Erythropoietin Pretreatment Attenuates Seawater Aspiration-Induced Acute Lung Injury in Rats.

Science.gov (United States)

Ji, Mu-Huo; Tong, Jian-Hua; Tan, Yuan-Hui; Cao, Zhen-Yu; Ou, Cong-Yang; Li, Wei-Yan; Yang, Jian-Jun; Peng, Y G; Zhu, Si-Hai

2016-02-01

Seawater drowning-induced acute lung injury (ALI) is a serious clinical condition characterized by increased alveolar-capillary permeability, excessive inflammatory responses, and refractory hypoxemia. However, current therapeutic options are largely supportive; thus, it is of great interest to search for alternative agents to treat seawater aspiration-induced ALI. Erythropoietin (EPO) is a multifunctional agent with antiinflammatory, antioxidative, and antiapoptotic properties. However, the effects of EPO on seawater aspiration-induced ALI remain unclear. In the present study, male rats were randomly assigned to the naive group, normal saline group, seawater group, or seawater + EPO group. EPO was administered intraperitoneally at 48 and 24 h before seawater aspiration. Arterial blood gas analysis was performed with a gas analyzer at baseline, 30 min, 1 h, 4 h, and 24 h after seawater aspiration, respectively. Histological scores, computed tomography scan, nuclear factor kappa B p65, inducible nitric oxide synthase, caspase-3, tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, IL-10, wet-to-dry weight ratio, myeloperoxidase activity, malondialdehyde, and superoxide dismutase in the lung were determined 30 min after seawater aspiration. Our results showed that EPO pretreatment alleviated seawater aspiration-induced ALI, as indicated by increased arterial partial oxygen tension and decreased lung histological scores. Furthermore, EPO pretreatment attenuated seawater aspiration-induced increase in the expressions of pulmonary nuclear factor kappa B p65, inducible nitric oxide synthase, caspase-3, tumor necrosis factor-alpha, IL-1β, myeloperoxidase activity, and malondialdehyde when compared with the seawater group. Collectively, our study suggested that EPO pretreatment attenuates seawater aspiration-induced ALI by down-regulation of pulmonary pro-inflammatory cytokines, oxidative stress, and apoptosis.

Increased serum erythropoietin activity in rats following intrarenal injection of nickel subsulfide

International Nuclear Information System (INIS)

Hopfer, S.M.; Sunderman, F.W. Jr.; Fredrickson, T.N.; Morse, E.E.

1979-01-01

To investigate the pathopysiologic mechanisms of nickel-induced erythocytosis, serum erythropoietin activities were measured in (a) pooled serum from rats at 2 wk after intrarenal injection of αNi 3 S 2 (5 mg/rat), and (b) pooled serum from control rats at 2 wk after intrarenal injection of sterile NaCl vehicle (0.4 ml/rat). A sensitive erythropoietin bioassay was employed, which entailed repetitive administration of test serums to post-hypoxic polycythemic mice in divided doses (12 s.c. injections of 0.5 ml of serum at 6 h intervals for 3 da; total dose = 6 ml of serum/mouse). The erythropoietin detection limit was approx. = 20 I.U./liter of serum. In mice which received pooled serum from αNi 3 S 2 -treated rats, erythrocyte 59 Fe-uptake averaged 28% (S.D. +- 5) (vs 3.7 +- 1.1% in control rats; P 3 S 2 -treated rats averaged 130 I.U./liter (S.D. +- 18) (vs 27 +- 6 I.U./liter in control rats; P 3 S 2 is mediated by increased serum erythropoietin activity

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.

Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression.

Directory of Open Access Journals (Sweden)

Marta Miró-Murillo

Full Text Available Von Hippel Lindau (Vhl gene inactivation results in embryonic lethality. The consequences of its inactivation in adult mice, and of the ensuing activation of the hypoxia-inducible factors (HIFs, have been explored mainly in a tissue-specific manner. This mid-gestation lethality can be also circumvented by using a floxed Vhl allele in combination with an ubiquitous tamoxifen-inducible recombinase Cre-ER(T2. Here, we characterize a widespread reduction in Vhl gene expression in Vhl(floxed-UBC-Cre-ER(T2 adult mice after dietary tamoxifen administration, a convenient route of administration that has yet to be fully characterized for global gene inactivation. Vhl gene inactivation rapidly resulted in a marked splenomegaly and skin erythema, accompanied by renal and hepatic induction of the erythropoietin (Epo gene, indicative of the in vivo activation of the oxygen sensing HIF pathway. We show that acute Vhl gene inactivation also induced Epo gene expression in the heart, revealing cardiac tissue to be an extra-renal source of EPO. Indeed, primary cardiomyocytes and HL-1 cardiac cells both induce Epo gene expression when exposed to low O(2 tension in a HIF-dependent manner. Thus, as well as demonstrating the potential of dietary tamoxifen administration for gene inactivation studies in UBC-Cre-ER(T2 mouse lines, this data provides evidence of a cardiac oxygen-sensing VHL/HIF/EPO pathway in adult mice.

Autosomal dominant familial erythrocytosis due to autonomous erythropoietin production

International Nuclear Information System (INIS)

Distelhorst, C.W.; Wagner, D.S.; Goldwasser, E.; Adamson, J.W.

1981-01-01

A family is described in which four members spanning three consecutive generations have erythrocytosis associated with a normal hemoglobin oxygen affinity. When bone marrow from one affected family member was cultured in vitro, erythroid colonies formed only when erythropoietin was added to the culture. Serum erythropoietin, measured by radioimmunoassay, was significantly elevated above normal in each of the affected family members. Bioassayable erythropoietin was detected in the urine of two of the three affected family members. In two of the affected family members, erythropoietin was measured in serum by radioimmunoassay and in urine by bioassay before and for 4 days following an isovolemic phlebotomy, which reduced the red cell mass by 20%. Neither serum nor urinary erythropoietin levels changed following phlebotomy. The erythrocytosis in this family appears to be secondary to inappropriately increased erythropoietin production unassociated with a decrease in the blood oxygen-carrying capacity. This is the first instance in which autonomous erythropoietin production appears to be inherited on an autosomal dominant basis

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.

Pump-induced optical distortions in disk amplifier modules: holographic and interferometric measurements

International Nuclear Information System (INIS)

Linford, G.J.; Chau, H.H.; Glaze, J.A.; Layne, C.B.; Rainer, F.

1975-01-01

Interferometric measurements have been made of the optical distortions induced in laser disk amplifiers during the flashlamp pumping pulse. Both conventional interferometric methods and the techniques of double exposure holographic interferometry were used to identify four major sources of pump-induced optical distortions: subsonic intrusion of hot gas (traced to leakage of atmospheric oxygen into the amplifier), microexplosions of dust particles, thermally induced optical distortions in the glass disks, and gaseous optical distortion effects caused by turbulent flow of the purging nitrogen gas supply used within the laser amplifier head. Methods for reducing or eliminating the effects of each of these optical distortions are described

21 CFR 864.7250 - Erythropoietin assay.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Erythropoietin assay. 864.7250 Section 864.7250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7250 Erythropoietin...

Role of Erythropoietin in Renal Anemia Therapy

African Journals Online (AJOL)

of erythropoietin and others drugs in renal anemia treatment, as well as the cause of erythropoietin resistance. .... mouth health, atrophy prevention, prevention of artery hardening ... Secondary hyperthyroidism can lead to osteitis fibrosa ...

Neuronal erythropoietin overexpression is protective against kanamycin-induced hearing loss in mice.

Science.gov (United States)

Bächinger, David; Horvath, Lukas; Eckhard, Andreas; Goosmann, Madeline M; Honegger, Tim; Gassmann, Max; Vogel, Johannes; Naldi, Arianne Monge

2018-07-01

Aminoglycosides have detrimental effects on the hair cells of the inner ear, yet these agents indisputably are one of the cornerstones in antibiotic therapy. Hence, there is a demand for strategies to prevent aminoglycoside-induced ototoxicity, which are not available today. In vitro data suggests that the pleiotropic growth factor erythropoietin (EPO) is neuroprotective against aminoglycoside-induced hair cell loss. Here, we use a mouse model with EPO-overexpression in neuronal tissue to evaluate whether EPO could also in vivo protect from aminoglycoside-induced hearing loss. Auditory brainstem response (ABR) thresholds were measured in 12-weeks-old mice before and after treatment with kanamycin for 15 days, which resulted in both C57BL/6 and EPO-transgenic animals in a high-frequency hearing loss. However, ABR threshold shifts in EPO-transgenic mice were significantly lower than in C57BL/6 mice (mean difference in ABR threshold shift 13.6 dB at 32 kHz, 95% CI 3.8-23.4 dB, p = 0.003). Correspondingly, quantification of hair cells and spiral ganglion neurons by immunofluorescence revealed that EPO-transgenic mice had a significantly lower hair cell and spiral ganglion neuron loss than C57BL/6 mice. In conclusion, neuronal overexpression of EPO is protective against aminoglycoside-induce hearing loss, which is in accordance with its known neuroprotective effects in other organs, such as the eye or the brain. Copyright © 2018 Elsevier B.V. All rights reserved.

Heat stroke induced cerebellar dysfunction: A “forgotten syndrome”

Science.gov (United States)

Kosgallana, Athula D; Mallik, Shreyashee; Patel, Vishal; Beran, Roy G

2013-01-01

We report a case of heat stroke induced acute cerebellar dysfunction, a rare neurological disease characterized by gross cerebellar dysfunction with no acute radiographic changes, in a 61 years old ship captain presenting with slurred speech and gait ataxia. A systematic review of the literature on heat stroke induced cerebellar dysfunction was performed, with a focus on investigations, treatment and outcomes. After review of the literature and detailed patient investigation it was concluded that this patient suffered heat stroke at a temperature less than that quoted in the literature. PMID:24340279

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.

Hypoxia and the initiation of erythropoietin production. [Rats

Energy Technology Data Exchange (ETDEWEB)

Schooley, J.C.; Mahlmann, L.J.

1975-01-01

The initiation of erythropoietin production in rats by hypoxia is dependent upon the magnitude of the hypoxic exposure, the position of the oxygen dissociation curve at the time of the hypoxic exposure, and the animal's endocrine status. Normal male rats produce more erythropoietin and elevate their intraerythrocytic 2,3-DPG levels more than female rats exposed to the same degree of hypoxia. Hypophysectomized rats produce erythropoietin following severe hypoxic exposure, but do not elevate their 2,3-DPG levels above control values. Respiratory acidosis in rats produced by breathing 10 percent CO/sub 2/ or by the injection of acetazolamide inhibits the initiation of erythropoietin production by hypoxic environments, but this inhibition is minimal in animals with metabolic acidosis produced by ureterligation. Changes in serum erythropoietin levels and the in vitro P/sub 50/ appear to be two separate but interrelated physiological events which occur during the adaptation of animals to hypoxic environments.

Mechanisms and mediators of hypertension induced by erythropoietin and related molecules.

Science.gov (United States)

Agarwal, Rajiv

2017-12-08

Hypertension is a common but frequently overlooked adverse effect of erythropoietin (EPO) therapy. Underreporting of hypertension with EPO is likely due to either more aggressively managing hypertension through the prescription of antihypertensive drugs or closer attention to dry weight. The purpose and focus of this review is to critically evaluate the mechanisms of EPO-induced hypertension. Preclinical data are considered first, followed by clinical data where available. Mediated by a variety of molecules, there is an imbalance in the vascular tone favoring net vasoconstriction that mediates EPO-induced hypertension. Animal studies show the primary importance of chronic kidney disease in the genesis of EPO-induced hypertension. Preclinical studies show deranged regulation of the nitric oxide, endothelins and porstanoids and the sympathoadrenal and renin-angiotensin pathways as causes of EPO-induced hypertension. Human studies suggest that EPO administration is also associated with increased responsiveness to catecholamines and angiotensin II on vascular tissue; in addition, hypoxia-induced vasodilation may be impaired in those with EPO-induced hypertension. There is little evidence for EPO as a direct vasoconstrictor or its effect on blood viscosity as a mechanism of EPO-induced hypertension. EPO-induced hypertension, at least in part, appears to be independent of an increase in hemoglobin, because experiments show that hemoglobin may be increased by EPO without an increase in blood pressure (BP) by simply treating the animals with EPO-binding protein and that treatment with EPO in the setting of iron deficiency may not increase hemoglobin but may still increase BP. However, experimental data are not consistent across studies and better mechanistic designs are needed, especially in patients with chronic kidney disease, to dissect the precise mechanism of EPO-induced hypertension. Animal studies suggest that hypoxia-inducible factor stablizers may induce

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  

FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell

International Nuclear Information System (INIS)

Chen, Yi; Xie, Xiaoyan; Li, Xinyi; Wang, Peiqi; Jing, Qian; Yue, Jiaqi; Liu, Yang; Cheng, Zhong; Li, Jingyi; Song, Haixing; Li, Guoyu; Liu, Rui; Wang, Jinhui

2016-01-01

Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.

FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell

Energy Technology Data Exchange (ETDEWEB)

Chen, Yi [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu (China); Xie, Xiaoyan; Li, Xinyi; Wang, Peiqi [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Jing, Qian; Yue, Jiaqi; Liu, Yang [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Cheng, Zhong [Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu (China); Li, Jingyi, E-mail: li--jingyi@hotmail.com [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Song, Haixing [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Li, Guoyu, E-mail: liguoyulisa@163.com [School of Pharmacy, Shihezi University, Shihezi 832003 (China); Liu, Rui, E-mail: liurui_scu@hotmail.com [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Wang, Jinhui [School of Pharmacy, Shihezi University, Shihezi 832003 (China)

2016-05-20

Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.

Determining Polarities Of Distant Lightning Strokes

Science.gov (United States)

Blakeslee, Richard J.; Brook, Marx

1990-01-01

Method for determining polarities of lightning strokes more than 400 km away. Two features of signal from each stroke correlated. New method based on fact each stroke observed thus far for which polarity determined unambiguously, initial polarity of tail same as polarity of initial deflection before initial-deflection signal altered by propagation effects. Receiving station equipped with electric-field-change antenna coupled to charge amplifier having time constant of order of 1 to 10 seconds. Output of amplifier fed to signal-processing circuitry, which determines initial polarity of tail.

The Relationship of Erythropoietin Receptor Expression and ...

African Journals Online (AJOL)

2018-04-04

Apr 4, 2018 ... brain tumor characterized with poor prognosis and short survival. In addition to the standard treatment protocols, targeted molecular treatment options are under trial. In the recent trials, erythropoietin and erythropoietin receptor were found to be linked with the progression of GBM cells. Aim: In this study, we.

Evaluation of functional erythropoietin receptor status in skeletal muscle in vivo

DEFF Research Database (Denmark)

Christensen, Britt; Lundby, Carsten; Jessen, Niels

2012-01-01

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...... 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...

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...

Molecular and Physiological Factors of Neuroprotection in Hypoxia-tolerant Models: Pharmacological Clues for the Treatment of Stroke

Directory of Open Access Journals (Sweden)

Thomas I. Nathaniel

2015-01-01

Full Text Available The naked mole-rat possesses several unique physiological and molecular features that underlie their remarkably and exceptional resistance to tissue hypoxia. Elevated pattern of Epo, an erythropoietin (Epo factor; c-fos; vascular endothelial growth factor (VEGF; and hypoxia-inducible factors (HIF-1α contribute to the adaptive strategy to cope with hypoxic stress. Moreover, the naked mole-rat has a lower metabolic rate than any other eutherian mammal of comparable size that has been studied. The ability to actively reduce metabolic rate represents a strategy widely used in the face of decreased tissue oxygen availability. Understanding the different molecular and physiological factors that induce metabolic suppression could guide the development of pharmacological agents for the clinical management of stroke patient.

Active Smoking and Hematocrit and Fasting Circulating Erythropoietin Concentrations in the General Population

NARCIS (Netherlands)

Eisenga, Michele F.; Kieneker, Lyanne M.; Touw, Daan J.; Nolte, Ilja M.; van der Meer, Peter; Huls, Gerwin; Gaillard, Carlo A. J. M.; Bakker, Stephan J. L.

Cigarette smoking continues to be one of the major risk factors for increased morbidity and mortality worldwide. Among many adverse health effects, smoking can induce erythrocytosis, which is commonly believed to result from elevated serum erythropoietin (EPO) levels. Currently, however, this notion

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.

Erythropoietin protects against rhabdomyolysis-induced acute kidney injury by modulating macrophage polarization

Science.gov (United States)

Wang, Shuo; Zhang, Chao; Li, Jiawei; Niyazi, Sidikejiang; Zheng, Long; Xu, Ming; Rong, Ruiming; Yang, Cheng; Zhu, Tongyu

2017-01-01

Erythropoietin (EPO) is a well-known hormone that is clinically used for the treatment of anemia. Very recently, an increasing body of evidence showed that EPO could still regulate bioactivities of macrophages. However, the details about the immunomodulatory effect of EPO on macrophages are not fully delineated, particularly in the setting of renal damages. Therefore, in the present study, we determined whether EPO could exert an impact on the dynamics of macrophages in a well-established model of rhabdomyolysis-induced acute kidney injury and explored the potential mechanisms. EPO was found to ameliorate kidney injuries by reducing macrophages recruitment and promoting phenotype switch toward M2 macrophages in vivo. It was also confirmed that EPO could directly suppress pro-inflammatory responses of M1 macrophages and promote M2 marker expression in vitro. Data indicated the possible involvement of Jak2/STAT3/STAT6 pathway in the augmentation of EPO on M2 polarization. These results improved the understanding of the immunoregulatory capacity of EPO on macrophages, which might optimize the therapeutic modalities of EPO. PMID:28383559

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.

Recovery of the Erythropoietin-Sensitive Stem-Cell Population following Total-Body X-Irradiation

Energy Technology Data Exchange (ETDEWEB)

Byron, J. W. [Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester (United Kingdom)

1968-08-15

Erythropoietin acts upon haemopoietic stem cells to initiate their differentiation into the erythroid series. This effect may be used in polycythaemic mice to estimate changes in the erythropoietin-sensitive stem-cell population following total-body irradiation (TBR). Generally, single doses of erythropoietin, less than that needed for maximum stem-cell response, are used to estimate changes in the stem-cell population. The validity of results using this test is based upon accepting several assumptions regarding erythropoietin kinetics. These are: (a) the contribution of endogenous erythropoietin is always negligible; (b) the origin of the dose-response curve to erythropoietin alters only because of changes in stem-cell numbers; (c) the proportion of stem cells responding to a given concentration of erythropoietin is independent of stem-cell numbers; (d) the slope of the dose-response curve does not alter; and (e) competition between erythropoietin and other factors for the stem cells remains unchanged. The studies to be reported indicate that some of these assumptions m a y not always be valid. Following 150 rad TBR, changes in erythropoietin dose-response curves were not always due to changes in the size of the stem-cell population, but also due to changes in erythropoietin kinetics. Changes in erythropoietin kinetics could be corrected for by using doses of erythropoietin which at any particular time after TBR gave maximum stem-cell response; through full dose-response studies, the nature of changes in erythropoietin kinetics following TBR could be established. These studies appear to explain discrepancies in results obtained in different laboratories using the erythropoietin test. The effect of 150 rad TBR on the erythropoietin-sensitive stem-cell population is an initial depression within 30 min to 20% of normal followed by a second depression (post-irradiation dip) at about 12 h. Twenty-four hours after TBR there is a recovery to the initial depression. This

Constraint-induced movement therapy after stroke

NARCIS (Netherlands)

Kwakkel, G.; Veerbeek, J.M.; van Wegen, E.E.H.; Wolf, S.L.

2015-01-01

Constraint-induced movement therapy (CIMT) was developed to overcome upper limb impairments after stroke and is the most investigated intervention for the rehabilitation of patients. Original CIMT includes constraining of the non-paretic arm and task-oriented training. Modified versions also apply

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

OpenAIRE

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

2015-01-01

Background and Purpose 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-?-d-glucoside, also known ...

Cervical spinal erythropoietin induces phrenic motor facilitation via ERK and Akt signaling

Science.gov (United States)

Dale, Erica A.; Satriotomo, Irawan; Mitchell, Gordon S.

2012-01-01

Erythropoietin (EPO) is typically known for its role in erythropoiesis, but is also a potent neurotrophic/neuroprotective factor for spinal motor neurons. Another trophic factor regulated by Hypoxia-Inducible Factor-1, vascular endothelial growth factor (VEGF), signals via ERK and Akt activation to elicit long-lasting phrenic motor facilitation (pMF). Since EPO also signals via ERK and Akt activation, we tested the hypothesis that EPO elicits similar pMF. Using retrograde labeling and immunohistochemical techniques, we demonstrate in adult, male, Sprague-Dawley rats that EPO and its receptor, EPO-R, are expressed in identified phrenic motor neurons. Intrathecal EPO at C4 elicits long-lasting pMF; integrated phrenic nerve burst amplitude increased >90 min post-injection (63±12% baseline 90 min post-injection; pphrenic motor neurons; EPO also increased pAkt (1.6 fold vs controls; pphrenic motor neurons (p<0.05), indicating a complex interaction between these kinases. We conclude that EPO elicits spinal plasticity in respiratory motor control. Since EPO expression is hypoxia-sensitive, it may play a role in respiratory plasticity in conditions of prolonged or recurrent low oxygen. PMID:22539857

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.

EFFECT OF MODIFIED CONSTRAINT INDUCED THERAPY ON UPPERLIMB FUNCTIONAL RECOVERY IN YOUNG STROKE SUBJECTS

Directory of Open Access Journals (Sweden)

Kiran Prakash Pappala

2014-10-01

Full Text Available Background: The aim of this study is to evaluate the effect of modified constraint induced therapy on upper limb functional recovery in young stroke subjects. Most of the stroke rehabilitation units following conventional rehabilitation methods for treatment of the stroke patients where these methods have been proved to be less useful especially in the young stroke subjects. Hence the purpose of this study is to see the effect of modified constraint induced therapy which is a task specific training method for upperlimb in young stroke subjects. Methods: Total of 40 young stroke subjects who is having minimal motor criterion and met other inclusion criteria were recruited from department of physiotherapy, g.s.l.general hospital. Pre and post intervention measures were taken using Wolf motor function test and Jebsen Taylor hand function test. Results: In this study had shown significant improvements in the modified constraint induced therapy group when compared to the conventional rehabilitation alone. P value between groups was < 0.05. Conclusion: In this study concludes that addition of 15 minutes modified constraint induced movement therapy to conventional physiotherapy is a useful adjunct in functional recovery of upper limb among young stroke subjects

Tissue inhibitor of matrix metalloproteinase-1 mediates erythropoietin-induced neuroprotection in hypoxia ischemia.

Science.gov (United States)

Souvenir, Rhonda; Fathali, Nancy; Ostrowski, Robert P; Lekic, Tim; Zhang, John H; Tang, Jiping

2011-10-01

Previous studies have shown that erythropoietin (EPO) is neuroprotective in both in vivo and in vitro models of hypoxia ischemia. However these studies hold limited clinical translations because the underlying mechanism remains unclear and the key molecules involved in EPO-induced neuroprotection are still to be determined. This study investigated if tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and its upstream regulator signaling molecule Janus kinase-2 (JAK-2) are critical in EPO-induced neuroprotection. Hypoxia ischemia (HI) was modeled in-vitro by oxygen and glucose deprivation (OGD) and in-vivo by a modified version of Rice-Vannucci model of HI in 10-day-old rat pups. EPO treated cells were exposed to AG490, an inhibitor of JAK-2 or TIMP-1 neutralizing antibody for 2h with OGD. Cell death, phosphorylation of JAK-2 and signal transducers and activators of transcription protein-3 (STAT-3), TIMP-1 expression, and matrix metalloproteinase-9 (MMP-9) activity were measured and compared with normoxic group. Hypoxic ischemic animals were treated one hour following HI and evaluated 48 h after. Our data showed that EPO significantly increased cell survival, associated with increased TIMP-1 activity, phosphorylation of JAK-2 and STAT-3, and decreased MMP-9 activity in vivo and in vitro. EPO's protective effects were reversed by inhibition of JAK-2 or TIMP-1 in both models. We concluded that JAK-2, STAT-3 and TIMP-1 are key mediators of EPO-induced neuroprotection during hypoxia ischemia injury. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Effect of erythropoietin on acoustically traumatized rat cochlea: an immunohistochemical study.

Science.gov (United States)

Gürgen, Oğuzhan; Gürgen, Seren Gülşen; Kirkim, Günay; Kolatan, Efsun; Gürkan, Selhan; Güvenç, Yeşim; Eskiizmir, Görkem

2014-08-01

To investigate the audiological and histopathological effects of erythropoietin on acoustic overstimulation in rats. Twenty-two male Wistar albino rats were divided into 3 groups: sham group (n = 7), erythropoietin injection group (n = 8), and saline injection group (n = 7). Both erythropoietin and saline injection groups were exposed to white noise (100 decibel [dB] sound pressure level [SPL]) for 3 hours. Auditory brainstem responses were measured before, immediately after, and on the 7th day of noise exposure. All animals were sacrificed on the 7th day and temporal bones were collected. The serial sections of the cochleae were stained by caspase-3 and caspase-9 immunostaining and by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method in order to detect apoptotic cells. In the saline group statistically significant differences were detected between the baseline and immediate postacoustic overstimulation thresholds of click and 6 kHz stimuli. However, when the baseline and immediate postacoustic overstimulation thresholds of click and 6 kHz stimuli were compared in the erythropoietin injection group, no statistically significant difference was determined. Histopathologic evaluations demonstrated that erythropoietin decreased the amount of apoptotic cells in the cochlea. Erythropoietin is likely to prevent the acute threshold changes and decrease the amount of apoptosis in cochlea after acoustic overstimulation in rats.

Constraint-induced movement therapy promotes brain functional reorganization in stroke patients with hemiplegia

Science.gov (United States)

Wang, Wenqing; Wang, Aihui; Yu, Limin; Han, Xuesong; Jiang, Guiyun; Weng, Changshui; Zhang, Hongwei; Zhou, Zhiqiang

2012-01-01

Stroke patients with hemiplegia exhibit flexor spasms in the upper limb and extensor spasms in the lower limb, and their movement patterns vary greatly. Constraint-induced movement therapy is an upper limb rehabilitation technique used in stroke patients with hemiplegia; however, studies of lower extremity rehabilitation are scarce. In this study, stroke patients with lower limb hemiplegia underwent conventional Bobath therapy for 4 weeks as baseline treatment, followed by constraint-induced movement therapy for an additional 4 weeks. The 10-m maximum walking speed and Berg balance scale scores significantly improved following treatment, and lower extremity motor function also improved. The results of functional MRI showed that constraint-induced movement therapy alleviates the reduction in cerebral functional activation in patients, which indicates activation of functional brain regions and a significant increase in cerebral blood perfusion. These results demonstrate that constraint-induced movement therapy promotes brain functional reorganization in stroke patients with lower limb hemiplegia. PMID:25337108

Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

Science.gov (United States)

Mao, Leilei; Li, Peiying; Zhu, Wen; Cai, Wei; Liu, Zongjian; Wang, Yanling; Luo, Wenli; Stetler, Ruth A; Leak, Rehana K; Yu, Weifeng; Gao, Yanqin; Chen, Jun; Chen, Gang; Hu, Xiaoming

2017-07-01

Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic

Biology of erythropoietin.

Science.gov (United States)

Lacombe, C; Mayeux, P

1998-08-01

Erythropoietin (Epo) controls the proliferation, differentiation and survival of the erythroid progenitors. This cytokine was cloned in 1985 and rapidly became used for treatment of anemia of renal failure, opening the way to the first clinical trials of a hematopoietic growth factor. The clonage of one chain of the Epo receptor followed in 1989, thereby opening the research on intracellular signal transduction induced by Epo. Epo is synthesized mainly by the kidney and the liver and sequences required for tissue-specific expression have been localized in the Epo gene. A 3'enhancer is responsible for hypoxia-inducible Epo gene expression. HIF-1 alpha and beta proteins bind to this enhancer. Gene regulation by hypoxia is widespread in many cells and involves numerous genes in addition to the Epo gene. The Epo receptor belongs to the cytokine receptor family and includes a p66 chain which is dimerized upon Epo activation; two accessory proteins defined by cross-linking remain to be characterized. Epo binding induces the stimulation of Jak2 tyrosine kinase. Jak2 activation leads to the tyrosine phosphorylation of several proteins including the Epo receptor itself. As a result, different intracellular pathways are activated: Ras/MAP kinase, phosphatidylinositol 3-kinase and STAT transcription factors. However, the exact mechanisms by which the proliferation and/or the differentiation of erythroid cells are regulated after Epo stimulation are not known. Furthermore, target disruption of both Epo and Epo receptor showed that Epo was not involved in the commitment of the erythroid lineage and seemed to act mainly as a survival factor.

Studying of the standardization principles of pharmacological activity of recombinant erythropoietin preparations

OpenAIRE

A. K. Yakovlev; L. A. Gayderova; N. A. Alpatova; T. N. Lobanova; E. L. Postnova; E. I. Yurchikova; T. A. Batuashvili; R. A. Volkova; V. N. Podkuiko; Yu. V. Olefir

2016-01-01

Analysis of the publications devoted to the structure, functions, mechanism of action of erythropoietin is given in the article. Erythropoietin preparations derived from recombinant DNA technology are a mixture of isoforms with different biological activity, which determine the biological properties pharmacological activity, pharmacokinetics, efficacy and safety of medicinal product. Erythropoietin preparations derived by using recombinant DNA technology are a mixture of isoforms with differe...

Recombinant Erythropoietin And Blood Transfusion In Very Low Birth Weight Infants

Directory of Open Access Journals (Sweden)

Keramat Nouri

2005-05-01

Full Text Available Backgroundp: Very low birth weight infants ( <1500 g frequently require blood transfusions because of repeated blood sampling accompanied by anemia of prematurity. Methods: In an attempt to identify the effect of human recombinant erythropoietin to decrease the requirement for blood transfusions, erythropoietin was administered to 24 pre term infants less than 1500 g prospectively from September 1999 till December2000. Data about the characteristics of the population, the severity of diseases, and treatment with erythropoietin, clinical diagnosis, initial and subsequent hemoglobin, volume of blood loss, and the number of blood transfusions were recorded. These results were compared with data from the recorded information of 49 infants who did not receive erythropoietin during those past 2 years. There were no differences between the 2 groups with regard to the gestational age, birth weight, clinical diagnosis, severity of the illness, primary causes of admission, and initial hematologic parameters such as hemoglobin, hematocrit and reticulocytes. Erythropoietin was administered in a dose of 200 ill/kg three times weekly for 6-8 weeks accompanied with iron supplement 6 mg/ kg/day. Transfusions were administered according to protocol. Results: There was no significant difference between the number of blood transfusion among these 2 groups (p= 0.07. However, transfusions in the erythropoietin treated group were fewer in comparison to the other group (1.9 +1-1.6 to 3.2 +/-1.1. No difference was observed between final hemoglobin and hematocrit levels among the two groups (10.3 +1- 0.9 vs. 10.4 +1- 0.7 and 33.7 +1- 2.3 vs. 32.2 +1- 2.2. Conclusion: Very low birth weight infants receive frequent blood transfusions but a reduction in transfusion requirements was not apparent after administration of erythropoietin and iron in preterm infants in this study. However, the lack of impact on transfusion requirements fails to support routine use of

Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid progenitors

NARCIS (Netherlands)

van den Akker, Emile; van Dijk, Thamar; Parren-van Amelsvoort, Martine; Grossmann, Katja S.; Schaeper, Ute; Toney-Earley, Kenya; Waltz, Susan E.; Löwenberg, Bob; von Lindern, Marieke

2004-01-01

Erythropoietin (EPO) is required for cell survival during differentiation and for progenitor expansion during stress erythropoiesis. Although signaling pathways may couple directly to docking sites on the EPO receptor (EpoR), additional docking molecules expand the signaling platform of the

Accuracy of erythropoietin determination in the dialysate of CAPD patients

NARCIS (Netherlands)

Struijk, D. G.; Koomen, G. C.; Krediet, R. T.; Arisz, L.

1990-01-01

In vitro experiments were performed to analyze problems with the determination of erythropoietin in dialysate. Human recombinant erythropoietin (EPO; 4000 U/L) was added to several fluids, to glass or polystyrene tubes with or without addition of bovine serum albumin (BSA) and to dialysate bags. The

Polarization-maintaining, double-clad fiber amplifier employing externally applied stress-induced birefringence

International Nuclear Information System (INIS)

Koplow, Jeffrey P.; Goldberg, Lew; Moeller, Robert P.; Kliner, Dahv A. V.

2000-01-01

We report a new approach to obtaining linear-polarization operation of a rare-earth-doped fiber amplifier in which the gain fiber is coiled under tension to induce birefringence. We demonstrated this method by constructing an Er/Yb-doped, double-clad, single-mode fiber amplifier with an output power of 530 mW and a polarization extinction ratio of >17 dB (when seeded with linearly polarized light) at a wavelength of ∼1.5 μm . The technique is achromatic, permits single- or multiple-pass operation of the amplifier, requires no additional components in the optical path, leaves the fiber ends unobstructed, and is inexpensive to implement. (c) 2000 Optical Society of America

Protective Effects of Erythropoietin and N-Acetylcysteine on Methotrexate-Induced Lung Injury in Rats

Directory of Open Access Journals (Sweden)

Hasan Kahraman

2013-03-01

Full Text Available Objective: Methotrexate (MTX is known to have deleterious side effects on lung tissue. We aimed to investigate the effects of erythropoietin (EPO and N-acetyl-cysteine (NAC on MTX-induced lung injury in rats. Study Design: Animal experiment. Material and Methods: Twenty-six female Sprague-Dawley rats were divided into 4 groups. Sham group, 0.3 mL saline; MTX group, 5 mg/kg MTX; EPO group, 5mg/kg MTX and 2000 IU/kg EPO; NAC group, 5 mg/kg MTX and 200 mg/kg NAC were administered once daily for 4 consecutive days. Malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT and inflammation and congestion scores in lung tissues were evaluated. Results: In MTX group MDA were significantly higher, CAT and SOD were significantly lower than in sham, EPO and NAC groups (p0.005. In group MTX both scores were significantly higher than in sham (p<0.005. The congestion score of group MTX was significantly higher than those of group EPO and NAC (p<0.005. Conclusion: EPO and NAC have significant preventive effects on MTX-induced lung injury in rats. Decreased antioxidant capacity and increased MDA level may cause the oxidative damage in MTX group. Also, higher antioxidant capacity and lower MDA level may be a response to oxidative stress in EPO and NAC groups.

Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds.

Science.gov (United States)

Galeano, Mariarosaria; Altavilla, Domenica; Bitto, Alessandra; Minutoli, Letteria; Calò, Margherita; Lo Cascio, Patrizia; Polito, Francesca; Giugliano, Giovanni; Squadrito, Giovanni; Mioni, Chiara; Giuliani, Daniela; Venuti, Francesco S; Squadrito, Francesco

2006-04-01

Erythropoietin interacts with vascular endothelial growth factor (VEGF) and stimulates endothelial cell mitosis and motility; thus it may be of importance in the complex phenomenon of wound healing. The purpose of this study was to investigate the effect of recombinant human erythropoietin (rHuEPO) on experimental burn wounds. Randomized experiment. Research laboratory. C57BL/6 male mice weighing 25-30 g. Mice were immersed in 80 degrees C water for 10 secs to achieve a deep-dermal second degree burn. Animals were randomized to receive either rHuEPO (400 units/kg/day for 14 days in 100 microL subcutaneously) or its vehicle alone (100 microl/day distilled water for 14 days subcutaneously). On day 14 the animals were killed. Burn areas were used for histologic examination, evaluation of neoangiogenesis by immunohistochemistry, and expression (Western blot) of the specific endothelial marker CD31 as well as quantification of microvessel density, measurement of VEGF wound content (enzyme-linked immunosorbent assay), expression (Western blot) of endothelial and inducible nitric oxide synthases, and determination of wound nitric oxide (NO) products. rHuEPO increased burn wound reepithelialization and reduced the time to final wound closure. These effects were completely abated by a passive immunization with specific antibodies against erythropoietin. rHuEPO improved healing of burn wound through increased epithelial proliferation, maturation of the extracellular matrix, and angiogenesis. The hematopoietic factor augmented neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of the specific endothelial marker CD31. Furthermore, rHuEPO enhanced the wound content of VEGF caused a marked expression of endothelial and inducible nitric oxide synthases and increased wound content of nitric oxide products. Our study suggests that rHuEPO may be an effective therapeutic approach to improve clinical outcomes after thermal injury.

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 levels...... and glucose tolerance, without altering total body weight or retroperitoneal fat mass. Concomitantly, EPO partially rescued insulin-stimulated AKT activation, reduced markers of oxidative stress, and restored heat-shock protein 72 expression in soleus muscles from HFD-fed rats. Incubation of skeletal muscle...... not directly activate the phosphorylation of AKT in muscle cells. We propose that the reduced systemic inflammation or oxidative stress that we observed after treatment with EPO could contribute to the improvement of whole-body glucose metabolism....

Drug-induced Hypothermia by 5HT1A Agonists Provide Neuroprotection in Experimental Stroke

DEFF Research Database (Denmark)

Johansen, Flemming Fryd; Hasseldam, Henrik; Nybro Smith, Matthias

2014-01-01

BACKGROUND: Drug-induced hypothermia reduces brain damage in animal stroke models and is an undiscovered potential in human stroke treatment. We studied hypothermia induced by the serotonergic agonists S14671 (1-[2-(2-thenoylamino)ethyl]-4[1-(7- methoxynaphtyl)]piperazine) and ipsapirone in a rat...... therapeutic hypothermia....

[Effects of intermittent hypoxic exposure on the parameter of erythrocyte and serum hypoxia inducible factor-1 alpha and erythropoietin levels].

Science.gov (United States)

Zhang, Cheng-yan; Zhang, Ji-xin; Lü, Xiao-tao; Li, Bao-yu

2009-10-01

To investigate the effects of intermittent hypoxic exposure and normoxic convalescence on the parameter of erythrocyte and serum hypoxia inducible factor-1 alpha (HIF-1alpha) and erythropoietin (EPO) levels. Rat models of intermittent hypoxic exposure were established, combined with the clinical research on volunteers experiencing the intermittent plateau work. Blood samples for red blood cell (RBC) counts, hemoglobin (Hb) and hematocrit (HCT) were collected, serum HIF-1alpha and EPO levels were measured using enzyme linked immunosorbent assay. RBC counts, Hb concentration and HCT were significantly higher than the normoxic group (P hypoxic exposure can enhance serum hypoxia inducible factor-1 alpha and erythropointin levels and the generation of red blood cells, which leads to an increase in hemoglobin concentration and hematocrit. The results have changed with the hypoxic exposure period prolonged. Normoxic convalescence after intermittent hypoxic exposure can make the related indexes reduced, and contribute to the organism recovery.

Protein-Energy Malnutrition Exacerbates Stroke-Induced Forelimb Abnormalities and Dampens Neuroinflammation.

Science.gov (United States)

Alaverdashvili, Mariam; Caine, Sally; Li, Xue; Hackett, Mark J; Bradley, Michael P; Nichol, Helen; Paterson, Phyllis G

2018-02-03

Protein-energy malnutrition (PEM) pre-existing at stroke onset is believed to worsen functional outcome, yet the underlying mechanisms are not fully understood. Since brain inflammation is an important modulator of neurological recovery after stroke, we explored the impact of PEM on neuroinflammation in the acute period in relation to stroke-initiated sensori-motor abnormalities. Adult rats were fed a low-protein (LP) or normal protein (NP) diet for 28 days before inducing photothrombotic stroke (St) in the forelimb region of the motor cortex or sham surgery; the diets continued for 3 days after the stroke. Protein-energy status was assessed by a combination of body weight, food intake, serum acute phase proteins and corticosterone, and liver lipid content. Deficits in motor function were evaluated in the horizontal ladder walking and cylinder tasks at 3 days after stroke. The glial response and brain elemental signature were investigated by immunohistochemistry and micro-X-ray fluorescence imaging, respectively. The LP-fed rats reduced food intake, resulting in PEM. Pre-existing PEM augmented stroke-induced abnormalities in forelimb placement accuracy on the ladder; LP-St rats made more errors (29 ± 8%) than the NP-St rats (15 ± 3%; P < 0.05). This was accompanied by attenuated astrogliosis in the peri-infarct area by 18% and reduced microglia activation by up to 41 and 21% in the peri-infarct area and the infarct rim, respectively (P < 0.05). The LP diet altered the cortical Zn, Ca, and Cl signatures (P < 0.05). Our data suggest that proactive treatment of pre-existing PEM could be essential for optimal post-stroke recovery.

[Correction of anemia in hemodialysis, effect of intravenous iron without erythropoietin].

Science.gov (United States)

Alvo, Miriam; Elgueta, Leticia; Aragón, Henry; Cotera, Alejandro

2002-08-01

In the last two decades, the use of erythropoietin for the correction of anemia in hemodialysis patients has been recommended. In Chile, only 10% of hemodialysis patients use erythropoietin, therefore, the correction of iron deficiency must be optimized. To report the effects of intravenous iron without erythropoietin in the management of anemia in hemodialysis patients. Retrospective analysis of 42 patients that received intravenous ferrous sacharate in doses of 100 mg/week during 5 weeks and 100 mg bimonthly during six months. These patients did not receive erythropoietin. Thirty six patients had iron deficiency. Basal ferritin was 137 +/- 22 micrograms/l and increased to 321 +/- 28 micrograms/l after treatment. Packed red cell volume increased from 24 +/- 2% to 29 +/- 3%. No adverse effects were reported. Iron deficiency is frequent in hemodialyzed patients. Intraveineous iron is safe and effective in the treatment of iron deficiency in these patients.

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.

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.

Discrete β-adrenergic mechanisms regulate early and late erythropoiesis in erythropoietin-resistant anemia.

Science.gov (United States)

Hasan, Shirin; Mosier, Michael J; Szilagyi, Andrea; Gamelli, Richard L; Muthumalaiappan, Kuzhali

2017-10-01

Anemia of critical illness is resistant to exogenous erythropoietin. Packed red blood cells transfusions is the only treatment option, and despite related cost and morbidity, there is a need for alternate strategies. Erythrocyte development can be divided into erythropoietin-dependent and erythropoietin-independent stages. We have shown previously that erythropoietin-dependent development is intact in burn patients and the erythropoietin-independent early commitment stage, which is regulated by β1/β2-adrenergic mechanisms, is compromised. Utilizing the scald burn injury model, we studied erythropoietin-independent late maturation stages and the effect of β1/β2, β-2, or β-3 blockade in burn mediated erythropoietin-resistant anemia. Burn mice were randomized to receive daily injections of propranolol (nonselective β1/β2 antagonist), nadolol (long-acting β1/β2 antagonist), butoxamine (selective β2 antagonist), or SR59230A (selective β3 antagonist) for 6 days after burn. Total bone marrow cells were characterized as nonerythroid cells, early and late erythroblasts, nucleated orthochromatic erythroblasts and enucleated reticulocyte subsets using CD71, Ter119, and Syto-16 by flow cytometry. Multipotential progenitors were probed for MafB expressing cells. Although propranolol improved early and late erythroblasts, only butoxamine and selective β3-antagonist administrations were positively reflected in the peripheral blood hemoglobin and red blood cells count. While burn impeded early commitment and late maturation stages, β1/β2 antagonism increased the early erythroblasts through commitment stages via β2 specific MafB regulation. β3 antagonism was more effective in improving overall red blood cells through late maturation stages. The study unfolds novel β2 and β3 adrenergic mechanisms orchestrating erythropoietin resistant anemia after burn, which impedes both the early commitment stage and the late maturation stages, respectively. Copyright © 2017

Erythropoietin abuse and erythropoietin gene doping: detection strategies in the genomic era.

Science.gov (United States)

Diamanti-Kandarakis, Evanthia; Konstantinopoulos, Panagiotis A; Papailiou, Joanna; Kandarakis, Stylianos A; Andreopoulos, Anastasios; Sykiotis, Gerasimos P

2005-01-01

The administration of recombinant human erythropoietin (rhEPO) increases the maximum oxygen consumption capacity, and is therefore abused as a doping method in endurance sports. The detection of erythropoietin (EPO) abuse is based on direct pharmacological and indirect haematological approaches, both of which have several limitations. In addition, current detection methods cannot cope with the emerging doping strategies of EPO mimicry, analogues and gene doping, and thus novel detection strategies are urgently needed. Direct detection methods for EPO misuse can be either pharmacological approaches that identify exogenous substances based on their physicochemical properties, or molecular methods that recognise EPO transgenes or gene transfer vectors. Since direct detection with molecular methods requires invasive procedures, it is not appropriate for routine screening of large numbers of athletes. In contrast, novel indirect methods based on haematological and/or molecular profiling could be better suited as screening tools, and athletes who are suspect of doping would then be submitted to direct pharmacological and molecular tests. This article reviews the current state of the EPO doping field, discusses available detection methods and their shortcomings, outlines emerging pharmaceutical and genetic technologies in EPO misuse, and proposes potential directions for the development of novel detection strategies.

TNF-alpha-induced apoptosis is prevented by erythropoietin treatment on SH-SY5Y cells

International Nuclear Information System (INIS)

Pregi, Nicolas; Wenker, Shirley; Vittori, Daniela; Leiros, Claudia Perez; Nesse, Alcira

2009-01-01

The growth factor erythropoietin (Epo) has shown neuronal protective action in addition to its well known proerythroid activity. Furthermore, Epo has dealt with cellular inflammation by inhibiting the expression of several proinflammatory cytokines, such as IL-1 and TNF-α. The action of TNF can have both apoptotic and antiapoptotic consequences due to altered balance between different cell signalling pathways. This work has focused on the apoptotic effects of this cytokine and the potential protective action of Epo. The model we used was neuroblastoma SH-SY5Y cells cultured in the presence of 25 ng/ml TNF-α or pretreated with 25 U/ml Epo for 12 h before the addition of TNF-α. Apoptosis was evaluated by differential cell count after Hoechst staining, analysis of DNA ladder pattern, and measurement of caspase activity. Despite its ability to induce NF-κB nuclear translocation, TNF-α induced cell death, which was found to be associated to upregulation of TNF Receptor 1 expression. On the other hand, cells activated by Epo became resistant to cell death. Prevention of death receptor upregulation and caspase activation may explain this antiapoptotic effect of Epo, which may be also favoured by the induction of a higher expression of protective factors, such as Bcl-2 and NF-κB, through mechanisms involving Jak/STAT and PI3K signalling pathways

Erythropoietin between therapy and doping : Two sides of the same coin

Directory of Open Access Journals (Sweden)

Ostojić Ana

2016-01-01

Full Text Available Erythropoietin is a hormone that promotes the formation of red blood cells by the bone marrow. In adults it is mainly produced by the kidneys as a response to hypoxia. Besides its main role, it also acts as antiapoptotic, anti-inflammatory and cytoprotective agent. Furthermore, it is produced in many non-hematopoietic tissues where it acts locally, stimulating angiogenesis. Erythropoietin binds cytokine receptors on target cells, such as erythrocyte precursor cells, neurons, glial and endothelial cells, cardiomyocytes, myocytes etc. The discovery of synthetic erythropoietin forms, in the late eighties of the last century, has significantly improved treatment outcome of patients with anaemia related to chronic diseases, especially chronic renal failure. Renal anaemia is multifactorial, but predominantly a consequence of erythropoietin deficiency. Today, three generations of erythropoiesis stimulating agents are available, differing in glycosylation pattern, molecular size, half-life and modes of administration and dosage. In anaemic patients this therapy significantly improves their quality of life, but may also have serious, potentially dangerous adverse effects. Synthesis of recombinant human erythropoietin, on the other hand, has improved possibilities for manipulations in sport, in the field of blood doping. Erythropoietin administration in athletes increases their maximum oxygen consumption capacity, improves endurance and performance, especially in aerobic exercise. This seriously undermines the spirit of sport, and also endangers athletes' health. Different anti-doping tests have been developed and used, still with limited success. At the same time, new illicit ways of malpractice are developing, such as variuos models of gene doping. Therefore, providing new models of anti-doping tests and strategies, together with better health control of athletes, still remains a considerable challenge.

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

Directory of Open Access Journals (Sweden)

Kausar Humera

2011-11-01

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

Raman and loss induced quantum noise in depleted fiber optical parametric amplifiers

DEFF Research Database (Denmark)

Friis, Søren Michael Mørk; Rottwitt, Karsten; McKinstrie, C. J.

2013-01-01

We present a semi-classical approach for predicting the quantum noise properties of fiber optical parametric amplifiers. The unavoidable contributors of noise, vacuum fluctuations, loss-induced noise, and spontaneous Raman scattering, are included in the analysis of both phase-insensitive and phase...

Bilateral brain reorganization with memantine and constraint-induced aphasia therapy in chronic post-stroke aphasia: An ERP study.

Science.gov (United States)

Barbancho, Miguel A; Berthier, Marcelo L; Navas-Sánchez, Patricia; Dávila, Guadalupe; Green-Heredia, Cristina; García-Alberca, José M; Ruiz-Cruces, Rafael; López-González, Manuel V; Dawid-Milner, Marc S; Pulvermüller, Friedemann; Lara, J Pablo

2015-01-01

Changes in ERP (P100 and N400) and root mean square (RMS) were obtained during a silent reading task in 28 patients with chronic post-stroke aphasia in a randomized, double-blind, placebo-controlled trial of both memantine and constraint-induced aphasia therapy (CIAT). Participants received memantine/placebo alone (weeks 0-16), followed by drug treatment combined with CIAT (weeks 16-18), and then memantine/placebo alone (weeks 18-20). ERP/RMS values (week 16) decreased more in the memantine group than in the placebo group. During CIAT application (weeks 16-18), improvements in aphasia severity and ERP/RMS values were amplified by memantine and changes remained stable thereafter (weeks 18-20). Changes in ERP/RMS occurred in left and right hemispheres and correlated with gains in language performance. No changes in ERP/RMS were found in a healthy group in two separated evaluations. Our results show that aphasia recovery induced by both memantine alone and in combination with CIAT is indexed by bilateral cortical potentials. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterization of recombinant human erythropoietin produced in Chinese hamster ovary cells

International Nuclear Information System (INIS)

Davis, J.M.; Arakawa, T.; Strickland, T.W.; Yphantis, D.A.

1987-01-01

Physicochemical properties of recombinant human erythropoietin were examined. This protein, produced in Chinese hamster ovary cells, showed a conformation apparently identical with the natural product isolated from human urine when examined by circular dichroism, UV absorbance, and fluorescence spectroscopy. Sedimentation equilibrium experiments showed the recombinant erythropoietin preparation to be essentially a single macromolecular component with a molecular weight of 30,400 and a carbohydrate content of 39%. The Stokes radius of recombinant erythropoietin was estimated to be 32 A from gel filtration, much larger than the 20-A radius calculated for a sphere of the observed molecular weight. This difference may be ascribed to the extensive glycosylation. The fluorescence and phosphorescence spectra showed that the luminescent tryptophan(s) is (are) solvent-exposed and can be quenched by I - and acrylamide but not by Cs + . On acid titration, the recombinant erythropoietin showed a conformational transition with a midpoint of pH 4.1. This suggests that the net charges on the protein moiety rather than on the whole molecule play a role in protein structure stability

High-dose phenobarbital or erythropoietin for the treatment of perinatal asphyxia in term newborns.

