WorldWideScience

Sample records for erythropoietin amplifies stroke-induced

  1. Erythropoietin

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Vinberg, Maj; Harmer, Catherine J

    2012-01-01

    Current pharmacological treatments for depression have a significant treatment-onset-response delay, an insufficient efficacy for many patients and fail to reverse cognitive dysfunction. Erythropoietin (EPO) has neuroprotective and neurotrophic actions and improves cognitive function in animal...... models of acute and chronic neurodegenerative conditions and in patients with cognitive decline....

  2. ERYTHROPOIETIN AS DOPING AGENT

    Directory of Open Access Journals (Sweden)

    Nina Đukanović

    2012-09-01

    Full Text Available Doping is the use of prohibited substances and/or methods that improve the abilities of athletes. Erythropoietin (EPO, the kidney hormone, belongs to a group of substances that are classified as blood doping, and it can be found on the list of banned substances from 1990. year. Its application leads to an increase in the number of red blood cells, which enables better supply of oxygen, and thus improve the aerobic performance of athletes. Because of that, EPO is very popular in sports where the endurance is predominantly required like a marathon, cycling, triathlon, nordic skiing. Erythropoietin can cause some adverse events, primarily to increase blood viscosity, which is associated with a higher risk of various thromboembolic complications. In detection of EPO use two groups of tests are available, through a urine sample (direct method and blood sample (indirect method.

  3. [Erythropoietin administration in diabetic patients].

    Science.gov (United States)

    Zukowska-Szczechowska, Ewa; Tomaszewski, Maciej; Sedkowska, Agnieszka; Grzeszczak, Władysław

    2003-01-01

    This paper presents the role of erythropoietin application in diabetic patients with accompanying renal failure. The main cause of anemia in diabetics are: nephropathy, structural lesions of erythrocyte membrane and blood loss connected with diagnostic and therapeutic actions. There are publications which demonstrate that in patients with diabetes type 1 or 2 with accompanying nephropathy, anemia appears more frequently than in the group of patients with chronic renal failure caused by other factors. It is supposed, that the impaired erythropoietin synthesis in diabetics can be caused by autonomic neuropathy. Erythropoietin administration in case of diabetic nephropathy has a beneficial influence on fat metabolism, immune response and reduction of insuline resistance. Erythropoietin because of reduction of vascular endothelial growth factor synthesis blocks the development of diabetic retinopathy and macroangiopathy. Erythropoietin reduces the risk of the left-ventricular hypertrophy caused by anemia. Very important is that the erythropoietin resistance is lower in diabetics. Scientists who are adverse to erythropoietin administration in patients with diabetic nephropathy maintain, that it can lead to vascular complications and the deterioration of glycemia control.

  4. Erythropoietin use and abuse

    Directory of Open Access Journals (Sweden)

    M Joseph John

    2012-01-01

    Full Text Available Recombinant human erythropoietin (rhEPO is arguably the most successful therapeutic application of recombinant DNA technology till date. It was isolated in 1977 and the gene decoded in 1985. Since then, it has found varied applications, especially in stimulating erythropoiesis in anemia due to chronic conditions like renal failure, myelodysplasia, infections like HIV, in prematurity, and in reducing peri-operative blood transfusions. The discovery of erythropoietin receptor (EPO-R and its presence in non-erythroid cells has led to several areas of research. Various types of rhEPO are commercially available today with different dosage schedules and modes of delivery. Their efficacy in stimulating erythropoiesis is dose dependent and differs according to the patient′s disease and nutritional status. EPO should be used carefully according to guidelines as unsolicited use can result in serious adverse effects. Because of its capacity to improve oxygenation, it has been abused by athletes participating in endurance sports and detecting this has proved to be a challenge.

  5. Erythropoietin during hypoglycaemia in type 1 diabetes

    DEFF Research Database (Denmark)

    Kristensen, Peter Lommer; Høi-Hansen, Thomas; Olsen, Niels Vidiendal

    2009-01-01

    AIMS: Preservation of cognitive function during hypoglycaemic episodes is crucial for patients with insulin-treated diabetes to avoid severe hypoglycaemic events. Erythropoietin has neuroprotective potential. However, the role of erythropoietin during hypoglycaemia is unclear. The aim of the stud....... CONCLUSIONS: Hypoglycaemia triggers a rise in plasma erythropoietin in patients with type 1 diabetes. The response is influenced by basal RAS activity. Erythropoietin may carry a neuroprotective potential during hypoglycaemia....... was to explore plasma erythropoietin response to hypoglycaemia and the relationship to basal renin-angiotensin system (RAS) activity and cognitive function. METHODS: We performed a single-blinded, controlled, cross-over study with induced hypoglycaemia or maintained glycaemic level. Nine patients with type 1......AIMS: Preservation of cognitive function during hypoglycaemic episodes is crucial for patients with insulin-treated diabetes to avoid severe hypoglycaemic events. Erythropoietin has neuroprotective potential. However, the role of erythropoietin during hypoglycaemia is unclear. The aim of the study...

  6. Fiber Amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten

    2017-01-01

    The chapter provides a discussion of optical fiber amplifiers and through three sections provides a detailed treatment of three types of optical fiber amplifiers, erbium doped fiber amplifiers (EDFA), Raman amplifiers, and parametric amplifiers. Each section comprises the fundamentals including...... the basic physics and relevant in-depth theoretical modeling, amplifiers characteristics and performance data as a function of specific operation parameters. Typical applications in fiber optic communication systems and the improvement achievable through the use of fiber amplifiers are illustrated....

  7. Recombinant human erythropoietin in sports: a review

    Directory of Open Access Journals (Sweden)

    Rafael Maia de Almeida Bento

    2003-06-01

    Full Text Available Erythropoietin is an endogenous hormone of glicoproteic nature secreted by the kidneys and is the main regulator of the erythropoiesis. An alteration in its production generates a disturbance in the plasmatic concentration giving rise to several types of pathologies related to the hematopoietic system. The recombinant forms of erythropoietin have indiscriminately been used by athletes, mainly in endurance sports, by increasing the erythrocytes concentration, generating a better delivery of oxygen to the muscle tissue. The administration of recombinant erythropoietin was prohibited by the International Olympic Committee and its use considered as doping. This review has the intention to describe the physical, biological and pharmacokinetic properties of the endogenous erythropoietin, as well as its recombinant form, describing also its use in sports and the process of searching methodologies for its detection in doping control.

  8. Erythropoietin in Brain Development and Beyond

    Directory of Open Access Journals (Sweden)

    Mawadda Alnaeeli

    2012-01-01

    Full Text Available Erythropoietin is known as the requisite cytokine for red blood cell production. Its receptor, expressed at a high level on erythroid progenitor/precursor cells, is also found on endothelial, neural, and other cell types. Erythropoietin and erythropoietin receptor expression in the developing and adult brain suggest their possible involvement in neurodevelopment and neuroprotection. During ischemic stress, erythropoietin, which is hypoxia inducible, can contribute to brain homeostasis by increasing red blood cell production to increase the blood oxygen carrying capacity, stimulate nitric oxide production to modulate blood flow and contribute to the neurovascular response, or act directly on neural cells to provide neuroprotection as demonstrated in culture and animal models. Clinical studies of erythropoietin treatment in stroke and other diseases provide insight on safety and potential adverse effects and underscore the potential pleiotropic activity of erythropoietin. Herein, we summarize the roles of EPO and its receptor in the developing and adult brain during health and disease, providing first a brief overview of the well-established EPO biology and signaling, its hypoxic regulation, and role in erythropoiesis.

  9. Operational amplifiers

    CERN Document Server

    Dostal, Jiri

    1993-01-01

    This book provides the reader with the practical knowledge necessary to select and use operational amplifier devices. It presents an extensive treatment of applications and a practically oriented, unified theory of operational circuits.Provides the reader with practical knowledge necessary to select and use operational amplifier devices. Presents an extensive treatment of applications and a practically oriented, unified theory of operational circuits

  10. Symmetric signaling by an asymmetric 1 erythropoietin: 2 erythropoietin receptor complex.

    Science.gov (United States)

    Zhang, Yingxin L; Radhakrishnan, Mala L; Lu, Xiaohui; Gross, Alec W; Tidor, Bruce; Lodish, Harvey F

    2009-01-30

    Via sites 1 and 2, erythropoietin binds asymmetrically to two identical receptor monomers, although it is unclear how asymmetry affects receptor activation and signaling. Here we report the design and validation of two mutant erythropoietin receptors that probe the role of individual members of the receptor dimer by selectively binding either site 1 or site 2 on erythropoietin. Ba/F3 cells expressing either mutant receptor do not respond to erythropoietin, but cells co-expressing both receptors respond to erythropoietin by proliferation and activation of the JAK2-Stat5 pathway. A truncated receptor with only one cytosolic tyrosine (Y343) is sufficient for signaling in response to erythropoietin, regardless of the monomer on which it is located. Similarly, only one receptor in the dimer needs a juxtamembrane hydrophobic L253 or W258 residue, essential for JAK2 activation. We conclude that despite asymmetry in the ligand-receptor interaction, both sides are competent for signaling, and appear to signal equally.

  11. Role of Erythropoietin in Renal Anemia Therapy

    African Journals Online (AJOL)

    Larramendi CH, Marco FM, Garcia-Abujeta JL, Mateo M, de la Vega A and Sempere JM. Acute allergic reaction to an iron compound in a milk-allergic patient. Pediatr. Allergy Immunol 2006; 17: 230-233. 18. Ksiazek A. Effect of recombinant human erythropoietin (r-. Hu EPO) therapy on blood pressure in dialysis patients.

  12. Polycythemia in transgenic mice expressing the human erythropoietin gene

    Energy Technology Data Exchange (ETDEWEB)

    Semenza, G.L.; Traystman, M.D.; Gearhart, J.D.; Antonarakis, S.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1989-04-01

    Erythropoietin is a glycoprotein hormone that regulates mammalian erythropoiesis. To study the expression of the human erythropoietin gene, EPO, 4 kilobases of DNA encompassing the gene with 0.4 kilobase of 5{prime} flanking sequence and 0.7 kilobase of 3{prime} flanking sequence was microinjected into fertilized mouse eggs. Transgenic mice were generated that are polycythemic, with increased erythrocytic indices in peripheral blood, increased numbers of erythroid precursors in hematopoietic tissue, and increased serum erythropoietin levels. Transgenic homozygotes show a greater degree of polycythemia than do heterozygotes as well as striking extramedullary erythropoiesis. Human erythropoietin RNA was found not only in fetal liver, adult liver, and kidney but also in all other transgenic tissues analyzed. Anemia induced increased human erythropoietin RNA levels in liver but not kidney. These transgenic mice represent a unique model of polycythemia due to increased erythropoietin levels.

  13. Use of Recombinant Human Erythropoietin in Renal Anemia in Children

    Directory of Open Access Journals (Sweden)

    Habibur Rahman

    2009-11-01

    Full Text Available Erythropoietin is a hormone highly effective as like as natural erythropoietin to maintain target hemoglobin and hematocrit level in renal anemia. Its advantage over blood transfusion has been proved by improving the quality of life and decreasing morbidity and mortality in ESRD patients. Effectiveness of r-erythropoietin depends on absences of infection, inflammation and vitamin deficiency and iron status. Iron supplementation is needed before r-erythropoietin administration and sub-cutaneous rout is better in renal anemia because of slow and sustained releases of r-erythropoietin from the site of administration. Target hemoglobin level is 11-12.5 gm/dl and hematocrit is 33% which can be achieved by this hormone therapy. Key words- Recombinant erythropoietin, renal anemia, end stage renal disease.DOI: 10.3329/bsmmuj.v2i1.3713 BSMMU J 2009; 2(1: 50-53  

  14. Amplified Policymaking

    Science.gov (United States)

    Prince, Katherine; Woempner, Carolyn

    2010-01-01

    This brief examines the policy implications of two drivers of change presented in the "2020 Forecast: Creating the Future of Learning"-- Pattern Recognition and Amplified Organization. These drivers point toward a series of cultural shifts and illuminate how we are developing new ways of organizing, constructing, and managing knowledge.…

  15. Stroke-induced immunodepression and dysphagia independently predict stroke-associated pneumonia - The PREDICT study.

    Science.gov (United States)

    Hoffmann, Sarah; Harms, Hendrik; Ulm, Lena; Nabavi, Darius G; Mackert, Bruno-Marcel; Schmehl, Ingo; Jungehulsing, Gerhard J; Montaner, Joan; Bustamante, Alejandro; Hermans, Marcella; Hamilton, Frank; Göhler, Jos; Malzahn, Uwe; Malsch, Carolin; Heuschmann, Peter U; Meisel, Christian; Meisel, Andreas

    2017-12-01

    Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia.

  16. Oxygen Transport Impairments in Miners with Ischemic Stroke-Induced Comas

    Directory of Open Access Journals (Sweden)

    Yu. A. Churlyaev

    2011-01-01

    Full Text Available Objective: to study oxygen transport impairments in ischemic stroke-induced coma in miners who have been doing underground work for more than 10 years. Subjects and methods. A prospective clinical study was conducted in 48 patients with coma caused by ischemic stroke. Group 1 included 12 miners. Group 2 comprised 36 men not working in coal miners. The groups did not differ in age, disease severity, and admission time. However, the group of miners had a higher incidence of pulmonary complications and therefore higher mortality rates. Comprehensive examination was performed and oxygen delivery index (DO2I, oxygen consumption index (VO2I, oxygen extraction ratio, and arteriovenous oxygen difference were calculated in all those admitted to hospital. Results. In ischemic stroke-induced comas, vasoconstriction resulted in the development of circulatory hypoxia with low DO2I. Then on day 3 respiratory and tissue hypoxia developed in the group of those who had a length of underground service. The relationship between DO2I and VO2I found in the miners suggests that impaired lung oxygenizing function was concurrent with oxygen transport system tension. The fact that there was no significant relationship of the oxygen saturation of hemoglobin in venous blood to VO2I in the miners had a high probability of indicating the development of tissue hypoxia. Such relationships were absent in the patients without underground length of service. Conclusion. The miners with an underground service length of 10 years or more and ischemic stroke-induced comas were found to have rapidly developing, more marked and long-term impairments of central hemodynamics, pulmonary oxygenizing function and hence the oxygen transport system as compared to those with no length of underground service. All the above characteristics are due to the lowered reserve capacities of the cardiovascular irnd respiratory systems upon long-term exposure to poor working conditions. Key words

  17. Recombinant human erythropoietin to target cognitive dysfunction in bipolar disorder

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla Woznica; Ehrenreich, Hannelore; Christensen, Ellen M

    2014-01-01

    in erythropoietin versus saline groups (P = .10). However, erythropoietin enhanced sustained attention (P = .001), recognition of happy faces (P = .03), and speed of complex information processing across learning, attention, and executive function (P = .01). These effects occurred in absence of changes in simple...

  18. Umbilical Cord Serum Erythropoietin Levels and Maternal Smoking in Pregnancy

    Directory of Open Access Journals (Sweden)

    Soner Sazak

    2012-01-01

    Full Text Available Objective. To evaluate the effect of maternal smoking during pregnancy on levels of umbilical cord erythropoietin. Methods. Erythropoietin levels were measured in umbilical cord sera of 60 newborns who were delivered vaginally at term. There were 20 (33% smoking and 40 (67% nonsmoking mothers. Results. Mean cord serum erythropoietin levels were significantly lower in the nonsmokers (nonsmokers, 24 ± 9 IU/L; smokers, 61 ± 46 IU/L; P<.001. There was a significant positive correlation between the number of cigarettes smoked per day and cord serum erythropoietin levels (r, 0.58; P≤.05. Conclusions. Smoking during pregnancy is associated with increased levels of umbilical cord erythropoietin at birth. This may indicate a risk of fetal hypoxia and growth restriction. Education and encouragement of cessation of smoking during pregnancy are important to avoid associated fetal and maternal morbidity and mortality.

  19. An abnormally glycosylated isoform of erythropoietin in hemangioblastoma is associated with polycythemia.

    Science.gov (United States)

    Delanghe, Sigurd E; Dierick, Jan; Maenhout, Thomas M; Zabeau, Lennart; Tavernier, Jan; Claes, Kathleen; Bleyen, Joris; Delanghe, Joris R

    2015-01-01

    Hemangioblastomas express erythropoietin and the patients often present with polycythemia. Serum erythropoietin was measured using a commercial immunoassay, a functional erythropoietin assay and iso-electric focusing. Despite the polycythemia, serum erythropoietin remained low, while a functional erythropoietin-assay showed a 4-5 higher activity in serum compared to the immunoassay. Iso-electric focusing of serum erythropoietin indicated overrepresentation of highly sialylated erythropoietin isoforms produced by the tumor. As a result, altered affinity of the monoclonal antibody used in the immunoassay for the hypersialylated isoforms was suggested. Analysis of erythropoietin isoforms may be helpful in distinguishing the ectopic erythropoietin isoforms from normally glycosylated erythropoietin. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Experiences of participation in goal setting for people with stroke-induced aphasia in Norway. A qualitative study.

    Science.gov (United States)

    Berg, Karianne; Askim, Torunn; Balandin, Susan; Armstrong, Elizabeth; Rise, Marit By

    2017-06-01

    The body of research into client participation in aphasia rehabilitation is increasing, but the evidence on how it is implemented into clinical practice is still scarce. Particularly, the importance of including the "insider's perspective" has been demanded. The aim of this study was to explore how people with aphasia experienced client participation during the process of goal setting and clinical decision making in language rehabilitation. Fifteen people with stroke-induced aphasia participated in semi-structured in-depth interviews. A qualitative analysis using Systematic Text Condensation was undertaken. Analysis revealed four main themes: (1) pleased with services, (2) vagueness in language rehabilitation, (3) personal goals exist, and (4) desired level of participation. Even though people with stroke-induced aphasia overall are pleased with the language rehabilitation, there is a need for greater emphasis on making the framework of language rehabilitation less vague. Therapists should also spend more time on collaboration with people with stroke-induced aphasia and use available methods to support communication and collaboration. The findings underscore the need for further exploration of the potential outcomes of implementing client participation in goal setting and clinical decision making for persons with stroke-induced aphasia. Implications for rehabilitation All persons with stroke induced aphasia should be asked about their goals for rehabilitation not only once, but during the whole continuum of their rehabilitation journey. Rehabilitation professionals should place greater emphasis on client participation by asking people with stroke induced aphasia how they prefer to participate at different stages of rehabilitation. To ensure active participation for those who wants it, existing tools and techniques which promoted collaborative goal setting should be better incorporated.

  1. Erythropoietin Pathway: A Potential Target for the Treatment of Depression

    Directory of Open Access Journals (Sweden)

    Chongyang Ma

    2016-05-01

    Full Text Available During the past decade, accumulating evidence from both clinical and experimental studies has indicated that erythropoietin may have antidepressant effects. In addition to the kidney and liver, many organs have been identified as secretory tissues for erythropoietin, including the brain. Its receptor is expressed in cerebral and spinal cord neurons, the hypothalamus, hippocampus, neocortex, dorsal root ganglia, nerve axons, and Schwann cells. These findings may highlight new functions for erythropoietin, which was originally considered to play a crucial role in the progress of erythroid differentiation. Erythropoietin and its receptor signaling through JAK2 activate multiple downstream signaling pathways including STAT5, PI3K/Akt, NF-κB, and MAPK. These factors may play an important role in inflammation and neuroprogression in the nervous system. This is particularly true for the hippocampus, which is possibly related to learning, memory, neurocognitive deficits and mood alterations. Thus, the influence of erythropoietin on the downstream pathways known to be involved in the treatment of depression makes the erythropoietin-related pathway an attractive target for the development of new therapeutic approaches. Focusing on erythropoietin may help us understand the pathogenic mechanisms of depression and the molecular basis of its treatment.

  2. Erythropoietin Pathway: A Potential Target for the Treatment of Depression.

    Science.gov (United States)

    Ma, Chongyang; Cheng, Fafeng; Wang, Xueqian; Zhai, Changming; Yue, Wenchao; Lian, Yajun; Wang, Qingguo

    2016-05-06

    During the past decade, accumulating evidence from both clinical and experimental studies has indicated that erythropoietin may have antidepressant effects. In addition to the kidney and liver, many organs have been identified as secretory tissues for erythropoietin, including the brain. Its receptor is expressed in cerebral and spinal cord neurons, the hypothalamus, hippocampus, neocortex, dorsal root ganglia, nerve axons, and Schwann cells. These findings may highlight new functions for erythropoietin, which was originally considered to play a crucial role in the progress of erythroid differentiation. Erythropoietin and its receptor signaling through JAK2 activate multiple downstream signaling pathways including STAT5, PI3K/Akt, NF-κB, and MAPK. These factors may play an important role in inflammation and neuroprogression in the nervous system. This is particularly true for the hippocampus, which is possibly related to learning, memory, neurocognitive deficits and mood alterations. Thus, the influence of erythropoietin on the downstream pathways known to be involved in the treatment of depression makes the erythropoietin-related pathway an attractive target for the development of new therapeutic approaches. Focusing on erythropoietin may help us understand the pathogenic mechanisms of depression and the molecular basis of its treatment.

  3. Statistical analysis plan for the Erythropoietin in Traumatic Brain Injury trial: a randomised controlled trial of erythropoietin versus placebo in moderate and severe traumatic brain injury.

    LENUS (Irish Health Repository)

    Presneill, Jeffrey

    2014-01-01

    The Erythropoietin in Traumatic Brain Injury (EPO-TBI) trial aims to determine whether the administration of erythropoietin to patients with moderate or severe traumatic brain injury improves patient-centred outcomes.

  4. Circadian Variation in the Incidence of Stroke-Induced Aphasia Types in Ahvaz, South-West of Iran

    Directory of Open Access Journals (Sweden)

    Zamani

    2015-12-01

    Full Text Available Background The incidence of the stroke and its associated disorders has a multifactorial nature. Nowadays, researchers are looking for the relationship between circadian variations and the stroke incidence. Objectives The current study aimed to compare the incidence of the different types of stroke-induced aphasia in Ahvaz, Iran, on seasonal, diurnal (weekly, and circadian variations. Patients and Methods In this retrospective hospital-based study, the medical records of 1817 patients with stroke were reread in Ahvaz hospitals in 2011. Types of aphasia were diagnosed based on speech and language symptoms in their records. The data were transferred into the SPSS version 16, for statistical comparison. Results According to the obtained results 39.9% of the studied patients had a stroke-induced aphasia. The highest incidence rates of aphasia due to the stroke in Ahvaz were, in the summer (38.2%, on Saturdays (16.1%, and 21.1% between 8:00 AM to noon. Chi-square test indicated a significant difference between the mentioned times and other time (P < 0.05. Conclusions It seems that the incidence of different types of stroke-induced aphasia in Ahvaz is influenced by the calendar-temporal changes. According to the findings, to prevent the occurrence of stroke-induced aphasia, necessary counseling should be provided for lifestyle changes.

  5. Endogenous CNTF mediates stroke-induced adult CNS neurogenesis in mice

    Science.gov (United States)

    Kang, Seong Su; Keasey, Matthew P.; Arnold, Sheila A.; Reid, Rollie; Geralds, Justin; Hagg, Theo

    2013-01-01

    Focal brain ischemia in adult rats rapidly and robustly induces neurogenesis in the subventricular zone (SVZ) but there are few and inconsistent reports in mice, presenting a hurdle to genetically investigate the endogenous neurogenic regulators such as ciliary neurotrophic factor (CNTF). Here, we first provide a platform for further studies by showing that middle cerebral artery occlusion in adult male C57BL/6 mice robustly enhances neurogenesis in the SVZ only under very specific conditions, i.e., 14 days after a 30 min occlusion. CNTF expression paralleled changes in the number of proliferated, BrdU-positive, SVZ cells. Stroke-induced proliferation was absent in CNTF−/− mice, suggesting that it is mediated by CNTF. MCAO-increased CNTF appears to act on C cell proliferation and by inducing FGF2 expression but not via EGF expression or Notch1 signaling of neural stem cells in the SVZ. CNTF is unique, as expression of other gp130 ligands, IL-6 and LIF, did not predict SVZ proliferation or showed no or only small compensatory increases in CNTF−/− mice. Expression of tumor necrosis factor-α, which can inhibit neurogenesis, and the presence of leukocytes in the SVZ were inversely correlated with neurogenesis, but pro-inflammatory cytokines did not affect CNTF expression in cultured astrocytes. These results suggest that slowly up-regulated CNTF in the SVZ mediates stroke-induced neurogenesis and is counteracted by inflammation. Further pharmacological stimulation of endogenous CNTF might be a good therapeutic strategy for cell replacement after stroke as CNTF regulates normal patterns of neurogenesis and is expressed almost exclusively in the nervous system. PMID:22960105

  6. Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle injury.

    Science.gov (United States)

    Sen, Chandan K; Khanna, Savita; Harris, Hallie; Stewart, Richard; Balch, Maria; Heigel, Mallory; Teplitsky, Seth; Gnyawali, Surya; Rink, Cameron

    2017-03-01

    The efficacy and optimization of poststroke physical therapy paradigms is challenged in part by a lack of objective tools available to researchers for systematic preclinical testing. This work represents a maiden effort to develop a robot-assisted mechanical therapy (RAMT) device to objectively address the significance of mechanical physiotherapy on poststroke outcomes. Wistar rats were subjected to right hemisphere middle-cerebral artery occlusion and reperfusion. After 24 h, rats were split into control (RAMT-) or RAMT+ groups (30 min daily RAMT over the stroke-affected gastrocnemius) and were followed up to poststroke d 14. RAMT+ increased perfusion 1.5-fold in stroke-affected gastrocnemius as compared to RAMT- controls. Furthermore, RAMT+ rats demonstrated improved poststroke track width (11% wider), stride length (21% longer), and travel distance (61% greater), as objectively measured using software-automated testing platforms. Stroke injury acutely increased myostatin (3-fold) and lowered brain-derived neurotrophic factor (BDNF) expression (0.6-fold) in the stroke-affected gastrocnemius, as compared to the contralateral one. RAMT attenuated the stroke-induced increase in myostatin and increased BDNF expression in skeletal muscle. Additional RAMT-sensitive myokine targets in skeletal muscle (IL-1ra and IP-10/CXCL10) were identified from a cytokine array. Taken together, outcomes suggest stroke acutely influences signal transduction in hindlimb skeletal muscle. Regimens based on mechanical therapy have the clear potential to protect hindlimb function from such adverse influence.-Sen, C. K., Khanna, S., Harris, H., Stewart, R., Balch, M., Heigel, M., Teplitsky, S., Gnyawali, S., Rink, C. Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle injury. © FASEB.

  7. Erythropoietine : enkele aspecten van de humorale regulatie van de erythropoiese

    NARCIS (Netherlands)

    G. Wagemaker (Gerard)

    1976-01-01

    textabstractDe regulatie van de erythropoiese verloopt in belangrijke mate via een humorale regulator. Deze wordt erythropoietine genoemd, en heeft een specifieke stimulerende werking op de erythropoiese, waarschiinliik in hoofdzaak door de inductie van erythroide differentiatie in een

  8. Effects of Recombinant Erythropoietin on Breast Cancer-Initiating Cells

    Directory of Open Access Journals (Sweden)

    Tiffany M. Phillips

    2007-12-01

    Full Text Available BACKGROUND: Cancer anemia causes fatigue and correlates with poor treatment outcome. Erythropoietin has been introduced in an attempt to correct these defects. However, five recent clinical trials reported a negative impact of erythropoietin on survival and/or tumor control, indicating that experimental evaluation of a possible direct effect of erythropoietin on cancer cells is required. Cancer recurrence is thought to rely on the proliferation of cancer initiating cells (CICs. In breast cancer, CICs can be identified by phenotypic markers and their fate is controlled by the Notch pathway. METHODS: In this study, we investigated the effect of erythropoietin on CICs in breast cancer cell lines. Levels of erythropoietin receptor (EpoR, CD24, CD44, Jagged-1 expression, activation of Notch-1 were assessed by flow cytometry. Self-renewing capacity of CICs was investigated in sphere formation assays. RESULTS: EpoR expression was found on the surface of CICs. Recombinant human Epo (rhEpo increased the numbers of CICs and self-renewing capacity in a Notch-dependent fashion by induction of Jagged-1. Inhibitors of the Notch pathway and P13-kinase blocked both effects. CONCLUSIONS: Erythropoietin functionally affects CICs directly. Our observation may explain the negative impact of recombinant Epo on local control and survival of cancer patients with EpoR-positive tumors.

  9. Basic conditions for radioimmunoassay of erythropoietin, and plasma levels of erythropoietin in normal subjects and anemic patients

    Energy Technology Data Exchange (ETDEWEB)

    Mizoguchi, Hideaki; Ohta, Kazuo; Suzuki, Toshiaki; Murakami, Akihiko; Ueda, Masatsugu; Sasaki, Ryuzou; Chiba, Hideo

    1987-02-01

    We have developed a specific and sensitive radioimmunoassay for erythropoietin. The sensitivity of our assay is 0.5 mU or 5 mU/ml and is sufficient to detect normal plasma erythropoietin levels. The mean plasma erythropoietin titer of normal Japanese with our radioimmunoassay was found to be 21.9 +- 12.0 mU/ml (n = 199). The validity of the method was further confirmed by the observations that the plasma erythropoietin titers were inversely related to hemoglobin levels in patients with nonuremic anemias, lower in uremic patients than in patients with nonuremic anemias with similar hemoglobin levels, markedly elevated in patients with aplastic anemia and pure red cell aplasia, and in a low normal range in patients with polycythemia vera.

  10. 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...... 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....

  11. Erythropoietin blockade inhibits the induction of tumor angiogenesis and progression.

    Directory of Open Access Journals (Sweden)

    Matthew E Hardee

    Full Text Available BACKGROUND: The induction of tumor angiogenesis, a pathologic process critical for tumor progression, is mediated by multiple regulatory factors released by tumor and host cells. We investigated the role of the hematopoietic cytokine erythropoietin as an angiogenic factor that modulates tumor progression. METHODOLOGY/PRINCIPAL FINDINGS: Fluorescently-labeled rodent mammary carcinoma cells were injected into dorsal skin-fold window chambers in mice, an angiogenesis model that allows direct, non-invasive, serial visualization and real-time assessment of tumor cells and neovascularization simultaneously using intravital microscopy and computerized image analysis during the initial stages of tumorigenesis. Erythropoietin or its antagonist proteins were co-injected with tumor cells into window chambers. In vivo growth of cells engineered to stably express a constitutively active erythropoietin receptor EPOR-R129C or the erythropoietin antagonist R103A-EPO were analyzed in window chambers and in the mammary fat pads of athymic nude mice. Co-injection of erythropoietin with tumor cells or expression of EPOR-R129C in tumor cells significantly stimulated tumor neovascularization and growth in window chambers. Co-injection of erythropoietin antagonist proteins (soluble EPOR or anti-EPO antibody with tumor cells or stable expression of antagonist R103A-EPO protein secreted from tumor cells inhibited angiogenesis and impaired tumor growth. In orthotopic tumor xenograft studies, EPOR-R129C expression significantly promoted tumor growth associated with increased expression of Ki67 proliferation antigen, enhanced microvessel density, decreased tumor hypoxia, and increased phosphorylation of extracellular-regulated kinases ERK1/2. R103A-EPO antagonist expression in mammary carcinoma cells was associated with near-complete disruption of primary tumor formation in the mammary fat pad. CONCLUSIONS/SIGNIFICANCE: These data indicate that erythropoietin is an

  12. Erythropoietin in Treatment of Methanol Optic Neuropathy.

    Science.gov (United States)

    Pakdel, Farzad; Sanjari, Mostafa S; Naderi, Asieh; Pirmarzdashti, Niloofar; Haghighi, Anousheh; Kashkouli, Mohsen B

    2018-01-03

    Methanol poisoning can cause an optic neuropathy that is usually severe and irreversible and often occurs after ingestion of illicit or homemade alcoholic beverages. In this study, we evaluated the potential neuroprotective effect of erythropoietin (EPO) on visual acuity (VA) in patients with methanol optic neuropathy. In a prospective, noncomparative interventional case series, consecutive patients with methanol optic neuropathy after alcoholic beverage ingestion were included. All patients initially received systemic therapy including metabolic stabilization and detoxification. Treatment with intravenous recombinant human EPO consisted of 20,000 units/day for 3 successive days. Depending on clinical response, some patients received a second course of EPO. VA, funduscopy, and spectral domain optical coherence tomography were assessed during the study. Main outcome measure was VA. Thirty-two eyes of 16 patients with methanol optic neuropathy were included. Mean age was 34.2 years (±13.3 years). The mean time interval between methanol ingestion and treatment with intravenous EPO was 9.1 days (±5.56 days). Mean follow-up after treatment was 7.5 months (±5.88 months). Median VA in the better eye of each patient before treatment was light perception (range: 3.90-0.60 logMAR). Median last acuity after treatment in the best eye was 1.00 logMAR (range: 3.90-0.00 logMAR). VA significantly increased in the last follow-up examination (P neuropathy and may represent a promising treatment for this disorder.

  13. Blood doping : infusions, erythropoietin and artificial blood.

    Science.gov (United States)

    Eichner, E Randy

    2007-01-01

    As science marches on, athletes and coaches march close behind. Researchers have long been interested in how red cell mass and blood volume affect exercise capacity. Interest in blood doping soared after the 1968 Mexico City Olympics. Studies in the 1970s and 1980s suggested that transfusing red cells could speed endurance performance. Diverse athletes of the time were accused of blood doping. In the late 1980s, recombinant human erythropoietin (EPO) began to supplant transfusion for doping. EPO use is a suspect in nearly 20 deaths in 4 years in European cyclists. In the 1998 Tour de France, a team was ejected for using EPO and six other teams quit the race. The beat goes on; in recent years, diverse endurance and sprint athletes have been caught or accused of using EPO. Tests to detect EPO are improving but are not yet foolproof. As EPO tests improve, blood transfusion is back in vogue and some athletes may have infused artificial blood. Tests for detecting artificial blood also exist, but it seems it will take widespread, year-round, unannounced, out-of-competition testing and stern penalties to deter blood doping.

  14. 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...

  15. Syntactic and Morphosyntactic Processing in Stroke-Induced and Primary Progressive Aphasia

    Directory of Open Access Journals (Sweden)

    Cynthia K. Thompson

    2013-01-01

    Full Text Available The paper reports findings derived from three experiments examining syntactic and morphosyntactic processing in individuals with agrammatic and logopenic variants of primary progressive aphasia (PPA-G and PPA-L, respectively and stroke-induced agrammatic and anomic aphasia (StrAg and StrAn, respectively. We examined comprehension and production of canonical and noncanonical sentence structures and production of tensed and nontensed verb forms using constrained tasks in experiments 1 and 2, using the Northwestern Assessment of Verbs and Sentences (NAVS [57] and the Northwestern Assessment of Verb Inflection (NAVI, Thompson and Lee, experimental version test batteries, respectively. Experiment 3 examined free narrative samples, focusing on syntactic and morphosyntactic measures, i.e. production of grammatical sentences, noun to verb ratio, open-class to closed-class word production ratio, and the production of correctly inflected verbs. Results indicate that the two agrammatic groups (i.e., PPA-G and StrAg pattern alike on syntactic and morphosyntactic measures, showing more impaired noncanonical compared to canonical sentence comprehension and production and greater difficulties producing tensed compared to nontensed verb forms. Their spontaneous speech also contained significantly fewer grammatical sentences and correctly inflected verbs, and they produced a greater proportion of nouns compared to verbs, than healthy speakers. In contrast, PPA-L and StrAn individuals did not display these deficits, and performed significantly better than the agrammatic groups on these measures. The findings suggest that agrammatism, whether induced by degenerative disease or stroke, is associated with characteristic deficits in syntactic and morphosyntactic processing. We therefore recommend that linguistically sophisticated tests and narrative analysis procedures be used to systematically evaluate the linguistic ability of individuals with PPA, contributing to

  16. Amplification variable factor amplifier

    NARCIS (Netherlands)

    Akitsugu, Oshita; Nauta, Bram

    2007-01-01

    PROBLEM TO BE SOLVED: To provide an amplification factor variable amplifier capable of achieving temperature compensation of an amplification factor over a wide variable amplification factor range. ; SOLUTION: A Gilbert type amplification factor variable amplifier 11 amplifies an input signal and

  17. Amplification variable factor amplifier

    NARCIS (Netherlands)

    Akitsugu, O.; Nauta, Bram

    2006-01-01

    PROBLEM TO BE SOLVED: To provide an amplification factor variable amplifier capable of achieving temperature compensation of an amplification factor over a wide variable amplification factor range. ; SOLUTION: A Gilbert type amplification factor variable amplifier 11 amplifies an input signal and

  18. Is the use of recombinant human erythropoietin in anaemia of ...

    African Journals Online (AJOL)

    In a double-blind placebo-eontrolled study we showed a 3-fold decrease in blood transfusions (BTFs) given to preterm infants with anaemia of prematurity who received recombinant erythropoietin. However, only 50% of placebo recipients required a BTF. Data from the placebo group indicated that either mean daily weight ...

  19. Erythropoietin protects the retinal pigment epithelial barrier against ...

    African Journals Online (AJOL)

    Erythropoietin (EPO) is not limited to hematopoiesis; it may act as a protective cytokine. In this study, the retinal pigment epithelial (RPE) cell viability, cell monolayer integrity, RPE barrier permeability, distribution of the junction proteins ZO-1, occludin and the levels of superoxide dismutase (SOD) and malondialdehyde ...

  20. Effect of recombinant human erythropoietin expressions of apoptosis ...

    African Journals Online (AJOL)

    Effect of recombinant human erythropoietin expressions of apoptosis genes in rats following traumatic brain injury. Xuesong Yuan1*, Xiaoxing Bian1, Wenfeng Wei1, Yin Tang2 and Qing Bao1. 1Department of Neurosurgery, 2Department of Pathology, The Affiliated Wujin Hospital of Jiangsu University, Changzhou. Jiangsu ...

  1. CORRECTION OF ANAEMIA WITH ERYTHROPOIETIN IN CKD/ESRD PATIENTS

    OpenAIRE

    Madhukar,; Shyamal; Rashmi; Anitha; Bhattacharjee; Anjaiah; Abdul; Kunal,

    2015-01-01

    Chronic kidney disease ( CKD) is characterized by gradual and permanent loss of kidney function. One of the most common complications of CKD is Anaemia . 1,3 Anaemia often appears earlier in course of CKD and worsens with disease progression. 1,2 Erythropoietin is a hormone synthesized in the kidney is deficient in the majority of ...

  2. Treatment of anemia of nephrotic syndrome with recombinant erythropoietin

    NARCIS (Netherlands)

    Gansevoort, RT; Vaziri, ND; deJong, PE

    Nephrotic syndrome has been recently shown to cause erythropoietin (EPO) deficiency in humans and experimental models. However, efficacy and safety of recombinant EPO (rEPO) in the treatment of the associated anemia has not been previously investigated. We report a patient with nephrotic syndrome

  3. Study the relationship of erythropoietin and chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    R.I. El-Korashy

    2012-07-01

    It also appeared that response to erythropoietin in COPD is probably blunted especially with increased severity of the condition. This might be considered as a contributing factor in the development of anemia in COPD which is considered as anemia of chronic disease.

  4. Recombinant erythropoietin found in seized blood bags from sportsmen.

    Science.gov (United States)

    Mallorquí, Joaquim; Segura, Jordi; de Bolòs, Carme; Gutiérrez-Gallego, Ricardo; Pascual, Jose A

    2008-02-01

    During an anti-doping investigation, the Spanish Guardia Civil confiscated blood bags from elite sportsmen. A novel immuno-purification method demonstrated that plasma samples with elevated erythropoietin (EPO) contained recombinant material (rEPO). This shows that rEPO is used before autologous blood transfusions and that rEPO analysis in plasma can be reliably addressed.

  5. The potential protective effects of erythropoietin and estrogen on ...

    African Journals Online (AJOL)

    Background: Renal ischemia–reperfusion (RIR) is an important etiopathological mechanism of acute renal failure (ARF). Erythropoietin (EPO) has been candidate as a nephroprotectant agent. However, its nephroprotective effect when it is accompanied with estrogen has not been studied in female. Methods: Fifty-six female ...

  6. Diurnal variations of serum erythropoietin at sea level and altitude

    DEFF Research Database (Denmark)

    Klausen, T; Poulsen, T D; Fogh-Andersen, N

    1996-01-01

    This study tested the hypothesis that the diurnal variations of serum-erythropoietin concentration (serum-EPO) observed in normoxia also exist in hypoxia. The study also attempted to investigate the regulation of EPO production during sustained hypoxia. Nine subjects were investigated at sea leve...

  7. Low noise tuned amplifier

    Science.gov (United States)

    Kleinberg, L. L. (Inventor)

    1984-01-01

    A bandpass amplifier employing a field effect transistor amplifier first stage is described with a resistive load either a.c. or directly coupled to the non-inverting input of an operational amplifier second stage which is loaded in a Wien Bridge configuration. The bandpass amplifier may be operated with a signal injected into the gate terminal of the field effect transistor and the signal output taken from the output terminal of the operational amplifier. The operational amplifier stage appears as an inductive reactance, capacitive reactance and negative resistance at the non-inverting input of the operational amplifier, all of which appear in parallel with the resistive load of the field effect transistor.

  8. Renal Cell Protection of Erythropoietin beyond Correcting The Anemia in Chronic Kidney Disease Patients.

    Science.gov (United States)

    Nasri, Hamid

    2014-01-01

    Currently many patients with chronic renal failure have profited from the use of erythropoietin to correct anemia (1,2). In chronic kidney disease, anemia is believed to be a surrogate index for tissue hypoxia that continues preexisting renal tissue injury (1-3). Erythropoietin is an essential glycoprotein that accelerates red blood cell maturation from erythroid progenitors and facilitates erythropoiesis. It is a 30.4 kD glycoprotein and class I cytokine containing 165 amino acids (3,4). Approximately 90% of systemic erythropoietin in adults is produced by peritubular interstitial fibroblasts in the renal cortex and outer medulla of the kidney (3-5). A feedback mechanism involving oxygen delivery to the tissues seems to regulate erythropoietin production. Hypoxia-inducible factor regulates transcription of the erythropoietin gene in the kidney, which determines erythropoietin synthesis (3-5). Erythropoietin is an essential glycoprotein that accelerates red blood cell maturation from erythroid progenitors and mediates erythropoiesis in the bone marrow (4-6). Kidney fibrosis is the last common pathway in chronic renal failure irrespective of the initial etiology (5,6). Constant inflammatory cell infiltration and pericyte-myofibroblast transition lead to renal fibrosis and insufficiency which result in decreased production of erythropoietin (4-7). Thus far, therapeutic efforts to treat patients with chronic renal failure by administering erythropoietin have been made only to correct anemia and putative hypoxic tissue damage. The introduction of recombinant human erythropoietin has marked a significant advance in the management of anemia associated with chronic renal failure (6-9). With an increasing number of patients with chronic renal failure receiving erythropoietin treatment, emerging evidence suggests that erythropoietin not only has an erythropoietic function, but also has renoprotective potential. In fact, in recent years, the additional non

  9. Evaluation of functional erythropoietin receptor status in skeletal muscle in vivo

    DEFF Research Database (Denmark)

    Christensen, Britt; Lundby, Carsten; Jessen, Niels

    2012-01-01

    as activation of Epo signalling pathways (STAT5, MAPK, Akt, IKK) were analysed by western blotting. Changes in muscle protein profiles after prolonged erythropoietin treatment were evaluated by 2D gel-electrophoresis and mass spectrometry. The presence of the erythropoietin receptor in skeletal muscle......Background: Erythropoietin receptors have been identified in human skeletal muscle tissue, but downstream signal transduction has not been investigated. We therefore studied in vivo effects of systemic erythropoietin exposure in human skeletal muscle. Methodology/Principal Findings: The protocols...... involved 1) acute effects of a single bolus injection of erythropoietin followed by consecutive muscle biopsies for 1-10 hours, and 2) a separate study with prolonged administration for 16 days with biopsies obtained before and after. The presence of erythropoietin receptors in muscle tissue as well...

  10. Anti-Erythropoietin Antibody Associated Pure Red Cell Aplasia Resolved after Liver Transplantation.

    Science.gov (United States)

    Hung, Annie K; Guy, Jennifer; Behler, Caroline M; Lee, Eugene E

    2015-01-01

    Patients undergoing antiviral therapy for chronic hepatitis C often develop anemia secondary to ribavirin and interferon. Recombinant erythropoietin has been used to improve anemia associated with antiviral therapy and to minimize dose reductions, which are associated with decreased rates of sustained virologic response. A rare potential side effect of recombinant erythropoietin is anti-erythropoietin antibody associated pure red cell aplasia. In chronic kidney disease patients with this entity, there have been good outcomes associated with renal transplant and subsequent immunosuppression. In this case, a chronic liver disease patient developed anti-erythropoietin associated pure red cell aplasia and recovered after liver transplantation and immunosuppression. It is unclear whether it is the transplanted organ, the subsequent immunosuppression, or the combination that contributed to the response. In conclusion, anti-erythropoietin associated pure red cell aplasia is a serious complication of erythropoietin therapy, but this entity should not be considered a contraindication for solid organ transplantation.

  11. Anti-Erythropoietin Antibody Associated Pure Red Cell Aplasia Resolved after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Annie K. Hung

    2015-01-01

    Full Text Available Patients undergoing antiviral therapy for chronic hepatitis C often develop anemia secondary to ribavirin and interferon. Recombinant erythropoietin has been used to improve anemia associated with antiviral therapy and to minimize dose reductions, which are associated with decreased rates of sustained virologic response. A rare potential side effect of recombinant erythropoietin is anti-erythropoietin antibody associated pure red cell aplasia. In chronic kidney disease patients with this entity, there have been good outcomes associated with renal transplant and subsequent immunosuppression. In this case, a chronic liver disease patient developed anti-erythropoietin associated pure red cell aplasia and recovered after liver transplantation and immunosuppression. It is unclear whether it is the transplanted organ, the subsequent immunosuppression, or the combination that contributed to the response. In conclusion, anti-erythropoietin associated pure red cell aplasia is a serious complication of erythropoietin therapy, but this entity should not be considered a contraindication for solid organ transplantation.

  12. Double conjugate laser amplifier

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, S.; Daunt, G.H.

    1991-01-29

    This paper describes a double conjugate laser amplifier system for producing a stable output laser beam in line with a laser oscillator input beam. It comprises: a laser oscillator which produces a low energy oscillator laser beam therefrom directly along a laser beam axis of the system; an amplification means comprised of double conjugate laser amplifiers further comprised of a first and a second singly phase conjugate amplifiers laterally opposite each other about the laser beam axis; polarizers with one of the polarizers positioned between each of the first and second singly phase conjugate amplifiers on the laser beam axis; Pockels cells with on of the Pockels cells positioned on the laser beam axis immediately prior to one of the polarizers; and a means for selectively switching the amplifier means comprised of applying a half-wave voltage at each of the Pockels cells to provide a polarization rotation of the input beam through 90{degrees} for routing of the oscillator laser beam directly through or reflected off the polarizes as an input beam to the amplification means wherein the amplification means amplifies the input beam twice in each of the first and second singly phase conjugate amplifiers and reflects the amplified laser beam off the polarizers as an amplified laser output beam in exactly the same direction as the input laser beam.

  13. Erythropoietin and carbamylated erythropoietin promote histone deacetylase 5 phosphorylation and nuclear export in rat hippocampal neurons

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Hye-Ryeong [Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering (Korea, Republic of); Kim, Yong-Seok [Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering (Korea, Republic of); Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791 (Korea, Republic of); Son, Hyeon, E-mail: hyeonson@hanyang.ac.kr [Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering (Korea, Republic of); Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791 (Korea, Republic of)

    2016-01-29

    Erythropoietin (EPO) produces neurotrophic effects in animal model of neurodegeneration. However, clinical use of EPO is limited due to thrombotic risk. Carbamylated EPO (cEPO), devoid of thrombotic risk, has been proposed as a novel neuroprotective and neurotrophic agent although the molecular mechanisms of cEPO remain incomplete. Here, we show a previously unidentified role of histone deacetylase 5 (HDAC5) in the actions of EPO and cEPO. EPO and cEPO regulate the HDAC5 phosphorylation at two critical sites, Ser259 and Ser498 through a protein kinase D (PKD) dependent pathway. In addition, EPO and cEPO rapidly stimulates nuclear export of HDAC5 in rat hippocampal neurons which expressing HDAC5-GFP. Consequently, EPO and cEPO enhanced the myocyte enhancer factor-2 (MEF2) target gene expression. Taken together, our results reveal that EPO and cEPO mediate MEF2 target gene expression via the regulation of HDAC5 phosphorylation at Ser259/498, and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of EPO and cEPO.

  14. Neuroprotective properties of a novel, non-haematopoietic agonist of the erythropoietin receptor

    DEFF Research Database (Denmark)

    Pankratova, Stanislava; Kiryushko, Dar'Ya; Sonn, Katrin

    2010-01-01

    , but with 10(3)-fold lower potency. Knockdown of the erythropoietin receptor or interference with its downstream signalling inhibited the Epotris-induced neuritogenic and pro-survival effect. Similarly to erythropoietin, Epotris penetrated the blood-brain barrier. Moreover, treatment with the peptide...... attenuated seizures, decreased mortality and reduced neurodegeneration in an in vivo model of kainic acid-induced neurotoxicity. In contrast to erythropoietin, Epotris did not stimulate erythropoiesis upon chronic administration. Thus, Epotris is a novel neuroprotective non-haematopoietic erythropoietin...

  15. Power amplifier circuit

    NARCIS (Netherlands)

    Takeya, Hideaki; Nauta, Bram

    2015-01-01

    PROBLEM TO BE SOLVED: To provide a power amplifier circuit which has high power efficiency while suppressing a fluctuation of output power relatively to a fluctuation of a power supply voltage in a high-efficiency switching amplifier which operates in a radio frequency band.SOLUTION: A duty ratio

  16. Oscillators and operational amplifiers

    DEFF Research Database (Denmark)

    Lindberg, Erik

    2005-01-01

    A generalized approach to the design of oscillators using operational amplifiers as active elements is presented. A piecewise-linear model of the amplifier is used so that it make sense to investigate the eigenvalues of the Jacobian of the differential equations. The characteristic equation...

  17. Erythropoietin and interleukin-2 activate distinct JAK kinase family members.

    OpenAIRE

    Barber, D L; D'Andrea, A D

    1994-01-01

    The erythropoietin (EPO) receptor and the interleukin-2 (IL-2) receptor beta-chain subunit are members of the cytokine receptor superfamily. They have conserved primary amino acid sequences in their cytoplasmic domains and activate phosphorylation of common substrates, suggesting common biochemical signaling mechanisms. We have generated a cell line, CTLL-EPO-R, that contains functional cell surface receptors for both EPO and IL-2. CTLL-EPO-R cells demonstrated similar growth kinetics in EPO ...

  18. Erythropoietin and hypothermia for hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Rogers, Elizabeth E; Bonifacio, Sonia L; Glass, Hannah C; Juul, Sandra E; Chang, Taeun; Mayock, Dennis E; Durand, David J; Song, Dongli; Barkovich, Anthony J; Ballard, Roberta A; Wu, Yvonne W

    2014-11-01

    Erythropoietin is neuroprotective in animal models of neonatal hypoxic-ischemic encephalopathy. We previously reported a phase I safety and pharmacokinetic study of erythropoietin in neonates. This article presents the neurodevelopmental follow-up of infants who were enrolled in the phase I clinical trial. We enrolled 24 newborns with hypoxic-ischemic encephalopathy in a dose-escalation study. Patients received up to six doses of erythropoietin in addition to hypothermia. All infants underwent neonatal brain magnetic resonance imaging (MRI) reviewed by a single neuroradiologist. Moderate-to-severe neurodevelopmental disability was defined as cerebral palsy with Gross Motor Function Classification System levels III-V or cognitive impairment based on Bayley Scales of Infant Development II mental developmental index or Bayley III cognitive composite score. Outcomes were available for 22 of 24 infants, at mean age 22 months (range, 8-34 months). There were no deaths. Eight (36%) had moderate-to-severe brain injury on neonatal MRI. Moderate-to-severe disability occurred in one child (4.5%), in the setting of moderate-to-severe basal ganglia and/or thalamic injury. Seven infants with moderate-to-severe watershed injury exhibited the following outcomes: normal (three), mild language delay (two), mild hemiplegic cerebral palsy (one), and epilepsy (one). All 11 patients with a normal brain MRI had a normal outcome. This study is the first to describe neurodevelopmental outcomes in infants who received high doses of erythropoietin and hypothermia during the neonatal period. The findings suggest that future studies are warranted to assess the efficacy of this new potential neuroprotective therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Does erythropoietin cause hemoglobin variability--is it 'normal'?

    Directory of Open Access Journals (Sweden)

    Ashwani K Gupta

    Full Text Available Hemoglobin variability (Hb-var in patients with chronic kidney disease has been stipulated to be a result of exogenous treatment with erythropoiesis stimulating agents (ESA and has been related to mortality in dialysis patients. We hypothesized the existence of Hb-var independent of ESA administration and compared it to that in healthy adults using data from the Scripps-Kaiser and NHANES III databases. We studied the Hb-var in 1571 peritoneal dialysis patients which included 116 patients not requiring treatment with erythropoietin. We systematically studied the differences between the groups that needed ESA therapy and those who did not. White race and male sex were significant predictors of need for erythropoietin therapy. We found peritoneal dialysis patients to exhibit significantly increased Hb-var independent of treatment with exogenous erythropoietin (0.99 gm/dL vs. 1.17 gm/dL, p-value60 years peritoneal dialysis patients was similar to that seen in healthy elders, suggesting similarity with anemia of aging. We conclude that exogenous ESA administration does not explain Hb-var entirely but may enhance it. Intrinsic factors affecting erythropoiesis including age may be the major determinants of Hb-var.

  20. Designing a small molecule erythropoietin mimetic.

    Science.gov (United States)

    Guarnieri, Frank

    2015-01-01

    Erythropoietin (EPO) is a protein made by the kidneys in response to low red blood cell count that is secreted into the bloodstream and binds to a receptor on hematopoietic stem cells in the bone marrow inducing them to become new red blood cells. EPO made with recombinant DNA technology was brought to market in the 1980s to treat anemia caused by kidney disease and cancer chemotherapy. Because EPO infusion was able to replace blood transfusions in many cases, it rapidly became a multibillion dollar per year drug and as the first biologic created with recombinant technology it launched the biotech industry. For many years intense research was focused on creating a small molecule orally available EPO mimetic. The Robert Wood Johnson (RWJ) group seemed to definitively establish that only large peptides with a minimum of 60 residues could replace EPO, as anything less was not a full agonist. An intense study of the published work led me to hypothesize that the size of the mimetic is not the real issue, but the symmetry making and breaking of the EPO receptor induced by the ligand is the key to activating the stem cells. This analysis meant that residues in the binding site of the receptor deemed absolutely essential for ligand binding and activation from mutagenesis experiments, were probably not really that important. My fundamental hypotheses were: (a) the symmetric state of the homodimeric receptor is the most stable state and thus must be the off-state, (b) a highly localized binding site exists at a pivot point where the two halves of the receptor meet, (c) small molecules can be created that have high potency for this site that will be competitive with EPO and thus can displace the protein-protein interaction, (d) small symmetric molecules will stabilize the symmetric off-state of the receptor, and (e) a key asymmetry in the small molecule will stabilize a mirror image asymmetry in the receptor resulting in the stabilization of the on-state and proliferation of

  1. Auto-Zero Differential Amplifier

    Science.gov (United States)

    Quilligan, Gerard T. (Inventor); Aslam, Shahid (Inventor)

    2017-01-01

    An autozero amplifier may include a window comparator network to monitor an output offset of a differential amplifier. The autozero amplifier may also include an integrator to receive a signal from a latched window comparator network, and send an adjustment signal back to the differential amplifier to reduce an offset of the differential amplifier.

  2. Erythropoietin in the general population: reference ranges and clinical, biochemical and genetic correlates.

    Directory of Open Access Journals (Sweden)

    Niels Grote Beverborg

    Full Text Available Although erythropoietin has been used for decades in the treatment of anemia, data regarding endogenous levels in the general population are scarce. Therefore, we determined erythropoietin reference ranges and its clinical, biochemical and genetic associations in the general population.We used data from 6,777 subjects enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND study. Fasting venous blood samples were obtained in the morning from all participants from 2001-2003. Serum erythropoietin concentrations were measured using a fully automated chemiluminescent enzyme-labeled immunometric assay. A genome-wide association study was performed to identify genetic determinants.Mean age (± SD was 53 ± 12 years and 50% were female. Median (IQR erythropoietin concentrations were 7.6 (5.8-9.9 IU/L in men and 7.9 (6.0-10.6 IU/L in women. A strong positive correlation was found between erythropoietin and waist circumference, glucose and systolic blood pressure (all P < 0.05. In subjects with normal renal function there was a strong exponential relation between hemoglobin and erythropoietin, whereas in renal impairment (eGFR < 60 mL/min/1.73m² this relation was linear (men or absent (women (P < 0.001 for interaction. Single-nucleotide polymorphisms at the HBS1L-MYB locus were shown to be related to erythropoietin levels (P < 9x10-21, more significantly than other erythrocyte parameters.We provide age-specific reference ranges for endogenous serum erythropoietin. Erythropoietin levels are positively associated with the components of the metabolic syndrome, except cholesterol. We show that even mild renal failure blunts erythropoietin production and propose the HBS1L-MYB locus as a regulator of erythropoietin.

  3. 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.

  4. Effect of a Structured Sensory Stimulation Program on the Sensory Function of Patients with Stroke-induced Disorder of Consciousness

    Directory of Open Access Journals (Sweden)

    Khadijeh Sargolzaei

    2017-07-01

    Full Text Available Background: About 50% of stroke patients suffer from the disorder of consciousness with such adverse effects as sensory deprivation. The provision of a care program consisting of simple and safe stimulations can prevent sensory deprivation and improve the patient’s sensory function. Aim: This study aimed to determine the effect of structured sensory stimulation program on the sensory function of the patients with stroke-induced disorder of consciousness. Method: This randomized clinical trial was conducted on 80 patients with stroke-induced disorder of consciousness admitted to the Intensive Care Unit and Emergency Department of Ghaem Hospital, Mashhad, Iran, in 2016. The participants were randomly assigned into two groups of control and intervention. The patients in the intervention group were subjected to a sensory stimulation program consisting of auditory, visual, olfactory, gustatory, tactile, and motor stimulations for 14 consecutive days. The sensory function was measured every day before and after the intervention using the Sensory Modality Assessment and Rehabilitation Technique (SMART instrument. On the other hand, the control group received the routine care. The data were analyzed in the SPSS version 11.5 using the Mann-Whitney test, Chi-square test, and independent t-test. Results: According to the results, the patients in the intervention and control groups had the mean ages of 66.2±8.9 and 63.8±10.8, respectively. The pre-intervention SMART scores of the two groups were homogenous (P=0.23. However, the independent t-test showed that the final SMART score was significantly higher (P

  5. The effect of erythropoietin on platelet function and fibrinolysis in chronic renal failure

    DEFF Research Database (Denmark)

    Stenver, Doris Irene; Jeppesen, L; Nielsen, B

    1994-01-01

    The influence of erythropoietin therapy on platelet function and fibrinolysis was evaluated in 12 anemic hemodialysis patients. Six months of therapy with human erythropoietin (50 to 80 IU/kg initially) raised the hemoglobin level to 10.8 g/dl but did not increase platelet activity in vivo as mea...

  6. The effect of erythropoietin on platelet function and fibrinolysis in chronic renal failure

    DEFF Research Database (Denmark)

    Stenver, Doris Irene; Jeppesen, L; Nielsen, B

    1994-01-01

    The influence of erythropoietin therapy on platelet function and fibrinolysis was evaluated in 12 anemic hemodialysis patients. Six months of therapy with human erythropoietin (50 to 80 IU/kg initially) raised the hemoglobin level to 10.8 g/dl but did not increase platelet activity in vivo...

  7. Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure

    NARCIS (Netherlands)

    Van der Meer, P.; Voors, Adriaan; Lipsic, Erik; Smilde, Tom; van Gilst, W.H.; Van Veldhuisen, D.J.

    2004-01-01

    Objectives This study aimed to investigate the prognostic importance of plasma erythropoietin (EPO) levels in chronic heart failure (CHF) patients. Background Anemia is common and is associated with an impaired survival in patients with CHF. Erythropoietin is a hematopoietic growth factor,

  8. Noise in Optical Amplifiers

    DEFF Research Database (Denmark)

    Jeppesen, Palle

    1997-01-01

    Noise in optical amplifiers is discussed on the basis of photons and electromagntic fields. Formulas for quantum noise from spontaneous emission, signal-spontaneous beat noise and spontaneous-spontaneous beat noise are derived.......Noise in optical amplifiers is discussed on the basis of photons and electromagntic fields. Formulas for quantum noise from spontaneous emission, signal-spontaneous beat noise and spontaneous-spontaneous beat noise are derived....

  9. Electrospun Amplified Fiber Optics

    OpenAIRE

    Morello, Giovanni; Camposeo, Andrea; Moffa, Maria; Pisignano, Dario

    2015-01-01

    A lot of research is focused on all-optical signal processing, aiming to obtain effective alternatives to existing data transmission platforms. Amplification of light in fiber optics, such as in Erbium-doped fiber amplifiers, is especially important for an efficient signal transmission. However, the complex fabrication methods, involving high-temperature processes performed in highly pure environment, slow down the fabrication and make amplified components expensive with respect to an ideal, ...

  10. Asymmetric Dimethylarginine Contributes to the Impaired Response to Erythropoietin in CKD-Anemia.

    Science.gov (United States)

    Yokoro, Miyuki; Nakayama, Yosuke; Yamagishi, Sho-Ichi; Ando, Ryotaro; Sugiyama, Miki; Ito, Sakuya; Yano, Junko; Taguchi, Kensei; Kaida, Yusuke; Saigusa, Daisuke; Kimoto, Masumi; Abe, Takaaki; Ueda, Seiji; Fukami, Kei

    2017-09-01

    Erythropoietin-resistant anemia is associated with adverse cardiovascular events in patients with ESRD, but the underlying mechanism remains unclear. Here, we evaluated the role of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). In 54 patients with advanced CKD, erythrocyte but not plasma ADMA levels independently associated with low hemoglobin values, although levels of both types of ADMA were elevated compared with those in healthy volunteers. Furthermore, erythrocyte ADMA level associated with the erythropoietin resistance index in patients receiving a weekly injected dose of erythropoiesis-stimulating agents standardized for hemoglobin levels and body weight, whereas it correlated with the erythropoietin demand index (plasma erythropoietin units divided by the hemoglobin value) in patients not receiving erythropoiesis-stimulating agents. Compared with sham-operated controls, wild-type mice with 5/6 subtotal nephrectomy (Nx), a remnant kidney model with advanced CKD, had decreased hemoglobin, hematocrit, and mean corpuscular volume values but increased erythrocyte and plasma ADMA and plasma erythropoietin levels. In comparison, dimethylarginine dimethlaminohydrolase-1 transgenic (DDAH-1 Tg) mice, which efficiently metabolized ADMA, had significant improvements in all of the values except those for erythropoietin after 5/6 Nx. Additionally, wild-type Nx mice, but not DDAH-1 Tg Nx mice, had reduced splenic gene expression of erythropoietin receptor and erythroferrone, which regulates iron metabolism in response to erythropoietin. This study suggests that erythrocyte ADMA accumulation contributes to impaired response to erythropoietin in predialysis patients and advanced CKD mice via suppression of erythropoietin receptor expression. Copyright © 2017 by the American Society of Nephrology.

