WorldWideScience

Sample records for human epo rhuepo

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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....

  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. 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.

  10. 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.

  11. Anti-Rh(c), "little c," isoimmunization: the role of rHuEpo in preventing late anemia.

    Science.gov (United States)

    Zuppa, Antonio A; Cardiello, Valentina; Alighieri, Giovanni; Cota, Francesco; D'Antuono, Annamaria; Riccardi, Riccardo; Catenazzi, Piero; Romagnoli, Costantino

    2013-08-01

    The overall prevalence of non-Rh-D isoimmunization seems to lie between 0.15% and 1.1%. Anti-Rh(c) alloimmunization, "little c," occurs in 0.07% of pregnancies and shows a quite broad clinical presentation. Late anemia is a frequent problem occurring in the setting of isoimmunization. It occurs more frequently after intrauterine blood transfusions or exsanguinotransfusion, and it can be thought as a hyporegenerative anemia. The authors describe the use of human recombinant erythropoietin in preventing late anemia in a case of anti-Rh(c) isoimmunization. The use of human recombinant erythropoietin is a valid tool for preventing late-onset anemia due to either anti-Rh-D or non-anti-Rh-D isoimmunization.

  12. 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

  13. 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.

  14. Prolonged administration of recombinant human erythropoietin increases submaximal performance more than maximal aerobic capacity

    DEFF Research Database (Denmark)

    Thomsen, J J; Rentsch, R L; Robach, P

    2007-01-01

    The effects of recombinant human erythropoietin (rHuEpo) treatment on aerobic power (VO2max) are well documented, but little is known about the effects of rHuEpo on submaximal exercise performance. The present study investigated the effect on performance (ergometer cycling, 20-30 min at 80...

  15. Human recombinant erythropoietin alters the flow-dependent vasodilatation of in vitro perfused rat mesenteric arteries with unbalanced endothelial endothelin-1 / nitric oxide ratio.

    Science.gov (United States)

    Barhoumi, Tlili; Jallat, Isabelle; Berthelot, Alain; Laurant, Pascal

    2011-06-01

    Chronic use of human recombinant erythropoietin (r-HuEPO) is accompanied by serious vascular side effects related to the rise in blood viscosity and shear stress. We investigated the direct effects of r-HuEPO on endothelium and nitric oxide (NO)-dependent vasodilatation induced by shear stress of cannulated and pressurized rat mesenteric resistance arteries. Intravascular flow was increased in the presence or absence of the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME; 10(-4) mol/L). In the presence of r-HuEPO, the flow-dependent vasodilatation was attenuated, while L-NAME completely inhibited it. The association of r-HuEPO and L-NAME caused a vasoconstriction in response to the rise in intravascular flow. Bosentan (10(-5) mol/L), an inhibitor of endothelin-1 (ET-1) receptors, corrected the attenuated vasodilatation observed with r-HuEPO and inhibited the vasoconstriction induced by flow in the presence of r-HuEPO and L-NAME. r-HuEPO and L-NAME exacerbated ET-1 vasoconstriction. At shear stress values of 2 and 14 dyn/cm(2) (1 dyn = 10(-5) N), cultured EA.hy926 endothelial cells incubated with r-HuEPO, L-NAME, or both released greater ET-1 than untreated cells. In conclusion, r-HuEPO diminishes flow-induced vasodilatation. This inhibitory effect seems to implicate ET-1 release. NO withdrawal exacerbates the vascular effects of ET-1 in the presence of r-HuEPO. These findings support the importance of a balanced endothelial ET-1:NO ratio to avoid the vasopressor effects of r-HuEPO.

  16. 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.

  17. 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.

  18. Efectos musculares y hematológicos del uso de rHuEpo en combinación con el entrenamiento físico : implicaciones de la demospresina y la hipoxia en el dopaje sanguíneo : estudios in vivo e in vitro

    OpenAIRE

    Martínez Bello, Vladimir Essau

    2011-01-01

    En la presente Tesis Doctoral hemos querido estudiar, en primer lugar, el efecto que tendría el incremento artificial de la capacidad de transporte de oxígeno, a través del tratamiento con rHuEpo, sobre distintos parámetros musculares así como su implicación en la mejora del rendimiento físico. Son muchos los autores que, tanto en el ámbito clínico (Winearls, Oliver y cols. 1986; Bommer, Muller-Buhl y cols. 1987) como en el ámbito deportivo (Berglund y Ekblom 1991; Lundby, Robach y cols. 2008...

  19. Effects of prolonged recombinant human erythropoietin administration on muscle membrane transport systems and metabolic marker enzymes

    DEFF Research Database (Denmark)

    Juel, C; Thomsen, J J; Rentsch, R L;

    2007-01-01

    Adaptations to chronic hypoxia involve changes in membrane transport proteins. The underlying mechanism of this response may be related to concomitant occurring changes in erythropoietin (Epo) levels. We therefore tested the direct effects of recombinant human erythropoietin (rHuEpo) treatment...... on the expression of muscle membrane transport proteins. Likewise, improvements in performance may involve upregulation of metabolic enzymes. Since Epo is known to augment performance we tested the effect of rHuEpo on some marker enzymes that are related to aerobic capacity. For these purposes eight subjects...... received 5,000 IU rHuEpo every second day for 14 days, and subsequently a single dose of 5,000 IU weekly for 12 weeks. Muscle biopsies were obtained before and after 14 weeks of rHuEpo treatment. The treatment increased hematocrit (from 44.7 to 48.8%), maximal oxygen uptake by 8.1%, and submaximal...

  20. Rechallenge with intravenous recombinant human erythropoietin can be successful following the treatment of anti-recombinant erythropoietin associated pure red cell aplasia.

    Science.gov (United States)

    Praditpornsilpa, Kearkiat; Tiranathanakul, Khajohn; Jootar, Saengsuree; Tungsanga, Kriang; Eiam-Ong, Somchai

    2014-05-01

    Anti recombinant human erythropoietin (r-HuEpo) associated pure red cell aplasia (PRCA) is an immunologic adverse effect of using subcutaneous r-HuEpo. Immunosuppressive agents have been suggested as treatment of this serious complication. After the reversal of anti-r-HuEpo antibody, the patients continue to have renal anemia and require long-term blood transfusion, albeit less frequently than when the antibody is positive. It is controversial whether re-challenging the patients with r-HuEpo is appropriate because re-challenging may cause the reappearance of the antibody. To balance the risk of antir-HuEpo antibody reappearance and longterm blood transfusion complications, we re-challenged r-HuEpo in five anti-r-HuEpo associated PRCA cases after a successful reversal of antibody using prednisolone in combination with cyclophosphamide. The rechallenge was performed intravenously since there were no reports of anti-r-HuEpo associated PRCA cases using this administration route. The duration after the reversal of antibody was 2.4 months before the re-challenge. Two patients were immediately re-challenged as soon as the antibodies reversed. After rechallenge with intravenous r-HuEpo, all patients responded to r-HuEpo: target level of Hb was maintained, blood transfusion was not required, and anti-r-HuEpo was consistently negative. All patients were followed for at least 6 months after re-challenge. Our data suggest that re-challenge with intravenous r-HuEpo can successfully treat anti- r-HuEpo associated PRCA.

  1. Use of recombinant human erythropoietin as an antianemic and performance enhancing drug.

    Science.gov (United States)

    Jelkmann, W

    2000-07-01

    The glycoprotein hormone erythropoietin is an essential viability and growth factor for the erythrocytic progenitors in the bone marrow. Tissue hypoxia is the main stimulus for the synthesis of the hormone in the kidneys and the liver. Endogenous erythropoietin and recombinant human erythropoietin (rHu-EPO) are similar with respect to their biological and chemical properties except for some microheterogeneities in their 4 carbohydrate chains. Generic products and alternatives to rHu-EPO are in development. Renal anemia can be corrected by rHu-EPO in a dose-dependent and predictable way without major side effects apart from a possible increase in arterial blood pressure. The optimal target hematocrit still needs to be defined. There are rare reports of antibody formation towards rHu-EPO in humans. Patients suffering from non-renal anemias may also benefit from the prescription of rHu-EPO. The drug has been approved for treatment of tumor patients with platinum-induced anemia. The cost-effectiveness and medical justification of the administration of rHu-EPO in tumor patients with respect to its positive effects on tumor oxygenation, tumor growth inhibition and support of chemo- and radiotherapy is still a matter of debate. In surgical patients, the pharmacological application of rHu-EPO can increase the yield of blood units in autologous blood donation programs and lower the severity and duration of postoperative anemia, if applicated some days prior to surgery. While rHu-EPO is a godsend in medical practice, its abuse as an performance enhancing drug by athletes in endurance sports is an unethical and potentially dangerous procedure. Unequivocal methods for detection of rHu-EPO doping still need to be established.

  2. 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.

  3. 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.

  4. 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.

  5. Recombinant human erythropoietin stimulates angiogenesis and wound healing in the genetically diabetic mouse.

    Science.gov (United States)

    Galeano, Mariarosaria; Altavilla, Domenica; Cucinotta, Domenico; Russo, Giuseppina T; Calò, Margherita; Bitto, Alessandra; Marini, Herbert; Marini, Rolando; Adamo, Elena B; Seminara, Paolo; Minutoli, Letteria; Torre, Valerio; Squadrito, Francesco

    2004-09-01

    The effects of recombinant human erythropoietin (rHuEPO) in diabetes-related healing defects were investigated by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ-m(+/+)Lept(db) mice (db(+)/db(+)) and their normoglycemic littermates (db(+/+)m). Animals were treated with rHuEPO (400 units/kg in 100 microl s.c.) or its vehicle alone (100 microl). Mice were killed on different days (3, 6, and 12 days after skin injury) for measurement of vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis, for monitoring angiogenesis by CD31 expression, and for evaluating histological changes. Furthermore, we evaluated wound-breaking strength at day 12. At day 6, rHuEPO injection in diabetic mice resulted in an increase in VEGF mRNA expression (vehicle = 0.33 +/- 0.1 relative amount of mRNA; rHuEPO = 0.9 +/- 0.09 relative amount of mRNA; P < 0.05) and protein wound content (vehicle = 23 +/- 5 pg/wound; rHuEPO = 92 +/- 12 pg/wound; P < 0.05) and caused a marked increase in CD31 gene expression (vehicle = 0.18 +/- 0.05 relative amount of mRNA; rHuEPO = 0.98 +/- 0.21 relative amount of mRNA; P < 0.05) and protein synthesis. Furthermore, rHuEPO injection improved the impaired wound healing and, at day 12, increased the wound-breaking strength in diabetic mice (vehicle = 12 +/- 2 g/mm; rHuEPO 21 +/- 5 g/mm; P < 0.05). Erythropoietin may have a potential application in diabetes-related wound disorders.

  6. 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.

  7. Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia.

    Science.gov (United States)

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

    2015-12-25

    This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum) protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy.

  8. 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

  9. Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin β Subunit to the N-Terminal and C-Terminal Coding Sequence

    Directory of Open Access Journals (Sweden)

    Fuad Fares

    2011-01-01

    Full Text Available A new analog of EPO was designed by fusing one and two CTPs to the N-terminal and C-terminal ends of EPO (EPO-(CTP3, respectively. This analog was expressed and secreted efficiently in CHO cells. The in vitro test shows that the activity of EPO-(CTP3 in TFI-1 cell proliferation assay is similar to that of EPO-WT and commercial rHEPO. However, in vivo studies indicated that treatment once a week with EPO-(CTP3 (15 μg/kg dramatically increased (~8 folds haematocrit as it was compared to rHuEPO. Moreover, it was found that EPO-(CTP3 is more effective than rHuEPO and Aranesp in increasing reticulocyte number in mice blood. The detected circulatory half-lives of rHuEPO, Aranesp, and EPO-(CTP3 following IV injection of 20 IU were 4.4, 10.8, and 13.1 h, respectively. These data established the rational for using this chimera as a long-acting EPO analog in clinics. The therapeutic efficacy of EPO-CTP analog needs to be established in higher animals and in human clinical trials.

  10. 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.

  11. Use of Aspirin in normalization of recombinant human erythropoietin-mediated hyper-reactivity of platelets in rats

    Directory of Open Access Journals (Sweden)

    Hitesh M Soni

    2014-01-01

    Conclusions: These findings suggest that rHuEPO increases platelet reactivity and aspirin normalizes the hyper-reactive platelet and may reduce the cardiovascular events associated with rHuEPO in CKD patients.

  12. Structural Identification of a Non-Glycosylated Variant at Ser126 for O-Glycosylation Site from EPO BRP, Human Recombinant Erythropoietin by LC/MS Analysis.

    Science.gov (United States)

    Byeon, Jaehee; Lim, Yu-Ri; Kim, Hyong-Ha; Suh, Jung-Keun

    2015-06-01

    A variant peak was detected in the analysis of RP-HPLC of rHu-EPO, which has about 7% relative content. Fractions of the main and the variant peaks were pooled separately and further analyzed to identify the molecular structure of the variant peak. Total mass analysis for each peak fraction using ESI-TOF MS shows differences in molecular mass. The fraction of the main peak tends to result in higher molecular masses than the fraction of the variant. The detected masses for the variant are about 600-1000 Da smaller than those for the main peak. Peptide mapping analysis for each peak fraction using Asp-N and Glu-C shows differences in O-glycopeptide profiles at Ser126. The O-glycopeptides were not detected in the fraction of the variant. It is concluded that the variant peak is non-O-glycosylated rHu-EPO and the main peak is fully O-glycosylated rHu-EPO at Ser126.

  13. 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.

  14. Recombinant human erythropoietin in the prevention of late anemia in intrauterine transfused neonates with Rh-isoimmunization.

    Science.gov (United States)

    Zuppa, Antonio Alberto; Alighieri, Giovanni; Calabrese, Valentina; Visintini, Federica; Cota, Francesco; Carducci, Chiara; Antichi, Eleonora; Noia, Giuseppe Antonio; Fortunato, Giuseppe; Romagnoli, Costantino

    2010-04-01

    The majority of neonates with Rh-isoimmunization develops late anemia between the second and the sixth week of life. We report the effectiveness of recombinant human erythropoietin (rHuEPO) in preventing late anemia in 25 intrauterine and nonintrauterine-transfused neonates. The neonates were treated from 11+/-4 days after birth to 26+/-14 days (400 U/kg/d of rHuEpo, administered subcutaneously). During rHuEpo therapy, vitamin E, calcium folinate, and iron maltose were administered intramuscularly on a daily basis. Hematocrit, platelet, and neutrophil counts did not differ significantly before and after 21-days therapy. However, average values for reticulocyte showed a significant increase. The hematocrit values in the non-intrauterine transfusion (IUT) group increased progressively from the beginning to the end of the treatment, whereas that in the IUT group remained stable. Reticulocyte count increased during treatment in both groups, but it was significantly elevated in the non-IUT group only. Moreover, we observed that only neonates transfused with IUTs needed transfusions before and after treatment. This study suggests the effectiveness of rHuEpo therapy in the treatment of neonates with Rh-isoimmunization and it highlights how IUTs decrease the neonatal response efficacy. Larger, better if multicentric, randomized controlled trial are needed to definitely state whether rHuEPO safely decreases the incidence of late onset anemia.

  15. Bioenergetics of the calf muscle in Friedreich ataxia patients measured by 31P-MRS before and after treatment with recombinant human erythropoietin.

    Directory of Open Access Journals (Sweden)

    Wolfgang Nachbauer

    Full Text Available Friedreich ataxia (FRDA is caused by a GAA repeat expansion in the FXN gene leading to reduced expression of the mitochondrial protein frataxin. Recombinant human erythropoietin (rhuEPO is suggested to increase frataxin levels, alter mitochondrial function and improve clinical scores in FRDA patients. Aim of the present pilot study was to investigate mitochondrial metabolism of skeletal muscle tissue in FRDA patients and examine effects of rhuEPO administration by phosphorus 31 magnetic resonance spectroscopy (31P MRS. Seven genetically confirmed FRDA patients underwent 31P MRS of the calf muscles using a rest-exercise-recovery protocol before and after receiving 3000 IU of rhuEPO for eight weeks. FRDA patients showed more rapid phosphocreatine (PCr depletion and increased accumulation of inorganic phosphate (Pi during incremental exercise as compared to controls. After maximal exhaustive exercise prolonged regeneration of PCR and slowed decline in Pi can be seen in FRDA. PCr regeneration as hallmark of mitochondrial ATP production revealed correlation to activity of complex II/III of the respiratory chain and to demographic values. PCr and Pi kinetics were not influenced by rhuEPO administration. Our results confirm mitochondrial dysfunction and exercise intolerance due to impaired oxidative phosphorylation in skeletal muscle tissue of FRDA patients. MRS did not show improved mitochondrial bioenergetics after eight weeks of rhuEPO exposition in skeletal muscle tissue of FRDA patients.EU Clinical Trials Register2008-000040-13.

  16. Serum zinc and hormonal profile in male dialysis patients receiving human recombinant erythropoietin Zinco sérico e perfil hormonal de pacientes do sexo masculino submetidos à hemodiálise em uso de eritropoetina humana recombinante

    Directory of Open Access Journals (Sweden)

    Maria Mouranilda Schleicher

    2005-08-01

    Full Text Available INTRODUCTION: Treatment with recombinant human erythropoietin (rHuEpo is associated with an improvement in well-being and quality of life in patients submitted to maintenance hemodialysis (HD. OBJECTIVES: The goal of this work was to evaluate the levels of sex hormones, hematocrit, albumin and zinc in HD patients with rHuEpo therapy and compare them with those observed in patients without rHuEpo treatment. MATERIAL AND METHODS: Two groups of twelve male HD patients each were selected for a transversal study; one did not receive rHuEpo (group 1 whereas the other one did (group 2. Levels of hematocrit, albumin, zinc, luteinizing hormone (LH, follicle-stimulating hormone (FSH, prolactin, and testosterone were determined. RESULTS: Group 2 patients showed significantly higher medians (p INTRODUÇÃO: Em pacientes submetidos à hemodiálise crônica (HD, o tratamento com eritropoetina humana recombinante (rHuEpo está associado a melhora no bem-estar geral e na qualidade de vida. OBJETIVOS: O objetivo do presente trabalho foi avaliar os níveis dos hormônios sexuais e do zinco em pacientes sob HD e em uso de rHuEpo em comparação com pacientes sem tratamento com essa droga. MATERIAL E MÉTODOS: Dois grupos de doze pacientes do sexo masculino cada um, submetidos à HD, sendo um deles sem uso de rHuEpo (grupo 1 e o outro utilizando a droga (grupo 2, foram selecionados para um estudo transversal, comparando-se os níveis séricos do zinco, da albumina, dos hormônios FSH, LH, prolactina, testosterona e do hematócrito. RESULTADOS: No grupo 2, os valores de testosterona (4,65 vs. 3,5ng/ml, hematócrito (30,5 vs. 22%, albumina (3,9 vs. 3,7g/dl e zinco (62,5 vs. 50,5microg/dl foram significativamente maiores do que no grupo 1 (p < 0,05. DISCUSSÃO: Sugere-se que, em pacientes recipientes da rHuEpo, os níveis mais altos de hematócrito, zinco, albumina e testosterona possam ser fatores que contribuam para melhorar a disfunção sexual e a qualidade de

  17. 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.

  18. 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.

  19. 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.

  20. Production and Characterization of Monoclonal Antibody Against Recombinant Human Erythropoietin

    Institute of Scientific and Technical Information of China (English)

    JIE-BO MI; JIN YAN; XIAO-JIE DING; ZHEN-QUAN GUO; MEI-PING ZHAO; WEN-BAO CHANG

    2007-01-01

    Objective To produce specific monoclonal antibody(mAb)against recombinant human erythropoietin(rHuEPO)for development of higmy efficient methods for erythropoietin detection in biological fluids.Methods rHuEPO was covalently coupled with bovine serum albumin(BSA)and the conjugate was used to immunize mice to produce specific mAb against rHuEPO based on hybridoma technology.The obtained F3-mAb was characterized by enzyme-linked immunosorbent assay (ELISA),SDS-PAGE and Western blot.Results The isotype of F3-mAb Was found to be IgM with an affinity constant of 2.1x108 L/mol.The competitive ELISA using the obtained IgM showed a broader linear range and lower detection limit compared with previous work.Conclusions The modification of rHuEPO was proved to be successful in generating required specific mAb with high avidity to rHuEPO.

  1. Study on methods of glycans for erythropoietin (EPO)%重组人促红素糖指纹图谱分析技术研究

    Institute of Scientific and Technical Information of China (English)

    周勇; 邵宝珠; YUEN Chun-ting; 王丽; 王军志

    2012-01-01

    目的:建立重组人促红素N-糖链特征性糖指纹图谱检测分析技术.方法:分别用外切糖苷酶(PNGase F)和神经氨酸酶酶切重组人促红素,超滤离心获得糖的各种组分,使用高pH离子色谱分析N-糖链的结构和组成并确定N-糖链指纹图谱.结果:建立的方法稳定可靠,重复性好,可用于重组人促红素糖结构和组成的研究和质量控制.结论:本研究建立了简便、有效的重组人促红素N-糖链特征性糖指纹图谱检测分析方法.%Objective:To establish analytical methods for N - glycans finger printing of human recombinant erythro- poietin (rHuEPO). Methods:The N - glycosidically - linked oligosaccharide chains and the terminal sialic acid residues of rHuEPO are released from the glycoprotein by N - glycosidase F and neuraminidase digestion separately. After removal of the protein fraction,the resultiant oligosaccharides are chromatographically separated using high pH anion - exchange chromatography with pulsed amperometric detection (HPAEC -PAD). Results; The methods are well suited for the study and quality control of N - glycans structure and composition of rHuEPO, and the results of all tests were reliable and reproducible. Conclusion; The analytical methods of characteristic N - glycans finger printing have been established for the analysis and quality control of rHuEPO N - glycans.

  2. [Neuroprotector effect of human recombinant erythropoietin sorbed on polymer nanoparticles studied on model of intracerebral post-traumatic hematoma (hemorrhagic stroke)].

    Science.gov (United States)

    Balaban'ian, V Iu; Solev, I N; Elizarova, O S; Garibova, T L; Litvinova, S A; Voronina, T A

    2011-01-01

    The neuroprotective activity of recombinant human erythropoietin (r-HuEpo) sorbed on poly(butyl)cyanoacrilate nanoparticles (EPO-PBCA) and on polylactic-co-glycolic acid nanoparticles (EPO-PLGA) has been studied on Wistar rats with intracerebral post-traumatic hematoma (model of hemorrhagic stroke) (IPH-HS) in comparison to native r-HuEpo. It is established that EPO-PBCA produced a protective effect in rats after IPH-HS that was manifested by a decrease in the number of animals with neurological disorders such as circus movement, paresis, and paralysis of hind limbs; the drug also improved coordination (rotating rod test), reduced the number of lost animals, and decreased the loss weight among survived rats. In addition, EPO-PBCA optimized the research behavior of rats with IPH-HS in the open field test and prevented amnesia of passive avoidance reflex (PAR), which was caused by the IPH-HS. These effects were manifested during a two-week observation period. EPO-PLGA has a similar but much less pronounced effect on the major disorders caused by IPH-HS. The efficiency of native r-HuEpo as a neuropotective agent was insignificant and only manifested by decrease in the number of lost animals with IPH-HS.

  3. Exercise aggravates cardiovascular risks and mortality in rats with disrupted nitric oxide pathway and treated with recombinant human erythropoietin.

    Science.gov (United States)

    Meziri, Fayçal; Binda, Delphine; Touati, Sabeur; Pellegrin, Maxime; Berthelot, Alain; Touyz, Rhian M; Laurant, Pascal

    2011-08-01

    Chronic administration of recombinant human erythropoietin (rHuEPO) can generate serious cardiovascular side effects such as arterial hypertension (HTA) in clinical and sport fields. It is hypothesized that nitric oxide (NO) can protect from noxious cardiovascular effects induced by chronic administration of rHuEPO. On this base, we studied the cardiovascular effects of chronic administration of rHuEPO in exercise-trained rats treated with an inhibitor of NO synthesis (L-NAME). Rats were treated or not with rHuEPO and/or L-NAME during 6 weeks. During the same period, rats were subjected to treadmill exercise. The blood pressure was measured weekly. Endothelial function of isolated aorta and small mesenteric arteries were studied and the morphology of the latter was investigated. L-NAME induced hypertension (197 ± 6 mmHg, at the end of the protocol). Exercise prevented the rise in blood pressure induced by L-NAME (170 ± 5 mmHg). However, exercise-trained rats treated with both rHuEPO and L-NAME developed severe hypertension (228 ± 9 mmHg). Furthermore, in these exercise-trained rats treated with rHuEPO/L-NAME, the acetylcholine-induced relaxation was markedly impaired in isolated aorta (60% of maximal relaxation) and small mesenteric arteries (53%). L-NAME hypertension induced an internal remodeling of small mesenteric arteries that was not modified by exercise, rHuEPO or both. Vascular ET-1 production was not increased in rHuEPO/L-NAME/training hypertensive rats. Furthermore, we observed that rHuEPO/L-NAME/training hypertensive rats died during the exercise or the recovery period (mortality 51%). Our findings suggest that the use of rHuEPO in sport, in order to improve physical performance, represents a high and fatal risk factor, especially with pre-existing cardiovascular risk.

  4. 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.

  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. 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...

  7. 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...

  8. Magnetic resonance imaging of the bone marrow following treatment with recombinant human erythropoietin in patients with end-stage renal disease

    DEFF Research Database (Denmark)

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

    1990-01-01

    We used magnetic resonance imaging (MRI) to study vertebral bone marrow in hemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). We found changes in T1 relaxation times and image contrast within 14 days after starting treatment, before any response was seen in the...

  9. 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

  10. Screening for recombinant human erythropoietin using [Hb], reticulocytes, the OFF(hr score), OFF(z score) and Hb(z score): status of the Blood Passport.

    Science.gov (United States)

    Bornø, Andreas; Aachmann-Andersen, Niels J; Munch-Andersen, Thor; Hulston, Carl J; Lundby, Carsten

    2010-06-01

    Haemoglobin concentration ([Hb]), reticulocyte percentage (retic%) and OFF(hr score) are well-implemented screening tools to determine potential recombinant human erythropoietin (rHuEpo) abuse in athletes. Recently, the International Cycling Union implemented the OFF(z score) and the Hb(z score) in their anti-doping testing programme. The aim of this study is to evaluate the sensitivity of these indirect screening methods. Twenty-four human subjects divided into three groups with eight subjects each (G1; G2 and G3) were injected with rHuEpo. G1 and G2 received rHuEpo for a 4-week period with 2 weeks of "boosting" followed by 2 weeks of "maintenance" and a wash-out period of 3 weeks. G3 received rHuEpo for a 10-week period (boost = 3 weeks; maintenance = 7 weeks; wash out = 1 week). Three, seven and eight of the 24 volunteers exceeded the cut-off limits for OFF(hr score), [Hb] and retic%, respectively. One subject from G1, nobody from G2, and seven subjects from G3 exceeded the cut-off limit for Hb(z score.) In total, ten subjects exceeded the cut-off limit for the OFF(z score); two subjects from G1, two subjects from G2 and six subjects from G3. In total, indirect screening methods were able to indicate rHuEpo injections in 58% of subjects. However, 42% of our rHuEpo-injected subjects were not detected. It should be emphasised that the test frequency in real world anti-doping is far less than the present study, and hence the detection rate will be lower.

  11. Meeting the challenges of a new millennium: optimizing the use of recombinant human erythropoietin.

    Science.gov (United States)

    Macdougall, I C

    1998-01-01

    Optimizing the use of recombinant human erythropoietin (r-HuEPO) involves choosing an appropriate dose regimen and target haemoglobin level, addressing factors that inhibit response, and considering appropriate adjuvant therapy. Subcutaneous administration of r-HuEPO two or three times weekly is optimal for most patients. Early detection and treatment of iron deficiency is mandatory. Measurement of the percentage of hypochromic red blood cells is a reliable marker of functional iron deficiency, and the treatment of choice is intravenous iron. Other factors that can affect the response to r-HuEPO include blood loss (sometimes occult), infection, inflammation, hyperparathyroidism with marrow fibrosis, aluminium toxicity, vitamin B12/folate deficiency, haemolysis, bone marrow disorders, haemoglobinopathies, under-dialysis and possibly angiotensin-converting enzyme inhibitors. These factors should be identified and corrected where possible. Ascorbic acid, vitamin D, folic acid, carnitine, other cytokines and growth factors have all been shown to augment the response to r-HuEPO in some patients. Further research is required before any of these adjuvant therapies can be incorporated into routine clinical practice. With regard to target haemoglobin value, the current practice is to aim for a level of 10-12 g/dl, but it may be argued that a higher target would achieve greater benefits in terms of physical performance, quality of life, and possibly cardiac morbidity and mortality. International multicentre trials are currently in progress to address this issue, as are studies on other substances that may be able to stimulate erythropoiesis.