Science.gov (United States)

Avasiloaiei, Andreea; Dimitriu, Cristina; Moscalu, Mihaela; Paduraru, Luminita; Stamatin, Maria

2013-10-01

The aim of this study was to compare two neuroprotective strategies to supportive care in the treatment of perinatal asphyxia. A total of 67 term newborns with perinatal asphyxia were included and randomized into three groups: one group received supportive treatment; another group received a single dose of 40 mg/kg phenobarbital; and the third received three daily doses of 1000 IU/kg erythropoietin. The following parameters were analyzed: gestational age, birthweight, Apgar scores, cord blood pH, total serum antioxidant status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA). The newborns were included in the follow-up program and examined up to 18 months of age. TAS was higher in the erythropoietin group than in the other groups. SOD and GPx were lower for infants treated with phenobarbital or erythropoietin compared to control infants. MDA was lower in the erythropoietin group compared to the other groups, although the difference was not statistically significant (P > 0.05). The mortality rate was lower in the phenobarbital and erythropoietin groups (both 4.6%) than in the control group (17.4%). Long-term neurologic follow up showed a high incidence of sequelae in the control group compared to the phenobarbital and erythropoietin groups. Follow-up results were better in the phenobarbital group than in the erythropoietin group for motor and cognitive function at 3 and 6 months and worse for expressive language. At 18 months, however, the differences between these two groups were not significant. High-dose phenobarbital or erythropoietin along with supportive treatment has a positive influence on the outcome of newborns with perinatal asphyxia. Phenobarbital has the advantage of low cost and simplicity. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

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

Routine physiotherapy does not induce a cardiorespiratory training effect post-stroke, regardless of walking ability.

Science.gov (United States)

Kuys, Suzanne; Brauer, Sandra; Ada, Louise

2006-12-01

Cardiorespiratory fitness is increasingly being recognized as an impairment requiring physiotherapy intervention after stroke. The present study seeks to investigate if routine physiotherapy treatment is capable of inducing a cardiorespiratory training effect and if stroke patients attending physiotherapy who are unable to walk experience less cardiorespiratory stress during physiotherapy when compared to those who are able to walk. A descriptive, observational study, with heart rate monitoring and video-recording of physiotherapy rehabilitation, was conducted. Thirty consecutive stroke patients from a geriatric and rehabilitation unit of a tertiary metropolitan hospital, admitted for rehabilitation, and requiring physiotherapy were included in the study. The main measures of the study were duration (time) and intensity (percentage of heart rate reserve) of standing and walking activities during physiotherapy rehabilitation for non-walking and walking stroke patients. Stroke patients spent an average of 21 minutes participating in standing and walking activities that were capable of inducing a cardiorespiratory training effect. Stroke patients who were able to walk spent longer in these activities during physiotherapy rehabilitation than non-walking stroke patients (p physiotherapy rehabilitation had insufficient duration and intensity to result in a cardiorespiratory training effect in our group of stroke patients.

"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.

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...

Erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles.

Science.gov (United States)

Hojman, Pernille; Brolin, Camilla; Gissel, Hanne; Brandt, Claus; Zerahn, Bo; Pedersen, Bente Klarlund; Gehl, Julie

2009-06-12

Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo.At 12 weeks, EPO expression resulted in a 23% weight reduction (Pincrease in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles.In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles.

Prolonged drug-induced hypothermia in experimental stroke

DEFF Research Database (Denmark)

Johansen, Flemming Fryd; Jørgensen, Henrik Stig; Reith, Jakob

2007-01-01

In experimental and human stroke, hypothermia is strongly related to a favorable outcome. Previous attempts to manipulate the core temperature in focal cerebral ischemia have been based on mechanical cooling. The purpose of the study is to establish a model for long-term drug-induced hypothermia...... in focal ischemia by pharmacological alteration of the central thermoregulatory set-point. We tested the hypothesis that the dopaminergic agonist Talipexole, which induces hypothermia, reduces infarct size. Body temperature was monitored by a radio-pill-implant. Rats had reversible occlusion of the middle...... that the core body temperature was reduced by 1.7 degrees C for 24 hours after MCAO in rats treated with Talipexole. This treatment induced a significant reduction of infarct volume at 7 days after focal ischemia by 47%. We suggest that the reduction in infarct volume is related to drug-induced hypothermia...

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.

Erythropoietin: ready for prime-time cardioprotection.

NARCIS (Netherlands)

Riksen, N.P.; Hausenloy, D.J.; Yellon, D.

2008-01-01

To improve clinical outcomes in patients presenting with an acute myocardial infarction, new strategies to limit infarct size and postinfarct remodelling are warranted. Recent animal studies have revealed that erythropoietin has the potential to achieve both these goals. Even more intriguing is the

Cytoprotective effect of glutaraldehyde erythropoietin on HEK293 kidney cells after silver nanoparticle exposure

Directory of Open Access Journals (Sweden)

Sooklert K

2016-02-01

Full Text Available Kanidta Sooklert,1,2 Supreecha Chattong,3 Krissanapong Manotham,3 Chawikan Boonwong,1 I-yanut Klaharn,1 Depicha Jindatip,4 Amornpun Sereemaspun1,4 1Nanobiomedicine Laboratory, Department of Anatomy, Faculty of Medicine, 2Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, 3Renal Unit, Department of Medicine, Lerdsin General Hospital, 4Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandAbstract: The toxic effects from exposure to silver nanoparticles (AgNPs, which are broadly present in many consumer products, have long raised concerns. Many studies have focused on the mechanisms of nanosilver, which cause toxicity in human cells, but little is known about prevention of this type of injury. This study investigated the in vitro effects of glutaraldehyde erythropoietin (GEPO, a cytoprotective compound derived from erythropoietin, in terms of cell protection against AgNP-induced injury. HEK293 cells were pretreated with or without GEPO before administration of AgNPs. The protective effects of GEPO in this cell line were assessed by the percentage of viable cells, alterations of cell morphology, and the proliferative capability of the cells. In addition, we assessed the role of GEPO in lowering cellular oxidative stress and regulating expression of the anti-apoptotic protein Bcl2. The results showed rescue effects on the percentage of viable and proliferative cells among GEPO pretreated cells. Pretreatment with GEPO maintained the normal cell shape and ultrastructural morphology. Moreover, GEPO reduced the generation of reactive oxygen species in cells and activated expression of Bcl2, which are the major mechanisms in protection against cellular toxicity induced by AgNPs. In conclusion, our study showed that the cytotoxic effects from exposure to AgNPs can be prevented by GEPO. Keywords: glutaraldehyde erythropoietin, silver nanoparticles, cytoprotection

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...... were unchanged. The conclude that, in spite of changes in rheologic variables, increasing viscosity of the blood and thus possibly increasing the peripheral resistance, these had no effect on the cardiovascular state. Erythropoietin treatment improves the subjective well-being in patients on chronic...

Inflammatory cytokine tumor necrosis factor α suppresses neuroprotective endogenous erythropoietin from astrocytes mediated by hypoxia-inducible factor-2α.

Science.gov (United States)

Nagaya, Yoshiaki; Aoyama, Mineyoshi; Tamura, Tetsuya; Kakita, Hiroki; Kato, Shin; Hida, Hideki; Saitoh, Shinji; Asai, Kiyofumi

2014-12-01

Interest in erythropoietin (EPO) as a neuroprotective mediator has grown since it was found that systemically administered EPO is protective in several animal models of disease. However, given that the blood-brain barrier limits EPO entry into the brain, alternative approaches that induce endogenous EPO production in the brain may be more effective clinically and associated with fewer untoward side-effects. Astrocytes are the main source of EPO in the central nervous system. In the present study we investigated the effect of the inflammatory cytokine tumor necrosis factor α (TNFα) on hypoxia-induced upregulation of EPO in rat brain. Hypoxia significantly increased EPO mRNA expression in the brain and kidney, and this increase was suppressed by TNFα in vivo. In cultured astrocytes exposed to hypoxic conditions for 6 and 12 h, TNFα suppressed the hypoxia-induced increase in EPO mRNA expression in a concentration-dependent manner. TNFα inhibition of hypoxia-induced EPO expression was mediated primarily by hypoxia-inducible factor (HIF)-2α rather than HIF-1α. The effects of TNFα in reducing hypoxia-induced upregulation of EPO mRNA expression probably involve destabilization of HIF-2α, which is regulated by the nuclear factor (NF)-κB signaling pathway. TNFα treatment attenuated the protective effects of astrocytes on neurons under hypoxic conditions via EPO signaling. The effective blockade of TNFα signaling may contribute to the maintenance of the neuroprotective effects of EPO even under hypoxic conditions with an inflammatory response. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Shortened constraint-induced movement therapy in subacute stroke - no effect of using a restraint

DEFF Research Database (Denmark)

Brogårdh, Christina; Vestling, Monika; Sjölund, Bengt H

2009-01-01

OBJECTIVE: To examine the effect of using a mitt during shortened constraint-induced movement therapy for patients in the subacute phase after stroke. SUBJECTS: Twenty-four patients with stroke (mean age 57.6 (standard deviation (SD) 8.5) years; average 7 weeks post-stroke) with mild to moderate......, no statistically significant differences between the groups were found in any measures at any point in time. CONCLUSION: In this study, no effect of using a restraint in patients with subacute stroke was found. Thus, this component in the constraint-induced therapy concept seems to be of minor importance...... Scale, the Sollerman hand function test, the 2-Point Discrimination test and Motor Activity Log test. RESULTS: Patients in both groups showed significant improvements in arm and hand motor performance and on self-reported motor ability after 2 weeks of therapy and at 3 months follow-up. However...

Pharmacokinetics of erythropoietin in intact and anephric dogs

International Nuclear Information System (INIS)

Fu, J.S.; Lertora, J.J.; Brookins, J.; Rice, J.C.; Fisher, J.W.

1988-01-01

The present studies were performed to determine the pharmacokinetic parameters of erythropoietin in intact and anephric dogs by use of unlabeled crude native erythropoietin (nEp) and iodine 125-labeled purified recombinant erythropoietin (rEp) given by intravenous infusion for 15 minutes. Sephadex G-75 gel filtration was used to confirm that the 125I-rEp molecule remained iodinated in dog plasma during the 24-hour period of these studies. The plasma disappearance of erythropoietin conformed to a biexponential equation for both nEp and 125I-rEp, with the central compartment being larger than the peripheral compartment. The mean distribution half-life of 75.3 +/- 21.2 minutes for nEp was significantly (p less than 0.05) longer than that of 125I-rEp (23.7 +/- 5.0 minutes) in intact dogs. The intercompartmental clearance (CIic) for nEp (0.018 +/- 0.006 L/kg/hr) was significantly smaller than that of 125I-rEp (0.068 +/- 0.018 L/kg/hr) in intact dogs (p less than 0.05). There were no significant differences in apparent volume of distribution, elimination half-life, and elimination clearance (CIe) for nEp and rEp in intact dogs. The mean elimination half-life for 125I-rEp in intact dogs (9.0 +/- 0.6 hours) and anephric dogs (13.8 +/- 1.4 hours) was significantly different (p less than 0.05). The CIe for 125I-rEp in anephric dogs (0.008 +/- 0.001 L/kg/hr) was significantly (p less than 0.05) smaller than that of 125I-rEp in intact dogs (0.011 +/- 0.001 L/kg/hr). There were no significant differences in apparent volume of distribution, distribution half-life, and CIic for 125I-rEp in intact and anephric dogs

Clinical evaluation of patients with migraine induced stroke in mashhad, iran.

Science.gov (United States)

Ghandehari, Kavian; Sharifi, Atena; Nikbin, Zeynab; Fadaei, Sahar; Meybodi, Meysam Aghaei; Moshfegh, Mehdi; Hosseini, Mohammad Reza; Sarabi, Mohammad Reza Gerami; Maarufi, Parham

2010-01-01

Migraine Induced Stroke (MIS) is an important cause of brain infarction in the young people. Consecutive patients with MIS admitted in Ghaem hospital, Mashhad during 2006-2010 enrolled a prospective clinical study. All of the patients suspected to MIS had brain MRI with a 0.5 Tesla generation, Philips NT Intra, Netherland. All of the MIS patients underwent a standard battery of diagnostic investigations for detecting etiology of stroke. Disability of MIS patients was detected based on the modified Rankin scale at 90 days post stroke. 32 MIS patients (18 females, 14 males) with mean age 37.2 ± 3.8 years ranged 15-58 years were evaluated. Hypodense area of infarction corresponding to clinical manifestations was detected in MRI in 32% of our MIS patients. The mean disability score in our MIS patients was 1.09 ± 0.32, which is significantly lower than other stroke patients (z = 2.55, P = 0.007) MIS is an important cause of stroke in Persian young adults which have good prognosis.

Increased preoperative collection of autologous blood with recombinant human erythropoietin therapy in tertiary care hospitals of Jammu

Directory of Open Access Journals (Sweden)

Kumkum Sharma

2013-01-01

Full Text Available Introduction: To study whether the administration of recombinant human erythropoietin increases the amount of autologous blood that can be collected before orthopaedic surgery. Materials and Methods: We conducted a randomized controlled trial of recombinant human erythropoietin in 68 adults scheduled for elective orthopedic procedures. The patients received either erythropoietin 600 units/kg of body weight or placebo intravenously every 5 th day prior to each phlebotomy for 21 days during which time up to 5 units of blood was collected. Patients were excluded from donation when their hematocrit values were less than 33%. All patients received iron sulphate 325mg orally 3 times daily. The mean number of units collected per patient was 4.33 ± 0.4 for erythropoietin group and 3.05± 0.71 for the placebo group. Results: The mean packed red cell volume donated by patients who received erythropoietin was 32% greater than that donated by patients who received placebo (196.3 vs. 169.4 ml, p<0.05. 68% in the placebo group and 9% of patients treated with erythropoietin were unable to donate ≥4 units. No adverse effects were attributed to erythropoietin. While participating in the study, complications developed in 2 patients one in each group necessitating their removal from the study. Conclusion: We conclude that recombinant human erythropoietin increases the ability of the patients about to undergo elective surgery to donate autologous blood units.

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...

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.

Diffusion tensor and volumetric magnetic resonance imaging using an MR-compatible hand-induced robotic device suggests training-induced neuroplasticity in patients with chronic stroke.

Science.gov (United States)

Lazaridou, Asimina; Astrakas, Loukas; Mintzopoulos, Dionyssios; Khanicheh, Azadeh; Singhal, Aneesh B; Moskowitz, Michael A; Rosen, Bruce; Tzika, Aria A

2013-11-01

Stroke is the third leading cause of mortality and a frequent cause of long-term adult impairment. Improved strategies to enhance motor function in individuals with chronic disability from stroke are thus required. Post‑stroke therapy may improve rehabilitation and reduce long-term disability; however, objective methods for evaluating the specific impact of rehabilitation are rare. Brain imaging studies on patients with chronic stroke have shown evidence for reorganization of areas showing functional plasticity after a stroke. In this study, we hypothesized that brain mapping using a novel magnetic resonance (MR)-compatible hand device in conjunction with state‑of‑the‑art magnetic resonance imaging (MRI) can serve as a novel biomarker for brain plasticity induced by rehabilitative motor training in patients with chronic stroke. This hypothesis is based on the premises that robotic devices, by stimulating brain plasticity, can assist in restoring movement compromised by stroke-induced pathological changes in the brain and that these changes can then be monitored by advanced MRI. We serially examined 15 healthy controls and 4 patients with chronic stroke. We employed a combination of diffusion tensor imaging (DTI) and volumetric MRI using a 3-tesla (3T) MRI system using a 12-channel Siemens Tim coil and a novel MR-compatible hand‑induced robotic device. DTI data revealed that the number of fibers and the average tract length significantly increased after 8 weeks of hand training by 110% and 64%, respectively (probotics in the molecular medicine era.

The effect of erythropoietin on healing of obstructive vs nonobstructive left colonic anastomosis: an experimental study

Directory of Open Access Journals (Sweden)

Renda Nurten

2007-05-01

Full Text Available Abstract Background Anastomotic leakage is an important problem following primary resection in the left colon and is even more prominent when obstruction is present. We aimed to evaluate the possible effects of erythropoietin on the healing of anastomosis under both obstructive and non-obstructive states. Methods Forty male Wistar albino rats were divided into four groups. In group I, two cm left colonic resection and primary anastomosis were done. In group II, left colon were completely ligated and 24 hours later animals were re-operated for segmental resection. The same procedures were performed for rats in group III and IV in respect to group I and II and, 500 IU/kg a day erythropoietin were given in the latter two groups for seven days. For the quantative description of anastomotic healing mechanical, biochemical and histopathological parameters were employed on the seventh day and the animals were sacrificied. Results Although erythropoietin had positive effects on bursting pressure in group IV when compared to group II, it has no effect in group III. Despite the increased tissue hydroxyproline levels in group IV, erythropoietin failed to show any effects in group III. Erythropoietin had positive effects on neovascularization, fibroblast proliferiation and storage of collagen in group IV. Conclusion We failed to find any direct and evident effects of erythropoietin on healing of left colonic anastomosis. On the other hand, erythropoietin might prevent negative effects of obstruction on healing.

The potential of erythropoietin to treat asphyxia in newborns

Directory of Open Access Journals (Sweden)

Pet GC

2014-11-01

Full Text Available Gillian C Pet, Sandra E Juul Department of Pediatrics, Division of Neonatology, University of Washington, Seattle, WA, USA Abstract: Perinatal asphyxia is a cause of significant neonatal morbidity worldwide. Lack of oxygenation and perfusion to the neonatal brain leads to energy failure and cell death. Currently, therapeutic hypothermia is the standard of care for term infants with hypoxic-ischemic encephalopathy, but as it has shown only modest effects on survival and morbidity, additional neuroprotective agents are needed. Erythropoietin has been extensively studied as a neuroprotective agent for infants who suffer a hypoxic-ischemic brain injury. It has multiple mechanisms of action, in both preventing cell death and promoting tissue repair. Studies have progressed over time from in vitro to in vivo studies, first in animals and now in humans, with several Phase I/II trials completed and Phase III trials underway. As therapeutic hypothermia has become the standard of care in treating term infants with hypoxic-ischemic encephalopathy, studies must now evaluate other neuroprotective agents, including erythropoietin, used in concert with therapeutic hypothermia. Erythropoietin has shown promise as a neuroprotective agent in animal and human models, both alone and together with hypothermia. Keywords: neonate, brain injury

Caveat oncologist: clinical findings and consequences of distributing counterfeit erythropoietin in the United States.

Science.gov (United States)

Qureshi, Zaina P; Norris, Leann; Sartor, Oliver; McKoy, June M; Armstrong, John; Raisch, Dennis W; Garg, Vishvas; Stafkey-Mailey, Dana; Bennett, Charles Lee

2012-03-01

Counterfeit pharmaceuticals pose risks domestically. Because of their cost, cancer pharmaceuticals are vulnerable. We review findings from a domestic counterfeiting episode involving erythropoietin and outline anticounterfeiting recommendations for policy makers, patients, and health care professionals. Information was obtained on patients who received counterfeit erythropoietin, its distribution, and criminal investigations into counterfeiting networks. Interview sources included a physician, an attorney, employees of the Florida Department of Health and Human Services and the US Food and Drug Administration's (FDA) Office of Criminal Investigation, manufacturers, and wholesalers. Other sources included the book "Dangerous Doses," LexisNexis (search terms "counterfeit" and "erythropoietin") and the FDA database. Counterfeit product consisted of 2,000 U vials with counterfeit labels denoting 40,000 U. The counterfeiters, in collaboration with a Miami pharmacy, purchased 110,000 erythropoietin 2,000 U vials and affixed counterfeit labels to each vial. Products were then sold via the pharmaceutical "gray market" to wholesalers, then pharmacy chains. Investigations by Florida government officials implicated 17 persons, all of whom were found guilty of trafficking in counterfeit pharmaceuticals. Despite the large size of the operation, the FDA received reports of only 12 patients who had received counterfeit erythropoietin and detailed information for only two individuals. A 17-year-old liver transplant recipient and a 61-year-old patient with breast cancer experienced loss of efficacy after receiving counterfeit erythropoietin. Wider use of FDA anticounterfeit initiatives, limiting pharmaceutical suppliers to reputable distributors, and educating providers and patients about signs of counterfeit drugs can improve the safety of cancer pharmaceuticals.

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.

Laser-induced breakdown ignition in a gas fed two-stroke engine

Science.gov (United States)

Loktionov, E. Y.; Pasechnikov, N. A.; Telekh, V. D.

2018-01-01

Laser-induced ignition for internal combustion engines is investigated intensively after demonstration of a compact ‘laser plug’ possibility. Laser spark benefits as compared to traditional spark plugs are higher compression rate, and possibility of almost any fuel ignition, so lean mixtures burning with lower temperatures could reduce harmful exhausts (NO x , CH, etc). No need in electrode and possibility for multi-point, linear or circular ignition can make combustion even more effective. Laser induced combustion wave appears faster and is more stable in time, than electric one, so can be used for ramjets, chemical thrusters, and gas turbines. To the best of our knowledge, we have performed laser spark ignition of a gas fed two-stroke engine for the first time. Combustion temperature and pressure, exhaust composition, ignition timing were investigated at laser and compared to a regular electric spark ignition in a two-stroke model engine. Presented results show possibility for improvement of two-stroke engines performance, in terms of rotation rate increase and NO x emission reduction. Such compact engines using locally mined fuel could be highly demanded in remote Arctic areas.

Erythropoiesis and erythropoietin in hypo- and hyperthyroidism.

Science.gov (United States)

Das, K C; Mukherjee, M; Sarkar, T K; Dash, R J; Rastogi, G K

1975-02-01

Qualitative and quantitative studies of erythropoiesis in 23 patients with hypothyroidism and 21 patients with hyperthryoidism included routine hematologic evaluation, bone marrow morphology, status of serum iron, B12 and folate red blood cell mass and plasma volume by radioisotope methods, erythrokinetics and radiobioassay of plasma erythropoietin. A majority of patients with the hypothyroid state had significant reduction in red blood cell mas per kg of body weight. The presence of anemia in many of these patients was not evident from hemoglobin and hematocrit values due to concomitant reduction of plasma volume. The erythrokinetic data in hypothyroid patients provided evidence of significant decline of the erythropoietic activity of the bone marrow. Erythroid cells in the marrow were depleted and also showed reduced proliferative activity as indicated by lower 3H-thymidine labeling index. Plasma erythropoietin levels were reduced, often being immeasurable by the polycythemic mouse bioassay technique. These changes in erythropoiesis in the hypothyroid state appear to be a part of physiological adjustment to the reduced oxygen requirement of the tissues due to diminished basal metabolic rate. Similar investigations revealed mild erythrocytosis in a significant proportion of patients with hyperthyroidism. Failure of erythrocytosis to occur in other patients of this group was associated with impaired erythropoiesis due to a deficiency of hemopoietic nutrients such as iron, vitamin B12 and folate. The mean plasma erythropoietin level of these patients was significantly elevated; in 4 patients the levels were in the upper normal range whereas in the rest, the values were above the normal range. The bone marrow showed erythyroid hyperplasia in all patients with hyperthyroidism. The mean 3H-thymidine labeling index of the erythroblasts was also significantly higher than normal in hyperthyroidism; in 8 patients the index was within the normal range whereas in the

Erythropoietin receptor signaling is membrane raft dependent

NARCIS (Netherlands)

K.L. McGraw (Kathy); G.M. Fuhler (Gwenny); J.O. Johnson (Joseph); J.A. Clark (Justine); G.C. Caceres (Gisela); L. Sokol (Lubomir); A.F. List (Alan)

2012-01-01

textabstractUpon erythropoietin (Epo) engagement, Epo-receptor (R) homodimerizes to activate JAK2 and Lyn, which phosphorylate STAT5. Although recent investigations have identified key negative regulators of Epo-R signaling, little is known about the role of membrane localization in controlling

A modular positive feedback-based gene amplifier

Directory of Open Access Journals (Sweden)

Bhalerao Kaustubh D

2010-02-01

Full Text Available Abstract Background Positive feedback is a common mechanism used in the regulation of many gene circuits as it can amplify the response to inducers and also generate binary outputs and hysteresis. In the context of electrical circuit design, positive feedback is often considered in the design of amplifiers. Similar approaches, therefore, may be used for the design of amplifiers in synthetic gene circuits with applications, for example, in cell-based sensors. Results We developed a modular positive feedback circuit that can function as a genetic signal amplifier, heightening the sensitivity to inducer signals as well as increasing maximum expression levels without the need for an external cofactor. The design utilizes a constitutively active, autoinducer-independent variant of the quorum-sensing regulator LuxR. We experimentally tested the ability of the positive feedback module to separately amplify the output of a one-component tetracycline sensor and a two-component aspartate sensor. In each case, the positive feedback module amplified the response to the respective inducers, both with regards to the dynamic range and sensitivity. Conclusions The advantage of our design is that the actual feedback mechanism depends only on a single gene and does not require any other modulation. Furthermore, this circuit can amplify any transcriptional signal, not just one encoded within the circuit or tuned by an external inducer. As our design is modular, it can potentially be used as a component in the design of more complex synthetic gene circuits.

Erythropoietin: a multimodal neuroprotective agent

OpenAIRE

Byts, Nadiya; Sir?n, Anna-Leena

2009-01-01

Abstract The tissue protective functions of the hematopoietic growth factor erythropoietin (EPO) are independent of its action on erythropoiesis. EPO and its receptors (EPOR) are expressed in multiple brain cells during brain development and upregulated in the adult brain after injury. Peripherally administered EPO crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells and ...

Pump RIN-induced impairments in unrepeatered transmission systems using distributed Raman amplifier.

Science.gov (United States)

Cheng, Jingchi; Tang, Ming; Lau, Alan Pak Tao; Lu, Chao; Wang, Liang; Dong, Zhenhua; Bilal, Syed Muhammad; Fu, Songnian; Shum, Perry Ping; Liu, Deming

2015-05-04

High spectral efficiency modulation format based unrepeatered transmission systems using distributed Raman amplifier (DRA) have attracted much attention recently. To enhance the reach and optimize system performance, careful design of DRA is required based on the analysis of various types of impairments and their balance. In this paper, we study various pump RIN induced distortions on high spectral efficiency modulation formats. The vector theory of both 1st and higher-order stimulated Raman scattering (SRS) effect using Jones-matrix formalism is presented. The pump RIN will induce three types of distortion on high spectral efficiency signals: intensity noise stemming from SRS, phase noise stemming from cross phase modulation (XPM), and polarization crosstalk stemming from cross polarization modulation (XPolM). An analytical model for the statistical property of relative phase noise (RPN) in higher order DRA without dealing with complex vector theory is derived. The impact of pump RIN induced impairments are analyzed in polarization-multiplexed (PM)-QPSK and PM-16QAM-based unrepeatered systems simulations using 1st, 2nd and 3rd-order forward pumped Raman amplifier. It is shown that at realistic RIN levels, negligible impairments will be induced to PM-QPSK signals in 1st and 2nd order DRA, while non-negligible impairments will occur in 3rd order case. PM-16QAM signals suffer more penalties compared to PM-QPSK with the same on-off gain where both 2nd and 3rd order DRA will cause non-negligible performance degradations. We also investigate the performance of digital signal processing (DSP) algorithms to mitigate such impairments.

Increased Levels of Erythropoietin in Nipple Aspirate Fluid and in Ductal Cells from Breast Cancer Patients

Directory of Open Access Journals (Sweden)

Ferdinando Mannello

2008-01-01

Full Text Available Background: Erythropoietin (Epo is an important regulator of erythropoiesis, and controls proliferation and differentiation of both erythroid and non-erythroid tissues. Epo is actively synthesized by breast cells during lactation, and also plays a role in breast tissues promoting hypoxia-induced cancer initiation. Our aims are to perform an exploratory investigation on the Epo accumulation in breast secretions from healthy and cancer patients and its localization in breast cancer cells.

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...

Therapeutic implications of recombinant human erythropoietin in ...

African Journals Online (AJOL)

AJB SERVER

2006-12-29

Dec 29, 2006 ... quence of both, RHUEPO has achieved the highest annual sales ... analysis of the US Medicare database (Ma et al., 1999) ... blood transfusions and improves quality of life (Eschbach, ... Large doses of EPO results increase in blood pressure .... human erythropoietin was obtained from human genomic.

Erythropoietin inhibits HIF-1α expression via upregulation of PHD-2 transcription and translation in an in-vitro model of hypoxia ischemia

Science.gov (United States)

Souvenir, Rhonda; Flores, Jerry J.; Ostrowski, Robert P.; Manaenko, Anatol; Duris, Kamil; Tang, Jiping

2014-01-01

Hypoxia inducible factor (HIF)-1α is the central transcriptional factor for the regulation of oxygen-associated genes in response to hypoxia. Erythropoietin (EPO), a hematopoietic growth factor, increases oxygen availability during hypoxia/ischemia and is associated with neuroprotection following hypoxia ischemia in laboratory models of stroke. However, EPO has failed to translate in a clinical setting. Thus it is critical to elucidate the key players in EPO-induced neuroprotection. Our preliminary studies have shown that EPO, as a downstream gene of hypoxia inducible factor (HIF), inhibits HIF-1α in a dose-dependent manner in an in-vitro model of hypoxia ischemia. This study is designed to elucidate the primary mediator of EPO-induced HIF-1α inhibition and subsequent cell survival/neuroprotection. Oxygen and glucose deprivation (OGD) of nerve growth factor (NGF) differentiated rat pheochromocytoma (PC-12) cells were used to model hypoxia ischemia in an in vitro environment. The profile of HIF-1α, HIF-2α and PHD-2 expression, HIF-1α and prolyl hydroxylase (PHD-2) mRNA levels, MMP-9 and cell death was evaluated in the presence and absence of either EPO or PHD-2 inhibitor during OGD. Our findings showed that EPO treatment resulted in an increase in PHD-2 transcription and translation, inhibition of HIF-1α expression, reactive oxygen species (ROS) formation and matrix metalloproteinase (MMP)-9 activity, resulting in increased cell survival after OGD. We also observed that EPO-induced cell survival/neuroprotection was reversed by siRNA silencing of PHD-2. This led to the conclusion that PHD-2 is a key mediator of EPO-induced HIF-1α inhibition and subsequent neuroprotection in an in vitro model of hypoxia ischemia. PMID:24323731

Predominance of granulocytopoiesis in bone marrow grafts in the omenta of mice treated with erythropoietin

International Nuclear Information System (INIS)

Meck, R.A.; Laissue, J.A.

1977-01-01

The effects of erythropoietin on the differentiation of murine bone marrow injected into the omenta of x-irradiated mice were investigated. Experimental hosts were injected with 2.5 units of erythropoietin on days 0-7 and sacrificed on day 10. Control hosts were injected with saline or sheep serum. After 10 days the grafts were > 95% granulocytic regardless of host treatment. Since these grafts contain multipotent hematopoietic stem cells and the experimental hosts were exposed to large doses of erythropoietin, the results of this experiment indicate that a specialized microenvironment is required for murine erythropoiesis in vivo. (author)

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

Science.gov (United States)

McGraw, Kathy L; Basiorka, Ashley A; Johnson, Joseph O; Clark, Justine; Caceres, Gisela; Padron, Eric; Heaton, Ruth; Ozawa, Yukiyasu; Wei, Sheng; Sokol, Lubomir; List, Alan F

2014-01-01

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.

Induced adult stem (iAS) cells and induced transit amplifying progenitor (iTAP) cells-a possible alternative to induced pluripotent stem (iPS) cells?

Science.gov (United States)

Heng, Boon Chin; Richards, Mark; Ge, Zigang; Shu, Yimin

2010-02-01

The successful derivation of iPSC lines effectively demonstrates that it is possible to reset the 'developmental clock' of somatic cells all the way back to the initial embryonic state. Hence, it is plausible that this clock may instead be turned back half-way to a less immature developmental stage that is more directly applicable to clinical therapeutic applications or for in vitro pharmacology/toxicology screening assays. Such a suitable developmental state is postulated to be either the putative transit amplifying progenitor stage or adult stem cell stage. It is hypothetically possible to reprogram mature and terminally differentiated somatic cells back to the adult stem cell or transit amplifying progenitor stage, in a manner similar to the derivation of iPSC. It is proposed that the terminology 'Induced Adult Stem Cells' (iASC) or 'Induced Transit Amplifying Progenitor Cells' (iTAPC) be used to described such reprogrammed somatic cells. Of particular interest, is the possibility of resetting the developmental clock of mature differentiated somatic cells of the mesenchymal lineage, explanted from adipose tissue, bone marrow and cartilage. The putative adult stem cell sub-population from which these cells are derived, commonly referred to as 'mesenchymal stem cells', are highly versatile and hold much therapeutic promise in regenerative medicine, as attested to by numerous human clinical trials and animal studies. Perhaps it may be appropriate to term such reprogrammed cells as 'Induced Mesenchymal Stem Cells' (iMSC) or as 'Induced Mesenchumal Progenitor Cells' (iMPC). Given that cells from the same organ/tissue will share some commonalities in gene expression, we hypothesize that the generation of iASC or iTAPC would be more efficient as compared to iPSC generation, since a common epigenetic program must exist between the reprogrammed cells, adult stem cell or progenitor cell types and terminally differentiated cell types from the same organ/tissue.

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

Directory of Open Access Journals (Sweden)

Shokofeh Banaei

2016-11-01

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

Reduction in central venous pressure enhances erythropoietin synthesis

DEFF Research Database (Denmark)

Montero, D.; Rauber, S.; Gøtze, Jens Peter

2016-01-01

AIMS: Erythropoiesis is a tightly controlled biological event, but its regulation under non-hypoxic conditions, however, remains unresolved. We examined whether acute changes in central venous blood pressure (CVP) elicited by whole-body tilting affect erythropoietin (EPO) concentration according...

Stroke And Substance Abuse

Directory of Open Access Journals (Sweden)

A Chitsaz

2017-02-01

Full Text Available Introduction: stroke in recreational substance users can be an indirect complication, like endocarditis and cardio embolism in parenteral drug users. With some drug like cocaine, stroke appear to be the result of a direct effect. In young subjects without other risk factors provide persuasive evidence for causality . OPIATES: Heroine is the most abused opiate drug, which is administered by injection, by snorting or by smoking. Stroke affects heroin users by diverse mechanisms,. Injectors are at risk of infections endocarditis, which carries risk for both ischemic and hemorrhagic stroke. Cerebral or subarachnoid hemorrhage usually occurs after rupture of a septic (mycotic aneurysm. Heroine users can are also at risk for hemorrhagic stroke secondary to liver failure with deranged clotting and to heroin nephropathy with uremia or malignant hypertension. In some heroin users the drug it self is directly causal due to vasculitis, hypersensitivity and immunologic changes. Embolization of foreign material to brain due to mixed of heroine with quinine can cause cerebral embolism. AMPHETAMINE AND other psychostimulants: In abuser of amphetamine hemorrhagic stroke can occur, oral, intravenous, nasal, and inhalational routes of administration have been reported. Most were chronic user, but in several patients, stroke followed a first exposure. Some of amphetamine induced intracranial hemorrhages are secondary to acute hypertension, some to cerebral vacuities, and some to a combination of two. Decongestants and diet pills: Phenylpropanolamine (PPA, an amphetamine – like drug, in decongestants and diet pills, induce acute hypertension, sever headache, psychiatric symptoms, seizures and hemorrhagic stroke. Ephedrine and pseudo ephedrine are present in decongestants and bronchodilators and induce headache, tachyarrhythmia, hypertensive emergency, and hemorrhagic and occlusive stroke. Ecstasy, 3,4 Methylenedioxymethamphetamin (MDMA with amphetamine like can

Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling

DEFF Research Database (Denmark)

Kammersgaard, L P; Rasmussen, B H; Jørgensen, Henrik Stig

2000-01-01

Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients...

Protein kinase C alpha controls erythropoietin receptor signaling.

NARCIS (Netherlands)

M.M. von Lindern (Marieke); M. Parren-Van Amelsvoort (Martine); T.B. van Dijk (Thamar); E. Deiner; B. Löwenberg (Bob); E. van den Akker (Emile); S. van Emst-de Vries (Sjenet); P.J. Willems (Patrick); H. Beug (Hartmut)

2000-01-01

textabstractProtein kinase C (PKC) is implied in the activation of multiple targets of erythropoietin (Epo) signaling, but its exact role in Epo receptor (EpoR) signal transduction and in the regulation of erythroid proliferation and differentiation remained elusive. We

Automatic error compensation in dc amplifiers

International Nuclear Information System (INIS)

Longden, L.L.

1976-01-01

When operational amplifiers are exposed to high levels of neutron fluence or total ionizing dose, significant changes may be observed in input voltages and currents. These changes may produce large errors at the output of direct-coupled amplifier stages. Therefore, the need exists for automatic compensation techniques. However, previously introduced techniques compensate only for errors in the main amplifier and neglect the errors induced by the compensating circuitry. In this paper, the techniques introduced compensate not only for errors in the main operational amplifier, but also for errors induced by the compensation circuitry. Included in the paper is a theoretical analysis of each compensation technique, along with advantages and disadvantages of each. Important design criteria and information necessary for proper selection of semiconductor switches will also be included. Introduced in this paper will be compensation circuitry for both resistive and capacitive feedback networks

High-level expression of human stem cell factor fused with erythropoietin mimetic peptide in Escherichia coli.

Science.gov (United States)

Su, Lin; Chen, Song-Sen; Yang, Ke-Gong; Liu, Chang-Zheng; Zhang, Yan-Li; Liang, Zhi-Quan

2006-06-01

Stem cell factor (SCF) and erythropoietin are essential for normal erythropoiesis and induce proliferation and differentiation synergistically for erythroid progenitor cells. Here, we report our work on construction of SCF/erythropoietin mimetic peptide (EMP) fusion protein gene, in which human SCF cDNA (1-165aa) and EMP sequence (20aa) were connected using a short (GGGGS) or long (GGGGSGGGGGS) linker sequence. The SCF/EMP gene was cloned into the pBV220 vector and expressed in the Escherichia coli DH5alpha strain. The expression level of the fusion protein was about 30% of total cell protein. The resulting inclusion bodies were solubilized with 8 M urea, followed by dilution refolding. The renatured protein was subsequently purified by Q-Sepharose FF column. The final product was >95% pure by SDS-PAGE and the yield of fusion protein was about 40 mg/L of culture. UT-7 cell proliferation and human cord blood cell colony-forming assays showed that the fusion proteins exhibited more potent activity than recombinant human SCF, suggesting a new strategy to enhance biological activities of growth factors.

Erythropoietin and radiotherapy; Erythropoietine et radiotherapie

Energy Technology Data Exchange (ETDEWEB)

Le Fur, E.; Albarghach, M.N.; Pradier, O. [CHU de Morvan, Dept. de radiotherapie, 29 - Brest (France)

2010-01-15

Erythropoietin (E.P.O.) is a glycoprotein hormone. This hormone is a growth factor for red blood cells precursors in the bone marrow. The decrease of oxygen partial pressure, a reduced number of erythrocytes caused by bleeding or excessive destruction, or increased tissues oxygen requirements lead to increased secretion of E.P.O.. Its action takes place on bone marrow erythroblastic cells through specific receptors. E.P.O. stimulates the proliferation of red cell precursors stem cells in the bone marrow, thus increasing their production in one to two weeks. The effectiveness of E.P.O. at increasing haemoglobin and improving patients quality of life has been demonstrated by several studies. However, its use in radiotherapy remains controversial. While tumour hypoxia caused by anaemia is a factor of radio resistance and thus a source of local failure, tumour expression of E.P.O. receptors presents a significant risk for tumour progression and neo-angiogenesis, which would be increased during the administration of E.P.O.. The purpose of this article is to answer the question: is there a place for E.P.O. in combination with radiotherapy in the management of cancer?

Portable Amplifier Design for a Novel EEG Monitor in Point-of-Care Applications.

Science.gov (United States)

Luan, Bo; Sun, Mingui; Jia, Wenyan

2012-01-01

The Electroencephalography (EEG) is a common diagnostic tool for neurological diseases and dysfunctions, such as epilepsy and insomnia. However, the current EEG technology cannot be utilized quickly and conveniently at the point of care due to the complex skin preparation procedures required and the inconvenient EEG data acquisition systems. This work presents a portable amplifier design that integrates a set of skin screw electrodes and a wireless data link. The battery-operated amplifier contains an instrumentation amplifier, two noninverting amplifiers, two high-pass filters, and a low-pass filter. It is able to magnify the EEG signals over 10,000 times and has a high impedance, low noise, small size and low weight. Our electrode and amplifier are ideal for point-of-care applications, especially during transportation of patients suffering from traumatic brain injury or stroke.

Erythropoietin inhibits HIF-1α expression via upregulation of PHD-2 transcription and translation in an in vitro model of hypoxia-ischemia.

Science.gov (United States)

Souvenir, Rhonda; Flores, Jerry J; Ostrowski, Robert P; Manaenko, Anatol; Duris, Kamil; Tang, Jiping

2014-02-01

Hypoxia inducible factor (HIF)-1α is the central transcriptional factor for the regulation of oxygen-associated genes in response to hypoxia. Erythropoietin (EPO), a hematopoietic growth factor, increases oxygen availability during hypoxia/ischemia and is associated with neuroprotection following hypoxia-ischemia in laboratory models of stroke. However, EPO has failed to translate in a clinical setting. Thus, it is critical to elucidate the key players in EPO-induced neuroprotection. Our preliminary studies have shown that EPO, as a downstream gene of HIF, inhibits HIF-1α in a dose-dependent manner in an in vitro model of hypoxia-ischemia. This study is designed to elucidate the primary mediator of EPO-induced HIF-1α inhibition and subsequent cell survival/neuroprotection. Oxygen and glucose deprivation (OGD) of nerve growth factor-differentiated rat pheochromocytoma (PC-12) cells were used to model hypoxia-ischemia in an in vitro environment. The profile of HIF-1α, HIF-2α and prolyl hydroxylase domain 2 (PHD-2) expression; HIF-1α and prolyl hydroxylase (PHD-2) mRNA levels; matrix metalloproteinase (MMP)-9; and cell death was evaluated in the presence and absence of either EPO or PHD-2 inhibitor during OGD. Our findings showed that EPO treatment resulted in an increase in PHD-2 transcription and translation, inhibition of HIF-1α expression, reactive oxygen species formation, and MMP-9 activity, resulting in increased cell survival after OGD. We also observed that EPO-induced cell survival/neuroprotection was reversed by siRNA silencing of PHD-2. This led to the conclusion that PHD-2 is a key mediator of EPO-induced HIF-1α inhibition and subsequent neuroprotection in an in vitro model of hypoxia-ischemia.

Stroke in thrombotic thrombocytopenic purpura induced by thyrotoxicosis: a case report.

Science.gov (United States)

Bellante, Flavio; Redondo Saez, Patricia; Springael, Cecile; Dethy, Sophie

2014-07-01

Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease involving the platelet aggregation and resulting in hemolytic anemia, thrombocytopenia, and microvascular occlusion. Although frequent neurologic features are headache and confusion, focal deficit is described in 30% of the cases. There are a lot of causes inducing thrombotic thrombocytopenic, but reports are lacking when associated with Grave disease. We describe the case of a 51-year-old Caucasian woman presenting a 24-hour story of sudden onset of dysarthria and left superior limb palsy. Four months before, she developed severe hyperthyroidism associated with petechiae, hemolytic anemia, thrombocytopenia, and schistocytes at blood film examination. Relapse of TTP in association with Grave disease was diagnosed. There are few reports describing association between Grave disease and TTP with only mild neurologic involvement. We described, to our knowledge, the first case of acute ischemic stroke secondary to thrombotic thrombocytopenic induced by thyrotoxicosis. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Protein kinase C alpha controls erythropoietin receptor signaling

NARCIS (Netherlands)

von Lindern, M.; Parren-van Amelsvoort, M.; van Dijk, T.; Deiner, E.; van den Akker, E.; van Emst-de Vries, S.; Willems, P.; Beug, H.; Löwenberg, B.

2000-01-01

Protein kinase C (PKC) is implied in the activation of multiple targets of erythropoietin (Epo) signaling, but its exact role in Epo receptor (EpoR) signal transduction and in the regulation of erythroid proliferation and differentiation remained elusive. We analyzed the effect of PKC inhibitors

Biomechanical mechanisms underlying exosuit-induced improvements in walking economy after stroke.

Science.gov (United States)

Bae, Jaehyun; Awad, Louis N; Long, Andrew; O'Donnell, Kathleen; Hendron, Katy; Holt, Kenneth G; Ellis, Terry D; Walsh, Conor J

2018-03-07

Stroke-induced hemiparetic gait is characteristically asymmetric and metabolically expensive. Weakness and impaired control of the paretic ankle contribute to reduced forward propulsion and ground clearance - walking subtasks critical for safe and efficient locomotion. Targeted gait interventions that improve paretic ankle function after stroke are therefore warranted. We have developed textile-based, soft wearable robots that transmit mechanical power generated by off-board or body-worn actuators to the paretic ankle using Bowden cables (soft exosuits) and have demonstrated the exosuits can overcome deficits in paretic limb forward propulsion and ground clearance, ultimately reducing the metabolic cost of hemiparetic walking. This study elucidates the biomechanical mechanisms underlying exosuit-induced reductions in metabolic power. We evaluated the relationships between exosuit-induced changes in the body center of mass (COM) power generated by each limb, individual joint power and metabolic power. Compared with walking with an exosuit unpowered, exosuit assistance produced more symmetrical COM power generation during the critical period of the step-to-step transition (22.4±6.4% more symmetric). Changes in individual limb COM power were related to changes in paretic ( R 2 =0.83, P= 0.004) and non-paretic ( R 2 = 0.73, P= 0.014) ankle power. Interestingly, despite the exosuit providing direct assistance to only the paretic limb, changes in metabolic power were related to changes in non-paretic limb COM power ( R 2 =0.80, P= 0.007), not paretic limb COM power ( P> 0.05). These findings contribute to a fundamental understanding of how individuals post-stroke interact with an exosuit to reduce the metabolic cost of hemiparetic walking. © 2018. Published by The Company of Biologists Ltd.

FGF23 modulates the effects of erythropoietin on gene expression in renal epithelial cells

Directory of Open Access Journals (Sweden)

Yashiro M

2018-04-01

Full Text Available Mitsuru Yashiro,1 Masaki Ohya,1 Toru Mima,1 Yumi Ueda,2 Yuri Nakashima,1 Kazuki Kawakami,1 Yohei Ishizawa,2 Shuto Yamamoto,1 Sou Kobayashi,1 Takurou Yano,1 Yusuke Tanaka,1 Kouji Okuda,1 Tomohiro Sonou,1 Tomohiro Shoshihara,1 Yuko Iwashita,1 Yu Iwashita,1 Kouichi Tatsuta,1 Ryo Matoba,2 Shigeo Negi,1 Takashi Shigematsu1 1Department of Nephrology, Wakayama Medical University, Wakayama, Japan; 2DNA Chip Research Inc., Minato, Japan Background: FGF23 plays an important role in calcium–phosphorus metabolism. Other roles of FGF23 have recently been reported, such as commitment to myocardium enlargement and immunological roles in the spleen. In this study, we aimed to identify the roles of FGF23 in the kidneys other than calcium–phosphorus metabolism. Methods: DNA microarrays and bioinformatics tools were used to analyze gene expression in mIMCD3 mouse renal tubule cells following treatment with FGF23, erythropoietin and/or an inhibitor of ERK. Results: Three protein-coding genes were upregulated and 12 were downregulated in response to FGF23. Following bioinformatics analysis of these genes, PPARγ and STAT3 were identified as candidate transcript factors for mediating their upregulation, and STAT1 as a candidate for mediating their downregulation. Because STAT1 and STAT3 also mediate erythropoietin signaling, we investigated whether FGF23 and erythropoietin might show interactive effects in these cells. Of the 15 genes regulated by FGF23, 11 were upregulated by erythropoietin; 10 of these were downregulated following cotreatment with FGF23. Inhibition of ERK, an intracellular mediator of FGF23, reversed the effects of FGF23. However, FGF23 did not influence STAT1 phosphorylation, suggesting that it impinges on erythropoietin signaling through other mechanisms. Conclusion: Our results suggest cross talk between erythropoietin and FGF23 signaling in the regulation of renal epithelial cells. Keywords: FGF23, STAT1, PPARγ, DNA microarray

Fibronectin potentiates topical erythropoietin-induced wound repair in diabetic mice.

Science.gov (United States)

Hamed, Saher; Ullmann, Yehuda; Egozi, Dana; Daod, Essam; Hellou, Elias; Ashkar, Manal; Gilhar, Amos; Teot, Luc

2011-06-01

Diabetes mellitus disrupts all phases of the wound repair cascade and leads to development of chronic wounds. We previously showed that topical erythropoietin (EPO) can promote wound repair in diabetic rats. Fibronectin (FN) has a critical role throughout the process of wound healing, yet it is deficient in wound tissues of diabetic patients. Therefore, we investigated the effect of topical treatment of both EPO and FN (EPO/FN) on wound repair in diabetic mice. Full-thickness excisional skin wounds in diabetic and nondiabetic mice were treated with a cream containing vehicle, EPO, FN, or EPO/FN. We assessed the rate of wound closure, angiogenesis, apoptosis, and expression of inflammatory cytokines, endothelial nitric oxide synthase (eNOS) and β1-integrin, in the wound tissues. We also investigated the effect of EPO, FN, and EPO/FN on human dermal microvascular endothelial cells and fibroblasts cultured on fibrin-coated plates, or in high glucose concentrations. EPO/FN treatment significantly increased the rate of wound closure and this effect was associated with increased angiogenesis, increased eNOS and β1-integrin expression, and reduced expression of inflammatory cytokines and apoptosis. Our findings show that EPO and FN have an additive effect on wound repair in diabetic mice.

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.

Stimulation of the sphenopalatine ganglion induces reperfusion and blood-brain barrier protection in the photothrombotic stroke model.

Directory of Open Access Journals (Sweden)

Haviv Levi

Full Text Available The treatment of stroke remains a challenge. Animal studies showing that electrical stimulation of the sphenopalatine ganglion (SPG exerts beneficial effects in the treatment of stroke have led to the initiation of clinical studies. However, the detailed effects of SPG stimulation on the injured brain are not known.The effect of acute SPG stimulation was studied by direct vascular imaging, fluorescent angiography and laser Doppler flowmetry in the sensory motor cortex of the anaesthetized rat. Focal cerebral ischemia was induced by the rose bengal (RB photothrombosis method. In chronic experiments, SPG stimulation, starting 15 min or 24 h after photothrombosis, was given for 3 h per day on four consecutive days. Structural damage was assessed using histological and immunohistochemical methods. Cortical functions were assessed by quantitative analysis of epidural electro-corticographic (ECoG activity continuously recorded in behaving animals.Stimulation induced intensity- and duration-dependent vasodilation and increased cerebral blood flow in both healthy and photothrombotic brains. In SPG-stimulated rats both blood brain-barrier (BBB opening, pathological brain activity and lesion volume were attenuated compared to untreated stroke animals, with no apparent difference in the glial response surrounding the necrotic lesion.SPG-stimulation in rats induces vasodilation of cortical arterioles, partial reperfusion of the ischemic lesion, and normalization of brain functions with reduced BBB dysfunction and stroke volume. These findings support the potential therapeutic effect of SPG stimulation in focal cerebral ischemia even when applied 24 h after stroke onset and thus may extend the therapeutic window of currently administered stroke medications.

In vitro expression of erythropoietin by transfected human mesenchymal stromal cells.

Science.gov (United States)

Mok, P-L; Cheong, S-K; Leong, C-F; Othman, A

2008-01-01

Mesenchymal stromal cells (MSC) are pluripotent progenitor cells that can be found in human bone marrow (BM). These cells have low immunogenicity and could suppress alloreactive T-cell responses. In the current study, MSC were tested for their capacity to carry and deliver the erythropoietin (EPO) gene in vitro. Expanded BM MSC was transfected with EPO-encoded plasmid pMCV1.2 and EPO-encoded MIDGE (minimalistic immunologically defined gene expression) vector by electroporation. The expressed EPO was used to induce hematopoietic stem cells (HSC) into erythroid colonies. The results showed that the MIDGE vector was more effective and stable than the plasmid (pMCV1.2) in delivering EPO gene into MSC. The supernatants containing EPO obtained from the transfected cell culture were able to induce the differentiation of HSC into erythroid colonies. MSC hold promise as a cell factory for the production of biologic molecules, and MIDGE vector is more effective and stable than the plasmid in nucleofection involving the EPO gene.