  11. Erythropoietin and the use of a transgenic model of erythropoietin-deficient mice

    Directory of Open Access Journals (Sweden)

    Pichon A

    2016-04-01

    Full Text Available Aurélien Pichon,1–3 Florine Jeton,1,2 Raja El Hasnaoui-Saadani,4 Luciana Hagström,5 Thierry Launay,6 Michèle Beaudry,1 Dominique Marchant,1 Patricia Quidu,1 Jose-Luis Macarlupu,7 Fabrice Favret,8 Jean-Paul Richalet,1,2 Nicolas Voituron1,2 1Laboratory “Hypoxia and Lung” EA 2363, University Paris 13, Sorbonne Paris Cité, Bobigny Cedex, 2Laboratory of Excellence GR-Ex, Paris, 3Laboratory MOVE EA 6314, FSS, Poitiers University, Poitiers, France; 4Research Unit, College of Medicine, Princess Noura University, Riyadh, Saudi Arabia; 5Laboratório Interdisciplinar de Biociências, Universidade de Brasília, Brasília, Brazil; 6Unité de Biologie Intégrative des Adaptations à l'Exercice, University Paris Saclay and Genopole®, University Sorbonne-Paris-Cité, Paris, France; 7High Altitude Unit, Laboratories for Research and Development, Universidad Peruana Cayetano Heredia, Lima, Peru; 8Laboratory “Mitochondrie, Stress Oxydant et Protection Musculaire” EA 3072, University of Strasbourg, Strasbourg, France Abstract: Despite its well-known role in red blood cell production, it is now accepted that erythropoietin (Epo has other physiological functions. Epo and its receptors are expressed in many tissues, such as the brain and heart. The presence of Epo/Epo receptors in these organs suggests other roles than those usually assigned to this protein. Thus, the aim of this review is to describe the effects of Epo deficiency on adaptation to normoxic and hypoxic environments and to suggest a key role of Epo on main physiological adaptive functions. Our original model of Epo-deficient (Epo-TAgh mice allowed us to improve our knowledge of the possible role of Epo in O2 homeostasis. The use of anemic transgenic mice revealed Epo as a crucial component of adaptation to hypoxia. Epo-TAgh mice survive well in hypoxic conditions despite low hematocrit. Furthermore, Epo plays a key role in neural control of ventilatory acclimatization and response to

  12. The relationship of serum erythropoietin level with coronary collateral grade.

    Science.gov (United States)

    Sahinarslan, Asife; Yalcin, Ridvan; Kocaman, Sinan Altan; Ercin, Ugur; Tanalp, Ali Cevat; Topal, Salih; Bukan, Neslihan; Boyaci, Bulent; Cengel, Atiye

    2011-01-01

    Erythropoietin has been shown to induce neovascularization and protect against ischemic vascular injury. We investigated whether a higher serum erythropoietin (EPO) level is related to better coronary collateral vessel grade. Ninety-nine patients with stable angina pectoris who have at least 1 coronary stenosis of equal to or greater than 70% at coronary angiography were prospectively enrolled. Serum EPO and vascular endothelial growth factor (VEGF) levels were studied. Coronary collateral degree was graded according to the Rentrop method. Patients with grade 2-3 collateral degree were included in the good collateral group and formed Group I. The patients with grade 0-1 collateral degree were included in the poor collateral group and formed Group II. The serum EPO level was significantly higher in the good collateral group (17.3 ± 9.3 mU/mL vs 11.7 ± 5.0 mU/mL; P < 0.001). There was also a positive correlation between serum EPO level and Rentrop score (r = 0.39; P < 0.001). In multivariate analysis, serum EPO level (odds ratio [OR] 1.336; 95% confidence interval [CI], 1.120-1.593; P = 0.001), oxygen saturation (OR 0.638; 95% CI, 0.422-0.963; P = 0.033) and presence of chronic total occlusion (CTO) (OR 26.7; 95% CI, 3.874-184.6; P = 0.001) were independently related to well-developed coronary collaterals. Higher serum EPO level is related to better coronary collateral development. Erythropoietin may have a positive effect on the development of collaterals and may provide a new agent for the treatment strategies to enhance coronary collateral vessel development. Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  13. Biological evaluation of recombinant human erythropoietin in pharmaceutical products

    Directory of Open Access Journals (Sweden)

    Ramos A.S.

    2003-01-01

    Full Text Available The potencies of mammalian cell-derived recombinant human erythropoietin pharmaceutical preparations, from a total of five manufacturers, were assessed by in vivo bioassay using standardized protocols. Eight-week-old normocythemic mice received a single subcutaneous injection followed by blood sampling 96 h later or multiple daily injections with blood sampling 24 h after the last injection. Reticulocyte counting by microscopic examination was employed as the end-point using the brilliant cresyl blue or selective hemolysis methods, together with automated flow cytometry. Different injection schedules were investigated and dose-response curves for the European Pharmacopoeia Biological Reference Preparation of erythropoietin were compared. Manual and automated methods of reticulocyte counting were correlated with respect to assay validity and precision. Using 8 mice per treatment group, intra-assay precision determined for all of the assays in the study showed coefficients of variation of 12.1-28.4% for the brilliant cresyl blue method, 14.1-30.8% for the selective hemolysis method and 8.5-19.7% for the flow cytometry method. Applying the single injection protocol, a combination of at least two independent assays was required to achieve the precision potency and confidence limits indicated by the manufacturers, while the multiple daily injection protocol yielded the same acceptable results within a single assay. Although the latter protocol using flow cytometry for reticulocyte counting gave more precise and reproducible results (intra-assay coefficients of variation: 5.9-14.2%, the well-characterized manual methods provide equally valid alternatives for the quality control of recombinant human erythropoietin therapeutic products.

  14. Hemopoietic cell precursor responses to erythropoietin in plasma clot cultures

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, W.L.

    1979-01-01

    The time dependence of the response of mouse bone marrow cells to erythropoietin (Ep) in vitro was studied. Experiments include studies on the Ep response of marrow cells from normal, plethoric, or bled mice. Results with normal marrow reveal: (1) Not all erythroid precursors (CFU-E) are alike in their response to Ep. A significant number of the precursors develop to a mature erythroid colony after very short Ep exposures, but they account for only approx. 13% of the total colonies generated when Ep is active for 48 hrs. If Ep is active more than 6 hrs, a second population of erythroid colonies emerges at a nearly constant rate until the end of the culture. Full erythroid colony production requires prolonged exposure to erythropoietin. (2) The longer erythropoietin is actively present, the larger the number of erythroid colonies that reach 17 cells or more. Two distinct populations of immediate erythroid precursors are also present in marrow from plethoric mice. In these mice, total colony numbers are equal to or below those obtained from normal mice. However, the population of fast-responding CFU-E is consistently decreased to 10 to 20% of that found in normal marrow. The remaining colonies are formed from plethoric marrow at a rate equal to normal marrow. With increasing Ep exposures, the number of large colonies produced increases. From the marrow of bled mice, total erythroid colony production is equal to or above that of normal marrow. Two populations of colony-forming cells are again evident, with the fast-responding CFU-E being below normal levels. The lack of colonies from this group was compensated in bled mice by rapid colony production in the second population. A real increase in numbers of precursors present in this pool increased the rate of colony production in culture to twice that of normal marrow. The number of large colonies obtained from bled mice was again increased as the Ep exposure was lengthened. (ERB)

  15. Effects of intraosseous erythropoietin during hemorrhagic shock in swine.

    Directory of Open Access Journals (Sweden)

    Vesna Borovnik-Lesjak

    Full Text Available OBJECTIVE: To determine whether erythropoietin given during hemorrhagic shock (HS ameliorates organ injury while improving resuscitation and survival. METHODS: Three series of 24 pigs each were studied. In an initial series, 50% of the blood volume (BV was removed in 30 minutes and normal saline (threefold the blood removed started at minute 90 infusing each third in 30, 60, and 150 minutes with shed blood reinfused at minute 330 (HS-50BV. In a second series, the same HS-50BV protocol was used but removing an additional 15% of BV from minute 30 to 60 (HS-65BV. In a final series, blood was removed as in HS-65BV and intraosseous vasopressin given from minute 30 (0.04 U/kg min(-1 until start of shed blood reinfusion at minute 150 (HS-65BV+VP. Normal saline was reduced to half the blood removed and given from minute 90 to 120 in half of the animals. In each series, animals were randomized 1:1 to receive erythropoietin (1,200 U/kg or control solution intraosseously after removing 10% of the BV. RESULTS: In HS-50BV, O2 consumption remained near baseline yielding minimal lactate increases, 88% resuscitability, and 60% survival at 72 hours. In HS-65BV, O2 consumption was reduced and lactate increased yielding 25% resuscitability. In HS-65BV+VP, vasopressin promoted hemodynamic stability yielding 92% resuscitability and 83% survival at 72 hours. Erythropoietin did not affect resuscitability or subsequent survival in any of the series but increased interleukin-10, attenuated lactate increases, and ameliorated organ injury based on lesser troponin I, AST, and ALT increases and lesser neurological deficits in the HS-65BV+VP series. CONCLUSIONS: Erythropoietin given during HS in swine failed to alter resuscitability and 72 hour survival regardless of HS severity and concomitant treatment with fluids and vasopressin but attenuated acute organ injury. The studies also showed the efficacy of vasopressin and restrictive fluid resuscitation for hemodynamic

  16. High-dose erythropoietin in patients with progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Schreiber, Karen; Magyari, Melinda; Sellebjerg, Finn

    2017-01-01

    BACKGROUND: Erythropoietin (EPO) is a part of an endogenous neuroprotective system in the brain and may address pathophysiological mechanisms in progressive multiple sclerosis (MS). OBJECTIVE: To evaluate a treatment effect of EPO on progressive MS. METHODS: This was a single-center, randomized......, double-blind, placebo-controlled phase 2 trial, in which 52 patients with secondary or primary progressive MS were allocated to treatment with recombinant EPO (48,000 IU) or placebo, administered intravenously 17 times during 24 weeks. Patients had an Expanded Disability Status Score (EDSS) from 4 to 6...

  17. Electrospun amplified fiber optics.

    Science.gov (United States)

    Morello, Giovanni; Camposeo, Andrea; Moffa, Maria; Pisignano, Dario

    2015-03-11

    All-optical signal processing is the focus of much research aiming to obtain effective alternatives to existing data transmission platforms. Amplification of light in fiber optics, such as in Erbium-doped fiber amplifiers, is especially important for efficient signal transmission. However, the complex fabrication methods involving high-temperature processes performed in a highly pure environment slow the fabrication process and make amplified components expensive with respect to an ideal, high-throughput, room temperature production. Here, we report on near-infrared polymer fiber amplifiers working over a band of ∼20 nm. The fibers are cheap, spun with a process entirely carried out at room temperature, and shown to have amplified spontaneous emission with good gain coefficients and low levels of optical losses (a few cm(-1)). The amplification process is favored by high fiber quality and low self-absorption. The found performance metrics appear to be suitable for short-distance operations, and the large variety of commercially available doping dyes might allow for effective multiwavelength operations by electrospun amplified fiber optics.

  18. Erythropoietin improves operant conditioning and stability of cognitive performance in mice

    Directory of Open Access Journals (Sweden)

    Ehrenreich Hannelore

    2009-07-01

    Full Text Available Abstract Background Executive functions, learning and attention are imperative facets of cognitive performance, affected in many neuropsychiatric disorders. Recently, we have shown that recombinant human erythropoietin improves cognitive functions in patients with chronic schizophrenia, and that it leads in healthy mice to enhanced hippocampal long-term potentiation, an electrophysiological correlate of learning and memory. To create an experimental basis for further mechanistic insight into erythropoietin-modulated cognitive processes, we employed the Five Choice Serial Reaction Time Task. This procedure allows the study of the effects of erythropoietin on discrete processes of learning and attention in a sequential fashion. Results Male mice were treated for 3 weeks with erythropoietin (5,000 IU/kg versus placebo intraperitoneally every other day, beginning at postnatal day 28. After termination of treatment, mice were started on the Five Choice Serial Reaction Time Task, with daily training and testing extending to about 3 months. Overall, a significantly higher proportion of erythropoietin-treated mice finished the task, that is, reached the criteria of adequately reacting to a 1.0 sec flash light out of five arbitrarily appearing choices. During acquisition of this capability, that is, over almost all sequential training phases, learning readouts (magazine training, operant and discriminant learning, stability of performance were superior in erythropoietin-treated versus control mice. Conclusion Early erythropoietin treatment leads to lasting improvement of cognitive performance in healthy mice. This finding should be exploited in novel treatment strategies for brain diseases.

  19. Pharmacological Effects of Erythropoietin and its Derivative Carbamyl erythropoietin in Cerebral White Matter Injury

    Science.gov (United States)

    Liu, Wei

    Periventricular leukomalacia (PVL) is the predominant form of brain injury in the premature infant and the most common cause of cerebral palsy, yet no therapy currently exists for this serious human disorder. As PVL often occurs in preterm infants suffering from cerebral hypoxia/ischemia with or without prior exposure to maternal-fetal infection/inflammation, we used hypoxia/ischemia with or without lipopolysaccharide (LPS) injection, to produce clinically relevant PVL-like lesions in the white matter in postnatal day six (P6) mice. We studied the white matter pathology under different conditions, such as different durations of hypoxia and different doses of LPS, to evaluate the effects of those etiological factors on neonatal white matter injury. Distinct related pathological events were investigated at different time points during the progression of PVL. We used immunohistochemistry, histological analysis, and electron microscopy (EM) to study demylination that occurs in the white matter area, which is consistent with the pathology of human PVL. Previous studies have shown that erythropoietin (EPO) and its derivative carbamylated EPO (CEPO) are neuroprotective in various experimental models of brain injury. However, none of these studies investigated their efficacy against white matter injury using appropriate animal models of PVL. We produced unilateral or bilateral white matter injury in P6 mice using unilateral carotid ligation (UCL) followed by hypoxia (6% oxygen, 35 min) or by UCL/hypoxia plus LPS injection, respectively. We administered a single intraperitoneal (i.p.) dose of EPO or CEPO (5000 IU/kg) immediately after the insult, and found both drugs to provide significant protection against white matter injury in PVL mice compared to vehicle-treated groups. In addition, EPO and CEPO treatments attenuated neurobehavioral dysfunctions in an acute manner after PVL injury. EPO and CEPO have relatively few adverse effects, and thus may be a therapeutic agent

  20. Erythropoietin inhibits osteoblast function in myelodysplastic syndromes via the canonical Wnt pathway.

    Science.gov (United States)

    Balaian, Ekaterina; Wobus, Manja; Weidner, Heike; Baschant, Ulrike; Stiehler, Maik; Ehninger, Gerhard; Bornhäuser, Martin; Hofbauer, Lorenz C; Rauner, Martina; Platzbecker, Uwe

    2018-01-01

    The effects of erythropoietin on osteoblasts and bone formation are controversial. Since patients with myelodysplastic syndromes often display excessively high erythropoietin levels, we aimed to analyze the effect of erythropoietin on osteoblast function in myelodysplastic syndromes and define the role of Wnt signaling in this process. Expression of osteoblast-specific genes and subsequent osteoblast mineralization was increased in mesenchymal stromal cells from healthy young donors by in vitro erythropoietin treatment. However, erythropoietin failed to increase osteoblast mineralization in old healthy donors and in patients with myelodysplasia, whereas the basal differentiation potential of the latter was already significantly reduced compared to that of age-matched controls ( P <0.01). This was accompanied by a significantly reduced expression of genes of the canonical Wnt pathway. Treatment of these cells with erythropoietin further inhibited the canonical Wnt pathway. Exposure of murine cells (C2C12) to erythropoietin also produced a dose-dependent inhibition of TCF/LEF promoter activity (maximum at 500 IU/mL, -2.8-fold; P <0.01). The decreased differentiation capacity of erythropoietin-pretreated mesenchymal stromal cells from patients with myelodysplasia could be restored by activating the Wnt pathway using lithium chloride or parathyroid hormone. Its hematopoiesis-supporting capacity was reduced, while reactivation of the canonical Wnt pathway in mesenchymal stromal cells could reverse this effect. Thus, these data demonstrate that erythropoietin modulates components of the osteo-hematopoietic niche in a context-dependent manner being anabolic in young, but catabolic in mature bone cells. Targeting the Wnt pathway in patients with myelodysplastic syndromes may be an appealing strategy to promote the functional capacity of the osteo-hematopoietic niche. Copyright© 2018 Ferrata Storti Foundation.

  1. Protective Effects of Salidroside on Mitochondrial Functions against Exertional Heat Stroke-Induced Organ Damage in the Rat

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2015-01-01

    Full Text Available Exertional heat stroke (EHS results in a constellation of systemic inflammatory responses resulting in multiorgan failure and an extremely high mortality. The present study was designed to evaluate the protective effects of salidroside on EHS by improving mitochondrial functions in the rat model. Liver and heart mitochondria were observed by transmission electron microscopy and mitochondrial membrane potential (ΔΨm was detected by a fluorescent probe. Intramitochondrial free Ca2+ concentration, mitochondrial respiratory control ratio (RCR, reactive oxygen species (ROS levels, superoxide dismutase (SOD, and malondialdehyde (MDA activity were detected by the corresponding kits. RT-PCR was performed to estimate peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α and manganese form of SOD (MnSOD mRNA expression. The results demonstrated that salidroside was able to relieve EHS damage by reducing the swelling of mitochondria, ROS levels, and MDA activity, as well as increasing ΔΨm, RCR, free Ca2+ concentration, SOD, PGC-1α, and MnSOD mRNA levels. In conclusion, salidroside has protective effects on mitochondrial functions against exertional heat stroke-induced organ damage in the rat.

  2. Benchmarking the state comparison amplifier

    Science.gov (United States)

    Kleczkowska, Klaudia; Puthoor, Ittoop Vergheese; Bain, Lauren; Andersson, Erika

    2017-10-01

    The state comparison amplifier is a recently proposed probabilistic quantum amplifier, intended especially for amplifying coherent states. Its realization is simple and uses only linear optics and photodetectors, and the preparation of a "guess" state, typically a coherent state. Fidelity and success probability can be high compared with other probabilistic amplifiers. State comparison amplification does, however, extract information about the amplified state, which means that it is especially important to benchmark it against a simple measure-and-resend procedure. We compare state comparison quantum amplifiers to measure-and-resend strategies, and identify parameter regimes and scenarios where these can and where they cannot provide an advantage.

  3. La eritropoyetina un neuroprotector potencial Erythropoietin: A potential neuroreceptor

    Directory of Open Access Journals (Sweden)

    Alain Valdivia Acosta

    2007-08-01

    Full Text Available La importante función fisiológica de la hormona eritropoyetina en el proceso eritropoyético se descubrió hace alrededor de un siglo. Mas recientemente se ha trabajado en su obtención por vía recombinante para su aplicación en pacientes con anemias agudas o crónicas, causadas por diferentes afecciones. Esta terapia mejora, sin lugar a duda, la calidad de vida de estos pacientes. A partir del año 1998, se reportaron por primera vez las propiedades neuroprotectoras de la eritropoyetina y se realizaron estudios que así lo corroboraron con el empleo de modelos de daño cerebral, tanto in vitro como in vivo. Los estudios actuales consisten en dilucidar a profundidad los mecanismos de acción por los cuales la eritropoyetina muestra sus propiedades neuroprotectoras y en obtener una adecuada biodisponibildad de la molécula para su aplicación segura en la terapéutica de afecciones del cerebro. El presente trabajo recopila información actualizada sobre la eritropoyetina como agente neuroprotector y refiere la continuidad de estudios para su aplicación en la clínica.A century ago, significant physiolgical function of Erithropoietin was discovered. More recently, it has been working on its obtention by a recombinant via for application in patients presenting with acute and chronic anemia, from different afections. This type of therapy improves undoubtedly, life quality of these patients. From 1998, neuroprotective properties of Erythropoietin were retorted for the first time, and we performed studies corroborating it b y means of use of bran damage model, both, in vitro and in vivo. Present studies are designed to elucidate deeply action mechanisms by which Erythropoietin shows its neuroprotective properties and to obtain a appropriate bioavailability of molecule for a accurate application in therapeutics of bran afections. Present paper collets updated information on Erythropoietin as a neuroprotective agent, and refers to continuity of

  4. Plasmodium berghei ANKA: erythropoietin activates neural stem cells in an experimental cerebral malaria model

    DEFF Research Database (Denmark)

    Core, Andrew; Hempel, Casper; Kurtzhals, Jørgen A L

    2011-01-01

    Cerebral malaria (CM) causes substantial mortality and neurological sequelae in survivors, and no neuroprotective regimens are currently available for this condition. Erythropoietin (EPO) reduces neuropathology and improves survival in murine CM. Using the Plasmodium berghei model of CM, we...

  5. Erythropoietin in traumatic brain injury: study protocol for a randomised controlled trial.

    LENUS (Irish Health Repository)

    Nichol, Alistair

    2015-02-08

    Traumatic brain injury is a leading cause of death and disability worldwide. Laboratory and clinical studies demonstrate a possible beneficial effect of erythropoietin in improving outcomes in the traumatic brain injury cohort. However, there are concerns regarding the association of erythropoietin and thrombosis in the critically ill. A large-scale, multi-centre, blinded, parallel-group, placebo-controlled, randomised trial is currently underway to address this hypothesis.

  6. The effect of erythropoietin on cognition in affective disorders

    DEFF Research Database (Denmark)

    Ott, Caroline Vintergaard; Vinberg, Maj; Kessing, Lars V

    2016-01-01

    This is a secondary data analysis from our erythropoietin (EPO) trials. We examine (I) whether EPO improves speed of complex cognitive processing across bipolar and unipolar disorder, (II) if objective and subjective baseline cognitive impairment increases patients׳ chances of treatment......-efficacy and (III) if cognitive improvement correlates with better subjective cognitive function, quality of life and socio-occupational capacity. Patients with unipolar or bipolar disorder were randomized to eight weekly EPO (N=40) or saline (N=39) infusions. Cognition, mood, quality of life and socio......-occupational capacity were assessed at baseline (week 1), after treatment completion (week 9) and at follow-up (week 14). We used repeated measures analysis of covariance to investigate the effect of EPO on speed of complex cognitive processing. With logistic regression, we examined whether baseline cognitive...

  7. Neuroprotective effects of erythropoietin in patients with carbon monoxide poisoning.

    Science.gov (United States)

    Pang, Li; Bian, Miao; Zang, Xiu-Xian; Wu, Yang; Xu, Da-Hai; Dong, Ning; Wang, Zhi-Hao; Yan, Bai-Ling; Wang, Da-Wei; Zhao, Hui-Jie; Zhang, Nan

    2013-05-01

    The purpose of this study was to evaluate the efficacy of erythropoietin (EPO) for treating patients with carbon monoxide (CO) poisoning. We conducted a randomized, prospective study of 103 patients with CO poisoning in two groups: an EPO group (n = 54; patients received EPO) and a placebo group (n = 49; patients received normal saline). The study endpoints were the functional outcome at day 30 (the Barthel index and neurologic sequelae), National Institutes of Health Stroke Scale (NIHSS) score, and the levels of S-100β. At 18 days, the NIHSS score improved significantly and S-100β levels significantly decreased in patients in the EPO group. At 30 days, patients in the EPO group had a superior Barthel index and fewer patients had delayed neurologic sequelae (DNS). This study demonstrated that early administration of EPO to patients with CO poisoning improved neurological outcomes and reduced the incidence of DNS. © 2013 Wiley Periodicals, Inc.

  8. Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhang

    2014-06-01

    Full Text Available Erythropoietin (EPO regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR, suggest the potential for EPO response in metabolism and disease.

  9. The Antioxidant Effect of Erythropoietin on Thalassemic Blood Cells

    Directory of Open Access Journals (Sweden)

    Johnny Amer

    2010-01-01

    Full Text Available Because of its stimulating effect on RBC production, erythropoietin (Epo is used to treat anemia, for example, in patients on dialysis or on chemotherapy. In β-thalassemia, where Epo levels are low relative to the degree of anemia, Epo treatment improves the anemia state. Since RBC and platelets of these patients are under oxidative stress, which may be involved in anemia and thromboembolic complications, we investigated Epo as an antioxidant. Using flow-cytometry technology, we found that in vitro treatment with Epo of blood cells from these patients increased their glutathione content and reduced their reactive oxygen species, membrane lipid peroxides, and external phosphatidylserine. This resulted in reduced susceptibility of RBC to undergo hemolysis and phagocytosis. Injection of Epo into heterozygous (Hbbth3/+ β-thalassemic mice reduced the oxidative markers within 3 hours. Our results suggest that, in addition to stimulating RBC and fetal hemoglobin production, Epo might alleviate symptoms of hemolytic anemias as an antioxidant.

  10. Erythropoietin enhances hippocampal response during memory retrieval in humans

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla; O'Sullivan, Ursula; Harmer, Catherine J

    2007-01-01

    Although erythropoietin (Epo) is best known for its effects on erythropoiesis, recent evidence suggests that it also has neurotrophic and neuroprotective properties in animal models of hippocampal function. Such an action in humans would make it an intriguing novel compound for the treatment......) or saline in a between-subjects, double-blind, randomized design. Neural response during picture encoding and retrieval was tested 1 week later. Epo increased hippocampus response during picture retrieval (n = 11) compared with placebo (n = 12; p = 0.04) independent of changes in hematocrit....... This is consistent with upregulation of hippocampal BDNF and neurotrophic actions found in animals and highlights Epo as a promising candidate for treatment of psychiatric disorders....

  11. 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....... rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p muscle....

  12. Effects of recombinant humant erythropoietin in normal humans

    DEFF Research Database (Denmark)

    Lundby, Carsten; Olsen, Niels Vidiendal

    2011-01-01

    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......, 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...

  13. Demonstration of SQUID Parametric Amplifier.

    Science.gov (United States)

    AMPLIFIERS, *PREAMPLIFIERS, *RECEIVERS, *SUPERCONDUCTIVITY, CEPHALOPODA , ELECTROMAGNETISM, HETERODYNING, INTERFERENCE, LEVEL(QUANTITY), LIMITATIONS, MILLIMETER WAVES, NOISE, QUANTUM THEORY, RADIOFREQUENCY, SURVIVABILITY, TEMPERATURE.

  14. Recombinant erythropoietin and analogues: a challenge for doping control.

    Science.gov (United States)

    Pascual, J A; Belalcazar, V; de Bolos, C; Gutiérrez, R; Llop, E; Segura, J

    2004-04-01

    Erythropoietin (EPO) increases the number of circulating erythrocytes and thus muscle oxygenation. The availability of the recombinant protein (rEPO) has increased the risk of its illegal use in sports, its detection being a difficult challenge. Five different hematopoietic parameters were initially chosen as indirect markers of rEPO abuse: concentration of serum EPO, concentration of serum-soluble transferrin receptors (sTFr), hematocrit, percentage of reticulocytes, and percentage of macrocytes. New models considering only hemoglobin, serum EPO concentration, and percentage of reticulocytes are simpler and seem to be more sensitive when low doses of rEPO are used. A more direct method of urine analysis (isoelectrofocusing, double blotting, and chemiluminescent detection) based on the charge differences between rEPO and endogenous EPO, related to their carbohydrate composition, provides proof of rEPO use. Furthermore, this approach permits the detection of darbepoetin, a direct analogue of EPO also known as NESP ("new erythropoiesis stimulating protein"). Recently a protein conjugate, "synthetic erythropoiesis protein" (SEP), containing precision-length, monodisperse, negatively charged polymers instead of oligosaccharides has been synthesized. Finally, EPO-mimetics are molecules capable of acting as EPO in dimerizing the EPO receptor. Two kinds of EPO-mimetics have been described: peptides and nonpeptides. The enhancement of oxygen availability to muscles by rEPO, analogues, and mimetics constitutes one of the main challenges to doping control. Major steps have already been developed for detection ofrEPO and some analogues. In the near future, the transfection to an athlete's body of genes that code for erythropoietin might be an emerging doping issue, and sports authorities have incorporated "gene doping" among the prohibited practices.

  15. Hepcidin clearance is associated with erythropoietin requirement in stable hemodialysis patients
.

    Science.gov (United States)

    Ashby, Damien; Busbridge, Mark; Hildebrand, Sarah; Clarke, Candice; Aldous, Georgina; Palan, Mitul; Murphy, Kevin; Duncan, Neill; Choi, Peter

    2017-05-01

    The discovery of hepcidin, the hormone regulating iron absorption and transport, has improved the understanding of anemia and erythropoietin treatment. Excessive hepcidin signaling causes anemia in chronic inflammatory conditions by restricting iron delivery to the bone marrow. Hepcidin is normally eliminated in the urine, and the high levels seen in renal failure are thought to contribute to renal anemia and resistance to erythropoietin. Clearance of hepcidin by hemodialysis was investigated in this study by measurement of plasma hepcidin before and after a single dialysis session in 204 patients. Results: Dialysis significantly reduced circulating hepcidin (p < 0.001) with median (IQR) clearance 47.7 (34.2 - 61.0)%. Dialytic hepcidin clearance was correlated with spKt/V (R = 0.202, p = 0.006), but not related to session length or membrane flux. There was also a strong correlation between hepcidin clearance and erythropoietin dose (R = -0.193, p = 0.007), sufficient to displace more traditional markers of erythropoietin resistance in a linear regression model, suggesting that increased dialytic removal of hepcidin could improve erythropoietin sensitivity. Hemodialysis reduces circulating hepcidin. Greater hepcidin clearance, which is related to spKt/V, is strongly associated with reduced erythropoietin requirement. This further implicates hepcidin in the pathogenesis of renal anemia and suggests that hepcidin could be a useful therapeutic target for dialysis patients.
.

  16. Swallowing Tablets and Capsules Increases the Risk of Penetration and Aspiration in Patients with Stroke-Induced Dysphagia.

    Science.gov (United States)

    Schiele, Julia T; Penner, Heike; Schneider, Hendrik; Quinzler, Renate; Reich, Gabriele; Wezler, Nikolai; Micol, William; Oster, Peter; Haefeli, Walter E

    2015-10-01

    We evaluated the prevalence of difficulties swallowing solid dosage forms in patients with stroke-induced dysphagia and whether swallowing tablets/capsules increases their risk of penetration and aspiration. Concurrently, we explored whether routinely performed assessment tests help identify patients at risk. Using video endoscopy, we evaluated how 52 patients swallowed four different placebos (round, oval, and oblong tablets and a capsule) with texture-modified water (TMW, pudding consistency) and milk and rated their swallowing performance according to the Penetration Aspiration Scale (PAS). Additionally, Daniels Test, Bogenhausener Dysphagiescore, Scandinavian Stroke Scale, Barthel Index, and Tinetti's Mobility Test were conducted. A substantial proportion of the patients experienced severe difficulties swallowing solid oral dosage forms (TMW: 40.4 %, milk: 43.5 %). Compared to the administration of TMW/milk alone, the placebos increased the PAS values in the majority of the patients (TMW: median PAS from 1.5 to 2.0; milk: median PAS from 1.5 to 2.5, each p value <0.0001) and residue values were significantly higher (p < 0.05). Whereas video-endoscopic examination reliably identified patients with difficulties swallowing medication, neither patients' self-evaluation nor one of the routinely performed bedside tests did. Therefore, before video-endoscopic evaluation, many drugs were modified unnecessarily and 20.8 % of these were crushed inadequately, although switching to another dosage form or drug would have been possible. Hence, safety and effectiveness of swallowing tablets and capsules should be evaluated routinely in video-endoscopic examinations, tablets/capsules should rather be provided with TMW than with milk, and the appropriateness of "non per os except medication" orders for dysphagic stroke patients should be questioned.

  17. Electronic amplifiers for automatic compensators

    CERN Document Server

    Polonnikov, D Ye

    1965-01-01

    Electronic Amplifiers for Automatic Compensators presents the design and operation of electronic amplifiers for use in automatic control and measuring systems. This book is composed of eight chapters that consider the problems of constructing input and output circuits of amplifiers, suppression of interference and ensuring high sensitivity.This work begins with a survey of the operating principles of electronic amplifiers in automatic compensator systems. The succeeding chapters deal with circuit selection and the calculation and determination of the principal characteristics of amplifiers, as

  18. Simplified design of IC amplifiers

    CERN Document Server

    Lenk, John

    1996-01-01

    Simplified Design of IC Amplifiers has something for everyone involved in electronics. No matter what skill level, this book shows how to design and experiment with IC amplifiers. For experimenters, students, and serious hobbyists, this book provides sufficient information to design and build IC amplifier circuits from 'scratch'. For working engineers who design amplifier circuits or select IC amplifiers, the book provides a variety of circuit configurations to make designing easier.Provides basics for all phases of practical design.Covers the most popular forms for amplif

  19. Effect of erythropoietin administration on proteins participating in iron homeostasis in Tmprss6-mutated mask mice.

    Science.gov (United States)

    Frýdlová, Jana; Rychtarčíková, Zuzana; Gurieva, Iuliia; Vokurka, Martin; Truksa, Jaroslav; Krijt, Jan

    2017-01-01

    Tmprss6-mutated mask mice display iron deficiency anemia and high expression of hepcidin. The aim of the study was to determine the effect of erythropoietin administration on proteins participating in the control of iron homeostasis in the liver and spleen in C57BL/6 and mask mice. Administration of erythropoietin for four days at 50 IU/mouse/day increased hemoglobin and hematocrit in C57BL/6 mice, no such increase was seen in mask mice. Erythropoietin administration decreased hepcidin expression in C57BL/6 mice, but not in mask mice. Erythropoietin treatment significantly increased the spleen size in both C57BL/6 and mask mice. Furthermore, erythropoietin administration increased splenic Fam132b, Fam132a and Tfr2 mRNA content. At the protein level, erythropoietin increased the amount of splenic erythroferrone and transferrin receptor 2 both in C57BL/6 and mask mice. Splenic ferroportin content was decreased in erythropoietin-treated mask mice in comparison with erythropoietin-treated C57BL/6 mice. In mask mice, the amount of liver hemojuvelin was decreased in comparison with C57BL/6 mice. The pattern of hemojuvelin cleavage was different between C57BL/6 and mask mice: In both groups, a main hemojuvelin band was detected at approximately 52 kDa; in C57BL/6 mice, a minor cleaved band was seen at 47 kDa. In mask mice, the 47 kDa band was absent, but additional minor bands were detected at approximately 45 kDa and 48 kDa. The results provide support for the interaction between TMPRSS6 and hemojuvelin in vivo; they also suggest that hemojuvelin could be cleaved by another as yet unknown protease in the absence of functional TMPRSS6. The lack of effect of erythropoietin on hepcidin expression in mask mice can not be explained by changes in erythroferrone synthesis, as splenic erythroferrone content increased after erythropoietin administration in both C57BL/6 and mask mice.

  20. Transplantation of erythropoietin gene-modified neural stem cells improves the repair of injured spinal cord

    Directory of Open Access Journals (Sweden)

    Min-fei Wu

    2015-01-01

    Full Text Available The protective effects of erythropoietin on spinal cord injury have not been well described. Here, the eukaryotic expression plasmid pcDNA3.1 human erythropoietin was transfected into rat neural stem cells cultured in vitro. A rat model of spinal cord injury was established using a free falling object. In the human erythropoietin-neural stem cells group, transfected neural stem cells were injected into the rat subarachnoid cavity, while the neural stem cells group was injected with non-transfected neural stem cells. Dulbecco′s modified Eagle′s medium/F12 medium was injected into the rats in the spinal cord injury group as a control. At 1-4 weeks post injury, the motor function in the rat lower limbs was best in the human erythropoietin-neural stem cells group, followed by the neural stem cells group, and lastly the spinal cord injury group. At 72 hours, compared with the spinal cord injury group, the apoptotic index and Caspase-3 gene and protein expressions were apparently decreased, and the bcl-2 gene and protein expressions were noticeably increased, in the tissues surrounding the injured region in the human erythropoietin-neural stem cells group. At 4 weeks, the cavities were clearly smaller and the motor and somatosensory evoked potential latencies were remarkably shorter in the human erythropoietin-neural stem cells group and neural stem cells group than those in the spinal cord injury group. These differences were particularly obvious in the human erythropoietin-neural stem cells group. More CM-Dil-positive cells and horseradish peroxidase-positive nerve fibers and larger amplitude motor and somatosensory evoked potentials were found in the human erythropoietin-neural stem cells group and neural stem cells group than in the spinal cord injury group. Again, these differences were particularly obvious in the human erythropoietin-neural stem cells group. These data indicate that transplantation of erythropoietin gene-modified neural stem

  1. Effect of erythropoietin administration on proteins participating in iron homeostasis in Tmprss6-mutated mask mice.

    Directory of Open Access Journals (Sweden)

    Jana Frýdlová

    Full Text Available Tmprss6-mutated mask mice display iron deficiency anemia and high expression of hepcidin. The aim of the study was to determine the effect of erythropoietin administration on proteins participating in the control of iron homeostasis in the liver and spleen in C57BL/6 and mask mice. Administration of erythropoietin for four days at 50 IU/mouse/day increased hemoglobin and hematocrit in C57BL/6 mice, no such increase was seen in mask mice. Erythropoietin administration decreased hepcidin expression in C57BL/6 mice, but not in mask mice. Erythropoietin treatment significantly increased the spleen size in both C57BL/6 and mask mice. Furthermore, erythropoietin administration increased splenic Fam132b, Fam132a and Tfr2 mRNA content. At the protein level, erythropoietin increased the amount of splenic erythroferrone and transferrin receptor 2 both in C57BL/6 and mask mice. Splenic ferroportin content was decreased in erythropoietin-treated mask mice in comparison with erythropoietin-treated C57BL/6 mice. In mask mice, the amount of liver hemojuvelin was decreased in comparison with C57BL/6 mice. The pattern of hemojuvelin cleavage was different between C57BL/6 and mask mice: In both groups, a main hemojuvelin band was detected at approximately 52 kDa; in C57BL/6 mice, a minor cleaved band was seen at 47 kDa. In mask mice, the 47 kDa band was absent, but additional minor bands were detected at approximately 45 kDa and 48 kDa. The results provide support for the interaction between TMPRSS6 and hemojuvelin in vivo; they also suggest that hemojuvelin could be cleaved by another as yet unknown protease in the absence of functional TMPRSS6. The lack of effect of erythropoietin on hepcidin expression in mask mice can not be explained by changes in erythroferrone synthesis, as splenic erythroferrone content increased after erythropoietin administration in both C57BL/6 and mask mice.

  2. Effect of erythropoietin administration on proteins participating in iron homeostasis in Tmprss6-mutated mask mice

    Science.gov (United States)

    Frýdlová, Jana; Rychtarčíková, Zuzana; Gurieva, Iuliia; Vokurka, Martin; Truksa, Jaroslav

    2017-01-01

    Tmprss6-mutated mask mice display iron deficiency anemia and high expression of hepcidin. The aim of the study was to determine the effect of erythropoietin administration on proteins participating in the control of iron homeostasis in the liver and spleen in C57BL/6 and mask mice. Administration of erythropoietin for four days at 50 IU/mouse/day increased hemoglobin and hematocrit in C57BL/6 mice, no such increase was seen in mask mice. Erythropoietin administration decreased hepcidin expression in C57BL/6 mice, but not in mask mice. Erythropoietin treatment significantly increased the spleen size in both C57BL/6 and mask mice. Furthermore, erythropoietin administration increased splenic Fam132b, Fam132a and Tfr2 mRNA content. At the protein level, erythropoietin increased the amount of splenic erythroferrone and transferrin receptor 2 both in C57BL/6 and mask mice. Splenic ferroportin content was decreased in erythropoietin-treated mask mice in comparison with erythropoietin-treated C57BL/6 mice. In mask mice, the amount of liver hemojuvelin was decreased in comparison with C57BL/6 mice. The pattern of hemojuvelin cleavage was different between C57BL/6 and mask mice: In both groups, a main hemojuvelin band was detected at approximately 52 kDa; in C57BL/6 mice, a minor cleaved band was seen at 47 kDa. In mask mice, the 47 kDa band was absent, but additional minor bands were detected at approximately 45 kDa and 48 kDa. The results provide support for the interaction between TMPRSS6 and hemojuvelin in vivo; they also suggest that hemojuvelin could be cleaved by another as yet unknown protease in the absence of functional TMPRSS6. The lack of effect of erythropoietin on hepcidin expression in mask mice can not be explained by changes in erythroferrone synthesis, as splenic erythroferrone content increased after erythropoietin administration in both C57BL/6 and mask mice. PMID:29073189

  3. Transplantation of erythropoietin gene-modified neural stem cells improves the repair of injured spinal cord.

    Science.gov (United States)

    Wu, Min-Fei; Zhang, Shu-Quan; Gu, Rui; Liu, Jia-Bei; Li, Ye; Zhu, Qing-San

    2015-09-01

    The protective effects of erythropoietin on spinal cord injury have not been well described. Here, the eukaryotic expression plasmid pcDNA3.1 human erythropoietin was transfected into rat neural stem cells cultured in vitro. A rat model of spinal cord injury was established using a free falling object. In the human erythropoietin-neural stem cells group, transfected neural stem cells were injected into the rat subarachnoid cavity, while the neural stem cells group was injected with non-transfected neural stem cells. Dulbecco's modified Eagle's medium/F12 medium was injected into the rats in the spinal cord injury group as a control. At 1-4 weeks post injury, the motor function in the rat lower limbs was best in the human erythropoietin-neural stem cells group, followed by the neural stem cells group, and lastly the spinal cord injury group. At 72 hours, compared with the spinal cord injury group, the apoptotic index and Caspase-3 gene and protein expressions were apparently decreased, and the bcl-2 gene and protein expressions were noticeably increased, in the tissues surrounding the injured region in the human erythropoietin-neural stem cells group. At 4 weeks, the cavities were clearly smaller and the motor and somatosensory evoked potential latencies were remarkably shorter in the human erythropoietin-neural stem cells group and neural stem cells group than those in the spinal cord injury group. These differences were particularly obvious in the human erythropoietin-neural stem cells group. More CM-Dil-positive cells and horseradish peroxidase-positive nerve fibers and larger amplitude motor and somatosensory evoked potentials were found in the human erythropoietin-neural stem cells group and neural stem cells group than in the spinal cord injury group. Again, these differences were particularly obvious in the human erythropoietin-neural stem cells group. These data indicate that transplantation of erythropoietin gene-modified neural stem cells into the

  4. Building valve amplifiers

    CERN Document Server

    Jones, Morgan

    2013-01-01

    Building Valve Amplifiers is a unique hands-on guide for anyone working with tube audio equipment--as an electronics hobbyist, audiophile or audio engineer. This 2nd Edition builds on the success of the first with technology and technique revisions throughout and, significantly, a major new self-build project, worked through step-by-step, which puts into practice the principles and techniques introduced throughout the book. Particular attention has been paid to answering questions commonly asked by newcomers to the world of the valve, whether audio enthusiasts tackling their first build or

  5. Wideband amplifier design

    CERN Document Server

    Hollister, Allen L

    2007-01-01

    In this book, the theory needed to understand wideband amplifier design using the simplest models possible will be developed. This theory will be used to develop algebraic equations that describe particular circuits used in high frequency design so that the reader develops a ""gut level"" understanding of the process and circuit. SPICE and Genesys simulations will be performed to show the accuracy of the algebraic models. By looking at differences between the algebraic equations and the simulations, new algebraic models will be developed that include parameters originally left out of the model

  6. Erythropoietin to Reduce Mortality in Traumatic Brain Injury: A Post-hoc Dose-effect Analysis.

    Science.gov (United States)

    Gantner, Dashiell C; Bailey, Michael; Presneill, Jeffrey; French, Craig J; Nichol, Alistair; Little, Lorraine; Bellomo, Rinaldo

    2017-02-01

    We aimed to assess whether the dosing regimen of erythropoietin shows a relationship to mortality in critically ill patients with traumatic brain injury (TBI). Erythropoietin may decrease mortality in patients with TBI; however, the optimal dosing regimen remains uncertain. We conducted a post-hoc analysis of a multicenter, randomized trial of weekly erythropoietin versus placebo in patients with moderate and severe TBI admitted to intensive care. We assessed whether the cumulative dosage of erythropoietin was differentially associated with all-cause patient mortality evaluated at 6 months after injury. There was a nonlinear relationship between dose and mortality (P = 0.008) that remained after adjustment for site and severity of illness (P = 0.01). Six-month mortality was lower in randomized patients who received 1 [adjusted hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.33-1.01; P = 0.06] or 2 doses of erythropoietin (HR 0.31, 95% CI 0.12-0.80; P = 0.02) compared with those who received no doses. No benefit was seen with 3 doses (HR 1.55, 95% CI 0.66-3.62; P = 0.33). There was no differential effect of dose on functional neurological outcomes. Results across subgroups and secondary intention to treat analyses were consistent with primary findings. This post-hoc, hypothesis-generating analysis found potential reductions in mortality following 1 or 2 weekly doses of 40,000 IU of erythropoietin in intensive care unit patients with moderate or severe TBI, but not with 3 doses. These findings will inform the design of future trials of erythropoietin in critically ill patients with TBI and trauma.

  7. Non-hematopoietic effects of endogenous erythropoietin on lean mass and body weight regulation.

    Science.gov (United States)

    Reinhardt, Martin; Dey, Soumyadeep; Tom Noguchi, Constance; Zhang, Yuanyuan; Krakoff, Jonathan; Thearle, Marie S

    2016-07-01

    To investigate the concurrent relationships between human plasma erythropoietin concentrations and energy expenditure (EE), body composition, plasma leptin concentrations, and associations with weight change. Plasma to measure erythropoietin and leptin; data for body composition; 24-h EE measured in a whole-room calorimeter; and 75 g oral glucose tolerance testing were available from 109 full-heritage Pima Indians (55% male) from a larger study designed to understand the causes of obesity. Seventy-nine subjects had data for weight at a later visit (mean follow-up = 4.3 ± 1.9 years) to calculate percent weight change per year. Erythropoietin, adjusted for covariates, correlated with 24-h EE (r = 0.26, P = 0.007), sleeping EE (r = 0.29, P = 0.003), fat-free mass (r = 0.19, P = 0.05), and fat mass (r = 0.27, P = 0.005), but not insulin or glucose measures. The association of erythropoietin with 24-h EE was fully mediated by fat-free mass. Erythropoietin associated with leptin in women (ρ = 0.36, P = 0.01), but not in men (P = 0.9), independently from fat mass. The association of erythropoietin with percent weight change per year was in opposing directions (interaction: P = 0.002) in males (r = -0.35, P = 0.02) versus females (r = 0.37, P = 0.02). Non-hematopoietic endogenous erythropoietin action may be involved in body weight regulation in opposing directions in men and women, i.e., weight loss in men and weight gain in women. © 2016 The Obesity Society.

  8. 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

  9. Communicative strategies used by spouses of individuals with communication disorders related to stroke-induced aphasia and Parkinson's disease.

    Science.gov (United States)

    Carlsson, Emilia; Hartelius, Lena; Saldert, Charlotta

    2014-11-01

    A communicative disability interferes with the affected person's ability to take active part in social interaction, but non-disabled communication partners may use different strategies to support communication. However, it is not known whether similar strategies can be used to compensate for different types of communicative disabilities, nor what factors contribute to the development of a particular approach by communication partners. To develop a set of categories to describe the strategies used by communication partners of adults who have problems expressing themselves due to neurogenic communicative disabilities. The reliability of assessment was a particular focus. The material explored consisted of 21 video-recorded everyday conversations involving seven couples where one spouse had a communicative disability. Three of the dyads included a person with dysarthria and anomia related to later stages of Parkinson's disease, while four of them included a person with stroke-induced aphasia involving anomia. First a qualitative interaction analysis was performed to explore the strategies used by the communication partners when their spouses had problems expressing themselves. The strategies were then categorized, the reliability of the categorizations was explored and the relative frequency of the various strategies was examined. The analysis of the conversational interactions resulted in a set of nine different strategies used by the communication partners without a communicative disability. Each of these categories belonged to one of three overall themes: No participation in repair; Request for clarification or modification; and Providing candidate solutions. The reliability of the categorization was satisfactory. There were no statistically significant differences between diagnoses in the frequency of use of strategies, but the spouses of the persons with Parkinson's disease tended to use open-class initiations of repair more often than the spouses of the persons

  10. Variability in blood oxygen level dependent (BOLD) signal in patients with stroke-induced and primary progressive aphasia.

    Science.gov (United States)

    Bonakdarpour, B; Beeson, P M; DeMarco, A T; Rapcsak, S Z

    2015-01-01

    Although fMRI is increasingly used to assess language-related brain activation in patients with aphasia, few studies have examined the hemodynamic response function (HRF) in perilesional, and contralesional areas of the brain. In addition, the relationship between HRF abnormalities and other variables such as lesion size and severity of aphasia has not been explored. The objective of this study was to investigate changes in HRF signal during language-related neural activation in patients with stroke-induced aphasia (SA). We also examined the status of the HRF in patients with aphasia due to nonvascular etiology, namely, primary progressive aphasia (PPA). Five right handed SA patients, three PPA patients, and five healthy individuals participated in the study. Structural damage was quantified with T1-weighted MR images. Functional MR imaging was performed with long trial event-related design and an overt naming task to measure BOLD signal time to peak (TTP) and percent signal change (ΔS). In SA patients, the average HRF TTP was significantly delayed in the left hemisphere regions involved in naming compared to healthy participants and PPA patients. However, ΔS was not different in SA patients compared to the other two groups. Delay in HRF TTP in the left hemisphere naming network of SA patients was correlated with lesion size and showed a negative correlation with global language function. There were no significant differences in the HRF TTP and ΔS in the right hemisphere homologues of the naming network or in the left and the right occipital control regions across the three groups. In PPA patients, HRF had a normal pattern. Our results indicate that abnormal task-related HRF is primarily found in the left hemisphere language network of SA patients and raise the possibility that abnormal physiology superimposed on structural damage may contribute to the clinical deficit. Follow-up investigations in a larger sample of age-matched healthy individuals, SA, and PPA

  11. The microstrip SQUID amplifier

    Science.gov (United States)

    Therrien, Roy

    A Superconducting Quantum Interference Devices (SQUIDS) can operate at frequencies up to several GHz and can be cooled to less than 100 mK. Such characteristics make the SQUID---a flux-to-voltage transducer---an excellent candidate for use as a low-noise rf amplifier. Coupling of input signals of frequencies larger than 200 MHz, however, has been limited by the parasitic capacitance between the input coil and SQUID body. We present experimental observations of a do SQUID-based rf amplifier which circumvents this problem by incorporating the input coil as a microstrip resonator. The microstrip input configuration uses the capacitance and inductance of the input coil to form a resonant cavity capable of operating up to several GHz. The input signal is applied between the SQUID body and one end of the input coil, while the other end of the coil is left open. We present data from microstrip SQUID amplifiers with gains of up to 22 dB at 900 MHz. In order to understand the gain and input impedance of the microstrip SQUID in greater detail, we made and studied a 1:190 scale analog patterned on a double-sided printed circuit board consisting of copper deposited on a kapton sheet. The measured input impedance of the analog SQUID is successfully modeled by describing the microstrip input as a low-loss transmission line. When operated with the slit in the copper washer ground plane shorted, the input coil behaves exactly like a linear resonator with the resonant frequency given by f = 1/2ℓ(L 0C0)1/2, where L0 and C0 are the inductance and capacitance per unit length and ℓ is the coil length. With the slit in the washer left open, the inductance of the input coil is significantly altered in a manner partially consistent with the Ketchen-Jaycox model in which the reflected inductance of the input coil is Li = n2L, where L is the inductance of the washer loop and n is the number of turns in the coil. We present input impedance measurements on microstrip SQUIDs cooled to 4

  12. "Erythropoietin Utilization Evaluation And Two Brand Products Comparison, Eprex and Eposim "

    Directory of Open Access Journals (Sweden)

    H. Khalili

    2006-06-01

    Full Text Available Background and Aim: Anemia is one of the common problems in patients with chronic renal impairment. The most common cause of anemia in this patients is a decreased in erythropoietin hormone excretion, however other common cause include low life of red blood cells, loss of blood during dialysis, frequent blood sampling, uremia, iron, vitamin B12 and folic acid deficiency. Until introduction of erythropoietin in 1982, blood transfusion was an alternative for correction and maintaining hematocrit in normal range in dialyze patients. In current date, any dialyzed patient take rh-erythropoietin . Materials and Methods: The goal of this study is to evaluate erythropoietin utilization and comparing the effectiveness of the commercial product in the Iranian drugs market. The study was performed at nephrology and dialyze ward of Immam Khomeini hospital in a one year period. Results and Conclusion: Of the 30 patients' subject of study, 13 patients received eprex and 17 received epocim. Average dose of erythropoietin 2000IU was three times per week. The average plasma hemoglobin and hematocrit of patients prior to the treatment were 9.38 g/dl and 28% respectively. Increase in the hemoglobin and hematocrit in the group who received eprex was significantly higher than epocim group (p=0.001 and p=0.026 respectively. The incidents of side effects including hypertension, headache, pain at injection site, and influenza-like in eposim group were considerably higher than eprex.

  13. Modeling of semiconductor optical amplifiers

    DEFF Research Database (Denmark)

    Mørk, Jesper; Bischoff, Svend; Berg, Tommy Winther

    We discuss the modelling of semiconductor optical amplifiers with emphasis on their high-speed properties. Applications in linear amplification as well as ultrafast optical signal processing are reviewed. Finally, the possible role of quantum-dot based optical amplifiers is discussed.......We discuss the modelling of semiconductor optical amplifiers with emphasis on their high-speed properties. Applications in linear amplification as well as ultrafast optical signal processing are reviewed. Finally, the possible role of quantum-dot based optical amplifiers is discussed....

  14. Erythropoietin and interleukin-2 activate distinct JAK kinase family members.

    Science.gov (United States)

    Barber, D L; D'Andrea, A D

    1994-01-01

    The erythropoietin (EPO) receptor and the interleukin-2 (IL-2) receptor beta-chain subunit are members of the cytokine receptor superfamily. They have conserved primary amino acid sequences in their cytoplasmic domains and activate phosphorylation of common substrates, suggesting common biochemical signaling mechanisms. We have generated a cell line, CTLL-EPO-R, that contains functional cell surface receptors for both EPO and IL-2. CTLL-EPO-R cells demonstrated similar growth kinetics in EPO and IL-2. Stimulation with EPO resulted in the rapid, dose-dependent tyrosine phosphorylation of JAK2. In contrast, stimulation with IL-2 or the related cytokine IL-4 resulted in the rapid, dose-dependent tyrosine phosphorylation of JAK1 and an additional 116-kDa protein. This 116-kDa protein was itself immunoreactive with a polyclonal antiserum raised against JAK2 and appears to be a novel member of the JAK kinase family. Immune complex kinase assays confirmed that IL-2 and IL-4 activated JAK1 and EPO activated JAK2. These results demonstrate that multiple biochemical pathways are capable of conferring a mitogenic signal in CTLL-EPO-R cells and that the EPO and IL-2 receptors interact with distinct JAK kinase family members within the same cellular background. Images PMID:7935373

  15. Radioimmunoassay of erythropoietin in chronic uraemia or anephric patients

    Energy Technology Data Exchange (ETDEWEB)

    Naets, J.P.; Waks, D.; Garcia, J.F.; Tousaaint, C.; Buset, M.

    1986-01-01

    The erythropoietin (Ep) plasma titre of 41 anaemic patients with normal renal function or with renal insufficiency (with or without kidney) was measured by RIA and compared to values observed with the polycythaemic mouse assay. A good correlation was found with both methods (r = 0.88). However, about 20% of samples gave higher values with the bioassay. 21 Ep titres measurable by the bioassay ranged from 40 to 4400 mU (mean 717.1 mU) compared to 14.8 to 3788 mU (mean 484.7 mU) measured by the RIA. Low levels of Ep plasma titre have been observed in patients with renal insufficiency and no difference was found between nephric uraemic patients and the anephric group. These results suggest that the increased blood requirements in anephrics are not due to a smaller production of Ep, but ultimately to the presence of an inhibitor of erythropoiesis. The well-known inverse relationship between haematocrit and Ep level was not found in renal insufficiency. However, some humoral regulation of erythropoiesis seems to persist in these patients since the elevation of red blood cells by transfusions was followed by a decrease of the Ep level.

  16. Erythropoietin reduces the expression of myostatin in mdx dystrophic mice

    Energy Technology Data Exchange (ETDEWEB)

    Feder, D.; Rugollini, M.; Santomauro, A. Jr; Oliveira, L.P.; Lioi, V.P. [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Santos, R. dos; Ferreira, L.G.; Nunes, M.T.; Carvalho, M.H. [Universidade de São Paulo, Instituto de Ciências Biomédicas, São Paulo, SP (Brazil); Delgado, P.O.; Carvalho, A.A.S. [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Fonseca, F.L.A. [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Universidade Federal de São Paulo, Ambientais e Farmacêuticas, Instituto de Ciências Químicas, Diadema, SP (Brazil)

    2014-09-05

    Erythropoietin (EPO) has been well characterized as a renal glycoprotein hormone regulating red blood cell production by inhibiting apoptosis of erythrocyte progenitors in hematopoietic tissues. EPO exerts regulatory effects in cardiac and skeletal muscles. Duchenne muscular dystrophy is a lethal degenerative disorder of skeletal and cardiac muscle. In this study, we tested the possible therapeutic beneficial effect of recombinant EPO (rhEPO) in dystrophic muscles in mdx mice. Total strength was measured using a force transducer coupled to a computer. Gene expression for myostatin, transforming growth factor-β1 (TGF-β1), and tumor necrosis factor-α (TNF-α) was determined by quantitative real time polymerase chain reaction. Myostatin expression was significantly decreased in quadriceps from mdx mice treated with rhEPO (rhEPO=0.60±0.11, control=1.07±0.11). On the other hand, rhEPO had no significant effect on the expression of TGF-β1 (rhEPO=0.95±0.14, control=1.05±0.16) and TNF-α (rhEPO=0.73±0.20, control=1.01±0.09). These results may help to clarify some of the direct actions of EPO on skeletal muscle.

  17. Erythropoietin elevation in the chronically hyperglycemic fetal lamb

    Energy Technology Data Exchange (ETDEWEB)

    Philipps, A.F. (Univ. of Connecticut Health Center, Farmington) Widness, J.A.; Garcia, J.F.; Raye, J.R.; Swartz, R.

    1982-05-01

    The effects of chronic fetal glucose infusion upon fetal oxygenation and endogenous erythropoietin (Ep) production were studied using the chronically catheterized fetal lamb. Fetal glucose infusion at rates between 5 and 20 mg/kg/min resulted in sustained fetal hyperglycemia. During glucose infusion (maximal glucose concentration achieved = 55.4 +/- 3.7 mg/dl) fetal arterial oxygen contents fell from 5.8 +/- 0.9 to 4.2 +/- 1.0 ml/dl while no changes were observed in simultaneously sampled, noninfused twins. Although plasma insulin concentration rose in the infused fetuses, the elevations were inconstant and no relationship between fetal plasma insulin concentration and decrement in fetal oxygen content was evident. The changes in plasma Ep concentration were noted prior to any significant fetal metabolic acidosis (as evidence of tissue hypoxia) and no changes in plasma Ep concentration were observed in simultaneously sampled noninfused twins. No relationship was apparent between fetal arterial plasma insulin and Ep concentrations. Since neither fetal anemia nor hemodilution occurred in these preparations, glucose-induced fetal hyposemia is the likely mechanism behind elevated fetal Ep concentrations in these experiments. Similarities between this animal model and human fetuses and infants of diabetic mothers suggest that chronic in utero hypoxemia may be a common feature responsible for such diverse abnomalities as polycythemia, hyperbilirubinemia, and late fetal demise. The mechanism behind the glucose-induced fetal hypoxemia is not known.

  18. Does Erythropoietin Regulate TRPC Channels in Red Blood Cells?

    Directory of Open Access Journals (Sweden)

    Jens Danielczok

    2017-03-01

    Full Text Available Background: Cation channels play an essential role in red blood cells (RBCs ion homeostasis. One set of ion channels are the transient receptor potential channels of canonical type (TRPC channels. The abundance of these channels in primary erythroblasts, erythroid cell lines and RBCs was associated with an increase in intracellular Ca2+ upon stimulation with Erythropoietin (Epo. In contrast two independent studies on Epo-treated patients revealed diminished basal Ca2+ concentration or reduced phosphatidylserine exposure to the outer membrane leaflet. Methods: To resolve the seemingly conflicting reports we challenged mature human and mouse RBCs of several genotypes with Epo and Prostaglandin E2 (PGE2 and recorded the intracellular Ca2+ content. Next Generation Sequencing was utilised to approach a molecular analysis of reticulocytes. Results/Conclusions: Our results allow concluding that Epo and PGE2 regulation of the Ca2+ homeostasis is distinctly different between murine and human RBCs and that changes in intracellular Ca2+ upon Epo treatment is a primary rather than a compensatory effect. In human RBCs, Epo itself has no effect on Ca2+ fluxes but inhibits the PGE2-induced Ca2+ entry. In murine mature RBCs functional evidence indicates TRPC4/C5 mediated Ca2+ entry activated by Epo whereas PGE2 leads to a TRPC independent Ca2+ entry.

  19. Effects of erythropoietin on angiogenesis after myocardial infarction in porcine.

    Science.gov (United States)

    Kawachi, Keisuke; Iso, Yoshitaka; Sato, Takatoshi; Wakabayashi, Kohei; Kobayashi, Youichi; Takeyama, Youichi; Suzuki, Hiroshi

    2012-01-01

    Erythropoietin (EPO) has recently been shown to confer cardioprotective effects via angiogenesis and antiapoptosis. The administration of EPO after myocardial infarction (MI) reduces infarct size and improves cardiac function in small animals. The purpose of this study is to investigate the protective effects of EPO in porcine MI. Each animal in the EPO group received four injections of recombinant human EPO (rhEPO; 6000 U per injection) at 2-day intervals, starting after coronary occlusion. Animals in the control group received saline. Left ventriculography was performed just after coronary occlusion and at 28 days. Time-course changes in serum levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and fibroblast growth factor (FGF) were measured. The number of vessels was calculated, and the mRNA expressions of VEGF and insulin-like growth factor (IGF) were examined. Left ventricular function was similar between the groups. The numbers of cells positive for anti-α-smooth muscle actin, von Willebrand factor, and c-kit were significantly higher in the EPO group than in the controls (P porcine MI.