  12. Recombinant human erythropoietin stimulates angiogenesis and healing of ischemic skin wounds.

    Science.gov (United States)

    Buemi, Michele; Galeano, Mariarosaria; Sturiale, Alessio; Ientile, Riccardo; Crisafulli, Costantino; Parisi, Alessandra; Catania, MariaAntonietta; Calapai, Gioacchino; Impalà, Patrizia; Aloisi, Carmela; Squadrito, Francesco; Altavilla, Domenica; Bitto, Alessandra; Tuccari, Giovanni; Frisina, Nicola

    2004-08-01

    Wound healing in ischemic tissues such as flap margins due to inadequate blood supply is still a source of considerable morbidity in surgical practice. Adequate tissue perfusion is particularly important in wound healing. We investigated the effects of recombinant human erythropoietin (rHuEPO) on wound healing in an ischemic skin wound model. Sixty-three Sprague-Dawley rats were used. Normal incisional wound and H-shaped double flaps were used as the wound models. Animals were treated with rHuEPO (400 IU/kg) or its vehicle. Rats were killed on different days (3, 5, and 10 days after skin injury) and the wounded skin tissues were used for immunohistochemistry and for analysis of vascular endothelial growth factor content and collagen content. Tissue transglutaminase immunostaining of histological specimens was used as a vascular marker to determine the level of microvessel density. The results showed a higher level of vascular endothelial growth factor protein and an increased microvessel density in ischemic wounds with rHuEPO treatment than the normal incisional wounds and ischemic control wounds. Collagen content was higher in the incisional wounds and in the ischemic wounds with rHuEPO treatment compared with the ischemic control wounds. Our results suggest that erythropoietin may be an effective therapeutic approach in improving healing in ischemic skin wounds.

  13. 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.

  14. Clinical recommendations for the use of recombinant human erythropoietin in patients with hepatitis C virus being treated with ribavirin.

    Science.gov (United States)

    Sherman, Morris; Cohen, Lawrence; Cooper, Mary Anne; Elkashab, Magdy; Feinman, Victor; Fletcher, David; Girgrah, Nigel; Heathcote, Jenny; Levstik, Mark; McNaull, William B; Wong, David; Wong, Florence; Yim, Colina

    2006-07-01

    Today, combination antiviral therapy with pegylated interferon-alpha and ribavirin (RBV) allows many patients infected with hepatitis C virus (HCV) to achieve a sustained virological response, which is equivalent to cure. Data also support the clinical benefit of combination antiviral therapy in patients coinfected with HCV and HIV, and in patients who have received a liver transplant. Antiviral therapy with pegylated interferon-alpha and RBV is, however, associated with a high incidence and significant magnitude of anemia. This anemia may have several mechanisms, including bone marrow suppression and hemolysis. In addition, patients coinfected with HIV may have both pre-existing and RBV-associated anemia. Management of anemia in patients with HCV through RBV dose reduction or treatment discontinuation may compromise the effectiveness of treatment, because studies have demonstrated that treatment adherence or maintenance of antiviral therapy dose is an important predictor of sustained virological response. Anemia associated with combination antiviral therapy in patients with HCV is frequently associated with an inadequate or blunted endogenous erythropoietin response. Accumulating evidence now supports the use of recombinant human erythropoietin (rHuEpo) to manage anemia in these patients, with the objective of maintaining the RBV dose, but clinical standards are lacking. The present article reviews the data relevant to the use of rHuEpo in this patient population and proposes a set of clinical practice standards to assist clinicians in selecting patients for rHuEpo and in implementing rHuEpo therapy effectively.

  15. Tratamiento con eritropoyetina humana recombinante Human recombinant erythropoietin therapy

    Directory of Open Access Journals (Sweden)

    Hugo Donato

    2006-02-01

    Full Text Available La eritropoyetina recombinante (rHuEPO se ha transformado en la citoquina más utilizada terapéuticamente en el mundo. Luego del éxito obtenido en pacientes con insuficiencia renal terminal, se pudo establecer la utilidad de la terapia con rHuEPO para mejorar otras anemias, incluso en pacientes pediátricos y neonatos. El tratamiento o la prevención de la anemia del prematuro mediante el uso de rHuEPO llevó a una significativa reducción en cantidad de transfusiones y en exposición a dadores. Aún debe establecerse una clara definición sobre cuáles niños prematuros deben recibir tratamiento rutinariamente. Otras indicaciones en período neonatal incluyen anemias hiporregenerativas y hemolíticas. La eficacia de la rHuEPO en niños mayores, con excepción de la insuficiencia renal crónica, no ha sido tan exhaustivamente evaluada como en adultos. Mientras que durante los últimos años se han realizado gran cantidad de estudios en adultos con anemia asociada al cáncer o a infección por HIV, permitiendo establecer conclusiones claras sobre su eficacia, sólo escasa cantidad de estudios con pequeño número de pacientes han sido realizados en niños. Hasta la fecha, los resultados sugieren que la terapia con rHuEPO en niños es tan útil como en adultos, pero la realización de estudios aleatorizados prospectivos incluyendo gran número de pacientes es esencial para alcanzar conclusiones definitivas. Los resultados de estudios dirigidos a evaluar la eficacia de la rHuEpo para mantener una dosis adecuada de ribavirina en pacientes en tratamiento por hepatitis C son alentadores. La utilización potencial de los efectos no hemopoyéticos de la rHuEPO en neonatos es un terreno novedoso y apasionante. El rol de la Epo como citoprotector para sistema nervioso central y mucosa intestinal está bajo investigación exhaustiva.Recombinant human erythropoietin (rHuEpo has become the most widely used cytokine in the world. Following the success of

  16. EPO gene expression promotes proliferation, migration and invasion via the p38MAPK/AP-1/MMP-9 pathway by p21WAF1 expression in vascular smooth muscle cells.

    Science.gov (United States)

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

    2015-03-01

    The use of recombinant human erythropoietin (rHuEpo) can lead to hypertrophy and hyperplasia, and has induced the proliferation of vascular smooth muscle cells (VSMCs). The effect of the EPO gene in the migration and invasion of VSMCs remains unclear. In this study, overexpression of the EPO gene increased the DNA synthesis and phosphorylation of ERK1/2 and p38MAPK in VSMCs. In addition, EPO gene expression induced the migration and invasion of VSMCs via the expression of MMP-9 by the activation of NF-κB and AP-1 binding. A blockade of p38MAPK by specific p38MAPK inhibitor SB203580 led to a suppression of the increased DNA synthesis, migration, and invasion of VSMCs that was induced by the EPO gene. SB203580 treatment blocked the increased expression of MMP-9 through the binding activity of AP-1. Transfection of the EPO gene with VSMCs was associated with the up-regulation of cyclin D1/CDK4, cyclin E/CDK2, and p21WAF1, and with the down-regulation of p27KIP1. The specific suppression of p21WAF1 expression by siRNA rescued the enhancement of DNA synthesis via the phosphorylation of p38MAPK and the increase in migration and invasion through AP-1-mediated MMP-9 expression in EPO gene transfectants. These novel findings demonstrate that p21WAF1 regulates the proliferation, migration and invasion of VSMC induced by EPO gene.

  17. Optimization of human erythropoietin gene and its expression in E.coli%人促红细胞生成素基因的优化及其在大肠杆菌中的表达

    Institute of Scientific and Technical Information of China (English)

    卢杨利; 梁洪; 容新宗; 王焰; 龚曼琳

    2015-01-01

    Objective Optimize human erythropoietin (HuEPO) gene to improve its expression in E.coli and the recovery in the process of purification.Methods The base sequence of HuEPO gene was designed by replacing the rare codons in E.coli with biased codons to construct the gene expressing recombinant HuEPO (rHuEPO).The sites of amino acid mutations of HuEPO were designed,and sitedirected mutagenesis was performed for these sites to obtain mutational rHuEPO (MrHuEPO) with high hydrophilia.The rHuEPO and MrHuEPO genes of were cloned into expression vector pET-15b and expressed in E.coli,and purification and renaturation of expression products were carried out.Solubility and recovery in the renaturation process were compared between rHuEPO and MrHuEPO.The activities of rHuEPO and MrHuEPO were detected using the HuEPO ELISA kit.Results rHuEPO and MrHuEPO were expressed successfully in E.coli,and the expression levels of both were more than 25%.The results of tertiary structure prediction showed that the design of mutation sites was reasonable.There were no difference in the expression levels between rHuEPO and MrHuEPO,but the solubility of MrHuEPO (recovery >90%) was significantly higher than that of rHuEPO (recovery <25%) in the renaturation process.The specific activities of rHuEPO and MrHuEPO were 2.36 × 105 and 2.33 × 105 IU/mg,respectively.Conclusion The genes expressing rHuEPO and MrHuEPO in E.coli are contructed successfully,and the solubility of MrHuEPO in the renaturation process is significantly improved by site-directed mutagenesis.%目的 对人促红细胞生成素(human erythropoietin,HuEPO)基因进行优化,提高其在大肠杆菌中的表达量以及纯化过程中的回收率.方法 对HuEPO基因的碱基序列进行设计,用大肠杆菌偏爱密码子替换稀有密码子,构建高效表达重组(r) HuEPO(rHuEPO)的基因.设计rHuEPO的氨基酸突变位点,并对这些位点进行定点诱变,获得高亲水性的突变(M) rHuEPO(MrHuEPO).

  18. [Predictive response variables to recombinant human erythropoietin treatment in patients with anemia and cancer].

    Science.gov (United States)

    Lastiri, José M; Specterman, Sergio R; Rendo, Pablo; Pallotta, María G; Varela, Mirta S; Goldstein, Sofía

    2002-01-01

    The use of human recombinant erythropoietin (rHuEpo) has been approved by the Food and Drug Administration (FDA) in patients with anemia and cancer. Although good results have been obtained, it is too expensive to permit its use massively. For the purpose of evaluating the therapeutic effect of rHuEpo, including toxicity, predictive response variables and quality of life parameters, a prospective trial was carried out in patients with anemia and cancer. Hematimetric parameters, ferritin, Epo, cytokines, transfusions and quality of life were registered. A total of 36 patients were treated in the protocol (34 were evaluable): 16 men and 20 women, with a medium age 56.4 years; 27 patients were treated with chemotherapy (16 with cisplatinum); 15 patients presented medullar infiltration. In 73.5% patients an increase in the level of hemoglobin was registered, and in 64.7% its normalisation was attained. Transfusional requirements were reduced by 50%. The hemoglobin increase greater than 0.5 g/dl at the second week of treatment was the most significant variable of early response. Patients treated with cisplatinum, seric ferritin lower than 1,100 ng/dl and those without medullar tumoral infiltration responded best. Serum Epo, cytokines (IL-1, IL-6 and TNF) and reticulocyte count at the second week did not correlate with response. Quality of life parameters were better in patients with good response to rHuEpo. It can be concluded that good results in the treatment of patients with anemia and cancer are obtained with rHuEpo.

  19. Recombinant human erythropoietin alpha improves the efficacy of radiotherapy of a human tumor xenograft, affecting tumor cells and microvessels

    Energy Technology Data Exchange (ETDEWEB)

    Loevey, J. [Dept. of Radiotherapy, National Inst. of Oncology, Budapest (Hungary); Bereczky, B.; Gilly, R.; Kenessey, I.; Raso, E.; Simon, E.; Timar, J. [Dept. of Tumor Progression, National Inst. of Oncology, Budapest (Hungary); Dobos, J. [Dept. of Tumor Progression, National Inst. of Oncology, Budapest (Hungary); National Koranyi Inst. of TBC and Pulmonology, Budapest (Hungary); Vago, A. [Central Lab., National Inst. of Oncology, Budapest (Hungary); Kasler, M. [Head and Neck Surgery, National Inst. of Oncology, Budapest (Hungary); Doeme, B. [National Koranyi Inst. of TBC and Pulmonology, Budapest (Hungary); Tovari, J. [National Koranyi Inst. of TBC and Pulmonology, Budapest (Hungary); 1. Inst. of Pathology and Experimental Cancer Research, Semmelweis Univ., Budapest (Hungary)

    2008-01-15

    Background and purpose: tumor-induced anemia often occurs in cancer patients, and is corrected by recombinant human erythropoietins (rHuEPOs). Recent studies indicated that, besides erythroid progenitor cells, tumor and endothelial cells express erythropoietin receptor (EPOR) as well; therefore, rHuEPO may affect their functions. Here, the effect of rHuEPO{alpha} on irradiation in EPOR-positive human squamous cell carcinoma xenograft was tested. Material and methods: A431 tumor-bearing SCID mice were treated from the tumor implantation with rHuEPO{alpha} at human-equivalent dose. Xenografts were irradiated (5 Gy) on day 14, and the final tumor mass was measured on day 22. The systemic effects of rHuEPO{alpha} on the hemoglobin level, on tumor-associated blood vessels and on hypoxia-inducible factor-(HIF-)1{alpha} expression of the tumor xenografts were monitored. The proliferation, apoptosis and clonogenic capacity of A431 cancer cells treated with rHuEPO{alpha} and irradiation were also tested in vitro. Results: in vitro, rHuEPO{alpha} treatment alone did not modify the proliferation of EPOR-positive A431 tumor cells but enhanced the effect of irradiation on proliferation, apoptosis and clonogenic capacity. In vivo, rHuEPO{alpha} administration compensated the tumor-induced anemia in SCID mice and decreased tumoral HIF-1{alpha} expression but had no effect on tumor growth. At the same time rHuEPO{alpha} treatment significantly increased the efficacy of radiotherapy in vivo (tumor weight of 23.9 {+-} 4.7 mg and 34.9 {+-} 4.6 mg, respectively), mediated by increased tumoral blood vessel destruction. Conclusion: rHuEPO{alpha} treatment may modulate the efficacy of cancer radiotherapy not only by reducing systemic hypoxia and tumoral HIF-1{alpha} expression, but also by destroying tumoral vessels. (orig.)

  20. [Use of human recombinant erythropoietin in children with cancer].

    Science.gov (United States)

    Guyot, D; Margueritte, G

    2005-09-01

    Eighty percent of children with cancer suffer from anemia at the time of diagnosis. The physiopathology of anemia is complex. Although anemia can be life threatening, its consequences on the physical, psychological and social state of the child are often minimized. Blood transfusion is the main treatment of anemia: its efficacy is immediate but shortlasting, and it involves infectious and hemolytic risks. The human recombinant erythropoietin has been used for more than 25-years, and is often prescribed to adults with cancer and anemia. The human recombinant erythropoietin rHuEPO is nowadays used when blood transfusion is contra-indicated because of religious or cultural considerations, although several promising studies have been conducted about rHuEPO and children with cancer since 1996: it might be soon the preferential alternative treatment to anemia in children with cancer.

  1. 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.

  2. 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.

  3. Cytoprotective effect of recombinant human erythropoietin produced in transgenic tobacco plants.

    Directory of Open Access Journals (Sweden)

    Farooqahmed S Kittur

    Full Text Available Asialo-erythropoietin, a desialylated form of human erythropoietin (EPO lacking hematopoietic activity, is receiving increased attention because of its broader protective effects in preclinical models of tissue injury. However, attempts to translate its protective effects into clinical practice is hampered by unavailability of suitable expression system and its costly and limit production from expensive mammalian cell-made EPO (rhuEPO(M by enzymatic desialylation. In the current study, we took advantage of a plant-based expression system lacking sialylating capacity but possessing an ability to synthesize complex N-glycans to produce cytoprotective recombinant human asialo-rhuEPO. Transgenic tobacco plants expressing asialo-rhuEPO were generated by stably co-expressing human EPO and β1,4-galactosyltransferase (GalT genes under the control of double CaMV 35S and glyceraldehyde-3-phosphate gene (GapC promoters, respectively. Plant-produced asialo-rhuEPO (asialo-rhuEPO(P was purified by immunoaffinity chromatography. Detailed N-glycan analysis using NSI-FTMS and MS/MS revealed that asialo-rhuEPO(P bears paucimannosidic, high mannose-type and complex N-glycans. In vitro cytoprotection assays showed that the asialo-rhuEPO(P (20 U/ml provides 2-fold better cytoprotection (44% to neuronal-like mouse neuroblastoma cells from staurosporine-induced cell death than rhuEPO(M (21%. The cytoprotective effect of the asialo-rhuEPO(P was found to be mediated by receptor-initiated phosphorylation of Janus kinase 2 (JAK2 and suppression of caspase 3 activation. Altogether, these findings demonstrate that plants are a suitable host for producing cytoprotective rhuEPO derivative. In addition, the general advantages of plant-based expression system can be exploited to address the cost and scalability issues related to its production.

  4. 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.

  5. Efficacy and safety of adjuvant recombinant human erythropoietin and ferrous sulfate as treatment for iron deficiency anemia during the third trimester of pregnancy.

    Science.gov (United States)

    Sanchez-Gonzalez, Luis Rodrigo; Castro-Melendez, Simón Enrique; Angeles-Torres, Alejandra Cristina; Castro-Cortina, Nohemi; Escobar-Valencia, Alfredo; Quiroga-Garza, Alejandro

    2016-10-01

    Gestational anemia increases the incidence of maternal and fetal complications. Adjuvant recombinant human erythropoietin (rHuEPO) has been used in patients who refuse blood transfusions, have a low response to treatment with iron sulfate, have limited time before birth, or have other illnesses that complicate the anemia. We demonstrated that the use of adjuvant rHuEPO with iron sulfate reduces the anemia time period and is innocuous to the fetus. An experimental longitudinal prospective study; 100 pregnant women in their third trimester were included. Group 1 (n=50) was set as control for prevalence of anemia and establish hematological maternal and fetal parameters at delivery for our population; 50 women diagnosed with iron deficiency anemia were randomly assigned to treatment groups. Group 2 (n=25) third trimester women with a hemoglobin of <11g/dL were treated with iron sulfate, 600mg administered orally daily for 4 weeks, evaluating the hematologic response for the mother weekly and for both mother and fetus at birth; Group 3 (n=25) women similar to group 2, treated in addition with adjuvant rHuEPO, 4000 units subcutaneously, three times a week, for 4 weeks evaluating the same parameters. Group 2 and 3 showed a corrected anemia before delivery (mean 11.1 vs 11.4g/dL), but Group 3 showed a statistically broader and more rapid increase in hemoglobin (1.22 vs 1.92g/dL, p value 0.013) with an rHuEPO dose of 4000 units, three times a week for 1 month. No clinical or hematologic difference or changes in growth were observed in the fetus. Erythropoietin is safe and effective for both mother and fetus, although an ideal pregnancy dose has not yet been established. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. 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.

  7. 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.

  8. Changes in the Expression of Transcription Factors Involved in Modulating the Expression of EPO-R in Activated Human CD4-Positive Lymphocytes.

    Science.gov (United States)

    Lisowska, Katarzyna A; Frackowiak, Joanna E; Mikosik, Anna; Witkowski, Jacek M

    2013-01-01

    We have recently described the presence of the erythropoietin receptor (EPO-R) on CD4(+) lymphocytes and demonstrated that its expression increases during their activation, reaching a level reported to be typical for erythroid progenitors. This observation suggests that EPO-R expression is modulated during lymphocyte activation, which may be important for the cells' function. Here we investigated whether the expression of GATA1, GATA3 and Sp1 transcription factors is correlated with the expression of EPO-R in human CD4(+) lymphocytes stimulated with monoclonal anti-CD3 antibody. The expression of GATA1, GATA3 and Sp1 transcription factors in CD4(+) cells was estimated before and after stimulation with anti-CD3 antibody by Western Blot and flow cytometry. The expression of EPO-R was measured using real-time PCR and flow cytometry. There was no change in the expression of GATA1 and GATA3 in CD4(+) lymphocytes after stimulation with anti-CD3 antibody. However, stimulation resulted in the significantly increased expression of the Sp1 factor. CD4(+) lymphocytes stimulated with anti-CD3 antibody exhibited an increase in both the expression level of EPOR gene and the number of EPO-R molecules on the cells' surface, the latter being significantly correlated with the increased expression of Sp1. Sp1 is noted to be the single transcription factor among the ones studied whose level changes as a result of CD4(+) lymphocyte stimulation. It seems that Sp1 may significantly affect the number of EPO-R molecules present on the surface of activated CD4(+) lymphocytes.

  9. 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

  10. Skin regeneration in deep second-degree scald injuries either by infusion pumping or topical application of recombinant human erythropoietin gel

    Directory of Open Access Journals (Sweden)

    Giri P

    2015-05-01

    Full Text Available Priya Giri,1 Sabine Ebert,1 Ulf-Dietrich Braumann,2 Mathias Kremer,3 Shibashish Giri,1 Hans-Günther Machens,4 Augustinus Bader1 1Department of Cell Techniques and Applied Stem Cell Biology, Center for Biotechnology and Biomedicine (BBZ, Faculty of Medicine, University of Leipzig, Leipzig, Germany; 2Interdisciplinary Center for Bioinformatics (IZBI, University of Leipzig, Leipzig, Germany; 3Department of Plastic and Hand Surgery, University of Lübeck, Lübeck, Germany; 4Department of Plastic and Hand Surgery, Technical University of Munich, Munich, Germany Abstract: Large doses of recombinant growth factors formulated in solution form directly injected into the body is usual clinical practice in treating second-degree scald injuries, with promising results, but this approach creates side effects; furthermore, it may not allow appropriate levels of the factor to be sensed by the target injured tissue/organ in the specific time frame, owing to complications arising from regeneration. In this research, two delivery methods (infusion pumping and local topical application were applied to deliver recombinant human erythropoietin (rHuEPO for skin regeneration. First, rHuEPO was given in deep second-degree scald injury sites in mice by infusion pump. Vascularization was remarkably higher in the rHuEPO pumping group than in controls. Second, local topical application of rHuEPO gel was given in deep second-degree scald injury sites in rats. Histological analysis showed that epithelialization rate was significantly higher in the rHuEPO gel-treated group than in controls. Immunohistochemical studies showed that the rHuEPO gel-treated group showed remarkably higher expression of skin regeneration makers than the control group. An accurate method for visualization and quantification of blood vessel networks in target areas has still not been developed up to this point, because of technical difficulties in detecting such thin blood vessels. A method which

  11. 重组人促红细胞生成素对SCI大鼠Akt和p-Akt表达的影响%The effect of recombinant human erythropoietin on the expression of Akt and p-Akt in spinal cord injury rat

    Institute of Scientific and Technical Information of China (English)

    车敏; 刘颖; 王岩峰

    2012-01-01

    目的 探讨重组人促红细胞生成素(recombinant human erythropoietin,rHuEPO)对脊髓损伤(spinal cord injury,SCI)大鼠Akt与p-Akt表达的影响.方法 成年健康Wistar大鼠72只,雌雄不限,按随机数字表法分为假手术组、脊髓损伤组和重组人促红细胞生成素治疗组,参照Nystrom's压迫方法制作大鼠脊髓压迫损伤模型,按照存活时间再分为脊髓损伤6h,12h,24h,3d组.免疫组化和Western blot方法检测Akt、p-Akt在各组大鼠脊髓表达的变化.结果 免疫组化和Western blot结果发现,脊髓Akt、p-Akt蛋白阳性表达的平均光密度值SCI组低于假手术组(P <0.05),重组人促红细胞生成素治疗组显著高于SCI组(P<0.05).结论 rHuEPO可通过上调Akt、p-Akt蛋白的表达参与脊髓损伤修复.%Objective To study the effect of recombinant human erythropoietin(rHuEPO) on the expressions of Akt and p-Akt in spinal cord injury rat. Methods 72 healthy adult Wistar rats were randomly divided into the sham group(n=8), the spinal cord injury group(n=32) and rHuEPO group(n=32). The spinal cord injury was induced with Nyslrom's way. The spinal cord injury group and rHuEPO group were further randomly subdivided into four subgroups (6h, 12h, 24h, 3d) according to the postoperative survival time. The expressions of Akt and p-Akt were observed by immunochemistry and Western blot methods. Results The mean optic density(MOD) values of Akt and p—Akt products in spinal cord were decreased in spinal cord injury than in sham group( P <0.05), but increased significantly in rHuEPO treated group than in spinal cord injury( P <0.05) by immunochemistry and Western blot. Conclusion The impairment effect of rHuEPO in spinal cord injury might be related to the upregulation of the expressions of Akt and p—Akt.

  12. Dynamic stability of locomotor respiratory coupling during cycling in humans.

    Science.gov (United States)

    Villard, Sébastien; Casties, Jean-François; Mottet, Denis

    2005-08-05

    We explored the locomotor respiratory coupling (LRC) during a 50-min constant-load submaximal cycling exercise. A 4-week recombinant human erythropoietin (r-HuEPO) treatment improved participants' aerobic capabilities, but did not elicit significant changes in LRC. The distributions of the respiratory frequency over pedalling frequency ratios were systematically bimodal, with a preferred use of 1/3 and 1/2, and a progressive shift of the higher mode from 1/3 towards 1/2 with exercise duration. These results are interpreted in the framework of the sine circle map as the result of coordination dynamics between the physiological subsystems involved in the breathing pedalling cooperation.

  13. 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

  14. Alternativa terapeutica en la isquemia cerebral empleando la Eritropoyetina humana recombinante (rHu-EPO CIM) como neuroprotector.

    OpenAIRE

    Iliana Sosa Testé; Jorge D. García Salman; Nelvys Subirós; Consuelo González; Yamila Rodríguez; Julio C. García Rodríguez

    2005-01-01

    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. ...

  15. [The correction of anemia with a high requirement for transfusion in patients on maintenance hemodialysis by conventional and reduced doses of recombinant human erythropoietin].

    Science.gov (United States)

    Sivak, L; Scuteri, R M; Cavalli, N H; Gotlieb, D; López Blanco, O A

    1992-01-01

    The hematologic findings of chronic renal failure are consistent with hypoproliferative anemia; the pathogenesis of the anemia is primarily due to decreased erythropoietin production by the diseased kidneys. There are aggravating factors (AF) contributing to this primordial cause: inhibitors to erythroid marrow function, shortened red cell survival, nonevident chronic blood loss (owing to uremic platelet dysfunction), iron and/or folate deficiency, aluminium toxicity, hemolysis (acute or chronic), etc. Ten patients with end stage renal disease, treated with maintenance hemodialysis and high transfusional requirement (more than 300 ml/month) are presented; in five the AF were discarded by a previously presented protocol (Table 1) and they were treated with human recombinant erythropoietin (r-HuEPO) intravenously, in conventional schemes (three times a week) and doses (195 +/- 41 Units/Kg)-Group A-. The AF were not studied in the other five and the r-HuEPO treatment employed different doses (125 +/- 70 U/K/W) and protocols (1.7 +/- 0.5 times a week)-Group B-(Table 2). The transfusional requirement disappeared and the hematocrit and the hemoglobin rose significantly in both groups (more in group A) (Table 3). The significant drop in ferritin levels (147 +/- 30 ng/ml vs 27.5 +/- 11 ng/ml at the 12th week) and the stabilization in reticulocyte count (1.4% at start vs 2% at 12th week) indicate iron consumption; in the meantime, the persistent increment in reticulocyte production index (1 at start vs 3 at 12th week) revealed a continuous stimulation of the erythropoiesis (Fig. 1). No clinical and/or vascular complications were observed; arterial pressure and serum potassium levels did not rise significantly so that r-HuEPO treatment was not canceled in any case.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Efeitos da eritropoetina recombinante humana em recém-nascidos pré-termo com doenças infecciosas Effects of recombinant human erythropoietin in preterm newborns with infectious diseases

    Directory of Open Access Journals (Sweden)

    Iara Flávia de Vasconcelos P. Aguiar

    2007-02-01

    Full Text Available OBJETIVO: Analisar os efeitos da eritropoetina recombinante humana (rHuEpo em recém-nascidos pré-termo com doenças infecciosas graves. MÉTODOS: Foi realizado um estudo controlado, não randomizado, em 34 recém-nascidos com diagnóstico de patologias infecciosas graves, peso de nascimento igual ou inferior a 1500 g, idade gestacional inferior a 35 semanas e estabilidade clínica. Os recém-nascidos designados para o tratamento com rHuEpo receberam a eritropoetina ß na dose de 400 UI/kg, duas vezes por semana, por via subcutânea. A suplementação oral com ferro foi iniciada quando os níveis de ferritina sérica foram inferiores a 60 mcg/L. O estudo foi realizado durante seis semanas ou até a alta hospitalar do paciente. Foram avaliados a eritropoese, o número de transfusões, o número de neutrófilos, a contagem de plaquetas e os episódios de novas infecções durante o tratamento com o hormônio. RESULTADOS: Houve aumento significativo do número de reticulócitos no grupo tratado; entretanto, não houve impacto sobre o número ou volume de transfusões. Não foram observadas alterações no número de neutrófilos ou plaquetas. CONCLUSÃO: O uso de rHuEpo em RNPT com doenças infecciosas, na dose de 800 UI/Kg/semana, foi efetivo para induzir eritropoese, sem ocorrerem alterações significativas sobre o número de neutrófilos ou plaquetas. Essa estratégia, associada ao controle rigoroso do volume de sangue retirado para exames, poderá ser benéfica na prevenção da anemia em RNPT com infecção grave.OBJECTIVE: To study the effects of recombinant human erythropoietin (rHuEpo in preterm newborns (PTNs with serious infectious diseases. METHODS: A not randomized case-control study was carried out in 34 preterm newborns with diagnosis of serious infectious pathologies, gestational age up to 35 weeks, birth weight less than 1500 g and clinical stability. Newborns selected for treatment with rHuEpo received 400 U/kg erythropoietin

  17. Recovery of motor spontaneous activity after intranasal delivery of human recombinant erythropoietin in a focal brain hypoxia model induced by CoCl2 in rats.

