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...

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

DEFF Research Database (Denmark)

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

2010-01-01

they are involved in tissue protection. However, the use of erythropoietin as a neuroprotective agent may be hampered by its erythropoietic activity. Therefore, developing non-haematopoietic erythropoietin mimetics is important. Based on the crystal structure of the complex of erythropoietin and its receptor, we...... attenuated seizures, decreased mortality and reduced neurodegeneration in an in vivo model of kainic acid-induced neurotoxicity. In contrast to erythropoietin, Epotris did not stimulate erythropoiesis upon chronic administration. Thus, Epotris is a novel neuroprotective non-haematopoietic erythropoietin...

Fetal plasma erythropoietin concentration in severe growth retardation.

Science.gov (United States)

Snijders, R J; Abbas, A; Melby, O; Ireland, R M; Nicolaides, K H

1993-02-01

The aim of this study was to determine whether hypoxemia induces an increase in plasma erythropoietin concentration in human fetal life and, if so, whether this response stimulates fetal erythropoiesis. The plasma erythropoietin concentration in blood samples from 33 small-for-gestational-age fetuses at 26 to 38 weeks' gestation was measured. Measurements were compared with the reference range for gestation, and associations with PO2, pH, and erythroblast and erythrocyte counts were examined. The mean plasma erythropoietin concentration in the small-for-gestational-age fetuses was significantly increased, and the degree of increase was significantly associated both with fetal acidemia and, more strongly, with fetal erythroblastosis. Erythropoietin production in response to tissue hypoxia occurs from at least 26 weeks' gestation with measurable physiologic effects on erythropoiesis. Furthermore, more accurate assessment of tissue oxygenation may be obtained by measuring the erythroblast count rather than the blood pH.

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

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

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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.

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

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.

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

Science.gov (United States)

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

2015-10-01

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

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

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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

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

Erythropoietin in stroke therapy: friend or foe.

Science.gov (United States)

Souvenir, Rhonda; Doycheva, Desislava; Zhang, John H; Tang, Jiping

2015-01-01

Recombinant human erythropoietin (rhEPO), over the past decade, was hailed as an auspicious therapeutic strategy for various types of brain injuries. The promising results from experiments conducted in animal models of stroke led to a hurried clinical trial that was swiftly aborted in Phase II. The multiple neuroprotective modalities of rhEPO failed to translate smoothly to human adult ischemic brain injury and provided limited aid to neonates. In light of the antithetical results, several questions were raised as to why and how this clinical trial failed. There was bolstering evidence from the preliminary studies that pointed to a bright future. Therefore, the objective of this review is to address these questions by discussing the signaling pathways of rhEPO that are reported to mediate the neuroprotective effect in various animal models of brain injury. Major biomedical bibliographical databases (MEDLINE, ISI, PubMed, and Cochrane Library) were searched with the use of keywords such as erythropoietin, stroke, neonatal hypoxia ischemia, intracerebral hemorrhage, etc. This article will discuss the confounding factors that influence the efficacy of rhEPO treatment hence challenging its clinical translatability. Lastly, rhEPO may still be a promising therapeutic candidate for neonates in spite of its shortcoming in clinical trial if caution is taken with the dose and duration of its administration.

[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.

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

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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.

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

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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

High-dose erythropoietin for tissue protection

DEFF Research Database (Denmark)

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

2014-01-01

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

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

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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...

Ethanol extract of Portulaca oleracea L. protects against hypoxia-induced neuro damage through modulating endogenous erythropoietin expression.

Science.gov (United States)

Wanyin, Wang; Liwei, Dong; Lin, Jia; Hailiang, Xin; Changquan, Ling; Min, Li

2012-04-01

In addition to its role in erythropoiesis, erythropoietin is also appreciated for its neuroprotective effects, and it has been suggested for treatment of some ischemic-hypoxic neurovascular diseases. The protective effects of endogenous erythropoietin in the brain give rise to the hypothesis that modulating erythropoietin expression might be a better way for treatment of ischemia-hypoxia neurovascular diseases. We have found that ethanol extract of Portulaca oleracea L. (EEPO) could increase erythropoietin expression in hypoxic mouse brain in our previous study. The present study is to investigate whether EEPO exerts its neuroprotective effects against hypoxia injury through regulating endogenous erythropoietin expression. The results demonstrated that EEPO decreased the serum neuron specific enolase level in hypoxia mice and the activity of caspase-3 in neuron, increased the neuron viability and attenuated the pathological damages caused by the hypoxia condition. Importantly, we also found that EEPO stimulated the endogenous erythropoietin expression at both mRNA and protein levels. Using the conditioned medium containing soluble erythropoietin receptor, we found that the neuroprotective effects of EEPO were dependent, at least partly, on erythropoietin expression. Although EEPO did not affect transcription of hypoxia inducible factor-1α (HIF-1α), it did stabilize expression of HIF-1α. It is concluded that EEPO has neuroprotective effects against hypoxia injury, which is at least partly through stimulating endogenous erythropoietin expression by stabilizing HIF-1α. Copyright © 2012 Elsevier Inc. All rights reserved.

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

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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

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

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...

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

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

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

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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.

Erythropoietin during hypoglycaemia in type 1 diabetes: relation to basal renin-angiotensin system activity and cognitive function

DEFF Research Database (Denmark)

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

2009-01-01

diabetes with high and nine with low activity in RAS were studied. Hypoglycaemia was induced using a standardized insulin-infusion. RESULTS: Overall, erythropoietin concentrations increased during hypoglycaemia. In the high RAS group erythropoietin rose 29% (p=0.032) whereas no significant response...... was observed in the low RAS group (7% increment; p=0.43). Independently, both hypoglycaemia and high RAS activity were associated with higher levels of erythropoietin (p=0.02 and 0.04, respectively). Low plasma erythropoietin at baseline was associated with poorer cognitive performance during hypoglycaemia...

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

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Iraj Ragerdi Kashani

2017-08-01

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

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...

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

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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

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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

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.

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

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.

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 ...

Does erythropoietin augment noise induced hearing loss?

DEFF Research Database (Denmark)

Frederiksen, Birgitte Lidegaard; Cayé-Thomasen, Per; Lund, Søren Peter

2007-01-01

Noise-induced hearing loss may result from excessive release of glutamate, nitrogen oxide and reactive oxygen species. The effects of these factors on the inner ear may potentially be prevented or reduced by erythropoietin (EPO), as indicated by previously demonstrated neuro-protective effects of...

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.

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)

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

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...

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

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?

Erythropoietin protects the retinal pigment epithelial barrier against ...

African Journals Online (AJOL)

O2-induced hyperpermeability. H Zhang, Y Gong, X Wu, Y Shi, L Yin, Y Qiu. Abstract. Erythropoietin (EPO) is not limited to hematopoiesis; it may act as a protective cytokine. In this study, the retinal pigment epithelial (RPE) cell viability, cell ...

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

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

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.

Comparison of erythropoietic response to erythropoietin-secreting stimuli in mice following polycythemia induced by transfusion or hypoxia

Energy Technology Data Exchange (ETDEWEB)

Alippi, R.M.; Barcelo, A.C.; Bozzini, C.E.

1985-03-01

The erythropoietic response, measured as RBC-/sup 59/Fe uptake, in response to either 24-h exposure to hypoxia or administration of dexamethasone, isoproterenol, testosterone, or erythropoietin, was determined in both posthypoxic (PH) and hypertransfused (HT) polycythemic mice. Highly significant differences between PH and HT mice exposed to hypoxia or injected with dexamethasone, isoproterenol, or testosterone were observed, isotope incorporation being always higher in PH than in HT mice. On the other hand, the response to erythropoietin did not show a significant difference between PH and HT mice. These results suggest that PH mice have been preconditioned by exposure to hypoxia in a way that makes them more sensitive to at least some kinds of erythropoietic stimuli. Since these stimuli have been shown by others to increase erythropoietin production, the results support the hypothesis that hypoxia induces sensitization of the erythropoietin- producing organ(s).

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...

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.

[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

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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.

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

[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.

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)

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...

Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism

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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.

Study the relationship of erythropoietin and chronic obstructive pulmonary disease

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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.

Modulation of erythropoietin concentrations by manipulation of hypercarbia

Energy Technology Data Exchange (ETDEWEB)

Miller, M.E.; Howard, D.

1979-01-01

The present studies were done to determine whether preventing the respiratory alkalosis, which is known to occur with acute hypoxic stimuli, would lead to alterations in plasma concentrations of erythropoietin (Ep). Rats were subjected to two acute stresses, hypoxia and blood loss, separately and in combination, with and without the added stress of hypercarbia. Hypercarbia in all experimental groups was associated with a decrease in plasma concentrations of Ep. This reduction in plasma Ep with hypercarbia could not be fully explained by the higher arterial pO/sub 2/s or p50s of the hypercarbic rats. Hypercarbia may have indirectly suppressed Ep production by increasing blood flow to the site of Ep production. Alternatively, the cell of origin of Ep could be sensitive to changes in pH and/or pCO/sub 2/. It was further demonstrated that neither the onset nor the degree of reticulocytosis could be predicted by the plasma Ep concentrations. It is likely that the removal of red blood cells led to a decrease in marrow transit time with the early emergence of reticulocytes after acute blood loss.

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)

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

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.

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

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....

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

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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.

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

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...

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

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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)

Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury

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Daniela Hoeber

2016-01-01

Full Text Available Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg at the onset of hyperoxia (24 hours, 80% oxygen in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.

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

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

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...

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.)

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...

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

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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.

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...

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.

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

Clinical applications of measurement of serum immunoreactive levels of erythropoietin

International Nuclear Information System (INIS)

Miller, M.E.; Chandra, M.; Garcia, J.F.

1985-01-01

The purification of erythropoietin (Ep) in 1977 enabled investigators to more clearly define the role of this hormone in erythropoiesis in man. Radioimmunoassays were rapidly developed. Undoubtedly differences between levels of immunoreactive and biologically active Ep will be found but the resolution of these discrepancies will expand our understanding of the erythron. Recently others described a monoclonal antibody against Ep. Because of this breakthrough, large quantities of pure hormone should soon be available to a larger number of investigators than currently have access to it. The major clinical use of this hormone will probably be in the treatment of the anemia of chronic renal disease. In the relatively few years since the radioimmunoassay (RIA) was developed, measurements of the levels of this hormone have been made in several disease states as well as in normal man. Most of the findings to date confirm the predictions that have been made over the years based on studies done using the rather crude bioassay for Ep. In the present study the authors shall review and expand on what is known about subjects with chronic lung and renal disease

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

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.

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...

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...

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

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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.

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.

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.

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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 homozygous VHL(D126N) missense mutation is associated with dramatically elevated erythropoietin levels, consequent polycythemia, and early onset severe pulmonary hypertension.

Science.gov (United States)

Sarangi, Susmita; Lanikova, Lucie; Kapralova, Katarina; Acharya, Suchitra; Swierczek, Sabina; Lipton, Jeffrey M; Wolfe, Lawrence; Prchal, Josef T

2014-11-01

von Hippel-Lindau (VHL) protein is the principal negative regulator of hypoxia sensing mediated by transcription factors. Mutations in exon 3 of the VHL gene lead to Chuvash (VHL(R200W)) and Croatian (VHL(H191D)) polycythemias. Here, we describe an infant of Bangladesh ethnicity with a novel homozygous VHL(D126N) mutation with congenital polycythemia and dramatically elevated erythropoietin (EPO) levels, who developed severe fatal pulmonary hypertension. In contrast to Chuvash polycythemia, erythroid progenitors (BFU-Es) did not reveal a marked EPO hypersensitivity. Further, NF-E2 and RUNX1 transcripts that correlate with BFU-Es EPO hypersensitivity in polycythemic mutations were not elevated. © 2014 Wiley Periodicals, Inc.

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.

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

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.

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)

A review of studies on community based early warning systems

Directory of Open Access Journals (Sweden)

Margaret Macherera

2016-04-01

Full Text Available Community-based early warning systems involve community driven collection and analysis of information that enable warning messages to help a community to react to a hazard and reduce the resulting loss or harm. Most early warning systems are designed at the national or global level. Local communities’ capacity to predict weather conditions using indigenous knowledge has been demonstrated in studies focusing on climate change and agriculture in some African countries. This review was motivated by successes made in non-disease specific community-based early warning systems with a view to identify opportunities for developing similar systems for malaria. This article reviewed the existing community-based early warning systems documented in literature. The types of disasters that are addressed by these systems and the methodologies utilised in the development of the systems were identified. The review showed that most of the documented community-based early warning systems focus on natural disasters such as floods, drought, and landslides. Community-based early warning systems for human diseases are very few, even though such systems exist at national and regional and global levels. There is a clear gap in terms of community-based malaria early warning systems. The methodologies for the development of the community-based early warning systems reviewed mainly derive from the four elements of early warning systems; namely risk knowledge, monitoring, warning communication and response capability. The review indicated the need for the development of community based early warning systems for human diseases. Keywords: community; early warning; disaster; hazards

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

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Palazzuoli A

2014-08-01

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

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.

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.

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,

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.

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

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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

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...

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.

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...

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

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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.

REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy ...

African Journals Online (AJOL)

REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy. AOK Johnson. Abstract. Conjugated hyperbilirubinaemia exists when the conjugated serum bilirubin level is more than 2 mg/dl or more than 20 per cent of the total serum bilirubin. It is always pathological in early infancy. The causes are many and diverse ...

Review of early assessment models of innovative medical technologies.

Science.gov (United States)

Fasterholdt, Iben; Krahn, Murray; Kidholm, Kristian; Yderstræde, Knud Bonnet; Pedersen, Kjeld Møller

2017-08-01

Hospitals increasingly make decisions regarding the early development of and investment in technologies, but a formal evaluation model for assisting hospitals early on in assessing the potential of innovative medical technologies is lacking. This article provides an overview of models for early assessment in different health organisations and discusses which models hold most promise for hospital decision makers. A scoping review of published studies between 1996 and 2015 was performed using nine databases. The following information was collected: decision context, decision problem, and a description of the early assessment model. 2362 articles were identified and 12 studies fulfilled the inclusion criteria. An additional 12 studies were identified and included in the review by searching reference lists. The majority of the 24 early assessment studies were variants of traditional cost-effectiveness analysis. Around one fourth of the studies presented an evaluation model with a broader focus than cost-effectiveness. Uncertainty was mostly handled by simple sensitivity or scenario analysis. This review shows that evaluation models using known methods assessing cost-effectiveness are most prevalent in early assessment, but seems ill-suited for early assessment in hospitals. Four models provided some usable elements for the development of a hospital-based model. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

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

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.

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

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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.

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.)

[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...

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

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

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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.

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

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....

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.

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

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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.

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...

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

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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.

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

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...

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

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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.

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

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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.

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

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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.

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

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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.

Applications and biomonitoring issues of recombinant erythropoietins for doping control.

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Tsitsimpikou, Christina; Kouretas, Demetrios; Tsarouhas, Konstantinos; Fitch, Kenneth; Spandidos, Demetrios A; Tsatsakis, Aristides

2011-02-01

The biochemical actions and side effects of recombinant erythropoietins (rhEPOs), their analogs and mimetics, their misuse as doping agents, and the principal analytical strategies developed to identify them in athletes' biologic fluids are reviewed. Patients who experience a range of pathologies have benefited from the administration of rhEPOs to correct severe anemia. Currently, monitoring the biologic effect of rhEPO in patients under treatment is by measuring the hemoglobin concentration. However, it may be valuable to directly monitor the actual levels of the administered drug and determine a dose-dependent correlation with any clinical adverse effect observed. This may permit the adoption of a patient-specific administration regime. Currently, the method of detecting EPO approved for doping control is an isoelectric-focusing, double-blotting, chemiluminescence assay based on charge differences between isoforms of rhEPOs and endogenous EPO in urine. The advantages and limitations of this method are presented. A new approach using sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a complementary tool to the established method is discussed. The application of matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography combined with tandem mass spectrometry for the direct detection of the rhEPO molecules may prove to be promising. Indirect evidence of rhEPO abuse by athletes is based on the analysis of blood parameters (hemoglobin hematocrit, reticulocytes, macrocytes, etc) and serum markers (concentration of EPO and serum transferrin receptors, etc). Enrichment of the screened parameters with gene or biochemical markers revealing altered erythropoiesis and adoption of longitudinal monitoring of athletes' hematologic and biochemical parameters could also be a complementary approach in the fight against doping.

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

Regulatory Review of Early Site Permit Applications

International Nuclear Information System (INIS)

Scott, Michael L.

2004-01-01

The U.S. Nuclear Regulatory Commission (NRC) has received and is reviewing three applications for early site permits (ESPs). The ESP process allows early resolution of site-related issues affecting possible construction and operation of a new nuclear power plant. The nuclear industry views a successful and predictable ESP process as an important step in assessing whether to seek authorization to construct and operate a new generation of nuclear power reactors in the United States. Because consideration of ESP applications is a first-of-a-kind activity, a number of issues have emerged prior to and during the reviews of the first three applications. Issues have included the need for design information at the ESP stage, accident analyses, quality assurance, and seismic analyses. The NRC has been working to resolve identified issues to support a Commission decision on whether to issue an ESP approximately 33-37 months after receipt of each ESP application. (authors)

78 FR 78369 - Submission for OMB Review; 30-Day Comment Request: Early Career Reviewer Program Online...

Science.gov (United States)

2013-12-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Submission for OMB Review; 30-Day Comment Request: Early Career Reviewer Program Online Application System--Center for Scientific Review (CSR) SUMMARY: Under the provisions of Section 3507(a)(1)(D) of the Paperwork Reduction Act...

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...

Extended Erythropoietin Treatment Prevents Chronic Executive Functional and Microstructural Deficits Following Early Severe Traumatic Brain Injury in Rats

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Shenandoah Robinson

2018-06-01

Full Text Available Survivors of infant traumatic brain injury (TBI are prone to chronic neurological deficits that impose lifelong individual and societal burdens. Translation of novel interventions to clinical trials is hampered in part by the lack of truly representative preclinical tests of cognition and corresponding biomarkers of functional outcomes. To address this gap, the ability of a high-dose, extended, post-injury regimen of erythropoietin (EPO, 3000U/kg/dose × 6d to prevent chronic cognitive and imaging deficits was tested in a postnatal day 12 (P12 controlled-cortical impact (CCI model in rats, using touchscreen operant chambers and regional analysis of diffusion tensor imaging (DTI. Results indicate that EPO prevents functional injury and MRI injury after infant TBI. Specifically, subacute DTI at P30 revealed widespread microstructural damage that is prevented by EPO. Assessment of visual discrimination on a touchscreen operant chamber platform demonstrated that all groups can perform visual discrimination. However, CCI rats treated with vehicle failed to pass reversal learning, and perseverated, in contrast to sham and CCI-EPO rats. Chronic DTI at P90 showed EPO treatment prevented contralateral white matter and ipsilateral lateral prefrontal cortex damage. This DTI improvement correlated with cognitive performance. Taken together, extended EPO treatment restores executive function and prevents microstructural brain abnormalities in adult rats with cognitive deficits in a translational preclinical model of infant TBI. Sophisticated testing with touchscreen operant chambers and regional DTI analyses may expedite translation and effective yield of interventions from preclinical studies to clinical trials. Collectively, these data support the use of EPO in clinical trials for human infants with TBI.

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

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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.

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.

Techniques for early diagnosis of oral squamous cell carcinoma: Systematic review

Science.gov (United States)

Carreras-Torras, Clàudia

2015-01-01

Background and objectives The diagnosis of early oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) is of paramount clinical importance given the mortality rate of late stage disease. The aim of this study is to review the literature to assess the current situation and progress in this area. Material and Methods A search in Cochrane and PubMed (January 2006 to December 2013) has been used with the key words “squamous cell carcinoma”, “early diagnosis” “oral cavity”, “Potentially Malignant Disorders” y “premalignant lesions”. The inclusion criteria were the use of techniques for early diagnosis of OSCC and OPMD, 7 years aged articles and publications written in English, French or Spanish. The exclusion criteria were case reports and studies in other languages. Results Out of the 89 studies obtained initially from the search 60 articles were selected to be included in the systematic review: 1 metaanalysis, 17 systematic reviews, 35 prospective studies, 5 retrospective studies, 1 consensus and 1 semi-structured interviews. Conclusions The best diagnostic technique is that which we have sufficient experience and training. Definitely tissue biopsy and histopathological examination should remain the gold standard for oral cancer diagnose. In this systematic review it has not been found sufficient scientific evidence on the majority of proposed techniques for early diagnosis of OSCC, therefore more extensive and exhaustive studies are needed. Key words: Squamous cell carcinoma, early diagnosis, oral cavity, potentially malignant disorders, premalignant lesions. PMID:25662554

Contemporary Management of Early-Stage Melanoma: A Systematic Review.

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Rosko, Andrew J; Vankoevering, Kyle K; McLean, Scott A; Johnson, Timothy M; Moyer, Jeffrey S

2017-05-01

The incidence of melanoma is increasing, with 76 380 new cases of invasive melanoma and 68 480 new cases of melanoma in situ expected in 2016. To review the contemporary management of early-stage melanoma. We searched PubMed, MEDLINE, and the Cochrane Database of Systematic Reviews databases from January 1, 2011, to May 1, 2016, yielding 966 articles. We focused our search on early-stage (melanoma in situ, stage I, and stage II) cutaneous melanoma. After excluding articles, 41 articles were manually reviewed. A review of the bibliographies of selected articles generated additional references. While the majority of recent advances have been in the treatment of advanced melanoma, surgical excision with margins based on the presence and depth of invasion continues to be the cornerstone of management. Sentinel lymph node biopsy plays a central role in the staging and treatment of melanoma. Accurate diagnosis and adequate surgical excision are critical in reducing local recurrences and improving outcomes. Sentinel lymph node biopsy is useful in staging the regional nodal basin and guiding treatment in appropriately selected patients.

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....

No evidence for protective erythropoietin alpha signalling in rat hepatocytes

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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

Excess iron: considerations related to development and early growth.

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Wessling-Resnick, Marianne

2017-12-01

What effects might arise from early life exposures to high iron? This review considers the specific effects of high iron on the brain, stem cells, and the process of erythropoiesis and identifies gaps in our knowledge of what molecular damage may be incurred by oxidative stress that is imparted by high iron status in early life. Specific areas to enhance research on this topic include the following: longitudinal behavioral studies of children to test associations between iron exposures and mood, emotion, cognition, and memory; animal studies to determine epigenetic changes that reprogram brain development and metabolic changes in early life that could be followed through the life course; and the establishment of human epigenetic markers of iron exposures and oxidative stress that could be monitored for early origins of adult chronic diseases. In addition, efforts to understand how iron exposure influences stem cell biology could be enhanced by establishing platforms to collect biological specimens, including umbilical cord blood and amniotic fluid, to be made available to the research community. At the molecular level, there is a need to better understand stress erythropoiesis and changes in iron metabolism during pregnancy and development, especially with respect to regulatory control under high iron conditions that might promote ineffective erythropoiesis and iron-loading anemia. These investigations should focus not only on factors such as hepcidin and erythroferrone but should also include newly identified interactions between transferrin receptor-2 and the erythropoietin receptor. Finally, despite our understanding that several key micronutrients (e.g., vitamin A, copper, manganese, and zinc) support iron's function in erythropoiesis, how these nutrients interact remains, to our knowledge, unknown. It is necessary to consider many factors when formulating recommendations on iron supplementation. © 2017 American Society for Nutrition.

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.

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...

An integrative 'omics' solution to the detection of recombinant human erythropoietin and blood doping.

Science.gov (United States)

Pitsiladis, Yannis P; Durussel, Jérôme; Rabin, Olivier

2014-05-01

Administration of recombinant human erythropoietin (rHumanEPO) improves sporting performance and hence is frequently subject to abuse by athletes, although rHumanEPO is prohibited by the WADA. Approaches to detect rHumanEPO doping have improved significantly in recent years but remain imperfect. A new transcriptomic-based longitudinal screening approach is being developed that has the potential to improve the analytical performance of current detection methods. In particular, studies are being funded by WADA to identify a 'molecular signature' of rHumanEPO doping and preliminary results are promising. In the first systematic study to be conducted, the expression of hundreds of genes were found to be altered by rHumanEPO with numerous gene transcripts being differentially expressed after the first injection and further transcripts profoundly upregulated during and subsequently downregulated up to 4 weeks postadministration of the drug; with the same transcriptomic pattern observed in all participants. The identification of a blood 'molecular signature' of rHumanEPO administration is the strongest evidence to date that gene biomarkers have the potential to substantially improve the analytical performance of current antidoping methods such as the Athlete Biological Passport for rHumanEPO detection. Given the early promise of transcriptomics, research using an 'omics'-based approach involving genomics, transcriptomics, proteomics and metabolomics should be intensified in order to achieve improved detection of rHumanEPO and other doping substances and methods difficult to detect such a recombinant human growth hormone and blood transfusions.

Early Childhood Discipline: A Review of the Literature

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Firmin, Michael W.; Castle, Sally L.

2008-01-01

In this literature review concerning early childhood discipline we particularly highlight American children's discipline with respect to historical perspectives, generational theories, gender issues, parental styles, methods of discipline, and corporal punishment. We also address corporal punishment's history, the debate among experts, beliefs and…

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-09-09

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

Erythropoietin receptor is not a surrogate marker for tumor hypoxia and does not correlate with survival in head and neck squamous cell carcinomas.

NARCIS (Netherlands)

Hoogsteen, I.J.; Peeters, W.J.M.; Marres, H.A.M.; Rijken, P.F.J.W.; Hoogen, F.J.A. van den; Kogel, A.J. van der; Kaanders, J.H.A.M.

