOS/II --like) apparati. Roughly speaking, the latter require event-by-event Doppler reconstruction simply to regain an even footing with the former. This suggests that APEX' or EPOS/II's coincident pair distributions must be statistically superior to those of EPOS/I or ORANGE in order to support a comparable inference about sharp structure. Under present circumstances, independent alternative data is invaluable. Therefore, a corroboration of Sakai's 330.1 keV (< 3 keV wide) electron line in few MeV e^+ or e^- bombardments of U and Th targets could prove crucial.

  14. EUDAT and EPOS moving towards the efficient management of scientific data sets

    Science.gov (United States)

    Fiameni, Giuseppe; Bailo, Daniele; Cacciari, Claudio

    2016-04-01

    interoperability among all involved communities, EPOS has designed an architecture capable to organize and manage distributed discipline-oriented centers (called Thematic Core Services - TCS). Such design envisage the creation of an integrating e-Infrastructure called Integrated Core Service (ICS), whose aim is to collect and integrate Data, Data Products, Software and Services, and provide homogeneous access to them to the end user, hiding all the complexity of the underlying network of TCS and National data centers. Therefore, EPOS can take advantage of EUDAT CDI at different levels: at the TCS level, providing technologies, knowledge and B2* services to discipline-oriented communities, and at the ICS level, by facilitating the integration and interoperability of different communities with different level of maturity in terms of technology expertise. EUDAT services are particularly suitable to facilitate this process as they can be deployed across the community centers to complement or augment existing services of more mature communities as well as be used by less mature communities as a gateway towards the EPOS integration. To this purpose, a pilot is being carried on in the context of the EPOS Seismological community to foster the uptake of EUDAT services among centers and thus ensure the efficient and sustainable management of scientific data sets. Data sets, e.g. seismic waveforms, collected through the Italian Seismic Network and the ORFEUS organization, are currently replicated onto EUDAT resources to ensure their long-term preservation and accessibility. The pilot will be extend to cover other use cases such as the management of meta-data and the fine-grained control of access.

  15. Capillary/myocyte mismatch in the heart in renal failure--a role for erythropoietin?

    Science.gov (United States)

    Amann, K; Buzello, M; Simonaviciene, A; Miltenberger-Miltenyi, G; Koch, A; Nabokov, A; Gross, M L; Gless, B; Mall, G; Ritz, E

    2000-07-01

    Chronic renal failure is characterized by remodeling of the heart with left ventricular hypertrophy (increasing oxygen demand) and capillary deficit leading to capillary/myocyte mismatch (decreasing oxygen supply). Erythropoietin (Epo) has known angiogenic properties causing endothelial cell activation, migration and sprouting, mediated at least in part via the JAK/STAT (Janus kinase/signal transducers and activators of transcription) pathway. In uraemic cardiac hypertrophy the presence of diminished capillary supply implies that capillary growth does not keep pace with development of hypertrophy. To investigate whether this was due to a deficit of the angiogenic hormone Epo we examined whether Epo levels are altered and whether an increase in haematocrit by administration of rhEpo influences capillary supply, i.e. capillary/myocyte mismatch in experimental renal failure. Male Spraque-Dawley rats were either subjected to partial renal ablation or sham operation. Only modest amounts of renal tissue were removed so that the rats were not anemic. Subgroups of rats received either human (rh)Epo alone or in combination with unspecific antihypertensive treatment (dihydralazine plus furosemide) in order to control the Epo induced rise in blood pressure. Capillary supply was measured stereologically as capillary length per volume myocardium using the orientator method. Capillary length density was reduced by approximately 25% after partial renal ablation (3237+/-601 vs 4293+/-501 mm/mm(3) in controls). It was not statistically different in animals with partial renal ablation+rhEpo+antihypertensive treatment (3620+/-828 mm/mm(3)) compared to partial ablation alone. The study shows that lack of Epo does not cause, or contribute to, the deficit of capillary growth in the hypertrophied left ventricle of rats with renal failure. In addition, a rise in haematocrit is not accompanied by beneficial effects on alterations of cardiovascular structure in experimental renal failure.

  16. Erythropoietin ameliorates renal interstitial fibrosis via the inhibition of fibrocyte accumulation.

    Science.gov (United States)

    Geng, Xu Chang; Hu, Zhou Pang; Lian, Guo Yong

    2015-05-01

    Erythropoietin (EPO) is a hematopoietic hormone that protects against renal interstitial fibrosis in animal models; however, the mechanism underlying the anti‑fibrotic activity of EPO has remained elusive. The present study aimed to elucidate this mechanism. Twenty‑four male C57BL6 mice were randomly divided into four groups, each comprising six mice: (i) control group (Sh); (ii) unilateral ureteral obstruction (UUO) plus vehicle group (U+V); (ⅲ) UUO plus 300 U/kg body weight recombinant human (rh)EPO (U+E1) and (ⅳ) UUO plus 1,000 U/kg body weight rhEPO (U+E2). Seven days post‑surgery, the mice were sacrificed for examination. UUO induced significant deposition of extracellular matrix, detected by picro‑sirius red staining, which was decreased following rhEPO treatment. UUO also induced deposition of collagen I and fibronectin, rhEPO treatment was able to attenuate this effect at protein and mRNA levels. Compared with the control groups, UUO resulted in the accumulation of α‑smooth muscle actin‑positive cells in the interstitium, an effect which was ameliorated by rhEPO. Furthermore, rhEPO abrogated the UUO‑induced increase in the number of bone marrow‑derived myofibroblasts. Mechanistically, it was discovered that rhEPO decreased CXC chemokine ligand 16 (CXCL16) expression at protein level. However, treatment with rhEPO did not alter the protein expression of CC chemokine ligand 21 or CXCL12. These results suggested that rhEPO decreased fibrocyte accumulation via the suppression of renal CXCL16, which resulted in the attenuation of renal fibrosis.

  17. Role of renal DJ-1 in the pathogenesis of hypertension associated with increased reactive oxygen species production.

    Science.gov (United States)

    Cuevas, Santiago; Zhang, Yanrong; Yang, Yu; Escano, Crisanto; Asico, Laureano; Jones, John E; Armando, Ines; Jose, Pedro A

    2012-02-01

    The D(2) dopamine receptor (D(2)R) is important in the pathogenesis of essential hypertension. We have already reported that systemic deletion of the D(2)R gene in mice results in reactive oxygen species (ROS)-dependent hypertension, suggesting that the D(2)R has antioxidant effects. However, the mechanism of this effect is unknown. DJ-1 is a protein that has antioxidant properties. D(2)R and DJ-1 are expressed in the mouse kidney and colocalize and coimunoprecipitate in mouse renal proximal tubule cells. We hypothesized that D(2)Rs regulate renal ROS production in the kidney through regulation of DJ-1 expression or function. Heterozygous D(2)(+/-) mice have increased blood pressure, urinary 8-isoprostanes, and renal Nox 4 expression, but decreased renal DJ-1 expression. Silencing D(2)R expression in mouse renal proximal tubule cells increases ROS production and decreases the expression of DJ-1. Conversely, treatment of these cells with a D(2)R agonist increases DJ-1 expression and decreases Nox 4 expression and NADPH oxidase activity, effects that are partially blocked by a D(2)R antagonist. Silencing DJ-1 expression in mouse renal proximal tubule cells increases ROS production and Nox 4 expression. Selective renal DJ-1 silencing by the subcapsular infusion of DJ-1 siRNA in mice increases blood pressure, renal Nox4 expression, and NADPH oxidase activity. These results suggest that the inhibitory effects of D(2)R on renal ROS production are at least, in part, mediated by a positive regulation of DJ-1 expression/function and that DJ-1 may have a role in the prevention of hypertension associated with increased ROS production.

  18. EPO gene expression induces the proliferation, migration and invasion of bladder cancer cells through the p21WAF1‑mediated ERK1/2/NF-κB/MMP-9 pathway.

    Science.gov (United States)

    Park, Sung Lyea; Won, Se Yeon; Song, Jun-Hui; Kim, Wun-Jae; Moon, Sung-Kwon

    2014-11-01

    Erythropoietin (EPO) is a cytokine that modulates the production of red blood cells. Previous studies have contradicted the assumed role of EPO in tumor cell proliferation. In the present study, we investigated the effect of EPO in the proliferation, migration and invasion that is involved in the signaling pathways and cell-cycle regulation of bladder cancer 5637 cells. The results showed that an overexpression of the EPO gene has a potent stimulatory effect on DNA synthesis, migration and invasion. EPO gene expression increased the expression of matrix metalloproteinase (MMP)-9 via the binding activity of NF-κB, AP-1 and Sp-1 in 5637 cells. The transfection of 5637 cells with the EPO gene induced the phosphorylation of ERK1/2. Treatment with ERK1/2 inhibitor U0126 significantly inhibited the increased proliferation, migration and invasion of EPO gene-transfected cells. U0126 treatment suppressed the induction of MMP-9 expression through NF-κB binding activity in EPO gene transfectants. In addition, EPO gene expression was correlated with the upregulation of cyclins/CDKs and the upregulation of the CDK inhibitor p21WAF1 expression. Finally, the inhibition of p21WAF1 function by siRNA blocked the proliferation, migration, invasion and phosphorylation of ERK1/2 signaling, as well as MMP-9 expression and activation of NF-κB in EPO gene-transfected cells. These novel findings suggest that the molecular mechanisms of EPO contribute to the progression and development of bladder tumors.

  19. RELATIONSHIP BETWEEN CYTOMEGALOVIRUS INFECTION AND THE PRODUCTION OF AN TICARDIOLIPIN ANTIBODY IN RENAL TRANSPLANT RECIPIENTS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the relationship bet wee n cytomegalovirus (CMV) infection and the production of anticardiolipin antibody (ACA) in renal transplant recipients.Methods Polymerase c hain reaction (PCR) was used qualitat ively for detection of CMV-DNA in 146 renal transplant recipients.Meanwhile,enz yme-linked immunosorbent assay (ELISA) was used for detection of ACA-IgG in bl ood serum samples from these recipients and 32 healthy individuals. Results The ACA positive rate was 17.1% among the 146 ren al transplant recipients,and that of the control group was 6.3%.There was no sig nificant difference.However,the ACA positive rate of the renal transplant recipi ents infected with CMV was 31.2%.It was clearly higher than that of those with n o infection of CMV and that of the control group (P<0.005). Con clusion The production of ACA was closely related to CMV infection.It m ight be one of the factors of chronic angiopathy of the transpl anted kidney due to CMV infection.

  20. Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes.

    Directory of Open Access Journals (Sweden)

    Yu-Yo Sun

    Full Text Available The neuroprotective effect of baicalein is generally attributed to inhibition of 12/15-lipoxygenase (12/15-LOX and suppression of oxidative stress, but recent studies showed that baicalein also activates hypoxia-inducible factor-α (HIF1α through inhibition of prolyl hydrolase 2 (PHD2 and activation of the phosphatidylinositide-3 kinase (PI3K/Akt signaling pathway. Yet, the significance and regulation of prosurvival cytokines erythropoietin (Epo and vascular endothelial growth factor (VEGF, two transcriptional targets of HIF1α, in baicalein-mediated neuroprotection in neurons and astrocytes remains unknown. Here we investigated the causal relationship between the PI3K/Akt signaling pathway and Epo/VEGF expression in baicalein-mediated neuroprotection in primary rat cortical neurons and astrocytes. Our results show that baicalein induced Epo and VEGF expression in a HIF1α- and PI3K/Akt-dependent manner in neurons. Baicalein also protected neurons against excitotoxicity in a PI3K- and Epo/VEGF-dependent manner without affecting neuronal excitability. In contrast, at least a 10-fold higher concentration of baicalein was needed to induce Epo/VEGF production and PI3K/Akt activity in astrocytes for protection of neurons. Moreover, only baicalein-induced astrocytic VEGF, but not Epo expression requires HIF1α, while PI3K/Akt signaling had little role in baicalein-induced astrocytic Epo/VEGF expression. These results suggest distinct mechanisms of baicalein-mediated Epo/VEGF production in neurons and astrocytes for neuroprotection, and provide new insights into the mechanisms and potential of baicalein in treating brain injury in vivo.

  1. Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes.

    Science.gov (United States)

    Sun, Yu-Yo; Lin, Shang-Hsuan; Lin, Hung-Cheng; Hung, Chia-Chi; Wang, Chen-Yu; Lin, Yen-Chu; Hung, Kuo-Sheng; Lien, Cheng-Chang; Kuan, Chia-Yi; Lee, Yi-Hsuan

    2013-01-01

    The neuroprotective effect of baicalein is generally attributed to inhibition of 12/15-lipoxygenase (12/15-LOX) and suppression of oxidative stress, but recent studies showed that baicalein also activates hypoxia-inducible factor-α (HIF1α) through inhibition of prolyl hydrolase 2 (PHD2) and activation of the phosphatidylinositide-3 kinase (PI3K)/Akt signaling pathway. Yet, the significance and regulation of prosurvival cytokines erythropoietin (Epo) and vascular endothelial growth factor (VEGF), two transcriptional targets of HIF1α, in baicalein-mediated neuroprotection in neurons and astrocytes remains unknown. Here we investigated the causal relationship between the PI3K/Akt signaling pathway and Epo/VEGF expression in baicalein-mediated neuroprotection in primary rat cortical neurons and astrocytes. Our results show that baicalein induced Epo and VEGF expression in a HIF1α- and PI3K/Akt-dependent manner in neurons. Baicalein also protected neurons against excitotoxicity in a PI3K- and Epo/VEGF-dependent manner without affecting neuronal excitability. In contrast, at least a 10-fold higher concentration of baicalein was needed to induce Epo/VEGF production and PI3K/Akt activity in astrocytes for protection of neurons. Moreover, only baicalein-induced astrocytic VEGF, but not Epo expression requires HIF1α, while PI3K/Akt signaling had little role in baicalein-induced astrocytic Epo/VEGF expression. These results suggest distinct mechanisms of baicalein-mediated Epo/VEGF production in neurons and astrocytes for neuroprotection, and provide new insights into the mechanisms and potential of baicalein in treating brain injury in vivo.

  2. EduBites: Cliffs Notes for EPO

    Science.gov (United States)

    Brinkworth, Carolyn; Bartolone, L.; Wenger, M.; Martin, A.; Nichols-Yehling, M.; Llamas, J.; Hurt, R. L.; Squires, G. K.

    2013-06-01

    We present a new resource for the astronomy education community, with the goal of improving our community’s knowledge and understanding of the educational research papers pertinent to our work. When launched, EduBites will be a searchable database of summaries of peer-reviewed education papers, written by astronomy educators and posted for the entire community to use. While we are all aware that we should be basing our E/PO work on a solid research foundation, many people in the community are pushed for time when it comes to staying on top of the educational literature. EduBites aims to reduce that workload for the benefit of the entire community. Our database will ultimately tackle papers across the whole of the astronomy education spectrum, including formal and informal education, outreach, grades K-16, pedagogy, evaluation, and many other topics. We are keen to hear from anyone on the community who would be interested in joining our review team, and will welcome feedback on the EduBites user experience. EduBites is still currently under development but, when launched, it will be found at edubites.ipac.caltech.edu

  3. Gender difference and sex hormone production in rodent renal ischemia reperfusion injury and repair

    Directory of Open Access Journals (Sweden)

    Ghazali Daniel

    2011-06-01

    Full Text Available Abstract Background Several lines of evidence suggest a protective effect of female sex hormones in several organs subjected to ischemia-reperfusion injury. The aim of the study was to investigate sex hormone production in male rats after a renal ischemia-reperfusion sequence and analyze the influence of gender differences on tissue remodelling during the recovery process. Method Age-matched sexually mature male and female rats were subjected to 60 min of renal unilateral ischemia by pedicle clamping with contralateral nephrectomy and followed for 1 or 5 days after reperfusion. Plasma creatinine, systemic testosterone, progesterone and estradiol levels were determined. Tubular injury, cell proliferation and inflammation, were evaluated as well as proliferating cell nuclear antigen, vimentin and translocator protein (TSPO expressions by immunohistochemistry. Results After 1 and 5 days of reperfusion, plasma creatinine was significantly higher in males than in females, supporting the high mortality in this group. After reperfusion, plasma testosterone levels decreased whereas estradiol significantly increased in male rats. Alterations of renal function, associated with tubular injury and inflammation persisted during the 5 days post-ischemia-reperfusion, and a significant improvement was observed in females at 5 days of reperfusion. Proliferating cell nuclear antigen and vimentin expression were upregulated in kidneys from males and attenuated in females, in parallel to injury development. TSPO expression was transiently increased in proximal tubules in male rats. Conclusions After ischemia, renal function recovery and tissue injury is gender-dependent. These differences are associated with a modulation of sex hormone production and a modification of tissue remodeling and proliferative cell processes.

  4. EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Sun, Jianmin [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Jögi, Annika [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Neumann, Drorit [Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Rönnstrand, Lars [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Påhlman, Sven, E-mail: sven.pahlman@med.lu.se [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel)

    2014-02-28

    Highlights: • New anti-human EPOR antibody confirms full-length EPOR expression in breast cancer cells. • Proliferation of breast cancer cells is not affected by rhEPO treatment in vitro. • EPOR knockdown impairs proliferation of ERa positive breast cancer cells. • EPOR knockdown reduces AKT phosphorylation and ERa activity. - Abstract: The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα{sup +}) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells.

  5. Integrating Near Fault Observatories (NFO) for EPOS Implementation Phase

    Science.gov (United States)

    Chiaraluce, Lauro

    2015-04-01

    Following the European Plate Observing System (EPOS) project vision aimed at creating a pan-European infrastructure for Earth sciences to support science for a more sustainable society, we are working on the integration of Near-Fault Observatories (NFOs). NFOs are state of the art research infrastructures consisting of advanced networks of multi-parametric sensors continuously monitoring the chemical and physical processes related to the common underlying earth instabilities governing active faults evolution and the genesis of earthquakes. Such a methodological approach, currently applicable only at the local scale (areas of tens to few hundreds of kilometres), is based on extremely dense networks and less common instruments deserving an extraordinary work on data quality control and multi-parameter data description. These networks in fact usually complement regional seismic and geodetic networks (typically with station spacing of 50-100km) with high-density distributions of seismic, geodetic, geochemical and geophysical sensors located typically within 10-20 km of active faults where large earthquakes are expected in the future. In the initial phase of EPOS-IP, seven NFO nodes will be linked: the Alto Tiberina and Irpinia Observatories in Italy, the Corinth Observatory in Greece, the South-Iceland Seismic Zone, the Valais Observatory in Switzerland, Marmara Sea GEO Supersite in Turkey (EU MARSite) and the Vrancea Observatory in Romania. Our work is aimed at establishing standards and integration within this first core group of NFOs while other NFOs are expected to be installed in the next years adopting the standards established and developed within the EPOS Thematic Core Services (TCS). The goal of our group is to build upon the initial development supported by these few key national observatories coordinated under previous EU projects (NERA and REAKT), inclusive and harmonised TCS supporting the installation over the next decade of tens of near

  6. 下一代广电宽带接入网技术——EPoC%EPoC:Next-generation Solution for Cable Broadband Access Network

    Institute of Scientific and Technical Information of China (English)

    李远东

    2012-01-01

    First, the background resulted in the tendency of EPoC is analysed. Then, EPoC's reference architecture, MAC layer, SDM for PHY modulation/demodulation etc. Are discussed. EPoC's field network architectures and the unified network management for EPON and EPoC are thirdly introduced. Some suggestions to EPoC are presented as well. Finally, it gives the conclusion that EPoC has the potential to be the most cost effective access network solution.%分析了下一代广电宽带接入网技术EPoC的背景,探讨了EPoC的参考架构、MAC原理、物理层调制SDM技术,还介绍了EPoC的组网、EPON与EPoC的统一网管,给出了EPoC的相关建议.最后得出“EPoC有望成为性价比最高的接入网解决方案”的结论.

  7. Detection of neutralizing antibodies to erythropoietin by inhibition of rHuEPO-stimulated EGR1 gene expression in the UT-7/EPO cell line.

    Science.gov (United States)

    Ferguson, Jackie; Bird, Chris; Wadhwa, Meenu; Burns, Chris

    2013-01-31

    Recombinant erythropoietin (rHuEPO) is used extensively to treat anaemia associated with chronic kidney disease. However, the development of neutralizing antibodies (NAbs) to rHuEPO can result in the development of antibody-mediated pure red cell aplasia (PRCA). The detection of NAb in patient sera by in vitro bioassay relies on the inhibition of a cellular response to rHuEPO. Current bioassays for rHuEPO measure proliferation in responsive cell lines such as the erythroleukaemic cell lines, UT-7 and UT-7/EPO, the latter sensitized to EPO. Using these cell lines, we show the dose-responsive induction of both PIM1 and EGR1 gene expression in UT-7 cells and of EGR1 in UT-7/EPO cells. The expression of EGR1 in UT-7/EPO cells in response to rHuEPO was comparable to the proliferative response measured by (3)H-thymidine incorporation and could be inhibited by serum from a patient with NAb-mediated PRCA in a dilution-dependent manner. Bioassays based on the induction of endogenous gene expression are comparable to current bioassays but are considerably quicker given that incubation time is decreased from 2-3 days to 50 min. Measurement of EGR1 gene expression in response to rHuEPO in UT-7/EPO cells offers a rapid, non-radioactive and automatable alternative to current assays for the detection of rHuEPO NAbs.

  8. Ethical implication of providing scientific data and services to diverse stakeholders: the case of the EPOS research infrastructure

    Science.gov (United States)

    Freda, Carmela; Atakan, Kuvvet; Cocco, Massimo

    2017-04-01

    EPOS, the European Plate Observing System, is an ESFRI infrastructure serving the needs of the solid Earth science community as a whole. EPOS promotes the use of multidisciplinary solid Earth data to improve the understanding of physical and chemical processes controlling earthquakes, volcanic eruptions, tsunamis as well as those driving tectonics and surface dynamics. The EPOS mission is to create a single, sustainable, and distributed infrastructure that integrates the diverse European research infrastructures for solid Earth science under a common framework with the final goal of delivering a suite of domain-specific and multidisciplinary data, products, and services in one single and integrated platform. Addressing ethics issues is a relevant challenge for any initiative, program or project dealing with scientific data and products provision, access to services for scientific purposes and communication with different stakeholders, including industry and society at large. In examining the role of EPOS on openly and freely delivering scientific data and products to diverse stakeholders including but not limited to scientists, we are looking at ethical issues associated with the use and re-use of these data and products possibly leading to a malevolent use and/or misuse of the data with implications on, for example, national security, environmental protection and risk communication. Moreover, EPOS is aware that the research promoted by the use of data delivered through its platform can have a profound influence on the environment, human health and wellbeing, economic development, and other facets of societies. We know there is nothing intrinsically bad about openly and freely delivering scientific data, as it serves as a tool for leveraging researches leading to solutions for a responsible management of Earth's resources and mitigation of natural hazards. However, we must evaluate the effects of such a data provision and feel the obligation to adopt a responsible

  9. Urinary collagen degradation products as early markers of progressive renal fibrosis.

    Science.gov (United States)

    Hijmans, Ryanne S; Rasmussen, Daniel Guldager Kring; Yazdani, Saleh; Navis, Gerjan; van Goor, Harry; Karsdal, Morten Asser; Genovese, Federica; van den Born, Jacob

    2017-03-20

    Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrotic S1P-receptor modulator FTY720 treatment. Proteinuria was induced in male Wistar rats by Adriamycin (ADR) injection (n = 16). Healthy rats served as controls (n = 12). Six weeks post-injection, all underwent renal biopsy, and FTY720-treatment started in ADR-rats (n = 8) and controls (n = 6). Others remained untreated. Rats were sacrificed after 12 weeks. Collagen type I (C1M) and III (C3M) degradation fragments were measured in blood and urine using ELISA. Kidneys were stained for various inflammatory and fibrotic markers. Six weeks post-injection proteinuria increased (versus controls, P < 0.001) and although no accumulation of interstitial renal collagen type III (iColl3) was observed at this time, urinary C3M (uC3M) and C1M (uC1M) were significantly increased (both P < 0.001). At 12 weeks, uC3M (P < 0.001) and uC1M (P < 0.01) further increased in ADR-rats versus controls, just as fibronectin, PDGF-β receptor, hyaluronan (all P < 0.01), iColl3, PAS, myofibroblasts, macrophages and T-cells (all P < 0.05). FTY720-treatment reduced accumulation of immune cells, α-SMA+ myofibroblasts and PAS-score, but not iColl3 and uC3M. Correlation analyses indicated that uC3M and uC1M reflected and predicted tubulointerstitial fibrogenesis. These data displayed urinary collagen breakdown products as sensitive early markers of interstitial fibrosis, preceding histological fibrotic changes, which might replace the invasive renal biopsy procedure to assess fibrosis. Anti-fibrotic FTY720 intervention reduced some fibrotic markers without affecting collagen type III metabolism.

  10. Incorporation of geomagnetic data and services into EPOS infrastructure

    Science.gov (United States)

    Hejda, Pavel; Chambodut, Aude; Curto, Juan-Jose; Flower, Simon; Kozlovskaya, Elena; Kubašta, Petr; Matzka, Jürgen; Tanskanen, Eija; Thomson, Alan

    2016-04-01

    Monitoring of the geomagnetic field has a long history across Europe that dates back to 1830', and is currently experiencing an increased interest within Earth observation and space weather monitoring. Our goals within EPOS-IP are to consolidate the community, modernise data archival and distribution formats for existing services and create new services for magnetotelluric data and geomagnetic models. Specific objectives are: • Enhance existing services providing geomagnetic data (INTERMAGNET- INTErnational Real-time MAGnetic observatory NETwork; World Data Centre for Geomagnetism; IMAGE- International Monitor for Auroral Geomagnetic Effects) and existing services providing geomagnetic indices (ISGI - International Service of Geomagnetic Indices). • Develop and enhance the geomagnetic community's metadata systems by creating a metadata database, filling it and putting in place processes to ensure that it is kept up to date in the future. • Develop and build access to magnetotelluric (MT) data including transfer functions and time series data from temporary, portable MT-arrays in Europe, as well as to lithospheric conductivity models derived from TM-data. • Develop common web and database access points to global and regional geomagnetic field and conductivity models. • Establish links from the geomagnetic data services, products and models to the Integrated Core Services. The immediate task in the current period is to identify data models of existing services, modify them and integrate into a common model of Geomagnetic Thematic Core Services.

  11. EPO relies upon novel signaling of Wnt1 that requires Akt1, FoxO3a, GSK-3β, and β-catenin to foster vascular integrity during experimental diabetes.

    Science.gov (United States)

    Chong, Zhao Zhong; Hou, Jinling; Shang, Yan Chen; Wang, Shaohui; Maiese, Kenneth

    2011-05-01

    Multiple complications can ensue in the cardiovascular, renal, and nervous systems during diabetes mellitus (DM). Given that endothelial cells (ECs) are susceptible targets to elevated serum D-glucose, identification of novel cellular mechanisms that can protect ECs may foster the development of unique strategies for the prevention and treatment of DM complications. Erythropoietin (EPO) represents one of these novel strategies but the dependence of EPO upon Wnt1 and its downstream signaling in a clinically relevant model of DM with elevated D-glucose has not been elucidated. Here we show that EPO can not only maintain the integrity of EC membranes, but also prevent apoptotic nuclear DNA degradation and the externalization of membrane phosphatidylserine (PS) residues during elevated D-glucose over a 48-hour period. EPO modulates the expression of Wnt1 and utilizes Wnt1 to confer EC protection during elevated D-glucose exposure, since application of a Wnt1 neutralizing antibody, treatment with the Wnt1 antagonist DKK-1, or gene silencing of Wnt1 with Wnt1 siRNA transfection abrogates the protective capability of EPO. EPO through a novel Wnt1 dependent mechanism controls the post-translational phosphorylation of the "pro-apoptotic" forkhead member FoxO3a and blocks the trafficking of FoxO3a to the cell nucleus to prevent apoptotic demise. EPO also employs the activation of protein kinase B (Akt1) to foster phosphorylation of GSK-3β that appears required for EPO vascular protection. Through this inhibition of GSK-3β, EPO maintains β-catenin activity, allows the translocation of β-catenin from the EC cytoplasm to the nucleus through a Wnt1 pathway, and requires β-catenin for protection against elevated D-glucose since gene silencing of β-catenin eliminates the ability of EPO as well as Wnt1 to increase EC survival. Subsequently, we show that EPO requires modulation of both Wnt1 and FoxO3a to oversee mitochondrial membrane depolarization, cytochrome c release, and

  12. NASA Astrophysics EPO Resources For Engaging Girls in Science

    Science.gov (United States)

    Sharma, M.; Mendoza, D.; Smith, D.; Hasan, H.

    2011-09-01

    A new collaboration among the NASA Science Mission Directorate (SMD) Astrophysics EPO community is to engage girls in science who do not self-select as being interested in science, through the library setting. The collaboration seeks to (i) improve how girls view themselves as someone who knows about, uses, and sometimes contributes to science, and (ii) increase the capacity of EPO practitioners and librarians (both school and public) to engage girls in science. As part of this collaboration, we are collating the research on audience needs and best practices, and SMD EPO resources, activities and projects that focus on or can be recast toward engaging girls in science. This ASP article highlights several available resources and individual projects, such as: (i) Afterschool Universe, an out-of-school hands-on astronomy curriculum targeted at middle school students and an approved Great Science for Girls curriculum; (ii) Big Explosions and Strong Gravity, a Girl Scout patch-earning event for middle school aged girls to learn astronomy through hands-on activities and interaction with actual astronomers; and (iii) the JWST-NIRCAM Train the Trainer workshops and activities for Girl Scouts of USA leaders; etc. The NASA Astrophysics EPO community welcomes the broader EPO community to discuss with us how best to engage non-science-attentive girls in science, technology, engineering, and mathematics (STEM), and to explore further collaborations on this theme.

  13. Detection of recombinant EPO in blood and urine samples with EPO WGA MAIIA, IEF and SAR-PAGE after microdose injections.

    Science.gov (United States)

    Dehnes, Yvette; Shalina, Alexandra; Myrvold, Linda

    2013-01-01

    The misuse of microdoses of performance enhancing drugs like erythropoietin (EPO) constitutes a major challenge in doping analysis. When injected intravenously, the half-life of recombinant human EPO (rhEPO) like epoetin alfa, beta, and zeta is only a few hours and hence, the window for direct detection of rhEPO in urine is small. In order to investigate the detection window for rhEPO directly in blood and urine with a combined affinity chromatography and lateral flow immunoassay (EPO WGA MAIIA), we recruited nine healthy people who each received six intravenously injected microdoses (7.5 IU/kg) of NeoRecormon (epoetin beta) over a period of three weeks. Blood and urine samples were collected in the days following the injections and analyzed with EPO WGA MAIIA as well as the current validated methods for rhEPO; isoelectric focusing (IEF) and sarcosyl polyacrylamide gel electrophoresis (SAR-PAGE). For samples collected 18 h after a microdose, the sensitivity of the EPO WGA MAIIA assay was 100% in plasma and 87.5% in urine samples at the respective 98% specificity threshold levels. In comparison, the sensitivity in plasma and urine was 75% and 100%, respectively, with IEF, and 87.5% in plasma and 100% in urine when analyzed with SAR-PAGE. We conclude that EPO WGA MAIIA is a sensitive assay for the detection of rhEPO, with the potential of being a fast, supplemental screening assay for use in doping analysis.

  14. Ethics issues in scientific data and service provision: evidence and challenges for the European Plate Observing System (EPOS)

    Science.gov (United States)

    Cocco, Massimo; Freda, Carmela; Haslinger, Florian; Consortium, Epos

    2016-04-01

    Addressing Ethics issues is nowadays a relevant challenge for any initiative, program or project dealing with scientific data and products provision, access to services for scientific purposes and communication with different stakeholders, including society. This is corroborated by the evidence that Ethics has very high priority in EU funded research. Indeed, all the activities carried out under Horizon 2020 must comply with ethical principles and national, Union and international legislation. This implies that "For all activities funded by the European Union, Ethics is an integral part of research from beginning to end, and ethical compliance is seen as pivotal to achieve real research excellence." Here, we present the experience of EPOS, a public pan-European research infrastructure. EPOS aims at integrating data, data products, services and software (DDSS) for solid Earth science generated and provided by monitoring networks, observing systems and facilities belonging to European countries. EPOS fosters the integrated use of multidisciplinary solid Earth data to improve the understanding of physical and chemical processes controlling earthquakes, volcanic eruptions, tsunamis as well as those driving tectonics and surface dynamics. The EPOS integration plan will make significant contributions to understanding and mitigating geo-hazards, yielding data for hazard assessment, data products for engaging different stakeholders, and services for training, education and communication to society. Numerous national research infrastructures engaged in EPOS are deployed for the monitoring of areas prone to geo-hazards and for the surveillance of the national territory including areas used for exploiting geo-resources. The EPOS community is therefore already trained to provide services to public (civil defence agencies, local and national authorities) and private (petroleum industry, mining industry, geothermal companies, aviation security) stakeholders. Our ability to

  15. Orally administrated Juzen-taiho-to/TJ-48 ameliorates erythropoietin (rHuEPO)-resistant anemia in patients on hemodialysis.

    Science.gov (United States)

    Nakamoto, Hidetomo; Mimura, Taku; Honda, Nobuko

    2008-10-01

    Maintenance of the red blood cell volume is a fundamental aspect of ensuring oxygen supply to the tissue. Recombinant human erythropoietin (rHuEPO) was approved for marketing in Japan in 1990 for the treatment of anemia in patients on dialysis. Recombinant human erythropoietin caused a significant increase in hemoglobin (Hb) levels in patients on dialysis. However, not all have a good response to rHuEPO therapy; the causes of rHuEPO failure include iron deficiency, infection, uremia, and interaction of some drugs. Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been used traditionally to treat patients with anemia, anorexia, or fatigue. To clarify the effect of TJ-48 on erythropoietin-resistant anemia, we studied the effect of TJ-48 in patients on hemodialysis with erythropoietin-resistant anemia. We divided 42 end-stage renal disease patients on hemodialysis with erythropoietin-resistant anemia (Hbrenal disease patients. This effect was, at least in part, due to the anti-inflammatory effect of TJ-48 in patients on hemodialysis.

  16. Epo/ Epo-R 在非小细胞肺癌中的表达和MVD 关系及意义%Expression and signifrcance of erythropoietin / erythropoietin receptor(Epo/ Epo-R) in non-small cell lung cancer (NSCLC) and the relation with microvessel density(MVD)

    Institute of Scientific and Technical Information of China (English)

    唐甜; 陕光

    2011-01-01

    目的 探讨Epo/ Epo-R在非小细胞肺癌中的表达和肿瘤微血管密度(MVD) 关系及意义.方法 收集武汉大学人民医院病理科2008-2010年非小细胞肺癌存档蜡块40例(男28例,女12例),采用免疫组织化学S-P法检测40例非小细胞肺癌及癌旁组织中Epo/Epo-R的表达水平,并采用HPIAS-1000 高清晰度彩色病理图文报告管理系统对Epo/Epo-R的表达进行定量分析,用SPSS11.5软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK(q)检验.同时检测肿瘤微血管密度(MVD),分析与临床病理之间的关系.结果 Epo/ Epo-R在非小细胞肺癌中的表达明显高于癌旁组织.图像分析结果显示:两组间差异有显著性意义(P<0.05).Epo/ Epo-R表达阳性组织中,MVD计数显著高于Epo/ Epo-R表达阴性者(P<0.05).结论 Epo/Epo-R在非小细胞肺癌中呈高表达,并与微血管密度(MVD) 密切关系,联合检测Epo/Epo-R 和MVD 更有利于正确判断疾病的临床病理特征及其预后.%Objective To explore the expression of Epo/Epo-R in non-small cell lung cancer (NSCLC) and relation with microvessel density (MVD). Methods Specimens from 40 cases (28 males and 12 females, from 2008 to 2010) of non-small cell lung cancer from Pathology Department in Renmin Hospital of Wuhan University were collected. The expression levels of Epo/Epo-R were detected by immuno-histochemical S-P staining in the 40 specimens of non-small cell lung cancer and adjacent tissues. Average optical density and positive area expression rates of Epo/Epo-R were measured by image analysis (HPIAS-1000). Statistical evaluations for average optic density and positive area rate of immunohistochemical reaction were performed by using one-way ANOVA and q-test. All data were processed by SPSS11. 5. We also detected the microvessel density (MVD) and analysis the relationship with clinical pathology. Results The expression of Epo/Epo-R in NSCLC was

  17. Chronic preclinical safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis-stimulating agent in monkeys and rats.

    Science.gov (United States)

    Gong, Xue-Lian; Gu, Xiao-Lei; Chen, Yong-Chun; Zhu, Hai; Xia, Zhen-Na; Li, Jian-Zhong; Lu, Guo-Cai

    2016-09-15

    EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is mainly designed for treatment of anemia caused by chronic renal failure and chemotherapy against cancer. It overcomes the deficiencies of currently approved ESA, including the frequent administration of temperature-sensitive recombinant protein and anti-EPO antibody-mediated pure red cell aplasia (PRCA). This study was designed to evaluate the potential chronic toxicity of EPO-018B. Subcutaneous administration doses were designed as 0, 0.2, 1 and 10mg/kg for six months for 160 rats (20/gender/group) and 0, 0.3, 3 and 20mg/kg for nine months for 32 monkeys (4/gender/group) once every three weeks. The vehicles received the same volume of physiological saline injection. All animals survived to the scheduled necropsies after six weeks (for rats) and fourteen weeks (for monkeys) recovery period, except for the two high-dose female rats and two high-dose male monkeys, which were considered related to the increased RBCs, chronic blood hyperviscosity and chronic cardiac injury. EPO-018B is supposed to be subcutaneously injected once every month and the intended human therapeutic dose is 0.025mg/kg. The study findings at 0.2mg/kg for rats and 0.3mg/kg for monkeys were considered to be the study NOAEL (the no observed adverse effect level), which were more than ten times the intended human therapeutic dose. Higher doses caused adverse effects related to the liver toxicity, cardiotoxicity, appearance of neutralizing antibodies of EPO-018B and the decrease of serum glucose and cholesterol. Most treatment-induced effects were reversible or revealed ongoing recovery upon the discontinuation of treatment. The sequelae occurred in rats and monkeys were considered secondary to exaggerated pharmacology and would less likely occur in the intended patient population. As to the differences between human beings and animals, the safety of EPO-018B need to be further confirmed in the future clinical studies.

  18. CREB is activated in EPO induced HEL cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    cAMP response element binding protein (CREB) is a transcription factor in nucleus. The activating CREB can specifically bind to the cAMP response element (CRE). The present result showed that erythropoietin (EPO) could induce the phosphorylation of CREB on Serine133(Pser133), as detected by Western blot analysis. In addition, the EPO-dependent activation of CREB binding to CRE element was demonstrated by electrophoretic mobility shift assay. However, the binding of CREB to CRE element could be inhibited by anti-CREB-Pser133antibody. The data obtained suggested that the EPO-mediated CREB phosphorylation might be critical to both the binding of CREB to the CRE element and the activation of the CREB transcription factor.

  19. Continuous production of erythropoietin by an established human renal carcinoma cell line: development of the cell line

    Energy Technology Data Exchange (ETDEWEB)

    Sherwood, J.B.; Shouval, D.

    1986-01-01

    Establishment of a stable, transformed human renal carcinoma cell line that produces erythropoietin in vitro and has maintained this function continuously since 1981 and for > 150 passages in monolayer culture was accomplished by transplantation of human renal clear cell carcinoma tissue from a patient with erythrocytosis into an immunosuppressed athymic mouse. In addition to its immunocrossreactivity with native human urinary erythropoietin, the tumor erythropoietin demonstrates biological activity in the in vitro mouse erythroid colony-forming unit assay and in tumor-bearing nude mice. The cloned renal carcinoma cell line has an abnormal human karyotype and has ultrastructural features characteristic of human renal clear cell carcinoma. This cell line provides a reproducible model system for the production of an erythropoietin-like material and for the study of its synthesis and secretion.

  20. Progress of Epo/EpoR system and traumatic brain injury%Epo/EpoR系统与创伤性颅脑损伤的研究进展

    Institute of Scientific and Technical Information of China (English)

    熊思华; 刘红梅; 孙海晨

    2012-01-01

    Traumatic brain injury is a leading cause of death in young adults. The high mortality and long-term morbidity of severe traumatic brain injury bring huge burden to the individuals, the family and even the whole society. No medications or procedures have been proven to improve the outcome of severe traumatic brain injury. Over the past twenty years, more and more evidences have revealed that erythropoietin therapy shows the most clinical significance to improve neurological outcomes in patients with severe traumatic brain injury,and its effect is mediated by erythropoietin receptor. It is suggested that the Epo/EpoR system plays a vital role in protecting the brain.%创伤性颅脑损伤(TBI)是导致青壮年患者死亡和长期残疾的主要病因之一.严重颅脑损伤的高死亡率、高致残率给个人、家庭乃至社会带来沉重的负担.如何改善颅脑损伤患者的预后一直是创伤研究的重要课题.近20年的研究发现,促红细胞生成素(Epo)很可能具有改善预后的潜力,该作用由促红细胞生成素受体(EpoR)介导.Epo/EpoR系统在脑保护方面担负着重要的角色.

  1. E-research platform of EPOS Thematic Core Service "ANTHROPOGENIC HAZARDS"

    Science.gov (United States)

    Orlecka-Sikora, Beata; Lasocki, Stanisław; Grasso, Jean Robert; Schmittbuhl, Jean; Kwiatek, Grzegorz; Garcia, Alexander; Cassidy, Nigel; Sterzel, Mariusz; Szepieniec, Tomasz; Dineva, Savka; Biggare, Pascal; Saccorotti, Gilberto; Sileny, Jan; Fischer, Tomas

    2016-04-01

    EPOS Thematic Core Service ANTHROPOGENIC HAZARDS (TCS AH) aims to create new research opportunities in the field of anthropogenic hazards evoked by exploitation of georesources. TCS AH, based on the prototype built in the framework of the IS-EPOS project (https://tcs.ah-epos.eu/), financed from Polish structural funds (POIG.02.03.00-14-090/13-00), is being further developed within EPOS IP project (H2020-INFRADEV-1-2015-1, INFRADEV-3-2015). TCS AH is designed as a functional e-research environment to ensure a researcher the maximum possible freedom for in silico experimentation by providing a virtual laboratory in which researcher will be able to create own workspace with own processing streams. The unique integrated RI is: (i) data gathered in the so- called "episodes", comprehensively describing a geophysical process, induced or triggered by human technological activity, which under certain circumstances can become hazardous for people, infrastructure and the environment and (ii) problem-oriented, specific high-level services, with the particular attention devoted to methods analyzing correlations between technology, geophysical response and resulting hazard. Services to be implemented are grouped within six blocks: (1) Basic services for data integration and handling; (2) Services for physical models of stress/strain changes over time and space as driven by geo-resource production; (3) Services for analysing geophysical signals; (4) Services to extract the relation between technological operations and observed induced seismic/deformation; (5) Services to quantitative probabilistic assessments of anthropogenic seismic hazard - statistical properties of anthropogenic seismic series and their dependence on time-varying anthropogenesis; ground motion prediction equations; stationary and time-dependent probabilistic seismic hazard estimates, related to time-changeable technological factors inducing the seismic process; (6) Simulator for Multi

  2. A Database of EPO-Patenting Firms in Denmark

    DEFF Research Database (Denmark)

    Nielsen, Anders Østergaard

    1998-01-01

    The first section gives a brief introduction of the basic stages to be observed by the patent applicant from idea to the patent is granted. Section two presents three examples of how patents are registered in the online patent database INPADOC. Section three accounts for the initial analysis...... of the existing patent stock issued to firms with domicile in Denmark. Sections four and five report the basic characteristics of the EPO-patent sample and the procedures for linking the patent statistics to accounting data at the firm level, and finally they present the basic properties of the resulting database...... containing 421 EPO-patenting firms in Denmark....

  3. Accumulation of advanced glycation end products, measured as skin autofluorescence, in renal disease.

    Science.gov (United States)

    Hartog, Jasper W L; de Vries, Aiko P J; Lutgers, Helen L; Meerwaldt, Robbert; Huisman, Roel M; van Son, Willem J; de Jong, Paul E; Smit, Andries J

    2005-06-01

    Advanced glycation end products (AGEs) accumulate during renal failure and dialysis. Kidney transplantation is thought to reverse this accumulation by restoring renal function. Using a noninvasive and validated autofluorescence reader, we evaluated AGE levels in 285 transplant recipients (mean age, 52 years; range, 41 to 60 years), 32 dialysis patients (mean age, 56 years; range, 43 to 65 years), and 231 normal control subjects (mean age, 51 years; range, 40 to 65 years). Measurements in transplant recipients were performed for a mean of 73 months (range, 32 to 143 months) after transplantation. Dialysis patients were on dialysis therapy for a mean of 42 months (range, 17 to 107 months). Fluorescence was significantly increased in dialysis patients compared with normal control subjects (2.8 vs. 2.0 arbitrary units [a.u.], P < .0001). Although fluorescence levels were significantly decreased in transplant recipients compared with dialysis patients (2.5 vs. 2.8 a.u., P < .0001), fluorescence in transplant recipients was higher than in controls (2.5 vs. 2.0 a.u., P < .0001). In transplant recipients, fluorescence correlated positively with the duration of dialysis prior to transplantation (R = 0.21, P < .0001), and negatively with creatinine clearance (R = -0.34, P < .0001). No correlation was found between time after transplantation and fluorescence in transplant recipients (R = -0.10, P = .10). Fluorescence in dialysis patients was positively correlated with duration of dialysis (R = 0.36, P = .042). Our results, like those of others, suggest that kidney transplantation does not fully correct increased AGE levels found in dialysis patients. The increased AGE levels in kidney transplant recipients cannot be explained by the differences in renal function alone. The availability of a simple, noninvasive method (AGE-Reader) to measure AGE accumulation may be used to monitor AGE accumulation in a clinical setting as well as in a study setting.

  4. Eudragit EPO nanoparticles: application in improving therapeutic efficacy and reducing ulcerogenicity of meloxicam on oral administration.

    Science.gov (United States)

    Khachane, Parag; Date, Abhijit A; Nagarsenker, Mangal S

    2011-08-01

    The objective of this investigation was to evaluate the potential of Eudragit EPO nanoparticles (EPO NP) in improving therapeutic efficacy of meloxicam (MLX). MLX loaded EPO NP were prepared by nanoprecipitation method and were characterized for particle size, encapsulation efficiency and for morphology. The in vitro dissolution profile of MLX loaded EPO NP and MLX suspension was evaluated. MLX loaded EPO NP had particle size of approximately 100 nm and the encapsulation efficiency of MLX was approximately 90%. The EPO NP significantly improved anti-inflammatory activity of MLX (P EPO NP Oral administration of MLX loaded EPO NP also resulted in lesser ulcerogenicity as compared to that of MLX suspension indicating that nanoparticles can also decrease the adverse effects associated with MLX treatment.

  5. The EGI-Engage EPOS Competence Center - Interoperating heterogeneous AAI mechanisms and Orchestrating distributed computational resources

    Science.gov (United States)

    Bailo, Daniele; Scardaci, Diego; Spinuso, Alessandro; Sterzel, Mariusz; Schwichtenberg, Horst; Gemuend, Andre

    2016-04-01

    manage the use of the subsurface of the Earth. EPOS started its Implementation Phase in October 2015 and is now actively working in order to integrate multidisciplinary data into a single e-infrastructure. Multidisciplinary data are organized and governed by the Thematic Core Services (TCS) - European wide organizations and e-Infrastructure providing community specific data and data products - and are driven by various scientific communities encompassing a wide spectrum of Earth science disciplines. TCS data, data products and services will be integrated into the Integrated Core Services (ICS) system, that will ensure their interoperability and access to these services by the scientific community as well as other users within the society. The EPOS competence center (EPOS CC) goal is to tackle two of the main challenges that the ICS are going to face in the near future, by taking advantage of the technical solutions provided by EGI. In order to do this, we will present the two pilot use cases the EGI-EPOS CC is developing: 1) The AAI pilot, dealing with the provision of transparent and homogeneous access to the ICS infrastructure to users owning different kind of credentials (e.g. eduGain, OpenID Connect, X509 certificates etc.). Here the focus is on the mechanisms which allow the credential delegation. 2) The computational pilot, Improve the back-end services of an existing application in the field of Computational Seismology, developed in the context of the EC funded project VERCE. The application allows the processing and the comparison of data resulting from the simulation of seismic wave propagation following a real earthquake and real measurements recorded by seismographs. While the simulation data is produced directly by the users and stored in a Data Management System, the observations need to be pre-staged from institutional data-services, which are maintained by the community itself. This use case aims at exploiting the EGI FedCloud e-infrastructure for Data

  6. Advanced glycation end products (AGEs) increase renal lipid accumulation: a pathogenic factor of diabetic nephropathy (DN).

    Science.gov (United States)

    Yuan, Yang; Sun, Hong; Sun, Zilin

    2017-06-28

    Advanced glycation end products (AGEs) are pathogenic factors of diabetic nephropathy (DN), causing renal damage in various ways. The aim of this study is to investigate the ectopic lipid accumulation caused by AGEs in human renal tubular epithelial cell line (HK-2) cells and the kidney of type 2 diabetic rats. In vivo study, diabetes was induced in male Sprague-Dawley rats through intraperitoneal injection of high-fat/high-sucrose diet and low-dose streptozocin (STZ). Two weeks after STZ injection, the diabetic rats were randomly divided into two groups, namely, untreated diabetic and Aminoguanidine Hydrochloride (AG, an AGEs formation inhibitor)-treated (100 mg/Kg/day, i.g., for 8 weeks) group. In vitro study, according to the different treatments, HK-2 were divided into 6 groups. Intracellular cholesterol content was assessed by Oil Red O staining and cholesterol enzymatic assay. Expression of mRNA and protein of molecules controlling cholesterol homeostasis in the treated cells was examined by real-time quantitative PCR and western blotting, respectively. SREBP cleavage-activating protein (SCAP) translocation was detected by confocal microscopy. Here we found Nε-(carboxymethyl) lysine (CML, a member of the AGEs family) increased Oil Red O staining and intracellular cholesterol ester (CE) in HK-2 cells; Anti-RAGE (AGEs receptor) reduced lipid droplets and the CE level. A strong staining of Oil Red O was also found in the renal tubules of the diabetic rats, which could be alleviated by AG. CML upregulated both mRNA and protein expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), LDL receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2) and SCAP, which were inhibited by anti-RAGE. The upregulation of these molecules in the kidney of the diabetic rats was also ameliorated by AG. Furthermore, AG reduced serum and renal CML deposition, and improved urine protein and u-NGAL in type 2 diabetic rats. Overall, these results

  7. Impaired renal H+ secretion and NH3 production in mineralocorticoid-deficient glucocorticoid-replete dogs.

    Science.gov (United States)

    Hulter, H N; Ilnicki, L P; Harbottle, J A; Sebastian, A

    1977-02-01

    When the administration of exogenous mineralocorticoid hormones was discontinued in adrenalectomized dogs maintained on glucocorticoid, net acid excretion decreased due largely to a reduction in urinary ammonium excretion (UNH4+V), and hyperchloremic hyperkalemic metabolic acidosis occurred and persisted. The reduction in UNH4+V was not associated with an increase in urine pH (UpH) or a decrease in urine flow, but correlated with the severity of hyperkalemia and was mitigated by dietary potassium restriction. UpH decreased to values as low as 5.3. During acidosis, UpH varied directly with UNH4+V, but in relation to UNH4+V, UpH exceeded that in acid-fed mineralocorticoid-replete dogs. Extrapolated to UNH4+V=0, however, UpH was not significantly different in the two groups (5.27 vs. 5.44). When distal delivery of sodium was increased by infusion of sodium phosphate, titratable acid excretion increased in both groups but pateaued at lower rates in the mineralocorticoid-deficient dogs. These results suggest that in mineralocorticoid-deficient dogs, renal ammonia production is diminished, in part due to potassium retention and hyperkalemia; renal hydrogen ion secretory capacity is reduced even when sodium and buffer delivery to the distal nephron is not reduced; and the ability of the kidney to generate normally steep urine-to-blood hydrogen ion concentration gradients is unimpaired.

  8. 促红细胞生成素对大鼠肾脏缺血再灌注损伤的抗炎保护作用及其机制%Protective effect of erythropoietin on inflammation of renal ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    汪悠悠; 贾宁; 彭莉; 张慧涛; 朱晔; 郑晶; 朱伟平; 张桦

    2013-01-01

    blot analyses. Results Compared with IRI group, the EPO treated group exhibited lower serum urea and creatinine levels(P<0.05) and limited the renal histopathological lesion. The concentration of TNF-α and the expression of p-p38MAPK in renal tissue were greatly increased by IRI, but significantly reduced by the treatment of EPO. Conclusion EPO can attenuate the renal injury and dysfunction caused by IRI via reducing the expression of p-p38MAPK and the production of TNF-α. The renoprotective effect of EPO might be mediated by its inhibition of inflammation.