  20. The anemia of microgravity and recumbency. Role of sympathetic neural control of erythropoietin production

    Science.gov (United States)

    Robertson, David; Krantz, Sanford B.; Biaggioni, Italo

    We hypothesize that reduced sympathetic stimulation of erythropoietin production may maintain the anemia which develops in virtually all space travellers. We tested this hypothesis in a human model of reduced sympathetic activity. Thirty-three patients with the Bradbury-Eggleston syndrome were divided into three groups according to their hemoglobin (Hgb) level. Patients with low Hgb had lower upright norepinephrine and lower upright renin. Patients with anemia also had inappropriately low plasma erythropoietin levels. We administered recombinant erythropoietin (Epogen) 25-50 units/kg s.c. 3 times per week and found that the anemia seen in autonomic failure could be reversed by this treatment. These results support the hypothesis that erythropoiesis is modulated by the sympathetic nervous system and that such mechanisms may also operate in the microgravity environment where sympathetic activity is reduced.

  1. Erythropoietin production by a hepatic adenoma in a patient with severe erythrocytosis.

    Science.gov (United States)

    Vik, Anders; Cui, Guanglin; Isaksen, Vidar; Wik, Trude; Hansen, John-Bjarne

    2009-01-01

    A 53-year-old woman with severe erythrocytosis (hemoglobin concentration 19.5 g/dl and hematocrit 0.59) was admitted to our hospital because of fatigue and headache. The serum erythropoietin (Epo) concentration was 68.6 U/l (reference range; 3.7-31.5). Further investigations excluded polycythemia vera or any lung or heart disease. Radiological examination showed a tumor in the left hepatic lobe. Needle biopsies were performed and the histopathological diagnosis was hepatocellular adenoma. Immunohistochemistry demonstrated erythropoietin expression in the adenomatous cells. Liver adenoma is a rare cause of erythrocytosis. For the first time, we report erythropoietin-positive immunoreactivity in liver adenomatous cells in a patient with erythrocytosis. (c) 2009 S. Karger AG, Basel.

  2. Testosterone Induces Erythrocytosis via Increased Erythropoietin and Suppressed Hepcidin: Evidence for a New Erythropoietin/Hemoglobin Set Point

    Science.gov (United States)

    Travison, Thomas G.; Basaria, Shehzad; Davda, Maithili N.; Guo, Wen; Li, Michelle; Connor Westfall, John; Bae, Harold; Gordeuk, Victor; Bhasin, Shalender

    2014-01-01

    Background. The mechanisms by which testosterone increases hemoglobin and hematocrit remain unclear. Methods. We assessed the hormonal and hematologic responses to testosterone administration in a clinical trial in which older men with mobility limitation were randomized to either placebo or testosterone gel daily for 6 months. Results. The 7%–10% increase in hemoglobin and hematocrit, respectively, with testosterone administration was associated with significantly increased erythropoietin (EPO) levels and decreased ferritin and hepcidin levels at 1 and 3 months. At 6 months, EPO and hepcidin levels returned toward baseline in spite of continued testosterone administration, but EPO levels remained nonsuppressed even though elevated hemoglobin and hematocrit higher than at baseline, suggesting a new set point. Consistent with increased iron utilization, soluble transferrin receptor (sTR) levels and ratio of sTR/log ferritin increased significantly in testosterone-treated men. Hormonal and hematologic responses were similar in anemic participants. The majority of testosterone-treated anemic participants increased their hemoglobin into normal range. Conclusions. Testosterone-induced increase in hemoglobin and hematocrit is associated with stimulation of EPO and reduced ferritin and hepcidin concentrations. We propose that testosterone stimulates erythropoiesis by stimulating EPO and recalibrating the set point of EPO in relation to hemoglobin and by increasing iron utilization for erythropoiesis. PMID:24158761

  3. Erythropoietin, ferritin, haptoglobin, hemoglobin and transferrin receptor in metabolic syndrome: a case control study

    Directory of Open Access Journals (Sweden)

    Hämäläinen Päivi

    2012-09-01

    Full Text Available Abstract Background Increased ferritin concentrations are associated with metabolic syndrome (MetS. The association between ferritin as well as hemoglobin level and individual MetS components is unclear. Erythropoietin levels in subjects with MetS have not been determined previously. The aim of this study was to compare serum erythropoietin, ferritin, haptoglobin, hemoglobin, and transferrin receptor (sTFR levels between subjects with and without MetS and subjects with individual MetS components. Methods A population based cross-sectional study of 766 Caucasian, middle-aged subjects (341 men and 425 women from five age groups born in Pieksämäki, Finland who were invited to a health check-up in 2004 with no exclusion criteria. Laboratory analyzes of blood samples collected in 2004 were done during year 2010. MetS was defined by National Cholesterol Education Program criteria. Results 159 (53% men and 170 (40% women of study population met MetS criteria. Hemoglobin and ferritin levels as well as erythropoietin and haptoglobin levels were higher in subjects with MetS (p  Conclusion Subjects with MetS have elevated hemoglobin, ferritin, erythropoietin and haptoglobin concentrations. Higher hemoglobin levels are related to all components of MetS. Higher ferritin levels associate with TG, abdominal obesity, elevated glucose or low high density cholesterol. Haptoglobin levels associate with blood pressure or elevated glucose. However, erythropoietin levels are related only with abdominal obesity. Higher serum erythropoietin concentrations may suggest underlying adipose tissue hypoxemia in MetS.

  4. Millimeter-wave power amplifiers

    CERN Document Server

    du Preez, Jaco

    2017-01-01

    This book provides a detailed review of millimeter-wave power amplifiers, discussing design issues and performance limitations commonly encountered in light of the latest research. Power amplifiers, which are able to provide high levels of output power and linearity while being easily integrated with surrounding circuitry, are a crucial component in wireless microwave systems. The book is divided into three parts, the first of which introduces readers to mm-wave wireless systems and power amplifiers. In turn, the second focuses on design principles and EDA concepts, while the third discusses future trends in power amplifier research. The book provides essential information on mm-wave power amplifier theory, as well as the implementation options and technologies involved in their effective design, equipping researchers, circuit designers and practicing engineers to design, model, analyze, test and implement high-performance, spectrally clean and energy-efficient mm-wave systems.

  5. Erythropoietin treatment does not compromise cardiovascular function in chronic renal failure

    DEFF Research Database (Denmark)

    Haedersdal, C; Mehlsen, J; Stenver, Doris Irene

    1994-01-01

    The anemia in patients with chronic renal failure can be corrected through treatment with recombinant human erythropoietin treatment. This correction is associated with changes in the rheologic variables, which could explain the changes in hemodynamics found by many investigators. The authors have...... followed up 11 patients with chronic renal failure on hemodialysis before and during six months of therapy with erythropoietin. The measurements were made before treatment, after four months of therapy, and after six months of therapy. The measurements included hematocrit, osmotic resistance of the red...

  6. Erythropoietin for neuroprotection in neonatal encephalopathy: safety and pharmacokinetics.

    Science.gov (United States)

    Wu, Yvonne W; Bauer, Larry A; Ballard, Roberta A; Ferriero, Donna M; Glidden, David V; Mayock, Dennis E; Chang, Taeun; Durand, David J; Song, Dongli; Bonifacio, Sonia L; Gonzalez, Fernando F; Glass, Hannah C; Juul, Sandra E

    2012-10-01

    To determine the safety and pharmacokinetics of erythropoietin (Epo) given in conjunction with hypothermia for hypoxic-ischemic encephalopathy (HIE). We hypothesized that high dose Epo would produce plasma concentrations that are neuroprotective in animal studies (ie, maximum concentration = 6000-10000 U/L; area under the curve = 117000-140000 U*h/L). In this multicenter, open-label, dose-escalation, phase I study, we enrolled 24 newborns undergoing hypothermia for HIE. All patients had decreased consciousness and acidosis (pH score ≤ 5, or ongoing resuscitation at 10 minutes. Patients received 1 of 4 Epo doses intravenously: 250 (N = 3), 500 (N = 6), 1000 (N = 7), or 2500 U/kg per dose (N = 8). We gave up to 6 doses every 48 hours starting at <24 hours of age and performed pharmacokinetic and safety analyses. Patients received mean 4.8 ± 1.2 Epo doses. Although Epo followed nonlinear pharmacokinetics, excessive accumulation did not occur during multiple dosing. At 500, 1000, and 2500 U/kg Epo, half-life was 7.2, 15.0, and 18.7 hours; maximum concentration was 7046, 13780, and 33316 U/L, and total Epo exposure (area under the curve) was 50306, 131054, and 328002 U*h/L, respectively. Drug clearance at a given dose was slower than reported in uncooled preterm infants. No deaths or serious adverse effects were seen. Epo 1000 U/kg per dose intravenously given in conjunction with hypothermia is well tolerated and produces plasma concentrations that are neuroprotective in animals. A large efficacy trial is needed to determine whether Epo add-on therapy further improves outcome in infants undergoing hypothermia for HIE.

  7. Small signal microwave amplifier design

    CERN Document Server

    Grosch, Theodore

    2000-01-01

    This book explains techniques and examples for designing stable amplifiers for high-frequency applications in which the signal is small and the amplifier circuit is linear. An in-depth discussion of linear network theory provides the foundation needed to develop actual designs. Examples throughout the book will show you how to apply the knowledge gained in each chapter leading to the complex design of low noise amplifiers. Many exercises at the end of each chapter will help students to practice their skills. The solutions to these design problems are available in an accompanying solutions book

  8. Current perspectives on protective roles of erythropoietin in cardiovascular system: erythropoietin receptor as a novel therapeutic target.

    Science.gov (United States)

    Kagaya, Yutaka; Asaumi, Yasuhide; Wang, Wanting; Takeda, Morihiko; Nakano, Makoto; Satoh, Kimio; Fukumoto, Yoshihiro; Shimokawa, Hiroaki

    2012-06-01

    Erythropoietin (EPO) is a principal regulator that promotes proliferation and terminal differentiation of erythroid progenitor cells. EPO receptors are expressed not only in hematopoietic lineage cells but also in the cardiovascular system. We performed animal experiments using transgene-rescued EPO receptor null mutant mice (EpoR-/- rescued) that express the EPO receptor exclusively in the hematopoietic cells. The results of these experiments suggest that endogenous EPO/EPO receptor system in the heart exerts cardioprotective effects against myocardial injury induced by ischemia followed by reperfusion and pressure-overload induced left ventricular dysfunction. Many animal experiments have shown that the administration of recombinant human EPO also elicits cardioprotective effects against myocardial injury induced by ischemia and reperfusion. In contrast to the promising results of these animal experiments, recent clinical trials failed to demonstrate the reduction in infarct size or improvement of cardiac function by the administration of recombinant human EPO in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention. It should be tested in future clinical studies whether a relatively low dose of recombinant human EPO or its derivatives that have no erythropoietic action reduces infarct size and ameliorates cardiac dysfunction in patients with acute myocardial infarction. In this article, we review implications of anemia associated with chronic heart failure, roles of the endogenous EPO/EPO receptor system, and the effects of the administration of erythropoiesis-stimulating agents in pathologic conditions of the heart by focusing on the EPO receptor as a potential candidate of novel therapeutic targets in cardiovascular diseases.

  9. PID Controller with Operational Amplifier

    Directory of Open Access Journals (Sweden)

    Cristian Paul Chioncel

    2009-01-01

    Full Text Available The paper presents a PID controller made with LM741 operational amplifier that implement the PID controllers laws and allow for a widerange of applications of in the field of automatic control of technicalprocesses and systems.

  10. Linearization of broadband microwave amplifier

    Directory of Open Access Journals (Sweden)

    Đorić Aleksandra

    2014-01-01

    Full Text Available The linearization of broadband power amplifier for application in the frequency range 0.9-1.3 GHz is considered in this paper. The amplifier is designed for LDMOSFET characterized by the maximum output power 4W designing the broadband lumped element matching circuits and matching circuits in topologies that combines LC elements and transmission lines. The linearization of the amplifier is carried out by the second harmonics of the fundamental signals injected at the input and output of the amplifier transistor. The effects of linearization are considered for the case of two sinusoidal signals separated in frequency by different intervals up to 80 MHz ranging input power levels to saturation. [Projekat Ministarstva nauke Republike Srbije, br. TR-32052

  11. Superluminal waves in amplifying media

    Energy Technology Data Exchange (ETDEWEB)

    Oraevsky, Anatolii N [P.N. Lebedev Physics Institute, Russian Academy of Sciences, Moscow (Russian Federation)

    1998-12-31

    In amplifying media steady-state waves can travel faster than the speed of light in vacuum without violating the principles of special relativity. The possibility of generating superluminal waves in induced elementary particle production processes is discussed. (methodological notes)

  12. Operational amplifiers theory and design

    CERN Document Server

    Huijsing, Johan

    2017-01-01

    This proven textbook guides readers to a thorough understanding of the theory and design of operational amplifiers (OpAmps). The core of the book presents systematically the design of operational amplifiers, classifying them into a periodic system of nine main overall configurations, ranging from one gain stage up to four or more stages. This division enables circuit designers to recognize quickly, understand, and choose optimal configurations. Characterization of operational amplifiers is given by macro models and error matrices, together with measurement techniques for their parameters. Definitions are given for four types of operational amplifiers depending on the grounding of their input and output ports. Many famous designs are evaluated in depth, using a carefully structured approach enhanced by numerous figures. In order to reinforce the concepts introduced and facilitate self-evaluation of design skills, the author includes problems with detailed solutions, as well as simulation exercises. Provides te...

  13. Self-biased transconductance amplifier

    Science.gov (United States)

    Amendola, Gilles; Blanchard, Yves; Exertier, Anne; Spirkovitch, Serge; Lu, Guo N.; Alquie, George

    1999-09-01

    A CMOS, self-biased transconductance amplifier has been designed to be associated and integrated with a silicon capacitive microphone. To meet requirements especially on gain sensitivity, power consumption, and minimization of parasite capacitance effect, we have proposed a cascode structure with the cascode transistor source used as signa input. Switched-capacitor techniques have been applied for realizing self-bias for the amplifier and ensuring its high- gain operation. The proposed amplifier has been designed and fabricated in a 0.8 micrometers CMOS process. It has a surface area of 210 micrometers by 170 micrometers . Experimental results obtained from measuring the fabricated chip show a high-gain sensitivity and a low power dissipation for the amplifier. Results of simulations and measurements have been discussed.

  14. New Packaging for Amplifier Slabs

    Energy Technology Data Exchange (ETDEWEB)

    Riley, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Thorsness, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Suratwala, T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Steele, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Rogowski, G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-03-18

    The following memo provides a discussion and detailed procedure for a new finished amplifier slab shipping and storage container. The new package is designed to maintain an environment of <5% RH to minimize weathering.

  15. Prediction of perinatal brain damage by cord plasma vasopressin, erythropoietin, and hypoxanthine values.

    Science.gov (United States)

    Ruth, V; Autti-Rämö, I; Granström, M L; Korkman, M; Raivio, K O

    1988-11-01

    For an assessment of whether cord plasma arginine vasopressin, erythropoietin, and hypoxanthine concentrations are predictors of perinatal brain damage, these concentrations were measured in 62 infants born after preeclampsia of pregnancy, 31 acutely asphyxiated infants, and 38 control infants. Follow-up at 2 years included neurologic examination and the determination of a Bayley mental score. Clear abnormality (death, cerebral palsy, or developmental delay) was found in four infants in the preeclampsia group and five in the asphyxia group; slight abnormality was found in 12 and 6 infants, respectively; and no abnormality was found in the remainder. Neither arginine vasopressin values nor hypoxanthine values predicted adverse outcome in either study group. A high erythropoietin level was found in infants born after preeclampsia regardless of outcome: normal outcome (geometric mean (GM), 102; 95% confidence interval [CI], 69 to 153 mU/ml), slightly abnormal outcome (GM, 100; 95% CI, 37 to 270 mU/ml) or clearly abnormal outcome (GM, 84; 95% CI, 19 to 378 mU/ml). However, asphyxiated infants with clearly abnormal outcome had higher erythropoietin values (GM, 67; 95% CI, 33 to 137 mU/ml; p less than 0.05) than the normal infants (GM, 37; 95% CI, 23 to 59 mU/ml). We conclude that a high erythropoietin level after normal pregnancy, but not after preeclampsia, indicates an increased risk for cerebral palsy or death.

  16. Glycoengineering of Chinese hamster ovary cells for enhanced erythropoietin N-glycan branching and sialylation

    DEFF Research Database (Denmark)

    Yin, Bojiao; Gao, Yuan; Chung, Cheng-yu

    2015-01-01

    -glycosylation of recombinant erythropoietin (rEPO), a human α2,6-sialyltransferase (ST6Gal1) was expressed in Chinese hamster ovary (CHO-K1) cells. Sialylation increased on both EPO and CHO cellular proteins as observed by SNA lectin analysis, and HPLC profiling revealed that the sialic acid content of total glycans on EPO...

  17. Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

    DEFF Research Database (Denmark)

    Caillaud, Corinne; Mechta, Mie; Ainge, Heidi

    2015-01-01

    Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose leve...

  18. How bio-questionable are the different recombinant human erythropoietin copy products in Thailand?

    NARCIS (Netherlands)

    Halim, Liem Andhyk|info:eu-repo/dai/nl/412608294; Brinks, Vera|info:eu-repo/dai/nl/31395979X; Jiskoot, Wim; Romeijn, Stefan; Praditpornsilpa, Kearkiat; Assawamakin, Anunchai; Schellekens, Huub|info:eu-repo/dai/nl/068406762

    2014-01-01

    PURPOSE: The high prevalence of pure red cell aplasia in Thailand has been associated with the sharp increase in number of recombinant human erythropoietin (rhEPO) copy products, based on a classical generic regulatory pathway, which have entered the market. This study aims to assess the quality of

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

    DEFF Research Database (Denmark)

    Martin, L.; Ashenden, M; Bejder, Jacob

    2016-01-01

    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...

  20. The Significance of Erythropoietin Receptor (EpoR) Acquisition by Breast Cancer Cells

    Science.gov (United States)

    2007-08-01

    CONTRACTING ORGANIZATION: Beth Israel Deaconess Medical Center...ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Beth Israel Deaconess Medical Center Boston, MA 02215 9. SPONSORING...Arcasoy MO, Kirkpatrick JP, Vujaskovic Z, Dewhirst MW, Blackwell KL. Erythropoietin inhibits apoptosis in breast cancer cells via an Akt-dependent

  1. Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial).

    Science.gov (United States)

    Endre, Zoltán H; Walker, Robert J; Pickering, John W; Shaw, Geoffrey M; Frampton, Christopher M; Henderson, Seton J; Hutchison, Robyn; Mehrtens, Jan E; Robinson, Jillian M; Schollum, John B W; Westhuyzen, Justin; Celi, Leo A; McGinley, Robert J; Campbell, Isaac J; George, Peter M

    2010-06-01

    We performed a double-blind placebo-controlled trial to study whether early treatment with erythropoietin could prevent the development of acute kidney injury in patients in two general intensive care units. As a guide for choosing the patients for treatment we measured urinary levels of two biomarkers, the proximal tubular brush border enzymes gamma-glutamyl transpeptidase and alkaline phosphatase. Randomization to either placebo or two doses of erythropoietin was triggered by an increase in the biomarker concentration product to levels above 46.3, with a primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days. Of 529 patients, 162 were randomized within an average of 3.5 h of a positive sample. There was no difference in the incidence of erythropoietin-specific adverse events or in the primary outcome between the placebo and treatment groups. The triggering biomarker concentration product selected patients with more severe illness and at greater risk of acute kidney injury, dialysis, or death; however, the marker elevations were transient. Early intervention with high-dose erythropoietin was safe but did not alter the outcome. Although these two urine biomarkers facilitated our early intervention, their transient increase compromised effective triaging. Further, our study showed that a composite of these two biomarkers was insufficient for risk stratification in a patient population with a heterogeneous onset of injury.

  2. Disease Activity and Conversion into Multiple Sclerosis after Optic Neuritis Is Treated with Erythropoietin

    Directory of Open Access Journals (Sweden)

    Kurt-Wolfram Sühs

    2016-09-01

    Full Text Available Changes in cerebral lesion load by magnetic resonance imaging (MRI in patients from a double-blind, placebo-controlled, phase II study on erythropoietin in clinically isolated optic neuritis (ClinicalTrials.gov, NCT00355095 were analyzed. Therefore, patients with acute optic neuritis were assigned to receive either 33,000 IU of recombinant human erythropoietin (IV daily for three days, or a placebo, as an add-on to methylprednisolone. Of 35 patients, we investigated changes in cerebral lesion load in MRIs obtained at baseline and at weeks 4, 8, and 16. In 5 of the 35 patients, we found conversion into multiple sclerosis (MS based on MRI progression only. These five patients had received the placebo. Another five patients showed MRI progression together with relapses. Three of these patients had received erythropoietin, and two the placebo. Yet, analyzing the change in absolute numbers of periventricular, juxtacortical, and infratentorial lesions including gadolinium-enhancing lesions, there were no significant differences between the groups. Although effective in terms of retinal nerve fiber layer protection, erythropoietin treatment of acute isolated optic neuritis did not influence further evolution of MRI lesions in the brain when comparing absolute numbers. However, early conversion from clinically isolated syndrome to MS assessed by MRI activity seemed to occur more frequently in the placebo-treated group.

  3. Carbon monoxide in chronic uraemia related to erythropoietin treatment and smoking habits

    DEFF Research Database (Denmark)

    Thunedborg, P; Nielsen, A L; Brinkenfeldt, H

    1995-01-01

    In 69 patients on chronic haemodialysis, blood sampled randomly during dialysis was analyzed for carboxyhaemoglobin (COHb). The median value was 1.40% (range 0.9-2.3) in non-smoking patients and (1.4-7.5) in smokers. In non-smokers treated with erythropoietin (EPO) correlation was found between C...

  4. Protective effects of erythropoietin in cardiac ischemia - From bench to bedside

    NARCIS (Netherlands)

    Lipsic, Erik; Schoemaker, Regien G.; van der Meer, Peter; Voors, Adriaan A.; van Veldhuisen, Dirk J.; van Gilst, Wiek H.

    2006-01-01

    Erythropoietin (EPO) is a hypoxia-induced hormone produced in the kidneys that stimulates hematopoiesis in the bone marrow. However, recent studies have also shown important nonhematopoietic effects of EPO. A functional EPO receptor is found in the cardiovascular system, including endothelial cells

  5. Release of erythropoietin and neuron-specific enolase after breath holding in competing free divers

    DEFF Research Database (Denmark)

    Kjeld, Thomas; Jattu, T; Nielsen, Henrik

    2015-01-01

    Free diving is associated with extreme hypoxia. This study evaluated the combined effect of maximal static breath holding and underwater swimming on plasma biomarkers of tissue hypoxemia: erythropoietin, neuron-specific enolase and S100B, C-reactive protein, pro-atrial natriuretic peptide...

  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. 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

    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

  8. Study of the erythropoiesis activity of nano-encapsulated forms of erythropoietin

    Directory of Open Access Journals (Sweden)

    Zhanagul Khasenbekova

    2014-01-01

    Full Text Available Introduction: The recombinant human erythropoietin (rhEPO is used in the treatment of anemia. In order to improve its pharmacokinetic properties, nanoparticles of biodegradable polymers of natural or synthetic origin were used. The aim of this study was to investigate the effect of new nano-encapsulated forms of recombinant human erythropoietin for oral use on the erythropoiesis in the cyclophosphamide immunosuppression model. Material and methods: The CHOpE immortalized cells culture (a primary producer of rhEPO "Vector" in Russia was used. The following biodegradable polymers were chosen: 0.05% and 0.005% carbopol, 0.05% and 0.005% kollidon, and 0.05% and 0.005% pectin. Immunosuppression was obtained by a single dose of i.p. injection of cyclophosphamide (250 mg/kg in white mice (18-20 g. During the next 5 days, the nano-encapsulated erythropoietin (100 ED/mouse was administered orally to each mouse. After 5 and 10 days, the cell count of the number of blood reticulocytes and the myelogram of bone marrow were performed. The control group of mice received injections of Eprex. Results: On the 5th day of the experiment, the highest level of reticulocyte was observed in the samples of erythropoietin with kollidon (0.05% and pectin (0.005% nanoparticles. On the 10th day, the highest activity was observed in the samples of erythropoietin substance with pectin at 0.05% and 0.005% concentrations. The levels of reticulocytes in these groups reached 13.53% and 14.55%, respectively. The results of the myelogram during immunosuppression showed some activity of erythropoietin in conjunction with both concentrations of pectin when a two-fold increase in the number of erythroblasts was observed on the 5th day. High degrees of erythrokaryocytes in the state of mitosis were observed in the 0.05% pectin samples. Similar results were observed in equivalent groups of control animals on the 10th day of the experiment, which is compatible with the data on Eprex

  9. 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

  10. Systemic administration of erythropoietin inhibits retinopathy in RCS rats.

    Directory of Open Access Journals (Sweden)

    Weiyong Shen

    Full Text Available OBJECTIVE: Royal College of Surgeons (RCS rats develop vasculopathy as photoreceptors degenerate. The aim of this study was to examine the effect of erythropoietin (EPO on retinopathy in RCS rats. METHODS: Fluorescein angiography was used to monitor retinal vascular changes over time. Changes in retinal glia and vasculature were studied by immunostaining. To study the effects of EPO on retinal pathology, EPO (5000 IU/kg was injected intraperitoneally in 14 week old normal and RCS rats twice a week for 4 weeks. Changes in the retinal vasculature, glia and microglia, photoreceptor apoptosis, differential expression of p75 neurotrophin receptor (p75NTR, pro-neurotrophin 3 (pro-NT3, tumour necrosis factor-α (TNFα, pigment epithelium derived factor (PEDF and vascular endothelial growth factor-A (VEGF-A, the production of CD34(+ cells and mobilization of CD34(+/VEGF-R2(+ cells as well as recruitment of CD34(+ cells into the retina were examined after EPO treatment. RESULTS: RCS rats developed progressive capillary dropout and subretinal neovascularization which were accompanied by retinal gliosis. Systemic administration of EPO stabilized the retinal vasculature and inhibited the development of focal vascular lesions. Further studies showed that EPO modulated retinal gliosis, attenuated photoreceptor apoptosis and p75NTR and pro-NT3 upregulation, promoted the infiltration of ramified microglia and stimulated VEGF-A expression but had little effect on TNFα and PEDF expression. EPO stimulated the production of red and white blood cells and CD34(+ cells along with effective mobilization of CD34(+/VEGF-R2(+ cells. Immunofluorescence study demonstrated that EPO enhanced the recruitment of CD34+ cells into the retina. CONCLUSIONS: Our results suggest that EPO has therapeutic potentials in treatment of neuronal and vascular pathology in retinal disease. The protective effects of EPO on photoreceptors and the retinal vasculature may involve multiple

  11. Erythropoietin Attenuates Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension through Interplay between Endothelial Progenitor Cells and Heme Oxygenase

    NARCIS (Netherlands)

    van Loon, Rosa Laura E; Bartelds, Beatrijs; Wagener, Frank A D T G; Affara, Nada; Mohaupt, Saffloer; Wijnberg, Hans; Pennings, Sebastiaan W C; Takens, Janny; Berger, Rolf M F

    2015-01-01

    BACKGROUND: Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial

  12. EMI-resilient amplifier circuits

    CERN Document Server

    van der Horst, Marcel J; Linnenbank, André C

    2014-01-01

    This book enables circuit designers to reduce the errors introduced by the fundamental limitations and electromagnetic interference (EMI) in negative-feedback amplifiers.  The authors describe a systematic design approach for application specific negative-feedback amplifiers, with specified signal-to-error ratio (SER).  This approach enables designers to calculate noise, bandwidth, EMI, and the required bias parameters of the transistors used in  application specific amplifiers in order to meet the SER requirements.   ·         Describes design methods that incorporate electromagnetic interference (EMI) in the design of application specific negative-feedback amplifiers; ·         Provides designers with a structured methodology to avoid the use of trial and error in meeting signal-to-error ratio (SER) requirements; ·         Equips designers to increase EMI immunity of the amplifier itself, thus avoiding filtering at the input, reducing the number of components and avoiding detr...

  13. Low-Noise Band-Pass Amplifier

    Science.gov (United States)

    Kleinberg, L.

    1982-01-01

    Circuit uses standard components to overcome common limitation of JFET amplifiers. Low-noise band-pass amplifier employs JFET and operational amplifier. High gain and band-pass characteristics are achieved with suitable choice of resistances and capacitances. Circuit should find use as low-noise amplifier, for example as first stage instrumentation systems.

  14. Capacitively-coupled chopper amplifiers

    CERN Document Server

    Fan, Qinwen; Huijsing, Johan H

    2017-01-01

    This book describes the concept and design of the capacitively-coupled chopper technique, which can be used in precision analog amplifiers. Readers will learn to design power-efficient amplifiers employing this technique, which can be powered by regular low supply voltage such as 2V and possibly having a +\\-100V input common-mode voltage input. The authors provide both basic design concepts and detailed design examples, which cover the area of both operational and instrumentation amplifiers for multiple applications, particularly in power management and biomedical circuit designs. Discusses basic working principles and details of implementation for proven designs; Includes a diverse set of applications, along with measurement results to demonstrate the effectiveness of the technique; Explains advantages and drawbacks of the technique, given particular circumstances.

  15. Linearisation of RF Power Amplifiers

    DEFF Research Database (Denmark)

    Nielsen, Per Asbeck

    2001-01-01

    of circuitry such as the linearisation circuit. The amplifier has the highest output power compared to other published class B power in the same process. The design phase including the on-chip inductor and the lateral flux capacitors is described. The other test chips designed are envelope detectors. Three......This thesis deals with linearisation techniques of RF power amplifiers (PA), PA design techniques and integration of the necessary building blocks in a CMOS technology. The opening chapters introduces the theory of transmitter architectures, RF-signal representation and the principles of digital...... modulation. Furthermore different types of power amplifiers, models and measures of non-linearities are presented. A chapter is also devoted to different types of linearisation systems. The work carried out and described in this thesis can be divided into a more theoretical and system oriented treatment...

  16. Incorporation of Ortho- and Meta-Tyrosine Into Cellular Proteins Leads to Erythropoietin-Resistance in an Erythroid Cell Line

    Directory of Open Access Journals (Sweden)

    Esztella Mikolás

    2014-04-01

    Full Text Available Background/Aims: Erythropoietin-resistance is an unsolved concern in the treatment of renal anaemia. We aimed to investigate the possible role of ortho- and meta-tyrosine - the hydroxyl free radical products of L-phenylalanine - in the development of erythropoietin-resistance. Methods: TF-1 erythroblast cell line was used. Cell concentration was determined on day 1; 2 and 3 by two independent observers simultaneously in Bürker cell counting chambers. Protein concentration was determined with colorimetric method. Para-, ortho- and meta-tyrosine levels were measured using reverse phase-HPLC with fluorescence detection. Using Western blot method activating phosphorylation of STAT5 and ERK1/2 were investigated. Results: We found a time- and concentration-dependent decrease of erythropoietin-induced proliferative activity in case of ortho- and meta-tyrosine treated TF-1 erythroblasts, compared to the para-tyrosine cultured cells. Decreased erythropoietin-response could be regained with a competitive dose of para-tyrosine. Proteins of erythroblasts treated by ortho- or meta-tyrosine had lower para-tyrosine and higher ortho- or meta-tyrosine content. Activating phosphorylation of ERK and STAT5 due to erythropoietin was practically prevented by ortho- or meta-tyrosine treatment. Conclusion: According to this study elevated ortho- and meta-tyrosine content of erythroblasts may lead to the dysfunction of intracellular signaling, resulting in erythropoietin-hyporesponsiveness.

  17. Protective effects of erythropoietin against cuprizone-induced oxidative stress and demyelination in the mouse corpus callosum

    Directory of Open Access Journals (Sweden)

    Iraj Ragerdi Kashani

    2017-08-01

    Full Text Available Objective(s: Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of multiple sclerosis. The aim of the present work is to investigate the protective effects of erythropoietin against cuprizone-induced oxidative stress. Materials and Methods: Adult male C57BL/6J mice were fed a chow containing 0.2 % cuprizone for 6 weeks. After 3 weeks, mice were simultaneously treated with erythropoietin (5,000 IU/ kg body weight by daily intraperitoneal injections. Results: Our results showed that cuprizone induced oxidative stress accompanied with down-regulation of subunits of the respiratory chain complex and demyelination of corpus callosum. Erythropoietin antagonized these effects. Biochemical analysis showed that oxidative stress induced by cuprizone was regulated by erythropoietin. Similarly, erythropoietin induced the expression of subunits of the respiratory chain complex over normal control values reflecting a mechanism to compensate cuprizone-mediated down-regulation of these genes. Conclusion: The data implicate that erythropoietin abolishes destructive cuprizone effects in the corpus callosum by decreasing oxidative stress and restoring mitochondrial respiratory enzyme activity.

  18. Lectin-binding assays for the isoforms of human erythropoietin: comparison of urinary and four recombinant erythropoietins.

    Science.gov (United States)

    Storring, P L; Tiplady, R J; Gaines Das, R E; Rafferty, B; Mistry, Y G

    1996-09-01

    Assays have been developed for the isoforms of erythropoietin (EPO) based on their binding to eight different lectins. These assays were used to compare the isoform compositions of two preparations of human urinary EPO (uEPO) and four preparations of recombinant DNA-derived human EPO (rEPO), which had been shown to differ in their biological and immunological properties and in their isoform composition as judged by isoelectric focusing and electrophoresis. Agarose-bound Ricinus communis agglutinin I (RCA), Erythrina cristagalli agglutinin (ECA), Maackia amurensis leukoagglutinin (MAL), Sambucus nigra agglutinin (SNA), Lycopersicon esculentum agglutinin (LEA), concanavalin A (Con A), Phaseolus vulgaris agglutinin-L4 (L-PHA) and Agaricus bisporus agglutinin (ABA) were used to bind EPO isoforms possessing: N-glycans containing non-sialylated outer Gal beta 1-4GlcNAc (RCA and ECA), NeuAc alpha 2-3Gal beta 1-4GlcNAc (MAL), NeuAc alpha 2-6Gal (SNA), or repeating Gal beta 1-4GlcNAc sequences (LEA); biantennary N-glycans (Con A); tetraantennary and 2,6-branched triantennary N-glycans (L-PHA); and O-glycans containing NeuAc alpha 2-6GalNAc (SNA) and Gal beta 1-3GalNAc (ABA). Free EPO was measured by mouse spleen cell bioassay or immunoassay. Estimates from most lectin-binding assays were reproducible between assays and batches of lectin-agarose, although batches of MAL- and ABA-agarose, and to a lesser extent LEA-agarose, differed in their EPO-binding. Lectin-binding assays showed differences between the isoform compositions of all EPOs, including the two Chinese hamster ovary cell-derived rEPOs, with RCA- and ECA-binding assays being the most discriminating. Lectin-binding estimates provided evidence that uEPO differs from these rEPOs in its lower content of isoforms with biantennary N-glycans and higher content of those with multiantennary N-glycans, and in its lower content of isoforms with N-glycans possessing repeating Gal beta 1-4GlcNAc sequences and of those with O

  19. Cryogenic MMIC Low Noise Amplifiers

    Science.gov (United States)

    Weinreb, S.; Gaier, T.; Fernandez, J.; Erickson, N.; Wielgus, J.

    2000-01-01

    Monolithic (MMIC) and discrete transistor (MIC) low noise amplifiers are compared on the basis of performance, cost, and reliability. The need for cryogenic LNA's for future large microwave arrays for radio astronomy is briefly discussed and data is presented on a prototype LNA for the 1 to 10 GZH range along with a very wideband LNA for the 1 to 60 GHz range.

  20. Erythropoietin resistance in end-stage renal disease patient with gastric antral vascular ectasia

    Directory of Open Access Journals (Sweden)

    Desiree Ji Re Lee

    2015-09-01

    Full Text Available AbstractWe observed a case of recombinant human erythropoietin resistance caused by Gastric Antral Vascular Ectasia in a 40-year-old female with ESRD on hemodialysis. Some associated factors such as autoimmune disease, hemolysis, heart and liver disease were discarded on physical examination and complementary tests. The diagnosis is based on the clinical history and endoscopic appearance of watermelon stomach. The histologic findings are fibromuscular proliferation and capillary ectasia with microvascular thrombosis of the lamina propria. However, these histologic findings are not necessary to confirm the diagnosis. Gastric Antral Vascular Ectasia is a serious condition and should be considered in ESRD patients on hemodialysis with anemia and resistance to recombinant human erythropoietin because GAVE is potentially curable with specific endoscopic treatment method or through surgical procedure.

  1. Erythropoietin may reduce the risk of germ cell loss in boys with cryptorchidism

    DEFF Research Database (Denmark)

    Cortes, D; Visfeldt, J; Thorup, J M

    2001-01-01

    of infertility. In order to increase the number of germ cells, and thereby the fertility potential, additional hormonal therapy has been attempted before surgery. In a study, small doses of the gonadotropin-releasing hormone analogue buserelin before orchiopexy caused higher values. Others have found......: Erythropoietin (Eprex) 100 IU/kg were administered subcutaneously weekly for 3 months prior to surgery in two cryptorchid boys, 6 months old and 1 year 9 months old, respectively, with renal function impairment. RESULTS: The number of spermatogonia per tubular cross-section in testicular biopsies was unusually...... that hormonal treatment with human chorionic gonadotropin or gonadotropin releasing hormone analogue may harm the germ cells in cryptorchidism. The aim of the study is to demonstrate that additional hormonal therapy with erythropoietin has a positive effect on the number of germ cells. MATERIALS AND METHODS...

  2. Intraosseous Erythropoietin for Acute Tissue Protection in Battlefield Casualties Suffering Hypovolemic Shock

    Science.gov (United States)

    2013-11-01

    Reserve University, Cleveland, OH. 2002 Acute Complications of Pericardial Disease or Injury. February 19th. Acute Complications of Diabetes Mellitus...Chile. [Arterial and venous prostagladin E2 levels in patients with valvular disease ]. Guarda E, Zamorano B, Gazmuri RJ, Escobar E. 1988 Best...AD Award Number: W81XWH-11-2-0019 TITLE: “Intraosseous Erythropoietin for Acute Tissue Protection in Battlefield Casualties

  3. Erythropoietin in patients with aneurysmal subarachnoid haemorrhage: a double blind randomised clinical trial

    DEFF Research Database (Denmark)

    Springborg, J B; Møller, C; Gideon, P

    2007-01-01

    BACKGROUND: Erythropoietin (EPO) is neuroprotective in experimental models of stroke and subarachnoid haemorrhage (SAH) and possibly in patients with thromboembolic stroke. We studied the efficacy and safety of EPO in patients with SAH. METHODS: A larger scale clinical trial was planned...... no statistically significant group differences in the primary or secondary outcome measures. EPO was well tolerated. CONCLUSIONS: Beneficial effects of EPO in patients with SAH cannot be excluded or concluded on the basis of this study and larger scale trials are warranted....

  4. Erythropoietin in the critically ill: do we ask the right questions?

    OpenAIRE

    McCook, Oscar; Georgieff, Michael; Scheuerle, Angelika; M?ller, Peter; Thiemermann, Christoph; Radermacher, Peter

    2012-01-01

    There is a plethora of experimental data on the potential therapeutic benefits of recombinant human erythropoietin (rhEPO) and its synthetic derivatives in critical care medicine, in particular in ischemia/reperfusion injury. Most of the recent clinical trials have not shown clear benefits, and, in some patients, EPO-aggravated morbidity and mortality was even reported. Treatment with rhEPO has been successfully used in patients with anemia resulting from chronic kidney disease, but even a su...

  5. Physician Education: The Erythropoietin Receptor and Signal Transduction.

    Science.gov (United States)

    Yoshimura; Arai

    1996-01-01

    ERYTHROPOIETIN (EPO): Erythropoietin (EPO) is a hormone that promotes the proliferation and differentiation of erythroid progenitor cells and regulates the number of erythrocytes in peripheral blood. EPO is produced mainly by the kidneys, and transcription of the EPO gene is promoted by a reduction in the oxygen concentration in the blood. The existence of EPO was suggested near the end of the 19th century by the discovery that hypoxia increases the production of red blood cells. EPO was identified as a serum factor in the 1950s, and in 1970 Miyake and coworkers succeeded in purifying it by using the urine of patients with aplastic anemia as a starting material. The human EPO gene was cloned in 1985 using a partial amino acid sequence from this purified EPO, and it is well known that recombinant EPO is currently used as a drug to treat anemia associated with chronic renal failure and other illnesses. ACTION OF EPO: When human bone marrow cells are cultured in a semisolid medium containing EPO, they form small erythroblast colonies in five to seven days, and by day 10 large erythroblast colonies appear that resemble fireworks ("burst" colonies). The original cells in the former colonies are called colony forming units-erythroid (CFU-E) or late-stage erythroblast progenitor cells and in the latter colonies they are called burst forming units-erythroid (BFU-E) or early-stage erythroblast progenitor cells. As shown in Figure 1, red blood cells are produced through differentiation from stem cells to BFU-E, CFU-E, and erythroblasts. Although EPO acts on both BFU-E and CFU-E cells, CFU-E cells show greater sensitivity to EPO, and other factors such as stem cell factor (SCF), interleukin (IL)-3, IL-4, and granulocyte macrophage colony-stimulating factor (GM-CSF) must be present together with EPO for BFU-E cell proliferation. In erythroblasts beyond the CFU-E stage, sensitivity to EPO decreases as the cells mature. THE EPO RECEPTOR AND THE CYTOKINE RECEPTOR FAMILY: The EPO

  6. Effects of acute exercise on plasma erythropoietin levels in trained runners.

    Science.gov (United States)

    Bodary, P F; Pate, R R; Wu, Q F; McMillan, G S

    1999-04-01

    The purpose of this study was to investigate further the influence of exercise on erythropoietin. We observed the effects of high intensity running on plasma erythropoietin concentration in competitive distance runners. A repeated measures design was used to compare the responses of intermittent high intensity (HIGH) exercise to continuous moderate intensity (MOD) exercise and rest (REST). The HIGH treatment consisted of 60 min of exercise alternating 5 min of running at approximately 90% of VO2max with 5 min of brisk walking. The MOD treatment consisted of a continuous 60-min run on the treadmill at 60% of VO2max. Blood samples were collected immediately before the exercise (PRE), immediately following the exercise (POST), and 4 (heart rate (4HR), 12 (12HR), 24 (24HR), and 48 (48HR)) h following the exercise. The variables examined included plasma erythropoietin concentration ([EPO]), hemoglobin (Hb) concentration ([Hb]), hematocrit (Hct), red blood cell count (RBC), and mean corpuscular volume (MCV). ANOVA revealed the expected treatment-by-time interaction for Hct and [Hb] suggesting a hemodilution at 24 and 48 h postexercise for the MOD and HIGH treatments. However, no significant treatment-by-time interactions were observed for [EPO], RBC, or MCV. These results indicate that intermittent high intensity exercise does not have a significant effect on [EPO] in trained distance runners.

  7. 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

  8. Single conversion stage amplifier - SICAM

    Energy Technology Data Exchange (ETDEWEB)

    Ljusev, P.

    2005-12-15

    This Ph.D. thesis presents a thorough analysis of the so called SICAM - SIngle Converter stage AMplifier approach to building direct energy conversion audio power amplifiers. The mainstream approach for building isolated audio power amplifiers today consists of isolated DC power supply and Class D amplifier, which essentially represents a two stage solution, where each of the components can be viewed as separate and independent part. The proposed SICAM solution strives for direct energy conversion from the mains to the audio output, by dedicating the operation of the components one to another and integrating their functions, so that the final audio power amplifier represents a single-stage topology with higher efficiency, lower volume, less board space, lower component count and subsequently lower cost. The SICAM approach is both applicable to non-isolated and isolated audio power amplifiers, but the problems encountered in these two cases are different. Non-isolated SICAM solutions are intended for both AC mains-connected and battery-powered devices. In non-isolated mains-connected SICAMs the main idea is to simplify the power supply or even provide integrated power factor correction (PFC) functions, while still maintaining low component stress and good audio performance by generally decreasing the input voltage level to the Class D audio power amplifier. On the other hand, non-isolated battery-powered SICAMs have to cope with the ever changing battery voltage and provide output voltage levels which are both lower and higher than the battery voltage, while still being simple and single-stage energy conversion solutions. In isolated SICAMs the isolation transformer adjusts the voltage level on the secondary side to the desired level, so the main challenges here are decreasing the size of the magnetic core and reducing the number and size of bulky reactive components as much as possible. The main focus of this thesis is directed towards the isolated SICAMs and

  9. Integrated waveguide amplifiers for optical backplanes

    NARCIS (Netherlands)

    Yang, J.; Lamprecht, T.; Worhoff, Kerstin; Driessen, A.; Horst, F.; Horst, F.; Offrein, B.J.; Offrein, B.J.; Ay, F.; Pollnau, Markus

    Amplifier performance of Nd3+-doped polymer and Al2O3 channel waveguides at 880 nm is investigated. Tapered amplifiers are embedded between optical backplane waveguides, and a maximum 0.21 dB net gain is demonstrated.

  10. Identification of amplified fragment length polymorphism (AFLP ...

    African Journals Online (AJOL)

    Identification of amplified fragment length polymorphism (AFLP) fragments linked to soybean mosaic virus resistance gene in Glycine soja and conversion to a sequence characterized amplified regions (SCAR) marker for rapid selection.

  11. Higher order mode optical fiber Raman amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten; Friis, Søren Michael Mørk; Usuga Castaneda, Mario A.

    2016-01-01

    We review higher order mode Raman amplifiers and discuss recent theoretical as well as experimental results including system demonstrations.......We review higher order mode Raman amplifiers and discuss recent theoretical as well as experimental results including system demonstrations....

  12. Analog circuit design designing high performance amplifiers

    CERN Document Server

    Feucht, Dennis

    2010-01-01

    The third volume Designing High Performance Amplifiers applies the concepts from the first two volumes. It is an advanced treatment of amplifier design/analysis emphasizing both wideband and precision amplification.

  13. Cascode-based voltage-amplifier stage

    Directory of Open Access Journals (Sweden)

    Pospisilik Martin

    2017-01-01

    Full Text Available Voltage-amplifier stages are the basic components of commonly used high gain amplifiers the bias and other parameters of whose are set by the external negative feedback. The typical device that uses the voltage-amplifier stage is the operational amplifier. Similar constructions can also be created on the basis of discrete transistors. From the circuit designer’s point of view, the voltage-amplifier stage defines the crucial parameters of the whole unit - the amplification factor, dominant pole of its transfer function and the slew rate. In this paper the proposal on construction of the voltage-amplifier stage based on discrete transistors is described. When connected between the input differential amplifier and the output stage, it allows creating of cheap amplifier for HiFi applications with considerable performance.

  14. High power gas laser amplifier

    Science.gov (United States)

    Leland, Wallace T.; Stratton, Thomas F.

    1981-01-01

    A high power output CO.sub.2 gas laser amplifier having a number of sections, each comprising a plurality of annular pumping chambers spaced around the circumference of a vacuum chamber containing a cold cathode, gridded electron gun. The electron beam from the electron gun ionizes the gas lasing medium in the sections. An input laser beam is split into a plurality of annular beams, each passing through the sections comprising one pumping chamber.

  15. SPS RF System Amplifier plant

    CERN Multimedia

    1977-01-01

    The picture shows a 2 MW, 200 MHz amplifier plant with feeder lines. The main RF-system of the SPS comprises four cavities: two of 20 m length and two of 16.5 m length. They are all installed in one long straight section (LSS 3). These cavities are of the travelling-wave type operating at a centre frequency of 200.2 MHz. They are wideband, filling time about 700 ns and untuned. The power amplifiers, using tetrodes are installed in a surface building 200 m from the cavities. Initially only two cavities were installed, a third cavity was installed in 1978 and a forth one in 1979. The number of power amplifiers was also increased: to the first 2 MW plant a second 2 MW plant was added and by end 1979 there were 8 500 kW units combined in pairs to feed each of the 4 cavities with up to about 1 MW RF power, resulting in a total accelerating voltage of about 8 MV. See also 7412016X, 7412017X, 7411048X.

  16. High power regenerative laser amplifier

    Science.gov (United States)

    Miller, John L.; Hackel, Lloyd A.; Dane, Clifford B.; Zapata, Luis E.

    1994-01-01

    A regenerative amplifier design capable of operating at high energy per pulse, for instance, from 20-100 Joules, at moderate repetition rates, for instance from 5-20 Hertz is provided. The laser amplifier comprises a gain medium and source of pump energy coupled with the gain medium; a Pockels cell, which rotates an incident beam in response to application of a control signal; an optical relay system defining a first relay plane near the gain medium and a second relay plane near the rotator; and a plurality of reflectors configured to define an optical path through the gain medium, optical relay and Pockels cell, such that each transit of the optical path includes at least one pass through the gain medium and only one pass through the Pockels cell. An input coupler, and an output coupler are provided, implemented by a single polarizer. A control circuit coupled to the Pockels cell generates the control signal in timed relationship with the input pulse so that the input pulse is captured by the input coupler and proceeds through at least one transit of the optical path, and then the control signal is applied to cause rotation of the pulse to a polarization reflected by the polarizer, after which the captured pulse passes through the gain medium at least once more and is reflected out of the optical path by the polarizer before passing through the rotator again to provide an amplified pulse.

  17. Challenges in higher order mode Raman amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten; Nielsen, Kristian; Friis, Søren Michael Mørk

    2015-01-01

    A higher order Raman amplifier model that take random mode coupling into account ispresented. Mode dependent gain and signal power fluctuations at the output of the higher order modeRaman amplifier are discussed......A higher order Raman amplifier model that take random mode coupling into account ispresented. Mode dependent gain and signal power fluctuations at the output of the higher order modeRaman amplifier are discussed...

  18. Spontaneous emission from saturated parametric amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten; Ott, Johan Raunkjær; Steffensen, Henrik

    2009-01-01

    Noise performance of parametric amplifiers is typically calculated assuming un-depleted operation. However, in many applications especially when applied as regenerative amplifiers in systems based on phase shift keyed modulation schemes, this assumption is not valid. Here we show the impact...... on accumulated spontaneous emission for a parametric amplifier operated in saturation....

  19. European Research on THz Vacuum Amplifiers

    DEFF Research Database (Denmark)

    Brunetti, F.; Cojocarua, C.-S.; de Rossi, A.

    2010-01-01

    The OPTHER (OPtically Driven TeraHertz AmplifiERs) project represents a considerable advancement in the field of high frequency amplification. The design and realization of a THz amplifier within this project is a consolidation of efforts at the international level from the main players of the Eu...

  20. low pump power photonic crystal fibre amplifiers

    DEFF Research Database (Denmark)

    Hougaard, Kristian G.; Broeng, Jes; Bjarklev, Anders Overgaard

    2003-01-01

    Designs of low pump power optical amplifiers, based on photonic crystal fibres are presented. The potential of these fibre amplifiers is investigated, and it is demonstrated that such amplifiers may deliver gains of more than 15 dB at 1550 nm with less than 1 mW of optical pump power....

  1. Cooled Low-Noise HEMT Microwave Amplifiers

    Science.gov (United States)

    Bautista, J. Javier; Ortiz, Gerardo G.; Duh, Kuanghann George

    1992-01-01

    Prototype cooled low-noise microwave amplifiers based on high-electron-mobility transistors (HEMT's) considered as replacements for cooled ruby masers used as low-noise receiver-front-end amplifiers in communications, radio science, radar systems, radio astronomy, and telemetry. HEMT amplifier operates at 12 K, requires less cooling power and operates at lower cost with simpler, more-reliable cooling system.

  2. The Effect of Erythropoietin on S100 Protein Expression in Cochlea After Acoustic Overstimulation: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Gulsen Gurgen

    2014-03-01

    Full Text Available Aim: To investigate the effect of Erythropoietin on acoustically overstimulated rat spiral ganglion neurons (SGNs using S100 protein immunostaining.Material and Method: Twenty-two Wistar albino rats were divided into three groups: healthy control group (n=7, Saline solution (n=7 and Erythropoietin injection groups (n=8. Saline solution and Erythropoietin injection groups received white noise (100 dB SPL for 3 hours. Cochlear sections were stained by silver staining technique and immunostained by S100 antibody. Results: Histochemical analysis of silver staining sections revealed normal structure and a weak staining in SGNs of healthy control group. However, dark-black cytoplasmic staining, cellular shrinkage and degeneration were detected in saline injection group. On the other hand, a few weakly stained neurons were observed in erythropoietin injection group. S100 staining demonstrated strong reaction in Schwann cells and myelin sheaths of SGNs in healthy control group (p<0.05. In saline solution injection group, Schwann cells showed moderate S100 reaction and other regions of SGNs showed weak reaction (p<0.05. In erythropoietin injection group, strong S100 expression almost similar to the healthy control group was determined, although there was an occasional decrease. Discussion: Erythropoetin may prevent noise induced SGN degeneration via protecting the Schwann cells in rat cochlea.

  3. Comparison of Umbilical Serum Copeptin Relative to Erythropoietin and S100B as Asphyxia Biomarkers at Birth.

    Science.gov (United States)

    Summanen, Milla; Seikku, Laura; Rahkonen, Petri; Stefanovic, Vedran; Teramo, Kari; Andersson, Sture; Kaila, Kai; Rahkonen, Leena

    2017-01-01

    Birth asphyxia, estimated to account for a million neonatal deaths annually, can cause a wide variety of neurodevelopmental impairments. There is a need to develop new, swift methods to identify those neonates who would benefit from neuroprotective treatments such as hypothermia. To examine the utility of cord serum copeptin, a stable byproduct of arginine vasopressin release, as a biomarker of birth asphyxia based on a comparison with 2 biomarkers of hypoxia and brain trauma: erythropoietin and S100B. The study population consisted of 140 singleton, term neonates: 113 controls and 27 with birth asphyxia (2/3 criteria met: umbilical artery pH Copeptin, S100B, and erythropoietin levels in umbilical artery samples were measured by immunoassays. Copeptin correlated in the entire study population more strongly with umbilical artery base excess than S100B and erythropoietin, and only copeptin correlated with arterial pH. Furthermore, only copeptin levels were significantly higher in cases of birth asphyxia, and in vaginally born neonates they were found to increase as a function of labor duration. Copeptin was elevated in neonates born via vacuum extraction, whereas erythropoietin levels showed a slight increase after emergency cesarean section. In this study population, S100B and erythropoietin were not valid biomarkers of birth asphyxia. In contrast, our work suggests that copeptin has high potential to become a routinely used biomarker for acute birth asphyxia and neonatal distress. © 2017 S. Karger AG, Basel.

  4. Enhancing Spinal Plasticity Amplifies the Benefits of Rehabilitative Training and Improves Recovery from Stroke.

    Science.gov (United States)

    Wiersma, Anna M; Fouad, Karim; Winship, Ian R

    2017-11-08

    The limited recovery that occurs following stroke happens almost entirely in the first weeks postinjury. Moreover, the efficacy of rehabilitative training is limited beyond this narrow time frame. Sprouting of spared corticospinal tract axons in the contralesional spinal cord makes a significant contribution to sensorimotor recovery, but this structural plasticity is also limited to the first few weeks after stroke. Here, we tested the hypothesis that inducing plasticity in the spinal cord during chronic stroke could improve recovery from persistent sensorimotor impairment. We potentiated spinal plasticity during chronic stroke, weeks after the initial ischemic injury, in male Sprague-Dawley rats via intraspinal injections of chondroitinase ABC. Our data show that chondroitinase injections into the contralesional gray matter of the cervical spinal cord administered 28 d after stroke induced significant sprouting of corticospinal axons originating in the peri-infarct cortex. Chondroitinase ABC injection during chronic stroke without additional training resulted in moderate improvements of sensorimotor deficits. Importantly, this therapy dramatically potentiated the efficacy of rehabilitative training delivered during chronic stroke in a skilled forelimb reaching task. These novel data suggest that spinal therapy during chronic stroke can amplify the benefits of delayed rehabilitative training with the potential to reduce permanent disability in stroke survivors. SIGNIFICANCE STATEMENT The brain and spinal cord undergo adaptive rewiring ("plasticity") following stroke. This plasticity allows for partial functional recovery from stroke induced sensorimotor impairments. However, the plasticity that underlies recovery occurs predominantly in the first weeks following stroke, and most stroke survivors are left with permanent disability even after rehabilitation. Using animal models, our data show that removal of plasticity-inhibiting signals in the spinal cord (via

  5. High temperature charge amplifier for geothermal applications

    Science.gov (United States)

    Lindblom, Scott C.; Maldonado, Frank J.; Henfling, Joseph A.

    2015-12-08

    An amplifier circuit in a multi-chip module includes a charge to voltage converter circuit, a voltage amplifier a low pass filter and a voltage to current converter. The charge to voltage converter receives a signal representing an electrical charge and generates a voltage signal proportional to the input signal. The voltage amplifier receives the voltage signal from the charge to voltage converter, then amplifies the voltage signal by the gain factor to output an amplified voltage signal. The lowpass filter passes low frequency components of the amplified voltage signal and attenuates frequency components greater than a cutoff frequency. The voltage to current converter receives the output signal of the lowpass filter and converts the output signal to a current output signal; wherein an amplifier circuit output is selectable between the output signal of the lowpass filter and the current output signal.

  6. 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....... In conclusion, the Epo-R is present in the vasculature and myocytes in human skeletal muscle, suggesting a role in both cell types. In accordance, a single injection of Epo regulates myoglobin, MRF-4, and transferrin receptor mRNA levels. However, in contrast to our hypothesis, prolonged Epo administration had...

  7. Audio power amplifier design handbook

    CERN Document Server

    Self, Douglas

    2013-01-01

    This book is essential for audio power amplifier designers and engineers for one simple reason...it enables you as a professional to develop reliable, high-performance circuits. The Author Douglas Self covers the major issues of distortion and linearity, power supplies, overload, DC-protection and reactive loading. He also tackles unusual forms of compensation and distortion produced by capacitors and fuses. This completely updated fifth edition includes four NEW chapters including one on The XD Principle, invented by the author, and used by Cambridge Audio. Cro

  8. Visual information: amplifying and foraging

    Science.gov (United States)

    Knight, Claire; Munro, Malcolm

    2001-05-01

    Visualization is an important weapon in the management and control of the vast flood of data now generated. In order to be effective and useful it is important that such visualizations are designed to accommodate the variabilities of the tasks to which they will be put, and for the data they will be expected to be able to display. Such a view necessarily means that not all visualizations are always applicable. To this end, work has been done on visualizing software and systems with the aim of creating intelligence amplifying tools that aid, rather than try to replace the user and his intuition and domain knowledge.

  9. Activating mitochondrial function and haemoglobin expression with EH-201, an inducer of erythropoietin in neuronal cells, reverses memory impairment.

    Science.gov (United States)

    Horng, Lin-Yea; Hsu, Pei-Lun; Chen, Li-Wen; Tseng, Wang-Zou; Hsu, Kai-Tin; Wu, Chia-Ling; Wu, Rong-Tsun

    2015-10-01

    Memory impairment can be progressive in neurodegenerative diseases, and physiological ageing or brain injury, mitochondrial dysfunction and oxidative stress are critical components of these issues. An early clinical study has demonstrated cognitive improvement during erythropoietin treatment in patients with chronic renal failure. As erythropoietin cannot freely cross the blood-brain barrier, we tested EH-201 (2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside, also known as TSG), a low MW inducer of erythropoietin, for its therapeutic effects on memory impairment in models of neurodegenerative diseases, physiological ageing or brain injury. The effects of EH-201 were investigated in astrocytes and PC12 neuronal-like cells. In vivo, we used sleep-deprived (SD) mice as a stress model, amyloid-β (Aβ)-injected mice as a physiological ageing model and kainic acid (KA)-injected mice as a brain damage model to assess the therapeutic effects of EH-201. EH-201 induced expression of erythropoietin, PPAR-γ coactivator 1α (PGC-1α) and haemoglobin in astrocytes and PC12 neuronal-like cells. In vivo, EH-201 treatment restored memory impairment, as assessed by the passive avoidance test, in SD, Aβ and KA mouse models. In the hippocampus of mice given EH-201 in their diet, levels of erythropoietin, PGC-1α and haemoglobin were increased The induction of endogenous erythropoietin in neuronal cells by inducers such as EH-201 might be a therapeutic strategy for memory impairment in neurodegenerative disease, physiological ageing or traumatic brain injury. © 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

  10. Management of anemia in patients undergoing curative radiotherapy. Erythropoietin, transfusions, or better nothing?

    Energy Technology Data Exchange (ETDEWEB)

    Dunst, J. [Dept. of Radiotherapy, Martin Luther Univ. Halle-Wittenberg, Halle (Germany)

    2004-11-01

    Background and results: anemia is a well-known risk factor for decreased local control and survival in patients undergoing curative radiotherapy. There is clear evidence from recent clinical investigations that anemia is an independent risk factor and hemoglobin (Hb) levels during radiotherapy are important (and not pretreatment Hb levels). The most likely explanation for the prognostic impact is the association with tumor hypoxia. An ''optimal'' Hb range with regard to tumor oxygenation seems to exist, and Hb levels < 11 g/dl and > {proportional_to}15 g/dl impair tumor oxygenation but have (over a broader range) no significant impact on normal tissue oxygenation. There is some evidence from retrospective and prospective studies that the response to radiotherapy and the prognosis, especially in cervical cancers, might be improved if the Hb levels during radiotherapy can be maintained in the optimal range, either by transfusions or by erythropoietin. The effect of any antianemic therapy should be analyzed according to whether or not treatment was successful with regard to achieving optimal Hb levels during irradiation. Erythropoietin is probably more effective in steadily increasing and stabilizing Hb levels, but bears the risk of overcorrection of Hb levels. The clinical relevance of erythropoietin receptors on tumor cells remains questionable. Conclusions: treatment of anemia with the objective of improving local control and survival in radiotherapy patients is probably more difficult and sophisticated than coping with symptoms of anemia or improving quality of life. Nevertheless, the potential of antianemic treatment is high on the basis of experimental and clinical data, and further clinical trials are warranted. (orig.)

  11. Erythropoietin modulates neural and cognitive processing of emotional information in biomarker models of antidepressant drug action in depressed patients

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Favaron, Elisa; Hafizi, Sepehr

    2010-01-01

    Erythropoietin (Epo) has neuroprotective and neurotrophic effects, and may be a novel therapeutic agent in the treatment of psychiatric disorders. We have demonstrated antidepressant-like effects of Epo on the neural and cognitive processing of facial expressions in healthy volunteers. The curren...... study investigates the effects of Epo on the neural and cognitive response to emotional facial expressions in depressed patients.......Erythropoietin (Epo) has neuroprotective and neurotrophic effects, and may be a novel therapeutic agent in the treatment of psychiatric disorders. We have demonstrated antidepressant-like effects of Epo on the neural and cognitive processing of facial expressions in healthy volunteers. The current...