    Science.gov (United States)

    Merelli, Amalia; Caltana, Laura; Girimonti, Patricia; Ramos, Alberto Javier; Lazarowski, Alberto; Brusco, Alicia

    2011-08-01

    Stroke is a major human health problem inducing long-term disability without any efficient therapeutic option being currently available. Under hypoxia, hypoxia-inducible factor-1α (HIF-1α) activates several genes as erythropoietin receptor (Epo-R) related with O(2) supply, and the multidrug-resistance gene (MDR-1) related with drug-refractory phenotype. Brain cortical injection of CoCl(2) produces focal hypoxia-like lesion with neuronal and glial alterations, as well as HIF-1α stabilization and MDR-1 overexpression. Intranasal (IN) drug delivery can by-pass blood-brain barrier (BBB) where MDR-1 is normally expressed. We evaluated the effects of IN-rHu-Epo administration on spontaneous motor activity (SMA) and the brain pattern expression of HIF-1α, MDR-1, and Epo-R in our cobalt-induced hypoxia model. Adult male Wistar rats were injected by stereotaxic surgery in frontoparietal cortex, with CoCl(2) (2 μl-50 mM; n = 20) or saline (controls; n = 20). Ten rats of each group were treated with IN-rHu-Epo 24 U or IN-saline. In addition, erythropoietic stimulation was evaluated by reticulocytes (Ret) account during three consecutive days, after intraperitoneal (i.p.)-recombinant-human Epo (rHu-Epo) (950 U; n = 6) or IN-rHu-Epo (24 U; n = 6) administration. SMA was evaluated by open field and rotarod tests, before and after surgical procedures during five consecutive days. Histological and immunostaining studies of HIF-1α, MDR-1, and Epo-R were performed on brain slides. A significant difference in SMA was observed in the hypoxic rats of IN-rHu-Epo-administered group as compared with Co-Saline-treated subjects and controls (p < 0.001). HIF-1α, EPO-R, and MDR-1 were overexpressed in the hypoxic cortex areas, while in contralateral hemisphere or controls, they were negatives. Reticulocytes were only increased in intraperitoneal (i.p.)-rHu-Epo-administered group. In spite of MDR-1 overexpression being detected in neurons, the coexpression of Epo-R could

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Erythropoietin augments the cytokine response to acute endotoxin-induced inflammation in humans

    DEFF Research Database (Denmark)

    Hojman, Pernille; Taudorf, Sarah; Lundby, Carsten;

    2009-01-01

    Recent studies have shown that erythropoietin (EPO) offers protection against ischemia, hemorrhagic shock and systemic inflammation in many tissues and it has been suggested that EPO has anti-inflammatory effects. With the aim of investigating the potential acute anti-inflammatory effects of EPO...... receiving either (1) LPS alone, (2) EPO alone (15,000 IE of rHuEPO) or (3) EPO and LPS. Endotoxin administration alone induced a 3-, 12- and 5-fold increase in plasma concentrations of TNF-alpha, IL-6 and IL-10, respectively, 3h after LPS challenge. When EPO was given prior to a bolus injection...... with endotoxin, the levels of TNF-alpha and IL-6 were enhanced by 5- and 40-fold, respectively, whereas the endotoxin-induced increase in IL-10 response was not influenced by EPO. In contrast to our hypothesis, we find that EPO augments the acute inflammatory effect....

  3. 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.

  4. 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.

  5. 重组人促红细胞生成素对脓毒症大鼠肺脏的保护作用%Protective effects of recombinant human erythropoietin on acute lung injury induced by sepsis in rats

    Institute of Scientific and Technical Information of China (English)

    桑珍珍; 许云; 盛英杰; 赵敏

    2013-01-01

    目的 探讨重组人促红细胞生成素(recombinant human erythropoietin,rHuEPO)对内毒素所致大鼠脓毒症急性肺损伤的保护作用.方法 45只雄性SD大鼠随机(随机数字法)分为对照组、模型组、rHuEPO组,每组均15只.经静脉推注脂多糖LPS(6 mg/kg)复制急性肺损伤(ALI)的动物模型,rHuEPO组造模前60 min静脉推注rHuEPO (5000 U/kg),观察12 h后处死.留取颈动脉血及肺组织标本.测定氧和指数(OI)、动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、pH值.采用酶联免疫法(ELISA法)测定大鼠血清TNF-α、IL-6、iNOS的水平.在光镜和透射电镜下观察肺组织的病理形态学变化,并取右肺下叶计算肺湿/干质量比(W/D).结果 (1)血气分析:与对照组相比,脓毒症组及rHuEPO组大鼠动脉血PaO2、pH显著降低,PaCO2显著升高;与脓毒症组相比,rHuEPO组PaO2、pH显著升高及PaCO2显著降低,差异具有统计学意义(P<0.05).(2)各组大鼠肺组织湿干质量比(W/D)变化:与对照组相比,脓毒症组及rHuEPO组肺组织W/D显著增加;与脓毒症组相比,rHuEPO组肺组织W/D显著降低,差异具有统计学意义(P<0.05).(3)各组大鼠12 h血清TNF-α、IL-6、iNOS水平的变化:脓毒症组及rHuEPO组上述指标明显高于对照组;与脓毒症组相比,rHuEPO组上述指标明显降低,差异具有统计学意义(P<0.01).(4)光镜及电镜观察脓毒症组病理学改变为急性弥漫性肺损伤,表现为肺泡腔内出血、渗出、炎性细胞浸润,肺微血管内皮细胞、Ⅰ型和Ⅱ型上皮细胞坏死;rHuEPO组急性肺损伤明显轻于脓毒症组,只可见到局灶性肺泡少量炎性细胞浸润.结论 rHuEPO能够降低血清TNF-α、IL-6、iNOS水平进而调节炎症反应,对脓毒症所致急性肺损伤具有一定的保护作用.%Objective To investigate the protective effects of recombinant human erythropoietin (rHuEPO) on acute lung injury (ALI) induced by lipopolysaccharide (LPS

  6. Phenotyping of human melanoma cells reveals a unique composition of receptor targets and a subpopulation co-expressing ErbB4, EPO-R and NGF-R.

    Science.gov (United States)

    Mirkina, Irina; Hadzijusufovic, Emir; Krepler, Clemens; Mikula, Mario; Mechtcheriakova, Diana; Strommer, Sabine; Stella, Alexander; Jensen-Jarolim, Erika; Höller, Christoph; Wacheck, Volker; Pehamberger, Hubert; Valent, Peter

    2014-01-01

    Malignant melanoma is a life-threatening skin cancer increasingly diagnosed in the western world. In advanced disease the prognosis is grave. Growth and metastasis formation in melanomas are regulated by a network of cytokines, cytokine-receptors, and adhesion molecules. However, little is known about surface antigens and target expression profiles in human melanomas. We examined the cell surface antigen profile of human skin melanoma cells by multicolor flow cytometry, and compared their phenotype with 4 melanoma cell lines (A375, 607B, Mel-Juso, SK-Mel28). Melanoma cells were defined as CD45-/CD31- cells co-expressing one or more melanoma-related antigens (CD63, CD146, CD166). In most patients, melanoma cells exhibited ErbB3/Her3, CD44/Pgp-1, ICAM-1/CD54 and IGF-1-R/CD221, but did not express CD20, ErbB2/Her2, KIT/CD117, AC133/CD133 or MDR-1/CD243. Melanoma cell lines were found to display a similar phenotype. In most patients, a distinct subpopulation of melanoma cells (4-40%) expressed the erythropoietin receptor (EPO-R) and ErbB4 together with PD-1 and NGF-R/CD271. Both the EPO-R+ and EPO-R- subpopulations produced melanoma lesions in NOD/SCID IL-2Rgamma(null) (NSG) mice in first and secondary recipients. Normal skin melanocytes did not express ErbB4 or EPO-R, but expressed a functional KIT receptor (CD117) as well as NGF-R, ErbB3/Her3, IGF-1-R and CD44. In conclusion, melanoma cells display a unique composition of surface target antigens and cytokine receptors. Malignant transformation of melanomas is accompanied by loss of KIT and acquisition of EPO-R and ErbB4, both of which are co-expressed with NGF-R and PD-1 in distinct subfractions of melanoma cells. However, expression of EPO-R/ErbB4/PD-1 is not indicative of a selective melanoma-initiating potential.

  7. Recommendations for the clinical practice: Standards, options and recommendations 2003 for the use of recombinant erythropoietin (alpha and beta epoetine, alpha darbepoetine, EPO) in the taking charge of anemia in oncology for the patients treated by radiotherapy, update; Recommandations pour la pratique clinique: Standards, Options et Recommandations 2003 pour l'utilisation de l'erythropoietine recombinante (epoetine alfa et beta, darbepoetine alfa, EPO) dans la prise en charge de l'anemie en cancerologie pour les patients traites par radiotherapie, mise a jour

    Energy Technology Data Exchange (ETDEWEB)

    Marchal, Ch. [Centre Alexis-Vautrin, oncologue-radiotherapeute, 54 - Nancy (France); Spaeth, C. [Centre Alexis-Vautrin, oncologue medical, 54 - Nancy (France); Casadevall, N. [Hopital Hotel-Dieu, hematologue, 75 - Paris (France); Daouphars, M. [Hopital Notre-Dame-de-Bon-Secours, pharmacien, 57 - Metz (France); Marec-Berard, P. [Centre Leon-Berard, oncologue-pediatre, 69 - Lyon (France); Fabre, N. [FNCLCC, methodologiste, 75 - Paris (France); Haugh, M. [FNCLCC, methodologiste, 75 - Paris (France)

    2004-06-01

    Standards, Options and Recommendations for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin alpha, EPO) in the management of anaemia in oncology for patient undergoing radiotherapy - UPDATE 2003. Context. - 'The Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the twenty French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. Objectives. - To update the Standards, Options and Recommendations clinical practice guidelines for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin-alpha, EPO) in the management of anaemia in oncology for patient undergoing radiotherapy. Methods. - The working group identified the questions requiring up-dating from the previous guideline. Medline and Embase were searched using specific search strategies from January 1999 to October 2002. Literature monitoring was performed to identify randomized clinical trials published between October 2002 to November 2003. In addition several Internet sites were searched in October 2002. Results. - There is no standard attitude for use of rHuEPO in patients undergoing radiotherapy. There is no evidence to support use of rHuEPO in patients with ENT cancer receiving radiotherapy alone. In patients undergoing curative radiotherapy, it is recommended to correct anaemia under 10 g/dL using transfusion rather than rHuEPO. When the haemoglobin concentration is between 12 g/dL and 14 g/dL initial use of rHuEPO can be an option under certain conditions for radio-chemotherapy if the risk of

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. The effect of recombinant human erythropoietin on the expression of NF-κB in acute spinal cord injury rat%重组人促红细胞生成素对大鼠脊髓损伤后NF-κB表达的影响

    Institute of Scientific and Technical Information of China (English)

    霍岩; 沈兆亮; 王冬; 王巍; 高爽

    2012-01-01

    目的 研究重组人促红细胞生成素(recombinant human erythropoietin,rHuEPO)对急性脊髓损伤大鼠核转录因子-κB(nuclear factor-kappaB,NF-κB)表达的影响.方法 参照Nystrom's压迫方法制作大鼠脊髓压迫损伤模型,成年健康Wistar大鼠72只,雌雄不限,按随机数字表法分为正常对照组8只、损伤组32只、重组人促红细胞生成素治疗组32只.术后应用联合行为评分( combined behavioral score,CBS)评价大鼠脊髓神经功能;免疫组化和Western blot检测各组大鼠NF-κB的表达.结果 三组CBS评分结果显示,损伤组>重组人促红细胞生成素治疗组>对照组.免疫组化结果显示,损伤组与rHuEPO治疗组NF- κB阳性产物的平均光密度值( MOD)显著高于正常对照组(P<0.01),而rHuEPO治疗组与损伤组相比MOD值明显降低(P<0.01).Western blot结果显示,与正常对照组比较,损伤组与rHuEPO治疗组组NF-κB的灰度值(IDV)与内参照IDV的比值明显升高(P<0.01),而rHuEPO治疗组则明显低于损伤组(P<0.01).结论 rHuEPO治疗组很可通过下调NF- κB的表达参与脊髓继发性损伤的修复.%Objective To study the effect of recombinant human erythropoietin (rHuEPO)on the expression of nuclear factor-kappa B(NF- k B)in acute spinal cord injury rat. Methods The spinal cord injury was induced with Nystrom's way, the healthy adult Wistar rats(72)were randomly divided into normal control group, spinal cord injury group, recombinant human erythropoietin group on average. The function of rats was determined by combined behavioral score(CBS), and the expression of NF- k B was observed by immunochemistry and western blot methods. Results The CBS score sequence was: spinal cord injury group> rHuEPO> normal control group. The mean optic density(MOD)of NF- kB positive product increased significantly in acute spinal cord injury group than in normal control by immunochemistry(p<0.01), but decreased in rHuEPO than in acute spinal cord

  14. 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.

  15. [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.

  16. Cardiovascular effects of recombinant human erythropoietin in predialysis patients.

    Science.gov (United States)

    Portolés, J; Torralbo, A; Martin, P; Rodrigo, J; Herrero, J A; Barrientos, A

    1997-04-01

    Treatment with recombinant human erythropoietin (rHuEPO) has solved the problem of anemia in patients on dialysis. However, its application to predialysis patients has raised some doubts about its effects on the progression of renal disease and on blood pressure (BP) and hemodynamic regulation. We have prospectively studied over at least 6 months a group of 11 predialysis patients receiving rHuEPO treatment (initial dose, 1,000 U subcutaneously three times a week). Clinical assessment and biochemical and hematologic measurements were made once every 2 weeks. Twenty-four-hour ambulatory BP monitoring, echocardiography, and determination of neurohumoral mediators of hemodynamics were performed once every 3 months. An adequate hematologic response was found (hemoglobin, 11.7 +/- 0.4 g/dL v 9 +/- 0.3 g/dL) without changes in the progression of renal disease. A decrease in cardiac output and an increase in total peripheral resistance was seen as anemia improved. A trend toward decreased left ventricular (LV) thickness and a significant decrease in LV mass index (from 178.2 +/- 20.6 g/m2 to 147.3 +/- 20.6 g/m2) were observed. Blood pressure control did not improve; moreover, in some patients an increase in systolic values was detected by ambulatory BP. Casual BP remained seemingly stable. Sequential determinations of neurohumoral mediators of hemodynamic substances (endothelin, renin, norepinephrine, epinephrine, dopamine) failed to explain these results. Ambulatory BP reveals a worse control in some patients who were previously hypertensive and confirms the utility of this technique in the assessment of patients under erythropoietin treatment. The trend toward LV hypertrophy regression without improved BP control confirms the role of anemia among the multiple factors leading to LV hypertrophy in end-stage renal disease (ESRD), and opens therapeutic possibilities. Better control of BP may avoid a potential offsetting of beneficial effects that correcting anemia would

  17. Recombinant human erythropoietin and hemoglobin concentration at operation and during the postoperative period

    DEFF Research Database (Denmark)

    Qvist, N; Boesby, S; Wolff, B

    1999-01-01

    and 750 ml, respectively. The number of blood transfusions given was significantly lower in the erythropoietin group, with a mean of 0.3 (range 0-6) units compared to 1.6 (0-9) units in the control group (p concentration at the time of surgery and during the week......In a double-blind placebo-controlled study we investigated the effect of recombinant human erythropoietin (r-HuEPO), on the perioperative hemoglobin concentration and the use of blood transfusions in patients undergoing elective colorectal surgery with a preoperative hemoglobin level ... for 4 days before surgery. There were no differences between the two groups with regard to sex, height, weight, serum electrolytes, and liver function tests at study entry. The preentry hemoglobin concentration was similar in the two groups, with a median value of 7.9 (range 5.3-8.5) mmol...

  18. Erythropoietin does not reduce plasma lactate, H+, and K+ during intense exercise

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai Baastrup; Robach, P; Boushel, R

    2015-01-01

    It is investigated if recombinant human erythropoietin (rHuEPO) treatment for 15 weeks (n = 8) reduces extracellular accumulation of metabolic stress markers such as lactate, H(+) , and K(+) during incremental exhaustive exercise. After rHuEPO treatment, normalization of blood volume and composit...

  19. 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

  20. 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

  1. The Effect of Human Recombinant Erythropoietin on Prevention of Anemia of Prematurity

    Directory of Open Access Journals (Sweden)

    K Hajian

    2007-06-01

    Full Text Available Objective: Premature infants often develop significant anemia that requires blood transfusion, this carries significant risks. This study was carried out to determine the effect of recombinant human erythropoietin (r-HuEPO on prevention of anemia of prematurity. Material & Methods: From April 2001 to March 2002, 24 neonates in  newborn services at Amirkola childrens hospital randomly were assigned to erythropoietin group and control (no treatment group. Inclusion criteria were birth weight of ≤1750 grams and gestational age ≤34 weeks. Exclusion criteria were problems of hemolytic anemia, congenital infections, congenital malformations, severe asphyxia, intraventricular hemorrhage (grade III and IV, need for exchange transfusion and death during the first week of life. Erythropoietin group received r-HuEPO400 unit/kg/dose subcutaneously three times a week plus 4 mg/kg/day iron orally. White blood cell, hemoglobin (Hgb, hematocrit (Hct, platelet and reticulocyte count were obtained every 2 weeks until the 42nd day of life. Anemia was defined as Hgb≤8gr/dl and Hct≤24%. Student t test and Fisher exact were used to evaluate differences between the two groups.Findings: Hemoglobin and hematocrit values were significantly higher in erythropoietin group than the control group after the 14th day of the study (P<0.04 and this difference was getting higher until the end of the trial (P<0.001. Five neonates developed anemia; all of them were from control group. One of these neonates required transfusion. None of the erythropoietin group newborns developed anemia.Conclusion: The results of this study confirm the efficacy of recombinant human erythropoietin in the prevention of anemia of prematurity.

  2. Historical review on the use of recombinant human erythropoietin in chronic renal failure.

    Science.gov (United States)

    Winearls, C G

    1995-01-01

    The success of maintenance haemodialysis in the 1960s was blighted by the problem of anaemia. Treatment with iron, folic acid, androgens and transfusions did no more than minimize its effects. The need for a renewable source of erythropoietin was appreciated very early but the hope took 25 years to realize. Cloning and expression of the human gene was achieved in 1984 and clinical trials planned even before the descriptions of the recombinant hormone were published. The Amgen material was tested in parallel studies in Seattle and England and by the end of 1986 the efficacy of recombinant human erythropoietin (r-HuEPO) given in large intravenous bolus doses in reversing the anaemia of uraemia was established. The benefits were immediately obvious: relief from transfusion dependence was the unequivocal evidence but the effect on 'wellbeing' though subjective was remarkable. Large clinical trials were completed in Europe and the USA so that r-HuEPO was licensed as a therapeutic drug less than two years later. The pilot studies flagged a number of key issues: hypertension, sometimes with encephalopathy, occurred in patients whose blood pressure was labile before treatment; vascular access failure seemed more frequent and hyperkalaemia was thought to reflect less efficient dialysis. Failure to respond focused attention on iron balance as well as on factors such as infection, aluminium, and hyperparathyroidism. A more clear understanding of the pathogenesis of the anaemia of uraemia was made possible by dissection of the specific effects of the exogenous erythropoietin on erythroid function.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. 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.

  4. 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

  5. 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.

  6. 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.

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

    Science.gov (United States)

    Cocco, Massimo; Consortium, Epos

    2016-04-01

    EPOS has been designed with the vision of creating a 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 science relying on new e-science opportunities to monitor and unravel the dynamic and complex Earth System. 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. To accomplish its mission, EPOS is engaging different stakeholders, not limited to scientists, to allow the Earth sciences to open new horizons in our understanding of the planet. EPOS also aims at contributing to prepare society for geo-hazards and to responsibly manage the exploitation of geo-resources. 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 human welfare. A long-term integration plan is necessary to accomplish the EPOS mission. EPOS is presently in its implementation phase further extending its pan-European dimension. The EPOS Implementation Phase builds on the achievements of the successful EPOS Preparatory Phase project and consists of two key activities: the legal establishment of the EPOS-ERIC and the EPOS IP project. The EPOS implementation phase will last from 2015 to 2019. 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

  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. The Nasal Route as a Potential Pathway for Delivery of Erythropoietin in the Treatment of Acute Ischemic Stroke in Humans

    Directory of Open Access Journals (Sweden)

    Julio Cesar García-Rodríguez

    2009-01-01

    Full Text Available Intranasal delivery provides a practical, noninvasive method of bypassing the blood-brain barrier (BBB in order to deliver therapeutic agents to the brain. This method allows drugs that do not cross the BBB to be delivered to the central nervous system in a few minutes. With this technology, it will be possible to eliminate systemic administration and its potential side effects. Using the intranasal delivery system, researchers have demonstrated neuroprotective effects in different animal models of stroke using erythropoietin (EPO as a neuroprotector or other different types of EPO without erythropoiesis-stimulating activity. These new molecules retain their ability to protect neural tissue against injury and they include Asialoerythropoietin (asialoEPO carbamylated EPO (CEPO, and rHu-EPO with low sialic acid content (Neuro-EPO. Contrary to the other EPO variants, Neuro-EPO is not chemically modified, making it biologically similar to endogenous EPO, with the advantage of less adverse reactions when this molecule is applied chronically. This constitutes a potential benefit of Neuro-EPO over other variants of EPO for the chronic treatment of neurodegenerative illnesses. Nasal administration of EPO is a potential, novel, neurotherapeutic approach. However, it will be necessary to initiate clinical trials in stroke patients using intranasal delivery in order to obtain the clinical evidence of its neuroprotectant capacity in the treatment of patients with acute stroke and other neurodegenerative disorders. This new therapeutic approach could revolutionize the treatment of neurodegenerative disorders in the 21st century.

  10. 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

  11. Iron as the Key Modulator of Hepcidin Expression in Erythroid Antibody-Mediated Hypoplasia

    Directory of Open Access Journals (Sweden)

    J. C. Fernandes

    2014-01-01

    Full Text Available Erythroid hypoplasia (EH is a rare complication associated with recombinant human erythropoietin (rHuEPO therapies, due to development of anti-rHuEPO antibodies; however, the underlying mechanisms remain poorly clarified. Our aim was to manage a rat model of antibody-mediated EH induced by rHuEPO and study the impact on iron metabolism and erythropoiesis. Wistar rats treated during 9 weeks with a high rHuEPO dose (200 IU developed EH, as shown by anemia, reduced erythroblasts, reticulocytopenia, and plasmatic anti-rHuEPO antibodies. Serum iron was increased and associated with mRNA overexpression of hepatic hepcidin and other iron regulatory mediators and downregulation of matriptase-2; overexpression of divalent metal transporter 1 and ferroportin was observed in duodenum and liver. Decreased EPO expression was observed in kidney and liver, while EPO receptor was overexpressed in liver. Endogenous EPO levels were normal, suggesting that anti-rHuEPO antibodies blunted EPO function. Our results suggest that anti-rHuEPO antibodies inhibit erythropoiesis causing anemia. This leads to a serum iron increase, which seems to stimulate hepcidin expression despite no evidence of inflammation, thus suggesting iron as the key modulator of hepcidin synthesis. These findings might contribute to improving new therapeutic strategies against rHuEPO resistance and/or development of antibody-mediated EH in patients under rHuEPO therapy.

  12. 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.

  13. 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.

  14. 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, ...

  15. 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...

  16. 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

  17. Mixed-effects modelling of the interspecies pharmacokinetic scaling of pegylated human erythropoietin.

    Science.gov (United States)

    Jolling, Koen; Perez Ruixo, Juan Jose; Hemeryck, Alex; Vermeulen, An; Greway, Tony

    2005-04-01

    The aim of this study was to develop a population pharmacokinetic model for interspecies allometric scaling of pegylated r-HuEPO (PEG-EPO) pharmacokinetics to man. A total of 927 serum concentrations from 193 rats, 6 rabbits, 34 monkeys, and 9 dogs obtained after a single dose of PEG-EPO, administered by the i.v. (dose range: 12.5-550 microg/kg) and s.c. (dose range: 12.5-500 microg/kg) routes, were pooled in this analysis. An open two-compartment model with first-order absorption and lag time (Tlag) and linear elimination from the central compartment was fitted to the data using the NONMEM V software. Body weight (WT) was used as a scaling factor and the effect of brain weight (BW), sex, and pregnancy status on the pharmacokinetic parameters was investigated. The final model was evaluated by means of a non-parametric bootstrap analysis and used to predict the PEG-EPO pharmacokinetic parameters in healthy male subjects. The systemic clearance (CL) in males was estimated to be 4.08WT1.030xBW-0.345 ml/h. In females, the CL was 90.7% of the CL in males. The volumes of the central (Vc) and the peripheral (Vp) compartment were characterized as 57.8WT0.959 ml, and 48.1WT1.150 ml, respectively. Intercompartmental flow was estimated at 2.32WT0.930 ml/h. Absorption rate constant (Ka) was estimated at 0.0538WT-0.149. The absolute s.c. bioavailability F was calculated at 52.5, 80.2, and 49.4% in rat, monkey, and dog, respectively. The interindividual variability in the population pharmacokinetic parameters was fairly low (parametric bootstrap confirmed the accuracy of the NONMEM estimates. The mean model predicted pharmacokinetic parameters in healthy male subjects of 70 kg were estimated at: CL: 26.2 ml/h; Vc: 3.6l; Q: 286 l/h; Vp: 6.9l, and Ka: 0.031 h-1. The population pharmacokinetic model developed was appropriate to describe the time course of PEG-EPO serum concentrations and their variability in different species. The model predicted pharmacokinetics of PEG-EPO in

  18. 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.

  19. Functional EpoR pathway utilization is not detected in primary tumor cells isolated from human breast, non-small cell lung, colorectal, and ovarian tumor tissues.