  9. Nasal neuro EPO could be a reliable choice for neuroprotective stroke treatment.

    Science.gov (United States)

    Parra, Alicia Lagarto; Rodriguez, Julio Cesar Garcia

    2012-03-01

    The most common cause of stroke is cerebral ischemia, where blood flow to the brain is interrupted due to a thrombus in a major cerebral artery. Currently, the only therapeutic approach available is thrombolysis. A more recent approach that has started to gain attention is neuroprotection, the ability to prevent neuronal death and enhance endogenous protective mechanisms. Several studies have shown the neuroprotective action of Erythropoietin (EPO). A potential problem in the use of EPO for neurodegenerative disorders is the undesirable erythropoietic side effects. In this context, investigations have been focused to develop derivatives of EPO lacking erythropoietic activity but retaining neuroprotective potential. Low sialic acid-containing EPO (Neuro EPO) is very similar to the one that occurs in the mammalian brain and is rapidly degraded by the liver. Similar neuroprotective effects had been observed with neuro EPO, original recombinant human EPO and EPO variants in ischemia models. Intranasal route could be safe and hematological side effects could be avoided. Neuro EPO that constitutes a new agent has retained the neuroprotective effects without stimulating the EPOR in the bone marrow and can therefore be used without increasing the hematocrit. This review gives a brief introduction to the no hematopoietic effects of EPO, the evidence of neuroprotective effect, the alternatives for obtaining an EPO derivate without hematological side effects and discusses the advantages of nasal administration of Neuro EPO for neuroprotective stroke treatment.

  10. Epo receptors are not detectable in primary human tumor tissue samples.

    Directory of Open Access Journals (Sweden)

    Steve Elliott

    Full Text Available Erythropoietin (Epo is a cytokine that binds and activates an Epo receptor (EpoR expressed on the surface of erythroid progenitor cells to promote erythropoiesis. While early studies suggested EpoR transcripts were expressed exclusively in the erythroid compartment, low-level EpoR transcripts were detected in nonhematopoietic tissues and tumor cell lines using sensitive RT-PCR methods. However due to the widespread use of nonspecific anti-EpoR antibodies there are conflicting data on EpoR protein expression. In tumor cell lines and normal human tissues examined with a specific and sensitive monoclonal antibody to human EpoR (A82, little/no EpoR protein was detected and it was not functional. In contrast, EpoR protein was reportedly detectable in a breast tumor cell line (MCF-7 and breast cancer tissues with an anti-EpoR polyclonal antibody (M-20, and functional responses to rHuEpo were reported with MCF-7 cells. In another study, a functional response was reported with the lung tumor cell line (NCI-H838 at physiological levels of rHuEpo. However, the specificity of M-20 is in question and the absence of appropriate negative controls raise questions about possible false-positive effects. Here we show that with A82, no EpoR protein was detectable in normal human and matching cancer tissues from breast, lung, colon, ovary and skin with little/no EpoR in MCF-7 and most other breast and lung tumor cell lines. We show further that M-20 provides false positive staining with tissues and it binds to a non-EpoR protein that migrates at the same size as EpoR with MCF-7 lysates. EpoR protein was detectable with NCI-H838 cells, but no rHuEpo-induced phosphorylation of AKT, STAT3, pS6RP or STAT5 was observed suggesting the EpoR was not functional. Taken together these results raise questions about the hypothesis that most tumors express high levels of functional EpoR protein.

  11. The Contribution of the Geodetic Community (WG4) to EPOS

    Science.gov (United States)

    Fernandes, R. M. S.; Bastos, L. C.; Bruyninx, C.; D'Agostino, N.; Dousa, J.; Ganas, A.; Lidberg, M.; Nocquet, J.-M.

    2012-04-01

    WG4 - "EPOS Geodetic Data and Infrastructure" is the Working Group of the EPOS project responsible to define and prepare the integration of the existing Pan-European Geodetic Infrastructures into a unique future consistent infrastructure that supports the European Geosciences, which is the ultimate goal of the EPOS project. The WG4 is formed by representatives of the participating EPOS countries and from EUREF (European Reference Frame), which also ensures the inclusion and the contact with countries that formally are not part of the current phase of EPOS. In reality, the fact that Europe is formed by many countries (having different laws and policies) lacking an infrastructure similar to UNAVCO (which concentrates the effort of the local geo-science community) raises the difficulties to create a common geodetic infrastructure serving not only the entire geo-science community, but also many other areas of great social-economic impact. The benefits of the creation of such infrastructure (shared and easily accessed by all) are evident in order to optimize the existing and future geodetic resources. This presentation intends to detail the work being produced within the working group WG4 related with the definition of strategies towards the implementation of the best solutions that will permit to the end-users, and in particular geo-scientists, to access the geodetic data, derived solutions, and associated metadata using transparent and uniform processes. Discussed issues include the access to high-rate data in near real-time, storage and backup of historical and future data, the sustainability of the networks in order to achieve long-term stability in the observation infrastructure, seamless access to the data, open data policies, and processing tools.

  12. The Geological information and modelling Thematic Core Service of EPOS

    Science.gov (United States)

    Robida, François; Wächter, Joachim; Tulstrup, Jørgen; Lorenz, Henning; Carter, Mary; Cipolloni, Carlo; Morel, Olivier

    2016-04-01

    Geological data and models are important assets for the EPOS community. The Geological information and modelling Thematic Core Service of EPOS is being designed and will be implemented in an efficient and sustainable access system for geological multi-scale data assets for EPOS through the integration of distributed infrastructure components (nodes) of geological surveys, research institutes and the international drilling community (ICDP/IODP). The TCS will develop and take benefit of the synergy between the existing data infrastructures of the Geological Surveys of Europe (EuroGeoSurveys / OneGeology-Europe / EGDI) and of the large amount of information produced by the research organisations. These nodes will offer a broad range of resources including: geological maps, borehole data, geophysical data (seismic data, borehole log data), archived information on physical material (samples, cores), geochemical and other analyses of rocks, soils and minerals, and Geological models (3D, 4D). The services will be implemented on international standards (such as INSPIRE, IUGS/CGI, OGC, W3C, ISO) in order to guarantee their interoperability with other EPOS TCS as well as their compliance with INSPIRE European Directive or international initiatives (such as OneGeology). This will provide future virtual research environments with means to facilitate the use of existing information for future applications. In addition, workflows will be established that allow the integration of other existing and new data and applications. Processing and the use of simulation and visualization tools will subsequently support the integrated analysis and characterization of complex subsurface structures and their inherent dynamic processes. This will in turn aid in the overall understanding of complex multi-scale geo-scientific questions. This TCS will work alongside other EPOS TCSs to create an efficient and comprehensive multidisciplinary research platform for the Earth Sciences in Europe.

  13. Mission and Research Scientists in NASA EPO and STEM Education: The Results of 15 Years of EPO

    Science.gov (United States)

    Lebofsky, L. A.; McCarthy, D. W.; Higgins, M. L.; Mueller, B.; Lebofsky, N. R.

    2014-07-01

    Exploration of the Solar System and beyond is a team effort, from research programs to space missions. The same is true for science education. James Webb Space Telescope's Near InfraRed Camera EPO Team has been teamed with Girl Scouts of Southern Arizona for nearly a decade. We now have collaborations throughout Arizona and across the nation.

  14. Increased EPO Levels Are Associated With Bone Loss in Mice Lacking PHD2 in EPO-Producing Cells.

    Science.gov (United States)

    Rauner, Martina; Franke, Kristin; Murray, Marta; Singh, Rashim Pal; Hiram-Bab, Sahar; Platzbecker, Uwe; Gassmann, Max; Socolovsky, Merav; Neumann, Drorit; Gabet, Yankel; Chavakis, Triantafyllos; Hofbauer, Lorenz C; Wielockx, Ben

    2016-10-01

    The main oxygen sensor hypoxia inducible factor (HIF) prolyl hydroxylase 2 (PHD2) is a critical regulator of tissue homeostasis during erythropoiesis, hematopoietic stem cell maintenance, and wound healing. Recent studies point toward a role for the PHD2-erythropoietin (EPO) axis in the modulation of bone remodeling, even though the studies produced conflicting results. Here, we used a number of mouse strains deficient of PHD2 in different cell types to address the role of PHD2 and its downstream targets HIF-1α and HIF-2α in bone remodeling. Mice deficient for PHD2 in several cell lineages, including EPO-producing cells, osteoblasts, and hematopoietic cells (CD68:cre-PHD2(f/f) ) displayed a severe reduction of bone density at the distal femur as well as the vertebral body due to impaired bone formation but not bone resorption. Importantly, using osteoblast-specific (Osx:cre-PHD2(f/f) ) and osteoclast-specific PHD2 knock-out mice (Vav:cre- PHD2(f/f) ), we show that this effect is independent of the loss of PHD2 in osteoblast and osteoclasts. Using different in vivo and in vitro approaches, we show here that this bone phenotype, including the suppression of bone formation, is directly linked to the stabilization of the α-subunit of HIF-2, and possibly to the subsequent moderate induction of serum EPO, which directly influenced the differentiation and mineralization of osteoblast progenitors resulting in lower bone density. Taken together, our data identify the PHD2:HIF-2α:EPO axis as a so far unknown regulator of osteohematology by controlling bone homeostasis. Further, these data suggest that patients treated with PHD inhibitors or EPO should be monitored with respect to their bone status. © 2016 American Society for Bone and Mineral Research.

  15. Chronic administration of phosphodiesterase type 5 inhibitor suppresses renal production of endothelin-1 in dogs with congestive heart failure.

    Science.gov (United States)

    Yamamoto, Takashi; Wada, Atsuyuki; Ohnishi, Masato; Tsutamoto, Takayoshi; Fujii, Masanori; Matsumoto, Takehiro; Takayama, Tomoyuki; Wang, Xinwen; Kurokawa, Kiyoshi; Kinoshita, Masahiko

    2002-08-01

    Endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) play important roles in the regulation of body fluid balance in congestive heart failure (CHF). Renal production of ET-1 increases in CHF and it is a significant independent predictor of sodium excretion. ANP inhibits the ET system through cGMP, a second messenger of ANP. However, in severe CHF, plasma cGMP levels reached a plateau despite the activation of ANP secretion. Thus, ANP does not seem to sufficiently oppose exaggerated ET-1 actions in severe CHF, partially due to the accelerated degradation of cGMP, through phosphodiesterase type 5 (PDE5). We examined the chronic effects of a PDE5 inhibitor, T-1032 (1 mg/kg per day, n=5), on renal function and renal production of ET-1 in dogs with CHF induced by rapid ventricular pacing (270 beats/min). Vehicle dogs were given a placebo (n=5) and normal dogs (n=5) served as normal controls without pacing. In this experimentally produced CHF, plasma levels of ET-1, ANP and cGMP were elevated and renal production of cGMP was increased compared with the normal group, associated with increases in renal expression of preproET-1 mRNA and the number of ET-1-positive cells in glomeruli. In the T-1032 group, systemic and renal production of cGMP were further increased compared with the vehicle group despite no significant difference in plasma ANP levels between the two groups. Subsequently, the agent significantly improved urine flow rate, sodium excretion rate and glomerular filtration rate (GFR) associated with reductions in renal expression of preproET-1 mRNA and the number of ET-1-positive cells compared with the vehicle group. Moreover, there was a significant negative correlation between the number of ET-1-positive cells and GFR (r=-0.802 and Prenal ANP and ET-1 through the cGMP pathway, subsequently preventing renal dysfunction during the progression of CHF.

  16. EPO reduces reactive gliosis and stimulates neurotrophin expression in Muller cells.

    Science.gov (United States)

    Hu, Liu-Mei; Luo, Yan; Zhang, Jingfa; Lei, Xia; Shen, Jianfeng; Wu, Yalan; Qin, Mei; Unver, Yaprak Banu; Zhong, Yong; Xu, Guo-Tong; Li, Weiye

    2011-06-01

    To characterize Müller cell-mediated neuroprotective and neurotrophic functions of the erythropoietin (EPO)/EPO receptor (EpoR) system in diabetic rat retina. A single intravitreal injection of EPO (8 mU/eye) was administered in rats 4 or 24 weeks after diabetes onset. The results showed that intravitreal EPO ameliorated the up-regulation of GFAP and vimentin in the diabetic retina evaluated by immunofluorescence and Western blotting; but up-regulated BDNF and CNTF expressions, quantified by real-time PCR and ELISA, in the 24-week diabetic rat retinas. In vitro, BDNF and CNTF expressions were stimulated by EPO through both extracellular signal-regulated kinase1/2 (ERK1/2) and Akt pathways. The neuro-regenerative function of EPO, as indicated by promotion of neurite outgrowth, was corroborated in vitro. BDNF was involved in EPO-induced neurite outgrowth of primary rat retinal neurons. Exogenous EPO exerts neuroprotective and neurotrophic functions by attenuating reactive gliosis and promoting neurotrophic factors in Muller cells in diabetic retina. Signaling pathways that are responsible for these Muller cell-mediated EPO/EpoR functions may be therapeutic targets for diabetic retinopathy.

  17. Coordinated response of renal medullary enzymes regulating net sorbitol production in diuresis and antidiuresis.

    Science.gov (United States)

    Sands, J M; Schrader, D C

    1990-07-01

    The renal response to changes in hydration includes variation in intracellular sorbitol, a major inner medullary osmolyte. To examine the mechanism for changes in net sorbitol production, we measured activities of enzymes regulating sorbitol production (aldose reductase) and degradation (sorbitol dehydrogenase) in untreated, water diuretic, and antidiuretic (water restriction and/or vasopressin administration) rats. Collecting duct segments dissected from collagenase-treated kidneys of Sprague-Dawley rats were divided into outer medullary and three distinct inner medullary regions. Aldose reductase activity increased during antidiuresis and decreased during diuresis. In contrast, sorbitol dehydrogenase activity was very low during antidiuresis and increased during diuresis. These changes in enzyme activity were found after 3 days, but not after 1 day, of water diuresis/antidiuresis. Enzyme activity changed only in the deepest 50% of the inner medullary collecting duct. Thus, there is coordinated regulation of aldose reductase and sorbitol dehydrogenase activities so that (a) during water diuresis, aldose reductase activity decreases while sorbitol dehydrogenase activity increases; and (b) during antidiuresis (water restriction and/or vasopressin administration), aldose reductase activity increases while sorbitol dehydrogenase activity remains low. We conclude that long-term osmoregulation in response to physiologic stimuli involves both aldose reductase and sorbitol dehydrogenase activities in rat terminal inner medullary collecting duct segments.

  18. Gene therapy for rat renal anemia with implantation of erythropoietin-transgenic myoblasts

    Institute of Scientific and Technical Information of China (English)

    刘永学; 魏汉东; 吴祖泽; 贺福初

    1999-01-01

    To investigate whether an erythropoietin (EPO) gene-based therapy could serve as an alternative to the repeated injection of rhEPO in treatment to renal anemia, the genetically modified myoblasts of rats, named Myo/ EPO, were implanted through intramuscular injection to model rats with renal anemia. The hemoglobin (Hb) and hematocrit (HCT) of the rats increased from (92. 5±3.0) g/L and 0.29 ±0.04 to the peak values of (103.8 ±5.0) g/L and 0. 32 ±0. 04 respectively 14 d after implantation, and sustained the pre-implantation level for 90 d. Otherwise, the control rats implanted with Myo/X, which carried the parent retroviral vector, gradually became severe in anemia. The PCR detection for hEPO cDNA in the rat muscle adjacent to injection sites indicated that the Myo/EPO cells survived for a long period in the muscle of rats. The results primarily demonstrate that myoblast gene transfer of EPO is effective for the treatment of rat renal anemia.

  19. Sestrin2 decreases renal oxidative stress, lowers blood pressure, and mediates dopamine D2 receptor-induced inhibition of reactive oxygen species production.

    Science.gov (United States)

    Yang, Yu; Cuevas, Santiago; Yang, Sufei; Villar, Van Anthony; Escano, Crisanto; Asico, Laureano; Yu, Peiying; Jiang, Xiaoliang; Weinman, Edward J; Armando, Ines; Jose, Pedro A

    2014-10-01

    The dopamine D2 receptor (D2R) decreases renal reactive oxygen species (ROS) production and regulates blood pressure, in part, via positive regulation of paraoxonase 2. Sestrin2, a highly conserved antioxidant protein, regulates intracellular ROS level by regenerating hyperoxidized peroxiredoxins. We hypothesized that sestrin2 may be involved in preventing excessive renal ROS production and thus contribute to the maintenance of normal blood pressure. Moreover, the D2R may decrease ROS production, in part, through the regulation of sestrin2. Renal sestrin2 expression was lower (-62±13%) in D2R(-/-) than in D2R(+/+) mice. Silencing D2R in human renal proximal tubule cells decreased sestrin2 expression (-53±3%) and increased hyperoxidized peroxiredoxins (2.9-fold). Stimulation of D2R in renal proximal tubule cells increased sestrin2 expression (1.6-fold), decreased hyperoxidized peroxiredoxins (-61±3%), and reduced ROS production (-31±4%). Silencing sestrin2 in renal proximal tubule cells increased hyperoxidized peroxiredoxins (2.1-fold) and ROS production (1.3-fold). Silencing sestrin2 also abolished D2R-induced decrease in peroxiredoxin hyperoxidation and partially prevented the inhibitory effect of D2R stimulation on ROS production. Silencing paraoxonase 2 increased sestrin2 ubiquitinylation (2.8-fold), decreased sestrin2 expression (-30±3%), and increased ROS production (1.3-fold), peroxiredoxin hyperoxidation (2.9-fold), and lipid peroxidation (2.3-fold), and blocked the increase in sestrin2 that occurs with D2R stimulation. In vivo renal selective silencing of sestrin2 by the renal subcapsular infusion of sestrin2 small interfering RNA (3 μg/day; 7 days) in mice increased renal oxidative stress (1.3-fold) and blood pressure. These results suggest that the D2R, via paraoxonase 2 and sestrin2, keeps normal renal redox balance, which contributes to the maintenance of normal blood pressure.

  20. EPOS Thematic Core Service ANTHROPOGENIC HAZARDS (TCS AH) - development of e-research platform

    Science.gov (United States)

    Orlecka-Sikora, Beata

    2017-04-01

    TCS AH is based on IS-EPOS Platform. The Platform facilitates research on anthropogenic hazards and is available online, free of charge https://tcs.ah-epos.eu/. The Platform is a final product of the IS-EPOS project, founded by the national programme - POIG - which was implemented in 2013-2015 (POIG.02.03.00-14-090/13-00). The platform is a result of a joint work of scientific community and industrial partners. Currently, the development of TCS AH is carried under EPOS IP project (H2020-INFRADEV-1-2015-1, INFRADEV-3-2015). Platform is an open virtual access point for researchers and Ph. D. students interested in anthropogenic seismicity and related hazards. This environment is designed to ensure a researcher the maximum possible liberty for experimentation by providing a virtual laboratory, in which the researcher can design own processing streams and process the data integrated on the platform. TCS AH integrates: data and specific high-level services. Data gathered in the so-called "episodes", comprehensively describing a geophysical process, induced or triggered by human technological activity, which, under certain circumstances can become hazardous for people, infrastructure and the environment. 7 sets of seismic, geological and technological data were made available on the Platform. The data come from Poland, Germany, UK and Vietnam, and refer to underground mining, reservoir impoundment, shale gas exploitation and geothermal energy production. The next at least 19 new episodes related to conventional hydrocarbon extraction, reservoir treatment, underground mining and geothermal energy production are being integrated within the framework of EPOS IP project. The heterogeneous multi-disciplinary data (seismic, displacement, geomechanical data, production data etc.) are transformed to unified structures to form integrated and validated datasets. To deal with this various data the problem-oriented services were designed and implemented. The particular attention

  1. EPO promotes bone repair through enhanced cartilaginous callus formation and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Lin Wan

    Full Text Available Erythropoietin (EPO/erythropoietin receptor (EPOR signaling is involved in the development and regeneration of several non-hematopoietic tissues including the skeleton. EPO is identified as a downstream target of the hypoxia inducible factor-α (HIF-α pathway. It is shown that EPO exerts a positive role in bone repair, however, the underlying cellular and molecular mechanisms remain unclear. In the present study we show that EPO and EPOR are expressed in the proliferating, pre-hypertrophic and hypertrophic zone of the developing mouse growth plates as well as in the cartilaginous callus of the healing bone. The proliferation rate of chondrocytes is increased under EPO treatment, while this effect is decreased following siRNA mediated knockdown of EPOR in chondrocytes. EPO treatment increases biosynthesis of proteoglycan, accompanied by up-regulation of chondrogenic marker genes including SOX9, SOX5, SOX6, collagen type 2, and aggrecan. The effects are inhibited by knockdown of EPOR. Blockage of the endogenous EPO in chondrocytes also impaired the chondrogenic differentiation. In addition, EPO promotes metatarsal endothelial sprouting in vitro. This coincides with the in vivo data that local delivery of EPO increases vascularity at the mid-stage of bone healing (day 14. In a mouse femoral fracture model, EPO promotes cartilaginous callus formation at days 7 and 14, and enhances bone healing at day 28 indexed by improved X-ray score and micro-CT analysis of microstructure of new bone regenerates, which results in improved biomechanical properties. Our results indicate that EPO enhances chondrogenic and angiogenic responses during bone repair. EPO's function on chondrocyte proliferation and differentiation is at least partially mediated by its receptor EPOR. EPO may serve as a therapeutic agent to facilitate skeletal regeneration.

  2. Human recombinant erythropoietin (rEpo) has no effect on tumour growth or angiogenesis.

    Science.gov (United States)

    Hardee, M E; Kirkpatrick, J P; Shan, S; Snyder, S A; Vujaskovic, Z; Rabbani, Z N; Dewhirst, M W; Blackwell, K L

    2005-12-12

    Tumour hypoxia has been shown to increase mutation rate, angiogenesis, and metastatic potential, and decrease response to conventional therapeutics. Improved tumour oxygenation should translate into increased treatment response. Exogenous recombinant erythropoietin (rEpo) has been recently shown to increase tumour oxygenation in a mammary carcinoma model. The mechanism of this action is not yet understood completely. The presence of Epo and its receptor (EpoR) have been demonstrated on several normal and neoplastic tissues, including blood vessels and various solid tumours. In addition, rEpo has been shown in two recent prospective, randomized clinical trials to negatively impact treatment outcome. In this study, we attempt to characterize the direct effects of rEpo on tumour growth and angiogenesis in two separate rodent carcinomas. The effect of rEpo on R3230 rat mammary adenocarcinomas, CT-26 mouse colon carcinomas, HCT-116 human colon carcinomas, and FaDu human head and neck tumours, all of which express EpoR, was examined. There were no differences in tumour growth or proliferation (measured by Ki-67) between placebo-treated and rEpo-treated tumours. In the mammary window chamber, vascular length density (VLD) measurements in serial images of both placebo-treated and Epo-treated rats revealed no difference in angiogenesis between the Epo-treated tumours and placebo-treated tumours at any time point. These experiments are important because they suggest that the recent clinical detriment seen with the use of Epo is not due to its tumour growth effects or angiogenesis. These studies also suggest that further preclinical studies need to examine rEpo's direct tumour effects in efforts to improve the therapeutic benefits of Epo in solid tumour patients.

  3. EPO promotes bone repair through enhanced cartilaginous callus formation and angiogenesis.

    Science.gov (United States)

    Wan, Lin; Zhang, Fengjie; He, Qiling; Tsang, Wing Pui; Lu, Li; Li, Qingnan; Wu, Zhihong; Qiu, Guixing; Zhou, Guangqian; Wan, Chao

    2014-01-01

    Erythropoietin (EPO)/erythropoietin receptor (EPOR) signaling is involved in the development and regeneration of several non-hematopoietic tissues including the skeleton. EPO is identified as a downstream target of the hypoxia inducible factor-α (HIF-α) pathway. It is shown that EPO exerts a positive role in bone repair, however, the underlying cellular and molecular mechanisms remain unclear. In the present study we show that EPO and EPOR are expressed in the proliferating, pre-hypertrophic and hypertrophic zone of the developing mouse growth plates as well as in the cartilaginous callus of the healing bone. The proliferation rate of chondrocytes is increased under EPO treatment, while this effect is decreased following siRNA mediated knockdown of EPOR in chondrocytes. EPO treatment increases biosynthesis of proteoglycan, accompanied by up-regulation of chondrogenic marker genes including SOX9, SOX5, SOX6, collagen type 2, and aggrecan. The effects are inhibited by knockdown of EPOR. Blockage of the endogenous EPO in chondrocytes also impaired the chondrogenic differentiation. In addition, EPO promotes metatarsal endothelial sprouting in vitro. This coincides with the in vivo data that local delivery of EPO increases vascularity at the mid-stage of bone healing (day 14). In a mouse femoral fracture model, EPO promotes cartilaginous callus formation at days 7 and 14, and enhances bone healing at day 28 indexed by improved X-ray score and micro-CT analysis of microstructure of new bone regenerates, which results in improved biomechanical properties. Our results indicate that EPO enhances chondrogenic and angiogenic responses during bone repair. EPO's function on chondrocyte proliferation and differentiation is at least partially mediated by its receptor EPOR. EPO may serve as a therapeutic agent to facilitate skeletal regeneration.

  4. CARCINOGENICITY OF INDIVIDUAL AND A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS IN A RAT MODEL OF HEREDITARY RENAL CELL CARCINOMA

    Science.gov (United States)

    Carcinogenicity of Individual and a Mixture of Drinking Water Disinfection By-Products in a Rat Model of Hereditary Renal Cell Carcinoma Eker rats develop hereditary renal cell carcinoma secondary to a germline mutation in the tuberous sclerosis 2 (Tsc2) gene and are ligh...

  5. Risk factors for chronic transplant dysfunction and cardiovascular disease are related to accumulation of advanced glycation end-products in renal transplant recipients

    NARCIS (Netherlands)

    Hartog, Jasper W. L.; de Vries, Aiko P. J.; Bakker, Stephan J. L.; Graaff, Reindert; van Son, Willem J.; van der Heide, Jaap J. Homan; Gans, Reinold O. B.; Wolffenbuttel, Bruce H. R.; de Jong, Paul E.; Smit, Andries J.

    2006-01-01

    Background. Accumulation of advanced glycation end-products (AGEs) has been implicated in the pathogenesis of chronic transplant dysfunction and cardiovascular disease in renal transplant recipients. We aimed to investigate which factors are associated with tissue AGE accumulation in renal transplan

  6. Plasminogen activator inhibitor-1 fused with erythropoietin (EPO) mimetic peptide (EMP) enhances the EPO activity of EMP.

    Science.gov (United States)

    Kuai, L; Wu, C; Qiu, Q; Zhang, J; Zhou, A; Wang, S; Zhang, H; Song, Q; Liao, S; Han, Y; Liu, J; Ma, Z

    2000-08-01

    Erythropoietin (EPO) mimetic peptide (EMP) encoding sequence was inserted into the gene of plasminogen activator inhibitor-1 (PAI-1) between Ala348 and Pro349 (P2'-P3'), generating a novel gene, PAI-1/EMP (PMP). This was cloned into pET32a expression vector, fused with TrxA peptide in the vector, and a 63-kDa protein was expressed in inclusion bodies with an expression level >50%. The TrxA/PMP protein was purified by Ni-NTA-agarose metal-ligand affinity chromatography to a purity >90%, showing a single, silver-stained band on SDS-PAGE. Using a reticulocyte counting assay, the EPO activity of PMP was determined to be 5,000 IU/mg, 2,500-fold that of EMP.

  7. Geological Survey data as a support for EPOS

    Science.gov (United States)

    Tulstrup, Jørgen; Robida, Francois; Harrison, Matthew; Bogaard, Paul; Pedersen, Mikael

    2015-04-01

    The National Geological Surveys of Europe have through many years collaborated on making their large possessions of geological data available for researchers, the general public and decision makers at all levels. Numerous projects have been carried out with the aim of harmonizing data across national boundaries and making data interoperable by delivering them according to international standards like those defined by INSPIRE, OGC, CGI and others. In 2012 - 2014 an EU co-funded study was carried out with the title of EGDI-Scope. The study showed how an integrated European Geological Data Infrastructure (EGDI) can be established so that all sorts of geological data form the Geological Surveys can be accessed in a common way by the relevant stakeholders. The establishment of such an EGDI is a cornerstone of the strategy of the organization of the Geological Surveys of Europe, EuroGeoSurveys, and the organization has decided to start implementing the infrastructure and establishing an organization which will ensure that this will be sustained. One of the most obvious user groups for the geological information is EPOS, the European Plate Observing System, which will be implemented in the coming years. The EPOS implementation project therefore contains a specific workpackage to establish the connection between the Geological Survey data and the rest of EPOS. A Thematic Core Service (TCS) for geological data and modeling will be built for making the data available for the Integrated Core Services of EPOS. The TCS will deal with borehole data, digital geological maps, geophysical data like seismics and borehole logs, archived physical geological material like samples and cores, geochemical and other analyses of rocks, soil and minerals as well as with 3D and 4D geological models of the subsurface. Great emphasis will be put on making the system sustainable and with easy access and the idea is also to further develop and promote the international standards for data exchange

  8. Sun-Earth Connection EPO's with Multiple Uses and Audiences

    Science.gov (United States)

    Foster, S. Q.; Johnson, R. M.; Russell, R.; Lu, G.; Richmond, A.; Maute, A.; Haller, D.; Conery, C.; Bintner, G.; Kiessling, D.; Hughes, W. J.

    2005-05-01

    The three-year life of an EPO grant can be a journey guided by clear goals and enriched by collaborative and outreach opportunities connecting Space sciences to Earth sciences for both K-12 and public audiences. This point is illustrated by two EPO projects funded by NASA Sun-Earth Connection research grants to the High Altitude Observatory (HAO) at the National Center for Atmospheric Research. They are entering their final year coordinated by the Office of Education and Outreach at University Corporation for Atmospheric Research. The content focus of both projects is well aligned with HAO's research mission and the expertise of our scientists, addressing solar dynamics, space weather, and the impacts of solar events on the magnetosphere, as well as societies inhabiting Earth's surface. The first project (Gang Lu, PI) develops presentation resources, inquiry activities, and tips that will help HAO scientists be better prepared to visit K-12 classrooms. Unexpectedly, the simultaneous development of a Teachers' Guide to NCAR's new Climate Discovery exhibit, which takes an Earth system approach to climate and global change, has created a niche for this EPO resource to be revised and repurposed for a needed unit in the guide about the exhibit's graphic panels on Sun-Earth connections. The second project (Art Richmond, PI) engages two high school "Teachers in Residence" to develop resources they can utilize with their students. Excited by exceptional educational graphics and animations in the new Physics of the Aurora: Earth Systems module co-produced by HAO and the COMET Program for advanced undergraduate courses, they chose to adapt appropriate sections of the module to enrich Earth science and math concepts addressed in their 9th and 10th grade astronomy and general physics classes. Simultaneously, the Windows to the Universe web site, which continuously updates space science content and is now developing a new Space Weather section with support from the Center for

  9. Early and sustained increase in the expression of hippocampal IGF-1, but not EPO, in a developmental rodent model of traumatic brain injury.

    Science.gov (United States)

    Schober, Michelle E; Block, Benjamin; Beachy, Joanna C; Statler, Kimberly D; Giza, Christopher C; Lane, Robert H

    2010-11-01

    Pediatric traumatic brain injury (pTBI) is the leading cause of traumatic death and disability in children in the United States. Impaired learning and memory in these young survivors imposes a heavy toll on society. In adult TBI (aTBI) models, cognitive outcome improved after administration of erythropoietin (EPO) or insulin-like growth factor-1 (IGF-1). Little is known about the production of these agents in the hippocampus, a brain region critical for learning and memory, after pTBI. Our objective was to describe hippocampal expression of EPO and IGF-1, together with their receptors (EPOR and IGF-1R, respectively), over time after pTBI in 17-day-old rats. We used the controlled cortical impact (CCI) model and measured hippocampal mRNA levels of EPO, IGF-1, EPOR, IGF-1R, and markers of caspase-dependent apoptosis (bcl2, bax, and p53) at post-injury days (PID) 1, 2, 3, 7, and 14. CCI rats performed poorly on Morris water maze testing of spatial working memory, a hippocampally-based cognitive function. Apoptotic markers were present early and persisted for the duration of the study. EPO in our pTBI model increased much later (PID7) than in aTBI models (12 h), while EPOR and IGF-1 increased at PID1 and PID2, respectively, similar to data from aTBI models. Our data indicate that EPO expression showed a delayed upregulation post-pTBI, while EPOR increased early. We speculate that administration of EPO in the first 1-2 days after pTBI would increase hippocampal neuronal survival and function.

  10. The EPOS Vision for the Open Science Cloud

    Science.gov (United States)

    Jeffery, Keith; Harrison, Matt; Cocco, Massimo

    2016-04-01

    Cloud computing offers dynamic elastic scalability for data processing on demand. For much research activity, demand for computing is uneven over time and so CLOUD computing offers both cost-effectiveness and capacity advantages. However, as reported repeatedly by the EC Cloud Expert Group, there are barriers to the uptake of Cloud Computing: (1) security and privacy; (2) interoperability (avoidance of lock-in); (3) lack of appropriate systems development environments for application programmers to characterise their applications to allow CLOUD middleware to optimize their deployment and execution. From CERN, the Helix-Nebula group has proposed the architecture for the European Open Science Cloud. They are discussing with other e-Infrastructure groups such as EGI (GRIDs), EUDAT (data curation), AARC (network authentication and authorisation) and also with the EIROFORUM group of 'international treaty' RIs (Research Infrastructures) and the ESFRI (European Strategic Forum for Research Infrastructures) RIs including EPOS. Many of these RIs are either e-RIs (electronic-RIs) or have an e-RI interface for access and use. The EPOS architecture is centred on a portal: ICS (Integrated Core Services). The architectural design already allows for access to e-RIs (which may include any or all of data, software, users and resources such as computers or instruments). Those within any one domain (subject area) of EPOS are considered within the TCS (Thematic Core Services). Those outside, or available across multiple domains of EPOS, are ICS-d (Integrated Core Services-Distributed) since the intention is that they will be used by any or all of the TCS via the ICS. Another such service type is CES (Computational Earth Science); effectively an ICS-d specializing in high performance computation, analytics, simulation or visualization offered by a TCS for others to use. Already discussions are underway between EPOS and EGI, EUDAT, AARC and Helix-Nebula for those offerings to be

  11. Korean red ginseng extract alleviates advanced glycation end product-mediated renal injury.

    Science.gov (United States)

    Quan, Hai Yan; Kim, Do Yeon; Chung, Sung Hyun

    2013-04-01

    The effect of Korean red ginseng (KRG) on diabetic renal damage was investigated using streptozotocin (STZ)-induced diabetic rats. The diabetic rats showed loss of body weight gain, and increases in kidney weight and urine volume, whereas the oral administration of KRG at a dose of 100 or 250 mg/kg of body weight per day for 28 d prevented these diabetes-induced physiological abnormalities. Among the kidney function parameters, elevated plasma levels of urea nitrogen and creatinine in diabetic control rats tended to be lowered in KRG-treated rats. In addition, administration of KRG at a dose of 100 mg/kg body weight in the diabetic rats showed significant decreases in serum glucose and tumor necrosis factor-α (TNF-α), implying that KRG might prevent the pathogenesis of diabetic complications caused by impaired glucose metabolism and oxidative stress. KRG also significantly reduced advanced glycation end product (AGE) formation and secretion from kidney of diabetic rats. Furthermore, KRG decreased the levels of N-(carboxymethyl) lysine and expression of AGE receptor. KRG also reduced the overexpression of cyclooxygenase-2 and inducible nitric oxide synthase in the kidney via deactivation of nuclear factor-kappa B. We also found that KRG prevented STZ-induced destruction of glomerular structure and significantly suppressed high glucose-induced fibronectin production. Taken together, KRG ameliorates abnormalities associated with diabetic nephropathy through suppression of inflammatory pathways activated by TNF-α and AGEs. These findings indicate that KRG has a beneficial effect on pathological conditions associated with diabetic nephropathy.

  12. Biphasic cultivation strategy to avoid Epo-Fc aggregation and optimize protein expression.

    Science.gov (United States)

    Kaisermayer, Christian; Reinhart, David; Gili, Andreas; Chang, Martina; Aberg, Per-Mikael; Castan, Andreas; Kunert, Renate

    2016-06-10

    In biphasic cultivations, the culture conditions are initially kept at an optimum for rapid cell growth and biomass accumulation. In the second phase, the culture is shifted to conditions ensuring maximum specific protein production and the protein quality required. The influence of specific culture parameters is cell line dependent and their impact on product quality needs to be investigated. In this study, a biphasic cultivation strategy for a Chinese hamster ovary (CHO) cell line expressing an erythropoietin fusion protein (Epo-Fc) was developed. Cultures were run in batch mode and after an initial growth phase, cultivation temperature and pH were shifted. Applying a DoE (Design of Experiments) approach, a fractional factorial design was used to systematically evaluate the influence of cultivation temperature and pH as well as their synergistic effect on cell growth as well as on recombinant protein production and aggregation. All three responses were influenced by the cultivation temperature. Additionally, an interaction between pH and temperature was found to be related to protein aggregation. Compared with the initial standard conditions of 37°C and pH 7.05, a parameter shift to low temperature and acidic pH resulted in a decrease in the aggregate fraction from 75% to less than 1%. Furthermore, the synergistic effect of temperature and pH substantially lowered the cell-specific rates of glucose and glutamine consumption as well as lactate and ammonium production. The optimized culture conditions also led to an increase of the cell-specific rates of recombinant Epo-Fc production, thus resulting in a more economic bioprocess.

  13. Expression of EPO Receptor in Pancreatic Cells and Its Effect on Cell Apoptosis

    Institute of Scientific and Technical Information of China (English)

    Hongxia SHUAI; Ji ZHANG; Yikai YU; Muxun ZHANG

    2008-01-01

    In order to explore the expression of erythropoietin receptor (EPOR) in pancreatic cell ine NIT-1 and its effect on cell apoptosis after binding with erythropoietin (EPO), NIT-1 cells were cultured and expanded. The expression of EPOR was detected using electrophoresis. NIT-1 apoptosis was induced by cytokines and their effects on cell apoptosis and cell insulin secretion were assayed after binding of EPO to EPOR. The results showed that EPOR was expressed in NIT-1 cells. Recom- binant human EPO (rHuEPO) had no effect on cell apoptosis but significantly inhibited apoptosis in- duced by cytokines, rHuEPO had no effect on cell insulin secretion but significantly improved insulin secretion inhibited by cytokines. From these findings, it was concluded that EPOR was expressed in NIT-1 cells and EPO could protect N1T-1 cells from apoptosis induced by cytokines.

  14. rhEPO affects apoptosis in hippocampus of aging rats by upregulating SIRT1

    Science.gov (United States)

    Wu, Haiqin; Wang, Huqing; Zhang, Wenting; Wei, Xuanhui; Zhao, Jiaxin; Yan, Pu; Liu, Chao

    2015-01-01

    The aim of this study was to elucidate the signaling pathway involved in the anti-aging effect of erythropoietin (EPO) and to clarify whether recombinant human EPO (rhEPO) affects apoptosis in the aging rat hippocampus by upregulating Sirtuin 1 (SIRT1). In this study, a rat model of aging was established using D-galactose. Behavioral changes were monitored by the Morris water maze test. Using immunohistochemistry, we studied the expression of SIRT1, B-cell lymphoma/leukemia-2 gene (Bcl-2), and Bcl-2 associated X protein (Bax) expression, and apoptotic cells in the hippocampus of a rat model of aging in which rhEPO was intraperitoneally injected. The escape latency in rats from the EPO group shortened significantly; however, the number of platform passes increased significantly from that in the D-gal group (P anti-aging property of EPO. PMID:26261574

  15. Evaluating effects of EPO in rodent behavioral assays related to depression.

    Science.gov (United States)

    Duman, Catharine H; Newton, Samuel S

    2013-01-01

    The cytokine erythropoietin (EPO) is an important regulator of hematopoesis and has well-known tissue protective properties. Neurotrophic action is implicated as mechanistically important in the treatment of depression, and neurotrophic actions of EPO suggest potential therapeutic utility of an EPO-like mechanism in depressive disorder. Rodent behavioral models that are responsive to clinically used antidepressants as well as to neurotrophic compounds can be used to assess potential antidepressant properties of EPO and EPO-like compounds. Rodent models described here are the forced-swim test (FST), a hyponeophagia test and the novel object recognition test. Each of these models provides different information and relevance to depression and each can be tested with EPO and similar compounds.

  16. Therapeutic levels of erythropoietin (EPO) achieved after gene electrotransfer to skin in mice

    DEFF Research Database (Denmark)

    Gothelf, A; Hojman, P; Gehl, Julie

    2010-01-01

    Gene electrotransfer refers to gene transfection by electroporation and is an effective non-viral method for delivering naked DNA into cells and tissues. This study presents data from gene electrotransfer with erythropoietin (EPO) to mouse skin. Nine-week-old female NMRI mice received one, two...... or three intradermal injections of 50 microg EPO plasmid and were subsequently electroporated. With plate electrodes and 100 microg of EPO, a significant increase in hemoglobin (P...

  17. Chronic overexpression of cerebral Epo improves the ventilatory response to acute hypoxia during the postnatal development.

    Science.gov (United States)

    Caravagna, Céline; Gasser, Edith M Schneider; Ballot, Orlane; Joseph, Vincent; Soliz, Jorge

    2015-08-01

    Clinicians observed that the treatment of premature human newborns for anemia with erythropoietin (Epo) also improved their respiratory autonomy. This observation is in line with our previous in vitro studies showing that acute and chronic Epo stimulation enhances fictive breathing of brainstem-spinal cord preparations of postnatal day 3-4 mice during hypoxia. Furthermore, we recently reported that the antagonization of the cerebral Epo (by using the soluble Epo receptor; sEpoR) significantly reduced the basal ventilation and the hypoxic ventilatory response of 10 days old mice. In this study, we used transgenic (Tg21) mice to investigate the effect of the chronic cerebral Epo overexpression on the modulation of the normoxic and hypoxic ventilatory drive during the post-natal development. Ventilation was evaluated by whole body plethysmography at postnatal ages 3 (P3), 7 (P7), 15 (P15) and 21 (P21). In addition Epo quantification was performed by RIA and mRNA EpoR was evaluated by qRT-PCR. Our results showed that compared to control animals the chronic Epo overexpression stimulates the hypoxic (but not the normoxic) ventilation assessed as VE/VO2 at the ages of P3 and P21. More interestingly, we observed that at P7 and P15 the chronic Epo stimulation of ventilation was attenuated by the down regulation of the Epo receptor in brainstem areas. We conclude that Epo, by stimulating ventilation in brainstem areas crucially helps tolerating physiological (e.g., high altitude) and/or pathological (e.g., respiratory disorders, prematurity, etc.) oxygen deprivation at postnatal ages.

  18. [Hematopoietic growth factor EPO has neuro-protective and neuro-trophic effects--review].

    Science.gov (United States)

    Zhou, Zhuo-Yan; Yang, Mo; Fok, Tai-Fai

    2005-04-01

    Erythropoietin (EPO) is an acidic glycoprotein that was first detected as a hematopoietic factor and its synthesis is triggered in response to cellular hypoxia-sensing. EPO binds to type I cytokine receptors, which associate with the non-receptor tyrosine kinase Jak2, and thereby activate Stat 5a/5b, Ras/MAPK, and PI3-K/Akt signaling pathways. The recent discovery shows that there is a specific EPO/EPO-receptor system in the central nervous system (CNS), independently of the haematopoietic system. Hypoxia and anemia can up-regulate EPO/EPOR expressions in the CNS. Further studies demonstrate that EPO has substantial neuro-protective effects and acts as a neurotrophic factor on central cholinergic neurons, influencing their differentiation and regeneration. EPO also exerts neuro-protective activities in different models of brain damage in vivo and in vitro, such as hypoxia, cerebral ischaemia and sub-arachnoid haemorrhage. EPO may also be involved in synaptic plasticity via the inhibition or stimulation of various neurotransmitters. Therefore, human recombinant EPO that activate its receptors in the central nervous system might be utilized in the future clinical practice involving neuroprotection and brain repair.

  19. Does recombinant human Epo increase exercise capacity by means other than augmenting oxygen transport?

    DEFF Research Database (Denmark)

    Lundby, C; Robach, P; Boushel, R;

    2008-01-01

    This study was performed to test the hypothesis that administration of recombinant human erythropoietin (rHuEpo) in humans increases maximal oxygen consumption by augmenting the maximal oxygen carrying capacity of blood. Systemic and leg oxygen delivery and oxygen uptake were studied during...... before rHuEpo treatment). Blood buffer capacity remained unaffected by rHuEpo treatment and hemodilution. The augmented hematocrit did not compromise peak cardiac output. In summary, in healthy humans, rHuEpo increases maximal oxygen consumption due to augmented systemic and muscular peak oxygen delivery....

  20. Combination Anti-Apoptotic Effect of Erythropoietin and Melatonin on Ischemia Reperfusion-Induced Renal Injury in Rats

    Directory of Open Access Journals (Sweden)

    Shokofeh Banaei

    2016-11-01

    Full Text Available Renal ischemia-reperfusion (IR contributes to the development of acute renal failure (ARF. Oxygen free radicals are considered to be principal components involved in the pathophysiological tissue alterations observed during renal IR. The purpose of this study was to investigate the combination effect of melatonin (MEL and erythropoietin (EPO, which are a potent antioxidant and anti-apoptotic agents, in IR-induced renal injury in rats. Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. MEL (10 mg/kg, i.p and EPO (5000 U/kg, i.p were administered prior to ischemia. After 24 h reperfusion, following decapitation, blood samples were collected for the determination of superoxide dismutase (SOD, glutathione peroxidase (GPx, and malondialdehyde (MDA levels. Also, renal samples were taken for histological evaluation and apoptosis assay. Ischemia-reperfusion increased SOD, GPx, MDA levels, and TUNEL positive cells. Histopathological findings of the IR group confirmed that there was renal impairment in the tubular epithelium. Treatment with EPO and MEL decreased SOD, GPx, and MDA levels, histopathological changes, and TUNEL positive cells. These results indicated that the combination of MEL and EPO could not exert more nephroprotective and anti-apoptotic effects than MEL treatment in renal ischemia-reperfusion injury.

  1. The European Plate Observing System (EPOS): Integrating Thematic Services for Solid Earth Science

    Science.gov (United States)

    Atakan, Kuvvet; Bailo, Daniele; Consortium, Epos

    2016-04-01

    The mission of EPOS is to monitor and understand the dynamic and complex Earth system by relying on new e-science opportunities and integrating diverse and advanced Research Infrastructures in Europe for solid Earth Science. EPOS will enable innovative multidisciplinary research for a better understanding of the Earth's physical and chemical processes that control earthquakes, volcanic eruptions, ground instability and tsunami as well as the processes driving tectonics and Earth's surface dynamics. Through integration of data, models and facilities EPOS will allow the Earth Science community to make a step change in developing new concepts and tools for key answers to scientific and socio-economic questions concerning geo-hazards and geo-resources as well as Earth sciences applications to the environment and to human welfare. EPOS, during its Implementation Phase (EPOS-IP), will integrate multidisciplinary data into a single e-infrastructure. Multidisciplinary data are organized and governed by the Thematic Core Services (TCS) and are driven by various scientific communities encompassing a wide spectrum of Earth science disciplines. These include Data, Data-products, Services and Software (DDSS), from seismology, near fault observatories, geodetic observations, volcano observations, satellite observations, geomagnetic observations, as well as data from various anthropogenic hazard episodes, geological information and modelling. In addition, transnational access to multi-scale laboratories and geo-energy test-beds for low-carbon energy will be provided. TCS DDSS will be integrated into Integrated Core Services (ICS), a platform that will ensure their interoperability and access to these services by the scientific community as well as other users within the society. This requires dedicated tasks for interactions with the various TCS-WPs, as well as the various distributed ICS (ICS-Ds), such as High Performance Computing (HPC) facilities, large scale data storage

  2. A Planetary Geophysicist Does EPO: Lessons Learned Along the Way

    Science.gov (United States)

    Kiefer, W. S.

    2011-12-01

    My "day job" is numerical modeling of the interiors of the terrestrial planets, but I have also done EPO projects for the last 17 years while at the Lunar and Planetary Institute. These range from single, hour long talks in classrooms or astronomy clubs, to week-long summer workshops for teachers and librarians, and even semester-long programs, along with a number of curriculum development projects. EPO projects are a great way to help develop both the next generation of scientists and, more importantly, of scientifically literate citizens and taxpayers. Here are a few lessons learned along the way in the school of hard knocks. (1) An engaging delivery style is even more important in EPO presentations than it is in college lectures or conference presentations. Emphasize a few key concepts rather than numerous facts, and keep the jargon out. Good analogies can go a long way towards explaining a concept to any age group. I teach the role of size in planetary cooling by first asking students how long it takes to cook food of various sizes (a hamburger, roast beef, turkey). (2) If you will be working with a group of students for more than one class period, classroom friendly activities strengthen the learning process. Such activities do not need to be elaborate - when teaching about the Moon, I sometimes assign students to take their parents outside at night and show them how to find lava flows on the Moon. Teachers usually need to have classroom activities that are aligned to state or national teaching standards. Fortunately, many effective, standards-aligned activities already exist, so you don't need to reinvent the wheel. For a useful listing of planetary science and astronomy activities, see the LPI website www.lpi.usra.edu/education/resources/ (3) Although EPO work can be personally rewarding, it is not always well rewarded in a professional context, and it can be difficult to find the time and financial resources to sustain major projects. We sometimes use a

  3. A Database of EPO-Patenting Firms in Denmark

    DEFF Research Database (Denmark)

    Nielsen, Anders Østergaard

    1998-01-01

    The first section gives a brief introduction of the basic stages to be observed by the patent applicant from idea to the patent is granted. Section two presents three examples of how patents are registered in the online patent database INPADOC. Section three accounts for the initial analysis...... of the existing patent stock issued to firms with domicile in Denmark. Sections four and five report the basic characteristics of the EPO-patent sample and the procedures for linking the patent statistics to accounting data at the firm level, and finally they present the basic properties of the resulting database...

  4. Epoetin Delta Reduces Oxidative Stress in Primary Human Renal Tubular Cells

    Directory of Open Access Journals (Sweden)

    Annelies De Beuf

    2010-01-01

    Full Text Available Erythropoietin (EPO exerts (renal tissue protective effects. Since it is unclear whether this is a direct effect of EPO on the kidney or not, we investigated whether EPO is able to protect human renal tubular epithelial cells (hTECs from oxidative stress and if so which pathways are involved. EPO (epoetin delta could protect hTECs against oxidative stress by a dose-dependent inhibition of reactive oxygen species formation. This protective effect is possibly related to the membranous expression of the EPO receptor (EPOR since our data point to the membranous EPOR expression as a prerequisite for this protective effect. Oxidative stress reduction went along with the upregulation of renoprotective genes. Whilst three of these, heme oxygenase-1 (HO-1, aquaporin-1 (AQP-1, and B-cell CLL/lymphoma 2 (Bcl-2 have already been associated with EPO-induced renoprotection, this study for the first time suggests carboxypeptidase M (CPM, dipeptidyl peptidase IV (DPPIV, and cytoglobin (Cygb to play a role in this process.

  5. Metformin Prevents Renal Fibrosis in Mice with Unilateral Ureteral Obstruction and Inhibits Ang II-Induced ECM Production in Renal Fibroblasts

    OpenAIRE

    Yang Shen; Naijun Miao; Jinlan Xu; Xinxin Gan; Dan Xu; Li Zhou; Hong Xue; Wei Zhang; Limin Lu

    2016-01-01

    Renal fibrosis is the final common pathway of chronic kidney disease (CKD), and no effective medication is available clinically for managing its progression. Metformin was initially developed as an anti-diabetic drug and recently gained attention for its potential in the treatment of other diseases. In this study, we investigated its effects on renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) in vivo and in angiotensin II (Ang II)–treated renal fibroblast NRK-49F cells...

  6. Tools for Scientist Engagement in E/PO: NASA SMD Community Workspace and Online Resources

    Science.gov (United States)

    Dalton, H.; Shipp, S. S.; Grier, J.; Gross, N. A.; Buxner, S.; Bartolone, L.; Peticolas, L. M.; Woroner, M.; Schwerin, T. G.

    2014-12-01

    The Science Mission Directorate (SMD) Science Education and Public Outreach (E/PO) Forums are here to help you get involved in E/PO! The Forums have been developing several online resources to support scientists who are - or who are interested in becoming - involved in E/PO. These include NASA Wavelength, EarthSpace, and the SMD E/PO online community workspace. NASA Wavelength is the one-stop shop of all peer-reviewed NASA education resources to find materials you - or your audiences - can use. Browse by audience (pre-K through 12, higher education, and informal education) or topic, or choose to search for something specific by keyword and audience. http://nasawavelength.org. EarthSpace, an online clearinghouse of Earth and space materials for use in the higher education classroom, is driven by a powerful search engine that allows you to browse the collection of resources by science topic, audience, type of material or key terms. All materials are peer-reviewed before posting, and because all submissions receive a digital object identifier (doi), submitted materials can be listed as publications. http://www.lpi.usra.edu/earthspace. The SMD E/PO online community workspace contains many resources for scientists. These include one-page guides on how to get involved, tips on how to make the most of your time spent on E/PO, and sample activities, as well as news on funding, policy, and what's happening in the E/PO community. The workspace also provides scientists and the public pathways to find opportunities for participation in E/PO, to learn about SMD E/PO projects and their impacts, to connect with SMD E/PO practitioners, and to explore resources to improve professional E/PO practice, including literature reviews, information about the Next Generation Science Standards, and best practices in evaluation and engaging diverse audiences. http://smdepo.org.