2005-01-01

BACKGROUND AND PURPOSE: To evaluate erythropoietin receptor (EPOR) expression in human head and neck squamous cell carcinomas and correlate this to the presence of tumor hypoxia and treatment outcome. PATIENTS AND METHODS: Eighty-five patients with locally advanced tumors of the head and neck were

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

DEFF Research Database (Denmark)

Aachmann-Andersen, Niels J.; Christensen, Soren J.; Lisbjerg, Kristian

2018-01-01

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...... 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....

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

DEFF Research Database (Denmark)

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

2016-01-01

The sensitivity of the adaptive model of the Athlete Biological Passport (ABP) and reticulocyte percentage (ret%) in detection of recombinant human erythropoietin (rHuEPO) misuse was evaluated using both a long-term normal dose and a brief high dose treatment regime. Sixteen subjects received...... initiation. The ABP based on haemoglobin concentration ([Hb]) and OFF-hr score ([Hb] - 60×√ret%) yielded atypical profiles following both normal-dose and high-dose treatment (0 %, 31 %, 13 % vs. 21 %, 33 %, 20 % at days 4, 11, and 25 after normal and high dose, respectively). Including ret% as a stand...... will present an atypical ABP profile. Including ret% as a stand-alone parameter improves the sensitivity two-fold....

Early economic evaluation of emerging health technologies: protocol of a systematic review

Science.gov (United States)

2014-01-01

Background The concept of early health technology assessment, discussed well over a decade, has now been collaboratively implemented by industry, government, and academia to select and expedite the development of emerging technologies that may address the needs of patients and health systems. Early economic evaluation is essential to assess the value of emerging technologies, but empirical data to inform the current practice of early evaluation is limited. We propose a systematic review of early economic evaluation studies in order to better understand the current practice. Methods/design This protocol describes a systematic review of economic evaluation studies of regulated health technologies in which the evaluation is conducted prior to regulatory approval and when the technology effectiveness is not well established. Included studies must report an economic evaluation, defined as the comparative analysis of alternatives with respect to their associated costs and health consequences, and must evaluate some regulated health technology such as pharmaceuticals, biologics, high-risk medical devices, or biomarkers. We will conduct the literature search on multiple databases, including MEDLINE, EMBASE, the Centre for Reviews and Dissemination Databases, and EconLit. Additional citations will be identified via scanning reference lists and author searching. We suspect that many early economic evaluation studies are unpublished, especially those conducted for internal use only. Additionally, we use a chain-referral sampling approach to identify authors of unpublished studies who work in technology discovery and development, starting out with our contact lists and authors who published relevant studies. Citation screening and full-text review will be conducted by pairs of reviewers. Abstracted data will include those related to the decision context and decision problem of the early evaluation, evaluation methods (e.g., data sources, methods, and assumptions used to

Diurnal variations of serum erythropoietin at sea level and altitude

DEFF Research Database (Denmark)

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

1996-01-01

in 2, 3 diphosphoglycerate. After 64 h at altitude, six of the nine subjects had down-regulated their serum-EPO concentrations so that median values were three times above those at sea level. These six subjects had significant diurnal variations of serum-EPO concentration at sea level; the nadir......This study tested the hypothesis that the diurnal variations of serum-erythropoietin concentration (serum-EPO) observed in normoxia also exist in hypoxia. The study also attempted to investigate the regulation of EPO production during sustained hypoxia. Nine subjects were investigated at sea level...... and during 4 days at an altitude of 4350 m. Median sea level serum-EPO concentration was 6 (range 6-13) U.l-1. Serum-EPO concentration increased after 18 and 42 h at altitude, [58 (range 39-240) and 54 (range 36-340) U.l-1, respectively], and then decreased after 64 and 88 h at altitude [34 (range 18...

Wound Healing and ndash; A Proteomic Analysis of the Effect of Erythropoietin on Granulation Tissue Isolated from ePTFE Implants

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Bekka Christensen

2014-02-01

Conclusion: Daily injection of recombinant human erythropoietin of 1000 IU/kg alters the protein expression of GAPDH, ENOA and TPIS in granulation tissue from wounds on postoperative day 9. The successful combination of proteomic analysis of wound tissue and the ePTFE wound model could advance our knowledge of the complex healing process. [Arch Clin Exp Surg 2014; 3(1.000: 26-33

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

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

OpenAIRE

Štambuk, Nikola; Manojlović, Zoran; Turčić, Petra; Martinić, Roko; Konjevoda, Paško; Weitner, Tin; Wardega, Piotr; Gabričević, Mario

2014-01-01

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 ...

Early diagnosis of autism and impact on prognosis: a narrative review

Directory of Open Access Journals (Sweden)

Fernell E

2013-02-01

Full Text Available Elisabeth Fernell,1 Mats Anders Eriksson,1,2 Christopher Gillberg11Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Department of Women's and Children's Health, Karolinska Institute, Stockholm, SwedenAbstract: Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neurodevelopmental deviations, with core symptoms that can probably be related to a deficiency in the social instinct. Underlying the cognitive impairments there are physiological brain problems, caused by a large number of medical factors. This narrative review of systematic reviews and meta-analyses from the last 5 years (2008–2012 presents aspects from many areas in autism spectrum disorder research, with a particular focus on early intervention and the subsequent impact on prognosis. Other major areas discussed are epidemiology, early symptoms and screening, early diagnosis, neuropsychology, medical factors, and the existence of comorbidities. There is limited evidence that any of the broadband “early intervention” programs are effective in changing the natural long-term outcome for many individuals with an early diagnosis of autism. However, there is some evidence that Early Intensive Behavioral Intervention (EIBI is an effective treatment for some children with ASD. Nevertheless, there is emerging consensus that early diagnosis and information are needed in order that an autism-friendly environment be “created” around affected individuals.Keywords: autism spectrum disorder, epidemiology, screening, etiology, intervention, outcome

Erythropoietin in Cardiorenal Anemia Syndrome

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Emir Fazlibegović

2008-11-01

Full Text Available Incidents of heart and renal failure (HF, RF together, are increasing in our country and all over the world, so a great attention has been dedicated to this problem recently. These diseases together have shown bad results because of the process of accelerated arteriosclerosis, structural changes of myocardium, oxidative stress, inflammation, increased activities of sympathetic nervous system (SNS, increased activities of a renin-angiotensin-aldosterone system (RAAS. These factors are crucial in the development of patho-physiological process and consequential development of anemia, that together with heart and renal failure through interaction, cause serious disorder that we call the cardio-renal anemia syndrome. We examined effects of erythropoietin (Epoetin beta at 90 (60 men and 30 women pre-dialysed and dialysed patients with HF signs during a period of three years in individual dozes of 2000-6000 units subcutaneous (sc weekly. Using computer S PLUS and SAS multiple variant analysis we have got correlations by Pearson. Epoetin beta significantly develops anemiaparameters: number of erythrocytes (r=0.51779; p<0.0001, hemoglobin (r=0.38811; p<0.0002, MCV (r=0.59876; p<0.0001 at patients with HF. Positive effects are seen at NYHA class (r=0.59906; p<0.0001, on quality of life before and after prescribing medicine. Parameters of renal functions are improving: more urea (r =0.45557; p<0.0001 than creatinine (r=0.26397; p<0.00119 and potassium values K(+ are not changed significantly (r=0.02060; p<0.8471. Epoetin beta has been useful in treatment of pre-dialysed and dialysed patients with HF and anemia by improving functional ability of myocardium and quality of life.

Serum erythropoietin levels by radioimmunoassay in polycythaemia

Energy Technology Data Exchange (ETDEWEB)

Birgegaard, G.; Miller, O.; Caro, J.; Erslev, A. (Cardeza Foundation for Hematological Research, Jefferson University, Philadelphia, Pa.)

1982-01-01

A radioimmunoassay (RIA) method for erythropoietin (Epo) was developed and validated against the polycythaemic mouse assay. The correlation was good, with a r=0.94. Several other criteria of specificity were also filled by the RIA, which had a lower detection limit of 5 mU/ml. The mean serum-Epo level in 6 patients with secondary polycythaemia, 50.2 +- 26.2 mU/ml, was significantly higher than in a group of 11 normal subjects, 28.7 +- 7.2 mU/ml (P<0.0002). However, the Epo level in 31 polycythaemia vera (PV) patients, M = 21.9 +- 6.6 mU/ml, was not significantly different from normal (P = 0.006). Since previous studies with bioassay of heat-treated and concentrated plasma samples have shown a decreased serum-Epo level in PV, Epo levels were measured before and after heat treatment and concentration of samples from normals and polycythaemics. It was found that the levels of immunoreactive material increased after heat treatment and 40 times concentration in samples from normals and patients with secondary polycythaemias, but decreased in PV. We conclude that the Epo levels in serum in the low range measured by our and previous RIA:s probably are not true Epo levels but are partly due to an unspecific serum effect, that was removed by heat treatment.

Lesbian and Gay Parents in Early Childhood Settings: A Systematic Review of the Research Literature

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Averett, Paige; Hegde, Archana; Smith, Justin

2017-01-01

This article presents the first systematic review of all the existing peer-reviewed literature (n = 20) on gay and lesbian parents and their children in early childhood education settings. The review includes articles that were empirical or pedagogical practice oriented, focused exclusively on early childhood education (Birth to 5 years), and…

Effects of erythropoietin administration on cerebral metabolism and exercise capacity in men

DEFF Research Database (Denmark)

Rasmussen, Peter; Foged, Eva M; Krogh-Madsen, Rikke

2010-01-01

administration of EPO. We recorded exercise capacity, transcranial ultrasonography-derived middle cerebral artery blood velocity, and arterial-internal jugular venous concentration differences of glucose and lactate. In addition, cognitive function, ratings of perceived exertion, ventilation and voluntary......Recombinant human erythropoietin (EPO) increases exercise capacity by stimulating erythropoiesis and subsequently enhancing oxygen delivery to the working muscles. In a large dose, EPO cross the blood brain barrier and may reduce central fatigue and improve cognition. In turn, this would augment...... exercise capacity independent of erythropoiesis. To test this hypothesis, 15 healthy young males (18-34 yo., 74 +/- 7 kg) received either 3 days of high dose (30,000 IU day(-1), N=7) double-blinded placebo controlled or 3 months of low dose (5,000 IU week(-1), N=8) counter-balanced open but controlled...

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...

Mentoring: A Review of Early Career Researcher Studies

Science.gov (United States)

Boeren, Ellen; Lokhtina-Antoniou, Irina; Sakurai, Yusuke; Herman, Chaya; McAlpine, Lynn

2015-01-01

This paper reviews 23 journal articles on "mentoring" in the context of Early Career Researchers, defined as those in academia with less than 10 years of experience from the start of their PhD. Achieving a better understanding of mentoring is important since within the higher education context new dynamics have created expectations…

Pretransplant HbA1c Is a Useful Predictor for the Development of New-Onset Diabetes in Renal Transplant Recipients Receiving No or Low-Dose Erythropoietin

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Kazuaki Tokodai

2014-01-01

Full Text Available Aims. To evaluate the predictive power of pretransplant HbA1c for new-onset diabetes after transplantation (NODAT in kidney transplant candidates, who had several predispositions for fluctuated HbA1c levels. Methods. We performed a retrospective study of 119 patients without diabetes who received kidney transplantation between March 2000 and January 2012. Univariate and multivariate logistic regression analyses were used to investigate the association of several parameters with NODAT. Predictive discrimination of HbA1c was assessed using a receiver-operating characteristic curve. Results. Seventeen patients (14.3% developed NODAT within 1 year of transplantation. Univariate logistic regression analysis revealed that recipient age, gender, and HbA1c were predictors of NODAT. In the multivariate analysis, the association between pretransplant HbA1c and NODAT development did not reach statistical significance (P=0.07. To avoid the strong influence of high-dose erythropoietin on HbA1c levels, we performed subgroup analyses on 85 patients receiving no or low-dose (≤6000 IU/week erythropoietin. HbA1c was again an independent predictor for NODAT. Receiver-operating characteristic analysis revealed a cut-off value of 5.2% with an optimal sensitivity of 64% and specificity of 78% for predicting NODAT. Conclusions. Our results reveal that the pretransplant HbA1c level is a useful predictor for NODAT in patients receiving no or low-dose erythropoietin.

Topical erythropoietin promotes wound repair in diabetic rats.

Science.gov (United States)

Hamed, Saher; Ullmann, Yehuda; Masoud, Muhannad; Hellou, Elias; Khamaysi, Ziad; Teot, Luc

2010-01-01

Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 38 rats, of which 30 had diabetes. The wounds were then treated topically with a cream that contained either vehicle, 600 IU ml(-1) EPO (low dose), or 3,000 IU ml(-1) (high dose) EPO. We assessed the rate of wound closure during the 12-day treatment period, and microvascular density (MVD), vascular endothelial growth factor (VEGF), and hydroxyproline (HP) contents, and the extent of apoptosis in wound tissues at the end of the 12-day treatment period. Topical EPO treatment significantly reduced the time to final wound closure. This increased rate of closure of the two EPO-treated wounds in diabetic rats was associated with increased MVD, VEGF, and HP contents, and a reduced extent of apoptosis. In light of our finding that topical EPO treatment promotes skin wound repair in diabetic rats, we propose that topical EPO treatment is a therapeutically beneficial method of treating chronic diabetic wounds.

Wood fuel from early thinning and plantation cleaning. An international review

International Nuclear Information System (INIS)

Puttock, D.; Richardsson, J.

1998-01-01

Activities 1.2 (Forest management) and 1.2 (Harvesting) of Task XII/IEA Bioenergy Agreement carried out an international review of wood fuel from plantation cleaning and early thinning. The participating countries were Canada, Denmark, Finland, the Netherlands, New Zealand, Sweden and the United Kingdom. The individual country reviews and an international summary are presented in this paper. Each report gives country-related background information on forestry and wood utilization, energy potential from plantation cleaning and early thinning, environmental considerations from the viewpoint of wood fuel recovery, silvicultural systems and methods, cost of wood fuel, and knowledge gaps and problems

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.

A systematic review of early intensive intervention for autism spectrum disorders.

Science.gov (United States)

Warren, Zachary; McPheeters, Melissa L; Sathe, Nila; Foss-Feig, Jennifer H; Glasser, Allison; Veenstra-Vanderweele, Jeremy

2011-05-01

Early intensive behavioral and developmental interventions for young children with autism spectrum disorders (ASDs) may enhance developmental outcomes. To systematically review evidence regarding such interventions for children aged 12 and younger with ASDs. We searched Medline, PsycINFO, and ERIC (Education Resources Information Center) from 2000 to May 2010. Two reviewers independently assessed studies against predetermined inclusion/exclusion criteria. Two reviewers independently extracted data regarding participant and intervention characteristics, assessment techniques, and outcomes and assigned overall quality and strength-of-evidence ratings using predetermined criteria. Thirty-four unique studies met inclusion criteria. Seventeen studies were case series; 2 were randomized controlled trials. We rated 1 study as good quality, 10 as fair quality, and 23 as poor quality. The strength of the evidence overall ranged from insufficient to low. Studies of University of California Los Angeles/Lovaas-based interventions and variants reported clinically significant gains in language and cognitive skills in some children, as did 1 randomized controlled trial of an early intensive developmental intervention approach (the Early Start Denver Model). Specific parent-training approaches yielded gains in short-term language function and some challenging behaviors. Data suggest that subgroups of children displayed more prominent gains across studies, but participant characteristics associated with greater gains are not well understood. Studies of Lovaas-based approaches and early intensive behavioral intervention variants and the Early Start Denver Model resulted in some improvements in cognitive performance, language skills, and adaptive behavior skills in some young children with ASDs, although the literature is limited by methodologic concerns.

Employment and educational outcomes in early intervention programmes for early psychosis: a systematic review.

Science.gov (United States)

Bond, G R; Drake, R E; Luciano, A

2015-10-01

Young adults with early psychosis want to pursue normal roles - education and employment. This paper summarises the empirical literature on the effectiveness of early intervention programmes for employment and education outcomes. We conducted a systematic review of employment/education outcomes for early intervention programmes, distinguishing three programme types: (1) those providing supported employment, (2) those providing unspecified vocational services and (3) those without vocational services. We summarised findings for 28 studies. Eleven studies evaluated early intervention programmes providing supported employment. In eight studies that reported employment outcomes separately from education outcomes, the employment rate during follow-up for supported employment patients was 49%, compared with 29% for patients receiving usual services. The two groups did not differ on enrolment in education. In four controlled studies, meta-analysis showed that the employment rate for supported employment participants was significantly higher than for control participants, odds ratio = 3.66 [1.93-6.93], p < 0.0001. Five studies (four descriptive and one quasi-experimental) of early intervention programmes evaluating unspecified vocational services were inconclusive. Twelve studies of early intervention programmes without vocational services were methodologically heterogeneous, using diverse methods for evaluating vocational/educational outcomes and precluding a satisfactory meta-analytic synthesis. Among studies with comparison groups, 7 of 11 (64%) reported significant vocational/education outcomes favouring early intervention over usual services. In early intervention programmes, supported employment moderately increases employment rates but not rates of enrolment in education. These improvements are in addition to the modest effects early programmes alone have on vocational/educational outcomes compared with usual services.

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)

Exemestane in early breast cancer: a review

Directory of Open Access Journals (Sweden)

Michael Untch

2008-12-01

Full Text Available Michael Untch1, Christian Jackisch21Interdisciplinary Breast Centre, Helios Klinikum Berlin-Buch, University Charité, Berlin, Germany; 2Department of Gynecology/Obstetrics, Klinikum Offenbach GmbH, Offenbach, GermanyAbstract: The adjuvant treatment of women with endocrine-sensitive early breast cancer has been dominated for the last 40 years by tamoxifen. However, the side-effects associated with this therapy have prompted a search for safer and biochemically more selective endocrine agents and led to the development of the third-generation aromatase inhibitors (AIs anastrozole, letrozole and exemestane. Promising results in advanced disease have paved the way for treating early breast cancer, and AIs are increasingly replacing tamoxifen in the adjuvant setting. Several large, randomized trials with AIs have been completed or are ongoing in women with early-stage breast cancer, documenting the significant impact that these drugs are making on the risk for recurrence of breast cancer. As a result, there is increasing and widespread use of AI therapy for the treatment of early-stage endocrine-responsive breast cancer. This review summarizes the data for exemestane in the adjuvant setting, showing that a switch to exemestane after 2 to 3 years of tamoxifen therapy is associated with a statistically significant survival benefit and is regarded as being sensitive by international and national experts.Keywords: early breast cancer, adjuvant setting, endocrine-sensitive, tamoxifen, aromatase inhibitor, exemestane, switch, IES 31, NSABP B-33, TEAM

Erythropoietin in Treatment of Methanol Optic Neuropathy.

Science.gov (United States)

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

2018-06-01

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

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

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.

Autologous blood transfusion with recombinant erythropoietin treatment in anaemic patients with rheumatoid arthritis.

Science.gov (United States)

Tanaka, N; Ito, K; Ishii, S; Yamazaki, I

1999-01-01

The aim of this study was to determine the conditions under which a sufficient preoperative amount of autologous blood could be obtained with administration of rHuEPO (recombinant human erythropoietin) in anaemic patients with rheumatoid arthritis (RA). Thirty-one patients (29 female, two male) with RA who were unable to donate any autologous blood owing to a haemoglobin level of less than 11 g/dl were recruited for this study. Their mean age at the time of operation was 59.3 years. The study protocol for preoperative autologous blood donations started 2.7 weeks before surgery. All patients received 6000 IU rHuEPO intravenously three times a week, supplemented with 40 mg intravenous saccharated ferric oxide at each rHuEPO administration. The protocol also included the provision that 200 g of blood at the first and third donations and 400 g of blood at the second donation were collected. The patients who were able or unable to donate 800 g of blood by this protocol were regarded as having a good or poor response, respectively, to rHuEPO. Patients with a poor response to rHuEPO showed greater clinical symptoms (morning stiffness, the number of swollen joints, Ritchie index) and higher laboratory inflammation parameters (ESR, CRP, platelets, IL-6, TNFalpha, IL-1beta) than patients with a good response to rHuEPO. The poor-response group showed a significant decrease in the progression of inflammation compared with the good-response group. Before treatment with rHuEPO, anaemia in the poor-response group was the same as that in the good-response group, except for impairment of UIBC (unsaturated iron-binding capacity). The poor-response group had a higher blood loss than the good-response group. In conclusion, anaemic RA patients should be considered as candidates for aggressive blood conservation interventions that depend on erythropoietin-modulated erythropoiesis. However, it is important to determine this approach under good control of inflammation.

Expression of platelet-derived growth factor BB, erythropoietin and erythropoietin receptor in canine and feline osteosarcoma.

Science.gov (United States)

Meyer, F R L; Steinborn, R; Grausgruber, H; Wolfesberger, B; Walter, I

2015-10-01

The discovery of expression of the erythropoietin receptor (EPO-R) on neoplastic cells has led to concerns about the safety of treating anaemic cancer patients with EPO. In addition to its endocrine function, the receptor may play a role in tumour progression through an autocrine mechanism. In this study, the expression of EPO, EPO-R and platelet-derived growth factor BB (PDGF-BB) was analysed in five feline and 13 canine osteosarcomas using immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). EPO expression was positive in all tumours by IHC, but EPO mRNA was only detected in 38% of the canine and 40% of the feline samples. EPO-R was expressed in all samples by quantitative RT-PCR (RT-qPCR) and IHC. EPO-R mRNA was expressed at higher levels in all feline tumours, tumour cell lines, and kidney when compared to canine tissues. PDGF-BB expression was variable by IHC, but mRNA was detected in all samples. To assess the functionality of the EPO-R on tumour cells, the proliferation of canine and feline osteosarcoma cell lines was evaluated after EPO administration using an alamarBlue assay and Ki67 immunostaining. All primary cell lines responded to EPO treatment in at least one of the performed assays, but the effect on proliferation was very low indicating only a weak responsiveness of EPO-R. In conclusion, since EPO and its receptor are expressed by canine and feline osteosarcomas, an autocrine or paracrine tumour progression mechanism cannot be excluded, although in vitro data suggest a minimal role of EPO-R in osteosarcoma cell proliferation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A review of studies on community based early warning systems

OpenAIRE

Margaret Macherera; Moses J. Chimbari

2016-01-01

Community-based early warning systems involve community driven collection and analysis of information that enable warning messages to help a community to react to a hazard and reduce the resulting loss or harm. Most early warning systems are designed at the national or global level. Local communities’ capacity to predict weather conditions using indigenous knowledge has been demonstrated in studies focusing on climate change and agriculture in some African countries. This review was motivated...

Early rehabilitation in the intensive care unit: an integrative literature review.

Science.gov (United States)

Sosnowski, Kellie; Lin, Frances; Mitchell, Marion L; White, Hayden

2015-11-01

The aim of this review is to appraise current research which examines the impact of early rehabilitation practices on functional outcomes and quality of life in adult intensive care unit (ICU) survivors. A systematic literature search was undertaken; retrieved data was evaluated against a recognised evaluation tool; research findings were analysed and categorised into themes; and a synthesis of conclusions from each theme was presented as an integrated summation of the topic. Electronic databases of PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Ovid Medline and Google Scholar were searched using key search terms 'ICU acquired weakness', 'early rehabilitation' 'early mobility' and 'functional outcomes' combined with 'intensive care' and 'critical illness'. Additional literature was sourced from reference lists of relevant original publications. Five major themes related to the review objectives emerged from the analysis. These themes included: critically ill patients do not always receive physical therapy as a standard of care; ICU culture and resources determine early rehabilitation success; successful respiratory and physical rehabilitation interventions are tailored according to individual patient impairment; early exercise in the ICU prevents the neuromuscular complications of critical illness and improves functional status; early exercise in the ICU is effective, safe and feasible. A limited body of research supports early rehabilitation interventions to optimise the short term outcomes and long term quality of life for ICU survivors. Critical care nurses are in an excellent position to drive change within their departments ensuring that early rehabilitation practices are adopted and implemented. Copyright © 2015 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

Hematopoietic cytokines as therapeutic players in early stages Parkinson’s disease

Directory of Open Access Journals (Sweden)

Kyle eFarmer

2015-07-01

Full Text Available Parkinson's disease (PD is a devastating age related neurodegenerative disease that is believed to have a lengthy prodromal state. It is critical to find methods of interfering with the progression of this early degenerative stage by inducing compensatory recovery processes to slow or prevent the eventual clinical symptoms. The current perspective article argues that immune system signalling molecules represent such a promising therapeutic approach. Two cytokines of interest are granulocyte macrophage-colony stimulating factor (GM-CSF and erythropoietin (EPO. These hematopoietic cytokines have been protective in models of stroke, neuronal injury, and more recently PD. It is our belief that these trophic cytokines can be used not only for cell protection but also regeneration. However, success is likely dependent on early intervention. This paper will outline our perspective on the development of novel trophic recovery treatments for PD. In particular, we present new data from our lab suggesting that EPO and GM-CSF can foster neural re-innervation in a mild or partial lesion PD model that could be envisioned as reflecting the early stages of the disease.