  12. High power RF solid state power amplifier system

    Science.gov (United States)

    Sims, III, William Herbert (Inventor); Chavers, Donald Gregory (Inventor); Richeson, James J. (Inventor)

    2011-01-01

    A high power, high frequency, solid state power amplifier system includes a plurality of input multiple port splitters for receiving a high-frequency input and for dividing the input into a plurality of outputs and a plurality of solid state amplifier units. Each amplifier unit includes a plurality of amplifiers, and each amplifier is individually connected to one of the outputs of multiport splitters and produces a corresponding amplified output. A plurality of multiport combiners combine the amplified outputs of the amplifiers of each of the amplifier units to a combined output. Automatic level control protection circuitry protects the amplifiers and maintains a substantial constant amplifier power output.

  13. 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 9)/L had a complete...... response, as did 3/9 with a neutrophil count 9)/L.Compared to rHuEpo or amifostine used as single agents, their combination did not offer substantial advantages....

  14. Pathogenesis and therapy of anemia in oncohemathology patients with recombinant erythropoietin agents (review

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2012-01-01

    Full Text Available The article presents a literature review on the mechanisms of anemia in patients with hematologic malignancies and a classification of chronic anemia and methods of its correction. It describes in detail the mechanism of action, indications and side effects of rembinant erythropoietin (rEPO. It gives anemia treatment algorithms with rEPO in patients with chronic blood malignancies. The analysis of rEPO efficacy is shown in anemia treatment in patients with various types of cancer. It presents the recommendations of ASCO/ASH for the use of rEPO in various patients categories.

  15. Pathogenesis and therapy of anemia in oncohemathology patients with recombinant erythropoietin agents (review

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2014-07-01

    Full Text Available The article presents a literature review on the mechanisms of anemia in patients with hematologic malignancies and a classification of chronic anemia and methods of its correction. It describes in detail the mechanism of action, indications and side effects of rembinant erythropoietin (rEPO. It gives anemia treatment algorithms with rEPO in patients with chronic blood malignancies. The analysis of rEPO efficacy is shown in anemia treatment in patients with various types of cancer. It presents the recommendations of ASCO/ASH for the use of rEPO in various patients categories.

  16. Switched-capacitor amplifier and applications

    Science.gov (United States)

    Seki, H.; Yamamoto, M.; Mori, S.

    1985-01-01

    A switched-capacitor (SC) amplifier in which the bias and load circuits are made of SC circuits is proposed. It is shown that by changing the control clock in the SC circuit, which is suitable for integration, the characteristics of the amplifier can be varied. An SC amplifier of the signal-recursion type is described. Since the SC amplifier is configured with only one active device and one set of peripheral components, it has a small size and a high gain. An example is given for an SC bandpass filter using the SC amplifier. It is concluded that the SC amplifier is useful for integration and low-power consumption of the SC network.

  17. Differential automatic zero-adjusting amplifier.

    Science.gov (United States)

    Broersen, B; Van Krevelen, F; van Heusden, J T; van Heukelom, J S

    1979-07-01

    A method is described for building a low-voltage-drift differential dc amplifier featuring automatic zero adjustment, a high input impedance, and a bandwidth of 10 kHz. This is achieved by an asymmetric two-step process between the input signal and ground. Bandwidth can be extended by the use of a second amplifier during the ground-sampling time. The amplifier can be made with standard electronic components. A major advantage of this method is that an existing amplifier can easily be converted into a low-voltage-drift amplifier by adding the essential elements of the described automatic zero-adjusting amplifier to its input stage. To illustrate the method a practical example is constructed featuring a drift of 0.2 microV/ degrees C.

  18. Enhanced Gain in Photonic Crystal Amplifiers

    DEFF Research Database (Denmark)

    Ek, Sara; Semenova, Elizaveta; Hansen, Per Lunnemann

    2012-01-01

    We experimentally demonstrate enhanced gain in the slow-light regime of quantum well photonic crystal amplifiers. A strong gain enhancement is observed with the increase of the group refractive index, due to light slow-down. The slow light enhancement is shown in a amplified spontaneous emission ....... These results are promising for short and efficient semiconductor optical amplifiers. This effect will also benefit other devices, such as mode locked lasers....

  19. Short Rayleigh Range Free Electron Laser Amplifiers

    CERN Document Server

    Yu, L H; Murphy, J B; Rose, J; Shaftan, T V; Wang, X J; Watanabe, T

    2005-01-01

    An important requirement for a high average power laser system is a manageable power density on the first optical element. One possibility to achieve this is a single pass amplifier which generates a short Rayleigh range (SRL) light beam. We present design parameters and calculated performances for several SRL configurations. These include a simulation of the optically guided (pinched) MW class FEL [1], the scalloped beam FEL amplifier [2] and high gain TOK amplifiers we propose to explore at our SDL facility.

  20. Silicon Germanium Cryogenic Low Noise Amplifiers

    Science.gov (United States)

    Bardin, J. C.; Montazeri, S.; Chang, Su-Wei

    2017-05-01

    Silicon germanium heterojunction bipolar transistors have emerged in the last decade as an excellent option for use in cryogenic low noise amplifiers. This paper begins with a review of the critical developments that have led to today’s cryogenic low noise amplifiers. Next, recent work focused on minimizing the power consumption of SiGe cryogenic amplifiers is presented. Finally, open issues related to the cryogenic noise properties of SiGe HBTs are discussed.

  1. Transverse pumped laser amplifier architecture

    Science.gov (United States)

    Bayramian, Andrew James; Manes, Kenneth; Deri, Robert; Erlandson, Al; Caird, John; Spaeth, Mary

    2013-07-09

    An optical gain architecture includes a pump source and a pump aperture. The architecture also includes a gain region including a gain element operable to amplify light at a laser wavelength. The gain region is characterized by a first side intersecting an optical path, a second side opposing the first side, a third side adjacent the first and second sides, and a fourth side opposing the third side. The architecture further includes a dichroic section disposed between the pump aperture and the first side of the gain region. The dichroic section is characterized by low reflectance at a pump wavelength and high reflectance at the laser wavelength. The architecture additionally includes a first cladding section proximate to the third side of the gain region and a second cladding section proximate to the fourth side of the gain region.

  2. Characterization of Josephson parametric amplifiers

    Energy Technology Data Exchange (ETDEWEB)

    Pogorzalek, Stefan; Fedorov, Kirill; Zhong, Ling; Bitzenbichler, Martin; Haeberlein, Max; Schwarz, Manuel J.; Eder, Peter; Goetz, Jan; Wulschner, Friedrich; Xie, Edwar; Baust, Alexander; Marx, Achim; Menzel, Edwin P.; Deppe, Frank; Gross, Rudolf [Walther-Meissner-Institut, Bayerische Akademie der Wissenschaften, Garching (Germany); Physik-Department, TU Muenchen, Garching (Germany); Nanosystems Initiative Munich (NIM), Muenchen (Germany)

    2015-07-01

    Propagating quantum microwaves are a promising building block for quantum communication. In particular, such itinerant quantum microwaves can be generated in the form of squeezed photon states using Josephson parametric amplifiers (JPA). A thorough experimental characterization of JPAs is therefore an essential prerequisite for further experiments towards quantum communication. For implementing JPAs we employ an established λ/4 bi-coplanar microwave resonator design where a dc-SQUID is biased by an external flux to tune the resonant frequency. An inductively coupled antenna acts as a pump for the JPA. We characterize several JPAs and evaluate the data within standard Josephson junction theory and the input-output formalism. In particular, we investigate hysteretic and bifurcation behavior of the JPAs in addition to usual non-degenerate JPA gain measurements.

  3. Design of an 1800nm Raman amplifier

    DEFF Research Database (Denmark)

    Svane, Ask Sebastian; Rottwitt, Karsten

    2013-01-01

    in transmission loss, but also the reduction in the Raman gain coefficient as the amplifier wavelength is increased. Both polarization components of the Raman gain is characterized, initially for linearly co-polarized signal and pump, subsequently linearly polarized orthogonal signal and pump. The noise......We present the experimental results for a Raman amplifier that operates at 1810 nm and is pumped by a Raman fiber laser at 1680 nm. Both the pump laser and the Raman amplifier is polarization maintaining. A challenge when scaling Raman amplifiers to longer wavelengths is the increase...

  4. Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins

    Energy Technology Data Exchange (ETDEWEB)

    Tsuda, E.; Goto, M.; Murakami, A.; Akia, K.; Ueda, M.; Kawanishi, G.; Takahashi, N.; Sasaki, R.; Chiba, H.; Ishihara, H.; Mori, M.

    1988-07-26

    The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPOI) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. More than 8 and 13 kinds of oligosaccharide fractions for u-EPO and r-EPO (BHK), respectively, were completely separated by the one-step HPLC procedure. The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. Furthermore, high-resolution proton nuclear magnetic resonance (/sup 1/H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK).

  5. 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 ...... 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.......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...... in a human in vivo model of acute systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of Escherichia coli endotoxin (LPS) bolus injection (0.1 ng/kg of body weight) in young healthy male subjects. The subjects were divided into three groups...

  6. Oxpentifylline versus placebo in the treatment of erythropoietin-resistant anaemia: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Fassett Robert G

    2008-08-01

    Full Text Available Abstract Background The main hypothesis of this study is that Oxpentifylline administration will effectively treat erythropoietin- or darbepoietin-resistant anaemia in chronic kidney disease patients. Methods/design Inclusion criteria are adult patients with stage 4 or 5 chronic kidney disease (including dialysis patients with significant anaemia (haemoglobin ≤ 110 g/L for at least 3 months for which there is no clear identifiable cause and that is unresponsive to large doses of either erythropoietin (≥ 200 IU/kg/week or darbepoetin (≥ 1 μg/kg/week. Patients will be randomized 1:1 to receive either placebo (1 tablet daily or oxpentifylline (400 mg daily per os for a period of 4 months. During this 4 month study period, haemoglobin measurements will be performed monthly. The primary outcome measure will be the difference in haemoglobin level between the 2 groups at the end of the 4 month study period, adjusted for baseline values. Secondary outcome measures will include erythropoiesis stimulating agent dosage, Key's index (erythropoiesis stimulating agent dosage divided by haemoglobin concentration, and blood transfusion requirement. Discussion This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their chronic kidney disease patients determine whether oxpentifylline represents a safe and effective strategy for treating erythropoiesis stimulating agent resistance in chronic kidney disease. Trial Registration Australian New Zealand Clinical Trials Registry Number ACTRN12608000199314.

  7. Erythropoietin combined with liposomal amphotericin b improves outcome during disseminated aspergillosis in mice

    Directory of Open Access Journals (Sweden)

    nathalie erousseau

    2014-10-01

    Full Text Available Disseminated aspergillosis is responsible for a high mortality rate despite the use of antifungal drugs. Adjuvant therapies are urgently needed to improve the outcome. The aim of this study was to demonstrate that the cytoprotective effect of erythropoietin combined to amphotericin b can reduce the mortality rate in a murine model of disseminated aspergillosis. After infection with Aspergillus fumigatus, neutropenic mice were randomized to receive vehicle or 7,5 mg/Kg of Liposomal Amphotericin B (LAmB or 7,5 mg/Kg of LAmB combined with 1000 IU/Kg of EPO (16 mice per group. Aspergillus galactomannan and organ cultures were performed to evaluate fungal burden at day 5. Cumulative long-term survival was analyzed at day 12 post-infection according to the Kaplan-Meier method. At day 5, fungal burden was similar between non-treated and treated groups. At day 12, mortality rates were 75 %, 62.5 % and 31 % in control group, LAmB group and EPO/LAmB group, respectively. We observed a significant decreased in mortality using EPO/LAmB combination compared to control group (p < 0.01. LAmB single treatment did not improve the survival rate compared to control group (p = 0.155.Our results provided the first evidence that erythropoietin improved the outcome of mice presenting disseminated aspergillosis when combined with amphotericin b.

  8. Ping-pong auto-zero amplifier with glitch reduction

    Science.gov (United States)

    Larson, Mark R [Maple Grove, MN

    2008-01-22

    A ping-pong amplifier with reduced glitching is described. The ping-pong amplifier includes a nulling amplifier coupled to a switching network. The switching network is used to auto-zero a ping amplifier within a ping-pong amplifier. The nulling amplifier drives the output of a ping amplifier to a proper output voltage level during auto-zeroing of the ping amplifier. By being at a proper output voltage level, glitches associated with transitioning between a ping amplifier and a pong amplifier are reduced or eliminated.

  9. 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...

  10. Effects of erythropoietin on emotional processing biases in patients with major depression: an exploratory fMRI study

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Favaron, Elisa; Hafizi, Sepehr

    2009-01-01

    INTRODUCTION: Erythropoietin (Epo) has neurotrophic effects and may be a novel therapeutic agent in the treatment of depression. We have found antidepressant-like effects of Epo on emotional processing and mood in healthy volunteers. OBJECTIVE: The current study aimed to explore the effects of Epo...

  11. Interactions of erythropoietin, granulocyte colony-stimulating factor, stem cell factor, and interleukin-11 on murine hematopoiesis during simultaneous administration

    NARCIS (Netherlands)

    Roeder, [No Value; de Haan, G; Engel, C; Nijhof, W; Dontje, B; Loeffler, M

    1998-01-01

    We investigated how in vivo effects of single hematopoietic cytokines change if given in combination for a prolonged time. Mice were treated with every combination of recombinant human (rh) erythropoietin (EPO), rh granulocyte colony-stimulating factor (G-CSF), recombinant rat (rr) stem cell factor

  12. Impact of hepcidin, interleukin 6, and other inflammatory markers with respect to erythropoietin on anemia in chronic hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Ihab A. Ibrahim

    2014-01-01

    Conclusion Serum hepcidin levels were associated with iron status and inflammation in maintenance hemodialysis patients, and the high hepcidin serum levels, found in hemodialysis (HD patients, are dependent on the magnitude of the inflammatory process and on recombinant human erythropoietin doses. Hepcidin and its regulatory pathways are potential therapeutic targets, which could lead to effective treatment of anemia in chronic hemodialysis.

  13. Effects of an 8-weeks erythropoietin treatment on mitochondrial and whole body fat oxidation capacity during exercise in healthy males

    DEFF Research Database (Denmark)

    Guadalupe-Grau, Amelia; Plenge, Ulla; Helbo, Signe

    2015-01-01

    Abstract The present investigation was performed to elucidate if the non-erythropoietic ergogenic effect of a recombinant erythropoietin treatment results in an impact on skeletal muscle mitochondrial and whole body fatty acid oxidation capacity during exercise, myoglobin concentration and angiog...

  14. Determinants of Red Cell Distribution Width (RDW) in Cardiorenal Patients : RDW is Not Related to Erythropoietin Resistance

    NARCIS (Netherlands)

    Emans, Mireille E.; van der Putten, Karien; van Rooijen, Karlijn L.; Kraaijenhagen, Rob J.; Swinkels, Dorine; van Solinge, Wouter W.; Cramer, Maarten J.; Doevendans, Pieter A. F. M.; Braam, Branko; Gaillard, Carlo A. J. M.

    Background: Studies have shown that red cell distribution width (RDW) is related to outcome in chronic heart failure (CHF). The pathophysiological process is unknown. We studied the relationship between RDW and erythropoietin (EPO) resistance, and related factors such as erythropoietic activity,

  15. The ergogenic effect of recombinant human erythropoietin on VO2max depends on the severity of arterial hypoxemia

    DEFF Research Database (Denmark)

    Robach, Paul; Calbet, Jose A L; Thomsen, Jonas J

    2008-01-01

    Treatment with recombinant human erythropoietin (rhEpo) induces a rise in blood oxygen-carrying capacity (CaO(2)) that unequivocally enhances maximal oxygen uptake (VO(2)max) during exercise in normoxia, but not when exercise is carried out in severe acute hypoxia. This implies that there should ...

  16. Effects of ganglioside G(M1 and erythropoietin on spinal cord lesions in rats: functional and histological evaluations

    Directory of Open Access Journals (Sweden)

    Raphael Martus Marcon

    Full Text Available OBJECTIVE: To evaluate the functional and histological effects of ganglioside G(M1 and erythropoietin after experimental spinal cord contusion injury. METHODS: Fifty male Wistar rats underwent experimental spinal cord lesioning using an NYU-Impactor device and were randomly divided into the following groups, which received treatment intraperitoneally. The G(M1 group received ganglioside G(M1 (30 mg/kg; the erythropoietin group received erythropoietin (1000 IU/kg; the combined group received both drugs; and the saline group received saline (0.9% as a control. A fifth group was the laminectomy group, in which the animals were subjected to laminectomy alone, without spinal lesioning or treatment. The animals were evaluated according to the Basso, Beattie and Bresnahan (BBB scale, motor evoked potential recordings and, after euthanasia, histological analysis of spinal cord tissue. RESULTS: The erythropoietin group had higher BBB scores than the G(M1 group. The combined group had the highest BBB scores, and the saline group had the lowest BBB scores. No significant difference in latency was observed between the three groups that underwent spinal cord lesioning and intervention. However, the combined group showed a significantly higher signal amplitude than the other treatment groups or the saline group (p<0.01. Histological tissue analysis showed no significant difference between the groups. Axonal index was significantly enhanced in the combined group than any other intervention (p<0.01. CONCLUSION: G(M1 and erythropoietin exert therapeutic effects on axonal regeneration and electrophysiological and motor functions in rats subjected to experimental spinal cord lesioning and administering these two substances in combination potentiates their effects.

  17. Self-pulsation in Raman fiber amplifiers

    DEFF Research Database (Denmark)

    Pedersen, Martin Erland Vestergaard; Ott, Johan Raunkjær; Rottwitt, Karsten

    2009-01-01

    Dynamic behavior caused by Brillouin scattering in Raman fiber amplifiers is studied. Modes of self-pulsation steady state oscillations are found. Their dependence on amplification scheme is demonstrated.......Dynamic behavior caused by Brillouin scattering in Raman fiber amplifiers is studied. Modes of self-pulsation steady state oscillations are found. Their dependence on amplification scheme is demonstrated....

  18. CMOS Current-mode Operational Amplifier

    DEFF Research Database (Denmark)

    Kaulberg, Thomas

    1992-01-01

    A fully differential-input differential-output current-mode operational amplifier (COA) is described. The amplifier utilizes three second generation current-conveyors (CCII) as the basic building blocks. It can be configured to provide either a constant gain-bandwidth product in a fully balanced...

  19. A CMOS current-mode operational amplifier

    DEFF Research Database (Denmark)

    Kaulberg, Thomas

    1993-01-01

    A fully differential-input, differential-output, current-mode operational amplifier (COA) is described. The amplifier utilizes three second-generation current conveyors (CCIIs) as the basic building blocks. It can be configured to provide either a constant gain-bandwidth product in a fully balanced...

  20. Design and performance of the beamlet amplifiers

    Energy Technology Data Exchange (ETDEWEB)

    Erlandson, A.C.; Rotter, M.D.; Frank, M.D.; McCracken, R.W.

    1996-06-01

    In future laser systems, such as the National Ignition Facility (NIF), multi-segment amplifiers (MSAs) will be used to amplify the laser beam to the required levels. As a prototype of such a laser architecture, the authors have designed, built, and tested flash-lamp-pumped, Nd:Glass, Brewster-angle slab MSAs for the Beamlet project. In this article, they review the fundamentals of Nd:Glass amplifiers, describe the MSA geometry, discuss parameters that are important in amplifier design, and present our results on the characterization of the Beamlet MSAs. In particular, gain and beam steering measurements show that the Beamlet amplifiers meet all optical performance specifications and perform close to model predictions.

  1. An Implantable CMOS Amplifier for Nerve Signals

    DEFF Research Database (Denmark)

    Nielsen, Jannik Hammel; Lehmann, Torsten

    2001-01-01

    In this paper, a low noise high gain CMOS amplifier for minute nerve signals is presented. By using a mixture of weak- and strong inversion transistors, optimal noise suppression in the amplifier is achieved. A continuous-time offset-compensation technique is utilized in order to minimize impact...... on the amplifier input nodes. The method for signal recovery from noisy nerve signals is presented. A prototype amplifier is realized in a standard digital 0.5 μm CMOS single poly, n-well process. The prototype amplifier features a gain of 80 dB over a 3.6 kHz bandwidth, a CMRR of more than 87 dB and a PSRR...

  2. Detection of Non-Amplified Genomic DNA

    CERN Document Server

    Corradini, Roberto

    2012-01-01

    This book offers a state-of-the-art overview on non amplified DNA detection methods and provides chemists, biochemists, biotechnologists and material scientists with an introduction to these methods. In fact all these fields have dedicated resources to the problem of nucleic acid detection, each contributing with their own specific methods and concepts. This book will explain the basic principles of the different non amplified DNA detection methods available, highlighting their respective advantages and limitations. The importance of non-amplified DNA sequencing technologies will be also discussed. Non-amplified DNA detection can be achieved by adopting different techniques. Such techniques have allowed the commercialization of innovative platforms for DNA detection that are expected to break into the DNA diagnostics market. The enhanced sensitivity required for the detection of non amplified genomic DNA has prompted new strategies that can achieve ultrasensitivity by combining specific materials with specifi...

  3. Calculations of superconducting parametric amplifiers performances

    Science.gov (United States)

    Goto, T.; Takeda, M.; Saito, S.; Shimakage, H.

    2017-07-01

    A superconducting parametric amplifier is an electromagnetic wave amplifier with high-quality characteristics such as a wide bandwidth, an extremely low noise, and a high dynamic range. In this paper, we report on the estimations of a YBCO superconducting parametric amplifier characteristic. The YBCO thin films were deposited on an MgO substrate by a pulsed laser deposition method. Based on the measured YBCO thin film parameters, theoretical calculations were implemented for evaluations of kinetic inductance nonlinearities and parametric gains. The nonlinearity of the YBCO thin film was estimated to be stronger than a single crystal NbTiN thin film. It is indicated that the YBCO parametric amplifier has a potential to be realized the amplifier with the high parametric gain. It is also expected that it could be operated in the range of the high frequency band, at the high temperature, and low applied current.

  4. Design of an 1800 nm Raman Amplifier

    DEFF Research Database (Denmark)

    Svane, Ask Sebastian; Rottwitt, Karsten

    in the pump power requirement and deteriorated noise properties. Here we demonstrate a Raman amplifier designed for signal wavelengths around 1800 nm. The amplification fiber is an OFS PM Raman fiber, and is pumped by a Raman fiber laser emitting at 1680 nm [4]. The amplifier was pumped co...... suggested as potential transmission fibers for extended wavelength operation, as low losses at long wavelengths have been predicted [3]. Fig. 1 illustrates the predicted low loss limit for a hollow core fiber and for comparison the measured loss of a OFS True Wave fiber. Besides low loss transmission fibers......, also extended band amplifiers are required. As a solution to the latter challenge, Raman amplifiers are suggested as promising candidates. The main hurdle when designing a long wavelength Raman amplifier is the increased intrinsic fiber attenuation which as a consequence leads to an increase...

  5. Quantum dots: lasers and amplifiers

    Energy Technology Data Exchange (ETDEWEB)

    Bimberg, Dieter; Ledentsov, Nikolai [Institut fuer Festkoerperphysik, PN5-2, Technische Universitaet Berlin, Hardenbergstrasse 36, 10623 (Germany)

    2003-06-25

    Continuous wave room-temperature output power of {approx} 3 W for edge emitters and of 1.2 mW for vertical-cavity surface-emitting lasers is realized for GaAs-based devices using InAs quantum dots (QDs) operating at 1.3 {mu}m. Characteristic temperatures up to 170 K below 330 K are realized. Simultaneously, differential efficiency exceeds 80% for these devices. Lasers emitting up to 12 W at 1140-1160 nm are useful as pump sources for Tm{sup 3+}-doped fibres for frequency up-conversion to 470 nm. Both types of lasers show transparency current densities of 6 A cm{sup -2} per dot layer, {eta}{sub int} = 98% and {alpha}{sub i} around 1.5 cm{sup -1}. Long operation lifetimes (above 3000 h at 50 deg C heatsink temperature at 1.5 W CW) and improved radiation hardness as compared to quantum well (QW) devices are manifested. Cut-off frequencies of about 10 GHz at 1100 nm and 6 GHz at 1300 nm and low {alpha} factors resulting in reduced filamentation and improved M{sup 2} values in single-mode operation are realized. Quantum dot semiconductor optical amplifiers (QD SOAs) demonstrate gain recovery times of 120-140 fs, 4-7 times faster than bulk/QW SOAs. The breakthrough became possible due to the development of self-organized growth in QD technology. (topical review)

  6. Free electron maser amplifier experiments

    CERN Document Server

    Whyte, C G; Cross, A W; He, W; Ronald, K; Young, A; Phelps, A D R

    2000-01-01

    We present results from the X-band reversed guide magnetic field Raman Free Electron Maser (FEM) amplifier experiment at Strathclyde University. The FEM has been designed for zero slippage to achieve maximum instantaneous bandwidth. The tuneablity is further extended by the adjustment of beam voltage and undulator field strength. A 1 kW TWT has been used as the input source for broadband measurements and two 25 kW magnetrons for saturated output power measurements at discrete frequencies. Results show an instantaneous -3 dB bandwidth of 30% for a fixed cathode voltage and magnetic field. The device can be tuned over a range of 65% of the centre frequency by adjusting the cathode voltage. A saturated power of over 1 MW has been measured for 50 A input current. Broadband unsaturated gains of over 35 dB have been measured. An experiment using a 50 A beam from a thermionic cathode electron gun designed at Strathclyde is currently in progress. This will theoretically allow CW operation of the FEM using a DC undula...

  7. Measuring Optimal Length of the Amplifying Fiber in Different Working Conditions of the Amplifier

    Directory of Open Access Journals (Sweden)

    Radek Poboril

    2014-01-01

    Full Text Available The aim of this article is to highlight possible unwanted behaviour of an EDFA optical amplifier during temperature changes. After a brief introduction dealing with amplifiers and doped fibers in general we focus on the assembly of our own EDFA amplifier with standard construction and the IsoGain I-6 amplifying fiber, and on the parameters of its individual components. Since an erbium doped fiber has usually no direct thermal stabilization, temperature changes can affect performance of the entire amplifier. The next part of the article therefore describes the impacts of such changes on behaviour of our amplifier. At the very end we performed a measurement of the amplifier deployed in the actual WDM-PON the description of which can be found in the last chapter.

  8. Post-treatment Effects of Erythropoietin and Nordihydroguaiaretic Acid on Recovery from Cisplatin-induced Acute Renal Failure in the Rat

    OpenAIRE

    Lee, Dong Won; Kwak, Ihm Soo; Lee, Soo Bong; Song, Sang Heon; Seong, Eun Young; Yang, Byeong Yun; Lee, Min Young; SOL, MEE YOUNG

    2009-01-01

    5-Lipoxygenase inhibitor and human recombinant erythropoietin might accelerate renal recovery in cisplatin-induced acute renal failure rats. Male Sprague-Dawley rats were randomized into four groups: 1) normal controls; 2) Cisplatin group-cisplatin induced acute renal failure (ARF) plus vehicle treatment; 3) Cisplatin+nordihydroguaiaretic acid (NDGA) group-cisplatin induced ARF plus 5-lipoxygenase inhibitor treatment; 4) Cisplatin+erythropoietin (EPO) group-cisplatin induced ARF plus erythrop...

  9. An Implantable CMOS Amplifier for Nerve Signals

    DEFF Research Database (Denmark)

    Nielsen, Jannik Hammel; Lehmann, Torsten

    2003-01-01

    In this paper, a low noise high gain CMOS amplifier for minute nerve signals is presented. The amplifier is constructed in a fully differential topology to maximize noise rejection. By using a mixture of weak- and strong inversion transistors, optimal noise suppression in the amplifier is achieved....... A continuous-time current-steering offset-compensation technique is utilized in order to minimize the noise contribution and to minimize dynamic impact on the amplifier input nodes. The method for signal recovery from noisy nerve signals is presented. A prototype amplifier is realized in a standard digital 0.......5 mum CMOS single poly, n-well process. The prototype amplifier features a gain of 80 dB over a 10 kHz bandwidth, a CMRR of more than 87 dB and a PSRR greater than 84 dB. The equivalent input referred noise in the bandwidth of interest is 4.8 nV/rootHz. The amplifier power consumption is 275 muW, drawn...

  10. Patient Blood Management in Major Orthopedic Surgery: Less Erythropoietin and More Iron?

    Science.gov (United States)

    Rineau, Emmanuel; Stoyanov, Alexandra; Samson, Emmanuel; Hubert, Laurent; Lasocki, Sigismond

    2017-11-01

    Erythropoietin (EPO) is proposed preoperatively to reduce blood transfusion in anemic patients (hemoglobin < 13 g/dL) scheduled for a major orthopedic surgery. New intravenous iron formulations allow infusion of higher doses, increasing EPO response. In that context, we evaluated in a before-after study (n = 62 and 65 patients for each period) a new EPO administration protocol (2 injections 4 and 3 weeks before surgery, and a third if hemoglobin <13 g/dL instead of <15 g/dL 2 weeks before surgery). After this protocol implementation, the mean (standard deviation) number of EPO injections decreased from 2.8 (0.5) to 2.2 (0.4)/patient (P < .0001) without changing transfusion rates (3% in the 2 periods).

  11. Erythropoietin may reduce the risk of germ cell loss in boys with cryptorchidism

    DEFF Research Database (Denmark)

    Cortes, Dina; Visfeldt, J; Thorup, J M

    2001-01-01

    In boys with cryptorchidism older than 2 years a testicular biopsy at time of orchiopexy shows lack of germ cells in 10-40% of the cases. The number of spermatogonia per tubule is prognostic for subsequent fertility potential. A biopsy without germ cells is associated with 33-100% risk...... of infertility. In order to increase the number of germ cells, and thereby the fertility potential, additional hormonal therapy has been attempted before surgery. In a study, small doses of the gonadotropin-releasing hormone analogue buserelin before orchiopexy caused higher values. Others have found...... that hormonal treatment with human chorionic gonadotropin or gonadotropin releasing hormone analogue may harm the germ cells in cryptorchidism. The aim of the study is to demonstrate that additional hormonal therapy with erythropoietin has a positive effect on the number of germ cells....

  12. Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Vinberg, Maj; Harmer, Catherine J

    2010-01-01

    BACKGROUND: Depression and bipolar disorder are associated with reduced neural plasticity and deficits in memory, attention and executive function. Drug treatments for these affective disorders have insufficient clinical effects in a large group and fail to reverse cognitive deficits. There is thus...... a need for more effective treatments which aid cognitive function. Erythropoietin (Epo) is involved in neuroplasticity and is a candidate for future treatment of affective disorders. The investigators have demonstrated that a single dose of Epo improves cognitive function and reduces neurocognitive...... processing of negative emotional information in healthy and depressed individuals similar to effects seen with conventional antidepressants. The current study adds to the previous findings by investigating whether repeated Epo administration has antidepressant effects in patients with treatment resistant...

  13. 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......HuEpo treatment VO2max increased (PVO2max) was increased by 54.0 and 54.3% (P... week 11), TTE was decreased by 26.8% as compared to pre rHuEpo administration. In conclusion, in healthy non-athlete subjects rHuEpo administration prolongs submaximal exercise performance by about 54% independently of the approximately 12% increase in VO2max....

  14. 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

    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...... 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...

  15. PRELIMINARY MODELING OF AN INDUSTRIAL RECOMBINANT HUMAN ERYTHROPOIETIN PURIFICATION PROCESS BY ARTIFICIAL NEURAL NETWORKS

    Directory of Open Access Journals (Sweden)

    R. H. R. Garcel1

    2015-09-01

    Full Text Available AbstractIn the present study a preliminary neural network modelling to improve our understanding of Recombinant Human Erythropoietin purification process in a plant was explored. A three layer feed-forward back propagation neural network was constructed for predicting the efficiency of the purification section comprising four chromatographic steps as a function of eleven operational variables. The neural network model performed very well in the training and validation phases. Using the connection weight method the predictor variables were ranked based on their estimated explanatory importance in the neural network and five input variables were found to be predominant over the others. These results provided useful information showing that the first chromatographic step and the third chromatographic step are decisive to achieve high efficiencies in the purification section, thus enriching the control strategy of the plant.

  16. CNS hypoxia is more pronounced in murine cerebral than noncerebral malaria and is reversed by erythropoietin

    DEFF Research Database (Denmark)

    Hempel, Casper; Combes, Valery; Hunt, Nicholas Henry

    2011-01-01

    observed in mice without CM, and hypoxia seemed to be confined to neuronal cell somas. PARP-1-deficient mice were not protected against CM, which argues against a role for cytopathic hypoxia. Erythropoietin therapy reversed the development of CM and substantially reduced the degree of neural hypoxia......Cerebral malaria (CM) is associated with high mortality and risk of sequelae, and development of adjunct therapies is hampered by limited knowledge of its pathogenesis. To assess the role of cerebral hypoxia, we used two experimental models of CM, Plasmodium berghei ANKA in CBA and C57BL/6 mice....... These findings demonstrate cerebral hypoxia in malaria, strongly associated with cerebral dysfunction and a possible target for adjunctive therapy....

  17. Effects of erythropoietin on memory-relevant neurocircuitry activity and recall in mood disorders

    DEFF Research Database (Denmark)

    Miskowiak, K W; Macoveanu, J; Vinberg, M

    2016-01-01

    OBJECTIVE: Erythropoietin (EPO) improves verbal memory and reverses subfield hippocampal volume loss across depression and bipolar disorder (BD). This study aimed to investigate with functional magnetic resonance imaging (fMRI) whether these effects were accompanied by functional changes in memory......MRI at 3T, mood ratings, and blood tests at baseline and week 14. During fMRI, participants performed a picture encoding task followed by postscan recall. RESULTS: Sixty-two patients had complete data (EPO: N = 32, saline: N = 30). EPO improved picture recall and increased encoding-related activity...... cohort. The effects of EPO were not correlated with change in mood, red blood cells, blood pressure, or medication. CONCLUSION: The findings highlight enhanced encoding-related dlPFC and temporo-parietal activity as key neuronal underpinnings of EPO-associated memory improvement....

  18. Neural correlates of improved executive function following erythropoietin treatment in mood disorders

    DEFF Research Database (Denmark)

    Miskowiak, K. W.; Vinberg, M.; Glerup, L.

    2016-01-01

    BACKGROUND: Cognitive dysfunction in depression and bipolar disorder (BD) is insufficiently targeted by available treatments. Erythropoietin (EPO) increases neuroplasticity and may improve cognition in mood disorders, but the neuronal mechanisms of these effects are unknown. This functional...... of EPO (40 000 IU) (N = 30) or saline (N = 26) in a double-blind, parallel-group design. Patients underwent fMRI, mood ratings and blood tests at baseline and week 14. During fMRI patients performed an n-back WM task. RESULTS: EPO improved WM accuracy compared with saline (p = 0.045). Whole......, baseline to follow-up changes in WM performance correlated positively with changes in WM-related SFG activity and negatively with hippocampal response (r = 0.28-0.30, p mood or red blood cells (p ⩾0.08). CONCLUSIONS: The present findings...

  19. Erythropoietin deficiency in acute crescentic glomerulonephritis and in total bilateral renal cortical necrosis

    DEFF Research Database (Denmark)

    Thaysen, J H; Nielsen, O J; Brandi, L

    1991-01-01

    Six patients with acute renal failure, in five cases due to acute crescentic glomerulonephritis and in one case due to total bilateral renal cortical necrosis, were studied. All had serum erythropoietin (EPO) concentrations in the normal range, despite a relatively severe anaemia. Half...... treated with rhEPO (Eprex). In marked contrast to untreated controls, both patients responded with vigorous reticulocytosis and normalization of haemoglobin levels while they were still in severe renal failure. These results are similar to our previous findings in patients with acute renal failure due...... of EPO is not only a permanent and irreversible feature of severe chronic renal failure, but that it is also present, usually in a transient and reversible form, in different types of acute renal failure....

  20. Satellite cell response to erythropoietin treatment and endurance training in healthy young men

    DEFF Research Database (Denmark)

    Hoedt, Andrea; Christensen, Britt; Nellemann, Birgitte

    2016-01-01

    KEY POINT: Erythropoietin (Epo) treatment may induce myogenic differentiation factor (MyoD) expression and prevent apoptosis in satellite cells (SCs) in murine and in vitro models. Endurance training stimulates SC proliferation in vivo in murine and human skeletal muscle. In the present study, we......-receptor interaction. Moreover, endurance training, but not Epo treatment, increases the SC content in type II myofibres, as well as the content of MyoD(+) SCs. Collectively, our results suggest that Epo treatment can regulate human SCs in vivo, supported by Epo receptor mRNA expression in human SCs. In effect, long......-term Epo treatment during disease conditions involving anaemia may impact SCs and warrants further investigation. Satellite cell (SC) proliferation is observed following erythropoitin treatment in vitro in murine myoblasts and endurance training in vivo in human skeletal muscle. The present study aimed...

  1. Common variants of the genes encoding erythropoietin and its receptor modulate cognitive performance in schizophrenia

    DEFF Research Database (Denmark)

    Kästner, Anne; Grube, Sabrina; El-Kordi, Ahmed

    2012-01-01

    Erythropoietin (EPO) improves cognitive performance in clinical studies and rodent experiments. We hypothesized that an intrinsic role of EPO for cognition exists, with particular relevance in situations of cognitive decline, which is reflected by associations of EPO and EPO receptor (EPOR......) genotypes with cognitive functions. To prove this hypothesis, schizophrenic patients (N > 1000) were genotyped for 5' upstream-located gene variants, EPO SNP rs1617640 (T/G) and EPORSTR(GA)(n). Associations of these variants were obtained for cognitive processing speed, fine motor skills and short......-term memory readouts, with one particular combination of genotypes superior to all others (p 800), these associations were confirmed. A matching preclinical study with mice demonstrated cognitive processing speed and memory enhanced upon transgenic...

  2. Erythropoietin levels in patients with sleep apnea: a meta-analysis.

    Science.gov (United States)

    Zhang, Xiao-Bin; Zeng, Yi-Ming; Zeng, Hui-Qing; Zhang, Hua-Ping; Wang, Hui-Ling

    2017-06-01

    Currently available data regarding the blood levels of erythropoietin (EPO) in sleep apnea (SA) patients are contradictory. The aim of the present meta-analysis was to evaluate the EPO levels in SA patients via quantitative analysis. A systematic search of Pubmed, Embase, and Web of Science were performed. EPO levels in SA group and control group were extracted from each eligible study. Weight mean difference (WMD) or Standard mean difference (SMD) with 95% confidence interval (CI) was calculated by using fixed-effects or random effect model analysis according to the degree of heterogeneity between studies. A total of 9 studies involving 407 participants were enrolled. The results indicated that EPO levels in SA group were significantly higher than that in control group (SMD 0.61, 95% CI 0.11-1.11, p = 0.016). Significantly higher EPO levels were found in patients with body mass index analysis (both p analysis.

  3. A Low-Noise Semiconductor Optical Amplifier

    Energy Technology Data Exchange (ETDEWEB)

    Ratowsky, R.P.; Dijaili, S.; Kallman, J.S.; Feit, M.D.; Walker, J.

    1999-03-23

    Optical amplifiers are essential devices for optical networks, optical systems, and computer communications. These amplifiers compensate for the inevitable optical loss in long-distance propagation (>50 km) or splitting (>10x). Fiber amplifiers such as the erbium-doped fiber amplifier have revolutionized the fiber-optics industry and are enjoying widespread use. Semiconductor optical amplifiers (SOAs) are an alternative technology that complements the fiber amplifiers in cost and performance. One obstacle to the widespread use of SOAs is the severity of the inevitable noise output resulting from amplified spontaneous emission (ASE). Spectral filtering is often used to reduce ASE noise, but this constrains the source spectrally, and improvement is typically limited to about 10 dB. The extra components also add cost and complexity to the final assembly. The goal of this project was to analyze, design, and take significant steps toward the realization of an innovative, low-noise SOA based on the concept of ''distributed spatial filtering'' (DSF). In DSF, we alternate active SOA segments with passive free-space diffraction regions. Since spontaneous emission radiates equally in all directions, the free-space region lengthens the amplifier for a given length of gain region, narrowing the solid angle into which the spontaneous emission is amplified [1,2]. Our innovation is to use spatial filtering in a differential manner across many segments, thereby enhancing the effect when wave-optical effects are included [3]. The structure quickly and effectively strips the ASE into the higher-order modes, quenching the ASE gain relative to the signal.

  4. Assessing the instability of the isoelectric focusing patterns of erythropoietin in urine.

    Science.gov (United States)

    Belalcazar, Viviana; Gutiérrez Gallego, Ricardo; Llop, Esther; Segura, Jordi; Pascual, José Antonio

    2006-11-01

    IEF can be used to differentiate human urinary erythropoietin (uEPO), recombinant human erythropoietin or epoetin (rEPO) and darbepoetin (novel erythropoiesis stimulating protein (NESP)). This is the basis of the method currently used to detect misuse of rEPO and NESP by elite athletes. Recently, an unknown activity has been attributed to some urine samples (denominated 'unstable' urine by the World Anti-Doping Agency; WADA). This activity has shown to give rise to artefactual profiles for both rEPO and NESP when incubated with such urine and, thus, raised concerns with respect to doping control. We have evaluated which charges produce the characteristic IEF profiles of uEPO, rEPO and NESP and how these profiles respond to distinct enzymatic reactions. From sialidase digestions it became evident that only uEPO contains charges different from sialic acid, and a comparison of all substances after complete de-N-glycosylation localized these charges in the carbohydrate moiety. Partial desialylation, or digestion with arylsulfatase from Helix pomatia yielded profiles for recombinants species similar to those observed for unstable urine samples. The contributions from our studies to the anti-doping problem include: (i) protocols that may corroborate the potential misuse of rEPO or NESP based on the particular enzymatic activity of an arylsulfatase preparation, or a broad-specificity sialidase; (ii) assurance that the instability observed in some urine samples may only result from false-negatives, but not from false-positive testing; and (iii) a simple remedy to prevent an unstable urine from altering the IEF profile by adding selective competitive substrates.

  5. The role of erythropoietin stimulating agents in anemic patients with heart failure: solved and unresolved questions

    Directory of Open Access Journals (Sweden)

    Palazzuoli A

    2014-08-01

    Full Text Available Alberto Palazzuoli, Gaetano Ruocco, Marco Pellegrini, Carmelo De Gori, Gabriele Del Castillo, Nicola Giordano, Ranuccio NutiDepartment of Internal Medicine and Metabolic Diseases, Cardiology Section, Le Scotte Hospital, University of Siena, Siena, ItalyAbstract: Anemia is a common finding in congestive heart failure (CHF and is associated with an increased mortality and morbidity. Several conditions can cause depression of erythroid progenitor cells: reduction of iron absorption and reuptake, decreased bone marrow activity, reduced endogenous erythropoietin production, and chronic inflammatory state. Anemia’s etiology in CHF is complex and partially understood; it involves several systems including impaired hemodynamic condition, reduced kidney and bone perfusion, increased inflammatory activity, and neurohormonal overdrive. The use of erythropoiesis stimulating agents (ESAs such as erythropoietin and its derivatives is recently debated; the last interventional trial seems to demonstrate a neutral or negative effect in the active arm with darbepoetin treatment. The current data is opposite to many single blind studies and previous meta-analysis showing an improvement in quality of life, New York Heart Association class, and exercise tolerance using ESA therapy. These contrasting data raise several concerns regarding the target of hemoglobin levels needing intervention, the exact anemia classification and categorization, and the standardization of hematocrit cutoffs. Some cardiac and systemic conditions (ie, hypertension, atrial fibrillation, prothrombotic status may predispose to adverse events, and ESA administration should be avoided. To prevent the negative effects, high-dosage and chronic administration should be avoided. Clarification of these items could probably identify patients that may benefit from additional iron or ESA treatment. In this review, we discuss the interventional trials made in anemic heart failure patients, the

  6. 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.

  7. Recombinant human erythropoietin therapy for anemic cancer patients receiving cisplatin chemotherapy.

    Science.gov (United States)

    Henry, D H; Brooks, B J; Case, D C; Fishkin, E; Jacobson, R; Keller, A M; Kugler, J; Moore, J; Silver, R T; Storniolo, A M; Abels, R I; Gordon, D S; Nelson, R; Larholt, K; Bryant, E; Rudnick, S

    1995-01-01

    To assess whether the administration of recombinant human erythropoietin (r-HuEPO) would increase the hematocrit, reduce the requirement for transfusion, and improve the quality of life in anemic cancer patients receiving myelosuppressive, cisplatin-based chemotherapy. One hundred thirty-two anemic cancer patients receiving cyclic, cisplatin-containing, myelosuppressive chemotherapy were evaluated. Patients received either r-HuEPO (150 U/kg) or placebo, subcutaneously, three times a week for 3 months. Responses were assessed by measuring changes in hemoglobin/hematocrit, transfusion requirement, and quality of life. The mean hematocrit increased by 6.0 percentage points in the r-HuEPO group versus 1.3 in the placebo group. A decrease in transfusion requirement did not reach significance over all 3 months, but there was a significant reduction in the percentage of patients transfused in the second and third months (27% r-HuEPO vs. 56% placebo) and a trend toward reduction in the mean total number of units transfused (1.20 units r-HuEPO vs. 2.02 units placebo), suggesting a lag of 1 month before r-HuEPO can affect the transfusion requirement. Pretreatment serum erythropoietin levels were lower in responders than in nonresponders (73.5 IU/L and 86.3 IU/L means, respectively). However, the magnitude of this difference was not helpful in defining which patients were likely to respond. There was a significant improvement in overall quality of life between the two treatment arms in favor of the r-HuEPO-treated group. There were no significant adverse effects associated with r-HuEPO. r-HuEPO is safe and can cause a significant improvement in the hematocrit and quality of life of anemic cancer patients receiving myelosuppressive, cisplatin-based chemotherapy. After 1 month of r-HuEPO, there is also a reduction in transfusion requirement.

  8. Recombinant human erythropoietin reduces plasminogen activator inhibitor and ameliorates pro-inflammatory responses following trauma

    Directory of Open Access Journals (Sweden)

    M Mojtahedzadeh

    2011-05-01

    Full Text Available "n  "n Background and the purpose of the study: Besides its hematopoietic effects, erythropoietin (EPO by mobilization of iron and modulation of some inflammatory cytokines has antioxidant and anti-inflammatory properties. The purpose of this study was to evaluate these effects of erythropoietin and its impact on organ function in traumatized patients. "n Methods: Twenty-six ICU-admitted traumatized patients within 24 hrs after trauma were randomly assigned to the EPO (received EPO, 300 units/Kg/day and Control (not received EPO groups. The inflammatory biomarkers including Tumor Necrosis Factor alpha (TNF-α, Interleukin 1 (IL-1, Plasminogen Activator Inhibitor 1 (PAI-1 and Nitrotyrosine were recorded at the admission, 3, 6 and 9 days thereafter. Acute Physiology and Chronic Health Evaluation (APACHE II and Sequential Organ Failure Assessment (SOFA scores were also recorded. "n Results: Among 12 patients (EPO group TNF-α level at the day of 9 (P=0.046, and within EPO group at the days of 3 (P=0.026 ameliorate, 6 (P=0.016, and 9 (P=0.052 were significantly lowered. Level of IL-1 and PAI-1 decreased significantly at days of 3, 6 and 9 post intervention. Also there were significant differences between two groups in the SOFA score during three measured time intervals (the first, third and seventh days. "n Conclusion: From the results of this study it seems that injection of erythrocyte stimulating agent is well tolerated and inhibits the inflammatory response and oxidative stress following trauma.

  9. 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.

  10. Broad-band semiconductor optical amplifiers

    Energy Technology Data Exchange (ETDEWEB)

    Ding Ying [Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China)]. E-mail: yingding@red.semi.ac.cn; Kan Qiang [Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China); Wang Junling [Institute of Optoelectronic Technology, Beijing Jiaotong University, Beijing 100044 (China); Pan Jiaoqing [Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China); Zhou Fan [Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China); Chen Weixi [School of Physics, Peking University, Beijing 100871 (China); Wang Wei [Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China)

    2007-01-15

    Broad-band semiconductor optical amplifiers (SOAs) with different thicknesses and thin bulk tensile-strained active layers were fabricated and studied. Amplified spontaneous emission (ASE) spectra and gain spectra of SOAs were measured and analyzed at different CW biases. A maximal 3 dB ASE bandwidth of 136 nm ranging from 1480 to 1616 nm, and a 3 dB optical amplifier gain bandwidth of about 90 nm ranging from 1510 to 1600 nm, were obtained for the very thin bulk active SOA. Other SOAs characteristics such as saturation output power and polarization sensitivity were measured and compared.

  11. A parallel input composite transimpedance amplifier

    Science.gov (United States)

    Kim, D. J.; Kim, C.

    2018-01-01

    A new approach to high performance current to voltage preamplifier design is presented. The design using multiple operational amplifiers (op-amps) has a parasitic capacitance compensation network and a composite amplifier topology for fast, precision, and low noise performance. The input stage consisting of a parallel linked JFET op-amps and a high-speed bipolar junction transistor (BJT) gain stage driving the output in the composite amplifier topology, cooperating with the capacitance compensation feedback network, ensures wide bandwidth stability in the presence of input capacitance above 40 nF. The design is ideal for any two-probe measurement, including high impedance transport and scanning tunneling microscopy measurements.

  12. Fundamentals of RF and microwave transistor amplifiers

    CERN Document Server

    Bahl, Inder J

    2009-01-01

    A Comprehensive and Up-to-Date Treatment of RF and Microwave Transistor Amplifiers This book provides state-of-the-art coverage of RF and microwave transistor amplifiers, including low-noise, narrowband, broadband, linear, high-power, high-efficiency, and high-voltage. Topics covered include modeling, analysis, design, packaging, and thermal and fabrication considerations. Through a unique integration of theory and practice, readers will learn to solve amplifier-related design problems ranging from matching networks to biasing and stability. More than 240 problems are included to help read

  13. Laser Cooled High-Power Fiber Amplifier

    OpenAIRE

    Nemova, Galina

    2009-01-01

    A theoretical model for laser cooled continuous-wave fiber amplifier is presented. The amplification process takes place in the Tm3+-doped core of the fluoride ZBLAN (ZrF4-BaF2-LaF3-AlF3-NaF) glass fiber. The cooling process takes place in the Yb3+:ZBLAN fiber cladding. It is shown that for each value of the pump power and the amplified signal there is a distribution of the concentration of the Tm3+ along the length of the fiber amplifier, which provides its athermal operation. The influence ...

  14. Phase noise in RF and microwave amplifiers.

    Science.gov (United States)

    Boudot, Rodolphe; Rubiola, Enrico

    2012-12-01

    Understanding amplifier phase noise is a critical issue in many fields of engineering and physics, such as oscillators, frequency synthesis, telecommunication, radar, and spectroscopy; in the emerging domain of microwave photonics; and in exotic fields, such as radio astronomy, particle accelerators, etc. Focusing on the two main types of base noise in amplifiers, white and flicker, the power spectral density of the random phase φ(t) is Sφ(f) = b(0) + b(-1)/f. White phase noise results from adding white noise to the RF spectrum in the carrier region. For a given RF noise level, b(0) is proportional to the reciprocal of the carrier power P(0). By contrast, flicker results from a near-dc 1/f noise-present in all electronic devices-which modulates the carrier through some parametric effect in the semiconductor. Thus, b(-1) is a parameter of the amplifier, constant in a wide range of P(0). The consequences are the following: Connecting m equal amplifiers in parallel, b(-1) is 1/m times that of one device. Cascading m equal amplifiers, b(-1) is m times that of one amplifier. Recirculating the signal in an amplifier so that the gain increases by a power of m (a factor of m in decibels) as a result of positive feedback (regeneration), we find that b(-1) is m(2) times that of the amplifier alone. The feedforward amplifier exhibits extremely low b(-1) because the carrier is ideally nulled at the input of its internal error amplifier. Starting with an extensive review of the literature, this article introduces a system-oriented model which describes the phase flickering. Several amplifier architectures (cascaded, parallel, etc.) are analyzed systematically, deriving the phase noise from the general model. There follow numerous measurements of amplifiers using different technologies, including some old samples, and in a wide frequency range (HF to microwaves), which validate the theory. In turn, theory and results provide design guidelines and give suggestions for CAD and

  15. Ultrashort pulse amplification in cryogenically cooled amplifiers

    Science.gov (United States)

    Backus, Sterling J.; Kapteyn, Henry C.; Murnane, Margaret Mary

    2004-10-12

    A laser amplifier system amplifies pulses in a single "stage" from .about.10.sup.-9 joules to more than 10.sup.-3 joules, with average power of 1-10 watts, and beam quality M.sup.2 characteristics of the medium. This is done with the medium inside a sealed, evacuated or purged cell to avoid moisture or other materials condensing on the surface. A "seed" pulse from a separate laser is passed through the laser medium, one or more times, in any of a variety of configurations including single-pass, multiple-pass, and regenerative amplifier configurations.

  16. Small signal microwave amplifier design solutions

    CERN Document Server

    Grosch, Theodore

    2000-01-01

    This book explains techniques and examples for designing stable amplifiers for high-frequency applications in which the signal is small and the amplifier circuit is linear. An in-depth discussion of linear network theory provides the foundation needed to develop actual designs. Examples throughout the book will show you how to apply the knowledge gained in each chapter leading to the complex design of low noise amplifiers. Many exercises at the end of each chapter will help students to practice their skills. The solutions to these design problems are available in an accompanying solutions book

  17. Noise Suppression Phenomenon in Fiber Raman Amplifier

    Directory of Open Access Journals (Sweden)

    Felinskyi Georgii

    2015-06-01

    Full Text Available The problem of small bit error rate is actual in fiber Raman amplifiers. Our experimental data on the amplified spontaneous emission (ASE with backward pumping as a base of optical noise evaluation are presented in this paper. Raman gain spectrum for useful Stokes low-powered signal is calculated and compared with obtained spectrum of non-coherent ASE noise. It is shown that output optical signal has better gain than the amplified spontaneous emission that leads to appreciable growth of output optical signal-to-noise ratio.

  18. Noiseless attenuation using an optical parametric amplifier

    Science.gov (United States)

    Brewster, R. A.; Nodurft, I. C.; Pittman, T. B.; Franson, J. D.

    2017-10-01

    The process of heralded noiseless amplification, and the inverse process of heralded noiseless attenuation, have potential applications in the context of quantum communications. Although several different physical implementations of heralded noiseless amplifiers have now been demonstrated, the research on heralded noiseless attenuators has been largely confined to a beam-splitter based approach. Here we show that an optical parametric amplifier (OPA), combined with appropriate heralding, can also serve as a heralded noiseless attenuator. The counterintuitive use of an optical amplifier as an attenuator is only possible due to the probabilistic nature of the device.

  19. Advanced Concepts in Josephson Junction Reflection Amplifiers

    Science.gov (United States)

    Lähteenmäki, Pasi; Vesterinen, Visa; Hassel, Juha; Paraoanu, G. S.; Seppä, Heikki; Hakonen, Pertti

    2014-06-01

    Low-noise amplification at microwave frequencies has become increasingly important for the research related to superconducting qubits and nanoelectromechanical systems. The fundamental limit of added noise by a phase-preserving amplifier is the standard quantum limit, often expressed as noise temperature . Towards the goal of the quantum limit, we have developed an amplifier based on intrinsic negative resistance of a selectively damped Josephson junction. Here we present measurement results on previously proposed wide-band microwave amplification and discuss the challenges for improvements on the existing designs. We have also studied flux-pumped metamaterial-based parametric amplifiers, whose operating frequency can be widely tuned by external DC-flux, and demonstrate operation at pumping, in contrast to the typical metamaterial amplifiers pumped via signal lines at.

  20. BROADBAND TRAVELLING WAVE SEMICONDUCTOR OPTICAL AMPLIFIER

    DEFF Research Database (Denmark)

    2010-01-01

    Broadband travelling wave semiconductor optical amplifier (100, 200, 300, 400, 800) for amplification of light, wherein the amplifier (100, 200, 300, 400, 800) comprises a waveguide region (101, 201, 301, 401, 801) for providing confinement of the light in transverse directions and adapted...... for propagation of the light in at least a first mode along a longitudinal axis (102, 202, 302) of the amplifier (100, 200, 300, 400, 800) in a propagation direction (103, 203, 303), and wherein the waveguide region (101, 201, 301, 401, 801) comprises a gain region (104, 204, 304, 404, 804) for amplifying......, 301, 401, 801) increases along the longitudinal axis (102, 202, 302), and wherein the ratio between the width (106, 206, 306) of the waveguide region (101, 201, 301, 401, 801) and the width (107, 207, 307) of the gain region (104, 204, 304, 404, 804) increases along the longitudinal axis (102, 202...

  1. High Energy Single Frequency Resonant Amplifier Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This SBIR phase I project proposes a single frequency high energy resonant amplifier for remote sensing. Current state-of-art technologies can not provide all...

  2. Ku band low noise parametric amplifier

    Science.gov (United States)

    1976-01-01

    A low noise, K sub u-band, parametric amplifier (paramp) was developed. The unit is a spacecraft-qualifiable, prototype, parametric amplifier for eventual application in the shuttle orbiter. The amplifier was required to have a noise temperature of less than 150 K. A noise temperature of less than 120 K at a gain level of 17 db was achieved. A 3-db bandwidth in excess of 350 MHz was attained, while deviation from phase linearity of about + or - 1 degree over 50 MHz was achieved. The paramp operates within specification over an ambient temperature range of -5 C to +50 C. The performance requirements and the operation of the K sub u-band parametric amplifier system are described. The final test results are also given.

  3. EQUIPMENT WITH HYDROSTATIC AMPLIFIER MODELED 3D

    Directory of Open Access Journals (Sweden)

    EFTIMIE Dorin

    2013-11-01

    Full Text Available The equipment with hydrostatic amplifier is a new constructive solution modeled 3D using NX 7.5 software. Hydraulic equipment allows the amplification of a constant torque of a DC electric motor of low power at a variable speed. The hydrostatic speed amplifier of constant torque with electric control device is a hydraulic device which provides by design a bridge between the conventional hydraulic and the servo-hydraulic.

  4. Phase Noise in RF and Microwave Amplifiers

    OpenAIRE

    Boudot, Rodolphe; Rubiola, Enrico

    2010-01-01

    Understanding the amplifier phase noise is a critical issue in numerous fields of engineering and physics, like oscillators, frequency synthesis, telecommunications, radars, spectroscopy, in the emerging domain of microwave photonics, and in more exotic domains like radio astronomy, particle accelerators, etc. This article analyzes the two main types of phase noise in amplifiers, white and flicker. White phase noise results from adding white noise to the RF spectrum around the carrier. For a ...

  5. Efficient Power Amplifier for Motor Control

    Science.gov (United States)

    Brown, R. J.

    1986-01-01

    Pulse-width-modulated amplifier supplies high current as efficiently as low current needed for starting and running motor. Key to efficiency of motor-control amplifier is V-channel metal-oxide/semiconductor transistor Q1. Device has low saturation resistance. However, has large gate input capacitance and small margin between its turn-on voltage and maximum allowable gate-to-source voltage. Circuits for output stages overcome limitations of VMOS device.

  6. Erythropoietin in patients with traumatic brain injury and extracranial injury-A post hoc analysis of the erythropoietin traumatic brain injury trial.

    Science.gov (United States)

    Skrifvars, Markus B; Bailey, Michael; French, Craig; Presneill, Jeffrey; Nichol, Alistair; Little, Lorraine; Duranteau, Jacques; Huet, Olivier; Haddad, Samir; Arabi, Yaseen; McArthur, Colin; Cooper, D James; Bellomo, Rinaldo

    2017-09-01

    Erythropoietin (EPO) may reduce mortality after traumatic brain injury (TBI). Secondary brain injury is exacerbated by multiple trauma, and possibly modifiable by EPO. We hypothesized that EPO decreases mortality more in TBI patients with multiple trauma, than in patients with TBI alone. A post hoc analysis of the EPO-TBI randomized controlled trial conducted in 2009 to 2014. To evaluate the impact of injuries outside the brain, we calculated an extracranial Injury Severity Score (ISS) that included the same components of the ISS, excluding head and face components. We defined multiple trauma as two injured body regions with an Abbreviated Injury Scale (AIS) score of 3 or higher. Cox regression analyses, allowing for potential differential responses per the presence or absence of extracranial injury defined by these injury scores, were used to assess the effect of EPO on time to mortality. Of 603 included patients, the median extracranial ISS was 6 (interquartile range, 1-13) and 258 (43%) had an AIS score of 3 or higher in at least two body regions. On Cox regression, EPO was associated with decreased mortality in patients with greater extracranial ISS (interaction p = 0.048) and weakly associated with differential mortality with multiple trauma (AIS score > 3 or in two regions, interaction p = 0.17). At 6 months in patients with extracranial ISS higher than 6, 10 (6.8%) of 147 EPO-treated patients compared with 26 (17%) of 154 placebo-treated patients died (risk reduction, 10%; 95% confidence interval, 2.9-17%; p = 0.007). In this post hoc analysis, EPO administration was associated with a potential differential improvement in 6-month mortality in TBI patients with more severe extracranial injury. These findings need confirmation in future clinical and experimental studies. Therapeutic study, level III.

  7. Hypoproduction of erythropoietin contributes to anemia in chronic cadmium intoxication: clinical study on Itai-itai disease in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Hyogo (Dept. of Public Health, Faculty of Medicine, Toyama Medical and Pharmaceutical Univ. (Japan)); Teranishi, Hidetoyo (Dept. of Public Health, Faculty of Medicine, Toyama Medical and Pharmaceutical Univ. (Japan)); Niiya, Kenji (Dept. of Clinical Lab. Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical Univ. (Japan)); Aoshima, Keiko (Dept. of Public Health, Faculty of Medicine, Toyama Medical and Pharmaceutical Univ. (Japan)); Katoh, Terutaka (Dept. of Public Health, Faculty of Medicine, Toyama Medical and Pharmaceutical Univ. (Japan)); Sakuragawa, Nobuo (Dept. of Clinical Lab. Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical Univ. (Japan)); Kasuya, Minoru (Dept. of Public Health, Faculty of Medicine, Toyama Medical and Pharmaceutical Univ. (Japan))

    1994-10-01

    Itai-itai disease is a condition caused by longterm exposure of the inhabitants of Toyama prefecture, Japan, to cadmium intoxication. The characteristic clinical features of this disease include renal tubular dysfunction, osteomalacia, and anemia. In order to clarify the pathogenesis of the anemia, the red blood cell count, hemoglobin concentration, hematocrit, serum iron level, total iron-binding capacity, serum ferritin level, serum erythropoietin level, creatinine clearance, fractional excretion of [beta][sub 2]-microglobulin, and bone marrow morphology were determined in ten patients with Itai-itai disease. Low serum iron or ferritin levels were not observed, and bone marrow aspiration did not reveal any specific hematological disorders. A close relationship was observed between the decrease in the hemoglobin level and the progression of renal dysfunction. Low serum erythropoietin levels were detected despite the presence of severe anemia. These results suggest an important role of renal damage in the anemia which develops in Itai-itai disease. (orig.)