  7. Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production

    DEFF Research Database (Denmark)

    Krag, Søren; Nyengaard, Jens R; Wogensen, Lise

    2007-01-01

    BACKGROUND: There is a correlation between renal graft rejection and blood glucose (BG) levels. Furthermore, diabetic patients may develop non-diabetic renal diseases, which in some circumstances progress rapidly. Since transforming growth factor-beta1 (TGF-beta) levels are elevated in many renal...... diseases, the accelerated progression may be due to interactions between glucose and locally produced TGF-beta1. Therefore, we investigated the effect of mild hyperglycaemia on glomerular morphology and collagen production in TGF-beta1 transgenic mice. METHODS: To achieve BG concentrations of approximately...... is involved. This emphasizes the importance of strict BG control in renal transplant patients and diabetic patients with renal malfunctions unrelated to diabetes. Udgivelsesdato: 2007-Sep...

  8. The role and regulation of erythropoietin (EPO) and its receptor in skeletal muscle: how much do we really know?

    Science.gov (United States)

    Lamon, Séverine; Russell, Aaron P

    2013-01-01

    Erythropoietin (EPO) primarily activates erythroid cell proliferation and growth and is active in several types of non-hematopoietic cells via its interaction with the EPO-receptor (EPO-R). This review focuses on the role of EPO in skeletal muscle. The EPO-R is expressed in skeletal muscle cells and EPO may promote myoblast differentiation and survival via the activation of the same signaling cascades as in hematopoietic cells, such as STAT5, MAPK and Akt. Inconsistent results exist with respect to the detection of the EPO-R mRNA and protein in muscle cells, tissue and across species and the use of non-specific EPO-R antibodies contributes to this problem. Additionally, the inability to reproducibly detect an activation of the known EPO-induced signaling pathways in skeletal muscle questions the functionality of the EPO-R in muscle in vivo. These equivocal findings make it difficult to distinguish between a direct effect of EPO on skeletal muscle, via the activation of its receptor, and an indirect effect resulting from a better oxygen supply to the muscle. Consequently, the precise role of EPO in skeletal muscle and its regulatory mechanism/s remain to be elucidated. Further studies are required to comprehensively establish the importance of EPO and its function in skeletal muscle health.

  9. EPOS LHC : test of collective hadronization with LHC data

    CERN Document Server

    Pierog, T; Katzy, J M; Yatsenko, E; Werner, K

    2013-01-01

    EPOS is a Monte-Carlo event generator for minimum bias hadronic interactions, used for both heavy ion interactions and cosmic ray air shower simulations. Since the last public release in 2009, the LHC experiments have provided a number of very interesting data sets comprising minimum bias p-p, p-Pb and Pb-Pb interactions. We describe the changes required to the model to reproduce in detail the new data available from LHC and the consequences in the interpretation of these data. In particular we discuss the effect of the collective hadronization in p-p scattering. A different parametrization of flow has been introduced in the case of a small volume with high density of thermalized matter (core) reached in p-p compared to large volume produced in heavy ion collisions. Both parametrizations depend only on the geometry and the amount of secondary particles entering in the core and not on the beam mass or energy. The transition between the two flow regimes can be tested with p-Pb data. EPOS LHC is able to reproduc...

  10. EPOS LHC. Test of collective hadronization with LHC data

    Energy Technology Data Exchange (ETDEWEB)

    Pierog, T. [Karlsruher Institut fuer Technologie (KIT), Karlsruhe (Germany); Karpenko, I. [Bogolyubov Institute for Theoretical Physics, Kiev (Ukraine); Katzy, J.M.; Yatsenko, E. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Werner, K. [Nantes Univ. (France). SUBATECH, IN2P3/CNRS

    2013-06-15

    EPOS is a Monte-Carlo event generator for minimum bias hadronic interactions, used for both heavy ion interactions and cosmic ray air shower simulations. Since the last public release in 2009, the LHC experiments have provided a number of very interesting data sets comprising minimum bias p-p, p-Pb and Pb-Pb interactions. We describe the changes required to the model to reproduce in detail the new data available from LHC and the consequences in the interpretation of these data. In particular we discuss the effect of the collective hadronization in p-p scattering. A different parametrization of flow has been introduced in the case of a small volume with high density of thermalized matter (core) reached in p-p compared to largest volume produced in heavy ion collisions. Both parametrizations depend only on the geometry and the amount of secondary particles entering in the core and not on the beam mass or energy. The transition between the two flow regimes can be tested with p-Pb data. EPOS LHC is able to reproduce all minimum bias results for all particles with transverse momentum from p{sub t}=0 to a few GeV/c.

  11. EPOS-WP16: A Platform for European Multi-scale Laboratories

    Science.gov (United States)

    Spiers, Chris; Drury, Martyn; Kan-Parker, Mirjam; Lange, Otto; Willingshofer, Ernst; Funiciello, Francesca; Rosenau, Matthias; Scarlato, Piergiorgio; Sagnotti, Leonardo; W16 Participants

    2016-04-01

    The participant countries in EPOS embody a wide range of world-class laboratory infrastructures ranging from high temperature and pressure experimental facilities, to electron microscopy, micro-beam analysis, analogue modeling and paleomagnetic laboratories. Most data produced by the various laboratory centres and networks are presently available only in limited "final form" in publications. As such many data remain inaccessible and/or poorly preserved. However, the data produced at the participating laboratories are crucial to serving society's need for geo-resources exploration and for protection against geo-hazards. Indeed, to model resource formation and system behaviour during exploitation, we need an understanding from the molecular to the continental scale, based on experimental data. This contribution will describe the work plans that the laboratories community in Europe is making, in the context of EPOS. The main objectives are: - To collect and harmonize available and emerging laboratory data on the properties and processes controlling rock system behaviour at multiple scales, in order to generate products accessible and interoperable through services for supporting research activities. - To co-ordinate the development, integration and trans-national usage of the major solid Earth Science laboratory centres and specialist networks. The length scales encompassed by the infrastructures included range from the nano- and micrometer levels (electron microscopy and micro-beam analysis) to the scale of experiments on centimetre sized samples, and to analogue model experiments simulating the reservoir scale, the basin scale and the plate scale. - To provide products and services supporting research into Geo-resources and Geo-storage, Geo-hazards and Earth System Evolution.

  12. Post-treatment effects of erythropoietin and nordihydroguaiaretic acid on recovery from cisplatin-induced acute renal failure in the rat.

    Science.gov (United States)

    Lee, Dong Won; Kwak, Ihm Soo; Lee, Soo Bong; Song, Sang Heon; Seong, Eun Young; Yang, Byeong Yun; Lee, Min Young; Sol, Mee Young

    2009-01-01

    5-lipoxygenase inhibitor and human recombinant erythropoietin might accelerate renal recovery in cisplatin-induced acute renal failure rats. Male Sprague-Dawley rats were randomized into four groups: 1) normal controls; 2) Cisplatin group-cisplatin induced acute renal failure (ARF) plus vehicle treatment; 3) Cisplatin+nordihydroguaiaretic acid (NDGA) group-cisplatin induced ARF plus 5-lipoxygenase inhibitor treatment; 4) Cisplatin+erythropoietin (EPO) group-cisplatin induced ARF plus erythropoietin treatment. On day 10 (after 7 daily injections of NDGA or EPO), urea nitrogen and serum Cr concentrations were significantly lower in the Cisplatin+NDGA and Cisplatin+EPO groups than in the Cisplatin group, and 24 hr urine Cr clearances were significantly higher in the Cisplatin+EPO group than in the Cisplatin group. Semi-quantitative assessments of histological lesions did not produce any significant differences between the three treatment groups. Numbers of PCNA(+) cells were significantly higher in Cisplatin, Cisplatin+NDGA, and Cisplatin+EPO groups than in normal controls. Those PCNA(+) cells were significantly increased in Cisplatin+NDGA group. These results suggest that EPO and also NDGA accelerate renal function recovery by stimulating tubular epithelial cell regeneration.

  13. Test of the hadronic interaction model EPOS with KASCADE air shower data

    Energy Technology Data Exchange (ETDEWEB)

    Hoerandel, J.R., E-mail: j.horandel@astro.ru.n [Institut fuer Experimentelle Kernphysik, Universitaet Karlsruhe, D-76021 Karlsruhe (Germany); Apel, W.D. [Institut fuer Kernphysik, Forschungszentrum Karlsruhe, D-76021 Karlsruhe (Germany); Arteaga, J.C. [Institut fuer Experimentelle Kernphysik, Universitaet Karlsruhe, D-76021 Karlsruhe (Germany); Badea, F.; Bekk, K. [Institut fuer Kernphysik, Forschungszentrum Karlsruhe, D-76021 Karlsruhe (Germany); Bertaina, M. [Dipartimento di Fisica Generale dell' Universita, 10125 Torino (Italy); Bluemer, J. [Institut fuer Experimentelle Kernphysik, Universitaet Karlsruhe, D-76021 Karlsruhe (Germany); Institut fuer Kernphysik, Forschungszentrum Karlsruhe, D-76021 Karlsruhe (Germany); Bozdog, H. [Institut fuer Kernphysik, Forschungszentrum Karlsruhe, D-76021 Karlsruhe (Germany); Brancus, I.M. [National Institute of Physics and Nuclear Engineering, P.O. Box Mg-6, RO-7690 Bucharest (Romania); Brueggemann, M.; Buchholz, P. [Fachbereich Physik, Universitaet Siegen, 57068 Siegen (Germany); Cantoni, E. [Dipartimento di Fisica Generale dell' Universita, 10125 Torino (Italy); Istituto di Fisica dello Spazio Interplanetario, INAF, 10133 Torino (Italy); Chiavassa, A. [Dipartimento di Fisica Generale dell' Universita, 10125 Torino (Italy); Cossavella, F. [Institut fuer Experimentelle Kernphysik, Universitaet Karlsruhe, D-76021 Karlsruhe (Germany); Daumiller, K. [Institut fuer Kernphysik, Forschungszentrum Karlsruhe, D-76021 Karlsruhe (Germany); Souza, V. de [Institut fuer Experimentelle Kernphysik, Universitaet Karlsruhe, D-76021 Karlsruhe (Germany); Di Pierro, F. [Dipartimento di Fisica Generale dell' Universita, 10125 Torino (Italy); Doll, P.; Engel, R.; Engler, J. [Institut fuer Kernphysik, Forschungszentrum Karlsruhe, D-76021 Karlsruhe (Germany)

    2009-12-15

    Predictions of the hadronic interaction model EPOS 1.61 as implemented in the air shower simulation program CORSIKA are compared to observations with the KASCADE experiment. The investigations reveal that the predictions of EPOS are not compatible with KASCADE measurements. The discrepancies seen are most likely due to use of a set of inelastic hadronic cross sections that are too high.

  14. STAT1 is involved in signal transduction in the EPO induced HEL cells

    Institute of Scientific and Technical Information of China (English)

    JIANGCHU; CHANGYUNGUI; 等

    1998-01-01

    Erythropoietin(EPO) is the major regulator of mamalian erythropoisis,which stimulates the growth and differentiation of hematopoietic cells through interaction with its receptor(EPO-R),Here we use HEL cells (a human erythro-leukemia cell line) as a model to elucidate the pathway of signal transduction in the EPO-induced HEL cells.Our data show that the EPOR (EPO receptor) on the surface of HEL cells interacts with the Janus tyrosine protein kinase(Jak2) to transduce intracellular signals through phosphorylation of cytoplasmic proteins in EPO-treated HEL cells.Both STAT1 and STAT5 in this cell line are tyrosine-phosphorylated and translocated to nucleus following the dinding of EPO to HEL cells.Furthermore,the dinding of both STAT1 and STAT5 proteins to specific DNA elements(SIE and PIE elements) is revealed in an EPO-dependent manner,Our data demonstrate that the pathway of signal transduction following the binding of EPO to HEL cells is similar to immature eryhroid cell from the spleen of mice infected with anemia strain of Friend virus.

  15. "Edigey" as the Common Heritage of the Turkic People: Historical Basis of the Epos

    Science.gov (United States)

    Assanov, Zhubanazar A.; Pangereyev, Abat Sh.; Baltymova, Mira R.; Borash, Bayan T.; Idrissova, Elmira T.

    2016-01-01

    Today we know that the heroic epos "Edigey" remained among the Turkic people living in the south from Turkmenistan and Uzbekistan to Siberia, as well as in foreign countries: Turkey and Romania. "Edigey" epos has more than 40 versions, some of which consist of fifteen or sixteen thousand lines. Therefore, a narrow study is not…

  16. Test of the hadronic interaction model EPOS with air shower data

    CERN Document Server

    Apel, W D

    2009-01-01

    Predictions of the hadronic interaction model EPOS~1.61 as implemented in the air shower simulation program CORSIKA are compared to observations with the KASCADE experiment. The investigations reveal that the predictions of EPOS are not compatible with KASCADE measurements. The discrepancies seen are most likely due to use of a set of inelastic hadronic cross sections that are too high.

  17. Automated Patent Searching in the EPO: From Online Searching to Document Delivery.

    Science.gov (United States)

    Nuyts, Annemie; Jonckheere, Charles

    The European Patent Office (EPO) has recently implemented the last part of its ambitious automation project aimed at creating an automated search environment for approximately 1200 EPO patent search examiners. The examiners now have at their disposal an integrated set of tools offering a full range of functionalities from online searching, via…

  18. Nocturnal Polyuria : Excess of Nocturnal Urine Production, Excess of Definitions-Influence on Renal Function Profile

    NARCIS (Netherlands)

    Goessaert, An-Sofie; Walle, Johan Vande; Bosch, JLHR; Hoebeke, Piet; Everaert, Karel

    2016-01-01

    PURPOSE: This study aimed to identify important differences in renal function profile, and potential water and sodium diuresis cutoffs among participants with nocturnal polyuria according to nocturnal polyuria definitions. MATERIALS AND METHODS: This post hoc analysis was based on a prospective stud

  19. Nocturnal Polyuria : Excess of Nocturnal Urine Production, Excess of Definitions-Influence on Renal Function Profile

    NARCIS (Netherlands)

    Goessaert, An-Sofie; Walle, Johan Vande; Bosch, JLHR|info:eu-repo/dai/nl/088914364; Hoebeke, Piet; Everaert, Karel

    2016-01-01

    PURPOSE: This study aimed to identify important differences in renal function profile, and potential water and sodium diuresis cutoffs among participants with nocturnal polyuria according to nocturnal polyuria definitions. MATERIALS AND METHODS: This post hoc analysis was based on a prospective stud

  20. Nocturnal Polyuria : Excess of Nocturnal Urine Production, Excess of Definitions-Influence on Renal Function Profile

    NARCIS (Netherlands)

    Goessaert, An-Sofie; Walle, Johan Vande; Bosch, JLHR; Hoebeke, Piet; Everaert, Karel

    2016-01-01

    PURPOSE: This study aimed to identify important differences in renal function profile, and potential water and sodium diuresis cutoffs among participants with nocturnal polyuria according to nocturnal polyuria definitions. MATERIALS AND METHODS: This post hoc analysis was based on a prospective

  1. Assessment of Erythropoietin Levels and Some Iron Indices in Chronic Renal Failure and Liver Cirrhosis Patients

    Directory of Open Access Journals (Sweden)

    Essam Mady

    1999-01-01

    Full Text Available This study was constructed to investigate the relationship between renal anaemia and erythropoietin (EPO concentrations in chronic renal failure (CRF patients and to evaluate the possible role of the liver. Serum EPO levels were measured in blood samples from 20 CRF patients on hemodialysis (HD, 20 liver cirrhosis (LC patients, 20 patients having both CRF and LC and undergoing HD, and 20 normal control subjects. Blood cell counts, iron indices (iron, total iron-binding capacity (TIBC and ferritin, renal function (blood urea nitrogen (BUN and creatinine, hepatic function (ALT, AST, ALP and bilirubin investigations were carried out for all the subjects enrolled in this study. CRF patients without LC had serum EPO concentration of 6.21 ± 0.53 mU/ml (mean ± SE, which was significantly higher than that in patients having both CRF and LC (4.32 ± 0.52 (p < 0.01. Both groups showed significantly lower values than the controls (12.75 ± 0.70 (p < 0.001. LC patients with intact kidneys had significantly higher EPO level (22.70 ± 1.70 (p < 0.001. No correlation was found between EPO level and any of the hematologic or iron indices.

  2. 重组EpoAB-NGF模拟肽的神经营养功能%Preliminary Study on Neurotrophic Activity of Recombinant Peptide Mimics EpoAB-NGF

    Institute of Scientific and Technical Information of China (English)

    潘勇昭; 陈虹; 王欣; 马晓骊; 黄秉仁

    2011-01-01

    Objective: To investigate the neurotrophic activity of recombinant fusion protein epopeptide ABnerve growth factor analog peptide (EpoAB-NGF9/12). Methods: The DNA fragments encoding the sequences of EpoAB-NGF9 and EpoAB-NGF12 polypeptide were amplified by PCR and cloned into the pET-42a prokaryotic expression vector. The recombinant plasmids of pET-42a-EpoAB-NGF9/12 were transformed into E. coli BL21 (DE3) and exogenous protein expression was induced by IPTG. Fusion proteins GST-EpoAB-NGF9/12 were purified by affinity chromatography. The biological activities were determined using the experiment of inducing axon outgrowth of PC12 cells and flow cytometry analysis of apoptotic rate in R2L1 cells. Results: Apparent molecular weight of fusion proteins GST-EpoAB-NGF9/12 were approximate 30kDa. Immunoblot analysis showed that the fusion proteins were immunoreactive with anti-GST antibody. Fusion proteins stimulate the differentiation and promote the axon outgrowth in PC12 cells. Cell apoptosis was induced in (31.7 ±0.60)% of R2L1 control cells by serum free incubation, whereas cell apoptosis rate were in ( 25.2 ± 3.52 ) % or ( 25.7 ± 1.46 ) % by adding GST-EpoAB-NGF9 or GST-EpoAB-NGF12 into serum free condition respectively. The result indicates that fusion proteins were enabling to prevent cell death in R2L1 cells. Conclusion: These findings in cell biology region suggest that recombinant fusion protein containing Epo-NGF peptide mimics have the neurotrophic effects similar to that of NGF.%目的:研究重组融合蛋白红细胞生成素AB肽-神经生长因子模拟肽(EpoAB-NGF9和EpoAB-NGF/12)的神经营养作用.方法:构建pET-42a-EpoAB-NGF9/12原核表达质粒,转化大肠杆菌BL21(DE3),以IPTG诱导表达,亲和层析纯化重组蛋白,显微镜观察PC12细胞诱导分化,流式细胞仪检测凋亡细胞.结果:大肠杆菌表达的重组融合蛋白GST-EpoAB-NGF9/12分子量约为30kDa,抗GST抗体免疫印迹反应呈阳

  3. Near Fault Observatories (NFO) services and integration plan for European Plate Observing System (EPOS) Implementation Phase

    Science.gov (United States)

    Chiaraluce, Lauro

    2016-04-01

    Coherently with the EPOS vision aimed at creating a pan-European infrastructure for Earth Sciences supporting research for a more sustainable society, we are working on the integration of NFOs and services implementation facilitating their data and products discovery and usage. NFOs are National Research Infrastructures (NRI) consisting of advanced networks of multi-parametric sensors continuously monitoring the chemical and physical processes related to the common underlying Earth instabilities governing active faults evolution and the genesis of earthquakes. These infrastructures will enable advancements in understanding of earthquakes generation processes and associated ground shaking due to their high-quality near-source multidisciplinary data. In EPOS-IP seven NFOs are going to be linked: 1) the Altotiberina and 2) Irpinia Observatories in Italy, 3) Corinth in Greece, 4) South-Iceland Seismic Zone, 5) Valais in Switzerland, 6) Marmara Sea (GEO Supersite) in Turkey and 7) Vrancea in Romania. EPOS-IP aims to implement integrated services from a technical, legal, governance and financial point of view. Accordingly, our first effort within this first core group of NFOs will be establishing legal governance for such a young community to ensure a long-term sustainability of the envisaged services including the full adoption of the EPOS data policy. The establishment of a Board including representatives of each NFO formally appointed by the Institutions supporting the NRI is a basic requirement to provide and validate a stable governance mechanism supporting the initiatives finalised to the services provision. Extremely dense networks and less common instruments deserve an extraordinary work on data quality control and description. We will work on linking all the NFOs in a single distributed network of observatories with instrumental and monitoring standards based on common protocols for observation, analysis, and data access and distributed channels. We will rely on

  4. Thrombosis in end-stage renal disease.

    Science.gov (United States)

    Casserly, Liam F; Dember, Laura M

    2003-01-01

    Although renal failure has classically been associated with a bleeding tendency, thrombotic events are common among patients with end-stage renal disease (ESRD). A variety of thrombosis-favoring hematologic alterations have been demonstrated in these patients. In addition, "nontraditional" risk factors for thrombosis, such as hyperhomocysteinemia, endothelial dysfunction, inflammation, and malnutrition, are present in a significant proportion of chronic dialysis patients. Hemodialysis (HD) vascular access thrombosis, ischemic heart disease, and renal allograft thrombosis are well-recognized complications in these patients. Deep venous thrombosis and pulmonary embolism are viewed as rare in chronic dialysis patients, but recent studies suggest that this perception should be reconsidered. Several ESRD treatment factors such as recombinant erythropoietin (EPO) administration, dialyzer bioincompatibility, and calcineurin inhibitor administration may have prothrombotic effects. In this article we review the pathogenesis and clinical manifestations of thrombosis in ESRD and evaluate the evidence that chronic renal failure or its management predisposes to thrombotic events.

  5. Recombinant human erythropoietin treatment of chronic renal failure patients normalizes altered phenotype and proliferation of CD4-positive T lymphocytes.

    Science.gov (United States)

    Lisowska, Katarzyna A; Debska-Slizien, Alicja; Radzka, Monika; Witkowski, Jacek M; Rutkowski, Boleslaw; Bryl, Ewa

    2010-03-01

    Patients with chronic renal failure (CRF) receive recombinant human erythropoietin (rhEPO) for the correction of anemia. However, rhEPO also has an immunomodulatory effect. Detailed changes of phenotype and function of CD4(+) T lymphocytes in CRF patients receiving rhEPO have not been reported yet; their study may bring insight into understanding of this immunomodulatory action of rhEPO. Two groups of CRF patients were included into the study: those treated; and those not receiving rhEPO. The expression of activation markers on CD4(+) lymphocytes was measured with flow cytometry, both ex vivo and in vitro. The kinetics of CD4(+) T lymphocytes proliferation was calculated using a dividing cells tracing method and numerical approach. Significantly higher percentages of CD4(+)CD95(+), CD4(+)HLA-DR(+) cells, and lower percentages of CD4(+)CD69(+) and CD4(+)CD28(+) cells were observed in both rhEPO-treated and untreated patients when compared with healthy controls. Changes in the proportions of CD4(+)CD28(+) and CD4(+)HLA-DR(+) subpopulations were dependent on the type of rhEPO, being more pronounced for rhEPObeta. CD4(+) lymphocytes from untreated patients exhibited decreased expression of CD28 and CD69 after stimulation in vitro, whereas the expression of these antigens on lymphocytes of rhEPO-treated patients was similar to that observed in healthy controls. Fewer CD4(+)CD28(+) T lymphocytes of untreated patients proliferated in vitro; these cells had longer G0-->G1 time, which negatively correlated with surface expression of CD28. Our study confirms that rhEPO treatment normalizes activation parameters of CD4(+) T lymphocytes and their proliferative capacity, which could explain earlier described immunomodulatory effects of rhEPO in patients suffering from CRF.

  6. 42 CFR 414.335 - Payment for EPO furnished to a home dialysis patient for use in the home.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Payment for EPO furnished to a home dialysis... for EPO furnished to a home dialysis patient for use in the home. Link to an amendment published at 75 FR 49202, Aug. 12, 2010. (a) Payment for EPO used at home by a home dialysis patient is made only...

  7. “Mythos, logos, epos son la palabra” (Heidegger

    Directory of Open Access Journals (Sweden)

    Éliane Escoubas

    2009-12-01

    Full Text Available Este texto se ocupa de dos volúmenes de la obra de Heidegger: el curso sobre Parménides de 1942 y la recopilación De camino al habla de 1950-1959. El curso sobre Parménides trabaja los términos griegos mythos, logos y epos, y los determina como “los mismos” –lo que no precisamente corresponde a la identidad–. En sus diferencias mismas, remiten a la “palabra” (das Wort. Varios años después, la “palabra” es invocada en la triple denominación de Sprache, Wort y Sage que, en sí mismos, no dependen de ninguna lógica de la identidad, sino más bien de una lógica de la “tautología”: la poesía misma.

  8. EPOS Multi-Scale Laboratory platform: a long-term reference tool for experimental Earth Sciences

    Science.gov (United States)

    Trippanera, Daniele; Tesei, Telemaco; Funiciello, Francesca; Sagnotti, Leonardo; Scarlato, Piergiorgio; Rosenau, Matthias; Elger, Kirsten; Ulbricht, Damian; Lange, Otto; Calignano, Elisa; Spiers, Chris; Drury, Martin; Willingshofer, Ernst; Winkler, Aldo

    2017-04-01

    With continuous progress on scientific research, a large amount of datasets has been and will be produced. The data access and sharing along with their storage and homogenization within a unique and coherent framework is a new challenge for the whole scientific community. This is particularly emphasized for geo-scientific laboratories, encompassing the most diverse Earth Science disciplines and typology of data. To this aim the "Multiscale Laboratories" Work Package (WP16), operating in the framework of the European Plate Observing System (EPOS), is developing a virtual platform of geo-scientific data and services for the worldwide community of laboratories. This long-term project aims at merging the top class multidisciplinary laboratories in Geoscience into a coherent and collaborative network, facilitating the standardization of virtual access to data, data products and software. This will help our community to evolve beyond the stage in which most of data produced by the different laboratories are available only within the related scholarly publications (often as print-version only) or they remain unpublished and inaccessible on local devices. The EPOS multi-scale laboratory platform will provide the possibility to easily share and discover data by means of open access, DOI-referenced, online data publication including long-term storage, managing and curation services and to set up a cohesive community of laboratories. The WP16 is starting with three pilot cases laboratories: (1) rock physics, (2) palaeomagnetic, and (3) analogue modelling. As a proof of concept, first analogue modelling datasets have been published via GFZ Data Services (http://doidb.wdc-terra.org/search/public/ui?&sort=updated+desc&q=epos). The datasets include rock analogue material properties (e.g. friction data, rheology data, SEM imagery), as well as supplementary figures, images and movies from experiments on tectonic processes. A metadata catalogue tailored to the specific communities

  9. Correlation Study between ERO,EPO-R and MVD on Patients with Gastrointestinal Cancer Anemia%胃肠癌贫血患者EPO、EPO-R和MVD的相关性研究

    Institute of Scientific and Technical Information of China (English)

    乔姝; 孙海凤; 白强; 马俊兵; 李雪飞; 解彩霞

    2016-01-01

    Objective:To discuss the relationship between EPO,EPO-R and microvascular density (MVD) expression on patients with gastrointestinal cancer anemia.Method:Used conventional methods to detect Hb and serum EPO concentration,EPO,EPO-R and MVD was detected by immunohischemical method for 177 patients with gastrointestinal cancer.Finally correlation analysis was carried on.Result:(1)EPO levels of 57 patients with anemia was obviously higher than that of Hb in without-anemia(P<0.05).There was obvious negative correlation between serum EPO level and Hb values(P<0.001).(2)MVD of EPO and EPO-R express positive patients was obviously higher than that of negative patients(P<0.05). There was obvious positive correlation between EPO and EPO-R and MVD(P<0.001).Conclusion:The Epo levels were increased significantly on patients with gastrointestinal cancer anemia and it’s relationship with Hb are significantly negative correlation. The expression of EPO,EPO-R and MVD were positively correlated.%目的:探讨胃肠癌贫血患者EPO、EPO-R和微血管密度(MVD)表达的关系。方法:对177例胃肠癌患者进行常规方法检测Hb、血浆EPO浓度,免疫组化法检测EPO、EPO-R、MVD,并进行相关分析。结果:(1)57例贫血患者的EPO水平明显高于无贫血者(P<0.05);血清EPO水平和Hb值呈明显负相关(P<0.001)。(2)EPO、EPO-R阳性患者的MVD明显高于EPO、EPO-R阴性患者(P<0.05);MVD与EPO、EPO-R呈正相关(P<0.001)。结论:胃肠癌贫血患者的EPO水平明显增高,并与Hb值呈明显的负相关关系;EPO、EPO-R的表达与MVD呈正相关。

  10. Compensatory Thrombopoietin Production from the Liver and Bone Marrow Stimulates Thrombopoiesis of Living Rat Megakaryocytes in Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Itsuro Kazama

    2011-10-01

    Full Text Available Background/Aims: Decreased thrombopoiesis has been ascribed a role in the pathogenesis of uremic bleeding in chronic renal failure (CRF. However, serum thrombopoietin (TPO levels are usually elevated in CRF patients, suggesting increased thrombopoiesis. The aim of this study was to determine the thrombopoietic activity in CRF. Methods: Male Sprague-Dawley rats that underwent 5/6 nephrectomy were used as the model of CRF. Age-matched sham-operated rats were used as controls. Single megakaryocytes were isolated from the rat bone marrow, and their size distribution was examined. Megakaryocyte membrane invaginations were monitored by confocal imaging of di-8-ANEPPS staining, and patch clamp whole-cell recordings of membrane capacitance. TPO gene expression was assessed in various tissues. Results: Circulating platelet counts and the number of large megakaryocytes were increased in the bone marrow of CRF rats. Massive di-8-ANEPPS staining and increased membrane capacitance in large megakaryocytes demonstrated increased membrane invaginations. Unaffected Kv1.3-channel currents per cell surface area demonstrated unaltered channel densities. TPO transcription was decreased in the renal cortex but increased in the liver and bone marrow of CRF rats. Conclusion: Increased thrombopoiesis in CRF was thought to be a reactive mechanism to platelet dysfunction. Increased TPO production from the liver and bone marrow compensated for decreased production from damaged kidneys.

  11. Treatment of renal anemia: Erythropoiesis stimulating agents and beyond

    Directory of Open Access Journals (Sweden)

    Patrick Biggar

    2017-09-01

    Full Text Available Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb levels up to 10-11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events. Recently, new developments offer interesting options not only via stimulating erythropoeisis but also by employing additional mechanisms. The inhibition of activin, a member of the transforming growth factor superfamily, has the potential to correct anemia by stimulating liberation of mature erythrocyte forms and also to mitigate disturbed mineral and bone metabolism as well. Hypoxia-inducible factor prolyl hydroxylase inhibitors also show pleiotropic effects, which are at the focus of present research and have the potential of reducing mortality. However, conventional ESAs offer an extensive body of safety evidence, against which the newer substances should be measured. Carbamylated EPO is devoid of Hb augmenting effects whilst exerting promising tissue protective properties. Additionally, the role of hepcidin antagonists is discussed. An innovative new hemodialysis blood tube system, reducing blood contact with air, conveys a totally different and innocuous option to improve renal anemia by reducing mechanical hemolysis.

  12. Neocytolysis contributes to the anemia of renal disease

    Science.gov (United States)

    Rice, L.; Alfrey, C. P.; Driscoll, T.; Whitley, C. E.; Hachey, D. L.; Suki, W.

    1999-01-01

    Neocytolysis is a recently described physiological process affecting the selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin (EPO) depression appears to initiate the process, providing the rationale to investigate its contributions to the anemia of renal disease. When EPO therapy was withheld, four of five stable hemodialysis patients showed chromium 51 (51Cr)-red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these four patients received oral 13C-glycine and 15N-glycine, and there was a suggestion of pathological isotope enrichment of stool porphyrins when EPO therapy was held, again supporting selective hemolysis of newly released red cells that take up the isotope (one patient had chronic hemolysis indicated by isotope studies of blood and stool). Thus, neocytolysis can contribute to the anemia of renal disease and explain some unresolved issues about such anemia. One implication is the prediction that intravenous bolus EPO therapy is metabolically and economically inefficient compared with lower doses administered more frequently subcutaneously.

  13. Recombinant human erythropoietin (rHuEPO): more than just the correction of uremic anemia.

    Science.gov (United States)

    Buemi, Michele; Aloisi, Carmela; Cavallaro, Emanuela; Corica, Francesco; Floccari, Fulvio; Grasso, Giovanni; Lasco, Antonino; Pettinato, Giuseppina; Ruello, Antonella; Sturiale, Alessio; Frisina, Nicola

    2002-01-01

    Hematopoiesis is controlled by numerous interdependent humoral and endocrine factors. Erythropoietin (EPO), a hydrophobic sialoglycoproteic hormone, plays a crucial role in the regulation of hematopoiesis, and induces proliferation, maturation and differentiation of the erythroid cell line precursors. Thanks to recombinant DNA techniques, different recombinant hormones can now be produced at low cost and in large amounts. This has led to greater understanding of the pathophysiological factors regulating hematopoiesis. This in turn, hasprompted the search for new therapeutic approaches. EPO might also be used to treat patients with different types of anemia: uremics, newborns, patients with anemia from cancer or myeloproliferative disease, thalassemia, bone marrow transplants, chronic infectious diseases. Besides erythroid cells, EPO affects other blood cell lines, such as myeloid cells, lymphocytes and megakaryocytes. It can also enhance polymorphonuclear cell phagocytosis and reduce macrophage activation, thus modulating the inflammatory process. Hematopoietic and endothelial cells probably have the same origin, and the discovery of eyrthropoietin receptors also on mesangial, myocardial and smooth muscle cells has prompted research into the non-erythropoietic function of the hormone. EPO has an important, direct, hemodynamic and vasoactive effect, which does not depend only on an increase in hematocrit and viscosity. Moreover, EPO and its receptors have been found in the brain, suggesting a role in preventing neuronal death. Finally, the recently discovered interaction between EPO and vascular endothelial growth factor (VEGF), and the ability of EPO to stimulate endothelial cell mitosis and motility may be of importance in neovascularization and wound healing.

  14. Current status of the EPOS WG4 - GNSS and Other Geodetic Data

    Science.gov (United States)

    Fernandes, Rui; Bastos, Luisa; Bruyninx, Carine; D'Agostino, Nicola; Dousa, Jan; Ganas, Athanassios; Lidberg, Martin; Nocquet, Jean-Mathieu

    2014-05-01

    WG4 - "EPOS Geodetic Data and Other Geodetic Data" is the Working Group of the EPOS project in charge of defining and preparing the integration of the existing Pan-European Geodetic Infrastructures that will support European Geosciences, which is the ultimate goal of the EPOS project. The WG4 is formed by representatives of the participating EPOS countries (23) but it is also open to the entire geodetic community. In fact, WG4 also already includes members from countries that formally are not integrating EPOS in this first step. The geodetic component of EPOS (WG4) is dealing essentially with Research Infrastructures focused on continuous operating GNSS (cGNSS) in the current phase. The option of concentrating the efforts on the presently most generalized geodetic tool supporting research on Solid Earth was decided in order to optimize the existing resources. Nevertheless, WG4 will continue to pursue the development of tools and methodologies that permit the access of the EPOS community to other geodetic information (e.g., gravimetry). Furthermore, although the focus is on Solid Earth applications, other research and technical applications (e.g., reference frames, meteorology, space weather) can also benefit from the efforts of WG4 EPOS towards the optimization of the geodetic resources in Europe. We will present and discuss the plans for the implementation of the thematic and core services (TCS) for geodetic data within EPOS and the related business plan. We will focus on strategies towards the implementation of the best solutions that will permit to the end-users, and in particular geo-scientists, to access the geodetic data, derived solutions, and associated metadata using transparent and uniform processes. Five pillars have been defined proposed for the TCS: Dissemination, Preservation, Monitoring, and Analysis of geodetic data plus the Support and Governance Infrastructure. Current proposals and remaining open questions will be discussed.

  15. EPO induces changes in synaptic transmission and plasticity in the dentate gyrus of rats.

    Science.gov (United States)

    Almaguer-Melian, William; Mercerón-Martínez, Daymara; Delgado-Ocaña, Susana; Pavón-Fuentes, Nancy; Ledón, Nuris; Bergado, Jorge A

    2016-06-01

    Erythropoietin has shown wide physiological effects on the central nervous system in animal models of disease, and in healthy animals. We have recently shown that systemic EPO administration 15 min, but not 5 h, after daily training in a water maze is able to induce the recovery of spatial memory in fimbria-fornix chronic-lesioned animals, suggesting that acute EPO triggers mechanisms which can modulate the active neural plasticity mechanism involved in spatial memory acquisition in lesioned animals. Additionally, this EPO effect is accompanied by the up-regulation of plasticity-related early genes. More remarkably, this time-dependent effects on learning recovery could signify that EPO in nerve system modulate specific living-cellular processes. In the present article, we focus on the question if EPO could modulate the induction of long-term synaptic plasticity like LTP and LTD, which presumably could support our previous published data. Our results show that acute EPO peripheral administration 15 min before the induction of synaptic plasticity is able to increase the magnitude of the LTP (more prominent in PSA than fEPSP-Slope) to facilitate the induction of LTD, and to protect LTP from depotentiation. These findings showing that EPO modulates in vivo synaptic plasticity sustain the assumption that EPO can act not only as a neuroprotective substance, but is also able to modulate transient neural plasticity mechanisms and therefore to promote the recovery of nerve function after an established chronic brain lesion. According to these results, EPO could be use as a molecular tool for neurorestaurative treatments.

  16. Treating anemia associated with chronic renal failure with erythropoiesis stimulators: recombinant human erythropoietin might be the best among the available choices.

    Science.gov (United States)

    Trkulja, Vladimir

    2012-01-01

    Chronic renal failure (CRF) is a widespread medical problem commonly accompanied by a hypoproliferative anemia ("renal anemia") due to erythropoietin deficiency. Anemia greatly contributes to reduced quality of life (Hr-QoL) and high morbidity and mortality in CRF patients. Recombinant human erythropoietin (rHu-Epo) was introduced to medical practice some 20years ago. It enables correction of anemia (hemoglobin levels, Hb) with dramatic immediate (Hr-QoL improvement) and long-term effects (reduced morbidity and mortality). Newer experimental data suggest that long-term benefits could be due not only to antianemic effect, but also to a direct organoprotective effect of (rHu)-Epo mediated through a receptor complex different from the "erythropoietic" erythropoietin receptor. During the last decade, two alternative treatments for renal anemia have been approved: darbepoetin and CERA. Both are direct agonists of the "erythropoietic" receptors and both were derived from rHu-Epo. Molecularly, they differ from rHu-Epo in that they are much larger molecules (darbepoetin is genetically modified rHu-Epo with a higher sugar content and CERA is pegylated rHu-Epo) with lower affinity for the erythropoietin receptor but with a longer circulating time. In terms of renal anemia correction, they are non-inferior to rHu-Epo and allow for less frequent dosing. They have never been compared to rHu-Epo regarding the long-term outcomes. It is hypothesized that regarding the long-term outcomes (morbidity, mortality), rHu-Epo might be superior to those larger molecules. The hypothesis is based on two types of observations. First, experimental data emphasize the role of small, erythropoietically less valuable rHu-Epo isoforms in its organoprotective effects. Second, clinical observations suggest that rHu-Epo enables for less variable Hb correction than the larger molecules, and pronounced within-subject Hb variability has been suggested as an independent predictor of poor long

  17. EPoC标准进展及与DOCSIS3.1的关系

    Institute of Scientific and Technical Information of China (English)

    吴广生; 姚永

    2013-01-01

    简述了EPoC标准的产生背景,主要针对中国的现状进行了介绍,介绍了标准的目标应用场景、标准研究范围、标准进展情况、标准讨论等若干重要技术问题.对EPoC标准与DOCSIS3.1的关系表明了作者的看法.最后肯定了EPoC是EPON+EoC的发展方向.

  18. Effects of rHu-EPO on Myocyte Apoptosis and Cardiac Function Follow-ing Acute Myocardial Infarction in Rats

    Institute of Scientific and Technical Information of China (English)

    YE Liang; DU Xinling; XIA Jiahong; JIANG Ping

    2005-01-01

    The mechanisms of rHu-EPO attenuating the apoptosis after myocardial infarction in rats were studied. Thirty-two rats were divided into three groups: sham operation group (Sham), acute myocardial infarction group (MI) and rHu-EPO-treated group (MI+ EPO). Acute myocardial infarction model was made by ligating the anterior descending coronary artery. rHu-EPO was administered i. p. in MI+EPO group at the dose of 5 000 IU/kg body weight immediately after the ligation. Each rat in MI+EPO group received the same dose of rHu-EPO daily the next 6 days. On the 14th day all rats underwent hemodynamic measurements and then killed. The samples were examined with HE stain, immunohistochemistry technique (bcl-2, bax) and TUNEL dyeing. The results showed that hemodynamic function in MI+ EPO group was much better than in MI group.The number of the cells positive for bax and TUNEL in MI+EPO group was less than that in MI group. The number of the cells positive for bcl-2 in MI+EPO group was more than that in MI group. These findings suggested that rHu-EPO could treat myocardial infarction by preventing apoptosis and attenuating post-infarction deterioration in hemodynamic function.

  19. The protective effect of erythropoietin pretreatment on ischemic acute renal failure in rats

    Institute of Scientific and Technical Information of China (English)

    Jing-Guang Liao; Min-Yan Li; Xiao-Hua Wang; Qiang Xie

    2016-01-01

    Objective: To investigate the protective effect of erythropoietin (EPO) pretreatment on ischemic acute renal failure in rats and its molecular mechanism. Methods: Male Sprague–Dawley rats were selected as experimental animals and they were randomly divided into the sham operation group (sham group), ischemia-reperfusion injury group (IRI group) and EPO pretreatment group (EPO group). Each group had 15 rats. Serum specimens and renal specimens were collected after a IRI model was built for 4, 12 and 24 h. The contents of creatinine, urea nitrogen tumor necrosis factor-alpha (TNF-a), interleukin-1 (IL-1), IL-6 and IL-8 in serum and the contents of TNF-a, IL-1, IL-6, IL-8, toll like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kB) in the kidney tissue were determined. Results: After 4, 12 and 24 h reperfusion, there were differences between the contents of creatinine, urea nitrogen TNF-a, IL-1, IL-6 and IL-8 in serum and the contents of TNF-a, IL-1, IL-6, IL-8, TLR4 and NF-kB in rats of the three groups (P Conclusions: EPO pretreatment can protect the renal function of rats with ischemic acute renal failure by inhibiting the TLR4/NF-kB pathway mediated inflammatory responses.

  20. The triad of renal function, erythropoietin and haemoglobin in old age

    NARCIS (Netherlands)

    Willems, Jorien M.

    2014-01-01

    Knowledge of physiological changes in renal function, EPO and haemoglobin level and their impact at old age are essential for clinicians especially those working with older patients. The results of the studies presented in this thesis provide more insight in the physiological aspects of age related

  1. Quality of Original and Biosimilar Epoetin Products

    NARCIS (Netherlands)

    Brinks, V.; Hawe, A.; Basmeleh, A.H.H.; Joachin-Rodriguez, L.; Haselberg, R.; Somsen, G.W.; Jiskoot, W.; Schellekens, H.

    2011-01-01

    Purpose: To compare the quality of therapeutic erythropoietin (EPO) products, including two biosimilars, with respect to content, aggregation, isoform profile and potency. Methods: Two original products, Eprex (epoetin alfa) and Dynepo (epoetin delta), and two biosimilar products, Binocrit (epoetin

  2. Ghrelin counteracts salt-induced hypertension via promoting diuresis and renal nitric oxide production in Dahl rats.

    Science.gov (United States)

    Aoki, Hirotaka; Nakata, Masanori; Dezaki, Katsuya; Lu, Ming; Gantulga, Darambazar; Yamamoto, Keiji; Shimada, Kazuyuki; Kario, Kazuomi; Yada, Toshihiko

    2013-01-01

    Ghrelin is the endogenous ligand for the growth hormone-secretagogue receptor expressed in various tissues including the heart, blood vessels and kidney. This study sought to determine the effects of long-term treatment with ghrelin (10 nmol/kg, twice a day, intraperitoneally) on the hypertension induced by high salt (8.0% NaCl) diet in Dahl salt-sensitive hypertensive (DS) rats. Systolic blood pressure (SBP) was measured by a tail cuff method. During the treatment period for 3 weeks, high salt diet increased blood pressure compared to normal salt (0.3% NaCl) diet, and this hypertension was partly but significantly (P<0.01) attenuated by simultaneous treatment with ghrelin. Ghrelin significantly increased urine volume and tended to increase urine Na⁺ excretion. Furthermore, ghrelin increased urine nitric oxide (NO) excretion and tended to increase renal neuronal nitric oxide synthase (nNOS) mRNA expression. Ghrelin did not alter the plasma angiotensin II level and renin activity, nor urine catecholamine levels. Furthermore, ghrelin prevented the high salt-induced increases in heart thickness and plasma ANP mRNA expression. These results demonstrate that long-term ghrelin treatment counteracts salt-induced hypertension in DS rats primarily through diuretic action associated with increased renal NO production, thereby exerting cardio-protective effects.

  3. Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Xu Wu

    2016-01-01

    Full Text Available Obstructive sleep apnea (OSA associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH triggered tissue damage. Receptor for advanced glycation end product (RAGE and its ligand high mobility group box 1 (HMGB1 are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE, the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1 normal air (NA, (2 CIH, (3 CIH+sRAGE, and (4 NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6, apoptotic (Bcl-2/Bax, and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.

  4. Short-term erythropoietin treatment does not substantially modulate monocyte transcriptomes of patients with combined heart and renal failure.

    Directory of Open Access Journals (Sweden)

    Kim E Jie

    Full Text Available BACKGROUND: Combined heart and renal failure is associated with high cardiovascular morbidity and mortality. Anti-oxidant and anti-inflammatory, non-hematopoietic effects of erythropoietin (EPO treatment have been proposed. Monocytes may act as biosensors of the systemic environment. We hypothesized that monocyte transcriptomes of patients with cardiorenal syndrome (CRS reflect the pathophysiology of the CRS and respond to short-term EPO treatment at a recommended dose for treatment of renal anemia. METHODS: Patients with CRS and anemia (n = 18 included in the EPOCARES trial were matched to healthy controls (n = 12. Patients were randomized to receive 50 IU/kg/week EPO or not. RNA from CD14(+-monocytes was subjected to genome wide expression analysis (Illumina at baseline and 18 days (3 EPO injections after enrolment. Transcriptomes from patients were compared to healthy controls and effect of EPO treatment was evaluated within patients. RESULTS: In CRS patients, expression of 471 genes, including inflammation and oxidative stress related genes was different from healthy controls. Cluster analysis did not separate patients from healthy controls. The 6 patients with the highest hsCRP levels had more differentially expressed genes than the 6 patients with the lowest hsCRP levels. Analysis of the variation in log(2 ratios of all individual 18 patients indicated that 4 of the 18 patients were different from the controls, whereas the other 14 were quite similar. After short-term EPO treatment, every patient clustered to his or her own baseline transcriptome. Two week EPO administration only marginally affected expression profiles on average, however, individual gene responses were variable. CONCLUSIONS: In stable, treated CRS patients with mild anemia, monocyte transcriptomes were modestly altered, and indicated imprints of inflammation and oxidative stress. EPO treatment with a fixed dose has hematopoietic effects, had no appreciable beneficial

  5. NASA Astrophysics EPO Community: Serving Groups Historically Underrepresented in STEM Fields

    Science.gov (United States)

    Meinke, B. K.; Smith, D. A.; Lawton, B.; Bartolone, L.; Schultz, G.; Manning, J.; NASA Astrophysics EPO Community

    2015-11-01

    Four Science Education and Public Outreach Forums support and coordinate the NASA Science Mission Directorate (SMD) education and public outreach (EPO) community. The mission- and grant-based EPO programs of this EPO community are uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise. The Forums engage underserved audiences through coordinated efforts such as NASAScience4Girls and Their Families, which partners NASA science education programs with public libraries to provide NASA-themed, hands-on education activities for girls and their families, along with training for librarians. We present examples of how the NASA EPO community and Forums serve groups historically underrepresented in STEM fields via the NASAScience4Girls and Their Families initiative, including associated metrics and evaluation findings.

  6. NASA Astrophysics EPO Community: Increasing and Sustaining Youth and Public Engagement in STEM

    Science.gov (United States)

    Lawton, B.; Smith, D. A.; Bartolone, L.; Meinke, B. K.; Schultz, G.; Manning, J.; NASA Astrophysics EPO Community

    2015-11-01

    The NASA Science Mission Directorate (SMD) Astrophysics Education and Public Outreach (EPO) community and Forum work together to capitalize on the cutting-edge discoveries of NASA Astrophysics missions to enable youth to engage directly in doing Science, Technology, Engineering, and Mathematics (STEM) inside and outside of school. The NASA SMD Astrophysics EPO community has proven expertise in providing student opportunities that reinforce research skills; exhibits, multimedia shows, and visualizations that inspire and engage; professional development for informal educators; and partnerships that provide local, regional, and national reach. These mission- and grant-based EPO programs are uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise. We present examples of how the NASA Astrophysics EPO community and Forum support youth and public engagement in STEM in these ways, including associated metrics and evaluation findings.

  7. Improving outcomes of acute kidney injury using mouse renal progenitor cells alone or in combination with erythropoietin or suramin.

    Science.gov (United States)

    Han, Xiao; Zhao, Li; Lu, Guodong; Ge, Junke; Zhao, Yalin; Zu, Shulu; Yuan, Mingzhen; Liu, Yuqiang; Kong, Feng; Xiao, Zhiying; Zhao, Shengtian

    2013-06-18

    So far, no effective therapy is available for acute kidney injury (AKI), a common and serious complication with high morbidity and mortality. Interest has recently been focused on the potential therapeutic effect of mouse adult renal progenitor cells (MRPC), erythropoietin (EPO) and suramin in the recovery of ischemia-induced AKI. The aim of the present study is to compare MRPC with MRPC/EPO or MRPC/suramin concomitantly in the treatment of a mouse model of ischemia/reperfusion (I/R) AKI. MRPC were isolated from adult C57BL/6-gfp mice. Male C57BL/6 mice (eight-weeks old, n = 72) were used for the I/R AKI model. Serum creatinine (Cr), blood urea nitrogen (BUN) and renal histology were detected in MRPC-, MRPC/EPO-, MRPC/suramin- and PBS-treated I/R AKI mice. E-cadherin, CD34 and GFP protein expression was assessed by immunohistochemical assay. MRPC exhibited characteristics consistent with renal stem cells. The features of MRPC were manifested by Pax-2, Oct-4, vimentin, α-smooth muscle actin positive, and E-cadherin negative, distinguished from mesenchymal stem cells (MSC) by expression of CD34 and Sca-1. The plasticity of MRPC was shown by the ability to differentiate into osteoblasts and lipocytes in vitro. Injection of MRPC, especially MRPC/EPO and MRPC/suramin in I/R AKI mice attenuated renal damage with a decrease of the necrotic injury, peak plasma Cr and BUN. Furthermore, seven days after the injury, MRPC/EPO or MRPC/suramin formed more CD34(+) and E-cadherin+ cells than MRPC alone. These results suggest that MRPC, in particular MRPC/EPO or MRPC/suramin, promote renal repair after injury and may be a promising therapeutic strategy.

  8. Scientists Delivering EPO Content - Lessons Learned and Advice from the Trenches

    Science.gov (United States)

    Petro, N. E.