Erythropoietin enhances hippocampal long-term potentiation and memory

Directory of Open Access Journals (Sweden)

El-Kordi Ahmed

2008-09-01

Full Text Available Abstract Background Erythropoietin (EPO improves cognition of human subjects in the clinical setting by as yet unknown mechanisms. We developed a mouse model of robust cognitive improvement by EPO to obtain the first clues of how EPO influences cognition, and how it may act on hippocampal neurons to modulate plasticity. Results We show here that a 3-week treatment of young mice with EPO enhances long-term potentiation (LTP, a cellular correlate of learning processes in the CA1 region of the hippocampus. This treatment concomitantly alters short-term synaptic plasticity and synaptic transmission, shifting the balance of excitatory and inhibitory activity. These effects are accompanied by an improvement of hippocampus dependent memory, persisting for 3 weeks after termination of EPO injections, and are independent of changes in hematocrit. Networks of EPO-treated primary hippocampal neurons develop lower overall spiking activity but enhanced bursting in discrete neuronal assemblies. At the level of developing single neurons, EPO treatment reduces the typical increase in excitatory synaptic transmission without changing the number of synaptic boutons, consistent with prolonged functional silencing of synapses. Conclusion We conclude that EPO improves hippocampus dependent memory by modulating plasticity, synaptic connectivity and activity of memory-related neuronal networks. These mechanisms of action of EPO have to be further exploited for treating neuropsychiatric diseases.

Diurnal levels of immunoreactive erythropoietin in normal subjects and subjects with chronic lung disease

Energy Technology Data Exchange (ETDEWEB)

Miller, M.E.; Garcia, J.F.; Cohen, R.A.; Cronkite, E.P.; Moccia, G.; Acevedo, J.

1981-10-01

Serum levels of immunoreactive erythropoietin (Ep) were measured in 48 normal male and female volunteers, ages 20-60 years, to establish a control value for Ep of 18.5 +/- 5.0 (mean +/- SD) mU/ml. Levels of the hormone were also measured sequentially over a 24 h period of time in an additional 17 normal volunteers with no diurnal variation. Diurnal levels of immunoreactive Ep were also measured in 30 subjects, with chronic lung disease. These patients, in contrast to normal subjects exhibited a diurnal variation in the level of immunoreactive Ep with peak levels occurring at midnight. The only variable measured which correlated with the serum immunoreactive Ep level in subjects with chronic lung disease was the level of carboxyhaemoglobin (P less than 0.02).

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.

Effect of recombinant erythropoietin on inflammatory markers in patients with affective disorders

DEFF Research Database (Denmark)

Vinberg, Maj; Weikop, Pia; Olsen, Niels Vidiendal

2016-01-01

Aim: This study investigated the effect of repeated infusions of recombinant human erythropoietin (EPO) on markers of inflammation in patients with affective disorders and whether any changes in inflammatory markers were associated with improvements on verbal memory. Methods: In total, 83 patients......). In both sub-studies, patients were randomised in a double-blind, parallel-group design to receive eight weekly intravenous infusions of EPO (Eprex; 40,000 IU/ml) or saline (0.9% NaCl). Plasma concentrations of interleukin 6 (IL-6), interleukin 18 (IL-18) and high sensitive c-reactive protein (hsCRP) were...... and change in verbal memory. Conclusions: Repeated EPO infusions had no effect on IL-6 and IL-18 levels but produced a modest increase in hsCRP levels in patients with TRD. Changes over time in inflammatory markers were not correlated with changes in cognition suggesting that modulation of the inflammatory...

Early site reviews for nuclear power facilities: procedures and possible technical review options. Draft

International Nuclear Information System (INIS)

1978-02-01

The document provides guidance for utility companies, State and other governmental agencies, and others who may request or may wish to participate in an early review of site suitability issues related to a site proposed for a nuclear power or test reactor. Although the emphasis of this document is on a nuclear electric generating station, the guidance provided can be used for a test reactor or other kinds of reactors. The procedures to be followed by applicants for construction permits and by others are described and the possible significant areas of technical review are delineated

Legitimation for Early and Rapid Internationalization: A Review of Research in International Entrepreneurship

DEFF Research Database (Denmark)

Laine, Igor; Kuivalainen, Olli; Marinova, Svetla Trifonova

In this paper we respond to Cavusgil and Knight’s call for future research to address the question of born global firms overcome inherent liabilities to achieve legitimacy in foreign markets. To contribute to this call, we have systematically reviewed the extant international entrepreneurship...... literature. By analyzing existing evidence on building organizational legitimacy by early and rapidly internationalizing firms, our review helps to understand reasons and underlying mechanisms of successful legitimation of early and rapid internationalization thus ultimately explaining existence...... entrepreneurship....

Living with early-stage dementia: a review of qualitative studies.

Science.gov (United States)

Steeman, Els; de Casterlé, Bernadette Dierckx; Godderis, Jan; Grypdonck, Mieke

2006-06-01

This paper presents a literature review whose aim was to provide better understanding of living with early-stage dementia. Even in the early stages, dementia may challenge quality of life. Research on early-stage dementia is mainly in the domain of biomedical aetiology and pathology, providing little understanding of what it means to live with dementia. Knowledge of the lived experience of having dementia is important in order to focus pro-active care towards enhancing quality of life. Qualitative research is fundamentally well suited to obtaining an insider's view of living with early-stage dementia. We performed a meta-synthesis of qualitative research findings. We searched MEDLINE, CINAHL, and PsycINFO and reviewed the papers cited in the references of pertinent articles, the references cited in a recently published book on the subjective experience of dementia, one thesis, and the journal Dementia. Thirty-three pertinent articles were identified, representing 28 separate studies and 21 different research samples. Findings were coded, grouped, compared and integrated. Living with dementia is described from the stage a person discovers the memory impairment, through the stage of being diagnosed with dementia, to that of the person's attempts to integrate the impairment into everyday life. Memory loss often threatens perceptions of security, autonomy and being a meaningful member of society. At early stages of memory loss, individuals use self-protecting and self-adjusting strategies to deal with perceived changes and threats. However, the memory impairment itself may make it difficult for an individual to deal with these changes, thereby causing frustration, uncertainty and fear. Our analysis supports the integration of proactive care into the diagnostic process, because even early-stage dementia may challenge quality of life. Moreover, this care should actively involve both the individual with dementia and their family so that both parties can adjust positively

Further evidence of the in vivo role of erythropoietin or companion molecules induced by hypoxia on proliferation and continuing differentiation of BFU-e in PCDC

International Nuclear Information System (INIS)

Harigaya, K.; Cronkite, E.P.; Miller, M.E.; Moccia, G.

1981-01-01

Normal and plethoric bone marrow cells were grown in plasma clot diffusion chambers (PCDC) implanted into the peritoneum of normal mice or mice submitted to 7 h of hypoxia (23,000 ft) daily, on a single day or on 2 consecutive days at different times after implantation of the PCDC's. Daily discontinuous hypoxia (DDH) produced more 6-day bursts than other treatments. Hypoxia on days 1 and 2 after implantation was nearly as effective as DDH on day-6 bursts. Erythropoietin (Ep) levels were measured by bioassay on both diffusion chamber (DC) contents and serum. Serum Ep levels peaked after a 7-hr hypoxic exposure while the DC content Ep levels were in the nondetectable range. The data implies that either higher than normal Ep levels or a companion molecule(s) produced by hypoxia are required for 1 to 2 days early in the culture period to force an increasing number of BFU-d-e down the erythrocytic pathway and thus increase red cell production at times of need in vivo

Pharmacodynamically optimized erythropoietin treatment combined with phlebotomy reduction predicted to eliminate blood transfusions in selected preterm infants.

Science.gov (United States)

Rosebraugh, Matthew R; Widness, John A; Nalbant, Demet; Cress, Gretchen; Veng-Pedersen, Peter

2014-02-01

Preterm very-low-birth-weight (VLBW) infants weighing eliminated by reducing laboratory blood loss in combination with pharmacodynamically optimized erythropoietin (Epo) treatment. Twenty-six VLBW ventilated infants receiving RBCTx were studied during the first month of life. RBCTx simulations were based on previously published RBCTx criteria and data-driven Epo pharmacodynamic optimization of literature-derived RBC life span and blood volume data corrected for phlebotomy loss. Simulated pharmacodynamic optimization of Epo administration and reduction in phlebotomy by ≥ 55% predicted a complete elimination of RBCTx in 1.0-1.5 kg infants. In infants 1.0 kg.

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

DEFF Research Database (Denmark)

Rasmussen, Peter; Nordsborg, Nikolai; Taudorf, Sarah

2012-01-01

these findings apply to humans remains unknown. We exposed healthy young subjects to hypoxia (equivalent to 3800 m) and measured EPO in arterial and jugular venous plasma and in cerebrospinal fluid. To examine the role of the skin for EPO production during hypoxia, subjects were exposed to 8 h of hypobaric......Erythropoietin (EPO) preserves arterial oxygen content by controlling red blood cell and plasma volumes. Synthesis of EPO was long thought to relate inversely to renal oxygenation, but in knockout mice, brain and skin have been identified as essential for the acute hypoxic EPO response. Whether...

Early management of acute pancreatitis: A review of the best evidence.

Science.gov (United States)

Stigliano, Serena; Sternby, Hanna; de Madaria, Enrique; Capurso, Gabriele; Petrov, Maxim S

2017-06-01

In the 20th century early management of acute pancreatitis often included surgical intervention, despite overwhelming mortality. The emergence of high-quality evidence (randomized controlled trials and meta-analyses) over the past two decades has notably shifted the treatment paradigm towards predominantly non-surgical management early in the course of acute pancreatitis. The present evidence-based review focuses on contemporary aspects of early management (which include analgesia, fluid resuscitation, antibiotics, nutrition, and endoscopic retrograde cholangiopancreatography) with a view to providing clear and succinct guidelines on early management of patients with acute pancreatitis in 2017 and beyond. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Effect of carbamylated erythropoietin on retinopathy of diabetic rats

Institute of Scientific and Technical Information of China (English)

Lin Jiang

2017-01-01

Objective:To study the effect of carbamylated erythropoietin (CEPO) on retinopathy of diabetic rats.Methods: Male SD rats were selected as experimental animals and randomly divided into control group, DM group and CEPO group, and diabetic animal models were established and then given CEPO intervention. 2 weeks after intervention, the retina was collected to detect the expression of angiogenesis molecules, apoptosis molecules and oxidative stress pathway molecules.Results: HIF-1α, VEGF, Ang-1, Bax, Caspase-3, Nrf-2, ARE, HO-1 and NQO-1 mRNA expression in retina of DM group were significantly higher than those of control group while TKLK, PEDF, Bcl-2 and Survivin mRNA expression were significantly lower than those of control group; HIF-1α, VEGF, Ang-1, TKLK and PEDF mRNA expression in retina of CEPO group were not significantly different from those of DM group, Bcl-2, Survivin, Nrf-2, ARE, HO-1 and NQO-1 mRNA expression were significantly higher than those of DM group, and Bax and Caspase-3 mRNA expression were significantly lower than those of DM group.Conclusion:CEPO can reduce the apoptosis and oxidative stress injury of the retina tissue in diabetic rats without affecting the angiogenesis.

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...

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

DEFF Research Database (Denmark)

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

2016-01-01

MRI at 3T, mood ratings, and blood tests at baseline and week 14. During fMRI, participants performed a picture encoding task followed by postscan recall. RESULTS: Sixty-two patients had complete data (EPO: N = 32, saline: N = 30). EPO improved picture recall and increased encoding-related activity......OBJECTIVE: Erythropoietin (EPO) improves verbal memory and reverses subfield hippocampal volume loss across depression and bipolar disorder (BD). This study aimed to investigate with functional magnetic resonance imaging (fMRI) whether these effects were accompanied by functional changes in memory...... in dorsolateral prefrontal cortex (dlPFC) and temporo-parietal regions, but not in hippocampus. Recall correlated with activity in the identified dlPFC and temporo-parietal regions at baseline, and change in recall correlated with activity change in these regions from baseline to follow-up across the entire...

[Early detection of ovarian cancer: tomorrow? A review].

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Chene, G; Penault-Llorca, F; Robin, N; Cayre, A; Provencher, D M; Dauplat, J

2013-02-01

Ovarian cancer is the most lethal of the gynaecological malignancies because this «silent killer» is almost always diagnosed at an advanced stage. Precursor lesions have at least been discovered. This review will describe in details specific features of tubal and ovarian preinvasive lesions and the old and novel techniques that could be used for early detection of ovarian cancer. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Methodological Reflections on the Use of Systematic Reviews in Early Childhood Research

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Ang, Lynn

2018-01-01

This article sets out to look critically at the use of systematic reviews in the cross-disciplinary field of early childhood and international development. Systematic reviews--a specialist methodology involving the secondary analysis of existing knowledge on a particular topic--is prevalently used to address complex questions in social and…

Early Pregnancy Losses: Review of Nomenclature, Histopathology, and Possible Etiologies.

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Pinar, M Halit; Gibbins, Karen; He, Mai; Kostadinov, Stefan; Silver, Robert

2018-05-08

Miscarriage is a frequent complication of human pregnancy: ∼50% to 70% of spontaneous conceptions are lost prior to the second trimester. Etiology of miscarriage includes genetic abnormalities, infections, immunological and implantation disorders, uterine and endocrine abnormalities, and lifestyle factors. Given such variability, knowledge regarding causes, pathophysiological mechanisms, and morphologies of primary early pregnancy loss has significant gaps; often, pregnancy losses remain unexplained. Pathologic evaluation of miscarriage tissue is an untapped source of knowledge. Although miscarriage specimens comprise a significant part of pathologists' workload, information reported from these specimens is typically of minimal clinical utility for delineating etiology or predicting recurrence risk. Standardized terminology is available, though not universally used. We reintroduce the terminology and review new information about early pregnancy losses and their morphologies. Current clinical terminology is inconsistent, hampering research progress. This review is a resource for diagnostic pathologists studying this complex problem.

Erythropoietin reduces the expression of myostatin in mdx dystrophic mice

International Nuclear Information System (INIS)

Feder, D.; Rugollini, M.; Santomauro, A. Jr; Oliveira, L.P.; Lioi, V.P.; Santos, R. dos; Ferreira, L.G.; Nunes, M.T.; Carvalho, M.H.; Delgado, P.O.; Carvalho, A.A.S.; Fonseca, F.L.A.

2014-01-01

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

Erythropoietin reduces the expression of myostatin in mdx dystrophic mice

Energy Technology Data Exchange (ETDEWEB)

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

2014-09-05

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

Radioimmunoassay of erythropoietin: analytical performance and clinical use in hematology.

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Schlageter, M H; Toubert, M E; Podgorniak, M P; Najean, Y

1990-10-01

We report here the performance of a recently commercialized radioimmunoassay kit for determining erythropoietin (EPO) in serum or plasma. The lower detection limit of the method was 3 U/L. Precision, analyzed by the variation coefficients between different assay runs and in the same experiment, was always less than 10%; accuracy was assessed by recovery and dilution tests. In anemic patients (hematocrit 18-39%), the concentration of EPO was logarithmically related to hematocrit. A relatively large dispersion of the results was noted, as reported by others with various RIAs. Patients with severe renal failure demonstrated a very low EPO value, whatever the degree of their anemia. In some chronic anemias resulting from malignancy, EPO concentrations were also relatively low. In the polycythemia vera group, the EPO mean was below normal for greater than 95% of the patients, whatever their clinical stage (first evaluation, relapse, or remission). In contrast, 91% of the patients with pure erythrocytosis had a normal or increased EPO value, even when the etiology was unknown. Measurement of EPO concentration may be useful for the clinical differentiation of myeloproliferative disorders and, subsequently, for their prognosis and choice of treatment.

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

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

2015-01-01

It is investigated if recombinant human erythropoietin (rHuEPO) treatment for 15 weeks (n = 8) reduces extracellular accumulation of metabolic stress markers such as lactate, H(+) , and K(+) during incremental exhaustive exercise. After rHuEPO treatment, normalization of blood volume...... and composition by hemodilution preceded an additional incremental test. Group averages were calculated for an exercise intensity ∼80% of pre-rHuEPO peak power output. After rHuEPO treatment, leg lactate release to the plasma compartment was similar to before (4.3 ± 1.6 vs 3.9 ± 2.5 mmol/min) and remained similar...... after hemodilution. Venous lactate concentration was higher (P release to the plasma compartment after rHuEPO was similar to before (19.6 ± 5.4 vs 17.6 ± 6.0 mmol/min) and remained similar after hemodilution. Nevertheless, venous p...

Practice patterns and outcomes associated with early sedation depth in mechanically ventilated patients: a systematic review protocol.

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Stephens, Robert J; Dettmer, Matthew R; Roberts, Brian W; Fowler, Susan A; Fuller, Brian M

2017-06-09

Mechanical ventilation is a commonly performed intervention in critically ill patients. Frequently, these patients experience deep sedation early in their clinical course. Emerging data suggest that the practice of early deep sedation may negatively impact patient outcomes. The purpose of this review is to assess the world's literature to describe and determine the impact of early deep sedation on the outcomes of mechanically ventilated patients. Randomised controlled trials and non-randomised studies will be eligible for inclusion in this systematic review. With the assistance of a medical librarian, we will comprehensively search MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews and Effects, and Cochrane Database of Systematic Reviews for peer-reviewed literature. Grey literature from appropriate professional society conferences, held from 2010 to 2017, will be reviewed manually. Two authors will independently review all search results, and disagreements will be resolved through arbitration by a third author. If appropriate, meta-analysis will be used for quantitative analysis of the data. Heterogeneity between studies will be assessed using the I 2 statistic. The proposed systematic review will not collect data that are associated with individual patients and does not require ethical approval. Results of this study will contribute to the understanding of early sedation, identify future research targets and guide early care in mechanically ventilated patients. This systematic review has been registered in the international prospective register of systematic reviews (PROSPERO #CRD42017057264). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Endogenous erythropoietin protects neuroretinal function in ischemic retinopathy.

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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.

Promoting Early Child Development With Interventions in Health and Nutrition: A Systematic Review.

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Vaivada, Tyler; Gaffey, Michelle F; Bhutta, Zulfiqar A

2017-08-01

Although effective health and nutrition interventions for reducing child mortality and morbidity exist, direct evidence of effects on cognitive, motor, and psychosocial development is lacking. To review existing evidence for health and nutrition interventions affecting direct measures of (and pathways to) early child development. Reviews and recent overviews of interventions across the continuum of care and component studies. We selected systematic reviews detailing the effectiveness of health or nutrition interventions that have plausible links to child development and/or contain direct measures of cognitive, motor, and psychosocial development. A team of reviewers independently extracted data and assessed their quality. Sixty systematic reviews contained the outcomes of interest. Various interventions reduced morbidity and improved child growth, but few had direct measures of child development. Of particular benefit were food and micronutrient supplementation for mothers to reduce the risk of small for gestational age and iodine deficiency, strategies to reduce iron deficiency anemia in infancy, and early neonatal care (appropriate resuscitation, delayed cord clamping, and Kangaroo Mother Care). Neuroprotective interventions for imminent preterm birth showed the largest effect sizes (antenatal corticosteroids for developmental delay: risk ratio 0.49, 95% confidence interval 0.24 to 1.00; magnesium sulfate for gross motor dysfunction: risk ratio 0.61, 95% confidence interval 0.44 to 0.85). Given the focus on high-quality studies captured in leading systematic reviews, only effects reported within studies included in systematic reviews were captured. These findings should guide the prioritization and scale-up of interventions within critical periods of early infancy and childhood, and encourage research into their implementation at scale. Copyright © 2017 by the American Academy of Pediatrics.

Effect of intravenous iron saccharate on the requirements ofErythropoietin in Hemodialysis patients

International Nuclear Information System (INIS)

Shaheen, F.A.M.; Akeel, N.; Souqiyye, M.Z.

2002-01-01

We attempt in this study to evaluate the effect of intravenous ironsaccharate (i.v. Sach) on the erythropoietin (EPO) requirements during theinitial phase of replacement therapy with recombinant human erythropoietin(r-HuEPO) in adult chronic hemodialysis (HD) patients. We evaluated 96 studypatients who completed 12 weeks of treatment with EPO. There were 69 (72%)males and 27 (28%) females with a mean age of 44+-10 years (range 24 to 74years). The patients were initiated on EPO at 50 units/kg body weightsubcutaneously post-dialysis two to three times weekly. Intravenous iron wasadministered to maintain the ferritin levels and transferrin saturation ratiowithin normal range. There were 36 (37.5%) patients who received i.v. Sach atdoses of 100 mg at the end of dialysis two or three times per week during thewhole study period (total dose 2400-3600 mg). Of the 96 study patients, 91(94.8%) responded to the EPO. The mean hemoglobin (Hb) at entry to the studywas 72+-84 g/L (range 52-88 g/L). There was significant increase of the meanHb to 108+-10 g/L (range 70-120 grams/L) at the end of study (P 0.2and ferritin 0.2 and ferritin >100ng/ml. There were 19 patients in group I (13 received i.v. Sach), 26 in groupII (16 received i.v. Sach) and 44 in group III (seven received i.v. Sach).There was a group of seven patients who had TSAT 100ng/ml, however, none received i.v. sach and they were not included in thestratification. There was no significant difference in the mean Hb betweenpatients who received and those who did not receive i.v. Sach in thesub-groups studied. However, there was a significant decrease in the meanweekly dose of EPO in the patients who received i.v. Sach. We conclude thatroutine use of i.v. iron supplementation in chronic HD patients receivingrecombinant EPO may be beneficial in the initial phase of treatment inattaining the target Hb with lower doses of EPO, regardless of the status ofthe iron indices. (author)

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

DEFF Research Database (Denmark)

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

2012-01-01

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

Prevention and early intervention to improve mental health in higher education students: a review.

Science.gov (United States)

Reavley, Nicola; Jorm, Anthony F

2010-05-01

The age at which most young people are in higher education is also the age of peak onset for mental and substance use disorders, with these having their first onset before age 24 in 75% of cases. In most developed countries, over 50% of young people are in higher education. To review the evidence for prevention and early intervention in mental health problems in higher education students. The review was limited to interventions targeted to anxiety, depression and alcohol misuse. Interventions to review were identified by searching PubMed, PsycINFO and the Cochrane Database of Systematic Reviews. Interventions were included if they were designed to specifically prevent or intervene early in the general (non-health professional) higher education student population, in one or more of the following areas: anxiety, depression or alcohol misuse symptoms, mental health literacy, stigma and one or more behavioural outcomes. For interventions to prevent or intervene early for alcohol misuse, evidence of effectiveness is strongest for brief motivational interventions and for personalized normative interventions delivered using computers or in individual face-to-face sessions. Few interventions to prevent or intervene early with depression or anxiety were identified. These were mostly face-to-face, cognitive-behavioural/skill-based interventions. One social marketing intervention to raise awareness of depression and treatments showed some evidence of effectiveness. There is very limited evidence that interventions are effective in preventing or intervening early with depression and anxiety disorders in higher education students. Further studies, possibly involving interventions that have shown promise in other populations, are needed.

Early Versus Delayed Motion After Rotator Cuff Repair: A Systematic Review of Overlapping Meta-analyses.

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Houck, Darby A; Kraeutler, Matthew J; Schuette, Hayden B; McCarty, Eric C; Bravman, Jonathan T

2017-10-01

Previous meta-analyses have been conducted to compare outcomes of early versus delayed motion after rotator cuff repair. To conduct a systematic review of overlapping meta-analyses comparing early versus delayed motion rehabilitation protocols after rotator cuff repair to determine which meta-analyses provide the best available evidence. Systematic review. A systematic review was performed by searching PubMed and Cochrane Library databases. Search terms included "rotator cuff repair," "early passive motion," "immobilization," "rehabilitation protocol," and "meta-analysis." Results were reviewed to determine study eligibility. Patient outcomes and structural healing were extracted from these meta-analyses. Meta-analysis quality was assessed using the Oxman-Guyatt and Quality of Reporting of Meta-analyses (QUOROM) systems. The Jadad decision algorithm was then used to determine which meta-analyses provided the best level of evidence. Seven meta-analyses containing a total of 5896 patients met the eligibility criteria (1 Level I evidence, 4 Level II evidence, 2 Level III evidence). None of these meta-analyses found immobilization to be superior to early motion; however, most studies suggested that early motion would increase range of motion (ROM), thereby reducing time of recovery. Three of these studies suggested that tear size contributed to the choice of rehabilitation to ensure proper healing of the shoulder. A study by Chan et al in 2014 received the highest QUOROM and Oxman-Guyatt scores, and therefore this meta-analysis appeared to have the highest level of evidence. Additionally, a study by Riboh and Garrigues in 2014 was selected as the highest quality study in this systematic review according to the Jadad decision algorithm. The current, best available evidence suggests that early motion improves ROM after rotator cuff repair but increases the risk of rotator cuff retear. Lower quality meta-analyses indicate that tear size may provide a better strategy in

[Effects of benazepril and valsartan on erythropoietin levels in patients with essential hypertension].

Science.gov (United States)

Guo, Lin-lin; Li, Min; Wang, Ai-hong

2011-10-01

To compare effects of valsartan and benazepril on erythropoietin (EPO) levels in essential hypertensive patients with normal renal function. Sixty essential hypertensive patients were randomly divided into valsartan group (n=30, valsartan 80 mg/day) and benazepril group (n=30, benazepril 10 mg/day). Plasma EPO and hemoglobin (Hb) levels were measured at the start of and at 4 and 8 weeks during the treatments. EPO and Hb levels were all in normal range in the two groups. Valsartan decreased EPO levels from 14.179∓3.214 U/L (baseline) to 12.138∓2.926 U/L (PBenazepril treatment did not resulted in any obvious changes in EPO or Hb levels (P>0.05). Valsartan may lower EPO and Hb levels in patients with essential hypertension, while benazepril does not have such effects. The safety of valsartan in anemic hypertensive patients should be further investigated.