  8. Captopril Modulates Hypoxia-Inducible Factors and Erythropoietin Responses in a Murine Model of Total Body Irradiation

    Science.gov (United States)

    2011-01-01

    erythroid cell loss/imbalance and erythroid demand with captopril- treatment. ACE inhibitors are being used extensively for treatment of breast cancer ...expression in tumor cells and other tissues. Oncologist. 2004;9(suppl 5):18–30. 28. Lam SY, Tipoe GL, Fung ML. Upregulation of erythropoietin and its...ers KE. Synergistic effects of co-administration of angiotensin 1-7 and Neupogen on hematopoietic recovery in mice. Cancer Chemother Pharmacol

  9. Diffuse bone marrow uptake on whole-body F-18 fluorodeoxyglucose positron emission tomography in a patient taking recombinant erythropoietin.

    Science.gov (United States)

    Blodgett, Todd M; Ames, Jennifer T; Torok, Frank S; McCook, Barry M; Meltzer, Carolyn C

    2004-03-01

    F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) is used extensively in oncology to diagnose, stage, and restage patients with various malignancies. Many patients treated for malignancies develop neutropenia secondary to marrow suppressive chemotherapy and are subsequently treated with synthetic hematopoietic growth factors (HGF), both granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF). Patients taking HGF can present a diagnostic challenge for those interpreting PET because they can demonstrate diffuse marrow uptake on FDG-PET scans, mimicking diffuse bone marrow metastases. It has not been reported whether bone marrow uptake is affected on PET scans in patients taking erythropoietin, the erythroid-specific cell-line stimulator. We report a case of extensive diffuse bone marrow uptake in a 77-year-old man with a history of colon cancer who began taking erythropoietin 3 weeks before his PET scan. This case demonstrates the need to consider erythropoietin in the differential diagnosis of possible etiologies causing diffuse bone marrow uptake on PET scans.

  10. Rapid isolation and detection of erythropoietin in blood plasma by magnetic core gold nanoparticles and portable Raman spectroscopy.

    Science.gov (United States)

    Agoston, Roland; Izake, Emad L; Sivanesan, Arumugam; Lott, William B; Sillence, Martin; Steel, Rohan

    2016-04-01

    Isolating, purifying, and identifying proteins in complex biological matrices are often difficult, time consuming, and unreliable. Herein we describe a rapid screening technique for proteins in biological matrices that combines selective protein isolation with direct surface enhanced Raman spectroscopy (SERS) detection. Magnetic core gold nanoparticles were synthesized, characterized, and subsequently functionalized with recombinant human erythropoietin (rHuEPO)-specific antibody. The functionalized nanoparticles were used to capture rHuEPO from horse blood plasma within 15 min. The selective binding between the protein and the functionalized nanoparticles was monitored by SERS. The purified protein was then released from the nanoparticles' surface and directly spectroscopically identified on a commercial nanopillar SERS substrate. ELISA independently confirmed the SERS identification and quantified the released rHuEPO. Finally, the direct SERS detection of the extracted protein was successfully demonstrated for in-field screening by a handheld Raman spectrometer within 1 min sample measurement time. The rapid detection of recombinant human erythropoietin (rHuEPO) is important in competitive sports to screen for doping offences. In this article, the authors reported their technique of direct surface enhanced Raman spectroscopy (SERS) detection using magnetic core gold nanoparticles functionalized with recombinant human erythropoietin-specific antibody. The findings should open a new way for future detection of other proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells

    Energy Technology Data Exchange (ETDEWEB)

    Uziel, Orit, E-mail: Oritu@clalit.org.il [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Kanfer, Gil [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Beery, Einat [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Yelin, Dana; Shepshelovich, Daniel [Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Bakhanashvili, Mary [Unit of Infectious Diseases, Sheba Medical Center, Tel-Hashomer (Israel); Nordenberg, Jardena [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Endocrinology Laboratory, Beilinson Medical Center, Petah-Tikva (Israel); Lahav, Meir [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel)

    2014-07-18

    Highlights: • We assumed that some of erythropoietin adverse effects may be mediated by telomerase activity. • EPO administration increased telomerase activity, cells proliferation and migration. • The inhibition of telomerase modestly repressed the proliferative effect of erythropoietin. • Telomere shortening caused by long term inhibition of the enzyme totally abolished that effect. • This effect was mediated via the Lyn–AKT axis and not by the canonical JAK2–STAT pathway. - Abstract: Treatment with erythropoietin (EPO) in several cancers is associated with decreased survival due to cancer progression. Due to the major importance of telomerase in cancer biology we hypothesized that some of these effects may be mediated through EPO effect on telomerase. For this aim we explored the possible effects of EPO on telomerase regulation, cell migration and chemosensitivity in non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase activity (TA) and cell migration increased in response to EPO. EPO had no effect on cancer cells sensitivity to cisplatinum and on the cell cycle status. The inhibition of telomerase modestly repressed the proliferative effect of EPO. Telomere shortening caused by long term inhibition of the enzyme abolished the effect of EPO, suggesting that EPO effects on cancer cells are related to telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA was mediated post-translationally through the Lyn-Src and not the canonical JAK2 pathway.

  12. Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathy

    Directory of Open Access Journals (Sweden)

    Egensperger Rupert

    2009-07-01

    Full Text Available Abstract Background Cisplatin mediates its antineoplastic activity by formation of distinct DNA intrastrand cross links. The clinical efficacy and desirable dose escalations of cisplatin are restricted by the accumulation of DNA lesions in dorsal root ganglion (DRG cells leading to sensory polyneuropathy (PNP. We investigated in a mouse model by which mechanism recombinant erythropoietin (rhEPO protects the peripheral nervous system from structural and functional damage caused by cisplatin treatment with special emphasis on DNA damage burden. Results A cumulative dose of 16 mg cisplatin/kg resulted in clear electrophysiological signs of neuropathy, which were significantly attenuated by concomitant erythropoietin (cisplatin 32,48 m/s ± 1,68 m/s; cisplatin + rhEPO 49,66 m/s ± 1,26 m/s; control 55,01 m/s ± 1,88 m/s; p Conclusion The protective effect of recombinant erythropoietin is not mediated by reducing the burden of DNA platination in the target cells, but it is likely to be due to a higher resistance of the target cells to the adverse effect of DNA damage. The increased frequency of intact mitochondria might also contribute to this protective role.

  13. New laser amplifier improves laser Doppler interferometry

    Science.gov (United States)

    1986-02-01

    The design of a laser light amplifier developed to improve the ability of a laser Doppler interferometry system to measure the high velocities of explosion-driven objects or targets is described. The amplifier increases the laser light intensity and S/N ratio. A green coumarin dye is utilized as if the lasing medium for an argon-ion laser and a blue dye as the frequency shifter to improve coupling between the light-pump power source and lasing medium. The arrangement of amplifier components and the frequency characteristics of the flash lamps and dyes are examined. The design requirements for eliminating chirping and achieving acoustic isolation are discussed. The control of the thermal gradients which produce lens effect is analyzed. The selection of a proper dye concentration for uniform excitation across the active volume of the amplifier is studied; an excitation absorption length of three diameters of active cross section is utilized. In order to increase the amount of pumping light reaching the laser dye and to reduce the number of unwanted wavelengths a optical frequency shifter is employed. The amplifier produces enough light to observe two or more spots on the target, record data for up to 12 microsec, and have an accuracy of 0.5 pct.

  14. Transpermeance Amplifier Applied to Magnetic Bearings

    Directory of Open Access Journals (Sweden)

    Jossana Ferreira

    2017-02-01

    Full Text Available The most conventional approach of controlling magnetic forces in active magnetic bearings (AMBs is through current feedback amplifiers: transconductance. This enables the operation of the AMB to be understood in terms of a relatively simple current-based model as has been widely reported on in the literature. The alternative notion of using transpermeance amplifiers, which approximate the feedback of gap flux rather than current, has been in commercial use in some form for at least thirty years, however is only recently seeing more widespread acceptance as a commercial standard. This study explores how such alternative amplifiers should be modeled and then examines the differences in behavior between AMBs equipped with transconductance and transpermeance amplifiers. The focus of this study is on two aspects. The first is the influence of rotor displacement on AMB force, commonly modeled as a constant negative equivalent mechanical stiffness, and it is shown that either scheme actually leads to a finite bandwidth effect, but that this bandwidth is much lower when transpermeance is employed. The second aspect is the influence of eddy currents. Using a very simple model of eddy currents (a secondary short-circuited coil, it is demonstrated that transpermeance amplifiers can recover significant actuator bandwidth compared with transconductance, but at the cost of needing increased peak current headroom.

  15. Nitric oxide and hypoxia stimulate erythropoietin receptor via MAPK kinase in endothelial cells.

    Science.gov (United States)

    Cokic, Bojana B Beleslin; Cokic, Vladan P; Suresh, Sukanya; Wirt, Stacey; Noguchi, Constance Tom

    2014-03-01

    Erythropoietin receptor (EPOR) expression level determines the extent of erythropoietin (EPO) response. Previously we showed that EPOR expression in endothelial cells is increased at low oxygen tension and that EPO stimulation of endothelial cells during hypoxia can increase endothelial nitric oxide (NO) synthase (eNOS) expression and activation as well as NO production. We now observe that while EPO can stimulate NO production, NO in turn can regulate EPOR expression. Human umbilical vein endothelial cells (HUVEC) treated with 10-50 μM of NO donor diethylenetriamine NONOate (DETANO) for 24h showed significant induction of EPOR gene expression at 5% and 2% of oxygen. Also human bone marrow microvascular endothelial cell line (TrHBMEC) cultured at 21 and 2% oxygen with 50 μM DETANO demonstrated a time and oxygen dependent induction of EPOR mRNA expression after 24 and 48 h, particularly at low oxygen tension. EPOR protein was also induced by DETANO at 2% oxygen in TrHBMEC and HUVEC. The activation of signaling pathways by NO donor stimulation appeared to be distinct from EPO stimulation. In reporter gene assays, DETANO treatment of HeLa cells at 2% oxygen increased EPOR promoter activity indicated by a 48% increase in luciferase activity with a 2 kb EPOR promoter fragment and a 71% increase in activity with a minimal EPOR promoter fragment containing 0.2 kb 5'. We found that DETANO activated MAPK kinase in TrHBMEC both in normoxia and hypoxia, while MAPK kinase inhibition showed significant reduction of EPOR mRNA gene expression at low oxygen tension, suggesting MAPK involvement in NO mediated induction of EPOR. Furthermore, DETANO stimulated Akt anti-apoptotic activity after 30 min in normoxia, whereas it inhibited Akt phosphorylation in hypoxia. In contrast, EPO did not significantly increase MAPK activity while EPO stimulated Akt phosphorylation in TrHBMEC in normoxia and hypoxia. These observations provide a new effect of NO on EPOR expression to enhance EPO

  16. 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.)

  17. Recombinant human erythropoietin therapy for anemic cancer patients on combination chemotherapy.

    Science.gov (United States)

    Case, D C; Bukowski, R M; Carey, R W; Fishkin, E H; Henry, D H; Jacobson, R J; Jones, S E; Keller, A M; Kugler, J W; Nichols, C R

    1993-05-19

    Patients with advanced cancer frequently experience clinically significant anemia, which is often exacerbated by myelosuppressive chemotherapy. Consistent with the anemia of chronic disease, studies have documented serum erythropoietin levels that are inappropriately low for the degree of anemia in cancer patients. Myelosuppressive chemotherapy impairs erythropoiesis, which may not fully recover between treatment cycles. Recombinant human erythropoietin (rHuEPO) has been used safely and effectively to treat anemia in AIDS patients receiving zidovudine (AZT) and in patients with chronic renal failure. This study was designed to evaluate the clinical role of rHuEPO in reducing symptomatic anemia in patients with advanced cancer who were receiving myelosuppressive chemotherapy (excluding cisplatin). We studied 153 anemic cancer patients receiving cyclic combination chemotherapy in a prospective multicenter, double-blind, placebo-controlled trial. The patients were randomly assigned to receive either rHuEPO (150 U/kg) or placebo subcutaneously three times a week for a maximum of 12 weeks or until the hematocrit level increased to 38%-40%. If the hematocrit reached this target level before 12 weeks, the rHuEPO dose could be reduced to maintain the hematocrit at that level for the duration of the study. Response to rHuEPO therapy was assessed by measuring changes in hematocrit level, transfusion requirements, and quality of life. Quality-of-life assessment was based on patients' responses to questionnaires before and after the courses of therapy. The increase in hematocrit in the rHuEPO-treated group compared with hematocrit in the placebo-treated group was statistically significant (P = .0001) as measured by percentage point of change from baseline to final evaluation, by an increase in hematocrit level of six percentage points or more unrelated to transfusion, and by a rise in hematocrit level to 38% or more unrelated to transfusion. There was a trend toward the

  18. Epoetin alfa and beta differ in their erythropoietin isoform compositions and biological properties.

    Science.gov (United States)

    Storring, P L; Tiplady, R J; Gaines Das, R E; Stenning, B E; Lamikanra, A; Rafferty, B; Lee, J

    1998-01-01

    Epoetin alfa and beta are the two forms of recombinant DNA-derived erythropoietin (rEPO), both synthesized in Chinese hamster ovary cells, which are used for the treatment of erythropoietin (EPO)-responsive anaemias. Several batches of each of these rEPOs were compared for differences in their EPO isoform compositions by isoelectric focusing (IEF) and in a range of lectin-binding assays, and for differences in their EPO activities by in-vivo and in-vitro mouse bioassays and by immunoassay. Epoetin beta was found to differ from epoetin alfa in containing: (a) a greater proportion of more basic isoforms, (b) a greater proportion of EPO binding to Erythrina cristagalli agglutinin (which binds N-glycans with nonsialylated outer Gal beta1-4GlcNAc moieties), and (c) isoforms with higher in-vivo:in-vitro bioactivity ratios. Epoetin beta also contained slightly more than epoetin alfa of EPO binding to Lycopersicon esculentum agglutinin (which binds N-glycans containing repeating Gal beta1-4GlcNAc sequences), to the leucoagglutinin of Phaseolus vulgaris (which binds tetraantennary and 2,6-branched triantennary N-glycans) and to Agaricus bisporus agglutinin (which binds Gal beta1-3GalNAc containing O-glycans). No differences were found between the two rEPOs in their binding to a further five lectins. The differences between the isoform composition of epoetin alfa and beta, and the smaller inter-batch differences appear to be due to differences in glycosylation. The higher murine in-vivo:in-vitro bioactivity ratio of epoetin beta compared to epoetin alfa could not be explained in terms of differences in their degrees of sialylation, but was consistent with differences in their pharmacokinetics and pharmacodynamics observed in human subjects. There have been no reports that epoetin alfa differs from epoetin beta in its clinical efficacy, but the differences between epoetin alfa and beta in some analytical systems suggest that there might be a need for separate international

  19. Determining level of endogenous serum erythropoietin for differential diagnosis of polycythemia vera and symptomatic polycythemia

    Directory of Open Access Journals (Sweden)

    Kostyukevych O.M.

    2013-06-01

    Full Text Available The article deals with determining possibility of the assessment of the level of endogenous serum erythropoietin (EPO for differential diagnosis of polycythemia vera (PV and secondary erythrocytosis (SE. The determination of subnormal level of this cytokine for the diagnosis of PV has been detected. The relation between the level of endogenous erythropoietin and iron metabolism also has been analyzed. The study involved 88 patients with PV and 119 patients with SE. Statistically significant decrease in EPO concentration level has been detected in PV patients. The mean EPO level was equal to 6.38 ± 0.84 mIU/mL and 17.98 ±2.48 mIU/mL in PV and SE patients respectively. In control group of individuals EPO concentration was equal to 9,81 ±0,58 mIU/mL, the significant difference was found between all studied groups (р<0.01. According to our data, EPO was increased in 28 SE patients (23.53%, it was not observed in control group and in group of PV patients (φ*emp = 4.355, р<0.01. The decrease of EPO level in PV patients has been detected more often than in SE patients (84.09% versus 11.76% , φ*emp = 5.218, р<0.01, it has not been observed in control group. Only 14 (15.91% PV patients had normal EPO level, in contrast 77 (64.71% SE patients demonstrated normal EPO level (φ*emp = 4.578, р<0.01. The average level of ferritin was equal to 57.41 ± 9.74 ng/mL in PV patients and 199.77 ± 14.32 ng/mL in SE patients (р<0.01. Significantly more patients with PV demonstrated decrease of ferritin level (31.81% versus 7.56%, φ*emp = 4.438, р<0.01. Patients with SE more often had raised level of EPO than PV patients (15.12% versus 4.54%, φ*emp = 2.453, р<0.01. The sensitivity of test with detecting of the reduced level of EPO for the diagnosis of PV was 84.1%, specificity - 87.4%, positive predictive value - 83.1%, negative predictive value - 88.1%. Normal range of EPO significantly (rs = 0,5494 correlated with decreased levels of serum ferritin in

  20. The OPTHER Project: Progress toward the THz Amplifier

    DEFF Research Database (Denmark)

    Paoloni, C; Brunetti, F; Di Carlo, A

    2011-01-01

    This paper describes the status of the OPTHER (OPtically driven TeraHertz AmplifiERs) project and progress toward the THz amplifier realization. This project represents a considerable advancement in the field of high frequency amplification. The design and realization of a THz amplifier within th...

  1. Wideband Low Noise Amplifiers Exploiting Thermal Noise Cancellation

    NARCIS (Netherlands)

    Bruccoleri, F.; Klumperink, Eric A.M.; Nauta, Bram

    2005-01-01

    Low Noise Amplifiers (LNAs) are commonly used to amplify signals that are too weak for direct processing for example in radio or cable receivers. Traditionally, low noise amplifiers are implemented via tuned amplifiers, exploiting inductors and capacitors in resonating LC-circuits. This can render

  2. ZigBee Radio with External Power Amplifier and Low-Noise Amplifier

    Directory of Open Access Journals (Sweden)

    Allan HUYNH

    2010-07-01

    Full Text Available This paper presents the performance study of a ZigBee module with both an external power amplifier and a low-noise amplifier, measured in outdoor and indoor environments, respectively. Our previous study has already shown that the indoor campus environment such as walls and floors would reduce the radio link range drastically and the packet error rate increased. In this study, both an external power amplifier and a low-noise amplifier have been added to a ZigBee module to increase both the transmitter power and receiver sensitivity. It is shown that with an external power amplifier and a low-noise amplifier the outdoor radio range can reach up to 1600 m with a negligible packet error rate compared to 144 m without any external amplifier for point-to-point radio connection. Thus, by increasing both the transmitter power and receiver sensitivity the radio range can be increased significantly. The power consumption issue with the added amplifiers is studied as well, indicating that the module can still be battery driven with a battery lifetime of about 9 years at a normal sampling rate to the sensor.

  3. Design Of A Doherty Power Amplifier For GSM Systems

    Directory of Open Access Journals (Sweden)

    Saad Wasmi Osman

    2013-04-01

    Full Text Available This paper presents the design and analysis of Doherty power amplifier. The Doherty amplifier is used in  a base station for mobile system because of its high efficiency. The class AB power amplifier used in the configuration of the main and auxiliary amplifier. The result obtained shows that the Doherty power amplifier can be used on a wide band spectrum, the amplifier works at 900MHz and has very good power added efficiency (PAE and gain. The amplifier can also work at 1800MHz at input power greater than 20dBm. 

  4. Distributed feedback laser amplifiers combining the functions of amplifiers and channel filters

    DEFF Research Database (Denmark)

    Wang, Z.; Durhuus, T.; Mikkelsen, Benny

    1994-01-01

    A dynamic model for distributed feedback amplifiers, including the mode coupled equations and the carrier rate equation, is established. The presented mode coupled equations have taken into account the interaction between fast changing optical signal and the waveguide with corrugations. By showin...... the possibility of amplifying 100 ps pulses without pulse broadening, we anticipate that a distributed feedback amplifier can be used as a combined amplifier and channel filter in high bit rate transmission systems.......A dynamic model for distributed feedback amplifiers, including the mode coupled equations and the carrier rate equation, is established. The presented mode coupled equations have taken into account the interaction between fast changing optical signal and the waveguide with corrugations. By showing...

  5. Wideband pulse amplifiers for the NECTAr chip

    Energy Technology Data Exchange (ETDEWEB)

    Sanuy, A., E-mail: asanuy@ecm.ub.es [Dept. AM i Dept. ECM, Institut de Ciencies del Cosmos (ICC), Universitat de Barcelona. Marti i Franques 1, E08028, Barcelona (Spain); Delagnes, E. [IRFU/DSM/CEA, CE-Saclay, Bat. 141 SEN Saclay, F-91191, Gif-sur-Yvette (France); Gascon, D. [Dept. AM i Dept. ECM, Institut de Ciencies del Cosmos (ICC), Universitat de Barcelona. Marti i Franques 1, E08028, Barcelona (Spain); Sieiro, X. [Departament d' Electronica, Universitat de Barcelona. Marti i Franques 1, E08028, Barcelona (Spain); Bolmont, J.; Corona, P. [LPNHE, Universite Paris VI and Universite Paris VII and IN2P3/CNRS, Barre 12-22, 1er etage, 4 place Jussieu, 75252 Paris (France); Feinstein, F. [LUPM, Universite Montpellier II and IN2P3/CNRS, CC072, bat. 13, place Eugene Bataillon, 34095 Montpellier (France); Glicenstein, J-F. [IRFU/DSM/CEA, CE-Saclay, Bat. 141 SEN Saclay, F-91191, Gif-sur-Yvette (France); Naumann, C.L.; Nayman, P. [LPNHE, Universite Paris VI and Universite Paris VII and IN2P3/CNRS, Barre 12-22, 1er etage, 4 place Jussieu, 75252 Paris (France); Ribo, M. [Dept. AM i Dept. ECM, Institut de Ciencies del Cosmos (ICC), Universitat de Barcelona. Marti i Franques 1, E08028, Barcelona (Spain); and others

    2012-12-11

    The NECTAr collaboration's FE option for the camera of the CTA is a 16 bits and 1-3 GS/s sampling chip based on analog memories including most of the readout functions. This works describes the input amplifiers of the NECTAr ASIC. A fully differential wideband amplifier, with voltage gain up to 20 V/V and a BW of 400 MHz. As it is impossible to design a fully differential OpAmp with an 8 GHz GBW product in a 0.35 CMOS technology, an alternative implementation based on HF linearized transconductors is explored. The output buffer is a class AB miller operational amplifier, with special non-linear current boost.

  6. Operational amplifier circuits analysis and design

    CERN Document Server

    Nelson, J C C

    1995-01-01

    This book, a revised and updated version of the author's Basic Operational Amplifiers (Butterworths 1986), enables the non-specialist to make effective use of readily available integrated circuit operational amplifiers for a range of applications, including instrumentation, signal generation and processing.It is assumed the reader has a background in the basic techniques of circuit analysis, particularly the use of j notation for reactive circuits, with a corresponding level of mathematical ability. The underlying theory is explained with sufficient but not excessive, detail. A range of compu

  7. Plasma Wave Seed for Raman Amplifiers

    Science.gov (United States)

    Qu, Kenan; Barth, Ido; Fisch, Nathaniel

    2016-10-01

    It is proposed to replace traditionally used laser seed in backward Raman amplifiers with initial plasma wave seed. We show, analytically and numerically, that similarly to laser seeds plasma seeds result in Raman amplified pulse in both the linear and nonlinear regimes. The plasma seed is prepared in advance with a certain wavevector and envelope at one edge of the plasma. This methodology is attractive because it avoids issues in preparing and synchronizing frequency shifted laser seed. This work was supported by NNSA Grant No. DE-NA0002948, AFOSR Grant No. FA9550-15-1-0391.

  8. Predistortion of a Bidirectional Cuk Audio Amplifier

    DEFF Research Database (Denmark)

    Birch, Thomas Hagen; Nielsen, Dennis; Knott, Arnold

    2014-01-01

    using predistortion. This paper suggests linearizing a nonlinear bidirectional Cuk audio amplifier using an analog predistortion approach. A prototype power stage was built and results show that a voltage gain of up to 9 dB and reduction in THD from 6% down to 3% was obtainable using this approach.......Some non-linear amplifier topologies are capable of providing a larger voltage gain than one from a DC source, which could make them suitable for various applications. However, the non-linearities introduce a significant amount of harmonic distortion (THD). Some of this distortion could be reduced...

  9. Pure red cell aplasia induced by anti-erythropoietin antibodies, well-controlled with tacrolimus.

    Science.gov (United States)

    Hashimoto, Koji; Harada, Makoto; Kamijo, Yuji

    2016-10-01

    Anti-erythropoietin (anti-EPO) antibody-related pure red cell aplasia (PRCA) is a rare but serious complication that can occur during the administration of erythropoiesis-stimulating agents. Treatment with the calcineurin inhibitor cyclosporine has shown benefits in patients with anti-EPO PRCA. The efficacy of tacrolimus, another calcineurin inhibitor, in patients with anti-EPO PRCA has not been determined. The present report is the first our knowledge to describe the successful treatment of a patient with anti-EPO PRCA using tacrolimus. A 73-year-old man was markedly anemic 8 months after starting epoetin beta treatment. He was diagnosed with anti-EPO PRCA. Cyclosporine was started, but he experienced side effects. He was switched from cyclosporine to tacrolimus. No side effects were observed, and his anti-EPO PRCA was improved 6 months later, despite the persistence of anti-EPO antibodies. Tacrolimus was continued until the disappearance of the antibodies. Following the cessation of tacrolimus, PRCA did not relapse. Antibody remained detectable at the time of clinical remission, indicating that immunosuppressive therapy should be continued while monitoring the antibody titer. When the antibody titer decreases to the negative range, cessation of the immunosuppressive therapy does not result in disease relapse.

  10. Protective effect of erythropoietin on renal injury induced in rats by four weeks of exhaustive exercise.

    Science.gov (United States)

    Lin, Xixiu; Jiang, Chonghe; Luo, Ziqiang; Qu, Shulin

    2013-06-24

    The protective effect of Erythropoietin (EPO) analogue rHuEPO on acute renal injury induced by exhaustive exercise had been reported. The purpose of this study is to probe into the protective effect of EPO on chronic renal injury induced by repeated exhaustive exercise for four weeks. Eighty adult male Sprague-Dawley rats were used in this experiment. The animals were randomly allocated to one of four groups: control (C), exhaustive exercise test (ET), ET plus EPO pre-treatement (ET+EPO) and ET+EPO plus LY294002 pretreatment (ET+EPO+LY). Compared with the rats in control group, there was considerable damage in kidney cells in rats of ET group as revealed by histological and ultrastructural examinations. However, treatment with EPO during the training, the exhaustive running distance was significant increased (P protective effect of EPO on chronic renal injury induced by repeated exhaustive exercise was demonstrated in the present study. We proposed that the effect could be due to inhibiting the cell apoptosis and blocking the formation of interstitial fibrosis via activation of the PI3K/Akt pathway, thus plays role in the endogenous protection of the kidney injury.

  11. Long-term cadmium exposure induces anemia in rats through hypoinduction of erythropoietin in the kidneys

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Hyogo [Department of Public Health, Fukushima Medical College, Fukushima (Japan); Sato, Masao [Department of Biomolecular Sciences, Institute of Biomedical Sciences, Fukushima Medical College, Fukushima (Japan); Konno, Nobuhiro [Department of Public Health, Fukushima Medical College, Fukushima (Japan); Fukushima, Masaaki [Department of Public Health, Fukushima Medical College, Fukushima (Japan)

    1996-11-01

    Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general environment of today. The characteristic clinical manifestations of chronic Cd intoxication include renal proximal tubular dysfunction, general osteomalacia with severe pains, and anemia. We have recently reported that the serum level of erythropoietin (EPO) remained low despite the severe anemia in patients with Itai-itai disease, the most severe form of chronic Cd intoxication. In order to prove that the anemia observed in chronic Cd intoxication arises from low production of EPO in the kidneys following the renal injury, we administered Cd to rats for a long period and performed the analysis of EPO mRNA inducibility in the kidneys. The rats administered Cd for 6 and 9 months showed anemia with low levels of plasma EPO as well as biochemical and histological renal tubular damage, and also hypoinduction of EPO mRNA in the kidneys. The results indicate that chronic Cd intoxication causes anemia by disturbing the EPO-production capacity of renal cells. (orig.). With 4 figs., 4 tabs.

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

    Science.gov (United States)

    Bejder, Jacob; Aachmann-Andersen, Niels Jacob; Bonne, Thomas Christian; Olsen, Niels Vidiendal; Nordsborg, Nikolai Baastrup

    2016-10-01

    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 either 65 IU rHuEPO × kg(-1) every second day for two weeks (normal-dose), 390 IU rHuEPO × kg(-1) on three consecutive days (high-dose), or frequent placebo treatment for 13 days in a randomized, placebo-controlled, double-blind crossover design. Blood variables were measured 4, 11, and 25 days following treatment initiation. The ABP based on haemoglobin concentration ([Hb]) and OFF-hr score ([Hb] - 60 × √ret%) yielded atypical profiles following both normal-dose and high-dose treatment (0 %, 31 %, 13 % vs. 21 %, 33 %, 20 % at days 4, 11, and 25 after normal and high dose, respectively). Including ret% as a stand-alone marker for atypical blood profiles increased (P Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Human fetal liver cells for regulated ex vivo erythropoietin gene therapy

    Directory of Open Access Journals (Sweden)

    Ebtisam El Filali

    2014-01-01

    Full Text Available Possible risks and lack of donor livers limit application of liver transplantation. Liver cell transplantation is, at this moment, not a feasible alternative because engraftment in the liver is poor. Furthermore, there is also shortage of cells suitable for transplantation. Fetal liver cells are able to proliferate in cell culture and could therefore present an alternative source of cells for transplantation. In this study, we investigated the utility of human fetal liver cells for therapeutic protein delivery. We transplanted human fetal liver cells in immunodeficient mice but were not able to detect engraftment of human hepatocytes. In contrast, transplantation of human adult hepatocytes led to detectable engraftment of hepatocytes in murine liver. Transplantation of fetal liver cells did lead to abundant reconstitution of murine liver with human endothelium, indicating that endothelial cells are the most promising cell type for ex vivo liver cell gene therapy. Human liver endothelial cells were subsequently transduced with a lentiviral autoregulatory erythropoietin expression vector. After transplantation in immunodeficient mice, these cells mediated long-term regulation of murine hematocrits. Our study shows the potential of human liver endothelial cells for long-term regulated gene therapy.

  14. The Effects of Erythropoietin Dose Titration during High-Fat Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Amanda Foskett

    2011-01-01

    Full Text Available Erythropoietin (Epo is a pleotropic cytokine with several nonhematopoietic tissue effects. High-dose Epo treatment-mediated effects on body weight, fat mass and glucose tolerance have recently been reported, thus extending its pleotropic effects to fat and glucose metabolism. However, the exact dose range of Epo treatment required for such effects remains unidentified to date. We investigated Epo dosage effect (up to 1000 U/kg on hematocrit, body weight, body composition, glucose metabolism, food intake, and physical activity, during high-fat diet-induced obesity. We report that Epo doses (1000, 600, 300, and 150 U/kg significantly reduced body weight gain and fat mass, while, only Epo doses of 300 U/kg and higher significantly affected glucose tolerance. None of the tested Epo doses showed any detectable effects on food intake, and only 1000 U/kg dose significantly increased physical activity, suggesting that these parameters may only be partially responsible for the metabolic effects of Epo treatment.

  15. High dose Erythropoietin increases Brain Tissue Oxygen Tension in Severe Vasospasm after Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Helbok Raimund

    2012-06-01

    Full Text Available Abstract Background Vasospasm-related delayed cerebral ischemia (DCI significantly impacts on outcome after aneurysmal subarachnoid hemorrhage (SAH. Erythropoietin (EPO may reduce the severity of cerebral vasospasm and improve outcome, however, underlying mechanisms are incompletely understood. In this study, the authors aimed to investigate the effect of EPO on cerebral metabolism and brain tissue oxygen tension (PbtO2. Methods Seven consecutive poor grade SAH patients with multimodal neuromonitoring (MM received systemic EPO therapy (30.000 IU per day for 3 consecutive days for severe cerebral vasospasm. Cerebral perfusion pressure (CPP, mean arterial blood pressure (MAP, intracranial pressure (ICP, PbtO2 and brain metabolic changes were analyzed during the next 24 hours after each dose given. Statistical analysis was performed with a mixed effects model. Results A total of 22 interventions were analyzed. Median age was 47 years (32–68 and 86 % were female. Three patients (38 % developed DCI. MAP decreased 2 hours after intervention (P btO2 significantly increased over time (P  Conclusions EPO increases PbtO2 in poor grade SAH patients with severe cerebral vasospasm. The effect on outcome needs further investigation.

  16. Erythropoietin Slows Photoreceptor Cell Death in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa.

    Science.gov (United States)

    Rex, Tonia S; Kasmala, Lorraine; Bond, Wesley S; de Lucas Cerrillo, Ana M; Wynn, Kristi; Lewin, Alfred S

    2016-01-01

    To test the efficacy of systemic gene delivery of a mutant form of erythropoietin (EPO-R76E) that has attenuated erythropoietic activity, in a mouse model of autosomal dominant retinitis pigmentosa. Ten-day old mice carrying one copy of human rhodopsin with the P23H mutation and both copies of wild-type mouse rhodopsin (hP23H RHO+/-,mRHO+/+) were injected into the quadriceps with recombinant adeno-associated virus (rAAV) carrying either enhanced green fluorescent protein (eGFP) or EpoR76E. Visual function (electroretinogram) and retina structure (optical coherence tomography, histology, and immunohistochemistry) were assessed at 7 and 12 months of age. The outer nuclear layer thickness decreased over time at a slower rate in rAAV.EpoR76E treated as compared to the rAAV.eGFP injected mice. There was a statistically significant preservation of the electroretinogram at 7, but not 12 months of age. Systemic EPO-R76E slows death of the photoreceptors and vision loss in hP23H RHO+/-,mRHO+/+ mice. Treatment with EPO-R76E may widen the therapeutic window for retinal degeneration patients by increasing the number of viable cells. Future studies might investigate if co-treatment with EPO-R76E and gene replacement therapy is more effective than gene replacement therapy alone.

  17. Evaluation of protein N-glycosylation in 2-DE: Erythropoietin as a study case.

    Science.gov (United States)

    Llop, Esther; Gallego, Ricardo Gutiérrez; Belalcazar, Viviana; Gerwig, Gerrit J; Kamerling, Johannis P; Segura, Jordi; Pascual, José A

    2007-12-01

    The structure, function, and physico-chemical properties of many proteins are determined by PTM, being glycosylation the most complex. This study describes how a combination of typical proteomics methods (2-DE) combines with glycomics strategies (HPLC, MALDI-TOF-MS, exoglycosidases sequencing) to yield comprehensive data about single spot-microheterogeneity, providing meaningful information for the detection of disease markers, pharmaceutical industry, antidoping control, etc. Recombinant erythropoietin and its hyperglycosylated analogue darbepoetin-alpha were chosen as showcases because of their relevance in these fields and the analytical challenge they represent. The combined approach yielded good results in terms of sample complexity (mixture glycoforms), reproducibility, sensitivity ( approximately 25 pmoles of glycoprotein/spot), and identification of the underlying protein. Heterogeneity was present in all spots but with a clear tendency; spots proximal to the anode contained the highest amount of tetra-antennary tetra-sialylated glycans, whereas the opposite occurred for spots proximal to the cathode with the majority of the structures being undersialylated. Spot microheterogeneity proved a consequence of the multiple glycosylation sites as they contributed directly to the number of possibilities to account for a discrete charge in a single spot. The interest of this combined glycoproteomics method resides in the efficiency for detecting and quantifying subtle dissimilarities originated from altered ratios of identical glycans including N-acetyl-lactosamine repeats, acetylation, or antigenic epitopes, that do not significantly contribute to the electrophoretic mobility, but affect the glycan microheterogeneity and the potential underlying related functionality.

  18. BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

    Energy Technology Data Exchange (ETDEWEB)

    Goupille, Olivier [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Penglong, Tipparat [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Lefevre, Carine; Granger, Marine; Kadri, Zahra [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Fucharoen, Suthat [Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Maouche-Chretien, Leila [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Leboulch, Philippe [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Genetics Division, Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Chretien, Stany, E-mail: stany.chretien@cea.fr [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer UT7 erythroleukemia cells are known to be refractory to differentiate. Black-Right-Pointing-Pointer Brief JQ1 treatment initiates the first steps of erythroid differentiation program. Black-Right-Pointing-Pointer Engaged UT7 cells then maturate in the presence of erythropoietin. Black-Right-Pointing-Pointer Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

  19. Effect of Autoantibodies to Erythropoietin Receptor in Systemic Lupus Erythematosus with Biopsy-proven Lupus Nephritis.

    Science.gov (United States)

    Hara, Akinori; Furuichi, Kengo; Yamahana, Junya; Yasuda, Haruka; Iwata, Yasunori; Sakai, Norihiko; Shimizu, Miho; Kaneko, Shuichi; Wada, Takashi

    2016-07-01

    We examined the clinical significance of autoantibodies to the erythropoietin receptor (EPOR) in patients with systemic lupus erythematosus (SLE) who had biopsy-proven lupus nephritis (LN). Forty-six Japanese patients with SLE with LN who had undergone renal biopsy during 1993-2014 were enrolled in this study and followed for a mean of 83 months. Sera from those patients were screened for anti-EPOR antibodies using ELISA. Anti-EPOR antibodies were detected in 18 (39%) of the 46 patients with SLE with anemia. Anti-EPOR antibodies were associated with low hemoglobin concentrations and reticulocytopenia. In addition, anti-EPOR antibodies were positively correlated with SLE disease activity, even though serum levels of the complement factors 3 and 4 did not differ between the 2 groups. In patients with International Society of Nephrology/Renal Pathology Society 2003 class IV LN, anti-EPOR antibodies were associated with active lesions including cellular crescents in glomeruli. Decrease in renal function was more frequently observed in patients without complete or partial renal response than in patients with it, and serum levels of the antibodies as well as renal response to treatment were significant risk factors for progression of renal dysfunction. The present study suggests that anti-EPOR antibodies might be involved in overall disease activity and active renal lesions, as well as in the impaired erythropoiesis in patients with SLE with LN. Further, the levels of anti-EPOR antibodies may be an additional predictor for renal injury.

  20. Potency Evaluation of Recombinant Human Erythropoietin in Brazil: Assessment of Reproducibility Using a Practical Approach

    Directory of Open Access Journals (Sweden)

    Michele Cardoso do Nascimento

    2015-08-01

    Full Text Available In this study, we compared the results of potency determination of recombinant human erythropoietin (rhEPO obtained between 2010 and 2012 by the National Institute of Quality Control in Health (INCQS/Fiocruz, i.e., the National Control Laboratory (NCL, and by a manufacturer of rhEPO. In total, 47 different batches of commercially prepared rhEPO (alpha isoform were analyzed. All results, including those of the control and warning limits, remained within the limits recommended by European Pharmacopoeia (Ph. Eur.. All relative error (RE values were less than ± 30%, wh ereas most were approximately ± 20%. Applying the Bland-Altman plot, only two of 47 values remained outside the limits of agreement (LA. In addition, agreement of potency determination between INCQS and the manufacturer coefficient of variation of reproducibility (% CVR was considered satisfactory. Taken together, our results demonstrate (i. the potency assay of rhEPO performed at INCQS, is standardized and controlled, (ii. the comparison of our results with those of the manufacturer, revealed an adequate inter-laboratory variation, and (iii. the critical appraisal proposed here appears to be a feasible tool to assess the reproducibility of biological activity, providing additional information regarding monitoring and production consistency to manufacturers and NCLs.

  1. Genistein attenuates hypoxic pulmonary hypertension via enhanced nitric oxide signaling and the erythropoietin system.

    Science.gov (United States)

    Kuriyama, Sachiko; Morio, Yoshiteru; Toba, Michie; Nagaoka, Tetsutaro; Takahashi, Fumiyuki; Iwakami, Shin-Ichiro; Seyama, Kuniaki; Takahashi, Kazuhisa

    2014-06-01

    Upregulation of the erythropoietin (EPO)/EPO receptor (EPOR) system plays a protective role against chronic hypoxia-induced pulmonary hypertension (hypoxic PH) through enhancement of endothelial nitric oxide (NO)-mediated signaling. Genistein (Gen), a phytoestrogen, is considered to ameliorate NO-mediated signaling. We hypothesized that Gen attenuates and prevents hypoxic PH. In vivo, Sprague-Dawley rats raised in a hypobaric chamber were treated with Gen (60 mkg/kg) for 21 days. Pulmonary hemodynamics and vascular remodeling were ameliorated in Gen-treated hypoxic PH rats. Gen also restored cGMP levels and phosphorylated endothelial NO synthase (p-eNOS) at Ser(1177) and p-Akt at Ser(473) expression in the lungs. Additionally, Gen potentiated plasma EPO concentration and EPOR-positive endothelial cell counts. In experiments with hypoxic PH rats' isolated perfused lungs, Gen caused NO- and phosphatidylinositol 3-kinase (PI3K)/Akt-dependent vasodilation that reversed abnormal vasoconstriction. In vitro, a combination of EPO and Gen increased the p-eNOS and the EPOR expression in human umbilical vein endothelial cells under a hypoxic environment. Moreover, Gen potentiated the hypoxic increase in EPO production from human hepatoma cells. We conclude that Gen may be effective for the prevention of hypoxic PH through the improvement of PI3K/Akt-dependent, NO-mediated signaling in association with enhancement of the EPO/EPOR system. Copyright © 2014 the American Physiological Society.

  2. Nitric oxide prevents axonal degeneration by inducing HIF-1-dependent expression of erythropoietin.

    Science.gov (United States)

    Keswani, Sanjay C; Bosch-Marcé, Marta; Reed, Nicole; Fischer, Angela; Semenza, Gregg L; Höke, Ahmet

    2011-03-22

    Nitric oxide (NO) is a signaling molecule that can trigger adaptive (physiological) or maladaptive (pathological) responses to stress stimuli in a context-dependent manner. We have previously reported that NO may signal axonal injury to neighboring glial cells. In this study, we show that mice deficient in neuronal nitric oxide synthase (nNOS-/-) are more vulnerable than WT mice to toxin-induced peripheral neuropathy. The administration of NO donors to primary dorsal root ganglion cultures prevents axonal degeneration induced by acrylamide in a dose-dependent manner. We demonstrate that NO-induced axonal protection is dependent on hypoxia-inducible factor (HIF)-1-mediated transcription of erythropoietin (EPO) within glial (Schwann) cells present in the cultures. Transduction of Schwann cells with adenovirus AdCA5 encoding a constitutively active form of HIF-1α results in amelioration of acrylamide-induced axonal degeneration in an EPO-dependent manner. Mice that are partially deficient in HIF-1α (HIF-1α+/-) are also more susceptible than WT littermates to toxic neuropathy. Our results indicate that NO→HIF-1→EPO signaling represents an adaptive mechanism that protects against axonal degeneration.

  3. Up-regulation of erythropoietin receptor by nitric oxide mediates hypoxia preconditioning.

    Science.gov (United States)

    Chen, Zhi-Yong; Wang, Li; Asavaritkrai, Pundit; Noguchi, Constance Tom

    2010-11-01

    Erythropoietin (Epo), known to stimulate erythroid progenitor cell survival, proliferation, and differentiation, has been shown to be neuroprotective against brain ischemia in animal models. Both Epo and Epo receptor (EpoR) are expressed in the brain and are up-regulated by hypoxia. Brain Epo signaling can stimulate neural cell survival and prevent neuron apoptosis. Neurons from EpoR null mice exhibit marked increased sensitivity to hypoxia. In endothelial cells, Epo has been shown to stimulate nitric oxide (NO) production, particularly at low pO(2). We found here that the EpoR expression on neural cells and Epo's neuroprotective effect were regulated by NO. Hypoxia increased NO production as well as EpoR expression, and inhibition of NOS activity reduced the proportion of EpoR-expressing neurons induced at low pO(2). Conversely, addition of NO donor to cultures grown under normoxia induced EpoR. Similarly, NO donor increased EpoR promoter activity in a reporter gene assay, suggesting that NO regulates EpoR at the transcription level. Preincubation of neurons with NO results in induction of EpoR, which gives rise to protection against hypoxia even in the absence of exogenous Epo, although at high concentration NO is toxic. These data provide evidence of a role for NO in Epo activity in brain and suggest links between NO production, EpoR expression, and Epo signaling in neuroprotection.

  4. Association between high-dose erythropoiesis-stimulating agents, inflammatory biomarkers, and soluble erythropoietin receptors

    Directory of Open Access Journals (Sweden)

    Inrig Jula K

    2011-12-01

    Full Text Available Abstract Background High-dose erythropoiesis-stimulating agents (ESA for anemia of chronic kidney disease (CKD have been associated with adverse clinical outcomes and do not always improve erythropoiesis. We hypothesized that high-dose ESA requirement would be associated with elevated inflammatory biomarkers, decreased adipokines, and increased circulating, endogenous soluble erythropoietin receptors (sEpoR. Methods A cross-sectional cohort of anemic 32 CKD participants receiving ESA were enrolled at a single center and cytokine profiles, adipokines, and sEpoR were compared between participants stratified by ESA dose requirement (usual-dose darbepoetin-α ( Results Baseline characteristics were similar between groups; however, hemoglobin was lower among participants on high-dose (1.4 μg/kg/week vs usual-dose (0.5 μg/kg/week ESA. In adjusted analyses, high-dose ESA was associated with an increased odds for elevations in c-reactive protein and interleukin-6 (p s = 0.39, p = 0.03. In adjusted analyses, higher ESA dose (per μcg/kg/week was associated with a 53% greater odds of sEpoR being above the median (p Conclusion High-dose ESA requirement among anemic CKD participants was associated with elevated inflammatory biomarkers and higher levels of circulating sEpoR, an inhibitor of erythropoiesis. Further research confirming these findings is warranted. Trial registration Clinicaltrials.gov NCT00526747

  5. Epidermal growth factor and erythropoietin infusion accelerate functional recovery in combination with rehabilitation.

    Science.gov (United States)

    Jeffers, Matthew S; Hoyles, Amy; Morshead, Cindi; Corbett, Dale

    2014-06-01

    Rehabilitation is the only treatment option for chronic stroke deficits, but unfortunately, it often provides incomplete recovery. In this study, a novel combination of growth factor administration and rehabilitation therapy was used to facilitate functional recovery in a rat model of cortical stroke. Ischemia was induced via injection of endothelin-1 into the sensorimotor cortex. This was followed by either a 2-week infusion of epidermal growth factor and erythropoietin or artificial cerebrospinal fluid into the ipsilateral lateral ventricle. Two weeks after ischemia, animals began an 8-week enriched rehabilitation program. Functional recovery was assessed after ischemia using the Montoya staircase-reaching task, beam-traversing, and cylinder test of forelimb asymmetry. The combination of growth factor infusion and rehabilitation led to a significant acceleration in recovery in the staircase task. When compared with controls, animals receiving the combination treatment attained significant recovery of function at 4 weeks after stroke, whereas those receiving rehabilitation alone did not recover until 10 weeks. Significant recovery was also observed on the beam-traversing and cylinder tasks. Combining behavioral rehabilitation with growth factor infusion accelerates motor recovery. These data suggest a promising new avenue of combination therapies that may have the potential to reduce the rehabilitation time necessary to recover from sensorimotor deficits arising from stroke. © 2014 American Heart Association, Inc.

  6. Erythropoietin protects epithelial cells from excessive autophagy and apoptosis in experimental neonatal necrotizing enterocolitis.

    Directory of Open Access Journals (Sweden)

    Yueyue Yu

    Full Text Available Neonatal necrotizing enterocolitis (NEC is a devastating gastrointestinal disease of preterm infants. Increased intestinal epithelium permeability is an early event in NEC pathogenesis. Autophagy and apoptosis are induced by multiple stress pathways which may impact the intestinal barrier, and they have been associated with pathogenesis of diverse gastrointestinal diseases including inflammatory bowel disease. Using both in vitro and in vivo models, this study investigates autophagy and apoptosis under experimental NEC stresses. Furthermore this study evaluates the effect of erythropoietin (Epo, a component of breast milk previously shown to decrease the incidence of NEC and to preserve intestinal barrier function, on intestinal autophagy and apoptosis. It was found that autophagy and apoptosis are both rapidly up regulated in NEC in vivo as indicated by increased expression of the autophagy markers Beclin 1 and LC3II, and by evidence of apoptosis by TUNEL and cleaved caspase-3 staining. In the rat NEC experimental model, autophagy preceded the onset of apoptosis in intestine. In vitro studies suggested that Epo supplementation significantly decreased both autophagy and apoptosis via the Akt/mTOR signaling pathway and the MAPK/ERK pathway respectively. These results suggest that Epo protects intestinal epithelium from excessive autophagy and apoptosis in experimental NEC.

  7. PRAS40 is an integral regulatory component of erythropoietin mTOR signaling and cytoprotection.

    Directory of Open Access Journals (Sweden)

    Zhao Zhong Chong

    Full Text Available Emerging strategies that center upon the mammalian target of rapamycin (mTOR signaling for neurodegenerative disorders may bring effective treatment for a number of difficult disease entities. Here we show that erythropoietin (EPO, a novel agent for nervous system disorders, prevents apoptotic SH-SY5Y cell injury in an oxidative stress model of oxygen-glucose deprivation through phosphatidylinositol-3-kinase (PI 3-K/protein kinase B (Akt dependent activation of mTOR signaling and phosphorylation of the downstream pathways of p70 ribosomal S6 kinase (p70S6K, eukaryotic initiation factor 4E-binding protein 1 (4EBP1, and proline rich Akt substrate 40 kDa (PRAS40. PRAS40 is an important regulatory component either alone or in conjunction with EPO signal transduction that can determine cell survival through apoptotic caspase 3 activation. EPO and the PI 3-K/Akt pathways control cell survival and mTOR activity through the inhibitory post-translational phosphorylation of PRAS40 that leads to subcellular binding of PRAS40 to the cytoplasmic docking protein 14-3-3. However, modulation and phosphorylation of PRAS40 is independent of other protective pathways of EPO that involve extracellular signal related kinase (ERK 1/2 and signal transducer and activator of transcription (STAT5. Our studies highlight EPO and PRAS40 signaling in the mTOR pathway as potential therapeutic strategies for development against degenerative disorders that lead to cell demise.

  8. Erythropoietin Exacerbates Inflammation and Increases the Mortality of Histoplasma capsulatum-Infected Mice

    Directory of Open Access Journals (Sweden)

    Gisele Aparecida Locachevic

    2015-01-01

    Full Text Available Erythropoietin (EPO is a key hormone involved in red blood cell formation, but its effects on nonerythroid cells, such as macrophages, have not been described. Macrophages are key cells in controlling histoplasmosis, a fungal infection caused by Histoplasma capsulatum (Hc. Considering that little is known about EPO’s role during fungal infections and its capacity to activate macrophages, in this study we investigated the impact of EPO pretreatment on the alveolar immune response during Hc infection. The consequence of EPO pretreatment on fungal infection was determined by evaluating animal survival, fungal burden, activation of bronchoalveolar macrophages, inflammatory mediator release, and lung inflammation. Pretreatment with EPO diminished mononuclear cell numbers, increased the recruitment of F4/80+/CD80+ and F4/80+/CD86+ cells to the bronchoalveolar space, induced higher production of IFN-γ, IL-6, MIP-1α, MCP-1, and LTB4, reduced PGE2 concentration, and did not affect fungal burden. As a consequence, we observed an increase in lung inflammation with extensive tissue damage that might account for augmented mouse mortality after infection. Our results demonstrate for the first time that EPO treatment has a deleterious impact on lung immune responses during fungal infection.

  9. Evaluation of the effect of pentoxifylline on erythropoietin-resistant anemia in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Amir-Hooshang Mohammadpour

    2014-01-01

    Full Text Available Use of recombinant human erythropoietin (rh-Epo improves hemoglobin (Hgb in 90-95% of the cases of anemia of chronic kidney disease (CKD. However, it is known that pro-inflammatory cytokines such as interferon-gamma (IFN-γ, tumor necrosis factor-alfa (TNF-α and interleukin-1 (IL-1 suppress erythropoiesis, resulting in inadequate response to rh-Epo. Pentoxifylline has been shown to have modulatory effects on the immune system. This prospec-tive study to evaluate the effect of pentoxyphylline on erythropoeisis was performed on 15 (eight males, seven females clinically stable patients who had been on hemodialysis for at least six months with anemia (Hgb of <10.7 g/dL unresponsive to rh-Epo despite high doses. They were treated with 400 mg pentoxifylline tablets once daily for 12 weeks. Hgb increased after one and two months of drug administration, but significant changes were observed in eight (53% patients after three months (P <0.05. Our study illustrates a probable new use for an old medicine. Three months treatment with pentoxifylline was seen to increase Hgb significantly in rh-Epo-resistant patients. More prospective studies with a larger sample size are needed to determine the inhi-bitory role of cytokines on hematopoiesis and exploring new drugs or new drug indications to overcome anemia in advanced renal failure.

  10. DNA methylation is necessary for erythropoietin to improve spatial learning and memory in SAMP8 mice.

    Science.gov (United States)

    Yu, Nengwei; Liu, Jie; Yi, Gang; Ye, Fang; Xiao, Jun; Guo, Fuqiang

    2015-09-01

    To reveal the role of Dnmts in the improvement of spatial learning and memory induced by erythropoietin (EPO) in SAMP8 mice. The Morris water maze (MWM) was used to assess spatial learning and memory. Mice were administered by intraperitoneal (i.p.) injection of recombinant human EPO and hippocamppi infusion (IH) of 5-aza-2'-deoxycytidine (5-AZA). The expression of genes Dnmt1, Dnmt3a and Dnmt3b in the hippocampus was detected by real-time qPCR. The level of proteins DNMT1, DNMT3A and DNMT3B was measured by Western blotting. Spatial learning and memory in SAMP8 were promoted after i.p. injection of EPO (5000IU/kg/day) and expression of Dnmt3b mRNA and DNMT3B proteins in the hippocampus increased. The improved memory by EPO was blocked after IH 5-AZA. DNA methylation is necessary for EPO to enhance spatial learning and memory in SAMP8 mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Increased Urinary Erythropoietin Excretion in Severe Sleep Apnea-Hipoapnea Syndrome: The Effect of CPAP.

    Science.gov (United States)

    Félez, Miquel; Grau, Nuria; Ruiz, Antonia; Guardiola, Encarna; Sanjuas, Carles; Estirado, Cristina; Navarro-Muñoz, Maribel; Pascual, Antoni; Orozco-Levi, Mauricio; Gea, Joaquim

    2017-12-04

    Tissue hypoxia stimulates the production of erythropoietin (EPO), the main effect of which is, in turn, to stimulate erythropoiesis. Sleep apnea-hypopnea syndrome (SAHS) is an entity characterized by repeated episodes of hypoxemia during sleep. To analyze whether hypoxemia stimulated increased urinary excretion of EPO, and if so, to evaluate if treatment with continuous positive airway pressure (CPAP) can inhibit this phenomenon. We studied 25 subjects with suspected SAHS who underwent a polysomnography study (PSG). EPO levels in first morning urine (uEPO) and blood creatinine and hemoglobin were determined in all patients. Patients with severe SAHS repeated the same determinations after CPAP treatment. Twelve subjects were diagnosed with severe SAHS (mean ± SD, AHI 53.1 ± 22.7). Creatinine and hemoglobin levels were normal in all subjects. uEPO was 4 times higher in the SAHS group than in the control group (1.32 ± 0.83 vs. 0.32 ± 0.35 UI/l, p <.002). CPAP treatment reduced uEPO to 0.61 ± 0.9 UI/l (p <.02), levels close to those observed in healthy subjects. No dose-response relationship was observed between severity of PSG changes and uEPO values. Patients with severe SAHS show increased uEPO excretion, but this normalizes after treatment with CPAP. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease.

    Science.gov (United States)

    Reza-Zaldívar, E E; Sandoval-Avila, S; Gutiérrez-Mercado, Y K; Vázquez-Méndez, E; Canales-Aguirre, A A; Esquivel-Solís, H; Gómez-Pinedo, U; Márquez-Aguirre, A L

    2017-11-10

    Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Optimization of amino acid-stabilized erythropoietin parenteral formulation: In vitro and in vivo assessment

    Directory of Open Access Journals (Sweden)

    Fayed Bahgat E.

    2016-03-01

    Full Text Available The aim of this study was to optimize the formulation of erythropoietin (EPO using amino acids instead of human serum albumin (HSA and to evaluate its in vivo stability in order to avoid the risk of viral contamination and antigenicity. Different EPO formulations were developed in such a way as to allow studying the effects of amino acids and surfactants on the EPO stability profile. The main techniques applied for EPO analysis were ELISA, Bradford method, and SDS gel electrophoresis. The in vivo stability was evaluated in a Balb-c mouse animal model. The results showed that the presence of surfactant was very useful in preventing the initial adsorption of EPO on the walls of vials and in minimizing protein aggregation. Amino acid combinations, glycine with glutamic acid, provided maximum stability. Formulation F4 (containing glycine, glutamic acid and Tween 20 showed minimum aggregation and degradation and in vivo activity equivalent to commercially available HSA-stabilized EPO (Eprex®.

  14. Erythropoietin-coated ZP-microneedle transdermal system: preclinical formulation, stability, and delivery.

    Science.gov (United States)

    Peters, Elaine E; Ameri, Mahmoud; Wang, Xiaomei; Maa, Yuh-Fun; Daddona, Peter E

    2012-06-01

    To evaluate the feasibility of coating formulated recombinant human erythropoietin alfa (EPO) on a titanium microneedle transdermal delivery system, ZP-EPO, and assess preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. EPO liquid formulation was coated onto titanium microneedles by dip-coating and drying. Stability of coated EPO was assessed by SEC-HPLC, CZE and potency assay. Preclinical in vivo delivery and pharmacokinetic studies were conducted in rats with EPO-coated microneedle patches and compared to subcutaneous EPO injection. Studies demonstrated successful EPO formulation development and coating on microneedle arrays. ZP-EPO patch was stable at 25°C for at least 3 months with no significant change in % aggregates, isoforms, or potency. Preclinical studies in rats showed the ZP-EPO microneedle patches, coated with 750 IU to 22,000 IU, delivered with high efficiency (75-90%) with a linear dose response. PK profile was similar to subcutaneous injection of commercial EPO. Results suggest transdermal microneedle patch delivery of EPO is feasible and may offer an efficient, dose-adjustable, patient-friendly alternative to current intravenous or subcutaneous routes of administration.

  15. Erythropoietin Promotes Neural Plasticity and Spatial Memory Recovery in Fimbria-Fornix-Lesioned Rats.

    Science.gov (United States)

    Almaguer-Melian, William; Mercerón-Martínez, Daymara; Pavón-Fuentes, Nancy; Alberti-Amador, Esteban; Leon-Martinez, Rilda; Ledón, Nuris; Delgado Ocaña, Susana; Bergado Rosado, Jorge A

    2015-01-01

    Erythropoietin (EPO) upregulates the mitogen activated protein kinase (MAPK) cascade, a central signaling pathway in cellular plastic mechanisms, and is critical for normal brain development. We hypothesized that EPO could modulate the plasticity mechanisms supporting spatial memory recovery in fimbria-fornix-transected animals. Fimbria-fornix was transected in 3 groups of rats. Seven days later, EPO was injected daily for 4 consecutive days within 10 minutes after training on a water maze task. Our results show that EPO injections 10 minutes after training produced a substantial spatial memory recovery in fimbria-fornix-lesioned animals. In contrast, an EPO injection shortly after fimbria-fornix lesion surgery does not promote spatial-memory recovery. Neither does daily EPO injection 5 hours after the water maze performance. EPO, on the other hand, induced the expression of plasticity-related genes like arc and bdnf, but this effect was independent of training or lesion. This finding supports our working hypothesis that EPO can modulate transient neuroplastic mechanisms triggered by training in lesioned animals. Consequently, we propose that EPO administration can be a useful trophic factor to promote neural restoration when given in combination with training. © The Author(s) 2015.

  16. The effects of erythropoietin dose titration during high-fat diet-induced obesity.

    Science.gov (United States)

    Foskett, Amanda; Alnaeeli, Mawadda; Wang, Li; Teng, Ruifeng; Noguchi, Constance T

    2011-01-01

    Erythropoietin (Epo) is a pleotropic cytokine with several nonhematopoietic tissue effects. High-dose Epo treatment-mediated effects on body weight, fat mass and glucose tolerance have recently been reported, thus extending its pleotropic effects to fat and glucose metabolism. However, the exact dose range of Epo treatment required for such effects remains unidentified to date. We investigated Epo dosage effect (up to 1000 U/kg) on hematocrit, body weight, body composition, glucose metabolism, food intake, and physical activity, during high-fat diet-induced obesity. We report that Epo doses (1000, 600, 300, and 150 U/kg) significantly reduced body weight gain and fat mass, while, only Epo doses of 300 U/kg and higher significantly affected glucose tolerance. None of the tested Epo doses showed any detectable effects on food intake, and only 1000 U/kg dose significantly increased physical activity, suggesting that these parameters may only be partially responsible for the metabolic effects of Epo treatment.

  17. Erythropoietin-Derived Peptide Protects Against Acute Lung Injury After Rat Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2017-04-01

    Full Text Available Background: Traumatic brain injury (TBI can be complicated by TBI-triggered acute lung injury (ALI, in which inflammation plays a central role. It has been reported that an Erythropoietin-derived peptide (pHBSP was able to ameliorate TBI; however, its function in TBI-caused ALI has not been reported yet. Methods: In this study, we studied the effect of pHBSP on TBI-caused ALI by using a weight-drop induced TBI model. At 8 h and 24 h post-TBI, pulmonary edema (PE and bronchoalveolar lavage fluid (BALF proteins were measured, and haematoxylin and eosin (H&E staining of lung sections was carried out. At 24 h following TBI, the lungs were harvested for immunofluorescence staining and qRT-PCR analysis. Results: At 8 h and 24 h post-TBI, pHBSP treatment significantly decreased wet/dry ratios, decreased total BALF protein, and attenuated the histological signs of pulmonary injury. At 24 h post-TBI, pHBSP treatment decreased the accumulation of CD68+ macrophages in the lung and reduced the mRNA levels of TNF-α, IL-6, IL-1β and iNOS in the lung. Conclusions: We identified the protective role that pHBSP played in TBI-caused ALI, suggesting that pHBSP is a potent candidate for systemic therapy in TBI patients.