    2012-12-01

    The need for scientists to participate in Education and Public Outreach events has perhaps never been greater than it is now. Between the need for schools to provide accurate science content to their students, the prevalence of misconceptions in the public regarding science issues, and communicating to the tax paying public what is being done on federally funded projects, it critically important that scientists be engaged in communicating with the public. However, the demand on a scientist's time to perform such activities, which are typically outside the scope of work for many professionals, can be taxing and presents roadblocks to performing such activities. While there may not be an optimal method for how to address the conflict between the time and demand to perform EPO activities, there are several possible approaches that may both reduce the impact on the scientist and provide maximum impact to the EPO community. One, do you really want to participate in EPO activities, knowing that it will require an amount of time and effort to perform and are there ways to ensure that the effort will be recognized as part of your job? In both cases, if the answer is no, it is probably not wise to continue, unless the scope of your job can be expanded. Two, it is vitally important to work with an EPO professional (if one exists at your location) and set realistic expectations for how much you are willing to do over a month/year. It is also important to work with an EPO professional to develop appropriate content for the audiences you'd work with. Ultimately, identifying an EPO professional that you can work with to both structure your involvement and develop an approach to EPO is vital. In the case where no such support is available, it is critical that you understand your audience and what they expect and need in order to understand the message. Three, funding opportunities often exist where EPO content can be developed in partnership with an EPO professional and present

  9. Trauma renal Renal trauma

    Directory of Open Access Journals (Sweden)

    Gerson Alves Pereira Júnior

    1999-02-01

    Full Text Available Apresentamos uma revisão sobre trauma renal, com ênfase na avaliação radiológica, particularmente com o uso da tomografia computadorizada, que tem se tornado o exame de eleição, ao invés da urografia excretora e arteriografia. O sucesso no tratamento conservador dos pacientes com trauma renal depende de um acurado estadiamento da extensão da lesão, classificado de acordo com a Organ Injury Scaling do Colégio Americano de Cirurgiões. O tratamento conservador não-operatório é seguro e consiste de observação contínua, repouso no leito, hidratação endovenosa adequada e antibioti- coterapia profilática, evitando-se uma exploração cirúrgica desnecessária e possível perda renal. As indicações para exploração cirúrgica imediata são abdome agudo, rápida queda do hematócrito ou lesões associadas determinadas na avaliação radiológica. Quando indicada, a exploração renal após controle vascular prévio é segura, permitindo cuidadosa inspeção do rim e sua reconstrução com sucesso, reduzindo a probabilidade de nefrectomia.We present a revision of the renal trauma with emphasis in the radiographic evaluation, particularly CT scan that it has largely replaced the excretory urogram and arteriogram in the diagnostic worh-up and management of the patient with renal trauma. The successful management of renal injuries depends upon the accurate assessment of their extent in agreement with Organ Injury Scaling classification. The conservative therapy managed by careful continuous observation, bed rest, appropriate fluid ressuscitation and prophylactic antibiotic coverage after radiographic staging for severely injured kidneys can yield favorable results and save patients from unnecessary exploration and possible renal loss. The indications for immediate exploratory laparotomy were acute abdomen, rapidly dropping hematocrit or associated injuries as determinated from radiologic evaluation. When indicated, renal exploration

  10. Differential proteomic analysis of human erythroblasts undergoing apoptosis induced by epo-withdrawal.

    Science.gov (United States)

    Pellegrin, Stéphanie; Heesom, Kate J; Satchwell, Timothy J; Hawley, Bethan R; Daniels, Geoff; van den Akker, Emile; Toye, Ashley M

    2012-01-01

    The availability of Erythropoietin (Epo) is essential for the survival of erythroid progenitors. Here we study the effects of Epo removal on primary human erythroblasts grown from peripheral blood CD34(+) cells. The erythroblasts died rapidly from apoptosis, even in the presence of SCF, and within 24 hours of Epo withdrawal 60% of the cells were Annexin V positive. Other classical hallmarks of apoptosis were also observed, including cytochrome c release into the cytosol, loss of mitochondrial membrane potential, Bax translocation to the mitochondria and caspase activation. We adopted a 2D DIGE approach to compare the proteomes of erythroblasts maintained for 12 hours in the presence or absence of Epo. Proteomic comparisons demonstrated significant and reproducible alterations in the abundance of proteins between the two growth conditions, with 18 and 31 proteins exhibiting altered abundance in presence or absence of Epo, respectively. We observed that Epo withdrawal induced the proteolysis of the multi-functional proteins Hsp90 alpha, Hsp90 beta, SET, 14-3-3 beta, 14-3-3 gamma, 14-3-3 epsilon, and RPSA, thereby targeting multiple signaling pathways and cellular processes simultaneously. We also observed that 14 proteins were differentially phosphorylated and confirmed the phosphorylation of the Hsp90 alpha and Hsp90 beta proteolytic fragments in apoptotic cells using Nano LC mass spectrometry. Our analysis of the global changes occurring in the proteome of primary human erythroblasts in response to Epo removal has increased the repertoire of proteins affected by Epo withdrawal and identified proteins whose aberrant regulation may contribute to ineffective erythropoiesis.

  11. Examination of the e{sup +} and e{sup +}e{sup -} pair emission from heavy ion collisions at the EPoS II spectrometer; Untersuchung der e{sup +}- und e{sup +}e{sup -}-Paaremission aus Schwerionenkollisionen mit dem EPoS II Spektrometer

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, J.

    1996-12-01

    In the course of examination of the positron and positron-electron pair emission from heavy ion collisions at the Coulomb barrier, the research groups EPOS I and ORANGE have found a number of line structures in the measured positron energy and cumulative pair energy spectra which up to present could not be fully explained, as theoretical interpretations so far remain inconsistent in some respects. For clarification, further measurements have been made at the completely new designed EPoS II spectrometer. Reproducibility of the lines is possible at a high level of statistical significance. (orig./CB) [Deutsch] Bei Untersuchungen der Positron- und Positron- Elektron- Paaremissionaus Schwerionenkollisionen an der Coulombbarriere wurde von den Gruppen EPOS I und ORANGE eine Reihe von Linienstrukturen in den gemessenen Positronenenergie- und Paarsummenenergiespektren beobachtet, fuer die bislang keine in allen Punkten konsistente, theoretische Erklaerunggefunden werden konnte. Um ihre Ursachen zu klaeren, wurden mit dem voellig neu aufgebauten EPoS II Spektrometer weitere Messreihen durgefuehrt. Die Reproduzierbarkeit der Linien ist auf einem hohen statistischen Signifikanzniveau moeglich.

  12. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans.

    Science.gov (United States)

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke; Lundby, Carsten; Olsen, Niels V; Secher, Niels H; van Lieshout, Johannes J

    2012-03-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic and cerebrovascular variables following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk; n=8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 ± 3.7 to 47.6 ± 4.1% (PEPO administration. Yet, the two EPO regimes increased arterial pressure similarly (by 8±4 and 7±3 mmHg, respectively; P=0.01) through reduced vascular conductance (by 7±3 and 5±2%; PEPO regimes widened the arterial-to-jugular O(2) differences at rest as well as during normoxic and hypoxic exercise (PEPO to healthy humans lowers systemic and cerebral conductance independent of its effect on hematocrit.

  13. Renal arteriography

    Science.gov (United States)

    ... Read More Acute arterial occlusion - kidney Acute kidney failure Aneurysm Atheroembolic renal disease Blood clots Renal cell carcinoma Renal venogram X-ray Review Date 1/5/2016 Updated by: Jason Levy, ...

  14. Spinal vascular endothelial growth factor (VEGF) and erythropoietin (EPO) induced phrenic motor facilitation after repetitive acute intermittent hypoxia.

    Science.gov (United States)

    Dale, Erica A; Mitchell, Gordon S

    2013-02-01

    Vascular endothelial growth factor (VEGF) and erythropoietin (EPO) exert neurotrophic and neuroprotective effects in the CNS. We recently demonstrated that VEGF, EPO and their receptors (VEGF-R2, EPO-R) are expressed in phrenic motor neurons, and that cervical spinal VEGF-R2 and EPO-R activation elicit long-lasting phrenic motor facilitation (pMF). Since VEGF, VEGF-R, EPO, and EPO-R are hypoxia-regulated genes, and repetitive exposure to acute intermittent hypoxia (rAIH) up-regulates these molecules in phrenic motor neurons, we tested the hypothesis that 4 weeks of rAIH (10 episodes per day, 3 days per week) enhances VEGF- or EPO-induced pMF. We confirm that cervical spinal VEGF and EPO injections elicit pMF. However, neither VEGF- nor EPO-induced pMF was affected by rAIH pre-conditioning (4 wks). Although our data confirm that spinal VEGF and EPO may play an important role in respiratory plasticity, we provide no evidence that rAIH amplifies their impact. Further experiments with more robust protocols are warranted.

  15. The Year of the Solar System: An E/PO Community's Approach to Sharing Planetary Science

    Science.gov (United States)

    Shipp, S. S.; Boonstra, D.; Shupla, C.; Dalton, H.; Scalice, D.; Planetary Science E/Po Community

    2010-12-01

    YSS offers the opportunity to raise awareness, build excitement, and make connections with educators, students and the public about planetary science activities. The planetary science education and public outreach (E/PO) community is engaging and educating their audiences through ongoing mission and program activities. Based on discussion with partners, the community is presenting its products in the context of monthly thematic topics that are tied to the big questions of planetary science: how did the Sun’s family of planets and bodies originate and how have they evolved; and how did life begin and evolve on Earth, has it evolved elsewhere in our solar system, and what are characteristics that lead to the origins of life? Each month explores different compelling aspects of the solar system - its formation, volcanism, ice, life. Resources, activities, and events are interwoven in thematic context, and presented with ideas through which formal and informal educators can engage their audiences. The month-to-month themes place the big questions in a logical sequence of deepening learning experiences - and highlight mission milestones and viewing events. YSS encourages active participation and communication with its audiences. It includes nation-wide activities, such as a Walk Through the Solar System, held between October 2010 to March 2011, in which museums, libraries, science centers, schools, planetariums, amateur astronomers, and others are kicking off YSS by creating their own scale models of the solar system and sharing their events through online posting of pictures, video, and stories. YSS offers the E/PO community the opportunity to collaborate with each other and partners. The thematic approach leverages existing products, providing a home and allowing a “shelf life” that can outlast individual projects and missions. The broad themes highlight missions and programs multiple times. YSS also leverages existing online resources and social media. Hosted on

  16. New Media E/PO: Building a Digital Astronomy Community

    Science.gov (United States)

    Gay, Pamela L.

    2008-05-01

    Today's communications landscape is rich with new technologies. Cell phones and laptops are the constant companions of content consumers, and as we plan tomorrow's Education and Public Outreach programs, we need to consider how to most effectively utilize these technologies with their new, dynamic content possibilities - We need to use New Media. The field of New Media includes dynamic content sites such as: blogs, pod/vodcasts, Flickr, Facebook, Ustream, Twitter, and Second Life. The first part of this talk will summarize what New Media is available in the field of astronomy. All new media technologies have one thing in common: Users can easily create and input their own content and/or comments. These new media users and content contributors can just as easily be professional researchers, E/PO professionals, amateur astronomers, stay-at-home parents, and school kids. All are welcome in the online community, and today, all voices are digitally joined in the cacophony of astronomy new media content. This rich diversity supports many opportunities for learning, mentoring, content distribution, and discussion of ideas (including the debunking of bad ideas). In the second half of this talk, ways to use new media to build a community that shares, promotes, and comments on content is discussed, and techniques for dealing with the high flux of content are outlined. Also covered are the considerations that need to be made to make content as broadly accessible as possible.

  17. EduBites: Cliffs Notes for E/PO

    Science.gov (United States)

    Brinkworth, Carolyn; Bartolone, L.; Wenger, M.; Martin, A.; Nichols-Yehling, M.; Hurt, R. L.; Squires, G. K.

    2013-01-01

    We present a new resource for the astronomy education community, with the goal of improving our community’s knowledge and understanding of the educational research papers relevant to our work. EduBites is a searchable database of summaries of peer-reviewed education papers, written by astronomy educators and posted for the entire community to use. While we are all aware that we should be basing our E/PO work on a solid research foundation, many people in the community are pushed for time when it comes to staying on top of the educational literature. EduBites aims to reduce that workload for the benefit of the entire community. Our database is small, but growing, and will ultimately tackle papers across the whole of the astronomy education spectrum, including formal and informal education, outreach, grades K-16, pedagogy, evaluation, and many other topics. We are keen to hear from anyone on the community who would be interested in joining our review team, and welcome feedback on the EduBites user experience.

  18. Treatment with nasal neuro-EPO improves the neurological, cognitive, and histological state in a gerbil model of focal ischemia.

    Science.gov (United States)

    Rodríguez Cruz, Yamila; Mengana Támos, Yuneidys; Muñoz Cernuda, Adriana; Subirós Martines, Nelvis; González-Quevedo, Alina; Sosa Testé, Iliana; García Rodríguez, Julio César

    2010-11-16

    Vascular illness of the brain constitutes the third cause of death and the first cause of disability in Cuba and many other countries. Presently, no medication has been registered as a neuroprotector. Neuroprotection with intranasal Neuro-EPO (EPO, erythropoietin) has emerged as a multifunctional therapy that plays a significant role in neural survival and functional recovery in an animal model of stroke. On the other hand, there is limited access to the brain through the blood brain barrier (BBB) for intravenously applied EPO, and the high EPO dosages needed to obtain a protective effect increase the danger of elevated hematocrit levels and practically exclude chronic or subchronic treatment with EPO. A promising approach has been recently developed with a nonerythropoietic variant of EPO, Neuro-EPO, with low sialic acid content, a very short plasma half-life, and without erythropoietic activity, probably similar to endogenous brain EPO. The objective of this work was to determine the neuroprotective effect of intranasal Neuro-EPO in comparison with the human recombinant EPO injected intraperitoneally in the acute phase of cerebral ischemia, employing the common carotid artery occlusion model in gerbils. Neuro-EPO has demonstrated a better neuroprotective effect, evidenced through increased viability, improvements of the neurological state and cognitive functions, as well as protection of the CA3 region of the hippocampus, temporal cortex, and the thalamus. In conclusion, the intranasal application of Neuro-EPO has a better neuroprotective effect than intraperitoneal EPO, evidenced by the significant improvement of neurological, cognitive, and histological status in the animal model of stroke employed.

  19. Paraoxonase 2 decreases renal reactive oxygen species production, lowers blood pressure, and mediates dopamine D2 receptor-induced inhibition of NADPH oxidase.

    Science.gov (United States)

    Yang, Yu; Zhang, Yanrong; Cuevas, Santiago; Villar, Van Anthony; Escano, Crisanto; D Asico, Laureano; Yu, Peiying; Grandy, David K; Felder, Robin A; Armando, Ines; Jose, Pedro A

    2012-08-01

    The dopamine D(2) receptor (D(2)R) regulates renal reactive oxygen species (ROS) production, and impaired D(2)R function results in ROS-dependent hypertension. Paraoxonase 2 (PON2), which belongs to the paraoxonase gene family, is expressed in various tissues, acting to protect against cellular oxidative stress. We hypothesized that PON2 may be involved in preventing excessive renal ROS production and thus may contribute to maintenance of normal blood pressure. Moreover, D(2)R may decrease ROS production, in part, through regulation of PON2. D(2)R colocalized with PON2 in the brush border of mouse renal proximal tubules. Renal PON2 protein was decreased (-33±6%) in D(2)(-/-) relative to D(2)(+/+) mice. Renal subcapsular infusion of PON2 siRNA decreased PON2 protein expression (-55%), increased renal oxidative stress (2.2-fold), associated with increased renal NADPH oxidase expression (Nox1, 1.9-fold; Nox2, 2.9-fold; and Nox4, 1.6-fold) and activity (1.9-fold), and elevated arterial blood pressure (systolic, 134±5 vs 93±6mmHg; diastolic, 97±4 vs 65±7mmHg; mean 113±4 vs 75±7mmHg). To determine the relevance of the PON2 and D(2)R interaction in humans, we studied human renal proximal tubule cells. Both D(2)R and PON2 were found in nonlipid and lipid rafts and physically interacted with each other. Treatment of these cells with the D(2)R/D(3)R agonist quinpirole (1μM, 24h) decreased ROS production (-35±6%), associated with decreased NADPH oxidase activity (-32±3%) and expression of Nox2 (-41±7%) and Nox4 (-47±8%) protein, and increased expression of PON2 mRNA (2.1-fold) and protein (1.6-fold) at 24h. Silencing PON2 (siRNA, 10nM, 48h) not only partially prevented the quinpirole-induced decrease in ROS production by 36%, but also increased basal ROS production (1.3-fold), which was associated with an increase in NADPH oxidase activity (1.4-fold) and expression of Nox2 (2.1-fold) and Nox4 (1.8-fold) protein. Inhibition of NADPH oxidase with diphenylene

  20. [Iron chelation therapy and its influence on the alleviation of EPO resistance in MDS patients].

    Science.gov (United States)

    Zhang, Yao; Xiao, Chao; Gu, Shu-Cheng; Chang, Chun-Kang

    2014-08-01

    This study was aimed to investigate the changes of erythropoietin (EPO), hemoglobin(Hb) and recombinant EPO (rEPO) levels in MDS patients receiving iron chelation therapy, and to explore the relationship between EPO and serum ferritin(SF). A total of 172 MDS patients and 30 healthy controls were studied. The levels of SF, EPO, serum iron (SI), total iron binding capacity (TIBC), C-reaction protein (CRP) and Hb were measured respectively, the level of SF was adjusted according to the changes of CRP. Among them, there were 34 cases of low-risk (SF>1 000 mg/L) receiving deferoxamine therapy, whose changes of SF, EPO, SI, TIBC, Hb levels were detected and compared before and after treatment. Besides, the difference in the incidence of EPO resistance in iron overload group and non-iron overload group was assessed before and after therapy, and 58 cases of low-risk and EPOEPO in non-iron overload group was higher than that in the normal control group (997.44 ± 473.48 vs 467.27 ± 238.49, P EPO in iron overload group was higher than that in non-iron overload group and control group (3257.59 ± 697.19 vs 997.44 ± 473.48, P = 0.012, 3257.59 ± 697.19 vs 467.27 ± 238.49, P = 0.002). Otherwise, the incidence of EPO resistance in iron overload group was higher than that in non-iron overload group (18/35 vs 2/23, P = 0.001), and the level of EPO and SF was positively related to each other in iron overload group (r = 0.310,P = 0.036). After receiving iron chelation therapy, the levels of SF, SI, TIBC and EPO in iron overload group were significantly lower than that before therapy (3942.38 ± 641.82 vs 2266.35 ± 367.31, P = 0.028;48.61 ± 10.65 vs 28.52 ± 12.61, P = 0.034;59.84 ± 12.62 vs 33.76 ± 15.43, P = 0.045;3808.01 ± 750.22 vs 1954.78 ± 473.18, P = 0.042). Moreover, the level of Hb increased (35 ± 18 vs 57 ± 21, P = 0.046) and the EPO resistance in some patients was decreased. It is concluded that iron chelation therapy can improve the efficacy of EPO to alleviate

  1. Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Visser, Folkert W.; Voors, Adriaan A.; Smilde, Tom D. J.; Lipsic, Erik; Navis, Gerjan; Hillege, Hans L.; van Gilst, Wiek H.; van Veldhuisen, Dirk J.

    2007-01-01

    Aims Anaemia is prevalent in the chronic heart failure (CHF) population, but its cause is often unknown. The present study aims to investigate the relation between anaemia, renal perfusion, erythropoietin production, and fluid retention in CHF patients. Methods and results We studied 97 patients wit

  2. Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Visser, Folkert W.; Voors, Adriaan A.; Smilde, Tom D. J.; Lipsic, Erik; Navis, Gerjan; Hillege, Hans L.; van Gilst, Wiek H.; van Veldhuisen, Dirk J.

    2007-01-01

    Aims Anaemia is prevalent in the chronic heart failure (CHF) population, but its cause is often unknown. The present study aims to investigate the relation between anaemia, renal perfusion, erythropoietin production, and fluid retention in CHF patients. Methods and results We studied 97 patients wit

  3. 基于EPO-PLS回归模型的盐渍化土壤含水率高光谱反演%Estimating soil moisture from hyperspectra in saline soil based on EPO-PLS regression

    Institute of Scientific and Technical Information of China (English)

    彭翔; 胡丹; 曾文治; 伍靖伟; 黄介生

    2016-01-01

    The information ofsurface soil moisture is of great importance for the irrigation and production of agriculture. Researches have shown that surface reflectance spectra of soils are often jointly affected by soil moisture content and salt content, whichhas not yet been sufficiently addressed. In this study, we investigated the external parameter orthogonalization (EPO) method to eliminate the effect of soil salinity by preprocessing soil spectral reflectance and establishing EPO-PLS (partial least squares regression after EPO pre-processing) model to predict soil moisture content. Soil salt composition and texture were obtained by taking soil samples in Hetao Irrigation District, Inner Mongolia, China in July 2014. The components of soil salt were mixed to artificially create 11 levels (percentage by weight, g/(100 g)) of salt salinity in the soil samples: 0.1 (natural soil salt content), 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 1.0, 2.0 and 5.0%. The moisture contents of total soil samples were designed as relative weight 38%. Filling 11 replicate dishes (12 cm in diameter) with each level of salinity soil, respectively. Each dish was filled with about 374 g wet soil with 3cm depth and a bulk density of 1.3.A controlled laboratory experiment was conducted by a way of continuously monitoring changes of soil moisture and salt content.Soil reflectance spectra were measured for each level of salt salinity samples in a darkroom using Analytical Spectral Device FieldSpec 3 Hi-Res (ASD, USA) spectrometer covering wavelengths from 350 to 2 500 nm at an interval of 1 nm. Reflectance spectra and weight of each soil samples were measured every day until the weights remained unvaried (completely air-dried). Based on laboratory controlled experiments, this paper is mainly focused on the changes of slightly and moderately salt-affected soil reflectance spectra in the process of evaporation. We quantitatively analyzed the changes in soil reflectance of overall bands and the results

  4. Effect of Shenkang injection combined with hemodialysis treatment on renal function, renal anemia and cytokine levels in patients with chronic renal failure

    Institute of Scientific and Technical Information of China (English)

    Rui Liu

    2016-01-01

    Objective:To study the effect of Shenkang injection combined with hemodialysis treatment on renal function, renal anemia and cytokine levels in patients with chronic renal failure. Methods: A total of 68 patients with chronic renal failure who received hemodialysis treatment in our hospital during between October 2013 and February 2016 were selected and randomly divided into two groups, the observation group received Shenkang injection treatment in the process of dialysis, and the control group only received conventional symptomatic and supportive treatment. 8 weeks after treatment, serum was collected to determine the levels of renal function indexes, nutritional status indexes, anemia indexes and cytokines, and urine was collected to determine renal function indexes.Results:β2-MG, UA, Cr, phosphorus, IL-17, IL-23, CTGF, TGF-β1, FGF-2 and FGF-23 levels in serum as well as NGAL, KIM-1 and RBP levels in urine of observation group were significantly lower than those of control group, and TP, Alb, PA, calcium, Hb, EPO, Fe, TRF and FER levels in serum were significantly higher than those of control group.Conclusion:Shenkang injection combined with hemodialysis treatment helps to improve renal function, nutritional status and renal anemia, and reduce the synthesis of inflammation and renal interstitial fibrosis-related cytokines in patients with chronic renal failure.

  5. EPOS-WP16: A coherent and collaborative network of Solid Earth Multi-scale laboratories

    Science.gov (United States)

    Calignano, Elisa; Rosenau, Matthias; Lange, Otto; Spiers, Chris; Willingshofer, Ernst; Drury, Martyn; van Kan-Parker, Mirjam; Elger, Kirsten; Ulbricht, Damian; Funiciello, Francesca; Trippanera, Daniele; Sagnotti, Leonardo; Scarlato, Piergiorgio; Tesei, Telemaco; Winkler, Aldo

    2017-04-01

    Laboratory facilities are an integral part of Earth Science research. The diversity of methods employed in such infrastructures reflects the multi-scale nature of the Earth system and is essential for the understanding of its evolution, for the assessment of geo-hazards and for the sustainable exploitation of geo-resources. In the frame of EPOS (European Plate Observing System), the Working Package 16 represents a developing community of European Geoscience Multi-scale laboratories. The participant and collaborating institutions (Utrecht University, GFZ, RomaTre University, INGV, NERC, CSIC-ICTJA, CNRS, LMU, C4G-UBI, ETH, CNR*) embody several types of laboratory infrastructures, engaged in different fields of interest of Earth Science: from high temperature and pressure experimental facilities, to electron microscopy, micro-beam analysis, analogue tectonic and geodynamic modelling and paleomagnetic laboratories. The length scales encompassed by these infrastructures range from the nano- and micrometre levels (electron microscopy and micro-beam analysis) to the scale of experiments on centimetres-sized samples, and to analogue model experiments simulating the reservoir scale, the basin scale and the plate scale. The aim of WP16 is to provide two services by the year 2019: first, providing virtual access to data from laboratories (data service) and, second, providing physical access to laboratories (transnational access, TNA). Regarding the development of a data service, the current status is such that most data produced by the various laboratory centres and networks are available only in limited "final form" in publications, many data remain inaccessible and/or poorly preserved. Within EPOS the TCS Multi-scale laboratories is collecting and harmonizing available and emerging laboratory data on the properties and process controlling rock system behaviour at all relevant scales, in order to generate products accessible and interoperable through services for supporting

  6. Climate Discovery: Integrating Research With Exhibit, Public Tours, K-12, and Web-based EPO Resources

    Science.gov (United States)

    Foster, S. Q.; Carbone, L.; Gardiner, L.; Johnson, R.; Russell, R.; Advisory Committee, S.; Ammann, C.; Lu, G.; Richmond, A.; Maute, A.; Haller, D.; Conery, C.; Bintner, G.

    2005-12-01

    The Climate Discovery Exhibit at the National Center for Atmospheric Research (NCAR) Mesa Lab provides an exciting conceptual outline for the integration of several EPO activities with other well-established NCAR educational resources and programs. The exhibit is organized into four topic areas intended to build understanding among NCAR's 80,000 annual visitors, including 10,000 school children, about Earth system processes and scientific methods contributing to a growing body of knowledge about climate and global change. These topics include: 'Sun-Earth Connections,' 'Climate Now,' 'Climate Past,' and 'Climate Future.' Exhibit text, graphics, film and electronic media, and interactives are developed and updated through collaborations between NCAR's climate research scientists and staff in the Office of Education and Outreach (EO) at the University Corporation for Atmospheric Research (UCAR). With funding from NCAR, paleoclimatologists have contributed data and ideas for a new exhibit Teachers' Guide unit about 'Climate Past.' This collection of middle-school level, standards-aligned lessons are intended to help students gain understanding about how scientists use proxy data and direct observations to describe past climates. Two NASA EPO's have funded the development of 'Sun-Earth Connection' lessons, visual media, and tips for scientists and teachers. Integrated with related content and activities from the NASA-funded Windows to the Universe web site, these products have been adapted to form a second unit in the Climate Discovery Teachers' Guide about the Sun's influence on Earth's climate. Other lesson plans, previously developed by on-going efforts of EO staff and NSF's previously-funded Project Learn program are providing content for a third Teachers' Guide unit on 'Climate Now' - the dynamic atmospheric and geological processes that regulate Earth's climate. EO has plans to collaborate with NCAR climatologists and computer modelers in the next year to develop

  7. Translating Research Into E/PO That Addresses Real Needs in K-12 Classrooms

    Science.gov (United States)

    van der Veen, Wil E.; Belbruno, E. A.; Roelofsen Moody, T.

    2009-01-01

    One of the challenges in NASA ROSES E/PO is translating cutting edge research into products for which there is a demonstrated need. Rather than working from the premise that the "research is so cool’ that K-12 students or the public should learn about it, it is key to consult with the target audience to identify what their needs really are. The partnership between NJACE, Innovative Orbital Design, Inc., and Princeton offered a unique opportunity to translate intriguing but theoretical and mathematical research related to low energy orbits into a valuable education product. NJACE worked with educators to identify several needs with an intellectual link to this research: 1) Understanding of Gravity and Newton's Laws, 2) Understanding of Energy and Energy Transformations, 3) Integration of the sciences with math and technology, and 4) Knowledge of NASA's past accomplishments (such as the moon landings). Based on these identified needs, two science units were developed for students in grades 5-12 that integrate astronomy, physics, and the life sciences with math and technology. In addition an engaging public lecture was developed that tells a personal story of the quest for more economic space travel. In the past year, the workshops have been presented on three occasions, reaching over 75 teachers and demand exceeded available space with numerous teachers on waiting lists. The lecture has been presented numerous times at planetariums, museums, amateur astronomy and other clubs. We hope that our partnership will serve as a useful example of how to translate cutting edge research into valuable education products with an identified need. We will provide handouts with links to a website where the products and training can be downloaded in hope that others will help disseminate our product.

  8. High doses of recombinant erythropoietin stimulate platelet production in mice

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, T.P.; Cottrell, M.B.; Clift, R.E.; Cullen, W.C.; Lin, F.K.

    1987-07-01

    Previously, recombinant erythropoietin (rEpo) was shown to increase the number and size of megakaryocytic colonies in vitro, and in vivo it elevates the number of megakaryocytes in mouse spleens. To test the hypothesis that rEpo would stimulate platelet production in mice, both normal mice and mice in rebound-thrombocytosis were injected with rEpo and the %35S incorporation into platelets was measured. A thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) was used as a positive control. rEpo increased isotopic incorporation into platelets of both normal mice and mice in rebound-thrombocytosis, as did TSF, but required large doses (15 U rEpo/mouse). In other mice, hematocrits, platelet counts, platelet sizes, and 24-hr %35S incorporation into platelets were measured 2 days after injection of two equally divided doses of either rEpo or TSF. Significant increases in both platelet sizes and %35S incorporation into platelets were found after injections of 15 U rEpo/mouse or 2.3 U TSF/mouse. These data indicate that rEpo, at high doses, will stimulate platelet production in mice, and may suggest molecular similarities between rEpo and TSF and their ability to compete for common receptor sites on megakaryocytes and their progenitor cells.

  9. 5-Lypoxygenase products are involved in renal tubulointerstitial injury induced by albumin overload in proximal tubules in mice.

    Directory of Open Access Journals (Sweden)

    Sharon Schilling Landgraf

    Full Text Available The role of albumin overload in proximal tubules (PT in the development of tubulointerstitial injury and, consequently, in the progression of renal disease has become more relevant in recent years. Despite the importance of leukotrienes (LTs in renal disease, little is known about their role in tubulointerstitial injury. The aim of the present work was to investigate the possible role of LTs on tubulointerstitial injury induced by albumin overload. An animal model of tubulointerstitial injury challenged by bovine serum albumin was developed in SV129 mice (wild-type and 5-lipoxygenase-deficient mice (5-LO(-/-. The changes in glomerular morphology and nestin expression observed in wild-type mice subjected to kidney insult were also observed in 5-LO(-/- mice. The levels of urinary protein observed in the 5-LO(-/- mice subjected or not to kidney insult were lower than those observed in respective wild-type mice. Furthermore, the increase in lactate dehydrogenase activity, a marker of tubule damage, observed in wild-type mice subjected to kidney insult did not occur in 5-LO(-/- mice. LTB4 and LTD4, 5-LO products, decreased the uptake of albumin in LLC-PK1 cells, a well-characterized porcine PT cell line. This effect correlated with activation of protein kinase C and inhibition of protein kinase B. The level of proinflammatory cytokines, tumor necrosis factor-α and interleukin (IL-6, increased in mice subjected to kidney insult but this effect was not modified in 5-LO(-/- mice. However, 5-LO(-/- mice subjected to kidney insult presented lower macrophage infiltration and higher levels of IL-10 than wild-type mice. Our results reveal that LTs have an important role in tubulointerstitial disease induced by albumin overload.

  10. 5-Lypoxygenase products are involved in renal tubulointerstitial injury induced by albumin overload in proximal tubules in mice.

    Science.gov (United States)

    Landgraf, Sharon Schilling; Silva, Leandro Souza; Peruchetti, Diogo Barros; Sirtoli, Gabriela Modenesi; Moraes-Santos, Felipe; Portella, Viviane Gomes; Silva-Filho, João Luiz; Pinheiro, Carla Silva; Abreu, Thiago Pereira; Takiya, Christina Maeda; Benjamin, Claudia Farias; Pinheiro, Ana Acacia Sá; Canetti, Claudio; Caruso-Neves, Celso

    2014-01-01

    The role of albumin overload in proximal tubules (PT) in the development of tubulointerstitial injury and, consequently, in the progression of renal disease has become more relevant in recent years. Despite the importance of leukotrienes (LTs) in renal disease, little is known about their role in tubulointerstitial injury. The aim of the present work was to investigate the possible role of LTs on tubulointerstitial injury induced by albumin overload. An animal model of tubulointerstitial injury challenged by bovine serum albumin was developed in SV129 mice (wild-type) and 5-lipoxygenase-deficient mice (5-LO(-/-)). The changes in glomerular morphology and nestin expression observed in wild-type mice subjected to kidney insult were also observed in 5-LO(-/-) mice. The levels of urinary protein observed in the 5-LO(-/-) mice subjected or not to kidney insult were lower than those observed in respective wild-type mice. Furthermore, the increase in lactate dehydrogenase activity, a marker of tubule damage, observed in wild-type mice subjected to kidney insult did not occur in 5-LO(-/-) mice. LTB4 and LTD4, 5-LO products, decreased the uptake of albumin in LLC-PK1 cells, a well-characterized porcine PT cell line. This effect correlated with activation of protein kinase C and inhibition of protein kinase B. The level of proinflammatory cytokines, tumor necrosis factor-α and interleukin (IL)-6, increased in mice subjected to kidney insult but this effect was not modified in 5-LO(-/-) mice. However, 5-LO(-/-) mice subjected to kidney insult presented lower macrophage infiltration and higher levels of IL-10 than wild-type mice. Our results reveal that LTs have an important role in tubulointerstitial disease induced by albumin overload.

  11. 促红细胞生成素通过 BMP/SMAD 通路对肾性贫血大鼠肾脏的保护作用及其机制%Renoprotective action by erythropoietin via BMP/SMAD signaling pathway in renal anemia in rats and its mechanism

    Institute of Scientific and Technical Information of China (English)

    张妍; 李银岚; 陈孟华

    2015-01-01

    目的:探讨促红细胞生成素(EPO)对肾性贫血大鼠肾脏的保护作用及其可能的作用机制。方法将实验大鼠随机分为对照组(NC 组,n=18)和实验组(n=72),采用腺嘌呤注射建立肾性贫血大鼠模型,再随机分为单纯贫血组(SA 组)、铁剂+促红素组(IR+EPO 组)、促红素组(EPO 组)、铁剂组(IR 组)。药物干预4周后,处死大鼠(心脏取血),自动化血液分析仪检测血清肌酐(Scr)、尿素氮(Bun)、血红蛋白(Hb)、血细胞比容(Hct);ELISA 法检测铁调素(Hepcidin)。免疫组织化学染色法和 Western blot 法分别检测大鼠肾脏骨形态蛋白-6(BMP-6)、丝/苏氨酸激酶受体-1(SMAD-1)和 SMAD-4的表达。结果①一般指标的比较:与 SA 组相比较,IR+EPO 组和 EPO 组 BUN、Scr 显著降低(P <0.01);IR+EPO 组和 EPO 组 Hb、Hct 显著升高(P <0.01)。②ELISA 法检测示 IR+EPO 组和 EPO 组铁调素显著降低(P <0.01)。③病理学观察提示 EPO 可以减轻大鼠肾脏病理及功能改变。④免疫组织化学染色示各组大鼠肾小球细胞胞质和肾小管上皮细胞内均表达 SMAD-4、SMAD-1、BMP-6。⑤Western blot 进一步提示,与 SA组相比,IR+EPO 组和 EPO 组 SMAD-4蛋白表达量显著下调(P <0.01),IR+EPO 组和 EPO 组 SMAD-1蛋白表达量下调(P <0.05),IR+EPO 组和 EPO 组 BMP-6蛋白表达量显著上调(P <0.01)。结论EPO 通过 BMP/SMAD 传导通路,抑制铁调素的表达及分泌,纠正贫血,发挥肾脏保护作用。%Objective To investigate the protective effect of erythropoietin (EPO)on the kidney of renal anemia rats and further explore the renoprotective action and possible mechanisms.Methods A total of 90 SD rats were randomly divided into 5 groups:normal control rats (NC),simple anemia group (SA),iron + EPO group (IR+EPO),erythropoietin group (EPO),and iron group (IR)with 18 in each.The rats were sacrificed after 4 weeks’ treatment with intragastrically-injected adenine.Serum creatinine (Scr

  12. Comparison of Neurite Outgrowth Induced by Erythropoietin (EPO) and Carbamylated Erythropoietin (CEPO) in Hippocampal Neural Progenitor Cells.

    Science.gov (United States)

    Oh, Dong Hoon; Lee, In Young; Choi, Miyeon; Kim, Seok Hyeon; Son, Hyeon

    2012-08-01

    A previous animal study has shown the effects of erythropoietin (EPO) and its non-erythropoietic carbamylated derivative (CEPO) on neurogenesis in the dentate gyrus. In the present study, we sought to investigate the effect of EPO on adult hippocampal neurogenesis, and to compare the ability of EPO and CEPO promoting dendrite elongation in cultured hippocampal neural progenitor cells. Two-month-old male BALB/c mice were given daily injections of EPO (5 U/g) for seven days and were sacrificed 12 hours after the final injection. Proliferation assays demonstrated that EPO treatment increased the density of bromodeoxyuridine (BrdU)-labeled cells in the subgranular zone (SGZ) compared to that in vehicle-treated controls. Functional differentiation studies using dissociated hippocampal cultures revealed that EPO treatment also increased the number of double-labeled BrdU/microtubule-associated protein 2 (MAP2) neurons compared to those in vehicle-treated controls. Both EPO and CEPO treatment significantly increased the length of neurites and spine density in MAP2(+) cells. In summary, these results provide evidences that EPO and CEPO promote adult hippocampal neurogenesis and neuronal differentiation. These suggest that EPO and CEPO could be a good candidate for treating neuropsychiatric disorders such as depression and anxiety associated with neuronal atrophy and reduced hippocampal neurogenesis.

  13. Novel, selective EPO receptor ligands lacking erythropoietic activity reduce infarct size in acute myocardial infarction in rats.

    Science.gov (United States)

    Kiss, Krisztina; Csonka, Csaba; Pálóczi, János; Pipis, Judit; Görbe, Anikó; Kocsis, Gabriella F; Murlasits, Zsolt; Sárközy, Márta; Szűcs, Gergő; Holmes, Christopher P; Pan, Yijun; Bhandari, Ashok; Csont, Tamás; Shamloo, Mehrdad; Woodburn, Kathryn W; Ferdinandy, Péter; Bencsik, Péter

    2016-11-01

    Erythropoietin (EPO) has been shown to protect the heart against acute myocardial infarction in pre-clinical studies, however, EPO failed to reduce infarct size in clinical trials and showed significant safety problems. Here, we investigated cardioprotective effects of two selective non-erythropoietic EPO receptor ligand dimeric peptides (AF41676 and AF43136) lacking erythropoietic activity, EPO, and the prolonged half-life EPO analogue, darbepoetin in acute myocardial infarction (AMI) in rats. In a pilot study, EPO at 100U/mL significantly decreased cell death compared to vehicle (33.8±2.3% vs. 40.3±1.5%, pEPO reduced infarct size significantly compared to vehicle (45.3±4.8% vs. 59.8±4.5%, pEPO receptor ligand dimeric peptides AF41676 and AF43136 administered before reperfusion are able to reduce infarct size in a rat model of AMI. Therefore, non-erythropoietic EPO receptor peptide ligands may be promising cardioprotective agents.

  14. The Use of Soluble Transferrin Receptor in the Detection of rHuEPO Abuse in Sports

    Directory of Open Access Journals (Sweden)

    Lorenzo Gordon

    2010-02-01

    Full Text Available Erythropoietin (EPO increases the number of circulating erythrocytes and muscle oxygenation. The recombinant forms of EPO have indiscriminately been used by athletes, mainly in endurance sports to increase their erythrocytes concentration, thus generating a better delivery of oxygen to the muscle tissue. The administration of recombinant human erythropoietin (rHuEPO except for therapeutic use was prohibited by the International Olympic Committee (IOC and its unauthorized use considered as doping. In the last few years, a number of studies using parameters indicative of accelerated erythropoiesis have investigated a number of indirect methods for the detection of rHuEPO abuse. No single indirect marker has been found that can satisfactorily demonstrated rHuEPO misuse. Soluble transferrin receptor (sTfR is a new marker of iron status and erythropoietic activity. It has been included in multivariable blood testing models for the detection of performance enhancing EPO abuse in sports. Indirect markers of altered erythropoiesis give reliable evidence of current or discontinued rHuEPO usage. This review describes the physical, biological and pharmacokinetic properties of endogenous EPO and its recombinant form. It also discusses the available strategies for the detection of rHuEPO abuse in sports, involving the use of sTfR concentration directly or in mathematical multivariate models.

  15. [Production of superoxide anion radical and nitric oxide in renal tissues sutured with different surgical suture material].

    Science.gov (United States)

    Kostenko, V O; Tsebrzhins'kii, O I

    2000-01-01

    The generation of superoxide anion radicals (in mitochondria, microsomes and under respiratory burst of leucocytes) and nitric oxide (NO) in renal tissue has been studied in the experiment with white rats, which had been carried out nephrotomy with following usage for suture such absorbable surgical threads as plain and chromic catgut, biofil (of dura mater spinalis of the cattle), Dexon II (polyglycolic acid) and biofil modified with aethonium, succinate and mexidol. The research proves the use of plai and chromic catgut leads to the development longer oxidative stress with increasing of cytotoxic agents production (superoxide anion and NO). The risk of longitudinal oxidative stress decreases under the use of biofil suture modified with biological active compounds (aethonium, succinate and mexidol). In this case, the generation of superoxide anion radicals in mitochondria and microsomes is normalised earlier. The superoxide generation with respiratory burst of leucocytes and NO production decreases in 14 day of postoperative period under the use of biofil suture modified with succinate and mexidol.

  16. Erythropoietin (EPO-receptor signaling induces cell death of primary myeloma cells in vitro

    Directory of Open Access Journals (Sweden)

    Thea Kristin Våtsveen

    2016-08-01

    Full Text Available Abstract Background Multiple myeloma is an incurable complex disease characterized by clonal proliferation of malignant plasma cells in a hypoxic bone marrow environment. Hypoxia-dependent erythropoietin (EPO-receptor (EPOR signaling is central in various cancers, but the relevance of EPOR signaling in multiple myeloma cells has not yet been thoroughly investigated. Methods Myeloma cell lines and malignant plasma cells isolated from bone marrow of myeloma patients were used in this study. Transcript levels were analysed by quantitative PCR and cell surface levels of EPOR in primary cells by flow cytometry. Knockdown of EPOR by short interfering RNA was used to show specific EPOR signaling in the myeloma cell line INA-6. Flow cytometry was used to assess viability in primary cells treated with EPO in the presence and absence of neutralizing anti-EPOR antibodies. Gene expression data for total therapy 2 (TT2, total therapy 3A (TT3A trials and APEX 039 and 040 were retrieved from NIH GEO omnibus and EBI ArrayExpress. Results We show that the EPOR is expressed in myeloma cell lines and in primary myeloma cells both at the mRNA and protein level. Exposure to recombinant human EPO (rhEPO reduced viability of INA-6 myeloma cell line and of primary myeloma cells. This effect could be partially reversed by neutralizing antibodies against EPOR. In INA-6 cells and primary myeloma cells, janus kinase 2 (JAK-2 and extracellular signal regulated kinase 1 and 2 (ERK-1/2 were phosphorylated by rhEPO treatment. Knockdown of EPOR expression in INA-6 cells reduced rhEPO-induced phospo-JAK-2 and phospho-ERK-1/2. Co-cultures of primary myeloma cells with bone marrow-derived stroma cells did not protect the myeloma cells from rhEPO-induced cell death. In four different clinical trials, survival data linked to gene expression analysis indicated that high levels of EPOR mRNA were associated with better survival. Conclusions Our results demonstrate for the first time

  17. Erythropoietin (EPO)-receptor signaling induces cell death of primary myeloma cells in vitro.

    Science.gov (United States)

    Våtsveen, Thea Kristin; Sponaas, Anne-Marit; Tian, Erming; Zhang, Qing; Misund, Kristine; Sundan, Anders; Børset, Magne; Waage, Anders; Brede, Gaute

    2016-08-31

    Multiple myeloma is an incurable complex disease characterized by clonal proliferation of malignant plasma cells in a hypoxic bone marrow environment. Hypoxia-dependent erythropoietin (EPO)-receptor (EPOR) signaling is central in various cancers, but the relevance of EPOR signaling in multiple myeloma cells has not yet been thoroughly investigated. Myeloma cell lines and malignant plasma cells isolated from bone marrow of myeloma patients were used in this study. Transcript levels were analysed by quantitative PCR and cell surface levels of EPOR in primary cells by flow cytometry. Knockdown of EPOR by short interfering RNA was used to show specific EPOR signaling in the myeloma cell line INA-6. Flow cytometry was used to assess viability in primary cells treated with EPO in the presence and absence of neutralizing anti-EPOR antibodies. Gene expression data for total therapy 2 (TT2), total therapy 3A (TT3A) trials and APEX 039 and 040 were retrieved from NIH GEO omnibus and EBI ArrayExpress. We show that the EPOR is expressed in myeloma cell lines and in primary myeloma cells both at the mRNA and protein level. Exposure to recombinant human EPO (rhEPO) reduced viability of INA-6 myeloma cell line and of primary myeloma cells. This effect could be partially reversed by neutralizing antibodies against EPOR. In INA-6 cells and primary myeloma cells, janus kinase 2 (JAK-2) and extracellular signal regulated kinase 1 and 2 (ERK-1/2) were phosphorylated by rhEPO treatment. Knockdown of EPOR expression in INA-6 cells reduced rhEPO-induced phospo-JAK-2 and phospho-ERK-1/2. Co-cultures of primary myeloma cells with bone marrow-derived stroma cells did not protect the myeloma cells from rhEPO-induced cell death. In four different clinical trials, survival data linked to gene expression analysis indicated that high levels of EPOR mRNA were associated with better survival. Our results demonstrate for the first time active EPOR signaling in malignant plasma cells. EPO

  18. Improvement of band segmentation in Epo images via column shift transformation with cost functions.

    Science.gov (United States)

    Stolc, S; Bajla, I

    2006-04-01

    In recent years, the development of methodology and laboratory techniques for doping control (DC) of recombinant erythropoietin (rEpo) has become one of the most important topics pursued by doping control laboratories accredited by World Anti-Doping Agency (WADA). The software system GASepo has been developed within the international WADA project as a support for Epo doping control. Although a great number of functions for automatic image processing have been involved in this software, for Epo images with considerably distorted bands additional effort is required from the user to interactively correct the results of improper band segmentation. In this paper a problem of geometrically distorted bands is addressed from the viewpoint of how to transform the lanes in distorted Epo images in order to reach better band segmentation. A method of band straightening via column shift transformation has been proposed that is formulated as an optimization procedure with cost functions. The method involves several novel approaches: two-stage optimization procedure, four cost functions and selection of relevant columns. The developed band straightening algorithm (BSA) has been tested on real Epo images with distorted bands. Based on the evaluation scheme involving the GASepo software itself a recommendation is made for implementation of the method with the cost function based on correlation matrix. Estimates of computational complexity of the individual steps of BSA are also given.

  19. Role of cytochrome P sub 450 in the control of the production of erythropoietin

    Energy Technology Data Exchange (ETDEWEB)

    Fandrey, J.; Seydel, F.P.; Siegers, C.P.; Jelkmann, W. (Medical Univ. of Luebeck (West Germany))

    1990-01-01

    Effects of agents affecting cytochrome P{sub 450} were studied on the production of erythropoietin (Epo) in cultures of the human hepatoma cell line HepG2. Epo was measured by radioimmunoassay of the culture media after 24 h of incubation. The addition of phenobarbital or 3-methylcholanthrene, which induce cytochrome P{sub 450}, significantly enhanced the formation of Epo. Likewise, the thyroid hormones T{sub 3} and T{sub 4} stimulated the rate of the production of Epo. On the other hand, the formation of Epo was lowered following the addition of diethyl-dithiocarbamate or cysteamine chloride, which inhibit cytochrome P{sub 450}. These findings support the idea that O{sub 2} sensitive hemoproteins of the microsomal mixed-functional oxidases play a role in the control of the synthesis of Epo.

  20. ACI患者血清EPO CRP水平的变化%The changes of the concentration of serum EPO and CRP of the ACI patients

    Institute of Scientific and Technical Information of China (English)

    刘小玲; 邰迎东

    2013-01-01

      目的观察内源性促红细胞生成素(erythropoietin,EPO)、C-反应蛋白(CRP)在急性脑梗死(acute cerebral infarction,ACI)中水平的变化,探讨EPO可能存在的神经保护作用及机制。方法 ACI患者64例,根据头颅CT或MRI梗死灶横断面最大直径分为小梗死灶组、中梗死灶组、大梗死灶组,与正常对照组35例作对照分析。采用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)双抗体夹心法测定血清EPO水平;采用免疫比浊法测定血清C-反应蛋白(C-reactive Protein,CRP)水平。结果脑梗死组血清EPO及CRP水平均高于正常对照组(P0.05)。随着梗死灶的增大,血清EPO水平有逐渐降低的趋势,血清CRP水平有逐渐升高的趋势。结论内源性EPO在ACI中可能存在着一定的神经保护作用,机制之一可能是减轻脑缺血区的炎症反应。外源性EPO有望成为ACI一种新的治疗选择。%  Objective To investigate the probable existence of neuroprotective effects and mechanism of endogenous EPO in the ACI and to provide evidences of the probability of the clinical application of EPO for curing ACI. Methods To select 64 cases of patients with acute cerebral infarction 35 cases of normal control group. The serum concentration of EPO was measured by ELISA and the serum concentration of CRP was measured by immuoturbidimetry. Results The concentrations of serum EPO、IL-6 and CRP of cerebral infarction group (CI)were higher than those of normal control group (P<0.01);According to the analysis of the bivariate correlation,there were negative correlations between EPO and CRP(r=-0.643,P<0.01);The serum concentrations of EPO of the small CI were higher than those of the medium or the large one(P<0.01),and the serum concentrations of EPO of the medium CI were higher than those of the large one (P<0.05).The more larger the cerebral infarction size became,the more lower the concentrations of

  1. A utilização da rhEPO no doping : estudo dos efeitos cardiovasculares e metabólicos em ratos submetidos a exercício físico

    OpenAIRE

    Albuquerque, Nuno Miguel Torres Piloto de

    2009-01-01

    Dissertação de mestrado em Medicina Legal e Ciências Forenses apresentada à Fac. de Medicina da Univ. de Coimbra tenebrosa sombra do doping tem pairado e obscurecido, através da constante suspeição, o mundo do desporto, seus resultados e proezas. A eritropoietina (EPO), uma hormona natural produzida principalmente a nível renal, estimula (regula) a produção de eritrócitos que, pela cooperação da hemoglobina, transportam o oxigénio para os tecidos periféricos. Aumentar a entrega de oxigénio...

  2. Advanced glycation end-products and skin autofluorescence in end-stage renal disease : a review

    NARCIS (Netherlands)

    Arsov, Stefan; Graaff, Reindert; van Oeveren, Wim; Stegmayr, Bernd; Sikole, Aleksandar; Rakhorst, Gerhard; Smit, Andries J.

    2014-01-01

    Chronic kidney disease (CKD), especially in its end stage, is marked by extremely high cardiovascular rates of morbidity and mortality; hemodialysis patients have a five-fold shorter life expectancy than healthy subjects of the same age. In CKD the metabolic products that accumulate in the body are

  3. Advanced glycation end-products and skin autofluorescence in end-stage renal disease : a review

    NARCIS (Netherlands)

    Arsov, Stefan; Graaff, Reindert; van Oeveren, Wim; Stegmayr, Bernd; Sikole, Aleksandar; Rakhorst, Gerhard; Smit, Andries J.

    2014-01-01

    Chronic kidney disease (CKD), especially in its end stage, is marked by extremely high cardiovascular rates of morbidity and mortality; hemodialysis patients have a five-fold shorter life expectancy than healthy subjects of the same age. In CKD the metabolic products that accumulate in the body are

  4. A Decade on the Global Change EPO Trail

    Science.gov (United States)

    Katzenberger, J. W.; Somerville, R. C.

    2002-12-01

    The Aspen Global Change Institute (AGCI) offers a variety of approaches to enhance K-12 Earth systems science education through pre- and in-service educator professional development workshops, materials development, and experiences for scientists on roles they can play in education and outreach. Partnering institutions have included the Space Science Institute, NASA Earth Science Enterprise, and NSF Geosciences. Here we review approaches and lessons learned from three projects. 1) The Ground Truth Studies teacher workshops and the development of the Ground Truth Studies Teacher Handbook, funded as a cooperative agreement with NASA and other sources. This project was developed with Earth system scientists, environmental education curriculum developers, K-12 teachers and was piloted in several states. The project culminated in the development of the teacher handbook which includes primers on global change, remote sensing, elementary and secondary level hands-on activities, and resources. This publication has been utilized in conjunction with other teacher training programs or as a stand-alone resource for teachers. 2) PESTO (Pre- and In-Service Earth Science Training Opportunity) funded by NASA, a residential week-long intensive experience for pre- and in-service teachers offered for graduate and undergraduate credit. The PESTO faculty included a senior research scientist, an environmental educator/curriculum developer, and an EPO specialist. Content included an overview of global environmental change with an emphasis on climate and atmospheric chemistry and a review of online and CD resources relevant to elementary and secondary Earth systems topics. Visiting scientists engaged the group in the process of science and issues associated with science in society. 3) Workshop on K-12 Education for Geoscientists, a NSF/Geosciences sponsored project was a mini-workshop embedded within one of AGCI's interdisciplinary science meetings on a topic in global change. The

  5. Detection of EPO-Fc fusion protein in human blood: screening and confirmation protocols for sports drug testing.

    Science.gov (United States)

    Reichel, Christian; Thevis, Mario

    2012-11-01

    The neonatal Fc receptor (FcRn) has been under investigation for several years as a pharmaceutical drug target. Clinical studies have shown that fusion proteins consisting of human recombinant erythropoietin (rhEPO) and the Fc-part of IgG can be transported after pulmonary administration via FcRn across the airway epithelium to the blood stream. So far, no clinically approved pharmaceutical formulation of EPO-Fc is available. Since various forms of recombinant erythropoietins have been frequently misused by athletes as performance-enhancing agents, EPO-Fc might play a similar role in sports in the future. In order to investigate the detectability of EPO-Fc in human blood, different strategies were tested and developed. Only two of them fulfilled the necessary requirements regarding sensitivity and specificity. A rapid protocol useful for screening purposes first enriches EPO-Fc from human serum via high capacity protein A beads and subsequently detects EPO-Fc in the eluate with a commercial EPO ELISA kit. The limit of detection (LOD) of the method is about 5 pg (45 amol) EPO-Fc and is independent of the serum volume used. For screening and/or confirmation purposes a second protocol was evaluated, which consists of a fast EPO immunopurification step followed by sodium dodecyl sulfate or sarcosyl polyacrylamide gel electrophoresis (SDS-PAGE, SAR-PAGE) and Western double-blotting with chemiluminescence detection - a method already established in routine EPO anti-doping control. The latter strategy allows the detection of EPO-Fc in serum together with all other recombinant erythropoietins and with an identical LOD (5 pg/45 amol) as for the rapid screening protocol.