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

DEFF Research Database (Denmark)

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

2011-01-01

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

Comparison of Dosage Requirement of Erythropoietin Stimulating Agent (ESA in Maintenance of Hemoglobin Concentration in patients undergoing twice weekly versus thrice weekly Hemodialysis in Pakistani Population

Directory of Open Access Journals (Sweden)

Osama Kunwer Naveed

2018-03-01

Full Text Available Anemia is one of the major complications of patients with chronic kidney disease (CKD undergoing hemodialysis (HD and is associated with left ventricular hypertrophy and also increases morbidity and mortality. Anemia in patients with CKD can be due to two major reasons; iron deficiency or erythropoietin insufficiency. Erythropoietin Stimulating Agent (ESAs administration is the mainstay in treating anemia if the patient is iron sufficient. However, higher doses of ESAs have been associated with increased cerebrovascular and cardiovascular events. We conducted this study to see how much erythropoietin is required in our setting in iron sufficient patients to maintain hemoglobin(Hb  level and the effect of dialysis frequency on ESA doses.  Methods and Findings: A cross-sectional study was conducted at the Department of Nephrology at Ziauddin University Hospital. Patients’ charts were reviewed for Hb levels and doses of ESA to maintain Hb between 10-12 mg/dl. Patients were excluded if they had iron deficiency, malignancy, were on immunosuppressive agents, had renal transplant, and with Hb >12 mg/dl or <10 mg/dl and their ferritin levels, transferrin saturation, hemoglobin concentration, frequency of hemodialysis and ESA dosage were monitored. We also compared these variables between patients undergoing hemodialysis thrice weekly with those undergoing hemodialysis twice a week. A total of 105 patients were analyzed. 24 were excluded as they did not match the inclusion criteria. 81 patients were included in the study. 36 (44.4% were males and 45 (55.6% were females. Mean age of the patient was 56.47 ± 11.72 years. The average dose of ESA was 106.91 ± 61.47 for patients undergoing hemodialysis thrice weekly and 183.94 ± 116.71 for patients undergoing hemodialysis twice a week. Significant difference was found to exist between dosage of patients undergoing thrice weekly dialysis versus twice weekly dialysis(p=<0.001.  Our study has limitations

Does Erythropoietin Regulate TRPC Channels in Red Blood Cells?

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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.

Optimizing Combinations of Flavonoids Deriving from Astragali Radix in Activating the Regulatory Element of Erythropoietin by a Feedback System Control Scheme

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Hui Yu

2013-01-01

Full Text Available Identifying potent drug combination from a herbal mixture is usually quite challenging, due to a large number of possible trials. Using an engineering approach of the feedback system control (FSC scheme, we identified the potential best combinations of four flavonoids, including formononetin, ononin, calycosin, and calycosin-7-O-β-D-glucoside deriving from Astragali Radix (AR; Huangqi, which provided the best biological action at minimal doses. Out of more than one thousand possible combinations, only tens of trials were required to optimize the flavonoid combinations that stimulated a maximal transcriptional activity of hypoxia response element (HRE, a critical regulator for erythropoietin (EPO transcription, in cultured human embryonic kidney fibroblast (HEK293T. By using FSC scheme, 90% of the work and time can be saved, and the optimized flavonoid combinations increased the HRE mediated transcriptional activity by ~3-fold as compared with individual flavonoid, while the amount of flavonoids was reduced by ~10-fold. Our study suggests that the optimized combination of flavonoids may have strong effect in activating the regulatory element of erythropoietin at very low dosage, which may be used as new source of natural hematopoietic agent. The present work also indicates that the FSC scheme is able to serve as an efficient and model-free approach to optimize the drug combination of different ingredients within a herbal decoction.

A critical review of the literature on early rehabilitation of patients with post-traumatic amnesia in acute care

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Langhorn, Leanne; Sorensen, Jens C; Pedersen, Preben U

2010-01-01

A critical review of the literature on early rehabilitation of patients with post-traumatic amnesia in acute care......A critical review of the literature on early rehabilitation of patients with post-traumatic amnesia in acute care...

Consequences of early extraction of compromised first permanent molar: a systematic review.

Science.gov (United States)

Saber, Afnan M; Altoukhi, Doua H; Horaib, Mariam F; El-Housseiny, Azza A; Alamoudi, Najlaa M; Sabbagh, Heba J

2018-04-05

The aim of this study was to systematically review the literature to determine the sequelae of early extraction of compromised first permanent molars (FPMs) with regard to the skeletal and dental development of 5- to 15-year-old children. Meta-analysis was conducted when applicable. Our research protocol included a search strategy, inclusion/exclusion criteria, and a data extraction plan. The search engines used were PubMed, Scopus, and Science Direct. Study selection was performed independently by three reviewers. Articles published from 1960 to 2017 were reviewed based on inclusion and exclusion criteria. Meta-analysis was performed to compare space closure between upper and lower arches. Eleven studies fulfilled the inclusion criteria. The consequences were decrease in post extraction space, accelerated development and eruption of second permanents molars (SPMs) and third molars, a decrease in caries and/or fillings on the proximal surfaces of adjacent teeth, lingual tipping and retrusion of incisors, and counter clockwise rotation of the occlusal plane. There were several consequences of early extraction of FPMs, which were related to skeletal and dental development. Our systematic review suggests that comprehensive evaluation of the compromised FPMs should be performed before planning an extraction. The ideal time for FPM extraction is when the SPM is at the early bifurcation stage in order to achieve complete closure of the extraction space by the SPM. Benefits should be weighed over the risks to decrease the risk of unfavorable outcomes as much as possible. However, due to the limited evidence on the outcomes and variables that influence them, high-quality prospective studies are needed.

Erythropoietin reduces neural and cognitive processing of fear in human models of antidepressant drug action

DEFF Research Database (Denmark)

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

2007-01-01

with reduced attention to fear. Erythropoietin additionally reduced recognition of fearful facial expressions without affecting recognition of other emotional expressions. These actions occurred in the absence of changes in hematological parameters. CONCLUSIONS: The present study demonstrates that Epo directly......) versus saline on the neural processing of happy and fearful faces in 23 healthy volunteers. Facial expression recognition was assessed outside the scanner. RESULTS: One week after administration, Epo reduced neural response to fearful versus neutral faces in the occipito-parietal cortex consistent...... study aimed to explore the effects of Epo on neural and behavioral measures of emotional processing relevant for depression and the effects of conventional antidepressant medication. METHODS: In the present study, we used functional magnetic resonance imaging to explore the effects of Epo (40,000 IU...

Stability of erythropoietin repackaging in polypropylene syringes for clinical use

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Angela Marsili

2017-02-01

Full Text Available Introduction: Epoetin alfa (Eprex® is a subcutaneous, injectable formulation of short half-life recombinant human erythropoietin (rHuEPO. To current knowledge there are no published studies regarding the stability of rHuEPO once repackaging occurs (r-EPO for clinical trial purposes. Materials and methods: We assessed EPO concentration in Eprex® and r-EPO syringes at 0, 60, 90, and 120 days after repackaging in polypropylene syringes. R-EPO was administered to 56 patients taking part in a clinical trial in Friedreich Ataxia. Serum EPO levels were measured at baseline and 48 h after r-EPO administration. Results: No differences were found between r-EPO and Eprex® syringes, but both globally decreased in total EPO content during storage at 4 °C. Patients receiving r-EPO had similar levels in EPO content as expected from previous trials in Friedreich Ataxia and from pharmacokinetics studies in healthy volunteers. Discussion: We demonstrate that repackaging of EPO does not alter its concentration if compared to the original product (Eprex®. This is true both for repackaging procedures and for the stability in polypropylene tubes. The expiration date of r-EPO can be extended from 1 to 4 months after repackaging, in accordance with pharmacopeia rules.

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

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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.

Blood rheology and 2,3-diphosphoglycerate levels after erythropoietin treatment.

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Crowley, J P; Chazan, J A; Metzger, J B; Pono, L; Valeri, C R

1993-01-01

Twenty-seven transfusion dependent patients with end-stage renal disease on long-term dialysis had blood cell counts, serum chemistries, blood pressure, and whole blood viscosity measured, as well as having transfusion requirements assessed. Three months after the institution of recombinant human erythropoietin (rHU-EPO) (75 u per kg per wk), there was an 88 percent fall in transfusion requirement. After four months, the hematocrit increased from 24 +/- 3.8 to 25.6 +/- 4.2 percent, mean corpuscular volume from 93 +/- 4.9 to 97 +/- 6.6 fl, 2-3-diphosphoglycerate (2,3-DPG) from 13.2 +/- 3.2 to 15.6 +/- 4.3 microM per g of Hb. Whole blood viscosity fell from 14.1 +/- 2.1 to 12.7 +/- 2.3 seconds, and ferritin levels fell from 3282 +/- 3889 to 2131 +/- 2441 ng per ml. In eight patients in whom the dose of rHU-EPO was further increased by up to 50 units per kg three times weekly for three months, the hematocrit rose further to 29.3 +/- 3.0 percent and the rise in hematocrit was accompanied by a further increase in 2,3-DPG to 17.9 +/- 2.8 microM per g of Hb (p < 0.03). There were no major side effects or vascular complications.

Increased red cell 2,3-diphosphoglycerate levels in haemodialysis patients treated with erythropoietin.

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Horina, J H; Schwaberger, G; Brussee, H; Sauseng-Fellegger, G; Holzer, H; Krejs, G J

1993-01-01

The efficacy of recombinant human erythropoietin (rHuEpo) for the treatment of renal anaemia is well established. To assess the effect of rHuEpo treatment on physical performance we evaluated physical working capacity, oxygen uptake and red cell 2,3-diphosphoglycerate (DPG) values at rest and during and after exercise on a bicycle spiroergometer in eight chronically haemodialysed patients. Follow-up examination was carried out after a mean of 14 weeks (range 9-19 weeks), when mean haemoglobin had increased from 7.8 to a stable value of 13.0 g/dl in response to rHuEpo treatment (P level without rHuEpo treatment than after correction of anaemia. Therefore rHuEpo treatment results both in better oxygen transport capacity and reduced intraerythrocytic oxygen affinity, which is followed by improved oxygen delivery to tissues per unit of haemoglobin. These effects may explain the improvement of exercise capacity observed in dialysis patients after rHuEpo treatment.

Beyond anaemia management: evolving role of erythropoietin therapy in neurological disorders, multiple myeloma and tumour hypoxia models.

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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.

THE ROLE OF ERYTHROPOIETIN IN TREATMENT OF ANEMIA IN CANCER PATIENTS

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P. G. Berezin

2017-01-01

Full Text Available Malignant neoplasms are a serious pathological condition, both in terms of the course of the disease and the need for treatment, and a prognosis for the life of patients. The deterioration in the quality of life, social disadaptation (reduced physical activity, job change, fatigue, etc. is a complication of the course of the disease caused by the development of anemia, which requires a vital need for its correction. This article analyzes the efficacy of recombinant erythropoietin — Epoetin-theta in the treatment of patients with NON — myeloid tumors and CRF (chronic renal failure in cancer patients. The high efficacy and safety of drug therapy in this category of patients are demonstrated. Recommendations are given on the optimal dose of the drug in order to obtain the most pronounced clinical effect of treatment, increasing the therapeutic dose of the drug with an insufficient increase in the hemoglobin level by 100% or more allows an individual approach to the correction of anemia. The possibility of its application in routine clinical practice of the oncologist’s doctor, namely in out-patientpolyclinic conditions, has been determined.

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

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

2015-12-01

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

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

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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 Effectiveness of Peer Review of Teaching When Performed between Early-Career Academics

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Woodman, Richard J.; Parappilly, Maria B.

2015-01-01

The success of peer review of teaching (PRT) in shaping teaching practice during an academic's formative years may depend on the peers' teaching experience and the frequency of evaluation. Two Australian early-career University lecturers with no previous experience of peer review performed a single PRT on one another following a one week academic…

Early years interventions to improve child health and wellbeing: what works, for whom and in what circumstances? Protocol for a realist review.

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Coles, Emma; Cheyne, Helen; Daniel, Brigid

2015-06-06

Child health and wellbeing is influenced by multiple factors, all of which can impact on early childhood development. Adverse early life experiences can have lasting effects across the life course, sustaining inequalities and resulting in negative consequences for the health and wellbeing of individuals and society. The potential to influence future outcomes via early intervention is widely accepted; there are numerous policy initiatives, programmes and interventions clustered around the early years theme, resulting in a broad and disparate evidence base. Existing reviews have addressed the effectiveness of early years interventions, yet there is a knowledge gap regarding the mechanisms underlying why interventions work in given contexts. This realist review seeks to address the question 'what works, for whom and in what circumstances?' in terms of early years interventions to improve child health and wellbeing. The review will be conducted following Pawson's five-stage iterative realist methodology: (1) clarify scope, (2) search for evidence, (3) appraise primary studies and extract data, (4) synthesise evidence and draw conclusions and (5) disseminate findings. The reviewers will work with stakeholders in the early stages to refine the focus of the review, create a review framework and build programme theory. Searches for primary evidence will be conducted iteratively. Data will be extracted and tested against the programme theory. A review collaboration group will oversee the review process. The review will demonstrate how early years interventions do or do not work in different contexts and with what outcomes and effects. Review findings will be written up following the RAMESES guidelines and will be disseminated via a report, presentations and peer-reviewed publications. PROSPERO CRD42015017832.

Integrating Early Child Development and Violence Prevention Programs: A Systematic Review

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Efevbera, Yvette; McCoy, Dana C.; Wuermli, Alice J.; Betancourt, Theresa S.

2018-01-01

Limited evidence describes promoting development and reducing violence in low- and middle-income countries (LMICs), a missed opportunity to protect children and promote development and human capital. This study presents a systematic literature review of integrated early childhood development plus violence prevention (ECD+VP) interventions in…

Use of Erythropoietin-Stimulating Agents (ESA) in Patients With End-Stage Renal Failure Decided to Forego Dialysis: Palliative Perspective.

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Cheng, Hon Wai Benjamin; Chan, Kwok Ying; Lau, Hoi To; Man, Ching Wah; Cheng, Suk Ching; Lam, Carman

2017-05-01

Normochromic normocytic anemia is a common complication in chronic kidney disease (CKD) and is associated with many adverse clinical consequences. Erythropoiesis-stimulating agents (ESAs) act to replace endogenous erythropoietin for patients with end-stage renal disease having anemia. Today, ESAs remain the main tool for treating anemia associated with CKD. In current practice, the use of ESA is not limited to the patients on renal replacement therapy but has extended to nondialysis patients under palliative care (PC). Current evidence on ESA usage in patients with CKD decided to forego dialysis often have to take reference from studies conducted in other groups of patients with CKD, including pre-dialysis patients and those on renal replacement therapy. There is paucity of studies targeting use of ESAs in renal PC patients. Small-scale retrospective study in renal PC patients had suggested clinical advantage of ESAs in terms of hemoglobin improvement, reduction in fatigue, and hospitalization rate. With the expected growth in elderly patients with CKD decided to forego dialysis and manage conservatively, there remains an urgent need to call for large-scale prospective trial in exploring efficacy of ESAs in this population, targeting on quality of life and symptoms improvement outcome. This article also reviews the mechanism of action, pharmacology, adverse effects, and clinical trial evidence for ESA in patients with CKD under renal PC.

Larynx cancer in early stages: bibliographic review

International Nuclear Information System (INIS)

Umana Herrera, Vanessa

2014-01-01

A bibliographical analysis on the subject of early laryngeal cancer (neoplams staged as Tis, T1-T2 N0) was carried out through a bibliographic review of updated articles. The anatomy, epidemiology, generalities, clinical presentation and behavior of cancer were described. The biopsy, the clinical history, the physical examination and radiodiagnostic studies are used for a correct staging and according to the stage, to select the appropriate treatment. Treatment modalities and prescription dose for this type of cancer are compared and explained. The locoregional evaluation of glottic cancer is performed by Computed Axial Tomography (CAT), Nuclear Magnetic Resonance (NMR), Ultrasound (US) and Positron Emission Tomography-Computed Tomography (PET/CT). CAT and NMR have shown to be more accurate in the evaluation of glottic larynx cancer compared with clinical endoscopic examination alone. CAT, NMR, US and PET/CT were clearly more sensitive and specific in the assessment of the neck that only palpation. The preservation of the voice is an important parameter in choosing a therapeutic modality. Radiotherapy has proven to be the most used and known treatment. Radiation therapy with Cobalt 60 is commonly used in Costa Rica for the treatment of early larynx cancer [es

Recombinant human erythropoietin therapy in critically ill Jehovah's Witnesses.

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Ball, Amanda M; Winstead, P Shane

2008-11-01

Blood transfusions and blood products are often given as a life-saving measure in patients with critical illness. However, some patients, such as Jehovah's Witnesses, may refuse their administration due to religious beliefs. Jehovah's Witnesses accept most available medical treatments, but not blood transfusions or blood products due to their religion's interpretation of several passages from the Bible. Since recombinant human erythropoietin (rHuEPO) became available, several cases have been reported in which rHuEPO was successfully administered to critically ill Jehovah's Witnesses. Administration of rHuEPO in combination with other blood conservation techniques has been shown to increase hemoglobin levels and survival in patients who experienced trauma, burns, general surgery, or gastrointestinal hemorrhage. We performed a literature search of the MEDLINE and International Pharmaceutical Abstracts databases of rHuEPO therapy in the Jehovah's Witness population. Fourteen cases were identified in which rHuEPO was administered to Jehovah's Witnesses who required the drug for critical care resuscitation as an alternative to blood products. In each clinical situation, rHuEPO enhanced erythropoiesis; however, time to the start of treatment, dosages, route of administration, and treatment duration varied widely. Supplementation with adjunctive agents, such as iron, folic acid, and vitamin B12, was also beneficial. Use of rHuEPO in Jehovah's Witnesses may provide an alternative to blood transfusions or blood products. Other alternatives, such as hemoglobin-based oxygen carriers and perfluorocarbons, are also being explored.

Early Interventions Following the Death of a Parent: Protocol of a Mixed Methods Systematic Review.

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Pereira, Mariana; Johnsen, Iren; Hauken, May Aa; Kristensen, Pål; Dyregrov, Atle

2017-06-29

Previous meta-analyses examined the effectiveness of interventions for bereaved children showing small to moderate effect sizes. However, no mixed methods systematic review was conducted on bereavement interventions following the loss of a parent focusing on the time since death in regard to the prevention of grief complications. The overall purpose of the review is to provide a rigorous synthesis of early intervention after parental death in childhood. Specifically, the aims are twofold: (1) to determine the rationales, contents, timeframes, and outcomes of early bereavement care interventions for children and/or their parents and (2) to assess the quality of current early intervention studies. Quantitative, qualitative, and mixed methods intervention studies that start intervention with parentally bereaved children (and/or their parents) up to 6 months postloss will be included in the review. The search strategy was based on the Population, Interventions, Comparator, Outcomes, and Study Designs (PICOS) approach, and it was devised together with a university librarian. The literature searches will be carried out in the Medical Literature Analysis and Retrieval System Online (MEDLINE), PsycINFO, Excerpta Medica Database (EMBASE), and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The Mixed Methods Appraisal Tool will be used to appraise the quality of eligible studies. All data will be narratively synthetized following the Guidance on the Conduct of Narrative Synthesis in Systematic Reviews. The systematic review is ongoing and the data search has started. The review is expected to be completed by the end of 2017. Findings will be submitted to leading journals for publication. In accordance with the current diagnostic criteria for prolonged grief as well as the users' perspectives literature, this systematic review outlines a possible sensitive period for early intervention following the death of a parent. The hereby presented protocol ensures

Erythropoietin doping in cycling: lack of evidence for efficacy and a negative risk-benefit.

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Heuberger, Jules A A C; Cohen Tervaert, Joost M; Schepers, Femke M L; Vliegenthart, Adriaan D B; Rotmans, Joris I; Daniels, Johannes M A; Burggraaf, Jacobus; Cohen, Adam F

2013-06-01

Imagine a medicine that is expected to have very limited effects based upon knowledge of its pharmacology and (patho)physiology and that is studied in the wrong population, with low-quality studies that use a surrogate end-point that relates to the clinical end-point in a partial manner at most. Such a medicine would surely not be recommended. The use of recombinant human erythropoietin (rHuEPO) to enhance performance in cycling is very common. A qualitative systematic review of the available literature was performed to examine the evidence for the ergogenic properties of this drug, which is normally used to treat anaemia in chronic renal failure patients. The results of this literature search show that there is no scientific basis from which to conclude that rHuEPO has performance-enhancing properties in elite cyclists. The reported studies have many shortcomings regarding translation of the results to professional cycling endurance performance. Additionally, the possibly harmful side-effects have not been adequately researched for this population but appear to be worrying, at least. The use of rHuEPO in cycling is rife but scientifically unsupported by evidence, and its use in sports is medical malpractice. What its use would have been, if the involved team physicians had been trained in clinical pharmacology and had investigated this properly, remains a matter of speculation. A single well-controlled trial in athletes in real-life circumstances would give a better indication of the real advantages and risk factors of rHuEPO use, but it would be an oversimplification to suggest that this would eradicate its use. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

A literature review of the relationship between breastfeeding and early childhood caries

OpenAIRE

Narjes Amiri TehraniZadeh; Nahid Asgarizadeh; Vajihe Kamel

2012-01-01

Background and Aims: Improper feeding is one of the most important etiologic factors in early childhood caries (ECC). In some clinical trials, breast feeding (BF) is mentioned as a causing factor in ECC. Results in this topic are different or even controversial. It is vital that all general advices given out are consistent with general health education messages. The aim of this study was to conduct a systematic review on the relationship between breast feeding and early childhood caries. Mate...

Erythropoietin and vascular endothelial growth factor as risk markers for severe hypoglycaemia in type 1 diabetes

DEFF Research Database (Denmark)

Kristensen, P L; Pedersen-Bjergaard, U; Schalkwijk, C

2010-01-01

OBJECTIVE: Circulating erythropoietin (EPO) and vascular endothelial growth factor (VEGF) increase during hypoglycaemia and may represent protective hormonal counter-regulatory responses. We tested the hypothesis that low levels of EPO and VEGF are associated with a higher frequency of severe....... Plasma EPO and serum VEGF levels were measured at baseline with ELISA. Events of severe hypoglycaemia defined by third party assistance were recorded and validated in telephone interviews within 24 h. RESULTS: Totally 235 episodes of severe hypoglycaemia (1.1 episodes per patient-year) were reported...... mass index, HbAlc, C-peptide level or hypoglycaemia awareness status. The levels of VEGF were positively associated with age and female sex. CONCLUSIONS: Although several studies suggest that VEGF and EPO may affect brain function during hypoglycaemia, this study does not support random VEGF or EPO...

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

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

The effect of early postnatal discharge from hospital for women and infants: a systematic review protocol.

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Jones, Eleanor; Taylor, Beck; MacArthur, Christine; Pritchett, Ruth; Cummins, Carole

2016-02-08

The length of postnatal hospital stay has declined over the last 40 years. There is little evidence to support a policy of early discharge following birth, and there is some concern about whether early discharge of mothers and babies is safe. The Cochrane review on the effects of early discharge from hospital only included randomised controlled trials (RCTs) which are problematic in this area, and a systematic review including other study designs is required. The aim of this broader systematic review is to determine possible effects of a policy of early postnatal discharge on important maternal and infant health-related outcomes. A systematic search of published literature will be conducted for randomised controlled trials, non-randomised controlled trials (NRCTs), controlled before-after studies (CBA), and interrupted time series studies (ITS) that report on the effect of a policy of early postnatal discharge from hospital. Databases including Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and Science Citation Index will be searched for relevant material. Reference lists of articles will also be searched in addition to searches to identify grey literature. Screening of identified articles and data extraction will be conducted in duplicate and independently. Methodological quality of the included studies will be assessed using the Effective Practice and Organisation of Care (EPOC) criteria for risk of bias tool. Discrepancies will be resolved by consensus or by consulting a third author. Meta-analysis using a random effects model will be used to combine data. Where significant heterogeneity is present, data will be combined in a narrative synthesis. The findings will be reported according to the preferred reporting items for systematic reviews (PRISMA) statement. Information on the effects of early postnatal discharge from hospital will be important for policy makers and clinicians providing maternity care. This review will also identify any gaps in the current

Antioxidants may Attenuate Plasma Erythropoietin Decline after Hyperbaric Oxygen Diving.

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Mutzbauer, T S; Schneider, M; Neubauer, B; Weiss, M; Tetzlaff, K

2015-11-01

According to previous studies, plasma erythropoietin (EPO) may decrease after hyperbaric oxygen exposure due to oxidative stress. It is hypothesized that the decrease of EPO can be attenuated by oxygen free radical scavengers.The aim of the present study was to evaluate whether EPO plasma levels can be influenced by oral application of vitamin C and E before repeated hyperbaric oxygen exposure during diving. 16 healthy male police task force divers performed 3 morning dives on oxygen within a regular diving schedule on 3 consecutive days. They were randomized into either the placebo group or the vitamin group, receiving 1 g ascorbic acid and 600 IU D-α-tocopherol orally 60 min before the dive. Blood samples for EPO measurement were taken on days 1, 2, and 3 at T1, T3 and T5 60 min before and at T2, T4 and T6 60 min after each dive, respectively. A moderate decrease of EPO was observed beginning at T3 until T6 in the placebo group. The EPO concentrations in the vitamin group did not show relevant variations compared to baseline. Radical scavenging vitamins C and D may counteract hyperbaric oxygen related mechanisms reducing EPO production in hyperbaric oxygen exposure during diving. © Georg Thieme Verlag KG Stuttgart · New York.