    Directory of Open Access Journals (Sweden)

    Scott D Patterson

    Full Text Available Several clinical trials in oncology have reported increased mortality or disease progression associated with erythropoiesis-stimulating agents. One hypothesis proposes that erythropoiesis-stimulating agents directly stimulate tumor proliferation and/or survival through cell-surface receptors. To test this hypothesis and examine if human tumors utilize the erythropoietin receptor pathway, the response of tumor cells to human recombinant erythropoietin was investigated in disaggregated tumor cells obtained from 186 patients with colorectal, breast, lung, ovarian, head and neck, and other tumors. A cocktail of well characterized tumor growth factors (EGF, HGF, and IGF-1 were analyzed in parallel as a positive control to determine whether freshly-isolated tumor cells were able to respond to growth factor activation ex vivo. Exposing tumor cells to the growth factor cocktail resulted in stimulation of survival and proliferation pathways as measured by an increase in phosphorylation of the downstream signaling proteins AKT and ERK. In contrast, no activation by human recombinant erythropoietin was observed in isolated tumor cells. Though tumor samples exhibited a broad range of cell-surface expression of EGFR, c-Met, and IGF-1R, no cell-surface erythropoietin receptor was detected in tumor cells from the 186 tumors examined (by flow cytometry or Western blot. Erythropoiesis-stimulating agents did not act directly upon isolated tumor cells to stimulate pathways known to promote proliferation or survival of human tumor cells isolated from primary and metastatic tumor tissues.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. CLINIC STUDY ON THE INFLUENCE OF RECOMBINANT HUMAN ERYTHROPOIETIN ON ERYTHROID PARAMETERS, NUTRITIONAL STATUS AND QUALITY OF LIFE IN CHRONIC RENAL FAILURE%rHuEPO对慢性肾衰竭患者红系参数、营养状态及生活质量影响的临床观察

    Institute of Scientific and Technical Information of China (English)

    李香玲; 赵学兰; 郭振涛; 李加村; 肖青

    2011-01-01

    [目的]探讨重组人促红细胞生成素(rHuEPO)对慢性肾衰竭(CRF)患者红系及营养状况与生活质量的影响.[方法]对24例CRF患者给予rHuEPO 1万IU皮下注射,每周1次,连续8周,在治疗前后分别对红系参数、营养状态和生活质量进行检测,并行自身对照.[结果]患者治疗后2、8周红系指标RBC、Hb、HCT、MCV、MCH、MCHC、Ret均明显升高(P< 0.05);IRF在2周时显著升高(P<0.01)而RDW 8周后明显升高(P<0.01);营养参数血清白蛋白(ALB)、总蛋白(TP)、转铁蛋白(Tf)治疗后明显增加,差异有统计学意义(P<0.05).生活质量中躯体功能、躯体职能、精力状况、社会功能、疼痛、总的健康状况治疗前后比较差异均有统计学意义(P<0.05).[结论]rHuEPO不仅能改善CRF患者的贫血状态,而且可改善患者的营养状况和生活质量.%[Objective] To study the recombinant human erythropoietin (rHuEPO) on erylhroid parameters and nutritional status and quality of life (QOL) in chronic renal failure (CRF) patients with anemia. [Methods] 24 patients with CRF patients received treatment of rHuEPO injection subcutaneous for 8 weeks, observed the variation of blood erythroid parameters, nutritional status and quality of life, before and after the treatment. [ Results] After 2 and 8 weeks of treatment, erythroid target RBC, Hb, HCT, MCV, MCH, MCHC and Ret were significantly increased (P<0.05), 1RF at 2 weeks was significantly higher (P < 0.01) and the RDW 8 weeks was significantly higher (P < 0.01), the nutritional status of ALB, TP and Tf were significantly increased (P < 0.05). QOL physical function, emotional function, energy status, emotional status, social function, pain and general health status were significantly different (P< 0.03). [Conclusion] rHuEPO can not only improve patients with renal anemia, but also improve the nutritional status and quality of life of the patients.

  7. 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.

  8. 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.

  9. 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).

  10. 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...

  11. High-dose erythropoietin for tissue protection

    DEFF Research Database (Denmark)

    Lund, Anton; Lundby, Carsten; Olsen, Niels Vidiendal

    2014-01-01

    BACKGROUND: The discovery of potential anti-apoptotic and cytoprotective effects of recombinant human erythropoietin (rHuEPO) has led to clinical trials investigating the use of high-dose, short-term rHuEPO therapy for tissue protection in conditions such as stroke and myocardial infarction....... Experimental studies have been favourable, but the clinical efficacy has yet to be validated. MATERIALS AND METHODS: We have reviewed clinical studies regarding the use of high-dose, short-term rHuEPO therapy for tissue protection in humans with the purpose to detail the safety and efficacy of r...... no effect of rHuEPO therapy on measures of tissue protection. Five trials including 1025 patients reported safety concerns in the form of increased mortality or adverse event rates. No studies reported reduced mortality. CONCLUSIONS: Evidence is sparse to support a tissue-protective benefit of r...

  12. Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Anita Rózsás

    Full Text Available Recombinant human erythropoietins (rHuEPOs are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR signaling in human non-small cell lung cancer (NSCLC also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOα were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOα with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOα treatment (either alone or in combination with gemcitabine did not alter ADC cell proliferation in vitro. However, rHuEPOα significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOα treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.

  13. 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

  14. 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

  15. Der Einfluss von Erythropoietin auf den Ischämie-/Reperfusionsschaden der Leber im Modell der orthotopen Rattenlebertransplantation

    OpenAIRE

    Hunold, Gerhard

    2010-01-01

    Human recombinant Erythropoietin (rHuEpo) has recently been shown to be a potent protector of ischemia- reperfusion injury in warm-liver ischemia. Significant enhancement of hepatic regeneration and survival after large volume partial hepatic resection has also been demonstrated. It was the aim of this study to evaluate the capacities of rHuEpo in the setting of rat liver transplantation. Sixty-eight Wistar rats were used: 39 rats received liver transplantation following donor organ treatment...

  16. 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

  17. Antiepoetin antibody-related pure red cell aplasia: successful remission with cessation of recombinant erythropoietin alone.

    Science.gov (United States)

    Katagiri, Daisuke; Shibata, Maki; Katsuki, Takashi; Masumoto, Shoichi; Katsuma, Ai; Minami, Eri; Hoshino, Taro; Inoue, Tsuyoshi; Tada, Manami; Hinoshita, Fumihiko

    2010-10-01

    An elderly patient with pure red cell aplasia (PRCA) with antierythropoietin (anti-EPO) antibodies is described. PRCA due to alloimmunization is a rare and severe complication of recombinant human erythropoietin (rHu-EPO) therapy. Most reported patients with PRCA were cured primarily by immunosuppressive drug therapy. The patient in this case, however, did not want to receive any immunosuppressive drugs. Therefore, rHu-EPO injection was simply discontinued, the severe anemia gradually improved, and the hemoglobin approached normal range. This case is very rare and significant in that there have been few such elderly patients with rHu-EPO-induced PRCA in whom PRCA remission was achieved, with decreasing antibody titers, after cessation of rHu-EPO alone. Further cases are needed to assess how PRCA should be treated in patients with anti-EPO antibodies.

  18. 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.

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

    Science.gov (United States)

    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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. [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.

  5. 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.

  6. 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

  7. Efficacy and safety of iron preparations combined with recombinant-human erythropoietin in the treatment of patients with chemotherapy-induced anemia: a meta-analysis%铁剂联合重组人促红细胞生成素治疗化疗诱导性贫血疗效与安全性的meta分析

    Institute of Scientific and Technical Information of China (English)

    于芝颖; 顾群; 张斌

    2011-01-01

    eiythropoietin (rHuEPO) , oral iron preparation plus rHuEPO, and rtiuEPO alone in treatment of patients with chemotherapy-induced anemia (CIA). Methods; PubMed (from 1966 to April 2011), Embase (from 1974 to April 2011), CBM (from 1978 to April 2011), CNKI ( from 1979 to April 2011), and Cochrane systematic evaluation and controlled trials register in Cochrane Library (from 1960 to Issue 1,2011) were searched using keywords "anemia" , "chemotherapy-induced anemia" , "ferrous sulfate", "ferrous fumarate" , "sodium ferric gluconate complex", "iron sucrose injection" , "iron dextran injection", "recombinant-human erylhropoietin" , "darbepoetin alfa", and"epoetin alfa". Randomized controlled trials (RCT) on the three different regimens in treatment of patients with CIA were collected. According to the inclusion criteria, the articles were selected and evaluated. All data were meta-analyzed using RevMan S. 0 software. After the patients received the three different regimens, the average value of haemoglobin ( Hb) level changes, the effective rate, the blood transfusion rate, the incidence of adverse drug reactions ( ADRs) , and the average value of quality of life score changes were calculated. Results: A total of 106 related articles were searched and 6 RCT were selected according to the inclusion criteria. A total of 1294 patients were entered in this study. The results of meta-analysis showed that the differences in the average value of Hb level changes, the effective rate, the blood transfusion rate, the incidence of ADRs between the parenteral iron and oral iron regimens were not significant (all P >0. 05). The weighed mean difference[95% confidence interval ( CI) ] of the average value of Hb level changes between the parenteral iron and no iron regimens was 0.54 (0.16-0.91, P = 0.005); the odds ratio (95% CI) of the effective rate and the blood transfusion rate between above 2 regimens were 2.07(1.18-3.65, P =0.01)and 0.66 (0.46-0.93, P=0.02), respectively. The differences were

  8. 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。

  9. 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.

  10. 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…

  11. 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…

  12. 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

    The ESFRI project European Plate Observing System (EPOS) was launched in November 2010 and has now completed its year 3 of the four-year preparatory phase. EPOS will create a single sustainable, permanent observation infrastructure, integrating existing geophysical monitoring networks, local observatories and experimental laboratories in Europe and adjacent regions. EPOS' technical Work Package 6 has developed a three layer architectural model for the construction of the EPOS Core Services (CS) during the subsequent implementation phase. The Poster will present and detail on these three layers, consisting of the EPOS Integrated Core Services (ICS), the Thematic Core Services (TCS) and the existing National Research Infrastructures & Data Centers. The basic layer of the architecture is established by the National Research Infrastructures (RIs) & Data Centers, which generate data and information and are responsible for the operation of the instrumentation. National RIs will provide their data to the Thematic Cores Services. The Thematic Core Services constitute the community layer of EPOS architecture and they will: 1) consist of existing (e.g. ORFEUS, EMSC), developing (e.g. EUREF/GNSS) or still to be developed Service Providers for specific thematic communities, as represented within EPOS through the technical EPOS Working Groups (e.g., seismology, volcanology, geodesy, geology, analytic labs for rock physics, geomagnetism, geo-resources ... and many others), 2) provide data services to specific communities, 3) link the National Research Infrastructures to the EPOS Integrated Services, 4) include Service Providers (e.g. OneGeology+, Intermagnet) that may be merely linked or partially integrated and 5) consist of Integrated Laboratories and RIs spanning multiple EPOS disciplines and taking advantage of other existing Thematic Services. The EPOS Integrated Services constitute the ICT layer of the EPOS portal and they will: 1) provide access to multidisciplinary data

  13. 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

  14. Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution

    DEFF Research Database (Denmark)

    Aachmann-Andersen, Niels Jacob; Just Christensen, Søren; Lisbjerg, Kristian

    2014-01-01

    The membrane-assisted isoform immunoassay (MAIIA) quantitates erythropoietin (EPO) isoforms as percentages of migrated isoforms (PMI). We evaluated the effect of recombinant human EPO (rhEPO) on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross...

  15. 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.

  16. Clinical efficacy of high-dose induction therapy by maintenance with recombinant human erythropoietin (rhEPO) in intestinal fistula patients complicated with intra-abdominal infection with anemia%rhEPO大剂量冲击维持疗法治疗肠瘘合并腹腔感染病人贫血的临床研究

    Institute of Scientific and Technical Information of China (English)

    洪之武; 任建安; 刘颂; 顾国胜; 袁玉杰; 周波; 闫冬升; 黎介寿

    2012-01-01

    目的 探讨重组人红细胞生成素(recombinant human erythropoietin,rhEPO)大剂量冲击维持疗法治疗肠瘘合并腹腔感染病人贫血的临床价值.方法 选择2010年9月至2011年12月南京军区南京总医院肠瘘治疗病区114例肠瘘致腹腔感染伴贫血且资料完整的病例,按照机体含铁量情况分为机体铁含量正常组和机体铁缺乏组,同时铁含量正常组再次随机分为单纯营养支持治疗(enteral nutrition/parenteral nutrition,EN/PN)组和EN/PN联合大剂量rhEPO冲击维持治疗组(各30例);铁缺乏组分为EN/PN联合铁剂(iron)组和EN/PN联合iron、大剂量rhEPO冲击维持治疗组(各27例).入组病例全部给予足量EN/PN、rhEPO和(或)蔗糖铁注射剂治疗并进行疗效观察.结果 两组病人治疗前后血红蛋白(Hb)比较,治疗前Hb差异无统计学意义(P>0.05).体内含铁量正常病人,在rhEPO治疗组2周后Hb明显高于未实施rhEPO干预组(P<0.05);体内含铁缺乏病人,铁剂联合rhEPO治疗组2周后Hb明显高于未实施rhEPO治疗组(P<0.05).大多数病人耐受良好.结论 肠瘘致腹腔感染伴贫血病人给予皮下注射rhEPO大剂量冲击维持疗法可有效快速提高病人的红细胞(RBC)及Hb水平,改善病人的贫血状况.该疗法耐受性较好,值得进一步扩大临床研究.%Objective To study clinical efficacy of recombinant human erythropoietin (rhEPO) in intestinal fistula patients complicated with intra-abdominal infection with anemia. Methods One hundred and fourteen patients with intestinal fistula complicated with intra-abdominal infection with anemia admitted from September 2010 to December 2011 in General Hospital of Nanjing Military Command were enrolled. In accordance with the iron content of the body the patients were divided into the group with the normal iron content in the body and the group with the deficient iron content. The normal iron content group was randomly divided into nutrition support

  17. 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

  18. 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

    This abstract presents the collaboration between the European Collaborative Data Infrastructure (EUDAT) and the pan-European infrastructure for solid Earth science (EPOS) which draws on the management of scientific data sets through a reciprocal support agreement. EUDAT is a Consortium of European Data Centers and Scientific Communities whose focus is the development and realisation of the Collaborative Data Infrastructure (CDI), a common model for managing data spanning all European research data centres and data repositories and providing an interoperable layer of common data services. The EUDAT Service Suite is a set of a) implementations of the CDI model and b) standards, developed and offered by members of the EUDAT Consortium. These EUDAT Services include a baseline of CDI-compliant interface and API services - a "CDI Gateway" - plus a number of web-based GUIs and command-line client tools. On the other hand,the EPOS initiative aims at creating a pan-European infrastructure for the solid Earth science to support a safe and sustainable society. In accordance with this scientific vision, the mission of EPOS is to integrate the diverse and advanced European Research Infrastructures for solid Earth Science relying on new e-science opportunities to monitor and unravel the dynamic and complex Earth System. 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 the 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. To achieve this integration challenge and the

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. No evidence for protective erythropoietin alpha signalling in rat hepatocytes

    Directory of Open Access Journals (Sweden)

    Frede Stilla

    2009-04-01

    Full Text Available Abstract Background Recombinant human erythropoietin alpha (rHu-EPO has been reported to protect the liver of rats and mice from ischemia-reperfusion injury. However, direct protective effects of rHu-EPO on hepatocytes and the responsible signalling pathways have not yet been described. The aim of the present work was to study the protective effect of rHu-EPO on warm hypoxia-reoxygenation and cold-induced injury to hepatocytes and the rHu-EPO-dependent signalling involved. Methods Loss of viability of isolated rat hepatocytes subjected to hypoxia/reoxygenation or incubated at 4°C followed by rewarming was determined from released lactate dehydrogenase activity in the absence and presence of rHu-EPO (0.2–100 U/ml. Apoptotic nuclear morphology was assessed by fluorescence microscopy using the nuclear fluorophores H33342 and propidium iodide. Erythropoietin receptor (EPOR, EPO and Bcl-2 mRNAs were quantified by real time PCR. Activation of JAK-2, STAT-3 and STAT-5 in hepatocytes and rat livers perfused in situ was assessed by Western blotting. Results In contrast to previous in vivo studies on ischemia-reperfusion injury to the liver, rHu-EPO was without any protective effect on hypoxic injury, hypoxia-reoxygenation injury and cold-induced apoptosis to isolated cultured rat hepatocytes. EPOR mRNA was identified in these cells but specific detection of the EPO receptor protein was not possible due to the lack of antibody specificity. Both, in the cultured rat hepatocytes (10 U/ml for 15 minutes and in the rat liver perfused in situ with rHu-EPO (8.9 U/ml for 15 minutes no evidence for EPO-dependent signalling was found as indicated by missing effects of rHu-EPO on phosphorylation of JAK-2, STAT-3 and STAT-5 and on the induction of Bcl-2 mRNA. Conclusion Together, these results indicate the absence of any protective EPO signalling in rat hepatocytes. This implies that the protection provided by rHu-EPO in vivo against ischemia-reperfusion and

  4. 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.

  5. Recombinant erythropoietin differently affects proliferation of mesothelioma cells but not sensitivity to cisplatin and pemetrexed.

    Science.gov (United States)

    Palumbo, Camilla; Battisti, Sonia; Carbone, Daniela; Albonici, Loredana; Alimandi, Maurizio; Bei, Roberto; Modesti, Andrea

    2008-04-01

    The combination of cisplatin and pemetrexed represents the newly established standard of care for patients with unresectable malignant mesothelioma (MM). However, this chemotherapy regimen appears to be associated with an increased prevalence of higher grade anemia as compared to treatment with cisplatin alone. Human recombinant erythropoietin (rHuEpo) is currently used for the treatment of anemia in cancer patients. Still, following the finding that the erythropoietin receptor (EpoR) is expressed by several tumor cells types and after the trials reporting that the recombinant cytokine can adversely affect tumor progression and patient survival, the clinical safety of rHuEpo administration to neoplastic patients has recently been questioned. The observation that the expression of EpoR, variably associated with the expression of the cognate ligand, is a common feature of MM cells prompted us to investigate whether treatment with rHuEpo could elicit proliferative and cytoprotective signals in EpoR-positive MM cell lines. Biochemical responsiveness of MM cells to rHuEpo was demonstrated by the time-course activation of both ERK1/2 and AKT following treatment with the recombinant cytokine. A moderately increased mitogenic activity was observed in two out of five MM cell lines treated with pharmacologically relevant concentrations of rHuEpo. On the other hand, the recombinant cytokine, administered either before or after cisplatin and pemetrexed, failed to interfere with the cytotoxic effects exerted by the chemotherapeutic drugs on the five MM cell lines. According to the presented findings, rHuEpo appears to have an overall limited impact on cell growth and no effect on MM sensitivity to chemotherapy.

  6. 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.

  7. 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

  8. Higher dose of erythropoietin for anemia correction in Balkan endemic nephropathy patients

    Directory of Open Access Journals (Sweden)

    Lukić Ljiljana

    2012-01-01

    Full Text Available Introduction. Balkan endemic nephropathy (BEN patients maintained with hemodialysis have more severe anemia than patients with other kidney diseases. Objective. The aim of the study was to compare the improvement of anemia in BEN patients and those with other kidney diseases during treatment with human recombinant erythropoietin (rHuEpo. Methods. The study involved 240 patients on regular hemodialysis for more than one year. Out of them 146 had BEN and 94 other kidney diseases (21 glomerulonephritis, 20 hypertension, 18 diabetes, 10 policystic kidney disease, 5 obstructive nephropathy, 18 other diseases. Treatment with rHuEpo was carried out according to European guidelines for the management of anemia. Results. Patients with BEN were older and were less frequently treated with ACEi than patients with other kidney diseases. At the onset of the study mean hemoglobin level (109.6±22.3 vs. 112.7±11.3 g/l was significantly lower, but serum ferritin level and rHuEpo dose (65.4±22.3 vs. 57.5±22.5 U/kg/week were significantly higher in BEN patients than in others. In prospective four months study these differences in hemoglobin levels and rHuEpo doses maintained. The rate of anemia improvement was examined in 15 BEN patients and 10 patients with other kidney diseases at the beginning of rHuEpo treatment. No difference in the rate of anemia improvement was found between the two groups but higher rHuEpo doses were used in BEN patients. Conclusion. Patients with BEN on regular hemodialysis had more severe anemia and required higher rHuEpo doses for maintaining target hemoglobin level.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 重组人促红细胞生成素对大鼠脊髓损伤后STAT5表达的影响%The effect of recombinant human erythropoietin on the expression of STAT5 in the acute spinal cord injury rat

    Institute of Scientific and Technical Information of China (English)

    邵博; 富长海; 李洪鹏

    2013-01-01

    Objective To study the effect of recombinant human erythropoietin(rHuEPO) on the expression of signal transducer and activator of transcription 5(STAT5) in the acute spinal cord injury rat. Methods 72 healthy adult SD rats were chose and randomly divided into the sham group, the acute spinal cord injury group and the recombinant human erythropoietin group. The spinal cord injury was established by Nystrom' s way. The expression of STAT5 in T10 segment was detected by immunochemistry and Western blot methods. Results Plenty of the positive STATS product in T10 segment of the spinal cord was found in sham group, and the positive expression level of STAT5 decreased significantly in spinal cord injury group than in sham control, lowest at 3 days after the injury, abut increassed significantly in rHuEPO treated group than in the acute spinal cord injury group by immunochemistry and Western blot methods. Conclusion rHuEPO can upregulate the expression of STAT5 in acute spinal cord injury rats.%目的 研究重组人促红细胞生成素(recombinant human erythropoietin,rHuEPO)对急性脊髓损伤大鼠信号传导子及转录激活-STAT5(signal transducer and activator of transcription 5)表达的影响.方法 成年健康SD大鼠72只,雌雄不限,切除T8、T9椎板,参照Nystrom's压迫方法制作大鼠脊髓压迫损伤模型,取T10节段脊髓组织,随机分为假手术组8只、急性脊髓损伤32只、rHuEPO处理组32只.利用免疫组化方法和Western blot方法检测各组大鼠STAT5的表达.结果 免疫组化和Western blot方法结果发现,假手术组大鼠脊髓有大量的STAT5阳性表达,急性脊髓损伤组大鼠的STAT5阳性表达明显降低,3d时降至最低;与脊髓损伤组相比,相同时间点的经重组人促红细胞生成素处理的大鼠脊髓STAT5阳性表达明显升高(P<0.05).结论 rHuEPO能够上调急性脊髓损伤大鼠STAT5的表达.

  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. 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.

  18. 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

  19. 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.

  20. 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....

  1. 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.

  2. 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

    monitor planet Earth is rapidly evolving through the development of new sensor technology and we can deliver this information with increasing rapidity, integrate it, provide solutions to scientific challenges and furnish essential information for decision makers. EPOS is aware that the research promoted by its data and service provision can have a profound influence on the environment, human health and wellbeing, economic development, national security, and other facets of human societies. For these reasons EPOS must address Ethics issues associated with the exploitation of its achievements involving security issues, use and misuse of data, environmental protection and risk communication. The EPOS community feels the obligation to adopt a responsible conduct, both within the scientific community and in the broader society, exploring the implications of open provisioning of data and services, up to imposing justified constraints. This requires that contributing to the DDSS provision cannot be simply limited to activities fostering the capacity (i.e., ability) to access scientific products, but must promote the creation of capabilities (i.e., conscious use of data) and the functioning (i.e., activities constitutive of a scientist's being) to access and use scientific products in an ethically consistent way. We will present and discuss Ethics issues envisaged in EPOS, focusing on the most relevant for its implementation phase: protection of personal data, misuse of data, communication, and societal impact.

  3. Effect of protein-energy malnutrition on erythropoietin requirement in maintenance hemodialysis patients.

    Science.gov (United States)

    Akgul, Arzu; Bilgic, Ayse; Sezer, Siren; Ozdemir, Fatma Nurhan; Olcay, Irem; Arat, Zubeyde; Haberal, Mehmet

    2007-04-01

    Possible interactions between inflammatory and nutritional markers and their impact on recombinant human erythropoietin (rHuEPO) hyporesponsiveness are not well understood. We investigated the role of nutritional status in rHuEPO requirement in maintenance hemodialysis (MHD) patients without evidence of inflammation. This cross-sectional study included 88 MHD patients. The associations between required rHuEPO dose and malnutrition-inflammation score (MIS) and several laboratory values known to be related to nutrition and/or inflammation were analyzed. Anthropometric measures including body mass index, triceps skinfold thickness, and midarm circumferences were also measured. Twenty-three patients with serum C-reactive protein levels >10 mg/L were excluded from the analysis. The remaining 65 patients (male/female, 41/24; age 49.1+/-11.4 years; dialysis duration 99.7+/-63.0 months) were studied. These patients had moderate malnutrition and the average MIS was 7.4 (range 3-17). The average weekly dose of administered rHuEPO was 69.1+/-63.1 U/kg. Malnutrition-inflammation score had a positive correlation with the serum concentration of tumor necrosis factor-alpha, whereas it had a negative correlation with anthropometric measures, total iron-binding capacity, prealbumin, phosphorus, creatinine, and triglyceride. According to Pearson's correlation analysis, significant relationships of increased MIS with increased required rHuEPO dose and rHuEPO responsiveness index (EPO divided by hematocrit) were observed (p=0.008, r=-0.326; p=0.017, r=-0.306, respectively). Recombinant human erythropoietin dose requirement is correlated with MIS and adverse nutritional status in MHD patients without evidence of inflammation. Further research should focus on reversing the undergoing microinflammation for a better outcome in dialysis patients.

  4. 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

  5. 重组人红细胞生成素在肿瘤相关贫血中的应用%Application of recombinat human erythropoietin in cancer-related anemia

    Institute of Scientific and Technical Information of China (English)

    谢晓冬; 孙静

    2002-01-01

    Recombinant human erythropoietin(rhEPO) is safe and effective in treating cancer related anemia and solid tumors in children through promoting recovery of hematopoietic function of bone marrow and replacing renal endogenous EPO.rhEPO can significantly elevate serum Hb levle and reduce transfusion dependancy in anemiac patients.Some studies showed rhEPO is especially effective for lymphoma and myeloma patients with lower concentration of serum EPO.EPO levle after treatment and dissolubilitive transferrin receptor 2 weeks after treatment are indexes for effectiveness of rhEPO.

  6. Effects of recombinant humant erythropoietin in normal humans

    DEFF Research Database (Denmark)

    Lundby, Carsten; Olsen, Niels Vidiendal

    2011-01-01

    , and although it has been speculated that non-erythropoietic effects of EPO (angiogenesis, shift in muscle fibre types, cognitive effects) may be responsible for the increase in exercise performance, this has not been confirmed. EPO induced haemodynamic effects call for careful monitoring during......This review describes some of the physiological effects of recombinant human erythropoietin (EPO) in healthy humans. At the blood level EPO increases the arterial O2 content not only by increasing red blood cell volume, but also by an equally important decrease in plasma volume. Well before that...... result in suppression of endogenous EPO production through a decrease in intrarenal oxygen consumption. EPO elevates the arterial blood pressure even in healthy subjects. The receptor for EPO is present in many tissues. However, the functional effects of EPO in the skeletal muscle seem limited...

  7. Short-term effect of erythropoietin on brain lesions and aquaporin-4 expression in a hypoxic-ischemic neonatal rat model assessed by magnetic resonance diffusion weighted imaging and immunohistochemistry.

    Science.gov (United States)

    Brissaud, Olivier; Villega, Frédéric; Pieter Konsman, Jan; Sanchez, Stéphane; Raffard, Gérard; Franconi, Jean-Michel; Chateil, Jean-François; Bouzier-Sore, Anne-Karine

    2010-08-01

    Erythropoietin (Epo) is an endogenous cytokine that regulates hematopoiesis and is widely used to treat anemia. In addition, it has recently increased interest in the neurosciences since the new concept of Epo as a neuroprotective agent has emerged. The potential protective effect of human recombinant Epo (r-hu-Epo) on a hypoxic-ischemic (HI) pup rat model was studied. Cerebral HI was obtained by permanent left carotid artery ligature of pups followed by a 2-h hypoxia. Three hours after carotid occlusion, brain lesions were assessed by magnetic resonance diffusion weighted imaging. Intraperitoneal administration of r-hu-Epo (30,000 U/kg dose) limited both the HI-induced brain lesion area and the decrease in apparent diffusion coefficient (ADC) in the lesion. To identify potential mechanisms underlying the effects of Epo, immunohistochemical detection of caspase-3 and water channel protein aquaporin-4 (AQP4) were performed. No early apoptosis was detected, but up-regulation of AQP4 expression was observed in HI pups that received r-hu-Epo compared with HI animals without treatment. This study demonstrates an early neuroprotective effect of Epo with regard to brain lesion area and ADC values. One possible mechanism of Epo for decreasing brain edema and cellular swelling could be a better clearance of water excess in brain tissue, a process possibly mediated by AQP4.