Simultaneous Expression from Both the Sense and Antisense Strand of the Erythropoietin Receptor Gene Mitigates Acute Lung Injury

Science.gov (United States)

2017-09-01

concept efficacy that increasing EpoR or RopE expression by cDNA delivery to lung cells in vitro enhances cytoprotection against hyperoxia-induced injury...oxidative damage, cell culture, rodent model, inhalation cDNA delivery, sense and antisense erythropoietin receptor transcripts 16. SECURITY...prevention of acute lung injury. 1-6 50% Subtask 1: Prepare plasmid cDNA of EpoR and RopE in nanoparticle formulation. 1 Completed 06.2017 Subtask 2

Late-onset radiation-induced vasculopathy and stroke in a child with medulloblastoma.

Science.gov (United States)

Bansal, Lalit R; Belair, Jeffrey; Cummings, Dana; Zuccoli, Giulio

2015-05-01

We report a case of a 15-year-old boy who presented to our institution with left-sided weakness and slurred speech. He had a history of medulloblastoma diagnosed at 3 years of age, status postsurgical resection and craniospinal radiation. Magnetic resonance imaging (MRI) of brain revealed a right paramedian pontine infarction, suspected secondary to late-onset radiation-induced vasculopathy of the vertebrobasilar system. Radiation to the brain is associated with increased incidence of ischemic stroke. Clinicians should have a high index of suspicion for stroke when these patients present with new neurologic symptoms. © The Author(s) 2014.

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

OpenAIRE

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 progenitor cells (EPCs) and activation of the cytoprotective enzyme heme oxygenase-1 (HO-1). METHODS: Rats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the pre...

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

OpenAIRE

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 progenitor cells (EPCs) and activation of the cytoprotective enzyme heme oxygenase-1 (HO-1). Methods Rats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO i...

Neurosurgical management of L-asparaginase induced haemorrhagic stroke.

LENUS (Irish Health Repository)

Ogbodo, Elisha

2012-01-01

The authors describe a case of L-asparaginase induced intracranial thrombosis and subsequent haemorrhage in a newly diagnosed 30-year-old man with acute lymphoblastic leukaemia who was successfully managed by surgical intervention. At presentation, he had a Glasgow Coma Score of 7\\/15, was aphasic and had dense right hemiplegia. Neuroimaging revealed an acute anterior left middle cerebral artery infarct with parenchymal haemorrhagic conversion, mass effect and subfalcine herniation. He subsequently underwent left frontal craniotomy and evacuation of large frontal haematoma and decompressive craniectomy for cerebral oedema. Six months postoperatively he underwent titanium cranioplasty. He had made good clinical recovery and is currently mobilising independently with mild occasional episodes of expressive dysphasia, difficulty with fine motor movement on the right side, and has remained seizure free. This is the first documented case of L-asparaginase induced haemorrhagic stroke managed by neurosurgical intervention. The authors emphasise the possible role of surgery in managing chemotherapy induced intracranial complications.

Haemostatic aspects of recombinant human erythropoietin in colorectal surgery

DEFF Research Database (Denmark)

Poulsen, K A; Qvist, N; Winther, K

1998-01-01

OBJECTIVE: To find out whether recombinant human erythropoietin (r-HuEPO) given perioperatively has any effect on haemostatic activity in patients undergoing elective colorectal resection. DESIGN: A placebo-controlled double-blind study. SETTING: Odense university hospital, Denmark. SUBJECTS: 24...

Caveat Oncologist: Clinical Findings and Consequences of Distributing Counterfeit Erythropoietin in the United States

Science.gov (United States)

Qureshi, Zaina P.; Norris, LeAnn; Sartor, Oliver; McKoy, June M.; Armstrong, John; Raisch, Dennis W.; Garg, Vishvas; Stafkey-Mailey, Dana; Bennett, Charles Lee

2012-01-01

Purpose: Counterfeit pharmaceuticals pose risks domestically. Because of their cost, cancer pharmaceuticals are vulnerable. We review findings from a domestic counterfeiting episode involving erythropoietin and outline anticounterfeiting recommendations for policy makers, patients, and health care professionals. Materials and Methods: Information was obtained on patients who received counterfeit erythropoietin, its distribution, and criminal investigations into counterfeiting networks. Interview sources included a physician, an attorney, employees of the Florida Department of Health and Human Services and the US Food and Drug Administration's (FDA) Office of Criminal Investigation, manufacturers, and wholesalers. Other sources included the book “Dangerous Doses,” LexisNexis (search terms “counterfeit” and “erythropoietin”) and the FDA database. Results: Counterfeit product consisted of 2,000 U vials with counterfeit labels denoting 40,000 U. The counterfeiters, in collaboration with a Miami pharmacy, purchased 110,000 erythropoietin 2,000 U vials and affixed counterfeit labels to each vial. Products were then sold via the pharmaceutical “gray market” to wholesalers, then pharmacy chains. Investigations by Florida government officials implicated 17 persons, all of whom were found guilty of trafficking in counterfeit pharmaceuticals. Despite the large size of the operation, the FDA received reports of only 12 patients who had received counterfeit erythropoietin and detailed information for only two individuals. A 17-year-old liver transplant recipient and a 61-year-old patient with breast cancer experienced loss of efficacy after receiving counterfeit erythropoietin. Conclusion: Wider use of FDA anticounterfeit initiatives, limiting pharmaceutical suppliers to reputable distributors, and educating providers and patients about signs of counterfeit drugs can improve the safety of cancer pharmaceuticals. PMID:23077434

Intrahemispheric Perfusion in Chronic Stroke-Induced Aphasia

Directory of Open Access Journals (Sweden)

Cynthia K. Thompson

2017-01-01

Full Text Available Stroke-induced alterations in cerebral blood flow (perfusion may contribute to functional language impairments and recovery in chronic aphasia. Using MRI, we examined perfusion in the right and left hemispheres of 35 aphasic and 16 healthy control participants. Across 76 regions (38 per hemisphere, no significant between-subjects differences were found in the left, whereas blood flow in the right was increased in the aphasic compared to the control participants. Region-of-interest (ROI analyses showed a varied pattern of hypo- and hyperperfused regions across hemispheres in the aphasic participants; however, there were no significant correlations between perfusion values and language abilities in these regions. These patterns may reflect autoregulatory changes in blood flow following stroke and/or increases in general cognitive effort, rather than maladaptive language processing. We also examined blood flow in perilesional tissue, finding the greatest hypoperfusion close to the lesion (within 0–6 mm, with greater hypoperfusion in this region compared to more distal regions. In addition, hypoperfusion in this region was significantly correlated with language impairment. These findings underscore the need to consider cerebral perfusion as a factor contributing to language deficits in chronic aphasia as well as recovery of language function.

Bobath Concept versus constraint-induced movement therapy to improve arm functional recovery in stroke patients: a randomized controlled trial.

Science.gov (United States)

Huseyinsinoglu, Burcu Ersoz; Ozdincler, Arzu Razak; Krespi, Yakup

2012-08-01

To compare the effects of the Bobath Concept and constraint-induced movement therapy on arm functional recovery among stroke patients with a high level of function on the affected side. A single-blinded, randomized controlled trial. Outpatient physiotherapy department of a stroke unit. A total of 24 patients were randomized to constraint-induced movement therapy or Bobath Concept group. The Bobath Concept group was treated for 1 hour whereas the constraint-induced movement therapy group received training for 3 hours per day during 10 consecutive weekdays. Main measures were the Motor Activity Log-28, the Wolf Motor Function Test, the Motor Evaluation Scale for Arm in Stroke Patients and the Functional Independence Measure. The two groups were found to be homogeneous based on demographic variables and baseline measurements. Significant improvements were seen after treatment only in the 'Amount of use' and 'Quality of movement' subscales of the Motor Activity Log-28 in the constraint-induced movement therapy group over the the Bobath Concept group (P = 0.003; P = 0.01 respectively). There were no significant differences in Wolf Motor Function Test 'Functional ability' (P = 0.137) and 'Performance time' (P = 0.922), Motor Evaluation Scale for Arm in Stroke Patients (P = 0.947) and Functional Independence Measure scores (P = 0.259) between the two intervention groups. Constraint-induced movement therapy and the Bobath Concept have similar efficiencies in improving functional ability, speed and quality of movement in the paretic arm among stroke patients with a high level of function. Constraint-induced movement therapy seems to be slightly more efficient than the Bobath Concept in improving the amount and quality of affected arm use.

Erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles.

Directory of Open Access Journals (Sweden)

Pernille Hojman

Full Text Available Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo.At 12 weeks, EPO expression resulted in a 23% weight reduction (P<0.01 in EPO transfected obese mice; thus the mice weighed 21.9+/-0.8 g (control, normal diet, 21.9+/-1.4 g (EPO, normal diet, 35.3+/-3.3 g (control, high-fat diet and 28.8+/-2.6 g (EPO, high-fat diet. Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass.The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance in the high-fat fed mice. EPO expression also induced a 14% increase in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles.In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles.

[Recombinant erythropoietin as treatment for hyporegenerative anemia following hemolytic disease of the newborn].

Science.gov (United States)

Donato, Hugo; Bacciedoni, Viviana; García, Cecilia; Schvartzman, Gabriel; Vain, Néstor

2009-04-01

The aim of the study is to report results of erythropoietin treatment for late hyporegenerative anemia in the hemolytic disease of the newborn (HDN). Reports previously published concern only a few cases, with controversial results. Case series report concerning 50 neonates with HDN due to Rh, ABO or KpA antigens, aged more than 7 days. Erythropoietin treatment started when hematocrit dropped to levels requiring transfusion, with an inappropriate reticulocyte response (Reticulocyte Production Index <1). At start of treatment mean age was 24.3 +/- 12.0 days (range 8-65 days), hematocrit 24.1 +/- 2.8% (range 18-30%), and Reticulocyte Production Index 0.34 +/- 0.25 (range 0.05-0.98). Hematocrit and Reticulocyte Production Index showed significant increases after 7 and 14 days of treatment (p <0.001). No difference was observed either between infants with Rh-HDN and ABO-HDN or between Rh-HDN patients with or without intrauterine transfusions. Seven infants (14%) required one packed RBC transfusion during erythropoietin therapy, 2 of them within 72 hours from starting treatment. The percentage of transfused infants showed no difference either between ABO-HDN and Rh-HDN or between Rh-HDN with and without intrauterine transfusions. Moderate, short-lasting neutropenia, not associated to infections, was observed in 11 patients. No other adverse effect was observed. The administration of erythropoietin appears to be a safe and useful therapy. Its efficacy should be confirmed by randomized studies.

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.

Influence of core NA on thermal-induced mode instabilities in high power fiber amplifiers

International Nuclear Information System (INIS)

Tao, Rumao; Ma, Pengfei; Wang, Xiaolin; Zhou, Pu; Liu, Zejin

2015-01-01

We report on the influence of core NA on thermal-induced mode instabilities (MI) in high power fiber amplifiers. The influence of core NA and the V-parameter on MI has been investigated numerically. It shows that core NA has a larger influence on MI for fibers with a smaller core-cladding-ratio, and the influence of core NA on the threshold is more obvious when the amplifiers are pumped at 915 nm. The dependence of the threshold on the V-parameter revealed that the threshold increases linearly as the V-parameter decreases when the V-parameter is larger than 3.5, and the threshold shows an exponential increase as the V-parameter decreases when the V-parameter is less than 3.5. We also discussed the effect of linewidth on MI, which indicates that the influence of linewidth can be neglected for a linewidth smaller than 1 nm when the fiber core NA is smaller than 0.07 and the fiber length is shorter than 20 m. Fiber amplifiers with different core NA were experimentally analyzed, which agreed with the theoretical predictions. (letter)

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

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.

[Overview of erythropoietin].

Science.gov (United States)

Lacombe, C; Mayeux, P; Casadevall, N

1991-01-01

Erythropoietin (Epo) is a glycoprotein that promotes the proliferation and differentiation of erythrocyte precursors. The major site of Epo production is the kidney and the liver is the main extra renal site of Epo production. Epo producing cells were identified by in situ hybridization, in the kidney, they are peritubular cells, most likely endothelial cells of the cortex and outer medulla; in the liver, they are mainly hepatocytes. The Epo secretion is stimulated by hypoxia, which is detected by an oxygen sensor. The Epo receptor is a multimeric protein, one chain which binds Epo has been cloned. However the structure of the Epo receptor is still puzzling, and one or more accessory chains remain to be identified. Since the clonage of the Epo gene, recombinant Epo has been available and allowed the treatment of patients with renal diseases with a constant efficacy.

Myeloperoxidase amplified high glucose-induced endothelial dysfunction in vasculature: Role of NADPH oxidase and hypochlorous acid.

Science.gov (United States)

Tian, Rong; Ding, Yun; Peng, Yi-Yuan; Lu, Naihao

2017-03-11

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H 2 O 2 ), have emerged as important molecules in the pathogenesis of diabetic endothelial dysfunction. Additionally, neutrophils-derived myeloperoxidase (MPO) and MPO-catalyzed hypochlorous acid (HOCl) play important roles in the vascular injury. However, it is unknown whether MPO can use vascular-derived ROS to induce diabetic endothelial dysfunction. In the present study, we demonstrated that NADPH oxidase was the main source of ROS formation in high glucose-cultured human umbilical vein endothelial cells (HUVECs), and played a critical role in high glucose-induced endothelial dysfunction such as cell apoptosis, loss of cell viability and reduction of nitric oxide (NO). However, the addition of MPO could amplify the high glucose-induced endothelial dysfunction which was inhibited by the presence of apocynin (NADPH oxidase inhibitor), catalase (H 2 O 2 scavenger), or methionine (HOCl scavenger), demonstrating the contribution of NADPH oxidase-H 2 O 2 -MPO-HOCl pathway in the MPO/high glucose-induced vascular injury. In high glucose-incubated rat aortas, MPO also exacerbated the NADPH oxidase-induced impairment of endothelium-dependent relaxation. Consistent with these in vitro data, in diabetic rat aortas, both MPO expresion and NADPH oxidase activity were increased while the endothelial function was simultaneously impaired. The results suggested that vascular-bound MPO could amplify high glucose-induced vascular injury in diabetes. MPO-NADPH oxidase-HOCl may represent an important pathogenic pathway in diabetic vascular diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Recombinant human erythropoietin and blood transfusion in low-birth weight preterm infants under restrictive transfusion guidelines

International Nuclear Information System (INIS)

Badiee, Z.; Pourmirzaiee, Mohmmad A.; Naseri, F.; Kelishadi, R.

2006-01-01

To compare the number and volume of red blood cell transfusions (RBCTs) in very low birth weight infants under restrictive red blood cell transfusion guidelines with and without erythropoietin administration. In a controlled clinical trial conducted at the neonatal intensive care unit of Alzahra Hospital, Isfahan, Iran, between April 2002 to April 2004, 60 premature infants with gestational age up to 34 weeks, birth weight up to 1500 g, and postnatal age between 8 and 14 days were included. The newborns were randomized into 2 groups: Group 1 received 3 doses of 400 IU/kg erythropoietin per week for 6 weeks, and Group 2 received no treatment aside from their conventional medications. The 2 groups did not differ significantly with respect to their mean gestational age, birth weight and hematocrit at the study entry. Fewer transfusions were administered to those receiving erythropoietin (26.7% versus 50%, p=0.03), but there was no statistically significant difference between groups with respect to volume of transfusion. Compared with the placebo group, the infants receiving erythropoietin had a higher mean hematocrit (34% +/- 4.3 versus 29% +/- 5.9, p<0.001) and absolute reticulocyte count (57 +/- 19 versus 10 +/- 4.8 x 106, p<0.001) at the end of the study. We found no significant difference in the incidence of thrombocytopenia and leukopenia between the 2 groups. We conclude that when the restrictive RBCT guidelines were followed, treatment with erythropoietin can be useful in reduction of the number of RBCTs. (author)

Erythropoietin Receptor Signaling Is Membrane Raft Dependent

Science.gov (United States)

McGraw, Kathy L.; Fuhler, Gwenny M.; Johnson, Joseph O.; Clark, Justine A.; Caceres, Gisela C.; Sokol, Lubomir; List, Alan F.

2012-01-01

Upon erythropoietin (Epo) engagement, Epo-receptor (R) homodimerizes to activate JAK2 and Lyn, which phosphorylate STAT5. Although recent investigations have identified key negative regulators of Epo-R signaling, little is known about the role of membrane localization in controlling receptor signal fidelity. Here we show a critical role for membrane raft (MR) microdomains in creation of discrete signaling platforms essential for Epo-R signaling. Treatment of UT7 cells with Epo induced MR assembly and coalescence. Confocal microscopy showed that raft aggregates significantly increased after Epo stimulation (mean, 4.3±1.4(SE) vs. 25.6±3.2 aggregates/cell; p≤0.001), accompanied by a >3-fold increase in cluster size (p≤0.001). Raft fraction immunoblotting showed Epo-R translocation to MR after Epo stimulation and was confirmed by fluorescence microscopy in Epo stimulated UT7 cells and primary erythroid bursts. Receptor recruitment into MR was accompanied by incorporation of JAK2, Lyn, and STAT5 and their activated forms. Raft disruption by cholesterol depletion extinguished Epo induced Jak2, STAT5, Akt and MAPK phosphorylation in UT7 cells and erythroid progenitors. Furthermore, inhibition of the Rho GTPases Rac1 or RhoA blocked receptor recruitment into raft fractions, indicating a role for these GTPases in receptor trafficking. These data establish a critical role for MR in recruitment and assembly of Epo-R and signal intermediates into discrete membrane signaling units. PMID:22509308

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

Effects of cadmium on hypoxia-induced expression of hemoglobin and erythropoietin in larval sheepshead minnow, Cyprinodon variegatus

Energy Technology Data Exchange (ETDEWEB)

Dangre, A.J.; Manning, S. [Department of Coastal Sciences, University of Southern Mississippi, 703 East Beach Drive, Ocean Springs, MS 39564 (United States); Brouwer, M., E-mail: marius.brouwer@usm.edu [Department of Coastal Sciences, University of Southern Mississippi, 703 East Beach Drive, Ocean Springs, MS 39564 (United States)

2010-08-15

Hypoxia and toxic metals are two common stressors found in the estuarine environment. To date little information is available on the combined effects of these stressors on early larval development in fish. We investigated the effect of cadmium and hypoxia exposure alone as well in combination on larval Cyprinodon variegatus. The LC{sub 10} for cadmium was determined to be 0.3 ppm in a 96 h acute exposure. This concentration was used in all studies. Cadmium in larvae increased significantly with exposure time (1, 3, 5 and 7 days post-hatch). The increase was proportional to body weight and not affected by hypoxia. Cadmium responsive genes were identified by suppression subtractive hybridization (SSH) in Cyprinodonvariegatus larvae after exposure to cadmium for 1, 3, 5 and 7 days. We obtained over 700 sequences from the cadmium cDNA library. Blast search of ESTs suggested that cadmium modulates multiple physiological processes. Pertinent to this study, cadmium was found to down-regulate both embryonic {alpha} and {beta} globin, which are expressed in erythrocytes generated during the first, or primitive, wave of erythropoiesis in teleosts. Hemoglobin (Hb) and erythropoietin (Epo) (the hormone that promotes red blood cell production) are known hypoxia-inducible genes. To explore the possibility that cadmium might offset the hypoxia-induced expression of Hb and Epo, we investigated the expression of both genes following hypoxia, cadmium and combined exposures for 1, 3, 5 and 7 days post-hatch. Since Epo had not yet been identified in C. variegatus we first successfully cloned a partial coding sequence of the C. variegatus hormone. Subsequent studies revealed that expression levels of Hb and Epo remained unchanged in the normoxic controls during the time course of the study. Hypoxia increased Epo expression relative to normoxic controls, on days 3, 5 and 7, while cadmium in hypoxia inhibited the increase. Only the changes on days 5 and 7 were statistically significant

General anesthetics inhibit erythropoietin induction under hypoxic conditions in the mouse brain.

Directory of Open Access Journals (Sweden)

Tomoharu Tanaka

Full Text Available Erythropoietin (EPO, originally identified as a hematopoietic growth factor produced in the kidney and fetal liver, is also endogenously expressed in the central nervous system (CNS. EPO in the CNS, mainly produced in astrocytes, is induced under hypoxic conditions in a hypoxia-inducible factor (HIF-dependent manner and plays a dominant role in neuroprotection and neurogenesis. We investigated the effect of general anesthetics on EPO expression in the mouse brain and primary cultured astrocytes.BALB/c mice were exposed to 10% oxygen with isoflurane at various concentrations (0.10-1.0%. Expression of EPO mRNA in the brain was studied, and the effects of sevoflurane, halothane, nitrous oxide, pentobarbital, ketamine, and propofol were investigated. In addition, expression of HIF-2α protein was studied by immunoblotting. Hypoxia-induced EPO mRNA expression in the brain was significantly suppressed by isoflurane in a concentration-dependent manner. A similar effect was confirmed for all other general anesthetics. Hypoxia-inducible expression of HIF-2α protein was also significantly suppressed with isoflurane. In the experiments using primary cultured astrocytes, isoflurane, pentobarbital, and ketamine suppressed hypoxia-inducible expression of HIF-2α protein and EPO mRNA.Taken together, our results indicate that general anesthetics suppress activation of HIF-2 and inhibit hypoxia-induced EPO upregulation in the mouse brain through a direct effect on astrocytes.

Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System.

Science.gov (United States)

Gennaro, Mariangela; Mattiello, Alessandro; Mazziotti, Raffaele; Antonelli, Camilla; Gherardini, Lisa; Guzzetta, Andrea; Berardi, Nicoletta; Cioni, Giovanni; Pizzorusso, Tommaso

2017-01-01

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.

Prospective multicentre cohort study of heparin-induced thrombocytopenia in acute ischaemic stroke patients

Science.gov (United States)

Kawano, Hiroyuki; Yamamoto, Haruko; Miyata, Shigeki; Izumi, Manabu; Hirano, Teruyuki; Toratani, Naomi; Kakutani, Isami; Sheppard, Jo-Ann I; Warkentin, Theodore E; Kada, Akiko; Sato, Shoichiro; Okamoto, Sadahisa; Nagatsuka, Kazuyuki; Naritomi, Hiroaki; Toyoda, Kazunori; Uchino, Makoto; Minematsu, Kazuo

2011-01-01

Acute ischaemic stroke patients sometimes receive heparin for treatment and/or prophylaxis of thromboembolic complications. This study was designed to elucidate the incidence and clinical features of heparin-induced thrombocytopenia (HIT) in acute stroke patients treated with heparin. We conducted a prospective multicentre cohort study of 267 patients who were admitted to three stroke centres within 7 d after stroke onset. We examined clinical data until discharge and collected blood samples on days 1 and 14 of hospitalization to test anti-platelet factor 4/heparin antibodies (anti-PF4/H Abs) using an enzyme-linked immunosorbent assay (ELISA); platelet-activating antibodies were identified by serotonin-release assay (SRA). Patients with a 4Ts score ≥4 points, positive-ELISA, and positive-SRA were diagnosed as definite HIT. Heparin was administered to 172 patients (64·4%: heparin group). Anti-PF4/H Abs were detected by ELISA in 22 cases (12·8%) in the heparin group. Seven patients had 4Ts ≥ 4 points. Among them, three patients (1·7% overall) were also positive by both ELISA and SRA. National Institutes of Health Stroke Scale score on admission was high (range, 16–23) and in-hospital mortality was very high (66·7%) in definite HIT patients. In this study, the incidence of definite HIT in acute ischaemic stroke patients treated with heparin was 1·7% (95% confidence interval: 0·4–5·0). The clinical severity and outcome of definite HIT were unfavourable. PMID:21671895

Identification of Cell Type-Specific Differences in Erythropoietin Receptor Signaling in Primary Erythroid and Lung Cancer Cells.

Directory of Open Access Journals (Sweden)

Ruth Merkle

2016-08-01

Full Text Available Lung cancer, with its most prevalent form non-small-cell lung carcinoma (NSCLC, is one of the leading causes of cancer-related deaths worldwide, and is commonly treated with chemotherapeutic drugs such as cisplatin. Lung cancer patients frequently suffer from chemotherapy-induced anemia, which can be treated with erythropoietin (EPO. However, studies have indicated that EPO not only promotes erythropoiesis in hematopoietic cells, but may also enhance survival of NSCLC cells. Here, we verified that the NSCLC cell line H838 expresses functional erythropoietin receptors (EPOR and that treatment with EPO reduces cisplatin-induced apoptosis. To pinpoint differences in EPO-induced survival signaling in erythroid progenitor cells (CFU-E, colony forming unit-erythroid and H838 cells, we combined mathematical modeling with a method for feature selection, the L1 regularization. Utilizing an example model and simulated data, we demonstrated that this approach enables the accurate identification and quantification of cell type-specific parameters. We applied our strategy to quantitative time-resolved data of EPO-induced JAK/STAT signaling generated by quantitative immunoblotting, mass spectrometry and quantitative real-time PCR (qRT-PCR in CFU-E and H838 cells as well as H838 cells overexpressing human EPOR (H838-HA-hEPOR. The established parsimonious mathematical model was able to simultaneously describe the data sets of CFU-E, H838 and H838-HA-hEPOR cells. Seven cell type-specific parameters were identified that included for example parameters for nuclear translocation of STAT5 and target gene induction. Cell type-specific differences in target gene induction were experimentally validated by qRT-PCR experiments. The systematic identification of pathway differences and sensitivities of EPOR signaling in CFU-E and H838 cells revealed potential targets for intervention to selectively inhibit EPO-induced signaling in the tumor cells but leave the responses in

Neural correlates of improved recognition of happy faces after erythropoietin treatment in bipolar disorder

DEFF Research Database (Denmark)

Miskowiak, K W; Petersen, N A; Harmer, C J

2018-01-01

-group design. Participants underwent whole-brain fMRI at 3T, mood ratings and blood tests at baseline and week 14. During fMRI, participants viewed happy and fearful faces and performed a gender discrimination task. RESULTS: Thirty-four patients had complete pre- and post-treatment fMRI data (EPO: N = 18......, saline: N = 16). Erythropoietin vs. saline increased right superior frontal response to happy vs. fearful faces. This correlated with improved happiness recognition in the EPO group. Erythropoietin also enhanced gender discrimination accuracy for happy faces. These effects were not influenced...

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.

Distribution of 131I-labeled recombinant human erythropoietin in maternal and fetal organs following intravenous administration in pregnant rats

International Nuclear Information System (INIS)

Yilmaz, O.; Lambrecht, F.Y.; Durkan, K.; Gokmen, N.; Erbayraktar, S.

2007-01-01

The aim of the present study was to demonstrate the possible transplacental transmission of 131 I labeled recombinant human erythropoietin ( 131 I-rh-EPO) in pregnant rats and its distribution through maternal and fetal organs. Six Wistar Albino Rats in their pregnancy of 18 days were used 131 I labeled recombinant human erythropoietin (specific activity = 2.4 μCi/IU) was injected into the tail vein of rats. After 30 minutes labeled erythropoietin infusion maternal stomach, kidney, lung, liver, brain and heart as well as fetus were removed. Then, the same organs were removed from each fetus. Measuring weight of maternal and fetal organs as well as placenta were followed by radioactivity count via Cd(Te) detector. 131 I labeled recombinant human erythropoietin was found to be able to pass rat placenta and its distribution order in fetal organs was similar to those of maternal organs. Besides, as measurements were performed closer to cornu uteri, uptakes were decreasing in every fetus and its corresponding placenta. (author)

Induced pluripotent stem cells for the treatment of stroke: the potential and the pitfalls.

Science.gov (United States)

Yu, Fenggang; Li, Yingying; Morshead, Cindi M

2013-09-01

The extraordinary discovery of induced pluripotent stem cells (iPSCs) has led to the very real possibility that patient-specific cell therapy can be realized. The potential to develop cell replacement therapies outside the ethical and legal limitations, has initiated a new era of hope for regenerative strategies to treat human neurological disease including stroke. In this article, we will review and compare the current approaches to derive iPSCs from different somatic cells, and the induction into neuronal phenotypes, considering the advantages and disadvantages to the methodologies of derivation. We will highlight the work relating to the use of iPSC-based therapies in models of stroke and their potential use in clinical trials. Finally, we will consider future directions and areas of exploration which may promote the realization of iPSC-based cell replacement strategies for the treatment of stroke.

Effects of Erythropoietin Administration on Adrenal Glands of Landrace/Large White Pigs after Ventricular Fibrillation

Directory of Open Access Journals (Sweden)

Armando Faa

2016-01-01

Full Text Available Aim. To evaluate the effects of erythropoietin administration on the adrenal glands in a swine model of ventricular fibrillation and resuscitation. Methods. Ventricular fibrillation was induced via pacing wire forwarded into the right ventricle in 20 female Landrace/Large White pigs, allocated into 2 groups: experimental group treated with bolus dose of erythropoietin (EPO and control group which received normal saline. Cardiopulmonary resuscitation (CPR was performed immediately after drug administration as per the 2010 European Resuscitation Council (ERC guidelines for Advanced Life Support (ALS until return of spontaneous circulation (ROSC or death. Animals who achieved ROSC were monitored, mechanically ventilated, extubated, observed, and euthanized. At necroscopy, adrenal glands samples were formalin-fixed, paraffin-embedded, and routinely processed. Sections were stained with hematoxylin-eosin. Results. Oedema and apoptosis were the most frequent histological changes and were detected in all animals in the adrenal cortex and in the medulla. Mild and focal endothelial lesions were also detected. A marked interindividual variability in the degree of the intensity of apoptosis and oedema at cortical and medullary level was observed within groups. Comparing the two groups, higher levels of pathological changes were detected in the control group. No significant difference between the two groups was observed regarding the endothelial changes. Conclusions. In animals exposed to ventricular fibrillation, EPO treatment has protective effects on the adrenal gland.

Novel Regenerative Therapies Based on Regionally Induced Multipotent Stem Cells in Post-Stroke Brains: Their Origin, Characterization, and Perspective.

Science.gov (United States)

Takagi, Toshinori; Yoshimura, Shinichi; Sakuma, Rika; Nakano-Doi, Akiko; Matsuyama, Tomohiro; Nakagomi, Takayuki

2017-12-01

Brain injuries such as ischemic stroke cause severe neural loss. Until recently, it was believed that post-ischemic areas mainly contain necrotic tissue and inflammatory cells. However, using a mouse model of cerebral infarction, we demonstrated that stem cells develop within ischemic areas. Ischemia-induced stem cells can function as neural progenitors; thus, we initially named them injury/ischemia-induced neural stem/progenitor cells (iNSPCs). However, because they differentiate into more than neural lineages, we now refer to them as ischemia-induced multipotent stem cells (iSCs). Very recently, we showed that putative iNSPCs/iSCs are present within post-stroke areas in human brains. Because iNSPCs/iSCs isolated from mouse and human ischemic tissues can differentiate into neuronal lineages in vitro, it is possible that a clearer understanding of iNSPC/iSC profiles and the molecules that regulate iNSPC/iSC fate (e.g., proliferation, differentiation, and survival) would make it possible to perform neural regeneration/repair in patients following stroke. In this article, we introduce the origin and traits of iNSPCs/iSCs based on our reports and recent viewpoints. We also discuss their possible contribution to neurogenesis through endogenous and exogenous iNSPC/iSC therapies following ischemic stroke.

Immuno-magnetic beads-based extraction-capillary zone electrophoresis-deep UV laser-induced fluorescence analysis of erythropoietin.

Science.gov (United States)

Wang, Heye; Dou, Peng; Lü, Chenchen; Liu, Zhen

2012-07-13

Erythropoietin (EPO) is an important glycoprotein hormone. Recombinant human EPO (rhEPO) is an important therapeutic drug and can be also used as doping reagent in sports. The analysis of EPO glycoforms in pharmaceutical and sports areas greatly challenges analytical scientists from several aspects, among which sensitive detection and effective and facile sample preparation are two essential issues. Herein, we investigated new possibilities for these two aspects. Deep UV laser-induced fluorescence detection (deep UV-LIF) was established to detect the intrinsic fluorescence of EPO while an immuno-magnetic beads-based extraction (IMBE) was developed to specifically extract EPO glycoforms. Combined with capillary zone electrophoresis (CZE), CZE-deep UV-LIF allows high resolution glycoform profiling with improved sensitivity. The detection sensitivity was improved by one order of magnitude as compared with UV absorbance detection. An additional advantage is that the original glycoform distribution can be completely preserved because no fluorescent labeling is needed. By combining IMBE with CZE-deep UV-LIF, the overall detection sensitivity was 1.5 × 10⁻⁸ mol/L, which was enhanced by two orders of magnitude relative to conventional CZE with UV absorbance detection. It is applicable to the analysis of pharmaceutical preparations of EPO, but the sensitivity is insufficient for the anti-doping analysis of EPO in blood and urine. IMBE can be straightforward and effective approach for sample preparation. However, antibodies with high specificity were the key for application to urine samples because some urinary proteins can severely interfere the immuno-extraction. Copyright © 2012 Elsevier B.V. All rights reserved.

Nonlinear instabilities induced by the F coil power amplifier at FTU: Modeling and control

International Nuclear Information System (INIS)

Zaccarian, L.; Boncagni, L.; Cascone, D.; Centioli, C.; Cerino, S.; Gravanti, F.; Iannone, F.; Mecocci, F.; Pangione, L.; Podda, S.; Vitale, V.; Vitelli, R.

2009-01-01

In this paper we focus on the instabilities caused by the nonlinear behavior of the F coil current amplifier at FTU. This behavior induces closed-loop instability of the horizontal position stabilizing loop whenever the requested current is below the circulating current level. In the paper we first illustrate a modeling phase where nonlinear dynamics are derived and identified to reproduce the open-loop responses measured by the F coil current amplifier. The derived model is shown to successfully reproduce the experimental behavior by direct comparison with experimental data. Based on this dynamic model, we then reproduce the closed-loop scenario of the experiment and show that the proposed nonlinear model successfully reproduces the nonlinear instabilities experienced in the experimental sessions. Given the simulation setup, we next propose a nonlinear control solution to this instability problem. The proposed solution is shown to recover stability in closed-loop simulations. Experimental tests are scheduled for the next experimental campaign after the FTU restart.

The Influence of Acute Hyperglycemia in an Animal Model of Lacunar Stroke That Is Induced by Artificial Particle Embolization

Science.gov (United States)

Tsai, Ming-Jun; Lin, Ming-Wei; Huang, Yaw-Bin; Kuo, Yu-Min; Tsai, Yi-Hung

2016-01-01

Animal and clinical studies have revealed that hyperglycemia during ischemic stroke increases the stroke's severity and the infarct size in clinical and animal studies. However, no conclusive evidence demonstrates that acute hyperglycemia worsens post-stroke outcomes and increases infarct size in lacunar stroke. In this study, we developed a rat model of lacunar stroke that was induced via the injection of artificial embolic particles during full consciousness. We then used this model to compare the acute influence of hyperglycemia in lacunar stroke and diffuse infarction, by evaluating neurologic behavior and the rate, size, and location of the infarction. The time course of the neurologic deficits was clearly recorded from immediately after induction to 24 h post-stroke in both types of stroke. We found that acute hyperglycemia aggravated the neurologic deficit in diffuse infarction at 24 h after stroke, and also aggravated the cerebral infarct. Furthermore, the infarct volumes of the basal ganglion, thalamus, hippocampus, and cerebellum but not the cortex were positively correlated with serum glucose levels. In contrast, acute hyperglycemia reduced the infarct volume and neurologic symptoms in lacunar stroke within 4 min after stroke induction, and this effect persisted for up to 24 h post-stroke. In conclusion, acute hyperglycemia aggravated the neurologic outcomes in diffuse infarction, although it significantly reduced the size of the cerebral infarct and improved the neurologic deficits in lacunar stroke. PMID:27226775

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

Directory of Open Access Journals (Sweden)

Farooqahmed S Kittur

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

Exercise-induced muscle fatigue in the unaffected knee joint and its influence on postural control and lower limb kinematics in stroke patients

Directory of Open Access Journals (Sweden)

Sun Wook Park

2017-01-01

Full Text Available This study aimed to investigate the effects of exercise-induced muscle fatigue in the unaffected knee joint on postural control and kinematic changes in stroke patients. Forty participants (20 stroke patients, 20 age-matched healthy participants were recruited. To induce fatigue, maximum voluntary isometric contractions were performed in the unaffected knee joint in a Leg Extension Rehab exercise machine using the pneumatic resistance. We measured static and dynamic balance and lower-limb kinematics during gait. Changes in postural control parameters anteroposterior sway speed and total center of pressure distance differed significantly between the stroke and control groups. In addition, changes in gait kinematic parameters knee and ankle angles of initial contact differed significantly between stroke (paretic and non-paretic and control groups. Muscle fatigue in the unaffected knee and ankle impaired postural control and debilitates kinematic movement of ipsilateral and contralateral lower limbs, and may place the fatigued stroke patients at greater risk for falls.

Lentivirus administration to rat muscle provides efficient sustained expression of erythropoietin

NARCIS (Netherlands)

Seppen, J.; Barry, S. C.; Harder, B.; Osborne, W. R.

2001-01-01

A lentivirus pseudotyped with vesicular stomatitis virus G protein (VSV-G) encoding rat erythropoietin (EPO) complementary DNA was administered to rat skeletal muscle and red blood cell production was serially monitored. After a single intramuscular injection hematocrit values increased and reached

Endogenous erythropoietin protects neuroretinal function in ischemic retinopathy.

Science.gov (United States)

Mowat, Freya M; Gonzalez, Francisco; Luhmann, Ulrich F O; Lange, Clemens A; Duran, Yanai; Smith, Alexander J; Maxwell, Patrick H; Ali, Robin R; Bainbridge, James W B

2012-04-01

Because retinal ischemia is a common cause of vision loss, we sought to determine the effects of ischemia on neuroretinal function and survival in murine oxygen-induced retinopathy (OIR) and to define the role of endogenous erythropoietin (EPO) in this model. OIR is a reproducible model of ischemia-induced retinal neovascularization; it is used commonly to develop antiangiogenic strategies. We investigated the effects of ischemia in murine OIR on retinal function and neurodegeneration by electroretinography and detailed morphology. OIR was associated with significant neuroretinal dysfunction, with reduced photopic and scotopic ERG responses and reduced b-wave/a-wave ratios consistent with specific inner-retinal dysfunction. OIR resulted in significantly increased apoptosis and atrophy of the inner retina in areas of ischemia. EPO deficiency in heterozygous Epo-Tag transgenic mice was associated with more profound retinal dysfunction after OIR, indicated by a significantly greater suppression of ERG amplitudes, but had no measurable effect on the extent of retinal ischemia, preretinal neovascularization, or neuroretinal degeneration in OIR. Systemic administration of recombinant EPO protected EPO-deficient mice against this additional suppression, but EPO supplementation in wild-type animals with OIR did not rescue neuroretinal dysfunction or degeneration. Murine OIR offers a valuable model of ischemic neuroretinal dysfunction and degeneration in which to investigate adaptive tissue responses and evaluate novel therapeutic approaches. Endogenous EPO can protect neuroretinal function in ischemic retinopathy. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Age-related pattern and monocyte-acquired haemozoin associated production of erythropoietin in children with severe malarial anaemia in Ghana.

Science.gov (United States)

Abugri, James; Tetteh, John Kweku Amissah; Oseni, Lateef Adebayo; Mensah-Brown, Henrietta Esi; Delimini, Rupert Kantunye; Obuobi, David Osei; Akanmori, Bartholomew Dicky

2014-08-20

Malaria continues to be a global health challenge, affecting more than half the world's population and causing approximately 660,000 deaths annually. The majority of malaria cases are caused by Plasmodium falciparum and occur in sub-Saharan Africa. One of the major complications asscociated with malaria is severe anaemia, caused by a cycle of haemoglobin digestion by the parasite. Anaemia due to falciparum malaria in children has multifactorial pathogenesis, which includes suppression of bone marrow activity. Recent studies have shown that haemozoin, which is a by-product of parasite haemoglobin digestion, may play an important role in suppression of haemoglobin production, leading to anaemia. In this study we correlated the levels of erythropoietin (EPO), as an indicator of stimulation of haemoglobin production, to the levels of monocyte acquired haemozoin in children with both severe and uncomplicated malaria. There was a significantly negative correlation between levels of haemozoin-containing monocytes and EPO, which may suggest that haemozoin suppresses erythropoiesis in severe malaria. A multiple linear regression analysis and simple bar was used to investigate associations between various haematological parameters. To examine the levels of erythropoietin in the age categories, the levels of erythropoietin was measured using a commercial Enyme-Linked Immunosorbent Assay (ELISA). Giemsa-stained blood smears were used to determine percentage pigment containing monocytes. The haemozoin containing monocytes was expressed as a percentage of the total number of monocytes. To obtain the number of haemozoin containing monocytes/μL the percentage of haemozoin containing monocytes was multiplied by the absolute number of monocytes/μL from the automated haematology analyzer. The levels of erythropoietin in younger children (<3 years) was significantly higher than in older children with a similar degree of malaria anaemia (Hb levels) (p < 0.005). Haemozoin

Form CMS-2728 data versus erythropoietin claims data: implications for quality of care studies.

Science.gov (United States)

Beaubrun, Anne C; Kanda, Eiichiro; Bond, T Christopher; McClellan, William M

2013-01-01

Medical Evidence Report Form CMS-2728 data is frequently used to study US dialysis patients, but the validity of these data have been called into question. We compared predialysis erythropoietin use as recorded on Form CMS-2728 with claims data as part of an assessment of quality of care among hemodialysis patients. Medicare claims were linked to Form CMS-2728 data for 18,870 patients. Dialysis patients, 67 years old or older, who started dialysis from 1 June 2005 to 31 May 2007 were eligible. Logistic and multivariate regressions were used to compare the use of either Form CMS-2728 or the corresponding claims data to predict mortality and the probability of meeting target hemoglobin levels. The sensitivity, specificity, and kappa coefficient for the predialysis erythropoietin indicator were 58.0%, 78.4%, and 0.36, respectively. Patients with a predialysis erythropoietin claim were less likely to die compared with patients without a claim (odds ratio = 0.80 and 95% confidence interval = 0.74-0.87), but there was no relationship observed between predialysis care and death using only Form CMS-2728 predictors. At the facility level, a predialysis erythropoietin claim was associated with a 0.085 increase in the rate of meeting target hemoglobin levels compared with patients without a claim (p = 0.041), but no statistically significant relationship was observed when using the Form CMS-2728 indicators. The agreement between Form CMS-2728 and claims data is poor and discordant results are observed when comparing the use of these data sources to predict health outcomes. Facilities with higher agreement between the two data sources may provide greater quality of care.

induced by cadmium using random amplified polymorphic DNA

African Journals Online (AJOL)

darya

2013-04-17

Apr 17, 2013 ... metallurgy, painting, plastic production, etc., and is being released into the biosphere, and ...... aquatic macrophytes: Random amplified polymorphic DNA analysis and identification of ... ecotoxicology. Toxicol. Ecotoxicol.

Effects of vibratory stimulation-induced kinesthetic illusions on the neural activities of patients with stroke.

Science.gov (United States)

Kodama, Takayuki; Nakano, Hideki; Ohsugi, Hironori; Murata, Shin

2016-01-01

[Purpose] This study evaluated the influence of vibratory stimulation-induced kinesthetic illusion on brain function after stroke. [Subjects] Twelve healthy individuals and 13 stroke patients without motor or sensory loss participated. [Methods] Electroencephalograms were taken at rest and during vibratory stimulation. As a neurophysiological index of brain function, we measured the μ-rhythm, which is present mainly in the kinesthetic cortex and is attenuated by movement or motor imagery and compared the data using source localization analyses in the Standardized Low Resolution Brain Electromagnetic Tomography (sLORETA) program. [Results] At rest, μ-rhythms appeared in the sensorimotor and supplementary motor cortices in both healthy controls and stroke patients. Under vibratory stimulation, no μ-rhythm appeared in the sensorimotor cortex of either group. Moreover, in the supplementary motor area, which stores the motor imagery required for kinesthetic illusions, the μ-rhythms of patients were significantly stronger than those of the controls, although the μ-rhythms of both groups were reduced. Thus, differences in neural activity in the supplementary motor area were apparent between the subject groups. [Conclusion] Kinesthetic illusions do occur in patients with motor deficits due to stroke. The neural basis of the supplementary motor area in stroke patients may be functionally different from that found in healthy controls.

Characterizing the protocol for early modified constraint-induced movement therapy in the EXPLICIT-stroke trial

NARCIS (Netherlands)

Nijland, R van; Wegen, E. van; Krogt, H. van der; Bakker, C.D.; Buma, F.; Klomp, A.; Kordelaar, J. van; Kwakkel, G.; Geurts, A.C.; Kuijk, A.A. van; Lindeman, E.; Visser-Meily, J.M.A.; Arendzen, H.J.; Meskers, C.G.; Helm, F.C.T. van der; Vlugt, E. de

2013-01-01

Constraint-induced movement therapy (CIMT) is a commonly used rehabilitation intervention to improve upper limb function after stroke. CIMT was originally developed for patients with a chronic upper limb paresis. Although there are indications that exercise interventions should start as early as

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

DEFF Research Database (Denmark)

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

1996-01-01

This study investigated the human erythropoietin (EPO) response to short-term hypocapnic hypoxia, its relationship to a normoxic or hypoxic increase of the haemoglobin oxygen affinity, and its suppression by the addition of CO2 to the hypoxic gas. On separate days, eight healthy male subjects were...

Clinical trial experience using erythropoietin during radiation therapy

International Nuclear Information System (INIS)

Lavey, R.S.

1998-01-01

Oncologists have several reasons for trying to maintain or increase hemoglobin levels in their patients during therapy. Relief of the symptoms of anemia, including fatigue and dyspnea, are traditional, well-accepted indications. A newer rationale is to enhance the efficacy of radiation therapy and/or chemotherapy in controlling tumors. A laboratory animal study found that administration of recombinant human erythropoietin (rHuEPO) increased intratumoral median oxygen levels and diminished the proportion of measurements in the very low ( [de

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....

Generation of a transplantable erythropoietin-producer derived from human mesenchymal stem cells.

Science.gov (United States)

Yokoo, Takashi; Fukui, Akira; Matsumoto, Kei; Ohashi, Toya; Sado, Yoshikazu; Suzuki, Hideaki; Kawamura, Tetsuya; Okabe, Masataka; Hosoya, Tatsuo; Kobayashi, Eiji

2008-06-15

Differentiation of autologous stem cells into functional transplantable tissue for organ regeneration is a promising regenerative therapeutic approach for cancer, diabetes, and many human diseases. Yet to be established, however, is differentiation into tissue capable of producing erythropoietin (EPO), which has a critical function in anemia. We report a novel EPO-producing organ-like structure (organoid) derived from human mesenchymal stem cells. Using our previously established relay culture system, a human mesenchymal stem cell-derived, human EPO-competent organoid was established in rat omentum. The organoid-derived levels of human EPO increased in response to anemia induced by rapid blood withdrawal. In addition, the presence of an organoid in rats suppressed for native (rat) EPO production enhanced recovery from anemia when compared with control animals lacking the organoid. Together these results confirmed the generation of a stem cell-derived organoid that is capable of producing EPO and sensitive to physiological regulation.

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

International Nuclear Information System (INIS)

Loevey, J.; Bereczky, B.; Gilly, R.; Kenessey, I.; Raso, E.; Simon, E.; Timar, J.; Dobos, J.; Vago, A.; Kasler, M.; Doeme, B.; Tovari, J.

2008-01-01

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 rHuEPOα 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 rHuEPOα 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 rHuEPOα on the hemoglobin level, on tumor-associated blood vessels and on hypoxia-inducible factor-(HIF-)1α expression of the tumor xenografts were monitored. The proliferation, apoptosis and clonogenic capacity of A431 cancer cells treated with rHuEPOα and irradiation were also tested in vitro. Results: in vitro, rHuEPOα 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, rHuEPOα administration compensated the tumor-induced anemia in SCID mice and decreased tumoral HIF-1α expression but had no effect on tumor growth. At the same time rHuEPOα 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: rHuEPOα treatment may modulate the efficacy of cancer radiotherapy not only by reducing systemic hypoxia and tumoral HIF-1α expression, but also by destroying tumoral vessels. (orig.)

Recovery in stroke rehabilitation through the rotation of preferred directions induced by bimanual movements: a computational study.

Directory of Open Access Journals (Sweden)

Ken Takiyama

Full Text Available Stroke patients recover more effectively when they are rehabilitated with bimanual movement rather than with unimanual movement; however, it remains unclear why bimanual movement is more effective for stroke recovery. Using a computational model of stroke recovery, this study suggests that bimanual movement facilitates the reorganization of a damaged motor cortex because this movement induces rotations in the preferred directions (PDs of motor cortex neurons. Although the tuning curves of these neurons differ during unimanual and bimanual movement, changes in PD, but not changes in modulation depth, facilitate such reorganization. In addition, this reorganization was facilitated only when encoding PDs are rotated, but decoding PDs are not rotated. Bimanual movement facilitates reorganization because this movement changes neural activities through inter-hemispheric inhibition without changing cortical-spinal-muscle connections. Furthermore, stronger inter-hemispheric inhibition between motor cortices results in more effective reorganization. Thus, this study suggests that bimanual movement is effective for stroke rehabilitation because this movement rotates the encoding PDs of motor cortex neurons.

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....... 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....

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...

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.

Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells

International Nuclear Information System (INIS)

Marrero, María Teresa; Estévez, Sara; Negrín, Gledy; Quintana, José; López, Mariana; Pérez, Francisco J.; Triana, Jorge; León, Francisco; Estévez, Francisco

2012-01-01

Highlights: ► Ayanin diacetate as apoptotic inducer in leukemia cells. ► Cell death was prevented by caspase inhibitors and by the overexpression of Bcl-x L . ► The intrinsic and the extrinsic pathways are involved in the mechanism of action. ► Death receptors are up-regulated and TRAIL enhances apoptotic cell death. -- Abstract: Here we demonstrate that the semi-synthetic flavonoid ayanin diacetate induces cell death selectively in leukemia cells without affecting the proliferation of normal lymphocytes. Incubation of human leukemia cells with ayanin diacetate induced G 2 -M phase cell cycle arrest and apoptosis which was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by the overexpression of Bcl-x L . Ayanin diacetate-induced cell death was found to be associated with: (i) loss of inner mitochondrial membrane potential, (ii) the release of cytochrome c, (iii) the activation of multiple caspases, (iv) cleavage of poly(ADP-ribose) polymerase and (v) the up-regulation of death receptors for TRAIL, DR4 and DR5. Moreover, the combined treatment with ayanin diacetate and TRAIL amplified cell death, compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer.

Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice.

Science.gov (United States)

Hitomi, Hirofumi; Kasahara, Tomoko; Katagiri, Naoko; Hoshina, Azusa; Mae, Shin-Ichi; Kotaka, Maki; Toyohara, Takafumi; Rahman, Asadur; Nakano, Daisuke; Niwa, Akira; Saito, Megumu K; Nakahata, Tatsutoshi; Nishiyama, Akira; Osafune, Kenji

2017-09-27

The production of erythropoietin (EPO) by the kidneys, a principal hormone for the hematopoietic system, is reduced in patients with chronic kidney disease (CKD), eventually resulting in severe anemia. Although recombinant human EPO treatment improves anemia in patients with CKD, returning to full red blood cell production without fluctuations does not always occur. We established a method to generate EPO-producing cells from human induced pluripotent stem cells (hiPSCs) by modifying previously reported hepatic differentiation protocols. These cells showed increased EPO expression and secretion in response to low oxygen conditions, prolyl hydroxylase domain-containing enzyme inhibitors, and insulin-like growth factor 1. The EPO protein secreted from hiPSC-derived EPO-producing (hiPSC-EPO) cells induced the erythropoietic differentiation of human umbilical cord blood progenitor cells in vitro. Furthermore, transplantation of hiPSC-EPO cells into mice with CKD induced by adenine treatment improved renal anemia. Thus, hiPSC-EPO cells may be a useful tool for clarifying the mechanisms of EPO production and may be useful as a therapeutic strategy for treating renal anemia. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Pharmacological strategies for blood conservation in cardiac surgery: erythropoietin and antifibrinolytics.