  18. Behavior of vascular endothelial growth factor and erythropoietin throughout the menstrual cycle in healthy women.

    Science.gov (United States)

    Caccamo, Chiara; Nostro, Lorena; Giorgianni, Giovanna; Mondello, Stefania; Crascì, Eleonora; Frisina, Nicola; Buemi, Michele

    2007-11-01

    To evaluate any correlations between erythropoietin (EPO) and vascular endothelial growth factor (VEGF) levels in the serum and the menstrual fluid of healthy women during the different phases of the menstrual cycle. Blood samples from 25 healthy female volunteers were obtained for serum VEGF and EPO detection on the 1st, 7th, 14th, 21st and 25th days of the menstrual cycle. Menstrual fluid samples for VEGF and EPO detection were obtained on the 1st and 4th days of menstruation. Circulating VEGF levels were found to increase in a stage-dependent cyclic manner. The mean VEGF concentration in menstrual blood on the 1st day of the cycle was significantly higher than the mean plasma value and was reduced to a significant extent on the 4th day of the cycle. We found no significant changes in serum EPO levels. Mean EPO concentration detected in menstrual blood was comparable to those in serum blood either on the 1st or 4th day of the menstrual cycle. During menstruation, a local production of VEGF occurs independent of systemic production, thus sustaining angiogenic activity in autonomous, independent ways. Our findings demonstrate the presence of an "open compartment" that reflects the systemic pattern of EPO at the uterine level that allows us to speculate on different effects beyond the angiogenic action of EPO.

  19. Vector-mediated expression of erythropoietin improves functional outcome after cervical spinal cord contusion injury.

    Science.gov (United States)

    Wang, S; Wu, Z; Chiang, P; Fink, D J; Mata, M

    2012-09-01

    We evaluated the therapeutic effect of erythropoietin (EPO) delivered by direct injection of a nonreplicating herpes simplex virus (HSV)-based vector coding for EPO (vEPO) in a model of cervical hemicord contusion at C7. At 1 h after spinal cord injury (SCI), either vEPO or control vector carrying a reporter gene (vC) was injected into the cord above and below the lesion. Animals injected with vEPO showed a statistically significant improvement in the ipsilateral forelimb function, as measured by open-field evaluation of motor performance, forelimb reaching in the cylinder test and misplacement in grid walk. This correlated with preservation of gray matter in the area of the lesion. There was also mild but significant improvement of hindlimb motor function measured by Basso-Beattie-Bresnahan score and computerized gait analysis in vEPO compared with control vector-injected animals. Microtubule-associated protein tau, phosphorylated and nonphosphorylated neurofilament protein and the synaptic proteins synaptophysin and PSD-95 were all significantly increased in the spinal cord of vEPO-treated animals compared with control vector-injected animals. These data suggest that gene transfer of EPO after cervical SCI by minimizing the injury size and enhancing tissue sparing preserves large-caliber axons and promotes synaptogenesis.

  20. Erythropoietin, 2,3 DPG, oxygen transport capacity, and altitude training in adolescent Alpine skiers.

    Science.gov (United States)

    Son, Hee Jeong; Kim, Hyo Jeong; Kim, Jin Hae; Ohno, Hideki; Kim, Chang Keun

    2012-01-01

    Rapid growth during adolescence caused by metabolic changes and their metabolic response to anaerobic and aerobic exercise differs considerably from that in adults and this is especially true in the responses to stresses, such as altitude exposure. However, there is little information on the suitability of exercise training at altitude for young athletes. Six male Korean adolescent alpine skiers (13-17 yr), with a skiing career of 3-5 yr, participated in the study. All subjects were exposed to an altitude of 2700 m (8858 ft) for 5 wk and altitude exposure consisted of 6 d/wk of training (4-5 h/d), with living quarters at 2100 m (-6890 ft) (Tignes, France). The 5 wk of ski training at altitude were maintained at the same level (the same number of slalom and giant slalom skiing trials) as at sea level. There was a significant increase in oxygen transport capacity, despite decreased erythropoietin (EPO) production (-31%) after altitude training. Red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), and 2,3 DPG concentrations increased significantly during altitude exposure and after return to sea level. Results indicate that applying altitude training in adolescent skiers may improve their endurance performance. However, EPO production during altitude training needs to be evaluated in larger future studies.

  1. In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy.

    Science.gov (United States)

    Kianmehr, Anvarsadat; Mohammadi, Hamid Shahbaz; Shokrgozar, Mohammad Ali; Omidinia, Eskandar

    2015-01-01

    The enhancement of glycosylation by applying glycoengineering approaches has become widely used to boost properties for protein therapeutics. The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. The EPO protein sequence was retrieved from NCBI protein sequence database. Prediction of N-glycosylation sites for the target protein was done using the prediction server, NetNGlyc. The three-dimensional model of glycoengineered EPO (named as kypoetin) was constructed using the homology modeling program. Ramchandran plot obtained from PROCHECK server was used to check stereochemical property. Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 3D structural modeling showed that attached carbohydrates were on the proper spatial position. The whole solvent accessible surface areas of kypoetin (15132.69) were higher than EPO (9938.62). Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug.

  2. Neuronal erythropoietin overexpression protects mice against age-related hearing loss (presbycusis).

    Science.gov (United States)

    Monge Naldi, Arianne; Belfrage, Celina; Jain, Neha; Wei, Eric T; Canto Martorell, Belén; Gassmann, Max; Vogel, Johannes

    2015-12-01

    So far, typical causes of presbycusis such as degeneration of hair cells and/or primary auditory (spiral ganglion) neurons cannot be treated. Because erythropoietin's (Epo) neuroprotective potential has been shown previously, we determined hearing thresholds of juvenile and aged mice overexpressing Epo in neuronal tissues. Behavioral audiometry revealed in contrast to 5 months of age, that 11-month-old Epo-transgenic mice had up to 35 dB lower hearing thresholds between 1.4 and 32 kHz, and at the highest frequencies (50-80 kHz), thresholds could be obtained in aged Epo-transgenic only but not anymore in old C57BL6 control mice. Click-evoked auditory brainstem response showed similar results. Numbers of spiral ganglion neurons in aged C57BL6 but not Epo-transgenic mice were dramatically reduced mainly in the basal turn, the location of high frequencies. In addition, there was a tendency to better preservation of inner and outer hair cells in Epo-transgenic mice. Hence, Epo's known neuroprotective action effectively suppresses the loss of spiral ganglion cells and probably also hair cells and, thus, development of presbycusis in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Erythropoietin ameliorates the motor and cognitive function impairments in a rat model of hepatic cirrhosis.

    Science.gov (United States)

    Aghaei, Iraj; Nazeri, Masoud; Shabani, Mohammad; Mossavinasab, Marziehsadat; Mirhosseini, Fatemeh Khaleghi; Nayebpour, Mohsen; Dalili, Afshin

    2015-02-01

    Hepatic encephalopathy (HE) is a serious consequence of hepatic cirrhosis (HC). Previous studies have demonstrated cognitive impairments in both clinical and animal experiments of HC. Some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of HC. In the current study, the possible effect of erythropoietin (ERY) as a potent neuroprotective agent on motor and cognitive impairments induced by HC has been studied. Male Wistar rats (180-200 g) underwent bile duct ligation (BDL) or sham surgery. Administration of ERY (5,000 IU/kg, i.p., daily for three days) was initiated 2 weeks after surgery and lasted for the next 28 days. Open field, rotarod, Morris water maze and passive avoidance learning was used to evaluate the motor and cognitive function of the animals. ANOVA and repeated measures ANOVA were used to analyze the data. p balance function by BDL was reversed by ERY. Spatial and passive avoidance learning impairments observed in BDL rats were also reversed by chronic administration of ERY. ERY can be offered as a potential neuroprotective agent in the treatment of patients with HC that manifest mental dysfunctions. Though further studies are needed to clarify the exact mechanisms, the neuroprotective properties of ERY against BDL impairments were demonstrated in the current study.

  4. Erythropoietin protects myocardin-expressing cardiac stem cells against cytotoxicity of tumor necrosis factor-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Madonna, Rosalinda [The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States); Institute of Cardiology, and Center of Excellence on Aging, ' G. d' Annunzio' University, Chieti (Italy); Shelat, Harnath; Xue, Qun; Willerson, James T. [The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States); The Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, Texas (United States); De Caterina, Raffaele [Institute of Cardiology, and Center of Excellence on Aging, ' G. d' Annunzio' University, Chieti (Italy); Geng, Yong-Jian, E-mail: yong-jian.geng@uth.tmc.edu [The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States); The Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, Texas (United States)

    2009-10-15

    Cardiac stem cells are vulnerable to inflammation caused by infarction or ischemic injury. The growth factor, erythropoietin (Epo), ameliorates the inflammatory response of the myocardium to ischemic injury. This study was designed to assess the role of Epo in regulation of expression and activation of the cell death-associated intracellular signaling components in cardiac myoblasts stimulated with the proinflammatory cytokine tumor necrosis factor (TNF)-{alpha}. Cardiac myoblasts isolated from canine embryonic hearts characterized by expression of myocardin A, a promyogenic transcription factor for cardiovascular muscle development were pretreated with Epo and then exposed to TNF-{alpha}. Compared to untreated cells, the Epo-treated cardiac myoblasts exhibited better morphology and viability. Immunoblotting revealed lower levels of active caspase-3 and reductions in iNOS expression and NO production in Epo-treated cells. Furthermore, Epo pretreatment reduced nuclear translocation of NF-{kappa}B and inhibited phosphorylation of inhibitor of kappa B (I{kappa}B) in TNF-{alpha}-stimulated cardiac myoblasts. Thus, Epo protects cardiac myocyte progenitors or myoblasts against the cytotoxic effects of TNF-{alpha} by inhibiting NF-{kappa}B-mediated iNOS expression and NO production and by preventing caspase-3 activation.

  5. Dexamethasone mimics aspects of physiological acclimatization to 8 hours of hypoxia but suppresses plasma erythropoietin

    Science.gov (United States)

    Liu, Chun; Croft, Quentin P. P.; Kalidhar, Swati; Brooks, Jerome T.; Herigstad, Mari; Smith, Thomas G.; Dorrington, Keith L.

    2013-01-01

    Dexamethasone ameliorates the severity of acute mountain sickness (AMS) but it is unknown whether it obtunds normal physiological responses to hypoxia. We studied whether dexamethasone enhanced or inhibited the ventilatory, cardiovascular, and pulmonary vascular responses to sustained (8 h) hypoxia. Eight healthy volunteers were studied, each on four separate occasions, permitting four different protocols. These were: dexamethasone (20 mg orally) beginning 2 h before a control period of 8 h of air breathing; dexamethasone with 8 h of isocapnic hypoxia (end-tidal Po2 = 50 Torr); placebo with 8 h of air breathing; and placebo with 8 h of isocapnic hypoxia. Before and after each protocol, the following were determined under both euoxic and hypoxic conditions: ventilation; pulmonary artery pressure (estimated using echocardiography to assess maximum tricuspid pressure difference); heart rate; and cardiac output. Plasma concentrations of erythropoietin (EPO) were also determined. Dexamethasone had no early (2-h) effect on any variable. Both dexamethasone and 8 h of hypoxia increased euoxic values of ventilation, pulmonary artery pressure, and heart rate, together with the ventilatory sensitivity to acute hypoxia. These effects were independent and additive. Eight hours of hypoxia, but not dexamethasone, increased the sensitivity of pulmonary artery pressure to acute hypoxia. Dexamethasone, but not 8 h of hypoxia, increased both cardiac output and systemic arterial pressure. Dexamethasone abolished the rise in EPO induced by 8 h of hypoxia. In summary, dexamethasone enhances ventilatory acclimatization to hypoxia. Thus, dexamethasone in AMS may improve oxygenation and thereby indirectly lower pulmonary artery pressure. PMID:23393065

  6. Effects of erythropoietin on memory-relevant neurocircuitry activity and recall in mood disorders.

    Science.gov (United States)

    Miskowiak, K W; Macoveanu, J; Vinberg, M; Assentoft, E; Randers, L; Harmer, C J; Ehrenreich, H; Paulson, O B; Knudsen, G M; Siebner, H R; Kessing, L V

    2016-09-01

    Erythropoietin (EPO) improves verbal memory and reverses subfield hippocampal volume loss across depression and bipolar disorder (BD). This study aimed to investigate with functional magnetic resonance imaging (fMRI) whether these effects were accompanied by functional changes in memory-relevant neuro-circuits in this cohort. Eighty-four patients with treatment-resistant unipolar depression who were moderately depressed or BD in remission were randomized to eight weekly EPO (40 000 IU) or saline infusions in a double-blind, parallel-group design. Participants underwent whole-brain fMRI at 3T, mood ratings, and blood tests at baseline and week 14. During fMRI, participants performed a picture encoding task followed by postscan recall. Sixty-two patients had complete data (EPO: N = 32, saline: N = 30). EPO improved picture recall and increased encoding-related activity in dorsolateral prefrontal cortex (dlPFC) and temporo-parietal regions, but not in hippocampus. Recall correlated with activity in the identified dlPFC and temporo-parietal regions at baseline, and change in recall correlated with activity change in these regions from baseline to follow-up across the entire cohort. The effects of EPO were not correlated with change in mood, red blood cells, blood pressure, or medication. The findings highlight enhanced encoding-related dlPFC and temporo-parietal activity as key neuronal underpinnings of EPO-associated memory improvement. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Erythropoietin: a candidate treatment for mood symptoms and memory dysfunction in depression.

    Science.gov (United States)

    Miskowiak, Kamilla W; Vinberg, Maj; Harmer, Catherine J; Ehrenreich, Hannelore; Kessing, Lars V

    2012-02-01

    Current pharmacological treatments for depression have a significant treatment-onset-response delay, an insufficient efficacy for many patients and fail to reverse cognitive dysfunction. Erythropoietin (EPO) has neuroprotective and neurotrophic actions and improves cognitive function in animal models of acute and chronic neurodegenerative conditions and in patients with cognitive decline. We systematically reviewed the published findings from animal and human studies exploring the potential of EPO to treat depression-related cognitive dysfunction and depression. We identified five animal studies (two in male rats, two in male mice and one in male rats and mice) and seven human proof-of-concept studies (five in healthy volunteers and two in depressed patients) that investigated the above. All of the reviewed animal studies but one and all human studies demonstrated beneficial effects of EPO on hippocampus-dependent memory and antidepressant-like effects. These effects appear to be mediated through direct neurobiological actions of EPO rather than upregulation of red cell mass. The reviewed studies demonstrate beneficial effects of EPO on hippocampus-dependent memory function and on depression-relevant behavior, thus highlighting EPO as a candidate agent for future management of cognitive dysfunction and mood symptoms in depression. Larger-scale clinical trials of EPO as a treatment for mood and neurocognitive symptoms in patients with mood disorder are therefore warranted.

  8. Erythropoietin as an adjunctive treatment for methanol-induced toxic optic neuropathy.

    Science.gov (United States)

    Pakravan, Mohammad; Esfandiari, Hamed; Sanjari, Nasrin; Ghahari, Elham

    2016-11-01

    Methanol-induced optic neuropathy (MTON) is frequently seen in countries where alcohol consumption is banned or poorly regulated. MTON frequently results in blindness and there is no empirically validated treatment. To evaluate the effect of erythropoietin (EPO) as an adjunctive treatment for MTON. In this nonrandomized interventional comparative study, all participants were diagnosed with MTON and received the steroid methylprednisolone. Eleven participants received intravenous EPO (10000 IU twice a day) for three days as an adjuvant to methylprednisolone (EPO group); 11 participants in a historical control group received methylprednisolone only (control group). Main outcomes were best-corrected visual acuity (BCVA), peripapillary retinal nerve fiber layer thickness (PRNFLT), and visual field mean deviation (MD). Mean BCVA improved significantly in both groups: from 2.93 ± 0.55 to 1.75 ± 1.16 LogMAR at month 3 (p < 0.001) in the EPO group, and from 2.65 ± 0.68 to 2.19 ± 0.75 at final visit in the control group (p = 0.001). The final BCVA was significantly better in the EPO group (p = 0.012). The mean PRNFLT decreased in both groups. However, at the final follow-up, PRNFLT was significantly thinner in the control group (53 ± 6 vs. 77 ± 26 microns, respectively; p < 0.001). Intravenous EPO plus high-dose intravenous steroid may be an effective combination therapy for the patients with MTON.

  9. Inhibition of erythropoietin siRNA on corneal neovascularization of rabbit

    Directory of Open Access Journals (Sweden)

    Yu-Shun Xue

    2017-03-01

    Full Text Available AIM: To observe the expression of erythropoietin(EPOon the corneal of rabbit and evaluate the inhibition effect of EPO siRNA on corneal neovascularization(CNV. METHODS: Totally 22 healthy rabbits were randomly divided into 2 groups, which were experimental group and normal control group. Both eyes of rabbits in experimental group were chosen to establish corneal neovascularization model by alkali burn. The morphologic change of corneal was observed with slit lamp microscope and the area of CNV was calculated every day. After alkali burn, the right eye of the experimental group was accepted EPO siRNA injection under the conjunctiva, and the left eye was assigned to be experimental control group. The corneal with CNV was collected for immunohistochemistry at 3d, 7d, 14d, 21d after alkali burn, and the expression of EPO was measured. RESULTS: CNV began growing at the 3d after alkali burn in experimental group, and it was vigorous growing at 7d-14d period. The result of immunohistochemistry shows that the expression of EPO increased after the operation. Compared with experimental group, the rabbits who were treated by EPO siRNA was found with less neovascularization on their corneal, and the expression of EPO decreased. There were statistical significance between the two group at different time(PCONCLUSION: EPO is likely to play an important role on CNV growth, and EPO siRNA can inhibit the growth of CNV by restraining the expression of EPO.

  10. Erythropoietin protects the in vitro blood-brain barrier against VEGF-induced permeability.

    Science.gov (United States)

    Martínez-Estrada, Ofelia María; Rodríguez-Millán, Elisabeth; González-De Vicente, Esther; Reina, Manuel; Vilaró, Senén; Fabre, Myriam

    2003-11-01

    The blood-brain barrier (BBB) ensures the homeostasis of the brain microenvironment, mostly through complex tight junctions between brain endothelial cells that prevent the passage of hydrophilic molecules from blood to brain and vice versa. A recent study has shown in vivo that systemic administration of erythropoietin (Epo) protects against brain injury. Using an in vitro model of the bovine BBB, we observed that the expression of the Epo receptor is modulated by its ligand and hypoxic stimuli such as vascular endothelial growth factor (VEGF) treatment. In addition, Epo protects against the VEGF-induced permeability of the BBB, decreases the levels of endothelial nitric oxide synthase and restores junction proteins. The kinetic transport experiments revealed the capacity of Epo to cross the in vitro BBB in a saturable and specific way. Our results suggest a new mechanism for Epo-induced neuroprotection, in which circulating Epo controls and maintains the BBB through an Epo receptor signalling pathway and the re-establishment of cell junctions.

  11. High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial.

    Science.gov (United States)

    Wu, Yvonne W; Mathur, Amit M; Chang, Taeun; McKinstry, Robert C; Mulkey, Sarah B; Mayock, Dennis E; Van Meurs, Krisa P; Rogers, Elizabeth E; Gonzalez, Fernando F; Comstock, Bryan A; Juul, Sandra E; Msall, Michael E; Bonifacio, Sonia L; Glass, Hannah C; Massaro, An N; Dong, Lawrence; Tan, Katherine W; Heagerty, Patrick J; Ballard, Roberta A

    2016-06-01

    To determine if multiple doses of erythropoietin (Epo) administered with hypothermia improve neuroradiographic and short-term outcomes of newborns with hypoxic-ischemic encephalopathy. In a phase II double-blinded, placebo-controlled trial, we randomized newborns to receive Epo (1000 U/kg intravenously; n = 24) or placebo (n = 26) at 1, 2, 3, 5, and 7 days of age. All infants had moderate/severe encephalopathy; perinatal depression (10 minute Apgar score in Epo-treated infants (median, 2 vs 11, P = .01). Moderate/severe brain injury (4% vs 44%, P = .002), subcortical (30% vs 68%, P = .02), and cerebellar injury (0% vs 20%, P = .05) were less frequent in the Epo than placebo group. At mean age 12.7 months (SD, 0.9), motor performance in Epo-treated (n = 21) versus placebo-treated (n = 20) infants were as follows: Alberta Infant Motor Scale (53.2 vs 42.8, P = .03); Warner Initial Developmental Evaluation (28.6 vs 23.8, P = .05). High doses of Epo given with hypothermia for hypoxic-ischemic encephalopathy may result in less MRI brain injury and improved 1-year motor function. Copyright © 2016 by the American Academy of Pediatrics.

  12. Erythropoietin preserves the integrity and quality of organs for transplantation after cardiac death.

    Science.gov (United States)

    Maio, Rui; Sepodes, Bruno; Patel, Nimesh S A; Thiemermann, Christoph; Mota-Filipe, Helder; Costa, Paulo

    2011-02-01

    Previous studies have shown that treatment with erythropoietin (EPO) exerts important cytoprotective and antiapoptotic effects. Donor organs recovered after cardiac death (DCD) can alleviate the shortage of organs required for transplantation. However, organs obtained subsequent to cardiac death demonstrate an increased incidence of delayed graft function and primary nonfunction. The aim of this study was to determine the effects of EPO administration to the donor in a porcine model of kidney transplantation under DCD conditions. Landrace pigs received 1,000 IU/kg i.v. EPO 30 min before cardiac arrest. Kidneys were then subjected to 30 min of warm ischemia and were transplanted after 24 h of cold storage. Renal dysfunction, injury, and inflammation were evaluated 4 h after transplantation. Transplantation of kidneys from DCD resulted in significant renal dysfunction, injury, and inflammation. This study provides the first evidence that pretreatment of the donor with a single pharmacologically relevant dose of EPO causes substantial attenuation of the dysfunction and injury associated with the transplantation of kidneys recovered after cardiac death.

  13. Early erythropoietin therapy attenuates remodeling and preserves function of left ventricle in porcine myocardial infarction.

    Science.gov (United States)

    Chua, Sarah; Leu, Steve; Lin, Yu-Chun; Sheu, Jiunn-Jye; Sun, Cheuk-Kwan; Chung, Sheng-Ying; Chai, Han-Tan; Lee, Fan-Yen; Kao, Ying-Hsien; Wu, Chiung-Jen; Chang, Li-Teh; Ko, Sheung-Fat; Yip, Hon-Kan

    2011-03-01

    Erythropoietin (EPO) has been shown to have anti-inflammatory, antiapoptotic, and proangiogenic effects. This study investigated whether early EPO treatment effectively preserves left ventricular (LV) function in porcine acute myocardial infarction (AMI). Eighteen male mini-pigs divided into groups 1 (sham), 2 (AMI), and 3 (AMI with 2 consecutive EPO doses [7500 IU per animal each time] at 30 minutes and 24 hours after AMI induction) underwent echocardiography before and 14 days after AMI induction through left anterior descending artery (LAD) ligation with myocardium harvested for analysis. Larger infarcted areas (IA) were noted in group 2 than in group 3. In both IA and peri-IA, percentage of apoptotic nuclei and CD40-positive cells, messenger RNA expressions of IL-8, matrix metalloproteinase-9, caspase-3, and Bcl-2 associated x protein were highest, whereas proliferator-activated receptor-γ coactivator-1α, endothelial nitric oxide synthase and Bcl-2 were lowest in group 2. Oxidative stress and cytosolic cytochrome c in IA were increased (P porcine AMI model effectively limits infarct size, attenuates LV remodeling, and preserves LV function.

  14. High‐Efficiency CMOS Power Amplifier Using Uneven Bias for Wireless LAN Application

    National Research Council Canada - National Science Library

    Ryu, Namsik; Jung, Jae‐Ho; Jeong, Yongchae

    2012-01-01

    This paper proposes a high‐efficiency power amplifier (PA) with uneven bias. The proposed amplifier consists of a driver amplifier, power stages of the main amplifier with class AB bias, and an auxiliary amplifier with class C bias...

  15. Frequency Compensation of an Audio Power Amplifier

    NARCIS (Netherlands)

    van der Zee, Ronan A.R.; van Heeswijk, R.

    2006-01-01

    A car audio power amplifier is presented that uses a frequency compensation scheme which avoids large compensation capacitors around the MOS power transistors, while retaining the bandwidth and stable load range of nested miller compensation. THD is 0.005%@(1kHz, 10W), SNR is 108dB, and the

  16. Molecular markers. Amplified fragment length polymorphism

    Directory of Open Access Journals (Sweden)

    Pržulj Novo

    2005-01-01

    Full Text Available Amplified Fragment Length Polymorphism molecular markers (AFLPs has been developed combining procedures of RFLPs and RAPDs molekular markers, i.e. the first step is restriction digestion of the genomic DNA that is followed by selective amplification of the restricted fragments. The advantage of the AFLP technique is that it allows rapid generation of a large number of reproducible markers. The reproducibility of AFLPs markers is assured by the use of restriction site-specific adapters and adapter-specific primers for PCR reaction. Only fragments containing the restriction site sequence plus the additional nucleotides will be amplified and the more selected nucleotides added on the primer sequence the fewer the number of fragments amplified by PCR. The amplified products are normally separated on a sequencing gel and visualized after exposure to X-ray film or by using fluorescent labeled primers. AFLP shave proven to be extremely proficient in revealing diversity at below the species level. A disadvantage of AFLP technique is that AFLPs are essentially a dominant marker system and not able to identify heterozygotes.

  17. Using optimized random amplified polymorphic DNA (RAPD ...

    African Journals Online (AJOL)

    Citrus nobilis Lour. Gonggan is an excellent fruit variety which is widely planted in South China. The origin of Gonggan is not clear. It is conjectured that its origin is from a cross between tangerine and orange; however, there is no direct evidence to confirm this. Here, we applied the optimized random amplified polymorphic ...

  18. Design of a lock-amplifier circuit

    Science.gov (United States)

    Liu, H.; Huang, W. J.; Song, X.; Zhang, W. Y.; Sa, L. B.

    2017-01-01

    The lock-in amplifier is recovered by phase sensitive detection technique for the weak signal submerged in the noise background. This design is based on the TI ultra low power LM358, INA129, OPA227, OP07 and other chips as the core design and production of the lock-in amplifier. Signal generator by 10m ohms /1K ohm resistance points pressure network 10 mu V 1mV adjustable sine wave signal s (T). The concomitant interference signal together through the AC amplifier and band-pass filter signal x (T), on the other hand reference signal R (T) driven by square wave phase shift etc. steps to get the signal R (T), two signals and by phase sensitive detector are a DC full wave, again through its low pass filter and a DC amplifier to be measured signal more accurate detection, the final circuit through the AD conversion and the use of single-chip will display the output.

  19. Stereoscopy Amplifies Emotions Elicited by Facial Expressions

    Directory of Open Access Journals (Sweden)

    Jussi Hakala

    2015-11-01

    Full Text Available Mediated facial expressions do not elicit emotions as strongly as real-life facial expressions, possibly due to the low fidelity of pictorial presentations in typical mediation technologies. In the present study, we investigated the extent to which stereoscopy amplifies emotions elicited by images of neutral, angry, and happy facial expressions. The emotional self-reports of positive and negative valence (which were evaluated separately and arousal of 40 participants were recorded. The magnitude of perceived depth in the stereoscopic images was manipulated by varying the camera base at 15, 40, 65, 90, and 115 mm. The analyses controlled for participants’ gender, gender match, emotional empathy, and trait alexithymia. The results indicated that stereoscopy significantly amplified the negative valence and arousal elicited by angry expressions at the most natural (65 mm camera base, whereas stereoscopy amplified the positive valence elicited by happy expressions in both the narrowed and most natural (15–65 mm base conditions. Overall, the results indicate that stereoscopy amplifies the emotions elicited by mediated emotional facial expressions when the depth geometry is close to natural. The findings highlight the sensitivity of the visual system to depth and its effect on emotions.

  20. Modeling Power Amplifiers using Memory Polynomials

    NARCIS (Netherlands)

    Kokkeler, Andre B.J.

    2005-01-01

    In this paper we present measured in- and output data of a power amplifier (PA). We compare this data with an AM-AM and AM-PM model. We conclude that a more sophisticated PA model is needed to cope with severe memory effects. We suggest to use memory polynomials and introduce two approaches to

  1. Fluorescent amplified fragment length polymorphism (AFLP ...

    African Journals Online (AJOL)

    Rosa rugosa is an excellent ornamental plant with important ecological, economical and medicinal values in China. Polymorphism amplifications of the genomic DNA of 5 wild R. rugosa accessions and 25 cultivars that originated from China with fluorescent amplified fragment length polymorphism molecular markers were ...

  2. A wideband RF amplifier for satellite tuners

    Science.gov (United States)

    Xueqing, Hu; Zheng, Gong; Yin, Shi; Foster, Dai Fa

    2011-11-01

    This paper presents the design and measured performance of a wideband amplifier for a direct conversion satellite tuner. It is composed of a wideband low noise amplifier (LNA) and a two-stage RF variable gain amplifier (VGA) with linear gain in dB and temperature compensation schemes. To meet the system linearity requirement, an improved distortion compensation technique and a bypass mode are applied on the LNA to deal with the large input signal. Wideband matching is achieved by resistive feedback and an off-chip LC-ladder matching network. A large gain control range (over 80 dB) is achieved by the VGA with process voltage and temperature compensation and dB linearization. In total, the amplifier consumes up to 26 mA current from a 3.3 V power supply. It is fabricated in a 0.35-μm SiGe BiCMOS technology and occupies a silicon area of 0.25 mm2.

  3. Relationship between morphological and amplified fragment length ...

    African Journals Online (AJOL)

    ... morphological and amplified fragment length polymorphism (AFLP) marker based genetic diversity, to estimate mid parent heterosis and to correlate the estimated parental genetic diversity with heterosis chilli. Five CMS B - lines and 30 testers were used for morphological and AFLP marker genetic divergence analysis.

  4. Random amplified polymorphic DNA (RAPD) marker associated ...

    African Journals Online (AJOL)

    Jane

    2011-06-29

    Jun 29, 2011 ... between the studied provenances were less than 39%. Key words: Acacia Senegal, provenance variation, random amplified polymorphic DNA (RAPD) marker, salt tolerance, seed germination, seedling growth. INTRODUCTION. Salinity is the major factor limiting plants growth, widely spread and has more ...

  5. Random amplified polymorphic DNA (RAPD) marker associated ...

    African Journals Online (AJOL)

    Jane

    2011-06-29

    Jun 29, 2011 ... bands detected were polymorphic for the provenances of A. senegal and the dissimilarity indices between the studied provenances were less than 39%. Key words: Acacia Senegal, provenance variation, random amplified polymorphic DNA (RAPD) marker, salt tolerance, seed germination, seedling growth ...

  6. Optimization of Pr3+:ZBLAN fiber amplifiers

    DEFF Research Database (Denmark)

    Pedersen, B.; Miniscalco, J. W.; Quimby, R. S.

    1992-01-01

    Experimental parameters have been measured and used in a quantitative model of Pr3+-doped fluorozirconate fiber amplifiers. The optimum cutoff wavelength was determined to be 800 nm and the gain for 400 mW of pump was found to increase from 12 to 34 dB if the NA was increased from 0.15 to 0...

  7. Reflected-wave maser. [low noise amplifier

    Science.gov (United States)

    Clauss, R. C. (Inventor)

    1976-01-01

    A number of traveling-wave, slow-wave maser structures, containing active maser material but absent the typical ferrite isolators, are immersed in a nonuniform magnetic field. The microwave signal to be amplified is inserted at a circulator which directs the signal to a slow-wave structure. The signal travels through the slow-wave structure, being amplified according to the distance traveled. The end of the slow-wave structure farthest from the circulator is arranged to be a point of maximum reflection of the signal traveling through the slow-wave structure. As a consequence, the signal to be amplified traverses the slow-wave structure again, in the opposite direction (towards the circulator) experiencing amplification equivalent to that achieved by a conventional traveling-wave maser having twice the length. The circulator directs the amplified signal to following like stages of amplification. Isolators are used in between stages to prevent signals from traveling in the wrong direction, between the stages. Reduced signal loss is experienced at each stage. The high gain produced by each slow-wave structure is reduced to a moderate value by use of a nonuniform magnetic field which also broadens the line width of the maser material. The resulting bandwidth can be exceptionally wide. Cascaded stages provide high gain, exceptionally wide bandwith and very low noise temperature.

  8. Multi-pass amplifier architecture for high power laser systems

    Science.gov (United States)

    Manes, Kenneth R; Spaeth, Mary L; Erlandson, Alvin C

    2014-04-01

    A main amplifier system includes a first reflector operable to receive input light through a first aperture and direct the input light along an optical path. The input light is characterized by a first polarization. The main amplifier system also includes a first polarizer operable to reflect light characterized by the first polarization state. The main amplifier system further includes a first and second set of amplifier modules. Each of the first and second set of amplifier modules includes an entrance window, a quarter wave plate, a plurality of amplifier slablets arrayed substantially parallel to each other, and an exit window. The main amplifier system additionally includes a set of mirrors operable to reflect light exiting the first set of amplifier modules to enter the second set of amplifier modules and a second polarizer operable to reflect light characterized by a second polarization state.

  9. The warm, rich sound of valve guitar amplifiers

    Science.gov (United States)

    Keeports, David

    2017-03-01

    Practical solid state diodes and transistors have made glass valve technology nearly obsolete. Nevertheless, valves survive largely because electric guitar players much prefer the sound of valve amplifiers to the sound of transistor amplifiers. This paper discusses the introductory-level physics behind that preference. Overdriving an amplifier adds harmonics to an input sound. While a moderately overdriven valve amplifier produces strong even harmonics that enhance a sound, an overdriven transistor amplifier creates strong odd harmonics that can cause dissonance. The functioning of a triode valve explains its creation of even and odd harmonics. Music production software enables the examination of both the wave shape and the harmonic content of amplified sounds.

  10. Low phase noise oscillator using two parallel connected amplifiers

    Science.gov (United States)

    Kleinberg, Leonard L.

    1987-01-01

    A high frequency oscillator is provided by connecting two amplifier circuits in parallel where each amplifier circuit provides the other amplifier circuit with the conditions necessary for oscillation. The inherent noise present in both amplifier circuits causes the quiescent current, and in turn, the generated frequency, to change. The changes in quiescent current cause the transconductance and the load impedance of each amplifier circuit to vary, and this in turn results in opposing changes in the input susceptance of each amplifier circuit. Because the changes in input susceptance oppose each other, the changes in quiescent current also oppose each other. The net result is that frequency stability is enhanced.

  11. Long-term L-Carnitine Administration reduces Erythropoietin Resistance in Chronic Hemodialysis Patients with Thalassemia Minor

    Directory of Open Access Journals (Sweden)

    Biagio R. Di Iorio

    2007-01-01

    Full Text Available Background and Aim: Both thalassemia and carnitine deficiency represent independent causes of erythropoietin resistance, and thus anemia, in uremic patients. We evaluated the unknown long-term effects of L-carnitine administration in β-thalassemic on chronic hemodialysis.Methods: We studied twelve subjects (M = 8; F = 4 affected by β-thalassemia minor (β-thal; HbA2 level = 6.6 ± 0.6% and forty non-thalassemic subjects (M = 24; F = 16 as controls (C, on chronic hemodialysis treatment. Patients and controls were at target hemoglobin levels (11–12g/dl prior to the study and underwent to i.v. L-carnitine administration for a one year period-time.Results: Groups were comparable for age, gender, serum levels of hemoglobin (Hb, iron, ferritine, PTH and aluminum, transferrin saturation, and dialysis modalities. During the study both groups showed signifi cant Hb increase and erythropoietin (EPO decrease; as a difference, such changes emerged at the 3rd month in C but at the 8th month in β-thal. At start, during the dialysis session the erythrocyte MCV reduced in C but not in β-thal (65.3 ± 3.2 to 65.5 ± 3.2 fl ; NS; along carnitine administration period, however, MCV during dialysis decreased also in β-thal, starting since the 9th month of treatment.Conclusion: This study provides evidence of the lowering of EPO resistance in β-thalassemia patients on hemodialysis due to long-term carnitine administration. Thus, prolonged carnitine supplementation should be suggested to patients on dialysis affected by β-thalassemia with poorly responsive anemia, or requiring large doses of erythropoietin.

  12. Long-term L-Carnitine Administration reduces Erythropoietin Resistance in Chronic Hemodialysis Patients with Thalassemia Minor

    Directory of Open Access Journals (Sweden)

    Biagio R. Di Iorio

    2007-01-01

    Full Text Available Background and Aim Both thalassemia and carnitine deficiency represent independent causes of erythropoietin resistance, and thus anemia, in uremic patients. We evaluated the unknown long-term effects of L-carnitine administration in β-thalassemic on chronic hemodialysis. Methods We studied twelve subjects (M = 8; F = 4 affected by β-thalassemia minor (β-thal; HbA2 level = 6.6 ± 0.6% and forty non-thalassemic subjects (M = 24; F = 16 as controls (C, on chronic hemodialysis treatment. Patients and controls were at target hemoglobin levels (11–12g/dl prior to the study and underwent to i.v. L-carnitine administration for a one year period-time. Results Groups were comparable for age, gender, serum levels of hemoglobin (Hb, iron, ferritine, PTH and aluminum, transferrin saturation, and dialysis modalities. During the study both groups showed significant Hb increase and erythropoietin (EPO decrease; as a difference, such changes emerged at the 3rd month in C but at the 8th month in β-thal. At start, during the dialysis session the erythrocyte MCV reduced in C but not in β-thal (65.3 ± 3.2 to 65.5 ± 3.2 fl; NS; along carnitine administration period, however, MCV during dialysis decreased also in β-thal, starting since the 9th month of treatment. Conclusion This study provides evidence of the lowering of EPO resistance in β-thalassemia patients on hemodialysis due to long-term carnitine administration. Thus, prolonged carnitine supplementation should be suggested to patients on dialysis affected by β-thalassemia with poorly responsive anemia, or requiring large doses of erythropoietin.

  13. Effect of relative hypoparathyroidism on the responsiveness to recombinant human erythropoietin in chronic hemodialysis patients: A single Saudi center experience

    Directory of Open Access Journals (Sweden)

    Khalid Al Saran

    2013-01-01

    Full Text Available Anemia is a common concomitant disorder in dialysis patients. The responsiveness to recombinant human erythropoietin in hemodialysis (HD patients with relative hypoparathyroidism [4 ≤ intact parathyroid hormone (iPTH ≤16.5 pmol/L] remains undetermined. We retrospectively studied 70 chronic hemodialysis patients who were divided into two groups: Group A (32 patients had 16.5 ≤ iPTH levels <33.5 pmol/L and Group B (38 patients had 4 ≥ iPTH≤16.5 pmol/L during the preceding six months without 1- (OH Vitamin D3 administration. The percentage of female gender was significantly higher in Group B compared with Group A (P = 0.018. In Groups A and B, the mean weekly recombinant human erythropoietin dose (U/kg/ week was 227.96 ± 95.24 vs. 154.1 ± 84.9 (P = 0.001 and the mean hemoglobin level was 11.15 ± 0.63 g/dL versus 11.62 ± 0.63 g/dL (P = 0.008. There was no significant statistical difference regarding the other biochemical markers (serum ferritin, iron saturation, serum Ca, serum alkaline phosphatase, C-reactive protein, serum B12, serum folate levels, residual renal function and Kt/v between the groups. If other factors related to anemia are excluded in chronic HD patients, the lower the iPTH level (relative hypoparathyroidism the better the responsiveness to recombinant human erythropoietin.

  14. Recombinant human erythropoietin pretreatment alleviates renal glomerular injury induced by cardiopulmonary bypass by reducing transient receptor potential channel 6-nuclear factor of activated T-cells pathway activation.

    Science.gov (United States)

    Liu, Xiaoming; Zhang, Tingting; Xia, Weiliang; Wang, Yingwei; Ma, Ke

    2013-09-01

    Acute renal injury after cardiopulmonary bypass is common and associated with high mortality. We aimed to demonstrate the glomerular protective effects of recombinant human erythropoietin using an in vivo rat cardiopulmonary bypass model and to explore the possible mechanism. Dose-related renal protective effects of recombinant human erythropoietin were studied in phase I. Male Sprague Dawley rats were randomly divided into 5 groups: sham group, cardiopulmonary bypass group, and 3 recombinant human erythropoietin-treated cardiopulmonary bypass groups (bolus doses of 500, 3000, and 5000 U/kg 24 hours before surgery). Blood and urine samples were collected just before surgery and at 2, 4, 24, 48, and 72 hours after surgery. In phase II, rats were divided into 3 groups: sham group, cardiopulmonary bypass group, and 5000 U/kg recombinant human erythropoietin group. Kidneys were harvested at 4, 24, 48, and 72 hours after surgery. Ultra-organization of glomeruli was observed. Glomerular transient receptor potential channel 6 (TRPC6) expression was studied by immunofluorescence and Western blot. Nuclei nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) activity was analyzed by enzyme-linked immunosorbent assays and electrophoretic mobility shift assay. Pretreatment of 5000 U/kg recombinant human erythropoietin decreased the urine protein (72 hours: 7.82 ± 1.13 g/L vs 11.28 ± 1.73 g/L), serum creatinine (72 hours: 35.0 ± 3.5 μmol/L vs 60.7 ± 7.6 μmol/L), and cystatin-C (2 hours: 336.5 ± 28.2 μg/L vs 452.6 ± 63.8 μg/L) compared with the control group (P Cardiopulmonary bypass induced morphologic abnormalities of podocyte foot processes and slit diaphragms, which was improved by recombinant human erythropoietin. Furthermore, recombinant human erythropoietin significantly relieved glomerular TRPC6 increase and NFATc1 activation induced by cardiopulmonary bypass. Pretreatment of 5000 U/kg recombinant human erythropoietin elicited

  15. Development and characterization of a human antibody reference panel against erythropoietin suitable for the standardization of ESA immunogenicity testing.

    Science.gov (United States)

    Mytych, Daniel T; Barger, Troy E; King, Chadwick; Grauer, Stephanie; Haldankar, Raj; Hsu, Eric; Wu, Michelle Min; Shiwalkar, Mukta; Sanchez, Sergio; Kuck, Andrew; Civoli, Francesca; Sun, Jilin; Swanson, Steven J

    2012-08-31

    Recombinant human erythropoietin (EPO) has been used therapeutically for more than two decades in the treatment of anemia. Although EPO is generally well tolerated, in rare cases, patients have developed anti-EPO antibodies that can negatively impact safety and efficacy. Therefore, the detection of antibodies against EPO is a regulatory requirement during clinical development and post-approval. Although it is a rare phenomenon, antibody-mediated pure red cell aplasia (PRCA) is a serious complication than can result from antibodies that develop and neutralize EPO as well as endogenous erythropoietin. Currently, there are no universally accepted analytical methods to detect the full repertoire of binding and neutralizing anti-EPO antibodies. A number of different methods that differ in terms of antibodies detected and assay sensitivities are used by different manufacturers. There is also a lack of antibody reference reagents, and therefore no consistent basis for detecting and measuring anti-EPO antibodies. Reference reagents, with established ranges, are essential to monitor the safety and efficacy of all erythropoiesis-stimulating agents (ESAs) structurally related to human erythropoietin. This is the first report of the development and characterization of a panel of fully human antibodies against EPO suitable as reference reagents. The characteristics of antibodies within the panel were selected based on the prevalence of non-neutralizing IgG and IgM antibodies in non-PRCA patients and neutralizing IgG antibodies, including IgG1 and IgG4, in antibody-mediated PRCA subjects. The reference panel includes antibodies of high- and low-affinity with binding specificity to neutralizing and non-neutralizing erythropoietin epitopes. The subclass of human antibodies in this reference panel includes an IgG1, IgG2, and IgG4, as well as an IgM isotype. This antibody panel could help select appropriate immunogenicity assays, guide validation, and monitor assay performance

  16. 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...... 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...

  17. Effects of continuous erythropoietin receptor activator in sepsis-induced acute kidney injury and multi-organ dysfunction.

    Directory of Open Access Journals (Sweden)

    Camila E Rodrigues

    Full Text Available BACKGROUND: Despite advances in supportive care, sepsis-related mortality remains high, especially in patients with acute kidney injury (AKI. Erythropoietin can protect organs against ischemia and sepsis. This effect has been linked to activation of intracellular survival pathways, although the mechanism remains unclear. Continuous erythropoietin receptor activator (CERA is an erythropoietin with a unique pharmacologic profile and long half-life. We hypothesized that pretreatment with CERA would be renoprotective in the cecal ligation and puncture (CLP model of sepsis-induced AKI. METHODS: RATS WERE RANDOMIZED INTO THREE GROUPS: control; CLP; and CLP+CERA (5 µg/kg body weight, i.p. administered 24 h before CLP. At 24 hours after CLP, we measured creatinine clearance, biochemical variables, and hemodynamic parameters. In kidney tissue, we performed immunoblotting--to quantify expression of the Na-K-2Cl cotransporter (NKCC2, aquaporin 2 (AQP2, Toll-like receptor 4 (TLR4, erythropoietin receptor (EpoR, and nuclear factor kappa B (NF-κB--and immunohistochemical staining for CD68 (macrophage infiltration. Plasma interleukin (IL-2, IL-1β, IL-6, IL-10, interferon gamma, and tumor necrosis factor alpha were measured by multiplex detection. RESULTS: Pretreatment with CERA preserved creatinine clearance and tubular function, as well as the expression of NKCC2 and AQP2. In addition, CERA maintained plasma lactate at normal levels, as well as preserving plasma levels of transaminases and lactate dehydrogenase. Renal expression of TLR4 and NF-κB was lower in CLP+CERA rats than in CLP rats (p<0.05 and p<0.01, respectively, as were CD68-positive cell counts (p<0.01, whereas renal EpoR expression was higher (p<0.05. Plasma levels of all measured cytokines were lower in CLP+CERA rats than in CLP rats. CONCLUSION: CERA protects against sepsis-induced AKI. This protective effect is, in part, attributable to suppression of the inflammatory response.

  18. "EFFECT OF HIGH VERSUS LOW DOSES OF HUMAN RECOMBINANT ERYTHROPOIETIN ON THE ANEMIA OF PREMATURITY"

    Directory of Open Access Journals (Sweden)

    A. Mohammadzadeh

    2005-05-01

    Full Text Available Recombinant human erythropoietin (rh-EPO is known to accelerate erythropoiesis in preterm infants. The purpose of this study was to compare the effectiveness of early treatment with two doses of rh-EPO (high vs. low dose in the management of anemia of prematurity. Twenty preterm infants with hematocrit (Hct < 30% when infant’s age was between 2 to 3 weeks after birth or Hct <25% when infant’s age was more than 3 weeks after birth, were divided randomly in two groups, each group including 10 babies. Infants in high dose group received 500 u/kg rh-EPO twice per week and the low dose group received 500 u/kg rh-EPO weekly. All infants were fed human milk supplemented with enteral iron. Hematocrit and reticulocyte counts were determined for each infant at the start of the study, 3 days after start of treatment and one week after the end of treatment. The means of gestational age in high dose and low dose groups were 31.4 ± 2.2 and 31.3±2.0 weeks, respectively. Means of birth weight in high dose and low dose groups were 1366 ± 243 and 1438±249 gr, respectively. The two groups were significantly different in reticulocyte count at 3 days after treatment (P = 0.047 and in hematocrit at the end of study (P < 0.0001. We concluded the early treatment of anemia of prematurity with high dose rh-EPO with supplemental iron significantly increases hematocrit and reticulocyte in preterm infants and reduce the need for blood transfusion in these high risk neonates.

  19. Lenalidomide induces lipid raft assembly to enhance erythropoietin receptor signaling in myelodysplastic syndrome progenitors.

    Directory of Open Access Journals (Sweden)

    Kathy L McGraw

    Full Text Available Anemia remains the principal management challenge for patients with lower risk Myelodysplastic Syndromes (MDS. Despite appropriate cytokine production and cellular receptor display, erythropoietin receptor (EpoR signaling is impaired. We reported that EpoR signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that MDS erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p = 0.005, raft number; p = 0.023, raft size. Because lenalidomide triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of lenalidomide on raft assembly in MDS erythroid precursors and UT7 cells. Lenalidomide treatment rapidly induced lipid raft formation accompanied by EpoR recruitment into raft fractions together with STAT5, JAK2, and Lyn kinase. The JAK2 phosphatase, CD45, a key negative regulator of EpoR signaling, was displaced from raft fractions. Lenalidomide treatment prior to Epo stimulation enhanced both JAK2 and STAT5 phosphorylation in UT7 and primary MDS erythroid progenitors, accompanied by increased STAT5 DNA binding in UT7 cells, and increased erythroid colony forming capacity in both UT7 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs EpoR signaling, and provides a novel strategy to enhance EpoR signal fidelity in non-del(5q MDS.

  20. Cell therapy with human renal cell cultures containing erythropoietin-positive cells improves chronic kidney injury.

    Science.gov (United States)

    Yamaleyeva, Liliya M; Guimaraes-Souza, Nadia K; Krane, Louis S; Agcaoili, Sigrid; Gyabaah, Kenneth; Atala, Anthony; Aboushwareb, Tamer; Yoo, James J

    2012-05-01

    New therapeutic strategies for chronic kidney disease (CKD) are necessary to offset the rising incidence of CKD and donor shortage. Erythropoietin (EPO), a cytokine produced by fibroblast-like cells in the kidney, has recently emerged as a renoprotective factor with anti-inflammatory, antioxidant properties. This study (a) determined whether human renal cultures (human primary kidney cells [hPKC]) can be enriched in EPO-positive cells (hPKC(F+)) by using magnetic-bead sorting; (b) characterized hPKC(F+) following cell separation; and (c) established that intrarenal delivery of enriched hPKC(F+) cells would be more beneficial in treatment of renal injury, inflammation, and oxidative stress than unsorted hPKC cultures in a chronic kidney injury model. Fluorescence-activated cell sorting analysis revealed higher expression of EPO (36%) and CD73 (27%) in hPKC(F+) as compared with hPKC. After induction of renal injury, intrarenal delivery of hPKC(F+) or hPKC significantly reduced serum creatinine, interstitial fibrosis in the medulla, and abundance of CD68-positive cells in the cortex and medulla (p renal cortex and decreased urinary albumin (3.5-fold) and urinary tubular injury marker kidney injury molecule 1 (16-fold). hPKC(F+) also significantly reduced levels of renal cortical monocyte chemotactic protein 1 (1.8-fold) and oxidative DNA marker 8-hydroxy-deoxyguanosine (8-OHdG) (2.4-fold). After 12 weeks, we detected few injected cells, which were localized mostly to the cortical interstitium. Although cell therapy with either hPKC(F+) or hPKC improved renal function, the hPKC(F+) subpopulation provides greater renoprotection, perhaps through attenuation of inflammation and oxidative stress. We conclude that hPKC(F+) may be used as components of cell-based therapies for degenerative kidney diseases.

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

    Directory of Open Access Journals (Sweden)

    N Taheri

    2006-10-01

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

  2. Erythropoietin enhances nerve repair in anti-ganglioside antibody-mediated models of immune neuropathy.

    Directory of Open Access Journals (Sweden)

    Gang Zhang

    Full Text Available Guillain-Barré syndrome (GBS is a monophasic immune neuropathic disorder in which a significant proportion of patients have incomplete recovery. The patients with incomplete recovery almost always have some degree of failure of axon regeneration and target reinnervation. Anti-ganglioside antibodies (Abs are the most commonly recognized autoimmune markers in all forms of GBS and specific Abs are associated with the slow/poor recovery. We recently demonstrated that specific anti-ganglioside Abs inhibit axonal regeneration and nerve repair in preclinical models by activation of small GTPase RhoA and its downstream effectors. The objective of this study was to determine whether erythropoietin (EPO, a pleiotropic cytokine with neuroprotective and neurotrophic properties, enhances nerve regeneration in preclinical cell culture and animal models of autoimmune neuropathy/nerve repair generated with monoclonal and patient derived Abs. Primary neuronal cultures and a standardized sciatic crush nerve model were used to assess the efficacy of EPO in reversing inhibitory effects of anti-ganglioside Abs on nerve repair. We found that EPO completely reversed the inhibitory effects of anti-ganglioside Abs on axon regeneration in cell culture models and significantly improved nerve regeneration/repair in an animal model. Moreover, EPO-induced proregenerative effects in nerve cells are through EPO receptors and Janus kinase 2/Signal transducer and activator of transcription 5 pathway and not via early direct modulation of small GTPase RhoA. These preclinical studies indicate that EPO is a viable candidate drug to develop further for neuroprotection and enhancing nerve repair in patients with GBS.

  3. Glycan Remodeling of Human Erythropoietin (EPO) Through Combined Mammalian Cell Engineering and Chemoenzymatic Transglycosylation.

    Science.gov (United States)

    Yang, Qiang; An, Yanming; Zhu, Shilei; Zhang, Roushu; Loke, Chun Mun; Cipollo, John F; Wang, Lai-Xi

    2017-06-16

    The tremendous structural heterogeneity of N-glycosylation of glycoproteins poses a great challenge for deciphering the biological functions of specific glycoforms and for developing protein-based therapeutics. We have previously reported a chemoenzymatic glycan remodeling method for producing homogeneous glycoforms of N-glycoproteins including intact antibodies, which consist of endoglycosidase-catalyzed deglycosylation and novel glycosynthase-catalyzed transglycosylation, but its application to complex glycoproteins carrying multiple N-glycans remains to be examined. We report here site-selective chemoenzymatic glycosylation remodeling of recombinant human erythropoietin (EPO) that contains three N-glycans. We found that the generation of a HEK293S GnT I knockout FUT8 overexpressing cell line enabled the production of an unusual Man 5 GlcNAc 2 Fuc glycoform, which could be converted to the core-fucosylated GlcNAc-EPO intermediate acceptor for enzymatic transglycosylation. With this acceptor, homogeneous sialylated glycoform or azide-tagged glycoform were produced using the glycosynthase (EndoF3-D165A) catalyzed transglycosylation. Interestingly, a remarkable site-selectivity was observed in the transglycosylation reactions, leading to the introduction of two N-glycans selectively at the Asn-38 and Asn-83 sites, which was confirmed by a detailed MS/MS analysis of the transglycosylation product. Finally, a different N-glycan was attached at the third (Asn-24) site by pushing the enzymatic transglycosylation with a distinct glycan oxazoline, achieving the site-selective glycosylation modification of the protein. This study represents the first example of site-selective chemoenzymatic glycan engineering of complex glycoproteins carrying multiple N-glycans.

  4. Efficacy of erythropoietin on dialysis in patients with beta thalassemia minor.

    Science.gov (United States)

    Di Iorio, Biagio; De Nicola, Luca; Bellizzi, Vincenzo; Minutolo, Roberto; Zamboli, Pasquale; Rubino, Roberto; Fuiano, Giorgio; Conte, Giuseppe

    2004-01-01

    It is unknown whether chronic erythropoietin (EPO) treatment is able to normalize hemoglobin (Hb) levels and ameliorate cardiac remodeling avoiding blood transfusions in uremic blood transfusion-dependent patients with beta-thalassemia minor (beta-thal). In 12 hemodialysis (HD) patients with beta-thal, requiring blood transfusions despite EPO therapy, we planned to increase Hb levels up to the target levels (11-12 g/dl) within a one-year period by administering progressively higher doses of EPO (correction phase). We also planned to maintain the Hb target for an additional year (maintenance phase). In the year before the study, patients required 3.3 +/- 0.9 units of packed red blood cells. At baseline, the Hb level obtained with an EPO dose of 212 +/- 73 U/kg/week i.v. was 8.2 +/- 0.8 g/dl. The EPO dose was gradually increased within the first year up to 458 +/- 78 U/kg/week at month 12 (correction phase) and then significantly tapered down during the maintenance phase (390 +/- 54 U/kg/week at month 24). During the correction phase, the Hb levels markedly increased (11.1 +/- 0.3 g/dl at month 12) and did not change in the maintenance phase. No blood transfusion was required throughout the 2 years of follow-up. Left ventricular (LV) mass index progressively decreased from the basal value of 144 +/- 12 to 124 +/- 11 g/m2 in the first year and normalized in all patients at month 24 (109 +/- 12 g/m2, p beta-thal, the administration of high EPO dose for 2 years permits the attainment and the maintenance of Hb targets without blood transfusions. This therapeutic approach permits a complete remission of concentric LV hypertrophy without any adverse effects on the vascular system.

  5. Association of Neutrophil-to-Lymphocyte Ratio With Inflammation and Erythropoietin Resistance in Chronic Dialysis Patients

    Directory of Open Access Journals (Sweden)

    Jérôme Pineault

    2017-11-01

    Full Text Available Background: Neutrophil-to-lymphocyte ratio (NLR was widely studied as a prognostic marker in various medical and surgical specialties, but its significance in nephrology is not yet established. Objective: We evaluated its accuracy as an inflammation biomarker in a dialysis population. Design setting: Single-center retrospective study. Patients: The records of all 550 patients who were treated with hemodialysis (HD or peritoneal dialysis (PD from September 2008 to March 2011 were included. Measurements: NLR was calculated from the monthly complete blood count. Methods: Association between NLR and markers of inflammation (C-reactive protein [CRP], serum albumin, and erythropoietin resistance index [ERI] was measured using Spearman coefficient. Results: In total, 120 patients were eligible for the correlation analyses. We found a positive correlation between NLR and CRP (all patients: r = 0.45, P < .001; HD: r = 0.47, P < .001; PD: r = 0.48, P = .13. NLR and albumin were inversely correlated ( r = −0.51, P < .001. Finally, high NLR was associated with a nonsignificant increased ERI, but we have not demonstrated a direct correlation. Limitations: CRP and albumin are not measured routinely and were ordered for a specific clinical reason leading to an indication bias. Also, no relationship with clinical outcome was established. Conclusions: NLR seems to be a good inflammatory biomarker in dialysis in addition to being easily available. However, controlled studies should be conducted to properly assess and validate NLR levels that would be clinically significant and relevant, as well as its prognostic significance and utility in a clinical setting.

  6. The development of indications for the preoperative use of recombinant erythropoietin

    Science.gov (United States)

    Dubois, Robert W.; Lim, Dorothy; Hebert, Paul; Sherwood, Marjorie; Growe, Gershon H.; Hardy, Jean-François; Park, Rolla Edward; Waddell, James P.

    1998-01-01

    Objective To develop indications for the preoperative use of recombinant erythropoietin (rHuEPO) alone and in conjunction with preoperative autologous donation (PAD). Design A 2-round modified Delphi-consensus process. Participants Nine physicians representing multiple clinical specialties, practice environments and geographic locations. Method From evidence tables and a literature summary (MEDLINE database from January 1985 to August 1996) provided and using the RAND-UCLA appropriateness method, the physicians developed 264 indications for the preoperative use of rHuEPO by permuting 7 clinical factors (age, history of transfusion or antibody incompatibility, hemoglobin level, anemia of chronic disease, expected blood loss, presence of cardiovascular or cardiopulmonary disease and patient anxiety). These indications were rated on a 9-point appropriateness scale. Median scores and measures of agreement were determined. Outcome measures The significance of cost constraints or cost and blood supply constraints and the impact of each clinical factor on the ratings as judged by statistical analysis. Results Of the 264 indications, 54% were rated appropriate, 18% uncertain and 28% inappropriate. Expected blood loss had the greatest impact on the ratings (high expected blood loss had a 5.9 point more appropriate rating on the 9-point scale than low expected blood loss [p < 0.0001]). Preoperative hemoglobin level also significantly influenced the ratings (p < 0.0001). Compared with the clinical context, the ratings under the cost constraint were 1.0 less appropriate (p < 0.0001) for rHuEPO alone and 1.2 less appropriate for rHuEPO and PAD (p < 0.0001). The ratings for patients with moderate expected blood loss were significantly influenced by the cost constraint (less appropriate). Conclusions Expected blood loss and preoperative hemoglobin level were the best indicators of rHuEPO appropriateness. Different contexts modify the appropriateness ratings of an expensive drug

  7. Aconitase regulation of erythropoiesis correlates with a novel licensing function in erythropoietin-induced ERK signaling.

    Directory of Open Access Journals (Sweden)

    Anne-Laure Talbot

    Full Text Available BACKGROUND: Erythroid development requires the action of erythropoietin (EPO on committed progenitors to match red cell output to demand. In this process, iron acts as a critical cofactor, with iron deficiency blunting EPO-responsiveness of erythroid progenitors. Aconitase enzymes have recently been identified as possible signal integration elements that couple erythropoiesis with iron availability. In the current study, a regulatory role for aconitase during erythropoiesis was ascertained using a direct inhibitory strategy. METHODOLOGY/PRINCIPAL FINDINGS: In C57BL/6 mice, infusion of an aconitase active-site inhibitor caused a hypoplastic anemia and suppressed responsiveness to hemolytic challenge. In a murine model of polycythemia vera, aconitase inhibition rapidly normalized red cell counts, but did not perturb other lineages. In primary erythroid progenitor cultures, aconitase inhibition impaired proliferation and maturation but had no effect on viability or ATP levels. This inhibition correlated with a blockade in EPO signal transmission specifically via ERK, with preservation of JAK2-STAT5 and Akt activation. Correspondingly, a physical interaction between ERK and mitochondrial aconitase was identified and found to be sensitive to aconitase inhibition. CONCLUSIONS/SIGNIFICANCE: Direct aconitase inhibition interferes with erythropoiesis in vivo and in vitro, confirming a lineage-selective regulatory role involving its enzymatic activity. This inhibition spares metabolic function but impedes EPO-induced ERK signaling and disturbs a newly identified ERK-aconitase physical interaction. We propose a model in which aconitase functions as a licensing factor in ERK-dependent proliferation and differentiation, thereby providing a regulatory input for iron in EPO-dependent erythropoiesis. Directly targeting aconitase may provide an alternative to phlebotomy in the treatment of polycythemia vera.

  8. Erythropoietin therapy after out-of-hospital cardiac arrest: A systematic review and meta-analysis.

    Science.gov (United States)

    Chaudhary, Rahul; Garg, Jalaj; Krishnamoorthy, Parasuram; Bliden, Kevin; Shah, Neeraj; Agarwal, Nayan; Gupta, Rahul; Sharma, Abhishek; Kern, Karl B; Patel, Nainesh C; Gurbel, Paul

    2017-12-26

    To assess safety and efficacy of early erythropoietin (Epo) administration in patients with out-of-hospital cardiac arrest (OHCA). A systematic literature search was performed using PubMed, MEDLINE, EMBASE, EBSCO, CINAHL, Web of Science and Cochrane databases, of all studies published from the inception through October 10, 2016. Inclusion criteria included: (1) Adult humans with OHCA and successful sustained return of spontaneous circulation; and (2) studies including mortality/brain death, acute thrombotic events as their end points. Primary efficacy outcome was "brain death or Cerebral Performance Category (CPC) score of 5". Secondary outcomes were "CPC score 1, and 2-4", "overall thrombotic events" and "acute coronary stent thrombosis". We analyzed a total of 606 participants (n = 276 received Epo and n = 330 with standard of care alone) who experienced OHCA enrolled in 3 clinical trials. No significant difference was observed between the Epo and no Epo group in brain death or CPC score 5 (OR = 0.77; 95%CI: 0.42-1.39), CPC score 1 (OR = 1.16, 95%CI: 0.82-1.64), and CPC score 2-4 (OR = 0.77, 95%CI: 0.44-1.36). Epo group was associated with increased thrombotic complications (OR = 2.41, 95%CI: 1.26-4.62) and acute coronary stent thrombosis (OR = 8.16, 95%CI: 1.39-47.99). No publication bias was observed. Our study demonstrates no improvement in neurological outcomes and increased incidence of thrombotic events and acute coronary stent thrombosis in OHCA patients who were treated with Epo in addition to standard therapy.