Targeting higher ferritin concentrations with intravenous iron dextran lowers erythropoietin requirement in hemodialysis patients.

Science.gov (United States)

DeVita, M V; Frumkin, D; Mittal, S; Kamran, A; Fishbane, S; Michelis, M F

2003-11-01

Although clinical use of recombinant human erythropoietin (rHuEPO) since 1989 has improved anemia in most end-stage renal disease patients, there are still many hemodialysis patients unable to maintain an adequate hematocrit (HCT) without large doses of rHuEPO. This suggests that anemia is not solely a consequence of rHuEPO deficiency, but may be due to other factors including functional iron deficiency. Since the optimal prescription for iron replacement is not yet known, we evaluated the effect of intravenous iron dextran (IVFe) infusion on serum ferritin (SFer) concentration and rHuEPO dose. Our objective was to raise and maintain serum ferritin concentrations to 2 different levels above the National Kidney Foundation Dialysis Outcome Quality Initiative standard of 100 ng/ml to determine whether, and by what degree rHuEPO dose could be lowered. HD patients on i.v. rHuEPO with a SFer concentration > or = 70 ng/ml and an HCT of requirements.

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.

Serum immunoreactive erythropoietin in high altitude natives with and without excessive erythrocytosis.

Science.gov (United States)

León-Velarde, F; Monge, C C; Vidal, A; Carcagno, M; Criscuolo, M; Bozzini, C E

1991-05-01

We report the estimation of blood hemoglobin (Hb), arterial blood oxygen saturation (SaO2), and serum immunoreactive erythropoietin (siEPO) in a group of Peruvian workers residing in Cerro de Pasco at 4300 m showing "excessive erythrocytosis" (EE, Monge's disease, chronic mountain sickness). These estimates were compared with those of humans residing either in Cerro de Pasco and showing "normal erythrocytosis" (NE) or in Lima (sea level, SL) to determine whether Hb and SaO2 are related to siEPO in high altitude (HA) natives with NE or EE. The three parameters showed statistically significant differences between HA and SL groups--the values in SL being lower. Significant differences were also found between NE and EE groups in Hb and SaO2. There was no statistical difference in siEPo between the two groups. The results indicate, therefore, that HA residents who develop EE are not distinguishable from residents who develop NE on the basis of estimates of siEPO. As a result, siEPO and Hb do not show a dose-response relationship in HA residents, and variation in EPO does not explain the striking variation in Hb at high altitudes.

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

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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

Use of high-dose erythropoietin for repair after injury: A comparison of outcomes in heart and kidney.

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

2013-07-01

There is a need to define the exact benefits and contraindications of use of high-dose recombinant human erythropoietin (EPO) for its non-hematopoietic function as a cytokine that enhances tissue repair after injury. This review compares the outcomes from use of EPO in the injured heart and kidney, two organs that are thought, traditionally, to have intrinsically-different repair mechanisms. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Ongoing work by us on EPO protection of ischemia-reperfusion-injured kidneys indicated, first, that EPO acutely enhanced kidney repair via anti-apoptotic, pro-regenerative mechanisms, and second, that EPO may promote chronic fibrosis in the long term. Work by others on the ischaemia-injured heart has also indicated that EPO promotes repair. Although myocardial infarcts are made up mostly of necrotic tissue, many publications state EPO is anti-apoptotic in the heart, as well as promoting healing via cell differentiation and stimulation of granulation tissue. In the case of the heart, promotion of fibrosis may be advantageous where an infarct has destroyed a zone of cardiomyocytes, but if EPO stimulates progressive fibrosis in the heart, this may promote cardiac failure. A major concern in relation to the use of EPO in a cytoprotective role is its stimulation of long-term inflammation and fibrosis. EPO usage for cytoprotection is undoubtedly advantageous, but it may need to be offset with an anti-inflammatory agent in some organs, like kidney and heart, where progression to chronic fibrosis after acute injury is often recorded.

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

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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

Chemoradiation for Advanced Head and Neck Cancer: Potential for Improving Results to Match Those of Current Treatment Modalities for Early-Stage Tumors-Long-Term Results of Hyperfractionated Chemoradiation With Carbogen Breathing and Anemia Correction With Erythropoietin

International Nuclear Information System (INIS)

Villar, Alfonso; Martinez, Jose Carlos; Serdio, Jose Luis de

2008-01-01

Purpose: To attempt to improve results of chemoradiation for head and neck cancer. Methods and Materials: From March 1996 to April 2007, 98 patients with head and neck cancer (15 Stage III and 83 Stage IV) were treated with a twice-daily hyperfractionated schedule. Eleven patients presented with N0, 11 with N1, 13 with N2A, 17 with N2B, 24 with N2C, and 22 with N3. Each fraction of treatment 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 corrected with erythropoietin. Results: Ninety-six patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Local toxicity remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Ninety-seven complete responses were achieved. After 11 years of follow-up (median, 81 months), actuarial locoregional control, cause-specific survival, overall survival, and nodal control rates at 5 and 10 years were, respectively, 83% and 83%, 68% and 68%, 57% and 55%, and 100% and 100%. Median follow-up of disease-free survivors was 80 months. No significant differences in survival were observed between the different subsites or between the pretreatment node status groups (N0 vs. N+, N0 vs. N1, N0 vs. N2A, N0 vs. N2B, N0 vs. N2C, and N0 vs. N3). Conclusions: Improving results of chemoradiation for advanced head and neck cancer up to the level obtained with current treatments for early-stage tumors is a potentially reachable goal

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.)

Interventions to Promote Cancer Awareness and Early Presentation: Systematic Review

OpenAIRE

J Austoker; C Bankhead; Lindsay J. L. Forbes; L Atkins; F Martin; K Robb; J Wardle; A J. Ramirez

2009-01-01

Background: Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research. Methods: We searched bibliographic databases and reference lists for randomised controlled trials of interventions delivered to individuals, and controlled or uncontrolled...

Utilização de eritropoetina por pacientes incidentes em hemodiálise no Sistema Único de Saúde, Brasil, 2002-2003 Erythropoietin use by incident hemodialysis patients in the Brazilian Unified National Health System, 2002-2003

Directory of Open Access Journals (Sweden)

Thaís Caroline Gurgel

2012-05-01

Full Text Available Este estudo visa a descrever o perfil demográfico e epidemiológico de pacientes incidentes em hemodiálise, que utilizaram eritropoetina em 2002 e 2003, no Brasil, e identificar fatores associados ao uso desse medicamento. Foram analisados dados demográficos, clínicos e relacionados à unidade de diálise de 32.136 pacientes, identificados por pareamento determinístico-probabilístico de dados do subsistema de autorização de procedimentos de alto custo e do Sistema de Informações sobre Mortalidade. Um modelo de regressão de Poisson foi usado para identificar fatores associados ao uso de eritropoetina. Sexo masculino; idade inferior a 65 anos; nefropatia diabética; fístula arteriovenosa ao iniciar hemodiálise e residir em outras Unidades Federativas diferentes do Mato Grosso foram fatores associados ao uso de eritropoetina. A política de atenção ao doente renal, a alocação de recursos para estados e municípios e o manejo da anemia, segundo o perfil farmacoterapêutico dos pacientes, devem ser revistos, a fim de reduzir as iniquidades observadas na utilização da eritropoetina.This study aimed to describe the demographic and epidemiological profile of Brazilian patients entering hemodialysis from 2002 to 2003 and identify predictors of erythropoietin use. The study analyzed demographic and clinical characteristics and dialysis facility-related variables from 32,136 patients identified by deterministic-probabilistic matching in the database of authorizations for high-cost procedures and the Mortality Information System. Poisson regression was used to identify predictors of erythropoietin use. Male gender, age < 65 years, diabetic renal failure, arteriovenous fistula at the beginning of hemodialysis, and living in States of Brazil other than Mato Grosso were predictors of erythropoietin use. The policy of care for chronic kidney disease, resource allocation for States and municipalities, and anemia management according to the

Early Citability of Data vs Peer-Review like Data Publishing Procedures

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Stockhause, Martina; Höck, Heinke; Toussaint, Frank; Lautenschlager, Michael

2014-05-01

The World Data Center for Climate (WDCC) hosted at the German Climate Computing Center (DKRZ) was one of the first data centers, which established a peer-review like data publication procedure resulting in DataCite DOIs. Data in the long-term archive (LTA) is diligently reviewed by data managers and data authors to grant high quality and widely reusability of the published data. This traditional data publication procedure for LTA data bearing DOIs is very time consuming especially for WDCC's high data volumes of climate model data in the order of multiple TBytes. Data is shared with project members and selected scientists months before the data is long-term archived. The scientific community analyses and thus reviews the data leading to data quality improvements. Scientists wish to cite these unstable data in scientific publications before the long-term archiving and the thorough data review process are finalized. A concept for early preprint DOIs for shared but not yet long-term archived data is presented. Requirements on data documentation, persistence and quality and use cases for preprint DOIs within the data life-cycle are discussed as well as questions of how to document the differences of the two DOI types and how to relate them to each other with the recommendation to use LTA DOIs in citations. WDCC wants to offer an additional user service for early citations of data of basic quality without compromising the LTA DOIs, i.e. WDCC's standard DOIs, as trustworthy indicator for high quality data. Referencing Links: World Data Center for Climate (WDCC): http://www.wdc-climate.de German Climate Computing Center (DKRZ): http://www.dkrz.de DataCite: http://datacite.org

Early social environment affects the endogenous oxytocin system: a review and future directions

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Emily eAlves

2015-03-01

Full Text Available Endogenous oxytocin plays an important role in a wide range of human functions including birth, milk ejection during lactation and facilitation of social interaction. There is increasing evidence that both variations in the oxytocin receptor (OXTR and concentrations of oxytocin are associated with differences in these functions. The causes for the differences that have been observed in tonic and stimulated oxytocin release remain unclear. Previous reviews have suggested that across the life course, these differences may be due to individual factors, e.g. genetic variation (of the OXTR, age or sex, or be the result of early environmental influences such as social experiences, stress or trauma partly by inducing epigenetic changes. This review has three aims. First, we briefly discuss the endogenous oxytocin system, including physiology, development, individual differences and function. Secondly, current models describing the relationship between the early life environment and the development of the oxytocin system in humans and animals are discussed. Finally, we describe research designs that can be used to investigate the effects of the early environment on the oxytocin system, identifying specific areas of research that need further attention.

Inhibition of erythropoietin siRNA on corneal neovascularization of rabbit

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Yu-Shun Xue

2017-03-01

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

Effects of Early Neglect Experience on Recognition and Processing of Facial Expressions: A Systematic Review

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Victoria Doretto

2018-01-01

Full Text Available Background: Child neglect is highly prevalent and associated with a series of biological and social consequences. Early neglect may alter the recognition of emotional faces, but its precise impact remains unclear. We aim to review and analyze data from recent literature about recognition and processing of facial expressions in individuals with history of childhood neglect. Methods: We conducted a systematic review using PubMed, PsycINFO, ScIELO and EMBASE databases in the search of studies for the past 10 years. Results: In total, 14 studies were selected and critically reviewed. A heterogeneity was detected across methods and sample frames. Results were mixed across studies. Different forms of alterations to perception of facial expressions were found across 12 studies. There was alteration to the recognition and processing of both positive and negative emotions, but for emotional face processing there was predominance in alteration toward negative emotions. Conclusions: This is the first review to examine specifically the effects of early neglect experience as a prevalent condition of child maltreatment. The results of this review are inconclusive due to methodological diversity, implement of distinct instruments and differences in the composition of the samples. Despite these limitations, some studies support our hypothesis that individuals with history of early negligence may present alteration to the ability to perceive face expressions of emotions. The article brings relevant information that can help in the development of more effective therapeutic strategies to reduce the impact of neglect on the cognitive and emotional development of the child.

Early Infantile Leigh-like Gene Defects Have a Poor Prognosis: Report and Review

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Majid Alfadhel

2017-10-01

Full Text Available Solute carrier family 19 (thiamine transporter, member 3 ( SCL19A3 gene defect produces an autosomal recessive neurodegenerative disorder associated with different phenotypes and acronyms. One of the common presentations is early infantile lethal Leigh-like syndrome. We report a case of early infantile Leigh-like SLC19A3 gene defects of patients who died at 4 months of age with no response to a high dose of biotin and thiamine. In addition, we report a novel mutation that was not reported previously. Finally, we review the literature regarding early infantile Leigh-like SLC19A3 gene defects and compare the literature with our patient.

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)

Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review.

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He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

2016-01-01

To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83-0.98, P=0.01; RR =0.84, 95% CI: 0.75-0.95, P=0.004; RR =0.77, 95% CI: 0.60-0.98, P=0.04; and RR =0.70, 95% CI: 0.52-0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88-0.98, P=0.003; RR =0.84, 95% CI

Family Quality of Life: A Key Outcome in Early Childhood Intervention Services--A Scoping Review

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Bhopti, Anoo; Brown, Ted; Lentin, Primrose

2016-01-01

A scoping review was conducted to identify factors influencing the quality of life of families of children with disability. The review also explored the scales used to measure family quality of life (FQOL) as an outcome in early childhood intervention services (ECIS). Multiple databases were searched from 2000 to 2013 to include studies pertinent…

Characterization of the structure of the erythropoietin receptor by ligand blotting

International Nuclear Information System (INIS)

Atkins, H.L.; Broudy, V.C.; Papayannopoulou, T.

1991-01-01

Erythropoietin (Epo) regulates the growth and differentiation of erythroid cells by binding to a specific receptor. We characterized the native Epo receptor on erythroleukemia cell lines by ligand blotting. Solubilized cell membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred onto nitrocellulose, and probed with 125I-Epo. Specificity was demonstrated by inhibition of 125I-Epo binding by unlabeled excess Epo but not other peptide growth factors and by the cellular distribution of the Epo binding protein. A single membrane protein of 61 Kd ± 4 Kd was sufficient to bind 125I Epo in both human (OCIM2, K562) and murine (GM979, Rauscher, DA-1) cell lines. This finding is consistent with the predicted size of the Epo receptor from the murine cDNA clone. However, chemical crosslinking of 125I-Epo to its receptor has identified two Epo binding proteins of 105 Kd and 85 Kd. This difference may occur because the receptor is size fractionated before Epo binding in the ligand blot, but after Epo binding in crosslinking studies. Ligand blotting demonstrates that the native Epo receptor is composed of a single 61-Kd Epo binding protein, and suggests the presence of additional proteins of 20 to 25 Kd that associate with the receptor after Epo binding

Long-term erythropoietin gene expression from transduced cells in bioisolator devices.

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Yanay, Ofer; Barry, Simon C; Flint, Lisa Y; Brzezinski, Margaret; Barton, Randall W; Osborne, William R A

2003-11-20

Recombinant erythropoietin (EPO) is widely administered for long-term treatment of anemia associated with renal failure and other chronic diseases. The ability to deliver EPO by gene therapy would have clinical and economic benefit. We compared autologous and allogeneic transduced primary vascular smooth muscle cells for their ability to provide sustained EPO gene expression when encapsulated in TheraCyte devices implanted subcutaneously (SQ) or intraperitoneally (IP) in rats. Cells were transduced with retrovirus vector LrEpSN encoding rat EPO cDNA. Rats that received either autologous or allogeneic transduced cells showed elevated hematocrits (HCTs) ranging from 50 to 79% that were sustained for more than 12 months. The HCT of control rats remained at baseline (45.8%). Rats that received second SQ implants of either autologous or allogeneic cells showed elevations in hematocrit that were sustained for up to 12 months, suggesting the absence of immunological responses to transduced cells or implant material. All experimental groups had statistically significant elevated HCT (p TheraCyte devices was well tolerated and histological evaluation of the devices up to 12 months after surgery revealed a high degree of vascularization and no evidence of host immune response. TheraCyte devices offer a simple and safe gene delivery system that provides sustained therapeutic gene expression, permit removal and implantation of new devices, and do not require immunosuppression of the host.

Early interventions to prevent retinal vasculopathy in diabetes: a review

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Harrison WW

2015-08-01

Full Text Available Wendy W Harrison, Vladimir YevseyenkovArizona College of Optometry, Midwestern University, Glendale, AZ, USAAbstract: Diabetic eye disease is a public health concern in all areas of the world as a leading cause of blindness in the working aged to elderly populations. Diabetes damages the lining of the microvasculature throughout the body through prolonged exposure to hyperglycemic conditions. The ocular changes are progressive with very little recourse for improvement once damage begins. Current treatments for the eye focus mainly on the late stages of the disease when neovascularization or edema threatens sight. Early interventions for diabetic vasculopathy involve metabolic therapy to improve blood glucose and blood pressure control. Technology improvements have a large part to play in advancing diagnosis of diabetic eye disease. These new technologies offer both structural and functional means for assessment of retinal health. This review focuses on current treatments for diabetic eye disease at all stages with an emphasis on new and early interventions. It also details established and emerging technologies used for earlier detection of diabetic eye disease, which is vital to the development and approval of much needed treatments targeted at earlier stages of diabetic retinopathy. Possible future treatments should be aimed to prevent retinal vasculopathy from progressing. This review will explore current research on this topic and what is needed moving forward.Keywords: diabetes, diabetic retinopathy, vascular disease

The impact of arthritis on the early employment experiences of young adults: A literature review.

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Jetha, Arif

2015-07-01

Young adulthood is an important transitional life phase that can determine a person's career trajectory. To date, little research has examined the influence of arthritis on early work experiences. This literature review aims at examining the impact of arthritis on the early career phase of young adults and identifying the barriers to employment. Two independent reviewers searched bibliographic databases for arthritis conditions and a series of employment-related keywords and subject headings. Information on authors, publication year; study design, sample characteristics (e.g., number of participants, age, gender, arthritis type); work outcomes measured; and specific barriers to employment was recorded. Nine studies were uncovered in the review. All studies examined young people with juvenile arthritis (9 of 9 studies) and consisted of sample sizes with less then 150 participants (6 of 9 studies) who were primarily recruited from clinics (7 of 9 studies). All were cross-sectional designs. Employment status was primarily examined and ranged from 11% to 71%. Although not always statistically significant, young adults with arthritis were less likely to be employed when compared to their healthy peers. Greater disease severity, less educational attainment and being female were related to not participating in paid work. This review brings to light the paucity of studies examining the early employment experiences of young adults with arthritis. There is a need to expand research to contribute to recommendations for sustained and productive employment across the working life course. Copyright © 2015 Elsevier Inc. All rights reserved.

Early diagnosis of atherosclerosis with panoramic radiographs: a review

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Daiane Landim Borba

Full Text Available Abstract Carotid artery disease has been linked with cerebral vascular accident, also known as stroke, cerebral hemorrhage, or cerebral ischemia. It is caused by narrowing or obstruction of arteries in the neck (the carotid arteries that are responsible for transporting blood from the aorta to the brain. Panoramic radiographs are used in dentistry to show both dental arches as a supplement to the clinical dental examination. The objective of this study is to highlight the importance of panoramic radiographs for diagnosis of arterial disease, by means of a bibliographic review. The PubMed database was searched using the keywords “atherosclerosis” and “panoramic”, with the filters “last 5 years” and “humans”. Twenty articles were identified, six of which were chosen for this study because they were open access. The review concluded that panoramic radiographs enable early diagnosis of carotid artery calcification, resulting in earlier interventions, and offer an accessible cost.

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

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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.

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

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Halim, Liem Andhyk; Brinks, Vera; Jiskoot, Wim; Romeijn, Stefan; Praditpornsilpa, Kearkiat; Assawamakin, Anunchai; Schellekens, Huub

2014-05-01

The high prevalence of pure red cell aplasia in Thailand has been associated with the sharp increase in number of recombinant human erythropoietin (rhEPO) copy products, based on a classical generic regulatory pathway, which have entered the market. This study aims to assess the quality of rhEPO copy products being used in Thailand. Twelve rhEPO copy products were purchased from pharmacies in Thailand, shipped under controlled cold chain conditions to the Netherlands and characterized using (1) high performance size-exclusion chromatography, (2) asymmetrical flow field-flow fractionation, (3) sodium dodecyl sulfate polyacrylamide gel electrophoresis in combination with (4) Western blotting and additionally tested for (5) host cell protein impurities as well as (6) endotoxin contamination. Some of the tested rhEPO copy products showed high aggregate levels and contained a substantial amount of protein fragments. Also, one of rhEPO copy products had a high endotoxin level, exceeding the FDA limit. Our observations show that some of the tested copy products on the Thai market differ significantly from the originator rhEPO product, Epogen®. This comparison study supports a link between the quality attributes of copy rhEPO products and their immunogenicity.

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

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Kostyukevych O.M.

2013-06-01

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

A Systematic Review of Fidelity of Implementation in Parent-Mediated Early Communication Intervention

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Lieberman-Betz, Rebecca G.

2015-01-01

This article examined the reporting of four elements of fidelity of implementation (FOI) in parent-mediated early communication treatment studies. Thirty-five studies were reviewed to extract information regarding reporting of dosage, adherence, quality, and participant responsiveness for both practitioners and parents involved in parent-delivered…

Emerging Use of Early Health Technology Assessment in Medical Product Development: A Scoping Review of the Literature.

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IJzerman, Maarten J; Koffijberg, Hendrik; Fenwick, Elisabeth; Krahn, Murray

2017-07-01

Early health technology assessment is increasingly being used to support health economic evidence development during early stages of clinical research. Such early models can be used to inform research and development about the design and management of new medical technologies to mitigate the risks, perceived by industry and the public sector, associated with market access and reimbursement. Over the past 25 years it has been suggested that health economic evaluation in the early stages may benefit the development and diffusion of medical products. Early health technology assessment has been suggested in the context of iterative economic evaluation alongside phase I and II clinical research to inform clinical trial design, market access, and pricing. In addition, performing early health technology assessment was also proposed at an even earlier stage for managing technology portfolios. This scoping review suggests a generally accepted definition of early health technology assessment to be "all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty". The present review also aimed to identify recent published empirical studies employing an early-stage assessment of a medical product. With most included studies carried out to support a market launch, the dominant methodology was early health economic modeling. Further methodological development is required, in particular, by combining systems engineering and health economics to manage uncertainty in medical product portfolios.

Molecular spectral imaging system for quantitative immunohistochemical analysis of early diabetic retinopathy.

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Li, Qingli; Zhang, Jingfa; Wang, Yiting; Xu, Guoteng

2009-12-01

A molecular spectral imaging system has been developed based on microscopy and spectral imaging technology. The system is capable of acquiring molecular spectral images from 400 nm to 800 nm with 2 nm wavelength increments. The basic principles, instrumental systems, and system calibration method as well as its applications for the calculation of the stain-uptake by tissues are introduced. As a case study, the system is used for determining the pathogenesis of diabetic retinopathy and evaluating the therapeutic effects of erythropoietin. Some molecular spectral images of retinal sections of normal, diabetic, and treated rats were collected and analyzed. The typical transmittance curves of positive spots stained for albumin and advanced glycation end products are retrieved from molecular spectral data with the spectral response calibration algorithm. To explore and evaluate the protective effect of erythropoietin (EPO) on retinal albumin leakage of streptozotocin-induced diabetic rats, an algorithm based on Beer-Lambert's law is presented. The algorithm can assess the uptake by histologic retinal sections of stains used in quantitative pathology to label albumin leakage and advanced glycation end products formation. Experimental results show that the system is helpful for the ophthalmologist to reveal the pathogenesis of diabetic retinopathy and explore the protective effect of erythropoietin on retinal cells of diabetic rats. It also highlights the potential of molecular spectral imaging technology to provide more effective and reliable diagnostic criteria in pathology.

Prognostic significance of erythropoietin in pancreatic adenocarcinoma.

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Thilo Welsch

Full Text Available BACKGROUND: Erythropoietin (Epo administration has been reported to have tumor-promoting effects in anemic cancer patients. We investigated the prognostic impact of endogenous Epo in patients with pancreatic ductal adenocarcinoma (PDAC. METHODOLOGY: The clinico-pathological relevance of hemoglobin (Hb, n = 150, serum Epo (sEpo, n = 87 and tissue expression of Epo/Epo receptor (EpoR, n = 104 was analyzed in patients with PDAC. Epo/EpoR expression, signaling, growth, invasion and chemoresistance were studied in Epo-exposed PDAC cell lines. RESULTS: Compared to donors, median preoperative Hb levels were reduced by 15% in both chronic pancreatitis (CP, p<0.05 and PDAC (p<0.001, reaching anemic grade in one third of patients. While inversely correlating to Hb (r = -0.46, 95% of sEPO values lay within the normal range. The individual levels of compensation were adequate in CP (observed to predicted ratio, O/P = 0.99 but not in PDAC (O/P = 0.85. Strikingly, lower sEPO values yielding inadequate Epo responses were prominent in non-metastatic M0-patients, whereas these parameters were restored in metastatic M1-group (8 vs. 13 mU/mL; O/P = 0.82 vs. 0.96; p<0.01--although Hb levels and the prevalence of anemia were comparable. Higher sEpo values (upper quartile ≥ 16 mU/ml were not significantly different in M0 (20% and M1 (30% groups, but were an independent prognostic factor for shorter survival (HR 2.20, 10 vs. 17 months, p<0.05. The pattern of Epo expression in pancreas and liver suggested ectopic release of Epo by capillaries/vasa vasorum and hepatocytes, regulated by but not emanating from tumor cells. Epo could initiate PI3K/Akt signaling via EpoR in PDAC cells but failed to alter their functions, probably due to co-expression of the soluble EpoR isoform, known to antagonize Epo. CONCLUSION/SIGNIFICANCE: Higher sEPO levels counteract anemia but worsen outcome in PDAC patients. Further trials are required to clarify how overcoming a sEPO threshold �

Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early stage Hodgkin lymphoma (Review)

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Blank, Oliver; von Tresckow, Bastian; Monsef, Ina

2017-01-01

BACKGROUND: Combined modality treatment consisting of chemotherapy followed by localised radiotherapy is the standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long- term adverse effects such as secondary malignancies the role of radiotherapy has been questioned...... recently and some clinical study groups advocate chemotherapy only for this indication. OBJECTIVES: To assess the effects of chemotherapy alone compared to chemotherapy plus radiotherapy in adults with early stage HL . SEARCH METHODS: For the or i ginal version of this review, we searched MEDLINE, Embase......-related mortality (RR 0.99; 95% CI 0.14 to 6.90; P = 0.99; low-quality evidence), there is no evidence for a difference between the use of chemotherapy alone and chemotherapy plus radiotherapy. CRR rate was not reported. AUTHORS' CONCLUSIONS: This systematic review compared the effects of chemotherapy alone...