Science.gov (United States)

Hardy, J F

2001-04-01

We review the clinically important benefits of the two principal pharmacological strategies, erythropoietin (EPO) and antifibrinolytics (aprotinin and lysine analogues), to decrease transfusion of allogeneic blood products (ABP) during and after cardiac surgery. Articles were selected from an ongoing review of the literature, with special attention to meta-analyses dealing with EPO and/or antifibrinolytics and cardiac surgery. The few studies available include a number of patients insufficient to allow definitive conclusions on the benefits of EPO in cardiac surgery. Further studies are required to determine the optimal dose of EPO and to compare its cost-effectiveness with other blood sparing strategies in this context. Both aprotinin and lysine analogues effectively decrease ABP transfusions and the incidence of re-thoracotomy. In addition, high-dose aprotinin reduces cerebrovascular morbidity and mortality after cardiopulmonary bypass. Several mechanisms have been put forward to explain these beneficial effects, some of which could well be common to all antifibrinolytics. The clinical benefits of aprotinin's unique anti-inflammatory effect are not entirely clear but the finding that it reduces the incidence of stroke and death is certainly a major argument in favor of its utilization. Yet, we have to ensure that aprotinin's benefits are not offset by side-effects such as allergy. We still need large scale studies to definitely confirm the benefits and exclude the deleterious effects of these drugs on outcomes other than ABP requirements. At present, aprotinin is the only agent that has been shown to reduce the risk of cerebrovascular accident and mortality after cardiac surgery in adults.

Single-mode operation of a coiled multimode fiber amplifier

International Nuclear Information System (INIS)

Koplow, Jeffrey P.; Kliner, Dahv A. V.; Goldberg, Lew

2000-01-01

We report a new approach to obtaining single-transverse-mode operation of a multimode fiber amplifier in which the gain fiber is coiled to induce significant bend loss for all but the lowest-order mode. We demonstrated this method by constructing a coiled amplifier using Yb-doped, double-clad fiber with a core diameter of 25 μm and a numerical aperture of ∼0.1 (V≅7.4) . When the amplifier was operated as an amplified-spontaneous-emission source, the output beam had an M 2 value of 1.09±0.09 ; when seeded at 1064 nm, the slope efficiency was similar to that of an uncoiled amplifier. This technique will permit scaling of pulsed fiber lasers and amplifiers to significantly higher pulse energies and peak powers and cw fiber sources to higher average powers while maintaining excellent beam quality. (c) 2000 Optical Society of America

Mechanisms of Short-Term Training-Induced Reaching Improvement in Severely Hemiparetic Stroke Patients: A TMS Study

Science.gov (United States)

Harris-Love, Michelle L.; Morton, Susanne M.; Perez, Monica A.; Cohen, Leonardo G.

2011-01-01

Background The neurophysiological mechanisms underlying improved upper-extremity motor skills have been partially investigated in patients with good motor recovery but are poorly understood in more impaired individuals, the majority of stroke survivors. Objective The authors studied changes in primary motor cortex (M1) excitability (motor evoked potentials [MEPs], contralateral and ipsilateral silent periods [CSPs and ISPs] using transcranial magnetic stimulation [TMS]) associated with training-induced reaching improvement in stroke patients with severe arm paresis (n = 11; Upper-Extremity Fugl-Meyer score (F-M) = 27 ± 6). Methods All patients underwent a single session of reaching training focused on moving the affected hand from a resting site to a target placed at 80% of maximum forward reaching amplitude in response to a visual “GO” cue. Triceps contribute primarily as agonist and biceps primarily as antagonist to the trained forward reaching movement. Response times were recorded for each reaching movement. Results Preceding training (baseline), greater interhemispheric inhibition (measured by ISP) in the affected triceps muscle, reflecting inhibition from the nonlesioned to the lesioned M1, was observed in patients with lower F-M scores (more severe motor impairment). Training-induced improvements in reaching were greater in patients with slower response times at baseline. Increased MEP amplitudes and decreased ISPs and CSPs were observed in the affected triceps but not in the biceps muscle after training. Conclusion These results indicate that along with training-induced motor improvements, training-specific modulation of intrahemispheric and interhemispheric mechanisms occurs after reaching practice in chronic stroke patients with substantial arm impairment. PMID:21343522

Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene

International Nuclear Information System (INIS)

Hoatlin, M.E.; Kozak, S.L.; Kabat, D.; Lilly, F.; Chakraborti, A.; Kozak, C.A.

1990-01-01

The leukemogenic membrane glycoprotein (gp55) encoded by Friend spleen focus-forming virus appears to bind to erythropoietin receptors (EpoR) to stimulate erythroblastosis. To directly compare the effects of gp55 with erythropoietin (Epo), the authors produced retrovirions that encode either gp55, Epo, or EpoR. After infection with EpoR virus, interleukin 3-dependent DA-3 cells bound 125 I-labeled Epo and grew without interleukin 3 in the presence of Epo. These latter cells, but not parental DA-3 cells, became factor-independent after superinfection either with Epo virus or with Friend spleen focus-forming virus. In addition, Epo virus caused a disease in mice that mimicked Friend erythroleukemia. Although Fv-2 r homozygotes are susceptible to all other retroviral diseases, they are resistant to both Epo viral and Friend viral erythroleukemia. These results indicate that both gp55 and Epo stimulate EpoR and that the Fv-2 gene encodes a protein that controls response to these ligands. However, the Fv-2 protein is not EpoR because the corresponding genes map to opposite ends of mouse chromosome 9. These results have important implications for understanding signal transduction by EpoR and the role of host genetic variation in controlling susceptibility to an oncogenic protein

Segregation of Spontaneous and Training Induced Recovery from Visual Field Defects in Subacute Stroke Patients

Directory of Open Access Journals (Sweden)

Douwe P. Bergsma

2017-12-01

Full Text Available Whether rehabilitation after stroke profits from an early start is difficult to establish as the contributions of spontaneous recovery and treatment are difficult to tease apart. Here, we use a novel training design to dissociate these components for visual rehabilitation of subacute stroke patients with visual field defects such as hemianopia. Visual discrimination training was started within 6 weeks after stroke in 17 patients. Spontaneous and training-induced recoveries were distinguished by training one-half of the defect for 8 weeks, while monitoring spontaneous recovery in the other (control half of the defect. Next, trained and control regions were swapped, and training continued for another 8 weeks. The same paradigm was also applied to seven chronic patients for whom spontaneous recovery can be excluded and changes in the control half of the defect point to a spillover effect of training. In both groups, field stability was assessed during a no-intervention period. Defect reduction was significantly greater in the trained part of the defect than in the simultaneously untrained part of the defect irrespective of training onset (p = 0.001. In subacute patients, training contributed about twice as much to their defect reduction as the spontaneous recovery. Goal Attainment Scores were significantly and positively correlated with the total defect reduction (p = 0.01, percentage increase reading speed was significantly and positively correlated with the defect reduction induced by training (epoch 1: p = 0.0044; epoch 2: p = 0.023. Visual training adds significantly to the spontaneous recovery of visual field defects, both during training in the early and the chronic stroke phase. However, field recovery as a result of training in this subacute phase was as large as in the chronic phase. This suggests that patients benefited primarily of early onset training by gaining access to a larger visual field sooner.

Dizziness in stroke

Directory of Open Access Journals (Sweden)

M. V. Zamergrad

2015-01-01

Full Text Available Differential diagnosis of new-onset acute vestibular vertigo is chiefly made between vestibular neuronitis and stroke. Dizziness in stroke is usually accompanied by other focal neurological symptoms of brainstem and cerebellar involvement. However, stroke may appear as isolated vestibular vertigo in some cases. An analysis of history data and the results of neurovestibular examination and brain magnetic resonance imaging allows stroke to be diagnosed in patients with acute isolated dizziness. The treatment of patients with stroke-induced dizziness involves a wide range of medications for the reduction of the degree of dizziness and unsteadiness and for the secondary prevention of stroke. Vestibular rehabilitation is an important component of treatment. The paper describes an observation of a patient with poorly controlled hypertension, who developed new-onset acute systemic dizziness. Vestibular neuronitis might be presumed to be a peripheral cause of vestibular disorders, by taking into account the absence of additional obvious neurological symptoms (such as pareses, defective sensation, diplopia, etc. and the nature of nystagmus. However, intention tremor in fingernose and heel-knee tests on the left side, a negative Halmagyi test, and results of Romberg’s test could suggest that stroke was a cause ofdizziness.

Development of a VHH-Based Erythropoietin Quantification Assay

DEFF Research Database (Denmark)

Kol, Stefan; Beuchert Kallehauge, Thomas; Adema, Simon

2015-01-01

Erythropoietin (EPO) quantification during cell line selection and bioreactor cultivation has traditionally been performed with ELISA or HPLC. As these techniques suffer from several drawbacks, we developed a novel EPO quantification assay. A camelid single-domain antibody fragment directed against...... human EPO was evaluated as a capturing antibody in a label-free biolayer interferometry-based quantification assay. Human recombinant EPO can be specifically detected in Chinese hamster ovary cell supernatants in a sensitive and pH-dependent manner. This method enables rapid and robust quantification...

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......-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...

Erythropoietin and radiotherapy

International Nuclear Information System (INIS)

Le Fur, E.; Albarghach, M.N.; Pradier, O.

2010-01-01

Erythropoietin (E.P.O.) is a glycoprotein hormone. This hormone is a growth factor for red blood cells precursors in the bone marrow. The decrease of oxygen partial pressure, a reduced number of erythrocytes caused by bleeding or excessive destruction, or increased tissues oxygen requirements lead to increased secretion of E.P.O.. Its action takes place on bone marrow erythroblastic cells through specific receptors. E.P.O. stimulates the proliferation of red cell precursors stem cells in the bone marrow, thus increasing their production in one to two weeks. The effectiveness of E.P.O. at increasing haemoglobin and improving patients quality of life has been demonstrated by several studies. However, its use in radiotherapy remains controversial. While tumour hypoxia caused by anaemia is a factor of radio resistance and thus a source of local failure, tumour expression of E.P.O. receptors presents a significant risk for tumour progression and neo-angiogenesis, which would be increased during the administration of E.P.O.. The purpose of this article is to answer the question: is there a place for E.P.O. in combination with radiotherapy in the management of cancer?

Expression of human erythropoietin gene in the mammary gland of a transgenic mouse

Czech Academy of Sciences Publication Activity Database

Mikuš, Tomáš; Malý, Petr; Poplštein, M.; Landa, Vladimír; Trefil, P.; Lidický, J.

2001-01-01

Roč. 47, č. 6 (2001), s. 187-195 ISSN 0015-5500 Institutional research plan: CEZ:AV0Z5052915 Keywords : erythropoietin, mammary gland, transgenic mouse Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.519, year: 2001

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...

Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke

Science.gov (United States)

Liu, Zhongwu; Chopp, Michael

2015-01-01

Astrocytes are the most abundant cell type within the central nervous system. They play essential roles in maintaining normal brain function, as they are a critical structural and functional part of the tripartite synapses and the neurovascular unit, and communicate with neurons, oligodendrocytes and endothelial cells. After an ischemic stroke, astrocytes perform multiple functions both detrimental and beneficial, for neuronal survival during the acute phase. Aspects of the astrocytic inflammatory response to stroke may aggravate the ischemic lesion, but astrocytes also provide benefit for neuroprotection, by limiting lesion extension via anti-excitotoxicity effects and releasing neurotrophins. Similarly, during the late recovery phase after stroke, the glial scar may obstruct axonal regeneration and subsequently reduce the functional outcome; however, astrocytes also contribute to angiogenesis, neurogenesis, synaptogenesis, and axonal remodeling, and thereby promote neurological recovery. Thus, the pivotal involvement of astrocytes in normal brain function and responses to an ischemic lesion designates them as excellent therapeutic targets to improve functional outcome following stroke. In this review, we will focus on functions of astrocytes and astrocyte-mediated events during stroke and recovery. We will provide an overview of approaches on how to reduce the detrimental effects and amplify the beneficial effects of astrocytes on neuroprotection and on neurorestoration post stroke, which may lead to novel and clinically relevant therapies for stroke. PMID:26455456

Therapy with recombinant human erythropoietin in patients with myelodysplastic syndromes.

Science.gov (United States)

Stone, R M; Bernstein, S H; Demetri, G; Facklam, D P; Arthur, K; Andersen, J; Aster, J C; Kufe, D

1994-10-01

We conducted a Phase I-II trial of recombinant human erythropoietin-beta (rhEPO) in patients with myelodysplastic syndrome (MDS). Patients with anemia and pathologically confirmed MDS were eligible for the study. Treatment consisted of rhEPO by subcutaneous injection thrice weekly for 6 weeks at one of three dose levels (100 U/kg (three patients), 200 U/kg (three patients) and 400 U/kg (14 patients)). Ferrous sulfate (325 mg po tid) was also administered if the transferrin saturation was below 30% (two patients). Patients were monitored with weekly CBC, white cell differential, and reticulocyte counts. Bone marrow examinations were performed at the conclusion of the treatment period and after a 2 week washout period. Patients who responded to therapy were continued on rhEPO at the same dose for 6 additional months. Response criteria included: 50% reduction in transfusion requirements compared with the 6 week pre-study period; doubling of reticulocyte count that was maintained on two determinations at least 1 week apart; or an increase in hemoglobin by at least 1.2 gm/dl without transfusions. Pre-treatment factors potentially predictive of response were analyzed by univariate analysis and in a multivariate fashion by classification and regression trees. Seven of the twenty patients sustained an untransfused rise in serum hemoglobin > or = 1.2 gm/dl. Four of the sixteen patients (including three of seven patients experiencing a rise in serum hemoglobin) who were transfusion-dependent prior to the study achieved a reduction or elimination of their transfusion requirements. Five of thirteen patients who received rhEPO during the extension phase had a continued response. A low baseline erythropoietin level (< 50 mU/ml) was the best predictor of hemoglobin response when controlling for other variables. rhEPO has a role in the treatment of certain patients with MDS, particularly in those whose endogenous serum erythropoietin levels are not markedly elevated.

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)

The Effect of Erythropoietin on Testosterone Levels During Ischemia Reperfusion Injury in Rats

Directory of Open Access Journals (Sweden)

Tsompos C.

2016-11-01

Full Text Available Objective: This experimental study examined the effect of erythropoietin (Epo in a rat model and particularly in an adrenal ischemia-reperfusion (IR protocol. The effect of that molecule was studied biochemically using blood mean testosterone levels (T.

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

NARCIS (Netherlands)

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

2001-01-01

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

Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells

Energy Technology Data Exchange (ETDEWEB)

Marrero, Maria Teresa; Estevez, Sara; Negrin, Gledy; Quintana, Jose [Departamento de Bioquimica, Unidad Asociada al Consejo Superior de Investigaciones Cientificas, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria (Spain); Lopez, Mariana; Perez, Francisco J.; Triana, Jorge [Departamento de Quimica, Universidad de Las Palmas de Gran Canaria, Instituto Canario de Investigacion del Cancer, 35017 Las Palmas de Gran Canaria (Spain); Leon, Francisco [Instituto de Productos Naturales y Agrobiologia, Consejo Superior de Investigaciones Cientificas, Avda. Astrofisico F. Sanchez 3, 38206 La Laguna, Tenerife (Spain); Estevez, Francisco, E-mail: festevez@dbbf.ulpgc.es [Departamento de Bioquimica, Unidad Asociada al Consejo Superior de Investigaciones Cientificas, Universidad de Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria (Spain)

2012-11-09

Highlights: Black-Right-Pointing-Pointer Ayanin diacetate as apoptotic inducer in leukemia cells. Black-Right-Pointing-Pointer Cell death was prevented by caspase inhibitors and by the overexpression of Bcl-x{sub L}. Black-Right-Pointing-Pointer The intrinsic and the extrinsic pathways are involved in the mechanism of action. Black-Right-Pointing-Pointer Death receptors are up-regulated and TRAIL enhances apoptotic cell death. -- Abstract: Here we demonstrate that the semi-synthetic flavonoid ayanin diacetate induces cell death selectively in leukemia cells without affecting the proliferation of normal lymphocytes. Incubation of human leukemia cells with ayanin diacetate induced G{sub 2}-M phase cell cycle arrest and apoptosis which was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by the overexpression of Bcl-x{sub L}. Ayanin diacetate-induced cell death was found to be associated with: (i) loss of inner mitochondrial membrane potential, (ii) the release of cytochrome c, (iii) the activation of multiple caspases, (iv) cleavage of poly(ADP-ribose) polymerase and (v) the up-regulation of death receptors for TRAIL, DR4 and DR5. Moreover, the combined treatment with ayanin diacetate and TRAIL amplified cell death, compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer.

The use of /sup 125/I recombinant DNA/sub 125/ derived human erythropoietin (R-HuEPO) as a replacement for /sup 125/I human urinary epo as tracer antigen in a radioimmunoassay for human epo

International Nuclear Information System (INIS)

Cotes, P.M.; Tam, R.C.; GainesDas, R.E.

1987-01-01

This paper represents evidence that in a radioimmunoassay for human erythropoietin, recombinant DNA derived human erythropoietin can replace highly purified human urinary erythropoietin in the preparation of radioiodinated tracer antigen

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...

The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk.

Directory of Open Access Journals (Sweden)

Denis N Silachev

Full Text Available BACKGROUND: Many ischemia-induced neurological pathologies including stroke are associated with high oxidative stress. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than non-mitochondrial cellular compartments. Besides direct antioxidative activity, these compounds are believed to activate numerous protective pathways. Endogenous anti-ischemic defense may involve the very powerful neuroprotective agent erythropoietin, which is mainly produced by the kidney in a redox-dependent manner, indicating an important role of the kidney in regulation of brain ischemic damage. The goal of this study is to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies. METHODOLOGY/PRINCIPAL FINDINGS: We used the cationic plastoquinone derivative, SkQR1, as a mitochondria-targeted antioxidant to alleviate the deleterious consequences of stroke. A single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduces infarction and improves functional recovery. Concomitantly, an increase in the levels of erythropoietin in urine and phosphorylated glycogen synthase kinase-3β (GSK-3β in the brain was detected 24 h after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with the nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s which are released from functional kidneys. Renal preconditioning also induced brain protection in rats accompanied by an increased erythropoietin level in urine and kidney tissue and P-GSK-3β in brain. Co-cultivation of SkQR1-treated

The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk.

Science.gov (United States)

Silachev, Denis N; Isaev, Nikolay K; Pevzner, Irina B; Zorova, Ljubava D; Stelmashook, Elena V; Novikova, Svetlana V; Plotnikov, Egor Y; Skulachev, Vladimir P; Zorov, Dmitry B

2012-01-01

Many ischemia-induced neurological pathologies including stroke are associated with high oxidative stress. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than non-mitochondrial cellular compartments. Besides direct antioxidative activity, these compounds are believed to activate numerous protective pathways. Endogenous anti-ischemic defense may involve the very powerful neuroprotective agent erythropoietin, which is mainly produced by the kidney in a redox-dependent manner, indicating an important role of the kidney in regulation of brain ischemic damage. The goal of this study is to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies. We used the cationic plastoquinone derivative, SkQR1, as a mitochondria-targeted antioxidant to alleviate the deleterious consequences of stroke. A single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduces infarction and improves functional recovery. Concomitantly, an increase in the levels of erythropoietin in urine and phosphorylated glycogen synthase kinase-3β (GSK-3β) in the brain was detected 24 h after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with the nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s) which are released from functional kidneys. Renal preconditioning also induced brain protection in rats accompanied by an increased erythropoietin level in urine and kidney tissue and P-GSK-3β in brain. Co-cultivation of SkQR1-treated kidney cells with cortical neurons resulted in enchanced

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

International Nuclear Information System (INIS)

Dunst, J.

2004-01-01

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 ∝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.)

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

Acupuncture Induces Time-Dependent Remodelling Brain Network on the Stable Somatosensory First-Ever Stroke Patients: Combining Diffusion Tensor and Functional MR Imaging

Directory of Open Access Journals (Sweden)

Lijun Bai

2014-01-01

Full Text Available Different treatment interventions induce distinct remodelling of network architecture of entire motor system. Acupuncture has been proved to be of a promising efficacy in motor recovery. However, it is still unclear whether the reorganization of motor-related brain network underlying acupuncture is related with time since stroke and severity of deficit at baseline. The aim of study was to characterize the relation between motor-related brain organization following acupuncture and white matter microstructural changes at an interval of two weeks. We demonstrated that acupuncture induced differential reorganization of motor-related network for stroke patients as time-lapse since stroke. At the baseline, acupuncture can induce the increased functional connectivity between the left primary motor cortex (M1 and the right M1, premotor cortex, supplementary motor area (SMA, thalamus, and cerebellum. After two-week recovery, the increased functional connectivity of the left M1 was more widely distributed and primarily located in the insula, cerebellum, basal ganglia, and SMA. Furthermore, a significant negative relation existed between the FA value in the left M1 at the baseline scanning and node centrality of this region following acupuncture for both baseline and two-week recovery. Our findings may shed a new insight on understanding the reorganization of motor-related theory underlying motor impairments after brain lesions in stroke patients.

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

DEFF Research Database (Denmark)

Gothelf, A; Hojman, P; Gehl, Julie

2010-01-01

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

Hepatic erythropoietin response in cirrhosis

DEFF Research Database (Denmark)

Risør, Louise M; Fenger, Mogens; Olsen, Niels Vidiendal

2016-01-01

The main function of erythropoietin (EPO) is to maintain red blood cell mass, but in recent years, increasing evidence has suggested a wider biological role not solely related to erythropoiesis, e.g. angiogenesis and tissue protection. EPO is produced in the liver during fetal life, but the main...... production shifts to the kidney after birth. The liver maintains a production capacity of up to 10% of the total EPO synthesis in healthy controls, but can be up-regulated to 90-100%. However, the hepatic EPO synthesis has been shown not to be adequate for correction of anemia in the absence of renal......, which lead to arterial hypotension, hepatic nephropathy and anemia. An increase in EPO due to renal hypoperfusion, hypoxia and anemia or an EPO-mediated hepato-protective and regenerative mechanism is plausible. However, poor hepatic synthesis capacity, a decreasing co-factor level and inflammatory...

Sit-to-Stand in People with Stroke: Effect of Lower Limb Constraint-Induced Movement Strategies

Directory of Open Access Journals (Sweden)

Charla Krystine Gray

2014-01-01

Full Text Available Background. Weight-bearing asymmetry and impaired balance may contribute to the increased fall risk in people with stroke when rising to stand from sitting. Objective. This study investigated the effect of constraint-induced movement (CIM strategies on weight-bearing symmetry and balance during sit-to-stand in people with stroke. Methods. A nonrandom convenience sample of fifteen people with stroke performed the sit-to-stand task using three CIM strategies including a solid or compliant (foam block strategy, with the unaffected limb placed on the block, and an asymmetrical foot position strategy, with the unaffected limb placed ahead of the affected limb. Duration of the task, affected limb weight-bearing, and centre of pressure and centre of mass displacement were measured in the frontal and sagittal plane. Results. Affected limb weight-bearing was increased and frontal plane centre of pressure and centre of mass moved toward the affected limb compared to baseline with all CIM strategies. Centre of mass displacement in the sagittal plane was greater with the compliant block and asymmetrical foot strategies. Conclusions. The CIM strategies demonstrated greater loading of the affected limb and movement of the centre of pressure and centre of mass toward the affected limb. The compliant block and asymmetrical foot conditions may challenge sagittal plane balance during sit-to-stand in people with stroke.

Nonlinear thermally induced distortions of a laser beam in a cryogenic disk amplifier

International Nuclear Information System (INIS)

Vyatkin, A G; Khazanov, Efim A

2009-01-01

Taking into account the temperature dependences of the heat conductivity, the refractive index, and the thermal expansion coefficient, we calculated the temperature, elastic stresses, a thermally induced lens and depolarisation of a beam in a cryogenic disk amplifier (an Yb:YAG disk placed between a copper cylinder and a sapphire disk cooled by liquid nitrogen). When the active element (the thickness is 0.6 mm, the orientation is [001], the atomic concentration of Yb is 10%) is pumped by radiation from a diode laser (the beam diameter is 6 mm), the temperature does not exceed 140 K for the heat release power of 100 W. In this case, elastic stresses in the active element are six times lower than the maximum permissible value. The focal distance of the thermally induced lens is 5.5 m and the depolarisation rate is 0.038% per two passes through the active element. Although the heat conductivity of the active element rapidly decreases with temperature, the thermal load can be increased by 1.5-2 times when the dimensions of the active element remain constant. (active media)

The use of laser-induced fluorescence or ultraviolet detectors for sensitive and selective analysis of tobramycin or erythropoietin in complex samples

Science.gov (United States)

Ahmed, Hytham M.; Ebeid, Wael B.

2015-05-01

Complex samples analysis is a challenge in pharmaceutical and biopharmaceutical analysis. In this work, tobramycin (TOB) analysis in human urine samples and recombinant human erythropoietin (rhEPO) analysis in the presence of similar protein were selected as representative examples of such samples analysis. Assays of TOB in urine samples are difficult because of poor detectability. Therefore laser induced fluorescence detector (LIF) was combined with a separation technique, micellar electrokinetic chromatography (MEKC), to determine TOB through derivatization with fluorescein isothiocyanate (FITC). Borate was used as background electrolyte (BGE) with negative-charged mixed micelles as additive. The method was successively applied to urine samples. The LOD and LOQ for Tobramycin in urine were 90 and 200 ng/ml respectively and recovery was >98% (n = 5). All urine samples were analyzed by direct injection without sample pre-treatment. Another use of hyphenated analytical technique, capillary zone electrophoresis (CZE) connected to ultraviolet (UV) detector was also used for sensitive analysis of rhEPO at low levels (2000 IU) in the presence of large amount of human serum albumin (HSA). Analysis of rhEPO was achieved by the use of the electrokinetic injection (EI) with discontinuous buffers. Phosphate buffer was used as BGE with metal ions as additive. The proposed method can be used for the estimation of large number of quality control rhEPO samples in a short period.

Functional significance of erythropoietin in renal cell carcinoma

International Nuclear Information System (INIS)

Morais, Christudas; Johnson, David W; Vesey, David A; Gobe, Glenda C

2013-01-01

One of the molecules regulated by the transcription factor, hypoxia inducible factor (HIF), is the hypoxia-responsive hematopoietic factor, erythropoietin (EPO). This may have relevance to the development of renal cell carcinoma (RCC), where mutations of the von Hippel-Lindau (VHL) gene are major risk factors for the development of familial and sporadic RCC. VHL mutations up-regulate and stabilize HIF, which in turn activates many downstream molecules, including EPO, that are known to promote angiogenesis, drug resistance, proliferation and progression of solid tumours. HIFs typically respond to hypoxic cellular environment. While the hypoxic microenvironment plays a critical role in the development and progression of tumours in general, it is of special significance in the case of RCC because of the link between VHL, HIF and EPO. EPO and its receptor, EPOR, are expressed in many cancers, including RCC. This limits the use of recombinant human EPO (rhEPO) to treat anaemia in cancer patients, because the rhEPO may be stimulatory to the cancer. EPO may also stimulate epithelial-mesenchymal transition (EMT) in RCC, and pathological EMT has a key role in cancer progression. In this mini review, we summarize the current knowledge of the role of EPO in RCC. The available data, either for or against the use of EPO in RCC patients, are equivocal and insufficient to draw a definitive conclusion

Spatial chirp in Ti:sapphire multipass amplifier

International Nuclear Information System (INIS)

Li Wenkai; Lu Jun; Li Yanyan; Guo Xiaoyang; Wu Fenxiang; Yu Linpeng; Wang Pengfei; Xu Yi; Leng Yuxin

2017-01-01

The spatial chirp generated in the Ti:sapphire multipass amplifier is numerically investigated based on the one-dimensional (1D) and two-dimensional (2D) Frantz–Nodvik equations. The simulation indicates that the spatial chirp is induced by the spatially inhomogeneous gain, and it can be almost eliminated by utilization of proper beam profiles and spot sizes of the signal and pump pulses, for example, the pump pulse has a top-hatted beam profile and the signal pulse has a super-Gaussian beam profile with a relatively larger spot size. In this way, a clear understanding of spatial chirp mechanisms in the Ti:sapphire multipass amplifier is proposed, therefore we can effectively almost eliminate the spatial chirp and improve the beam quality of a high-power Ti:sapphire chirped pulse amplifier system. (paper)

Erythropoietin in radiotherapy

International Nuclear Information System (INIS)

Guttenburger, R.

2003-01-01

A high blood hemoglobin level is an independent factor for good prognosis as demonstrated in retrospective and prospective studies in a number of cancer sites. However, there is still debate on how hemoglobin affects outcome after radiotherapy. The issues are: 1. How about the predictive power and the magnitude of effect in various tumor entities? 2. Are all potential mechanisms for the hemoglobin effect considered? 3. Do EPO receptors found on tumor and normal cells outside the bone marrow play a role? Experimental and clinical data on anemia and its treatment have been extensively discussed. So far, the means to manipulate the hemoglobin level, their indication and administration are to be clarified. The issues are: 1. Why does transfusion not improve prognosis? 2. What have we learned from trials using EPO to stimulate endogenous Hb production? 3. What are the potential pitfalls of correcting anemia with EPO? 4. What is the optimal design of EPO-RT trials? Although there are still more questions than answers, the therapeutic potential of erythropoietin is of considerable interest to radiation oncologists. This report gives a summary reviewing the topic and ends on a note of caution: Mild anemia in cancer patients is no indication to use EPO outside clinical trials

Strokes Associated With Pregnancy and Puerperium: A Nationwide Study by the Japan Stroke Society.

Science.gov (United States)

Yoshida, Kazumichi; Takahashi, Jun C; Takenobu, Yohei; Suzuki, Norihiro; Ogawa, Akira; Miyamoto, Susumu

2017-02-01

The incidence and cause of strokes associated with pregnancy and the puerperium are still not fully understood. The aim of this study was to characterize pregnancy-related strokes in Japan using a large-scale survey with current imaging techniques. A retrospective analysis was conducted based on clinical chart reviews in 736 stroke teaching hospitals certified by the Japan Stroke Society between 2012 and 2013, using a web-based questionnaire requesting the detailed clinical course without any personally identifying information. The collection rate of this questionnaire was 70.5%, with 151 pregnancy-associated strokes extracted. Hemorrhagic strokes were observed in 111 cases (73.5%), ischemic strokes in 37 (24.5%), and mixed type in 3 cases (2.0%). The estimated incidence of pregnancy-associated stroke was 10.2 per 100 000 deliveries. Major causes of hemorrhage were aneurysm (19.8%), arteriovenous malformation (17.1%), pregnancy-induced hypertension (11.7%), and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) (8.1%). Preexisting cerebrovascular diseases responsible for hemorrhage were detected in 59 cases (53.1%). Among the ischemic strokes, 28 (75.7%) were arterial and 9 (24.3%) were venous infarctions. The most frequent cause of arterial infarctions was reversible cerebral vasoconstriction syndrome. Hemorrhagic stroke showed much poorer prognosis than ischemic stroke. The incidence of pregnancy-associated stroke in Japan did not seem higher than that in other Asian and Western countries. The proportion of hemorrhagic stroke among Japanese women was much higher than that in white women. Preexisting cerebrovascular diseases and reversible cerebral vasoconstriction syndrome play a key role in hemorrhagic and ischemic stroke, respectively. © 2016 American Heart Association, Inc.

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

-life and plasma clearance of intravenously injected recombinant human erythropoietin (rhEPO) were determined. The results indicate that the lack of compensatory increase in serum EPO to the anaemic stimulus is not due to increased catabolism, but to decreased synthesis of the renal hormone. Two patients were...

Mechanical Amplifier for a Piezoelectric Transducer

Science.gov (United States)

Moore, James; Swain, Mark; Lawson, Peter; Calvet, Robert

2003-01-01

A mechanical amplifier has been devised to multiply the stroke of a piezoelectric transducer (PZT) intended for use at liquid helium temperatures. Interferometry holds the key to high angular resolution imaging and astrometry in space. Future space missions that will detect planets around other solar systems and perform detailed studies of the evolution of stars and galaxies will use new interferometers that observe at mid- and far-infrared wavelengths. Phase-measurement interferometry is key to many aspects of astronomical interferometry, and PZTs are ideal modulators for most methods of phase measurement, but primarily at visible wavelengths. At far infrared wavelengths of 150 to 300 m, background noise is a severe problem and all optics must be cooled to about 4 K. Under these conditions, piezos are ill-suited as modulators, because their throw is reduced by as much as a factor of 2, and even a wavelength or two of modulation is beyond their capability. The largest commercially available piezo stacks are about 5 in. (12.7 cm) long and have a throw of about 180 m at room temperature and only 90 m at 4 K. It would seem difficult or impossible to use PZTs for phase measurements in the far infrared were it not for the new mechanical amplifier that was designed and built.

Hyperfractionated chemoradiation with carbogen breathing, with or without erythropoietin: A stepwise developed treatment schedule for advanced head-and-neck cancer

International Nuclear Information System (INIS)

Martinez, Jose Carlos; Villar, Alfonso; Cabezon, Maria Auxiliadora; Serdio, Jose Luis de; Fuentes, Claudio; Espineira, Manuel; Perez, Maria Dolores; Gil, Jose; Artazkoz, Juan Jose; Borque, Carlos; Suner, Marcos; Saavedra, Juan Antonio

2001-01-01

Purpose: To investigate the influence of carbogen breathing on chemoradiation and the effects of erythropoietin on transfusions. Methods and Materials: From March 1996 to April 2000, 42 (4 Stage III and 38 Stage IV) patients with head and neck cancer were treated with a twice-a-day hyperfractionated schedule. Each fraction consisted of 5 mg/m 2 of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m 2 of carboplatin plus 8050 cGy in 7 weeks. Anemia was treated either by transfusion or by erythropoietin. Results: Forty-one patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Five transfusions were given in the first group, but no transfusion was needed in the erythropoietin group. Local toxicities remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Forty-two complete responses were achieved. At two years actuarial local control, cause-specific survival and overall survival are respectively 85%, 69%, and 68%. At four years estimated probabilities of local control, cause-specific survival and overall survival are also 85%, 69%, and 68%. Conclusions: These results compare favorably with those of most reported studies. The addition of carbogen breathing appears to improve the results of chemoradiation alone. Erythropoietin therapy avoided transfusions

Operation amplifier

NARCIS (Netherlands)

Tetsuya, Saito; Nauta, Bram

2008-01-01

To provide an operation amplifier which improves power source voltage removal ratios while assuring phase compensation characteristics, and therefore can be realized with a small-scale circuit and low power consumption. SOLUTION: The operation amplifier comprises: a differential amplifier circuit 1;

Altered Neuromodulatory Drive May Contribute to Exaggerated Tonic Vibration Reflexes in Chronic Hemiparetic Stroke

Directory of Open Access Journals (Sweden)

Jacob G. McPherson

2018-04-01

Full Text Available Exaggerated stretch-sensitive reflexes are a common finding in elbow flexors of the contralesional arm in chronic hemiparetic stroke, particularly when muscles are not voluntarily activated prior to stretch. Previous investigations have suggested that this exaggeration could arise either from an abnormal tonic ionotropic drive to motoneuron pools innervating the paretic limbs, which could bring additional motor units near firing threshold, or from an increased influence of descending monoaminergic neuromodulatory pathways, which could depolarize motoneurons and amplify their responses to synaptic inputs. However, previous investigations have been unable to differentiate between these explanations, leaving the source(s of this excitability increase unclear. Here, we used tonic vibration reflexes (TVRs during voluntary muscle contractions of increasing magnitude to infer the sources of spinal motor excitability in individuals with chronic hemiparetic stroke. We show that when the paretic and non-paretic elbow flexors are preactivated to the same percentage of maximum prior to vibration, TVRs remain significantly elevated in the paretic arm. We also show that the rate of vibration-induced torque development increases as a function of increasing preactivation in the paretic limb, even though the amplitude of vibration-induced torque remains conspicuously unchanged as preactivation increases. It is highly unlikely that these findings could be explained by a source that is either purely ionotropic or purely neuromodulatory, because matching preactivation should control for the effects of a potential ionotropic drive (and lead to comparable tonic vibration reflex responses between limbs, while a purely monoaminergic mechanism would increase reflex magnitude as a function of preactivation. Thus, our results suggest that increased excitability of motor pools innervating the paretic limb post-stroke is likely to arise from both ionotropic and

Succinate-induced neuronal mitochondrial fission and hexokinase II malfunction in ischemic stroke: Therapeutical effects of kaempferol.

Science.gov (United States)

Wu, Bin; Luo, Hong; Zhou, Xu; Cheng, Cai-Yi; Lin, Lin; Liu, Bao-Lin; Liu, Kang; Li, Ping; Yang, Hua

2017-09-01

Mitochondrial dysfunction is known as one of causative factors in ischemic stroke, leading to neuronal cell death. The present work was undertaken to investigate whether succinate induces neuron apoptosis by regulating mitochondrial morphology and function. In neurons, oxygen-glucose deprivation induced succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation, leading to mitochondrial fission. Kaempferol inhibited mitochondrial fission and maintained mitochondrial HK-II through activation of Akt, and thereby protected neurons from succinate-mediated ischemi injury. Knockdown of Akt2 with siRNA diminished the effect of kaempferol, indicating that kaempferol suppressed dynamin-related protein 1 (Drp1) activation and promoted HK-II mitochondrial binding dependently on Akt. Moreover, we demonstrated that kaempferol potentiated autophagy during oxygen and glucose deprivation, contributing to protecting neuron survival against succinate insult. In vivo, oral administration of kaempferol in mice attenuated the infract volume after ischemic and reperfusion (I/R) injury and reproduced the similar mitochondrial protective effect in the brain infract area. This study indicates that succinate accumulation plays a pivotal role in I/R injury-induced neuronal mitochondrial dysfunction, and suggests that modulation of Drp1 phosphorylation might be potential therapeutic strategy to protect neuron mitochondrial integrity and treat ischemic stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

Erythropoietin-derived nonerythropoietic peptide ameliorates experimental autoimmune neuritis by inflammation suppression and tissue protection.

Directory of Open Access Journals (Sweden)

Yuqi Liu

Full Text Available Experimental autoimmune neuritis (EAN is an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system. Erythropoietin (EPO has been known to promote EAN recovery but its haematopoiesis stimulating effects may limit its clinic application. Here we investigated the effects and potential mechanisms of an EPO-derived nonerythropoietic peptide, ARA 290, in EAN. Exogenous ARA 290 intervention greatly improved EAN recovery, improved nerve regeneration and remyelination, and suppressed nerve inflammation. Furthermore, haematopoiesis was not induced by ARA 290 during EAN treatment. ARA 290 intervention suppressed lymphocyte proliferation and altered helper T cell differentiation by inducing increase of Foxp3+/CD4+ regulatory T cells and IL-4+/CD4+ Th2 cells and decrease of IFN-γ+/CD4+ Th1 cells in EAN. In addition, ARA 290 inhibited inflammatory macrophage activation and promoted its phagocytic activity. In vitro, ARA 290 was shown to promote Schwann cell proliferation and inhibit its inflammatory activation. In summary, our data demonstrated that ARA 290 could effectively suppress EAN by attenuating inflammation and exerting direct cell protection, indicating that ARA 290 could be a potent candidate for treatment of autoimmune neuropathies.

Sickle Mice Are Sensitive to Hypoxia/Ischemia-Induced Stroke but Respond to Tissue-Type Plasminogen Activator Treatment.

Science.gov (United States)

Sun, Yu-Yo; Lee, Jolly; Huang, Henry; Wagner, Mary B; Joiner, Clinton H; Archer, David R; Kuan, Chia-Yi

2017-12-01

The effects of lytic stroke therapy in patients with sickle cell anemia are unknown, although a recent study suggested that coexistent sickle cell anemia does not increase the risk of cerebral hemorrhage. This finding calls for systemic analysis of the effects of thrombolytic stroke therapy, first in humanized sickle mice, and then in patients. There is also a need for additional predictive markers of sickle cell anemia-associated vasculopathy. We used Doppler ultrasound to examine the carotid artery of Townes sickle mice tested their responses to repetitive mild hypoxia-ischemia- and transient hypoxia-ischemia-induced stroke at 3 or 6 months of age, respectively. We also examined the effects of tPA (tissue-type plasminogen activator) treatment in transient hypoxia-ischemia-injured sickle mice. Three-month-old sickle cell (SS) mice showed elevated resistive index in the carotid artery and higher sensitivity to repetitive mild hypoxia-ischemia-induced cerebral infarct. Six-month-old SS mice showed greater resistive index and increased flow velocity without obstructive vasculopathy in the carotid artery. Instead, the cerebral vascular wall in SS mice showed ectopic expression of PAI-1 (plasminogen activator inhibitor-1) and P-selectin, suggesting a proadhesive and prothrombotic propensity. Indeed, SS mice showed enhanced leukocyte and platelet adherence to the cerebral vascular wall, broader fibrin deposition, and higher mortality after transient hypoxia-ischemia. Yet, post-transient hypoxia-ischemia treatment with tPA reduced thrombosis and mortality in SS mice. Sickle mice are sensitive to hypoxia/ischemia-induced cerebral infarct but benefit from thrombolytic treatment. An increased resistive index in carotid arteries may be an early marker of sickle cell vasculopathy. © 2017 American Heart Association, Inc.

Amplifier Distortion

Science.gov (United States)

Keeports, David

2006-12-01

By definition, a high fidelity amplifier's instantaneous output voltage is directly proportional to its instantaneous input voltage. While high fidelity is generally valued in the amplification of recorded music, nonlinearity, also known as distortion, is desirable in the amplification of some musical instruments. In particular, guitar amplifiers exploit nonlinearity to increase both the harmonic content and sustain of a guitar's sound. I will discuss how both modifications in sound result from saturation of triode tubes and transistors. Additionally, I will describe the difference in the symmetry of saturation curves for transistors and tubes and the reason why tube guitar amplifiers are generally considered to be superior to solid-state amplifiers. Finally, I will discuss attempts to use solid-state electronics to replicate the sound of tube amplifiers.

Effects of modified constraint-induced movement therapy on reach-to-grasp movements and functional performance after chronic stroke: a randomized controlled study.

Science.gov (United States)

Lin, K-C; Wu, C-Y; Wei, T-H; Lee, C-Y; Liu, J-S

2007-12-01

To evaluate changes in (1) motor control characteristics of the hemiparetic hand during the performance of a functional reach-to-grasp task and (2) functional performance of daily activities in patients with stroke treated with modified constraint-induced movement therapy. Two-group randomized controlled trial with pretreatment and posttreatment measures. Rehabilitation clinics. Thirty-two chronic stroke patients (21 men, 11 women; mean age=57.9 years, range=43-81 years) 13-26 months (mean 16.3 months) after onset of a first-ever cerebrovascular accident. Thirty-two patients were randomized to receive modified constraint-induced movement therapy (restraint of the unaffected limb combined with intensive training of the affected limb) or traditional rehabilitation for three weeks. Kinematic analysis was used to assess motor control characteristics as patients reached to grasp a beverage can. Functional outcomes were evaluated using the Motor Activity Log and Functional Independence Measure. There were moderate and significant effects of modified constraint-induced movement therapy on some aspects of motor control of reach-to-grasp and on functional ability. The modified constraint-induced movement therapy group preplanned reaching and grasping (P=0.018) more efficiently and depended more on the feedforward control of reaching (P=0.046) than did the traditional rehabilitation group. The modified constraint-induced movement therapy group also showed significantly improved functional performance on the Motor Activity Log (Pcontrol strategy during goal-directed reaching, a possible mechanism for the improved movement performance of stroke patients undergoing this therapy.

Gene doping detection: evaluation of approach for direct detection of gene transfer using erythropoietin as a model system.

Science.gov (United States)

Baoutina, A; Coldham, T; Bains, G S; Emslie, K R

2010-08-01

As clinical gene therapy has progressed toward realizing its potential, concern over misuse of the technology to enhance performance in athletes is growing. Although 'gene doping' is banned by the World Anti-Doping Agency, its detection remains a major challenge. In this study, we developed a methodology for direct detection of the transferred genetic material and evaluated its feasibility for gene doping detection in blood samples from athletes. Using erythropoietin (EPO) as a model gene and a simple in vitro system, we developed real-time PCR assays that target sequences within the transgene complementary DNA corresponding to exon/exon junctions. As these junctions are absent in the endogenous gene due to their interruption by introns, the approach allows detection of trace amounts of a transgene in a large background of the endogenous gene. Two developed assays and one commercial gene expression assay for EPO were validated. On the basis of ability of these assays to selectively amplify transgenic DNA and analysis of literature on testing of gene transfer in preclinical and clinical gene therapy, it is concluded that the developed approach would potentially be suitable to detect gene doping through gene transfer by analysis of small volumes of blood using regular out-of-competition testing.

Xylometazoline abuse induced ischemic stroke in a young adult.

Science.gov (United States)

Leupold, Daniela; Wartenberg, Katja E

2011-01-01

substance abuse is an important cause of ischemic stroke in the young. This includes over-the-counter dietary supplements and cough and cold remedies, which were reported to be an independent risk factor for hemorrhagic stroke. this article describes a young male patient with acute ischemic infarctions in the posterior inferior cerebellar and posterior cerebral artery territories bilaterally, the right cerebral peduncle, the left pontine tegmentum, and lateral pons following abuse of xylometazoline-containing nasal decongestant for 10 years. this is the first report in the literature of posterior circulation strokes because of chronic xylometazoline abuse. We hope to contribute to increase knowledge and awareness of the public about these serious complications of cough-and-cold remedies as well as dietary supplements containing sympathomimetics.

The neuroanatomy of pure apraxia of speech in stroke.

Science.gov (United States)

Graff-Radford, Jonathan; Jones, David T; Strand, Edythe A; Rabinstein, Alejandro A; Duffy, Joseph R; Josephs, Keith A

2014-02-01

The left insula or Broca's area have been proposed as the neuroanatomical correlate for apraxia of speech (AOS) based on studies of patients with both AOS and aphasia due to stroke. Studies of neurodegenerative AOS suggest the premotor area and the supplementary motor areas as the anatomical correlates. The study objective was to determine the common infarction area in patients with pure AOS due to stroke. Patients with AOS and no or equivocal aphasia due to ischemic stroke were identified through a pre-existing database. Seven subjects were identified. Five had pure AOS, and two had equivocal aphasia. MRI lesion analysis revealed maximal overlap spanning the left premotor and motor cortices. While both neurodegenerative AOS and stroke induced pure AOS involve the premotor cortex, further studies are needed to establish whether stroke-induced AOS and neurodegenerative AOS share a common anatomic substrate. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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

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...

Transcranial direct-current stimulation induced in stroke patients with aphasia: a prospective experimental cohort study

OpenAIRE

Santos,Michele Devido; Gagliardi,Rubens José; Mac-Kay,Ana Paula Machado Goyano; Boggio,Paulo Sergio; Lianza,Roberta; Fregni,Felipe

2013-01-01

CONTEXT AND OBJECTIVE: Previous animal and human studies have shown that transcranial direct current stimulation can induce significant and lasting neuroplasticity and may improve language recovery in patients with aphasia. The objective of the study was to describe a cohort of patients with aphasia after stroke who were treated with transcranial direct current stimulation. DESIGN AND SETTING: Prospective cohort study developed in a public university hospital. METHODS: Nineteen patients with ...

Combined aprotinin and erythropoietin use for blood conservation: results with Jehovah's Witnesses.

Science.gov (United States)

Rosengart, T K; Helm, R E; Klemperer, J; Krieger, K H; Isom, O W

1994-11-01

Despite recent advances in blood conservation techniques, major risks persist for excessive bleeding and blood transfusion after open heart operations. We reviewed the records of 100 consecutive patients undergoing first-time coronary artery bypass grafting at our institution to define these risks and develop a multimodality blood conservation program based on the results. This program was subsequently applied on a prospective basis to a select group of patients who refuse blood transfusion on religious grounds (Jehovah's Witnesses [JW]) (n = 15). Encouraging initial results with coronary artery bypass grafting in this group (n = 8) led to the application of the program to more complex operations (n = 7), including repeat bypass grafting with use of the internal mammary artery, repeat mitral valve replacement, aortic and mitral valve replacement with coronary artery bypass grafting, mitral valve replacement with bypass grafting, chronic type 1 dissection repair, aortic valve replacement, and atrial septal defect repair in 1 patient each. The blood conservation program employed in these patients included the use of (1) aprotinin (full Hammersmith regimen), (2) high-dose erythropoietin, (3) "maximal"-volume intraoperative autologous blood donation, (4) low-prime cardiopulmonary bypass, (5) exclusive use of intraoperative cell salvage, and (6) continuous reinfusion of shed mediastinal blood. There were no deaths in the JW group. Thromboembolic complications consisted of a transient posterior circulation stroke in only 1 patient (dissection repair). No blood or blood products were transfused compared with the transfusion of 5.1 +/- 7.8 units (mean +/- standard deviation) in the 100 primary coronary bypass patients in whom the blood conservation program was not employed.(ABSTRACT TRUNCATED AT 250 WORDS)

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

DEFF Research Database (Denmark)

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

2007-01-01

on the expression of muscle membrane transport proteins. Likewise, improvements in performance may involve upregulation of metabolic enzymes. Since Epo is known to augment performance we tested the effect of rHuEpo on some marker enzymes that are related to aerobic capacity. For these purposes eight subjects...... performance by approximately 54%. Membrane transport systems and carbonic anhydrases involved in pH regulation remained unchanged. Of the Na(+), K(+)-pump isoforms only the density of the alpha2 subunit was decreased (by 22%) after treatment. The marker enzymes cytochrom c and hexokinase remained unchanged......Adaptations to chronic hypoxia involve changes in membrane transport proteins. The underlying mechanism of this response may be related to concomitant occurring changes in erythropoietin (Epo) levels. We therefore tested the direct effects of recombinant human erythropoietin (rHuEpo) treatment...

Generating and measuring photochemical changes inside the brain using optical fibers: exploring stroke.

Science.gov (United States)

Tsiminis, Georgios; Klarić, Thomas S; Schartner, Erik P; Warren-Smith, Stephen C; Lewis, Martin D; Koblar, Simon A; Monro, Tanya M

2014-11-01

We report here on the development of a method for inducing a stroke in a specific location within a mouse brain through the use of an optical fiber. By capturing the emitted fluorescence signal generated using the same fiber it is possible to monitor photochemical changes within the brain in real-time, and directly measure the concentration of the stroke-inducing dye, Rose Bengal, at the infarct site. This technique reduces the requirement for post-operative histology to determine if a stroke has successfully been induced within the animal, and therefore opens up the opportunity to explore the recovery of the brain after the stroke event.

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.

The effect of erythropoietin on calcium levels during hypoxia reoxygenation injury in rats

Directory of Open Access Journals (Sweden)

Constantinos Tsompos

2016-04-01

Full Text Available This experimental study examined the effect of erythropoietin (Epo on rat model and particularly in a hypoxia-reoxygenation protocol. The effect of that molecule was studied biochemically using blood mean calcium levels (Ca++. Forty rats of mean weight 247.7 g were used in the study. Ca++ levels were measured at 60 min (groups A and C and at 120 min (groups B and D of reoxygenation. Erythropoietin was administered only in groups C and D. Epo administration non-significantly decreased the Ca++ levels by 0.56%±1.13% (P=0.5761. Reoxygenation time non-significantly increased the Ca++ levels by 0.65%±1.12% (P=0.5281. However, Epo administration and reoxygenation time together non-significantly decreased the Ca++ levels by 0.34%±0.68% (P=0.6095. Epo administration whether it interacted or not with reoxygenation time had non-significant decreasing short-term effects on calcium levels. Perhaps, a longer study time than 2 h or a higher Epo dose may reveal more significant effects.

Anemia in kidney transplants without erythropoietic agents: levels of erythropoietin and iron parameters.