  9. Neuroprotective effect of erythropoietin against pressure ulcer in a mouse model of small fiber neuropathy.

    Directory of Open Access Journals (Sweden)

    Aurore Danigo

    Full Text Available An increased risk of skin pressure ulcers (PUs is common in patients with sensory neuropathies, including those caused by diabetes mellitus. Recombinant human erythropoietin (rhEPO has been shown to protect the skin against PUs developed in animal models of long-term diabetes. The aim of this work was to determine whether rhEPO could prevent PU formation in a mouse model of drug-induced SFN. Functional SFN was induced by systemic injection of resiniferatoxin (RTX, 50 µg/kg, i.p.. RhEPO (3000 UI/kg, i.p. was given the day before RTX injection and then every other day. Seven days after RTX administration, PUs were induced by applying two magnetic plates on the dorsal skin. RTX-treated mice expressed thermal and mechanical hypoalgesia and showed calcitonin gene-related peptide (CGRP and substance P (SP depletion without nerve degeneration or vascular dysfunction. RTX mice developed significantly larger stage 2 PUs than Vehicle mice. RhEPO prevented thermal and mechanical hypoalgesia and neuropeptide depletion in small nerve fibers. RhEPO increased hematocrit and altered endothelium-dependent vasodilatation without any effect on PU formation in Vehicle mice. The characteristics of PUs in RTX mice treated with rhEPO and Vehicle mice were found similar. In conclusion, RTX appeared to increased PU development through depletion of CGRP and SP in small nerve fibers, whereas systemic rhEPO treatment had beneficial effect on peptidergic nerve fibers and restored skin protective capacities against ischemic pressure. Our findings support the evaluation of rhEPO and/or its non-hematopoietic analogs in preventing to prevent PUs in patients with SFN.

  10. Nonclinical evaluation of the potential for mast cell activation by an erythropoietin analog

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, James L., E-mail: James.Weaver@fda.hhs.gov [Division of Applied Regulatory Science, OCP/OTS/CDER/FDA, Silver Spring, MD (United States); Boyne, Michael, E-mail: mboyne@biotechlogic.com [Division of Pharmaceutical Analysis, OTR/OPQ/CDER/FDA, Silver Spring, MD (United States); Pang, Eric, E-mail: Eric.Pang@fda.hhs.gov [Division of Applied Regulatory Science, OCP/OTS/CDER/FDA, Silver Spring, MD (United States); Chimalakonda, Krishna, E-mail: Krishna.Chimalakonda@fda.hhs.gov [Division of Applied Regulatory Science, OCP/OTS/CDER/FDA, Silver Spring, MD (United States); Howard, Kristina E., E-mail: Kristina.Howard@fda.hhs.gov [Division of Applied Regulatory Science, OCP/OTS/CDER/FDA, Silver Spring, MD (United States)

    2015-09-15

    The erythropoietin analog peginesatide was withdrawn from marketing due to unexpected severe anaphylactic reactions associated with administration of the multi-use formulation. The adverse events occurred rapidly following the first ever administration of the drug with most affected patients becoming symptomatic in less than 30 min. This is most consistent with an anaphylactoid reaction due to direct activation of mast cells. Laboratory evaluation was undertaken using rat peritoneal mast cells as the model system. Initial studies showed that high concentrations of the formulated drug as well as formulated vehicle alone could cause mast cell degranulation as measured by histamine release. The purified active drug was not able to cause histamine release whereas the vehicle filtrate and lab created drug vehicle were equally potent at causing histamine release. Individual formulations of vehicle leaving one component out showed that histamine release was due to phenol. Dose response studies with phenol showed a very sharp dose response curve that was similar in three buffer systems. Cellular analysis by flow cytometry showed that the histamine release was not due to cell death, and that changes in light scatter parameters consistent with degranulation were rapidly observed. Limited testing with primary human mast cells showed a similar dose response of histamine release with exposure to phenol. To provide in vivo confirmation, rats were injected with vehicle formulated with various concentrations of phenol via a jugular vein cannula. Significant release of histamine was detected in blood samples taken 2 min after dosing at the highest concentrations tested. - Highlights: • Peginesatide caused severe anaphylactoid reactions in 0.2% of patients. • Both formulated drug and vehicle cause degranulation of rat mast cells. • Phenol was identified as the vehicle component causing degranulation. • Human mast cells show similar dose response to phenol as rat mast cells

  11. Expression of hypoxia-inducible factor-1α and erythropoietin at corneal neovascularization in rats

    Directory of Open Access Journals (Sweden)

    Ji-Min Wang

    2014-12-01

    Full Text Available AIM: To describe the expression of hypoxia-inducible factor-1α(HIF-1αand erythropoietin(EPOin rats' corneal and evaluate its potential effect on corneal neovascularization(CNVgrowth. METHODS: The young SD rats(3mowas chosen and randomly divided into 2 groups, which were experimental group and normal control group. CNV model was established by alkali burn, and the length and area of CNV was observed everyday after operation by slit lamp. After that, the expression of HIF-1α and EPO was measured by SABC and RT-PCR methods at 1, 3, 5, 7, and 14d after alkali burn. The data was analyzed by SPSS 20.0. RESULTS: The area of CNV was increasing at 1, 3, 5, 7, and 14d after alkali burn, and the peak point appear at 7d. The growth speed was decreased after 14d. SABC method told us that no HIF-1α and very tiny amount EPO was detected at normal rats' corneal. The expression of the two factors increased at 1d after alkali burn in corneal epithelium and endoderm. The results of RT-PCR showed that a few amounts of HIF-1α and EPO mRNA were detected at normal group. The expression of the two factors was increased at 3d after alkali burn, and the peak value was found at 7d, however, it was decreased at 14d. Statistical difference was found at different time(PCONCLUSION: HIF-1α and EPO is closely related to CNV.

  12. Erythropoietin improves functional and histological recovery of traumatized skeletal muscle tissue.

    Science.gov (United States)

    Rotter, Robert; Menshykova, Marija; Winkler, Tobias; Matziolis, Georg; Stratos, Ioannis; Schoen, Matthias; Bittorf, Thomas; Mittlmeier, Thomas; Vollmar, Brigitte

    2008-12-01

    Apart from its hematopoietic effect, erythropoietin (EPO) is known as pleiotropic cytokine with anti-inflammatory and anti-apoptotic properties. Here, we evaluated for the first time the EPO-dependent regeneration capacity in an in vivo rat model of skeletal muscle trauma. A myoblast cell line was used to study the effect of EPO on serum deprivation-induced cell apoptosis in vitro. A crush injury was performed to the left soleus muscle in 80 rats treated with either EPO or saline. Muscle recovery was assessed by analysis of contraction capacities. Intravital microscopy, BrdU/laminin double immunohistochemistry and cleaved caspase-3 immunohistochemistry of muscle tissue on days 1, 7, 14, and 42 posttrauma served for assessment of local microcirculation, tissue integrity, and cell proliferation. Serum deprivation-induced myoblast apoptosis of 23.9 +/- 1.5% was reduced by EPO to 17.2 +/- 0.8%. Contraction force analysis in the EPO-treated animals revealed significantly improved muscle strength with 10-20% higher values of twitch and tetanic forces over the 42-day observation period. EPO-treated muscle tissue displayed improved functional capillary density as well as reduced leukocytic response and consecutively macromolecular leakage over day 14. Concomitantly, muscle histology showed significantly increased numbers of BrdU-positive satellite cells and interstitial cells as well as slightly lower counts of cleaved caspase-3-positive interstitial cells. EPO results in faster and better regeneration of skeletal muscle tissue after severe trauma and goes along with improved microcirculation. Thus, EPO, a compound established as clinically safe, may represent a promising therapeutic option to optimize the posttraumatic course of muscle tissue healing.

  13. THE COMBINATION OF α-LIPOIC ACID INTAKE WITH ECCENTRIC EXERCISE MODULATES ERYTHROPOIETIN RELEASE

    Directory of Open Access Journals (Sweden)

    B. Morawin

    2014-08-01

    Full Text Available The generation of reactive nitrogen/oxygen species (RN/OS represents an important mechanism in erythropoietin (EPO expression and skeletal muscle adaptation to physical and metabolic stress. RN/OS generation can be modulated by intense exercise and nutrition supplements such as α-lipoic acid, which demonstrates both anti- and pro-oxidative action. The study was designed to show the changes in the haematological response through the combination of α-lipoic acid intake with running eccentric exercise. Sixteen healthy young males participated in the randomised and placebo-controlled study. The exercise trial involved a 90-min run followed by a 15-min eccentric phase at 65% VO2max (-10% gradient. It significantly increased serum concentrations of nitric oxide (NO, hydrogen peroxide (H2O2 and pro-oxidative products such as 8-isoprostanes (8-iso, lipid peroxides (LPO and protein carbonyls (PC. α-Lipoic acid intake (Thiogamma: 1200 mg daily for 10 days prior to exercise resulted in a 2-fold elevation of serum H2O2 concentration before exercise, but it prevented the generation of NO, 8-iso, LPO and PC at 20 min, 24 h, and 48 h after exercise. α-Lipoic acid also elevated serum EPO level, which highly correlated with NO/H2O2 ratio (r=0.718, P<0.01. Serum total creatine kinase (CK activity, as a marker of muscle damage, reached a peak at 24 h after exercise (placebo 732 ± 207 IU · L-1, α-lipoic acid 481 ± 103 IU · L-1, and correlated with EPO (r = 0.478, P<0.01 in the α-lipoic acid group. In conclusion, the intake of high α-lipoic acid modulates RN/OS generation, enhances EPO release and reduces muscle damage after running eccentric exercise.

  14. The Insect Ortholog of the Human Orphan Cytokine Receptor CRLF3 Is a Neuroprotective Erythropoietin Receptor

    Directory of Open Access Journals (Sweden)

    Nina Hahn

    2017-07-01

    Full Text Available The cytokine erythropoietin (Epo mediates various cell homeostatic responses to environmental challenges and pathological insults. While stimulation of vertebrate erythrocyte production is mediated by homodimeric “classical” Epo receptors, alternative receptors are involved in neuroprotection. However, their identity remains enigmatic due to complex cytokine ligand and receptor interactions and conflicting experimental results. Besides the classical Epo receptor, the family of type I cytokine receptors also includes the poorly characterized orphan cytokine receptor-like factor 3 (CRLF3 present in vertebrates including human and various insect species. By making use of the more simple genetic makeup of insect model systems, we studied whether CRLF3 is a neuroprotective Epo receptor in animals. We identified a single ortholog of CRLF3 in the beetle Tribolium castaneum, and established protocols for primary neuronal cell cultures from Tribolium brains and efficient in vitro RNA interference. Recombinant human Epo as well as the non-erythropoietic Epo splice variant EV-3 increased the survival of serum-deprived brain neurons, confirming the previously described neuroprotective effect of Epo in insects. Moreover, Epo completely prevented hypoxia-induced apoptotic cell death of primary neuronal cultures. Knockdown of CRLF3 expression by RNA interference with two different double stranded RNA (dsRNA fragments abolished the neuroprotective effect of Epo, indicating that CRLF3 is a crucial component of the insect Epo-responsive receptor. This suggests that a common urbilaterian ancestor of the orphan human and insect cytokine receptor CRLF3 served as a neuroprotective receptor for an Epo-like cytokine. Our work also suggests that vertebrate CRLF3, like its insect ortholog, might represent a tissue protection-mediating receptor.

  15. Effects of Erythropoietin on Hippocampal Volume and Memory in Mood Disorders.

    Science.gov (United States)

    Miskowiak, Kamilla W; Vinberg, Maj; Macoveanu, Julian; Ehrenreich, Hannelore; Køster, Nicolai; Inkster, Becky; Paulson, Olaf B; Kessing, Lars V; Skimminge, Arnold; Siebner, Hartwig R

    2015-08-15

    Persistent cognitive dysfunction in depression and bipolar disorder (BD) impedes patients' functional recovery. Erythropoietin (EPO) increases neuroplasticity and reduces cognitive difficulties in treatment-resistant depression (TRD) and remitted BD. This magnetic resonance imaging study assessed the neuroanatomical basis for these effects. Patients with TRD who were moderately depressed or BD in partial remission were randomized to 8 weekly EPO (40,000 IU) or saline infusions in a double-blind, parallel-group design. Patients underwent magnetic resonance imaging, memory assessment with the Rey Auditory Verbal Learning Test, and mood ratings with the Beck Depression Inventory, Hamilton Depression Rating Scale, and Young Mania Rating Scale at baseline and week 14. Hippocampus segmentation and analysis of hippocampal volume, shape, and gray matter density were conducted with FMRIB Software Library tools. Memory change was analyzed with repeated-measures analysis of covariance adjusted for depression symptoms, diagnosis, age, and gender. Eighty-four patients were randomized; 1 patient withdrew and data collection was incomplete for 14 patients; data were thus analyzed for 69 patients (EPO: n = 35, saline: n = 34). Compared with saline, EPO was associated with mood-independent memory improvement and reversal of brain matter loss in the left hippocampal cornu ammonis 1 to cornu ammonis 3 and subiculum. Using the entire sample, memory improvement was associated with subfield hippocampal volume increase independent of mood change. EPO-associated memory improvement in TRD and BD may be mediated by reversal of brain matter loss in a subfield of the left hippocampus. EPO may provide a therapeutic option for patients with mood disorders who have impaired neuroplasticity and cognition. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Skeletal muscle alterations and exercise performance decrease in erythropoietin-deficient mice: a comparative study

    Directory of Open Access Journals (Sweden)

    Mille-Hamard Laurence

    2012-06-01

    Full Text Available Abstract Background Erythropoietin (EPO is known to improve exercise performance by increasing oxygen blood transport and thus inducing a higher maximum oxygen uptake (VO2max. Furthermore, treatment with (or overexpression of EPO induces protective effects in several tissues, including the myocardium. However, it is not known whether EPO exerts this protective effect when present at physiological levels. Given that EPO receptors have been identified in skeletal muscle, we hypothesized that EPO may have a direct, protective effect on this tissue. Thus, the objectives of the present study were to confirm a decrease in exercise performance and highlight muscle transcriptome alterations in a murine EPO functional knock-out model (the EPO-d mouse. Methods We determined VO2max peak velocity and critical speed in exhaustive runs in 17 mice (9 EPO-d animals and 8 inbred controls, using treadmill enclosed in a metabolic chamber. Mice were sacrificed 24h after a last exhaustive treadmill exercise at critical speed. The tibialis anterior and soleus muscles were removed and total RNA was extracted for microarray gene expression analysis. Results The EPO-d mice’s hematocrit was about 50% lower than that of controls (p  1.4 and 115 were strongly down-regulated (normalized ratio  Conclusions Our results showed that the lack of functional EPO induced a decrease in the aerobic exercise capacity. This decrease was correlated with the hematocrit and reflecting poor oxygen supply to the muscles. The observed alterations in the muscle transcriptome suggest that physiological concentrations of EPO exert both direct and indirect muscle-protecting effects during exercise. However, the signaling pathway involved in these protective effects remains to be described in detail.

  17. A biomathematical model of human erythropoiesis under erythropoietin and chemotherapy administration.

    Directory of Open Access Journals (Sweden)

    Sibylle Schirm

    Full Text Available Anaemia is a common haematologic side effect of dose-dense multi-cycle cytotoxic polychemotherapy requiring erythrocyte transfusions or erythropoietin (EPO administration. To simulate the effectiveness of different EPO application schedules, we performed both modelling of erythropoiesis under chemotherapy and pharmacokinetic and dynamic modelling of EPO applications in the framework of a single comprehensive biomathematical model. For this purpose, a cell kinetic model of bone marrow erythropoiesis was developed that is based on a set of differential compartment equations describing proliferation and maturation of erythropoietic cell stages. The system is regulated by several feedback loops comprising those mediated by EPO. We added a model of EPO absorption after injection at different sites and a pharmacokinetic model of EPO derivatives to account for the effects of external EPO applications. Chemotherapy is modelled by a transient depletion of bone marrow cell stages. Unknown model parameters were determined by fitting the predictions of the model to data sets of circulating erythrocytes, haemoglobin, haematocrit, percentage of reticulocytes or EPO serum concentrations derived from the literature or cooperating clinical study groups. Parameter fittings resulted in a good agreement of model and data. Depending on site of injection and derivative (Alfa, Beta, Delta, Darbepoetin, nine groups of EPO applications were distinguished differing in either absorption kinetics or pharmacokinetics. Finally, eight different chemotherapy protocols were modelled. The model was validated on the basis of scenarios not used for parameter fitting. Simulations were performed to analyze the impact of EPO applications on the risk of anaemia during chemotherapy. We conclude that we established a model of erythropoiesis under chemotherapy that explains a large set of time series data under EPO and chemotherapy applications. It allows predictions regarding yet

  18. A biomathematical model of human erythropoiesis under erythropoietin and chemotherapy administration.

    Science.gov (United States)

    Schirm, Sibylle; Engel, Christoph; Loeffler, Markus; Scholz, Markus

    2013-01-01

    Anaemia is a common haematologic side effect of dose-dense multi-cycle cytotoxic polychemotherapy requiring erythrocyte transfusions or erythropoietin (EPO) administration. To simulate the effectiveness of different EPO application schedules, we performed both modelling of erythropoiesis under chemotherapy and pharmacokinetic and dynamic modelling of EPO applications in the framework of a single comprehensive biomathematical model. For this purpose, a cell kinetic model of bone marrow erythropoiesis was developed that is based on a set of differential compartment equations describing proliferation and maturation of erythropoietic cell stages. The system is regulated by several feedback loops comprising those mediated by EPO. We added a model of EPO absorption after injection at different sites and a pharmacokinetic model of EPO derivatives to account for the effects of external EPO applications. Chemotherapy is modelled by a transient depletion of bone marrow cell stages. Unknown model parameters were determined by fitting the predictions of the model to data sets of circulating erythrocytes, haemoglobin, haematocrit, percentage of reticulocytes or EPO serum concentrations derived from the literature or cooperating clinical study groups. Parameter fittings resulted in a good agreement of model and data. Depending on site of injection and derivative (Alfa, Beta, Delta, Darbepoetin), nine groups of EPO applications were distinguished differing in either absorption kinetics or pharmacokinetics. Finally, eight different chemotherapy protocols were modelled. The model was validated on the basis of scenarios not used for parameter fitting. Simulations were performed to analyze the impact of EPO applications on the risk of anaemia during chemotherapy. We conclude that we established a model of erythropoiesis under chemotherapy that explains a large set of time series data under EPO and chemotherapy applications. It allows predictions regarding yet untested EPO schedules

  19. Erythropoietin Attenuates Postoperative Cognitive Dysfunction by Shifting Macrophage Activation toward the M2 Phenotype

    Directory of Open Access Journals (Sweden)

    Jae Hoon Lee

    2017-11-01

    Full Text Available Postoperative cognitive dysfunction (POCD may be driven by transference of the innate immune response to the brain after aseptic surgical damage. Macrophages are key mediators of innate immunity that can display a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype. Erythropoietin (EPO is a hematopoietic hormone that exerts anti-inflammatory effects by influencing macrophage function. We hypothesized that EPO would prevent POCD by promoting macrophage phenotype switching to the M2 phenotype post-surgery. To evaluate the effects of EPO on POCD and macrophage polarization post-surgery, we administered EPO (5,000 U/kg with or without an arginase inhibitor (amino-6-boronohexanoic acid, 10 mg/kg to ICR mice before and after abdominal surgery. Forty-eight hours post-surgery, we assessed memory, synapse function, and macrophage/microglial phenotypes in the spleen and hippocampus. We also investigated M1/M2 phenotypes in RAW264.7 and BV2 cells stimulated with lipopolysaccharide and interferon-γ (M1 inducers in the presence or absence of EPO. EPO prevented POCD, decreased surgery-related synaptic dysfunction, and attenuated pro-inflammatory cytokine generation in the hippocampus. Moreover, EPO suppressed M1-related genes expression and promoted M2 genes expression in the spleen and hippocampus post-surgery. Furthermore, EPO decreased the proportions of macrophages/microglia expressing an M1 surface marker (CD40 and increased those expressing an M2 surface marker (CD206. Arginase inhibition abolished the beneficial effects of EPO on POCD. In vitro, EPO treatment promoted switching of RAW264.7 and BV2 cells stimulated with M1 inducers to an M2 phenotype. In conclusion, EPO prevents POCD by promoting macrophage phenotype switching toward the M2 phenotype.

  20. Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder

    Directory of Open Access Journals (Sweden)

    Paulson Olaf B

    2010-10-01

    Full Text Available Abstract Background Depression and bipolar disorder are associated with reduced neural plasticity and deficits in memory, attention and executive function. Drug treatments for these affective disorders have insufficient clinical effects in a large group and fail to reverse cognitive deficits. There is thus a need for more effective treatments which aid cognitive function. Erythropoietin (Epo is involved in neuroplasticity and is a candidate for future treatment of affective disorders. The investigators have demonstrated that a single dose of Epo improves cognitive function and reduces neurocognitive processing of negative emotional information in healthy and depressed individuals similar to effects seen with conventional antidepressants. The current study adds to the previous findings by investigating whether repeated Epo administration has antidepressant effects in patients with treatment resistant depression and reverses cognitive impairments in these patients and in patients with bipolar disorder in remission. Methods/design The trial has a double-blind, placebo-controlled, parallel-group design. 40 patients with treatment-resistant major depression and 40 patients with bipolar disorder in remission are recruited and randomised to receive weekly infusions of Epo (Eprex; 40,000 IU or saline (NaCl 0.9% for 8 weeks. Randomisation is stratified for age and gender. The primary outcome parameters for the two studies are: depression severity measured with the Hamilton Depression Rating Scale 17 items (HDRS-17 1 in study 1 and, in study 2, verbal memory measured with the Rey Auditory Verbal Learning Test (RAVLT 23. With inclusion of 40 patients in each study we obtain 86% power to detect clinically relevant differences between intervention and placebo groups on these primary outcomes. Trial registration The trial is approved by the Local Ethics Committee: H-C-2008-092, Danish Medicines Agency: 2612-4020, EudraCT: 2008-04857-14, Danish Data Agency

  1. Effect of fiber length of carbon nanotubes on the absorption of erythropoietin from rat small intestine.

    Science.gov (United States)

    Ito, Yukako; Venkatesan, Natarajan; Hirako, Noriko; Sugioka, Nobuyuki; Takada, Kanji

    2007-06-07

    Erythropoietin (EPO) loaded carbon nanotubes (CNTs) with surfactant as an absorption enhancer were prepared for the oral delivery of EPO using two types of CNTs, long and short fiber length CNTs, and the effect of CNT fiber length on the absorption efficiency of EPO was studied. After Labrasol, PEG-8 caprylic/capric glycerides, as absorption enhancer was adsorbed into long fiber CNTs of which mean fiber length was 20-80 microm, as a carrier, EPO and casein as protease inhibitor and Explotab (sodium starch glycolate) as a disintegrating agent, were mixed. The resulting solid preparation was administered into the rat jejunum and serum EPO levels were measured by ELISA. The dose of EPO, CNTs, casein and Explotab were 100 IU/kg, 5mg/kg, 25mg/kg and 2.5mg/kg, respectively. Serum EPO level reached to C(max), 69.0+/-3.9 mIU/ml, at 3.5+/-0.1h and AUC was 175.7+/-13.8 mIU h/ml. These values were approximately half of that obtained with short fiber length CNTs of which C(max) was 143.1+/-15.2 mIU/ml and AUC was 256.3+/-9.7 mIU h/ml. When amphoteric surfactant, Lipomin LA, sodium beta-alkylaminopropionic acid, was used to accelerate the disaggregation of long fiber length CNTs, C(max) was 36.0+/-4.9 and AUC was 96.9+/-11.9, which showed less bioavailability (BA) of EPO. These results suggest that the short fiber length CNTs deliver more both EPO and absorption enhancer to the absorptive cells of the rat small intestine and the aggregation of CNTs is not the critical factor for the oral delivery of EPO.

  2. High gain, multiatmosphere CO2 laser amplifier

    Science.gov (United States)

    Stuart, G. C.; Houtman, H.; Meyer, J.

    1987-02-01

    A novel TE discharge, 15-mm aperture, multiatmosphere, CO2 laser amplifier is described, with measured electrical characteristics and gain measurements on the 9.294-micron, 9R (16) line. The electrical circuit used in this amplifier is a realistic alternative to the Marx bank or conventional LC inversion circuit and, similarly, it would be useful for excitation of other gas lasers as well. This automatically preionized, double-sided, fourfold LC inversion circuit uses only one spark gap, and it is shown to provide small-signal gains of 5.7 percent/cm, at 120 J/l atm and 10 atm. The generalization to an n-stage device, which would be suitable for higher pressures, and larger apertures, is discussed.

  3. Amplified music exposure carries risks to hearing.

    Science.gov (United States)

    da Silva, Valéria Gomes; de Oliveira, Carlos Augusto Costa Pires; Tauil, Pedro Luíz; de Castro Silva, Isabella Monteiro; Sampaio, André Luiz Lopes

    2017-02-01

    To investigate the association between changes in the outer hair cells and exposure to amplified music in a group of high-school students. In this retrospective, case-control study, 86 subjects underwent audiometry, immittance audiometry, and distortion-product otoacoustic emission tests. The subjects were questioned about their listening habits and divided into 2 groups: exposed and unexposed. Most of the subjects had reduced function in their outer hair cells, mainly beginning at 8 kHz. Among 60 subjects-30 cases and 30 controls-75% were considered exposed and 25% unexposed. The exposed subjects were 9.33 times more likely to have altered outer hair cells than the unexposed subjects were. Exposure to amplified music is associated with reduced function in the hair cells. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  4. Noise Gain Features of Fiber Raman Amplifier

    Directory of Open Access Journals (Sweden)

    Georgii S. Felinskyi

    2016-01-01

    Full Text Available The formation dynamics of the optical noise in a silica single mode fiber (SMF as function of the pump power variation in the counter pumped fiber Raman amplifier (FRA is experimentally studied. The ratio between the power of amplified spontaneous emission and the power of incoherent optical noise is quantitatively determined by detailed analysis of experimental data in the pump powers range of 100–300 mW within the full band of Stokes frequencies, including FRA working wavelengths over the C + L transparency windows. It is found out the maximum of Raman gain coefficient for optical noise does not exceed ~60% of corresponding peak at the gain profile maximum of coherent signal. It is shown that the real FRA noise figure may be considerably less than 3 dB over a wide wavelength range (100 nm at a pump power of several hundreds of mW.

  5. Cryogenic cooling for high power laser amplifiers

    Directory of Open Access Journals (Sweden)

    Perin J.P.

    2013-11-01

    Full Text Available Using DPSSL (Diode Pumped Solid State Lasers as pumping technology, PW-class lasers with enhanced repetition rates are developed. Each of the Yb YAG amplifiers will be diode-pumped at a wavelength of 940 nm. This is a prerequisite for achieving high repetition rates (light amplification duration 1 millisecond and repetition rate 10 Hz. The efficiency of DPSSL is inversely proportional to the temperature, for this reason the slab amplifier have to be cooled at a temperature in the range of 100 K–170 K with a heat flux of 1 MW*m−2. This paper describes the thermo-mechanical analysis for the design of the amplification laser head, presents a preliminary proposal for the required cryogenic cooling system and finally outlines the gain of cryogenic operation for the efficiency of high pulsed laser.

  6. Fundamentals of fiber lasers and fiber amplifiers

    CERN Document Server

    Ter-Mikirtychev, Valerii (Vartan)

    2014-01-01

    This book covers the fundamental aspects of fiber lasers and fiber amplifiers, and includes a wide range of material from laser physics fundamentals to state-of-the-art topics in this rapidly growing field of quantum electronics. Emphasis is placed on the nonlinear processes taking place in fiber lasers and amplifiers, their similarities, differences to, and their advantages over other solid-state lasers. The reader will learn basic principles of solid-state physics and optical spectroscopy of laser active centers in fibers, main operational laser regimes, and practical recommendations and suggestions on fiber laser research, laser applications, and laser product development. The book will be useful for students, researchers, and professionals who work with lasers, in the optical communications, chemical and biological industries, etc.

  7. SINGLE CONVERSION ISOLATED IMPEDANCE TRANSFORMATION AMPLIFIER

    DEFF Research Database (Denmark)

    2003-01-01

    The invention relates to a switch mode power amplifier. A first and a second change-over switch are inserted between a DC voltage supply and a primary side of an isolation transformer. Two secondary windings are connected to a power output terminal. A first and a second secondary side power switch...... are adapted to connect the two secondary windings to the power connector of the power output terminal. The pulse width modulation means is adapted to generate control signals for the driver means of the first and the second change-over switch so as to cause every second pulse to be inverted. The pulse width...... modulation means is also adapted to generate a third and a fourth control signal for said driver means of the power switches of said first and said second secondary. The invention also relates to a method of controlling a switch mode power amplifier...

  8. Conversion of the random amplified polymorphic DNA (RAPD ...

    African Journals Online (AJOL)

    Conversion of the random amplified polymorphic DNA (RAPD) marker UBC#116 linked to Fusarium crown and root rot resistance gene (Frl) into a co-dominant sequence characterized amplified region (SCAR) marker for marker-assisted selection of tomato.

  9. A SIMULATION OF 450MHz AMPLIFIER WITH DISTRIBUTED ...

    African Journals Online (AJOL)

    DR. AMINU

    USING BIPOLAR JUNCTION TRANSISTOR FROM NI- CIRCUIT DESIGN ... amplifier and multistage distributed amplifier is carried out. In this ... namely, bandwidth, signal power and noise are the .... and Engineers', Prentice-Hall International.

  10. Reconfigurable Josephson Circulator/Directional Amplifier

    Directory of Open Access Journals (Sweden)

    K. M. Sliwa

    2015-11-01

    Full Text Available Circulators and directional amplifiers are crucial nonreciprocal signal routing and processing components involved in microwave read-out chains for a variety of applications. They are particularly important in the field of superconducting quantum information, where the devices also need to have minimal photon losses to preserve the quantum coherence of signals. Conventional commercial implementations of each device suffer from losses and are built from very different physical principles, which has led to separate strategies for the construction of their quantum-limited versions. However, as recently theoretically, by establishing simultaneous pairwise conversion and/or gain processes between three modes of a Josephson-junction-based superconducting microwave circuit, it is possible to endow the circuit with the functions of either a phase-preserving directional amplifier or a circulator. Here, we experimentally demonstrate these two modes of operation of the same circuit. Furthermore, in the directional amplifier mode, we show that the noise performance is comparable to standard nondirectional superconducting amplifiers, while in the circulator mode, we show that the sense of circulation is fully reversible. Our device is far simpler in both modes of operation than previous proposals and implementations, requiring only three microwave pumps. It offers the advantage of flexibility, as it can dynamically switch between modes of operation as its pump conditions are changed. Moreover, by demonstrating that a single three-wave process yields nonreciprocal devices with reconfigurable functions, our work breaks the ground for the development of future, more complex directional circuits, and has excellent prospects for on-chip integration.

  11. Amplifying the Hawking Signal in BECs

    Directory of Open Access Journals (Sweden)

    Roberto Balbinot

    2014-01-01

    Full Text Available We consider simple models of Bose-Einstein condensates to study analog pair-creation effects, namely, the Hawking effect from acoustic black holes and the dynamical Casimir effect in rapidly time-dependent backgrounds. We also focus on a proposal by Cornell to amplify the Hawking signal in density-density correlators by reducing the atoms’ interactions shortly before measurements are made.

  12. Fast Electrocardiogram Amplifier Recovery after Defibrillation Shock

    Directory of Open Access Journals (Sweden)

    Ivan Dotsinsky

    2005-04-01

    Full Text Available A procedure for fast ECG amplifier recovery after defibrillation shocks was developed and simulated in the MATLAB environment. Exponentially decaying post-shock voltages have been recorded. Signals from the AHA database are taken and mixed with the recorded exponential disturbances. The algorithm applies moving averaging (comb filter on the compound input signal, thereby obtaining the samples of the disturbance. They are currently subtracted from the input signal. The results obtained show that its recovery is practically instantaneous.

  13. Ultra-low Voltage CMOS Cascode Amplifier

    DEFF Research Database (Denmark)

    Lehmann, Torsten; Cassia, Marco

    2000-01-01

    In this paper, we design a folded cascode operational transconductance amplifier in a standard CMOS process, which has a measured 69 dB DC gain, a 2 MHz bandwidth and compatible input- and output voltage levels at a 1 V power supply. This is done by a novel Current Driven Bulk (CDB) technique......, which reduces the MOST threshold voltage by forcing a constant current though the transistor bulk terminal. We also look at limitations and improvements of this CDB technique....

  14. Predistortion for Nonlinear Power Amplifiers with Memory

    OpenAIRE

    Nizamuddin, Muhammad Ali

    2002-01-01

    The fusion of voice and data applications, along with the demand for high data-rate applications such as video-on-demand, is making radio frequency (RF) spectrum an increasingly expensive commodity for current and future communications. Although bandwidth-efficient digital modulation alleviates part of the problem by requiring a minimal use of spectral resources, they put an extra design burden on RF engineers. RF transmitters and power amplifiers account for more t...

  15. Self-amplifying mRNA vaccines.

    Science.gov (United States)

    Brito, Luis A; Kommareddy, Sushma; Maione, Domenico; Uematsu, Yasushi; Giovani, Cinzia; Berlanda Scorza, Francesco; Otten, Gillis R; Yu, Dong; Mandl, Christian W; Mason, Peter W; Dormitzer, Philip R; Ulmer, Jeffrey B; Geall, Andrew J

    2015-01-01

    This chapter provides a brief introduction to nucleic acid-based vaccines and recent research in developing self-amplifying mRNA vaccines. These vaccines promise the flexibility of plasmid DNA vaccines with enhanced immunogenicity and safety. The key to realizing the full potential of these vaccines is efficient delivery of nucleic acid to the cytoplasm of a cell, where it can amplify and express the encoded antigenic protein. The hydrophilicity and strong net negative charge of RNA impedes cellular uptake. To overcome this limitation, electrostatic complexation with cationic lipids or polymers and physical delivery using electroporation or ballistic particles to improve cellular uptake has been evaluated. This chapter highlights the rapid progress made in using nonviral delivery systems for RNA-based vaccines. Initial preclinical testing of self-amplifying mRNA vaccines has shown nonviral delivery to be capable of producing potent and robust innate and adaptive immune responses in small animals and nonhuman primates. Historically, the prospect of developing mRNA vaccines was uncertain due to concerns of mRNA instability and the feasibility of large-scale manufacturing. Today, these issues are no longer perceived as barriers in the widespread implementation of the technology. Currently, nonamplifying mRNA vaccines are under investigation in human clinical trials and can be produced at a sufficient quantity and quality to meet regulatory requirements. If the encouraging preclinical data with self-amplifying mRNA vaccines are matched by equivalently positive immunogenicity, potency, and tolerability in human trials, this platform could establish nucleic acid vaccines as a versatile new tool for human immunization. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Charge sensitive amplifies. The state of arts

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Kunishiro [Clear Pulse Co., Tokyo (Japan)

    1996-07-01

    In the radiation detectors, signals are essentially brought with charges produced by radiation, then it is naturally the best way to use a charge sensitive amplifier (CSA) system to extract those signals. The CSA is thought to be the best amplifier suitable to almost all the radiation detectors, if neglecting economical points of view. The CSA has been only applied to special fields like radiation detection because the concept of `charges` is not so universal against the concepts of `voltage` and `current`. The CSA, however, is low in noise and a high speed amplifier and may be applicable not only to radiation measurement but also piezoelectric devices and also bolometers. In this article, noise in the CSA, basic circuit on the CSA, concepts of `equivalent noise charge` (ENC), a method for the ENC, and importance of the `open-loop gain` in the CSA to achieve better performance of it and how to realize in a practical CSA were described. And, characteristics on a counting rate of the CSA, various circuit used in the CSA, and CSAs which are commercially available at present and special purpose CSAs were also introduced. (G.K.)

  17. A 205GHz Amplifier in 90nm CMOS Technology

    Science.gov (United States)

    2017-03-01

    A 205GHz Amplifier in 90nm CMOS Technology Shahab Ardalan, Senior Member, IEEE Electrical Department, Charles W. Davidson College of Engineering...greater CMOS technologies . Keywords: Amplifier, neutralization, parasitic, Psat, P1dB.   Introduction Millimeter-wave and sub-mm-wave (THz band...amplifier has been implemented and fabricated in 90nm CMOS technology . The proposed amplifier attained a gain of 10.5 dB whilst consuming a dc power

  18. Noise and saturation properties of semiconductor quantum dot optical amplifiers

    DEFF Research Database (Denmark)

    Berg, Tommy Winther; Mørk, Jesper

    2002-01-01

    We present a detailed theoretical analysis of quantum dot optical amplifiers. Due to the presence of a reservoir of wetting layer states, the saturation and noise properties differ markedly from bulk or QW amplifiers and may be significantly improved.......We present a detailed theoretical analysis of quantum dot optical amplifiers. Due to the presence of a reservoir of wetting layer states, the saturation and noise properties differ markedly from bulk or QW amplifiers and may be significantly improved....

  19. Pump to signal noise transfer in parametric fiber amplifiers

    DEFF Research Database (Denmark)

    Lund-Hansen, Toke; Rottwitt, Karsten; Peucheret, Christophe

    2010-01-01

    Fiber optic parametric amplifiers have been suggested due to their potential low spontaneous emission. However, by nature the parametric amplifier only work in a forward pumped configuration, which result in transfer of relative intensity noise in the pump to the signal.......Fiber optic parametric amplifiers have been suggested due to their potential low spontaneous emission. However, by nature the parametric amplifier only work in a forward pumped configuration, which result in transfer of relative intensity noise in the pump to the signal....

  20. Exploration of Single-Chip Phase-Sensitive Amplifiers

    Science.gov (United States)

    2015-11-05

    PERCENT_SUPPORTEDNAME FTE Equivalent: Total Number: ...... ...... Inventions (DD882) Scientific Progress First single -chip photonic integrated phase -sensitive amplifier...Sep-2015 Approved for Public Release; Distribution Unlimited Final Report: Exploration of Single -Chip Phase -Sensitive Amplifiers The views, opinions...published in non peer-reviewed journals: Final Report: Exploration of Single -Chip Phase -Sensitive Amplifiers Report Title A monolithically integrated

  1. The Use of Cryogenic HEMT Amplifiers in Wide Band Radiometers

    OpenAIRE

    Jarosik, Norman

    2000-01-01

    Advances in device fabrication, modelling and design techniques have made wide band, low noise cryogenic amplifiers available at frequencies up to 106 GHz. Microwave radiometry applications as used in radio astronomy capitalize on the low noise and large bandwidths of these amplifiers. Radiometers must be carefully designed so as to preclude sensitivity degradations caused by small, low frequency gain fluctuations inherent in these amplifiers.

  2. The response of the juxtaglomerular apparatus to stimuli effecting renin or erythropoietin release in canine renal allografts.

    Science.gov (United States)

    Varkarakis, M J; Mirand, E A; Murphy, G P

    1976-03-01

    The functioning canine renal allograft produces plasma renin activity (PRA) and erythropoietin (ESF) activity and can maintain normal blood pressure and normal erythropoiesis. Moreover, in response to various provocative stimuli it can: (i) increase plasma renin activity in response to low sodium intake; (ii) suppress PRA in response to high sodium intake; (iii) produce increased serum erythropoietin in response to hypoxia. The granulation activity of the juxtaglomerular apparatus correlates best with the degree of graft rejection and with the PRA in groups manipulated by changing sodium balance. This is not the case with hypoxia. Thus, the juxtaglomerular apparatus, even in the presence of vascular changes seen with the severe degree of rejection in renal allografts, can respond to stimuli that can regulate renin release. Renin production by the transplanted kidney can be dissociated from ESF secretion. Blood pressure changes in the present model were not directly associated with increased PRA or juxtaglomerular apparatus activity. In such conditions hypertension can exist in the presence of suppressed PRA and without hypergranulation of the apparatus. The majority of correlations of this study thus establish a close association of the degree of juxtaglomerular index activity with PRA levels, rather than ESF.

  3. Deletion of von Hippel–Lindau Protein Converts Renin-Producing Cells into Erythropoietin-Producing Cells

    Science.gov (United States)

    Paliege, Alexander; Willam, Carsten; Schwarzensteiner, Ilona; Schucht, Kathrin; Neymeyer, Hanna; Sequeira-Lopez, Maria Luisa S.; Bachmann, Sebastian; Gomez, R. Ariel; Eckardt, Kai-Uwe; Kurtz, Armin

    2013-01-01

    States of low perfusion pressure of the kidney associate with hyperplasia or expansion of renin-producing cells, but it is unknown whether hypoxia-triggered genes contribute to these changes. Here, we stabilized hypoxia-inducible transcription factors (HIFs) in mice by conditionally deleting their negative regulator, Vhl, using the Cre/loxP system with renin-1d promoter-driven Cre expression. Vhl −/−REN mice were viable and had normal BP. Deletion of Vhl resulted in constitutive accumulation of HIF-2α in afferent arterioles and glomerular cells and HIF-1α in collecting duct cells of the adult kidney. The preglomerular vascular tree developed normally, but far fewer renin-expressing cells were present, with more than 70% of glomeruli not containing renin cells at the typical juxtaglomerular position. Moreover, these mice had an attenuated expansion of renin-producing cells in response to a low-salt diet combined with an ACE inhibitor. However, renin-producing cells of Vhl −/−REN mice expressed the erythropoietin gene, and they were markedly polycythemic. Taken together, these results suggest that hypoxia-inducible genes, regulated by VHL, are essential for normal development and physiologic adaptation of renin-producing cells. In addition, deletion of Vhl shifts the phenotype of juxtaglomerular cells from a renin- to erythropoietin-secreting cell type, presumably in response to HIF-2 accumulation. PMID:23393316

  4. Co-overexpression of Mgat1 and Mgat4 in CHO cells for production of highly sialylated albumin-erythropoietin.

    Science.gov (United States)

    Cha, Hyun-Myoung; Lim, Jin-Hyuk; Yeon, Jung-Heum; Hwang, Jeong-Min; Kim, Dong-Il

    2017-08-01

    Terminal sialic acids on N-glycan of recombinant human erythropoietin are very important for in vivo half-life, as this glycoprotein has three N-glycosylation sites. N-acetylglucosaminyltransferases I, II, IV, and V (i.e. Mgat1, Mgat2, Mgat4, and Mgat5) catalyze the formation of a glycan antennary structure. These enzymes display different reaction kinetics for a common substrate and generally show low expression in Chinese hamster ovary (CHO) cells. Therefore, genetic control of Mgat expression is an effective method to increase sialic acid contents by enhancing glycan antennarity. To produce highly sialylated albumin-erythropoietin (Alb-EPO), we co-overexpressed the Mgat1 and Mgat4 genes in CHO cells and determined the optimal ratio of Mgat1:Mgat4 gene expression. All transfected cell lines showed increased gene expression of Mgat4, including Mgat1 overexpressing cell line. Sialic acid content of Alb-EPO was highest in co-transfected cells with excess Mgat4 gene, and these cells showed a higher tri- and tetra-antennary structure than control cells. Based on these results, we suggest that co-transfection of the Mgat1 and Mgat4 genes at a ratio of 2:8 is optimal for extension of antennary structures. Also, regulation of Mgat gene expression in the glycan biosynthesis pathway can be a novel approach to increase the terminal sialic acids of N-glycans. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A low-voltage sense amplifier with two-stage operational amplifier clamping for flash memory

    Science.gov (United States)

    Guo, Jiarong

    2017-04-01

    A low-voltage sense amplifier with reference current generator utilizing two-stage operational amplifier clamp structure for flash memory is presented in this paper, capable of operating with minimum supply voltage at 1 V. A new reference current generation circuit composed of a reference cell and a two-stage operational amplifier clamping the drain pole of the reference cell is used to generate the reference current, which avoids the threshold limitation caused by current mirror transistor in the traditional sense amplifier. A novel reference voltage generation circuit using dummy bit-line structure without pull-down current is also adopted, which not only improves the sense window enhancing read precision but also saves power consumption. The sense amplifier was implemented in a flash realized in 90 nm flash technology. Experimental results show the access time is 14.7 ns with power supply of 1.2 V and slow corner at 125 °C. Project supported by the National Natural Science Fundation of China (No. 61376028).

  6. The extract of Ziziphus jujuba fruit (jujube) induces expression of erythropoietin via hypoxia-inducible factor-1α in cultured Hep3B cells.

    Science.gov (United States)

    Chen, Jianping; Lam, Candy T W; Kong, Ava Y Y; Zhang, Wendy L; Zhan, Janis Y X; Bi, Cathy W C; Chan, Gallant K L; Lam, Kelly Y C; Yao, Ping; Dong, Tina T X; Tsim, Karl W K

    2014-11-01

    The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly consumed as health supplement or herbal medicine worldwide. To study the beneficial role of jujube in enhancing hematopoietic function, we investigated its roles on the expression of erythropoietin in cultured Hep3B human hepatocellular carcinoma cells. Application of chemically standardized jujube water extract stimulated erythropoietin expression in a dose-dependent manner, with the highest response by ~ 100 % of increase. A plasmid containing hypoxia response element, a critical regulator for erythropoietin transcription, was transfected into Hep3B cells. Application of jujube water extract onto the transfected cells induced the transcriptional activity of the hypoxia response element. To account for its transcriptional activation, the expression of hypoxia-inducible factor-1α was increased after treatment with jujube water extract: the increase was in both mRNA and protein levels. These results confirmed the hematopoietic function of jujube in the regulation of erythropoietin expression in liver cells. Georg Thieme Verlag KG Stuttgart · New York.

  7. 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...

  8. Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury

    Directory of Open Access Journals (Sweden)

    Daniela Hoeber

    2016-01-01

    Full Text Available Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg at the onset of hyperoxia (24 hours, 80% oxygen in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.

  9. Erythropoietin-induced serine 727 phosphorylation of STAT3 in erythroid cells is mediated by a MEK-, ERK-, and MSK1-dependent pathway

    NARCIS (Netherlands)

    Wierenga, Albertus T.J.; Vogelzang, Irma; Eggen, BJL; Vellenga, E

    Objective. Erythropoietin (EPO) is a key regulator of erythropoiesis, playing a role in both the proliferation and differentiation of erythroid cells. One of the signal transduction molecules activated upon EPO stimulation is signal transducer and activator of transcription (STAT) 3. Besides

  10. 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...

  11. EPOR-Based Purification and Analysis of Erythropoietin Mimetic Peptides from Human Urine by Cys-Specific Cleavage and LC/MS/MS

    Science.gov (United States)

    Vogel, Matthias; Thomas, Andreas; Schänzer, Wilhelm; Thevis, Mario

    2015-09-01

    The development of a new class of erythropoietin mimetic agents (EMA) for treating anemic conditions has been initiated with the discovery of oligopeptides capable of dimerizing the erythropoietin (EPO) receptor and thus stimulating erythropoiesis. The most promising amino acid sequences have been mounted on various different polymeric structures or carrier molecules to obtain highly active EPO-like drugs exhibiting beneficial and desirable pharmacokinetic profiles. Concomitant with creating new therapeutic options, erythropoietin mimetic peptide (EMP)-based drug candidates represent means to artificially enhance endurance performance and necessitate coverage by sports drug testing methods. Therefore, the aim of the present study was to develop a strategy for the comprehensive detection of EMPs in doping controls, which can be used complementary to existing protocols. Three model EMPs were used to provide proof-of-concept data. Following EPO receptor-facilitated purification of target analytes from human urine, the common presence of the cysteine-flanked core structure of EMPs was exploited to generate diagnostic peptides with the aid of a nonenzymatic cleavage procedure. Sensitive detection was accomplished by targeted-SIM/data-dependent MS2 analysis. Method characterization was conducted for the EMP-based drug peginesatide concerning specificity, linearity, precision, recovery, stability, ion suppression/enhancement, and limit of detection (LOD, 0.25 ng/mL). Additionally, first data for the identification of the erythropoietin mimetic peptides EMP1 and BB68 were generated, demonstrating the multi-analyte testing capability of the presented approach.

  12. Analysis of multipass laser amplifier systems for storage laser media

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, J.F.

    1980-03-25

    The performance characteristics of single pass and multipass storage laser amplifiers are presented and compared. The effects of the multipass amplifier parameters on the extraction characteristics are examined. For a wide range of conditions the multipass amplifier is found to provide high energy gain and high efficiency simultaneously. This is a significant advantage over the single pass laser amplifier. Finally, three specific storage laser amplifier systems, flashlamp pumped V:MgF/sub 2/, XeF laser pumped Tm:Glass, and photolytically pumped Selenium, are examined. The performance characteristics for each of the three systems are calculated and compared.

  13. 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

  14. 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

    humans suggest a less frequent dosing regimen relative to erythropoietin and darbepoetin, potentially leading to a simplification of anemia management.

  15. Diurnal changes of arterial oxygen saturation and erythropoietin concentration in male and female highlanders.

    Science.gov (United States)

    Cristancho, Edgar; Riveros, Alain; Sánchez, Armando; Peñuela, Oscar; Böning, Dieter

    2016-09-01

    In Caucasians and Native Americans living at altitude, hemoglobin mass is increased in spite of erythropoietin concentrations ([Epo]) not markedly differing from sea level values. We hypothesized that a nocturnal decrease of arterial oxygen saturation (SaO2) causes a temporary rise of [Epo] not detected by morning measurements. SaO2 (continuous, finger oximeter) and [Epo] (ELISA, every 4 h) were determined in young highlanders (altitude 2600 m) during 24 h of usual daily activity. In Series I (six male, nine female students), SaO2 fell during the night with the nadir occurring between 01:00 and 03:00; daily means (range 92.4-95.2%) were higher in females (+1.7%, P < 0.01). [Epo] showed opposite changes with zenith occurring at 04:00 without a sex difference. Mean daily values (22.9 ± 10.7SD U/L) were higher than values obtained at 08:00 (17.2 ± 9.5 U/L, P < 0.05). In Series II (seven females), only SaO2 was measured. During follicular and luteal phases, SaO2 variation was similar to Series I, but the rhythm was disturbed during menstruation. While daily [Epo] variations at sea level are not homogeneous, there is a diurnal variation at altitude following changes in SaO2 Larger hypoventilation-dependent decreases of alveolar PO2 decreases during the night probably cause a stronger reduction of SaO2 in highlanders compared to lowlanders. This variation might be enlarged by a diurnal fluctuation of Hb concentration. In spite of a lower [Hb], the higher SaO2 in women compared to men led to a similar arterial oxygen content, likely explaining the absence of differences in [Epo] between sexes. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  16. Class D audio amplifiers for high voltage capacitive transducers

    DEFF Research Database (Denmark)

    Nielsen, Dennis

    Audio reproduction systems contains two key components, the amplifier and the loudspeaker. In the last 20 – 30 years the technology of audio amplifiers have performed a fundamental shift of paradigm. Class D audio amplifiers have replaced the linear amplifiers, suffering from the well-known issues...... of high volume, weight, and cost. High efficient class D amplifiers are now widely available offering power densities, that their linear counterparts can not match. Unlike the technology of audio amplifiers, the loudspeaker is still based on the traditional electrodynamic transducer invented by C.W. Rice......-of-the-art for class D audio amplifiers driving the electrodynamic transducer is presented. Chapter 3 gives an introduction to the DEAP transducer as a load in loudspeaker systems. The main purpose being to established the frequency response of the DEAP input impedance, but also investigate the large signal...

  17. Envelope tracking CMOS power amplifier with high-speed CMOS envelope amplifier for mobile handsets

    Science.gov (United States)

    Yoshida, Eiji; Sakai, Yasufumi; Oishi, Kazuaki; Yamazaki, Hiroshi; Mori, Toshihiko; Yamaura, Shinji; Suto, Kazuo; Tanaka, Tetsu

    2014-01-01

    A high-efficiency CMOS power amplifier (PA) based on envelope tracking (ET) has been reported for a wideband code division multiple access (W-CDMA) and long term evolution (LTE) application. By adopting a high-speed CMOS envelope amplifier with current direction sensing, a 5% improvement in total power-added efficiency (PAE) and a 11 dB decrease in adjacent channel leakage ratio (ACLR) are achieved with a W-CDMA signal. Moreover, the proposed PA achieves a PAE of 25.4% for a 10 MHz LTE signal at an output power (Pout) of 25.6 dBm and a gain of 24 dB.

  18. EMG amplifier with wireless data transmission

    Science.gov (United States)

    Kowalski, Grzegorz; Wildner, Krzysztof

    2017-08-01

    Wireless medical diagnostics is a trend in modern technology used in medicine. This paper presents a concept of realization, architecture of hardware and software implementation of an elecromyography signal (EMG) amplifier with wireless data transmission. This amplifier consists of three components: analogue processing of bioelectric signal module, micro-controller circuit and an application enabling data acquisition via a personal computer. The analogue bioelectric signal processing circuit receives electromyography signals from the skin surface, followed by initial analogue processing and preparation of the signals for further digital processing. The second module is a micro-controller circuit designed to wirelessly transmit the electromyography signals from the analogue signal converter to a personal computer. Its purpose is to eliminate the need for wired connections between the patient and the data logging device. The third block is a computer application designed to display the transmitted electromyography signals, as well as data capture and analysis. Its purpose is to provide a graphical representation of the collected data. The entire device has been thoroughly tested to ensure proper functioning. In use, the device displayed the captured electromyography signal from the arm of the patient. Amplitude- frequency characteristics were set in order to investigate the bandwidth and the overall gain of the device.

  19. Quantum dots for lasers, amplifiers and computing

    Energy Technology Data Exchange (ETDEWEB)

    Bimberg, Dieter [Technische Universitaet Berlin, Hardenbergstr. 36, 10623, Berlin (Germany)

    2005-07-07

    For InAs-GaAs based quantum dot lasers emitting at 1300 nm, digital modulation showing an open eye pattern up to 12 Gb s{sup -1} at room temperature is demonstrated, at 10 Gb s{sup -1} the bit error rate is below 10{sup -12} at -2 dB m receiver power. Cut-off frequencies up to 20 GHz are realised for lasers emitting at 1.1 {mu}m. Passively mode-locked QD lasers generate optical pulses with repetition frequencies between 5 and 50 GHz, with a minimum Fourier limited pulse length of 3 ps. The uncorrelated jitter is below 1 ps. We use here deeply etched narrow ridge waveguide structures which show excellent performance similar to shallow mesa structures, but a circular far field at a ridge width of 1 {mu}m, improving coupling efficiency into fibres. No beam filamentation of the fundamental mode, low a-factors and strongly reduced sensitivity to optical feedback are observed. QD lasers are thus superior to QW lasers for any system or network. Quantum dot semiconductor optical amplifier (QD SOAs) demonstrate gain recovery times of 120-140 fs, 4-7 times faster than bulk/QW SOAs, and a net gain larger than 0.4 dB/(mm*QD-layer) providing us with novel types of booster amplifiers and Mach-Zehnder interferometers. These breakthroughs became possible due to systematic development of self-organized growth technologies.

  20. Impedance of the Microstrip SQUID Amplifier

    Science.gov (United States)

    Therrien, Roy; Kinion, Darin; Mueck, Michael; Clarke, John

    2003-03-01

    We present measurements of the input impedance of microstrip SQUID amplifiers cooled to 4.2 K. A low-loss transmission line model fits the real and imaginary parts of this impedance quite accurately. We map the low-loss transmission line model into an equivalent parallel RLC circuit in which a resistance R, inductance L, and capacitance C are calculated from the characteristic impedance and attenuation factor determined from fits to the input impedance data. Using this equivalent RLC circuit, we model the microstrip SQUID and input network with a lumped circuit model which accurately predicts the observed gain of the amplifier. We find that the gain is maximized when the input circuit is critically matched, with the imaginary part of the input impedance summing to zero and the real part equal to the 50 ohm resistance of the coaxial input line. Work in progress is aimed at expressing the equivalent circuit parameters in terms of the device parameters. This work was supported by DOE.

  1. Discretization analysis of bifurcation based nonlinear amplifiers

    Directory of Open Access Journals (Sweden)

    S. Feldkord

    2017-09-01

    Full Text Available Recently, for modeling biological amplification processes, nonlinear amplifiers based on the supercritical Andronov–Hopf bifurcation have been widely analyzed analytically. For technical realizations, digital systems have become the most relevant systems in signal processing applications. The underlying continuous-time systems are transferred to the discrete-time domain using numerical integration methods. Within this contribution, effects on the qualitative behavior of the Andronov–Hopf bifurcation based systems concerning numerical integration methods are analyzed. It is shown exemplarily that explicit Runge–Kutta methods transform the truncated normalform equation of the Andronov–Hopf bifurcation into the normalform equation of the Neimark–Sacker bifurcation. Dependent on the order of the integration method, higher order terms are added during this transformation.A rescaled normalform equation of the Neimark–Sacker bifurcation is introduced that allows a parametric design of a discrete-time system which corresponds to the rescaled Andronov–Hopf system. This system approximates the characteristics of the rescaled Hopf-type amplifier for a large range of parameters. The natural frequency and the peak amplitude are preserved for every set of parameters. The Neimark–Sacker bifurcation based systems avoid large computational effort that would be caused by applying higher order integration methods to the continuous-time normalform equations.

  2. Silicon on insulator MESFETs for RF amplifiers

    Science.gov (United States)

    Wilk, Seth J.; Balijepalli, Asha; Ervin, Joseph; Lepkowski, William; Thornton, Trevor J.

    2010-03-01

    CMOS compatible, high voltage SOI MESFETs have been fabricated using a standard 3.3 V CMOS process without any changes to the process flow. A 0.6 μm gate length device operates with a cut-off frequency of 7.3 GHz and a maximum oscillation frequency of 21 GHz. There is no degradation in device performance up to its breakdown voltage, which greatly exceeds that of CMOS devices on the same process. Other figures-of-merit of relevance to RF front-end design are presented, including the maximum stable gain and noise figure. An accurate representation of the device in SPICE has been developed using the commercially available TOM3 model. Using the SOI MESFET model, a source degenerated low noise RF amplifier targeting operation near 1 GHz has been designed. The amplifier was fabricated on a PCB board and operates at 940 MHz with a minimum NF of 3.8 dB and RF gain of 9.9 dB while only consuming 5mW of DC power.

  3. Discretization analysis of bifurcation based nonlinear amplifiers

    Science.gov (United States)

    Feldkord, Sven; Reit, Marco; Mathis, Wolfgang

    2017-09-01

    Recently, for modeling biological amplification processes, nonlinear amplifiers based on the supercritical Andronov-Hopf bifurcation have been widely analyzed analytically. For technical realizations, digital systems have become the most relevant systems in signal processing applications. The underlying continuous-time systems are transferred to the discrete-time domain using numerical integration methods. Within this contribution, effects on the qualitative behavior of the Andronov-Hopf bifurcation based systems concerning numerical integration methods are analyzed. It is shown exemplarily that explicit Runge-Kutta methods transform the truncated normalform equation of the Andronov-Hopf bifurcation into the normalform equation of the Neimark-Sacker bifurcation. Dependent on the order of the integration method, higher order terms are added during this transformation.A rescaled normalform equation of the Neimark-Sacker bifurcation is introduced that allows a parametric design of a discrete-time system which corresponds to the rescaled Andronov-Hopf system. This system approximates the characteristics of the rescaled Hopf-type amplifier for a large range of parameters. The natural frequency and the peak amplitude are preserved for every set of parameters. The Neimark-Sacker bifurcation based systems avoid large computational effort that would be caused by applying higher order integration methods to the continuous-time normalform equations.

  4. A Low Power RC-Coupled VHF Amplifier Designed for Fabrication by Hybrid Microcircuit Techniques.

    Science.gov (United States)

    RADIOFREQUENCY AMPLIFIERS, HYBRID CIRCUITS, MICROMINIATURIZATION , VERY HIGH FREQUENCY, MODULES(ELECTRONICS), TRANSISTOR AMPLIFIERS, RADIO RECEIVERS, COMMUNICATION EQUIPMENT, SATELLITE COMMUNICATIONS.

  5. Tuneable, non-degenerated, nonlinear, parametrically-excited amplifier

    Science.gov (United States)

    Dolev, Amit; Bucher, Izhak

    2016-01-01

    The proposed parametric amplifier scheme can be tuned to amplify a wide range of input frequencies by altering the parametric excitation with no need to physically modify the oscillator. Parametric amplifiers had been studied extensively, although most of the work focused on amplifiers that are parametrically excited at a frequency twice the amplifier's natural frequency. These amplifiers are confined to amplifying predetermined frequencies. The proposed parametric amplifier's bandwidth is indeed tuneable to nearly any input frequency, not bound to be an integer multiple of a natural frequency. In order to tune the stiffness and induce a variable frequency parametric excitation, a digitally controlled electromechanical element must be incorporated in the realization. We introduce a novel parametric amplifier with nonlinearity, Duffing type hardening, that bounds the otherwise unlimited amplitude. Moreover, we present a multi degree of freedom system in which a utilization of the proposed method enables the projection of low frequency vector forces on any eigenvector and corresponding natural frequency of the system, and thus to transform external excitations to a frequency band where signal levels are considerably higher. Using the method of multiple scales, analytical expressions for the responses have been retrieved and verified numerically. Parametric studies of the amplifiers' gain, sensitivities and spatial projection of the excitation on the system eigenvectors were carried out analytically. The results demonstrate the advantage of the proposed approach over existing schemes. Practical applications envisaged for the proposed method will be outlined.

  6. Erythropoietin Attenuates the Memory Deficits in Aging Rats by Rescuing the Oxidative Stress and Inflammation and Promoting BDNF Releasing.

    Science.gov (United States)

    Jia, Zhankui; Xue, Rui; Ma, Shengli; Xu, Jingjing; Guo, Si; Li, Songchao; Zhang, Erwei; Wang, Jun; Yang, Jinjian

    2016-10-01

    Aging is a natural process accompanied with many disorders, including the memory decline. The underlying mechanisms for the age-related memory decline are complicated. Previous work suggested that oxidative stress, inflammatory disturbance, and the neurotropic absence play important roles in the age-related disorders. Thus, to seek a drug to target those abnormalities might be a possible protective approach for aging. Here, we reported that supplements with exogenous erythropoietin (EPO) for 4 weeks could partially rescue the spatial and fear memory impairments in aged rats. The EPO treatment also suppresses the oxidative stress and inflammatory response. Most importantly, EPO supplement restores the mRNA and protein levels of brain-derived neurotrophic factor (BDNF), the critical neurotropic factor for synaptic plasticity and memory. Our study strongly suggests the potential usage of EPO in an anti-aging agent clinically.