Diagnoses of Early and Late Readmissions after Hospitalization for Pneumonia. A Systematic Review

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Sjoding, Michael W.; Iwashyna, Theodore J.

2014-01-01

Rationale: Pneumonia is a frequent cause of hospitalization, yet drivers of post-pneumonia morbidity remain poorly characterized. Causes of hospital readmissions may elucidate important sources of morbidity and are of particular interest given the U.S. Hospital Readmission Reductions Program. Objectives: To review the primary diagnoses of early (≤30 d) and late (≥31 d) readmissions after pneumonia hospitalization. Methods: Systematic review of MEDLINE, Embase, and CINAHL databases. We identified original research studies of adults aged 18 years or older, hospitalized for pneumonia, and for whom cause-specific readmission rates were reported. Two authors abstracted study results and assessed study quality. Measurements and Main Results: Of the 1,243 citations identified, 12 met eligibility criteria. Included studies were conducted in the United States, Spain, Canada, Croatia, and Sweden. All-cause 30-day readmission rates ranged from 16.8 to 20.1% across administrative studies; the weighted average for the studies using chart review was 11.6% (15.6% in United States–based studies). Pneumonia, heart failure/cardiovascular causes, and chronic obstructive pulmonary disease/pulmonary causes are the most common reasons for early readmission after pneumonia hospitalization. Although it was the single most common cause for readmission, pneumonia accounted for only 17.9 to 29.4% of all 30-day readmissions in administrative studies and a weighted average of 23.0% in chart review studies. After accounting for study population, there was no clear difference in findings between claims-based versus chart-review studies. Few studies assessed readmissions beyond 30 days, although the limited available data suggest similar primary diagnoses for early and late readmissions. No studies assessed whether reasons for readmission were similar to patients’ reasons for healthcare use before hospitalization. Conclusions: Pneumonia, heart failure/cardiovascular disease, and chronic

Impact of early in-hospital medication review by clinical pharmacists on health services utilization.

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Corinne M Hohl

Full Text Available Adverse drug events are a leading cause of emergency department visits and unplanned admissions, and prolong hospital stays. Medication review interventions aim to identify adverse drug events and optimize medication use. Previous evaluations of in-hospital medication reviews have focused on interventions at discharge, with an unclear effect on health outcomes. We assessed the effect of early in-hospital pharmacist-led medication review on the health outcomes of high-risk patients.We used a quasi-randomized design to evaluate a quality improvement project in three hospitals in British Columbia, Canada. We incorporated a clinical decision rule into emergency department triage pathways, allowing nurses to identify patients at high-risk for adverse drug events. After randomly selecting the first eligible patient for participation, clinical pharmacists systematically allocated subsequent high-risk patients to medication review or usual care. Medication review included obtaining a best possible medication history and reviewing the patient's medications for appropriateness and adverse drug events. The primary outcome was the number of days spent in-hospital over 30 days, and was ascertained using administrative data. We used median and inverse propensity score weighted logistic regression modeling to determine the effect of pharmacist-led medication review on downstream health services use.Of 10,807 high-risk patients, 6,416 received early pharmacist-led medication review and 4,391 usual care. Their baseline characteristics were balanced. The median number of hospital days was reduced by 0.48 days (95% confidence intervals [CI] = 0.00 to 0.96; p = 0.058 in the medication review group compared to usual care, representing an 8% reduction in the median length of stay. Among patients under 80 years of age, the median number of hospital days was reduced by 0.60 days (95% CI = 0.06 to 1.17; p = 0.03, representing 11% reduction in the median length of stay

Early versus delayed rehabilitation following arthroscopic rotator cuff repair: A systematic review.

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Gallagher, Brian P; Bishop, Meghan E; Tjoumakaris, Fotios P; Freedman, Kevin B

2015-05-01

Early passive range of motion (ROM) following arthroscopic cuff repair is thought to decrease postoperative stiffness and improve functionality. However, early aggressive rehabilitation may compromise repair integrity. Our purpose was to perform a systematic review to determine if there are differences between early and delayed rehabilitation after arthroscopic rotator cuff repair in terms of clinical outcomes and healing. We performed a literature search with the terms 'arthroscopic rotator cuff', 'immobilization', 'early', 'delayed', 'late', and 'rehabilitation' using PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Selection criteria included: level I/II evidence ≤ 6 months in duration, comparing early versus delayed rehabilitation following arthroscopic repair. Data regarding demographics, sample sizes, duration, cuff pathology, surgery, rehabilitation, functional outcomes, pain, ROM and anatomic assessment of healing were analyzed. PRIMSA criteria were followed. We identified six articles matching our criteria. Three reported significantly increased functional scores within the first 3-6 months with early rehabilitation compared to the delayed group, only one of which continued to observe a difference at a final follow-up of 15 months. Four articles showed improved ROM in the first 3-6 months post-operatively with early rehabilitation. One noted transient differences in pain scores. Only one study noted significant differences in ROM at final follow-up. No study reported any significant difference in rates of rotator cuff re-tear. However, two studies noted a trend towards increased re-tear with early rehabilitation that did not reach significance. This was more pronounced in studies including medium-large tears. Early rehabilitation after arthroscopic cuff repair is associated with some initial improvements in ROM and function. Ultimately, similar clinical and anatomical outcomes between groups existed at 1 year. While there was no

Radiotherapy in fascial fibromatosis: a case series, literature review and considerations for treatment of early-stage disease

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Grenfell, Solveig; Borg, Martin

2014-01-01

Palmar and plantar fascial fibromatoses are benign hyperproliferative disorders of the deep fascia of the palm and sole. This study seeks to examine the role of radiotherapy in the management of fascial fibromatosis. Six consecutive cases of early-stage fascial fibromatosis treated with radiotherapy at the Adelaide Radiotherapy Centre between July 2008 and May 2011 were analysed. The results of the case series were compared with a systematic review of the literature. All six cases regressed or showed a reduction of symptoms following radiotherapy. Treatment was well tolerated with minor toxicities. Median follow-up for the case series was 38.5 months. The systematic review identified seven studies describing the use of radiotherapy as primary treatment for fascial fibromatosis between 1946 and 2013. The literature indicates that radiotherapy can prevent disease progression and improve symptoms for early-stage disease, with low likelihood of significant toxicities. Early results from our case series are consistent with the literature, showing that radiotherapy can provide an effective management option for patients with early-stage fascial fibromatosis, and justify consideration of radiotherapy as a primary treatment for early-stage disease.

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

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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.

Early parenteral nutrition and growth outcomes in preterm infants: a systematic review and meta-analysis.

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Moyses, Helen E; Johnson, Mark J; Leaf, Alison A; Cornelius, Victoria R

2013-04-01

The achievement of adequate nutritional intakes in preterm infants is challenging and may explain the poor growth often seen in this group. The use of early parenteral nutrition (PN) is one potential strategy to address this problem, although the benefits and harms are unknown. We determined whether earlier administration of PN benefits growth outcomes in preterm infants. We conducted a systematic review of randomized controlled trials (RCTs) and observational studies. Eight RCTs and 13 observational studies met the inclusion criteria (n = 553 and 1796 infants). The meta-analysis was limited by disparate growth-outcome measures. An assessment of bias was difficult because of inadequate reporting. Results are given as mean differences (95% CIs). Early PN reduced the time to regain birth weight by 2.2 d (1.1, 3.2 d) for RCTs and 3.2 d (2.0, 4.4 d) in observational studies. The maximum percentage weight loss with early PN was lower by 3.1 percentage points (1.7, 4.5 percentage points) for RCTs and by 3.5 percentage points (2.6, 4.3 percentage points) for observational studies. Early PN improved weight at discharge or 36 wk postmenstrual age by 14.9 g (5.3, 24.5 g) (observational studies only), but no benefit was shown for length or head circumference. There was no evidence that early PN significantly affects risk of mortality, necrotizing enterocolitis, sepsis, chronic lung disease, intraventricular hemorrhage, or cholestasis. The results of this review, although subject to some limitations, show that early PN provides a benefit for some short-term growth outcomes. No evidence that early PN increases morbidity or mortality was found. Neonatal research would benefit from the development of a set of core growth outcome measures.

How Well Prepared Are Pre-Service Teachers to Teach Early Reading? A Systematic Review of the Literature

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Meeks, Linda; Stephenson, Jennifer; Kemp, Coral; Madelaine, Alison

2016-01-01

This review examined studies that had addressed opinions of pre-service teachers (PSTs) concerning their preparedness for teaching early reading skills to all students, the extent of their content knowledge, and their attitudes towards code-based and/or meaning-based approaches to early reading. From the limited amount of research available, it…

HPLC-MS/MS investigation of biochemical markers for the disclosure of erythropoietin abuse in sports

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Appolonova, S. A.; Dikunets, M. A.; Rodchenkov, G. M.

2009-04-01

The polypeptide hormone erythropoietin (EPO), which is a forbidden doping drug, was determined by high-performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS). The hypothesis about the influence of EPO on the asymmetric dimethylarginine (ADMA)-dimethylargininedime-thylaminohydrolase (DDAH)-NO-synthase system was verified. Changes in this system can serve as indirect biochemical markers of the presence of the forbidden EPO drug in the organism. In the test group, the concentrations of biochemical markers varied from 10 to 40 μg/ml for ADMA and symmetrical DMA (SDMA) and from 0.5 to 10 μg/ml for arginine and citrulline. A single intravenous administration of r-HuEPO (Epocrin, 2000 ME/day) for two volunteers reliably increased ADMA, SDMA, arginine, and citrulline concentrations to 40-270 μg/ml, 40-240μg/ml, 10-60 μg/ml, and 12-140 μg/ml, respectively, with respect to the reference values. The simultaneous increase in arginine, methylarginines, and citrulline contents could be an indirect marker of EPO abuse. The method is recommended for fast screening analysis.

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

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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.

Metabolic effects of keto acid--amino acid supplementation in patients with chronic renal insufficiency receiving a low-protein diet and recombinant human erythropoietin--a randomized controlled trial.

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Teplan, V; Schück, O; Votruba, M; Poledne, R; Kazdová, L; Skibová, J; Malý, J

2001-09-17

Supplement with keto acids/amino acids (KA) and erythropoietin can independently improve the metabolic sequels of chronic renal insufficiency. Our study was designed to establish whether a supplementation with keto acids/amino acids (KA) exerts additional beneficial metabolic effects in patients with chronic renal insufficiency (CRF) treated with a low-protein diet (LPD) and recombinant human erythropoietin (EPO). In a prospective randomized controlled trial over a period of 12 months, we evaluated a total of 38 patients (20 M/18 F) aged 32-68 years with a creatinine clearance (CCr) of 20-36 ml/min. All patients were receiving EPO (40 U/kg twice a week s.c.) and a low-protein diet (0.6 g protein/kg/day and 145 kJ/kg/day). The diet of 20 patients (Group I) was supplemented with KA at a dosage of 100 mg/kg/day while 18 patients (Group II) received no supplementation. During the study period, the glomerular filtration rate slightly decreased (CCr from 28.2 +/- 3.4 to 26.4 +/- 4.1 ml/min and 29.6 +/- 4.8 to 23.4 +/- 4.4 ml/min in groups I and II, respectively and Cin); this however was more marked in Group II (Group I vs. Group II, p diet presents an effective treatment modality in the conservative management of CRF.

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

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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

Review of Amanda E. Herbert, Female Alliances: Gender, Identity, and Friendship in Early Modern Britain

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Angela Rehbein

2015-03-01

Full Text Available Review of Amanda E. Herbert, Female Alliances: Gender, Identity, and Friendship in Early Modern Britain. New Haven: Yale UP, 2014. xi, 256 pages: illustrations; 24 cm. ISBN 978-0-300-17740-4.

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

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

2010-01-01

. The current study investigates the effects of Epo on the neural and cognitive response to emotional facial expressions in depressed patients. METHOD: Nineteen acutely depressed patients were randomized to receive Epo (40,000 IU) or saline intravenously in a double-blind, parallel-group design. On day 3, we......OBJECTIVE: 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...... assessed neuronal responses to fearful and happy faces using functional magnetic resonance imaging and measured facial expression recognition after the scan. RESULTS: Epo reduced neural response to fearful vs. happy faces in the amygdala and hippocampus, and to fearful faces vs. baseline in superior...

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

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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.

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

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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.

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

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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.

Early childhood neurodevelopment after intrauterine growth restriction: a systematic review.

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Levine, Terri A; Grunau, Ruth E; McAuliffe, Fionnuala M; Pinnamaneni, RagaMallika; Foran, Adrienne; Alderdice, Fiona A

2015-01-01

Children who experienced intrauterine growth restriction (IUGR) may be at increased risk for adverse developmental outcomes in early childhood. The objective of this study was to carry out a systematic review of neurodevelopmental outcomes from 6 months to 3 years after IUGR. PubMed, Embase, PsycINFO, Maternity and Infant Care, and CINAHL databases were searched by using the search terms intrauterine, fetal, growth restriction, child development, neurodevelopment, early childhood, cognitive, motor, speech, language. Studies were eligible for inclusion if participants met specified criteria for growth restriction, follow-up was conducted within 6 months to 3 years, methods were adequately described, non-IUGR comparison groups were included, and full English text of the article was available. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-documented quality-appraisal guidelines. Of 731 studies reviewed, 16 were included. Poorer neurodevelopmental outcomes after IUGR were described in 11. Ten found motor, 8 cognitive, and 7 language delays. Other delays included social development, attention, and adaptive behavior. Only 8 included abnormal Doppler parameters in their definitions of IUGR. Evidence suggests that children are at risk for poorer neurodevelopmental outcomes following IUGR from 6 months to 3 years of age. The heterogeneity of primary outcomes, assessment measures, adjustment for confounding variables, and definitions of IUGR limits synthesis and interpretation. Sample sizes in most studies were small, and some examined preterm IUGR children without including term IUGR or AGA comparison groups, limiting the value of extant studies. Copyright © 2015 by the American Academy of Pediatrics.

Epidemiology of early-onset dementia: a review of the literature

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Vieira, Renata Teles; Caixeta, Leonardo; Machado, Sergio; Silva, Adriana Cardoso; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Carta, Mauro Giovanni

2013-01-01

Presenile Dementia or Early Onset Dementia (EOD) is a public health problem, it differs from Senile Dementia, and encloses a significant number of cases; nevertheless, it is still poorly understood and underdiagnosed. This study aims to review the prevalence and etiology of EOD, comparing EOD with Senile Dementia, as well as to show the main causes of EOD and their prevalence in population and non-population based studies. The computer-supported search used the following databases: Pubmed/Medline, ISI Web of Knowledge and Scielo. The search terms were alcohol-associated dementia, Alzheimer’s disease, dementia, Creutzfeldt-jakob disease, dementia with lewy bodies, early onset dementia, frontotemporal lobar degeneration, Huntington’s disease, mixed dementia, neurodegenerative disorders, Parkinson’s disease dementia, presenile dementia, traumatic brain injury, vascular dementia. Only papers published in English and conducted from 1985 up to 2012 were preferentially reviewed. Neurodegenerative diseases are the most common etiologies seen in EOD. Among the general population, the prevalence of EOD was found to range between 0 to 700 per 100.000 habitants in groups of 25-64 years old, with an increasing incidence with age. The progression of EOD was found to range between 8.3 to 22.8 new cases per 100.000 in those aged under 65 years. Alzheimer's disease (AD) is the major etiology, followed by Vascular Dementia (VaD) and Frontotemporal Lobar Degeneration (FTLD). A larger number of epidemiological studies to elucidate how environmental issues contribute to EOD are necessary, thus, we can collaborate in the planning and prevention of services toward dementia patients. PMID:23878613

The uses of outcome measures within multidisciplinary early childhood intervention services: a systematic review.

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Calder, Samuel; Ward, Roslyn; Jones, Megan; Johnston, Jenelle; Claessen, Mary

2017-07-18

Purpose of the article: To review the use of outcome measures, across the domains of activity, participation, and environment, within multidisciplinary early childhood intervention services. A systematic literature search was undertaken that included four electronic databases: Medline, CINAHL, EMBASE, and the Cochrane Library and Cochrane Database of Systematic Review. Inclusion criteria were age 0-24 months, having or at risk of a developmental disability, in receipt of multidisciplinary early childhood intervention services, and included outcome measures across all domains of the International Classification of Functioning-Child & Youth (ICF-CY). Only peer-reviewed journal articles were considered. Eligible studies were coded using the Oxford Levels of Evidence. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) Scale for randomised controlled trials and the QualSyst for non-randomised control trials. Of the total of 5764 records identified, 10 were considered to meet inclusion criteria. Fourteen outcome measures were identified, addressing the domains of activity, participation, and environment. Of these, eight have been recommended in the early intervention literature. While the methodological quality of the 10 studies varied, these papers make a contribution to the body of research that acknowledges the role of routine and enriched environments. Implications for Rehabilitation Core practice elements of multidisciplinary early childhood intervention services indicate it is necessary to select outcome measures framed within the International Classification of Functioning-Child & Youth to inform clinical decision-making for measuring intervention effectiveness across the domains of activity, participation and environment. Of the identified measures, three (Canadian Occupational Performance Measure, Pediatric Evaluation of Disability Inventory, and Goal Attainment Scaling) are well-established and identified in the literature as

Impact of body size, nutrition and socioeconomic position in early life on the epigenome: a systematic review protocol.

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Maddock, Jane; Wulaningsih, Wahyu; Hardy, Rebecca

2017-07-05

Body size, nutrition and socioeconomic position (SEP) in early life have been associated with a range of later life health outcomes. Epigenetic regulation is one mechanism through which these early life factors may impact later life health. The aim of this review protocol is to outline procedures to document the influence of body size, nutrition and SEP in early life on the epigenome. MEDLINE, Embase and BIOSIS will be systematically searched using pre-defined keywords. Additional studies will be identified through manual searching of reference lists. Two independent researchers will assess the eligibility and quality of each study, with disagreements being resolved through discussion or a third reviewer. Studies will be included if they have epigenetic markers measured either at the same time as, or after, the early life exposure and, have a measure of body size, nutrition or SEP in early life (up to 12 years), are in the English language and are from a sample of community-dwelling participants. This protocol will be used to collate the evidence for the effect of early life factors on the epigenome. Findings will form a component of a wider research study examining epigenetic responses to exposures in early life and over the life course and its impact on healthy ageing using data from population-based cohort studies. PROSPERO CRD42016050193.

PECULIARITIES OF THE TRANSITION OF EARLY STURGEON (ACIPENSERIDAE FRY TO ARTIFICIAL FORMULATED FEEDS IN RAS (A REVIEW

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M. Simon

2016-03-01

Full Text Available Purpose. To review scientific sources on the morphological and ecophysiological peculiarities of the transition of early sturgeon fry (Acipenseridae to artificial formulated feeds. To summarize the biotechnological fundamentals of the use of artificial formulated feeds in the conditions of recirculating aquaculture systems (RAS. Findings. The transition of early sturgeon fry to artificial formulated feeds is one of the most difficult stages of their rearing, even under controlled conditions of RAS. The review contains the description of the peculiarities of sturgeon embryogenesis, their behavior and morpho-physiological changes at this stage of their development. It contains main requirements for the rearing of sturgeon larvae in RAS. We showed that the ultimate refuse from natural (live or frozen forage organisms is not advisable; the optimum is their combination with artificial feeds with gradual predominance of the latters. We provided the schemes of their feeding based on the combination of natural and artificial feeds. We reviewed the most common biologically active supplements, which contributed to better feed digestion during the periods of the transition to exogenous feeding. We highlighted the effect of feeding with brine shrimp nauplii enriched with polyunsaturated fatty acids on the growth and development of early sturgeon fry. Practical value. The array of the summarized information will be important for scientists who study the peculiarities of the transition of early sturgeon fry to artificial formulated feeds in RAS. The data on the biotechnologies of rational feeding of early sturgeon fry in RAS in this period are important in the conditions of continuous search for the most effective replacement of live forage organisms and reduction of fish fry mortality in postembryogenesis.

Driving in Early-Stage Alzheimer's Disease: An Integrative Review of the Literature.

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Davis, Rebecca L; Ohman, Jennifer M

2017-03-01

One of the most difficult decisions for individuals with Alzheimer's disease (AD) is when to stop driving. Because driving is a fundamental activity linked to socialization, independent functioning, and well-being, making the decision to stop driving is not easy. Cognitive decline in older adults can lead to getting lost while driving, difficulty detecting and avoiding hazards, as well as increased errors while driving due to compromised judgment and difficulty in making decisions. The purpose of the current literature review was to synthesize evidence regarding how individuals with early-stage AD, their families, and providers make determinations about driving safety, interventions to increase driving safety, and methods to assist cessation and coping for individuals with early-stage AD. The evidence shows that changes in driving ability start early and progress throughout the trajectory of AD. Some individuals with mild cognitive impairment or early-stage AD may be safe to drive for a period of time. Support groups aimed at helping with the transition have been shown to be helpful for individuals who stop driving. Research and practice must support interventions to help individuals maintain safety while driving, as well as cope with driving cessation. [Res Gerontol Nurs. 2017; 10(2):86-100.]. Copyright 2016, SLACK Incorporated.

Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: a Systematic Review and Meta-analysis.

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Immanuel, Jincy; Simmons, David

2017-10-02

We conducted a systematic review to evaluate the current evidence for screening and treatment for early-onset gestational diabetes mellitus (GDM) RECENT FINDINGS: Many of the women with early GDM in the first trimester do not have evidence of hyperglycemia at 24-28 weeks' gestation. A high proportion (15-70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. However, there remains no good evidence for any of the diagnostic criteria for early-onset GDM. In a meta-analysis of 13 cohort studies, perinatal mortality (relative risk (RR) 3.58 [1.91, 6.71]), neonatal hypoglycemia (RR 1.61 [1.02, 2.55]), and insulin use (RR 1.71 [1.45, 2.03]) were greater among early-onset GDM women compared to late-onset GDM women, despite treatment. Considering the high likelihood of benefit from treatment, there is an urgent need for randomized controlled trials that investigate any benefits and possible harms of treatment of early-onset GDM.

Understanding Factors that Shape Gender Attitudes in Early Adolescence Globally: A Mixed-Methods Systematic Review.

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Kågesten, Anna; Gibbs, Susannah; Blum, Robert Wm; Moreau, Caroline; Chandra-Mouli, Venkatraman; Herbert, Ann; Amin, Avni

2016-01-01

Early adolescence (ages 10-14) is a period of increased expectations for boys and girls to adhere to socially constructed and often stereotypical norms that perpetuate gender inequalities. The endorsement of such gender norms is closely linked to poor adolescent sexual and reproductive and other health-related outcomes yet little is known about the factors that influence young adolescents' personal gender attitudes. To explore factors that shape gender attitudes in early adolescence across different cultural settings globally. A mixed-methods systematic review was conducted of the peer-reviewed literature in 12 databases from 1984-2014. Four reviewers screened the titles and abstracts of articles and reviewed full text articles in duplicate. Data extraction and quality assessments were conducted using standardized templates by study design. Thematic analysis was used to synthesize quantitative and qualitative data organized by the social-ecological framework (individual, interpersonal and community/societal-level factors influencing gender attitudes). Eighty-two studies (46 quantitative, 31 qualitative, 5 mixed-methods) spanning 29 countries were included. Ninety percent of studies were from North America or Western Europe. The review findings indicate that young adolescents, across cultural settings, commonly express stereotypical or inequitable gender attitudes, and such attitudes appear to vary by individual sociodemographic characteristics (sex, race/ethnicity and immigration, social class, and age). Findings highlight that interpersonal influences (family and peers) are central influences on young adolescents' construction of gender attitudes, and these gender socialization processes differ for boys and girls. The role of community factors (e.g. media) is less clear though there is some evidence that schools may reinforce stereotypical gender attitudes among young adolescents. The findings from this review suggest that young adolescents in different cultural

Understanding Factors that Shape Gender Attitudes in Early Adolescence Globally: A Mixed-Methods Systematic Review.