  8. Association of I/D angiotensin-converting enzyme genotype with erythropoietin stimulation in kidney failure

    Directory of Open Access Journals (Sweden)

    Savin Marina

    2017-01-01

    Full Text Available Angiotensin-converting enzyme (ACE-gene polymorphism is a possible predisposing factor of erythropoietin response under hypoxic conditions. However, it is not completely clear whether the ACE insertion/deletion (I/D genotype has an impact on anemia in patients with permanent kidney failure. A 9-month prospective trial was conducted on 53 patients on hemodialysis aimed at determining the beneficial effect of oral vs intravenous iron in anemia management with recombinant human erythropoietin (rHuEpo, and identifying a possible association of the ACE gene I/D polymorphism with the response to rHuEpo. Patients were randomly allocated to receive 50-100 mg daily of ferrous gluconate orally (N=26 or intravenously every two weeks (N=27, together with rHuEpo-beta (200 IU/kg subcutaneously, to achieve a hemoglobin increase to 105 g/L; subsequently the rHuEpo dose was adjusted at one or two week intervals. In 34 patients who regularly received ACE-inhibitor (ACEi medication, genotyping for ACE-gene I/D polymorphism was performed using PCR, gel analysis and appropriate restriction digestion. After prolonged rHuEpo treatment, 24.5% of patients attained the targeted 9th-month hemoglobin concentration (105 g/L. Of these, 6/26 of patients received elemental iron orally and 7/27 received it intravenously. We observed an association between homozygous DD (deletion of the ACE gene and a remarkable early increase in blood hemoglobin (p=0.028, erythrocyte count (p=0.020 and hematocrit (p=0.043 after reduction of the dose of rHuEpo (F=3.95; p=0.029, irrespective of the iron repletion mode (p=0.960. This is the first report on DD genotype as a linkage marker for the optimization of rHuEpo dose for anemia management in hemodialysis patients.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Autologous blood collection in anemic patients using low-dose erythropoietin therapy.

    Science.gov (United States)

    Mott, L S; Bechinski, J; Jones, M J

    1997-06-01

    Autologous donation of blood for use during elective surgery is being recommended and used more frequently. Autologous donation and transfusion represent the safest way to handle elective surgical blood requirements because they eliminate the risk of transfusion-transmitted disease and alloimmunization, and significantly reduce the other risks associated with homologous transfusion. Many individuals, particularly women and the elderly, do not have sufficient initial hemoglobin concentration or hemopoietic reserve to effectively use autologous donation. Use of standard-dose recombinant human erythropoietin (rHuEPO) (600 units/kg) to mitigate these limitations is costly. The optimal dose, interval, and route of administration for rHuEPO therapy has yet to be perfected. This article describes a program using low-dose (effectiveness, cost savings, and clinical indications for the use of low-dose rHuEPO.

  16. 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.

  17. 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.

  18. Anemia in peritoneal dialysis patients

    Directory of Open Access Journals (Sweden)

    Laušević Mirjana

    2006-01-01

    Full Text Available A normocytic normochromic anemia is one of the first signs of renal failure. Since anemia increases morbidity and mortality, its elimination is one of the essential objectives of the treatment. Human recombinant erythropoietin (rHuEPO has changed the therapeutical approach to anemia. The aim of the present study was to compare efficacy of anemia correction in peritoneal dialysis patients depending on treatment and dialysis modality. The study is the retrospective analysis of 64 patients who presented to our Clinic in 2003. Eighteen (28.13% patients were treated with rHuEPO, 14 (28% underwent continuous ambulatory peritoneal dialysis (CAPD, 2 (100% - automated peritoneal dialysis (APD and 2 (33.3% - intermittent peritoneal dialysis (IPD. Mean hemoglobin level was 98.6±17.82 g/l in patients treated with rHuEPO versus 98.81±15.14 g/I in patients without rHuEPO treatment. Erythropoietin requirements were 3392.85±1211.77 IU/week. AII patients received iron supplementation during rHuEPO therapy. Mean serum ferritin levels were 463.41 ±360 μg/l. Transferrin saturation (TSAT was 0.35±0.16%. No difference of serum iron and TSAT levels was found between CAPD and IPD patients. The degree of anemia significantly differed between CAPD and IPD patients. A total of 17.11% of PD patients were given blood transfusions, most frequently during the first three months after the onset of dialysis. Our conclusion is that the number of patients receiving rHuEPO should be increased, as 50% of our patients should be substituted, while only 28% are being treated. As 50% of patients receiving rHuEPO failed to reach target Hgb levels, higher EPO doses should be considered. Iron stores should be continuously monitored, particularly in patients receiving rHuEPO, since iron deficiency is an important problem for patients undergoing peritoneal dialysis, especially during erythropoietin therapy. Oral iron supplementation is satisfactory in the majority of patients, and

  19. The Role of Endothelin and Prostacyclin on Recombinant Erythropoietin-α Induced Hypertension in Hemodialysis Patients

    Directory of Open Access Journals (Sweden)

    Türkmen, Kültigin

    2013-01-01

    Full Text Available OBJECTIVE: Recombinant human erythropoietin (r-HuEPO was found to be associated with increased blood pressure in hemodialysis (HD patients. Plasma endothelin-1(ET-1 was reported to be increased during treatment with r-huEPO in HD patients. Prostacyclin (PGI2 was found to be associated with the reduction in vascular resistance. We aimed to determine the role of ET-1 and PGI2 on r-huEPO-induced hypertension in HD patients.MATERIAL and METHODS: 43 HD patients (19 females, 24 males were randomly assigned to groups. Group 1 (n=15 consisted of patients receiving r-HuEPO-α subcutaneously after each dialysis session for 6 to 42 months. Group 2 (n=15, control group consisted of patients who did not receive any r-huEPO and group 3 (n=13 consisted of patients who received r-huEPO-α subcutaneously after each dialysis session for 12 weeks. Plasma ET-1,2 and 6-keto-PGF1-α were measured.RESULTS: There were no differences in terms of ET-1,2 and 6-keto-PGF1-α, systolic and diastolic BP and hematocrit levels in group 1 and group 2 patients. However, in group 3 patients, hematocrit, plasma ET1,2 and 6-keto PGF1-α levels were significantly elevated after 12 weeks of rHuEPO treatment.CONCLUSION: We showed that ET-1.2 and 6-keto-PGF1-α levels were found to be significantly increased with 12 weeks of rHu-EPO therapy in HD patients.

  20. 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.

  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. 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.

  3. 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.

  4. On the antioxidant properties of erythropoietin and its association with the oxidative–nitrosative stress response to hypoxia in humans

    DEFF Research Database (Denmark)

    Bailey, D M; Lundby, C; Berg, R M G

    2014-01-01

    resonance spectroscopy, ELISA and ozone-based chemiluminescence were employed for direct detection of ascorbate (A(˙-) ) and N-tert-butyl-α-phenylnitrone spin-trapped alkoxyl (PBN-OR) radicals, 3-nitrotyrosine (3-NT) and nitrite (NO2-). RESULTS: We found rHuEPO to be a potent scavenger of HO˙ (kr = 1.......03-1.66 × 10(11) m(-1) s(-1) ) with the capacity to inhibit Fenton chemistry through catalytic iron chelation. Its ability to scavenge DPPH˙ and ROO˙ was also superior compared to other more conventional antioxidants. Hypoxia was associated with a rise in arterial EPO and free radical-mediated reduction...... in nitric oxide, indicative of oxidative-nitrosative stress. The latter was confirmed by an increased systemic formation of A˙(-) , PBN-OR, 3-NT and corresponding loss of NO2- (P

  5. 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

  6. 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

  7. 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

  8. Effects of erythropoietin and vitamin E-modified membrane on plasma oxidative stress markers and anemia of hemodialyzed patients.

    Science.gov (United States)

    Usberti, Mario; Gerardi, GianMario; Bufano, Giuseppe; Tira, Paola; Micheli, Annamaria; Albertini, Alberto; Floridi, Ardesio; Di Lorenzo, Diego; Galli, Francesco

    2002-09-01

    Oxidant stress has a pathogenic role in uremic anemia, possibly interfering with erythropoietin (EPO) function and red blood cell (RBC) survival. Therefore, it is expected that antioxidant therapy might exert a beneficial effect on these parameters. To test this hypothesis, we investigated some oxidant stress indices, anemia levels, and RBC survival in 47 hemodialysis (HD) patients randomly assigned to three groups. Patients in groups A (n = l8) and B (n = 20) were on dialysis therapy using conventional cellulosic and synthetic membranes and were administered high and low doses of recombinant human EPO (rHuEPO), respectively. Patients in group C (n = 9) were dialyzed with vitamin E-modified membranes (CL-Es) and investigated in a two-step prospective study. In step Cl, patients were administered rHuEPO doses similar to those of group A. In step C2, rHuEPO doses were reduced to those of group B. As oxidant stress markers, we determined in plasma the susceptibility of lipids to undergo iron-catalyzed oxidation (reactive oxygen molecules [ROMs] test) and malondialdehyde-4-hydroxynonenal (MDA-4HNE), alpha-tocopherol (alpha-T), total thiol (-SH), and total antioxidant activity. RBC survival was measured using the chromium 51 T/2 technique in 22 patients. Results show that: (1) high rHuEPO doses (groups A and C1) were associated with decreased ROM production, low alpha-T levels, and slightly increased -SH levels compared with corresponding groups on low rHuEPO doses (groups B and C2); (2) treatment with CL-Es (group C) increased plasma alpha-T and decreased -SH levels; these data were associated with decreased indices of lipid peroxidation, particularly MDA-4HNE 1evels, only in patients administered low rHuEPO doses; (3) alpha-T concentration influenced RBC survival, which was remarkably decreased in HD patients; patients treated with CL-Es showed a better degree of anemia correction; and (4) alpha-T level correlated negatively with -SH level and seemed to be independent

  9. 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.

  10. 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.

  11. Erythropoietin Receptor in Human Tumor Cells: Expression and Aspects Regarding Functionality

    NARCIS (Netherlands)

    T.A. Knoch (Tobias); G. Westphal; E. Niederberger; C. Blum; Y. Wollman; W. Rebel; J. Debus; E. Friedrich

    2001-01-01

    textabstractRecombinant human erythropoietin (Epo)and granu l o cy t e - c o l o ny - s t i mulating factor (G-CSF) are used to stimulate hematopoiesis in patients with malignant dise a s e s . These cytokines transduce their biological signal via the Epo receptor (EpoR) and G-CSF receptor (G-CSF-R)

  12. In-vivo detection of the erythropoietin receptor in tumours using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Fuge, Felix; Doleschel, Dennis; Rix, Anne; Gremse, Felix; Lederle, Wiltrud; Kiessling, Fabian [RWTH Aachen University, Department for Experimental Molecular Imaging (ExMI), Medical Faculty, Aachen (Germany); Wessner, Axel [Roche Diagnostics GmbH, R and D RPD Protein Chemistry, Penzberg (Germany); Winz, Oliver; Mottaghy, Felix [University Clinic RWTH Aachen, Clinic for Nuclear Medicine, Aachen (Germany)

    2014-09-09

    Recombinant human erythropoietin (rhuEpo) is used clinically to treat anaemia. However, rhuEpo-treated cancer patients show decreased survival rates and erythropoietin receptor (EpoR) expression has been found in patient tumour tissue. Thus, rhuEpo application might promote EpoR{sup +} tumour progression. We therefore developed the positron emission tomography (PET)-probe {sup 68}Ga-DOTA-rhuEpo and evaluated its performance in EpoR{sup +} A549 non-small-cell lung cancer (NSCLC) xenografts. {sup 68}Ga-DOTA-rhuEpo was generated by coupling DOTA-hydrazide to carbohydrate side-chains of rhuEpo. Biodistribution was determined in tumour-bearing mice 0.5, 3, 6, and 9 h after probe injection. Competition experiments were performed by co-injecting {sup 68}Ga-DOTA-rhuEpo and rhuEpo in five-fold excess. Probe specificity was further evaluated histologically using Epo-Cy5.5 stainings. The blood half-life of {sup 68}Ga-DOTA-rhuEpo was 2.6 h and the unbound fraction was cleared by the liver and kidney. After 6 h, the highest tumour to muscle ratio was reached. The highest {sup 68}Ga-DOTA-rhuEpo accumulation was found in liver (10.06 ± 6.26%ID/ml), followed by bone marrow (1.87 ± 0.53%ID/ml), kidney (1.58 ± 0.39 %ID/ml), and tumour (0.99 ± 0.16%ID/ml). EpoR presence in these organs was histologically confirmed. Competition experiments showed significantly (p < 0.05) lower PET-signals in tumour and bone marrow at 3 and 6 h. {sup 68}Ga-DOTA-rhuEpo shows favourable pharmacokinetic properties and detects EpoR specifically. Therefore, it might become a valuable radiotracer to monitor EpoR status in tumours and support decision-making in anaemia therapy. (orig.)

  13. 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...

  14. 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

  15. 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

  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. 人EPO基因真核表达载体的构建及其在人脐血间充质干细胞中的表达%Construction of eukaryotic expression vector of human EPO gene and its expression in mesenchymal stem cells derived from human umbilical cord blood

    Institute of Scientific and Technical Information of China (English)

    夏桂枝; 张国成; 陈新民; 洪新如

    2008-01-01

    目的: 构建人EPO基因真核表达载体并转染人脐血间充质干细胞,获得稳定表达人EPO的人脐血间充质干细胞.方法: 从人胎肝细胞中提取总RNA,经过RTPCR方法扩增人EPO全长cDNA,应用基因重组技术将EPO cDNA基因亚克隆至pcDNA3真核表达载体内,以酶切和测序方法鉴定重组质粒pcDNA3-EPO构建的正确性,再将pcDNA3-EPO经脂质体介导转染人脐血间充质干细胞,经G418筛选后获得稳定转染EPO基因的人脐血间充质干细胞,用RT-PCR,Western Blot和细胞免疫化学方法鉴定外源人EPO基因在人脐血间充质干细胞中的表达.结果: 酶切和测序结果均证实pcDNA3-EPO构建正确,RT-PCR,Western blot和细胞免疫化学结果显示转染人EPO基因的人脐血间充质干细胞体外能表达EPO.结论: 构建成功人EPO基因真核表达载体,转染人脐血间充质干细胞后在体外可获得稳定表达.

  18. 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

  19. 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

  20. 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...

  1. 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.

  2. Effect of PEG-modification on the pharmacokinetics of recombinant human erythropoietin in rats%聚乙二醇修饰对重组人促红细胞生成素在大鼠体内药代动力学的影响

    Institute of Scientific and Technical Information of China (English)

    王诗鸿; 王秀中; 董立厚; 陈方; 宋海峰

    2013-01-01

    Objective: To determine the effect of PEG-modification on the pharmacokinetics of recombinant human erythropoietin in rats. Methods: Eighteen rats were equally randomized into three groups. EPO, M-PEG-EPO and G-PEG-EPO at 5 μg·kg were subcutaneously injected, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the plasma concentrations of EPO, M-PEG-EPO and G-PEG-EPO. Results: After administration, the Tmax of M-PEG-EPO and G-PEG-EPO was later than that of EPO. The peak concentrations of M-PEG-EPO and G-PEG-EPO in plasma were lower than that of EPO. M-PEG-EPO and G-PEG-EPO were cleared slower as the terminal half-life was prolonged relatively. There was no statistically significant difference between M-PEG-EPO and G-PEG-EPO in pharmacokinetics parameters except AUC0-inf and Cls. Conclusion: PEG-modification of EPO can prolong the terminal half-life of EPO in rats. The pharmacokinetics of M-PEG-EPO and G-PEG-EPO in rats is similar.%目的:研究聚乙二醇修饰对重组人促红细胞生成素在大鼠体内药代动力学的影响.方法:大鼠随机分成3组,分别单次皮下注射5 μg· kg-1氨基葡萄糖-聚乙二醇-EPO(G-PEG-EPO)、甲氧基-聚乙二醇-EPO(M-PEG-EPO)和未经修饰的EPO原液后采集血样,采用酶联免疫吸附分析(ELISA)测定大鼠血浆样品中的EPO浓度.结果:给药后,与EPO相比,M-PEG-EPO,G-PEG-EPO较EPO吸收过程缓慢,峰浓度Cmax水平显著降低,代谢清除相对缓慢,末端消除相半衰期t1/2明显延长.而M-PEG-EPO,G-PEG-EPO的药代动力学参数除AUC0-inf和Cls外均无统计学差异.结论:聚乙二醇修饰能显著延长EPO在大鼠的末端消除相半衰期,G-PEG-EPO和M-PEG-EPO在大鼠的药代动力学性质相似.

  3. 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.

  4. 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.

  5. Combined therapy with amifostine plus erythropoietin for the treatment of myelodysplastic syndromes

    DEFF Research Database (Denmark)

    Musto, Pellegrino; Santini, Valeria; Balestri, Francesca;

    2002-01-01

    Twelve patients with myelodysplasia were treated with amifostine plus recombinant human erythropoietin (rHuEpo) for 6 weeks. A complete erythroid response was obtained in 2/12(16.6%) and a partial response in 4/12 (33.3%). Two of 8 patients with a platelet count

  6. Detection of erythropoietin misuse by the Athlete Biological Passport combined with reticulocyte percentage

    DEFF Research Database (Denmark)

    Bejder, Jacob; Aachmann-Andersen, Niels Jacob; Bonne, Thomas Christian

    2016-01-01

    The sensitivity of the adaptive model of the Athlete Biological Passport (ABP) and reticulocyte percentage (ret%) in detection of recombinant human erythropoietin (rHuEPO) misuse was evaluated using both a long-term normal dose and a brief high dose treatment regime. Sixteen subjects received...

  7. 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...

  8. 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.

  9. 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.

  10. 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

  11. "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…

  12. 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.

  13. 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…

  14. 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

  15. 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.

  16. Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial.

    Science.gov (United States)

    Casadevall, Nicole; Durieux, Pierre; Dubois, Stéphanie; Hemery, François; Lepage, Eric; Quarré, Marie-Catherine; Damaj, Gandhi; Giraudier, Stéphane; Guerci, Agnès; Laurent, Guy; Dombret, Hervé; Chomienne, Christine; Ribrag, Vincent; Stamatoullas, Aspasia; Marie, Jean-Pierre; Vekhoff, Anne; Maloisel, Frédéric; Navarro, Robert; Dreyfus, François; Fenaux, Pierre

    2004-07-15

    In myelodysplastic syndromes (MDS), anemia responds to recombinant human erythropoietin (rHuEPO) alone and in combination with recombinant human granulocyte-colony-stimulating factor (rHuGCSF) in 10% to 20% and in 35% to 40% of patients, respectively. We randomly divided 60 patients with low-grade anemic MDS and serum EPO levels lower than 500 IU/L (500 mU/mL) into 2 groups: rHuEPO + rHuG-CSF (arm A) and supportive care (arm B). After 12 weeks, those who had erythroid responses were given rHuEPO alone for 40 additional weeks. They were also given rHuG-CSF if they had relapses. A response was considered major if the hemoglobin (Hb) level was 115 g/L (11.5 g/dL) or higher and minor Hb increase was 15 g/L (1.5 g/dL) or more or if it remained stable without transfusion. Ten of 24 patients responded in arm A, and 0 of 26 responded in arm B (P =.01). Eight patients in arm A continued rHuEPO therapy alone, and 6 had relapses. Responses were always restored when rHuG-CSF was reintroduced. Mean direct costs per patient were 26,723 euros (arm A) and 8,746 euros (arm B). Quality of life was assessed with a Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale. Similar percentages of patients from both arms showed significant clinical improvement. rHuEPO plus rHuG-CSF led to responses in 41.7% of MDS patients. This treatment was expensive. No effect on quality of life was demonstrated.

  17. 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

  18. 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...

  19. Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle

    DEFF Research Database (Denmark)

    Lundby, Carsten; Hellsten, Ylva; Jensen, Mie B. F.;

    2008-01-01

    The presence and potential physiological role of the erythropoietin receptor (Epo-R) were examined in human skeletal muscle. In this study we demonstrate that Epo-R is present in the endothelium, smooth muscle cells, and in fractions of the sarcolemma of skeletal muscle fibers. To study...... the potential effects of Epo in human skeletal muscle, two separate studies were conducted: one to study the acute effects of a single Epo injection on skeletal muscle gene expression and plasma hormones and another to study the effects of long-term (14 wk) Epo treatment on skeletal muscle structure. Subjects...... (n = 11) received a single Epo injection of 15,000 IU (double blinded, cross over, placebo). A single Epo injection reduced myoglobin and increased transferrin receptor and MRF-4 mRNA content within 10 h after injection. Plasma hormones remained unaltered. Capillarization and fiber hypertrophy...

  20. 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.

  1. 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.

  2. “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.

  3. 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。

  4. 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.

  5. 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

  6. 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.

  7. Therapeutic efficacy of a biosimilar epoetin alfa in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Amel Harzallah

    2015-01-01

    Full Text Available Anemia is a frequent complication in patients with chronic kidney disease. However, human recombinant erythropoietin (rHu-EPO has revolutionized the management of anemia in chronically dialyzed patients. Epomax ® is a new rHu-EPO alfa manufactured in Tunisia (Medis Laboratories. The aim of this study was to evaluate the efficacy and tolerance of Epomax ® in chronic hemodialysis (HD patients in a phase-III, multicenter, clinical trial. Fiftythree HD patients (mean age 47.7 ± 13 years who received a stable dose of rHu-EPO (Hemax ® , a rHu-EPO alfa manufactured by Biosidus Laboratories subcutaneously were switched to Epomax ® via the same route of administration. At baseline, the mean systolic pressure was 132 ± 18 mm Hg and the mean diastolic pressure was 79 ± 8 mm Hg. The mean blood hemoglobin was 10.2 g/dL and the median ferritin level was 667 ng/mL. After a follow-up of 43 days, the mean blood hemoglobin was 10.5 g/dL under the effect of Epomax ® . There was no significant difference in the mean hemoglobin levels between the treatments with both drugs. Few adverse events were reported during the study. We conclude that Epomax ® was effective at maintaining the hemoglobin levels at target concentrations and was well tolerated in HD patients.

  8. Delivery of erythropoietin with a needleless injection system during hemodialysis maintains plasma levels.

    Science.gov (United States)

    Petersen, J; Jani, A

    2001-01-01

    Recent Occupational Safety and Health Administration guidelines require the implementation of needleless systems in dialysis units in the state of California. It is not known whether needleless systems deliver medication as well as traditional low dead-space needle/syringes. The purpose of this study was to compare the delivery of recombinant human erythropoietin (rHuEpo) by a needleless system (Medic Plastic Anti-Stick Needle/Connector, Medisystems, Seattle, WA) with delivery using a traditional low dead-space needle/syringe. We also studied the Medisystems High Flow venous chamber with integral injection site that is designed to prevent the formation of a separate serum layer within which rHuEpo may become trapped. There was no significant difference in the mean serum rHuEpo concentration achieved by either the needleless system, or traditional low dead-space needle/syringe, whether using the venous chamber's integral injection site or the postvenous chamber in-line injection site. This study demonstrates for the first time that a needleless system of delivery can reliably achieve serum rHuEpo comparable to traditional low dead-space needle/syringes.

  9. 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

  10. 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.

  11. Erythropoietin inhibits gamma-irradiation-induced apoptosis by upregulation of Bcl-2 and decreasing the activation of caspase 3 in human UT-7/erythropoietin cell line.

    Science.gov (United States)

    Liu, Yuan-Yuan; She, Zhen-Jue; Yao, Ming-Hui

    2010-05-01

    1. Erythropoietin (EPO) can reverse radiotherapy-induced anaemia by stimulating bone marrow cells to produce erythrocytes. However, there are limited studies that address the mechanisms by which EPO exerts its beneficial effects in radiotherapy-induced anaemia. In the present study, we used a human bone marrow-derived EPO-dependent leukaemia cell line UT-7/EPO that progressed further in erythroid development to evaluate the anti-apoptotic effects of EPO on irradiated human erythroid progenitor. 2. The UT-7/EPO cells exposed to gamma-irradiation were cultured in the presence or absence of EPO at a concentration of 7 U/mL. The cell viability, cell apoptosis and the expression of apoptosis-related proteins Bcl-2, Bax and caspase 3 were examined. 3. The results showed that EPO protected the viability of human UT-7/EPO cells exposed to gamma-irradiation. EPO significantly inhibited gamma-irradiation-induced apoptosis in human UT-7/EPO cells: a significant decrease in the percentage of apoptotic cells was observed (62, 69 and 62% at 24, 48 and 72 h, respectively). Furthermore, EPO significantly increased the expression of Bcl-2 protein and the relative Bcl-2/Bax ratio, and decreased the activation of caspase 3 and formation of the p17 and p12 cleavage in similar conditions. 4. In conclusion, EPO exerts anti-apoptotic effects on irradiated human UT-7/EPO cells through upregulation of Bcl-2 protein and the relative Bcl-2/Bax ratio, and by decreasing the activation of caspase 3. These findings may contribute to our understanding of the beneficial function of EPO in radiotherapy-induced anaemia.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. A Novel EPO Receptor Agonist Improves Glucose Tolerance via Glucose Uptake in Skeletal Muscle in a Mouse Model of Diabetes

    Directory of Open Access Journals (Sweden)

    Michael S. Scully

    2011-01-01

    Full Text Available Patients treated with recombinant human Epo demonstrate an improvement in insulin sensitivity. We aimed to investigate whether CNTO 530, a novel Epo receptor agonist, could affect glucose tolerance and insulin sensitivity. A single administration of CNTO 530 significantly and dose-dependently reduced the area under the curve in a glucose tolerance test in diet-induced obese and diabetic mice after 14, 21, and 28 days. HOMA analysis suggested an improvement in insulin sensitivity, and this effect was confirmed by a hyperinsulinemic-euglycemic clamp. Uptake of 14C-2-deoxy-D-glucose indicated that animals dosed with CNTO 530 transported more glucose into skeletal muscle and heart relative to control animals. In conclusion, CNTO530 has a profound effect on glucose tolerance in insulin-resistant rodents likely because of improving peripheral insulin sensitivity. This effect was observed with epoetin-α and darbepoetin-α, suggesting this is a class effect, but the effect with these compounds relative to CNTO530 was decreased in duration and magnitude.

  3. [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

  4. Pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin-loaded poly(lactic-co-glycolic acid) microspheres in rats

    Institute of Scientific and Technical Information of China (English)

    Xiang-lian ZHOU; in-tian HE; Hui-juan DU; Yang-yang FAN; Ying WANG; Hong-xia ZHANG; Yang JIANG

    2012-01-01

    To characterize the pharmacokinetic and pharmacodynamic profiles of the recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in rats.Methods:The rhEPO-loaded microspheres were prepared using a solid-in-oil-in-water emulsion method.Pharmacokinetics and pharmacodynamics of the rhEPO-loaded microspheres were evaluated in male Sprague-Dawley rats.The serum rhEPO level was determined with ELISA.The level of anti-rhEPO antibody in the serum was measured to assess the immunogenicity of rhEPO released from the microspheres.Results:rhEPO was almost completely released from the PLGA microspheres in vitro,following zero-order release kinetics over approximately 30 d.After intramuscular injection (10 000 or 30 000 IU rhEPO/kg) in the rats,the serum rhEPO concentration reached maximum levels on d 1,then decreased gradually and was maintained at nearly steady levels for approximately 4 weeks.Furthermore,the release of rhEPO from the PLGA microspheres was found to be controlled mainly by a dissolution/diffusion mechanism.A good linear correlation (R2=0.98) was obtained between the in vitro and in vivo release data.A single intramuscular injection of the rhEPO-loaded PLGA microspheres (10 000 or 30 000 IU rhEPO/kg) in the rats resulted in elevated hemoglobin and red blood cell concentrations for more than 28 d.Moreover,the immunogenicity of rhEPO released from the PLGA microspheres was comparable with that of the unencapsulated rhEPO.Conclusion:The results prove the feasibility of using the PLGA-based microspheres to deliver rhEPO for approximately 1 month.

  5. 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.

  6. Central nervous system frontiers for the use of erythropoietin

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    2003-01-01

    Recombinant human erythropoietin (r-HuEPO; epoetin alfa) is well established as safe and effective for the treatment of anemia. In addition to the erythropoietic effects of endogenous erythropoietin (EPO), recent evidence suggests that it may elicit a neuroprotective effect in the central nervous...... system (CNS). Preclinical studies have demonstrated the presence of EPO receptors in the brain that are up-regulated under hypoxic or ischemic conditions. Intracerebral and systemic administration of epoetin alfa have been demonstrated to elicit marked neuroprotective effects in multiple preclinical...