  7. Topical erythropoietin as a novel preventive and therapeutic agent in bisphosphonate-related osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    Pantea Nazeman

    2016-01-01

    Full Text Available Introduction: One of the most common side effects of bisphosphonate intake is osteonecrosis of the jaw (ONJ which may develop following dentoalveolar interventions. Despite the vast available protocols, there is no clear guideline in the management of this condition. In osteonecrosis, the number and proliferation of bone-forming cells as well as vascularity are disturbed. Erythropoietin (EPO is a hematopoietic hormone with angiogenic, osteogenic, and antiapoptotic properties. The Hypothesis: It is suggested to utilize poly lactic-co-glycolic acid hydrogel containing 1500-3000 IU/kg EPO following dentoalveolar surgery in samples receiving bisphosphonates as a preventive or therapeutic agent. Evaluation of the Hypothesis: Considering the pathophysiology of ONJ and therapeutic properties of EPO, it is assumed that EPO may be effective in treatment of ONJ. Furthermore, as a preventive measure, utilizing EPO following dentoalveolar surgery may be beneficial in the patients at risk of ONJ.

  8. Autocrine/paracrine erythropoietin regulates migration and invasion potential and the stemness of human breast cancer cells

    Science.gov (United States)

    Liang, Ke; Qiu, Songbo; Lu, Yang; Fan, Zhen

    2014-01-01

    Recent studies suggest that erythropoietin (EPO) has pleiotropic effects in several cell types in addition to hematopoietic cells; however, the role of EPO-mediated cell signaling in nonhematopoietic cells, including in cancer cells, remains controversial. Here, we report our findings of autocrine/paracrine production of EPO by breast cancer cells and its functional significance. We detected a significant level of autocrine/paracrine EPO in the conditioned medium from the culture of SKBR3 breast cancer cells, particularly when the cells were cultured in hypoxia. Through knockdown of EPO and EPO receptor expression and experimental elevation of EPO receptor expression in SKBR3 breast cancer cells, we demonstrated novel roles of autocrine/paracrine EPO-mediated cell signaling in regulating migration and invasion potential and stemness-like properties of breast cancer cells. PMID:24100272

  9. The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla; Hoejman, Pernille

    2015-01-01

    UNLABELLED: The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO) on plasma brain derived neurotrophic factor (BDNF) levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment......-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ≤ 14) (study 2). In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU......) or saline (0.9% NaCl) infusions in a double-blind, placebo-controlled, parallel--group design. Plasma BDNF levels were measured at baseline and at weeks 5, 9 and at follow up, week 14. In contrast with our hypothesis, EPO down regulated plasma BDNF levels in patients with TRD (mean reduction at week 9 (95...

  10. 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.)

  11. Absence of hematological side effects in acute and subacute nasal dosing of erythropoietin with a low content of sialic acid.

    Science.gov (United States)

    Lagarto, Alicia; Bueno, Viviana; Guerra, Isbel; Valdés, Odalys; Couret, Micaela; López, Raisel; Vega, Yamile

    2011-09-01

    The use of human recombinant erythropoietin (EPO) as a neuroprotective agent is limited due to its hematological side effects. An erythropoietin along with a low content of sialic acid (rhEPOb), similar to that produced in the brain during hypoxia, may be used as a neuroprotective agent without risk of thrombotic events. The objective of this investigation was to assess the toxicological potential of a nasal formulation with rhEPOb in acute, subacute and nasal irritation assays in rats. Healthy Wistar rats (Cenp:Wistar) were used for the assays. In an irritation test, animals received 15 μl of rhEPOb into the right nostril. Rats were sacrificed after 24 h and slides of the nasal mucosa tissues were examined. Control and treated groups showed signs of a minimal irritation consisting of week edema and vascular congestion in all animals. In the acute toxicity test, the dose of 47,143 UI/kg was administered by nasal route. Hematological patterns, body weight, relative organ weight, and organ integrity were not affected by single dosing with rhEPOb. In the subacute toxicity test, Wistar rats of both sexes received 6,600 UI/kg/day for 14 days. The toxicological endpoints examined included animal body weight, food consumption, hematological and biochemical patterns, selected tissue weights, and histopathological examinations. An increase of lymphocytes was observed in males that was considered to reflect an immune response to treatment. Histopathological examination of organs and tissues did not reveal treatment-induced changes. The administration of rhEPOb at daily doses of 6,600 UI/kg during 14 days did not produce hematological side effects. These results suggest that rhEPOb could offer the same neuroprotection as EPO, without hematological side effects. Copyright © 2010 Elsevier GmbH. All rights reserved.

  12. Erythropoietin enhances mitochondrial biogenesis in cardiomyocytes exposed to chronic hypoxia through Akt/eNOS signalling pathway.

    Science.gov (United States)

    Qin, Chuan; Zhou, Shengkai; Xiao, Yingbin; Chen, Lin

    2014-03-01

    Adaptation of cardiomyocytes to chronic hypoxia in cyanotic patients remains unclear. Mitochondrial biogenesis is enhanced in myocardium from cyanotic patients, which is possibly an adaptive response. Erythropoietin (EPO) in blood and its receptor (EPOR) on cardiomyocytes are upregulated by chronic hypoxia, suggesting that EPO-EPOR interaction is increased, which is inferred to positively regulate mitochondrial biogenesis through protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) signalling pathway. H9c2 cardiomyocytes were exposed to hypoxia (1% O(2)) for 1 week and treated with different doses of recombinant human erythropoietin (rhEPO). Mitochondrial number, mitochondrial DNA (mtDNA) copy number and peroxisome proliferator activated receptor gamma coactivator alpha (PGC-1α) mRNA expression increased in a dose-dependent manner induced by rhEPO. Akt and eNOS were significantly phosphorylated by rhEPO. Both blocking Akt with Wortmannin and silencing eNOS expression with shRNA plasmid decreased the mtDNA copy number and PGC-1α mRNA expression induced by rhEPO. Blocking Akt was associated with the decreased phosphorylation of Akt and eNOS. RNA interference led to a reduction in the total and phosphorylated proteins of eNOS. Thus EPO enhances mitochondrial biogenesis in cardiomyocytes exposed to chronic hypoxia, at least partly through Akt/eNOS signalling, which might be an adaptive mechanism of cardiomyocytes associated with the increased EPO-EPOR interaction in patients with cyanotic congenital heart disease (CCHD). © 2013 International Federation for Cell Biology.

  13. Erythropoietin increases bioavailability of tetrahydrobiopterin and protects cerebral microvasculature against oxidative stress induced by eNOS uncoupling.

    Science.gov (United States)

    Santhanam, Anantha Vijay R; d'Uscio, Livius V; Katusic, Zvonimir S

    2014-11-01

    This study was designed to determine whether treatment with erythropoietin (EPO) could protect cerebral microvasculature against the pathological consequences of endothelial nitric oxide (NO) synthase uncoupling. Wild-type and GTP cyclohydrolase I (GTPCH-I)-deficient hph1 mice were administered EPO (1000 U/kg/day, s.c., 3 days). Cerebral microvessels of hph1 mice demonstrated reduced tetrahydrobiopterin (BH4) bioavailability, increased production of superoxide anions and impaired endothelial NO signaling. Treatment of hph1 mice with EPO attenuated the levels of 7,8-dihydrobiopterin, the oxidized product of BH4, and significantly increased the ratio of BH4 to 7,8-dihydrobiopterin. Moreover, EPO decreased the levels of superoxide anions and increased NO bioavailability in cerebral microvessels of hph1 mice. Attenuated oxidation of BH4 and inhibition of endothelial NO synthase uncoupling were explained by the increased expression of antioxidant proteins, manganese superoxide dismutase, and catalase. The protective effects of EPO observed in cerebral microvessels of hph1 mice were also observed in GTPCH-I siRNA-treated human brain microvascular endothelial cells exposed to EPO (1 U/mL or 10 U/mL; 3 days). Our results suggest that EPO might protect the neurovascular unit against oxidative stress by restoring bioavailability of BH4 and endothelial NO in the cerebral microvascular endothelium. We demonstrate that treatment with erythropoietin (EPO) could protect cerebral microvasculature against the pathological consequences of endothelial nitric oxide (NO) synthase uncoupling. Our results suggest that EPO might protect the neurovascular unit against oxidative stress by restoring bioavailability of tetrahydrobiopterin (BH4) and endothelial nitric oxide. © 2014 International Society for Neurochemistry.

  14. Optimizing preoperative haemoglobin in major orthopaedic surgery using intravenous iron with or without erythropoietin. An epidemiologic study.

    Science.gov (United States)

    Basora, M; Colomina, M J; Tio, M; Mora, L; Sánchez-Etayo, G; Salazar, F; Ciércoles, E; Paños, M; Guerrero, E; Berge, R

    2015-01-01

    To evaluate the effectiveness of intravenous iron treatment, with or without associated erythropoietin (rHuEPO), measured as haemoglobin (Hb) increase. The relationships between the Hb increase and parameters used to evaluate anaemia were analysed. Retrospective observational study carried out in two third-level hospitals between January 2005 and December 2009. The study included patients with iron deficiency anaemia scheduled for elective orthopaedic surgery and treated with intravenous iron sucrose alone or associated with rHuEPO. Treatment efficacy was analysed based on the Hb increase from baseline to just before surgery. A total of 412 patients who received a median of 800mg of iron sucrose were included; 125 of them (30.4%) additionally received 2.4 vials of rHuEPO. The Hb increase was 0.8 (1.1) g/dL in patients treated with intravenous iron and 1.5 (1.3) g/dL in those additionally given rHuEPO(P<.01). The percentage of hypochromic red blood cells (r=0.52) and soluble transferrin receptor (r=0.59) value were significantly correlated to the Hb increase in patients receiving iron. In patients with iron deficiency anaemia, the effectiveness of iron sucrose treatment to optimize Hb before surgery was moderate; adjuvant administration of erythropoietin improved the results. Determination of functional iron status parameters may improve the treatment effectiveness. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Protective effect of recombinant human erythropoietin on liver and kidney injury as well as endoplasmic reticulum stress caused by infec

    Directory of Open Access Journals (Sweden)

    Yan-Li Jiang

    2016-03-01

    Full Text Available Objective: To study the protective effect of recombinant human erythropoietin on liver and kidney injury as well as endoplasmic reticulum stress caused by infection. Methods: Male Wistar rats were randomly divided into negative control group, LPS group and LPS+EPO group, LPS group and LPS+EPO group received injection of LPS via caudal vein to establish infection models, and LPS+EPO group received injection of rHuEPO via caudal vein for intervention; before intervention as well as 6 and 12 h after intervention, serum was collected to detect TNF-α, iNOS, BUN, Cr, ALT and AST contents; 12 h after intervention, liver and kidney tissue was collected to detect mRNA contents of endoplasmic reticulum stress molecules (GRP78, CHOP and Caspase-12. Results: After model establishment and before rHuEPO intervention, serum TNF-α, iNOS, BUN, Cr, ALT and AST contents of LPS group and LPS+EPO group had no differences and were higher than those of negative control group; 6 and 12 h after intervention, serum TNF-α, iNOS, BUN, Cr, ALT and AST contents of LPS+EPO group were lower than those of LPS group; 12 h after intervention, mRNA contents of GRP78, CHOP and Caspase-12 in liver and kidney tissue of LPS+EPO group were lower than those of LPS group. Conclusions: Recombinant human erythropoietin has protective effect on liver and kidney injury as well as endoplasmic reticulum stress caused by infection.

  16. Beyond anaemia management: evolving role of erythropoietin therapy in neurological disorders, multiple myeloma and tumour hypoxia models.

    Science.gov (United States)

    Boogaerts, Marc; Mittelman, Moshe; Vaupel, Peter

    2005-01-01

    Recombinant human erythropoietin (epoetin) has become the standard of care in the treatment of anaemia resulting from cancer and its treatment, and chronic kidney disease. The discovery that erythropoietin and its receptor are located in regions outside the erythropoietic system has led to interest in the potential role of epoetin in other tissues, such as the central nervous system. Animal studies have shown that systemically applied epoetin can cross the blood-brain barrier, where it reduces tissue injury associated with stroke, blunt trauma and experimental autoimmune encephalomyelitis. Pilot studies in humans have shown that epoetin treatment given within 8 h of stroke reduces infarct size and results in a significantly better outcome when compared with placebo treatment. Studies also suggest that epoetin has the potential to improve cognitive impairment associated with adjuvant chemotherapy in patients with cancer. Anaemia is a major factor causing tumour hypoxia, a condition that can promote changes within neoplastic cells that further tumour survival and malignant progression and also reduces the effectiveness of several anticancer therapies including radiotherapy and oxygen-dependent cytotoxic agents. Use of epoetin to prevent or correct anaemia has the potential to reduce tumour hypoxia and improve treatment outcome. Several therapeutic studies in anaemic animals with experimental tumours have shown a beneficial effect of epoetin on delaying tumour growth. Furthermore, clinical observations in patients with multiple myeloma and animal studies have suggested that epoetin has an antimyeloma effect, mediated via the immune system through activation of CD8+ T cells. Therefore, the role of epoetin may go well beyond that of increasing haemoglobin levels in anaemic patients, although additional studies are required to confirm these promising results. Copyright 2005 S. Karger AG, Basel.

  17. Erythropoietin and a nonerythropoietic peptide analog promote aortic endothelial cell repair under hypoxic conditions: role of nitric oxide

    Directory of Open Access Journals (Sweden)

    Heikal L

    2016-08-01

    Full Text Available Lamia Heikal,1 Pietro Ghezzi,1 Manuela Mengozzi,1 Blanka Stelmaszczuk,2 Martin Feelisch,2 Gordon AA Ferns1 1Brighton and Sussex Medical School, Falmer, Brighton, 2Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital and Institute for Life Sciences, Southampton, UK Abstract: The cytoprotective effects of erythropoietin (EPO and an EPO-related nonerythropoietic analog, pyroglutamate helix B surface peptide (pHBSP, were investigated in an in vitro model of bovine aortic endothelial cell injury under normoxic (21% O2 and hypoxic (1% O2 conditions. The potential molecular mechanisms of these effects were also explored. Using a model of endothelial injury (the scratch assay, we found that, under hypoxic conditions, EPO and pHBSP enhanced scratch closure by promoting cell migration and proliferation, but did not show any effect under normoxic conditions. Furthermore, EPO protected bovine aortic endothelial cells from staurosporine-induced apoptosis under hypoxic conditions. The priming effect of hypoxia was associated with stabilization of hypoxia inducible factor-1α, EPO receptor upregulation, and decreased Ser-1177 phosphorylation of endothelial nitric oxide synthase (NOS; the effect of hypoxia on the latter was rescued by EPO. Hypoxia was associated with a reduction in nitric oxide (NO production as assessed by its oxidation products, nitrite and nitrate, consistent with the oxygen requirement for endogenous production of NO by endothelial NOS. However, while EPO did not affect NO formation in normoxia, it markedly increased NO production, in a manner sensitive to NOS inhibition, under hypoxic conditions. These data are consistent with the notion that the tissue-protective actions of EPO-related cytokines in pathophysiological settings associated with poor oxygenation are mediated by NO. These findings may be particularly relevant to atherogenesis and postangioplasty restenosis. Keywords

  18. Layered-nanomaterial-amplified chemiluminescence systems and their analytical applications.

    Science.gov (United States)

    Zhong, Jinpan; Yuan, Zhiqin; Lu, Chao

    2016-12-01

    Layered nanomaterial has become a popular hierarchical material for amplifying chemiluminescence (CL) in recent years, mainly because of its ease of preparation and modification, large specific surface area, and high catalytic activity. In this review, we mainly discuss layered-nanomaterial-amplified CL systems based on graphene and its derivatives, layered double hydroxides, and clay. Detection mechanisms and strategies of layered-nanomaterial-amplified CL systems are provided to show the basic concepts for designing sensitive and selective sensing systems. Strategies for expanding the applications of layered-nanomaterial-amplified CL systems by combination with surfactants, quantum dots, organic dyes, and nanoparticles are introduced for the analysis of various analytes in real samples. The challenges and future trends of layered-nanomaterial-amplified CL systems are discussed at the end of the review. Graphical Abstract Schematic illustration of layered nanomaterial amplified chemiluminescence.

  19. Method and apparatus for linear low-frequency feedback in monolithic low-noise charge amplifiers

    Science.gov (United States)

    DeGeronimo, Gianluigi

    2006-02-14

    A charge amplifier includes an amplifier, feedback circuit, and cancellation circuit. The feedback circuit includes a capacitor, inverter, and current mirror. The capacitor is coupled across the signal amplifier, the inverter is coupled to the output of the signal amplifier, and the current mirror is coupled to the input of the signal amplifier. The cancellation circuit is coupled to the output of the signal amplifier. A method of charge amplification includes providing a signal amplifier; coupling a first capacitor across the signal amplifier; coupling an inverter to the output of the signal amplifier; coupling a current mirror to the input of the signal amplifier; and coupling a cancellation circuit to the output of the signal amplifier. A front-end system for use with radiation sensors includes a charge amplifier and a current amplifier, shaping amplifier, baseline stabilizer, discriminator, peak detector, timing detector, and logic circuit coupled to the charge amplifier.

  20. Satellite cell response to erythropoietin treatment and endurance training in healthy young men.

    Science.gov (United States)

    Hoedt, Andrea; Christensen, Britt; Nellemann, Birgitte; Mikkelsen, Ulla Ramer; Hansen, Mette; Schjerling, Peter; Farup, Jean

    2016-02-01

    Erythropoietin (Epo) treatment may induce myogenic differentiation factor (MyoD) expression and prevent apoptosis in satellite cells (SCs) in murine and in vitro models. Endurance training stimulates SC proliferation in vivo in murine and human skeletal muscle. In the present study, we show, in human skeletal muscle, that treatment with an Epo-stimulating agent (darbepoetin-α) in vivo increases the content of MyoD(+) SCs in healthy young men. Moreover, we report that Epo receptor mRNA is expressed in adult human SCs, suggesting that Epo may directly target SCs through ligand-receptor interaction. Moreover, endurance training, but not Epo treatment, increases the SC content in type II myofibres, as well as the content of MyoD(+) SCs. Collectively, our results suggest that Epo treatment can regulate human SCs in vivo, supported by Epo receptor mRNA expression in human SCs. In effect, long-term Epo treatment during disease conditions involving anaemia may impact SCs and warrants further investigation. Satellite cell (SC) proliferation is observed following erythropoitin treatment in vitro in murine myoblasts and endurance training in vivo in human skeletal muscle. The present study aimed to investigate the effects of prolonged erythropoiesis-stimulating agent (ESA; darbepoetin-α) treatment and endurance training, separately and combined, on SC quantity and commitment in human skeletal muscle. Thirty-five healthy, untrained men were randomized into four groups: sedentary-placebo (SP, n = 9), sedentary-ESA (SE, n = 9), training-placebo (TP, n = 9) or training-ESA (TE, n = 8). ESA/placebo was injected once weekly and training consisted of ergometer cycling three times a week for 10 weeks. Prior to and following the intervention period, blood samples and muscle biopsies were obtained and maximal oxygen uptake (V̇O2, max) was measured. Immunohistochemical analyses were used to quantify fibre type specific SCs (Pax7(+)), myonuclei and active SCs (Pax7(+)/MyoD(+)). ESA

  1. GaN-based Power amplifiers for microwave applications

    Directory of Open Access Journals (Sweden)

    Jorge Julián Moreno-Rubio

    2016-01-01

    Full Text Available This paper presents a discussion about the design strategies of different kind of power amplifiers for RF/Microwave appli- cations, such as the tuned load power amplifier, class F, class F-1 and Doherty. Furthermore, it is shown the continuous wave characterization of the amplifiers above mentioned. A comparison between the obtained results, in terms of gain, efficiency and output power is presented.

  2. InP Heterojunction Bipolar Transistor Amplifiers to 255 GHz

    Science.gov (United States)

    Radisic, Vesna; Sawdai, Donald; Scott, Dennis; Deal, William; Dang, Linh; Li, Danny; Cavus, Abdullah; To, Richard; Lai, Richard

    2009-01-01

    Two single-stage InP heterojunction bipolar transistor (HBT) amplifiers operate at 184 and 255 GHz, using Northrop Grumman Corporation s InP HBT MMIC (monolithic microwave integrated circuit) technology. At the time of this reporting, these are reported to be the highest HBT amplifiers ever created. The purpose of the amplifier design is to evaluate the technology capability for high-frequency designs and verify the model for future development work.

  3. Modeling and design techniques for RF power amplifiers

    CERN Document Server

    Raghavan, Arvind; Laskar, Joy

    2008-01-01

    The book covers RF power amplifier design, from device and modeling considerations to advanced circuit design architectures and techniques. It focuses on recent developments and advanced topics in this area, including numerous practical designs to back the theoretical considerations. It presents the challenges in designing power amplifiers in silicon and helps the reader improve the efficiency of linear power amplifiers, and design more accurate compact device models, with faster extraction routines, to create cost effective and reliable circuits.

  4. Isolation Amplifier Based On Sigma-Delta Modulation

    Science.gov (United States)

    Harres, Daniel N.

    1994-01-01

    Improved isolation amplifier transmits dc or low-frequency analog signal by use of digital pulses. Relatively imprecise digital pulses convey analog signal with relatively high precision. Amplifier implements sigma-delta modulation scheme. Circuit used wherever conventional amplifier needed. Includes medical instrumentation, switching-type power supplies, and other applications in which input voltages must be measured in presence of large common-mode voltages.

  5. A high performance switching audio amplifier using sliding mode control

    OpenAIRE

    Pillonnet, Gael; Cellier, Rémy; Abouchi, Nacer; Chiollaz, Monique

    2008-01-01

    International audience; The switching audio amplifiers are widely used in various portable and consumer electronics due to their high efficiency, but suffers from low audio performances due to inherent nonlinearity. This paper presents an integrated class D audio amplifier with low consumption and high audio performances. It includes a power stage and an efficient control based on sliding mode technique. This monolithic class D amplifier is capable of delivering up to 1W into 8Ω load at less ...

  6. Multimode Traveling-Wave Amplifier Tubes

    Science.gov (United States)

    Buck, E.

    1981-02-01

    The paper examines the recent developments which makes the Traveling Wave Tube (TWT) more powerful and efficient as a microwave amplifier than the solid state devices. Basic workings and efficiency, which can run, but usually do not, to 55%, are examined. The dependence of the performance of a given TWT upon the qualities of the beam and the manner of its focusing is described. Also described is the development of a multistage depressed collector (MDC) and its first application to a Communication Technology Satellite (CTS) tube, a 12 GHz, coupled-cavity, 200 watt TWT, which resulted in being operated in space for nearly four years and was both the most powerful and the most efficient (around 50%) communications TWT ever flown. It is predicted that the application of efficient refocusing and MDCs, made possible by computer simulations, will greatly increase tube efficiency, and thereby make practical, new multimode tubes which operate, as least partly, in a linear fashion.

  7. Stochastic phenomena in a fiber Raman amplifier

    CERN Document Server

    Kalashnikov, Vladimir; Ania-Castanón, Juan Diego; Jacobsen, Gunnar; Popov, Sergei

    2016-01-01

    The interplay of such cornerstones of modern nonlinear fiber optics as a nonlinearity, stochasticity and polarization leads to variety of the noise induced instabilities including polarization attraction and escape phenomena harnessing of which is a key to unlocking the fiber optic systems specifications required in high resolution spectroscopy, metrology, biomedicine and telecommunications. Here, by using direct stochastic modeling, the mapping of interplay of the Raman scattering-based nonlinearity, the random birefringence of a fiber, and the pump-to-signal intensity noise transfer has been done in terms of the fiber Raman amplifier parameters, namely polarization mode dispersion, the relative intensity noise of the pump laser, fiber length, and the signal power. The obtained results reveal conditions for emergence of the random birefringence-induced resonance-like enhancement of the gain fluctuations (stochastic anti-resonance) accompanied by pulse broadening and rare events in the form of low power outpu...

  8. Self-amplified optical pattern recognition system

    Science.gov (United States)

    Liu, Hua-Kuang (Inventor)

    1994-01-01

    A self amplifying optical pattern recognizer includes a geometric system configuration similar to that of a Vander Lugt holographic matched filter configuration with a photorefractive crystal specifically oriented with respect to the input beams. An extraordinarily polarized, spherically converging object image beam is formed by laser illumination of an input object image and applied through a photorefractive crystal, such as a barium titanite (BaTiO.sub.3) crystal. A volume or thin-film dif ORIGIN OF THE INVENTION The invention described herein was made in the performance of work under a NASA contract, and is subject to the provisions of Public Law 96-517 (35 USC 202) in which the Contractor has elected to retain title.

  9. A Superconducting Linac for the Energy Amplifier

    Science.gov (United States)

    Ruggiero, A. G.

    1997-05-01

    Because of the safer and more reliable mode of operation, a Superconducting Linac is proposed here as the proton beam accelerator which drives a nuclear plant based on the concept of the Energy Amplifier. The accelerator has also high electric power efficiency, estimated around 40%. An example based on the net generation of 400 MW (electric) is described here. This requires a proton beam energy of 1 GeV with a continuous beam current of 10 mA, corresponding to a beam power of 10 MW. The study compares the cost and performance of several rf cavity frequencies, namely 350 versus 800 MHz. Higher power values can be obtained with larger beam energy and intensity. A re-circulation configuration mode of the Linac is also proposed and studied.

  10. Rippled beam free electron Laser Amplifier

    Energy Technology Data Exchange (ETDEWEB)

    Carlsten, Bruce E.

    1998-04-21

    A free electron laser amplifier provides a scalloping annular electron beam that interacts with the axial electric field of a T{sub 0n} mode. A waveguide defines an axial centerline and . A solenoid arranged about the waveguide produces an axial constant magnetic field within the waveguide. An electron beam source outputs a annular electron beam that interacts with the axial magnetic field to have an equilibrium radius and a ripple radius component having a variable radius with a ripple period along the axial centerline. An rf source outputs an axial electric field that propagates within the waveguide coaxial with the electron beam and has a radial mode that interacts at the electron beam at the equilibrium radius component of the electron beam.

  11. Compressed magnetic flux amplifier with capacitive load

    Energy Technology Data Exchange (ETDEWEB)

    Stuetzer, O.M.

    1980-03-01

    A first-order analysis is presented for a compressed magnetic flux (CMF) current amplifier working into a load with a capacitive component. Since the purpose of the investigation was to gain a general understanding of the arrangement, a number of approximations and limitations were accepted. The inductance of the transducer varies with time; the inductance/resistance/capacitance (LRC) circuit therefore is parametric and solutions are different for the stable regime (high C), the oscillation regime (low C), and the transition case. Solutions and performance depend strongly on circuit boundary conditions, i.e., energization of the circuit by either an injected current or by an applied capacitor charge. The behavior of current and energy amplification for the various cases are discussed in detail. A number of experiments with small CMF devices showed that the first-order theory presented predicts transducer performance well in the linear regime.

  12. Parametric Amplifiers for Microwave Kinectic Inductance Detector (MKID) Readout Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Find numerical solutions to the non-linear partial differential equations describing our amplifier transmission lines. Optimize periodic choke structure to block...

  13. Saturation and noise properties of quantum-dot optical amplifiers

    DEFF Research Database (Denmark)

    Berg, Tommy Winther; Mørk, Jesper

    2004-01-01

    Based on extensive numerical calculations, quantum-dot (QD) amplifiers are predicted to offer higher output power and lower noise figure compared to bulk as well as quantum well amplifiers. The underlying physical mechanisms are analyzed in detail, leading to the identification of a few key...... requirements that QD amplifiers should meet in order to achieve such superior linear characteristics. The existence of a highly inverted wetting layer or barrier region, acting as a carrier reservoir, is central to this performance enhancement. It is shown that amplified spontaneous emission acts to decrease...

  14. Dual Band High Efficiency Power Amplifier Based on CRLH Lines

    Directory of Open Access Journals (Sweden)

    D. Segovia-Vargas

    2009-12-01

    Full Text Available In this paper we propose the use of Composite Right/Left Hand (CRLH and Extended Composite Right/Left Hand (ECRLH transmission lines for the design of dual band high efficiency power amplifiers working in CE class. The harmonic termination can be synthesized using the meta-lines is particularly suitable for CE class amplifiers, which have a termination not as sensitive to the third harmonic as F class amplifier. This paper presents the design procedure and the design equations. The nonlinear phase response of a CRLH and ECRLH transmission line has been utilized to design arbitrary dual-band amplifiers.

  15. Modeling a Common-Source Amplifier Using a Ferroelectric Transistor

    Science.gov (United States)

    Sayyah, Rana; Hunt, Mitchell; MacLeond, Todd C.; Ho, Fat D.

    2010-01-01

    This paper presents a mathematical model characterizing the behavior of a common-source amplifier using a FeFET. The model is based on empirical data and incorporates several variables that affect the output, including frequency, load resistance, and gate-to-source voltage. Since the common-source amplifier is the most widely used amplifier in MOS technology, understanding and modeling the behavior of the FeFET-based common-source amplifier will help in the integration of FeFETs into many circuits.

  16. Digitally gain controlled linear high voltage amplifier for laboratory applications

    Science.gov (United States)

    Koçum, C.

    2011-08-01

    The design of a digitally gain controlled high-voltage non-inverting bipolar linear amplifier is presented. This cost efficient and relatively simple circuit has stable operation range from dc to 90 kHz under the load of 10 kΩ and 39 pF. The amplifier can swing up to 360 Vpp under these conditions and it has 2.5 μs rise time. The gain can be changed by the aid of JFETs. The amplifiers have been realized using a combination of operational amplifiers and high-voltage discrete bipolar junction transistors. The circuit details and performance characteristics are discussed.

  17. Time-Domain UWB RFID Tag Based on Reflection Amplifier

    OpenAIRE

    Girbau, D.; Villarino, R.; Ramos, A.; Lazaro, A.

    2013-01-01

    10.1109/LAWP.2013.2257653 This letter describes an active ultrawideband (UWB) tag for radio frequency identification (RFID) and wireless sensor applications. The tag is composed by a UWB antenna connected to a one-port reflection amplifier. A UWB impulse radar is used as the reader. The reader sends a short pulse, and its echo is amplified and reflected back due to the return gain of the tag amplifier. The amplitude of the reflected pulse is modulated by controlling the amplifier bias. Th...

  18. Switching-mode Audio Power Amplifiers with Direct Energy Conversion

    DEFF Research Database (Denmark)

    Ljusev, Petar; Andersen, Michael Andreas E.

    2005-01-01

    This paper presents a new class of switching-mode audio power amplifiers, which are capable of direct energy conversion from the AC mains to the audio output. They represent an ultimate integration of a switching-mode power supply and a Class D audio power amplifier, where the intermediate DC bus...... has been replaced with a high frequency AC link. When compared to the conventional Class D amplifiers with a separate DC power supply, the proposed single conversion stage amplifier provides simple and compact solution with better efficiency and higher level of integration, leading to reduced...

  19. Nylon Sleeve for Cavity Amplifier Holds Tuning Despite Heat

    Science.gov (United States)

    Derr, Lloyd

    1964-01-01

    The problem: Detuning of cavity amplifiers with change in temperature. This results in deterioration of the performance of the amplifier at its design frequency. In cavity amplifiers and filters it is desirable that constant performance be maintained regardless of thermal changes. These changes often cause an "off resonance shift" in a cavity filter and a deterioration of performance in a cavity amplifier. The solution: Mount the tuning probe in a nylon sleeve. Thermal expansion and contraction of the nylon nullifies unwanted capacitive and inductive changes in the resonant elements.

  20. Visible-infrared self-amplified spontaneous emission amplifier free electron laser undulator

    Directory of Open Access Journals (Sweden)

    Roger Carr

    2001-12-01

    Full Text Available The visible-infrared self-amplified spontaneous emission amplifier (VISA free electron laser (FEL is an experimental device designed to show self-amplified spontaneous emission (SASE to saturation in the near infrared to visible light energy range. It generates a resonant wavelength output from 800–600 nm, so that silicon detectors may be used to characterize the optical properties of the FEL radiation. VISA is designed to show how SASE FEL theory corresponds with experiment in this wavelength range, using an electron beam with emittance close to that planned for the future Linear Coherent Light Source at SLAC. VISA comprises a 4 m pure permanent magnet undulator with four 99 cm segments, each of 55 periods, 18 mm long. The undulator has distributed focusing built into it, to reduce the average beta function of the 70–85 MeV electron beam to about 30 cm. There are four FODO cells per segment. The permanent magnet focusing lattice consists of blocks mounted on either side of the electron beam, in the undulator gap. The most important undulator error parameter for a free electron laser is the trajectory walk-off, or lack of overlap of the photon and electron beams. Using pulsed wire magnet measurements and magnet shimming, we were able to control trajectory walk-off to less than ±50 μm per field gain length.

  1. Slow Light at High Frequencies in an Amplifying Semiconductor Waveguide

    DEFF Research Database (Denmark)

    Öhman, Filip; Yvind, Kresten; Mørk, Jesper

    2006-01-01

    We demonstrate slow-down of a modulated light signal in a semiconductor waveguide. Concatenated amplifying and absorbing sections simultaneously achieve both amplification and a controllable time delay at 15 GHz.......We demonstrate slow-down of a modulated light signal in a semiconductor waveguide. Concatenated amplifying and absorbing sections simultaneously achieve both amplification and a controllable time delay at 15 GHz....

  2. Phase Sensitive Amplifier Based on Ultrashort Pump Pulses

    CERN Document Server

    Gershikov, Alexander

    2016-01-01

    We demonstrate a narrow band phase sensitive amplifier in the pump degenerate configuration which employs ps pump pulses. Control of the amplifier bandwidth is achieved via changes of the pump spectral width. A phase sensitive gain between -6 and 6 decibels, with an overall system gain of 28dB was demonstrated.

  3. Energy Efficient and Compact RF High-Power Amplifiers

    NARCIS (Netherlands)

    Calvillo Cortés, D.A.

    2014-01-01

    The main objectives of this thesis are to improve the energy efficiency and physical form-factor of high-power amplifiers in base station applications. As such, the focus of this dissertation is placed on the outphasing amplifier concept, which can offer high-efficiency, good linearity and excellent

  4. Gain characteristics of a saturated fiber optic parametric amplifier

    DEFF Research Database (Denmark)

    Rottwitt, Karsten; Lorenzen, Michael Rodas; Noordegraaf, Danny

    2008-01-01

    In this work we discuss saturation performance of a fiber optic parametric amplifier. A simple numerical model is described and applied to specific cases. A system experiment using a saturated amplifier illustrates a 4 dB improvement in required signal to noise ratio for a fixed bit error ratio....

  5. The design of erbium-doped fiber amplifiers

    DEFF Research Database (Denmark)

    Pedersen, Bo; Bjarklev, Anders Overgaard; Povlsen, Jørn Hedegaard

    1991-01-01

    An accurate model for the erbium-doped fiber amplifier is presented. The model is used to design the index profile of the doped fiber, optimizing with regard to efficiency for inline- and preamplifiers as well as for power booster amplifiers. The predicted pump efficiencies (maximum gain to pump...

  6. Series-Tuned High Efficiency RF-Power Amplifiers

    DEFF Research Database (Denmark)

    Vidkjær, Jens

    2008-01-01

    An approach to high efficiency RF-power amplifier design is presented. It addresses simultaneously efficiency optimization and peak voltage limitations when transistors are pushed towards their power limits.......An approach to high efficiency RF-power amplifier design is presented. It addresses simultaneously efficiency optimization and peak voltage limitations when transistors are pushed towards their power limits....

  7. Optically amplifying planar glass waveguides: Laser on a chip

    DEFF Research Database (Denmark)

    Guldberg-Kjær, Søren Andreas

    The objective of this work was to devlop optically amplifying planar wavguides, using erbium-doped germano-silicate glass films deposited by PECVD (Plasma Enhanced Chemical Vapour Deposition). The waveguides should exhibit enough gain to be useful as optical amplifiers in integrated planar lightw...

  8. Ultrafast Dynamics of Quantum-Dot Semiconductor Optical Amplifiers

    DEFF Research Database (Denmark)

    Poel, Mike van der; Hvam, Jørn Märcher

    2007-01-01

    We report on a series of experiments on the dynamical properties of quantum-dot semiconductor optical amplifiers. We show how the amplifier responds to one or several ultrafast (170 fs) pulses in rapid succession and our results demonstrate applicability and ultimate limitations to application...

  9. The Warm, Rich Sound of Valve Guitar Amplifiers

    Science.gov (United States)

    Keeports, David

    2017-01-01

    Practical solid state diodes and transistors have made glass valve technology nearly obsolete. Nevertheless, valves survive largely because electric guitar players much prefer the sound of valve amplifiers to the sound of transistor amplifiers. This paper discusses the introductory-level physics behind that preference. Overdriving an amplifier…

  10. PHEMT Distributed Power Amplifier Adopting Broadband Impedance Transformer

    DEFF Research Database (Denmark)

    Narendra, K.; Limiti, E.; Paoloni, C.

    2013-01-01

    A non-uniform drain line distributed power amplifier (DPA) employing a broadband impedance transformer is presented. The DPA is based on GaAs PHEMT technology. The impedance transformer employs asymmetric coupled lines and transforms a low output impedance of the amplifier to a standard 50 Ω...

  11. Fast processes in semiconductor optical amplifiers: theory and experiment

    DEFF Research Database (Denmark)

    Mørk, Jesper

    2002-01-01

    We review the physical processes responsible for ultrafast gain and index dynamics in semiconductor optical amplifiers and discuss their impact on optical switching applications......We review the physical processes responsible for ultrafast gain and index dynamics in semiconductor optical amplifiers and discuss their impact on optical switching applications...

  12. Externally pumped millimeter-wave Josephson-junction parametric amplifier

    DEFF Research Database (Denmark)

    Levinsen, M.T; Pedersen, Niels Falsig; Sørensen, Ole

    1980-01-01

    A unified theory of the singly and doubly degenerate Josephson-junction parametric amplifier is presented. Experiments with single junctions on both amplifier modes at frequencies 10, 35, and 70 GHz are discussed. Low-noise temperature (∼100 K, single sideband (SSB)) and reasonable gain (∼8 d...

  13. A Review of High Voltage Drive Amplifiers for Capacitive Actuators

    DEFF Research Database (Denmark)

    Huang, Lina; Zhang, Zhe; Andersen, Michael A. E.

    2012-01-01

    This paper gives an overview of the high voltage amplifiers, which are used to drive capacitive actuators. The amplifiers for both piezoelectric and DEAP (dielectric electroactive polymer) actuator are discussed. The suitable topologies for driving capacitive actuators are illustrated in detail...

  14. A Power Efficient Audio Amplifier Combining Switching and Linear Techniques

    NARCIS (Netherlands)

    van der Zee, Ronan A.R.; van Tuijl, Adrianus Johannes Maria

    1998-01-01

    Integrated Class D audio amplifiers are very power efficient, but require an external filter which prevents further integration. Also due to this filter, large feedback factors are hard to realise, so that the load influences the distortion- and transfer characteristics. The amplifier presented in

  15. Subjective test of class D amplifiers without output filter

    DEFF Research Database (Denmark)

    Agerkvist, Finn T.; Fenger, Lars M.

    2004-01-01

    This paper presents the results of subjective listening tests designed to determine whether the output filter on class D amplifiers used in active loudspeakers can be omitted without audible errors occurring. The frequency range of the amplifiers was limited to 0-3 kHz corresponding to a woofer...

  16. 21 CFR 870.2050 - Biopotential amplifier and signal conditioner.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Biopotential amplifier and signal conditioner. 870.2050 Section 870.2050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... conditioner is a device used to amplify or condition an electrical signal of biologic origin. (b...

  17. Ferroelectric Field-Effect Transistor Differential Amplifier Circuit Analysis

    Science.gov (United States)

    Phillips, Thomas A.; MacLeod, Todd C.; Ho, Fat D.

    2008-01-01

    There has been considerable research investigating the Ferroelectric Field-Effect Transistor (FeFET) in memory circuits. However, very little research has been performed in applying the FeFET to analog circuits. This paper investigates the use of FeFETs in a common analog circuit, the differential amplifier. The two input Metal-Oxide-Semiconductor (MOS) transistors in a general MOS differential amplifier circuit are replaced with FeFETs. Resistors are used in place of the other three MOS transistors. The FeFET model used in the analysis has been previously reported and was based on experimental device data. Because of the FeFET hysteresis, the FeFET differential amplifier has four different operating modes depending on whether the FeFETs are positively or negatively polarized. The FeFET differential amplifier operation in the different modes was analyzed by calculating the amplifier voltage transfer and gain characteristics shown in figures 2 through 5. Comparisons were made between the FeFET differential amplifier and the standard MOS differential amplifier. Possible applications and benefits of the FeFET differential amplifier are discussed.

  18. RAMAN amplifier gain dynamics with ASE : Numerical analysis and ...

    African Journals Online (AJOL)

    Spontaneous Raman scattering add up with the amplified signal and reflect as a noise because of random phases linked with all spontaneously generated photons. The amplified spontaneous emission noise in systems with distributed Raman gain for single pump amplification is diagnosed numerically and simulated using ...

  19. External Peltier Cooler For Low-Noise Amplifier

    Science.gov (United States)

    Soper, Terry A.

    1990-01-01

    Inexpensive Peltier-effect cooling module made of few commercially available parts used to reduce thermal noise in microwave amplifier. Retrofitted to almost any microwave low-noise amplifier or receiver preamplifier used in communication, telemetry, or radar. Includes copper or aluminum cold plate held tightly against unit to be cooled by strap-type worm-gear clamps.

  20. Cross-talk free, low-noise optical amplifier

    Science.gov (United States)

    Dijaili, Sol P.; Patterson, Frank G.; Deri, Robert J.

    1995-01-01

    A low-noise optical amplifier solves crosstalk problems in optical amplifiers by using an optical cavity oriented off-axis (e.g. perpendicular) to the direction of a signal amplified by the gain medium of the optical amplifier. Several devices are used to suppress parasitic lasing of these types of structures. The parasitic lasing causes the gain of these structures to be practically unusable. The lasing cavity is operated above threshold and the gain of the laser is clamped to overcome the losses of the cavity. Any increase in pumping causes the lasing power to increase. The clamping action of the gain greatly reduces crosstalk due to gain saturation for the amplified signal beam. It also reduces other nonlinearities associated with the gain medium such as four-wave mixing induced crosstalk. This clamping action can occur for a bandwidth defined by the speed of the laser cavity. The lasing field also reduces the response time of the gain medium. By having the lasing field off-axis, no special coatings are needed. Other advantages are that the lasing field is easily separated from the amplified signal and the carrier grating fluctuations induced by four-wave mixing are decreased. Two related methods reduce the amplified spontaneous emission power without sacrificing the gain of the optical amplifier.

  1. Amplifying Islam : Pluralism, Secularism, and Religious Sounds in The Netherlands

    NARCIS (Netherlands)

    Tamimi Arab, P.

    2015-01-01

    This dissertation is an ethnographic study of the amplified azan, the Islamic call to prayer, in the Netherlands, adding a sonic dimension to analyses of the politics of Islamic aesthetics in the western world. Often rejected by opponents as noise pollution, facilitating the amplified azan is an

  2. Comparative Study of Two Multilevel Converters for Envelope Amplifier

    Directory of Open Access Journals (Sweden)

    Miroslav Vasić

    2010-06-01

    Full Text Available Modern transmitters usually have to amplify and transmit signals with simultaneous envelope and phase modulation. Due to this property of the transmitted signal, linear power amplifiers (class A, B or AB are usually used as a solution for the power amplifier stage. These amplifiers have high linearity, but suffer from low efficiency when the transmitted signal has low peak-to-average power ratio. The Kahn envelope elimination and restoration (EER technique is used to enhance efficiency of RF transmitters, by combining highly efficient,nonlinear RF amplifier (class D or E with a highly efficient envelope amplifier in order to obtain linear and highly efficientRF amplifier. This paper compares two solutions for the envelope amplifier based on a combination of multilevel converter and linear regulator. The solutions are compared regarding their efficiency, size and weight. Both solutions can reproduce any signal with maximal spectral component of 2 MHz and give instantaneous maximal power of 50 W. The efficiency measurements show that when the signals with low average value are transmitted, the implemented prototypes have up to 20% higher efficiency than linear regulator that is used as a conventional solution.

  3. A novel method to design variable gain amplifier | Mahdavi | Journal ...

    African Journals Online (AJOL)

    A novel method to design variable gain amplifier. S Mahdavi, A Soltani, M Jafarzadeh, T Moradi Khanshan. Abstract. A novel method to design of Variable gain Amplifiers (VGAs) is proposed. A low power VGA with wide range of gain variation and appropriate bandwidth using new technique is presented in this paper.

  4. Identification and utility of sequence related amplified polymorphism ...

    African Journals Online (AJOL)

    Identification and utility of sequence related amplified polymorphism (SRAP) markers linked to bacterial wilt resistance genes in potato. ... The results show that this marker system could be used in marker assisted selection (MAS) breeding program. Keywords: Sequence related amplified polymorphism (SRAP) marker, ...

  5. Fabrication of an on-line enzyme micro-reactor coupled to liquid chromatography-tandem mass spectrometry for the digestion of recombinant human erythropoietin.

    Science.gov (United States)

    Foo, Hsiao Ching; Smith, Norman W; Stanley, Shawn M R

    2015-04-01

    Our aim was to develop a fast and efficient on-line method using micro-reactors for the digestion and deglycosylation of recombinant human erythropoietin extracted from equine plasma. The trypsin digestion micro reactors were fabricated using fused silica capillaries with either a dextran-modified coating or a porous monolith that was able to immobilise the enzyme. These were both found to be reasonably robust and durable, with the trypsin immobilised on dextran-modified fused silica capillaries offering better reproducibility than the micro-reactor based upon covalent attachment of this enzyme to the polymer. It is also evident that the enzyme attached micro reactors produced some tryptic peptides in a greater yield than in-solution digestion. A peptide-N-glycosidase F reactor was also fabricated and, when coupled with the trypsin reactor, the deaminated peptides T5 DAM and T9 DAM from recombinant human erythropoietin could also be detected by LC-ESI-MS/MS analysis. These results were better than those achieved using off-line digestion plus deglycosylation reactions and the analysis required far less time and effort to complete. The use of this on-line approach improved the sensitivity, efficiency and speed of our confirmation methodology that is based upon detecting the unique peptide segments of recombinant human erythropoietin that has been affinity extracted from positive equine plasma samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Multi Carrier Modulation Audio Power Amplifier with Programmable Logic

    DEFF Research Database (Denmark)

    Christiansen, Theis; Andersen, Toke Meyer; Knott, Arnold

    2009-01-01

    . Analytically expressions, simulations and measurements result in reduced switching frequency amplitudes using MCM techniques. It is also shown that the Total Harmonic Distortion (THD) tends to be compromised compared to conventional class D amplifiers due to intermodulation products of the switching......While switch-mode audio power amplifiers allow compact implementations and high output power levels due to their high power efficiency, they are very well known for creating electromagnetic interference (EMI) with other electronic equipment. To lower the EMI of switch-mode (class D) audio power...... amplifiers while keeping the performance measures to excellent levels is therefore of high interest. In this paper a class D audio amplifier utilising Multi Carrier Modulation (MCM) will be analysed, and a prototype Master-Slave Multi Carrier Modulated (MS MCM) amplifier has been constructed and measured...

  7. Pulse-width-modulated amplifier drives for machine tools

    Energy Technology Data Exchange (ETDEWEB)

    Barkman, W.E.

    1979-11-01

    The function of a dc servo controller is to convert command and feedback information into an error signal that is used to drive a dc motor. To accomplish this, the controller utilizes a summing technique that compares an input-command voltage with a feedback voltage from an external transducer. The resultant error signal is applied to a linear or a switching servo amplifier. While the output of the linear amplifier may have the ideal representation of the desired drive signal, it does result in substantial power dissipation within the amplifier and requires forced-air cooling for power ratings above 100 to 200 W. The switching amplifier avoids this problem by rapidly changing the state of its output stage from a conducting to a nonconducting condition, thereby minimizing the operation of the output stage in the high power-dissipation region. The design and operation of the amplifier drive are described. (TFD)

  8. Cryogenic ultra-low-noise SiGe transistor amplifier.

    Science.gov (United States)

    Ivanov, B I; Trgala, M; Grajcar, M; Il'ichev, E; Meyer, H-G

    2011-10-01

    An ultra-low-noise one-stage SiGe heterojunction bipolar transistor amplifier was designed for cryogenic temperatures and a frequency range of 10 kHz-100 MHz. A noise temperature T(N) ≈ 1.4 K was measured at an ambient temperature of 4.2 K at frequencies between 100 kHz and 100 MHz for a source resistance of ~50 Ω. The voltage gain of the amplifier was 25 dB at a power consumption of 720 μW. The input voltage noise spectral density of the amplifier is about 35 pV/√Hz. The low noise resistance and power consumption makes the amplifier suitable for readout of resistively shunted DC SQUID magnetometers and amplifiers.

  9. Capacitive Trans-Impedance Amplifier Circuit with Charge Injection Compensation

    Science.gov (United States)

    Milkov, Mihail M. (Inventor); Gulbransen, David J. (Inventor)

    2016-01-01

    A capacitive trans-impedance amplifier circuit with charge injection compensation is provided. A feedback capacitor is connected between an inverting input port and an output port of an amplifier. A MOS reset switch has source and drain terminals connected between the inverting input and output ports of the amplifier, and a gate terminal controlled by a reset signal. The reset switch is open or inactive during an integration phase, and closed or active to electrically connect the inverting input port and output port of the amplifier during a reset phase. One or more compensation capacitors are provided that are not implemented as gate oxide or MOS capacitors. Each compensation capacitor has a first port connected to a compensation signal that is a static signal or a toggling compensation signal that toggles between two compensation voltage values, and a second port connected to the inverting input port of the amplifier.

  10. Fishing amplifies forage fish population collapses.

    Science.gov (United States)

    Essington, Timothy E; Moriarty, Pamela E; Froehlich, Halley E; Hodgson, Emma E; Koehn, Laura E; Oken, Kiva L; Siple, Margaret C; Stawitz, Christine C

    2015-05-26

    Forage fish support the largest fisheries in the world but also play key roles in marine food webs by transferring energy from plankton to upper trophic-level predators, such as large fish, seabirds, and marine mammals. Fishing can, thereby, have far reaching consequences on marine food webs unless safeguards are in place to avoid depleting forage fish to dangerously low levels, where dependent predators are most vulnerable. However, disentangling the contributions of fishing vs. natural processes on population dynamics has been difficult because of the sensitivity of these stocks to environmental conditions. Here, we overcome this difficulty by collating population time series for forage fish populations that account for nearly two-thirds of global catch of forage fish to identify the fingerprint of fisheries on their population dynamics. Forage fish population collapses shared a set of common and unique characteristics: high fishing pressure for several years before collapse, a sharp drop in natural population productivity, and a lagged response to reduce fishing pressure. Lagged response to natural productivity declines can sharply amplify the magnitude of naturally occurring population fluctuations. Finally, we show that the magnitude and frequency of collapses are greater than expected from natural productivity characteristics and therefore, likely attributed to fishing. The durations of collapses, however, were not different from those expected based on natural productivity shifts. A risk-based management scheme that reduces fishing when populations become scarce would protect forage fish and their predators from collapse with little effect on long-term average catches.

  11. Efficient and Compact Optical Amplifier Using EYDF

    Directory of Open Access Journals (Sweden)

    Sulaiman Wadi Harun

    2010-09-01

    Full Text Available An efficient Erbium/Ytterbium doped fiber amplifier (EYDFA is demonstrated using a 1058nm pumping wavelength, where the amplification is assisted by energy transfer between Yb and Er ions. The energy transfer increases the limit of erbium doping concentration that is imposed by concentration quenching in Erbium-doped fiber (EDF. Therefore, the gain and noise figure are severely degraded with 1480 nm pumping, where the energy transfer cannot be achieved. The use of optical isolator improves the small signal gain and noise figure by about 4.8 dB and 1.6 dB, respectively. By employing a double-pass configuration, a higher gain can be obtained with an expense of a noise figure penalty. The gain improvement of 17.0 dB is obtained at 20 mW and -50 dBm of pump and input signal powers. This shows that the double-pass configuration is an important aspect to consider when designing an efficient EYDFA.

  12. Input Impedance of the Microstrip SQUID Amplifier

    Science.gov (United States)

    Kinion, Darin; Clarke, John

    2008-03-01

    We present measurements of the complex scattering parameters of microstrip SQUID amplifiers (MSA) cooled to 4.2 K. The input of the MSA is a microstrip transmission line in the shape of a square spiral coil surrounding the hole in the SQUID washer that serves as the ground plane. The input impedance is found by measuring the reverse scattering parameter (S11) and is described well by a low-loss transmission line model. We map the low-loss transmission line model into an equivalent parallel RLC circuit in which a resistance R, inductance L, and capacitance C are calculated from the resonant frequency, characteristic impedance and attenuation factor. Using this equivalent RLC circuit, we model the MSA and input network with a lumped circuit model that accurately predicts the observed gain given by the forward scattering parameter (S21). We will summarize results for different coil geometries and terminations as well as SQUID bias conditions. A portion of this work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory in part under Contract W-7405-Eng-48 and in part under Contract DE-AC52-07NA27344 and by Lawrence Berkeley National Laboratory under Contract No. DE-AC02-05CH11231.

  13. Status Report on the Energy Amplifier

    CERN Document Server

    Rubbia, Carlo

    1994-01-01

    0ne year after its first presentation,the Energy Amplifier (EA) Project holds its promises for a environmentally acceptable form of energy extraction from nuclei, namely to eliminate or at least greatly reduce(i) the environmental impact of the long-lived highly radioactive waste;(ii) the possibility of diversions toward military applications;(iii) the risks of an accidental divergence related to the critical operation of the chain reaction and (iv) make a more efficient use of a fuel which is less radio-toxic to extract and more abundant on Earth than Uranium. In these respects the EA (or equivalent scenarios from Los Alamos and elsewhere) is comparable in performance to Thermonuclear Fusion. Bot h approches offer pratically unl;imited fuel resources: the energetic content of Lithium on the Earth's crust needed by Fusion is estimated to be seven times the one of Thorium and they are both adequate for millions of years of very intensived utilisation.However the EA can be built economically,in a variety of siz...

  14. Gold Nanoparticle Labels Amplify Ellipsometric Signals

    Science.gov (United States)

    Venkatasubbarao, Srivatsa

    2008-01-01

    The ellipsometric method reported in the immediately preceding article was developed in conjunction with a method of using gold nanoparticles as labels on biomolecules that one seeks to detect. The purpose of the labeling is to exploit the optical properties of the gold nanoparticles in order to amplify the measurable ellipsometric effects and thereby to enable ultrasensitive detection of the labeled biomolecules without need to develop more-complex ellipsometric instrumentation. The colorimetric, polarization, light-scattering, and other optical properties of nanoparticles depend on their sizes and shapes. In the present method, these size-and-shape-dependent properties are used to magnify the polarization of scattered light and the diattenuation and retardance of signals derived from ellipsometry. The size-and-shape-dependent optical properties of the nanoparticles make it possible to interrogate the nanoparticles by use of light of various wavelengths, as appropriate, to optimally detect particles of a specific type at high sensitivity. Hence, by incorporating gold nanoparticles bound to biomolecules as primary or secondary labels, the performance of ellipsometry as a means of detecting the biomolecules can be improved. The use of gold nanoparticles as labels in ellipsometry has been found to afford sensitivity that equals or exceeds the sensitivity achieved by use of fluorescence-based methods. Potential applications for ellipsometric detection of gold nanoparticle-labeled biomolecules include monitoring molecules of interest in biological samples, in-vitro diagnostics, process monitoring, general environmental monitoring, and detection of biohazards.

  15. Stochastic phenomena in a fiber Raman amplifier

    Energy Technology Data Exchange (ETDEWEB)

    Kalashnikov, Vladimir [Aston Institute of Photonic Technologies, Aston University, Birmingham (United Kingdom); Institute of Photonics, Vienna University of Technology (Austria); Sergeyev, Sergey V. [Aston Institute of Photonic Technologies, Aston University, Birmingham (United Kingdom); Ania-Castanon, Juan Diego [Instituto de Optica CSIC, Madrid (Spain); Jacobsen, Gunnar [Acreo, Kista (Sweden); Popov, Sergei [Royal Institute of Technology (KTH), Stockholm (Sweden)

    2017-01-15

    The interplay of such cornerstones of modern nonlinear fiber optics as a nonlinearity, stochasticity and polarization leads to variety of the noise induced instabilities including polarization attraction and escape phenomena harnessing of which is a key to unlocking the fiber optic systems specifications required in high resolution spectroscopy, metrology, biomedicine and telecommunications. Here, by using direct stochastic modeling, the mapping of interplay of the Raman scattering-based nonlinearity, the random birefringence of a fiber, and the pump-to-signal intensity noise transfer has been done in terms of the fiber Raman amplifier parameters, namely polarization mode dispersion, the relative intensity noise of the pump laser, fiber length, and the signal power. The obtained results reveal conditions for emergence of the random birefringence-induced resonance-like enhancement of the gain fluctuations (stochastic anti-resonance) accompanied by pulse broadening and rare events in the form of low power output signals having probability heavily deviated from the Gaussian distribution. (copyright 2016 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  16. Mutation in the negative regulatory element of the erythropoietin receptor gene in a case of sporadic primary polycythemia.

    Science.gov (United States)

    Sokol, L; Prchal, J F; D'Andrea, A; Rado, T A; Prchal, J T

    1994-05-01

    A 42-year-old Caucasian male with sporadic primary polycythemia has been followed by us for 13 years. During the time of observation, his hemoglobin had been stable, and he has never had an elevated white count or platelet count or any other stigmata of polycythemia vera (PV). Both of his parents, his three children, and all siblings have been hematologically normal. The in vitro culture of erythroid progenitors revealed an absence of autonomous erythropoietin (Epo)-independent erythroid colonies but demonstrated a marked increase in the sensitivity of erythroid progenitors to Epo. We have undertaken a study designed to determine whether a mutation in the Epo receptor (Epo-R) gene could cause the polycythemia phenotype seen in either dominant or recessive primary polycythemia described by us and others, or in polycythemia vera. We have sequenced the cytoplasmic positive and negative regulatory domains of the Epo-R genomic DNA, and a transversion of C to T in nucleotide 6148 was found in one of the patient's chromosomes. This mutation is located in the negative regulatory domain and results in a change from proline to serine (P488S). We have subsequently analyzed more than 40 chromosomes from unrelated normal subjects, as well as autosomal dominant, recessive, and sporadic primary polycythemia and polycythemia vera subjects. In no instance was the same or any other mutation in the Epo-R found. To determine if this Epo-R mutation is a cause of increased sensitivity of erythroid progenitors to erythropoietin, Ba/F3 cells (interleukin-3-dependent murine lymphoid line) were transfected with normal and mutated Epo-R cDNA, rendering the transfected cells viable and able to proliferate in Epo. Transfectants with wild-type and mutant Epo-R cDNA exhibited no difference in the presence of Epo. More recently, we were able to obtain DNA from the seven family members of the propositus and found that the nonpolycythemic mother and one of the siblings have the same Epo-R mutation

  17. Performance Optimization of a Low Noise Amplifier

    Science.gov (United States)

    Hatta, S. F. Wan Muhamad; Soin, N.

    2009-06-01

    This work presents potential performance optimization techniques that can be applied to an RF CMOS low noise amplifier (LNA). LNA noise optimization methods namely the Conjugate Noise Match (CNM), the Simultaneous Noise and Input Matching (SNIM), the Power Constrained Noise Optimization (PCNO) and the Power Constrained Simultaneous Noise and Input Matching (PCSNIM) are introduced and discussed. Through detailed analysis and review, it has been realized that the PCSNIM technique implies to be the best method in optimizing the noise performance of the LNA. The gain enhancement technique is another technique that is introduced in this work where positive feedback is employed to reduce the total conductance of the circuit and subsequently boosting the gain performance of the design. This work will also show how the amount of the gain enhancement technique is governed by stability considerations. Substrate biasing is additionally recommended to further boost the performance of the LNA so that the device employed can work more efficiently at low power voltage. To implement the forward body-biased NMOS scheme, a deep N-well process is needed, which can provide separate body region for the transistor. To demonstrate the above suggested optimization techniques, a fully-integrated narrow-band source degenerated cascode RF LNA that dissipates 19.89 mW from a 0.9 V power supply is designed and simulated using Cadence Virtuoso and Cadence's Analog Design Environment respectively, based on a 0.18 μm RF-CMOS process. The layout of the LNA is additionally presented at the end section of this paper.

  18. Class-E Amplifier Design Improvements for GSM Frequencies

    Directory of Open Access Journals (Sweden)

    Z. Nadir

    2011-06-01

    Full Text Available Efficient power amplifiers are essential in portable battery-operated systems such as mobile phones. Also, the power amplifier (PA is the most power-consuming building block in the transmitter of a portable system. This paper investigates how the efficiency of the power amplifier (which is beneficial for multiple applications in communcation sector can be improved by increasing the efficiency of switching mode class E power amplifiers for frequencies of 900 MHz and 1800 MHz. The paper tackles modeling, design improvements and verification through simulation for higher efficiencies. This is the continuation of previous work by the authors. These nonlinear power amplifiers can only amplify constant-envelope RF signals without introducing significant distortion. Mobile systems such as Advanced Mobile Phone System (AMPS and Global System for Mobile communications (GSM use modulation schemes which generate constant amplitude RF outputs in order to use efficient but nonlinear power amplifiers. Improvements in designs are suggested and higher efficiencies are achieved, to the tune of 67.1% (for 900 MHz and 67.0% (1800 MHz.

  19. Efficient performance simulation of class D amplifier output stages

    DEFF Research Database (Denmark)

    Nyboe, Flemming; Risbo, Lars; Andreani, Pietro

    2005-01-01

    Straightforward simulation of amplifier distortion involves transient simulation of operation on a sine wave input signal, and a subsequent FFT of the output voltage. This approach is very slow on class D amplifiers, since the switching behavior forces simulation time steps that are many orders...... of magnitude smaller than the duration of one period of an audio sine wave. This work presents a method of simulating the amplifier transfer characteristic using a minimum amount of simulation time, and then deriving THD from the results....

  20. FDML swept source at 1060 nm using a tapered amplifier

    DEFF Research Database (Denmark)

    Marschall, Sebastian; Klein, Thomas; Wieser, Wolfgang

    2010-01-01

    We present a novel frequency-swept light source working at 1060nm that utilizes a tapered amplifier as gain medium. These devices feature significantly higher saturation power than conventional semiconductor optical amplifiers and can thus improve the limited output power of swept sources...... in this wavelength range. We demonstrate that a tapered amplifier can be integrated into a fiber-based swept source and allows for high-speed FDML operation. The developed light source operates at a sweep rate of 116kHz with an effective average output power in excess of 30mW. With a total sweep range of 70 nm...