Science.gov (United States)

Florit, E A; Hadad, F; Rodriguez Cubillo, B; De la Flor, J C; Valga, F; Perez Flores, I; Calvo Romero, N; Valero San Cecilio, R; Barrientos Guzman, A; Sanchez Fructuoso, A

2012-11-01

To study the association between hemoglobin, endogenous erythropoietin (EPO) levels and ferric parameters in kidney recipients not treated with EPO-stimulating agents. Transverse study of 219 kidney transplant outpatients. The median time after transplantation was 54 months (P(25-75), 23-107). We assessed blood counts, ferric parameters, EPO levels, renal function (MDRD-4), and adjuvant treatment. We performed a linear regression analysis to predict hemoglobin. Median EPO values were 14.05 mUI/mL (P(25-75) = 10.2-19.7). Applying the formulas described by Beguin, kidney transplant recipients showed a low observed/expected ratio of erythropoietin and of transferrin. Considering anemia to be an hemoglobin of calculate hemoglobin was: hemoglobin = 11829-0909 log (EPG level) - 0455 (if female) + 0.010 0.013 transferrin + 0.013 creatinine clearance (r = .424, P < .001). Treatment with ACEI and/or ARBs seemed to produce a defect in the synthesis of EPO, while those treated with mTORi, a hyporesponsive state. Copyright © 2012 Elsevier Inc. All rights reserved.

Op-amp based low noise amplifier for magnetic particle spectroscopy

Directory of Open Access Journals (Sweden)

Malhotra Ankit

2017-09-01

Full Text Available Magnetic particle spectrometry (MPS is a novel technique used to measure the magnetization response of superparamagnetic iron oxide nanoparticles (SPIONs. Therefore, it is one of the most important tools for the characterization of the SPIONs for imaging modalities such as magnetic particle imaging (MPI and Magnetic Resonance Imaging (MRI. In MPS, change in the particle magnetization induces a voltage in a dedicated receive coil. The amplitude of the signal can be very low (ranging from a few nV to 100 μV depending upon the concentration of the nanoparticles. Hence, the received signal needs to be amplified with a low noise amplifier (LNA. LNA’s paramount task is to amplify the received signal while keeping the noise induced by its own circuitry minimum. In the current research, we purpose modeling, design, and development of a prototyped LNA for MPS. The designed prototype LNA is based on the parallelization technique of Op-amps. The prototyped LNA consists of 16 Op-amps in parallel and is manufactured on a printed circuit board (PCB, with a size of 110.38 mm × 59.46 mm and 234 components. The input noise of the amplifier is approx. 546 pV/√Hz with a noise figure (NF of approx. 1.4 dB with a receive coil termination. Furthermore, a comparison between the prototyped LNA and a commercially available amplifier is shown.

Prevalence of stroke/cardiovascular risk factors in Hungary

Science.gov (United States)

Bodo, M.; Sipos, K.; Thuroczy, G.; Panczel, G.; Ilias, L.; Szonyi, P.; Bodo, M., Jr.; Nebella, T.; Banyasz, A.; Nagy, Z.

2010-04-01

A cross-sectional survey was conducted in Hungary using the Cerberus system which includes: 1) a questionnaire addressing the risk factors for stroke/cardiovascular disease; 2) amplifiers to record the pulse waves of cerebral arteries (rheoencephalography) and peripheral arteries, electrocardiogram and electroencephalogram. Additionally, subjects were measured for carotid stenosis by Doppler ultrasound and 12-lead electrocardiogram; subjects were also screened for blood cholesterol, glucose, and triglyceride levels. Prevalence of the following stroke risk factors was identified: overweight, 63.25%; sclerotic brain arteries (by rheoencephalogram), 54.29%; heart disease, 37.92%; pathologic carotid flow, 34.24%; smoking, 30.55%; high blood cholesterol, 28.70%; hypertension, 27.83%; high triglyceride, 24.35%; abnormality in electrocardiogram, 20%; high glucose, 15.95%; symptoms of transient ischemic attack, 16.07%; alcohol abuse, 6.74%; and diabetes, 4.53%. The study demonstrates a possible model for primary cardiovascular disease/stroke prevention. This method offers a standardizable, cost effective, practical technique for mass screenings by identifying the population at high risk for cardiovascular disturbances, especially cerebrovascular disease (primary prevention). In this model, the rheoencephalogram can detect cerebrovascular arteriosclerosis in the susceptibility/presymptomatic phase, earlier than the Doppler ultrasound technique. The method also provides a model for storing analog physiological signals in a computer-based medical record and is a first step in applying an expert system to stroke prevention.

CLINICAL APPLICATION OF RECOMBINANT ERYTHROPOIETIN IN BETA-THALASSAEMIA INTERMEDIA.

Science.gov (United States)

Asadov, Ch; Alimirzoyeva, Z; Hasanova, M; Mammadova, T; Shirinova, A

2016-06-01

Research objective is to study the efficacy of recombinant erythropoietin (epoetin alfa) as alternative method of treatment beta-thalassemia intermedia. Study involved 58 patients with beta-thalassemia intermedia (23 women and 35 men). In all observed patients was defined levels of hemoglobin (Hb), red blood cells (RBC), erythrocyte indexes (MCV, MCH, MCHC), hemoglobin fractions (HbA, HbA2, HbF), serum ferritin, serum erythropoietin before and after administrated rEPO. All patients received rEPO during 6 month at the dose - 10000 IU subcutaneously. The majority of patients - 39 (67%) had a good response to rEPO (increase in hemoglobin level more than 20 g/l); 16 patients (28%) had a mean response (increase in Hb 10 - 20 g/l); in 3 (5%) patients occurred poor response to rEPO therapy (increase in Hb intermedia patients there was a statistically significant change in the number of RBC, levels of HbF and sEPO. The evaluation of interdependence between the indices of the baseline sEPO and increased Hb values in patients after rEPO treatment revealed the presence of the reverse direct relationship (r=-0.67). Based on the results, it can be concluded that the use of rEPO in complex therapy of beta-thalassemia intermedia leads to increased levels of Hb and consequently reducing the need for blood transfusions, and accordingly expected to prevent severe complications of blood transfusion (alloimmunization, hypersplenism, iron overload, contamination transmissible infections) facilitating normal growth and development, and a better quality of life.

Pathological links between stroke and cardiac arrest

Institute of Scientific and Technical Information of China (English)

Shaila Ghanekar; Sydney Corey; Trenton Lippert; Cesar V.Borlongan

2017-01-01

There may be a pathological connection between cardiac failure and ischemic stroke.In this article we describe pertinent research that demonstrates subsequent death of cardiac and neural myocytes in the post ischemic stroke brain.Current stroke therapy overlooks the connection between cardiac and cerebrovascular events and fails to address the shared risk factors.Current pre-clinical stroke investigations have provided evidence that suggests the presence of an indirect cell death pathway in which toxic molecules emanate from the stroke brain and trigger cardiac cell death.On the other hand,other studies highlight the presence of a reverse cell death cascade in which toxic molecules from the heart,following cardiac arrest,travel to the brain and induce ischemic cell death.Further examination of these putative cell death pathways between ischemic stroke and cardiac arrest will prompt the advancement of innovative treatments specifically targeting both diseases,leading to ameliorated clinical results of patients diagnosed with heart failure and ischemic stroke.

Erythropoietin in the cerebrospinal fluid of patients with aneurysmal subarachnoid haemorrhage originates from the brain

DEFF Research Database (Denmark)

Springborg, Jacob Bertram; Sonne, Bjarne; Frederiksen, Hans Jørgen

2003-01-01

Recent years' research has revealed a specific, neuroprotective erythropoietin (EPO) system in the central nervous system (CNS) that is upregulated by hypoxia. The presence and dynamics of EPO in the cerebrospinal fluid (CSF) of patients with subarachnoid haemorrhage (SAH) has not been investigated...

Garlic accelerates red blood cell turnover and splenic erythropoietic gene expression in mice: evidence for erythropoietin-independent erythropoiesis.

Directory of Open Access Journals (Sweden)

Bünyamin Akgül

2010-12-01

Full Text Available Garlic (Allium sativum has been valued in many cultures both for its health effects and as a culinary flavor enhancer. Garlic's chemical complexity is widely thought to be the source of its many health benefits, which include, but are not limited to, anti-platelet, procirculatory, anti-inflammatory, anti-apoptotic, neuro-protective, and anti-cancer effects. While a growing body of scientific evidence strongly upholds the herb's broad and potent capacity to influence health, the common mechanisms underlying these diverse effects remain disjointed and relatively poorly understood. We adopted a phenotype-driven approach to investigate the effects of garlic in a mouse model. We examined RBC indices and morphologies, spleen histochemistry, RBC half-lives and gene expression profiles, followed up by qPCR and immunoblot validation. The RBCs of garlic-fed mice register shorter half-lives than the control. But they have normal blood chemistry and RBC indices. Their spleens manifest increased heme oxygenase 1, higher levels of iron and bilirubin, and presumably higher CO, a pleiotropic gasotransmitter. Heat shock genes and those critical for erythropoiesis are elevated in spleens but not in bone marrow. The garlic-fed mice have lower plasma erythropoietin than the controls, however. Chronic exposure to CO of mice on garlic-free diet was sufficient to cause increased RBC indices but again with a lower plasma erythropoietin level than air-treated controls. Furthermore, dietary garlic supplementation and CO treatment showed additive effects on reducing plasma erythropoietin levels in mice. Thus, garlic consumption not only causes increased energy demand from the faster RBC turnover but also increases the production of CO, which in turn stimulates splenic erythropoiesis by an erythropoietin-independent mechanism, thus completing the sequence of feedback regulation for RBC metabolism. Being a pleiotropic gasotransmitter, CO may be a second messenger for garlic

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

International Nuclear Information System (INIS)

Uziel, Orit; Kanfer, Gil; Beery, Einat; Yelin, Dana; Shepshelovich, Daniel; Bakhanashvili, Mary; Nordenberg, Jardena; Lahav, Meir

2014-01-01

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

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.

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.

Synthesis and biological evaluation of 125I-erythropoietin as a potential radiopharmaceutical agent for tumours

International Nuclear Information System (INIS)

Clemente, Goncalo dos Santos; Duarte, Vera Lucia Serra

2011-01-01

Erythropoietin (EPO) is a glycoprotein hormone responsible for regulating erythropoiesis. Expression of EPO and EPO receptors (EPOr) has recently been demonstrated in some neoplastic cell lines and tumours, suggesting a potential new target for therapy. In this work, EPO was labeled with iodine-125 using the lactoperoxidase method, known to prevent damage to protein during radioiodination, and labeling conditions were optimized. In vitro stability studies have shown that 125 I-EPO is radiochemically stable for 20 days after radiolabeling. In vitro cell binding studies have demonstrated very low binding ( 125 I-EPO. In mice with induced melanoma, only a residual fixation in the tumour was evident. Further studies are warranted on other tumoral cell lines to better understand the binding process and internalization into cells. Studies on EPO labeled with carbon-11 could be valuable, since there is a greater chance of preserving the biological activity of the protein using this method. (author)

Unilateral versus bilateral upper limb training after stroke: the ULTRA-Stroke clinical trial

NARCIS (Netherlands)

van Delden, A.E.Q.; Peper, C.E.; Nienhuys, K.; Zijp, N.I.; Beek, P.J.; Kwakkel, G.

2013-01-01

Background and Purpose - Unilateral and bilateral training protocols for upper limb rehabilitation after stroke represent conceptually contrasting approaches with the same ultimate goal. In a randomized controlled trial, we compared the merits of modified constraint-induced movement therapy,

Significant association between polymorphism of the erythropoietin gene promoter and myelodysplastic syndrome

Directory of Open Access Journals (Sweden)

O'Brien Susan

2010-11-01

Full Text Available Abstract Background Myelodysplastic syndrome (MDS may be induced by certain mutagenic environmental or chemotherapeutic toxins; however, the role of susceptibility genes remains unclear. The G/G genotype of the single-nucleotide polymorphism (SNP rs1617640 in the erythropoietin (EPO promoter has been shown to be associated with decreased EPO expression. We examined the association of rs1617640 genotype with MDS. Methods We genotyped the EPO rS1617640 SNP in 189 patients with MDS, 257 with acute myeloid leukemia (AML, 106 with acute lymphoblastic leukemia, 97 with chronic lymphocytic leukemia, 353 with chronic myeloid leukemia, and 95 healthy controls. Results The G/G genotype was significantly more common in MDS patients (47/187; 25.1% than in controls (6/95; 6.3% or in patients with other leukemias (101/813; 12.4% (all P P = 0.03. Time to neutrophils recovery after therapy was significantly longer in MDS patients with the G/G genotype (P = 0.02. Conclusions These findings suggest a strong association between the rs1617640 G/G genotype and MDS. Further studies are warranted to investigate the utility of screening for this marker in individuals exposed to environmental toxins or chemotherapy.

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.

Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

Science.gov (United States)

Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

2016-01-01

Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions

Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

Directory of Open Access Journals (Sweden)

Gemma Chiva-Blanch

Full Text Available Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke.Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls.Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions.Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger

Prevention of contrast-induced nephropathy with single bolus erythropoietin in patients with diabetic kidney disease: A randomized controlled trial.

Science.gov (United States)

Shema-Didi, Lilach; Kristal, Batya; Eizenberg, Sarit; Marzuq, Nabil; Sussan, Majdy; Feldman-Idov, Yulie; Ofir, Pnina; Atar, Shaul

2016-04-01

Contrast-induced-nephropathy (CIN) is associated with poor outcomes, thus prevention of CIN may be of clinical value. Erythropoietin (EPO) has been shown to elicit tissue-protective effects in experimental models and in clinical studies of acute kidney injury. We therefore evaluated its effectiveness for prevention of CIN after coronary angiography (CA) ± percutaneous coronary intervention (PCI) in diabetic patients with chronic kidney disease. A prospective, randomized, controlled trial was carried out in 138 diabetic patients with eGFR <60 mL/min who underwent non-urgent CA ± PCI. Patients received normal saline and n-acetyl cysteine before CA, with or without 50,000 U of EPO administered 30 min prior to CA. CIN was defined as an increase in serum creatinine of at least 0.5 mg/dL during the first 2 days after exposure to contrast media. Primary outcome was the incidence of CIN. Secondary outcomes were the sensitivity and positive predictive value (PPV) of Cystatin C (CC) and Neutrophil-gelatinase-associated-lipocalin (NGAL) for diagnosis of CIN. The observed incidence of CIN was 8.7%, significantly lower than the expected for such high-risk population. The administration of EPO prior to CA did not reduce the incidence of CIN (9.7% vs. 7.6%, P = 0.65). CC and NGAL demonstrated a low sensitivity (16.6%) and low PPV (6.7 and 33.3%, respectively) for detecting CIN. The administration of EPO prior to CA did not reduce the incidence of CIN. Additional prospective research with a larger sample size and in other patient categories is essential to further define the potential protective effect of EPO on prevention of CIN. © 2015 Asian Pacific Society of Nephrology.

Portable musical instrument amplifier

Science.gov (United States)

Christian, David E.

1990-07-24

The present invention relates to a musical instrument amplifier which is particularly useful for electric guitars. The amplifier has a rigid body for housing both the electronic system for amplifying and processing signals from the guitar and the system's power supply. An input plug connected to and projecting from the body is electrically coupled to the signal amplifying and processing system. When the plug is inserted into an output jack for an electric guitar, the body is rigidly carried by the guitar, and the guitar is operatively connected to the electrical amplifying and signal processing system without use of a loose interconnection cable. The amplifier is provided with an output jack, into which headphones are plugged to receive amplified signals from the guitar. By eliminating the conventional interconnection cable, the amplifier of the present invention can be used by musicians with increased flexibility and greater freedom of movement.

PELATIHAN MIRROR NEURON SYSTEM SAMA DENGAN PELATIHAN CONSTRAINT INDUCED MOVEMENT THERAPY DALAM MENINGKATKAN KEMAMPUAN FUNGSIONAL ANGGOTA GERAK ATAS PASIEN STROKE

Directory of Open Access Journals (Sweden)

Abdul chalik meidian

2014-03-01

Full Text Available Stroke is an interruption of blood vasculature system in the brain that causes suddenly neurological dysfunction, resulted in clinically brain tissue damage in a relatively long time period, decreased physical mobility and functional ability impaired of upper limb. The purpose of this study is to know an increasing in upper limb functional ability among stroke patients after mirror neuron system exercise and constraint induced movement therapy exercise and to know the comparison of both exercise. This study uses an experimental research with pre-test and post-test control group design. Number of samples of the first group is 13 patients given mirror neuron system exercise for 30-60 minutes , while the second group 13 patients were given constraint induced movement therapy exercise for 30-60 minutes. The research was conducted in 2 month period time. Each patient is taught a variety of upper limb functional ability in accordance with the operational concept guidance and patients were asked to repeat the exercise independently at home as directed. Measuring test of upper limb functional ability is using the wolf motor function test instruments. The result is an increase the upper limb functional ability of 21.7% in the mirror neuron system exercise group and proved a significant difference (p<0.05 and an increase in the upper limb functional ability of 17.1% in the constraint induced movement therapy exercise group and proved a significant difference (p<0.05 while the difference of increasing of upper limb functional ability of the two groups showed no significant difference (p>0,05. It was concluded that the mirror neuron system exercise is similar with constraint induced movement therapy exercise in increasing the upper limb functional ability among stroke patients.

Use of recombinant erythropoietin for the management of severe hemolytic disease of the newborn of a K0 phenotype mother.

Science.gov (United States)

Manoura, Antonia; Korakaki, Eftychia; Hatzidaki, Eleftheria; Saitakis, Emmanuel; Maraka, Sofia; Papamastoraki, Isabella; Matalliotakis, Emmanuel; Foundouli, Kaliopi; Giannakopoulou, Christine

2007-01-01

Very few people do not express any Kell antigens on their red blood cells (K0 phenotype). They can be immunized by transfusion or pregnancy and develop antibodies against Kell system antigens. These maternal antibodies can cause severe hemolytic disease of the fetus/newborn, as a result of the suppression of erythropoiesis and hemolysis. Multiple intrauterine transfusions in the management of severe hemolytic disease have been shown to cause erythropoietic suppression as well. Recombinant erythropoietin has been successfully used in the management of late anemia of infants with Rh hemolytic disease and in 1 case of KEL1 (Kell)-associated hemolytic disease. The authors present the case of severe hemolytic disease of a newborn due to KEL5 (Ku) isoimmunization of his K0 phenotype mother. Regular intrauterine transfusions were performed to manage the severe fetal anemia (Hb 3 g/dL). A male infant was born at the 36th week of gestation having normal hemoglobin (15.8 g/dL) and developed only mild hyperbilirubinemia. On the 15th day of life, the infant's hematocrit had fallen to 27.3%, with low reticulocyte count and low erythropoietin level. The infant was managed successfully with recombinant erythropoietin.

Control of erythropoiesis by erythropoietin and stem cell factor: a novel role for Bruton's tyrosine kinase

NARCIS (Netherlands)

von Lindern, Marieke; Schmidt, Uwe; Beug, Hartmut

2004-01-01

Erythropoietin (Epo) and stem cell factor (SCF) are essential factors in the control of survival, expansion and differentiation of erythroid progenitors. Upon activation, their receptors, the EpoR and c-Kit, initiate multiple signalling pathways that control many cellular processes. To control

Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin

DEFF Research Database (Denmark)

Robach, Paul; Recalcati, Stefania; Girelli, Domenico

2009-01-01

healthy volunteers were treated with recombinant erythropoietin (rhEpo) for 1 month. As expected, the treatment efficiently increased erythropoiesis and stimulated bone marrow iron use. It was also associated with a prompt and considerable decrease in urinary hepcidin and a slight transient increase...

National Cooperative rHu Erythropoietin Study in patients with chronic renal failure--an interim report. The National Cooperative rHu Erythropoietin Study Group.

Science.gov (United States)

Levin, N W; Lazarus, J M; Nissenson, A R

1993-08-01

This second interim report of the National Cooperative rHu Erythropoietin Study presents data from 324 patients new to recombinant human erythropoietin (Epoetin alfa) who completed at least 12 months of study participation. Mean hematocrit levels increased to approximately 30% by month 3 in patients on hemodialysis (n = 293) and stabilized for the remainder of the study whether Epoetin alfa was administered by the intravenous (n = 250) or subcutaneous (n = 42) route. The intravenous dosage level ranged between 106.9 and 121.6 U/kg/wk; subcutaneous dosing ranged between 87.4 and 108.0 U/kg/wk; dosing levels in patients on peritoneal dialysis (n = 31) were similar, although there was a trend towards slightly higher hematocrit levels. Throughout the 12 months of the study, there was no relationship between blood pressure and either hematocrit level or Epoetin alfa dose. Approximately two thirds of the patients were receiving iron supplementation at any given time, and there was a trend towards the increased use of oral iron supplements. The incidence of adverse events in this cohort of patients was low throughout the study, and there was no relationship between the incidence of adverse events and either hematocrit level or Epoetin alfa dose. Based on an analysis of data from baseline to first follow-up, Epoetin alfa therapy resulted in improvement in several quality-of-life factors, most notable of which was vitality. Improvement occurred in all patient subgroups with some variability in the level and intensity of effect. Overall, these data demonstrate that Epoetin alfa therapy is safe and effective when used in a broad cross-section of patients on dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain-Heart Interaction: Cardiac Complications After Stroke.

Science.gov (United States)

Chen, Zhili; Venkat, Poornima; Seyfried, Don; Chopp, Michael; Yan, Tao; Chen, Jieli

2017-08-04

Neurocardiology is an emerging specialty that addresses the interaction between the brain and the heart, that is, the effects of cardiac injury on the brain and the effects of brain injury on the heart. This review article focuses on cardiac dysfunction in the setting of stroke such as ischemic stroke, brain hemorrhage, and subarachnoid hemorrhage. The majority of post-stroke deaths are attributed to neurological damage, and cardiovascular complications are the second leading cause of post-stroke mortality. Accumulating clinical and experimental evidence suggests a causal relationship between brain damage and heart dysfunction. Thus, it is important to determine whether cardiac dysfunction is triggered by stroke, is an unrelated complication, or is the underlying cause of stroke. Stroke-induced cardiac damage may lead to fatality or potentially lifelong cardiac problems (such as heart failure), or to mild and recoverable damage such as neurogenic stress cardiomyopathy and Takotsubo cardiomyopathy. The role of location and lateralization of brain lesions after stroke in brain-heart interaction; clinical biomarkers and manifestations of cardiac complications; and underlying mechanisms of brain-heart interaction after stroke, such as the hypothalamic-pituitary-adrenal axis; catecholamine surge; sympathetic and parasympathetic regulation; microvesicles; microRNAs; gut microbiome, immunoresponse, and systemic inflammation, are discussed. © 2017 American Heart Association, Inc.

Neuroimaging Correlates of Post-Stroke Aphasia Rehabilitation in a Pilot Randomized Trial of Constraint-Induced Aphasia Therapy.

Science.gov (United States)

Nenert, Rodolphe; Allendorfer, Jane B; Martin, Amber M; Banks, Christi; Ball, Angel; Vannest, Jennifer; Dietz, Aimee R; Szaflarski, Jerzy P

2017-07-18

BACKGROUND Recovery from post-stroke aphasia is a long and complex process with an uncertain outcome. Various interventions have been proposed to augment the recovery, including constraint-induced aphasia therapy (CIAT). CIAT has been applied to patients suffering from post-stroke aphasia in several unblinded studies to show mild-to-moderate linguistic gains. The aim of the present study was to evaluate the neuroimaging correlates of CIAT in patients with chronic aphasia related to left middle cerebral artery stroke. MATERIAL AND METHODS Out of 24 patients recruited in a pilot randomized blinded trial of CIAT, 19 patients received fMRI of language. Eleven of them received CIAT (trained) and eight served as a control group (untrained). Each patient participated in three fMRI sessions (before training, after training, and 3 months later) that included semantic decision and verb generation fMRI tasks, and a battery of language tests. Matching healthy control participants were also included (N=38; matching based on age, handedness, and sex). RESULTS Language testing showed significantly improved performance on Boston Naming Test (BNT; paphasia with no specific effect from CIAT training.

Operation Amplifier

NARCIS (Netherlands)

Tetsuya, Saito; Nauta, Bram

2011-01-01

PROBLEM TO BE SOLVED: To provide an operation amplifier which improves power source voltage removal ratios while assuring phase compensation characteristics, and therefore can be realized with a small-scale circuit and low power consumption. SOLUTION: The operation amplifier comprises: a

Operation Amplifier

NARCIS (Netherlands)

Tetsuya, S.; Nauta, Bram

2007-01-01

PROBLEM TO BE SOLVED: To provide an operation amplifier which improves power source voltage removal ratios while assuring phase compensation characteristics, and therefore can be realized with a small-scale circuit and low power consumption. ; SOLUTION: The operation amplifier comprises: a

Circulating and brain BDNF levels in stroke rats. Relevance to clinical studies.

Directory of Open Access Journals (Sweden)

Yannick Béjot

Full Text Available BACKGROUND: Whereas brain-derived neurotrophic factor (BDNF levels are measured in the brain in animal models of stroke, neurotrophin levels in stroke patients are measured in plasma or serum samples. The present study was designed to investigate the meaning of circulating BDNF levels in stroke patients. METHODS AND RESULTS: Unilateral ischemic stroke was induced in rats by the injection of various numbers of microspheres into the carotid circulation in order to mimic the different degrees of stroke severity observed in stroke patients. Blood was serially collected from the jugular vein before and after (4 h, 24 h and 8 d embolization and the whole brains were collected at 4, 24 h and 8 d post-embolization. Rats were then selected from their degree of embolization, so that the distribution of stroke severity in the rats at the different time points was large but similar. Using ELISA tests, BDNF levels were measured in plasma, serum and brain of selected rats. Whereas plasma and serum BDNF levels were not changed by stroke, stroke induced an increase in brain BDNF levels at 4 h and 24 h post-embolization, which was not correlated with stroke severity. Individual plasma BDNF levels did not correlate with brain levels at any time point after stroke but a positive correlation (r = 0.67 was observed between individual plasma BDNF levels and stroke severity at 4 h post-embolization. CONCLUSION: Circulating BDNF levels do not mirror brain BDNF levels after stroke, and severe stroke is associated with high plasma BDNF in the very acute stage.

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

International Nuclear Information System (INIS)

Jo, Hye-Ryeong; Kim, Yong-Seok; Son, Hyeon

2016-01-01

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.

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.

Multi-path interferometric Josephson directional amplifier for qubit readout

Science.gov (United States)

Abdo, Baleegh; Bronn, Nicholas T.; Jinka, Oblesh; Olivadese, Salvatore; Brink, Markus; Chow, Jerry M.

2018-04-01

We realize and characterize a quantum-limited, directional Josephson amplifier suitable for qubit readout. The device consists of two nondegenerate, three-wave-mixing amplifiers that are coupled together in an interferometric scheme, embedded in a printed circuit board. Nonreciprocity is generated by applying a phase gradient between the same-frequency pumps feeding the device, which plays the role of the magnetic field in a Faraday medium. Directional amplification and reflection-gain elimination are induced via wave interference between multiple paths in the system. We measure and discuss the main figures of merit of the device and show that the experimental results are in good agreement with theory. An improved version of this directional amplifier is expected to eliminate the need for bulky, off-chip isolation stages that generally separate quantum systems and preamplifiers in high-fidelity, quantum-nondemolition measurement setups.

Specific binding of 125I-rErythropoietin to Friend polycythemia virus-transformed erythroleukemia cells purified by centrifugal elutriation

International Nuclear Information System (INIS)

Correa, P.N.; Bard, V.; Axelrad, A.A.

1990-01-01

We have used countercurrent centrifugal elutriation (CCE) to determine the distribution of cells with respect to cell volume and buoyant density for an erythroleukemia cell line (JG6) transformed by the polycythemia strain of Friend virus (FV-P), and to determine the effect of inducing the cells to differentiate with dimethylsulfoxide (DMSO) on this distribution. CCE made it possible to obtain suspensions of modal JG6 populations virtually free of dead cells and uniform with respect to volume and buoyant density. These modal populations were assayed for specific binding of erythropoietin (Epo). Between 500 and 550 Epo receptors per cell were detected. These belonged to a single class having a dissociation constant of 0.36 nM. DMSO induction of differentiation of the JG6 cells had no effect on the number of Epo receptors expressed

The Therapeutic Potential of Induced Pluripotent Stem Cells After Stroke : Evidence from Rodent Models

NARCIS (Netherlands)

Zents, Karlijn; Copray, Sjef

2016-01-01

Stroke is the second most common cause of death and the leading cause of disability in the world. About 30% of the people that are affected by stroke die within a year; 25% of the patients that survive stroke remain in need of care after a year. Therefore, stroke is a major burden for health care

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,

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....

Role of neuroinflammation in ischemic stroke

Institute of Scientific and Technical Information of China (English)

Rui Liu; Meng-Xian Pan; Jun-Chun Tang; Ya Zhang; Hua-Bao Liao; Yang Zhuang; Dan Zhao; Qi Wan

2017-01-01

Ischemic stroke causes the depletion of energy and induce excitotoxicity and neuroinflammation in the brain that results from thrombotic blockage. Neuroinflammation occurs initially depending on activated resident microglia that has the same function as the macrophage. Activated microglia participates in the neuroinflammatory process by phagocytosing the injured brain cells and producing the pro- and anti-inflammatory mediators. In this review, the authors present an overview of the role of microglia in mediating neuroinflammation in ischemic stroke.

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......: This study provides class II evidence that treatment with high-dose EPO is not an effective treatment in patients with moderately advanced progressive MS....

Effects of low-dose recombinant human erythropoietin treatment on cognitive performance

DEFF Research Database (Denmark)

Viuff, Søren Lundgaard; Plenge, Ulla; Belhage, Bo

2017-01-01

, NUFI or self-reported results between the groups. CONCLUSIONS: In this small study, we found no significant effect of low-dose or micro-dose rhEpo on visual attention, cognitive performance in complex cognitive tasks or self-experienced cognitive performance compared with placebo. FUNDING: The Aase......INTRODUCTION: High-dose recombinant human erythropoietin (rhEpo) has been shown to improve cognitive performance in both healthy volunteers and in patients suffering from diseases affecting the brain. The aim of this study was to examine whether administration of low-dose and even micro-dose rh...

Effects of low-dose recombinant human erythropoietin treatment on cognitive performance

DEFF Research Database (Denmark)

Viuff, Søren Lundgaard; Plenge, Ulla; Belhage, Bo

2017-01-01

-reported results between the groups. Conclusions: In this small study, we found no significant effect of low-dose or micro-dose rhEpo on visual attention, cognitive performance in complex cognitive tasks or self-experienced cognitive performance compared with placebo. Funding: The Aase and Ejnar Danielsen......Introduction: High-dose recombinant human erythropoietin (rhEpo) has been shown to improve cognitive performance in both healthy volunteers and in patients suffering from diseases affecting the brain. The aim of this study was to examine whether administration of low-dose and even micro-dose rh...

Identification of Sleep-Modulated Pathways Involved in Neuroprotection from Stroke.

Science.gov (United States)

Pace, Marta; Baracchi, Francesca; Gao, Bo; Bassetti, Claudio

2015-11-01

Sleep deprivation (SDp) performed before stroke induces an ischemic tolerance state as observed in other forms of preconditioning. As the mechanisms underlying this effect are not well understood, we used DNA oligonucleotide microarray analysis to identify the genes and the gene-pathways underlying SDp preconditioning effects. Gene expression was analyzed 3 days after stroke in 4 experimental groups: (i) SDp performed before focal cerebral ischemia (IS) induction; (ii) SDp performed before sham surgery; (iii) IS without SDp; and (iv) sham surgery without SDp. SDp was performed by gentle handling during the last 6 h of the light period, and ischemia was induced immediately after. Basic sleep research laboratory. Stroke induced a massive alteration in gene expression both in sleep deprived and non-sleep deprived animals. However, compared to animals that underwent ischemia alone, SDp induced a general reduction in transcriptional changes with a reduction in the upregulation of genes involved in cell cycle regulation and immune response. Moreover, an upregulation of a new neuroendocrine pathway which included melanin concentrating hormone, glycoprotein hormones-α-polypeptide and hypocretin was observed exclusively in rats sleep deprived before stroke. Our data indicate that sleep deprivation before stroke reprogrammed the signaling response to injury. The inhibition of cell cycle regulation and inflammation are neuroprotective mechanisms reported also for other forms of preconditioning treatment, whereas the implication of the neuroendocrine function is novel and has never been described before. These results therefore provide new insights into neuroprotective mechanisms involved in ischemic tolerance mechanisms. © 2015 Associated Professional Sleep Societies, LLC.

Hemoglobin and hematocrit at the end of hemodialysis: a better way to adjust erythropoietin dose?

Science.gov (United States)

Rangel, Erika B; Andreoli, Maria Claudia; Matos, Ana Cristina C; Guimarães-Souza, Nadia K; Mallet, Ana Cláudia; Carneiro, Fabiana D; Santos, Bento C

2010-04-01

A severe disadvantage of administration of recombinant human erythropoietin to hemodialysis patients has been reported. A significant correlation has been shown with hemoglobin values determined online by use of the blood volume monitor (BVM) and by laboratory measurement. Online hemoglobin and hematocrit were measured by use of the BVM during hemodialysis session. Data were analyzed by t test and statistical significance was defined as a P of hemoglobin and hematocrit from 11.6 +/- 1.9 to 13.9 +/- 2.4 g/dL (17.4 +/- 7.1%, P = 0.02) and from 34.4 +/- 6.8 to 42 +/- 8.3% (20.6 +/- 8.8%, P = 0.022), respectively, were observed from the beginning to the end of dialysis. We hypothesize that a new strategy for adjusting erythropoietin dose may be based on hemoglobin and hematocrit values evaluated at the end of hemodialysis, when patients are no longer hypervolemic. Inadvertent high levels of hemoglobin could be one explanation why patients present higher rates of cardiovascular and access-related events, especially when monitored online by use of the BVM to achieve the dry weight.

Positive effects of intermittent fasting in ischemic stroke.

Science.gov (United States)

Fann, David Yang-Wei; Ng, Gavin Yong Quan; Poh, Luting; Arumugam, Thiruma V

2017-03-01

Intermittent fasting (IF) is a dietary protocol where energy restriction is induced by alternate periods of ad libitum feeding and fasting. Prophylactic intermittent fasting has been shown to extend lifespan and attenuate the progress and severity of age-related diseases such as cardiovascular (e.g. stroke and myocardial infarction), neurodegenerative (e.g. Alzheimer's disease and Parkinson's disease) and cancerous diseases in animal models. Stroke is the second leading cause of death, and lifestyle risk factors such as obesity and physical inactivity have been associated with elevated risks of stroke in humans. Recent studies have shown that prophylactic IF may mitigate tissue damage and neurological deficit following ischemic stroke by a mechanism(s) involving suppression of excitotoxicity, oxidative stress, inflammation and cell death pathways in animal stroke models. This review summarizes data supporting the potential hormesis mechanisms of prophylactic IF in animal models, and with a focus on findings from animal studies of prophylactic IF in stroke in our laboratory. Copyright © 2017 Elsevier Inc. All rights reserved.

Strokes In Young Adults And Children

Directory of Open Access Journals (Sweden)

Farhad Iranmanesh

2017-02-01

Full Text Available Stroke is in second place on a mortality list in the world. Also, stroke is a leading cause of disability. Approximately 20% of all strokes occur in Children and young adults. The etiology of stroke in Children and young adults is different from that in older patients, and has an influence on diagnostic evaluation and treatment, so knowledge about older patients cannot always be applied to these patients. The list of stroke etiologies among young adults and children is extensive. Ischemic stroke are more frequent than hemorrhagic strokes in both groups. Stroke in young adults had been thought to be associated with   risk factors, including arterial (such as dissection, reversible cerebral vasoconstriction syndrome, inflammatory arteritis ,moyamoya ,migraine - induced stroke, genetic or inherted arteriopathy, premature atherosclerosis cardiac (such as patent foramen ovale, cardiomyopathy , congenital heart disease and   hematologic (such as  deficiencies of protein S,protein C,or antithrombin;factor V lieden mutation . Common risk factors for stroke in children include: Sickle-cell disease, diseases of the arteries, abnormal blood clotting, head or neck trauma. There are no specific recommendations or guidelines for primary or secondary stroke prevention in young adults. Primary prevention focused on identifying and managing known vascular risk factors, such as hypertension, disorders of lipid metabolism, and diabetes, and non-drug strategies and lifestyle changes, including smoking, reducing body weight, increasing regular aerobic physical activity, and adopting a healthy diet with more fruit and vegetables and less salt. For secondary stroke prevention, identification of the etiologic mechanism of the initial stroke and the presence of any additional risk factors is most important. It consists of optimal treatment of vascular risk factors administering antiplatelet or anticoagulant therapy, and if indicated, invasive surgical or

Differential effects of erythropoietin on neural and cognitive measures of executive function 3 and 7 days post-administration

DEFF Research Database (Denmark)

Miskowiak, Kamilla; Inkster, Becky; O'Sullivan, Ursula

2008-01-01

Erythropoietin (Epo) has neuroprotective and neurotrophic effects and improves cognitive function in animal models of neurodegenerative and neuropsychiatric illness. In humans, weekly Epo administration over 3 months improves cognitive function in schizophrenia. The neural underpinnings and time...

Neurobehavioral and cytotoxic effects of vanadium during oligodendrocyte maturation: a protective role for erythropoietin.

Science.gov (United States)

Mustapha, Oluwaseun; Oke, Bankole; Offen, Nils; Sirén, Anna-Leena; Olopade, James

2014-07-01

Vanadium exposure has been known to lead to lipid peroxidation, demyelination and oligodendrocytes depletion. We investigated behaviour and glial reactions in juvenile mice after early neonatal exposure to vanadium, and examined the direct effects of vanadium in oligodendrocyte progenitor cultures from embryonic mice. Neonatal pups exposed to vanadium via lactation for 15 and 22 days all had lower body weights. Behavioural tests showed in most instances a reduction in locomotor activity and negative geotaxis. Brain analyses revealed astrocytic activation and demyelination in the vanadium exposed groups compared to the controls. In cell culture, exposure of oligodendrocytes to 300 μM sodium metavanadate significantly increased cell death. Expression of the oligodendrocyte specific proteins, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and oligodendrocyte specific protein (OSP/Claudin) were reduced upon vanadium treatment while simultaneous administration of erythropoietin (EPO; 4-12 U/ml) counteracted vanadium-toxicity. The data suggest that oligodendrocyte damage may explain the increased vulnerability of the juvenile brain to vanadium and support a potential for erythropoietin as a protective agent against vanadium-toxicity during perinatal brain development and maturation. Copyright © 2014 Elsevier B.V. All rights reserved.

A Simple Three-Step Method for Design and Affinity Testing of New Antisense Peptides: An Example of Erythropoietin

Directory of Open Access Journals (Sweden)

Nikola Štambuk

2014-05-01

Full Text Available Antisense peptide technology is a valuable tool for deriving new biologically active molecules and performing peptide–receptor modulation. It is based on the fact that peptides specified by the complementary (antisense nucleotide sequences often bind to each other with a higher specificity and efficacy. We tested the validity of this concept on the example of human erythropoietin, a well-characterized and pharmacologically relevant hematopoietic growth factor. The purpose of the work was to present and test simple and efficient three-step procedure for the design of an antisense peptide targeting receptor-binding site of human erythropoietin. Firstly, we selected the carboxyl-terminal receptor binding region of the molecule (epitope as a template for the antisense peptide modeling; Secondly, we designed an antisense peptide using mRNA transcription of the epitope sequence in the 3'→5' direction and computational screening of potential paratope structures with BLAST; Thirdly, we evaluated sense–antisense (epitope–paratope peptide binding and affinity by means of fluorescence spectroscopy and microscale thermophoresis. Both methods showed similar Kd values of 850 and 816 µM, respectively. The advantages of the methods were: fast screening with a small quantity of the sample needed, and measurements done within the range of physicochemical parameters resembling physiological conditions. Antisense peptides targeting specific erythropoietin region(s could be used for the development of new immunochemical methods. Selected antisense peptides with optimal affinity are potential lead compounds for the development of novel diagnostic substances, biopharmaceuticals and vaccines.

Fiber amplifiers under thermal loads leading to transverse mode instability

DEFF Research Database (Denmark)

Johansen, Mette Marie; Hansen, Kristian Rymann; Alkeskjold, Thomas Tanggaard

2014-01-01

Transverse mode instability (TMI) in rare-earth doped fiber amplifiers operating above an average power threshold is caused by intermodal stimulated thermal Rayleigh scattering due to quantum defect heating. We investigate thermally induced longitudinal waveguide perturbations causing power...

Post-stroke infection: a role for IL-1ra?

Science.gov (United States)

Tanzi, Pat; Cain, Kevin; Kalil, Angela; Zierath, Dannielle; Savos, Anna; Gee, J Michael; Shibata, Dean; Hadwin, Jessica; Carter, Kelly; Becker, Kyra

2011-04-01

Infection is common following stroke and is independently associated with worse outcome. Clinical studies suggest that infections occur more frequently in those individuals with stroke-induced immunologic dysfunction. This study sought to explore the contribution of immunomodulatory cytokines and hormones to lymphocyte function and infection risk. Patients (N = 112) were enrolled as soon as possible after the onset of ischemic stroke. Blood was drawn to assess plasma cortisol, IL-10, IL-1ra, lymphocyte numbers, and lymphocyte function at 72 h after stroke onset; infections were censored through 21 days after stroke onset. Infection occurred in 25% of patients. Stroke severity was the most important predictor of infection risk. Increased plasma cortisol, IL-10, and IL-1ra, as well as decreased lymphocyte numbers, at 72 h after stroke onset were associated with risk of subsequent infection. After controlling for stroke severity, only IL-1ra was independently associated with infection risk, and the degree of risk was consistent throughout the post-stroke period. Infection, but not IL-1ra itself, was associated with worse outcome at 3 months. In this study cohort, increased plasma IL-1ra was independently associated with the risk of post-stroke infection. Further studies are needed to validate this finding, which could have important implications for stroke therapy.

Antares laser power amplifier

International Nuclear Information System (INIS)

Stine, R.D.; Ross, G.F.; Silvernail, C.

1979-01-01

The overall design of the Antares laser power amplifier is discussed. The power amplifier is the last stage of amplification in the 100-kJ Antares laser. In the power amplifier a single, cylindrical, grid-controlle, cold-cathode electron gun is surrounded by 12 large-aperture CO 2 electron-beam sustained laser discharge sectors. Each power amplifier will deliver 18 kJ and the six modules used in Antares will produce the required 100 kJ for delivery to the target. A large-scale interaction between optical, mechanical, and electrical disciplines is required to meet the design objectives. Significant component advances required by the power amplifier design are discussed

Constraint-Induced Movement Therapy Combined with Transcranial Direct Current Stimulation over Premotor Cortex Improves Motor Function in Severe Stroke: A Pilot Randomized Controlled Trial

Directory of Open Access Journals (Sweden)

Suellen M. Andrade

2017-01-01

Full Text Available Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex combined with constraint-induced movement therapy for treatment of stroke patients. Design. Sixty patients were randomly distributed into 3 groups: Group A, anodal stimulation on premotor cortex and constraint-induced movement therapy; Group B, anodal stimulation on primary motor cortex and constraint-induced movement therapy; Group C, sham stimulation and constraint-induced movement therapy. Evaluations involved analysis of functional independence, motor recovery, spasticity, gross motor function, and muscle strength. Results. A significant improvement in primary outcome (functional independence after treatment in the premotor group followed by primary motor group and sham group was observed. The same pattern of improvement was highlighted among all secondary outcome measures regarding the superior performance of the premotor group over primary motor and sham groups. Conclusions. Premotor cortex can contribute to motor function in patients with severe functional disabilities in early stages of stroke. This study was registered in ClinicalTrials.gov database (NCT 02628561.

mStroke: "Mobile Stroke"-Improving Acute Stroke Care with Smartphone Technology.

Science.gov (United States)

Andrew, Benjamin Y; Stack, Colleen M; Yang, Julian P; Dodds, Jodi A

2017-07-01

This study aimed to evaluate the effect of method and time of system activation on clinical metrics in cases utilizing the Stop Stroke (Pulsara, Inc.) mobile acute stroke care coordination application. A retrospective cohort analysis of stroke codes at 12 medical centers using Stop Stroke from March 2013 to May 2016 was performed. Comparison of metrics (door-to-needle time [DTN] and door-to-CT time [DTC], and rate of DTN ≤ 60 minutes [goal DTN]) was performed between subgroups based on method (emergency medical service [EMS] versus emergency department [ED]) and time of activation. Effects were adjusted for confounders (age, sex, National Institutes of Health Stroke Scale [NIHSS] score) using multiple linear and logistic regression. The final dataset included 2589 cases. Cases activated by EMS were more severe (median NIHSS score 8 versus 4, P technology provides unique insight into acute stroke codes. Activation of mobile electronic stroke coordination in the field appears to promote a more expedited and successful care process. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Amplification factor variable 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

Use of erythropoietin is associated with threshold retinopathy of prematurity (ROP) in preterm ELBW neonates: a retrospective, cohort study from two large tertiary NICUs in Italy.

Science.gov (United States)

Manzoni, Paolo; Memo, Luigi; Mostert, Michael; Gallo, Elena; Guardione, Roberta; Maestri, Andrea; Saia, Onofrio Sergio; Opramolla, Anna; Calabrese, Sara; Tavella, Elena; Luparia, Martina; Farina, Daniele

2014-09-01

Retinopathy of prematurity (ROP) is a multifactorial disease with evidence of many associated risk factors. Erythropoietin has been reported to be associated with this disorder in a murine model, as well as in humans in some single-center reports. We reviewed the data from two large tertiary NICUs in Italy to test the hypothesis that the use of erythropoietin may be associated with the development of the most severe stages of ROP in extremely low birth weight (ELBW) neonates. Retrospective study by review of patient charts and eye examination index cards on infants with birth weight large tertiary NICUs in Northern Italy (Sant'Anna Hospital NICU in Torino, and Ca' Foncello Hospital Neonatology in Treviso) in the years 2005 to 2007. Standard protocol of administration of EPO in the two NICUs consisted of 250 UI/kg three times a week for 6-week courses (4-week in 1001-1500g infants). Univariate analysis was performed to assess whether the use of EPO was associated with severe (threshold) ROP. A control, multivariate statistical analysis was performed by entering into a logistic regression model a number of neonatal and perinatal variables that - in univariate analysis - had been associated with threshold ROP. During the study period, 211 ELBW infants were born at the two facilities and survived till discharge. Complete data were obtained for 197 of them. Threshold retinopathy of prematurity occurred in 26.9% (29 of 108) of ELBW infants who received erythropoietin therapy, as compared with 13.5% (12 of 89) of those who did not receive erythropoietin (OR 2.35; 95% CI 1.121-4.949; p=0.02 in univariate analysis, and p=0.04 at multivariate logistic regression after controlling for the following variables: birth weight, gestational age, days on supplemental oxygen, systemic fungal infection, vaginal delivery). Use of erythropoietin was not significantly associated with other major sequelae of prematurity (intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing

Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke

Directory of Open Access Journals (Sweden)

Valérie Wolff

2015-01-01

Full Text Available Cannabis has potential therapeutic use but tetrahydrocannabinol (THC, its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities Vmax (complexes I, III, and IV activities, Vsucc (complexes II, III, and IV activities, Vtmpd (complex IV activity, together with mitochondrial coupling (Vmax/V0, were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2 production, measured with Amplex Red. THC significantly decreased Vmax (−71%; P<0.0001, Vsucc (−65%; P<0.0001, and Vtmpd (−3.5%; P<0.001. Mitochondrial coupling (Vmax/V0 was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P<0.001. Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P<0.05 and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P<0.001. Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient’s vulnerability to stroke.

Antidepressant-like effects of erythropoietin: a focus on behavioural and hippocampal processes.

Science.gov (United States)

Osborn, Meagan; Rustom, Nazneen; Clarke, Melanie; Litteljohn, Darcy; Rudyk, Chris; Anisman, Hymie; Hayley, Shawn

2013-01-01

Depression is a chronic and debilitating condition with a significant degree of relapse and treatment resistance that could stem, at least in part, from disturbances of neuroplasticity. This has led to an increased focus on treatment strategies that target brain derived neurotrophic factor (BDNF), synaptic plasticity and adult neurogenesis. In the current study we aimed to assess whether erythropoietin (EPO) would have antidepressant-like effects given its already established pro-trophic actions. In particular, we assessed whether EPO would diminish the deleterious effects of a social stressor in mice. Indeed, EPO induced anxiolytic and antidepressant-like responses in a forced swim test, open field, elevated-plus maze, and a novelty test, and appeared to blunt some of the negative behavioural effects of a social stressor. Furthermore, EPO promoted adult hippocampal neurogenesis, an important feature of effective antidepressants. Finally, a separate study using the mTOR inhibitor rapamycin revealed that antagonizing this pathway prevented the impact of EPO upon forced swim performance. These data are consistent with previous findings showing that the mTOR pathway and its neurogenic and synaptogenic effects might mediate the behavioral consequences of antidepressant agents. Our findings further highlight EPO as a possible adjunct treatment for affective disorders, as well as other stressor associated disorders of impaired neuroplasticity.

Amplification factor variable amplifier

NARCIS (Netherlands)

Akitsugu, Oshita; Nauta, Bram

2010-01-01

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 can

Early Rehabilitation After Stroke: a Narrative Review.

Science.gov (United States)

Coleman, Elisheva R; Moudgal, Rohitha; Lang, Kathryn; Hyacinth, Hyacinth I; Awosika, Oluwole O; Kissela, Brett M; Feng, Wuwei

2017-11-07

Despite current rehabilitative strategies, stroke remains a leading cause of disability in the USA. There is a window of enhanced neuroplasticity early after stroke, during which the brain's dynamic response to injury is heightened and rehabilitation might be particularly effective. This review summarizes the evidence of the existence of this plastic window, and the evidence regarding safety and efficacy of early rehabilitative strategies for several stroke domain-specific deficits. Overall, trials of rehabilitation in the first 2 weeks after stroke are scarce. In the realm of very early mobilization, one large and one small trial found potential harm from mobilizing patients within the first 24 h after stroke, and only one small trial found benefit in doing so. For the upper extremity, constraint-induced movement therapy appears to have benefit when started within 2 weeks of stroke. Evidence for non-invasive brain stimulation in the acute period remains scant and inconclusive. For aphasia, the evidence is mixed, but intensive early therapy might be of benefit for patients with severe aphasia. Mirror therapy begun early after stroke shows promise for the alleviation of neglect. Novel approaches to treating dysphagia early after stroke appear promising, but the high rate of spontaneous improvement makes their benefit difficult to gauge. The optimal time to begin rehabilitation after a stroke remains unsettled, though the evidence is mounting that for at least some deficits, initiation of rehabilitative strategies within the first 2 weeks of stroke is beneficial. Commencing intensive therapy in the first 24 h may be harmful.

Pediatric Stroke

Science.gov (United States)

... and Patient Resources Home » Patients & Families » About Stroke » Pediatric Stroke » Introduction Introduction What is a Stroke? Ischemic Stroke Intracerebral Hemorrhage Subarachnoid Hemorrhage Pediatric Stroke Introduction Types of Stroke Diagnosis and Treatment ...

Development of stroke-induced quadriplegia after endovascular repair of blunt aortic injury pseudoaneurysm.

Science.gov (United States)

Amoudi, Abdullah S; Merdad, Anas A; Makhdoom, Ahmed Q; Jamjoom, Reda A

2015-01-01

Endovascular repair of blunt aortic injury is now a first-line approach in management. This can warrant coverage of the left subclavian artery (LSA), which could lead to posterior strokes. In this case report, we present a severe complication of endovascular repair of a traumatic aortic aneurysm. A 53-year-old man presented with blunt aortic injury, endovascular repair was carried out where the left subclavian artery was covered. The intervention had a 100% technical success. Twelve hours later, he was discovered to have quadriplegia, a CT scan showed a large left cerebellar infarction extending to the medulla oblongata and proximal spinal cord. Strokes complicate 3% of thoracic endovascular aortic repairs, 80% of those strokes occur in patients who had their LSA`s covered. Most patients however, tolerate the coverage. Although our patient had a dominant right vertebral artery, and lacked risks for these strokes, he developed an extensive stroke that left him quadriplegic.