  7. Hematological parameters, and hematopoietic growth factors: EPO and IL-3 in response to whole-body cryostimulation (WBC in military academy students.

    Directory of Open Access Journals (Sweden)

    Zbigniew Szygula

    Full Text Available The effects of extreme cold on the human body are not fully understood, there are also no reports on the effect of cryogenic temperatures on the levels of erythropoietin (EPO and interleukin 3 (IL-3, two important factors that regulate hematopoiesis.determination of changes in peripheral blood cell counts and EPO and IL-3 levels induced by a series of 10, 20 and 30 standard whole-body cryostimulation (WBC treatments. The study involved 45 men, experimental group (EXP, n = 30 subjected to 30 WBC treatments (-130°C, treatment duration: 3 minutes and a control group (CON, n = 15. Blood samples were collected before the series of treatments and after 10, 20 and 30 treatments. After 10 and 20 treatments we observed lower red blood cell counts and hematocrit and hemoglobin levels compared to baseline (p<0.05 and the control group (p<0.05. Additionally we observed an increase in hemoglobin concentration in plasma (p<0.05, and bilirubin after 10 and 20 treatments, and a decrease in plasma concentration of haptoglobin after 10, 20 and 30 treatments (p<0.05. The number of leukocytes was higher after 10 and 20 WBC treatments compared to baseline and the CON group. EPO concentration in plasma was elevated and the concentration of IL-3 was lower after 10, 20 and 30 WBC treatments. The decrease in indices of the erythrocytic system, plasma hemoglobin and bilirubin, with a simultaneous decrease in haptoglobin concentrations after 10 and 20 WBC treatments, may be due to increased intravascular hemolysis. At the same time there was a small, but statistically significant increase in the concentration of EPO stimulated erythropoiesis which could facilitate a return of erythrocytic system indices to initial levels after 30 WBC treatments. Changes in the white blood cell system showed transient mobilization of this system under the influence of WBC.

  8. 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...

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

    Science.gov (United States)

    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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Erythropoietin reduces ischemia-reperfusion injury after liver transplantation in rats.

    Science.gov (United States)

    Schmeding, Maximilian; Hunold, Gerhard; Ariyakhagorn, Veravoorn; Rademacher, Sebastian; Boas-Knoop, Sabine; Lippert, Steffen; Neuhaus, Peter; Neumann, Ulf P

    2009-07-01

    Human recombinant Erythropoietin (rHuEpo) has recently been shown to be a potent protector of ischemia- reperfusion injury in warm-liver ischemia. Significant enhancement of hepatic regeneration and survival after large volume partial hepatic resection has also been demonstrated. It was the aim of this study to evaluate the capacities of rHuEpo in the setting of rat liver transplantation. One-hundred-and-twenty Wistar rats were used: 60 recipients received liver transplantation following donor organ treatment (60 donors) with either 1000 IU rHuEpo or saline injection (controls) into portal veins (cold ischemia 18 h, University of Wisconsin (UW) solution). Recipients were allocated to two groups, which either received 1000 IU rHuEpo at reperfusion or an equal amount of saline (control). Animals were sacrificed at defined time-points (2, 4.5, 24, 48 h and 7 days postoperatively) for analysis of liver enzymes, histology [hematoxylin-eosin (HE) staining, periodic acid Schiff staining (PAS)], immunostaining [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Hypoxyprobe] and real-time polymerase chain reaction (RT-PCR) of cytokine mRNA (IL-1, IL-6). Lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) values were significantly reduced among the epo-treated animals 24 and 48 h after liver transplantation (LT). The TUNEL and Hypoxyprobe analyses as well as necrotic index evaluation displayed significant reduction of apoptosis and necrosis in rHuEpo-treated graft livers. Erythropoietin reduces ischemia-reperfusion injury after orthotopic liver transplantation in rats.

  20. 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.

  1. 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

  2. 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

  3. 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。

  4. 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.

  5. Regulated expression of erythropoietin by two human hepatoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, M.A.; Glass, G.A.; Cunningham, J.M.; Bunn, H.F.

    1987-11-01

    The development of a cell culture system that produces erythropoietin (Epo) in a regulated manner has been the focus of much effort. The authors have screened multiple renal and hepatic cell lines for either constitutive or regulated expression of Epo. Only the human hepatoma cell lines, Hep3B and HepG2, made significant amounts of Epo as measured both by radioimmunoassay and in vitro bioassay (as much as 330 milliunits per 10/sup 6/ cells in 24 hr). The constitutive production of Epo increased dramatically as a function of cell density in both cell lines. At cell densities < 3.3 x 10/sup 5/ cells per cm/sup 2/, there was little constitutive release of Epo in the medium. With Hep3B cells grown at low cell densities, a mean 18-fold increase in Epo expression was seen in response to hypoxia and a 6-fold increase was observed in response to incubation in medium containing 50 ..mu..M cobalt(II) chloride. At similar low cell densities, Epo production in HepG2 cells could be enhanced an average of about 3-fold by stimulation with either hypoxia or cobalt(II) chloride. Upon such stimulation, both cell lines demonstrated markedly elevated levels of Epo mRNA. Hence, both Hep3B and HepG2 cell lines provide an excellent in vitro system in which to study the physiological regulation of Epo expression.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. Recombinant Human Erythropoietin in the Treatment of Acute Ischemic Stroke

    NARCIS (Netherlands)

    Ehrenreich, Hannelore; Weissenborn, Karin; Prange, Hilmar; Schneider, Dietmar; Weimar, Christian; Wartenberg, Katja; Schellinger, Peter D.; Bohn, Matthias; Becker, Harald; Wegrzyn, Martin; Jaehnig, Peter; Herrmann, Manfred; Knauth, Michael; Baehr, Mathias; Heide, Wolfgang; Wagner, Armin; Schwab, Stefan; Reichmann, Heinz; Schwendemann, Guenther; Dengler, Reinhard; Kastrup, Andreas; Bartels, Claudia

    2009-01-01

    Background and Purpose-Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ischemic stroke. Although EPO has been considered to be a safe and well-tolerated dru

  11. Detection of DNA-recombinant human epoetin-alfa as a pharmacological ergogenic aid.

    Science.gov (United States)

    Wilber, Randall L

    2002-01-01

    The use of DNA-recombinant human epoetin-alfa (rhEPO) as a pharmacological ergogenic aid for the enhancement of aerobic performance is estimated to be practised by at least 3 to 7% of elite endurance sport athletes. rhEPO is synthesised from Chinese hamster ovary cells, and is nearly identical biochemically and immunologically to endogenous epoetin-alfa (EPO). In a clinical setting, rhEPO is used to stimulate erythrocyte production in patients with end-stage renal disease and anaemia. A limited number of human studies have suggested that rhEPO provides a significant erythropoietic and ergogenic benefit in trained individuals as evidenced by increments in haemoglobin, haematocrit, maximal oxygen uptake (VO2max) and exercise endurance time. The purpose of this review is to summarise the various technologies and methodologies currently available for the detection of illicit use of rhEPO in athletes. The International Olympic Committee (IOC) banned the use of rhEPO as an ergogenic aid in 1990. Since then a number of methods have been proposed as potential techniques for detecting the illegal use of rhEPO. Most of these techniques use indirect markers to detect rhEPO in blood samples. These indirect markers include macrocytic hypochromatic erythrocytes and serum soluble transferrin receptor (sTfr) concentration. Another indirect technique uses a combination of 5 markers of enhanced erythropoiesis (haematocrit, reticulocyte haematocrit, percentage of macrocytic red blood cells, serum EPO, sTfr) to detect rhEPO. The electrophoretic mobility technique provides a direct measurement of urine and serum levels of rhEPO, and is based on the principle that the rhEPO molecule is less negatively charged versus the endogenous EPO molecule. Isoelectric patterning/focusing has emerged recently as a potential method for the direct analysis of rhEPO in urine. Among these various methodologies, the indirect technique that utilises multiple markers of enhanced erythropoiesis appears to

  12. 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.

  13. 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...

  14. 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.

  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. 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.

  2. Erythropoietin treatment enhances muscle mitochondrial capacity in humans

    DEFF Research Database (Denmark)

    Plenge, Ulla; Belhage, Bo; Guadalupe-Grau, Amelia;

    2012-01-01

    Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity...... in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis...... before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler...

  3. Erythropoietin: physiology and pharmacology update.

    Science.gov (United States)

    Fisher, James W

    2003-01-01

    smooth muscle cell proliferation. Recombinant human EPO (rHuEPO) is currently being used to treat patients with anemias associated with chronic renal failure, AIDS patients with anemia due to treatment with zidovudine, nonmyeloid malignancies in patients treated with chemotherapeutic agents, perioperative surgical patients, and autologous blood donation. A novel erythropoiesis-stimulating factor (NESP, darbepoetin) has been synthesized and when compared with rHuEPO, NESP has a higher carbohydrate content (52% vs 40%), a longer plasma half-life, the amino acid sequence differs from that of native human EPO at five positions, and has been reported to maintain hemoglobin levels just as effectively in patients with chronic renal failure as rHuEPO at less frequent dosing. The use of rHuEPO and darbepoetin to enhance athletic performance is officially banned by most sports-governing bodies because the excessive erythrocytosis can lead to increased thrombogenicity and can cause deep vein, coronary, and cerebral thromboses.

  4. 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.

  5. Erythropoietin against cisplatin-induced peripheral neurotoxicity in rats.

    Science.gov (United States)

    Orhan, Bulent; Yalcin, Suayib; Nurlu, Gulay; Zeybek, Dilara; Muftuoglu, Sevda

    2004-01-01

    Cisplatin (CDDP) is a potent anticancer drug, and neurotoxicity is one of its most important dose-limiting toxicities. In this study we investigated the role of recombinant human erythropoietin (rhuEPO) for protection against CDDP-induced neurotoxicity. All experiments were conducted on female Wistar-albino rats. Animals were randomly assigned to three groups. Group A received only CDDP, group B received CDDP plus rhuEPO, and group C received only rhuEPO. Electroneurography (ENG) was done in the beginning and at the end of 7 wk, then the rats were sacrificed and the sciatic nerve was removed for histopathological examination. The mean initial latency was 2.7438 ms in group A, 2.4875 ms in group B, and 2.62 ms in group C. After 7 wk of treatment, the latency was 2.4938, 2.6313, and 2.3900 ms, respectively. The difference in latencies was not statistically significant. The amplitude of compound muscle action potential (CMAP) was 12.8125 mV, 14.3875 mV, and 14.5600 mV before the treatment and 8.4875, 12.8250, and, 13.0800 mV after treatment, respectively. Amplitude of CMAP was significantly greater in rhuEPO-treated groups (groups B and C) compared to cisplatin only Group A. The mean area of CMAP was 12.2625, 12.3500, and, 12.2800 mV s before the treatment and 5.7125, 10.6463, and 9.1600 mV s after the treatment, respectively. The area of CMAP was significantly larger in rhuEPO-treated groups. In histopathological studies thick, thin, and total number of nerve fibers were 4053, 5050, and 9103, in group A, 5100, 8231, and 13331, in group B, and 5264, 6010, and 11274, in group C respectively. In the microscopic examination active myelinization process was observed in rhuEPO-treated groups. We concluded that at the given dose and schedule CDDP-induced motor neuropathy and rhuEPO prevented this neuropathy by sparing the number of normal nerve fibers and by protecting the amplitude and area of CMAP. We concluded that rhuEPO may also play a role in active myelinization and

  6. 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.

  7. Erythropoietin, Iron Depletion and Relative Thrombocytosis: A Possible Explanation for Hemoglobin-Survival Paradox in Chronic Kidney Disease

    Science.gov (United States)

    Streja, Elani; Kovesdy, Csaba P; Greenland, Sander; Kopple, Joel D.; McAllister, Charles J; Nissenson, Allen R; Kalantar-Zadeh, Kamyar

    2017-01-01

    Background High doses of human recombinant erythropoietin (rHuEPO) to achieve hemoglobin levels above 13 g/dL in chronic kidney disease appear associated with elevated mortality. Study Design We conducted logistic regression and survival analyses in a retrospective cohort of maintenance hemodialysis (MHD) patients to examine the hypothesis that the induced iron depletion with resultant relative thrombocytosis may be a possible contributor to the link between the high rHuEPO dose associated hemoglobin ≥13 g/dL and mortality. Setting & Participants The national database of a large dialysis organization (DaVita) with 40,787 MHD patients during July to December 2001 and their survival up to July 2004 were examined. Predictors Hemoglobin level, platelet count and administered rHuEPO dose during each calendar quarter. Outcomes & other Measurements Case-mix adjusted 3-year all-cause mortality; and measures of iron stores including serum ferritin and iron saturation ratio (ISAT). Results Higher platelet count was associated with lower iron stores and higher prescribed rHuEPO dose. Compared to hemoglobin of 12-13 g/dL, hemoglobin ≥13 g/dL was associated with increased mortality in the presence of relative thrombocytosis, i.e., platelet count ≥300,000/μl, (case-mix adjusted death-rate ratio [RR]: 1.21, 95% confidence limits [CL]: 1.02–1.44, P=0.03) as opposed to the absence of relative thrombocytosis (RR: 1.04, 95% CL: 0.98–1.08, P=0.13). Prescribed rHuEPO dose >20,000 units/week was associated with higher likelihood of iron depletion (ISATthrombocytosis (case-mix adjusted odds ratio: 2.53 [CL: 2.37–2.69] and 1.36 [CL: 1.30–1.42], respectively, pthrombocytosis might contribute to increased mortality when administering high rHuEPO doses to achieve hemoglobin ≥13 g/dL in MHD patients. Randomized trials are needed to test these observational associations. PMID:18760517

  8. 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、

  9. 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.

  10. 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

  11. Expression of GPI anchored human recombinant erythropoietin in CHO cells is devoid of glycosylation heterogeneity.

    Science.gov (United States)

    Singh, Pankaj Kumar; Devasahayam, Mercy; Devi, Sobita

    2015-04-01

    Erythropoietin is a glycohormone involved in the regulation of the blood cell levels. It is a 166 amino acid protein having 3 N-glycosylation and one O-linked glycosylation sites, and is used to treat anaemia related illness. Though human recombinant erythropoietin (rEPO) is produced in CHO cells, the loss in quality control is 80% due to incomplete glycosylation of the rEPO with low levels of fully glycosylated active rEPO. Here, we describe the expression from CHO cells of fully glycosylated human rEPO when expressed as a GPI anchored molecule (rEPO-g). The results demonstrated the production of a homogenous completely glycosylated human rEPO-g as a 42 kD band without any low molecular weight glycoform variants as shown by affinity chromatography followed by SDS-PAGE and anti-human EPO specific western blot. The western blot using specific monoclonal antibody is the available biochemical technique to prove the presence of homogeneity in the expressed recombinant protein. The GPI anchor can be removed during the purification process to yield a therapeutically relevant recombinant erythropoietin molecule cells with a higher in vivo biological activity due to its high molecular weight of 40 kD. This is possibly the first report on the production of a homogenous and completely glycosylated human rEPO from CHO cells for efficient therapy.

  12. Brain and skin do not contribute to the systemic rise in erythropoietin during acute hypoxia in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Nordsborg, Nikolai; Taudorf, Sarah;

    2012-01-01

    Erythropoietin (EPO) preserves arterial oxygen content by controlling red blood cell and plasma volumes. Synthesis of EPO was long thought to relate inversely to renal oxygenation, but in knockout mice, brain and skin have been identified as essential for the acute hypoxic EPO response. Whether...... these findings apply to humans remains unknown. We exposed healthy young subjects to hypoxia (equivalent to 3800 m) and measured EPO in arterial and jugular venous plasma and in cerebrospinal fluid. To examine the role of the skin for EPO production during hypoxia, subjects were exposed to 8 h of hypobaric...... hypoxia with or without breathing oxygen-enriched air to ensure systemic normoxemia. With 9 h of hypoxia, arterial EPO increased (from 6.0±2.2 to 22.0±6.0 mU/ml, n=11, P...

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution.

    Directory of Open Access Journals (Sweden)

    Niels Jacob Aachmann-Andersen

    Full Text Available The membrane-assisted isoform immunoassay (MAIIA quantitates erythropoietin (EPO isoforms as percentages of migrated isoforms (PMI. We evaluated the effect of recombinant human EPO (rhEPO on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13; high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13; or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3 % (mean (SD. High-dose Epoetin beta decreased PMI on days 4 and 11 to 31.0 (4.2% (p<0.00001 and 45.2 (7.3% (p<0.00001. Low-dose Epoetin beta decreased PMI on days 4 and 11 to 46.0 (12.8% (p<0.00001 and 46.1 (10.4% (p<0.00001. In both rhEPO groups, PMI on day 25 was still decreased (high-dose Epoetin beta: 72.9 (19.4% (p=0.029; low-dose Epoetin beta: 73.1 (17.8% (p=0.039. In conclusion, Epoetin beta leaves a footprint in the plasma-EPO isoform pattern. MAIIA can detect changes in EPO isoform distribution up til at least three weeks after administration of Epoetin beta even though the total EPO concentration has returned to normal.

  18. Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution.

    Science.gov (United States)

    Aachmann-Andersen, Niels Jacob; Just Christensen, Søren; Lisbjerg, Kristian; Oturai, Peter; Meinild-Lundby, Anne-Kristine; Holstein-Rathlou, Niels-Henrik; Lundby, Carsten; Vidiendal Olsen, Niels

    2014-01-01

    The membrane-assisted isoform immunoassay (MAIIA) quantitates erythropoietin (EPO) isoforms as percentages of migrated isoforms (PMI). We evaluated the effect of recombinant human EPO (rhEPO) on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13); high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13); or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3) % (mean (SD)). High-dose Epoetin beta decreased PMI on days 4 and 11 to 31.0 (4.2)% (p<0.00001) and 45.2 (7.3)% (p<0.00001). Low-dose Epoetin beta decreased PMI on days 4 and 11 to 46.0 (12.8)% (p<0.00001) and 46.1 (10.4)% (p<0.00001). In both rhEPO groups, PMI on day 25 was still decreased (high-dose Epoetin beta: 72.9 (19.4)% (p=0.029); low-dose Epoetin beta: 73.1 (17.8)% (p=0.039)). In conclusion, Epoetin beta leaves a footprint in the plasma-EPO isoform pattern. MAIIA can detect changes in EPO isoform distribution up til at least three weeks after administration of Epoetin beta even though the total EPO concentration has returned to normal.

  19. 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.

  20. EPOS--The European E-Portfolio of Languages

    Science.gov (United States)

    Kühn, Bärbel

    2016-01-01

    Democratic principles and human rights, the core values of the Council of Europe, informed the development of the "Common European Framework of Reference for Languages" (CEFR; Council of Europe 2001. "Common European framework of reference for languages: Learning, teaching, assessment." Cambridge: Cambridge University Press.…

  1. EPOS--The European E-Portfolio of Languages

    Science.gov (United States)

    Kühn, Bärbel

    2016-01-01

    Democratic principles and human rights, the core values of the Council of Europe, informed the development of the "Common European Framework of Reference for Languages" (CEFR; Council of Europe 2001. "Common European framework of reference for languages: Learning, teaching, assessment." Cambridge: Cambridge University Press.…

  2. 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...

  3. 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.

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

    Science.gov (United States)

    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.

  5. 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...

  6. 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.

  7. Factors Affecting Successful use of Erythropoietin in the Treatment of Anemia in Patients on Hemodialysis: Experience in Hajjah Region, Yemen

    Directory of Open Access Journals (Sweden)

    AL-Rohani Muhamed

    2001-01-01

    Full Text Available The use of recombinant human erythropoietin (rHuEpo became an essential part of the treatment of anemia in patients with end stage renal failure (ESRF. Our experience at the Hajjah region, Yemen, confirms that the use of rHuEpo significantly increases the level of hemoglobin (HB and hematocrit (Hct, improves work tolerance and overall quality of life of patients on hemodialysis. The observable improvement occurred in 87.5% of patients. The most prominent factors that caused deterioration in the increment of HB and Hct were infection with malaria and chronic infection. Failure of patients′ compliance, largely due to lack of education, was another important factor effecting the results. Many of our patients did not understand the importance of diet and drug regime. It is very important to spend more time on educating such patients.

  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. 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.

  12. 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.

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

    Science.gov (United States)

    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.

  14. Influence de l'érythropoïétine recombinante humaine sur les fonctions cardiovasculaire et rénale chez le rat présentant une dysfonction endothéliale : effets des interactions avec l'exercice chronique

    OpenAIRE

    Meziri, Fayçal

    2011-01-01

    The chronic administration of rHuEPO can engender side effects. An increase of the hematocritinduced by rHuEPO, by increasing the erythrocytosis, the blood viscosity and the shear stress onvascular surface, can be responsible of arterial high blood pressure and arterial thrombosis. Thepresence of a normal endothelial function and nitric oxide (NO) can counter the noxious effectsof rHuEPO. On these bases, we studied the cardiovascular effects of a chronic administration ofrHuEPO in various fra...

  15. 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

  16. 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

    The mission of EGI-Engage project [1] is to accelerate the implementation of the Open Science Commons vision, where researchers from all disciplines have easy and open access to the innovative digital services, data, knowledge and expertise they need for collaborative and excellent research. The Open Science Commons is grounded on three pillars: the e-Infrastructure Commons, an ecosystem of services that constitute the foundation layer of distributed infrastructures; the Open Data Commons, where observations, results and applications are increasingly available for scientific research and for anyone to use and reuse; and the Knowledge Commons, in which communities have shared ownership of knowledge, participate in the co-development of software and are technically supported to exploit state-of-the-art digital services. To develop the Knowledge Commons, EGI-Engage is supporting the work of a set of community-specific Competence Centres, with participants from user communities (scientific institutes), National Grid Initiatives (NGIs), technology and service providers. Competence Centres collect and analyse requirements, integrate community-specific applications into state-of-the-art services, foster interoperability across e-Infrastructures, and evolve services through a user-centric development model. One of these Competence Centres is focussed on the European Plate Observing System (EPOS) [2] as representative of the solid earth science communities. EPOS is a pan-European long-term plan to integrate data, software and services from the distributed (and already existing) Research Infrastructures all over Europe, in the domain of the 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

  17. 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.

  18. Erythropoietin treatment enhances mitochondrial function in human skeletal muscle

    Directory of Open Access Journals (Sweden)

    Ulla ePlenge

    2012-03-01

    Full Text Available Abstract Erythropoietin (Epo treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over eight weeks with oral iron (100 mg supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92±5 to 113±7 pmol.sec-1.mg-1 and ETS (107±4 to 143±14 pmol.sec-1.mg-1, P<0.05, demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

  19. Erythropoietin regulations in humans under different environmental and experimental conditions.

    Science.gov (United States)

    Gunga, H-C; Kirsch, K A; Roecker, L; Kohlberg, E; Tiedemann, J; Steinach, M; Schobersberger, W

    2007-09-30

    In the adult human, the kidney is the main organ for the production and release of erythropoietin (EPO). EPO is stimulating erythropoiesis by increasing the proliferation, differentiation and maturation of the erythroid precursors. In the last decades, enormous efforts were made in the purification, molecular encoding and description of the EPO gene. This led to an incredible increase in the understanding of the EPO-feedback-regulation loop at a molecular level, especially the oxygen-dependent EPO gene expression, a key function in the regulation loop. However, studies in humans at a systemic level are still very scanty. Therefore, it is the purpose of the present review to report on the main recent investigations on EPO production and release in humans under different environmental and experimental conditions, including: (i) studies on EPO circadian, monthly and even annual variations, (ii) studies in connection with short-, medium- and long-term exercise at sea-level which will be followed (iii) by studies performed at moderate and high altitude.

  20. Hematopoietic response to lineage-non-specific (rrIL-3) and lineage-specific (rhG-CSF, rhEpo, rhTpo) cytokine administration in SIV-infected rhesus macaques is related to stage of infection.

    Science.gov (United States)

    Bucur, S Z; Gillespie, T W; Lee, M E; Adams, J W; Bray, R A; Villinger, F; Ansari, A A; Hillyer, C D

    2000-04-01

    The present study reports the hematopoietic response to the exogenous administration of recombinant rhesus interleukin-3 (rrIL-3) or a combination of recombinant human granulocyte colony-stimulating factor (rhG-CSF)/erythropoietin (Epo)/thrombopoietin (Tpo) at two different stages of SIV infection: Early-stage (n = 6, CD4 + > 1000/microl and mild splenomegaly) and late-stage (n = 6, CD4 + < 500/microl, progressive hepatosplenomegaly and/or weight loss). SIV-infected animals exhibited significantly impaired bone marrow (BM) and peripheral blood (PB) responses to both rrIL-3 and rhG-CSF/Epo/Tpo administration, as compared to historic controls. In addition, compared to early-stage SIV-infected animals, late-stage SIV-infected macaques demonstrated a more marked dysfunction, as assessed by PB and BM CD34 + content and clonogenic progenitors (colony-forming unit). Neither rrIL-3 nor rhG-CSF/Epo/Tpo administration during either early-stage or late-stage SIV infection increased the viral load, as assessed by bDNA assay. These data suggest that hematopoietic reserve and the response to various cytokines is decreased even in early-stage SIV infection, with the hematopoietic dysfunction progressing in parallel to SIV infection.

  1. Successful treatment of severe anemia using erythropoietin in a Jehovah Witness with non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Alexandra Agapidou

    2014-12-01

    Full Text Available Blood transfusion many times works in a life-saving way when a patient is facing a critical situation. However, some patients, such as Jehovah’s Witnesses, may refuse their administration because it opposes to their religion beliefs. Thus, clinicians are forced to respect patients’ preferences and seek other treatments in order to overcome the obstacle of the transfusion. In 1989, recombinant human erythropoietin (rHuEPO was approved by the United States Food and Drug Administration (FDA for the treatment of anemia associated with chronic renal failure. This is an amino acid glycol-protein that stimulates red blood cell production in the same manner as endogenous erythropoietin. Other treatment indications approved by the FDA include anemia due to chronic kidney disease, anemia secondary to zidovudine therapy in patients with human immunodeficiency virus infection, and anemia secondary to cancer chemotherapy. The drug also has been used for many off-label indications. Many Jehovah’s Witnesses have accepted rHuEPO as a treatment option to maintain and enhance erythropoiesis. This paper reports the case of a 57-year-old Jehovah’s Witness man, who was diagnosed with severe anemia due to aggressive non Hodgkin lymphoma and refused transfusion of blood; thanks to the treatment with rHuEPO he has managed to complete chemotherapy and has survived a life threatening situation.

  2. Predialysis versus postdialysis hematocrit evaluation during erythropoietin therapy.

    Science.gov (United States)

    Movilli, Ezio; Pertica, Nicoletta; Camerini, Corrado; Cancarini, Giovanni C; Brunori, Giuliano; Scolari, Francesco; Maiorca, Rosario

    2002-04-01

    American guidelines for the management of renal anemia by recombinant human erythropoietin (rHuEPO) recommend collecting a predialysis blood sample to evaluate hemoglobin (Hb) and hematocrit (Hct) levels in hemodialysis patients. Although a predialysis blood sample is appropriate for evaluating when to start rHuEPO treatment, the same sample would not be appropriate for evaluating the target Hb/Hct to be maintained, particularly when normal or near-normal values are pursued. We measured the degree of intradialytic and extradialytic variation of Hb, Hct, and body weight in 68 stable hemodialysis patients on maintenance subcutaneous rHuEPO treatment. Hb and Hct concentrations were determined before and after dialysis. In 16 patients, Hb and Hct concentrations also were assessed 24 hours after the end of dialysis. Predialysis versus postdialysis Hb and Hct concentrations for all patients were 10.5 +/- 1.3 g/dL versus 11.5 +/- 1.3 g/dL (P < 0.0001) and 32 +/- 4% versus 35 +/- 4% (P < 0.0001). The intradialytic percent variation (%Delta) of Hct and body weight were 10 +/- 6% and -6.3 +/- 3.5%. There was a close inverse correlation between %Delta of Hct and Hb and %Delta of body weight (P < 0.0001). In patients with body weight losses 2.5 kg or more per session, the mean %Delta of Hct was 12 +/- 7%. In the 16 patients studied 24 hours after the end of the dialysis session, Hct and Hb values remained significantly higher compared with the predialysis levels (P < 0.001), suggesting a slow reequilibration of the intravascular volume in the first 24 hours after hemodialysis. For these reasons, predialysis samples for monitoring the target Hb and Hct levels in patients treated by rHuEPO should be considered with caution.