  6. Meclofenamate elicits a nephropreventing effect in a rat model of ischemic acute kidney injury by suppressing indoxyl sulfate production and restoring renal organic anion transporters

    Directory of Open Access Journals (Sweden)

    Saigo C

    2014-08-01

    Full Text Available Chika Saigo,1 Yui Nomura,1 Yuko Yamamoto,1 Masataka Sagata,1 Rika Matsunaga,1 Hirofumi Jono,1,2 Kazuhiko Nishi,3 Hideyuki Saito1,2 1Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 2Department of Pharmacy, Kumamoto University Hospital, 3Department of Hemo-Dialysis, Kumamoto University Hospital, Kumamoto, Japan Abstract: Indoxyl sulfate (IS, a putative low-molecular weight uremic toxin, is excreted in the urine under normal kidney function, but is retained in the circulation and tissues during renal dysfunction in acute kidney injury and chronic kidney disease. IS, which is one of the most potent inducers of oxidative stress in the kidney and cardiovascular system, is enzymatically produced in the liver from indole by cytochrome P450-mediated hydroxylation to indoxyl, followed by sulfotransferase-mediated sulfate conjugation. We used rat liver S9 fraction to identify inhibitors of IS production. After testing several compounds, including phytochemical polyphenols, we identified meclofenamate as a potent inhibitor of IS production with an apparent IC50 value of 1.34 µM. Ischemia/reperfusion (I/R of rat kidney caused a marked elevation in the serum IS concentration 48 hours after surgery. However, intravenous administration of meclofenamate (10 mg/kg significantly suppressed this increase in the serum level of IS. Moreover, IS concentrations in both kidney and liver were dramatically elevated by renal I/R treatment, but this increase was blocked by meclofenamate. Serum creatinine and blood urea nitrogen were markedly elevated in rats after renal I/R treatment, but these increases were significantly restored by administration of meclofenamate. Renal expression of both basolateral membrane-localized organic anion transporters rOAT1 and rOAT3 was downregulated by I/R treatment. However, expression of rOAT1 and rOAT3 recovered after administration of meclofenamate, which is associated

  7. Fertility and contraception in end-stage renal disease.

    Science.gov (United States)

    Schmidt, R J; Holley, J L

    1998-01-01

    The hormonal aberrations that occur with end-stage renal disease (ESRD) are presented in this review in relation to fertility and conception among women on dialysis. The imbalance in gonadotropin production in dialysis-dependent men and women is characterized by elevations in luteinizing hormone (LH). In women dialysis patients, the normal estradiol-stimulated LH surge does not occur, resulting in anovulation. In men dialysis patients spermatogenesis is impaired, and low testosterone levels cause elevated LH. Infertility in those with ESRD is a culmination of many factors, including impotence and loss of libido, anovulation, and an altered hormonal milieu. Despite these inhibitors of conception, women on dialysis can conceive; pregnancy has been reported in 1% to 7% of women on dialysis in survey studies. The influence of dialysis mode (hemodialysis v peritoneal dialysis), recombinant human erythropoietin (EPO), and dialysis adequacy on the likelihood of conception among patients of either sex on dialysis is unknown. Reduced sexual activity and interest has consistently been reported in the ESRD population. The reasons for this are complex and likely involve the effects of comorbid illnesses, overall health status, body image factors, and hormonal alterations. Nephrologists rarely discuss conception and contraception with their women dialysis patients. Greater attention to these issues is needed.

  8. Uso da eritropoetina recombinante humana no tratamento da anemia associada à insuficiência renal crônica

    OpenAIRE

    Carvalho, Mauricio de

    2013-01-01

    Resumo: A anemia acompanha a insuficiencia renal cronica e esta presente na maioria dos pacientes em dialise. O objetivo deste estudo foi analisar o efeito de seis meses de tratamento com a eritropoetina recombinante humana (EPO-rHu) na anemia associada a insuficiencia renal cronica terminal em vinte pacientes mantidos em programa de hemodialise. Os criterios de inclusao foram: pacientes que estivessem em hemodialise por pelo menos 3 meses, com idade maior que 18 ou menor que 70 anos; hematoc...

  9. Mass spectrometric analysis of EPO IEF-PAGE interfering substances in nitrile examination gloves.

    Science.gov (United States)

    Reichel, Christian

    2012-10-01

    Direct detection of doping with recombinant erythropoietins (rhEPO) is accomplished by isoelectric focusing (IEF) or sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis (PAGE). In a recent publication, Lasne et al. (Electrophoresis 2011, 32, 1444) showed that improper use of nitrile examination gloves during sample collection, sample preparation, and IEF-PAGE may lead to distorted or absent EPO IEF-profiles. In order to clarify which substances are responsible for this observation, a mass spectrometric study on water extractable compounds found in nitrile gloves was performed. Several substance classes were shown to be present, among them polyethylene glycols (PEG), anionic and nonionic surfactants, as well as alcohol ethoxylates and plasticizers. It could be demonstrated that alkylbenzenesulfonates, the main category of detectable anionic detergents, and among them sodium dodecylbenzenesulfonate (SDBS) and its homologs, are the prime reason for the interference of nitrile gloves with EPO IEF-PAGE. Copyright © 2012 John Wiley & Sons, Ltd.

  10. The Global ALMA EPO programme: Communicating astronomy with the public at millimetre and submillimetre wavelengths

    Science.gov (United States)

    Adams, M.; Boffin, H. J.; Garnier, W.; Iono, D.

    2008-06-01

    The Atacama Large Millimeter/submillimeter Array (ALMA) is a major 21st century international science research facility that will open new windows on celestial origins. ALMA construction is underway in the high-elevation Atacama Desert of northern Chile. Science operations will begin in 2010, and full science operations will start in 2013. The ALMA Education and Public Outreach (EPO) programme is a global collaboration that seeks to communicate the excitement and value of the ALMA mission, science, and technology to international audiences effectively. The ALMA EPO programme is the responsibility of the Joint ALMA Observatory (JAO), the National Radio Astronomy Observatory (NRAO), the European Organisation for Astronomical Research in the Southern Hemisphere (ESO), and the National Astronomical Observatory of Japan (NAOJ). This contribution provides an overview of the ALMA Project and the global ALMA EPO programme.

  11. Lactulose efficacy in reduction of nitrogen products, blood potassium and fluid overload in patients with end-stage renal failure

    Directory of Open Access Journals (Sweden)

    Negin Aleagha

    2017-06-01

    Full Text Available Introduction: Chronic kidney disease (CKD is a major public health problem that often goes unrecognized until its late-stage. Patients with chronic kidney disease face uremic toxins and hyperkalemia. Also, fluid overload in CKD patients is associated with rapid decline in kidney function. Lactulose is a hyperosmotic agent and as a prebiotic, it plays an important role in regulating serum urea and potassium levels and has some effects on fluid overload. The aim of this study was to evaluate the effect of lactulose on serum levels of biochemical products in patients with CKD. Materials and Methods: In this interventional study, 17 patients with end stage of CKD ( 76.47 % men; mean age 65.88 ± 13.4 were evaluated.All patients received lactulose, 10 ml, 3 times per day for 3 months. Blood samples from all participants were collected before and at the end of intervention to examine changes in biochemical parameters, including potassium, urea, creatinine and uric acid. Results: Lactulose significantly decreased urea levels (p=0.001, blood potassium (0.001 and fluid overload(considering the patient’s weight p=0.001 in patients with end-stage renal failure. The decrease in serum creatinine and uric acid were not significant. Conclusion: Lactulose administration in CKD patients could decrease levels of various deleterious elements, especially urea and blood potassium and its daily use can be recommended in these patients.

  12. Renal Osteodystrophy

    Directory of Open Access Journals (Sweden)

    Aynur Metin Terzibaşoğlu

    2004-12-01

    Full Text Available Chronic renal insufficiency is a functional definition which is characterized by irreversible and progressive decreasing in renal functions. This impairment is in collaboration with glomeruler filtration rate and serum creatinine levels. Besides this, different grades of bone metabolism disorders develop in chronic renal insufficiency. Pathologic changes in bone tissue due to loss of renal paranchyme is interrelated with calcium, phosphorus vitamine-D and parathyroid hormone. Clinically we can see high turnover bone disease, low turnover bone disease, osteomalacia, osteosclerosis and osteoporosis in renal osteodystropy. In this article we aimed to review pathology of bone metabolism disorders due to chronic renal insufficiency, clinic aspects and treatment approaches briefly.

  13. We Need You! The Importance of Scientist Involvement in Education and Public Outreach (E/PO)

    Science.gov (United States)

    Buxner, S.; Hsu, B. C.; Meinke, B. K.; Shipp, S. S.; Schwerin, T. G.; Peticolas, L. M.; Smith, D.; Dalton, H.

    2013-12-01

    Active engagement of scientists in education and public outreach (E/PO) activities is beneficial for scientists, classrooms, and the general public. Scientist visibility in the public arena is important to garner public support, whose tax dollars fund scientific programs. Scientists are important disseminators of current, accurate scientific knowledge. They also, perhaps more importantly, understand the nature and process of science and have the means of understanding and addressing many of the issues facing society. Research has shown that while the public is interested in science, not all members are necessarily scientifically literate; additionally there is evidence than many students are not prepared for, or choosing to participate in science careers. And yet, a scientifically engaged, literate, and supportive public is a necessary partner in addressing important global challenges of the future. E/PO is a wonderful opportunity for scientists to demonstrate that science is interesting, exciting, fun, challenging, and relevant to society. In doing so, they can transfer ownership of science to the public through a variety of vehicles by increasing access to scientific thought and discovery. Through partnerships with E/PO professionals, teachers, or journalists, scientists can improve their communication and teaching skills, whether in an E/PO setting or their higher education careers. Sharing with the public what scientists do is an effective way to engage people in the scientific process and to express scientists' enthusiasm for what they do. Scientist involvement in E/PO also shows the public that scientists are real people and provides important role models for the next generation of scientists. There are many opportunities to get involved in E/PO! Find information on EarthSpace, a national clearinghouse for higher education materials in Earth and space science through an abstract by Nicholas Gross, et al. Learn about NASA Science Mission Directorate (SMD

  14. 中国EPoG频率的灵活规划

    Institute of Scientific and Technical Information of China (English)

    高登·李; 张亮; 埃德·博伊德

    2012-01-01

    EPoC技术与中国有着紧密的联系。实际上,这个概念最初是博通公司针对中国有线市场所提出的一种高级数据接入技术。虽然从那以后EPoC这项技术被认为对于国际市场也同样具有普遍的适用性.但是它毫无置疑的是源于对于中国有线接入网的全面研究。

  15. Astronomy EPO and the 2012 Hysteria: Your Personal Guide to Joining the Battle

    Science.gov (United States)

    Larsen, K.

    2011-09-01

    Individual members of the astronomical community have, in recent months, begun to take up the charge and rally against the vast army of pseudoscience, superstition, and snake oil salesmen that is the 2012 phenomenon. EPO specialists and facilities are in a unique and vitally important position to move to the forefront of this battle, given our long-standing dedication to improving the astronomical education of the general public. This poster documents concrete ways in which the astronomy EPO community can (and should) combat the 2012 movement.

  16. Progress of clinical study on renal anemia treated with single dosage of recombinant human erythropoietin%单次不同剂量重组人促红细胞生成素治疗肾性贫血的临床研究进展

    Institute of Scientific and Technical Information of China (English)

    陈存海; 宋艳梅

    2015-01-01

    贫血是在慢性肾脏病(CKD)进展过程中最为常见的并发症。红细胞生成素主要是由肾脏产生的一种糖蛋白,用于调节红细胞的生成,它的缺乏是肾性贫血的重要原因。诸多研究显示,对于 Hb 水平不达标的患者,运用单次大剂量(每次10000 IU)的重组人促红细胞生成素(rHuEPO)治疗是有效的和安全的。本文就肾性贫血患者的 Hb 水平现状、不同剂量 rHuEPO 给药方式的药代动力学特点及相关临床应用及进展予以综述。%Anemia is the most common complication in the progression of chronic kidney disease (CKD).Erythropoietin is a kind of glycoprotein mainly produced by the kidney,and regulates production of erythrocytes.The lack of erythropoietin is the important reason for renal anemia.Multiple studies showed treatment with a single high dosage (1 0 000 IU /time)of recombinant human erythropoietin (rHuEPO)is effective and safe in patients with hemoglobin levels lower than the standard.This present paper reviewed the current status of hemoglobin levels in renal anemic patients,pharmacokinetic characteristics of different doses of rHuEPO,and related clinical applications and advancement.

  17. Structural identification of modified amino acids on the interface between EPO and its receptor from EPO BRP, human recombinant erythropoietin by LC/MS analysis.

    Science.gov (United States)

    Song, Kwang-Eun; Byeon, Jaehee; Moon, Dae-Bong; Kim, Hyong-Ha; Choi, Yoo-Joo; Suh, Jung-Keun

    2014-11-01

    Protein modifications of recombinant pharmaceuticals have been observed both in vitro and in vivo. These modifications may result in lower efficacy, as well as bioavailability changes and antigenicity among the protein pharmaceuticals. Therefore, the contents of modification should be monitored for the quality and efficacy of protein pharmaceuticals. The interface of EPO and its receptor was visualized, and potential amino acids interacting on the interface were also listed. Two different types of modifications on the interface were identified in the preparation of rHu-EPO BRP. A UPLC/Q-TOF MS method was used to evaluate the modification at those variants. The modification of the oxidized variant was localized on the Met54 and the deamidated variants were localized on the Asn47 and Asn147. The extent of oxidation at Met54 was 3.0% and those of deamidation at Asn47 and Asn147 were 2.9% and 4.8%, respectively.

  18. An Optimized Method for Suspension Culture of CHO Cells to Produce Recombinant Human Erythropoietin (EPO)%悬浮培养CHO细胞生产重组人促红细胞生成素条件的优化

    Institute of Scientific and Technical Information of China (English)

    杨栋; 牛红军; 陆刚; 史嘉林; 孙浩明; 李晖

    2012-01-01

    Objective: To screen and domesticate the adherent cultured CHO cells to obtain high expression of cell suspension culture for production of recombinant human erythropoietin erythropoietin (rHuEPO). Methods: Using 96-well and 24-well plates culture method to screen and domesticate the highly expressing CHO cell strain. Acclimate the high expression cell strain and make it suitable for suspension culture. It's inoculated into the bioreactor in serum-free culture after amplified by the shake flask, and monitoring of glucose content, measuring rHuEPO expression of daily. Results: The suspension culture of CHO cell production of rHuEPO has short production period, higher expression than adherent culture. On the other hand, it is easy to operate and scale-up, but not easy to pollute. Furthermore, we established of the CHO cell strain for suspension culture,which provided a technical basis for industrial production of CHO cells the rHuEPO. Conclusion: After process optimization, the use of serum-free suspension culture production of erythropoietin average expression has high, short production period, low cost of production.than adherent culture.%目的:通过对贴壁培养CHO细胞筛选驯化,得到高表达的细胞后进行悬浮培养生产重组人促红细胞生成素(rHuEPO).方法:利用96孔板和24孔板对CHO细胞进行筛选,得到高表达细胞株后进行驯化,使其适合悬浮培养,经过摇瓶扩增后接种到生物反应器中无血清培养,每天监测葡萄糖含量,测rHuEPO表达量.结果:悬浮培养CHO细胞生产rHuEPO,生产周期短,表达量比贴壁培养高出很多,操作方便,减少污染,易于放大,并建立了适合悬浮培养的CHO细胞株,为工业化悬浮培养CHO细胞生产rHuEPO提供了技术基础.结论:经过工艺优化后利用无血清悬浮培养生产促红细胞生成素平均表达量较贴壁培养高,生产周期短,有利于降低生产成本.

  19. Advanced glycation end products, carotid atherosclerosis, and circulating endothelial progenitor cells in patients with end-stage renal disease.

    Science.gov (United States)

    Ueno, Hiroki; Koyama, Hidenori; Fukumoto, Shinya; Tanaka, Shinji; Shoji, Takuhito; Shoji, Tetsuo; Emoto, Masanori; Tahara, Hideki; Inaba, Masaaki; Kakiya, Ryusuke; Tabata, Tsutomu; Miyata, Toshio; Nishizawa, Yoshiki

    2011-04-01

    Numbers of endothelial progenitor cells (EPCs) have been shown to be decreased in subjects with end-stage renal disease (ESRD), the mechanism of which remained poorly understood. In this study, mutual association among circulating EPC levels, carotid atherosclerosis, serum pentosidine, and skin autofluorescence, a recently established noninvasive measure of advanced glycation end products accumulation, was examined in 212 ESRD subjects undergoing hemodialysis. Numbers of circulating EPCs were measured as CD34+ CD133+ CD45(low) VEGFR2+ cells and progenitor cells as CD34+ CD133+ CD45(low) fraction by flow cytometry. Skin autofluorescence was assessed by the autofluorescence reader; and serum pentosidine, by enzyme-linked immunosorbent assay. Carotid atherosclerosis was determined as intimal-medial thickness (IMT) measured by ultrasound. Circulating EPCs were significantly and inversely correlated with skin autofluorescence in ESRD subjects (R = -0.216, P = .002), but not with serum pentosidine (R = -0.079, P = .25). Circulating EPCs tended to be inversely associated with IMT (R = -0.125, P = .069). Intimal-medial thickness was also tended to be correlated positively with skin autofluorescence (R = 0.133, P = .054) and significantly with serum pentosidine (R = 0.159, P = .019). Stepwise multiple regression analyses reveal that skin autofluorescence, but not serum pentosidine and IMT, was independently associated with low circulating EPCs. Of note, skin autofluorescence was also inversely and independently associated with circulating progenitor cells. Thus, tissue accumulated, but not circulating, advanced glycation end products may be a determinant of a decrease in circulating EPCs in ESRD subjects.

  20. Prostaglandin-E-2 enhances EPO-mediated STAT5 transcriptional activity by serine phosphorylation of CREB

    NARCIS (Netherlands)

    Boer, AK; Drayer, AL; Rui, H; Vellenga, E

    2002-01-01

    Erythroid colony formation in response to erythropoietin (EPO) stimulation is enhanced by costimulating the cells with prostaglandin-E-2 (PGE(2)). The present study further analyzed the underlying mechanisms and demonstrated that EPO-mediated STAT5 transactivation in the erythroid AS-E-2 cell line w

  1. Preparation and characterization of a powder containing an oily liquid drug with Eudragit EPO or L100 copolymer.

    Science.gov (United States)

    Fujii, Makiko; Kawakami, Ayari; Saito, Asumi; Tuchiya, Haruna; Koizumi, Naoya; Watanabe, Yoshiteru

    2016-12-01

    Oily liquid drugs are not convenient for oral administration. We developed a powder containing clofibrate (CF), a model of an oily drug, using aminoalkyl methacrylate copolymer (EPO) or methacrylic acid copolymer (L100). CF or a mixture of CF and soybean oil was emulsified with EPO or L100 aqueous solution. Using a high-pressure homogenizer, a stable emulsion was obtained, and a powder was then obtained by lyophilization of the emulsion. The content of CF in the powder depended on the formulation, with the highest contents being 24.6% and 27.1% for EPO and L100, respectively. The incorporation ratio of CF was higher for L100 than for EPO. The powder using EPO was sticky because of leaked CF and the low glass transition temperature of EPO. The powder using L100 was a typical powder obtained by lyophilization. The leakage of CF from the powder was EPO powder. The dissolution of CF from powder using EPO was fast, regardless of the pH of the medium, but the powder using L100 showed enteric-soluble characteristics, indicating that CF is well incorporated in L100.

  2. Combined Effect of EPO and Radiotherapy on the Expression of Endogenous Molecular Markers of Tumor Metabolism and Metastasis

    NARCIS (Netherlands)

    Mees, Gilles; Fonteyne, Philippe; Ceelen, Wim; Boterberg, Tom; Pauwels, Patrick; Vangestel, Christel; Van Damme, Nancy; Peeters, Marc; Dierckx, Rudi; Van De Wiele, Christophe

    2009-01-01

    Erythropoietin (EPO) has been used to correct cancer-related anemia and to improve tumor hypoxia, which both adversely affect the clinical condition of cancer patients and response to radiotherapy. Data available on the effects of EPO treatment in cancer are, however, conflicting. Several clinical s

  3. Evaluation of AMGEN clone 9G8A anti-Epo antibody for application in doping control.

    Science.gov (United States)

    Reichel, Christian; Benetka, Wolfgang; Lorenc, Barbara; Thevis, Mario

    2016-11-01

    The two mouse monoclonal anti-erythropoietin (EPO) antibodies clone AE7A5 (generated by using a 26 amino acid N-terminal EPO-peptide) and 9G8A (developed by immunizing mice with full length human EPO) are both directed against linear epitopes at the N-terminus of EPO. While AE7A5 has been commercially available for many years, 9G8A was made for Amgen's internal research purposes. In the past, the commercial antibody was shown to cross-react with several proteins unrelated to EPO (e.g. E. coli thioredoxin reductase, zinc-α2-glycoprotein, S. cerevisiae enolase, human neuron-specific enolase, and human non-neuronal enolase). However, it displayed high sensitivity for detecting recombinant EPO (rEPO) misuse by athletes on Western blots. We evaluated the potential use of clone 9G8A for doping control purposes. While 9G8A showed lower sensitivity than AE7A5 (ca 45% on isoelectric focusing (IEF)-polyacrylamide gel electrophoresis (PAGE), ca 40% on sodium dodecyl sulfate (SDS)- and sarcosyl (SAR)-PAGE), non-specific binding of the five proteins was not observed. The cross-reactivity of AE7A5 can be overcome by immunoaffinity purification of EPO before electrophoresis and Western blotting. Similar to AE7A5, clone 9G8A is also suited for Western double-blotting. Copyright © 2016 John Wiley & Sons, Ltd.

  4. EPOS Thematic Core Service Anthropogenic Hazards for SHEER project: maintain, process and manage your project research data

    Science.gov (United States)

    Orlecka-Sikora, Beata; Lasocki, Stanislaw; Staszek, Monika; Olszewska, Dorota; Urban, Pawel; Jaroslawski, Janusz; Cielesta, Szymon; Mirek, Janusz; Wiszniowski, Jan; Picozzi, Matteo; Solaro, Giuseppe; Pringle, Jamie; Toon, Sam; Cesca, Simone; Kuehn, Daniela; Ruigrok, Elmer; Gunning, Andrew; Isherwood, Catherine

    2017-04-01

    The main objective of the "Shale gas exploration and exploitation induced risks - SHEER" project (Horizon 2020, call LCE 16-2014) is to develop a probabilistic methodology to assess and mitigate the short- and the long-term environmental risks associated with the exploration and exploitation of shale gas. To this end, the SHEER project makes use of a large amount of heterogeneous data of various types. This data, from different disciplines of science e.g. geophysical, geochemical, geological, technological, etc., must be homogenized, harmonized and made accessible exclusively for all project participants. This requires to develop an over-arching structure for high-level multidisciplinary data integration. The bespoke solution is provided by Thematic Core Service Anthropogenic Hazards (TCS AH) developed in the framework of European Plate Observing System Program (https://tcs.ah-epos.eu/, infrastructural projects IS-EPOS, POIG.02.03.00-14-090/13-00 and EPOS IP, H2020-INFRADEV-1-2015-1). TCS AH provides virtual access to a comprehensive, wide-scale and high quality research infrastructure in the field of induced seismicity and other anthropogenic hazards evoked by exploration and exploitation of geo-resources. TCS AH is designed as a functional e-research environment to ensure a researcher the maximum possible freedom for experimentation by providing a virtual laboratory flexible to create own workspace for processing streams. A data-management process promotes the use of research infrastructure in novel ways providing an access to (i) data gathered in the so-called "episodes", comprehensively describing a geophysical process, induced or triggered by human technological activity, which under certain circumstances can become hazardous for people, infrastructure and the environment, (ii) problem-oriented, specific services, with the particular attention devoted to methods analyzing correlations between technology, geophysical response and resulting hazards, (iii) the

  5. Engaging Scientists in Meaningful E/PO: How the NASA SMD E/PO Community Addresses the Needs of the Higher Ed Community

    Science.gov (United States)

    Manning, James; Meinke, Bonnie K.; Schultz, Gregory R.; Smith, Denise A.; Lawton, Brandon L.; Gurton, Suzanne; NASA Astrophysics E/PO Community

    2015-01-01

    The NASA Astrophysics Science Education and Public Outreach Forum (SEPOF) coordinates the work of NASA Science Mission Directorate (SMD) Astrophysics EPO projects and their teams to bring cutting-edge discoveries of NASA missions to the introductory astronomy college classroom. The Astrophysics Forum assists scientist and educator involvement in SMD E/PO (uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise) and makes SMD E/PO resources and expertise accessible to the science and education communities. We present three new opportunities for college instructors to bring the latest NASA discoveries in Astrophysics into their classrooms.To address the expressed needs of the higher education community, the Astrophysics Forum collaborated with the Astrophysics E/PO community, researchers, and Astronomy 101 instructors to place individual science discoveries and learning resources into context for higher education audiences. Among these resources are two Resource Guides on the topics of cosmology and exoplanets, each including a variety of accessible sources.The Astrophysics Forum also coordinates the development of the Astro 101 slide set series--5 to 7-slide presentations on new discoveries from NASA Astrophysics missions relevant to topics in introductory astronomy courses. These sets enable Astronomy 101 instructors to include new discoveries not yet in their textbooks into the broader context of the course: http://www.astrosociety.org/education/astronomy-resource-guides/.The Astrophysics Forum also coordinated the development of 12 monthly Universe Discovery Guides, each featuring a theme and a representative object well-placed for viewing, with an accompanying interpretive story, strategies for conveying the topics, and supporting NASA-approved education activities and background information from a spectrum of NASA missions and programs: http://nightsky.jpl.nasa.gov/news-display.cfm?News_ID=611

  6. The efficacy of darbepoetin alpha in hemodialysis patients resistant to human recombinant erythropoietin (rHuEpo

    Directory of Open Access Journals (Sweden)

    Hejaili Fayez

    2009-01-01

    Full Text Available Darbepoetin due to longer half life is convenient and effective for long term. This study was done to assess the efficacy of darbepoetin in the treatment of patients on high doses of erythropoietin (EPO and to compare its efficacy in patients resistant and responsive to EPO. This is a prospective, controlled open label study assessing the efficacy of darbepoetin in 55 hemodialysis patients on high dose EPO and comparing its efficacy in the patients who were "EPO -resistant" (group 1, n= 28 and in those who were "EPO-responsive" (group 2, n= 27. The initial conversion ratio was 380 mcg darbepoetin: 1 U EPO/ week and the dose of darbepoetin was adjusted thereafter at fortnightly intervals with the aim of achieving and maintaining the hemoglobin level between 11-12 g/dL. The patients were followed up for 12 weeks following the introduction of darbepoetin. The impact of gender, baseline PTH, age, Kt/V, duration on dialysis, initial EPO dose on the response to darbepoetin was investigated. Continuous variables were compared using two tailed t-test and non-parametric by Fisher exact test. Overall darbepoetin was effective with 85.5 % of the patients responding and 21.8 % of the patients′ able to maintain their hemoglobin with once fortnightly dose by the end of the study. Mean darbepoetin dose and the mean EPO to darbepoetin conversion ratio on completion of the study were 58.2 (42.4 mcg/week (0.983 (0.87 mcg/kg/week and 384:1 respectively. Hemoglobin levels in groups 1 improved from 9.8 ± 0.9 g/dL to 12.0 ± 1.4 g/dL (0.0001 and 2 were and maintained it in group 2 at 11.9 ± 1.3 g/dL (P= 0.79. The doses of darbepoetin required in groups 1 and 2 were similar (54.3 ± 33 and 53.9 ± 47 mcg/week (P= 0.97 respectively and 0.89 ± 0.6 and 0.98 ± 1.0 mcg/kg/week (P= 0.8. 22 (78.6 % of the EPO resistant patients responded to darbepoetin. In conclusion conversion from high dose EPO to darbepoetin proved successful even in patients who were resistant to

  7. The efficacy of darbepoetin alpha in hemodialysis patients resistant to human recombinant erythropoietin (rHuEpo).

    Science.gov (United States)

    Hejaili, Fayez

    2009-07-01

    Darbepoetin due to longer half life is convenient and effective for long term. This study was done to assess the efficacy of darbepoetin in the treatment of patients on high doses of erythropoietin (EPO) and to compare its efficacy in patients resistant and responsive to EPO. This is a prospective, controlled open label study assessing the efficacy of darbepoetin in 55 hemodialysis patients on high dose EPO and comparing its efficacy in the patients who were "EPO -resistant" (group 1, n= 28) and in those who were "EPO-responsive" (group 2, n= 27). The initial conversion ratio was 380 mcg darbepoetin: 1 U EPO/ week and the dose of darbepoetin was adjusted thereafter at fortnightly intervals with the aim of achieving and maintaining the hemoglobin level between 11-12 g/dL. The patients were followed up for 12 weeks following the introduction of darbepoetin. The impact of gender, baseline PTH, age, Kt/V, duration on dialysis, initial EPO dose on the response to darbepoetin was investigated. Continuous variables were compared using two tailed t-test and non-parametric by Fisher exact test. Overall darbepoetin was effective with 85.5 % of the patients responding and 21.8 % of the patients' able to maintain their hemoglobin with once fortnightly dose by the end of the study. Mean darbepoetin dose and the mean EPO to darbepoetin conversion ratio on completion of the study were 58.2 (42.4) mcg/week (0.983 (0.87) mcg/kg/week) and 384:1 respectively. Hemoglobin levels in groups 1 improved from 9.8 +/- 0.9 g/dL to 12.0 +/- 1.4 g/dL (0.0001) and 2 were and maintained it in group 2 at 11.9 +/- 1.3 g/dL (P= 0.79). The doses of darbepoetin required in groups 1 and 2 were similar (54.3 +/- 33 and 53.9 +/- 47 mcg/week (P= 0.97) respectively and 0.89 +/- 0.6 and 0.98 +/- 1.0 mcg/kg/week (P= 0.8). 22 (78.6 %) of the EPO resistant patients responded to darbepoetin. In conclusion conversion from high dose EPO to darbepoetin proved successful even in patients who were resistant to EPO

  8. OPTIMAL ERYTHROID CELL PRODUCTION DURING ERYTHROPOIETIN TREATMENT OF MICE OCCURS BY EXPLOITING THE SPLENIC MICROENVIRONMENT

    NARCIS (Netherlands)

    NIJHOF, W; GORIS, H; DONTJE, B; DRESZ, J; LOEFFLER, M

    1993-01-01

    In this study, quantitative effects on erythroid cell production by a prolonged recombinant human erythropoietin (rhEpo) treatment of mice are presented. Epo treatments, given subcutaneously (s.c.) twice per day in doses of 0.5 to 500 U per day, were performed under steady-state production condition

  9. NKCC2A and NFAT5 regulate renal TNF production induced by hypertonic NaCl intake.

    Science.gov (United States)

    Hao, Shoujin; Bellner, Lars; Ferreri, Nicholas R

    2013-03-01

    Pathways that contribute to TNF production by the kidney are not well defined. Mice given 1% NaCl in the drinking water for 3 days exhibited a 2.5-fold increase in urinary, but not plasma, TNF levels compared with mice given tap water. Since furosemide attenuated the increase in TNF levels, we hypothesized that hypertonic NaCl intake increases renal TNF production by a pathway involving the Na(+)-K(+)-2Cl(-) cotransporter (NKCC2). A 2.5-fold increase in NKCC2A mRNA accumulation was observed in medullary thick ascending limb (mTAL) tubules from mice given 1% NaCl; a concomitant 2-fold increase in nuclear factor of activated T cells 5 (NFAT5) mRNA and protein expression was observed in the outer medulla. Urinary TNF levels were reduced in mice given 1% NaCl after an intrarenal injection of a lentivirus construct designed to specifically knockdown NKCC2A (EGFP-N2A-ex4); plasma levels of TNF did not change after injection of EGFP-N2A-ex4. Intrarenal injection of EGFP-N2A-ex4 also inhibited the increase of NFAT5 mRNA abundance in the outer medulla of mice given 1% NaCl. TNF production by primary cultures of mTAL cells increased approximately sixfold in response to an increase in osmolality to 400 mosmol/kgH2O produced with NaCl and was inhibited in cells transiently transfected with a dnNFAT5 construct. Transduction of cells with EGFP-N2A-ex4 also prevented increases in TNF mRNA and protein production in response to high NaCl concentration and reduced transcriptional activity of a NFAT5 promoter construct. Since NKCC2A expression is restricted to the TAL, NKCC2A-dependent activation of NFAT5 is part of a pathway by which the TAL produces TNF in response to hypertonic NaCl intake.

  10. Advanced glycosylation end products, protein kinase C and renal alterations in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To sludy the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on ranal alteration in diabetic rats. Methods Insulin or anlinoguanidine was administered to diabetic rats. Blood glucose, hermoglobin A1c (HbA1c ), glomemlar tissue extracts AGE ( GTE AGE ), PKC, glomerular basement membrane thickness ( GBMT ) and udne protein/creatinine (Pr/Cr) ratio in diabetic rats were measured and analysed. Results LeveLs of blood glucose, HbA1C and AGE, PKC activity, the Pr/Or ratio and GBMT were all significantly increased ( p values all less than 0.01 ) in diabetic rats. Insulin could decrease the formation of kbAlc and AGE, and improve PKC activity. Aminoguanidine had no influecce on PKC activity (P>O.05) although it decreased the formation of AGE. Botah drugs could de4ay the increase of urine Pr/Cr ratio and GBMT ( P<0.05 or P< 0.01). Conclusions Chronic hyperglycemia may lead to an increase of PKC activity. HbAlc and AGE may not directly coritribute to alterations of PKC activity, but the increase of PKC activity could promote the action of AGE on GEM thickening. It is important to inhibit the formanion of AGE and reduce the PKC activity so as to pceveat or delay the development of diabetic nephropathy.

  11. Monosialylated biantennary N-glycoforms containing GalNAc-GlcNAc antennae predominate when human EPO is expressed in goat milk

    NARCIS (Netherlands)

    Montesino, R.; Toledo, J.R.; Sánchez, O.; Sánchez, A.; Harvey, D.J.; Royle, L.; Dwek, R.A.; Rudd, P.M.; Gerwig, G.J.; Kamerling, J.P.; Cremata, J.A.

    2008-01-01

    Recently, our group reported the expression of recombinant human erythropoietin in goat milk (rhEPO-milk) as well as in the mammary epithelial cell line GMGE (EPO-GMGE) by cell culture using the adenoviral transduction system. N-Glycosylation characterization of rhEPO-milk by Normal-Phase HPLC profi

  12. Renal perfusion scintiscan

    Science.gov (United States)

    Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...

  13. System-scale network modeling of cancer using EPoC.

    Science.gov (United States)

    Abenius, Tobias; Jörnsten, Rebecka; Kling, Teresia; Schmidt, Linnéa; Sánchez, José; Nelander, Sven

    2012-01-01

    One of the central problems of cancer systems biology is to understand the complex molecular changes of cancerous cells and tissues, and use this understanding to support the development of new targeted therapies. EPoC (Endogenous Perturbation analysis of Cancer) is a network modeling technique for tumor molecular profiles. EPoC models are constructed from combined copy number aberration (CNA) and mRNA data and aim to (1) identify genes whose copy number aberrations significantly affect target mRNA expression and (2) generate markers for long- and short-term survival of cancer patients. Models are constructed by a combination of regression and bootstrapping methods. Prognostic scores are obtained from a singular value decomposition of the networks. We have previously analyzed the performance of EPoC using glioblastoma data from The Cancer Genome Atlas (TCGA) consortium, and have shown that resulting network models contain both known and candidate disease-relevant genes as network hubs, as well as uncover predictors of patient survival. Here, we give a practical guide how to perform EPoC modeling in practice using R, and present a set of alternative modeling frameworks.

  14. Therapeutic levels of erythropoietin (EPO) achieved after gene electrotransfer to skin in mice

    DEFF Research Database (Denmark)

    Gothelf, A; Hojman, P; Gehl, Julie

    2010-01-01

    Gene electrotransfer refers to gene transfection by electroporation and is an effective non-viral method for delivering naked DNA into cells and tissues. This study presents data from gene electrotransfer with erythropoietin (EPO) to mouse skin. Nine-week-old female NMRI mice received one, two...

  15. Desert Research and Technology Studies (DRATS) 2010 Education and Public Outreach (EPO)

    Science.gov (United States)

    Paul, Heather L.

    2013-10-01

    The Exploration Systems Mission Directorate, Directorate Integration Office conducts analog field test activities, such as Desert Research and Technology Studies (DRATS), to validate exploration system architecture concepts and conduct technology demonstrations. Education and Public Outreach (EPO) activities have been a part of DRATS missions in the past to engage students, educators, and the general public in analog activities. However, in 2010, for the first time, EPO was elevated as a principal task for the mission and metrics were collected for all EPO activities. EPO activities were planned well in advance of the mission, with emphasis on creating a multitude of activities to attract students of all ages. Web-based and social media interaction between August 31 and September 14, 2010 resulted in 62,260 DRATS Flickr views; 10,906 views of DRATS videos on YouTube; 1,483 new DRATS Twitter followers; and a 111% increase in DRATS Facebook fan interactions. Over 7,000 outreach participants were directly involved in the DRATS 2010 analog mission via student visitations at both the integrated dry-runs prior to the field mission and during the field mission; by participating in live, interactive webcasts and virtual events; and online voting to determine a traverse site as part of the NASA initiative for Participatory Exploration (PE).

  16. Altered Expression of EPO Might Underlie Hepatic Hemangiomas in LRRK2 Knockout Mice.

    Science.gov (United States)

    Wu, Ben; Xiao, Kaifu; Zhang, Zhuohua; Ma, Long

    2016-01-01

    Parkinson's disease (PD) is a severe neurodegenerative disorder caused by progressive loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. The molecular mechanism of PD pathogenesis is unclear. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a common genetic cause of familial and sporadic PD. However, studies on LRRK2 mutant mice revealed no visible dopaminergic neuronal loss in the midbrain. While surveying a LRRK2 knockout mouse strain, we found that old animals developed age-dependent hepatic vascular growths similar to cavernous hemangiomas. In livers of these hemangioma-positive LRRK2 knockout mice, we detected an increased expression of the HIF-2α protein and significant reactivation of the expression of the HIF-2α target gene erythropoietin (EPO), a finding consistent with a role of the HIF-2α pathway in blood vessel vascularization. We also found that the kidney EPO expression was reduced to 20% of the wild-type level in 18-month-old LRRK2 knockout mice. Unexpectedly, this reduction was restored to wild-type levels when the knockout mice were 22 months to 23 months old, implying a feedback mechanism regulating kidney EPO expression. Our findings reveal a novel function of LRRK2 in regulating EPO expression and imply a potentially novel relationship between PD genes and hematopoiesis.

  17. EPO reverses defective wound repair in hypercholesterolaemic mice by increasing functional angiogenesis.

    Science.gov (United States)

    Elsherbiny, Ahmed; Högger, Dominik C; Borozadi, Meisam Khorrami; Schmidt, Christian A; Plock, Jan; Largo, Rene D; Lindenblatt, Nicole; Giovanoli, Pietro; Contaldo, Claudio

    2012-11-01

    This study aims to elucidate the effect of erythropoietin (EPO) on the microcirculation during wound healing in mice genetically depleted of apolipoprotein E (ApoE(-/-)). The skinfold chamber in mice was used for intravital microscopy, whereby an incisional wound was created within the chamber. Animals received Recormon(®) 1000 U kg(-1) body weight (BW) intra-peritoneally (i.p.) at day 1, 3, 5, 7, 9 and 11 post-wounding at a concentration of 100 Uml(-1) (n=42). Normal healing and vehicle-treated wild type animals (WT) served as controls. The microcirculation of the wound was analysed quantitatively in vivo using epi-illumination intravital fluorescence microscopy. Microtomography (micro-CT) analysis of casted wound microvessels was performed allowing three-dimensional (3D) histomorphometric analysis. Tissue samples were examined ex vivo for wound scoring and for expression analysis of EPO-Receptor (Epo-R) and endothelial nitric oxide synthase (eNOS). Upon EPO treatment, the total wound score in ApoE(-/-) mice was increased by 23% on day 3, by 26% on day 7 and by 18% on day 13 when compared to untreated ApoE(-/-) mice (all PEpo-R expression (4.6-fold on day 3 and 13.5-fold on day 7) and eNOS expression (2.4-fold on day 7) (all PEPO treatment reverses microvascular dysfunction during wound healing in hypercholesterolaemic mice by inducing new vessel formation and by providing the wound with more oxygen.

  18. The industrial application requirement for biotech inventions in light of recent EPO & UK case law:

    DEFF Research Database (Denmark)

    Minssen, Timo; Nilsson, David

    2012-01-01

    at the date of filing to demonstrate a credible – or to use the terminology of the EPO – a plausible industrial application. In the final section of the article we shall also discuss various policy considerations relevant for the biotech industry and briefly refer to corresponding developments in the US...

  19. L-carnitine supplementation and EPO requirement in children on chronic hemodialysis.

    Science.gov (United States)

    Aoun, Bilal; Bérard, Etienne; Vitkevic, Renata; Dehée, Axelle; Bensman, Albert; Ulinski, Tim

    2010-03-01

    L-carnitine supplementation has been the subject of heated discussion in the context of the treatment of pediatric hemodialysis patients. The aim of this study was to analyze the effect of intravenous L-carnitine supplementation on the erythropoetin (EPO) requirement in six pediatric hemodialysis patients. All patients were on intravenous L-carnitine (2.5 g per session for patients >30 kg and 1 g for those carnitine supplementation, the EPO requirement was 1.15 +/- 0.22 (range 0.37-1.75) microg/kg darbepoetin alpha. Free carnitine (FC) levels were measured before (40.4 +/- 4.9 micromol/l), immediately after the 9-month L-carnitine supplementation period (378.5 +/- 77.3 micromol/l), and 4 months after withdrawal of L-carnitine (95.6 +/- 4.0 micromol/l). After 9 months, the EPO dose was 0.47 +/- 0.10 microg/kg (p carnitine supplementation, FC levels were higher and persisted longer than expected. This rise was associated with increased Hb levels and decreased EPO requirement. Since controls were missing for this study, prospective long-term multi-center studies on a large number of patients are required to provide solid answers to the controversial question of L-carnitine supplementation in hemodialyzed children.

  20. EMSODEV and EPOS-IP: key findings for effective management of EU research infrastructure projects

    Science.gov (United States)

    Materia, Paola; Bozzoli, Sabrina; Beranzoli, Laura; Cocco, Massimo; Favali, Paolo; Freda, Carmela; Sangianantoni, Agata

    2017-04-01

    EMSO (European Multidisciplinary Seafloor and water-column Observatory, http://www.emso-eu.org) and EPOS (European Plate Observing System, https://www.epos-ip.org) are pan-European Research Infrastructures (RIs) in the ESFRI 2016 Roadmap. EMSO has recently become an ERIC (European Research Infrastructure Consortium), whilst EPOS application is in progress. Both ERICs will be hosted in Italy and the "Representing Entity" is INGV. EMSO consists of oceanic environment observation systems spanning from the Arctic through the Atlantic and Mediterranean, to the Black Sea for long-term, high-resolution, real-time monitoring of natural and man-induced processes such as hazards, climate, and marine ecosystems changes to study their evolution and interconnections. EPOS aims at creating a pan-European infrastructure for solid Earth science to support a safe and sustainable society. EPOS will enable innovative multidisciplinary research for a better understanding of Earth's physical and chemical processes controlling earthquakes, volcanic eruptions, ground instability, tsunami, and all those processes driving tectonics and Earth's surface dynamics. Following the conclusion of their Preparatory Phases the two RIs are now in their Implementation Phase still supported by the EC through the EMSODEV and EPOS-IP projects, both run by dedicated Project Management Offices at INGV with sound experience in EU projects. EMSODEV (H2020 project, 2015-2018) involves 11 partners and 9 associate partners and aims at improving the harmonization among the EMSO ERIC observation systems through the realization of EMSO Generic Instrument Modules (EGIMs), and a Data Management Platform (DMP) to implement interoperability and standardization. The DMP will provide access to data from all EMSO nodes, providing a unified, homogeneous, infrastructure-scale and user-oriented platform integrated with the increased measurement capabilities and functions provided by the EGIMs. EPOS IP (H2020 project, 2015

  1. The feed-back regulation of erythropoietin production in healthy humans

    Energy Technology Data Exchange (ETDEWEB)

    Klausen, T

    1998-10-01

    The proposed oxygen-dependent feed-back loop regulation of EPO (erythropoietin) production is mainly supported by data from studies in animals and cell cultures. The feed-back loop and its dependence on oxygen was therefore challenged by studies in healthy humans: Exposure of humans to different levels of acute and continued altitude hypobaria provided evidence for an oxygen dependence of the EPO response. This response is consistent with the proposed feed-back loop regulation of EPO production; Exposure to continued altitude hypobaria demonstrated that the decline in human EPO production is initiated before an EPO-induced erythopoiesis is detectable, and that this decline is related to a concomitant decrease in the haemoglobin-oxygen affinity. Contrary to the feed-back loop, this time-relation indicate that the feed-back regulation of EPO production during continued hypobaric hypoxia is exerted primarily through a decrease in the haemoglobin-oxygen affinity, rather than by the effects of an EPO-stimulated erythropoiesis; Increased circulating levels of the proinflammatory cytokine IL-6 was found in healthy humans during four days of altitude exposure as compared with sea level. The other proinflammatory cytokines IL-1 beta, and TNF alpha remained unchanged, and the increased serum IL-6 did not induce production of c-reactive protein; Comparable circadian variations in human EPO production were shown in sedentary subjects, athletes, and healthy but hypoxaemic subjects. Human EPO production could not be triggered by one hour of high-intensity exercise, whereas longitudinal changes in exercise showed a trend of relation between human EPO production, serum concentration of free testosterone, and indices of body composition. These results have demonstrated and endogenous, probably hormonal, and oxygen-independent regulation of human EPO production, which is at variance with the oxygen dependent feed-back loop regulation of EPO production. Conclusively, the present

  2. Erythropoietin (EPO) protects against high glucose-induced apoptosis in retinal ganglional cells.

    Science.gov (United States)

    Wang, Yunxiao; Zhang, Hui; Liu, Yanping; Li, Ping; Cao, Zhihong; Cao, Yu

    2015-03-01

    The aim of this study was to investigate the protective effect and mechanism of EPO on the apoptosis induced by high levels of glucose in retinal ganglial cells (RGCs). High glucose-induced apoptosis model was established in RGCs isolated from SD rats (1-3 days old) and identified with Thy1.1 mAb and MAP-2 pAb. The apoptosis was determined by Hochest assay. The levels of ROS were quantitated by staining the cells with dichloro-dihydro-fluorescein diacetate (DCFH-DA) and measure by flow cytometry. The SOD, GSH-Px, CAT activities, and levels of T-AOC and MDA were determined by ELISA. Change in mitochondrial membrane potential (Δψm) was also assessed by flow cytometry, and expressions of Bcl-2, Bax, caspase-3, caspase-9, and cytochrome C were assessed by western blotting. The RGCs treated with high glucose levels exhibited significantly increased apoptotic rate and concentrations of ROS and MDA. Pretreatment of the cells with EPO caused a significant blockade of the high glucose-induced increase in ROS and MDA levels and apoptotic rate. EPO also increased the activities of SOD, GSH-Px, and CAT, and recovered the levels of T-AOC levels. As a consequence, the mitochondrial membrane potential was improved and Cyt c release into the cytoplasm was prevented which led to significantly suppressed up-regulation of Bax reducing the Bax/Bcl-2 ratio. The expressions of caspase-3 and caspase-9 induced by high glucose exposure were also ameliorated in the RGCs treated with EPO. The protective effect of EPO against apoptosis was mediated through its antioxidant action. Thus, it blocked the generation of pro-apoptotic proteins and apoptotic degeneration of the RGCs by preventing the mitochondrial damage.

  3. Bovine renal lipofuscinosis: Prevalence, genetics and impact on milk production and weight at slaughter in Danish cattle

    Directory of Open Access Journals (Sweden)

    Flagstad Pia

    2009-02-01

    Full Text Available Abstract Background Bovine renal lipofuscinosis (BRL is an incidental finding in cattle at slaughter. Condemnation of the kidneys as unfit for human consumption was until recently considered the only implication of BRL. Recent studies have indicated a negative influence on the health of affected animals. The present study investigated the prevalence, genetics and effect of BRL on milk yield and weight at slaughter. Methods BRL status of slaughter cattle was recorded at four abattoirs during a 2-year-period. Data regarding breed, age, genetic descent, milk yield and weight at slaughter were extracted from the Danish Cattle Database. The prevalence of BRL was estimated stratified by breed and age-group. Furthermore, total milk yield, milk yield in last full lactation and weight at slaughter were compared for BRL-affected and non-affected Danish Holsteins and Danish Red cattle. Results 433,759 bovines were slaughtered and 787 of these had BRL. BRL was mainly diagnosed in Danish Red, Danish Holstein and crossbreds. The age of BRL affected animals varied from 11 months to 13 years, but BRL was rarely diagnosed in cattle less than 2 years of age. The total lifelong energy corrected milk (ECM yields were 3,136 and 4,083 kg higher for BRL affected Danish Red and Danish Holsteins, respectively. However, the median life span of affected animals was 4.9 months longer, and age-corrected total milk yield was 1,284 kg lower for BRL affected Danish Red cows. These cows produced 318 kg ECM less in their last full lactation. Weight at slaughter was not affected by BRL status. The cases occurred in patterns consistent with autosomal recessive inheritance and several family clusters of BRL were found. Analysis of segregation ratios demonstrated the expected ratio for Danish Red cattle, but not for Danish Holsteins. Conclusion The study confirmed that BRL is a common finding in Danish Holsteins and Danish Red cattle at slaughter. The disorder is associated with

  4. Effects of recombinant human erythropoietin on the haemopoietic bone marrow monitored by magnetic resonance spectroscopy in patients with end-stage renal disease

    DEFF Research Database (Denmark)

    Jensen, K E; Stenver, D; Jensen, M;

    1990-01-01

    Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate changes in the haemopoietic bone marrow in patients with end-stage renal disease undergoing treatment with recombinant human erythropoietin (rHuEPO). Significant changes could be detected in the spectra 14 days...

  5. The Effect of EPO Gene Overexpression on Proliferation and Migration of Mouse Bone Marrow-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Lin, Haihong; Luo, Xinping; Jin, Bo; Shi, Haiming; Gong, Hui

    2015-04-01

    The aim of this study is to investigate the effect of erythropoietin (EPO) gene overexpression on proliferation and migration of mouse bone marrow-derived mesenchymal stem cells (MSCs), and to determine the underlying signaling pathway. Mouse MSCs were cultured in vitro and EPO gene was transfected into the 6th generation of MSCs via lentivirus vector. The transfected cells were identified by flow cytometry and the EPO levels in supernatant were measured with ELISA. In addition, cell proliferation was assessed by CCK-8 assay and cell migration was evaluated by Transwell assay. The activation of Akt, ERK1/2, and p38MAPK signaling was detected by western blotting. The lentivirus vector containing EPO was successfully constructed and transfected into MSCs. No remarkable change was found in the cell surface markers after transfection while a significant increase of EPO level in supernatant was noticed in transfected MSCs compared to controls (P EPO modification enhanced the phosphorylation of PI3K/Akt and ERK signaling pathway, and suppressed the phosphorylation of p38MAPK without affecting the levels of total Akt, ERK1/2, and p38MAPK in MSCs. After transfection, MSCs secreted more EPO which enhanced the capability of proliferation and migration. Moreover, our results suggested that the enhanced proliferation and migration might be associated with activation of PI3K/Akt and ERK or inhibition of P38MAPK signaling pathway.