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Anna Kågesten

Full Text Available Early adolescence (ages 10-14 is a period of increased expectations for boys and girls to adhere to socially constructed and often stereotypical norms that perpetuate gender inequalities. The endorsement of such gender norms is closely linked to poor adolescent sexual and reproductive and other health-related outcomes yet little is known about the factors that influence young adolescents' personal gender attitudes.To explore factors that shape gender attitudes in early adolescence across different cultural settings globally.A mixed-methods systematic review was conducted of the peer-reviewed literature in 12 databases from 1984-2014. Four reviewers screened the titles and abstracts of articles and reviewed full text articles in duplicate. Data extraction and quality assessments were conducted using standardized templates by study design. Thematic analysis was used to synthesize quantitative and qualitative data organized by the social-ecological framework (individual, interpersonal and community/societal-level factors influencing gender attitudes.Eighty-two studies (46 quantitative, 31 qualitative, 5 mixed-methods spanning 29 countries were included. Ninety percent of studies were from North America or Western Europe. The review findings indicate that young adolescents, across cultural settings, commonly express stereotypical or inequitable gender attitudes, and such attitudes appear to vary by individual sociodemographic characteristics (sex, race/ethnicity and immigration, social class, and age. Findings highlight that interpersonal influences (family and peers are central influences on young adolescents' construction of gender attitudes, and these gender socialization processes differ for boys and girls. The role of community factors (e.g. media is less clear though there is some evidence that schools may reinforce stereotypical gender attitudes among young adolescents.The findings from this review suggest that young adolescents in different

Modulation of early stress-induced neurobiological changes: a review of behavioural and pharmacological interventions in animal models.

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Harrison, E L; Baune, B T

2014-05-13

Childhood adversity alters the predisposition to psychiatric disorders later in life. Those with psychiatric conditions and a history of early adversity exhibit a higher incidence of treatment resistance compared with individuals with no such history. Modulation of the influence early stress exerts over neurobiology may help to prevent the development of psychiatric disorders in some cases, while attenuating the extent of treatment resistance in those with established psychiatric disorders. This review aims to critically evaluate the ability of behavioural, environmental and pharmacologic interventions to modulate neurobiological changes induced by early stress in animal models. Databases were systematically searched to locate literature relevant to this review. Early adversity was defined as stress that resulted from manipulation of the mother-infant relationship. Analysis was restricted to animal models to enable characterisation of how a given intervention altered specific neurobiological changes induced by early stress. A wide variety of changes in neurobiology due to early stress are amenable to intervention. Behavioural interventions in childhood, exercise in adolescence and administration of epigenetic-modifying drugs throughout life appear to best modulate cellar and behavioural alterations induced by childhood adversity. Other pharmacotherapies, such as endocannabinoid system modulators, anti-inflammatories and antidepressants can also influence these neurobiological and behavioural changes that result from early stress, although findings are less consistent at present and require further investigation. Further work is required to examine the influence that behavioural interventions, exercise and epigenetic-modifying drugs exert over alterations that occur following childhood stress in human studies, before possible translational into clinical practice is possible.

Invited review: Carryover effects of early lactation feeding on total lactation performance in dairy cows

DEFF Research Database (Denmark)

Jørgensen, Carina; Spörndly, R; Bertilsson, J

2016-01-01

In comparison with the intensive research on the direct effects of energy supply on dairy cow lactation performance, little attention has been paid to the effect of early lactation feeding on subsequent production. The present paper reviews 9 studies carried out with the aim of quantifying...... the immediate and subsequent responses in milk production and body weight to early lactation feeding. Most results showed that a more generous feeding in early lactation caused a positive carryover effect on subsequent production, whereas an inadequate level of feed in early lactation has been shown to reduce...... to be determined by several factors including duration of the treatment and post-treatment feeding level. The most important factor though appears to be the magnitude of over- or underfeeding (i.e., a strong relationship between the treatment period feeding level and the subsequent response in production)....

Erythropoietin Attenuates the Memory Deficits in Aging Rats by Rescuing the Oxidative Stress and Inflammation and Promoting BDNF Releasing.

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Jia, Zhankui; Xue, Rui; Ma, Shengli; Xu, Jingjing; Guo, Si; Li, Songchao; Zhang, Erwei; Wang, Jun; Yang, Jinjian

2016-10-01

Aging is a natural process accompanied with many disorders, including the memory decline. The underlying mechanisms for the age-related memory decline are complicated. Previous work suggested that oxidative stress, inflammatory disturbance, and the neurotropic absence play important roles in the age-related disorders. Thus, to seek a drug to target those abnormalities might be a possible protective approach for aging. Here, we reported that supplements with exogenous erythropoietin (EPO) for 4 weeks could partially rescue the spatial and fear memory impairments in aged rats. The EPO treatment also suppresses the oxidative stress and inflammatory response. Most importantly, EPO supplement restores the mRNA and protein levels of brain-derived neurotrophic factor (BDNF), the critical neurotropic factor for synaptic plasticity and memory. Our study strongly suggests the potential usage of EPO in an anti-aging agent clinically.

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

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Liu, Wei

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

Stabilization of bacterially expressed erythropoietin by single site-specific introduction of short branched PEG chains at naturally occurring glycosylation sites.

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Hoffmann, E; Streichert, K; Nischan, N; Seitz, C; Brunner, T; Schwagerus, S; Hackenberger, C P R; Rubini, M

2016-05-24

The covalent attachment of polyethylene glycol (PEG) to therapeutic proteins can improve their physicochemical properties. In this work we utilized the non-natural amino acid p-azidophenylalanine (pAzF) in combination with the chemoselective Staudinger-phosphite reaction to install branched PEG chains to recombinant unglycosylated erythropoietin (EPO) at each single naturally occurring glycosylation site. PEGylation with two short 750 or 2000 Da PEG units at positions 24, 38, or 83 significantly decreased unspecific aggregation and proteolytic degradation while biological activity in vitro was preserved or even increased in comparison to full-glycosylated EPO. This site-specific bioconjugation approach permits to analyse the impact of PEGylation at single positions. These results represent an important step towards the engineering of site-specifically modified EPO variants from bacterial expression with increased therapeutic efficacy.

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

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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.

Effects of healthcare professional delivered early feeding interventions on feeding practices and dietary intake: A systematic review.

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Matvienko-Sikar, Karen; Toomey, Elaine; Delaney, Lisa; Harrington, Janas; Byrne, Molly; Kearney, Patricia M

2018-04-01

Childhood obesity is a global public health challenge. Parental feeding practices, such as responsive feeding, are implicated in the etiology of childhood obesity. This systematic review aimed to examine of effects of healthcare professional-delivered early feeding interventions, on parental feeding practices, dietary intake, and weight outcomes for children up to 2 years. The role of responsive feeding interventions was also specifically examined. Databases searched included: CINAHL, the Cochrane Library, EMBASE, Medline, PubMed, PsycINFO, and Maternity and Infant Care. participants are parents of children ≤2 years; intervention includes focus on early child feeding to prevent overweight and obesity; intervention delivered by healthcare professionals. Sixteen papers, representing 10 trials, met inclusion criteria for review. Six interventions included responsive feeding components. Interventions demonstrated inconsistent effects on feeding practices, dietary intake, and weight outcomes. Findings suggest some reductions in pressure to eat and infant consumption of non-core beverages. Responsive feeding based interventions demonstrate greater improvements in feeding approaches, and weight outcomes. The findings of this review highlight the importance of incorporating responsive feeding in healthcare professional delivered early feeding interventions to prevent childhood obesity. Observed inconsistencies across trials may be explained by methodological limitations. Copyright © 2017 Elsevier Ltd. All rights reserved.

ERYTHROPOIETIN TREATMENT FOR ANEMIA IN CHILDREN WITH CANCER – SINGLE CENTRE EXPERIENCES

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Polona Mali

2004-12-01

Full Text Available Background. Anemia, a common complication during treatment of malignant disease in children, was frequently treated with red blood cell transfusions. Several studies have shown, that the introduction of recombinant human erythropoietin (rh EPO for treating anemia in patients has been effective in reducing the need for transfusions. Variable doses of EPO from 150 to 900 IU/kg body weight have been used usually three times weekly. Recently some studies showed equally effective once weekly administration of EPO with proposed doses for children of 450 to 600 IU/ kg body weight.Efficacy and safety of once weekly EPO therapy was tested in 8/10 children treated in our Unit for solid tumors and nonHodgkin’s lymphoma. In this article we would like to present our one year experience with EPO treatment.Patients and methods. Patients have subcutaneously received the EPO dose of 600 UI/ kg body weight once weekly. Hemoglobin response and transfusion needs before and during treatment with EPO were analyzed.Results. Response was seen in 7/8 of patient, with increased hemoglobin level and lower transfusion needs. Only one patient was poor responder at first, but responded perfect after twice weekly EPO application. No adverse reaction related to EPO therapy was observed.Conclusions. Our experience with treating anemia in pediatric cancer patients who undergo intensive and aggressive chemotherapy treatment regimens are good and promising. Once weekly dosage regimen is child friendly and acceptable way of treating anemia.

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

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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.

Feed-Back Regulation of Haemopoiesis

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Feldman, M. [Department of Cell Biology, Weizmann Institute of Science, Rehovoth (Israel)

1968-08-15

Studies ate reported on the feed-back regulation of erythropoiesis by means of the intrasplenic cloning system of haemopoietic cells. Polycythaemia, produced by passive transfusion of synzeneic, allogeneic or xenogeneic red blood cells, inhibited the formation of bone-marrow derived erythroid clones. Polycythaemia also inhibited the formation of erythroid clones of endogenous stem cells. Oxygen overloading was found to be a necessary factor in the suppression of erythroid clone formation: no suppression of erythroid colonies was observed when polycythaemic animals were kept under hypoxic conditions. Erythropoietin, either of exogenous or of endogenous origin, elicited a reformation of erythroid clones in 'suppressed' animals. Studies on the kinetics of reformation of erythroid clones after the administration of erythropoietin suggested that the colony-forming stem cell can replicate a few times in the absence of erythropoietin and the cell progeny thus formed are the target cells for erythropoietin action. If, indeed, the colony-forming cell replicates in the absence of the specific inducer, then the cells thus formed should themselves be stem cells. This was substantiated by demonstrating that the cloning efficiency of spleens of polycythaemic recipients was higher than that of non-polycythaemic animals. Experiments indicating that erythroid clones produced by erythropoietin in polycythaemic animals disappeared after the discontinuance of erythropoietin application demonstrated the distinction between the 'mitogenic' and the 'morphogenetic' effects of erythropoietin. The latter seemed to be operated by an early transcription of RNA for proteins necessary for the complete maturation of the red blood cell, Erythroid clones produced by foetal haemopoietic stem cells seemed to be regulated by a different mechanism from that which controls the formation of bone-marrow derived clones. Clones produced by foetal cells were only partially suppressed in the polycythaemic

Erythropoietin in the treatment of carbon monoxide neurotoxicity in rat.

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Moallem, Seyed Adel; Mohamadpour, Amir Hooshang; Abnous, Khalil; Sankian, Mojtaba; Sadeghnia, Hamid Reza; Tsatsakis, Aristidis; Shahsavand, Shabnam

2015-12-01

Erythropoietin (EPO) plays a critical role in the development of the nervous system. In this study, the effects of EPO in carbon monoxide (CO) neurotoxicity were examined. Rats were exposed to 3000 ppm CO for 1 h and then different doses of EPO were administrated intraperitoneally. After 24 h, glial fibrillary acidic protein (GFAP) levels in the serum were determined and water content of brain and the extravasation of a tracer (Evans blue) were measured. Brain lipid peroxidation, myeloperoxidase activity Myelin basic protein (MBP) and BAX/BcL2 protein relative expressions were determined. Cation exchange chromatography was used to evaluate MBP alterations. Seven days after exposure, pathological assessment was performed after Klüver-Barrera staining. EPO reduced malondialdehyde levels at all doses (2500, 5000 and 10,000 u/kg). Lower doses of EPO (625, 1250, 2500 u/kg) significantly decreased the elevated serum levels of GFAP. EPO could not reduce the water content of the edematous poisoned brains. However, at 5000 and 10,000 u/kg it protected the blood brain barrier against integrity loss as a result of CO. EPO could significantly decrease the MPO activity. CO-mediated oxidative stress caused chemical alterations in MBP and EPO could partially prevent these biochemical changes. Fewer vacuoles and demyelinated fibers were found in the EPO-treated animals. EPO (5000 u/kg) could restore the MBP density. CO increased brain BAX/Bcl-2 ratio 38.78%. EPO reduced it 38.86%. These results reveal that EPO could relatively prevent different pathways of neurotoxicity by CO poisoning and thus has the potential to be used as a novel approach to manage this poisoning. Copyright © 2015 Elsevier Ltd. All rights reserved.

Erythropoietin's Beta Common Receptor Mediates Neuroprotection in Spinal Cord Neurons.

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Foley, Lisa S; Fullerton, David A; Mares, Joshua; Sungelo, Mitchell; Weyant, Michael J; Cleveland, Joseph C; Reece, T Brett

2017-12-01

Paraplegia from spinal cord ischemia-reperfusion (SCIR) remains an elusive and devastating complication of complex aortic operations. Erythropoietin (EPO) attenuates this injury in models of SCIR. Upregulation of the EPO beta common receptor (βcR) is associated with reduced damage in models of neural injury. The purpose of this study was to examine whether EPO-mediated neuroprotection was dependent on βcR expression. We hypothesized that spinal cord neurons subjected to oxygen-glucose deprivation would mimic SCIR injury in aortic surgery and EPO treatment attenuates this injury in a βcR-dependent fashion. Lentiviral vectors with βcR knockdown sequences were tested on neuron cell cultures. The virus with greatest βcR knockdown was selected. Spinal cord neurons from perinatal wild-type mice were harvested and cultured to maturity. They were treated with knockdown or nonsense virus and transduced cells were selected. Three groups (βcR knockdown virus, nonsense control virus, no virus control; n = 8 each) were subjected to 1 hour of oxygen-glucose deprivation. Viability was assessed. βcR expression was quantified by immunoblot. EPO preserved neuronal viability after oxygen-glucose deprivation (0.82 ± 0.04 versus 0.61 ± 0.01; p neuron preservation was similar in the nonsense virus and control mice (0.82 ± 0.04 versus 0.80 ± 0.05; p = 0.77). EPO neuron preservation was lost in βcR knockdown mice compared with nonsense control mice (0.46 ± 0.03 versus 0.80 ± 0.05; p neuronal loss after oxygen-glucose deprivation in a βcR-dependent fashion. This receptor holds immense clinical promise as a target for pharmacotherapies treating spinal cord ischemic injury. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Systemic administration of erythropoietin inhibits retinopathy in RCS rats.

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Weiyong Shen

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

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

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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.

Erythropoietin improves the survival of fat tissue after its transplantation in nude mice.

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Hamed, Saher; Egozi, Dana; Kruchevsky, Danny; Teot, Luc; Gilhar, Amos; Ullmann, Yehuda

2010-11-15

Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

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

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

2012-01-01

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

Early orthodontic treatment for Class III malocclusion: A systematic review and meta-analysis.

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Woon, See Choong; Thiruvenkatachari, Badri

2017-01-01

Class III malocclusion affects between 5% and 15% of our population. The 2 most common dilemmas surrounding Class III treatment are the timing of treatment and the type of appliance. A number of appliances have been used to correct a Class III skeletal discrepancy, but there is little evidence available on their effectiveness in the long term. Similarly, early treatment of Class III malocclusion has been practiced with increasing interest. However, there has been no solid evidence on the benefits in the long term. The aim of this systematic review was to evaluate the effectiveness of orthodontic/orthopedic methods used in the early treatment of Class III malocclusion in the short and long terms. Several sources were used to identify all relevant studies independently of language. The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase (Ovid), and MEDLINE (Ovid) were searched to June 2016. The selection criteria included randomized controlled trials (RCTs) and prospective controlled clinical trials (CCTs) of children between the ages of 7 and 12 years on early treatment with any type of orthodontic/orthopedic appliance compared with another appliance to correct Class III malocclusion or with an untreated control group. The primary outcome measure was correction of reverse overjet, and the secondary outcomes included skeletal changes, soft tissue changes, quality of life, patient compliance, adverse effect, Peer Assessment Rating score, and treatment time. The search results were screened for inclusion, and the data extracted by 2 independent authors. The data were analyzed using software (version 5.1, Review Manager; The Nordic Cochrane Centre, The Cochrane Collaboration; Copenhagen, Denmark). The mean differences with 95% confidence intervals were expressed for the continuous data. Random effects were carried out with high levels of clinical or statistical heterogeneity and fixed affects when the heterogeneity was low

Influence of shift work on early reproductive outcomes: a systematic review and meta-analysis.

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Stocker, Linden J; Macklon, Nicholas S; Cheong, Ying C; Bewley, Susan J

2014-07-01

To determine whether an association exists between shift work and early reproductive outcomes. MEDLINE, Embase, and Web of Science were searched. Additional sources included Google Scholar, the Cochrane Library, online publications of national colleges, the ClinicalTrials.gov, and references of retrieved papers. Included studies compared female shift workers (work outside 8:00 AM to 6:00 PM) with nonshift workers with menstrual disruption (cycles less than 25 days or greater than 31 days), infertility (time-to-pregnancy exceeding 12 months), or early spontaneous pregnancy loss (less than 25 weeks). Two reviewers extracted adjusted and raw data. Random effect models were used to pool data weighting for the inverse of variance. Assessments of heterogeneity, bias, and subgroup analyses were performed. Sixteen independent cohorts from 15 studies (123,403 women) were subject to analysis. Shift workers had increased rates of menstrual disruption (16.05% [2,207/13,749] compared with 13.05% [7,561/57,932] [n=71.681, odds ratio {OR} 1.22, 95% confidence interval {CI} 1.15-1.29, I 0%]) and infertility (11.3% [529/4,668] compared with 9.9% [2,354/23,811] [OR 1.80, 95% CI 1.01-3.20, I 94%]) but not early spontaneous pregnancy loss (11.84% [939/7,931] compared with 12.11% [1,898/15,673] [n=23,604, OR 0.96, 95% CI 0.88-1.05, I 0%]). Night shifts were associated with increased early spontaneous pregnancy loss (n=13,018, OR 1.29, 95% CI 1.11-1.50, I 0%). Confounder adjustment led to persistent relationships between shift work and menstrual disruption (adjusted OR 1.15, 95% CI 1.01-1.31, I 70%) but not infertility (adjusted OR 1.11 95% CI 0.86-1.44, I 61%). The association between night shifts and early spontaneous pregnancy loss remained (adjusted OR 1.41 95% CI 1.22-1.63, I 0%). This review provides evidence for an association between performing shift work and early reproductive outcomes, consistent with later pregnancy findings. However, there is currently insufficient evidence

Understanding Factors that Shape Gender Attitudes in Early Adolescence Globally: A Mixed-Methods Systematic Review

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Gibbs, Susannah; Blum, Robert Wm; Moreau, Caroline; Chandra-Mouli, Venkatraman; Herbert, Ann; Amin, Avni

2016-01-01

Background Early adolescence (ages 10–14) is a period of increased expectations for boys and girls to adhere to socially constructed and often stereotypical norms that perpetuate gender inequalities. The endorsement of such gender norms is closely linked to poor adolescent sexual and reproductive and other health-related outcomes yet little is known about the factors that influence young adolescents’ personal gender attitudes. Objectives To explore factors that shape gender attitudes in early adolescence across different cultural settings globally. Methods A mixed-methods systematic review was conducted of the peer-reviewed literature in 12 databases from 1984–2014. Four reviewers screened the titles and abstracts of articles and reviewed full text articles in duplicate. Data extraction and quality assessments were conducted using standardized templates by study design. Thematic analysis was used to synthesize quantitative and qualitative data organized by the social-ecological framework (individual, interpersonal and community/societal-level factors influencing gender attitudes). Results Eighty-two studies (46 quantitative, 31 qualitative, 5 mixed-methods) spanning 29 countries were included. Ninety percent of studies were from North America or Western Europe. The review findings indicate that young adolescents, across cultural settings, commonly express stereotypical or inequitable gender attitudes, and such attitudes appear to vary by individual sociodemographic characteristics (sex, race/ethnicity and immigration, social class, and age). Findings highlight that interpersonal influences (family and peers) are central influences on young adolescents’ construction of gender attitudes, and these gender socialization processes differ for boys and girls. The role of community factors (e.g. media) is less clear though there is some evidence that schools may reinforce stereotypical gender attitudes among young adolescents. Conclusions The findings from this

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

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AL-Rohani Muhamed

2001-01-01

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

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

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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.

Review of conservative surgery in early breast cancer. British Columbia experience.

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Holmvang, A M; Grafton, C; Sandy, J T

1985-05-01

Conservation mastectomy in combination with radiotherapy is becoming an accepted treatment for early breast cancer. No absolute guidelines exist as to appropriate patient selection or correct surgical technique, but certain unifying trends can be ascertained from the current literature. The purpose of this study was to review the literature and to identify areas of incongruence between present management of patients in British Columbia and suggestions in the current literature. One hundred patients were reviewed. Twenty-six percent of them did not receive preoperative mammograms, and tumor stage was inappropriate in 9 percent. Thirteen percent had excisional biopsies only. A quarter of the patients had tumor resection through unfavorably placed incisions. Eight percent did not have estrogen receptor determination. Thirty-nine percent of the pathology reports made no comment as to adequacy of resection margins. It is hoped that these areas that, with proper attention, can improve cosmetic results and decrease the incidence of local tumor recurrence.

Practitioner Research in Early Childhood Education and Care: A 21-Year Review of the Literature

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Shannon, Darbianne; Smith, Sara; Dana, Nancy

2016-01-01

Practitioner research has the potential to facilitate the ongoing knowledge and skill development of preservice and in-service early childhood education and care teachers. The purpose of this systematic literature review is to describe the landscape of practitioner research conducted in the United States. This study synthesizes more than 20 years…

Everyday Decision Making in Individuals with Early-Stage Alzheimer's Disease: An Integrative Review of the Literature.

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Davis, Rebecca; Ziomkowski, Mary K; Veltkamp, Amy

2017-09-01

Individuals with Alzheimer's disease (AD) demonstrate fluctuation in cognitive abilities that can affect their ability to make decisions. Everyday decision making encompasses the types of decisions about typical daily activities, such as what to eat, what to do, and what to wear. Everyday decisions are encountered many times per day by individuals with AD/dementia and their caregivers. However, not much is known about the ability of individuals with AD/dementia to make these types of decisions. The purpose of the current literature review was to synthesize the evidence regarding everyday decision making in individuals with early-stage AD/dementia. Findings from the review indicate there is beginning evidence that individuals with early to moderate stages of AD/dementia desire to have input in daily decisions, have the ability to state their wishes consistently at times, and having input in decision making is important to their selfhood. The literature revealed few interventions to assist individuals with AD/dementia in everyday decision making. Findings from the review are discussed with implications for nursing practice and research. [Res Gerontol Nurs. 2017; 10(5):240-247.]. Copyright 2017, SLACK Incorporated.

Review of Structural Social Determinants of Health in Early Childhood Development

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Firoozeh Sajedi

2015-09-01

Full Text Available Development is a dynamic and continuous phenomenon  that is under the influence of various factors forming a complicated multidimensional system together. Any impairment in these factors can lead to impaired development in children, which is one of the most common problems in children. Therefore, this study provides a brief overview of these factors and the way they affect early childhood development. A brief review was performed in databases including Google scholar, PUBMED, Proquest, SID, Magiran, Iranmedex, Irandoc with following keywords: child  development, income, occupation, education, employment, boy, girl,  gender, sex, social class, Race and Ethnicity. All of article was reviewed then categorized based on WHO model. Among the papers reviewed, most of the studies were about employment, education, and income and most of them investigated these risk factors in terms of socioeconomic status. Structural factors of social determinants of health had a close relationship with each other, and they  had affected development through each other. Given that, only few studies on structural factors, except for socioeconomic factors, have been conducted and little attention has been paid to the way these factors affect child development, further studies in this area are required to propose a model in order to better understand the interaction between these factors.

Effects of recombinant human erythropoietin injections on physical self in endurance athletes.

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Ninot, Grégory; Connes, Philippe; Caillaud, Corrine

2006-04-01

This study examined the time course of mean self-esteem and physical self scores in three groups: male endurance athletes treated with recombinant human erythropoietin (rHuEPO group, n = 6), a placebo group (n = 5) injected with a sodium chloride solution and a control group who did not receive any injection (n = 6). Each participant completed the Physical Self Inventory twice a day (between 07.00 and 09.00 h and between 19.00 and 21.00 h). Using a 10 cm visual analog scale, the participants assessed global self-esteem, physical self-worth and the sub-domains of physical condition, sport competence, attractive body and physical strength (Fox & Corbin, 1989). This was conducted over three consecutive periods: in the 2 weeks before the course of injections, during the 6 weeks of injections and for 4 weeks after the injections. Aerobic capacity was assessed before and after 4 weeks of treatment. The results showed a significant increase in aerobic physical fitness in the rHuEPO group and a significant increase in perceived physical condition and physical strength scores at the end of treatment. The main psychological result was that endurance athletes were highly sensitive to the effects of rHuEPO on physical fitness. The perception of increased physical condition may lead to a stronger commitment to training. The rHuEPO injections presented a dangerous hedonic effect linked to endurance training. These results confirm the need to tackle rHuEPO abuse at any time during the training season.

Falls and Fall Prevention in Older Adults With Early-Stage Dementia: An Integrative Review.

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Lach, Helen W; Harrison, Barbara E; Phongphanngam, Sutthida

2017-05-01

Older adults with mild cognitive impairment (MCI) and early-stage dementia have an increased risk of falling, with risks to their health and quality of life. The purpose of the current integrative review was to evaluate evidence on fall risk and fall prevention in this population. Studies were included if they examined falls or fall risk factors in older adults with MCI or early-stage dementia, or reported interventions in this population; 40 studies met criteria. Evidence supports the increased risk of falls in individuals even in the early stages of dementia or MCI, and changes in gait, balance, and fear of falling that may be related to this increased fall risk. Interventions included exercise and multifactorial interventions that demonstrated some potential to reduce falls in this population. Few studies had strong designs to provide evidence for recommendations. Further study in this area is warranted. [Res Gerontol Nurs. 2017; 10(03):139-148.]. Copyright 2016, SLACK Incorporated.