  3. Transplantation of genetically engineered cardiac fibroblasts producing recombinant human erythropoietin to repair the infarcted myocardium

    Directory of Open Access Journals (Sweden)

    Ruvinov Emil

    2008-11-01

    Full Text Available Abstract Background Erythropoietin possesses cellular protection properties. The aim of the present study was to test the hypothesis that in situ expression of recombinant human erythropoietin (rhEPO would improve tissue repair in rat after myocardial infarction (MI. Methods and results RhEPO-producing cardiac fibroblasts were generated ex vivo by transduction with retroviral vector. The anti-apoptotic effect of rhEPO-producing fibroblasts was evaluated by co-culture with rat neonatal cardiomyocytes exposed to H2O2-induced oxidative stress. Annexin V/PI assay and DAPI staining showed that compared with control, rhEPO forced expression markedly attenuated apoptosis and improved survival of cultured cardiomyocytes. To test the effect of rhEPO on the infarcted myocardium, Sprague-Dawley rats were subjected to permanent coronary artery occlusion, and rhEPO-producing fibroblasts, non-transduced fibroblasts, or saline, were injected into the scar tissue seven days after infarction. One month later, immunostaining identified rhEPO expression in the implanted engineered cells but not in controls. Compared with non-transduced fibroblasts or saline injection, implanted rhEPO-producing fibroblasts promoted vascularization in the scar, and prevented cell apoptosis. By two-dimensional echocardiography and postmortem morphometry, transplanted EPO-engineered fibroblasts did not prevent left ventricular (LV dysfunction and adverse LV remodeling 5 and 9 weeks after MI. Conclusion In situ expression of rhEPO enhances vascularization and reduces cell apoptosis in the infarcted myocardium. However, local EPO therapy is insufficient for functional improvement after MI in rat.

  4. 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...

  5. Bloodless surgery in a patient with thalassemia minor. Usefulness of erythropoietin, preoperative blood donation and intraoperative blood salvage.

    Science.gov (United States)

    Pérez Ferrer, A; Ferrazza, V; Gredilla, E; de Vicente, J; de la Rua, A; Larrea, A

    2007-05-01

    A patient with thalassemia minor and idiopathic scoliosis was scheduled for posterior vertebral arthrodesis. The diagnosis of thalassemia minor was made during the preoperative assessment. Preoperative blood cell count displayed the following data: red blood count 5.4 x 106/microL, haemoglobin 11.6 g/dL and hematocrit 36.9%. As corrective surgery for scoliosis is associated with major blood loss, the patient was scheduled for preoperative treatment with human recombinant erythropoietin (rHuEPO), autologous blood donation, intraoperative blood cell salvage and administration of tranexamic acid. The use of rHuEPO was intended to increase hemoglobin (12.1 g/dL) levels at the moment of surgery following the donation of 2 autologous blood units. 1000 mL of salvaged blood were processed. The output line of the blood cell salvage machine did not show any sign of increased red cell haemolysis. The postoperative course was uneventful and the patient was discharged from the postoperative intensive care unit on day 7 after surgery with no allogenic blood transfusion. No references detailing the use of rHuEPO and autologous blood donation preoperatively in patients with thalassemia minor and only one case report discussed the utility of intraoperative blood cell salvage in a patient with thalassemia intermedia. Although further experience is needed, this case report suggests that even for patients with thalassemia minor, methods focused on allogenic blood salvage can be used safely.

  6. Fed-batch methanol feeding strategy for recombinant protein production by Pichia pastoris in the presence of co-substrate sorbitol.

    Science.gov (United States)

    Celik, Eda; Calik, Pinar; Oliver, Stephen G

    2009-09-01

    Batch-wise sorbitol addition as a co-substrate at the induction phase of methanol fed-batch fermentation by Pichia pastoris (Mut(+)) was proposed as a beneficial recombinant protein production strategy and the metabolic responses to methanol feeding rate in the presence of sorbitol was systematically investigated. Adding sorbitol batch-wise to the medium provided the following advantages over growth on methanol alone: (a) eliminating the long lag-phase for the cells and reaching 'high cell density production' at t = 24 h of the process (C(X) = 70 g CDW/l); (b) achieving 1.8-fold higher recombinant human erythropoietin (rHuEPO) (at t = 18 h); (c) reducing specific protease production 1.2-fold; (d) eliminating the lactic acid build-up period; (e) lowering the oxygen uptake rate two-fold; and (f) obtaining 1.4-fold higher overall yield coefficients. The maximum specific alcohol oxidase activity was not affected in the presence of sorbitol, and it was observed that sorbitol and methanol were utilized simultaneously. Thus, in the presence of sorbitol, 130 mg/l rHuEPO was produced at t = 24 h, compared to 80 mg/l rHuEPO (t = 24 h) on methanol alone. This work demonstrates not only the ease and efficiency of incorporating sorbitol to fermentations by Mut(+) strains of P. pastoris for the production of any bio-product, but also provides new insights into the metabolism of the methylotrophic yeast P. pastoris.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Recombinant Human Erythropoietin for Treating Treatment-Resistant Depression

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Vinberg, Maj; Christensen, Ellen M;

    2014-01-01

    Pharmacological treatments for depression have insufficient efficacy in 30-40% of patients and fail to reverse cognitive deficits. Erythropoietin (EPO) has neurotrophic actions and aids neurocognitive function. The aim of this exploratory study was to determine whether recombinant human EPO...... improves mood and memory in treatment-resistant depression. Forty treatment-resistant depressed unipolar patients with Hamilton Depression Rating Scale-17 (HDRS-17) score ≥ 17 were randomized to eight weekly EPO (Eprex; 40,000 IU) or saline infusions in a double-blind, placebo-controlled, parallel...

  15. 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.

  16. 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...

  17. 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...

  18. 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.

  19. Effect of Erythropoietin Carried by Stearic Acid-Grafted Chitosan Micelle on Epilepsy Seizure in Mice%促红细胞生成素胶束给药系统对小鼠癫痫的影响

    Institute of Scientific and Technical Information of China (English)

    曹高扬; 胡薇薇; 俞栋栋; 于亚赛; 谢贻珽; 袁弘; 陆源; 厉旭云; 戴海斌; 陈忠

    2013-01-01

    探讨载促红细胞生成素的壳聚糖-硬脂酸(CS-SA)胶束给药系统对戊四唑诱导的小鼠癫痫的影响.小鼠给予载人重组促红细胞生成素的壳聚糖-硬脂酸(r-HuEPO-CS-SA)胶束制剂和r-HuEPO普通制剂24 h后,观察对戊四唑(PTZ)诱导的急性癫痫模型中发作潜伏时间、发作级别、大发作持续时间以及次数的影响.此外,小鼠隔天注射r-HuEPO-CS-SA胶束制剂和普通制剂,观察对PTZ诱导的癫痫形成过程的影响.结果:在PTZ急性模型中,给予r-HuEPO普通制剂仅4 000 IU/kg剂量组在降低发作级别、减少大发作持续时间和减少发作次数方面有显著差异(P<0.05).而给予r-HuEPO-CSCS-SA胶束制剂2 000 IU/kg就可显著增加潜伏时间,降低大发作持续时间(P<0.05).并且给予r-HuEPO-CS-SA胶束制剂4 000 IU/kg、8 000 IU/kg,在延长潜伏时间、降低发作级别、减少大发作持续时间和减少发作次数方面均有显著差异(P<0.05).但在慢性癫痫点燃过程中,给予r-HuEPO-CS-SA胶束制剂和普通制剂均不能缓解癫痫形成的进程.本研究表明r-HuEPO-CS-SA胶束制剂可以显著缓解PTZ诱导的急性癫痫发作,作用较r-HuEPO普通制剂更明显,但对于PTZ诱导的癫痫形成过程无明显作用,提示载促红细胞生成素的CS-SA胶束给药系统有望更好的用于防治癫痫发作.%To study the effect of erythropoietin carried by stearic acid-grafted chitosan ( CS-SA) micelle on pentylenetetrazol (PTZ)-induced seizure in mice, in PTZ induced acute seizure model, the seizure latency, stage, seizure duration, and number of convulsive episodes were recorded at 24 h after administration of r-HuEPO ( recombinant human erythropoietin) carried by CS-SA micelle or r-HuEPO common formulation. The development of PTZ-induced kindling was examined after administration of r-HuEPO carried by CS-SA micelle or r-HuEPO common formulation every other day. The results showed that the administration of r-HuEPO

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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...

  5. 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.

  6. 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.

  7. Protective effects of erythropoietin pretreatment on myocardium with hypoxia/reoxygenation injury in rats

    Institute of Scientific and Technical Information of China (English)

    QIN Chuan; XIAO Ying-bin; ZHONG Qan-jin; CHEN Lin; WANG Xue-feng

    2004-01-01

    To establish the rat model with myocardial hypoxia/reoxygenation (H/R) injury, and investigatethe protective effect of EPO pretreatment on the myocardium. Methods: Sixty male adult Wistar rats were randomly divided in-to 3 groups: control group, H/R group, and EPO group, 20 in each group. The rats in EPO group accepted injection of 5 000U/kg recombinant human erythropoietin (RHuEPO) through vein, and the other rats accepted the injection of the same volumeof saline. Twenty-four hours after the injection, rats in the EPO and H/R groups were put into the hypoxia environment for 12h and then returned to the normoxic environment for 2 h, and then the samples of blood and myocardium were collected. Serummyocardial enzyme activity, apoptosis, ultrastructure, myocardial MDA contents, EPO receptor (EPOR) expression in cardiacmyocytes and cardiac functions were tested. Results: EPOR expression was positive in cardiac myocytes of adult rat according to the result of immunohistochemitry assaying. Compared to those in H/R group, rats in EPO group presented lighter injury ofmyocardial ultrastructure, the reduction of serum myocardial enzyme activity, inhibition of apoptosis, the better recovery ofcardiac functions, and the Ness production of oxygen-derived free radicals. Conclusion: Adult rat cardiac myocytes could ex-press EPOR, and EPO pretreatment produced protective effects on myocardium with H/R injury.

  8. 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.

  9. 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.

  10. 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

  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. 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

  14. Effect of early correction of anemia with erythropoietin on left ventricular mass in predialysis patients:a multi-center trial

    Institute of Scientific and Technical Information of China (English)

    Fanfan HOU; Weihua PENG; Jianping WU; Zhongmin YANG; Jianping JIANG; Lizhen GAO; Yangbin PAN; Niansheng YANG; Wei CHEN; Guiyang SHU; Youming CHEN; Jian CHEN

    2005-01-01

    Objective To assess the effects of early correction of anemia with recombinant human erythropoietin (rHuEPO) on the development and progression of left ventricular hypertrophy (LVH) in patients with mild-to-moderate chronic renal insufficiency (CRI) who are not on hemodialysis. Methods A total of 158 patients with serum creatinine from 147μmol/L to 400μmol/L were nrolled in this prospective, multicenter study. Eighty-six patients with hemoglobin (Hb)<110g/L received rHuEPO treatment with a target Hb of ≥110g/L (Group A). Forty patients with comparable Hb concentration (<110g/L) but did not receive rHuEPO (Group B) and 32 patients with Hb≥110g/L and without rHuEPO treatment (Group C) were served as controls. Left ventricular mass index (LVMI) was evaluated by echocardiography at baseline and every 3 months for 2 years. Results There was no difference in age, gender, etiology of renal failure, blood pressure and cardiovascular risk factors among the 3 groups. At baseline, the prevalence of LVH was 72.1% in group A,72.5% in group B and 59.4% in group C. LVMI was inversely correlated with Hb levels (r=0.70, P<0.01). During the 2-year period, the mean LVMI decreased from 142.6±25.7g/m2 to 132.4±18.5 g/m2 in group A, while increased significantly in both group B and group C. The mean Hb concentration increased from 93.8±14.6g/L to 111.2±10.3g/L (P<0.05) in group A, but tended to decrease in group B and group C. There was no significant change of the mean blood pressure, number of anti-hypertensive drugs and serum creatinine concentrations in all 3 groups. However, patients' serum creatinine doubled more often in group B and group C than in group A.Conclusions LVH was common in predialysis CRI patients and was associated with the severity of anemia. Early intervention with rHuEPO may reverse LVH in these patients.

  15. 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.

  16. 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.

  17. 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.

  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. Effects of erythropoietin and its receptor on nervous system

    Institute of Scientific and Technical Information of China (English)

    Ping Wang; Wei Zhou

    2006-01-01

    OBJECTIVE: To investigate the effects of erythropoietin (EPO) and its receptor (EPOR) on nervous system, and its possible mechanism.DATA SOURCES: By inputting the key words "erythropoietin ,nervous system", we performed a search of Medline for English articles, which were published during September 1996 to August 2006, about EPO and EPOR in nervous system.STUDY SELECTION: The materials were selected firstly, literatures were chosen for treatment group and control group and those obviously non-randomized studies were excluded. The full texts of the left literatures were searched. Inclusive criteria: ① Randomized controlled study. ②Experimental or clinical studies (parallel control group included). ③Treatment group was recombinant human erythropoietin(rHuEPO)-treated group. Exclusive criteria: repetitive study.DATA EXTRACTION: A number of 380 randomized or non-randomized articles about the effect of EPO on nervous system were collected, and 49 experiments or clinical trials met the inclusive criteria. Among 331 exclusive articles, 237 were non-randomized or repetitive studies and 94 were review articles. DATA SYNTHESIS: Forty-nine experiments or clinical trials confirmed that EPO and EPOR were expressed in the central nervous system (CNS) and peripheral nervous system(PNS) of gnawer, primate and human being; rHuEPO had obvious neuroprotective effects on brain hypoxia, brain ischemia, experimental intracranial hemorrhage, brain trauma, experimental autoimmune encephalomyelitis, human immunodeficiency virus (HIV)-related sensory neuropathy, distal axonopathy, experimental diabetic neuropathy and acute spinal injury models. Its mechanism maybe involve anti-excitatory toxicity, preventing the production of nitric oxide (NO), lessening inflammatory reaction, resisting apoptosis, maintaining vascular integrity, promoting angiogenesis, promoting the proliferation and differentiation of neural stem cells and progenitor cells and so on. Exogenous EPO could be

  1. Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria

    DEFF Research Database (Denmark)

    Wiese, Lothar; Hempel, Casper; Penkowa, Milena;

    2008-01-01

    with recombinant human Epo (rhEpo; 50-5000 U/kg/OD, i.p.) at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labelling), as a marker of apoptosis. Gene...... expression in brain tissue was measured by real time PCR. RESULTS: Treatment with rhEpo increased survival in mice with CM in a dose- and time-dependent manner and reduced apoptotic cell death of neurons as well as the expression of pro-inflammatory cytokines in the brain. This neuroprotective effect...

  2. 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.

  3. 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

  4. Role of recombinant human erythropoietin loading chitosan-tripolyphosphate nanoparticles in busulfan-induced genotoxicity: Analysis of DNA fragmentation via comet assay in cultured HepG2 cells.

    Science.gov (United States)

    Ghassemi-Barghi, Nasrin; Varshosaz, Jaleh; Etebari, Mahmoud; Jafarian Dehkordi, Abbas

    2016-10-01

    Busulfan is one of the most effective chemotherapeutic agents used for the treatment of chronic myeloid leukemia. Busulfan is involved in secondary malignancy due to its genotoxic potential in normal tissues. As an alkylating agent busulfan can cause DNA damage by cross-linking DNAs and DNA and proteins, induces senescence in normal cells via transient depletion of intracellular glutathione (GSH) and subsequently by a continuous increase in reactive oxygen species (ROS) production. Erythropoietin, a glycoprotein widely used against drug induced anemia in cancerous patients and regulates hematopoiesis, has been shown to exert an important cyto-protective effect in many tissues. Recombinant human erythropoietin has been demonstrated to directly limit cell injury and ROS generation during oxidative stress. Furthermore, rhEPO decreased levels of pro-apoptotic factor (Bax) and also increased expression of the anti-apoptotic factor Bcl2. According to EPO's short half-life and requirements for the frequently administration, finding the new strategies to attenuate its side effects is important. The aim of this study was to explore whether rhEPO loading chitosan-tripolyphosphate nanoparticles protects against busulfan-induced genotoxicity in HepG2 cells. For this purpose cells were incubated with busulfan alone, regular rhEPO alone and regular rhEPO and CS-TPP-EPO nanoparticles along with busulfan in pre and co-treatment condition. Our results showed that busulfan induced a noticeable genotoxic effects in HepG2 cells (pDNA damage via blocking ROS generation, and enhancement intracellular glutathione levels. CS-TPP-EPO nanoparticles were more effective than regular rhEPO in both pre and co-treatment conditions. In conclusion, our results show that administration of rhEPO and CS-TPP-EPO nanoparticles especially in the pre-treatment conditions, significantly decreased the level of DNA damage induced by busulfan, measured with the comet assay, in HepG2 cells compared to the

  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. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Human mesenchymal stromal cells could deliver erythropoietin and migrate to the basal layer of hair shaft when subcutaneously implanted in a murine model.

    Science.gov (United States)

    Mok, P L; Cheong, S K; Leong, C F; Chua, K H; Ainoon, O

    2012-08-01

    Mesenchymal stromal cells (MSC) are an attractive cell-targeting vehicle for gene delivery. MIDGE (an acronym for Minimalistic, Immunologically Defined Gene Expression) construct is relatively safer than the viral or plasmid expression system as the detrimental eukaryotic and prokaryotic gene and sequences have been eliminated. The objective of this study was to test the ability of the human MSC (hMSC) to deliver the erythropoietin (EPO) gene in a nude mice model following nucleofection using a MIDGE construct. hMSC nucleofected with MIDGE encoding the EPO gene was injected subcutaneously in Matrigel at the dorsal flank of nude mice. Subcutaneous implantation of nucleofected hMSC resulted in increased hemoglobin level with presence of human EPO in the peripheral blood of the injected nude mice in the first two weeks post-implantation compared with the control groups. The basal layer of the hair shaft in the dermal layer was found to be significantly positive for immunohistochemical staining of a human EPO antibody. However, only a few basal layers of the hair shaft were found to be positively stained for CD105. In conclusion, hMSC harboring MIDGE-EPO could deliver and transiently express the EPO gene in the nude mice model. These cells could be localized to the hair follicle and secreted EPO protein might have possible role in hair regeneration.

  14. Erythropoietin has an anti-myeloma effect - a hypothesis based on a clinical observation supported by animal studies.

    Science.gov (United States)

    Mittelman, Moshe; Zeidman, Aliza; Kanter, Pazit; Katz, Odelia; Oster, Howard; Rund, Debbora; Neumann, Drorit

    2004-03-01

    Recombinant human erythropoietin (rHuEpo) was introduced into clinical practice more than a decade ago, and has been found to be effective in the treatment of several types of anemia, including anemia of end-stage renal failure and cancer-related anemia. No study has suggested that Epo might have an effect on the biology of the disease, nor any survival advantage to cancer patients treated with Epo for anemia has been reported. Here we report six patients with advanced multiple myeloma (MM) with very poor prognostic features, whose expected survival was cells. We then presented evidence that the mechanism is a new immune-mediated phenomenon, via activation of CD8+ T cells. Furthermore, evidence from the literature supports the antineoplastic effect of Epo. Epo might be used as an adjunct immune treatment in various malignant diseases, in addition to the current regimens and chemotherapeutic protocols. Future trials should determine the role of Epo in myeloma and cancer treatment, besides clarifying concerns about the presence of Epo receptors on some tumor cells.

  15. 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.

  16. 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.

  17. 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!

  18. 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.

  19. 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.

  20. 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)?

  1. Amplified voltammetric detection of glycoproteins using 4-mercaptophenylboronic acid/biotin-modified multifunctional gold nanoparticles as labels

    Directory of Open Access Journals (Sweden)

    Liu L

    2014-05-01

    Full Text Available Lin Liu,1,2 Yun Xing,1 Hui Zhang,1 Ruili Liu,1 Huijing Liu,1 Ning Xia1,21College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang, Henan, People’s Republic of China; 2College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, People’s Republic of ChinaAbstract: Ultrasensitive detection of protein biomarkers is essential for early diagnosis and therapy of many diseases. Glycoproteins, differing from other types of proteins, contain carbohydrate moieties in the oligosaccharide chains. Boronic acid can form boronate ester covalent bonds with diol-containing species. Herein, we present a sensitive and cost-effective electrochemical method for glycoprotein detection using 4-mercaptophenylboronic acid (MBA/biotin-modified gold nanoparticles (AuNPs (MBA-biotin-AuNPs as labels. To demonstrate the feasibility and sensitivity of this method, recombinant human erythropoietin (rHuEPO was tested as a model analyte. Specifically, rHuEPO was captured by the anti-rHuEPO aptamer-covered electrode and then derivatized with MBA-biotin-AuNPs through the boronic acid–carbohydrate interaction. The MBA-biotin-AuNPs facilitated the attachment of streptavidin-conjugated alkaline phosphatase for the production of electroactive p-aminophenol from p-aminophenyl phosphate substrate. A detection limit of 8 fmol L-1 for rHuEPO detection was achieved. Other glycosylated and non-glycosylated proteins, such as horseradish peroxidase, prostate specific antigen, metallothionein, streptavidin, and thrombin showed no interference in the detection assay.Keywords: electrochemical biosensor, boronic acid, signal amplification, alkaline phosphatase

  2. Human recombinant erythropoietin does not promote cancer growth in presence of functional receptors expressed in cancer cells.

    Science.gov (United States)

    Belda-Iniesta, Cristóbal; Perona, Rosario; Carpeño, Javier de Castro; Cejas, Paloma; Casado, Enrique; Manguan-García, Cristina; Ibanez de Caceres, Inmaculada; Sanchez-Perez, Isabel; Andreu, Francisco Bernabeu; Ferreira, Javier Alves; Aguilera, Alfredo; de la Peña, Javier; Perez-Sánchez, Elia; Madero, Rosario; Feliu, Jaime; Sereno, María; González-Barón, Manuel

    2007-10-01

    Human recombinant erythropoietin (hrEPO) therapy might be associated with tumor progression and death. This effect has been suggested to be secondary to rhEPO binding to its receptor (EPOR) expressed on cancer cells. However, there are several concerns about EPOR functionality when expressed on cancer cells. In this paper we have provided evidence that EPOR expressed in cancer cells could be implicated in proliferation events because a transfection of EPOR siRNA to EPOR-expressing bladder cancer cells resulted in a marked reduction in cell growth. However, these cell lines do not grow in the presence of hrEPO. Furthermore, bladder cancer patients that expressed EPOR in tumor samples had a reduced survival in absence of rhEPO treatment. Therefore, EPOR is implicated in bladder cancer growth but this effect appears to be independent from rhEPO supplementation. Reports which suggest that rhEPO promotes cancer growth due to the expression of EPOR in cancer cells must be observed with caution since in the presence of functional EPOR rhEPO does not promote growth.

  3. Regenerative medicine: does Erythropoietin have a role?

    Science.gov (United States)

    Buemi, Michele; Lacquaniti, Antonio; Maricchiolo, Giulia; Bolignano, Davide; Campo, Susanna; Cernaro, Valeria; Sturiale, Alessio; Grasso, Giovanni; Buemi, Antoine; Allegra, Alessandro; Donato, Valentina; Genovese, Lucrezia

    2009-01-01

    Regenerative Medicine, a recent new medical domain, aims to develop new therapies through the stimulation of natural regenerative processes also in human beings. In this field, Erythropoietin (EPO) represents a significant subject of research. Several studies allow the assertion that EPO, in different concentrations, has protective effects mainly on the central nervous system, cardiovascular system and renal tissue. This action is carried out through one of few regenerative activities of human beings: angiogenesis. This mechanism, which involves endothelial stem cells and VEGF (Vascular Endothelial Growth Factor), has been experimentally demonstrated with Recombinant human erythropoietin (rHuEPO) and Darbepoetin, a long-acting EPO derivate. Furthermore, the demonstration of a cardiac production of EPO in Fugu rubripes and in Zebrafish has led cardiologists to "discover" Erythropoietin, postulating a hypothetical role in treatment of cardiovascular disease for this hormone. This is some of the experimental evidence which demonstrates that EPO can be in reason considered an important element of research of Regenerative Medicine and put in the network of drugs able to regenerate tissues and organs.

  4. Human erythropoietin response to hypocapnic hypoxia, normocapnic hypoxia, and hypocapnic normoxia

    DEFF Research Database (Denmark)

    Klausen, T; Christensen, H; Hansen, J M

    1996-01-01

    This study investigated the human erythropoietin (EPO) response to short-term hypocapnic hypoxia, its relationship to a normoxic or hypoxic increase of the haemoglobin oxygen affinity, and its suppression by the addition of CO2 to the hypoxic gas. On separate days, eight healthy male subjects were...... (10% Co2 with 10% O2) to the hypoxic gas mixture. This elicited an increased ventilation, unaltered arterial pH and haemoglobin oxygen affinity, a lower degree of hypoxia than during hypocapnic hypoxia, and no significant changes in serum-EPO (ANOVA P > 0.05). Hypocapnic normoxia, produced...... by hyperventilation of room air, elicited a normoxic increase in the haemoglobin oxygen affinity without changing serum-EPO. Among the measured blood gas and acid-base parameters, only the partial pressures of oxygen in arterial blood during hypocapnic hypoxia were related to the peak values of serum-EPO (r = -0...

  5. 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

  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. 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.

  9. 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.

  10. 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.

  11. Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin

    Directory of Open Access Journals (Sweden)

    Yun Seong-Jo

    2012-01-01

    Full Text Available Abstract Background Dimeric human erythropoietin (dHuEPO peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg mice expressing dHuEPO and to investigate the characteristics of these mice. Methods A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile, was constructed and injected into 1-cell fertilized embryos by microinjection. Mice were screened using genomic DNA samples obtained from tail biopsies. Blood samples were obtained by heart puncture using heparinized tubes, and hematologic parameters were assessed. Using the microarray analysis tool, we analyzed differences in gene expression in the spleens of tg and control mice. Results A high rate of spontaneous abortion or death of the offspring was observed in the recipients of dHuEPO embryos. We obtained 3 founder lines (#4, #11, and #47 of tg mice expressing the dHuEPO gene. However, only one founder line showed stable germline integration and transmission, subsequently establishing the only transgenic line (#11. We obtained 2 F1 mice and 3 F2 mice from line #11. The dHuEPO protein could not be obtained because of repeated spontaneous abortions in the tg mice. Tg mice exhibited symptoms such as short lifespan and abnormal blood composition. The red blood cell count, white blood cell count, and hematocrit levels in the tg mice were remarkably higher than those in the control mice. The spleens of the tg mice (F1 and F2 females were 11- and -21-fold larger than those of the control mice. Microarray analysis revealed 2,672 spleen-derived candidate genes; more genes were downregulated than upregulated (849/764. Reverse transcriptase-polymerase chain reaction (RT-PCR and quantitative real-time PCR (qRT-PCR were used for validating the results of the microarray

  12. Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria

    Directory of Open Access Journals (Sweden)

    Hempel Casper

    2008-01-01

    Full Text Available Abstract Background Cerebral malaria (CM is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. In children CM induces cognitive impairment in about 10% of the survivors. Erythropoietin (Epo has – besides of its well known haematopoietic properties – significant anti-inflammatory, antioxidant and anti-apoptotic effects in various brain disorders. The neurobiological responses to exogenously injected Epo during murine CM were examined. Methods Female C57BL/6j mice (4–6 weeks, infected with Plasmodium berghei ANKA, were treated with recombinant human Epo (rhEpo; 50–5000 U/kg/OD, i.p. at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT-mediated deoxyuridine triphosphate (dUTP-digoxigenin nick end labelling, as a marker of apoptosis. Gene expression in brain tissue was measured by real time PCR. Results Treatment with rhEpo increased survival in mice with CM in a dose- and time-dependent manner and reduced apoptotic cell death of neurons as well as the expression of pro-inflammatory cytokines in the brain. This neuroprotective effect appeared to be independent of the haematopoietic effect. Conclusion These results and its excellent safety profile in humans makes rhEpo a potential candidate for adjunct treatment of CM.