  6. Gain-of-function Lyn induces anemia: appropriate Lyn activity is essential for normal erythropoiesis and Epo receptor signaling.

    Science.gov (United States)

    Slavova-Azmanova, Neli S; Kucera, Nicole; Satiaputra, Jiulia; Stone, Leah; Magno, Aaron; Maxwell, Mhairi J; Quilici, Cathy; Erber, Wendy; Klinken, S Peter; Hibbs, Margaret L; Ingley, Evan

    2013-07-11

    Lyn is involved in erythropoietin (Epo)-receptor signaling and erythroid homeostasis. Downstream pathways influenced following Lyn activation and their significance to erythropoiesis remain unclear. To address this, we assessed a gain-of-function Lyn mutation (Lyn(up/up)) on erythropoiesis and Epo receptor signaling. Adult Lyn(up/up) mice were anemic, with dysmorphic red cells (spherocyte-like, acanthocytes) in their circulation, indicative of hemolytic anemia and resembling the human disorder chorea acanthocytosis. Heterozygous Lyn(+/up) mice became increasingly anemic with age, indicating that the mutation was dominant. In an attempt to overcome this anemia, extramedullary erythropoiesis was activated. As the mice aged, the levels of different immature erythroid populations changed, indicating compensatory mechanisms to produce more erythrocytes were dynamic. Changes in Epo signaling were observed in Lyn(+/up) erythroid cell lines and primary CD71(+) Lyn(up/up) erythroblasts, including significant alterations to the phosphorylation of Lyn, the Epo receptor, Janus kinase 2, Signal Transducer and Action of Transcription-5, GRB2-associated-binding protein-2, Akt, and Forkhead box O3. As a consequence of altered Lyn signaling, Lyn(+/up) cells remained viable in the absence of Epo but displayed delayed Epo-induced differentiation. These data demonstrate that Lyn gene dosage and activity are critical for normal erythropoiesis; constitutively active Lyn alters Epo signaling, which in turn produces erythroid defects.

  7. 下一代广电接入技术EPoC五月最新进展

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    2012年5月15~16日,IEEEEPoC研究组在美国明尼苏达州召开了第3次临时会议。在此次会议上,研究组成员们展示了他们关于EPoC技术需求、技术架构、技术可行性、EPoC工作目标、EPoC五点评判准则、

  8. EPO-dependent activation of PI3K/Akt/FoxO3a signalling mediates neuroprotection in in vitro and in vivo models of Parkinson's disease.

    Science.gov (United States)

    Jia, Yu; Mo, Shi-Jing; Feng, Qi-Qi; Zhan, Ma-Li; OuYang, Li-Si; Chen, Jia-Chang; Ma, Yu-Xin; Wu, Jia-Jia; Lei, Wan-Long

    2014-05-01

    Erythropoietin (EPO) may become a potential therapeutic candidate for the treatment of the neurodegenerative disorder -- Parkinson's disease (PD), since EPO has been found to prevent neuron apoptosis through the activation of cell survival signalling. However, the underlying mechanisms of how EPO exerts its neuroprotective effect are not fully elucidated. Here we investigated the mechanism by which EPO suppressed 6-hydroxydopamine (6-OHDA)-induced neuron death in in vitro and in vivo models of PD. EPO knockdown conferred 6-OHDA-induced cytotoxicity. This effect was reversed by EPO administration. Treatment of PC12 cells with EPO greatly diminished the toxicity induced by 6-OHDA in a dose- and time-dependent manner. EPO effectively reduced apoptosis of striatal neurons and induced a significant improvement on the neurological function score in the rat models of PD. Furthermore, EPO increased the expression of phosphorylated Akt and phosphorylated FoxO3a, and abrogated the 6-OHDA-induced dysregulation of Bcl-2, Bax and Caspase-3 in PC12 cells and in striatal neurons. Meanwhile, the EPO-dependent neuroprotection was notably reversed by pretreatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). Our data suggest that PI3K/Akt/FoxO3a signalling pathway may be a possible mechanism involved in the neuroprotective effect of EPO in PD.

  9. Engaging Scientists in Meaningful E/PO: How the NASA SMD E/PO Community Addresses Informal Educators' Preferences for PD and Materials

    Science.gov (United States)

    Bartolone, Lindsay; Nelson, Andi; Smith, Denise A.; NASA SMD Astrophysics E/PO Community

    2015-01-01

    The NASA Astrophysics Science Education and Public Outreach Forum (SEPOF) coordinates the work of NASA Science Mission Directorate (SMD) Astrophysics EPO projects. These teams work together to capitalize on the cutting-edge discoveries of NASA Astrophysics missions to support educators in Science, Technology, Engineering, and Math (STEM) and to enable youth to engage in doing STEM inside and outside of school. The Astrophysics Forum assists scientists and educators with becoming involved in SMD E/PO, which is uniquely poised to foster collaboration between scientists with content expertise and educators with pedagogy expertise, and makes SMD E/PO resources and expertise accessible to the science and education communities. Informal educators participated in a recent nationally-distributed survey from the NASA SMD SEPOF Informal Education Working Group. The results show the preferences of staff from museums, parks, public libraries, community/afterschool centers, and others with regard to professional development and material resources. The results of the survey will be presented during this session.In addition, we present opportunities for the astronomy community to participate in collaborations supporting the NASA SMD efforts in K-12 Formal Education, Informal Science Education, and Outreach. These efforts focus on enhancing instruction, as well as youth and public engagement, in STEM via use of research-based best practices, collaborations with libraries, partnerships with local and national organizations, and remote engagement of audiences. The Forums' efforts for the Formal, Informal Science Education and Outreach communities include a literature review, appraisal of informal educators' needs, coordination of audience-based NASA resources and opportunities, professional development, plus support with the Next Generation Science Standards. Learn how to join in our collaborative efforts to support the K-12 Formal Education community and to reach the informal

  10. Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease.

    Directory of Open Access Journals (Sweden)

    Martin Wagner

    Full Text Available Anemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD. It may be explained by reduced erythropoietin (EPO synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25--the key hormone of iron-metabolism--on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels.249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD, were enrolled (2003-2005, if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine were analyzed by Cox proportional hazards models.Patients (age 67 yrs, 53% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7% and forty (16.1% patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05. Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05. Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05.We found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the

  11. Daily rhythms in renal blood flow and urine production rate in the near-term sheep fetus

    NARCIS (Netherlands)

    Poortinga, FMI; Aarnoudse, JG

    2000-01-01

    Daily rhythmicity of renal blood flow (RBF) and urine flow (UF) was studied in fetal sheep between 121-125 d of gestation. Fetal arterial blood pressure, heart rate, UF, and right RBF were measured continuously for 24-h periods in 10 sheep, Rhythmic variations during a 24-h period were found for all

  12. Daily rhythms in renal blood flow and urine production rate in the near-term sheep fetus

    NARCIS (Netherlands)

    Poortinga, FMI; Aarnoudse, JG

    Daily rhythmicity of renal blood flow (RBF) and urine flow (UF) was studied in fetal sheep between 121-125 d of gestation. Fetal arterial blood pressure, heart rate, UF, and right RBF were measured continuously for 24-h periods in 10 sheep, Rhythmic variations during a 24-h period were found for all

  13. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  14. Renal angiomyolipoma

    DEFF Research Database (Denmark)

    Holm-Nielsen, P; Sørensen, Flemming Brandt

    1988-01-01

    lesion. Three cases of renal angiomyolipoma, 2 of which underwent perfusion-fixation, were studied by electron microscopy to clarify the cellular composition of this lesion. In the smooth muscle cells abundant accumulation of glycogen was found, whereas the lipocytes disclosed normal ultrastructural......-specific vesicular structures. These findings suggest a secondary vascular damage, i.e. the thickened vessels may not be a primary, integral part of renal angiomyolipoma. Evidence of a common precursor cell of renal angiomyolipoma was not disclosed. It is concluded that renal angiomyolipoma is a hamartoma composed...

  15. EPO for the NASA SDO Extreme Ultraviolet Variability Experiment (EVE) Learning Suite for Educators

    Science.gov (United States)

    Kellagher, Emily; Scherrer, D. K.

    2013-07-01

    EVE Education and Public Outreach (EPO) promotes an understanding of the process of science and concepts within solar science and sun-earth connections. EVE EPO also features working scientists, current research and career awareness. One of the highlights for of this years projects is the digitization of solar lessons and the collaboration with the other instrument teams to develop new resources for students and educators. Digital lesson suite: EVE EPO has taken the best solar lessons and reworked then to make then more engaging, to reflect SDO data and made them SMARTboard compatible. We are creating a website that Students and teachers can access these lesson and use them online or download them. Project team collaboration: The SDO instruments (EVE, AIA and HMI) teams have created a comic book series for upper elementary and middle school students with the SDO mascot Camilla. These comics may be printed or read on mobile devices. Many teachers are looking for resources to use with their students via the Ipad so our collaboration helps supply teachers with a great resource that teachers about solar concepts and helps dispel solar misconceptions.Abstract (2,250 Maximum Characters): EVE Education and Public Outreach (EPO) promotes an understanding of the process of science and concepts within solar science and sun-earth connections. EVE EPO also features working scientists, current research and career awareness. One of the highlights for of this years projects is the digitization of solar lessons and the collaboration with the other instrument teams to develop new resources for students and educators. Digital lesson suite: EVE EPO has taken the best solar lessons and reworked then to make then more engaging, to reflect SDO data and made them SMARTboard compatible. We are creating a website that Students and teachers can access these lesson and use them online or download them. Project team collaboration: The SDO instruments (EVE, AIA and HMI) teams have created a

  16. Education and Professional Outreach for Scientists: Producing and Leveraging EPO Objects for Inquiry-Based Learning

    Science.gov (United States)

    Koppers, A. A.; Staudigel, H.

    2007-12-01

    Most Education and Professional Outreach (EPO) by scientists reaches relatively small audiences. Most scientists also see their contributions to K-12 teaching rather limited due to their lack of experience in primary and secondary school education. These limitations remain a major barrier in bridging the gap between science and education, and in optimizing the effectiveness of EPO by scientists. As part of the Enduring Resources for Earth Science Education (ERESE) project, we have started to use web- templates in our EPO creation (http://earthref.org/ERESE). These templates are now being developed into web- based tools and services that will be served from the ERESE website and archived by the National Science Digital Library (NSDL). At EarthRef.org these EPO objects can be linked to teaching materials in the ERDA digital archive that can be displayed in a fashion allowing selection based on expert level and file type, in what we dubbed the "resource matrix" view. This is a powerful search mechanism for learners of all levels in which they can pre-screen materials to their own level, while allowing them to venture up to higher expert levels or to explore more simple cases at lower levels. This stimulates inquiry- based learning by permitting as much roaming freedom as possible in a "science-data- based" online environment. The current EarthRef.org and ERESE collections include websites for scientific projects, for classes taught and for expeditions, as well as a wide range of materials including press releases, video footage, science illustrations, interviews, data and diagrams, student reports and lesson plans. This collection is representative for EPO in any STEM discipline and provides much interesting materials that are useful for education. Our main goal is to provide scientists with tools so they can obtain an easy-to-use and highly leveraged outlet for their EPO efforts, where they can reach substantial numbers of learners and educators, and where their

  17. [Overview of erythropoietin].

    Science.gov (United States)

    Lacombe, C; Mayeux, P; Casadevall, N

    1991-01-01

    Erythropoietin (Epo) is a glycoprotein that promotes the proliferation and differentiation of erythrocyte precursors. The major site of Epo production is the kidney and the liver is the main extra renal site of Epo production. Epo producing cells were identified by in situ hybridization, in the kidney, they are peritubular cells, most likely endothelial cells of the cortex and outer medulla; in the liver, they are mainly hepatocytes. The Epo secretion is stimulated by hypoxia, which is detected by an oxygen sensor. The Epo receptor is a multimeric protein, one chain which binds Epo has been cloned. However the structure of the Epo receptor is still puzzling, and one or more accessory chains remain to be identified. Since the clonage of the Epo gene, recombinant Epo has been available and allowed the treatment of patients with renal diseases with a constant efficacy.

  18. Training Young Astronomers in EPO: An Update on the AAS Astronomy Ambassadors Program

    Science.gov (United States)

    Fraknoi, A.; Fienberg, R. T.; Gurton, S.; Schmitt, A. H.; Schatz, D.; Prather, E. E.

    2014-07-01

    The American Astronomical Society, with organizations active in EPO, has launched professional-development workshops and a community of practice to help improve early-career astronomers' ability to communicate effectively. Called “Astronomy Ambassadors,” the program provides mentoring and training for participants, from advanced undergraduates to beginning faculty. By learning to implement effective EPO strategies, Ambassadors become better teachers, meeting presenters, and representatives of our science to the public and government. Because young astronomers are a more diverse group than those who now do most outreach, they help the astronomy community present a more multicultural and gender-balanced face to the public, enabling underserved groups to see themselves as scientists. Ambassadors are given a library of outreach activities and materials, including many developed by cooperating organizations such as the ASP, plus some that have been created by Andrew Fraknoi specifically for this program.

  19. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all acknowle

  20. Renal fallure

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920705 Endothelin and acute renal failure:study on their relationship and possiblemechanisms. LIN Shanyan(林善锬), et al.Renal Res Lab, Huashan Hosp, Shanghai MedUniv, Shanghai, 200040. Natl Med J China 1992;72(4): 201-205. In order to investigate the role of endothelin

  1. Renal cancer.

    NARCIS (Netherlands)

    Corgna, E.; Betti, M.; Gatta, G.; Roila, F.; Mulder, P.H.M. de

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  2. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  3. The Earliest Phases of Star Formation (EPoS): A Herschel Key Program - The precursors to high-mass stars and clusters

    CERN Document Server

    Ragan, Sarah; Krause, Oliver; Pitann, Jan; Beuther, Henrik; Linz, Hendrik; Tackenberg, Jochen; Balog, Zoltan; Hennemann, Martin; Launhardt, Ralf; Lippok, Nils; Nielbock, Markus; Schmiedeke, Anika; Schuller, Frederic; Steinacker, Juergen; Stutz, Amelia; Vasyunina, Tatiana

    2012-01-01

    (Abridged) We present an overview of the sample of high-mass star and cluster forming regions observed as part of the Earliest Phases of Star Formation (EPoS) Herschel Guaranteed Time Key Program. A sample of 45 infrared-dark clouds (IRDCs) were mapped at PACS 70, 100, and 160 micron and SPIRE 250, 350, and 500 micron. In this paper, we characterize a population of cores which appear in the PACS bands and place them into context with their host cloud and investigate their evolutionary stage. We construct spectral energy distributions (SEDs) of 496 cores which appear in all PACS bands, 34% of which lack counterparts at 24 micron. From single-temperature modified blackbody fits of the SEDs, we derive the temperature, luminosity, and mass of each core. These properties predominantly reflect the conditions in the cold, outer regions. Taking into account optical depth effects and performing simple radiative transfer models, we explore the origin of emission at PACS wavelengths. The core population has a median tem...

  4. Transfection of mEpo gene to intestinal epithelium in vivo mediated by oral delivery of chitosan-DNA nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Jing Chen; Wu-Li Yang; Ge Li; Ji Qian; Jing-Lun Xue; Shou-Kuan Fu; Da-Ru Lu

    2004-01-01

    AIM: To prepare the chitosan-pmEpo nanoparticles and to study their ability for transcellular and paracellular transport across intestinal epithelia by oral administration.METHODS: ICR mice were fed with recombinant plasmid AAV-tetO-CMV-mEpo (containing mEpo gene) or pCMVβ (containing LacZ gene), whether it was wrapped by chitosan or no. Its size and shape were observed by transmission electron microscopy. Agarose gel electrophoresis was used to assess the efficiency of encapsulation and stability against nuclease digestion. Before and after oral treatmant, blood samples were collected by retro-orbital puncture, and hematocrits were used to show the physiological effect of mEpo.RESULTS: Chitosan was able to successfully wrap the plasmid and to protect it from DNase degradation. Transmission electron microscopy showed that freshly prepared particles were approximately 70-150 nm in size and fairly spherical.Three days after fed the chitosan-pCrvlVβ complex was fed,the mice were killed and most of the stomach and 30% of the small intestine were stained. Hematocrit was not modified in naive and ′naked′mEpo-fed mice, a rapid increase of hematocrit was observed during the first 4 days of treatment in chitosan-mEpo-fed animals, reaching 60.9±1.2% (P<0.01),and sustained for a week. The second feed (6 days after the first feed) was still able to promote a second hematocrit increase in chitosan-mEpo-fed animals, reaching 65.9±1.4%(P<0.01), while the second hematocrit increase did not appear in the ′naked′ mEpo-second-fed mice.CONCLUSION: Oral chitosan-DNA nanoparticles can efficiently deliver genes to enterocytes, and may be used as a useful tool for gene transfer.

  5. Spleen tyrosine kinase mediates the actions of EPO and GM-CSF and coordinates with TGF-β in erythropoiesis.

    Science.gov (United States)

    Chang, Hua-Ching; Huang, Duen-Yi; Wu, Mai-Szu; Chu, Ching-Liang; Tzeng, Shiang-Jong; Lin, Wan-Wan

    2017-04-01

    Erythropoietin (EPO) and GM-CSF are involved in erythropoiesis, while TGF-β inhibits proliferation but potentiates differentiation of erythroblasts. Since Syk inhibitor may induce anemia side effect in clinic, here we investigated the role of Syk in the biological actions of EPO and GM-CSF in erythropoiesis. In human erythroleukemia cell line TF-1, Syk inhibitor R406 exerts an enhancement effect with TGF-β to decrease cell viability, either in the absence or presence of EPO or GM-CSF. Such effect of R406 results from the reduced cell cycle progression and increased cell apoptosis. Notably, unlike Syk, Src family kinases are not involved in the viability control of TF-1 cells. Signaling studies showed that Syk is required for STAT5 and ERK activation induced by EPO, and Akt and ERK activation induced by GM-CSF. Nevertheless, R406 does not change the Smad2/3 signal caused by TGF-β, and TGF-β neither affects above signal pathways of EPO and GM-CSF. Of note, Syk is constitutively associated with EPOR in plasma membrane and can bind to STAT5 at active status upon EPO stimulation. Furthermore, EPO-induced hemoglobin γ expression was reduced by R406. In BFU-E and CFU-E colony formation assays in Syk-deficient erythroid progenitor cells, we confirmed the essential role of Syk in erythropoiesis mediated by EPO. Taken together, Syk is a novel upstream signaling molecule of EPOR, and contributes to erythroblast proliferation, survival and differentiation.

  6. Erythropoietin (EPO)-receptor signaling induces cell death of primary myeloma cells in vitro

    OpenAIRE

    Thea Kristin Våtsveen; Anne-Marit Sponaas; Erming Tian; Qing Zhang; Kristine Misund; Anders Sundan; Magne Børset; Anders Waage; Gaute Brede

    2016-01-01

    Background: Multiple myeloma is an incurable complex disease characterized by clonal proliferation of malignant plasma cells in a hypoxic bone marrow environment. Hypoxia-dependent erythropoietin (EPO)-receptor (EPOR) signaling is central in various cancers, but the relevance of EPOR signaling in multiple myeloma cells has not yet been thoroughly investigated. Methods: Myeloma cell lines and malignant plasma cells isolated from bone marrow of myeloma patients were used in this st...

  7. Ethos y epos en 2666 de Roberto Bolaño

    OpenAIRE

    Rojas Sierra, Sergio Daniel

    2011-01-01

    La percepción y crítica de la obra de Roberto Bolaño es un trabajo en marcha para los estudios literarios. Como parte de esa dinámica, esta tesis tiene como objetivo comprender el ethos presente en la novela 2666 de Roberto Bolaño a través del análisis de epos de la misma.

  8. Interactive Panel and Audience Discussion: The Future is Here: Can EPO Navigate the Digital Age?

    Science.gov (United States)

    Shipp, S. S.; Dribin, N.; Gay, P. L.; Stockman, S.

    2010-08-01

    The digital divide refers to the gap between individuals with access to digital technology and those with limited or no access. In the EPO profession there is another digital divide: the divide between EPO practitioners who believe Twitter and other forms of social networking are the downfall of literacy—and perhaps of American society, and those who see boundless potential for engaging a global audience in Earth and space science. One thing is certain: we're not in our parent's world anymore—our's is a world increasingly run by electrons and hand-held devices that inform, entertain, connect, and fragment our audiences into an infinite number of special-interest groups with shortened attention spans that form and reform in nonlinear ways. How does EPO evolve to match the new media and electronic realities? Is there still a place for storytelling, for laddered learning experiences, for traditional methods? How do we adapt? How do we rise to the new challenges of the new media age?

  9. Centre for Research Infrastructure of Polish GNSS Data - response and possible contribution to EPOS

    Science.gov (United States)

    Araszkiewicz, Andrzej; Rohm, Witold; Bosy, Jaroslaw; Szolucha, Marcin; Kaplon, Jan; Kroszczynski, Krzysztof

    2017-04-01

    In the frame of the first call under Action 4.2: Development of modern research infrastructure of the science sector in the Smart Growth Operational Programme 2014-2020 in the late of 2016 the "EPOS-PL" project has launched. Following institutes are responsible for the implementation of this project: Institute of Geophysics, Polish Academy of Sciences - Project Leader, Academic Computer Centre Cyfronet AGH University of Science and Technology, Central Mining Institute, the Institute of Geodesy and Cartography, Wrocław University of Environmental and Life Sciences, Military University of Technology. In addition, resources constituting entrepreneur's own contribution will come from the Polish Mining Group. Research Infrastructure EPOS-PL will integrate both existing and newly built National Research Infrastructures (Theme Centre for Research Infrastructures), which, under the premise of the program EPOS, are financed exclusively by the national founds. In addition, the e-science platform will be developed. The Centre for Research Infrastructure of GNSS Data (CIBDG - Task 5) will be built based on the experience and facilities of two institutions: Military University of Technology and Wrocław University of Environmental and Life Sciences. The project includes the construction of the National GNNS Repository with data QC procedures and adaptation of two Regional GNNS Analysis Centres for rapid and long-term geodynamical monitoring.

  10. Screening of lectins from South American plants used as affinity ligands to purify rhEPO

    Directory of Open Access Journals (Sweden)

    G.I. Amadeo

    2003-03-01

    Full Text Available Two groups of isoforms of rhEPO, at a concentration of 300 µg/ml, were tested as putative inhibitors of the lectinic hemagglutination reaction in order to obtain affinity ligand(s for hormone purification: groups I (pI: 3.80; 3.89; 3.95; 4.07, 4.15 and 4.26 and groups II (pI: 4.15, 4.26; 4.38; 4.51; 4.72 and 4.93 Crude extracts from the vegetable materials Abrus precatorious (Abrin, Artocarpus incisa (Frutalin, Artocarpus integrifolia (Jacalin, Canavalia ensiformes (ConA, Canavalia brasiliensis (Conbr, Cratylia floribunda, Dioclea altissima (DAL, Dioclea grandiflora (DGL, Erythrina vellutina (EVL, Erythrina cristagalli, Lutaelburgia auriculata (lectin not fully characterized yet, Lycopersicum esculentum (LEA, Phaseolus vulgaris (PHA, Ricinus communis (Ricin and Triticum vulgaris (WGA were used. Only some of the galactose-specific lectins and the GlcNAc-specific lectins showed rapid full inhibition of the hemagglutination reaction for the less acidic isoforms and the total isoforms of rhEPO, respectively. On this basis, the selected lectins were purified by affinity chromatoghraphy and covalently coupled to cyanogen bromide activated Sepharose® (Amersham-Pharmacia. CHO.K1 cell culture supernatant containing rhEPO was loaded onto the lectin resins and the recoveries were calculated by using specific elutions.

  11. Enhancement of bioavailability by formulating rhEPO ionic complex with lysine into PEG-PLA micelle

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yanan; Sun, Fengying; Wang, Dan; Zhang, Renyu [Jilin University, College of Life Science (China); Dou, Changlin; Liu, Wanhui; Sun, Kaoxiang, E-mail: sunkx@ytu.edu.cn [Yantai University, School of Pharmacy (China); Li, Youxin, E-mail: liyouxin@jlu.edu.cn [Jilin University, College of Life Science (China)

    2013-10-15

    A composite micelle of ionic complex encapsulated into poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) di-block copolymeric micelles was used for protein drug delivery to improve its pharmacokinetic performance. In this study, recombinant human erythropoietin (rhEPO, as a model protein) was formulated with lysine into composite micelles at a diameter of 71.5 nm with narrow polydispersity indices (PDIs < 0.3). Only a trace amount of protein was in aggregate form. The zeta potential of the spherical micelles was ranging from -0.54 to 1.39 mv, and encapsulation efficiency is high (80 %). The stability of rhEPO was improved significantly in composite micelles in vitro. Pharmacokinetic studies in rats showed significant, enhanced plasma retention of the composite micelles in comparison with native rhEPO. Areas under curve (AUCs) of the rhEPO released from the composite micelles were 4.5- and 2.3-folds higher than those of the native rhEPO and rhEPO-loaded PEG-PLA micelle, respectively. In addition, the composite micelles exhibited good biocompatibility using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293T) cells. All these features are preferable for utilizing the composite micelles as a novel protein delivery system.

  12. Effect of cyclosporine, dexamethasone, and human CTLA4-Ig on production of cytokines in lymphocytes of clinically normal cats and cats undergoing renal transplantation.

    Science.gov (United States)

    Aronson, Lillian R; Stumhofer, Jason S; Drobatz, Kenneth J; Hunter, Christopher A

    2011-04-01

    To evaluate effects of cyclosporine, dexamethasone, and the immunosuppressive agent human CTLA4-Ig on cytokine production by feline lymphocytes in vitro and to assess patterns of cytokine production for 5 immunosuppressed renal transplant recipient cats. 21 clinically normal cats and 5 immunosupressed renal transplant recipient cats. Peripheral blood mononuclear cells were isolated from clinically normal cats and stimulated with concanavalin A (Con A; 10 μg/mL) alone or Con A with cyclosporine (0.05 μg/mL), dexamethasone (1 × 10(-7)M), a combination of cyclosporine-dexamethasone, or human CTLA4-Ig (10 g/mL). Cells from transplant recipients were stimulated with Con A alone. An ELISA was performed to measure production of interferon (IFN)-γ, granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-2, IL-4, and IL-10. Proliferation of CD4+ and CD8+T cells from immunosuppressed cats were also evaluated. Pairwise comparisons were performed via a Wilcoxon signed rank test or Wilcoxon rank sum test. Cyclosporine, dexamethasone, cyclosporine-dexamethasone combination, and CTLA4-Ig caused a significant decrease in IL-2, IFN-γ, and GM-CSF production. Cyclosporine and cyclosporine-dexamethasone, but not human CTLA4-Ig, caused a significant decrease in IL-10 production. High basal concentrations of IL-2 and IL-10 were identified in transplant recipients, and IL-10 was significantly increased in stimulated cultures. In immunosuppressed cats, there was a decrease in frequency of responders and proliferative capacity of CD4+ and CD8+T cells. CTLA4-Ig successfully inhibited proinflammatory cytokines while sparing cytokines critical for allograft tolerance. These data may be useful for developing better strategies to prevent rejection while sparing other immune functions.

  13. Setting up The Geological information and modelling Thematic Core Service for EPOS

    Science.gov (United States)

    Grellet, Sylvain; Häner, Rainer; Pedersen, Mikael; Lorenz, Henning; Carter, Mary; Cipolloni, Carlo; Robida, François

    2017-04-01

    Geological data and models are key assets for the EPOS community. The Geological information and modelling Thematic Core Service of EPOS is being designed as an efficient and sustainable access system for geological multi-scale data assets for EPOS through the integration of distributed infrastructure components (nodes) of geological surveys, research institutes and the international drilling community (ICDP/IODP). The TCS will develop and take benefit of the synergy between the existing data infrastructures of the Geological Surveys of Europe (EuroGeoSurveys / OneGeology-Europe / EGDI) and of the large amount of information produced by the research organisations. These nodes will offer a broad range of resources including: geological maps, borehole data, borehole associated observations (borehole log data, groundwater level, groundwater quality…) and archived information on physical material (samples, cores), geological models (3D, 4D), geohazards, geophysical data such as active seismic data and other analyses of rocks, soils and minerals. The services will be implemented based on international standards (such as INSPIRE, IUGS/CGI, OGC, W3C, ISO) in order to guarantee their interoperability with other EPOS TCS as well as their compliance with INSPIRE European Directive or international initiatives (such as OneGeology). We present the implementation of the thematic core services for geology and modelling, including scheduling of the development of the different components. The activity with the OGC groups already started in 2016 through an ad-hoc meeting on Borehole and 3D/4D and the way both will be interlinked will also be introduced. This will provide future virtual research environments with means to facilitate the use of existing information for future applications. In addition, workflows will be established that allow the integration of other existing and new data and applications. Processing and the use of simulation and visualization tools will

  14. Renal teratogens.

    Science.gov (United States)

    Morgan, Thomas M; Jones, Deborah P; Cooper, William O

    2014-09-01

    In utero exposure to certain drugs early in pregnancy may adversely affect nephrogenesis. Exposure to drugs later in pregnancy may affect the renin-angiotensin system, which could have an impact on fetal or neonatal renal function. Reduction in nephron number and renal function could have adverse consequences for the child several years later. Data are limited on the information needed to guide decisions for patients and providers regarding the use of certain drugs in pregnancy. The study of drug nephroteratogenicity has not been systematized, a large, standardized, global approach is needed to evaluate the renal risks of in utero drug exposures.

  15. 乳腺癌组织Epo/Epo-R表达和MVD关系及其临床意义%The Relationship between Expression of Erythropoietin/erythropoietin-receptor and Neovascularization in Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    李蓉; 陆晔; 潘湘涛; 杨育生; 严敏; 顾凤华; 顾国健

    2009-01-01

    目的研究乳腺癌患者促红细胞生成素(Epo)及受体(Epo-R)、肿瘤血管生成及其与临床病理特征之间的关系.方法对本院60例乳腺癌患者应用酶联免疫法测定Epo浓度;应用免疫组化方法检测Epo-R的表达.同时检测肿瘤微血管密度(MVD),并分析与临床病理之间的关系.结果①60例患者的Epo水平为18.50±13.29mu/ml,明显高于对照组8.10±4.96mu/ml(P0.05);④Epo-R与临床分期、有无淋巴结转移和肿瘤大小均明显相关(均为P<0.01);MVD与有无转移有关,与分期及肿块大小无关.结论乳腺癌贫血患者的Epo水平明显增高,并与Hb值呈明显的负相关关系.乳腺癌患者高表达Epo-R,并与MVD呈正相关关系;但均与有无贫血不相关.Epo-R与MVD两项指标分别与乳腺癌的临床病理有关,联合检测Epo-R和MVD更有利于正确判断患者的临床病理特征及其预后.

  16. Everolimus: the first approved product for patients with advanced renal cell cancer after sunitinib and/or sorafenib

    Directory of Open Access Journals (Sweden)

    Chris Coppin

    2010-04-01

    Full Text Available Chris CoppinMedical Oncology, BC Cancer Agency and University of British Columbia, Vancouver, CanadaAbstract: Everolimus (RAD001, Afinitor® Novartis is the first oral inhibitor of mTOR (mammalian target of rapamycin to reach the oncology clinic. Everolimus 10 mg daily achieves complete inhibition of its target at below the maximum tolerable dose for most patients. A phase III randomized placebo-controlled trial has examined the impact of everolimus in patients with clear cell renal cancers and progressive disease on or within 6 months of the VEGFR tyrosine kinase inhibitors sunitinib and/or sorafenib. The primary endpoint of progression-free survival was increased from median 1.9 to 4.9 months (hazard ratio 0.33, P < 0.001 and 25% were still progression-free after 10 months of everolimus therapy. There was a delay in time to decline of performance status and trends to improvement in quality of life, disease-related symptoms, and overall survival despite crossover of the majority of patients assigned to placebo. In 2009, everolimus was approved in the US and Europe as the only validated option for this indication. Toxicities are usually mild to moderate and can be managed with dose reduction or interruption if necessary. Opportunistic infections and non-infectious pneumonitis are seen as a class effect. Management of common practical management issues are discussed. Clinical trials are in progress to examine additional roles for everolimus in renal cancer, alone and in combination with other agents.Keywords: everolimus, drug therapy, advanced renal cancer

  17. Sarcoidose renal

    Directory of Open Access Journals (Sweden)

    AQUINO MARIA ENEDINA CLAUDINO DE

    2001-01-01

    Full Text Available Em uma mulher de 62 anos, branca, em avaliação pré-operatória de facectomia, foram detectadas alterações urinárias, tendo sido firmados os diagnósticos de calculose renal esquerda e exclusão renal homolateral. No pré-operatório da nefrectomia foram evidenciados processo pulmonar intersticial bilateral e adenopatia torácica, cuja investigação foi adiada para após a cirurgia. No rim retirado foram detectados granulomas epitelióides não necrotizantes, o mesmo ocorrendo posteriormente em biópsia transbrônquica. A paciente foi tratada com metilprednisolona, com discreta melhora pulmonar, o que não ocorreu com a função renal. O diagnóstico final foi de sarcoidose com envolvimento pulmonar, ganglionar torácico e renal.

  18. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930150 Epidermal growth factor and its recep-tor in the renal tissue of patients with acute re-nal failure and normal persons.LIU Zhihong(刘志红),et al.Jinling Hosp,Nanjing,210002.Natl Med J China 1992;72(10):593-595.Epidermal growth factor(EGF)and its receptor(EGF-R)were identified by immunohis-tochemical method(4 layer PAP)in the renaltissue specimens obtained from 11 normal kid-neys and 17 cases of acute renal failure(ARF).The quantitative EGF and EGF-R in the tissuewere expressed as positive tubules per mm~2.The amount of EGF and EGF-R in renal tissue

  19. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005234 Association between serum fetuin-A and clinical outcome in end-stage renal disease patients. WANG Kai(王开), Dept Renal Dis, Renji Hosp Shanghai, 2nd Med Univ, Shanghai 200001. Chin J Nephrol, 2005;21(2):72-75. Objective: To investigate the change of serum fetuin-A level before and after dialysis, and the association of serum fetuin-A level with clinical parameters

  20. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950351 Serum erythropoietin levels in chronic renalinsufficiency.ZHAI Depei(翟德佩),et al.DeptNephrol.General Hosp,Tianjin Med Univ,Tianjin,300000.Tianjin Med J 1995;23(1):19-21.Patients with chronic renal insufficiency(CRI) areoften associated with anemia.The deficiency of EPOproduction in the kidney is thought to be a key factorin the pathogenesis of renal anemia.Serum erythropoi-

  1. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008463 Protective effect of recombination rat augmenter of liver regeneration on kidney in acute renal failure rats. TANG Xiaopeng(唐晓鹏), et al. Dept Nephrol, 2nd Affili Hosp Chongqing Med Univ, Chongqing 400010.Chin J Nephrol 2008;24(6):417-421. Objective To investigate the protective effects of recombination rat augmenter of liver regeneration (rrALR) on tubular cell injury and renal dysfunction

  2. Renal Hemangiopericytoma

    Directory of Open Access Journals (Sweden)

    İbrahim Halil Bozkurt

    2015-03-01

    Full Text Available Hemangiopericytoma is an uncommon perivascular tumor originating from pericytes in the pelvis, head and tneck, and the meninges; extremely rarely in the urinary system. We report a case of incidentally detected renal mass in which radiologic evaluation was suggestive of renal cell carcinoma. First, we performed partial nephrectomy, and then, radical nephrectomy because of positive surgical margins and the pathological examination of the surgical specimen that revealed a hemangiopericytoma. No additional treatment was administered.

  3. The mechanisms of protective effects of erythropoietin (EPO) on sepsis induced myocardial injury in rat%促红细胞生成素对脓毒症大鼠心肌损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    秦延军; 张新亮; 于悦卿; 卞晓华; 董士民

    2014-01-01

    the EPO group (P < 0.01); (4) Compared with the Sham group,membrane potential levels of chondriosome of myocardial cell in the CLP group decreased (P <0.01),while it increased in the EPO group in comparison with the CLP group (P < 0.01) ; (5) Pathological changes of myocardium after the CLP could be lessened by the EPO treatment.Conclusions EPO may increase membrane potential levels of chondriosome and decrease the apoptosis rates of myocardial cell in rats after sepsis,and it may reduced the production of inflammatory factors to protect the myocardial cell by down-regulating NF-κB p65.Both increased membrane potential level of chonriosome and decreased inflammatory factor may implicate in myocardium protection thereby improving cardiac function after sepsis.%目的 探讨促红细胞生成素(EPO)对脓毒症大鼠心肌损伤的保护作用及其机制.方法 通过盲肠结扎穿孔引流术(CLP)建立脓毒症大鼠模型.健康SD大鼠96只,随机(随机数字法)分为3组:假手术组(Sham组,n=32)、脓毒症组(CLP组,n=32)、EPO组(n=32,脓毒症模型基础上EPO 1000 IU/kg腹腔内注射).分别于造模术后3、6、12、24 h记录心脏血流动力学指标变化,测定血清炎症反应因子水平及心肌酶变化,应用流式细胞仪检测心肌细胞线粒体膜电位、心肌细胞凋亡及心肌组织核因子-κB (NF-κB p65)表达水平;光镜下观察大鼠心肌细胞的病理学变化.所有数据以均数±标准差(-x±s)表示,采用SPSS 13.0统计软件分析,组间比较采用t检验,以P <0.05为差异具有统计学意义.结果 (1)与Sham组相比,CLP组大鼠左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室压力上升最大速度(+dp/dtmax)、左室压力下降最大速度(-dp/dtmax)均有不同程度恶化(P <0.05,P<0.01),EPO组各指标降低幅度小于CLP组(P<0.05,P<0.01);(2)与Sham组相比,CLP组各时间点血清肿瘤坏死因子-α(TNF-α)、白介素-6 (IL-6)、C-反应蛋白水平(CRP)、

  4. Arginine vasopressin increases cellular free calcium concentration and adenosine 3',5'-monophosphate production in rat renal papillary collecting tubule cells in culture

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, S.; Okada, K.; Saito, T.

    1988-09-01

    The role of calcium (Ca) in the cellular action of arginine vasopressin (AVP) was examined in rat renal papillary collecting tubule cells in culture. AVP increased both the cellular free Ca concentration ((Ca2+)i) using fura-2, and cAMP production in a dose-dependent manner. AVP-induced cellular Ca mobilization was totally blocked by the antagonist to the antidiuretic action of AVP, and somewhat weakened by the antagonist to the vascular action of AVP. 1-Deamino-8-D-AVP (dDAVP). an antidiuretic analog of AVP, also increased (Ca2+) significantly. Cellular Ca mobilization was not obtained with cAMP, forskolin (a diterpene activator of adenylate cyclase), or phorbol-12-myristate-13-acetate. The early phase of (Ca2+)i depended on the intracellular Ca pool, since an AVP-induced rise in (Ca2+)i was obtained in cells pretreated with Ca-free medium containing 1 mM EGTA, verapamil, or cobalt, which blocked cellular Ca uptake. Also, AVP increased /sup 45/Ca2+ influx during the initial 10 min, which initiated the sustained phase of cellular Ca mobilization. However, cellular cAMP production induced by AVP during the 10-min observation period was diminished in the cells pretreated with Ca-free medium, verapamil, or cobalt, but was still significantly higher than the basal level. This was also diminished by a high Ca concentration in medium. These results indicate that 1) AVP concomitantly regulates cellular free Ca as well as its second messenger cAMP production; 2) AVP-induced elevation of cellular free Ca is dependent on both the cellular Ca pool and extracellular Ca; and 3) there is an optimal level of extracellular Ca to modulate the AVP action in renal papillary collecting tubule cells.

  5. Epo Is Relevant Neither for Microvascular Formation Nor for the New Formation and Maintenance of Mice Skeletal Muscle Fibres in Both Normoxia and Hypoxia

    OpenAIRE

    Luciana Hagström; Onnik Agbulut; Raja El-Hasnaoui-Saadani; Dominique Marchant; Fabrice Favret; Jean-Paul Richalet; Michèle Beaudry; Thierry Launay

    2010-01-01

    Erythropoietin (Epo) and vascular growth factor (VEGF) are known to be involved in the regulation of cellular activity when oxygen transport is reduced as in anaemia or hypoxic conditions. Because it has been suggested that Epo could play a role in skeletal muscle development, regeneration, and angiogenesis, we aimed to assess Epo deficiency in both normoxia and hypoxia by using an Epo-deficient transgenic mouse model ( E p o - T A g h ). Histoimmunology, ELISA and real time RT-PCR did not sh...

  6. Hypogonadism and renal failure: An update

    Directory of Open Access Journals (Sweden)

    Nannan Thirumavalavan

    2015-01-01

    Full Text Available The prevalence of both hypogonadism and renal failure is increasing. Hypogonadism in men with renal failure carries with it significant morbidity, including anemia and premature cardiovascular disease. It remains unclear whether testosterone therapy can affect the morbidity and mortality associated with renal failure. As such, in this review, we sought to evaluate the current literature addressing hypogonadism and testosterone replacement, specifically in men with renal failure. The articles chosen for this review were selected by performing a broad search using Pubmed, Embase and Scopus including the terms hypogonadism and renal failure from 1990 to the present. This review is based on both primary sources as well as review articles. Hypogonadism in renal failure has a multifactorial etiology, including co-morbid conditions such as diabetes, hypertension, old age and obesity. Renal failure can lead to decreased luteinizing hormone production and decreased prolactin clearance that could impair testosterone production. Given the increasing prevalence of hypogonadism and the potential morbidity associated with hypogonadism in men with renal failure, careful evaluation of serum testosterone would be valuable. Testosterone replacement therapy should be considered in men with symptomatic hypogonadism and renal failure, and may ameliorate some of the morbidity associated with renal failure. Patients with all stages of renal disease are at an increased risk of hypogonadism that could be associated with significant morbidity. Testosterone replacement therapy may reduce some of the morbidity of renal failure, although it carries risk.

  7. Hypogonadism and renal failure: An update.

    Science.gov (United States)

    Thirumavalavan, Nannan; Wilken, Nathan A; Ramasamy, Ranjith

    2015-01-01

    The prevalence of both hypogonadism and renal failure is increasing. Hypogonadism in men with renal failure carries with it significant morbidity, including anemia and premature cardiovascular disease. It remains unclear whether testosterone therapy can affect the morbidity and mortality associated with renal failure. As such, in this review, we sought to evaluate the current literature addressing hypogonadism and testosterone replacement, specifically in men with renal failure. The articles chosen for this review were selected by performing a broad search using Pubmed, Embase and Scopus including the terms hypogonadism and renal failure from 1990 to the present. This review is based on both primary sources as well as review articles. Hypogonadism in renal failure has a multifactorial etiology, including co-morbid conditions such as diabetes, hypertension, old age and obesity. Renal failure can lead to decreased luteinizing hormone production and decreased prolactin clearance that could impair testosterone production. Given the increasing prevalence of hypogonadism and the potential morbidity associated with hypogonadism in men with renal failure, careful evaluation of serum testosterone would be valuable. Testosterone replacement therapy should be considered in men with symptomatic hypogonadism and renal failure, and may ameliorate some of the morbidity associated with renal failure. Patients with all stages of renal disease are at an increased risk of hypogonadism that could be associated with significant morbidity. Testosterone replacement therapy may reduce some of the morbidity of renal failure, although it carries risk.

  8. Renal accumulation of pentosidine in non-diabetic proteinuria-induced renal damage in rats

    NARCIS (Netherlands)

    Waanders, F; Greven, WL; Baynes, JW; Thorpe, [No Value; Kramer, AB; Nagai, R; Sakata, N; van Goor, H; Navis, G

    2005-01-01

    Background. Advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetic glomerulopathy. The role of AGEs in non-diabetic renal damage is not well characterized. First, we studied whether renal AGE accumulation occurs in non-diabetic proteinuria-induced renal damage and whether

  9. Renal accumulation of pentosidine in non-diabetic proteinuria-induced renal damage in rats

    NARCIS (Netherlands)

    Waanders, F; Greven, WL; Baynes, JW; Thorpe, [No Value; Kramer, AB; Nagai, R; Sakata, N; van Goor, H; Navis, G

    2005-01-01

    Background. Advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetic glomerulopathy. The role of AGEs in non-diabetic renal damage is not well characterized. First, we studied whether renal AGE accumulation occurs in non-diabetic proteinuria-induced renal damage and whether

  10. Effect of small dose of EPO after PCI on cardiac function and myocardial injury in patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Guo-Min Li

    2016-01-01

    Objective:To study the effect of small dose of erythropoietin (EPO) after PCI on cardiac function and myocardial injury in patients with acute myocardial infarction.Methods:A total of 86 patients with acute ST-elevation myocardial infarction who received percutaneous coronary intervention in our hospital from April 2012 to June 2015 were selected and randomly divided into EPO group and control group, serum was collected 1 week after operation to determine myocardial injury indexes, inflammation indexes, oxidative stress indexes and ventricular remodeling indexes, and color Doppler echocardiography was conducted 6 months after surgery to determine ventricular systolic and diastolic function indexes.Results:One week after operation, serum LDH, CK, CK-MB, cTnI, cTnT, sCD40L, E-selectin, P-selectin, sICAM-1, MDA, O2-, ox-LDL, PICP, CITP and PIIINP levels of EPO group were significantly lower than those of control group while GSH-Px and SOD levels were significantly higher than those of control group; 6 months after operation, LVEF of EPO group was significantly higher than that of control group while LVEDVI and LVESVI were significantly lower than those of control group.Conclusions:Small dose of EPO after PCI can alleviate myocardial damage, relieve inflammation and oxidative stress, and improve myocardial remodeling and cardiac diastolic and systolic function in patients with AMI.

  11. Mechanisms leading to sustained reversion of beta-thalassemia in mice by doxycycline-controlled Epo delivery from muscles.

    Science.gov (United States)

    Samakoglu, Selda; Bohl, Delphine; Heard, Jean Michel

    2002-12-01

    Erythropoiesis has been considered as a potential treatment for beta-thalassemia. Although Epo secretion from genetically engineered muscles allowed long-term correction of the disease in the mouse, repeated injections of rHuEpo were disappointing in human patients. Whether different mechanisms operate in humans and mice or whether Epo exhibits different biological activity depending on the administration route is currently unknown. We provide evidence that mechanisms recruited over a 36-week follow-up in beta-thalassemic mice were similar to those acting during stress-induced erythropoiesis in humans. beta-Thalassemic mice were rendered steadily normocythemic by the intramuscular injection of a tetracycline-inducible AAV vector encoding mouse Epo. Doxycycline dosage was adapted to hematocrit. Circulating red blood cells essentially synthesized beta-minor globin, the mouse equivalent to human gamma-globin. Quantification of erythroid progenitors indicated a steady-state expansion of erythroid burst-forming units programmed for beta-minor globin synthesis and a hastening of their maturation to hemoglobin-synthesizing cells. We discuss hypotheses that could account for the failure to recruit this mechanism over the long term in beta-thalassemic patients and raise the possibility of Epo gene therapy trials to treat beta-thalassemia.

  12. Use of EPO as an adjuvant in PDT of brain tumors to reduce damage to normal brain

    Science.gov (United States)

    Rendon, Cesar A.; Lilge, Lothar

    2004-10-01

    In order to reduce damage to surrounding normal brain in the treatment of brain tumors with photodynamic therapy (PDT), we have investigated the use of the cytokine erythropoietin (EPO) to exploit its well-established role as a neuroprotective agent. In vitro experiments demonstrated that EPO does not confer protection from PDT to rat glioma cells. In vivo testing of the possibility of EPO protecting normal brain tissue was carried out. The normal brains of Lewis rats were treated with Photofrin mediated PDT (6.25 mg/Kg B.W. 22 hours pre irradiation) and the outcome of the treatment compared between animals that received EPO (5000 U/Kg B.W. 22 hours pre irradiation) and controls. This comparison was made based on the volume of necrosis, as measured with the viability stain 2,3,5- Triphenyl tetrazoium chloride (TTC), and incidence of apoptosis, as measured with in situ end labeling assay (ISEL). Western blotting showed that EPO reaches the normal brain and activates the anti-apoptotic protein PKB/AKT1 within the brain cortex. The comparison based on volume of necrosis showed no statistical significance between the two groups. No clear difference was observed in the ISEL staining between the groups. A possible lack of responsivity in the assays that give rise to these results is discussed and future corrections are described.

  13. EPO protects Müller cell under high glucose state through BDNF/TrkB pathway.

    Science.gov (United States)

    Wang, Ping; Xia, Fei

    2015-01-01

    Neurotrophic factor decreased in the early stage of diabetic retinal nerve cells. Neurons damage brain derived neurotrophic factor (BDNF) and receptor TrkB expression reduced. Erythropoietin (EPO) plays an important role in protecting early diabetic retinopathy. The rats were euthanized at 24 h after EPO vitreous injection and the retina was separated. HE staining was applied to observe the pathological tissue morphology. Immunohistochemistry, immunofluorescence, and Western blot were used to detect BDNF, TrkB, extracellular signal-regulated kinase (ERK), and glial fibrillary acidic portein (GFAP) expression. Retinal structure was clear in group C, while the retinal thickness and RGCs number decreased in group B at 24 w. Retinal thickness in group E was greater than in group B but lower than in group C. GFAP and ERK expression increased in both group B and E, whereas the latter was significantly lower than the former. TrkB protein level was in group E > B > C at 4 w, while it was in group C > group E > group B at 24 w. BDNF expression in group B was higher than in group C at 4 w, whereas it was opposite at 24 w. BDNF expression increased in group E at 4 w, and it was similar in group E compared with group C at 24 w. EPO vitreous injection can increase BDNF and TrkB expression, while reduce GFAP and ERK expression in diabetes rat retina. It could protect Müller cells through BDNF/TrkB pathway to play a role of nerve nutrition.

  14. PEG化重组人促红素质量控制方法和标准研究%Study on methods and requirements for quality control of Pegylated Erythropoietin ( PEG-EPO)

    Institute of Scientific and Technical Information of China (English)

    周勇; 王丽; 于传飞; 杨鹏云; 王箐舟; 侯继锋; 王军志

    2012-01-01

    To establish methods and requirements for the quality control of PEG - EPO. Methods -.In vivo bioactivity of PEG - EPO was determined by the count of reticulocytes in normocythaemic mice. Isoforms were analyzed by cIEF. Oligosaccharide fingerprint profiling was determined by HPAEC. Purity and peptide mapping were analyzed by reverse HPLC system. Other routine tests were all carried out according to the Chinese pharmacopoeia (volume HI ,2010 edition). Results;The requirements and methods for the quality control of PEG - EPO have been established. The results of all tests were reliable and reproducible, and complied with the Chinese pharmacopoeia and guidelines for the quality control of recombinant DNA products. Conclusion;The methods and requirements for PEG - EPO showed the characteristics of assuring the products safety and efficacy, which can be used for the quality control of PEG - EPO.%目的:建立PEG化重组人促红素质量控制方法和质量标准.方法:用正常小鼠网织红细胞计数法测定体内生物学活性,使用iCE毛细管等电聚焦电泳分析异构体,用离子色谱确定N-糖链指纹图谱,反相HPLC进行Lys -C蛋白内切酶酶切的肽图分析以及纯度测定.其余检测项目按2010年版中国药典三部方法进行.结果:建立的方法经过比较和对PEG化重组人促红素的检测,结果稳定可靠,重复性好,各指标符合《人用重组DNA制品质量控制技术指导原则》和2010年版中国药典三部的要求.结论:本研究建立了一套完善的PEG化重组人促红素质量控制体系.

  15. Role of alpha-lipoic acid in the management of anemia in patients with chronic renal failure undergoing hemodialysis

    Science.gov (United States)

    El-Nakib, Gehad A; Mostafa, Tarek M; Abbas, Tarek M; El-Shishtawy, Mamdouh M; Mabrouk, Mokhtar M; Sobh, Mohammed A

    2013-01-01

    Introduction Anemia associated with chronic kidney disease is a serious complication necessitating expenditure of huge medical efforts and resources. This study investigates the role of alpha-lipoic acid (ALA) in end stage renal disease patients undergoing hemodialysis. By the virtue of its antioxidative effects, ALA is expected to act as an erythropoietin (EPO) adjuvant, and also has extended beneficial effects on endothelial dysfunction. Methods Forty-four patients undergoing hemodialysis and receiving EPO were randomized into two groups: the first group received ALA 600 mg once daily for 3 months; while the other group represented the control group. Parameters measured at baseline and at end of study were hemoglobin, EPO doses, EPO resistance index (ERI), iron store indices, malondialdehyde, oxidized low-density lipoprotein (ox-LDL), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and asymmetric dimethylarginine (ADMA), as well as routine laboratory follow-up. Results EPO doses and ERI were significantly decreased in the treatment group, while they did not change in the control group. Hemoglobin, iron store indices, malondialdehyde, oxidized ox-LDL, IL-6, TNF-α, and ADMA were similar in both treatment and control groups at baseline, and did not change by the end of study period. Likewise, routine laboratory measures were not affected by the treatment. Conclusion ALA could be used in hemodialysis patients to reduce requirements for EPO. However, larger and longer term studies are required to clarify the exact role of ALA in hemodialysis as well as in pre-hemodialysis patients. PMID:24023521

  16. Study of Immunoassay Methods for Recombinant Human Erythropoietin(rhEPO)Using Competitive ELISA

    Institute of Scientific and Technical Information of China (English)

    Jin YAN; Jie Bo MI; Wen Bao CHANG

    2004-01-01

    Two different immunoassay methods, competitive indirect enzyme-linked immuno- sorbent assay (CI-ELISA) and amplificative competitive indirect ELISA (ACI-ELISA) using biotin-avidin complex system were studied to detect rhEPO.The linear ranges were 50-20000 ng/mL and 10-50000 ng/mL for CI-ELISA and ACI-ELISA, respectively.The low detection limits of CI-ELISA and ACI-ELISA were 62.8 ng/mL and 8.5 ng/mL, respectively.