CMOS Current-mode Operational Amplifier

DEFF Research Database (Denmark)

Kaulberg, Thomas

1992-01-01

current-mode feedback amplifier or a constant bandwidth in a transimpedance feedback amplifier. The amplifier is found to have a gain bandwidth product of 8 MHz, an offset current of 0.8 ¿A (signal-range ±700¿A) and a (theoretically) unlimited slew-rate. The amplifier is realized in a standard CMOS 2......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...

Trial manufacture of an insulated amplifier

International Nuclear Information System (INIS)

Okuno, Shigeo; Matsuura, Kiyokata.

1978-10-01

Trial manufacture of an insulated amplifier was carried out. The input signals are divided by filters Th and Tl into high frequency component and low frequency component. The high frequency component drives a transformer T 1 , and secondary signals are induced. The low frequency component drives a transformer T 2 through a buffer and a modulator. The secondary signals from both transformers are recombined to make the output signals. Compensation for the frequency characteristics of the high frequency transformer and that for the effect of a filter in the demodulation circuit for low frequency component are considered. The time constant of output signals for rectangular input signals was 30 microsec, when only the low frequency part is operated. The drift of the direct current level is within 5 mV. The characteristic features of the high frequency part was also investigated. The overall characteristic features of this amplifier were good for the frequency range of 0 to 500 kHz. (Kato, T.)

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

Immunoreactive erythropoietin concentrations in neonatal rats and the effects of hypoxia

International Nuclear Information System (INIS)

Clemons, G.K.; Fitzsimmons, S.L.; DeManincor, D.

1987-01-01

We attempted to find answers to what are the circulating, hepatic and renal erythropoietin (Ep) levels in normal rat neonates measured daily through the first three weeks of life and when they attain sexual maturity, how are these Ep levels altered by exposure to hypoxia, and whether can it be transferred to the nursing neonatal animals? Since we established earlier that in the fetal rat the liver is the main Ep producing tissue, we attempted to determine the age at which the switch from liver to kidney occurred in both the normal and the hypoxic neonatal rat. 2 figs

Stroke mimic diagnoses presenting to a hyperacute stroke unit.

Science.gov (United States)

Dawson, Ang; Cloud, Geoffrey C; Pereira, Anthony C; Moynihan, Barry J

2016-10-01

Stroke services have been centralised in several countries in recent years. Diagnosing acute stroke is challenging and a high proportion of patients admitted to stroke units are diagnosed as a non-stroke condition (stroke mimics). This study aims to describe the stroke mimic patient group, including their impact on stroke services. We analysed routine clinical data from 2,305 consecutive admissions to a stroke unit at St George's Hospital, London. Mimic groupings were derived from 335 individual codes into 17 groupings. From 2,305 admissions, 555 stroke mimic diagnoses were identified (24.2%) and 72% of stroke mimics had at least one stroke risk factor. Common mimic diagnoses were headache, seizure and syncope. Medically unexplained symptoms and decompensation of underlying conditions were also common. Median length of stay was 1 day; a diagnosis of dementia (p=0.028) or needing MRI (p=0.006) was associated with a longer stay. Despite emergency department assessment by specialist clinicians and computed tomography brain, one in four suspected stroke patients admitted to hospital had a non-stroke diagnosis. Stroke mimics represent a heterogeneous patient group with significant impacts on stroke services. Co-location of stroke and acute neurology services may offer advantages where service reorganisation is being considered. © Royal College of Physicians 2016. All rights reserved.

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.

CMOS Current-mode Operational Amplifier

OpenAIRE

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 current-mode feedback amplifier or a constant bandwidth in a transimpedance feedback amplifier. The amplifier is found to have a gain bandwidth product of 8 MHz, an offset current of 0.8 ¿A (signal-r...

Default Mode Network Connectivity in Stroke Patients.

Science.gov (United States)

Tuladhar, Anil Man; Snaphaan, Liselore; Shumskaya, Elena; Rijpkema, Mark; Fernandez, Guillén; Norris, David G; de Leeuw, Frank-Erik

2013-01-01

The pathophysiology of episodic memory dysfunction after infarction is not completely understood. It has been suggested that infarctions located anywhere in the brain can induce widespread effects causing disruption of functional networks of the cortical regions. The default mode network, which includes the medial temporal lobe, is a functional network that is associated with episodic memory processing. We investigated whether the default mode network activity is reduced in stroke patients compared to healthy control subjects in the resting state condition. We assessed the whole brain network properties during resting state functional MRI in 21 control subjects and 20 'first-ever' stroke patients. Patients were scanned 9-12 weeks after stroke onset. Stroke lesions were located in various parts of the brain. Independent component analyses were conducted to identify the default mode network and to compare the group differences of the default mode network. Furthermore, region-of-interest based analysis was performed to explore the functional connectivity between the regions of the default mode network. Stroke patients performed significantly worse than control subjects on the delayed recall score on California verbal learning test. We found decreased functional connectivity in the left medial temporal lobe, posterior cingulate and medial prefrontal cortical areas within the default mode network and reduced functional connectivity between these regions in stroke patients compared with controls. There were no significant volumetric differences between the groups. These results demonstrate that connectivity within the default mode network is reduced in 'first-ever' stroke patients compared to control subjects. This phenomenon might explain the occurrence of post-stroke cognitive dysfunction in stroke patients.

Study to assess the effectiveness of modified constraint-induced movement therapy in stroke subjects: A randomized controlled trial

Directory of Open Access Journals (Sweden)

Priyanka Singh

2013-01-01

Full Text Available Background and Purpose: The purpose of this study was to assess the effectiveness of modified constraint induced movement therapy (m-CIMT in stroke subjects. Materials and Methods: A total of forty sub-acute stroke subjects were randomly assigned to either a m-CIMT (n = 20 or in a control group (n = 20. The m-CIMT group (14 men, 6 women; mean age = 55.2 years consisted of structured 2 h therapy sessions emphasizing affected arm use, occurring 5 times/week for 2 weeks. A mitt was used to restrain the unaffected arm for 10 h/day for 2 week. The control group (11 men, 9 women; mean age = 56.4 years consisted of conventional rehabilitation for time-matched exercise program. The outcome measures were evaluated at pre- and post-intervention by using the Wolf Motor Function Test (WMFT and Fugl-Meyer assessment (FMA of motor recovery after stroke. Results: After intervention significant effects were observed in m-CIMT group on WMFT (pre-test and post-test score was 28.04 ± 6.58, 13.59 ± 2.86; P =0.003. Similarly on FMA (pre- and post-test score was 31.15 ± 6.37, 55.7 ± 6.4; P = 0.00. Conclusion: There is a significant improvem ent in upper extremity function so it indicates that m-CIMT is effective in improving the motor function of the affected arm in stroke subjects. However, its long-term effect has not proved since there was no follow-up after intervention.

Stroke rehabilitation.

Science.gov (United States)

Langhorne, Peter; Bernhardt, Julie; Kwakkel, Gert

2011-05-14

Stroke is a common, serious, and disabling global health-care problem, and rehabilitation is a major part of patient care. There is evidence to support rehabilitation in well coordinated multidisciplinary stroke units or through provision of early supported provision of discharge teams. Potentially beneficial treatment options for motor recovery of the arm include constraint-induced movement therapy and robotics. Promising interventions that could be beneficial to improve aspects of gait include fitness training, high-intensity therapy, and repetitive-task training. Repetitive-task training might also improve transfer functions. Occupational therapy can improve activities of daily living; however, information about the clinical effect of various strategies of cognitive rehabilitation and strategies for aphasia and dysarthria is scarce. Several large trials of rehabilitation practice and of novel therapies (eg, stem-cell therapy, repetitive transcranial magnetic stimulation, virtual reality, robotic therapies, and drug augmentation) are underway to inform future practice. Copyright © 2011 Elsevier Ltd. All rights reserved.

Blood leptin levels and erythropoietin requirement in Iranian hemodialysis patients

Directory of Open Access Journals (Sweden)

Rahimi A

2008-12-01

Full Text Available "nBackground: Anemia is a common complication accompanied by high morbidity and mortality in hemodialysis patients. Considering the fact that the reduction of erythropoietin (EPO synthesis is the main cause of uremic anemia, receiving recombinant human erythropoietin (rHuEPO can improve the condition in these patients. Some of these hemodialysis patients, however, have acceptable hemoglobin levels without any need to EPO. Higher BMI, higher albumin and leptin plasma levels and longer durations of hemodialysis are possible factors contributing to the reduced need for rHuEPO in these patients. The present study is designed to asses the relationship between the plasma levels of leptin and the reduced EPO need. "nMethods: Fifty eligible hemodialysis patients with hemoglobin levels higher than 11 mg/dl were enrolled in the cross-sectional study. The information on age, sex, hemodialysis duration and the cause of renal dysfunction were extracted from the files. The baseline plasma levels of Leptin and albumin were measured. The patients BMI and the weekly need for rHuEPO were also calculated. "nResults: There was no correlation between the weekly need for rHuEPO and sex, BMI, the cause of renal dysfunction and the plasma levels of albumin and leptin; it, however, was related with age and the duration of dialysis. While age negatively influences the weekly need, the duration of dialysis has a positive effect on the need. "nConclusion: The plasma levels of leptin are not directly correlated with the required amounts of rHuEPO, indicating that leptin is not an effective factor in erythropoiesis. Conversely, older age and shorter hemodialysis durations are accompanied by reduced need for rHuEPO.

Preschool Assessment of Preterm Infants Treated With Darbepoetin and Erythropoietin.

Science.gov (United States)

Ohls, Robin K; Cannon, Daniel C; Phillips, John; Caprihan, Arvind; Patel, Shrena; Winter, Sarah; Steffen, Michael; Yeo, Ronald A; Campbell, Richard; Wiedmeier, Susan; Baker, Shawna; Gonzales, Sean; Lowe, Jean

2016-03-01

We previously reported improved neurodevelopmental outcomes at 2 years among infants treated with the erythropoiesis-stimulating agents (ESAs) darbepoetin alfa (darbepoetin) or erythropoietin. Here we characterize 4-year outcomes. Former preterm infants randomly assigned to receive darbepoetin (10 μg/kg, once per week), erythropoietin (400 U/kg, 3 times/week), or placebo through 35 weeks' postconceptual age were evaluated at 3.5 to 4 years of age. For comparison, healthy children formerly delivered full term (term controls [TCs]) were also recruited. All participants were assessed by using measures of full-scale IQ (FSIQ) and general language from the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, and an overall measure of executive function, on the basis of tests evaluating inhibitory control and spatial working memory. Rates of neurodevelopmental impairment were compared across groups. Multivariate analysis of variance compared children randomly assigned to ESAs (n = 39), placebo (n =14), and TCs (n = 24). FSIQ and performance IQ were significantly higher in the ESA group than in the placebo group (FSIQ: 91.1 ± 17.5 vs 79.2 ± 18.5, P = .036; performance IQ: 93.0 ± 17.0 vs 79.5 ± 19.5, P = .018). Follow-up analyses revealed that the children receiving ESAs performed better than those who received placebo on executive function tasks. The ESA group's performance was below that of TCs, but the results did not reach significance on executive function. The incidence of neurodevelopmental impairment was greater in the placebo group than in the ESA group. ESA-treated infants had better cognitive outcomes and less developmental impairment at 3.5 to 4 years of age compared with placebo-treated infants. ESAs show promise in improving long-term cognitive outcomes of infants born prematurely. Copyright © 2016 by the American Academy of Pediatrics.

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.

The Migraine-Ischemic Stroke Relation in Young Adults

Directory of Open Access Journals (Sweden)

Alessandro Pezzini

2011-01-01

Full Text Available In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1 the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2 migraine is associated with an increased prevalence of cardiovascular risk factors; (3 the link is caused by migraine-specific drugs; (4 migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions.

The Migraine-Ischemic Stroke Relation in Young Adults

Science.gov (United States)

Pezzini, Alessandro; Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Dalla Volta, Giorgio; Padovani, Alessandro

2011-01-01

In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2) migraine is associated with an increased prevalence of cardiovascular risk factors; (3) the link is caused by migraine-specific drugs; (4) migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions. PMID:21197470

Recrudescence of Focal Stroke Symptoms During Pain Management with Hydromorphone

Directory of Open Access Journals (Sweden)

Joshua D. Bernstock

2016-03-01

Full Text Available Abstract: Patients who have recovered from a prior stroke may experience a reemergence of their original stroke syndrome secondary to metabolic derangements, sedation, infection, and/or fatigue. Critically, the molecular/cellular mechanisms mediating symptom recurrence after exposure to analgesic agents remain unknown. Accordingly, herein we report a unique case of a patient with hydromorphone-induced recrudescence 30 years after her initial stroke event(s, and in so doing propose a putative mechanism related to post-infarction functional neuroplasticity.

Anabolic steroids abuse-induced cardiomyopathy and ischaemic stroke in a young male patient.

Science.gov (United States)

Shamloul, Reham Mohammed; Aborayah, Ahmed Fathy; Hashad, Assem; Abd-Allah, Foad

2014-02-26

We report a case of a 37-year-old man presented with acute stroke and hepatorenal impairment which were associated with anabolic-androgenic steroids (AAS) abuse over 2 years. Despite the absence of apparent symptoms and signs of congestive heart failure at presentation, an AAS-induced dilated cardiomyopathy with multiple thrombi in the left ventricle was attributed to be the underlying cause of his condition. Awareness of the complications of AAS led to the prompt treatment of the initially unrecognised dilated cardiomyopathy, and improved the liver and kidney functions. However, the patient was exposed to a second severe ischaemic event, which led to his death. This unique and complex presentation of AAS complications opens for better recognition and treatment of their potentially fatal effects.

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

A novel biological function of soluble biglycan: Induction of erythropoietin production and polycythemia.

Science.gov (United States)

Frey, Helena; Moreth, Kristin; Hsieh, Louise Tzung-Harn; Zeng-Brouwers, Jinyang; Rathkolb, Birgit; Fuchs, Helmut; Gailus-Durner, Valérie; Iozzo, Renato V; de Angelis, Martin Hrabě; Schaefer, Liliana

2017-06-01

Secondary polycythemia, a disease characterized by a selective increase in circulating mature erythrocytes, is caused by enhanced erythropoietin (Epo) concentrations triggered by hypoxia-inducible factor-2α (HIF-2α). While mechanisms of hypoxia-dependent stabilization of HIF-2α protein are well established, data regarding oxygen-independent regulation of HIF-2α are sparse. In this study, we generated a novel transgenic mouse model, in which biglycan was constitutively overexpressed and secreted by hepatocytes (BGN Tg ), thereby providing a constant source of biglycan released into the blood stream. We discovered that although the mice were apparently normal, they harbored an increase in mature circulating erythrocytes. In addition to erythrocytosis, the BGN Tg mice showed elevated hemoglobin concentrations, hematocrit values and enhanced total iron binding capacity, revealing a clinical picture of polycythemia. In BGN Tg mice markedly enhanced Epo mRNA expression was observed in the liver and kidney, while elevated Epo protein levels were found in liver, kidney and blood. Mechanistically, we showed that the transgenic animals had an abundance of HIF-2α protein in the liver and kidney. Finally, by transiently overexpressing circulating biglycan in mice deficient in various Toll-like receptors (TLRs), we determined that this novel function of biglycan to promote Epo synthesis was specifically mediated by a selective interaction with TLR2. Thus, we discovered a novel biological pathway of soluble biglycan inducing HIF-2α protein stabilization and Epo production presumably in an oxygen-independent manner, ultimately giving rise to secondary polycythemia.

Determinations of vertical stroke V{sub cb} vertical stroke and vertical stroke V{sub ub} vertical stroke from baryonic Λ{sub b} decays

Energy Technology Data Exchange (ETDEWEB)

Hsiao, Y.K. [Shanxi Normal University, School of Physics and Information Engineering, Linfen (China); National Tsing Hua University, Department of Physics, Hsinchu (China); Geng, C.Q. [Shanxi Normal University, School of Physics and Information Engineering, Linfen (China); National Tsing Hua University, Department of Physics, Hsinchu (China); Hunan Normal University, Synergetic Innovation Center for Quantum Effects and Applications (SICQEA), Changsha (China)

2017-10-15

We present the first attempt to extract vertical stroke V{sub cb} vertical stroke from the Λ{sub b} → Λ{sub c}{sup +}l anti ν{sub l} decay without relying on vertical stroke V{sub ub} vertical stroke inputs from the B meson decays. Meanwhile, the hadronic Λ{sub b} → Λ{sub c}M{sub (c)} decays with M = (π{sup -},K{sup -}) and M{sub c} =(D{sup -},D{sup -}{sub s}) measured with high precisions are involved in the extraction. Explicitly, we find that vertical stroke V{sub cb} vertical stroke =(44.6 ± 3.2) x 10{sup -3}, agreeing with the value of (42.11 ± 0.74) x 10{sup -3} from the inclusive B → X{sub c}l anti ν{sub l} decays. Furthermore, based on the most recent ratio of vertical stroke V{sub ub} vertical stroke / vertical stroke V{sub cb} vertical stroke from the exclusive modes, we obtain vertical stroke V{sub ub} vertical stroke = (4.3 ± 0.4) x 10{sup -3}, which is close to the value of (4.49 ± 0.24) x 10{sup -3} from the inclusive B → X{sub u}l anti ν{sub l} decays. We conclude that our determinations of vertical stroke V{sub cb} vertical stroke and vertical stroke V{sub ub} vertical stroke favor the corresponding inclusive extractions in the B decays. (orig.)

Improved-Bandwidth Transimpedance Amplifier

Science.gov (United States)

Chapsky, Jacob

2009-01-01

The widest available operational amplifier, with the best voltage and current noise characteristics, is considered for transimpedance amplifier (TIA) applications where wide bandwidth is required to handle fast rising input signals (as for time-of-flight measurement cases). The added amplifier inside the TIA feedback loop can be configured to have slightly lower voltage gain than the bandwidth reduction factor.

Blood-brain barrier and cerebral blood flow: Age differences in hemorrhagic stroke

Directory of Open Access Journals (Sweden)

Semyachkina-Glushkovskaya Oxana

2015-11-01

Full Text Available Neonatal stroke is similar to the stroke that occurs in adults and produces a significant morbidity and long-term neurologic and cognitive deficits. There are important differences in the factors, clinical events and outcomes associated with the stroke in infants and adults. However, mechanisms underlying age differences in the stroke development remain largely unknown. Therefore, treatment guidelines for neonatal stroke must extrapolate from the adult data that is often not suitable for children. The new information about differences between neonatal and adult stroke is essential for identification of significant areas for future treatment and effective prevention of neonatal stroke. Here, we studied the development of stress-induced hemorrhagic stroke and possible mechanisms underlying these processes in newborn and adult rats. Using histological methods and magnetic resonance imaging, we found age differences in the type of intracranial hemorrhages. Newborn rats demonstrated small superficial bleedings in the cortex while adult rats had more severe deep bleedings in the cerebellum. Using Doppler optical coherent tomography, we found higher stress-reactivity of the sagittal sinus to deleterious effects of stress in newborn vs. adult rats suggesting that the cerebral veins are more vulnerable to negative stress factors in neonatal vs. adult brain in rats. However, adult but not newborn rats demonstrated the stroke-induced breakdown of blood brain barrier (BBB permeability. The one of possible mechanisms underlying the higher resistance to stress-related stroke injures of cerebral vessels in newborn rats compared with adult animals is the greater expression of two main tight junction proteins of BBB (occludin and claudin-5 in neonatal vs. mature brain in rats.

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.)

Human Motor Cortex Functional Changes in Acute Stroke: Gender Effects

Directory of Open Access Journals (Sweden)

Vincenzo eDi Lazzaro

2016-01-01

Full Text Available The acute phase of stroke is accompanied by functional changes in the activity and interplay of both hemispheres. In healthy subjects, gender is known to impact the functional brain organization.We investigated whether gender influences also acute stroke functional changes. In thirty-five ischemic stroke patients, we evaluated the excitability of the affected (AH and unaffected hemisphere (UH by measuring resting and active motor threshold and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation (iTBS of AH. We also computed an index of the excitability balance between the hemispheres, laterality indexes (LI, to evidence hemispheric asymmetry. Active motor threshold differed significantly between AH and UH only in the male group (p=0.004, not in females (p>0.200, and both LIAMT and LIRMT were significantly higher in males than in females (respectively p=0.033 and p=0.042. LTP-like activity induced by iTBS in AH was more frequent in females. Gender influences the functional excitability changes that take place after human stroke and the level of LTP that can be induced by repetitive stimulation. This knowledge is of high value in the attempt of individualizing to different genders any non-invasive stimulation strategy designed to foster stroke recovery.

Human Motor Cortex Functional Changes in Acute Stroke: Gender Effects

Science.gov (United States)

Di Lazzaro, Vincenzo; Pellegrino, Giovanni; Di Pino, Giovanni; Ranieri, Federico; Lotti, Fiorenza; Florio, Lucia; Capone, Fioravante

2016-01-01

The acute phase of stroke is accompanied by functional changes in the activity and interplay of both hemispheres. In healthy subjects, gender is known to impact the functional brain organization. We investigated whether gender influences also acute stroke functional changes. In thirty-five ischemic stroke patients, we evaluated the excitability of the affected (AH) and unaffected hemisphere (UH) by measuring resting and active motor threshold (AMT) and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation (iTBS) of AH. We also computed an index of the excitability balance between the hemispheres, laterality indexes (LI), to evidence hemispheric asymmetry. AMT differed significantly between AH and UH only in the male group (p = 0.004), not in females (p > 0.200), and both LIAMT and LIRMT were significantly higher in males than in females (respectively p = 0.033 and p = 0.042). LTP-like activity induced by iTBS in AH was more frequent in females. Gender influences the functional excitability changes that take place after human stroke and the level of LTP that can be induced by repetitive stimulation. This knowledge is of high value in the attempt of individualizing to different genders any non-invasive stimulation strategy designed to foster stroke recovery. PMID:26858590

Cryptogenic Stroke

Directory of Open Access Journals (Sweden)

Mohammad Saadatnia

2017-02-01

Full Text Available Cryptogenic stroke is defined as brain infarction that is not attributable to a source of definite embolism, large artery atherosclerosis, or small artery disease despite a thorough vascular, cardiac, and serologic evaluation. Despite many advances in our understanding of ischemic stroke, cryptogenic strokes remain a diagnostic and therapeutic challenge. The pathophysiology of cryptogenic stroke is likely various. Probable mechanisms include cardiac embolism secondary to occult paroxysmal atrial fibrillation, aortic atheromatous disease or other cardiac sources, paradoxical embolism from atrial septal abnormalities such as patent foramen ovale, hypercoagulable states, and preclinical or subclinical cerebrovascular disease.  Cryptogenic stroke is one-fourth among cerebral infarction, but most of them could be ascribed to embolic stroke. A significant proportion of cryptogenic strokes adhere to embolic infarct topography on brain imaging and improvement in our ability to detect paroxysmal atrial fibrillation in patients with cryptogenic stroke has strengthened the idea that these strokes are embolic in nature. a significant proportion of cryptogenic strokes adhere to embolic infarct topography on brain imaging.embolic stroke of undetermined sources(ESUS was planned for unifying embolic stroke of undetermined source.  The etiologies underlying ESUS included minor-risk potential cardioembolic sources, covert paroxysmal atrial fibrillation, cancer-associated coagulopathy and embolism, arteriogenic emboli, and paroxysmal embolism. Extensive evaluation including transesophageal echocardiography and cardiac monitoring for long time could identify the etiology of these patients. Therefore cryptogenic stroke is a diagnosis of exclusion. Compared with other stroke subtypes, cryptogenic stroke tends to have a better prognosis and lower long-term risk of recurrence.

Crosstalk in 1.5-μm InGaAsP optical amplifiers

DEFF Research Database (Denmark)

Lassen, H. E.; Hansen, Peter Bukhave; Stubkjær, Kristian

1988-01-01

A dynamical model for multichannel amplification by near-traveling-wave optical amplifiers is presented, and results on crosstalk induced by either amplitude modulation or frequency modulation are given. The mechanisms influencing the crosstalk most are the residual facet reflectivities...... and the detuning of the channels relative to the amplifier Fabry-Perot spectrum. Calculations of worst-case crosstalk levels are included. The model is verified experimentally for amplitude-modulated signals, and crosstalk levels up to -7 dB are reported. For frequency-modulated signals, estimated crosstalk...

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.

Comparing unilateral and bilateral upper limb training: the ULTRA-stroke program design

NARCIS (Netherlands)

van Delden, A.E.Q.; Peper, C.E.; Harlaar, J.; Daffertshofer, A.; Zijp, N.I.; Nienhuys, K.; Koppe, P.; Kwakkel, G.; Beek, P.J.

2009-01-01

Background: About 80% of all stroke survivors have an upper limb paresis immediately after stroke, only about a third of whom (30 to 40%) regain some dexterity within six months following conventional treatment programs. Of late, however, two recently developed interventions - constraint-induced

Late night activity regarding stroke codes: LuNAR strokes.

Science.gov (United States)

Tafreshi, Gilda; Raman, Rema; Ernstrom, Karin; Rapp, Karen; Meyer, Brett C

2012-08-01

There is diurnal variation for cardiac arrest and sudden cardiac death. Stroke may show a similar pattern. We assessed whether strokes presenting during a particular time of day or night are more likely of vascular etiology. To compare emergency department stroke codes arriving between 22:00 and 8:00 hours (LuNAR strokes) vs. others (n-LuNAR strokes). The purpose was to determine if late night strokes are more likely to be true strokes or warrant acute tissue plasminogen activator evaluations. We reviewed prospectively collected cases in the University of California, San Diego Stroke Team database gathered over a four-year period. Stroke codes at six emergency departments were classified based on arrival time. Those arriving between 22:00 and 8:00 hours were classified as LuNAR stroke codes, the remainder were classified as 'n-LuNAR'. Patients were further classified as intracerebral hemorrhage, acute ischemic stroke not receiving tissue plasminogen activator, acute ischemic stroke receiving tissue plasminogen activator, transient ischemic attack, and nonstroke. Categorical outcomes were compared using Fisher's Exact test. Continuous outcomes were compared using Wilcoxon's Rank-sum test. A total of 1607 patients were included in our study, of which, 299 (19%) were LuNAR code strokes. The overall median NIHSS was five, higher in the LuNAR group (n-LuNAR 5, LuNAR 7; P=0·022). There was no overall differences in patient diagnoses between LuNAR and n-LuNAR strokes (P=0·169) or diagnosis of acute ischemic stroke receiving tissue plasminogen activator (n-LuNAR 191 (14·6%), LuNAR 42 (14·0%); P=0·86). Mean arrival to computed tomography scan time was longer during LuNAR hours (n-LuNAR 54·9±76·3 min, LuNAR 62·5±87·7 min; P=0·027). There was no significant difference in 90-day mortality (n-LuNAR 15·0%, LuNAR 13·2%; P=0·45). Our stroke center experience showed no difference in diagnosis of acute ischemic stroke between day and night stroke codes. This

Oscillators and operational amplifiers

OpenAIRE

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 of the general circuit is derived. The dynamic nonlinear transfer characteristic of the amplifier is investigated. Examples of negative resistance oscillators are discussed.

FLUIDIC AC AMPLIFIERS.

Science.gov (United States)

Several fluidic tuned AC Amplifiers were designed and tested. Interstage tuning and feedback designs are considered. Good results were obtained...corresponding Q’s as high as 12. Element designs and test results of one, two, and three stage amplifiers are presented. AC Modulated Carrier Systems

Does acupuncture ameliorate motor impairment after stroke? An assessment using the CatWalk gait system.

Science.gov (United States)

Cao, Yan; Sun, Ning; Yang, Jing-Wen; Zheng, Yang; Zhu, Wen; Zhang, Zhen-Hua; Wang, Xue-Rui; Shi, Guang-Xia; Liu, Cun-Zhi

2017-07-01

The effect of acupuncture on gait deficits after stroke is uncertain. This animal study was designed to determine whether acupuncture improves gait impairment following experimentally induced ischemic stroke. Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO) in rats. After 7 days' of acupuncture treatment, assessment of gait changes using the CatWalk automated gait analysis system was performed. Comparison of the CatWalk gait parameters among the groups showed that gait function was impaired after ischemic stroke and acupuncture treatment was effective in improving a variety of gait parameters including intensity, stance and swing time, swing speed and stride length at postoperative day 8. This study demonstrates a beneficial effect of acupuncture on gait impairment in rats following ischemic stroke. Further studies aimed to investigate the effects of acupuncture at different stages during stroke using the CatWalk system are required. Copyright © 2016 Elsevier Ltd. All rights reserved.

Child-Mediated Stroke Communication: findings from Hip Hop Stroke.

Science.gov (United States)

Williams, Olajide; DeSorbo, Alexandra; Noble, James; Gerin, William

2012-01-01

Low thrombolysis rates for acute ischemic stroke are linked to delays in seeking immediate treatment due to low public stroke awareness. We aimed to assess whether "Child-Mediated Stroke Communication" could improve stroke literacy of parents of children enrolled in a school-based stroke literacy program called Hip Hop Stroke. Parents of children aged 9 to 12 years from 2 public schools in Harlem, New York City, were recruited to participate in stroke literacy questionnaires before and after their child's participation in Hip Hop Stroke, a novel Child-Mediated Stroke Communication intervention delivered in school auditoriums. Parental recall of stroke information communicated through their child was assessed 1-week after the intervention. Fifth and sixth grade students (n=182) were enrolled into Hip Hop Stroke. One hundred two parents were approached in person to participate; 75 opted to participate and 71 completed both the pretest and post-test (74% response rate and 95% retention rate). Parental stroke literacy improved after the program; before the program, 3 parents of 75 (3.9%) were able to identify the 5 cardinal stroke symptoms, distracting symptom (chest pains), and had an urgent action plan (calling 911) compared with 21 of 71 parents (29.6%) postintervention (P<0.001). The FAST mnemonic was known by 2 (2.7%) of participants before the program versus 29 (41%) after program completion (P<0.001). Knowledge of stroke signs and symptoms remains low among residents of this high-risk population. The use of Child-Mediated Stroke Communication suggests that school children aged 9 to 12 years may be effective conduits of critical stroke knowledge to their parents.

Thermo-optical effects in high-power Ytterbium-doped fiber amplifiers

DEFF Research Database (Denmark)

Hansen, Kristian Rymann; Alkeskjold, Thomas Tanggaard; Broeng, Jes

2011-01-01

We investigate the effect of temperature gradients in high-power Yb-doped fiber amplifiers by a numerical beam propagation model, which takes thermal effects into account in a self-consistent way. The thermally induced change in the refractive index of the fiber leads to a thermal lensing effect...

[Renal cell carcinoma producing erythrocytosis due to inappropriate production of erythropoietin].

Science.gov (United States)

Villanueva-Gimeno, M M; Vicario-Bermúdez, J M; Fonseca-López, Ch; Caballero-Castro, J P; Zabala-López, S I; Sánchez-Elipe, M A; González-Gómez, N

2013-01-01

Erythrocytosis, or polycythaemia, is an increase, in absolute terms, of the erythrocyte mass. The most common solid tumour related to this phenomenon is renal cell carcinoma, which can produce erythrocytosis by increasing erythropoietin production. About 30% of symptomatic renal cell carcinomas are diagnosed due to the appearance of a paraneoplastic syndrome. Polycythaemia is one of these. Surgery, (radical or partial nephrectomy), is the treatment of choice in renal cell carcinoma and helps to keep the erythrocytosis situation under control. Copyright © 2011 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Comparison of Hemoglobin Levels Before and After Hemodialysis and Their Effects on Erythropoietin Dosing and Cost

OpenAIRE

Sagheb; Fallahzadeh; Moaref; Fallahzadeh; Dormanesh

2016-01-01

Background Hemoglobin levels measured after hemodialysis, as compared to hemoglobin levels measured before hemodialysis, are suggested to be a more accurate reflection of the hemoglobin levels between hemodialysis sessions, and to be a better reference point for adjusting erythropoietin dosing. Objectives The aim of this study was to compare the hemoglobin levels before and after hemodialysis, to calculate the required erythropoie...

Neuroplastic changes in resting-state functional connectivity after stroke rehabilitation

Directory of Open Access Journals (Sweden)

Yang-teng eFan

2015-10-01

Full Text Available Most neuroimaging research in stroke rehabilitation mainly focuses on the neural mechanisms underlying the natural history of post-stroke recovery. However, connectivity mapping from resting-state fMRI is well suited for different neurological conditions and provides a promising method to explore plastic changes for treatment-induced recovery from stroke. We examined the changes in resting-state functional connectivity (RS-FC of the ipsilesional primary motor cortex (M1 in 10 post-acute stroke patients before and immediately after 4 weeks of robot-assisted bilateral arm therapy (RBAT. Motor performance, functional use of the affected arm, and daily function improved in all participants. Reduced interhemispheric RS-FC between the ipsilesional and contralesional M1 (M1-M1 and the contralesional-lateralized connections were noted before treatment. In contrast, greater M1-M1 functional connectivity and disturbed resting-state networks were observed after RBAT relative to pre-treatment. Increased changes in M1-M1 RS-FC after RBAT were coupled with better motor and functional improvements. Mediation analysis showed the pre-to-post difference in M1-M1 RS-FC was a significant mediator for the relationship between motor and functional recovery. These results show neuroplastic changes and functional recoveries induced by RBAT in post-acute stroke survivors and suggest that interhemispheric functional connectivity in the motor cortex may be a neurobiological marker for recovery after stroke rehabilitation.

A soft robotic exosuit improves walking in patients after stroke.

Science.gov (United States)

Awad, Louis N; Bae, Jaehyun; O'Donnell, Kathleen; De Rossi, Stefano M M; Hendron, Kathryn; Sloot, Lizeth H; Kudzia, Pawel; Allen, Stephen; Holt, Kenneth G; Ellis, Terry D; Walsh, Conor J

2017-07-26

Stroke-induced hemiparetic gait is characteristically slow and metabolically expensive. Passive assistive devices such as ankle-foot orthoses are often prescribed to increase function and independence after stroke; however, walking remains highly impaired despite-and perhaps because of-their use. We sought to determine whether a soft wearable robot (exosuit) designed to supplement the paretic limb's residual ability to generate both forward propulsion and ground clearance could facilitate more normal walking after stroke. Exosuits transmit mechanical power generated by actuators to a wearer through the interaction of garment-like, functional textile anchors and cable-based transmissions. We evaluated the immediate effects of an exosuit actively assisting the paretic limb of individuals in the chronic phase of stroke recovery during treadmill and overground walking. Using controlled, treadmill-based biomechanical investigation, we demonstrate that exosuits can function in synchrony with a wearer's paretic limb to facilitate an immediate 5.33 ± 0.91° increase in the paretic ankle's swing phase dorsiflexion and 11 ± 3% increase in the paretic limb's generation of forward propulsion ( P exosuit was sufficient to facilitate more normal walking in ambulatory individuals after stroke. Future work will focus on understanding how exosuit-induced improvements in walking performance may be leveraged to improve mobility after stroke. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Generation and phenotypic analysis of a transgenic line of rabbits secreting active recombinant human erythropoietin in the milk

Czech Academy of Sciences Publication Activity Database

Mikuš, Tomáš; Poplštein, M.; Sedláková, J.; Landa, Vladimír; Jeníková, Gabriela; Trefil, P.; Lidický, J.; Malý, Petr

2004-01-01

Roč. 13, č. 5 (2004), s. 487-498 ISSN 0962-8819 R&D Projects: GA ČR GA304/03/0090 Institutional research plan: CEZ:AV0Z5052915 Keywords : erythropoietin, mammary gland, transgenic rabbit Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.107, year: 2004

Improvement in performance status after erythropoietin treatment in lung cancer patients undergoing concurrent chemoradiotherapy

International Nuclear Information System (INIS)

Casas, Francesc; Vinolas, Nuria; Ferrer, Ferran; Farrus, Blanca; Gimferrer, Josep Maria; Agusti, Carles; Belda, Josep; Luburich, Patricio

2003-01-01

Purpose: A prospective Phase II trial was carried out to evaluate the effectiveness of erythropoietin in improving or maintaining performance status as determined by the Karnofsky performance status (KPS) score and hemoglobin (Hb) levels in lung cancer patients treated with concurrent chemoradiation (CH-RT). Methods and Materials: A total of 51 patients with lung cancer (11 with small-cell, limited stage and 40 with non-small-cell disease, 17 with Stage IIIA and 23 with Stage IIIB), who underwent three different concurrent CH-RT protocols were enrolled. Baseline Hb and KPS values were recorded, as were the nadir Hb and KPS values before concurrent CH-RT. The final Hb and KPS values were recorded the last week of concurrent CH-RT. An Hb level of ≤11 g/dL before concurrent CH-RT was required before receiving erythropoietin. Prognostic factors for KPS improvement and survival were assessed by univariate and multivariate studies. Results: Of the 51 patients, 47 (92.3%) were men (mean age 63.6 years, range 40-75). The median baseline KPS score was 80, and the mean baseline Hb was 12.2 ± 1.76 g/dL (range 9-16.9). The mean nadir and final Hb value was 9.98±0.67 g/dL (range 8.6-11) and 11.33±1.59 g/dL (range 6.9-14.4), respectively. A significant increase was seen in the Hb and KPS score (p<0.05) in the final measurements. Differences were found between the final and nadir Hb in the predictive value for differences in performance status (p=0.001). On univariate study, pathologic findings (p=0.0234), weight loss (p=0.0049), baseline Hb (p=0.0057), and final Hb improvement (p=0.0237) were prognostic factors for survival. Nadir Hb (p=0.027), final Hb improvement (p=0.0069), pathologic findings (p = 0.0006), and weight loss (p=0.0001) had significant prognostic value for survival in multivariate analysis. Conclusion: In this study, erythropoietin appears to have a significant, beneficial impact on the KPS and Hb of patients undergoing concurrent CH-RT

Post-stroke angiotensin II type 2 receptor activation provides long-term neuroprotection in aged rats.

Directory of Open Access Journals (Sweden)

Douglas M Bennion

Full Text Available Activation of the angiotensin II type 2 receptor (AT2R by administration of Compound 21 (C21, a selective AT2R agonist, induces neuroprotection in models of ischemic stroke in young adult animals. The mechanisms of this neuroprotective action are varied, and may include direct and indirect effects of AT2R activation. Our objectives were to assess the long-term protective effects of post-stroke C21 treatments in a clinically-relevant model of stroke in aged rats and to characterize the cellular localization of AT2Rs in the mouse brain of transgenic reporter mice following stroke. Intraperitoneal injections of C21 (0.03mg/kg after ischemic stroke induced by transient monofilament middle cerebral artery occlusion resulted in protective effects that were sustained for up to at least 3-weeks post-stroke. These included improved neurological function across multiple assessments and a significant reduction in infarct volume as assessed by magnetic resonance imaging. We also found AT2R expression to be on neurons, not astrocytes or microglia, in normal female and male mouse brains. Stroke did not induce altered cellular localization of AT2R when assessed at 7 and 14 days post-stroke. These findings demonstrate that the neuroprotection previously characterized only during earlier time points using stroke models in young animals is sustained long-term in aged rats, implying even greater clinical relevance for the study of AT2R agonists for the acute treatment of ischemic stroke in human disease. Further, it appears that this sustained neuroprotection is likely due to a mix of both direct and indirect effects stemming from selective activation of AT2Rs on neurons or other cells besides astrocytes and microglia.

Post-stroke angiotensin II type 2 receptor activation provides long-term neuroprotection in aged rats.

Science.gov (United States)

Bennion, Douglas M; Isenberg, Jacob D; Harmel, Allison T; DeMars, Kelly; Dang, Alex N; Jones, Chad H; Pignataro, Megan E; Graham, Justin T; Steckelings, U Muscha; Alexander, Jon C; Febo, Marcelo; Krause, Eric G; de Kloet, Annette D; Candelario-Jalil, Eduardo; Sumners, Colin

2017-01-01

Activation of the angiotensin II type 2 receptor (AT2R) by administration of Compound 21 (C21), a selective AT2R agonist, induces neuroprotection in models of ischemic stroke in young adult animals. The mechanisms of this neuroprotective action are varied, and may include direct and indirect effects of AT2R activation. Our objectives were to assess the long-term protective effects of post-stroke C21 treatments in a clinically-relevant model of stroke in aged rats and to characterize the cellular localization of AT2Rs in the mouse brain of transgenic reporter mice following stroke. Intraperitoneal injections of C21 (0.03mg/kg) after ischemic stroke induced by transient monofilament middle cerebral artery occlusion resulted in protective effects that were sustained for up to at least 3-weeks post-stroke. These included improved neurological function across multiple assessments and a significant reduction in infarct volume as assessed by magnetic resonance imaging. We also found AT2R expression to be on neurons, not astrocytes or microglia, in normal female and male mouse brains. Stroke did not induce altered cellular localization of AT2R when assessed at 7 and 14 days post-stroke. These findings demonstrate that the neuroprotection previously characterized only during earlier time points using stroke models in young animals is sustained long-term in aged rats, implying even greater clinical relevance for the study of AT2R agonists for the acute treatment of ischemic stroke in human disease. Further, it appears that this sustained neuroprotection is likely due to a mix of both direct and indirect effects stemming from selective activation of AT2Rs on neurons or other cells besides astrocytes and microglia.

Post-stroke angiotensin II type 2 receptor activation provides long-term neuroprotection in aged rats

DEFF Research Database (Denmark)

Bennion, Douglas M; Isenberg, Jacob D; Harmel, Allison T

2017-01-01

Activation of the angiotensin II type 2 receptor (AT2R) by administration of Compound 21 (C21), a selective AT2R agonist, induces neuroprotection in models of ischemic stroke in young adult animals. The mechanisms of this neuroprotective action are varied, and may include direct and indirect....... These findings demonstrate that the neuroprotection previously characterized only during earlier time points using stroke models in young animals is sustained long-term in aged rats, implying even greater clinical relevance for the study of AT2R agonists for the acute treatment of ischemic stroke in human....... Intraperitoneal injections of C21 (0.03mg/kg) after ischemic stroke induced by transient monofilament middle cerebral artery occlusion resulted in protective effects that were sustained for up to at least 3-weeks post-stroke. These included improved neurological function across multiple assessments...

The feed-back regulation of erythropoietin production in healthy humans

International Nuclear Information System (INIS)

Klausen, T.

1998-01-01

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

Stress Recovery Effects of High- and Low-Frequency Amplified Music on Heart Rate Variability.

Science.gov (United States)

Nakajima, Yoshie; Tanaka, Naofumi; Mima, Tatsuya; Izumi, Shin-Ichi

Sounds can induce autonomic responses in listeners. However, the modulatory effect of specific frequency components of music is not fully understood. Here, we examined the role of the frequency component of music on autonomic responses. Specifically, we presented music that had been amplified in the high- or low-frequency domains. Twelve healthy women listened to white noise, a stress-inducing noise, and then one of three versions of a piece of music: original, low-, or high-frequency amplified. To measure autonomic response, we calculated the high-frequency normalized unit (HFnu), low-frequency normalized unit, and the LF/HF ratio from the heart rate using electrocardiography. We defined the stress recovery ratio as the value obtained after participants listened to music following scratching noise, normalized by the value obtained after participants listened to white noise after the stress noise, in terms of the HFnu, low-frequency normalized unit, LF/HF ratio, and heart rate. Results indicated that high-frequency amplified music had the highest HFnu of the three versions. The stress recovery ratio of HFnu under the high-frequency amplified stimulus was significantly larger than that under the low-frequency stimulus. Our results suggest that the high-frequency component of music plays a greater role in stress relief than low-frequency components.

The Role of Omega-3 Polyunsaturated Fatty Acids in Stroke

Directory of Open Access Journals (Sweden)

Jiyuan Bu

2016-01-01

Full Text Available Stroke is the third commonest cause of death following cardiovascular diseases and cancer. In particular, in recent years, the morbidity and mortality of stroke keep remarkable growing. However, stroke still captures people attention far less than cardiovascular diseases and cancer. Past studies have shown that oxidative stress and inflammation play crucial roles in the progress of cerebral injury induced by stroke. Evidence is accumulating that the dietary supplementation of fish oil exhibits beneficial effects on several diseases, such as cardiovascular diseases, metabolic diseases, and cancer. Omega-3 polyunsaturated fatty acids (n-3 PUFAs, the major component of fish oil, have been found against oxidative stress and inflammation in cardiovascular diseases. And the potential of n-3 PUFAs in stroke treatment is attracting more and more attention. In this review, we will review the effects of n-3 PUFAs on stroke and mainly focus on the antioxidant and anti-inflammatory effects of n-3 PUFAs.

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.

Stroke Treatments

Science.gov (United States)

... Stroke Association.org Professionals for Stroke Association.org Shop for Stroke Association.org Support for Stroke Association. ... works by dissolving the clot and improving blood flow to the part of the brain being deprived ...

Post-stroke depression among stroke survivors attending two ...

African Journals Online (AJOL)

Background: The burden of stroke worldwide is increasing rapidly. There is paucity of data on post-stroke depression (PSD) among stroke survivors in Uganda, despite the high prevalence of PSD reported elsewhere. Methods: In a cross-sectional study, we assessed adult participants with confirmed first stroke with a ...

Transport in coherently absorbing or amplifying media

International Nuclear Information System (INIS)

Sen, A.K.

1995-11-01

We study electronic transport in a one-dimensional ordered chain in the presence of either absorption or amplification at each site (the site-potential having an imaginary positive or negative part) within a single-band tightbinding Hamiltonian. The spectrum in either case for the isolated (closed) quantum system is found to become broader compared to the regular Bloch case where there is no absorption or amplification at any site. Interestingly for the transport through an infinitely long ordered chain (open quantum system), the reflectance saturates to a value greater (lesser) than unity in the amplifying (absorbing) case and the transmittance decays to zero in either case. This fact implies that the transmittance does not grow indefinitely even for an ordered, amplifying (active or lasing) medium and that it is not necessary to have any disorder or interaction induced confining mechanism on the transmitted wave, so as to achieve an amplification in the backscattered wave. (author). 8 refs, 2 figs

A CMOS current-mode operational amplifier

DEFF Research Database (Denmark)

Kaulberg, Thomas

1993-01-01

current-mode feedback amplifier or a constant bandwidth in a transimpedance feedback amplifier. The amplifier is found to have a gain-bandwidth product of 3 MHz, an offset current of 0.8 μA (signal range ±700 μA), and a (theoretically) unlimited slew rate. The amplifier is realized in a standard CMOS 2......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...

Characteristics and adaptive strategies linked with falls in stroke survivors from analysis of laboratory-induced falls

Science.gov (United States)

Honeycutt, Claire F.; Nevisipour, Masood; Grabiner, Mark D.

2016-01-01

Falls are the most common and expensive medical complication in stroke survivors. There is remarkably little information about what factors lead to a fall in stroke survivors. With few exceptions, the falls literature in stroke has focused on relating metrics of static balance and impairment to fall outcomes in the acute care setting or in community. While informative, these studies provide little information about what specific impairments in a stroke-survivor’s response to dynamic balance challenges lead to a fall. We identified the key kinematic characteristics of stroke survivors’ stepping responses following a balance disturbance that are associated with a fall following dynamic balance challenges. Stroke survivors were exposed to posteriorly-directed translations of a treadmill belt that elicited a stepping response. Kinematics were compared between successful and failed recovery attempts (i.e. a fall). We found that the ability to arrest and reverse trunk flexion and the ability to perform an appropriate initial compensatory step were the most critical response contributors to a successful recovery. We also identified 2 compensatory strategies utilized by stroke survivors to avoid a fall. Despite significant post-stroke functional impairments, the biomechanical causes of trip-related falls by stroke survivors appear to be similar to those of unimpaired older adults and lower extremity amputees. However, compensatory strategies (pivot, hopping) were observed. PMID:27614614

Perioperative erythropoietin protects the CNS against ischemic lesions in patients after open heart surgery.

Science.gov (United States)

Lakič, Nikola; Mrak, Miha; Šušteršič, Miha; Rakovec, Peter; Bunc, Matjaž

2016-12-01

The aim of this study was to establish erythropoietin as a protective factor against brain ischemia during open heart surgery. A total of 36 consecutive patients scheduled for revascularization heart surgery were included in the study. Of the patients 18 received 3 intravenous doses of recombinant human erythropoietin (rHuEpo, 24,000 IU) and 18 patients received a placebo. Magnetic resonance imaging (MRI) to detect new brain ischemic lesions was performed. Additionally, S100A, S100B, neuron-specific enolase A and B (NSE-A and B) and the concentration of antibodies against N‑methyl-D-aspartate receptors (NMDAR) to identify new neurological complications were determined. Patients who received rHuEpo showed no postoperative ischemic changes in the brain on MRI images. In the control group 5 (27.8 %) new ischemic lesions were found. The NMDAR antibody concentration, S100A, S100B and NSE showed no significant differences between the groups for new cerebral ischemia. High levels of lactate before and after external aortic compression (p = 0.022 and p = 0.048, respectively) and duration of operation could predict new ischemic lesions (p = 0.009). The addition of rHuEpo reduced the formation of lesions detectable by MRI in the brain and could be used clinically as neuroprotection in cardiac surgery.

Stem Cell-Based Therapies for Ischemic Stroke

Directory of Open Access Journals (Sweden)

Lei Hao

2014-01-01

Full Text Available In recent years, stem cell-based approaches have attracted more attention from scientists and clinicians due to their possible therapeutical effect on stroke. Animal studies have demonstrated that the beneficial effects of stem cells including embryonic stem cells (ESCs, inducible pluripotent stem cells (iPSCs, neural stem cells (NSCs, and mesenchymal stem cell (MSCs might be due to cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation on inflammation and immune response. Although several clinical studies have shown the high efficiency and safety of stem cell in stroke management, mainly MSCs, some issues regarding to cell homing, survival, tracking, safety, and optimal cell transplantation protocol, such as cell dose and time window, should be addressed. Undoubtably, stem cell-based gene therapy represents a novel potential therapeutic strategy for stroke in future.

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....

NASA developments in solid state power amplifiers

Science.gov (United States)

Leonard, Regis F.

1990-01-01

Over the last ten years, NASA has undertaken an extensive program aimed at development of solid state power amplifiers for space applications. Historically, the program may be divided into three phases. The first efforts were carried out in support of the advanced communications technology satellite (ACTS) program, which is developing an experimental version of a Ka-band commercial communications system. These first amplifiers attempted to use hybrid technology. The second phase was still targeted at ACTS frequencies, but concentrated on monolithic implementations, while the current, third phase, is a monolithic effort that focusses on frequencies appropriate for other NASA programs and stresses amplifier efficiency. The topics covered include: (1) 20 GHz hybrid amplifiers; (2) 20 GHz monolithic MESFET power amplifiers; (3) Texas Instruments' (TI) 20 GHz variable power amplifier; (4) TI 20 GHz high power amplifier; (5) high efficiency monolithic power amplifiers; (6) GHz high efficiency variable power amplifier; (7) TI 32 GHz monolithic power amplifier performance; (8) design goals for Hughes' 32 GHz variable power amplifier; and (9) performance goals for Hughes' pseudomorphic 60 GHz power amplifier.

MEMORY SONGS DECREASE DEPRESSION FOR STROKE PATIENTS

Directory of Open Access Journals (Sweden)

Harmayetty Harmayetty

2017-07-01

Full Text Available Introduction: Biological, physical and phsycosocial changes in stroke patient could be a stressor that induced a depression state. There would be an emotional disturbance in stroke patient and stroke attack would be recurrent, if it was not treated. One of the alternative techniques to reduce depression is musical therapy especially memory songs. Method: This study was used a quasy experimental pre-post test purposive sampling design. The population was stroke patients who treated in Neurological Ward A and Stroke Unit Dr Soetomo Hospital Surabaya. There were 12 respondents divided into 6 respondents for treatment group and 6 respondents for control group. The independent variable was music (memory song and dependent variable was depression. Data were collected by using questionnaire which adapted from Hamilton Depression Rating Scale and Geriatric Depression Rating Scale, then analyzed by using Wilcoxon Signed Rank Test and Mann Whitney U Test with significance level α≤0.05. Result: The result showed that there was a difference between pre test and post test in depression (p=0.0196 and there was a difference in the depression between treatment group and control group (p=0.002. Discussion: It can be concluded that music (memory songs has an effect to the depression of stroke patient. Further studies are needed to concerning other factors that may affect the relaxation technique especially in listening music.