  13. 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.

  14. 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。

  15. 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

  16. 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

  17. 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

  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. Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle

    Directory of Open Access Journals (Sweden)

    Shi YN

    2012-12-01

    Full Text Available Yanan Shi,1,2,* Wan Huang,1,* Rongcai Liang,1–3 Kaoxiang Sun,2,3 Fangxi Zhang,2,3 Wanhui Liu,2,3 Youxin Li1–31College of Life Science, Jilin University, Changchun, China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharmaceutical Co, Ltd, Yantai, China; 3School of Pharmacy, Yantai University, Yantai, China*These authors contributed equally to this workAbstract: To improve the pharmacokinetics and stability of recombinant human erythropoietin (rhEPO, rhEPO was successfully formulated into poly(ethylene glycol–poly(d,l-lactide (PEG–PLA di-block copolymeric micelles at diameters ranging from 60 to 200 nm with narrow polydispersity indices (PDIs; PDI < 0.3 and trace amount of protein aggregation. The zeta potential of the spherical micelles was in the range of −3.78 to 4.65 mV and the highest encapsulation efficiency of rhEPO in the PEG–PLA micelles was about 80%. In vitro release profiles indicated that the stability of rhEPO in the micelles was improved significantly and only a trace amount of aggregate was found. Pharmacokinetic studies in rats showed highly enhanced plasma retention time of the rhEPO-loaded PEG-PLA micelles in comparison with the native rhEPO group. Increased hemoglobin concentrations were also found in the rat study. Native polyacrylamide gel electrophoresis results demonstrated that rhEPO was successfully encapsulated into the micelles, which was stable in phosphate buffered saline with different pHs and concentrations of NaCl. Therefore, PEG–PLA micelles can be a potential protein drug delivery system.Keywords: rhEPO, PEG–PLA micelle, in vitro, pharmacokinetics, pharmacodynamics

  20. New insights for identification of doping with recombinant human erythropoietin micro-doses after high hydration.

    Science.gov (United States)

    Martin, L; Ashenden, M; Bejder, J; Hoffmann, M; Nordsborg, N; Karstoft, K; Morkeberg, J; Sharpe, K; Lasne, F; Marchand, A

    2016-11-01

    To minimize the chances of being caught after doping with recombinant human erythropoietins (rhEPO), athletes have turned to new practices using micro-doses and excess fluid ingestion to accelerate elimination and decrease the probability of detection. Our objective was to test the sensitivity of detection by validated methods (IEF: isoelectric focusing; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis) when such practices are used. First, after a three-week rhEPO boost period and 10 days of wash out, detection of a single 900 IU micro-dose of Eprex® was evaluated in healthy male subjects. After an injection in the evening, urine and plasma samples were collected the following morning. Half of the subjects then drank a bolus of water and new samples were collected 80 min later. Interestingly, rhEPO was detected in 100% of the samples even after water ingestion. A second similar protocol was then performed with a single injection of a micro-dose of rhEPO (500 IU or 900 IU), without a prior rhEPO boost. In addition, urine and plasma samples were also collected 15 and 20 h post rhEPO administration. Once again drinking water did not affect the rate of detection. Urine appeared a better matrix to detect micro-doses after 10 h, enabling between 92% and 100% of identification at that time. The rate of identification decreased rapidly thereafter, in particular for the 500 IU micro-dose. However IEF analysis still resulted in 71% identification of rhEPO in urine after 20 h. These results could help to define a better strategy for controlling and identifying athletes using rhEPO micro-doses. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. 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.

  2. 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.

  3. 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.

  4. Effect of recombinant human erythropoietin on mitomycin C-induced oxidative stress and genotoxicity in rat kidney and heart tissues.

    Science.gov (United States)

    Rjiba-Touati, K; Ayed-Boussema, I; Guedri, Y; Achour, A; Bacha, H; Abid-Essefi, S

    2016-01-01

    Mitomycin C (MMC) is an antineoplastic agent used for the treatment of several human malignancies. Nevertheless, the prolonged use of the drug may result in a serious heart and kidney injuries. Recombinant human erythropoietin (rhEPO) has recently been shown to exert an important cytoprotective effect in experimental brain injury and ischemic acute renal failure. The aim of the present work is to investigate the cardioprotective and renoprotective effects of rhEPO against MMC-induced oxidative damage and genotoxicity. Our results showed that MMC induced oxidative stress and DNA damage. rhEPO administration in any treatment conditions decreased oxidative damage induced by MMC. It reduced malondialdehyde and protein carbonyl levels. rhEPO ameliorated reduced glutathione plus oxidized glutathione modulation and the increased catalase activity after MMC treatment. Furthermore, rhEPO restored DNA damage caused by MMC. We concluded that rhEPO administration especially in pretreatment condition protected rats against MMC-induced heart and renal oxidative stress and genotoxicity.

  5. Estudio en poblaciones seleccionadas de la fiabilidad de nuevos protocolos de detección de consumo de hormonas recombinantes (hgH y EPO)

    OpenAIRE

    Abellán Sánchez, María Rosario

    2006-01-01

    Las hormonas recombinantes eritropoyetina (EPO) y hormona de crecimiento (GH), prácticamente iguales a las endógenas y de corta vida media en circulación, son de difícil detección directa en el control antidopaje. Se determinaron los valores poblacionales de los biomarcadores indirectos EPO, receptor soluble de la transferrina, insulin-like growth factor-I (IGF-I) y procolágeno tipo III péptido (P-III-P), en poblaciones seleccionadas de deportistas, y el efecto del ejercicio y los distintos t...

  6. 乳腺癌促红细胞生成素及其受体表达和肿瘤微血管生成关系研究%The correlation between the expression of Epo/Epo-R and MVD in patients with breast cancer

    Institute of Scientific and Technical Information of China (English)

    陆晔; 严敏; 潘湘涛; 程旭; 李蓉

    2009-01-01

    目的 研究乳腺癌患者Epo/Epo-R表达及其与肿瘤血管生成的关系.方法 对82例患者分别应用常规方法检测血红蛋白(Hb)值、用酶联免疫法检测血清Epo水平和应用免疫组化法检测Epo-R和肿瘤微血管密度(MVD),并进行相关分析.结果 (1)82例肿瘤患者的Epo为(18.64±20.42)mU/ml,明显高于对照组的(8.10±4.96)mU/ml(P0.05);贫血和无贫血患者的MVD分别为28.31±8.07和32.00±7.66(P>0.05).(4)Epo-R的表达与Epo水平和Hb值的高低无关;肿瘤血管的生成与Epo-R的表达和Epo水平、Hb值均不相关.结论 乳腺癌患者的Epo水平明显增高,并与Hb值呈负相关;Epo-R和MVD的表达与患者有无贫血无关;肿瘤血管的生成与Epo-R的表达和Epo水平、Hb值均不相关.

  7. Planting local seed for growth to nationwide E/PO efforts

    Science.gov (United States)

    Fox, N.; Beisser, K.; Mendez, F.; Cockrell, D.; Wilhide, B.

    The Johns Hopkins University Applied Physics Laboratory (JHU/APL) is the home to hundreds of scientists and engineers, all involved in research, design and implementation of space missions. Many of these people actively seek out ways to raise awareness and interest in the local community by visiting schools, giving public lectures and supporting events held at the laboratory. During the past few years, APL has begun to foster a number of firm partnerships with organizations to further these community opportunities and provide a test bed for both formal and informal education activities through the Space Department E/PO office One of our ongoing partnerships is with the Maryland Science Center in Baltimore. A continual challenge faced by museums is how to stay current and allow visitors to experience the immediacy and excitement of scientific discovery. To help meet these challenges, the Maryland Science Center houses "SpaceLink", the Nation's first space, science and astronomy update center. Part media center, part discovery room, and part newsroom, the exhibit is a multi-purpose Professional Development Site for educators and a "classroom of the future" for K 12 students. APL scientists and- engineers regularly support SpaceLink's flexible programming, including scientist in residence, monthly credited seminars for educators (Teachers' Thursdays), a menu of Classroom Programs on request, Distance Learning Teacher Presentations, and special Live Events to highlight mission milestones and space-related anniversaries. This allows the guest scientists and engineers to interact directly with the public. These events also compliment the APL exhibits housed at the Science Center. JHU/APL offers an exciting environment for the study of applications in space by hosting the annual Maryland Summer Center for Space Science sponsored by the Maryland State Department of Education. Rising 6t h and 7t h grade students learn to harness the power of technology and keep pace with

  8. Online Citizen Science with Clickworkers & MRO HiRISE E/PO

    Science.gov (United States)

    Gulick, V. C.; Deardorff, G.; Kanefsky, B.; HiRISE Science Team

    2010-12-01

    The High-Resolution Imaging Science Experiment’s E/PO has fielded several online citizen science projects. Our efforts are guided by HiRISE E/PO’s philosophy of providing innovative opportunities for students and the public to participate in the scientific discovery process. HiRISE Clickworkers, a follow-on to the original Clickworkers crater identification and size diameter marking website, provides an opportunity for the public to identify & mark over a dozen landform feature types in HiRISE images, including dunes, gullies, patterned ground, wind streaks, boulders, craters, layering, volcanoes, etc. In HiRISE Clickworkers, the contributor views several sample images showing variations of different landforms, and simply marks all the landform types they could spot while looking at a small portion of a HiRISE image. Contributors then submit their work & once validated by comparison to the output of other participants, results are then added to geologic feature databases. Scientists & others will eventually be able to query these databases for locations of particular geologic features in the HiRISE images. Participants can also mark other features that they find intriguing for the HiRISE camera to target. The original Clickworkers website pilot study ran from November 2000 until September 2001 (Kanefsky et al., 2001, LPSC XXXII). It was among the first online Citizen Science efforts for planetary science. In its pilot study, we endeavored to answer two questions: 1) Was the public willing & able to help science, & 2) Can the public produce scientifically useful results? Since its inception over 3,500,000 craters have been identified, & over 350,000 of these craters have been classified. Over 2 million of these craters were marked on Viking Orbiter image mosaics, nearly 800,000 craters were marked on Mars Orbiter Camera (MOC) images. Note that these are not counts of distinct craters. For example, each crater in the Viking orbiter images was counted by about 50

  9. Static Compression Performance of EPO Foam and Comparison between EPO,EPS and EPE Foam%EPO泡沫的静态压缩性能及其与EPS和EPE泡沫的比较

    Institute of Scientific and Technical Information of China (English)

    温时宝

    2010-01-01

    EPO(发泡聚烯烃)、EPS和EPE泡沫进行截面泡孔结构、静态压缩试验以及使用性能比较.应力-应变曲线分析表明,EPO泡沫变形分为弹性段、塑性屈服平台段及致密段;由3者截面泡孔结构、应力-应变关系和缓冲系数-静应力关系的比较表明,EPO静态缓冲性能介于EPS与EPE之间,但与EPS更为接近;使用性能比较表明,EPO泡沫衬垫避免了EPS和EPE的缺点,集合了EPE柔软性、反复冲击性能好和EPS可模制成型的优点.

  10. Impact of Eudragit EPO and hydroxypropyl methylcellulose on drug release rate, supersaturation, precipitation outcome and redissolution rate of indomethacin amorphous solid dispersions.

    Science.gov (United States)

    Xie, Tian; Gao, Wei; Taylor, Lynne S

    2017-10-05

    The purpose of this work was to evaluate the impact of polymer(s) on the dissolution rate, supersaturation and precipitation of indomethacin amorphous solid dispersions (ASD), and to understand the link between precipitate characteristics and redissolution kinetics. The crystalline and amorphous solubilities of indomethacin were determined in the absence and presence of hydroxypropylmethyl cellulose (HPMC) and/or Eudragit (®) EPO to establish relevant phase boundaries. At acidic pH, HPMC could maintain supersaturation of the drug by effectively inhibiting solution crystallization while EPO increased both the crystalline and amorphous solubility of the drug, but did not inhibit crystallization. The HPMC dispersion dissolved relatively slowly without undergoing crystallization while the supersaturation generated by rapid dissolution of the EPO ASD was short-lived due to crystallization. The crystals thus generated underwent rapid redissolution upon pH increase, dissolving faster than the reference crystalline material, and at a comparable rate to the amorphous HPMC dispersion. A ternary dispersion containing both EPO and HPMC dissolved rapidly, generating an apparent drug concentration that exceeded the amorphous solubility of indomethacin, leading to the formation of a new nanosized droplet phase. These nanodroplets dissolved virtually immediately when the pH was increased. In conclusion, the concentration-time profiles achieved from indomethacin ASD dissolution are a complex interplay of drug release rate, precipitation kinetics and outcome, and precipitate redissolution rate, whereby each of these processes is highly dependent on the polymer(s) employed in the formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Hypoxia pretreatment and EPO-modification enhance the protective effects of MSC on neuron-like PC12 cells in a similar way.

    Science.gov (United States)

    Feng, Jinli; Wang, Wei

    2017-01-08

    Mesenchymal stem cells (MSC) based cell transplantation therapy is proved to be an attractive strategy with great potential for improvement of hypoxia induced neural damage. In the present study, MSCs were co-culture with PC12 to investigate its protective effects against hypoxia pretreatment, and the Lactate dehydrogenase (LDH) release assay, MTT and Anexin V staining were performed to analysis the cellular damage or apoptotic. RT-PCR and Western blotting were further used to investigate the underlying mechanism. The results indicate that hypoxia treatment results in the decrease of PC12 cell viability, yet co-culture with MSC could protect the PC12 from hypoxia induced damage. Hypoxia pre-activated or EPO transduced MSC with up-regulated erythropoietin (EPO) expression could further enhance MSC's protective effect against hypoxia induced cell damage, which was associated with high level of anti-apoptotic p-Akt and ration Bcl-2/Bax, and decreased Caspase 3 in PC12. Taken together, these data suggests high levels of MSC-mediated cyto-protection is closely tied to high gene expression levels of EPO. The up-regulation of EPO for enhanced MSC-mediated cyto-protection may has great potential for the MSC cellular therapy of neural or neuronal injuries induced by hypoxia.

  12. 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.

  13. 间接抗体夹心酶联免疫吸附法测定人红细胞生成素(EPO)体外活性%Determination of Erythropoietin (EPO) potency in vitro with indirection antibodies sandwich in enzyme linked immunosorbent method

    Institute of Scientific and Technical Information of China (English)

    于萍; 赵先亮; 张利宁

    2005-01-01

    目的介绍一种经济、实用的红细胞生成素(EPO)体外活性检测方法-间接抗体夹心酶联免疫吸附法.方法采用捕捉抗体(单克隆抗体:鼠抗EPO)包被酶标板,然后用封闭液封闭酶标板,加入稀释成合适浓度的EPO样品进行温育,再加入EPO第二抗体(多克隆抗体:兔抗EPO)温育,然后加入酶连抗体(HRP-羊抗兔)温育,最后加入底物缓冲液显色,用酶标仪读数,计算出EPO体外效价.结果该方法重复性好(CV<5%),与ELISA 试剂盒比较,两法测定的结果相符(P>0.5).结论该方法是一种经济、实用、准确、可靠的红细胞生成素(EPO)体外活性检测方法,与EPO ELISA 试剂盒比较,大大降低了实验费用.

  14. Characterization of the pharmacokinetics of human recombinant erythropoietin in blood and brain when administered immediately after lateral fluid percussion brain injury and its pharmacodynamic effects on IL-1beta and MIP-2 in rats.

    Science.gov (United States)

    Lieutaud, Thomas; Andrews, Peter J D; Rhodes, Jonathan K J; Williamson, Robert

    2008-10-01

    This study sought to determine the bio-availability of recombinant human erythropoietin (EPO) in the brain and blood and its effects on the cerebral concentrations of the inflammatory mediators interleukin-1beta (IL-1beta) and macrophage-inflammation protein-2 (MIP-2) following lateral fluid percussion brain injury (FPI) in the rat. After induction of moderate FPI (1.6-1.8 atm), EPO was injected intraperitoneally (IP) or intravenously (IV) at doses of 1000-5000 U/kg in a randomized and blinded manner. Animals were then sacrificed at time points (4, 8, 12, 24 h) post-trauma, and the brain concentrations of EPO, IL-1beta, and MIP-2 were determined. EPO administration leads to a dose-dependent increase in the brain concentration of the drug; however, this could only be detected at doses of 3000 and 5000 U/kg. The cerebral concentration peaked in the first 4 h following trauma. EPO concentrations were significantly higher and decreased more slowly in the traumatized cortex compared to the contralateral side (p<0.0125). IV EPO (5000 U/kg) produced slightly higher concentrations of EPO than same doses injected IP; however, this was not significant. At a dose of 5000 U/kg, EPO significantly reduced the increase in IL-1beta at 8 and 12 h in both cortical sides. It also reduced the increase in MIP-2 but only after 8 h, on the contralateral side and after 12 h on the ipsilateral side. Our results suggest that EPO crosses the blood-brain barrier (BBB) by 4 h after trauma and is localized primarily in the traumatized cortex. Further, it has biological efficacy at 8 h on several inflammatory proteins, yet must be employed at high doses to cross the BBB.

  15. 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

  16. Our Place in Space: Exploring the Earth-Moon System and Beyond with NASA's CINDI E/PO Program

    Science.gov (United States)

    Urquhart, M. L.; Hairston, M. R.

    2010-12-01

    Where does space begin? How far is the Moon? How far is Mars? How does our dynamic star, the Sun, affect its family of planets? All of these questions relate to exploration of our Solar System, and are also part of the Education/Public Outreach (E/PO) Program for NASA’s CINDI project, a space weather mission of opportunity. The Coupled Ion Neutral Dynamics Investigation has been flying aboard the US Air Force Communication/Navigation Outage Forecast System (C/NOFS) satellite in the upper atmosphere of the Earth since April 2008. The Earth’s ionosphere, the part of the atmosphere CINDI studies, is also in space. The CINDI E/PO program uses this fact in lessons designed to help students in middle schools and introductory astronomy classes develop a sense of their place in space. In the activity "How High is Space?" students’ start by building an 8-page scale model of the Earth’s atmosphere with 100 km/page. The peak of Mount Everest, commercial airplanes, and the tops of thunderheads all appear at the bottom of the first page of the model, with astronaut altitude -where space begins- at the top of the same sheet of paper. In "Where Would CINDI Be?" the idea of scale is further developed by modeling the Earth-Moon system to scale first in size, then in distance, using half of standard containers of play dough. With a lowest altitude of about 400 km, similar to that of the International Space Station and orbiting Space Shuttle, CINDI is close to the Earth when compared with the nearly thousand times greater distance to the Moon. Comparing and combining the atmosphere and Earth-Moon system models help reinforce ideas of scale and build student understanding of how far away the Moon actually is. These scale models have also been adapted for use in Family Science Nights, and to include the planet Mars. In this presentation, we will show how we use CINDI’s scale modeling activities and others from our broader space sciences E/PO program in formal and informal

  17. Acoustic rhinometry in persons recruited from the general population and diagnosed with chronic rhinosinusitis according to EPOS

    DEFF Research Database (Denmark)

    Lange, B; Thilsing, T; Baelum, J

    2014-01-01

    rhinometry (AR) is an objective method to determine nasal cavity geometry. The technique is based on a sound pulse reflection analysis in the nasal cavity and determines cross-sectional areas as a function of distance as well as volume. AR measurements in persons recruited from the general population......, with and without CRS based on the clinical EPOS criteria, were investigated. As part of a trans-European study, 362 persons, comprising 91 persons with CRS and 271 persons without CRS, were examined by an otolaryngologist including rhinoscopy. Minimum cross-sectional area, distance to minimum cross-sectional area...... and PNIF was found and AR was capable of identifying mucosal oedema and septum deviation visualised by rhinoscopy. In conclusion, AR, as a single instrument, was not capable of discriminating persons with CRS from persons without CRS in the general population. However, AR correlates well with PNIF...

  18. 胃肠道恶性肿瘤组织Epo-R受体的表达与肿瘤血管生成的相关性及其意义

    Institute of Scientific and Technical Information of China (English)

    姜付涛; 徐琳娜

    2015-01-01

    目的研究胃肠道肿瘤患者的促红细胞生成素受体(Epo-R)表达及其与肿瘤血管生成的关系.方法:应用免疫组化方法检测41 例胃癌和36 例结直肠癌患者的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:①77 例MVD 平均计数为(28.72±8.61)个,66 例表达Epo-R(平均阳性率为39.98±25.01%);②MVD 与Epo-R 呈正相关(r=0.3514、t=3.340、p〈0.001);Epo-R 阳性表达患者的MVD 明显高于Epo-R阴性患者(t=2.9565、p〈0.01);③MVD 和Epo-R 均与有无转移、分期、分化程度和肿块大小均无关(均为p〉0.05).结论:胃癌和结直肠癌患者高表达Epo-R,并与MVD 呈正相关关系.MVD 和Epo-R 均与临床病理特征之间无明确关系.

  19. The clinical research of Thalidomide and cyclosporine +EPO 3 drugs in the treatment of myelodysplastic syndrome%沙利度胺+环孢素+EPO 3联用药治疗骨髓增生异常综合征临床研究

    Institute of Scientific and Technical Information of China (English)

    李艳玲

    2016-01-01

    目的:研究沙利度胺+环孢素+EPO 3联用药治疗骨髓增生异常综合征临床效果。方法:收治60例MDS 患者,将60例患者分成三组,A 组给予沙利度胺,B 组给予沙利度胺+环孢素,C 组给予沙利度胺+环孢素+EPO 三种药物。结果:三组患者病情改善效果、治疗后预后有差异,并发症比较无差异。结论:沙利度胺+环孢素+EPO 3联用药治疗 MDS 可减轻病症,提高患者临床疗效和生存质量,延长生存期限,增加治愈疾病的可能性,可在临床推广。%Objective To study the thalidomide + cyclosporine +EPO 3 drugs in the treatment of myelodysplastic syndrome clinical effect. Methods were treated 60 cases of MDS patients, 60 cases were divided into three groups, group a given thalido-mide, group B given thalidomide + CSA, group C given thalidomide plus cyclosporine with EPO three drugs. Results: there were no differences in the improvement effect and prognosis of the three groups. Conclusion thalidomide plus cyclosporine with EPO 3 combination therapy in the treatment of MDS can alleviate symptoms, improve clinical efficacy and quality of life of patients, prolong the survival period, increase the likelihood of cure the disease, in clinical practice.

  20. 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

  1. Effects of rhEPO on Expressions of GLT-1 and GLAST in Rat Astrocyte of Cultured by Oxygen-glucose Deprivation%rhEPO 对缺糖缺氧大鼠星形胶质细胞GLT-1和 GLAST 表达的影响

    Institute of Scientific and Technical Information of China (English)

    庞一强; 杨静; 吴刚; 汪静; 姜树原

    2016-01-01

    为了研究重组人促红细胞生成素(rhEPO)对缺糖缺氧(OGD)培养大鼠星形胶质细胞 GLT-1和 GLAST 表达的影响,将缺糖缺氧培养星形胶质细胞分成不同浓度 rhEPO 处理组:0、20、100 U/mL,不同浓度 rhEPO 与星形胶质细胞在缺氧缺糖条件下培养6 h,用 RT-PCR 测定 GLT-1和 GLAST 的 mRNA 表达变化,免疫印迹技术测定 GLT-1和 GLAST 蛋白的表达变化。20、100 U/mL rhEPO 星形胶质细胞 GLT-1的 mRNA 和蛋白质水平较 OGD 对照组明显升高(P <0.05),GLAST 的 mRNA 和蛋白质水平变化不明显(P >0.05)。GLT-1水平可能与 rhEPO 对缺糖缺氧培养大鼠星形胶质细胞的保护作用有关。%In order to study effects of rhEPO on the expressions of GLT-1 and GLAST in rat astrocytes cul-tured by oxygen-glucose deprivation,the astrocytes of rats cultured by oxygen-glucose deprivation were di-vided into three groups with different concentrations of rhEPO 0,20,100 U/mL and cultured for 6 hours by hypoxia-glucose deprivation.The real-time PCR and Western blot were used to detect the changes of mRNA and protein expressions of GLT-1 and GLAST,respectively.In comparison with OGD control,mR-NA and protein levels of GLT-1 were found to be increased in the groups of 20 and 100 U/mL rhEPO (P 0.05).The changes of GLT-1 may be related to protective effects of rhEPO on astrocytes of rats cultured by oxygen-glucose deprivation.

  2. 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

  3. Effect of Recombinant Human Erythropoietin on Proliferation of Breast Cancer MDA-MB-231 Cells and Its Mechanism%重组人促红细胞生成素对人乳腺癌MDA-MB-231细胞增殖的影响及其作用机制研究

    Institute of Scientific and Technical Information of China (English)

    晋雯; 孔令英; 张小容; 杨丽

    2013-01-01

    目的 探讨重组人促红细胞生成素(recombinant human erythropoietin,rh-EPO)对人乳腺癌MDA-MB-231细胞增殖的影响及其作用机制.方法 将人乳腺癌 MDA-MB-231 细胞进行培养.传至5~6代,细胞生长状态稳定后,收集人乳腺癌 MDA-MB-231细胞用于MTT实验.采用MTT法检测 5 组(阴性对照组、rh-EPO A 组、rh-EPO B组、rh-EPO C 组和rh-EPO D 组)MDA-MB-231细胞增殖的情况.用10 μmol·L-1p38MAPK抑制剂SB203580、ERK抑制剂U0126、JNK抑制剂SP600125和NF-κB 抑制剂PDTC预处理人乳腺癌 MDA-MB-231 细胞后,用MTT法检测经100、200、300和400 U·mL-1的rh-EPO(PDTC+EPO 组、SB203580+EPO 组、SP600125+EPO组和U0126+EPO组)诱导后细胞增殖的情况.结果 阴性对照组、rh-EPO A 组、rh-EPO B组、rh-EPO C 组和rh-EPO D 组 72 h PI值分别为:1.000 0±1.000 0、1.231 8±0.133 0、1.323 9±0.136 0、1.351 7±0.146 0和1.423 1±0.084 0;96 h PI值分别为:1.000 0±1.000 0、1.352 5±0.036 0、1.359 7±0.112 0、1.387 2±0.063 0和1.410 8±0.060 0.rh-EPO A 组、rh-EPO B组、rh-EPO C 组和rh-EPO D 组 72、96 h PI值与阴性对照组比较差异均有统计学意义(均P<0.05).PDTC+EPO 组、SB203580+EPO 组72、96 h PI值均较EPO组明显降低(均P<0.05),SP600125+EPO组、U0126+EPO组72、96 h PI值与EPO组比较差异均无统计学意义(均P>0.05).结论 rh-EPO可能是通过NF-κB、MAPK传导通路发挥效应,促进人乳腺癌MDA-MB-231细胞增殖.

  4. The "Volcano Observations" Thematic Core Service of the European Plate Observing System (EPOS): status of the implementation.

    Science.gov (United States)

    Puglisi, Giuseppe

    2017-04-01

    The European volcanological community contributes to implementation of European Plate Observing System (EPOS) by making operational an integrated platform to guarantee a seamless access to the data provided by the European Solid Earth communities. To achieve this objective, the Volcano Observations Work Package (WP11) will implement a Thematic Core Services (TCS) which is planned to give access to the data and services provided by the European Volcano Observatories (VO) and some Volcanological Research Institutions (VRI; as university departments, laboratories, etc.); both types are considered as national research infrastructures (RI) over which to build the TCS. Currently, the networks on European volcanoes consist of thousands of stations or sites where volcanological parameters are continuously or periodically measured. These sites are equipped with instruments for geophysical (seismic, geodetic, gravimetric, electromagnetic), geochemical (volcanic plumes, fumaroles, groundwater, rivers, soils), environmental observations (e.g. meteorological and air quality parameters), as well as various prototypal monitoring systems (e.g. Doppler radars, ground based SAR). In Europe also operate laboratories for sample analysis (rocks, gases, isotopes, etc.), and almost continuous analysis of space-borne data (SAR, thermal imagery, SO2 and ash), as well as high-performance computing centres. All these RIs provide high-quality information (observations) on the current status of European volcanoes and the geodynamic background of the surrounding areas. The implementation of the Volcano Observations TCS is addressing technical and management issues, both considering the current heterogeneous state of the art of the volcanological research infrastructures in Europe. Indeed, the frame of the VO and VRI is now too fragmented to be considered as a unique distributed infrastructure, thus the main effort planned in the frame of the EPOS-IP is focused to create services aimed at

    <