  17. QGSjet II and EPOS hadronic interaction models: comparison with the Yakutsk EAS array data

    Energy Technology Data Exchange (ETDEWEB)

    Knurenko, S.P.; Sabourov, A.V. [Yu. G. Shafer Institute for Cosmophysical Research and Aeronomy (Russian Federation)

    2009-12-15

    Various hadronic interaction models were used in extensive air showers simulations. This resulted in ambiguous estimation of primary energy, cosmic ray flux intensity, mass composition, etc. Several revisions of models have been made recently; for example, third major version of QGSjet II (QGSjet II-03) model was released, new models based on actual accelerator data appeared (EPOS). Employment of newer models always leads to new comprehension of experimental results. Nevertheless, in this case there still is some ambiguity. It is a matter of how correct does the model extrapolate characteristics of primary particle interaction with nuclei of the air from high energies to ultra-high.

  18. Comparison of EPOS and QGSJET-II in EAS Simulation using CORSIKA code

    CERN Document Server

    Thakuria, Chabin Ch

    2012-01-01

    In this work we compare the predictions of two representative hadronic interaction models, EPOS 1.99, and QGSJET II-03 with several extensive air showers (EAS) parameters for proton and iron primaries in the energy range $10^{17}$ - $10^{19} eV$ using CORSIKA-6990. The EAS parameters depth of shower maximum, shower size, size of muon shower, muon number distribution, electron number distribution,size of hadron shower, hadron energy sum, electron muon correlations, and, hadron energy spectra are studied in this paper.

  19. Role of NF-κB in protection of EPO pretreatment on neonatal rat cardiac myocytes with hypoxia/reoxygenation injury

    Institute of Scientific and Technical Information of China (English)

    QIN Chuan; XIAO Ying-bin; ZHONG Qian-jin; CHEN Lin; WANG Xue-feng

    2005-01-01

    Objective:To observe the protective effects of erythropoietin (EPO) pretreatment on cardiac myocyte with hypoxia/reoxygenation (H/R) injury and the role of NF-κB in this effects. Methods:After the H/R model of cardiac myocytes of neonatal rats was established, the cultured cardiac myocytes were divided into 4 groups, including EPO pretreatment group ( EPO 10 U/ml 24 h before H/R), EPO pretreatment + PDTC group( EPO 10 U/ml and PDTC 5 μg/ml 24 h before H/R), PDTC group (PDTC 5 μg /ml 24 h before H/R) and control group. Before and after the H/R, assay of LDH concentration in the culture medium, the survival rate of the myocytes tested by MTT chromatometry and the apoptosis by flow cytometry were undertaken. Activation of NF-κB was determined by EMSA before and after H/R. Results:EPO pretreatment markedly reduced the LDH concentration in the medium, elevated the survival rate of myocytes and inhibited the apoptosis after H/R. Addition of PDTC during the pretreatment abolished the protective effects of EPO pretreatment. NF-κB was markedly activated during EPO pretreatment and PDTC inhibited the activation. However, after H/R, the activity of NF-κB in myocytes with EPO pretreatment was significantly inhibited compared to the other myocytes. Conclusion:NF-κB is significantly activated during EPO pretreatment, but is inhibited after H/R, which is correlated with the protective effects of EPO pretreatment on cardiac myocytes with H/R. This phenomenon can be explained as the negative feedback mechanism of the activation of NF-κB.

  20. The protective effect of erythropoietin pretreatment on ischemic acute renal failure in rats

    Directory of Open Access Journals (Sweden)

    Jing-Guang Liao

    2016-09-01

    Full Text Available Objective: To investigate the protective effect of erythropoietin (EPO pretreatment on ischemic acute renal failure in rats and its molecular mechanism. Methods: Male Sprague–Dawley rats were selected as experimental animals and they were randomly divided into the sham operation group (sham group, ischemia-reperfusion injury group (IRI group and EPO pretreatment group (EPO group. Each group had 15 rats. Serum specimens and renal specimens were collected after a IRI model was built for 4, 12 and 24 h. The contents of creatinine, urea nitrogen tumor necrosis factor-alpha (TNF-a, interleukin-1 (IL-1, IL-6 and IL-8 in serum and the contents of TNF-a, IL- 1, IL-6, IL-8, toll like receptor 4 (TLR4 and nuclear factor-kappa B (NF-kB in the kidney tissue were determined. Results: After 4, 12 and 24 h reperfusion, there were differences between the contents of creatinine, urea nitrogen TNF-a, IL-1, IL-6 and IL-8 in serum and the contents of TNF-a, IL-1, IL-6, IL-8, TLR4 and NF-kB in rats of the three groups (P < 0.05. The contents of creatinine, urea nitrogen TNF-a, IL-1, IL-6 and IL-8 in serum and the contents of TNF-a, IL-1, IL-6, IL-8, TLR4 and NF-kB in the kidney tissue in rats of the IRI group were significantly higher than those of the sham group; and the contents of creatinine, urea nitrogen TNF-a, IL-1, IL-6 and IL-8 in serum and the contents of TNF-a, IL-1, IL-6, IL- 8, TLR4 and NF-kB in the kidney tissue in rats of the EPO group were distinctly lower than those of the IRI group. Conclusions: EPO pretreatment can protect the renal function of rats with ischemic acute renal failure by inhibiting the TLR4/NF-kB pathway mediated inflammatory responses.

  1. The use of vertical and horizontal surface displacements at EPOS GNSS stations in Greenland to study ice sheet mass balance

    DEFF Research Database (Denmark)

    Khan, Shfaqat Abbas

    2014-01-01

    and present-day changes in ice mass. Superimposed on longer-term trends, an anomalous ‘pulse’ of uplift accumulated at many GNSS stations during an approximate six-month period in 2010 and 2012. This anomalous uplift is spatially correlated with the 2010 melting day anomaly (Bevis et al.,2012) and show...... present data from arctic GNSS stations included in the EPOS network. The arctic EPOS GNSS network consists of 16 continuous GPS stations spread across Greenland. This network is able to map the velocity fields associated with, plate motion, postglacial rebound and improve our understanding of tectonic...... processes and present-day ice mass changes in Greenland, allowing scientists to quickly detect and analyze any abrupt changes in the rate of ice loss in this region. Recent analyses of the EPOS-GNSS data and GNET data (Greenland GPS Network) show that the entire network is uplifting in response to past...

  2. Tolerability and efficacy of erythropoietin (EPO) treatment in traumatic spinal cord injury: a preliminary randomized comparative trial vs. methylprednisolone (MP).

    Science.gov (United States)

    Costa, Davide Dalla; Beghi, Ettore; Carignano, Paola; Pagliacci, Cristina; Faccioli, Franco; Pupillo, Elisabetta; Messina, Paolo; Gorio, Alfredo; Redaelli, Tiziana

    2015-09-01

    The only available treatment of traumatic spinal cord injury (TSCI) is high-dose methylprednisolone (MP) administered acutely after injury. However, as the efficacy of MP is controversial, we assessed the superiority of erythropoietin (EPO) versus MP in improving clinical outcome of acute TSCI. Patients aged 18 to 65 years after C5-T12 injury, and grade A or B of the ASIA Impairment Scale (AIS), admitted within 8 h, hemodynamically stable, were randomized to MP according to the NASCIS III protocol or EPO iv (500 UI/kg, repeated at 24 and 48 h). Patients were assessed by an investigator blind to treatment assignment at baseline and at day 3, 7, 14, 30, 60 and 90. Primary end point: number of responders (reduction of at least one AIS grade). Secondary end points: treatment safety and the effects of drugs on a number of disability measures. Frequentistic and post hoc Bayesian analyses were performed. Eight patients were randomized to MP and 11 to EPO. Three patients (27.3 %) on EPO and no patients on MP reached the primary end point (p = 0.17). No significant differences were found for the other disability measures. No adverse events or serious adverse events were reported in both groups. The Bayesian analysis detected a 91.8 % chance of achieving higher success rates on the primary end point with EPO in the intention-to-treat population with a 95 % chance the difference between EPO and MP falling in the range (-0.10, 0.51) and a median value of 0.2. The results of Bayesian analysis favored the experimental treatment.

  3. Enduring Power of Attorney (EPoA – comparison between Austrian and German Law

    Directory of Open Access Journals (Sweden)

    Michael Ganner

    2015-04-01

    Full Text Available ENGLISH: With the establishment of the United Nations Convention on the Rights of Persons with Disabilities (CRPD the treatment of people with disabilities is changing from a protective perspective to a rights - based approach. The Enduring Power of Attorney (EPoA is an important instrument, which helps with the implementation of the CRPD into national law. As an instrument of self - determined substituted decision - making it is recognised as the best practice model to safeguard the autonomy of people suffering the deprivations of age and other disabilities. This article touches briefly on general supported and substituted decision - making instruments and then goes on to examine the differences and similarities, advantages and disadvantages b e- tween Austrian and German laws concerning EPoAs. DEUTSCH: Mit der Umsetzung der UN-Behindertenrechtskonvention findet ein Paradigmenwechsel und Umdenken im Umgang mit Personen mit Behinderungen statt. Der Primat der Fürsorge weicht einem liberalen, auf Menschenrechten basierenden Ansatz. In diesem Kontext ist die Vorsorgevollmacht ein effektives Mittel, das die Implementation der UN-Behindertenrechtskonvention in nationales Recht vorantreibt und die Selbstbestimmung und Eigenständigkeit altersbedingt eingeschränkter Menschen und von Menschen mit Behinderungen gewährleistet. Dieser Artikel beschäftigt sich einleitend mit allgemeinen Rechtsinstrumenten der (unterstützten Entscheidungsfindung bei nicht selbst entscheidungsfähigen Personen und analysiert in weiterer Folge Gemeinsamkeiten und Unterschiede sowie Vor- und Nachteile der Vorsorgevollmacht nach österreichischem und deutschem Recht.

  4. Exposure parameters in proton beam writing for KMPR and EPO Core negative tone photoresists

    Energy Technology Data Exchange (ETDEWEB)

    Ynsa, M.D., E-mail: m.ynsa@uam.es [Centro de Micro-Analisis de Materiales (CMAM), Universidad Autonoma de Madrid, Campus de Cantoblanco Edif. 22, Faraday 3, E-28049 Madrid (Spain); Departamento de Fisica Aplicada C-12, Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid (Spain); Shao, P.; Kulkarni, S.R.; Liu, N.N.; Kan, J.A. van [Centre for Ion Beam Applications (CIBA), Department of Physics, National University of Singapore ,117542 Singapore (Singapore)

    2011-10-15

    In spite of its recent establishment, proton beam writing (PBW) has already demonstrated to be a highly competitive lithographic technique. PBW is a fast direct-write technique capable of producing high-aspect-ratio micro- and nano-structures in resist material. Typical applications can be found in nanoimprinting, biomedical research, photonics, and optics, among other fields. The progress of PBW is linked to the successful introduction of new resist materials. In this paper, KMPR and EPO Core, negative tone photoresists are tested on their compatibility with PBW. KMPR resist has similar chemical and process properties compared to SU-8. Employing UV lithography on KMPR resist, details of 30 {mu}m have been obtained in Ni, indicating a possible advantage compared to SU-8 for optical lithography . In this study, the sensitivity to MeV proton exposure and sub-micron feature sizes are presented in KMPR. PBW has been also combined with Ni electroplating in order to determine the suitability of KMPR and EPO Core resist to fabricate 3D metallic moulds and stamps.

  5. The Solar System Radio Explorer Kiosk - Leveraging Other E/PO Programs for Greater Impact

    Science.gov (United States)

    Garcia, L. N.; Reinisch, B. W.; Taylor, W. W.; Thieman, J. R.; Mendez, F.; Riccobono, M.

    2004-12-01

    The Solar System Radio Explorer Kiosk (SSREK) - a newly won small E/PO follow-on to a NASA/OSS research grant - is designed to leverage existing NASA E/PO projects and other education programs to enable a large return from a small investment. The SSREK project will create an interactive museum kiosk to engage and teach visitors about Jupiter and the Sun by learning what their low frequency radio bursts may be telling us about these worlds. This project will work with the network of radio observers and the archive of data obtained through the NASA-sponsored Radio Jove project. The SSREK project is partnering with the Maryland Science Center (MSC) as a test site for the SSREK. The MSC will enable us to ensure that this project meets the requirements of their museum environment. We are also partnering with the National Federation of the Blind (NFB) to help us enable museum visitors with visual impairments to share in the excitement of science and help these visitors recognize how other senses besides sight can be used to do science. Both the MSC and NFB will assist us in formative and summative evaluation of the project. All of the software and designs for the wheelchair-accessible arcade-style cabinet will be made available on the associated web site hosted at NASA/GSFC - further extending the reach of the project.

  6. Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO

    Directory of Open Access Journals (Sweden)

    Ebert S

    2012-03-01

    Full Text Available Augustinus Bader1, Sabine Ebert1, Shibashish Giri1, Mathias Kremer2, Shuhua Liu2, Andreas Nerlich5, Christina I Günter³, Dagmar U Smith4, Hans-Günther Machens2,31Department of Applied Stem Cell Biology and Cell Techniques, Centre for Biotechnology and Biomedicine, University of Leipzig, Leipzieg, 2Department of Plastic and Hand Surgery, University of Lübeck, Lübeck, 3Department of Plastic and Hand Surgery, Technische Universität München, Munich, 4Münchner Studienzentrum, Technische Universität München, Munich, 5Institute of Pathology, Klinikum München-Bogenhausen, Munich, GermanyBackground: Acceleration of skin regeneration is still an unsolved problem in the clinical treatment of patients suffering from deep burns and scalds. Although erythropoietin (EPO has a protective role in a wide range of organs and cells during ischemia and after trauma, it has been recently discovered that EPO is not tissue-protective in the common β subunit receptor (βCR knockout mouse. The protective capacity of EPO in tissue is mediated via a heteroreceptor complex comprising both the erythropoietin receptor (EPOR and βCR. However, proof of coexpression of these heterogenic receptors in regenerating skin after burns is still lacking.Methods: To understand the role of nanosized recombinant human erythropoietin (rhEPO in wound healing, we investigated the effects of subcutaneous injections of EPO on skin regeneration after deep second-degree scalding injuries. Our aim was to determine if joint expression of EPOR and βCR is a prerequisite for the tissue-protective effect of rhEPO. The efficiency in wound regeneration in a skin scalding injury mouse model was examined. A deep second-degree dermal scald injury was produced on the backs of 20 female Balb/c mice which were subsequently randomized to four experimental groups, two of which received daily subcutaneous injections of rhEPO. At days 7 and 14, the mice were sacrificed and the effects of rhEPO were

  7. Women in EPOS: the role of women in a large pan-European Research Infrastructure for Solid Earth sciences

    Science.gov (United States)

    Calignano, Elisa; Freda, Carmela; Baracchi, Laura

    2017-04-01

    Women are outnumbered by men in geosciences senior research positions, but what is the situation if we consider large pan-European Research Infrastructures? With this contribution we want to show an analysis of the role of women in the implementation of the European Plate Observing System (EPOS): a planned research infrastructure for European Solid Earth sciences, integrating national and transnational research infrastructures to enable innovative multidisciplinary research. EPOS involves 256 national research infrastructures, 47 partners (universities and research institutes) from 25 European countries and 4 international organizations. The EPOS integrated platform demands significant coordination between diverse solid Earth disciplinary communities, national research infrastructures and the policies and initiatives they drive, geoscientists and information technologists. The EPOS architecture takes into account governance, legal, financial and technical issues and is designed so that the enterprise works as a single, but distributed, sustainable research infrastructure. A solid management structure is vital for the successful implementation and sustainability of EPOS. The internal organization relies on community-specific Working Packages (WPs), Transversal WPs in charge of the overall EPOS integration and implementation, several governing, executive and advisory bodies, a Project Management Office (PMO) and the Project Coordinator. Driven by the timely debate on gender balance and commitment of the European Commission to promote gender equality in research and innovation, we decided to conduct a mapping exercise on a project that crosses European national borders and that brings together diverse geoscience disciplines under one management structure. We present an analysis of women representation in decision-making positions in each EPOS Working Package (WP Leader, proxy, legal, financial and IT contact persons), in the Boards and Councils and in the PMO

  8. Tearing down the barriers to daily home hemodialysis and achieving the highest value renal therapy through holistic product design.

    Science.gov (United States)

    Kenley, R S

    1996-04-01

    Renal therapy value can be defined as the ratio of outcomes achieved by a dialytic therapy to the total cost of providing that therapy. One desirable goal of any dialysis modality would be the achievement of maximum value. Unfortunately, with conventional hemodialysis and peritoneal dialysis modalities, improving outcomes has always been linked to a simultaneous increase in costs, thereby leaving value relatively unchanged. However, a new modality, daily home hemodialysis, finally may allow this linkage to be broken. The outcomes are dramatically improved as a result of a higher quantity and quality of dialysis dose resulting from the greater frequency of treatments. The costs can be reduced by minimizing the consumed items, avoiding the labor and overhead of dialysis clinics, and reducing the costs associated with morbidity. Provision of this therapy is, however, predicated on the availability of instrumentation designed specifically for it because conventional equipment designed for in-center use is not suitable. By starting with a clean sheet of paper and incorporating such features as insitu reuse of the entire extracorporeal circuit, remote telemonitoring, automated system disinfection, and integrated water purification, most of the impediments to performing this modality can be overcome.

  9. Renal Cysts

    Science.gov (United States)

    ... as “simple” cysts, meaning they have a thin wall and contain water-like fluid. Renal cysts are fairly common in ... simple kidney cysts, meaning they have a thin wall and only water-like fluid inside. They are fairly common in ...

  10. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970363 Effect on serum PTH and 1, 25(OH)2 D3levels of rapid correction of metabolic acidosis in CRFpatients with secondary hyperparathyroidism. YUANQunsheng(袁群生), et al. Renal Div, PUMC Hosp,Beijing, 100730. Chin J Nephrol 1996; 12(6): 328-331.

  11. Urotensin II Induces ER Stress and EMT and Increase Extracellular Matrix Production in Renal Tubular Epithelial Cell in Early Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Xin-Xin Pang

    2016-07-01

    Full Text Available Background/Aims: Urotensin II (UII and its receptor are highly expressed in the kidney tissue of patients with diabetic nephropathy (DN. The aim of this study is to examine the roles of UII in the induction of endoplasmic reticulum stress (ER stress and Epithelial-mesenchymal transition (EMT in DN in vivo and in vitro. Methods: Kidney tissues were collected from patients with DN. C57BL/6 mice and mice with UII receptor knock out were injected with two consecutive doses of streptozotocin to induce diabetes and were sacrificed at 3th week for in vivo study. HK-2 cells in vitro were cultured and treated with UII. Markers of ER stress and EMT, fibronectin and type IV collagen were detected by immunohistochemistry, real time PCR and western blot. Results: We found that the expressions of protein of UII, GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were upregulated while E-cadherin protein was downregulated as shown by immunohistochemistry or western blot analysis in kidney of diabetic mice in comparison to normal control; moreover expressions of GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were inhibited while E-caherin expression was enhanced in kidney in diabetic mice with UII receptor knock out in comparison to C57BL/6 diabetic mice. In HK-2 cells, UII induced upregulation of GRP78, CHOP, ALPHA-SMA, fibroblast-specifc protein 1(FSP-1, fibronectin and type collagen and downregulation of E-cadherin. UII receptor antagonist can block UII-induced ER stress and EMT; moreover, 4-PBA can inhibit the mRNA expression of ALPHA-SMA and FSP1 induced by UII in HK-2 cells. Conclusions: We are the first to verify UII induces ER stress and EMT and increase extracellular matrix production in renal tubular epithelial cell in early diabetic mice. Moreover, UII may induce renal tubular epithelial EMT via triggering ER stress pathway in vitro, which might be the new pathogenic pathway for the development of renal fibrosis in DN.

  12. Drug-induced renal injury

    African Journals Online (AJOL)

    Drugs can cause acute renal failure by causing pre-renal, intrinsic or post-renal toxicity. Pre-renal ... incidence of drug dose adjustment in renal impairment in the SAMJ. ... Fever, haemolytic anaemia, thrombocytopenia, renal impairment and.

  13. Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen-glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

    DEFF Research Database (Denmark)

    Montero, Maria; Rom Poulsen, Frantz; Noraberg, Jens;

    2007-01-01

    of hematopoietic bioactivity, is the chemically modified, EPO-derivative carbamylerythropoietin (CEPO). For comparison of the neuroprotective effects of CEPO and EPO, we subjected organotypic hippocampal slice cultures to oxygen-glucose deprivation (OGD) or N-methyl-d-aspartate (NMDA) excitotoxicity. Hippocampal...

  14. Dose effect evaluation and therapeutic window of the neuro-EPO nasal application for the treatment of the focal ischemia model in the Mongolian gerbil.

    Science.gov (United States)

    Teste, Iliana Sosa; Tamos, Yuneidys Mengana; Cruz, Yamila Rodríguez; Cernada, Adriana Muñoz; Rodríguez, Janette Cruz; Martínez, Nelvis Subirós; Antich, Rosa Maria Coro; González-Quevedo, Alina; Rodríguez, Julio Cesar García

    2012-01-01

    Cerebrovascular disease is the third leading cause of death and the leading cause of disability in Cuba and in several developed countries. A possible neuroprotective agent is the rHu-EPO, whose effects have been demonstrated in models of brain ischemia. The Neuro-EPO is a derivative of the rHu-EPO that avoids the stimulation of erythropoiesis. The aim of this study was to determine the Neuro-EPO delivery into the central nervous system (CNS) to exert a neuroprotective effect in cerebral ischemia model of the Mongolian gerbil. The Neuro-EPO in a rate of 249.4 UI every 8 hours for 4 days showed 25% higher viability efficacy (P > 0.01), improving neurological score and behavior of the spontaneous exploratory activity, the preservation of CA3 areas of the hippocampus, the cortex, and thalamic nuclei in the focal ischemia model of the Mongolian gerbil. In summary, this study, the average dose-used Neuro-EPO (249.4 UI/10 μL/every 8 hours for 4 days), proved to be valid indicators of viability, neurological status, and spontaneous exploratory activity, being significantly lower than that reported for the systemically use of the rHu-EPO as a neuroprotectant. Indeed, up to 12 h after brain ischemia is very positive Neuro-EPO administration by the nasal route as a candidate for neuroprotection.

  15. Central Administration of Insulin and Leptin Together Enhance Renal Sympathetic Nerve Activity and Fos Production in the Arcuate Nucleus

    Science.gov (United States)

    Habeeballah, Hamza; Alsuhaymi, Naif; Stebbing, Martin J.; Jenkins, Trisha A.; Badoer, Emilio

    2017-01-01

    There is considerable interest in the central actions of insulin and leptin. Both induce sympatho-excitation. This study (i) investigated whether centrally administered leptin and insulin together elicits greater increases in renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) than when given alone, and (ii) quantified the number of activated neurons in brain regions influencing SNA, to identify potential central sites of interaction. In anesthetised (urethane 1.4–1.6 g/kg iv) male Sprague-Dawley rats, RSNA, MAP, and HR were recorded following intracerebroventricular (ICV) saline (control; n = 5), leptin (7 μg; n = 5), insulin (500 mU; n = 4) and the combination of leptin and insulin; (n = 4). Following leptin or insulin alone, RSNA was significantly increased (74 and 62% respectively). MAP responses were not significantly different between the groups. Insulin alone significantly increased HR. Leptin alone also increased HR but it was significantly less than following insulin alone (P < 0.005). When leptin and insulin were combined, the RSNA increase (124%) was significantly greater than the response to either alone. There were no differences between the groups in MAP responses, however, the increase in HR induced by insulin was attenuated by leptin. Of the brain regions examined, only in the arcuate nucleus did leptin and insulin together increase the number of Fos-positive cell nuclei significantly more than leptin or insulin alone. In the lamina terminalis and rostroventrolateral medulla, leptin and insulin together increased Fos, but the effect was not greater than leptin alone. The results suggest that when central leptin and insulin levels are elevated, the sympatho-excitatory response in RSNA will be greater. The arcuate nucleus may be a common site of cardiovascular integration. PMID:28119622

  16. Renal failure (chronic)

    OpenAIRE

    Clase, Catherine

    2011-01-01

    Chronic renal failure is characterised by a gradual and sustained decline in renal clearance or glomerular filtration rate (GFR). Continued progression of renal failure will lead to renal function too low to sustain healthy life. In developed countries, such people will be offered renal replacement therapy in the form of dialysis or renal transplantation. Requirement for dialysis or transplantation is termed end-stage renal disease (ESRD).Diabetes, glomerulonephritis, hypertension, pyelone...

  17. MAIIA EPO SeLect-a rapid screening kit for the detection of recombinant EPO analogues in doping control: inter-laboratory prevalidation and normative study of athlete urine and plasma samples.

    Science.gov (United States)

    Dehnes, Yvette; Myrvold, Linda; Ström, Helene; Ericsson, Magnus; Hemmersbach, Peter

    2014-01-01

    Recombinant analogues of erythropoietin (EPO), epoetins, have been misused by athletes due to their performance enhancing effect since the first pharmaceutical epoetin was launched in 1987. The current methods for screening urine and plasma samples for the presence of epoetins, IEF and SAR-PAGE, have high sensitivity but are time-consuming to carry out. In an effort to ease and speed up the screening procedure for EPO, MAIIA Diagnostics has developed a combined affinity chromatography and lateral flow immunoassay, MAIIA EPO SeLect, which determines the percentage of migrated isoforms (PMI) of EPO in a sample. The reproducibility of the kit was tested by analyzing a set of negative and positive urine and plasma samples in three different laboratories. All data were analyzed with both curve fit parameters from the individual assay runs, and with lot-specific predefined curve calibration. To get a measure of endogenous variation, a normative study with athlete urine and plasma samples was conducted. The average intra-laboratory variation was 6.7% while the inter-laboratory variation for all samples was calculated to 8.8%. The athlete samples yielded an average PMI and standard deviation of 71.4 ± 7.7 for urine and 83.1 ± 10.2 for plasma, respectively. There were no signs of deviating results from tested effort urines. The results also support the use of predefined curve parameters.

  18. Fc-fragment removal allows the EPO-Fc fusion protein to be detected in blood samples by IEF-PAGE.

    Science.gov (United States)

    Postnikov, Pavel; Krotov, Grigory; Mesonzhnik, Natalia; Efimova, Yulia; Rodchenkov, Grigory

    2015-01-01

    EPO-Fc proteins have been under investigation as a potential drug for treating anaemia and have shown larger half-life values than other erythropoiesis-stimulating agents (ESAs). Sodium dodecyl sulfate/sodium N-lauroylsarcosinate polyacrylamide gel electrophoresis (SDS/SAR-PAGE) methods and subsequent immunoblotting are used for routine anti-doping analysis. This paper reports that EPO-Fc fusion proteins can be detected in serum samples by isoelectric focusing-polyacrylamide gel electrophoresis (IEF-PAGE) in carrier ampholyte-based gels with a pH 2-6 gradient after removing the Fc part via site-specific IdeS protease cleavage. The IdeS-digested EPO-Fc protein yields three fragments: two Fc fragments and one dimeric EPO-hinge fragment. After IEF-PAGE was followed by double Western blotting with chemiluminescent detection, the dimeric EPO-hinge fragment showed a unique isoelectric pattern, which differed from those of any other currently known analogue of EPO. We observed that the removal of the Fc fragment from EPO-Fc reduced the apparent molecular weight of entire fusion protein and increased its electrophoretic mobility. As a result, the band for the EPO-hinge fragment was located in a region between the rEPO and NESP standards, at which lower amounts of serum proteins are present. Simple and selective protocols for determining the EPO-Fc protein in human serum were developed to extend the methodological anti-doping arsenal. This protocol has been characterized. The limit of detection (LOD) of the IEF-PAGE method was 20 pg, and that of SDS/SAR-PAGE was 15 pg.

  19. EPO improves the proliferation and inhibits apoptosis of trophoblast and decidual stromal cells through activating STAT-5 and inactivating p38 signal in human early pregnancy.

    Science.gov (United States)

    Ji, Yu Qing; Zhang, Yu Quan; Li, Ming Qing; Du, Mei Rong; Wei, Wei Wei; Li, Da Jin

    2011-01-01

    The erythropoietin (EPO) belongs to the family of angiogenic factors, which is regulated by Hypoxia-inducible factor- 1α (HIF-1α). As known, EPO are expressed in human villi and decidua, but the function is not clear. In this study, we investigated the expression and roles of HIF-1α, EPO and its receptor (EPOR) in the biological functions of trophoblast and decidual stromal cell (DSC) in human early pregnancy. The expression of EPO, EPOR and HIF-1α was evaluated in the villi and deciduas by RT-PCR and immunohistochemistry. Thereafter, we silenced HIF-1α expression in HTR-8/SVneo cell line and decidual stromal cells (DSCs). The effects of EPO on the proliferation and apoptosis of trophoblasts and DSCs, and activation of signal molecules were investigated by BrdU proliferation assay, flow cytometry and western blot, respectively. We have observed that the HIF-1α silence results in the lower expression of EPO in trophoblasts and DSCs. The anti-EPO neutralizing antibody can inactivate the phosphorylation of STAT5 and activate p38 of these cells in a dosage-dependent manner. Furthermore, the expressions of EPO, EPOR and HIF-1α in the villi and decidua from the unexplained miscarriage were significantly lower than that of the normal early pregnancy. This study suggests that HIF-1α may regulate the expression of EPO, which plays a favorable regulatory role in the proliferation and survival of human first-trimester trophoblast cells and DSCs via inactivating p38 and activating STAT5 in an autocrine manner, while the inadequate EPO expression at maternal-fetal interface may lead to pregnancy wastage in humans.

  20. An Intranasal Formulation of Erythropoietin (Neuro-EPO) Prevents Memory Deficits and Amyloid Toxicity in the APPSwe Transgenic Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Rodríguez Cruz, Yamila; Strehaiano, Manon; Rodríguez Obaya, Teresita; García Rodríguez, Julío César; Maurice, Tangui

    2017-01-01

    Erythropoietin (EPO) is a cytokine known to have effective cytoprotective action in the brain, particularly in ischemic, traumatic, inflammatory, and neurodegenerative conditions. We previously reported the neuroprotective effect of a low sialic form of EPO, Neuro-EPO, applied intranasally in rodent models of stroke or cerebellar ataxia and in a non-transgenic mouse model of Alzheimer's disease (AD). Here we analyzed the protective effect of Neuro-EPO in APPSwe mice, a reference transgenic mouse model of AD. Mice were administered 3 times a day, 3 days in the week with Neuro-EPO (125, 250 μg/kg) intranasally, between 12 and 14 months of age. Motor responses, general activity, and memory responses were analyzed during and after treatment. The deficits in spontaneous alternation, place learning in the water-maze, and novel object recognition observed in APPSwe mice were alleviated by the low dose of Neuro-EPO. Oxidative stress, neuroinflammation, trophic factor levels, and a synaptic marker were analyzed in the hippocampus or cortex of the animals. The increases in lipid peroxidation or in GFAP and Iba-1 contents in APPSwe mice were significantly reduced after Neuro-EPO. Activation of intrinsic and extrinsic apoptotic pathways was analyzed. The increases in Bax/Bcl-2 ratio, TNFα, or Fas ligand levels observed in APPSwe mice were reduced by Neuro-EPO. Finally, immunohistochemical and ELISA analyses of Aβ1-42 levels in the APPSwe mouse cortex and hippocampus showed a marked reduction in Aβ deposits and in soluble and insoluble Aβ1-42 forms. This study therefore confirmed the neuroprotective activity of EPO, particularly for an intranasally deliverable formulation, devoid of erythropoietic side effects, in a transgenic mouse model of AD. Neuro-EPO alleviated memory alterations, oxidative stress, neuroinflammation, apoptosis induction, and amyloid load in 14-month-old APPSwe mice.

  1. Renal papillary necrosis and pyelonephritis accompanying fenoprofen therapy.

    Science.gov (United States)

    Husserl, F E; Lange, R K; Kantrow, C M

    1979-10-26

    Renal papillary necrosis occurred after fenoprofen calcium administration in a patient with systemic lupus erythematosus and urinary tract infection. Possible mechanisms of renal damage may be hypersensitivity, decreased blood flow, and decreased production of a prostaglandin E-like substance.

  2. Inhibition of endogenous hydrogen sulfide production in clear-cell renal cell carcinoma cell lines and xenografts restricts their growth, survival and angiogenic potential.

    Science.gov (United States)

    Sonke, Eric; Verrydt, Megan; Postenka, Carl O; Pardhan, Siddika; Willie, Chantalle J; Mazzola, Clarisse R; Hammers, Matthew D; Pluth, Michael D; Lobb, Ian; Power, Nicholas E; Chambers, Ann F; Leong, Hon S; Sener, Alp

    2015-09-15

    Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H2S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H2S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism and angiogenesis. Using the H2S-specific probe MeRhoAz, it was found that H2S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H2S-producing enzymes could reduce the proliferation, metabolism and survival of ccRCC cell lines, as determined by live-cell imaging, XTT/ATP assay, and flow cytometry respectively. Using the chorioallantoic membrane angiogenesis model, it was found that systemic inhibition of endogenous H2S production was able to decrease vascularization of VHL-deficient ccRCC xenografts. Endogenous H2S production is an attractive new target in ccRCC due to its involvement in multiple aspects of disease.

  3. Hepatic erythropoietin response in cirrhosis

    DEFF Research Database (Denmark)

    Risør, Louise M; Fenger, Mogens; Olsen, Niels V;

    2016-01-01

    BACKGROUND: Erythropoietin (EPO) is produced in the liver during fetal life, but after birth the production shifts to the kidneys. The liver maintains a production capacity of 10% of the total EPO-production, but can be up-regulated to 100%. Previous studies have demonstrated both elevated...... and reduced concentrations of EPO in cirrhosis. Increased EPO concentrations could be expected due to anemia, hypoxia, renal hypoperfusion, or EPO-mediated hepatoprotective mechanisms. In contrast, poor hepatic production capacity may cause reduced EPO concentrations in cirrhosis. In the present paper we...... aimed to study hepatic and renal venous concentrations of EPO in relation to the severity of the disease. MATERIALS AND METHODS: We included 24 patients with alcoholic cirrhosis and eight age-matched healthy controls. All had a full catheterization performed with the determination of EPO concentrations...

  4. Development and evaluation of gastroretentive raft forming systems incorporating curcumin-Eudragit® EPO solid dispersions for gastric ulcer treatment.

    Science.gov (United States)

    Kerdsakundee, Nattha; Mahattanadul, Sirima; Wiwattanapatapee, Ruedeekorn

    2015-08-01

    Novel raft forming systems incorporating curcumin-Eudragit® EPO solid dispersions were developed to prolong the gastric residence time and provide for a controlled release therapy of curcumin to treat gastric ulcers. The solid dispersions of curcumin with Eudragit® EPO were prepared by the solvent evaporation method at various ratios to improve the solubility and the dissolution of curcumin. The optimum weight ratio of 1:5 for curcumin to Eudragit® EPO was used to incorporate into the raft forming systems. The raft forming formulations were composed of curcumin-Eudragit® EPO solid dispersions, sodium alginate as a gelling polymer and calcium carbonate for generating divalent Ca(2+) ions and carbon dioxide to form a floating raft. All formulations formed a gelled raft in 1min and sustained buoyancy on the 0.1N hydrochloric acid (pH 1.2) surface with a 60-85% release of curcumin within 8h. The curative effect on the acetic acid-induced chronic gastric ulcer in rats was determined. The curcumin raft forming formulations at 40mg/kg once daily showed a superior curative effect on the gastric ulcer in terms of the ulcer index and healing index than the standard antisecretory agent: lansoprazole (1mg/kg, twice daily) and a curcumin suspension (40mg/kg, twice daily). These studies demonstrated that the new raft forming systems containing curcumin solid dispersions are promising carriers for a stomach-specific delivery of poorly soluble lipophilic compounds.

  5. EPO-dependent induction of erythroferrone drives hepcidin suppression and systematic iron absorption under phenylhydrazine-induced hemolytic anemia.

    Science.gov (United States)

    Jiang, Xingkang; Gao, Ming; Chen, Yue; Liu, Jing; Qi, Shiyong; Ma, Juan; Zhang, Zhihong; Xu, Yong

    2016-05-01

    Hemolytic anemia is a common form of anemia due to hemolysis, resulting in disordered iron homeostasis. In this study, a dose of 40mg/kg phenylhydrazine (PHZ) was injected into mice to successfully establish a pronounced anemia animal model, which resulted in stress erythropoiesis and iron absorption. We found that serum erythropoietin (EPO) concentration was dramatically elevated by nearly 5000-fold for the first 2days, and then drop to the basal level on day 6 after PHZ injection. Mirrored with serum EPO concentration, the mRNA expression of erythroferrone (ERFE) was rapidly increased in the bone marrow and spleen 3days after injection of PHZ, and then gradually decreased but was still higher than baseline on day 6. In addition, we also found that the hepcidin mRNA levels were gradually reduced almost up to 8-fold on day 5, and then was ameliorated compared to the untreated control. Mechanistic investigation manifested that the increase of serum EPO essentially determined the induction of ERFE expression particular at the first 3days after PHZ treatment. Lentiviral mediated ERFE knockdown significantly restrained hepcidin suppression under PHZ treatment. Thus, our data unearthed EPO-dependent ERFE expression acts as an erythropoiesis-driven regulator of iron metabolism under PHZ-induced hemolytic anemia.

  6. THE EFFECTS OF IL-1 AND IL-4 ON THE EPO-INDEPENDENT ERYTHROID PROGENITOR IN POLYCYTHEMIA-VERA

    NARCIS (Netherlands)

    DEWOLF, JTM; HENDRIKS, DW; ESSELINK, MT; HALIE, MR; VELLENGA, E

    1994-01-01

    Human recombinant interleukin-1 (IL-1) was studied for its effects on the erythroid progenitors from normal subjects and from patients with polycythaemia vera (PV). No supportive effect of IL-1 was noticed on the normal, erythropoietin (Epo) dependent, erythroid burst-forming unit (BFU-E) using peri

  7. Renale Osteopathie

    OpenAIRE

    Horn S

    2001-01-01

    Die renale Osteopathie umfaßt Erkrankungen des Knochens, die bei Patienten mit chronischen Nierenerkrankungen auftreten, wie den sekundären bzw. tertiären Hyperparathyreoidismus, die adynamische Knochenerkrankung und die Osteopathie nach Nierentransplantation. Durch die Identifikation des Kalzium-Sensing-Rezeptors bzw. des Vitamin D-Rezeptors hat sich unser Verständnis der Zusammenhänge in den letzten Jahren erheblich verbessert. Neue Medikamente versprechen effizientere Prophylaxe- und Thera...

  8. Renale Knochenerkrankungen

    Directory of Open Access Journals (Sweden)

    Mayer G

    2008-01-01

    Full Text Available Störungen des Mineral- und Knochenstoffwechsels sind bei fast allen Patienten mit chronischen Nierenerkrankungen anzutreffen. Pathogenetisch spielt eine Neigung zur Phosphatretention bei einer Reduktion der glomerulären Filtrationsrate die zentrale Rolle. Neben typischen, aber sehr variablen Veränderungen der Knochenstruktur (renale Osteopathie besteht auch eine sehr enge Assoziation zwischen diesen Störungen und dem massiv erhöhten kardiovaskulären Risiko der Patienten.

  9. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile

  10. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile inde

  11. What We Need: The 2012 NASA EPO Forum Survey on Two-Year College STEM Teaching

    Science.gov (United States)

    Low, R.; CoBabe-Ammann, E.; Schultz, G.

    2014-07-01

    A survey of community college STEM faculty, administered by the NASA SMD Higher Education Working Group (HEWG), was administered in fall 2012 in an effort to document the demographic make-up and views of community college faculty who teach NASA science-related STEM courses in astronomy, physics, Earth science, and engineering. Nearly half of respondents reported that less than 10% of students in their classroom are “STEMward bound” and indicated the need for STEM resources that can relate science course content and be relevant to the daily life of their students. A number of respondents also noted a new or renewed emphasis on outreach activities within the community served by their institution as part of their job description. The survey suggests specific directions and ways that the NASA SMD EPO forum can support two-year college stakeholders.

  12. IEEE802.3工作组批准成立EPoC研究组

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    北京时间11月11日,在美国亚特兰大举行的”2011lEEE局域网/城域网标准委员会全体会议”上,IEEE802.3工作组批准并成立了EPONP HYfor Copper Study Group(面向同轴接入的EPONPHY研究组)。该研究组将致力于同轴专用接入技术EPoC(EPONProtocalover Coaxial Distribution Network.基于EPON协议的同轴分配网络1的市场需求考察、网络兼容性考量、基于现有技术的物理层标准制定。

  13. Engaging Scientists in Meaningful E/PO: The Universe Discovery Guides

    Science.gov (United States)

    Meinke, B. K.; Lawton, B.; Gurton, S.; Smith, D. A.; Manning, J. G.

    2014-12-01

    For the 2009 International Year of Astronomy, the then-existing NASA Origins Forum collaborated with the Astronomical Society of the Pacific (ASP) to create a series of monthly "Discovery Guides" for informal educator and amateur astronomer use in educating the public about featured sky objects and associated NASA science themes. Today's NASA Astrophysics Science Education and Public Outreach Forum (SEPOF), one of a new generation of forums coordinating the work of NASA Science Mission Directorate (SMD) EPO efforts—in collaboration with the ASP and NASA SMD missions and programs--has adapted the Discovery Guides into "evergreen" educational resources suitable for a variety of audiences. The Guides focus on "deep sky" objects and astrophysics themes (stars and stellar evolution, galaxies and the universe, and exoplanets), showcasing EPO resources from more than 30 NASA astrophysics missions and programs in a coordinated and cohesive "big picture" approach across the electromagnetic spectrum, grounded in best practices to best serve the needs of the target audiences. Each monthly guide features a theme and a representative object well-placed for viewing, with an accompanying interpretive story, finding charts, strategies for conveying the topics, and complementary supporting NASA-approved education activities and background information from a spectrum of NASA missions and programs. The Universe Discovery Guides are downloadable from the NASA Night Sky Network web site at nightsky.jpl.nasa.gov. We will share the Forum-led Collaborative's experience in developing the guides, how they place individual science discoveries and learning resources into context for audiences, and how the Guides can be readily used in scientist public outreach efforts, in college and university introductory astronomy classes, and in other engagements between scientists, students and the public.

  14. Alternativa terapeutica en la isquemia cerebral empleando la Eritropoyetina humana recombinante (rHu-EPO CIM como neuroprotector.

    Directory of Open Access Journals (Sweden)

    Iliana Sosa Testé

    2005-01-01

    Full Text Available Las enfermedades vasculares constituyen las terceras causas de muerte en Cuba. Su variante isquémica es causa de invalidez y perdida de la calidad de la vida. La búsqueda de agentes neuroprotectores es muy importante sí tenemos en cuenta que nuestra población está envejecida. Muchos son las razones por la que una molécula con propiedades neuroprotectoras en los modelos animales no tenga los resultados en ensayos clínicos en humanos. Este trabajo analiza y discute como mejorar estos aspectos. La Eritropoyetina humana recombinante (rHu EPO, conocido por su papel en la diferenciación del eritrocito, ha mostrado ser neuroprotector durante la isquemia cerebral en los modelos de animales adultos. De esta molécula se exponen los mecanismos de acción, que son las bases de los resultados positivos alcanzaron en las investigaciones preclínicas y los ensayos clínicos, que lo proponen como el neuroprotector ideal. Finalmente se comparan los resultados alcanzados por los autores en las investigaciones con la rHu EPO producida por el Centro Molecular de Inmunología de Cuba (CIM. El efecto de la aplicación de rHu EPO se evidenció por la disminución del edema cerebral, preservación de la conducta exploratoria y la disminución de la incidencia de señales clínicas de infarto cerebral y alteraciones patológicas. El grupo de resultados demostró las diferencias significantes entre los animales controles y tratados con el rHu EPO con los no tratados que sugieren que el rHu EPO debe ser considerado como una alternativa terapéutica contra el infarto cerebral en su fase aguda.

  15. Bilateral Renal Mass-Renal Disorder: Tuberculosis

    Directory of Open Access Journals (Sweden)

    Ozlem Tiryaki

    2013-01-01

    Full Text Available A 30-year-old woman has presented complaining of weakness and fatigue to her primary care physician. The renal sonography is a routine step in the evaluation of new onset renal failure. When the renal masses have been discovered by sonography in this setting, the functional imaging may be critical. We reported a case about bilateral renal masses in a young female patient with tuberculosis and renal insufficiency. Magnetic resonance (MR has revealed the bilateral renal masses in patient, and this patient has been referred to our hospital for further management. The patient’s past medical and surgical history was unremarkable.

  16. Distal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA ... excreting it into the urine. Distal renal tubular acidosis (Type I RTA) is caused by a defect ...

  17. Proximal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  18. Defining an EPOR- regulated transcriptome for primary progenitors, including Tnfr-sf13c as a novel mediator of EPO- dependent erythroblast formation.

    Directory of Open Access Journals (Sweden)

    Seema Singh

    Full Text Available Certain concepts concerning EPO/EPOR action modes have been challenged by in vivo studies: Bcl-x levels are elevated in maturing erythroblasts, but not in their progenitors; truncated EPOR alleles that lack a major p85/PI3K recruitment site nonetheless promote polycythemia; and Erk1 disruption unexpectedly bolsters erythropoiesis. To discover novel EPO/EPOR action routes, global transcriptome analyses presently are applied to interrogate EPO/EPOR effects on primary bone marrow-derived CFUe-like progenitors. Overall, 160 EPO/EPOR target transcripts were significantly modulated 2-to 21.8-fold. A unique set of EPO-regulated survival factors included Lyl1, Gas5, Pim3, Pim1, Bim, Trib3 and Serpina 3g. EPO/EPOR-modulated cell cycle mediators included Cdc25a, Btg3, Cyclin-d2, p27-kip1, Cyclin-g2 and CyclinB1-IP-1. EPO regulation of signal transduction factors was also interestingly complex. For example, not only Socs3 plus Socs2 but also Spred2, Spred1 and Eaf1 were EPO-induced as negative-feedback components. Socs2, plus five additional targets, further proved to comprise new EPOR/Jak2/Stat5 response genes (which are important for erythropoiesis during anemia. Among receptors, an atypical TNF-receptor Tnfr-sf13c was up-modulated >5-fold by EPO. Functionally, Tnfr-sf13c ligation proved to both promote proerythroblast survival, and substantially enhance erythroblast formation. The EPOR therefore engages a sophisticated set of transcriptome response circuits, with Tnfr-sf13c deployed as one novel positive regulator of proerythroblast formation.

  19. Defining an EPOR- regulated transcriptome for primary progenitors, including Tnfr-sf13c as a novel mediator of EPO- dependent erythroblast formation.

    Science.gov (United States)

    Singh, Seema; Dev, Arvind; Verma, Rakesh; Pradeep, Anamika; Sathyanarayana, Pradeep; Green, Jennifer M; Narayanan, Aishwarya; Wojchowski, Don M

    2012-01-01

    Certain concepts concerning EPO/EPOR action modes have been challenged by in vivo studies: Bcl-x levels are elevated in maturing erythroblasts, but not in their progenitors; truncated EPOR alleles that lack a major p85/PI3K recruitment site nonetheless promote polycythemia; and Erk1 disruption unexpectedly bolsters erythropoiesis. To discover novel EPO/EPOR action routes, global transcriptome analyses presently are applied to interrogate EPO/EPOR effects on primary bone marrow-derived CFUe-like progenitors. Overall, 160 EPO/EPOR target transcripts were significantly modulated 2-to 21.8-fold. A unique set of EPO-regulated survival factors included Lyl1, Gas5, Pim3, Pim1, Bim, Trib3 and Serpina 3g. EPO/EPOR-modulated cell cycle mediators included Cdc25a, Btg3, Cyclin-d2, p27-kip1, Cyclin-g2 and CyclinB1-IP-1. EPO regulation of signal transduction factors was also interestingly complex. For example, not only Socs3 plus Socs2 but also Spred2, Spred1 and Eaf1 were EPO-induced as negative-feedback components. Socs2, plus five additional targets, further proved to comprise new EPOR/Jak2/Stat5 response genes (which are important for erythropoiesis during anemia). Among receptors, an atypical TNF-receptor Tnfr-sf13c was up-modulated >5-fold by EPO. Functionally, Tnfr-sf13c ligation proved to both promote proerythroblast survival, and substantially enhance erythroblast formation. The EPOR therefore engages a sophisticated set of transcriptome response circuits, with Tnfr-sf13c deployed as one novel positive regulator of proerythroblast formation.

  20. Renal tuberculosis

    Directory of Open Access Journals (Sweden)

    Džamić Zoran

    2016-01-01

    Full Text Available Tuberculosis is still a significant health problem in the world, mostly in developing countries. The special significance lies in immunocompromised patients, particularly those suffering from the HIV. Urogenital tuberculosis is one of the most common forms of extrapulmonary tuberculosis, while the most commonly involved organ is the kidney. Renal tuberculosis occurs by hematogenous dissemination of mycobacterium tuberculosis from a primary tuberculosis foci in the body. Tuberculosis is characterized by the formation of pathognomonic lesions in the tissues - granulomata. These granulomata may heal spontaneously or remain stable for years. In certain circumstances in the body associated with immunosuppression, the disease may be activated. Central caseous necrosis occurs within tuberculoma, leading to formation of cavities that destroy renal parenchyma. The process may gain access to the collecting system, forming the caverns. In this way, infection can be spread distally to renal pelvis, ureter and bladder. Scaring of tissue by tuberculosis process may lead to development of strictures of the urinary tract. The clinical manifestations are presented by nonspecific symptoms and signs, so tuberculosis can often be overlooked. Sterile pyuria is characteristic for urinary tuberculosis. Dysuric complaints, flank pain or hematuria may be presented in patients. Constitutional symptoms of fever, weight loss and night sweats are presented in some severe cases. Diagnosis is made by isolation of mycobacterium tuberculosis in urine samples, by cultures carried out on standard solid media optimized for mycobacterial growth. Different imaging studies are used in diagnostics - IVU, CT and NMR are the most important. Medical therapy is the main modality of tuberculosis treatment. The first line anti-tuberculosis drugs include isoniazid, rifampicin, pyrazinamide and ethambutol. Surgical treatment is required in some cases, to remove severely damaged kidney, if

  1. Renale Osteopathie

    Directory of Open Access Journals (Sweden)

    Horn S

    2001-01-01

    Full Text Available Die renale Osteopathie umfaßt Erkrankungen des Knochens, die bei Patienten mit chronischen Nierenerkrankungen auftreten, wie den sekundären bzw. tertiären Hyperparathyreoidismus, die adynamische Knochenerkrankung und die Osteopathie nach Nierentransplantation. Durch die Identifikation des Kalzium-Sensing-Rezeptors bzw. des Vitamin D-Rezeptors hat sich unser Verständnis der Zusammenhänge in den letzten Jahren erheblich verbessert. Neue Medikamente versprechen effizientere Prophylaxe- und Therapiemöglichkeiten. Wir beeinflussen dadurch nicht nur die Morbidität und Lebensqualität, sondern auch die Mortalität unserer Patienten.

  2. Renal disease in pregnancy.

    Science.gov (United States)

    Thorsen, Martha S; Poole, Judith H

    2002-03-01

    Anatomic and physiologic adaptations within the renal system during pregnancy are significant. Alterations are seen in renal blood flow and glomerular filtration, resulting in changes in normal renal laboratory values. When these normal renal adaptations are coupled with pregnancy-induced complications or preexisting renal dysfunction, the woman may demonstrate a reduction of renal function leading to an increased risk of perinatal morbidity and mortality. This article will review normal pregnancy adaptations of the renal system and discuss common pregnancy-related renal complications.

  3. Renal calculus

    CERN Document Server

    Pyrah, Leslie N

    1979-01-01

    Stone in the urinary tract has fascinated the medical profession from the earliest times and has played an important part in the development of surgery. The earliest major planned operations were for the removal of vesical calculus; renal and ureteric calculi provided the first stimulus for the radiological investigation of the viscera, and the biochemical investigation of the causes of calculus formation has been the training ground for surgeons interested in metabolic disorders. It is therefore no surprise that stone has been the subject of a number of monographs by eminent urologists, but the rapid development of knowledge has made it possible for each one of these authors to produce something new. There is still a technical challenge to the surgeon in the removal of renal calculi, and on this topic we are always glad to have the advice of a master craftsman; but inevitably much of the interest centres on the elucidation of the causes of stone formation and its prevention. Professor Pyrah has had a long an...