HIGH AVERAGE POWER OPTICAL FEL AMPLIFIERS

International Nuclear Information System (INIS)

2005-01-01

Historically, the first demonstration of the optical FEL was in an amplifier configuration at Stanford University [l]. There were other notable instances of amplifying a seed laser, such as the LLNL PALADIN amplifier [2] and the BNL ATF High-Gain Harmonic Generation FEL [3]. However, for the most part FELs are operated as oscillators or self amplified spontaneous emission devices. Yet, in wavelength regimes where a conventional laser seed can be used, the FEL can be used as an amplifier. One promising application is for very high average power generation, for instance FEL's with average power of 100 kW or more. The high electron beam power, high brightness and high efficiency that can be achieved with photoinjectors and superconducting Energy Recovery Linacs (ERL) combine well with the high-gain FEL amplifier to produce unprecedented average power FELs. This combination has a number of advantages. In particular, we show that for a given FEL power, an FEL amplifier can introduce lower energy spread in the beam as compared to a traditional oscillator. This properly gives the ERL based FEL amplifier a great wall-plug to optical power efficiency advantage. The optics for an amplifier is simple and compact. In addition to the general features of the high average power FEL amplifier, we will look at a 100 kW class FEL amplifier is being designed to operate on the 0.5 ampere Energy Recovery Linac which is under construction at Brookhaven National Laboratory's Collider-Accelerator Department

EFFECT OF SELF-SELECTED AND INDUCED SLOW AND FAST PADDLING ON STROKE KINEMATICS DURING 1000 M OUTRIGGER CANOEING ERGOMETRY

Directory of Open Access Journals (Sweden)

Rebecca M. Sealey

2011-03-01

Full Text Available This study aimed to identify the effect of different stroke rates on various kinematic parameters during 1000 m outrigger canoeing. Sixteen, experienced female outrigger canoeists completed three 1000 m outrigger ergometer time trials, one trial each using a self-selected, a Hawaiian ( 65 strokes·min-1 stroke rate. Stroke rate, stroke length, stroke time, proportion of time spent in propulsion and recovery, torso flexion angle and 'twist' were measured and compared with repeated measures ANOVAs. Stroke rate, stroke length and stroke time were significantly different across all interventions (p < 0.05 despite no difference in the percentage of time spent in the propulsive and recovery phases of the stroke. Stroke length and stroke time were negatively correlated to stroke rate for all interventions (r = -0.79 and -0.99, respectively. Female outrigger canoeists maintain consistent stroke kinematics throughout a 1000 m time trial, most likely as a learned skill to maximize crew paddling synchrony when paddling on-water. While the Hawaiian stroke rate resulted in the greatest trunk flexion movement and 'twist' action, this potential increased back injury risk may be offset by the slow stroke rate and long stroke length and hence slow rate of force development.

NCYM promotes calpain-mediated Myc-nick production in human MYCN-amplified neuroblastoma cells

Energy Technology Data Exchange (ETDEWEB)

Shoji, Wataru [Division of Biochemistry and Innovative Cancer Therapeutics and Children' s Cancer Research Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717 (Japan); Department of Pediatric Surgery, Graduate School of Medicine, Tohoku University, Sendai 980-8574 (Japan); Suenaga, Yusuke, E-mail: ysuenaga@chiba-cc.jp [Division of Biochemistry and Innovative Cancer Therapeutics and Children' s Cancer Research Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717 (Japan); Cancer Genome Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717 (Japan); Kaneko, Yoshiki; Islam, S.M. Rafiqul; Alagu, Jennifer [Division of Biochemistry and Innovative Cancer Therapeutics and Children' s Cancer Research Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717 (Japan); Yokoi, Sana [Cancer Genome Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717 (Japan); Nio, Masaki [Department of Pediatric Surgery, Graduate School of Medicine, Tohoku University, Sendai 980-8574 (Japan); Nakagawara, Akira, E-mail: nakagawara-a@koseikan.jp [Division of Biochemistry and Innovative Cancer Therapeutics and Children' s Cancer Research Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717 (Japan)

2015-06-05

NCYM is a cis-antisense gene of MYCN and is amplified in human neuroblastomas. High NCYM expression is associated with poor prognoses, and the NCYM protein stabilizes MYCN to promote proliferation of neuroblastoma cells. However, the molecular mechanisms of NCYM in the regulation of cell survival have remained poorly characterized. Here we show that NCYM promotes cleavage of MYCN to produce the anti-apoptotic protein, Myc-nick, both in vitro and in vivo. NCYM and Myc-nick were induced at G2/M phase, and NCYM knockdown induced apoptotic cell death accompanied by Myc-nick downregulation. These results reveal a novel function of NCYM as a regulator of Myc-nick production in human neuroblastomas. - Highlights: • NCYM promotes cleavages of MYC and MYCN to produce Myc-nick in vitro. • NCYM increases Myc-nick production in MYCN-amplified neuroblastoma cells. • NCYM knockdown decreases Myc-nick production and induces apoptosis at G2/M phase.

NCYM promotes calpain-mediated Myc-nick production in human MYCN-amplified neuroblastoma cells

International Nuclear Information System (INIS)

Shoji, Wataru; Suenaga, Yusuke; Kaneko, Yoshiki; Islam, S.M. Rafiqul; Alagu, Jennifer; Yokoi, Sana; Nio, Masaki; Nakagawara, Akira

2015-01-01

NCYM is a cis-antisense gene of MYCN and is amplified in human neuroblastomas. High NCYM expression is associated with poor prognoses, and the NCYM protein stabilizes MYCN to promote proliferation of neuroblastoma cells. However, the molecular mechanisms of NCYM in the regulation of cell survival have remained poorly characterized. Here we show that NCYM promotes cleavage of MYCN to produce the anti-apoptotic protein, Myc-nick, both in vitro and in vivo. NCYM and Myc-nick were induced at G2/M phase, and NCYM knockdown induced apoptotic cell death accompanied by Myc-nick downregulation. These results reveal a novel function of NCYM as a regulator of Myc-nick production in human neuroblastomas. - Highlights: • NCYM promotes cleavages of MYC and MYCN to produce Myc-nick in vitro. • NCYM increases Myc-nick production in MYCN-amplified neuroblastoma cells. • NCYM knockdown decreases Myc-nick production and induces apoptosis at G2/M phase

Risk Factors and Stroke Characteristic in Patients with Postoperative Strokes.

Science.gov (United States)

Dong, Yi; Cao, Wenjie; Cheng, Xin; Fang, Kun; Zhang, Xiaolong; Gu, Yuxiang; Leng, Bing; Dong, Qiang

2017-07-01

Intravenous thrombolysis and intra-arterial thrombectomy are now the standard therapies for patients with acute ischemic stroke. In-house strokes have often been overlooked even at stroke centers and there is no consensus on how they should be managed. Perioperative stroke happens rather frequently but treatment protocol is lacking, In China, the issue of in-house strokes has not been explored. The aim of this study is to explore the current management of in-house stroke and identify the common risk factors associated with perioperative strokes. Altogether, 51,841 patients were admitted to a tertiary hospital in Shanghai and the records of those who had a neurological consult for stroke were reviewed. Their demographics, clinical characteristics, in-hospital complications and operations, and management plans were prospectively studied. Routine laboratory test results and risk factors of these patients were analyzed by multiple logistic regression model. From January 1, 2015, to December 31, 2015, over 1800 patients had neurological consultations. Among these patients, 37 had an in-house stroke and 20 had more severe stroke during the postoperative period. Compared to in-house stroke patients without a procedure or operation, leukocytosis and elevated fasting glucose levels were more common in perioperative strokes. In multiple logistic regression model, perioperative strokes were more likely related to large vessel occlusion. Patients with perioperative strokes had different risk factors and severity from other in-house strokes. For these patients, obtaining a neurological consultation prior to surgery may be appropriate in order to evaluate the risk of perioperative stroke. Copyright © 2017. Published by Elsevier Inc.

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.

Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin-angiotensin-aldosterone system.

Science.gov (United States)

Aachmann-Andersen, Niels J; Christensen, Soren J; Lisbjerg, Kristian; Oturai, Peter; Johansson, Pär I; Holstein-Rathlou, Niels-Henrik; Olsen, Niels V

2018-03-01

The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance). rhEPO increased arterial blood pressure, total peripheral resistance, and renal vascular resistance, and decreased renal plasma flow in the high-dose rhEPO intervention and tended to decrease GFR. In spite of the decrease in renal perfusion, rhEPO tended to decrease reabsorption of sodium and water in the proximal tubule and induced a prompt decrease in circulating levels of renin and aldosterone, independent of changes in red blood cell mass, blood volumes, and blood pressure. We also found changes in biomarkers showing evidence that rhEPO induced a prothrombotic state. Our results suggest that rhEPO causes a direct downregulation in proximal tubular reabsorption that seems to decouple the activity of the renin-angiotensin-aldosterone system from changes in renal hemodynamics. This may serve as a negative feed-back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect of rhEPO on renal hemodynamics and a decoupling of the renin-angiotensin-aldosterone system. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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; Bønding, Signe Helbo

2015-01-01

fat oxidation were measured. Biopsies of the vastus lateralis muscle were obtained before and after the intervention. Recombinant erythropoietin treatment increased mitochondrial O2 flux during ADP stimulated state 3 respiration in the presence of complex I and II substrates (malate, glutamate...

Regulation of Hypertension for Secondary Prevention of Stroke: The Possible 'Bridging Function' of Acupuncture.

Science.gov (United States)

Zheng, Haizhen; Han, Yuhui; Du, Yuzheng; Shi, Xuemin; Huang, Huiyuan; Yu, Xiaoyang; Tan, Xiaochan; Hu, Chunxiao; Wang, Yue; Zhou, Shiyuan

2018-01-01

Worldwide, stroke is the leading cause of mortality and disability, with hypertension being an independent risk factor for a secondary stroke. Acupuncture for the treatment of hypertension gains more attention in alternative and complementary medicine, but the results are inconsistent. Few studies regarding the secondary prevention of stroke by managing hypertension with acupuncture have been carried out as there are some problems regarding the antihypertensive drug status in the secondary prevention of stroke. Still, the potential of acupuncture in regulating the blood pressure for secondary stroke prevention deserves our focus. This review is based on papers recorded in the PubMed, Embase, and Web of Science databases, from their inception until March 28, 2017, and retrieved with the following search terms: hypertension and acupuncture, limited in spontaneously hypertensive rats (SHRs), stress-induced (or cold-induced) hypertensive or pre-hypertensive models. We find that, in these hypertensive animals, acupuncture could mainly influence factors related to the nervous system, oxidative stress, the endocrine system, cardiovascular function, and hemorheology, which are closely associated with the stroke outcome. This trend may give us a hint that acupuncture might well participate in the secondary prevention of stroke through these pathways when used in the management of hypertension. © 2018 S. Karger GmbH, Freiburg.

A new theory of cryptogenic stroke and its relationship to patent foramen ovale; or, the puzzle of the missing extra risk.

Science.gov (United States)

Eggers, Arnold E

2006-01-01

Cryptogenic stroke (or stroke of undetermined cause) is a common cause of stroke and is statistically associated with patent foramen ovale (PFO). The largest study of cryptogenic stroke is the Homma study, which is a sub-study of the WARSS trial; it produced the following data: cryptogenic stroke patients with and without PFO, when treated with either aspirin or warfarin, all had identical recurrence rates. This is puzzling because it seems as though there ought to have been some extra risk in one of the two groups under one of the two treatments. How could everything come out the same? A review of the epidemiology of cryptogenic stroke shows that, compared to patients with stroke of determined cause, cryptogenic stroke patients are a little younger and have lower doses of the usual risk factors (hypertension and diabetes mellitus) but more PFO. Cryptogenic strokes appear to be embolic strokes from an unknown source. A previously published article setting forth a hypothetical theory of stress-induced stroke was used to analyze these data. It is suggested that stress can induce episodic systemic platelet activation and hypercoagulability, which causes transient thrombus formation and subsequent embolization on both the arterial and venous sides of the circulation; the latter requires a PFO to cause a stroke (paradoxical embolism). The sum of these two mechanisms explains cryptogenic stroke. The PFO subset of cryptogenic stroke includes patients with both early and late stage disease who have an aggregate risk approximately equal to that of patients without PFO. Cryptogenic stroke is part of the disease of stress-induced cerebrovascular disease. Aspirin and warfarin have already been shown to be equally effective in secondary prevention of ischemic stroke.

Protective effect of bone marrow mesenchymal stem cells combined with erythropoietin therapy on spinal cord injury rat model

Directory of Open Access Journals (Sweden)

Peng Xie

2016-01-01

Full Text Available Objective: To study the protective effect of bone marrow mesenchymal stem cells combined with erythropoietin therapy on spinal cord injury rat model. Methods: SD rats were selected as experimental animals, spinal cord injury rat model was built by striking spinal cord with Hatteras Instruments PCI3000, and model rats were divided into control group, bone marrow mesenchymal stem cells (BMSCs group, erythropoietin (EPO group and BMSCs combined with EPO group according to different treatment methods. Then number of apoptotic cells in spinal cord tissue, contents of neural markers and neurotrophic factors as well as expression of apoptosis and injury molecules was detected. Results: Number of apoptotic cells as well as mRNA contents of Caspase-3 and c-fos of BMSCs group, EPO group and BMSCs+EPO group was lower than those of control group, and number of apoptotic cells as well as mRNA contents of Caspase-3 and c-fos of BMSCs+EPO group were lower than those of BMSCs group and EPO group; mRNA contents of NF-200 and MBP as well as protein contents of NGF and BDNF in spinal cord tissue of BMSCs group, EPO group and BMSCs+EPO group were higher than those of control group, and mRNA contents of NF-200 and MBP as well as protein contents of NGF and BDNF in spinal cord tissue of BMSCs+EPO group were higher than those of BMSCs group and EPO group. Conclusions: Bone marrow mesenchymal stem cells combined with erythropoietin therapy can inhibit cell apoptosis in the injured spinal cord tissue, increase neurotrophic factor levels and inhibit apoptosis and injury molecule expression; it has protective effect on spinal cord injury.

Fast pulse amplifier

International Nuclear Information System (INIS)

Lepetit, J.; Poussier, E.

1984-01-01

This amplifier comprises an inverter transformer, the primary circuit of which receives a pulse and the secondary circuit of which is connected to several amplifying elements in parallel. The inverter transformer is made of coaxial cable segments winded around a magnetic torus; the cable cores connected in series constitute the primary circuit and the braiding of cables, connected in parallel, are the secondary circuit. The transformer comprises, besides, delay lines in series with each braiding of the secondary circuit, these ones are such that pulses issued from each braiding arrive together to the secondary circuit connectors. This invention applies, noticeably in the case of a high voltage amplifier, to the control of deflection blocks of particles used in medicine or in particle accelerators [fr

Ischemic stroke destabilizes circadian rhythms

Directory of Open Access Journals (Sweden)

Borjigin Jimo

2008-10-01

Full Text Available Abstract Background The central circadian pacemaker is a remarkably robust regulator of daily rhythmic variations of cardiovascular, endocrine, and neural physiology. Environmental lighting conditions are powerful modulators of circadian rhythms, but regulation of circadian rhythms by disease states is less clear. Here, we examine the effect of ischemic stroke on circadian rhythms in rats using high-resolution pineal microdialysis. Methods Rats were housed in LD 12:12 h conditions and monitored by pineal microdialysis to determine baseline melatonin timing profiles. After demonstration that the circadian expression of melatonin was at steady state, rats were subjected to experimental stroke using two-hour intralumenal filament occlusion of the middle cerebral artery. The animals were returned to their cages, and melatonin monitoring was resumed. The timing of onset, offset, and duration of melatonin secretion were calculated before and after stroke to determine changes in circadian rhythms of melatonin secretion. At the end of the monitoring period, brains were analyzed to determine infarct volume. Results Rats demonstrated immediate shifts in melatonin timing after stroke. We observed a broad range of perturbations in melatonin timing in subsequent days, with rats exhibiting onset/offset patterns which included: advance/advance, advance/delay, delay/advance, and delay/delay. Melatonin rhythms displayed prolonged instability several days after stroke, with a majority of rats showing a day-to-day alternation between advance and delay in melatonin onset and duration. Duration of melatonin secretion changed in response to stroke, and this change was strongly determined by the shift in melatonin onset time. There was no correlation between infarct size and the direction or amplitude of melatonin phase shifting. Conclusion This is the first demonstration that stroke induces immediate changes in the timing of pineal melatonin secretion, indicating

A fluidic/pneumatic interface amplifier

Science.gov (United States)

Limbert, D. E.; Kegel, T. M.

The development of a low cost, reliable, linear pressure amplifier to interface Laminar Proportional Amplifiers (LPA) to pneumatic controllers is presented. The amplifier consists of an LPA input stage and an output stage consisting of a venturi in series with a bellows nozzle valve. The LPA output drives the bellows nozzle valve thereby altering the flowrate through the venturi. The pressure within the venturi throat region, which is the amplifier output, changes with the flowrate. Non-linear characteristics, due to supersonic flow within the venturi, are altered through the use of feedback to the LPA input. A computer based model, to aid in optimizing the amplifier design, is developed. This model incorporates the effects of shock waves and boundary layers within the venturi. Good correspondence between the model and an experimental prototype is shown.

A review of Constraint-Induced Therapy applied to aphasia rehabilitation in stroke patients

Directory of Open Access Journals (Sweden)

Joana Bisol Balardin

Full Text Available Abstract Constraint-induced aphasia therapy (CIAT is an intensive therapy model based on the forced use of verbal oral language as the sole channel of communication, while any alternative communication mode such as writing, gesturing or pointing are prevented. Objectives: This critical review involved the analysis of studies examining CIAT applied to stroke patients. Methods and Results: Using keywords, the Medline database was searched for relevant studies published between 2001 and 2008 (Medline 2001-2008. The critical evaluation of the articles was based on the classifications described by the ASNS (Cicerone adaptation. Two studies were categorized as level Ia, two as level II and one study as level IV. Conclusions: These recommendations should be interpreted with caution, given the small number of studies involved, but serve as a guideline for future studies in aphasia therapy.

Amplifier for nuclear spectrometry

International Nuclear Information System (INIS)

Suarez Canner, E.

1996-01-01

The spectroscopy amplifier model AE-020 is designed to adjust suitable the pulses coming from nuclear radiation detectors. Due to is capacity and specifications, the amplifier can be used together with high and medium resolution spectroscopy system

Modeling FWM and impairments aware amplifiers placement technique for an optical MAN/WAN: Inline amplifiers case

Science.gov (United States)

Singh, Gurpreet; Singh, Maninder Lal

2015-08-01

A new four wave mixing (FWM) model for an optical network with amplifiers and a comparative analysis among three proposed amplifiers placement techniques have been presented in this paper. The FWM model is validated with the experimental measured data. The novelty of this model is its uniqueness that on direct substitutions of network parameters like length, it works even for unequal inter amplifier separations. The novelty of the analysis done among three schemes is that it presents fair choice of amplifiers placement methods for varied total system length. The appropriateness of these three schemes has been analyzed on the basis of critical system length, critical number of amplifiers and critical bit error rate (10-9) in presence of four wave mixing (FWM) and amplified spontaneous emission noise (ASE). The implementation of analysis done has been given with the help of an example of a regenerative metropolitan area network (MAN). The results suggest that the decreasing fiber section scheme should be avoided for placements of amplifiers and schemes IUFS and EFS shows their importance interchangeably for different set of parameters.

Semiconductor quantum-dot lasers and amplifiers

DEFF Research Database (Denmark)

Hvam, Jørn Märcher; Borri, Paola; Ledentsov, N. N.

2002-01-01

-power surface emitting VCSELs. We investigated the ultrafast dynamics of quantum-dot semiconductor optical amplifiers. The dephasing time at room temperature of the ground-state transition in semiconductor quantum dots is around 250 fs in an unbiased amplifier, decreasing to below 50 fs when the amplifier...... is biased to positive net gain. We have further measured gain recovery times in quantum dot amplifiers that are significantly lower than in bulk and quantum-well semiconductor optical amplifiers. This is promising for future demonstration of quantum dot devices with high modulation bandwidth...

NIF/LMJ prototype amplifier mechanical design

International Nuclear Information System (INIS)

Horvath, J.

1996-10-01

Amplifier prototypes for the National Ignition Facility and the Laser Megajoule will be tested at Lawrence Livermore National Laboratory. The prototype amplifier, which is an ensemble of modules from LLNL and Centre d'Etudes de Limeil-Valenton, is cassette-based with bottom access for maintenance. A sealed maintenance transfer vehicle which moves optical cassettes between the amplifier and the assembly cleanroom, and a vacuum gripper which holds laser slabs during cassette assembly will also be tested. The prototype amplifier will be used to verify amplifier optical performance, thermal recovery time, and cleanliness of mechanical operations

Knowledge of Stroke Risk Factors among Stroke Survivors in Nigeria

OpenAIRE

Grace Vincent-Onabajo; Taritei Moses

2016-01-01

Background. Knowledge of stroke risk factors is expected to reduce the incidence of stroke?whether first-ever or recurrent. This study examined knowledge of stroke risk factors and its determinants among stroke survivors. Methods. A cross-sectional survey of consenting stroke survivors at two physiotherapy facilities in Nigeria was carried out. Sociodemographic and clinical data were obtained and knowledge of stroke risk factors (defined as the ability to mention at least one correct risk fac...

Ischemic stroke following abuse of Marijuana in a Nigerian adult male

Directory of Open Access Journals (Sweden)

Olalekan Oyinloye

2014-01-01

Full Text Available Cannabis is the most widely used illicit drug among adolescents and young adults. Despite its widespread use, only a few reports exist on the association of cannabis use and stroke. A 26-year-old Nigerian male, developed right-sided ischemic stroke few hours after smoking three wraps of cannabis. He had smoked cannabis consistently for the past 4 years prior to the development of the stroke. Known stroke etiology and abuse of other illicit drugs were ruled out from history and investigations. Neuroimaging studies of the brain revealed infarcts in basal ganglia secondary to occlusion of blood flow in the left anterior and middle cerebral arteries. The mechanism of stroke in this patient was thought to be a cannabis-induced vasculopathy. Many cases of stroke in the young are increasingly being seen in hospitals in resource scarce countries. There seems to be a predilection for the basal ganglia in ischemic stroke following cannabis abuse. Therefore, cannabis abuse should be considered in young adults with basal ganglia infarcts, after excluding other known etiologies.

Localization of the cochlear amplifier in living sensitive ears.

Directory of Open Access Journals (Sweden)

Tianying Ren

Full Text Available BACKGROUND: To detect soft sounds, the mammalian cochlea increases its sensitivity by amplifying incoming sounds up to one thousand times. Although the cochlear amplifier is thought to be a local cellular process at an area basal to the response peak on the spiral basilar membrane, its location has not been demonstrated experimentally. METHODOLOGY AND PRINCIPAL FINDINGS: Using a sensitive laser interferometer to measure sub-nanometer vibrations at two locations along the basilar membrane in sensitive gerbil cochleae, here we show that the cochlea can boost soft sound-induced vibrations as much as 50 dB/mm at an area proximal to the response peak on the basilar membrane. The observed amplification works maximally at low sound levels and at frequencies immediately below the peak-response frequency of the measured apical location. The amplification decreases more than 65 dB/mm as sound levels increases. CONCLUSIONS AND SIGNIFICANCE: We conclude that the cochlea amplifier resides at a small longitudinal region basal to the response peak in the sensitive cochlea. These data provides critical information for advancing our knowledge on cochlear mechanisms responsible for the remarkable hearing sensitivity, frequency selectivity and dynamic range.

The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro

NARCIS (Netherlands)

von Lindern, M.; Zauner, W.; Mellitzer, G.; Steinlein, P.; Fritsch, G.; Huber, K.; Löwenberg, B.; Beug, H.

1999-01-01

Although erythropoietin (Epo) is essential for the production of mature red blood cells, the cooperation with other factors is required for a proper balance between progenitor proliferation and differentiation. In avian erythroid progenitors, steroid hormones cooperate with tyrosine kinase receptors

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).

Identification of stroke mimics among clinically diagnosed acute strokes.

Science.gov (United States)

Tuntiyatorn, Lojana; Saksornchai, Pichaya; Tunlayadechanont, Supoch

2013-09-01

Stroke is a clinically syndrome of a sudden onset of neurological deficit in a vascular cause. Stroke mimics is the non-vascular disorders with stroke-like clinical symptoms. It is important to distinguish true stroke from mimics since treatment plan may differ To determine the incidence of the stroke mimics and identify their etiologies. All non-contrast head CT of the patients with clinically diagnosed stroke who immediately received imaging upon arrival at the emergency department of the university hospital were retrospectively reviewed in 12-month period between January 1 and December 31, 2008. Medical records, laboratory results, MRI, and 6-month clinical follow-up records were reviewed for final diagnosis. Seven hundred four patients were included in this study, including 363 (51.5%) men and 341 (48.5%) women with range in age from 24 to 108 years. Amongst those, 417 (59.2%) were ischemic stroke, 80 (11.40%) were hemorrhagic stroke, 186 (26.4%) were stroke-mimics, and 21 (3%) were inconclusive. The etiologies among stroke-mimics were metabolic/intoxication (35, 18.8%), sepsis (28, 15.0%), seizure (21, 11.3%), syncope (20, 10.8%), subdural hemorrhage (14, 7.5%), vertigo (11, 6.0%), brain tumor (10, 5.30%), central nervous system infection (5, 2.7%), others (26, 14.0%), and unspecified (16, 8.6%). Incidence rates and etiologies of the stroke mimics were similar to the western reports. However the frequency of each mimic was not.

Constraint-Induced Aphasia Therapy for Treatment of Chronic Post-Stroke Aphasia: A Randomized, Blinded, Controlled Pilot Trial.

Science.gov (United States)

Szaflarski, Jerzy P; Ball, Angel L; Vannest, Jennifer; Dietz, Aimee R; Allendorfer, Jane B; Martin, Amber N; Hart, Kimberly; Lindsell, Christopher J

2015-09-24

To provide a preliminary estimate of efficacy of constraint-induced aphasia therapy (CIAT) when compared to no-intervention in patients with chronic (>1 year) post-stroke aphasia in order to plan an appropriately powered randomized controlled trial (RCT). We conducted a pilot single-blinded RCT. 24 patients were randomized: 14 to CIAT and 10 to no-intervention. CIAT groups received up to 4 hours/day of intervention for 10 consecutive business days (40 hours or therapy). Outcomes were assessed within 1 week of intervention and at 1 and 12 weeks after intervention and included several linguistic measures and a measure of overall subjective communication abilities (mini-Communicative Abilities Log (mini-CAL)). Clinicians treating patients (CIAT group) did not communicate with other team members to maintain blinding and the testing team members were blinded to treatment group assignment. Overall, the results of this pilot RCT support the results of previous observational studies that CIAT may lead to improvements in linguistic abilities. At 12 weeks, the treatment group reported better subjective communication abilities (mini-CAL) than the no-intervention group (p=0.019). Other measures trended towards better performance in the CIAT group. In this pilot RCT intensive language therapy led to an improvement in subjective language abilities. The effects demonstrated allow the design of a definitive trial of CIAT in patients with a variety of post-stroke aphasia types. In addition, our experiences have identified important considerations for designing subsequent trial(s) of CIAT or other interventions for post-stroke aphasia.

Topical Erythropoietin Treatment Accelerates the Healing of Cutaneous Burn Wounds in Diabetic Pigs Through an Aquaporin-3-Dependent Mechanism.

Science.gov (United States)

Hamed, Saher; Ullmann, Yehuda; Egozi, Dana; Keren, Aviad; Daod, Essam; Anis, Omer; Kabha, Hoda; Belokopytov, Mark; Ashkar, Manal; Shofti, Rona; Zaretsky, Asaph; Schlesinger, Michal; Teot, Luc; Liu, Paul Y

2017-08-01

We have previously reported that the topical application of erythropoietin (EPO) to cutaneous wounds in rats and mice with experimentally induced diabetes accelerates their healing by stimulating angiogenesis, reepithelialization, and collagen deposition, and by suppressing the inflammatory response and apoptosis. Aquaporins (AQPs) are integral membrane proteins whose function is to regulate intracellular fluid hemostasis by enabling the transport of water and glycerol. AQP3 is the AQP that is expressed in the skin where it facilitates cell migration and proliferation and re-epithelialization during wound healing. In this report, we provide the results of an investigation that examined the contribution of AQP3 to the mechanism of EPO action on the healing of burn wounds in the skin of pigs with experimentally induced type 1 diabetes. We found that topical EPO treatment of the burns accelerated their healing through an AQP3-dependent mechanism that activates angiogenesis, triggers collagen and hyaluronic acid synthesis and the formation of the extracellular matrix (ECM), and stimulates reepithelialization by keratinocytes. We also found that incorporating fibronectin, a crucial constituent of the ECM, into the topical EPO-containing gel, can potentiate the accelerating action of EPO on the healing of the burn injury. © 2017 by the American Diabetes Association.

Prevention Of Stroke

Directory of Open Access Journals (Sweden)

Nagaraja D

2005-01-01

Full Text Available Stroke is an important cause for neurological morbidity and mortality. Prevention of ischemic stroke involves identification and prevention of risk factors and optimal use of pharmacotherapy. Risk factors have been classified as modifiable and non-modifiable; control of modifiable factors should prevent stroke occurrence. Stroke prevention has been described at three levels: primary, secondary and tertiary. Prolonged hypertension increases an individual′s risk for developing fatal or nonfatal stroke by three times and its control has been shown to prevent stroke. Diabetes mellitus is an important cause for microangiopathy and predisposes to stroke. Statin trials have shown significant reduction in stroke in those who were treated with statins. Stroke risk can be reduced by avoiding tobacco use, control of obesity and avoiding sedentary life style. Anti platelet medications are effective for secondary prevention of stroke. Educating society regarding modifiable risk factors and optimal use of pharmacotherapy form the cornerstone for the prevention of stroke.

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

International Nuclear Information System (INIS)

Goupille, Olivier; Penglong, Tipparat; Lefèvre, Carine; Granger, Marine; Kadri, Zahra; Fucharoen, Suthat; Maouche-Chrétien, Leila; Leboulch, Philippe; Chrétien, Stany

2012-01-01

Highlights: ► UT7 erythroleukemia cells are known to be refractory to differentiate. ► Brief JQ1 treatment initiates the first steps of erythroid differentiation program. ► Engaged UT7 cells then maturate in the presence of erythropoietin. ► 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.

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.

Review of the randomized clinical stroke rehabilitation trials in 2009.

Science.gov (United States)

Rabadi, Meheroz H

2011-02-01

Recent review of the available evidence on interventions for motor recovery after stroke, showed that improvements in recovery of arm function were seen for constraint-induced movement therapy, electromyographic biofeedback, mental practice with motor imagery, and robotics. Similar improvement in transfer ability or balance were seen with repetitive task training, biofeedback, and training with a moving platform. Walking speed was improved by physical fitness training, high-intensity physiotherapy and repetitive task training. However, most of these trials were small and had design limitations. In this article, randomized control trials (RCT's) published in 2009 of rehabilitation therapies for acute (≤ 2 weeks), sub-acute (2 to 12 weeks) and chronic (≥ 12 weeks) stroke was reviewed. A Medline search was performed to identify all RCT's in stroke rehabilitation in the year 2009. The search strategy that was used for PubMed is presented in the Appendix 1. The objective was to examine the effectiveness of these treatment modalities in stroke rehabilitation. This generated 35 RCT's under 5 categories which were found and analyzed. The methodological quality was assessed by using the PEDro scale for external and internal validity. These trials were primarily efficacy studies. Most of these studies enrolled small numbers of patient which precluded their clinical applicability (limited external validity). However, the constraint induced movement therapy (CIT), regularly used in chronic stroke patients did not improve affected arm-hand function when used in acute stroke patients at ≤ 4 weeks. Intensive CIT did not lead to motor improvement in arm-hand function. Robotic arm treatment helped decrease motor impairment and improved function in chronic stroke patients only. Therapist provided exercise programs (when self-administered by patients during their off-therapy time in a rehabilitation setting) did improve arm-hand function. Tai Chi exercises helped improve

Stroke risk perception among participants of a stroke awareness campaign

Science.gov (United States)

Kraywinkel, Klaus; Heidrich, Jan; Heuschmann, Peter U; Wagner, Markus; Berger, Klaus

2007-01-01

Background Subjective risk factor perception is an important component of the motivation to change unhealthy life styles. While prior studies assessed cardiovascular risk factor knowledge, little is known about determinants of the individual perception of stroke risk. Methods Survey by mailed questionnaire among 1483 participants of a prior public stroke campaign in Germany. Participants had been informed about their individual stroke risk based on the Framingham stroke risk score. Stroke risk factor knowledge, perception of lifetime stroke risk and risk factor status were included in the questionnaire, and the determinants of good risk factor knowledge and high stroke risk perception were identified using logistic regression models. Results Overall stroke risk factor knowledge was good with 67–96% of the participants recognizing established risk factors. The two exceptions were diabetes (recognized by 49%) and myocardial infarction (57%). Knowledge of a specific factor was superior among those affected by it. 13% of all participants considered themselves of having a high stroke risk, 55% indicated a moderate risk. All major risk factors contributed significantly to the perception of being at high stroke risk, but the effects of age, sex and education were non-significant. Poor self-rated health was additionally associated with high individual stroke risk perception. Conclusion Stroke risk factor knowledge was high in this study. The self perception of an increased stroke risk was associated with established risk factors as well as low perception of general health. PMID:17371603

Assembly and maintenance of full scale NIF amplifiers in the amplifier module prototype laboratory (AMPLAB)

International Nuclear Information System (INIS)

Horvath, J. A.

1998-01-01

Mechanical assembly and maintenance of the prototype National Ignition Facility amplifiers in the Amplifier Module Prototype Laboratory (AMPLAB) at Lawrence Livermore National Laboratory requires specialized equipment designed to manipulate large and delicate amplifier components in a safe and clean manner. Observations made during the operation of this assembly and maintenance equipment in AMPLAB provide design guidance for similar tools being built for the National Ignition Facility. Fixtures used for amplifier frame installation, laser slab and flashlamp cassette assembly, transport, and installation, and in-situ blastshield exchange are presented. Examples include a vacuum slab gripper, slab handling clean crane, slab cassette assembly fixture, sealed transport vehicle for slab cassette movement between the cleanroom and amplifier, slab cassette transfer fixture between the cleanroom and transport vehicle, and equipment needed for frame assembly unit, blastshield, an d flashlamp cassette installation and removal. The use of these tools for amplifier assembly, system reconfiguration, reflector replacement, and recovery from an abnormal occurrence such as a flashlamp explosion is described. Observations are made on the design and operation of these tools and their contribution to the final design

Study of synergism effect between TID and ATREE on the response of the LM124 operational amplifier

International Nuclear Information System (INIS)

Roche, N.J.H.; Perez, S.; Mekki, J.; Gonzalez Velo, Y.; Dusseau, L.; Boch, J.; Saigne, F.; Vaille, J.R.; Vaille, J.R.; Marec, R.; Calvel, P.; Bezerra, F.; Auriel, G.; Azais, B.; Buchner, S.P.

2011-01-01

The Synergistic effect between Total Ionizing Dose (TID) and Analog Transient Radiation Effects in Electronics (ATREE) in an operational amplifier (LM124) is investigated. A predictive methodology, based on a previously developed ATREEs simulation tool, is used to model the synergistic phenomena. This phenomenon is simulated for the first time and the duration of the ATREEs' is found to be identical to those measured experimentally. ATREEs induced by high dose-rate X-ray pulses are investigated using a flash X-ray facility. The ATREEs induced in the LM124 operational amplifier configured in three different bias configurations are investigated and simulated. (authors)

EFFECTS OF MODIFIED CONSTRAINT-INDUCED MOVEMENT THERAPY FOR LOWER LIMB ON MOTOR FUNCTION IN STROKE PATIENTS: A RANDOMIZED CONTROLLED STUDY

Directory of Open Access Journals (Sweden)

Sevim ACAROZ CANDAN

2017-10-01

Full Text Available Background: Few studies have examined the effectiveness of modified constraint-induced movement therapy (mCIMT for the paretic lower limb following stroke. This study aimed to investigate the effects of mCIMT on motor function of the lower limb in stroke patients. Methods: A randomized, controlled study of 30 participants, who were randomized to 2 groups, was conducted. The study group received mCIMT, and the control group received neurodevelopmental therapy (NDT for two weeks. All were evaluated for motor function through the Functional Ambulation Classification (FAC, Berg Balance Scale (BBS,10-Meter Walk Test, gait parameters (cadence and step length ratio and postural symmetry ratio at pretreatment and post-treatment, like two times. Results: The improvements in BBS score, postural symmetry ratio, step length ratio, cadence and walking velocity had greater in the study group than the control group (P < 0.05. The improvement of FAC score was more pronounced in the study group (P = 0.005. Conclusion: mCIMT for paretic lower limb had superior effect against the NDT to enhance the motor function (gait parameters, balance, ambulation, and symmetry in patients with stroke. mCIMT may be used as a new alternative treatment for lower limb rehabilitation.

Acupuncture therapy for stroke patients.

Science.gov (United States)

Li, Xin; Wang, Qiang

2013-01-01

Acupuncture is one of the most important parts of Traditional Chinese Medicine, has been used for more than 3000 years as prevention and treatment for various diseases in China as well as in adjacent regions, and is widely accepted in western countries in recent years. More and more clinical trials revealed that acupuncture shows positive effect in stroke, not only as a complementary and alternative medicine for poststroke rehabilitation but also as a preventive strategy which could induce cerebral ischemic tolerance, especially when combined with modern electrotherapy. Acupuncture has some unique characteristics, which include acupoint specificity and parameter-dependent effect. It also involves complicated mechanism to exert the beneficial effect on stroke. Series of clinical trials have shown that acupuncture primarily regulates the release of neurochemicals, hemorheology, cerebral microcirculation, metabolism, neuronal activity, and the function of specific brain region. Animal studies showed that the effects of acupuncture therapy on stroke were possibly via inhibition of postischemic inflammatory reaction, stimulation of neurogenesis and angiogenesis, and influence on neural plasticity. Mechanisms for its preconditioning effect include activity enhancement of antioxidant, regulation of the endocannabinoid system, and inhibition of apoptosis. Although being controversial, acupuncture is a promising preventive and treatment strategy for stroke, but further high-quality clinical trials would be needed to provide more confirmative evidence. © 2013 Elsevier Inc. All rights reserved.

Reactive Balance in Individuals With Chronic Stroke: Biomechanical Factors Related to Perturbation-Induced Backward Falling.

Science.gov (United States)

Salot, Pooja; Patel, Prakruti; Bhatt, Tanvi

2016-03-01

An effective compensatory stepping response is the first line of defense for preventing a fall during sudden large external perturbations. The biomechanical factors that contribute to heightened fall risk in survivors of stroke, however, are not clearly understood. It is known that impending sensorimotor and balance deficits poststroke predispose these individuals to a risk of fall during sudden external perturbations. The purpose of this study was to examine the mechanism of fall risk in survivors of chronic stroke when exposed to sudden, slip-like forward perturbations in stance. This was a cross-sectional study. Fourteen individuals with stroke, 14 age-matched controls (AC group), and 14 young controls (YC group) were exposed to large-magnitude forward stance perturbations. Postural stability was computed as center of mass (COM) position (XCOM/BOS) and velocity (ẊCOM/BOS) relative to the base of support (BOS) at first step lift-off (LO) and touch-down (TD) and at second step TD. Limb support was quantified as vertical hip descent (Zhip) from baseline after perturbation onset. All participants showed a backward balance loss, with 71% of the stroke group experiencing a fall compared with no falls in the control groups (AC and YC groups). At first step LO, no between-group differences in XCOM/BOS and ẊCOM/BOS were noted. At first step TD, however, the stroke group had a significantly posterior XCOM/BOS and backward ẊCOM/BOS compared with the control groups. At second step TD, individuals with stroke were still more unstable (more posterior XCOM/BOS and backward ẊCOM/BOS) compared with the AC group. Individuals with stroke also showed greater peak Zhip compared with the control groups. Furthermore, the stroke group took a larger number of steps with shorter step length and delayed step initiation compared with the control groups. Although the study highlights the reactive balance deficits increasing fall risk in survivors of stroke compared with healthy

Progress in sensorimotor rehabilitative physical therapy programs for stroke patients

Science.gov (United States)

Chen, Jia-Ching; Shaw, Fu-Zen

2014-01-01

Impaired motor and functional activity following stroke often has negative impacts on the patient, the family and society. The available rehabilitation programs for stroke patients are reviewed. Conventional rehabilitation strategies (Bobath, Brunnstrom, proprioception neuromuscular facilitation, motor relearning and function-based principles) are the mainstream tactics in clinical practices. Numerous advanced strategies for sensory-motor functional enhancement, including electrical stimulation, electromyographic biofeedback, constraint-induced movement therapy, robotics-aided systems, virtual reality, intermittent compression, partial body weight supported treadmill training and thermal stimulation, are being developed and incorporated into conventional rehabilitation programs. The concept of combining valuable rehabilitative procedures into “a training package”, based on the patient’s functional status during different recovery phases after stroke is proposed. Integrated sensorimotor rehabilitation programs with appropriate temporal arrangements might provide great functional benefits for stroke patients. PMID:25133141

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...

Blood Pressure Control: Stroke and Stroke Prevention

Directory of Open Access Journals (Sweden)

Hans-Christoph Diener

2005-03-01

Full Text Available Hypertension is the most important modifiable risk factor for primary and secondary stroke prevention.All antihypertensive drugs are effective in primary prevention: the risk reduction for stroke is 30—42%. However, not all classes of drugs have the same effects: there is some indication that angiotensin receptor blockers may be superior to other classes of antihypertensive drugs in stroke prevention.Seventy-five percent of patients who present to hospital with acute stroke have elevated blood pressure within the first 24—48 hours. Extremes of systolic blood pressure (SBP increase the risk of death or dependency. The aim of treatment should be to achieve and maintain the SBP in the range 140—160 mmHg. However, fast and drastic blood pressure lowering can have adverse consequences.The PROGRESS trial of secondary prevention with perindopril + indapamide versus placebo + placebo showed a decrease in numbers of stroke recurrences in patients given both active antihypertensive agents, more impressive for cerebral haemorrhage.There were also indications that active treatment might decrease the development of post-stroke dementia.

Hemorrhagic and ischemic strokes compared: stroke severity, mortality, and risk factors.

Science.gov (United States)

Andersen, Klaus Kaae; Olsen, Tom Skyhøj; Dehlendorff, Christian; Kammersgaard, Lars Peter

2009-06-01

Stroke patients with hemorrhagic (HS) and ischemic strokes were compared with regard to stroke severity, mortality, and cardiovascular risk factors. A registry started in 2001, with the aim of registering all hospitalized stroke patients in Denmark, now holds information for 39,484 patients. The patients underwent an evaluation including stroke severity (Scandinavian Stroke Scale), CT, and cardiovascular risk factors. They were followed-up from admission until death or censoring in 2007. Independent predictors of death were identified by means of a survival model based on 25,123 individuals with a complete data set. Of the patients 3993 (10.1%) had HS. Stroke severity was almost linearly related to the probability of having HS (2% in patients with the mildest stroke and 30% in those with the most severe strokes). Factors favoring ischemic strokes vs HS were diabetes, atrial fibrillation, previous myocardial infarction, previous stroke, and intermittent arterial claudication. Smoking and alcohol consumption favored HS, whereas age, sex, and hypertension did not herald stroke type. Compared with ischemic strokes, HS was associated with an overall higher mortality risk (HR, 1.564; 95% CI, 1.441-1.696). The increased risk was, however, time-dependent; initially, risk was 4-fold, after 1 week it was 2.5-fold, and after 3 weeks it was 1.5-fold. After 3 months stroke type did not correlate to mortality. Strokes are generally more severe in patients with HS. Within the first 3 months after stroke, HS is associated with a considerable increase of mortality, which is specifically associated with the hemorrhagic nature of the lesion.

Middle cerebral artery occlusion in Macaca fascicularis: acute and chronic stroke evolution.

Science.gov (United States)

D'Arceuil, Helen E; Duggan, Michael; He, Julian; Pryor, Johnny; de Crespigny, Alex

2006-04-01

An intravascular stroke model designed for magnetic resonance imaging was developed in Macaca fascicularis (M. fascicularis) to characterize serial stroke lesion evolution. This model produces a range of stroke lesion sizes which closely mimics human stroke evolution. This paper describes the care of animals undergoing this stroke procedure, the range of outcomes we experienced and the cause of mortality in this model. Anesthesia was induced with atropine and ketamine and maintained with isoflurane or propofol. Non-invasive blood pressure, oxygen saturation, heart rate, respiration rate, temperature and end tidal CO2 were monitored continuously. The stroke was created by occluding a distal branch of the middle cerebral artery. During catheter placement animals were heparinized and vasospasm was minimized using verapamil. Anesthetic induction and maintenance were smooth. Animals with small strokes showed very rapid recovery, were able to ambulate and self-feed within 2 hours of recovery. Animals with strokes of >or=4% of the hemispheric volume required lengthy observation during recovery and parenteral nutrition. Large strokes resulted in significant brain edema, herniation and brainstem compression. Intracerebral hemorrhage and or subarachnoid hemorrhage coupled with a stroke of any size was acutely fatal. In the absence of an effective acute stroke therapy, the spectrum of outcomes seen in our primate model is very similar to that observed in human stroke patients.

Stroke Care 2: Stroke rehabilitation

NARCIS (Netherlands)

Langhorne, P.; Bernhardt, J.; Kwakkel, G.

2011-01-01

Stroke is a common, serious, and disabling global health-care problem, and rehabilitation is a major part of patient care. There is evidence to support rehabilitation in well coordinated multidisciplinary stroke units or through provision of early supported provision of discharge teams. Potentially

Investigation of Genetic Disturbances in Oxygen Sensing and Erythropoietin Signaling Pathways in Cases of Idiopathic Erythrocytosis

Directory of Open Access Journals (Sweden)

Carla Luana Dinardo

2013-01-01

Full Text Available Background. Idiopathic erythrocytosis is the term reserved for cases with unexplained origins of abnormally increased hemoglobin after initial investigation. Extensive molecular investigation of genes associated with oxygen sensing and erythropoietin signaling pathways, in those cases, usually involves sequencing all of their exons and it may be time consuming. Aim. To perform a strategy for molecular investigation of patients with idiopathic erythrocytosis regarding oxygen sensing and erythropoietin signaling pathways. Methods. Samples of patients with idiopathic erythrocytosis were evaluated for the EPOR, VHL, PHD2, and HIF-2α genes using bidirectional sequencing of their hotspots. Results. One case was associated with HIF-2α mutation. Sequencing did not identify any pathogenic mutation in 4 of 5 cases studied in any of the studied genes. Three known nonpathogenic polymorphisms were found (VHL p.P25L, rs35460768; HIF-2α p.N636N, rs35606117; HIF-2α p.P579P, rs184760160. Conclusion. Extensive molecular investigation of cases considered as idiopathic erythrocytosis does not frequently change the treatment of the patient. However, we propose a complementary molecular investigation of those cases comprising genes associated with erythrocytosis phenotype to meet both academic and genetic counseling purposes.

Theoretical analysis of mode instability in high-power fiber amplifiers

DEFF Research Database (Denmark)

Hansen, Kristian Rymann; Alkeskjold, Thomas Tanggaard; Broeng, Jes

2013-01-01

We present a simple theoretical model of transverse mode instability in high-power rare-earth doped fiber amplifiers. The model shows that efficient power transfer between the fundamental and higher-order modes of the fiber can be induced by a nonlinear interaction mediated through the thermo......-optic effect, leading to transverse mode instability. The temporal and spectral characteristics of the instability dynamics are investigated, and it is shown that the instability can be seeded by both quantum noise and signal intensity noise, while pure phase noise of the signal does not induce instability...

Airplane stroke syndrome.

Science.gov (United States)

Humaidan, Hani; Yassi, Nawaf; Weir, Louise; Davis, Stephen M; Meretoja, Atte

2016-07-01

Only 37 cases of stroke during or soon after long-haul flights have been published to our knowledge. In this retrospective observational study, we searched the Royal Melbourne Hospital prospective stroke database and all discharge summaries from 1 September 2003 to 30 September 2014 for flight-related strokes, defined as patients presenting with stroke within 14days of air travel. We hypothesised that a patent foramen ovale (PFO) is an important, but not the only mechanism, of flight-related stroke. We describe the patient, stroke, and flight characteristics. Over the study period, 131 million passengers arrived at Melbourne airport. Our centre admitted 5727 stroke patients, of whom 42 (0.73%) had flight-related strokes. Flight-related stroke patients were younger (median age 65 versus 73, p<0.001), had similar stroke severity, and received intravenous thrombolysis more often than non-flight-related stroke patients. Seven patients had flight-related intracerebral haemorrhage. The aetiology of the ischaemic strokes was cardioembolic in 14/35 (40%), including seven patients with confirmed PFO, one with atrial septal defect, four with atrial fibrillation, one with endocarditis, and one with aortic arch atheroma. Paradoxical embolism was confirmed in six patients. Stroke related to air travel is a rare occurrence, less than one in a million. Although 20% of patients had a PFO, distribution of stroke aetiologies was diverse and was not limited to PFO and paradoxical embolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

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 European research, academy and industry in vacuum electronics. This paper describes the status of the project and progress towards the THz amplifier realization....

Integrated amplifying circuit with MOS transistors

Energy Technology Data Exchange (ETDEWEB)

Baylac, B; Merckel, G; Meunier, P

1974-01-25

The invention relates to a feedback-pass-band amplifier with MOS-transistors. The differential stage of conventional amplifiers is changed into an adding state, whereas the differential amplification stages are changed into amplifier inverter stages. All MOS transistors used in that amplifier are of similar configuration and are interdigitized, whereby the operating speed dispersion is reduced. This can be applied to obtaining a measurement channel for proportional chambers.

Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke.

Science.gov (United States)

Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H

2015-10-01

In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on

Effects of Unilateral Upper Limb Training in Two Distinct Prognostic Groups Early After Stroke: The EXPLICIT-Stroke Randomized Clinical Trial

NARCIS (Netherlands)

Kwakkel, G.; Winters, C.; Wegen, E.E.H. van; Nijland, R.H.; Kuijk, A.A. van; Visser-Meily, A.; Groot, J. de; Vlugt, E. de; Arendzen, J.H.; Geurts, A.C.H.; Meskers, C.G.

2016-01-01

Background and Objective Favorable prognosis of the upper limb depends on preservation or return of voluntary finger extension (FE) early after stroke. The present study aimed to determine the effects of modified constraint-induced movement therapy (mCIMT) and electromyography-triggered

Effects of Unilateral Upper Limb Training in Two Distinct Prognostic Groups Early after Stroke : The EXPLICIT-Stroke Randomized Clinical Trial

NARCIS (Netherlands)

Kwakkel, Gert; Winters, Caroline; Van Wegen, Erwin E.H.; Nijland, Rinske H.M.; Van Kuijk, Annette A.A.; Visser-Meily, Anne; De Groot, Jurriaan; De Vlugt, Erwin; Arendzen, J. Hans; Geurts, Alexander C.H.; Meskers, Carel G.M.

2016-01-01

Background and Objective. Favorable prognosis of the upper limb depends on preservation or return of voluntary finger extension (FE) early after stroke. The present study aimed to determine the effects of modified constraint-induced movement therapy (mCIMT) and electromyography-triggered

Stroke Rehabilitation.

Science.gov (United States)

Belagaje, Samir R

2017-02-01

Rehabilitation is an important aspect of the continuum of care in stroke. With advances in the acute treatment of stroke, more patients will survive stroke with varying degrees of disability. Research in the past decade has expanded our understanding of the mechanisms underlying stroke recovery and has led to the development of new treatment modalities. This article reviews and summarizes the key concepts related to poststroke recovery. Good data now exist by which one can predict recovery, especially motor recovery, very soon after stroke onset. Recent trials have not demonstrated a clear benefit associated with very early initiation of rehabilitative therapy after stroke in terms of improvement in poststroke outcomes. However, growing evidence suggests that shorter and more frequent sessions of therapy can be safely started in the first 24 to 48 hours after a stroke. The optimal amount or dose of therapy for stroke remains undetermined, as more intensive treatments have not been associated with better outcomes compared to standard intensities of therapy. Poststroke depression adversely affects recovery across a variety of measures and is an important target for therapy. Additionally, the use of selective serotonin reuptake inhibitors (SSRIs) appears to benefit motor recovery through pleiotropic mechanisms beyond their antidepressant effect. Other pharmacologic approaches also appear to have a benefit in stroke rehabilitation. A comprehensive rehabilitation program is essential to optimize poststroke outcomes. Rehabilitation is a process that uses three major principles of recovery: adaptation, restitution, and neuroplasticity. Based on these principles, multiple different approaches, both pharmacologic and nonpharmacologic, exist to enhance rehabilitation. In addition to neurologists, a variety of health care professionals are involved in stroke rehabilitation. Successful rehabilitation involves understanding the natural history of stroke recovery and a

Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence.

Science.gov (United States)

Vidal, Ana C; Banca, Paula; Pascoal, Augusto G; Cordeiro, Gustavo; Sargento-Freitas, João; Gouveia, Ana; Castelo-Branco, Miguel

2018-01-01

Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used a functional magnetic resonance imaging block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction (n = 20, with balanced left/right lesion sites). Results Analysis of 10 right hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right hemispheric stroke. Left hemispheric stroke was, in general, characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts is novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.

Power Amplifiers in CMOS Technology: A contribution to power amplifier theory and techniques

NARCIS (Netherlands)

Acar, M.

2011-01-01

In order to meet the demands from the market on cheaper, miniaturized mobile communications devices realization of RF power amplifiers in the mainstream CMOS technology is essential. In general, CMOS Power Amplifiers (PAs) require high voltage to decrease the matching network losses and for high

Ethnic differences in ischemic stroke subtypes in young-onset stroke: the Stroke Prevention in Young Adults Study.

Science.gov (United States)

Trivedi, Megh M; Ryan, Kathleen A; Cole, John W

2015-10-29

Prior studies indicate that young African-Americans (AA) have a greater frequency of ischemic stroke than similarly aged European-Americans (EA). We hypothesized that differences in stroke subtype frequency mediated through sex and differing risk factor profiles may play a role in ethnicity-specific stroke. Utilizing our biracial young-onset stroke population, we explored these relationships. Fifty nine hospitals in the Baltimore-Washington area participated in a population-based study of young-onset stroke in men (218-AA, 291-EA) and women (219-AA, 222-EA) aged 16-49. Data on age, sex, ethnicity and stroke risk factors (hypertension (HTN) and smoking) were gathered through standardized interview. A pair of vascular neurologists adjudicated each case to determine TOAST subtype. Logistic regression analyses evaluating for differences in stroke risk factors by TOAST subtype were performed. Analyses controlling for age and sex demonstrated that AA were more likely to have a lacunar stroke than EA (OR = 1.61; 95% CI = 1.12-2.32; p = 0.011) when utilizing the other TOAST subtypes as the reference group. This effect was mediated by HTN, which increases the risk of lacunar stroke (OR = 2.03; 95% CI = 1.38-2.98; p = 0.0003) and large artery stroke (OR = 1.70; 95% CI = 1.01-2.88; p = 0.048) when controlling for sex, ethnicity, and age. Cases below age 40 were more likely to have a cardioembolic stroke than those above age 40 (OR = 1.62; 95% CI = 1.15-2.27; p = 0.006), controlling for sex and ethnicity. Lastly, current smokers were more likely to have a large artery stroke than non-smokers (OR = 1.79; 95% CI = 1.08-2.98; p = 0.024). Our population-based data demonstrate ethnic differences in ischemic stroke subtypes. These findings may help clarify mechanisms of stroke in young adults which may in part be driven by ethnic-specific differences in early-onset traditional risk factors, thereby indicating differing emphasis on workup and prevention.

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.

Autologous Bone Marrow Mononuclear Cells Intrathecal Transplantation in Chronic Stroke

Directory of Open Access Journals (Sweden)

Alok Sharma

2014-01-01

Full Text Available Cell therapy is being widely explored in the management of stroke and has demonstrated great potential. It has been shown to assist in the remodeling of the central nervous system by inducing neurorestorative effect through the process of angiogenesis, neurogenesis, and reduction of glial scar formation. In this study, the effect of intrathecal administration of autologous bone marrow mononuclear cells (BMMNCs is analyzed on the recovery process of patients with chronic stroke. 24 patients diagnosed with chronic stroke were administered cell therapy, followed by multidisciplinary neurorehabilitation. They were assessed on functional independence measure (FIM objectively, along with assessment of standing and walking balance, ambulation, and hand functions. Out of 24 patients, 12 improved in ambulation, 10 in hand functions, 6 in standing balance, and 9 in walking balance. Further factor analysis was done. Patients of the younger groups showed higher percentage of improvement in all the areas. Patients who underwent cell therapy within 2 years after the stroke showed better changes. Ischemic type of stroke had better recovery than the hemorrhagic stroke. This study demonstrates the potential of autologous BMMNCs intrathecal transplantation in improving the prognosis of functional recovery in chronic stage of stroke. Further clinical trials are recommended. This trial is registered with NCT02065778.

Enhanced performance CCD output amplifier

Science.gov (United States)

Dunham, Mark E.; Morley, David W.

1996-01-01

A low-noise FET amplifier is connected to amplify output charge from a che coupled device (CCD). The FET has its gate connected to the CCD in common source configuration for receiving the output charge signal from the CCD and output an intermediate signal at a drain of the FET. An intermediate amplifier is connected to the drain of the FET for receiving the intermediate signal and outputting a low-noise signal functionally related to the output charge signal from the CCD. The amplifier is preferably connected as a virtual ground to the FET drain. The inherent shunt capacitance of the FET is selected to be at least equal to the sum of the remaining capacitances.

GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats.

Science.gov (United States)

Wang, Wei; Li, Mingchang; Wang, Yuefei; Li, Qian; Deng, Gang; Wan, Jieru; Yang, Qingwu; Chen, Qianxue; Wang, Jian

2016-12-01

Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke who are treated with tissue plasminogen activator (tPA). It is associated with high morbidity and mortality, but no effective treatments are currently available to reduce HT risk. Therefore, methods to prevent HT are urgently needed. In this study, we used TWS119, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt/β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke and then were administered rtPA, rtPA combined with TWS119, or vehicle at 4 h. The animals were sacrificed 24 h after infarct induction. Rats treated with rtPA showed evident HT, had more severe neurologic deficit, brain edema, and blood-brain barrier breakdown, and had larger infarction volume than did the vehicle group. Rats treated with TWS119 had significantly improved outcomes compared with those of rats treated with rtPA alone. In addition, Western blot analysis showed that TWS119 increased the protein expression of β-catenin, claudin-3, and ZO-1 while suppressing the expression of GSK-3β. These results suggest that TWS119 reduces rtPA-induced HT and attenuates blood-brain barrier disruption, possibly through activation of the Wnt/β-catenin signaling pathway. This study provides a potential therapeutic strategy to prevent tPA-induced HT after acute ischemic stroke.

RECOMBINANT HUMAN MAST-CELL GROWTH-FACTOR SUPPORTS ERYTHROID COLONY FORMATION IN POLYCYTHEMIA-VERA IN THE PRESENCE AND ABSENCE OF ERYTHROPOIETIN AND SERUM

NARCIS (Netherlands)

MULLER, EW; DEWOLF, JTM; HENDRIKS, DW; ESSELINK, MT; HALIE, MR; VELLENGA, E

The effect of mast cell growth factor (MGF) was studied on erythropoietin (Epo)-dependent and Epo-independent (''spontaneous'') erythroid colony formation in patients with polycythemia vera (PV). MGF stimulated both Epo-dependent and Epo-independent erythroid colony formation from PV peripheral

Outcome Determinants of Stroke in a Brazilian Primary Stroke Center

Directory of Open Access Journals (Sweden)

Gustavo W. Kuster

2014-01-01

Full Text Available Background. Stroke mortality in Brazil is one of the highest among Western countries. Nonetheless, stroke outcome determinants are still poorly known in this country. In this study we evaluate outcome determinants of stroke in a primary stroke center in São Paulo, Brazil. Methods. We evaluated demographic, clinical, and outcome data of patients with ischemic stroke (IS, transient ischemic attack (TIA, and intracerebral hemorrhage (ICH admitted at “Hospital Paulistano,” São Paulo, Brazil. In-hospital mortality and functional outcome determinants were assessed. Univariate and binary logistic regression analysis were performed. Results. Three hundred forty-one patients were included in the study, 52.2% being male with 66.8±15.7 years. The stroke type distribution was IS: 59.2%, TIA: 29.6%, and ICH: 11.1%. ICH was associated with greater severity and poorer functional outcome. The determinants of poorer functional outcome were higher NIHSS, lower Glasgow score, and lower oxygen saturation level. The most important mortality determinant was the presence of visual symptoms. Conclusions. The stroke mortality and stroke outcome determinants found in the present study do not remarkably differ from studies carried out in developed countries. Stroke prognosis studies are crucial to better understand the high burden of stroke in Brazil.

Comparing unilateral and bilateral upper limb training: The ULTRA-stroke program design

Directory of Open Access Journals (Sweden)

Koppe Peter

2009-11-01

Full Text Available Abstract Background About 80% of all stroke survivors have an upper limb paresis immediately after stroke, only about a third of whom (30 to 40% regain some dexterity within six months following conventional treatment programs. Of late, however, two recently developed interventions - constraint-induced movement therapy (CIMT and bilateral arm training with rhythmic auditory cueing (BATRAC - have shown promising results in the treatment of upper limb paresis in chronic stroke patients. The ULTRA-stroke (acronym for Upper Limb TRaining After stroke program was conceived to assess the effectiveness of these interventions in subacute stroke patients and to examine how the observed changes in sensori-motor functioning relate to changes in stroke recovery mechanisms associated with peripheral stiffness, interlimb interactions, and cortical inter- and intrahemispheric networks. The present paper describes the design of this single-blinded randomized clinical trial (RCT, which has recently started and will take several years to complete. Methods/Design Sixty patients with a first ever stroke will be recruited. Patients will be stratified in terms of their remaining motor ability at the distal part of the arm (i.e., wrist and finger movements and randomized over three intervention groups receiving modified CIMT, modified BATRAC, or an equally intensive (i.e., dose-matched conventional treatment program for 6 weeks. Primary outcome variable is the score on the Action Research Arm test (ARAT, which will be assessed before, directly after, and 6 weeks after the intervention. During those test sessions all patients will also undergo measurements aimed at investigating the associated recovery mechanisms using haptic robots and magneto-encephalography (MEG. Discussion ULTRA-stroke is a 3-year translational research program which aims (1 to assess the relative effectiveness of the three interventions, on a group level but also as a function of patient

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.

Transmission characteristics of acoustic amplifier in thermoacoustic engine

International Nuclear Information System (INIS)

Sun Daming; Qiu Limin; Wang Bo; Xiao Yong

2008-01-01

Thermoacoustic engines are promising in practical applications for the merits of simple configuration, reliable operation and environmentally friendly working gas. An acoustic amplifier can increase the output pressure amplitude of a thermoacoustic engine (TE) and improve the matching between the engine and its load. In order to make full use of an acoustic amplifier, the transmission characteristics are studied based on linear thermoacoustic theory. Computational and experimental results show that the amplifying ability of an acoustic amplifier is mainly determined by its geometry parameters and output resistance impedance. The amplifying ability of an acoustic amplifier with appropriate length and diameter reaches its maximum when the output resistance impedance is infinite. It is also shown that the acoustic amplifier consumes an amount of acoustic power when amplifying pressure amplitude and the acoustic power consumption increases with amplifying ratio. Furthermore, a novel cascade acoustic amplifier is proposed, which has a much stronger amplifying ability with reduced acoustic power consumption. In experiments, a two-stage cascade acoustic amplifier amplifies the pressure ratio from 1.177 to 1.62 and produces a pressure amplitude of 0.547 MPa with nitrogen of 2.20 MPa as working gas. Good agreements are obtained between the theoretical analysis and experimental results. This research is instructive for comprehensively understanding the mechanism and making full use of the acoustic amplifier

Drug abuse, a rare cause of stroke: Case report

Directory of Open Access Journals (Sweden)

Zeynep Özözen Ayas

2017-04-01

Full Text Available At the present time the incidence of illicit drug use increases worldwide among young adults. Abuse of these substances is a rare cause of stroke in young adults. Cocaine, heroin, cannabis, and amphetamines use increase the risk of stroke. Cannabis sativa induce main effects by delta-9-hydrocannabinol. The main mechanism of marijuana-related stroke in young patients is vasospazm. The other possible mechanisms are systemic hypotension, impaired cerebral autoregulation, alteration of cerebral blood flow, cardioembolism due to atrial fibrillation. In this article a 25-year-old young male patient with paresia and paresthesia of right side who had chronic abuse of marijuana is reported. Clinicians must be alert about marijuana can be seriously harmful to cerebrovascular system in chronic use.

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.

Atherosclerosis and Stroke

Science.gov (United States)

... Stroke Association.org Professionals for Stroke Association.org Shop for Stroke Association.org Support for Stroke Association. ... endothelium significantly. The artery’s diameter shrinks and blood flow decreases, reducing oxygen supply. How atherosclerotic plaque causes ...

Hemorrhagic and Ischemic Strokes Compared Stroke Severity, Mortality, and Risk Factors

DEFF Research Database (Denmark)

Andersen, Klaus Kaae; Olsen, T. S.; Dehlendorff, Christian

2009-01-01

were diabetes, atrial fibrillation, previous myocardial infarction, previous stroke, and intermittent arterial claudication. Smoking and alcohol consumption favored HS, whereas age, sex, and hypertension did not herald stroke type. Compared with ischemic strokes, HS was associated with an overall...... higher mortality risk (HR, 1.564; 95% CI, 1.441-1.696). The increased risk was, however, time-dependent; initially, risk was 4-fold, after 1 week it was 2.5-fold, and after 3 weeks it was 1.5-fold. After 3 months stroke type did not correlate to mortality. Conclusion-Strokes are generally more severe...... based on 25 123 individuals with a complete data set. Results-Of the patients 3993 (10.1%) had HS. Stroke severity was almost linearly related to the probability of having HS (2% in patients with the mildest stroke and 30% in those with the most severe strokes). Factors favoring ischemic strokes vs HS...

Stroke etiology and collaterals: atheroembolic strokes have greater collateral recruitment than cardioembolic strokes.

Science.gov (United States)

Rebello, L C; Bouslama, M; Haussen, D C; Grossberg, J A; Dehkharghani, S; Anderson, A; Belagaje, S R; Bianchi, N A; Grigoryan, M; Frankel, M R; Nogueira, R G

2017-06-01

Chronic hypoperfusion from athero-stenotic lesions is thought to lead to better collateral recruitment compared to cardioembolic strokes. It was sought to compare collateral flow in stroke patients with atrial fibrillation (AF) versus stroke patients with cervical atherosclerotic steno-occlusive disease (CASOD). This was a retrospective review of a prospectively collected endovascular database. Patients with (i) anterior circulation large vessel occlusion stroke, (ii) pre-treatment computed tomography angiography (CTA) and (iii) intracranial embolism from AF or CASOD were included. CTA collateral patterns were evaluated and categorized into two groups: absent/poor collaterals (CTA collateral score 0-1) versus moderate/good collaterals (CTA collateral score 2-4). CT perfusion was also utilized for baseline core volume and evaluation of infarct growth. A total of 122 patients fitted the inclusion criteria, of whom 88 (72%) had AF and 34 (27%) CASOD. Patients with AF were older (P Collateral scores were lower in the AF group (P = 0.01) with patients having poor collaterals in 28% of cases versus 9% in the CASOD group (P = 0.03). Mortality rates (20% vs. 0%; P = 0.02) were higher in the AF patients whilst rates of any parenchymal hemorrhage (6% vs. 26%; P collaterals (odds ratio 4.70; 95% confidence interval 1.17-18.79; P = 0.03). Atheroembolic strokes seem to be associated with better collateral flow compared to cardioembolic strokes. This may in part explain the worse outcomes of AF-related stroke. © 2017 EAN.

Constraint-induced movement therapy in treatment of acute and sub-acute stroke: a meta-analysis of 16 randomized controlled trials

Directory of Open Access Journals (Sweden)

Xi-hua Liu

2017-01-01

Results: A total of 16 prospective randomized controlled trials (379 patients in the constraint-induced movement-therapy group and 359 in the control group met inclusion criteria. Analysis showed significant mean differences in favor of constraint-induced movement therapy for the Fugl–Meyer motor assessment of the arm (weighted mean difference (WMD = 10.822; 95% confidence intervals (95% CI: 7.419–14.226, the action research-arm test (WMD = 10.718; 95% CI: 5.704–15.733, the motor activity log for amount of use and quality of movement (WMD = 0.812; 95% CI: 0.331–1.293 and the modified Barthel index (WMD = 10.706; 95% CI: 4.417–16.966. Conclusion: Constraint-induced movement therapy may be more beneficial than traditional rehabilitation therapy for improving upper limb function after acute or sub-acute stroke.

Radioimmunoassay of erythropoietin and its potential in the diagnosis of fetal hypoxia

International Nuclear Information System (INIS)

Fingerova, H.

1993-01-01

Radioimmunoassay (RIA) for erythropoietin (EPO) in the serum and amniotic fluid was set up, based on donated rabbit antibody and a commercial tracer. EPO levels obtained by means of the RIA correlated well with the results obtained by means of ELISA or a commercial RIA kit. Retrospective evaluations of EPO levels in umbilical cord serum and amniotic fluid samples obtained during 171 vaginal or Cesarean section deliveries have shown that already in the course of spontaneous vaginal delivery a moderate increase of EPO in umbilical cord serum can be detected. The marked increase of EPO levels in both cord serum and amniotic fluid was always observed in relation to a severe fetal distress. (author) 3 figs., 3 refs

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...... was studied in subjects (n = 8) who received long-term Epo administration, and muscle biopsies were obtained before and after. Epo treatment did not alter mean fiber area (0.84 +/- 0.2 vs. 0.72 +/- 0.3 mm(2)), capillaries per fiber (4.3 +/- 0.5 vs. 4.4 +/- 1.3), or number of proliferating endothelial cells...

Fundamentos del uso clínico de la eritropoyetina como neuroprotector Foundations of the clinical use of erythropoietin as a neuroprotective agent

Directory of Open Access Journals (Sweden)

Alain Valdivia Acosta

2008-08-01

Full Text Available Hace aproximadamente una década, se reportaron por primera vez, las propiedades neuroprotectoras de la eritropoyetina en estudios preclínicos. Todavía no se ha podido esclarecer con firmeza el posible mecanismo de acción neuroprotector de esta hormona, pero existen varias hipótesis. La eritropoyetina ha mostrado buenos resultados en preclínica como agente neuroprotector y todavía queda mucho camino por recorrer para lograr una adecuada efectividad y seguridad en la clínica en este sentido. Se investiga para lograr una eritropoyetina con actividad neuroprotectora que carezca, o al menos tenga disminuida su actividad hematopoyética. Disminuir sus efectos adversos, lograr una significativa biodisponibilidad al sistema nervioso central, alargar el tiempo de vida media y con ello evitar una alta frecuencia de administración al paciente, es lo que principalmente se está buscando. En este trabajo se realizó una búsqueda sobre los mecanismos de acción neuroprotectora hasta ahora propuestos para la eritropoyetina y se detallaron importantes consideraciones a tomar en cuenta, que pudieran influir sobre su utilización en la clínica.The neuroprotective properties of erythropoietin were reported for the first time in preclinical studies approximately a decade ago. The possible mechanism of neuroprotective action of this hormone has not been cleared yet, but here are diverse hypotheses. Erythropoietin has showed good results in preclinic as a neuroprotective agent and there is still a long way to go to attain an adequate effectivity and safety in the clinic in this sense. Research is being carried out to obtain an erythropoietin with neuroprotective activity that lacks or at least has a diminished hematopoietic activity. To reduce its adverse effects, to achieve a significant bioavailability to the central nervous system, to prolong its mean life and to avoid this way a high frequency of administration to the patient, is our main objective. In

Poly(norepinephrine)-coated open tubular column for the separation of proteins and recombination human erythropoietin by capillary electrochromatography.

Science.gov (United States)

Xiao, Xue; Zhang, Yamin; Wu, Jia; Jia, Li

2017-12-01

Recombinant human erythropoietin is an important therapeutic protein with high economic interest due to the benefits provided by its clinical use for the treatment of anemias associated with chronic renal failure and chemotherapy. In this work, a poly(norepinephrine)-coated open tubular column was successfully prepared based on the self-polymerization of norepinephrine under mild alkaline condition, the favorable film forming and easy adhesive properties of poly(norepinephrine). The poly(norepinephrine) coating was characterized by scanning electron microscopy and measurement of the electro-osmotic flow. The thickness of the coating was about 431 nm. The electrochromatographic performance of the poly(norepinephrine)-coated open tubular column was evaluated by separation of proteins. Some basic and acidic proteins including two variants of bovine serum albumin and two variants of β-lactoglobulin achieved separation in the poly(norepinephrine)-coated open tubular column. More importantly, the column demonstrated separation ability for the glycoforms of recombinant human erythropoietin. In addition, the column demonstrated good repeatability with the run-to-run, day-to-day, and column-to-column relative standard deviations of migration times of proteins less than 3.40%. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Erythropoietin Receptor Positive Circulating Progenitor Cells and Endothelial Progenitor Cells in Patients with Different Stages of Diabetic Retinopathy

Institute of Scientific and Technical Information of China (English)

Liu-mei Hu; Guo-xu Xu; Guo-tong XU; Wei-ye Li; Xia Lei; Bo Ma; Yu Zhang; Yan Yan; Ya-lan Wu; Ge-zhi Xu; Wen Ye; Ling Wang

2011-01-01

Objective To investigate the possible involvement of erythropoietin (EPO)/erythropoietin receptor(EPOR) system in neovascularization and vascular regeneration in diabetic retinopathy (DR).Methods EPOR positive circulating progenitor cells (CPCs: CD34+) and endothelial progenitor cells (EPCs: CD34+KDR+) were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes (n=7), non-prolif-erative DR (NPDR, n=7), proliferative DR (PDR, n=8), and PDR complicated with diabetic nephropathy (PDR-DN, n=7). Results The numbers of EPOR+ CPCs and EPOR+ EPCs were reduced remarkably in NPDR compared with the control group (both P<0.01), whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR+ CPCs in CPCs (NPDR vs.control, P< 0.01) and that of EPOR+ EPCs in EPCs (NPDR vs. control, P< 0.05). Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the im-paired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR+ EPCs associated with ischemia.

Stroke treatment outcomes in hospitals with and without Stroke Units.

Science.gov (United States)

Masjuan, J; Gállego Culleré, J; Ignacio García, E; Mira Solves, J J; Ollero Ortiz, A; Vidal de Francisco, D; López-Mesonero, L; Bestué, M; Albertí, O; Acebrón, F; Navarro Soler, I M

2017-10-23

Organisational capacity in terms of resources and care circuits to shorten response times in new stroke cases is key to obtaining positive outcomes. This study compares therapeutic approaches and treatment outcomes between traditional care centres (with stroke teams and no stroke unit) and centres with stroke units. We conducted a prospective, quasi-experimental study (without randomisation of the units analysed) to draw comparisons between 2 centres with stroke units and 4 centres providing traditional care through the neurology department, analysing a selection of agreed indicators for monitoring quality of stroke care. A total of 225 patients participated in the study. In addition, self-administered questionnaires were used to collect patients' evaluations of the service and healthcare received. Centres with stroke units showed shorter response times after symptom onset, both in the time taken to arrive at the centre and in the time elapsed from patient's arrival at the hospital to diagnostic imaging. Hospitals with stroke units had greater capacity to respond through the application of intravenous thrombolysis than centres delivering traditional neurological care. Centres with stroke units showed a better fit to the reference standards for stroke response time, as calculated in the Quick study, than centres providing traditional care through the neurology department. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Stroke: advances in medical therapy and acute stroke intervention.

Science.gov (United States)

Barrett, Kevin M; Lal, Brajesh K; Meschia, James F

2015-10-01

Evidence-based therapeutic options for stroke continue to emerge based on results from well-designed clinical studies. Ischemic stroke far exceeds hemorrhagic stroke in terms of prevalence and incidence, both in the USA and worldwide. The public health effect of reducing death and disability related to ischemic stroke justifies the resources that have been invested in identifying safe and effective treatments. The emergence of novel oral anticoagulants for ischemic stroke prevention in atrial fibrillation has introduced complexity to clinical decision making for patients with this common cardiac arrhythmia. Some accepted ischemic stroke preventative strategies, such as carotid revascularization for asymptomatic carotid stenosis, require reassessment, given advances in risk factor management, antithrombotic therapy, and surgical techniques. Intra-arterial therapy, particularly with stent retrievers after intravenous tissue plasminogen activator, has recently been demonstrated to improve functional outcomes and will require investment in system-based care models to ensure that effective treatments are received by patients in a timely fashion. The purpose of this review is to describe recent advances in medical and surgical approaches to ischemic stroke prevention and acute treatment. Results from recently published clinical trials will be highlighted along with ongoing clinical trials addressing key questions in ischemic stroke management and prevention where equipoise remains.

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

Science.gov (United States)

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

2004-09-01

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

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

Science.gov (United States)

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

2011-08-01

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

Sensorimotor control of tracking movements at various speeds for stroke patients as well as age-matched and young healthy subjects.

Directory of Open Access Journals (Sweden)

Di Ao

Full Text Available There are aging- and stroke-induced changes on sensorimotor control in daily activities, but their mechanisms have not been well investigated. This study explored speed-, aging-, and stroke-induced changes on sensorimotor control. Eleven stroke patients (affected sides and unaffected sides and 20 control subjects (10 young and 10 age-matched individuals were enrolled to perform elbow tracking tasks using sinusoidal trajectories, which included 6 target speeds (15.7, 31.4, 47.1, 62.8, 78.5, and 94.2 deg/s. The actual elbow angle was recorded and displayed on a screen as visual feedback, and three indicators, the root mean square error (RMSE, normalized integrated jerk (NIJ and integral of the power spectrum density of normalized speed (IPNS, were used to investigate the strategy of sensorimotor control. Both NIJ and IPNS had significant differences among the four groups (P<0.01, and the values were ranked in the following order: young controls < age-matched controls stroke patients stroke patients, which could be explained by the stroke- and aging-induced increase in reliance on feedback control. The RMSE increased with the increase in the target speed and the NIJ and IPNS initially declined and then remained steady for all four groups, which indicated a shift from feedback to feedforward control as the target speed increased. The feedback-feedforward trade-off induced by stroke, aging and speed might be explained by a change in the transmission delay and neuromotor noise. The findings in this study improve our understanding of the mechanism underlying the sensorimotor control and neurological changes caused by stroke and aging.

Potential of Stem Cell-Based Therapy for Ischemic Stroke

Directory of Open Access Journals (Sweden)

Hany E. Marei

2018-02-01

Full Text Available Ischemic stroke is one of the major health problems worldwide. The only FDA approved anti-thrombotic drug for acute ischemic stroke is the tissue plasminogen activator. Several studies have been devoted to assessing the therapeutic potential of different types of stem cells such as neural stem cells (NSCs, mesenchymal stem cells, embryonic stem cells, and human induced pluripotent stem cell-derived NSCs as treatments for ischemic stroke. The results of these studies are intriguing but many of them have presented conflicting results. Additionally, the mechanism(s by which engrafted stem/progenitor cells exert their actions are to a large extent unknown. In this review, we will provide a synopsis of different preclinical and clinical studies related to the use of stem cell-based stroke therapy, and explore possible beneficial/detrimental outcomes associated with the use of different types of stem cells. Due to limited/short time window implemented in most of the recorded clinical trials about the use of stem cells as potential therapeutic intervention for stroke, further clinical trials evaluating the efficacy of the intervention in a longer time window after cellular engraftments are still needed.

Comparison of the Protective Effects of Erythropoietin and Melatonin on Renal Ischemia-Reperfusion Injury.

Science.gov (United States)

Banaei, Shokofeh; Ahmadiasl, Nasser; Alihemmati, Alireza

2016-07-01

Renal ischemia-reperfusion (IR) contributes to the development of acute renal failure (ARF). Oxygen free radicals are considered to be the principal components involved in the pathophysiological tissue alterations observed during renal IR. In this study, we compared the effects of melatonin (MEL) and erythropoietin (EPO), both known antioxidant and anti-inflammatory agents, on IR-induced renal injury in rats. Wistar albino rats were unilaterally nephrectomized and then subjected to 45 minutes of renal pedicle occlusion followed by 24 hours of reperfusion. MEL (10 mg/kg, i.p) and EPO (5000 U/kg, i.p) were administered prior to the onset of ischemia. After 24 hours of reperfusion and following decapitation, blood samples were collected for the determination of the hemoglobin (Hb) and hematocrit (Hct) levels. Additionally, renal samples were taken for histological evaluation. Ischemia-reperfusion significantly decreased the observed Hb and Hct values. The histopathological findings in the IR group confirmed that there was an increase in the hyaline cast and thickening of the Bowman capsule basement membrane. Treatment with EPO or MEL significantly increased the Hb and Hct values. In the MEL + IR group, the histopathological changes were lower than those found in the EPO + IR group. Treatment with EPO and MEL had a beneficial effect on renal IR injury. The results may also indicate that MEL protects against morphological damage better than EPO in renal IR injury.

Stroking and tapping the skin: behavioral and electrodermal effects.

Science.gov (United States)

Etzi, Roberta; Carta, Carlotta; Gallace, Alberto

2018-02-01

Being caressed represents one of the most typical expressions of affection conveyed by touch. Converging evidence suggests that the pleasant perception of gentle and slow stroking delivered to the hairy skin is mediated by C-Tactile afferents (CTs). While behavioral and neural responses to CT-optimal touch have been moderately explored so far, less is known about the autonomic reaction to different kinds of touch (both CT-optimal and not). Here, we investigated whether physiological arousal varies as a function of the specific tactile stimulation provided. Stroking (slow: 3 cm/s 'CT-optimal'; or fast: 30 cm/s) and tapping (random or fixed spatial order) stimulations were delivered to the participants' forearm with a brush, for durations of 9 or 60 s. Participants' skin conductance response (SCR) and level (SCL), as well as subjective evaluations, were recorded. The results revealed that being stroked (at both the velocities) induced higher SCR and SCL than being tapped. Moreover, while higher SCR was elicited by CT-suboptimal stroking compared to CT-optimal stroking, SCL was not affected differently by CT-optimal touch. No differences were found between the effects of 9 and 60 s stimulations. Slow stroking was evaluated as the most pleasant, relaxing and 'social' type of touch compared to the other tactile stimulations. Taken together, these findings shed light on the psychophysiological responses to stroking (including CT-optimal touch) and tapping, and contribute to elucidate the mechanisms underlying hedonic tactile perception.

Impact of early applied upper limb stimulation: The EXPLICIT-stroke programme design

Directory of Open Access Journals (Sweden)

Lindeman Eline

2008-12-01

Full Text Available Abstract Background Main claims of the literature are that functional recovery of the paretic upper limb is mainly defined within the first month post stroke and that rehabilitation services should preferably be applied intensively and in a task-oriented way within this particular time window. EXplaining PLastICITy after stroke (acronym EXPLICIT-stroke aims to explore the underlying mechanisms of post stroke upper limb recovery. Two randomized single blinded trials form the core of the programme, investigating the effects of early modified Constraint-Induced Movement Therapy (modified CIMT and EMG-triggered Neuro-Muscular Stimulation (EMG-NMS in patients with respectively a favourable or poor probability for recovery of dexterity. Methods/design 180 participants suffering from an acute, first-ever ischemic stroke will be recruited. Functional prognosis at the end of the first week post stroke is used to stratify patient into a poor prognosis group for upper limb recovery (N = 120, A2 project and a group with a favourable prognosis (N = 60, A1 project. Both groups will be randomized to an experimental arm receiving respectively modified CIMT (favourable prognosis or EMG-NMS (poor prognosis for 3 weeks or to a control arm receiving usual care. Primary outcome variable will be the Action Research Arm Test (ARAT, assessed at 1,2,3,4,5, 8, 12 and 26 weeks post stroke. To study the impact of modified CIMT or EMG-NMS on stroke recovery mechanisms i.e. neuroplasticity, compensatory movements and upper limb neuromechanics, 60 patients randomly selected from projects A1 and A2 will undergo TMS, kinematical and haptic robotic measurements within a repeated measurement design. Additionally, 30 patients from the A1 project will undergo fMRI at baseline, 5 and 26 weeks post stroke. Conclusion EXPLICIT stroke is a 5 year translational research programme which main aim is to investigate the effects of early applied intensive intervention for regaining dexterity

Final amplifier design and mercury

International Nuclear Information System (INIS)

Rose, E.A.; Hanson, D.E.

1991-01-01

The final amplifier for the Mercury KrF excimer facility is being designed. The design exercise involves extensive modeling to predict amplifier performance. Models of the pulsed-power system, including a Child-Langmuir diode with closure, electron-beam energy deposition, KrF laser kinetics, amplified spontaneous emission (ASE), a time-dependent laser extraction in the presence of ASE are presented as a design package. The design exercise indicates that the energy objective of Phase I -- 100 joules -- will be met

A pulse amplifier for nuclear instrumentation

International Nuclear Information System (INIS)

Martin, D.; Cliff, P.

1987-01-01

A Class-A 1 Watt amplifier has been designed and optimized for nanosecond pulses. Spanning .01MHz to 1300Mhz, signal gain is 26dB with gain flatness of 1dB. The amplifier drive +- 10 volts across 500 with 350ps risetime. Each amplifier is housed in a 2-wide NIM

Erythropoietin as an add-on treatment for cognitive side effects of electroconvulsive therapy

DEFF Research Database (Denmark)

Schmidt, Lejla Sjanic; Petersen, Jeff Zarp; Vinberg, Maj

2018-01-01

trial investigates (1) whether short-term add-on treatment with erythropoietin (EPO) can reduce the cognitive side -effects of ECT and (2) whether such effects are long-lasting. Further, structural and functional magnetic resonance imaging (MRI) will be used to explore the neural underpinnings...... cognitive benefits of EPO are investigated with structural and functional MRI after the final EPO/saline infusion. The primary outcome is change from baseline to after EPO treatment (3 days after eight ECT sessions) in a cognitive composite score spanning attention, psychomotor speed, and executive...... of covariance. Functional MRI data will be preprocessed and analyzed using the FMRIB Software Library....

Vitamin D2 Supplementation Amplifies Eccentric Exercise-Induced Muscle Damage in NASCAR Pit Crew Athletes

Directory of Open Access Journals (Sweden)

David C. Nieman

2013-12-01

Full Text Available This study determined if 6-weeks vitamin D2 supplementation (vitD2, 3800 IU/day had an influence on muscle function, eccentric exercise-induced muscle damage (EIMD, and delayed onset of muscle soreness (DOMS in National Association for Stock Car Auto Racing (NASCAR NASCAR pit crew athletes. Subjects were randomized to vitD2 (n = 13 and placebo (n = 15, and ingested supplements (double-blind for six weeks. Blood samples were collected and muscle function tests conducted pre- and post-study (leg-back and hand grip dynamometer strength tests, body weight bench press to exhaustion, vertical jump, 30-s Wingate test. Post-study, subjects engaged in 90 min eccentric-based exercise, with blood samples and DOMS ratings obtained immediately after and 1- and 2-days post-exercise. Six weeks vitD2 increased serum 25(OHD2 456% and decreased 25(OHD3 21% versus placebo (p < 0.001, p = 0.036, respectively, with no influence on muscle function test scores. The post-study eccentric exercise bout induced EIMD and DOMS, with higher muscle damage biomarkers measured in vitD2 compared to placebo (myoglobin 252%, 122% increase, respectively, p = 0.001; creatine phosphokinase 24 h post-exercise, 169%, 32%, p < 0.001, with no differences for DOMS. In summary, 6-weeks vitD2 (3800 IU/day significantly increased 25(OHD2 and decreased 25(OHD3, had no effect on muscle function tests, and amplified muscle damage markers in NASCAR pit crew athletes following eccentric exercise.

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...

Fast logarithmic amplifier

International Nuclear Information System (INIS)

Tai, I.; Hasegawa, K.

1975-01-01

This paper reports on the improvement of frequency characteristics of a logarithmic amplifier with a Paterson transdiode connection. The improvement of the response speed has been achieved by using a phase compensation technique. Small signal response analyses of the logging circuit revealed the effects of a series resistor Rsub(p) and a parallel capacitance Csub(p) on the response of the circuit. The improvement of the frequency characteristics are remarkable at higher current levels. These facts were proved by the practical logarithmic amplifier. (auth.)

Increase of Meningitis Risk in Stroke Patients in Taiwan

Directory of Open Access Journals (Sweden)

Chie-Hong Wang

2018-03-01

Full Text Available Background and purposeThe blood–brain barrier (BBB not only provides a physical obstruction but also recruits and activates neutrophils in cases of infection. Hemorrhagic or ischemic stroke reportedly induces the disruption of the BBB. However, few studies have reported a correlation between the incidence of meningitis in patients with a history of stroke. This study tested the hypothesis that patients with a history of stroke may be more vulnerable to meningitis.MethodsStroke and age-matched comparison (n = 29,436 and 87,951, respectively cohorts were recruited from the Taiwan National Health Insurance database (2000–2011. Correlations between the two cohorts were evaluated by Cox proportional hazard regression model, Kaplan–Meier curve, and log-rank tests.ResultsThe incidence of meningitis was higher in the stroke cohort compared to that in the comparison cohort [hazard ratio (HR, 2.89; 95% confidence interval (CI, 2.23–3.74, p < 0.001]. After adjusting for age, sex, and comorbidities, the estimated HR in the stroke cohort was 2.55-fold higher than that in the comparison cohort (CI, 1.94–3.37; p < 0.001. Notably, patients who had experienced hemorrhagic stroke had a higher incidence rate of meningitis than those with a history of ischemic stroke, except for patients older than 75 years (incidence rates in hemorrhagic/ischemic stroke patients, 3.14/1.48 in patients younger than 45 years, 1.52/0.41 in 45- to 64-year group, 1.15/0.90 in 65- to 74-year group, 0.74/0.93 in patients older than 75 years. Moreover, stroke patients who had undergone head surgery had the highest meningitis risk (adjusted HR, 8.66; 95% CI, 5.55–13.5; p < 0.001 followed by stroke patients who had not undergone head surgery (adjusted HR, 2.11; 95% CI, 1.57–2.82; p < 0.001.ConclusionOur results indicated that stroke patients have higher risks of meningitis. Compromised BBB integrity in stroke patients may lead to increased

Cerebral and extracerebral vasoreactivity in symptomatic lacunar stroke patients: a case-control study.

Science.gov (United States)

Deplanque, Dominique; Lavallee, Philippa C; Labreuche, Julien; Gongora-Rivera, Fernando; Jaramillo, Arturo; Brenner, David; Abboud, Halim; Klein, Isabelle F; Touboul, Pierre-Jean; Vicaut, Eric; Amarenco, Pierre

2013-08-01

Whether cerebral artery endothelial dysfunction is a key factor of symptomatic lacunar stroke and cerebral small vessel disease remains unclear. Cerebral and extracerebral vasoreactivity were measured in 81 patients with recent symptomatic lacunar stroke and in 81 control subjects matched for main vascular risk factors. Cerebral vasoreactivity and carotid endothelial-dependent vasodilation were measured after five-minutes of carbon dioxide-induced hypercapnia. Brachial endothelial-dependent vasodilation was assessed after hyperemia induced by deflating a cuff around the forearm previously inflated to 200 mmHg for four-minutes. Carotid and brachial endothelial-independent vasodilation were measured five-minutes after administration of sublingual nitroglycerin 300 μg. Brain magnetic resonance imaging were analyzed in lacunar stroke patients. One-month after stroke onset, patients had more severely impaired cerebral vasoreactivitys than matched controls (mean ± standard deviation, 14·4 ± 12·1% vs. 19·4 ± 17·4%; P = 0·049). Severe alterations of both carotid and brachial endothelial-dependent and at a lesser degree of carotid and brachial endothelial-independent vasodilation were observed in both groups. After adjustment for confounders, subjects with a cerebral vasoreactivity value in the two lower tertiles (≤19·6%) were more likely to have had a symptomatic lacunar stroke (adjusted odds ratio, 3·78; 95% confidence interval, 1·42 to 10·08; P = 0·008). Only alteration of brachial endothelial-independent vasodilation correlated with parenchymal abnormalities, namely microbleeds and leukoaraiosis. While abnormalities in extracerebral vasoreactivity seem related to vascular risk factors, the severity of endothelial dysfunction in cerebral arteries may be determinant in the occurrence of symptomatic lacunar stroke in patients with small vessel disease. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke

Acute stroke unit improves stroke management-four years on from INASC.

Science.gov (United States)

Shanahan, E; Keenan, R; Cunningham, N; O'Malley, G; O'Connor, M; Lyons, D; Peters, C

2015-02-01

The Irish Heart Foundation carried out the Irish National Audit of Stroke Care (INASC) in 2008. Management practices were significantly poorer than those in the UK Sentinel audits. Since then an acute stroke unit has been established in University Hospital Limerick. A stroke database was established. 12 key indicators of stroke management audited by INASC were identified. Results were compared to those in INASC. 89 stroke patients were admitted. 8 of the 12 key indicators scored significantly better than in INASC. 92.5% had a brain scan within 24hrs (INASC-40%, p = strokes received anti-thrombotics (INASC-85%, p = 0.001). 94% had rehab goals agreed by MDT (22% in INASC p = 0.0000). 55% were treated in stroke unit (2% in INASC, p = 0.0000). MDT input improved with regard to physiotherapy (87% vs 43% in INASC, p = Stroke management has significantly improved from 2008, however some deficiencies remain.

Flashlamp excited fluid laser amplified

International Nuclear Information System (INIS)

1976-01-01

The patent describes a laser amplifier with chambers for containing and amplifying an intensifier medium. It serves the need for a large impulse repetition rate and high intensities as required e.g. for laser isotope separation

Design considerations for RF power amplifiers demonstrated through a GSM/EDGE power amplifier module

NARCIS (Netherlands)

Baltus, P.G.M.; Bezooijen, van A.; Huijsing, J.H.; Steyaert, M.; Roermund, van A.H.M.

2002-01-01

This paper describes the design considerations for RF power amplifiers in general, including trends in systems, linearity and efficiency, the PA environment, implementation is sues and technology. As an example a triple-band (900/1800/1900MHz) dual mode (GSMIEdge) power amplifier module is described

Effects of a Single Dose of Erythropoietin on Motor Function and Cognition after Focal Brain Ischemia in Adult Rats

Directory of Open Access Journals (Sweden)

Michaela Hralová

2014-01-01

Full Text Available We tested the influence of erythropoietin (EPO, a basic cytokine in erythropoiesis regulation, on the process of motor function and cognition after focal brain ischemia induced by a local application of endothelin. Endothelin-1 (ET-1 induced short lasting strong vasoconstriction, with described impact on the structure and on the function of neuronal cells. Neurological description of motor function and Morris water maze test (the swimming test is one of most widely used methods for studying cognitive functions in rodents were used to study the process of learning and memory in three-month-old male albino Wistar rats (n=52. Both tests were performed one week before, and three weeks after ischemia induction (endothelin application on the cortex in the area of a. cerebri media dx.. Experimental group received i.p. injection of EPO (5,000 IU/kg body weight, 10 min before endothelin application. Control group of animals received one i.p. injection of saline at the dose of 1 ml/kg body weight at the same time. Only sham surgery was performed in the third group of animals. Rats with EPO pretreatment before the experimental lesion exhibited significantly better motor and cognitive function then those with saline injection. No significant changes in the motor and cognitive function were found in the third group of rats (sham operated controls.

Innate Immunity and Inflammation Post-Stroke: An α7-Nicotinic Agonist Perspective

Directory of Open Access Journals (Sweden)

Silke Neumann

2015-12-01

Full Text Available Stroke is one of the leading causes of death and long-term disability, with limited treatment options available. Inflammation contributes to damage tissue in the central nervous system across a broad range of neuropathologies, including Alzheimer’s disease, pain, Schizophrenia, and stroke. While the immune system plays an important role in contributing to brain damage produced by ischemia, the damaged brain, in turn, can exert a powerful immune-suppressive effect that promotes infections and threatens the survival of stroke patients. Recently the cholinergic anti-inflammatory pathway, in particular its modulation using α7-nicotinic acetylcholine receptor (α7-nAChR ligands, has shown potential as a strategy to dampen the inflammatory response and facilitate functional recovery in stroke patients. Here we discuss the current literature on stroke-induced inflammation and the effects of α7-nAChR modulators on innate immune cells.

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.

Is erythropoietin gene a modifier factor in amyotrophic lateral sclerosis?

Science.gov (United States)

Ghezzi, Serena; Del Bo, Roberto; Scarlato, Marina; Nardini, Martina; Carlesi, Cecilia; Prelle, Alessandro; Corti, Stefania; Mancuso, Michelangelo; Briani, Chiara; Siciliano, Gabriele; Murri, Luigi; Bresolin, Nereo; Comi, Giacomo Pietro

2009-05-01

To investigate the role of erythropoietin (EPO) as genetic determinant in the susceptibility to sporadic amyotrophic lateral sclerosis (SALS). We sequenced a 259-bp region spanning the 3'hypoxia-responsive element of the EPO gene in 222 Italian SALS patients and 204 healthy subjects, matched for age and ethnic origin. No potentially causative variation was detected in SALS subjects; in addition, two polymorphic variants (namely C3434T and G3544T) showed the same genotype and haplotype frequencies in patients and controls. Conversely, a weak but significant association between G3544T and age of disease onset was observed (p=0.04). Overall, our data argue against the hypothesis of EPO as a genetic risk factor for motor neuron dysfunction, at least in Italian population. However, further studies on larger cohort of patients are needed to confirm the evidence of EPO gene as modifier factor.

Analysis of DNA methylation of maize in response to osmotic and salt stress based on methylation-sensitive amplified polymorphism.

Science.gov (United States)

Tan, Ming-pu

2010-01-01

Water stress is known to alter cytosine methylation, which generally represses transcription. However, little is known about the role of methylation alteration in maize under osmotic stress. Here, methylation-sensitive amplified polymorphism (MSAP) was used to screen PEG- or NaCl-induced methylation alteration in maize seedlings. The sequences of 25 differentially amplified fragments relevant to stress were successfully obtained. Two stress-specific fragments from leaves, LP166 and LPS911, shown to be homologous to retrotransposon Gag-Pol protein genes, suggested that osmotic stress-induced methylation of retrotransposons. Three MSAP fragments, representing drought-induced or salt-induced methylation in leaves, were homologous to a maize aluminum-induced transporter. Besides these, heat shock protein HSP82, Poly [ADP-ribose] polymerase 2, Lipoxygenase, casein kinase (CK2), and dehydration-responsive element-binding (DREB) factor were also homologs of MSAP sequences from salt-treated roots. One MSAP fragment amplified from salt-treated roots, designated RS39, was homologous to the first intron of maize protein phosphatase 2C (zmPP2C), whereas - LS103, absent from salt-treated leaves, was homologous to maize glutathione S-transferases (zmGST). Expression analysis showed that salt-induced intron methylation of root zmPP2C significantly downregulated its expression, while salt-induced demethylation of leaf zmGST weakly upregulated its expression. The results suggested that salinity-induced methylation downregulated zmPP2C expression, a negative regulator of the stress response, while salinity-induced demethylation upregulated zmGST expression, a positive effecter of the stress response. Altered methylation, in response to stress, might also be involved in stress acclimation. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Measuring of vertical stroke Vub vertical stroke in the forthcoming decade

International Nuclear Information System (INIS)

Kim, C.S.

1997-01-01

I first introduce the importance of measuring V ub precisely. Then, from a theoretician's point of view, I review (a) past history, (b) present trials, and (c) possible future alternatives on measuring vertical stroke V ub vertical stroke and/or vertical stroke V ub /V cb vertical stroke. As of my main topic, I introduce a model-independent method, which predicts Γ(B→X u lν)/Γ(B→X c lν)≡(γ u /γ c ) x vertical stroke V ub /V cb vertical stroke 2 ≅(1.83±0.28) x vertical stroke V ub /V cb vertical stroke 2 and vertical stroke V ub /V cb vertical stroke ≡(γ c /γ u ) 1/2 x [B(B→X u lν)/B(B→ X c lν]) 1/2 ≅(0.74±0.06) x [B(B→X u lν/)B(B→X c lν)] 1/2 , based on the heavy quark effective theory I also explore the possible experimental options to separate B→X u lν from the dominant B→X c lν: the measurement of inclusive hadronic invariant mass distributions, and the 'D-π' (and 'K-π') separation conditions I also clarify the relevant experimental backgrounds. (orig.)

Stroke

Science.gov (United States)

... doctor Preventing falls Stroke - discharge Swallowing problems Images Brain Carotid stenosis, x-ray of the left artery Carotid stenosis, x-ray of the right artery Stroke Brainstem function Cerebellum - function Circle of Willis Left cerebral hemisphere - ...

Stroke prevention in atrial fibrillation: findings from Tuscan FADOI Stroke Registry

Directory of Open Access Journals (Sweden)

Luca Masotti

2014-06-01

Full Text Available Despite vitamin K antagonists (VKAs are considered the first choice treatment for stroke prevention in atrial fibrillation (AF, literature shows their underuse in this context. Since data about VKAs use prior and after acute stroke lack, the aim of this study was to focus on management of anticoagulation with VKAs in this context. Data were retrieved from Tuscan FADOI Stroke Registry, an online data bank aimed to report on characteristics of stroke patients consecutively admitted in Internal Medicine wards in 2010 and 2011. In this period 819 patients with mean age 76.5±12.3 years were enrolled. Data on etiology were available for 715 of them (88.1%, 87% being ischemic and 13% hemorrhagic strokes. AF was present in 238 patients (33%, 165 (69.3% having a known AF before hospitalization, whereas 73 patients (31.7% received a new diagnosis of AF. A percentage of 89% of strokes in patients with known AF were ischemic and 11% hemorrhagic. A percentage of 86.7% of patients with known AF had a CHADS2 ≥2, but only 28.3% were on VKAs before hospitalization. A percentage of 78.8% of patients treated with VKAs before stroke had an international normalized ratio (INR ≤2.0; 68.7% of patients with VKAs-related hemorrhagic strokes had INR ≤3.0. Combined endpoint mortality or severe disability in patients with ischemic stroke associated with AF was present in 47%, while it was present in 19.30% and 19.20% of atherothrombotic and lacunar strokes, respectively. At hospital discharge, VKAs were prescribed in 25.9% of AF related ischemic stroke patients. AF related strokes are burdened by severe outcome but VKAs are dramatically underused in patients with AF, even in higher risk patients. Efforts to improve anticoagulation in this stroke subtype are warranted.

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...... subjects. After an injection in the evening, urine and plasma samples were collected the following morning. Half of the subjects then drank a bolus of water and new samples were collected 80 min later. Interestingly, rhEPO was detected in 100% of the samples even after water ingestion. A second similar...

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...

S-band low noise amplifier and 40 kW high power amplifier subsystems of Japanese Deep Space Earth Station