  4. The Time History of Events and Macroscale Interactions during Substorms (THEMIS) Education and Outreach (E/PO) Program

    Science.gov (United States)

    Peticolas, L. M.; Craig, N.; Odenwald, S. F.; Walker, A.; Russell, C. T.; Angelopoulos, V.; Willard, C.; Larson, M. B.; Hiscock, W. A.; Stoke, J. M.; Moldwin, M. B.

    2008-12-01

    During the pre-launch phase of NASA’s THEMIS mission, the Education and Public Outreach (E/PO) program successfully brought the excitement of THEMIS to the public, students and teachers through a variety of programs. The Geomagnetic Event Observation Network by Students (GEONS) was the main effort during this time, a project in which 13 magnetometers were placed in or near 13 rural schools across the country. High school teachers and a few middle school teachers at these and/or neighboring schools took part in a long-term professional development program based around space science and the magnetometer data. The teachers created week-long to semester-long projects during which their students worked on THEMIS lessons that they, their colleagues, and the E/PO team created. In addition to this program, THEMIS E/PO also launched the only Lawrence Hall of Science (LHS) Great Explorations in Mathematics and Science (GEMS) site in Nevada. This site provides a sustainable place for teacher professional development using hands-on GEMS activities, and has been used by teachers around the state of Nevada. Short-term professional development for K-12 teachers (one-hour to two-day workshops), with a focus on the Tribal College and Society for the Advancement of Chicanos and Native Americans in Science (SACNAS) communities have reached hundreds of teachers across the country. A Space Telescope Science Institute (STScI) ViewSpace show on auroras and THEMIS was created and distributed, and shown in over a hundred science centers and museums nationwide. The THEMIS E/PO program developed and maintained a THEMIS E/PO Website for dissemination of (1) information and multimedia about the science and engineering of THEMIS, (2) updated news about the mission in language appropriate for the public, (3) the GEONS data, the GEONS teacher guides with classroom activities, and (4) information about the THEMIS E/PO program. Hundreds of thousands of visitors have viewed this website. In this

  5. Adaptation of CHO cells in serum-free conditions for erythropoietin production: Application of EVOP technique for process optimization.

    Science.gov (United States)

    Jukić, Suzana; Bubenik, Dijana; Pavlović, Nediljko; Tušek, Ana Jurinjak; Srček, Višnja Gaurina

    2016-09-01

    Mammalian cell cultures are the preferred expression systems for the production of biopharmaceuticals requiring posttranslational processing. Usually, cell cultures are cultivated in medium supplemented with serum, which supports cell proliferation, viability, and productivity. However, due to scientific and regulatory concerns, serum-free conditions are required in recombinant protein production. Cell lines that are intended for commercial recombinant protein production have to adapt to serum- or protein-free conditions early in their development. This is a labor- and time-consuming process because of the specific cell requirements related to their adaptation in new microenvironment. In the present study, a Chinese hamster ovary (CHO) cell line producing glycosylated recombinant human erythropoietin (rhEPO) was adapted for growth and rhEPO production in serum- and protein-free conditions. The physiology, growth parameters, and morphology of the CHO cells and rhEPO biosynthesis and structure were closely monitored during the adaptation process to avoid unwanted selection of cell subpopulations. The results showed that the CHO cells were successfully adapted to suspension growth and rhEPO production in the protein-free conditions and that the structure of rhEPO remained nearly unchanged. In addition, during rhEPO production in the protein-free suspension conditions, the agitation rate seem to be significant for optimal process performance in contrast to the initial cell concentration, evaluated through evolutionary operation method.

  6. 2004 Japanese Society for Dialysis Therapy guidelines for renal anemia in chronic hemodialysis patients.

    Science.gov (United States)

    Gejyo, Fumitake; Saito, Akira; Akizawa, Tadao; Akiba, Takashi; Sakai, Tatsuya; Suzuki, Masashi; Nishi, Shinichi; Tsubakihara, Yoshiharu; Hirakata, Hideki; Bessho, Masami

    2004-12-01

    The guideline committee of Japanese Society for Dialysis Therapy (JSDT), chaired by Professor F. Gejyo of Niigata University, now publishes an original Japanese guideline entitled 'Guidelines for Renal Anemia in Chronic Hemodialysis Patients'. It includes the re-evaluation of the usage of recombinant human erythropoietin (rHuEPO) with the medical and economical arguments regarding the prognosis and the quality of life of Japanese hemodialysis patients. This guideline consists of 7 sections. The first section comprises the general definition and the differential diagnosis of anemia. The hemoglobin (Hb) level of the Japanese population seemed to be low when compared with that of the European and American populations. The second section describes the target Hb level in hemodialysis patients. Multivariate analysis of the data that were collected from dialysis institutions throughout the country showed that an Hb level of 10-11 g/dL (Ht level 30-33%) at the first dialysis session in a week is the ideal range for chronic hemodialysis patients in terms of the 3-5 year survival rate. The supine position at blood sampling and the sampling timing at the first dialysis session in a week might affect the lower setting of target Hb hematocrit (Ht), compared to that of European and American guidelines. However, we particularly recommended that an Hb level of 11-12 g/dL (Ht level from 33 to 36%) at the first dialysis session in a week is desirable in relatively young patients. In the third section, the markers of iron deficiency are discussed. The Transferin saturation test (TSAT) and serum ferritin were emphasized as the standard markers. The routes of administration of rHuEPO and its dosages are written in the fourth section. The subcutaneous route was associated with the occurrence of secondary red cell aplasia due to anti-rHuEPO antibodies; however, secondary red cell aplasia was seldom observed in the venous injection. From this fact we recommend venous injection for chronic

  7. Erythropoietin reduces the expression of myostatin in mdx dystrophic mice

    OpenAIRE

    D Feder; Rugollini, M.; Santomauro Jr,A.; de Oliveira, L. P.; Lioi,V.P.; R. dos Santos; Ferreira, L.G.; Nunes,M.T.; M.H. Carvalho; P.O. Delgado; A.A.S. Carvalho; Fonseca, F.L.A.

    2014-01-01

    Erythropoietin (EPO) has been well characterized as a renal glycoprotein hormone regulating red blood cell production by inhibiting apoptosis of erythrocyte progenitors in hematopoietic tissues. EPO exerts regulatory effects in cardiac and skeletal muscles. Duchenne muscular dystrophy is a lethal degenerative disorder of skeletal and cardiac muscle. in this study, we tested the possible therapeutic beneficial effect of recombinant EPO (rhEPO) in dystrophic muscles in mdx mice. Total strength ...

  8. Renal actinomycosis with concomitant renal vein thrombosis.

    Science.gov (United States)

    Chang, Dong-Suk; Jang, Won Ik; Jung, Ji Yoon; Chung, Sarah; Choi, Dae Eun; Na, Ki-Ryang; Lee, Kang Wook; Shin, Yong-Tai

    2012-02-01

    Renal actinomycosis is a rare infection caused by fungi of the genus Actinomyces. A 74-year-old male was admitted to our hospital because of gross hematuria with urinary symptoms and intermittent chills. Computed tomography of the abdomen showed thrombosis in the left renal vein and diffuse, heterogeneous enlargement of the left kidney. After nephrectomy, sulfur granules with chronic suppurative inflammation were seen microscopically, and the histopathological diagnosis was renal actinomycosis. Our case is the first report of renal actinomycosis with renal vein thrombosis.

  9. TRANSPLANTE RENAL

    Directory of Open Access Journals (Sweden)

    Soraia Geraldo Rozza Lopes

    2014-01-01

    Full Text Available El objetivo del estudio fue comprender el significado de espera del trasplante renal para las mujeres en hemodiálisis. Se trata de un estudio cualitativo-interpretativo, realizado con 12 mujeres en hemodiálisis en Florianópolis. Los datos fueron recolectados a través de entrevistas en profundidad en el domicilio. Fue utilizado el software Etnografh 6.0 para la pre-codificación y posterior al análisis interpretativo emergieron dos categorías: “las sombras del momento actual”, que mostró que las dificultades iniciales de la enfermedad están presentes, pero las mujeres pueden hacer frente mejor a la enfermedad y el tratamiento. La segunda categoría, “la luz del trasplante renal”, muestra la esperanza impulsada por la entrada en la lista de espera para un trasplante.

  10. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930564 Dwell times affect the local host de-fence mechanism of peritoneal dialysis patients.WANG Tao(汪涛),et al.Renal Instit,SunYatsen Med Univ,Guangzhou,510080.Chin JNephrol 1993;9(2):75—77.The effect of different intraperitoneal awelltimes on the local host defence in 6 peritonealdialysis patients was studied.A significant de-crease in the number of peritoneal cells,IgG con-centration and the phagoeytosis and bactericidalactivity of macrophages was determined when thedwell time decreased from 12 to 4 hs or form 4 to0.5hs,but the peroxidase activity in macrophagesincreased significantly.All variables,except theperoxidase activity in macrophages,showed nosignificant difference between patients of high or

  11. Traumatismo renal

    OpenAIRE

    Rocha, Sofia Rosa Moura Gomes da

    2009-01-01

    Introdução: A realização deste trabalho visa a elaboração de uma revisão sistematizada subordinada à temática da traumatologia renal. Objectivos: Os principais objectivos deste trabalho são: apurar a etiologia, definir a classificação, analisar o diagnóstico e expôr o tratamento e as complicações. Desenvolvimento: Os traumatismos são a principal causa de morte antes dos 40 anos. O rim é o órgão do aparelho génito-urinário mais frequentemente atingido. Os traumatismos renais são mais fre...

  12. Dual Delivery of EPO and BMP2 from a Novel Modular Poly-ɛ-Caprolactone Construct to Increase the Bone Formation in Prefabricated Bone Flaps.

    Science.gov (United States)

    Patel, Janki Jayesh; Modes, Jane E; Flanagan, Colleen L; Krebsbach, Paul H; Edwards, Sean P; Hollister, Scott J

    2015-09-01

    Poly-ɛ-caprolactone (PCL) is a biocompatible polymer that has mechanical properties suitable for bone tissue engineering; however, it must be integrated with biologics to stimulate bone formation. Bone morphogenetic protein-2 (BMP2) delivered from PCL produces bone when implanted subcutaneously, and erythropoietin (EPO) works synergistically with BMP2. In this study, EPO and BMP2 are adsorbed separately on two 3D-printed PCL scaffold modules that are assembled for codelivery on a single scaffold structure. This assembled modular PCL scaffold with dual BMP2 and EPO delivery was shown to increase bone growth in an ectopic location when compared with BMP2 delivery along a replicate scaffold structure. EPO (200 IU/mL) and BMP2 (65 μg/mL) were adsorbed onto the outer and inner portions of a modular scaffold, respectively. Protein binding and release studies were first quantified. Subsequently, EPO+BMP2 and BMP2 scaffolds were implanted subcutaneously in mice for 4 and 8 weeks, and the regenerated bone was analyzed with microcomputed tomography and histology; 8.6±1.4 μg BMP2 (22%) and 140±29 IU EPO (69.8%) bound to the scaffold and EPO was released in 7 days. Increased endothelial cell proliferation on EPO-adsorbed PCL discs indicated protein bioactivity. At 4 and 8 weeks, dual BMP2 and EPO delivery regenerated more bone (5.1±1.1 and 5.5±1.6 mm(3)) than BMP2 alone (3.8±1.1 and 4.3±1.7 mm(3)). BMP2 and EPO scaffolds had more ingrowth (1.4%±0.6%) in the outer module when compared with BMP2 (0.8%±0.3%) at 4 weeks. Dual delivery produced more dense cellular marrow, while BMP2 had more fatty marrow. Dual EPO and BMP2 delivery is a potential method to regenerate bone faster for prefabricated flaps.

  13. 促EPO生成抗脑缺血中药的研究%Neuroprotection of herbs promoting EPO on cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    李许; 白镇亚; 张飞燕; 徐晓玉

    2015-01-01

    Amounts of researches show that EPO is characterized with neurotrophic and neuroprotective manner,especially in brain stroke,which attracts a large numbers of researchers to study it.With the accumulating researches on its neuroprotection,many related mechanisms were revealed,such as antioxidant,anti-apoptosis,angiogenesis,anti-inflammatory,which suggests a multiple targets role of EPO on brain stroke.However,because of the high risk of thromboembolism in clinical administration of rhEPO and its analogs,the herbs are potential to be a replacer for its less side effects.Many researchers suggested that a larger of herbs were founded having the action of increasing the endogenous EPO in the model of anemia and cerebral ischemia.At the same time,there herbs were also proved that they had the action of against cerebral ischemia while some without considering the role of EPO in the reports.Considering of the action of promoting EPO of these herbs and the neural protection of EPO,this essay mainly summarizes the studies of herbs promoting EPO in the cerebral ischemia and discusses the mechanism of regulating the EPO of these herbs,for the aim of finding the potential drugs against cerebral ischemia.%促红细胞生成素(EPO)在抗脑缺血方面具有重要作用,是近年来研究的一个热点.但重组人促红细胞生成素(rHuEPO)在临床应用中发现有较多副作用,特别是有增加血栓的危险.近年来发现一些中药有增加内源性EPO的作用,且副作用较小.该文就促EPO生成中药在抗脑缺血方面的研究进行综述,同时对其调控EPO可能的机制进行简单总结,为寻找潜在的新的抗脑缺血药物提供线索.

  14. Effects of advanced glycosylation end products and rosiglitazone on the expression and secretion of galectin-3 in human renal mesangial cells

    Institute of Scientific and Technical Information of China (English)

    SUN Zi-lin; MA Chan-juan; JIN Hui; YUAN Yang; LIU Nai-feng

    2009-01-01

    Background Galectin-3 is the most recently identified advanced glycosylation end products (AGEs) binding protein. This study aimed to investigate the effects of AGEs and rosiglitazone on the expression and secretion of galectin-3 in cultured human renal mesangial cells (HRMCs).Methods HRMCs were incubated with different concentrations of AGE-bovine serum albumin (BSA) (0, 50, 100, 200, and 400 mg/L) for different time (0, 24, 36, 48, and 72 hours), and exposed to AGE-BSA in the presence of different concentrations of rosiglitazone (1, 10, and 100 μmol/L). The mRNA and protein expression of galectin-3 in HRMCs were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Westem blotting. The culture medium of HRMCs was collected and concentrated, and the content of galectin-3 in the medium was detected by Western blotting. Results Both RT-PCR and Western blotting revealed that AGE-BSA up-regulated the expression of galectin-3 in HRMCs in a concentration- (P<0.05) and time-dependent (P<0.05) manner compared with the control. Compared with the control, AGE-BSA elevated the content of galectin-3 in the culture medium of HRMCs time- and concentration-dependently (P<0.05, respectively). Both protein and mRNA expression of galectin-3, and its content in the medium of HRMCs exposed to different concentrations of rosiglitazone in the presence of AGE-BSA were increased compared with those of cells exposed to AGE-BSA alone (P<0.05). Rosiglitazone increased the expression and secretion of galectin-3 in a dose-dependent manner (P<0.05).Conclusions AGEs up-regulates the expression and secretion of galectin-3 in HRMCs. Rosiglitazone further enhances the upregulation of galectin-3 in HRMCs induced by AGEs, which suggests that rosiglitazone may play a role of reno-protection via up-regulation of galectin-3.

  15. Receptors for advanced glycation end products (RAGE) is associated with microvessel density and is a prognostic biomarker for clear cell renal cell carcinoma.

    Science.gov (United States)

    Guo, Yong; Xia, Peng; Zheng, Jian-Jian; Sun, Xian-Bin; Pan, Xiao-Dong; Zhang, Xing; Wu, Cun-Zao

    2015-07-01

    The receptor for advanced glycation end products (RAGE) is involved in a variety of biological processes, including tumorigenisis. Previous studies have demonstrated that RAGE regulates the neo-angiogenesis related downstream molecule - vascular endothelial growth factor receptor 2 (VEGFR-2). Here, we investigated the potential relationship between RAGE, VEGFR-2 and angiogenesis in 80 renal cell carcinoma (RCC) patients. Real-time quantitative PCR and ELISA analysis were used to explore the RAGE and VEGFR-2 gene expression levels and the protein of VEGFR-2 expression. Meanwhile, angiogenesis was detected by the semi-quantification of endothelial cell marker CD34 combined with caldesmon, which was detected by microvessel density (MVD) technique and immunohistochemistry. Tumors were classified as low or high RAGE-expressing using the median as the cut-off. Immunofluorescence staining for RAGE protein was performed as well. Additionally, the median gene expression levels of VEGFR-2 in the tumors were significantly lower expressing low levels of RAGE expression, 0.34 (95% CI, 0.28-0.39) compared to the expressing high levels of RAGE expression, 0.45 (95% CI, 0.29-0.61), (P=0.03). The median MVD was significantly lower in the tumors expressing low levels of RAGE, 6.5 (95% CI, 6.21-7.43), compared to the expressing high levels, 7.9 (95% CI, 6.25-8.93), (PRAGE expression are associated with high VEGFR-2 mRNA/protein levels and a higher density of microvessels; conversely, Kaplan-Meier survival analysis suggests that a significant correlation of elevated RAGE expression with decreased overall survival and metastasis-free survival. Our results establish that RAGE was identified as a potential prognostic biomarker for disease prognosis of RCC. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Metformin inhibits advanced glycation end products (AGEs)-induced renal tubular cell injury by suppressing reactive oxygen species generation via reducing receptor for AGEs (RAGE) expression.

    Science.gov (United States)

    Ishibashi, Y; Matsui, T; Takeuchi, M; Yamagishi, S

    2012-11-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in tubulointerstitial damage in diabetic nephropathy. Recently, metformin has been shown to ameliorate tubular injury both in cell culture and diabetic animal model. However, effects of metformin on AGEs-induced tubular cell apoptosis and damage remain unknown. We examined here whether and how metformin could block the AGEs-RAGE-elicited tubular cell injury in vitro. Gene expression level was evaluated by real-time reverse-transcription polymerase chain reactions. Reactive oxygen species (ROS) generation was measured with dihydroethidium staining. Apoptosis was evaluated by DNA fragmentation and annexin V expression level. AGEs upregulated RAGE mRNA levels and subsequently increased ROS generation and intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and transforming growth factor-β gene expression in human renal proximal tubular cells, all of which were significantly blocked by the treatment of 0.01 and 0.1 mM metformin. Compound C, an inhibitor of AMP-activated protein kinase significantly blocked the effects of metformin on RAGE gene expression and ROS generation in AGEs-exposed tubular cells. Furthermore, metformin dose-dependently inhibited the AGEs-induced apoptotic cell death of tubular cells; 1 mM metformin completely suppressed the pro-apoptotic effects of AGEs in 2 different assay systems. Our present study suggests that metformin could inhibit the AGEs-induced apoptosis and inflammatory and fibrotic reactions in tubular cells probably by reducing ROS generation via suppression of RAGE expression through AMP-activated protein kinase activation. Metformin may protect against tubular cell injury in diabetic nephropathy by blocking the AGEs-RAGE-ROS axis.

  17. A Conjugated Aptamer-Gold Nanoparticle Fluorescent Probe for Highly Sensitive Detection of rHuEPO

    Directory of Open Access Journals (Sweden)

    Zhaoyang Zhang

    2011-11-01

    Full Text Available We present here a novel conjugated aptamer-gold nanoparticle (Apt-AuNPs fluorescent probe and its application for specific detection of recombinant human erythropoietin-α (rHuEPO-α. In this nanobiosensor, 12 nm AuNPs function as both a nano-scaffold and a nano-quencher (fluorescent energy acceptor, on the surface of which the complementary sequences are linked (as cODN-AuNPs and pre-hybridized with carboxymethylfluorescein (FAM-labeled anti-rHuEPO-α aptamers. Upon target protein binding, the aptamers can be released from the AuNP surface and the fluorescence signal is restored. Key variables such as the length of linker, the hybridization site and length have been designed and optimized. Full performance evaluation including sensitivity, linear range and interference substances are also described. This nanobiosensor provides a promising approach for a simple and direct quantification of rHuEPO-α concentrations as low as 0.92 nM within a few hours.

  18. AKT induces erythroid-cell maturation of JAK2-deficient fetal liver progenitor cells and is required for Epo regulation of erythroid-cell differentiation.

    Science.gov (United States)

    Ghaffari, Saghi; Kitidis, Claire; Zhao, Wei; Marinkovic, Dragan; Fleming, Mark D; Luo, Biao; Marszalek, Joseph; Lodish, Harvey F

    2006-03-01

    AKT serine threonine kinase of the protein kinase B (PKB) family plays essential roles in cell survival, growth, metabolism, and differentiation. In the erythroid system, AKT is known to be rapidly phosphorylated and activated in response to erythropoietin (Epo) engagement of Epo receptor (EpoR) and to sustain survival signals in cultured erythroid cells. Here we demonstrate that activated AKT complements EpoR signaling and supports erythroid-cell differentiation in wild-type and JAK2-deficient fetal liver cells. We show that erythroid maturation of AKT-transduced cells is not solely dependent on AKT-induced cell survival or proliferation signals, suggesting that AKT transduces also a differentiation-specific signal downstream of EpoR in erythroid cells. Down-regulation of expression of AKT kinase by RNA interference, or AKT activity by expression of dominant negative forms, inhibits significantly fetal liver-derived erythroid-cell colony formation and gene expression, demonstrating that AKT is required for Epo regulation of erythroid-cell maturation.

  19. Forty Years of E/PO: Can You Have it All? (Invited)

    Science.gov (United States)

    Reiff, P. H.

    2013-12-01

    In forty years of education and public outreach (E/PO), 25 years of which have been funded by various NSF and NASA programs, several lessons (some tough) have been learned. We have done teacher workshops, teacher semester-long courses, student summer programs, outreach fairs and exhibits, and generally the response of the participants has been very high. Generally the longer programs reach fewer people but in greater depth and impact; the shorter programs reach more, but with lesser depth. This paper shows some of the statistics of learning in our various venues, include teacher courses, online material, and planetarium shows. We also performed an online survey of users of NASA materials and contrasted with a random group of 144 adults. We find that teachers and museum educators have nearly all been "significantly" or "changed my life" impacted by NASA educational materials, and even 24% of the general public have as well, with 14% of the general public reporting that NASA encouraged them to study STEM and go into STEM careers. Virtually all said that NASA should continue producing educational materials. Some of the stumbling blocks include: the difficulty of obtaining funds, the general lack of recognition for outreach in tenure decisions, the difficulty of trying to keep active in research while also active in outreach; and the general problem of "having a life" while juggling many responsibilities. Yet it is worth it!

  20. Federal STEM Policy and Politics and Their Impact on Astronomy EPO: Reflections and Provocations

    Science.gov (United States)

    Schultz, G.; Storksdieck, M.; Canright, S.

    2015-11-01

    The federal government invests more than $3 billion each year across its various units in supporting STEM education and outreach. Efforts in recent years to understand and better coordinate these investments have resulted in considerable pushback, particularly those efforts that aimed at consolidation and elimination of programs deemed ineffective or duplicative. While initial plans to streamline federal STEM education were defeated, many agencies nonetheless saw cuts and elimination, and a high-level effort to coordinate STEM education at the cross-agency level is now gaining steam (CoSTEM: Committee on Science, Technology, Engineering, and Mathematics Education). What do all of these developments mean for education and public outreach in astronomy and related fields? How should this community operate within the opportunities and threats that CoSTEM might pose? Former director of the National Academy of Science's Board on Science Education, and now director of the Center for Research on Lifelong STEM Learning, Martin Storksdieck, reflected on past and recent developments from the perspective of a close observer, and from the perspective of someone who has been involved in astronomy education research and evaluation for nearly 20 years. Shelley Canright, Senior Advisor for Education Integration at the NASA Office of Education, shared her insights and perspectives with respect to CoSTEM and EPO, in particular from co-chairing the Federal Coordination in Science, Technology, Engineering, and Mathematics Education (FC-STEM) group.

  1. THE BURYAT EPOS «GESER» AND THE ANGLO-SAXON EPOPEE «BEOWULF»

    Directory of Open Access Journals (Sweden)

    KHUNDAEVA ELIZAVETA OCHIROVNA

    2015-01-01

    Full Text Available Cultures are not isolated from one another and are of no significance all by themselves, taken separately. Each culture carries in itself the energy of neighboring and other cultures. The warrior who personifies all the strength and might of his community is showered gifts on by nature for his chief mission is protection of his tribes and kin from all kinds of misfortune. The Buryat epos “Geser” and the Anglo-Saxon epopee “Beowulf” have much in common regarding the historical epoch, content, episodes and motives, characters, morals and style features. The discourse of both the texts is noted for the features of typological similarity, among which most prominent are ethnic and historical background, textual build-up, heroic deeds. The epical consciousness of both the peoples was noted for their symbolical, mythological, totemic, animistic features, pagan and shaman beliefs somewhat mixed up with some other religious tendencies like Christian and Buddhist ones respectively. Both possess some common features that can play a positive role in the dialogue between the two cultures.

  2. Implications of the Next Generation Science Standards for K-12, EPO, and Higher Education

    Science.gov (United States)

    Schultz, G.; Barber, J.; Pomeroy, R.; Reagan, G.

    2014-07-01

    The newly-released Next Generation Science Standards (NGSS) have been under development for a few years with broad community input and explicit involvement of many states likely to adopt these as their own science standards. Several key features of the NGSS make these a substantial advance from the existing National Science Education Standards (NRC 1996), including focus on three dimensions previously outlined in A Framework for K-12 Science Education (NRC 2011): Science and Engineering Practices; Cross-cutting Concepts; and Disciplinary Core Ideas. What are the implications of all this now for K-12 educators, in the immediate term and in the long-term? What do the NGSS imply for EPO professionals, especially those involved in science curriculum development and teacher professional development? What should higher education faculty know about the NGSS, especially as it relates to the preparation of incoming college students, as well as the education of future elementary and secondary science teachers in college (including in Astro 101-type courses)?

  3. Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells.

    Science.gov (United States)

    Kimura, Hideki; Mikami, Daisuke; Kamiyama, Kazuko; Sugimoto, Hidehiro; Kasuno, Kenji; Takahashi, Naoki; Yoshida, Haruyoshi; Iwano, Masayuki

    2014-11-14

    Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis.

  4. Renal metabolism of calcitonin

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, R.E.; Hjelle, J.T.; Mahoney, C.; Deftos, L.J.; Lisker, W.; Kato, P.; Rabkin, R.

    1988-04-01

    The kidneys account for approximately two-thirds of the metabolism of calcitonin, but relatively little is known regarding the details thereof. To further characterize this process, we examined the renal handling and metabolism of human calcitonin (hCT) by the isolated perfused rat kidney. We also studied the degradation of radiolabeled salmon calcitonin (sCT) by subcellular fractions prepared from isolated rabbit proximal tubules. The total renal (organ) clearance of immunoreactive hCT by the isolated kidney was 1.96 +/- 0.18 ml/min. This was independent of the perfusate total calcium concentration from 5.5 to 10.2 mg/dl. Total renal clearance exceeded the glomerular filtration rate (GFR, 0.68 +/- 0.05 ml/min), indicating filtration-independent removal. Urinary calcitonin clearance as a fraction of GFR averaged 2.6%. Gel filtration chromatography of medium from isolated kidneys perfused with /sup 125/I-labeled sCT showed the principal degradation products to be low molecular weight forms eluting with monoiodotyrosine. Intermediate size products were not detected. In the subcellular fractionation experiments, when carried out at pH 5.0, calcitonin hydrolysis exclusively followed the activities of the lysosomal enzyme N-acetyl-beta-glucosaminidase. Typically, at pH 7.5, 42% of total degradation occurred in the region of the brush-border enzyme alanyl aminopeptidase and 29% occurred in the region of the cytosolic enzyme phosphoglucomutase. Although 9% of the calcitonin-degrading activity was associated with basolateral membrane fractions, most of this activity could be accounted for by the presence of brush-border membranes.

  5. NASA Astrophysics Education and Public Outreach Forum: Product and Activity Analysis

    Science.gov (United States)

    Ryer, Holly; Eisenhamer, B.; Knisely, L.; McCallister, D.; Smith, D. A.

    2013-01-01

    The NASA Science Education and Public Outreach Forums (SEPOFs) have been working together to conduct a detailed analysis of SMD E/PO products and activities. The goal of this effort is to characterize individual SMD E/PO products and the collection as a whole, while identifying gaps in the SMD E/PO portfolio. The Astrophysics Forum has undertaken the task of analyzing the astrophysics portfolio of formal, informal, and outreach products and programs. The astrophysics analysis team has been characterizing products based upon AAAS Project 2061 benchmarks addressed, target audience, instructional strategies used, and types of assessments included. All formal education activities that have been analyzed to date have been compiled into a populated database that includes analyzed activities from all four SEPOFs. The database will be used to inform the development of a product and resources catalog. It also will be used to begin a gap analysis for SMD products and activities. Ultimately, we hope to help end users easily find resources, we hope to identify progressions and connections between SMD E/PO resources and programming, and we hope to provide guidance to the E/PO community in developing materials that will help bridge gaps for both NASA SMD and target audiences. This poster highlights the astrophysics product analysis process, and the preliminary findings and results of product analysis to date.

  6. Insights into atomic-level interaction between mefenamic acid and eudragit EPO in a supersaturated solution by high-resolution magic-angle spinning NMR spectroscopy.

    Science.gov (United States)

    Higashi, Kenjirou; Yamamoto, Kazutoshi; Pandey, Manoj Kumar; Mroue, Kamal H; Moribe, Kunikazu; Yamamoto, Keiji; Ramamoorthy, Ayyalusamy

    2014-01-06

    The intermolecular interaction between mefenamic acid (MFA), a poorly water-soluble nonsteroidal anti-inflammatory drug, and Eudragit EPO (EPO), a water-soluble polymer, is investigated in their supersaturated solution using high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy. The stable supersaturated solution with a high MFA concentration of 3.0 mg/mL is prepared by dispersing the amorphous solid dispersion into a d-acetate buffer at pH 5.5 and 37 °C. By virtue of MAS at 2.7 kHz, the extremely broad and unresolved (1)H resonances of MFA in one-dimensional (1)H NMR spectrum of the supersaturated solution are well-resolved, thus enabling the complete assignment of MFA (1)H resonances in the aqueous solution. Two-dimensional (2D) (1)H/(1)H nuclear Overhauser effect spectroscopy (NOESY) and radio frequency-driven recoupling (RFDR) under MAS conditions reveal the interaction of MFA with EPO in the supersaturated solution at an atomic level. The strong cross-correlations observed in the 2D (1)H/(1)H NMR spectra indicate a hydrophobic interaction between the aromatic group of MFA and the backbone of EPO. Furthermore, the aminoalkyl group in the side chain of EPO forms a hydrophilic interaction, which can be either electrostatic or hydrogen bonding, with the carboxyl group of MFA. We believe these hydrophobic and hydrophilic interactions between MFA and EPO molecules play a key role in the formation of this extremely stable supersaturated solution. In addition, 2D (1)H/(1)H RFDR demonstrates that the molecular MFA-EPO interaction is quite flexible and dynamic.

  7. The AIA Solar Learning Center: Taking Inquiry-based EPO Online

    Science.gov (United States)

    Wills-Davey, Meredith; Attrill, G. D. R.; Engell, A.

    2009-05-01

    The observations of the Atmospheric Imaging Assembly aboard the Solar Dynamics Observatory (SDO-AIA) are expected to be groundbreaking within the field of heliophysics. To properly promote and explain the data produced by AIA, it is important that an innovative EPO effort be put forth. This has led to the development of "The AIA Solar Learning Center” (SLC), an inquiry-based educational website geared towards teaching about AIA and the Sun in general. The goal of the SLC is to provide K-12 students, teachers, parents, and homeschoolers with information and education about the Sun, primarily through hands-on activity modules that explain different aspects of our nearest star and the methods of observing it. While each module ultimately aims to impart information about the Sun or some related physical process, the activities also range across a host of different disciplines, including geology, chemistry, history, music, and art. In order to make the content applicable and accessible, activities are tailored to multiple difficulty levels, catering to different age groups. There is also a strong push towards facilitating teachers; activities are designed to fulfill specific teaching standards, and a host of additional teaching material is provided, including lesson plans and powerpoint presentations. Ultimately, the SLC aims to make science and the Sun inviting and accessible. The "Meet the Scientists” page will provide pictures and personal bios of participating scientists. Students will have the opportunity to interactively ask solar-related questions. There is even a host of lighter fare, such as a solar music playlist and links to relevant Facebook pages.

  8. Developing an Education and Public Outreach (EPO) program for Caltech's Tectonics Observatory

    Science.gov (United States)

    Kovalenko, L.; Jain, K.; Maloney, J.

    2012-12-01

    The Caltech Tectonics Observatory (TO) is an interdisciplinary center, focused on geological processes occurring at the boundaries of Earth's tectonic plates (http://www.tectonics.caltech.edu). Over the past four years, the TO has made a major effort to develop an Education and Public Outreach (EPO) program. Our goals are to (1) inspire students to learn Earth Sciences, particularly tectonic processes, (2) inform and educate the general public about science in the context of TO discoveries, and (3) provide opportunities for graduate students, postdocs, and faculty to do outreach in the local K-12 schools and community colleges. Our work toward these goals includes hosting local high school teachers and students each summer for six weeks of research experience (as part of Caltech's "Summer Research Connection"); organizing and hosting an NAGT conference aimed at Geoscience teachers at community colleges; participating in teacher training workshops (organized by the local school district); hosting tours for K-12 students from local schools as well as from China; and bringing hands-on activities into local elementary, middle, and high school classrooms. We also lead local school students and teachers on geology field trips through nearby canyons; develop education modules for undergraduate classes (as part of MARGINS program); write educational web articles on TO research (http://www.tectonics.caltech.edu/outreach/highlights/), and regularly give presentations to the general public. This year, we started providing content expertise for the development of video games to teach Earth Science, being created by GameDesk Institute. And we have just formed a scientist/educator partnership with a 6th grade teacher, to help in the school district's pilot program to incorporate new national science standards (NSTA's Next Generation Science Standards, current draft), as well as use Project-Based Learning. This presentation gives an overview of these activities.

  9. Scientific Subsurface data for EPOS - integration of 3D and 4D data services

    Science.gov (United States)

    Kerschke, Dorit; Hammitzsch, Martin; Wächter, Joachim

    2016-04-01

    The provision of efficient and easy access to scientific subsurface data sets obtained from field studies and scientific observatories or by geological 3D/4D-modeling is an important contribution to modern research infrastructures as they can facilitate the integrated analysis and evaluation as well as the exchange of scientific data. Within the project EPOS - European Plate Observing System, access to 3D and 4D data sets will be provided by 'WP15 - Geological information and modeling' and include structural geology models as well as numerical models, e.g., temperature, aquifers, and velocity. This also includes validated raw data, e.g., seismic profiles, from which the models where derived. All these datasets are of high quality and of unique scientific value as the process of modeling is time and cost intensive. However, these models are currently not easily accessible for the wider scientific community, much less to the public. For the provision of these data sets a data management platform based on common and standardized data models, protocols, and encodings as well as on a predominant use of Free and Open Source Software (FOSS) has been devised. The interoperability for disciplinary and domain applications thus highly depends on the adoption of generally agreed technologies and standards (OGC, ISO…) originating from Spatial Data Infrastructure related efforts (e.g., INSPIRE). However, since not many standards for 3D and 4D geological data exists, this work also includes new approaches for project data management, interfaces for tools used by the researchers, and interfaces for the sharing and reusing of data.

  10. Insulin production and signaling in renal tubules of Drosophila is under control of tachykinin-related peptide and regulates stress resistance.

    Directory of Open Access Journals (Sweden)

    Jeannette A E Söderberg

    Full Text Available The insulin-signaling pathway is evolutionarily conserved in animals and regulates growth, reproduction, metabolic homeostasis, stress resistance and life span. In Drosophila seven insulin-like peptides (DILP1-7 are known, some of which are produced in the brain, others in fat body or intestine. Here we show that DILP5 is expressed in principal cells of the renal tubules of Drosophila and affects survival at stress. Renal (Malpighian tubules regulate water and ion homeostasis, but also play roles in immune responses and oxidative stress. We investigated the control of DILP5 signaling in the renal tubules by Drosophila tachykinin peptide (DTK and its receptor DTKR during desiccative, nutritional and oxidative stress. The DILP5 levels in principal cells of the tubules are affected by stress and manipulations of DTKR expression in the same cells. Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype. Thus, stress seems to induce hormonal release of DTK that acts on the renal tubules to regulate DILP5 signaling. Manipulations of S6 kinase and superoxide dismutase (SOD2 in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation. Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone.

  11. Fibrate therapy and renal function.

    Science.gov (United States)

    Sica, Domenic A

    2009-09-01

    Fibrates are a class of lipid-lowering medications primarily used as second-line agents behind statins. The adverse-effect profile of fibrates has been marked by a puzzling yet reversible rise in serum creatinine values with their use. It is not known whether this finding represents a true change in renal function. One proposed explanation for this phenomenon is that fibrates increase the production of creatinine, in which case a rise in serum creatinine values would not represent a true deterioration in renal function. An alternative theory is that fibrates reduce the production of vasodilatory prostaglandins, which would lead to a true change in renal function in patients who experience a rise in serum creatinine values. Routine serum creatinine monitoring is advisable in fibrate-treated patients, particularly in those with preexisting renal disease. A 30% increase in serum creatinine values in the absence of other causes of serum creatinine change warrants discontinuation of fibrate therapy. Serum creatinine values can take several weeks to return to their baseline values following discontinuation of a fibrate.

  12. Impacts of parathyroidectomy on renal anemia and nutritional status of hemodialysis patients with secondary hyperparathyroidism.

    Science.gov (United States)

    Chen, Chen; Wu, Hua; Zhong, Lin; Wang, Xin; Xing, Zhuang-Jie; Gao, Bi-Hu

    2015-01-01

    The aim of this study was to investigate the impacts of parathyroidectomy (PTX) towards the renal anemia and nutritional status of hemodialysis patients with secondary hyperparathyroidism (SHPT). 32 patients, enrolled into the blood purification center of our hospital for the hemodialysis treatment, were collected and divided into the PTX group and the non-PTX group, with 16 patients in each group. The changes of relevant indicators such as immunoreactive parathyroid hormone (iPTH), anemia and nutrition were observed before, 1-, 3-, 6-month after the treatment. The contents of iPTH, Ca, P and Ca × P of the PTX group decreased rapidly 1 month after the surgery; while Hb and Hct increased significantly from the 1st postoperative month; the dosage of EPO was significantly reduced 3-month after the surgery; the content of Alb gradually increased from the 3(rd) postoperative month; the content of TG decreased significantly from the 6(th) postoperative month; while the contents of BMI and TSF increased significantly from the 6(th) postoperative month, which exhibited the statistically significant differences when compared with the preoperative and the non-PTX group (P anemia and nutritional status; SHPT was the important factor that would affect the renal anemia and malnutrition; PTX could reduce the amount of EPO, and reduce the economic burden of patients.

  13. Kidney (Renal) Failure

    Science.gov (United States)

    ... How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain proper fluid ... marrow and strengthen the bones. The term kidney (renal) failure describes a situation in which the kidneys have ...

  14. Renal arteries (image)

    Science.gov (United States)

    A renal angiogram is a test used to examine the blood vessels of the kidneys. The test is performed ... main vessel of the pelvis, up to the renal artery that leads into the kidney. Contrast medium ...

  15. The effect of Vitamin D administration on treatment of anemia in end-stage renal disease patients with Vitamin D deficiency on hemodialysis: A placebo-controlled, double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    Afsoon Emami Naini

    2015-01-01

    Full Text Available Background: Chronic kidney disease is a progressive and irreversible loss of renal function. Anemia is one of the main complications of end-stage renal disease (ESRD which is linked closely with other complications of the disease. The primary therapy for anemia in these patients is erythropoietin (EPO. The goal of this study was to find the effect of Vitamin D administration in addition to the appropriate dose of EPO in ESRD patients with Vitamin D deficiency. Materials and Methods: This was a double-blind clinical trial on 64 ESRD patients undergoing hemodialysis in Amin and Noor Hospitals of Isfahan, Iran. The patients were divided into two groups of control and intervention. The intervention group was given Vitamin D supplements and the control group received placebo. The required dose of EPO to reach the target hemoglobin (Hb was measured and statistically analyzed. Results: A total number of 32 females and 32 males were included in this study. All the patients in the treatment group were aged between 18 and 76 and the patients in the control group were aged between 21 and 76 years old. There was a significant statistical relationship between Vitamin D administration and the required dose of EPO in both groups (P = 0.013. However, there was no correlation between the concentration of Hb and serum Vitamin D levels. Conclusion: Based on the main finding of this study, the relationship between Vitamin D administration and required dose of EPO seems that the predicted dose of Vitamin D prescribing strategy in Kidney Disease Outcomes Quality Initiative guidelines is not adequate to achieve normal serum Vitamin D in ESRD patients.

  16. Why a Combination of WP 631 and Epo B is an Improvement on the Drugs Singly - Involvement in the Cell Cycle and Mitotic Slippage.

    Science.gov (United States)

    Bukowska, Barbara; Rogalska, Aneta; Forma, Ewa; Brys, Magdalena; Marczak, Agnieszka

    2016-01-01

    Our previous studies clearly demonstrated that a combination of WP 631 and Epo B has higher activity against ovarian cancer cells than either of these compounds used separately. In order to fully understand the exact mechanism of action in combination, we assessed effects on the cell cycle of SKOV-3 cells. We evaluated three control points essential for WP 631 and Epo B action to determine which cell cycle-regulating proteins (CDK1/cyclin B complex, EpCAM or HMGB1) mediate activity. The effects of the drug on the cell cycle were measured based on the nuclear DNA content using flow cytometry. Expression of cell cycle-regulating genes was analyzed using real-time PCR. It was discovered that WP 631, at the tested concentration, did not affect the SKOV-3 cell cycle. Epo B caused significant G2/M arrest, whereas the drug combination induced stronger apoptosis and lower mitotic arrest than Epo B alone. This is very important information from the point of view of the fight against cancer, as, while mitotic arrest in Epo B-treated cells could be overcame after DNA damage repair, apoptosis which occurs after mitotic slippage in combination-treated cells is irreversible. It clearly explains the higher activity of the drug combination in comparison to Epo B alone. Epo B acts via the CDK1/cyclin B complex and has the ability to inhibit CDK1, which may be a promising strategy for ovarian cancer treatment in the future. The drug combination diminishes EpCAM and HMGB1 expression to a greater degree than either WP 631 and Epo B alone. Owing to the fact that the high expression of these two proteins is a poor prognostic factor for ovarian cancer, a decrease in their expression, observed in our studies, may result in improved efficacy of cancer therapy. The presented findings show that the combination of WP 631 and Epo B is a better therapeutic option than either of these drugs alone.

  17. [Renal leiomyoma. Case report].

    Science.gov (United States)

    Joual, A; Guessous, H; Rabii, R; Benjelloun, M; Benlemlih, A; Skali, K; el Mrini, M; Benjelloun, S

    1999-01-01

    The authors report a case of renal leiomyoma observed in a 56-year-old man. This cyst presented in the from of loin pain. Computed tomography revealed a homogeneous renal tumor. Treatment consisted of radical nephrectomy. Histological examination of the specimen showed benign renal leiomyoma.

  18. Renal inflammatory myofibroblastic tumor

    DEFF Research Database (Denmark)

    Heerwagen, S T; Jensen, C; Bagi, P

    2007-01-01

    Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated...

  19. Melamine Impairs Renal and Vascular Function in Rats.

    Science.gov (United States)

    Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Wang, Yi-Xiang; Cheang, Wai San; Liu, Jian; Lu, Ye; Huang, Huihui; Xia, Yin; Chen, Zhen Yu; Mok, Chuen-Shing; Lau, Chau-Ming; Huang, Yu

    2016-06-21

    Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products.

  20. Application of EPO indices in Training for Endurance Sports%血清EPO指标在耐力运动训练中的应用

    Institute of Scientific and Technical Information of China (English)

    潘孝贵; 陈文鹤

    2001-01-01

    By literature, the analysis on the biological features of EPO and in accordance with the relationship between EPO and the capacity of endurance sports and the relationship between EPO and low-baric oxygen cabin, this paper probes into the changing rules of EPO both for altitude training and training in low-baric oxygen cabin. The authors hold that EPO could be used as an index for predicting and evaluating the training of endurance sports; that the discontinuous application of low baric oxygen cabin may be the main means for the training of endurance sports in the future.%采用文献资料研究方法,从EPO的生物学特性、EPO与耐力运动能力、EPO与低压氧舱等方面分析入手,探讨EPO在高原训练和低压氧舱训练中的变化规律。认为,EPO可作为耐力运动训练的预见及评价指标;间断低压氧舱应用,很可能是今后耐力运动训练的主要手段。

  1. Comparison between two treatment protocols with recombinant Human Erythropoietin (rHuEpo in the treatment of late anemia in neonates with Rh-Isoimmunization

    Directory of Open Access Journals (Sweden)

    A.A. Zuppa

    2012-08-01

    Full Text Available Objectve. The Rh-hemolytic disease can lead to a late anemia by hemolytic and hyporigenerative mechanism. We compared the effectiveness of rHuEPO in two care protocols that differ for doses of rHuEPO administrated and for timing of administration. Methods. A cohort of 14 neonates was investigated. The neonates were treated with two different protocols. Protocol A: a dose of 200 U/kg/day of rHuEpo administered subcutaneously starting from the end of the second week of life; Protocol B: a dose of 400 U/kg/day of rHuEpo administered subcutaneously starting from the end of the first week of life. Results. The hematocrit values in the protocol A group decreased during treatment (32,5% vs 25,2%, whereas the hematocrit value in protocol B group remained almost stable (38,7% vs 42,8%. The mean numbers of platelets remained stable in both groups while neutrophils increased in protocol A group and decreased in protocol B (p<0,05. Reticulocyte count increased during treatment in both groups, although only in protocol B group it was statistically significative (p<0,05. Conclusions. Our results suggest a similar efficacy between the two treatment protocols. Increasing doses of rHuEPO do not seem enhancing their effectiveness and the incidence of side effects.

  2. Role of alpha-lipoic acid in the management of anemia in patients with chronic renal failure undergoing hemodialysis

    Directory of Open Access Journals (Sweden)

    El-Nakib GA

    2013-08-01

    Full Text Available Gehad A El-Nakib,1 Tarek M Mostafa,2 Tarek M Abbas,4 Mamdouh M El-Shishtawy,3 Mokhtar M Mabrouk,2 Mohammed A Sobh41Mansoura University Hospitals, Mansoura, Egypt; 2Faculty of Pharmacy, Tanta University, Tanta, Egypt; 3Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 4Urology and Nephrology Centre, Faculty of Medicine, Mansoura University, Mansoura, EgyptIntroduction: Anemia associated with chronic kidney disease is a serious complication necessitating expenditure of huge medical efforts and resources. This study investigates the role of alpha-lipoic acid (ALA in end stage renal disease patients undergoing hemodialysis. By the virtue of its antioxidative effects, ALA is expected to act as an erythropoietin (EPO adjuvant, and also has extended beneficial effects on endothelial dysfunction.Methods: Forty-four patients undergoing hemodialysis and receiving EPO were randomized into two groups: the first group received ALA 600 mg once daily for 3 months; while the other group represented the control group. Parameters measured at baseline and at end of study were hemoglobin, EPO doses, EPO resistance index (ERI, iron store indices, malondialdehyde, oxidized low-density lipoprotein (ox-LDL, interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and asymmetric dimethylarginine (ADMA, as well as routine laboratory follow-up.Results: EPO doses and ERI were significantly decreased in the treatment group, while they did not change in the control group. Hemoglobin, iron store indices, malondialdehyde, oxidized ox-LDL, IL-6, TNF-α, and ADMA were similar in both treatment and control groups at baseline, and did not change by the end of study period. Likewise, routine laboratory measures were not affected by the treatment.Conclusion: ALA could be used in hemodialysis patients to reduce requirements for EPO. However, larger and longer term studies are required to clarify the exact role of ALA in hemodialysis as well as in pre-hemodialysis patients

  3. Collaboration as a Strategy to Transform the Impact of EPO Efforts in the New York Center for Astrobiology

    Science.gov (United States)

    Svirsky, A.; Rogers, K. L.; Meissner, M.; Busby, G.; Roberge, W.

    2014-12-01

    The New York Center for Astrobiology (NYCA) EPO effort is a collaboration combining expertise in evaluation and assessment of STEM educational modules with disciplinary expertise in astrobiology. In practice, the NYCA partners with external experts in professional development, informal education and evaluation to assist in developing and implementing certain programs of the NYCA EPO activities. Two specific program initiatives of the NYCA EPO effort offer excellent examples of programs with strong science content knowledge as well as using effective tools to address the NSF impact categories. These are the ExxonMobil Bernard Harris Summer Science Camp (EMBHSSC, in conjunction with RPI's STEM Pipeline Initiative) and the Astrobiology Teachers Academy (ATA). The EMBHSSC for middle school students focuses on NASA astrobiology initiatives around the "Quest for Life" theme. The Camp has a comprehensive evaluation component and uses pre-and post- assessment of student knowledge and interest in STEM. Recent data suggest that every student has shown a measurable gain in these areas. The ATA is a weeklong summer intensive professional development program for P-12 STEM teachers that combines discipline scientists in the NYCA with an external evaluation organization, the Association for the Cooperative Advancement of Science and Education (ACASE). The goal is for teachers to develop a new learning module for a course they teach that uses astrobiology as a content focus to engage students. The Academy has scientists collaborating with teachers in this effort, providing content and assistance in designing instructional activities. Assessments are woven into the fabric of the work in a few ways: 1. There is a purposeful focus on assessment as part of the learning module, and the content of the ATA; 2. ACASE offers teachers a tool for tracking their students' attainment of the learning goals identified in their learning module; 3. There are daily evaluations of the teachers

  4. Postpartum renal vein thrombosis.

    Science.gov (United States)

    Rubens, D; Sterns, R H; Segal, A J

    1985-01-01

    Renal vein thrombosis in adults is usually a complication of the nephrotic syndrome. Rarely, it has been reported in nonnephrotic women postpartum. The thrombosis may be a complication of the hypercoagulable state associated with both the nephrotic syndrome and pregnancy. Two postpartum patients with renal vein thrombosis and no prior history of renal disease are reported here. Neither patient had heavy proteinuria. In both cases, pyelonephritis was suspected clinically and the diagnosis of renal vein thrombosis was first suggested and confirmed by radiologic examination. Renal vein thrombosis should be considered in women presenting postpartum with flank pain.

  5. Renal infarction resulting from traumatic renal artery dissection.

    Science.gov (United States)

    Kang, Kyung Pyo; Lee, Sik; Kim, Won; Jin, Gong Yong; Na, Ki Ryang; Yun, Il Yong; Park, Sung Kwang

    2008-06-01

    Renal artery dissection may be caused by iatrogenic injury, trauma, underlying arterial diseases such as fibromuscular disease, atherosclerotic disease, or connective tissue disease. Radiological imaging may be helpful in detecting renal artery pathology, such as renal artery dissection. For patients with acute, isolated renal artery dissection, surgical treatment, endovascular management, or medical treatment have been considered effective measures to preserve renal function. We report a case of renal infarction that came about as a consequence of renal artery dissection.

  6. Adoption of the B2SAFE EUDAT replication service by the EPOS community

    Science.gov (United States)

    Cacciari, Claudio; Fares, Massimo; Fiameni, Giuseppe; Michelini, Alberto; Danecek, Peter; Wittenburg, Peter

    2014-05-01

    B2SAFE is the EUDAT service for moving and replicating data between sites and storage systems for different purposes. The goal of B2SAFE is to keep the data from a repository safe by replicating it across different geographical and administrative zones according to a set of well-defined policies. It is also a way to store large volumes of data permanently at those sites which are providing powerful on-demand data analysis facilities. In particular, B2SAFE operates on the domain of registered data where data objects are referable via persistent identifiers (PIDs). B2SAFE is more than just copying data because the PIDs must be carefully managed when data objects are moved or replicated. The EUDAT B2SAFE Service offers functionality to replicate datasets across different data centres in a safe and efficient way while maintaining all information required to easily find and query information about the replica locations. The information about the replica locations and other important information is stored in PID records, each managed in separate administrative domains. The B2SAFE Service is implemented as an iRODS module providing a set of iRODS rules or policies to interface with the EPIC handle API and uses the iRODS middleware to replicate datasets from a source data (or community) centre to a destination data centre. The definition of the dataset(s) to replicate is flexible and up to the communities using the B2SAFE service. While the B2SAFE is internally using the EPIC handle API, communities have the choice to use any PID system they prefer to assign PIDs to their digital objects. A reference to one or more EUDAT B2SAFE PIDs is returned by the B2SAFE service when a dataset is replicated. The presentation will introduce the problem space of B2SAFE, presents the achievements that have been made during the last year for enabling communities to make use of the B2SAFE service, demonstrates a EPOS use cases, outlines the commonalities and differences between the policies