Effects of need supportive teaching on early adolescents' motivation and engagement : A review of the literature

NARCIS (Netherlands)

Stroet, Kim; Opdenakker, Marie; Minnaert, Alexander

In the present paper we systematically review the corpus of evidence on the effects of need supportive teaching on early adolescents' motivation and engagement for school. Based on Self-Determination Theory, we define need supportive teaching in terms of teachers' provision of autonomy support,

Non-pharmacological and pharmacological interventions in patients with early arthritis: a systematic literature review informing the 2016 update of EULAR recommendations for the management of early arthritis

NARCIS (Netherlands)

Daien, Claire Immediato; Hua, Charlotte; Combe, Bernard; Landewe, Robert

2017-01-01

To perform a systematic literature review (SLR) on pharmacological and non-pharmacological treatments, in order to inform the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis (EA). The expert committee defined research questions concerning

Recommendations for the clinical practice: Standards, options and recommendations 2003 for the use of recombinant erythropoietin (alpha and beta epoetine, alpha darbepoetine, EPO) in the taking charge of anemia in oncology for the patients treated by radiotherapy, update

International Nuclear Information System (INIS)

Marchal, Ch.; Spaeth, C.; Casadevall, N.; Daouphars, M.; Marec-Berard, P.; Fabre, N.; Haugh, M.

2004-01-01

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

Serum level of vascular endothelial growth factor is influenced by erythropoietin treatment in peritoneal dialysis patients. (Grupo de Estudios Peritoneales de Madrid).

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del Peso, G; Selgas, R; Bajo, M A; Fernández de Castro, M; Aguilera, A; Cirugeda, A; Jiménez, C

2000-01-01

Some patients on long-term peritoneal dialysis (PD) develop a hyperpermeability state, owing to peritoneal neoangiogenesis. Vascular endothelial growth factor (VEGF), a potent mitogen for endothelial cells, has been implicated in most diseases characterized by microvascular neoformation. Erythropoietin (EPO) is able to induce endothelial proliferation in vitro. Our aim was to elucidate whether VEGF serum levels are influenced by EPO treatment, and whether VEGF serum level maintains a relationship with peritoneal transport data. We analyzed serum levels of VEGF in 35 PD patients (18 males, 17 females). Mean age was 58 years, with a mean time on PD of 98 +/- 75 months. Of the 35 patients, 19 were on automated peritoneal dialysis, and 16 were on continuous ambulatory peritoneal dialysis. Seven patients had diabetes. Peritoneal transport parameters were: urea mass transfer coefficient (MTC), 19.5 +/- 6.6 mL/min; creatinine MTC, 9.9 +/- 4.7 mL/min; net ultrafiltration, 491 +/- 166 mL per 4-hour dwell. Twenty seven patients were under therapy with recombinant human erythropoietin (rHuEPO). Mean serum VEGF levels were 347 +/- 203 pg/mL (range 66-857 pg/mL), with most patients in the normal range (60-700 pg/mL). VEGF levels did not correlate with age, sex, primary renal disease, diabetes, type of PD, time on PD, peritonitis, and cumulative glucose load. We found no correlation with urea MTC, creatinine MTC, ultrafiltration rate, or protein effluent levels. However, a significant negative correlation with residual renal function was seen (r = -0.39, p < 0.05). Patients treated with rHuEPO showed significantly higher serum levels of VEGF than non treated patients (375 +/- 220 pg/mL vs 251 +/- 75 pg/mL, p < 0.05), although they had similar residual renal function. We conclude that increased serum VEGF levels are associated with EPO treatment. Consequently, VEGF might have a role in the EPO effects found in PD patients. Whether both agents are related to peritoneal

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

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

2016-09-01

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

Erythropoietin improves the survival of fat tissue after its transplantation in nude mice.

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Saher Hamed

Full Text Available BACKGROUND: Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. METHODOLOGY/PRINCIPAL FINDINGS: Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF-treated and phosphate-buffered saline (PBS-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. CONCLUSIONS/SIGNIFICANCE: Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

Cost analysis of erythropoietin versus blood transfusions for cervical cancer patients receiving chemoradiotherapy

International Nuclear Information System (INIS)

Kavanagh, Brian D.; Fischer, Bernard A.; Segreti, Eileen M.; Wheelock, John B.; Boardman, Cecilia; Roseff, Susan D.; Cardinale, Robert M.; Benedict, Stanley H.; Goram, Adrian L.

2001-01-01

Purpose: Red blood cell (RBC) transfusions or erythropoietin (EPO) can be used to evade the detrimental effects of anemia during radiotherapy, but the economic consequences of selecting either intervention are not well defined. The RBC transfusion needs during chemoradiotherapy for cervix cancer were quantified to allow comparison of RBC transfusion costs with the projected cost of EPO in this setting. Methods and Materials: For patients receiving pelvic radiotherapy, weekly cisplatin, and brachytherapy, the RBC units transfused during treatment were tallied. RBC transfusion costs per unit included the blood itself, laboratory fees, and expected value (risk multiplied by cost) of transfusion-related viral illness. EPO costs included the drug itself and supplemental RBC transfusions when hemoglobin was not adequately maintained. An EPO dosage based on reported usage in cervix cancer patients was applied. Results: Transfusions were given for hemoglobin <10 g/dL. Among 12 consecutive patients, 10 needed at least 1 U of RBC before or during treatment, most commonly after the fifth week. A total of 37 U was given during treatment, for an average of 3.1 U/patient. The sum total of the projected average transfusion-related costs was $990, compared with the total projected EPO-related costs of $3869. Conclusions: Because no proven clinical advantage has been documented for EPO compared with RBC transfusions to maintain hemoglobin during cervix cancer treatment, for most patients, transfusions are an appropriate and appealingly less expensive option

Utilisation of helicopter emergency medical services in the early medical response to major incidents: a systematic literature review.

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Johnsen, Anne Siri; Fattah, Sabina; Sollid, Stephen J M; Rehn, Marius

2016-02-09

This systematic review identifies, describes and appraises the literature describing the utilisation of helicopter emergency medical services (HEMS) in the early medical response to major incidents. Early prehospital phase of a major incident. Systematic literature review performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Web of Science, PsycINFO, Scopus, Cinahl, Bibsys Ask, Norart, Svemed and UpToDate were searched using phrases that combined HEMS and 'major incidents' to identify when and how HEMS was utilised. The identified studies were subjected to data extraction and appraisal. The database search identified 4948 articles. Based on the title and abstract, the full text of 96 articles was obtained; of these, 37 articles were included in the review, and an additional five were identified by searching the reference lists of the 37 articles. HEMS was used to transport medical and rescue personnel to the incident and to transport patients to the hospital, especially when the infrastructure was damaged. Insufficient air traffic control, weather conditions, inadequate landing sites and failing communication were described as challenging in some incidents. HEMS was used mainly for patient treatment and to transport patients, personnel and equipment in the early medical management of major incidents, but the optimal utilisation of this specialised resource remains unclear. This review identified operational areas with improvement potential. A lack of systematic indexing, heterogeneous data reporting and weak methodological design, complicated the identification and comparison of incidents, and more systematic reporting is needed. CRD42013004473. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

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Michele Cardoso do Nascimento

2015-08-01

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

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

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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.

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

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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.

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

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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.

Social marketing approaches to nutrition and physical activity interventions in early care and education centres: a systematic review.

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Luecking, C T; Hennink-Kaminski, H; Ihekweazu, C; Vaughn, A; Mazzucca, S; Ward, D S

2017-12-01

Social marketing is a promising planning approach for influencing voluntary lifestyle behaviours, but its application to nutrition and physical activity interventions in the early care and education setting remains unknown. PubMed, ISI Web of Science, PsycInfo and the Cumulative Index of Nursing and Allied Health were systematically searched to identify interventions targeting nutrition and/or physical activity behaviours of children enrolled in early care centres between 1994 and 2016. Content analysis methods were used to capture information reflecting eight social marketing benchmark criteria. The review included 135 articles representing 77 interventions. Two interventions incorporated all eight benchmark criteria, but the majority included fewer than four. Each intervention included behaviour and methods mix criteria, and more than half identified audience segments. Only one-third of interventions incorporated customer orientation, theory, exchange and insight. Only six interventions addressed competing behaviours. We did not find statistical significance for the effectiveness of interventions on child-level diet, physical activity or anthropometric outcomes based on the number of benchmark criteria used. This review highlights opportunities to apply social marketing to obesity prevention interventions in early care centres. Social marketing could be an important strategy for early childhood obesity prevention efforts, and future research investigations into its effects are warranted. © 2017 World Obesity Federation.

Effect of women's nutrition before and during early pregnancy on maternal and infant outcomes: a systematic review.

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Ramakrishnan, Usha; Grant, Frederick; Goldenberg, Tamar; Zongrone, Amanda; Martorell, Reynaldo

2012-07-01

Current understanding of biologic processes indicates that women's nutritional status before and during early pregnancy may play an important role in determining early developmental processes and ensuring successful pregnancy outcomes. We conducted a systematic review of the evidence for the impact of maternal nutrition before and during early pregnancy (health outcomes and included 45 articles (nine intervention trials and 32 observational studies) that were identified through PubMed and EMBASE database searches and examining review articles. Intervention trials and observational studies show that periconceptional (importance of women's nutrition prior to and during the first trimester of pregnancy, but there is a need for well-designed prospective studies and controlled trials in developing country settings that examine relationships with low birthweight, SGA, PTD, stillbirth and maternal and neonatal mortality. The knowledge gaps that need to be addressed include the evaluation of periconceptional interventions such as food supplements, multivitamin-mineral supplements and/or specific micronutrients (iron, zinc, iodine, vitamin B-6 and B-12) as well as the relationship between measures of prepregnancy body size and composition and maternal, neonatal and child health outcomes. © 2012 Blackwell Publishing Ltd.

Early Diagnosis, Treatment, and Care of Cancer Patients

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2010-09-01

W81XWH-07-1-0601 17 Key Research Accomplishments We have discovered a remarkable protective capacity of EPO against neurotoxic activities of 5...Xue, Y.Q., et al., Intrastriatal administration of erythropoietin protects dopaminergic neurons and improves neurobehavioral outcome in a rat model of...W81XWH-07-1-0601 7 begin testing to provide proof of principle for protective strategies that involve administration of N-acetyl-L-cysteine (alone or

Early infant male circumcision: Systematic review, risk-benefit analysis, and progress in policy.

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Morris, Brian J; Kennedy, Sean E; Wodak, Alex D; Mindel, Adrian; Golovsky, David; Schrieber, Leslie; Lumbers, Eugenie R; Handelsman, David J; Ziegler, John B

2017-02-08

To determine whether recent evidence-based United States policies on male circumcision (MC) apply to comparable Anglophone countries, Australia and New Zealand. Articles in 2005 through 2015 were retrieved from PubMed using the keyword "circumcision" together with 36 relevant subtopics. A further PubMed search was performed for articles published in 2016. Searches of the EMBASE and Cochrane databases did not yield additional citable articles. Articles were assessed for quality and those rated 2+ and above according to the Scottish Intercollegiate Grading System were studied further. The most relevant and representative of the topic were included. Bibliographies were examined to retrieve further key references. Randomized controlled trials, recent high quality systematic reviews or meta-analyses (level 1++ or 1+ evidence) were prioritized for inclusion. A risk-benefit analysis of articles rated for quality was performed. For efficiency and reliability, recent randomized controlled trials, meta-analyses, high quality systematic reviews and large well-designed studies were used if available. Internet searches were conducted for other relevant information, including policies and Australian data on claims under Medicare for MC. Evidence-based policy statements by the American Academy of Pediatrics (AAP) and the Centers for Disease Control and Prevention (CDC) support infant and later age male circumcision (MC) as a desirable public health measure. Our systematic review of relevant literature over the past decade yielded 140 journal articles that met our inclusion criteria. Together, these showed that early infant MC confers immediate and lifelong benefits by protecting against urinary tract infections having potential adverse long-term renal effects, phimosis that causes difficult and painful erections and "ballooning" during urination, inflammatory skin conditions, inferior penile hygiene, candidiasis, various sexually transmissible infections in both sexes, genital

Review of the Ethical Issues of a Biomarker-Based Diagnoses in the Early Stage of Alzheimer's Disease.

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Vanderschaeghe, Gwendolien; Dierickx, Kris; Vandenberghe, Rik

2018-03-12

Today, many healthcare or dementia organizations, clinicians, and companies emphasize the importance of detection of Alzheimer's disease in an early phase. This idea has gained considerable momentum due to the development of biomarkers, the recent FDA and EMA approval of three amyloid tracers, and the failure of a number of recent therapeutic trials conducted in the early dementia phase. On the one hand, an early etiological diagnosis can lead to early and more efficacious intervention. On the other hand, it is questioned how early an etiological diagnosis is beneficial to the patient. Here we consider ethical issues related to the process of biomarker testing and the impact on the diagnostic disclosure to patients with mild cognitive impairment due to prodromal Alzheimer's disease. A systematic review of the theoretical bioethics literature was performed by using electronic databases. The review was limited to articles published in English between 2003 and 2016. A total of twenty articles were included in our effort to make an analysis of the ethical challenges. One of the biggest challenges was the uncertainty and the predictive value of the biomarker-based diagnosis where patients can be amyloid positive without full certainty whether or when they will develop symptomatic decline due to Alzheimer's disease. Another challenge was the tension between the right to know versus the wish not to know, the limited efficacy of currently available treatment options, and the opportunities and consequences after receiving such an early diagnosis. Based on the results and the additional comments in the discussion, several unanswered questions emerged. Therefore, careful consideration of all these ethical issues is required before the disclosure of a biomarker-based diagnosis to the patient with mild cognitive impairment due to Alzheimer's disease.

Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo.

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Ohls, Robin K; Kamath-Rayne, Beena D; Christensen, Robert D; Wiedmeier, Susan E; Rosenberg, Adam; Fuller, Janell; Lacy, Conra Backstrom; Roohi, Mahshid; Lambert, Diane K; Burnett, Jill J; Pruckler, Barbara; Peceny, Hannah; Cannon, Daniel C; Lowe, Jean R

2014-06-01

We previously reported decreased transfusions and donor exposures in preterm infants randomized to Darbepoetin (Darbe) or erythropoietin (Epo) compared with placebo. As these erythropoiesis-stimulating agents (ESAs) have shown promise as neuroprotective agents, we hypothesized improved neurodevelopmental outcomes at 18 to 22 months among infants randomized to receive ESAs. We performed a randomized, masked, multicenter study comparing Darbe (10 μg/kg, 1×/week subcutaneously), Epo (400 U/kg, 3×/week subcutaneously), and placebo (sham dosing 3×/week) given through 35 weeks' postconceptual age, with transfusions administered according to a standardized protocol. Surviving infants were evaluated at 18 to 22 months' corrected age using the Bayley Scales of Infant Development III. The primary outcome was composite cognitive score. Assessments of object permanence, anthropometrics, cerebral palsy, vision, and hearing were performed. Of the original 102 infants (946 ± 196 g, 27.7 ± 1.8 weeks' gestation), 80 (29 Epo, 27 Darbe, 24 placebo) returned for follow-up. The 3 groups were comparable for age at testing, birth weight, and gestational age. After adjustment for gender, analysis of covariance revealed significantly higher cognitive scores among Darbe (96.2 ± 7.3; mean ± SD) and Epo recipients (97.9 ± 14.3) compared with placebo recipients (88.7 ± 13.5; P = .01 vs ESA recipients) as was object permanence (P = .05). No ESA recipients had cerebral palsy, compared with 5 in the placebo group (P < .001). No differences among groups were found in visual or hearing impairment. Infants randomized to receive ESAs had better cognitive outcomes, compared with placebo recipients, at 18 to 22 months. Darbe and Epo may prove beneficial in improving long-term cognitive outcomes of preterm infants. Copyright © 2014 by the American Academy of Pediatrics.

Erythropoietin promotes network formation of transplanted adipose tissue-derived microvascular fragments

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P Karschnia

2018-05-01

Full Text Available The seeding of tissue constructs with adipose tissue-derived microvascular fragments (ad-MVF is an emerging pre-vascularisation strategy. Ad-MVF rapidly reassemble into new microvascular networks after in vivo implantation. Herein it was analysed whether this process was improved by erythropoietin (EPO. Ad-MVF were isolated from green fluorescent protein (GFP+ as well as wild-type C57BL/6 mice and cultivated for 24 h in medium supplemented with EPO (20 IU/mL or vehicle. Freshly isolated, non-cultivated ad-MVF served as controls. Protein expression, cell viability and proliferation of ad-MVF were assessed by proteome profiler array and fluorescence microscopy. GFP+ ad-MVF were seeded on collagen-glycosaminoglycan matrices, which were implanted into dorsal skinfold chambers of C57BL/6 mice, to analyse their vascularisation over 14 d by intravital fluorescence microscopy, histology and immunohistochemistry. Cultivation up-regulated the expression of pro- and anti-angiogenic factors within both vehicle- and EPO-treated ad-MVF when compared with non-cultivated controls. Moreover, EPO treatment suppressed cultivation-associated apoptosis and significantly increased the number of proliferating endothelial cells in ad-MVF when compared with vehicle-treated and non-cultivated ad-MVF. Accordingly, implanted matrices seeded with EPO-treated ad-MVF exhibited an improved vascularisation, as indicated by a significantly higher functional microvessel density. The matrices of the three groups contained a comparably large fraction of GFP+ microvessels originating from the ad-MVF, whereas the tissue surrounding the matrices seeded with EPO-treated ad-MVF exhibited a significantly increased microvessel density when compared with the other two groups. These findings indicated that EPO represents a promising cytokine to further boost the excellent vascularisation properties of ad-MVF in tissue-engineering applications.

Thrombolysis in the age of Primary Percutaneous Coronary Intervention: Mini-Review and Meta-analysis of Early PCI.

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Al Shammeri, O; Garcia, LA

2013-01-01

Primary Percutaneous Coronary Intervention (PCI) is the treatment of choice for ST-segment Elevation Myocardial Infarction (STEMI) if performed within 90 minutes from first medical contact. However, primary PCI is only available for less than 25% of patients with STEMI. Early PCI or Pharmaco-invasive strategy has evolved from facilitated PCI but with more delayed timing from thrombolysis to PCI. Assess the safety and effectiveness of Early PCI. We reviewed the data of the available therapy options for patients with STEMI. Then we performed a meta-analysis for all randomized controlled trials of early PCI versus standard therapy. Five studies fulfilled our inclusion criteria. Our meta-analysis showed improved cardiovascular events with early PCI compared to standard therapy (odd ratio of 0.54; 95% Confidence interval 0.47-0.7, pearly PCI 4 to 24 hours after successful thrombolysis. Early PCI should be done to all STEMI patients within 24 hours after successful thrombolysis.

Thrombolysis in the age of Primary Percutaneous Coronary Intervention: Mini-Review and Meta-analysis of Early PCI

Science.gov (United States)

Al Shammeri, O; Garcia, LA

2013-01-01

Objective Primary Percutaneous Coronary Intervention (PCI) is the treatment of choice for ST-segment Elevation Myocardial Infarction (STEMI) if performed within 90 minutes from first medical contact. However, primary PCI is only available for less than 25% of patients with STEMI. Early PCI or Pharmaco-invasive strategy has evolved from facilitated PCI but with more delayed timing from thrombolysis to PCI. Aim Assess the safety and effectiveness of Early PCI. Patients and Method We reviewed the data of the available therapy options for patients with STEMI. Then we performed a meta-analysis for all randomized controlled trials of early PCI versus standard therapy Results Five studies fulfilled our inclusion criteria. Our meta-analysis showed improved cardiovascular events with early PCI compared to standard therapy (odd ratio of 0.54; 95% Confidence interval 0.47-0.7, pPCI 4 to 24 hours after successful thrombolysis Conclusion Early PCI should be done to all STEMI patients within 24 hours after successful thrombolysis. PMID:23559909

77 FR 56853 - Submission for OMB Review; Comment Request: Process Evaluation of the Early Independence Award...

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2012-09-14

... respondents is estimated at $9,774. There are no Capital Costs to report. A.12.1--Annualized Estimate of Hour... Collection: Title: Process Evaluation of the Early Independence Award (EIA) Program. Type of Information.... Type of Respondents: Applicants, reviewers, and awardees. The annual reporting burden is as follows...

REVIEW: The early years of single photon emission computed tomography (SPECT): an anthology of selected reminiscences

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Jaszczak, Ronald Jack

2006-07-01

The origin of SPECT can be found in pioneering experiments on emission tomography performed approximately 50 years ago. This historical review consists of a compilation of first person recollections from nine trailblazing scientists who shaped the early years of SPECT instrumentation during the 1960s and 1970s.

[Evaluation of quality of service in Early Intervention: A systematic review].

Science.gov (United States)

Jemes Campaña, Inmaculada Concepción; Romero-Galisteo, Rita Pilar; Labajos Manzanares, María Teresa; Moreno Morales, Noelia

2018-06-07

Early Intervention (EI), as a paediatric service, has the duty of quantifying the results and the quality of its services provided. The accessibility of valid and reliable tools allows professionals to evaluate the quality of these services. The aim of this study is to review the scientific literature on tools used to measure the methodological and service quality in EI. A search was made in different databases: Medline (from PubMed), Web of Science, PsycINFO, Cochrane, Scopus, ERIC and Scielo. The methodological quality of the studies was tested using the COSMIN scale. A total of 13 manuscripts met the criteria to be included in this review. Ten of them received a "good" or "reasonable" score based on the COSMIN scale. Despite its importance, there is no consensus among authors on the measurement of service quality in EI. It is often the family of the children attended in EI that are considered the target to study, although the opinion of professionals carries more weight and completes the information. Copyright © 2018. Publicado por Elsevier España, S.L.U.

Design, modeling, expression, and chemoselective PEGylation of a new nanosize cysteine analog of erythropoietin

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Ahangari Cohan R

2011-06-01

Full Text Available Reza Ahangari Cohan1, Armin Madadkar-Sobhani2,3, Hossein Khanahmad1, Farzin Roohvand4, Mohammad Reza Aghasadeghi4, Mohammad Hossein Hedayati5, Zahra Barghi5, Mehdi Shafiee Ardestani4, Davoud Nouri Inanlou1, Dariush Norouzian11Research and Development Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran; 2Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; 3Department of Life Sciences, Barcelona Supercomputing Center, Barcelona, Spain; 4Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, Iran; 5Quality Control Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, IranBackground: Recombinant human erythropoietin (rhEPO is considered to be one of the most pivotal pharmaceutical drugs in the market because of its clinical application in the treatment of anemia-associated disorders worldwide. However, like other therapeutic proteins, it does not have suitable pharmacokinetic properties for it to be administrated at least two to three times per week. Chemoselective cysteine PEGylation, employing molecular dynamics and graphics in in silico studies, can be considered to overcome such a problem.Methods: A special kind of EPO analog was elicited based on a literature review, homology modeling, molecular dynamic simulation, and factors affecting the PEGylation reaction. Then, cDNA of the selected analog was generated by site-directed mutagenesis and subsequently cloned into the expression vector. The construct was transfected to Chinese hamster ovary/dhfr- cells, and highly expressed clones were selected via methotrexate amplification. Ion-immobilized affinity and size exclusion (SE chromatography techniques were used to purify the expressed analog. Thereafter, chemoselective PEGylation was performed and a nanosize PEGylated EPO was obtained through dialysis. The in vitro biologic assay and in vivo pharmacokinetic parameters were

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

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

Pacemaker implantation rate after transcatheter aortic valve implantation with early and new-generation devices: a systematic review.

Science.gov (United States)

van Rosendael, Philippe J; Delgado, Victoria; Bax, Jeroen J

2018-02-06

The incidence of new-onset conduction abnormalities requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) with new-generation prostheses remains debated. This systematic review analyses the incidence of PPI after TAVI with new-generation devices and evaluates the electrical, anatomical, and procedural factors associated with PPI. In addition, the incidence of PPI after TAVI with early generation prostheses was reviewed for comparison. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist, this systematic review screened original articles published between October 2010 and October 2017, reporting on the incidence of PPI after implantation of early and new-generation TAVI prostheses. Of the 1406 original articles identified in the first search for new-generation TAVI devices, 348 articles were examined for full text, and finally, 40 studies (n = 17 139) were included. The incidence of a PPI after the use of a new-generation TAVI prosthesis ranged between 2.3% and 36.1%. For balloon-expandable prostheses, the PPI rate remained low when using an early generation SAPIEN device (ranging between 2.3% and 28.2%), and with the new-generation SAPIEN 3 device, the PPI rate was between 4.0% and 24.0%. For self-expandable prostheses, the PPI rates were higher with the early generation CoreValve device (16.3-37.7%), and despite a reduction in PPI rates with the new Evolut R, the rates remained relatively higher (14.7-26.7%). When dividing the studies according to the highest (>26.0%) and the lowest (left ventricular outflow tract (anatomical factor), and balloon valvuloplasty and depth of implantation (procedural factors) were associated with increased risk of PPI. The rate of PPI after TAVI with new-generation devices is highly variable. Specific recommendations for implantation of each prosthesis, taking into consideration the presence of pre-existent conduction abnormalities and

Early post-operative psychosocial and weight predictors of later outcome in bariatric surgery: a systematic literature review.

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Hindle, A; de la Piedad Garcia, X; Brennan, L

2017-03-01

This is the first systematic review to synthesize the evidence concerning early post-operative variables predictive of later weight and psychosocial outcomes in bariatric surgery. Eight electronic databases for empirical studies were searched (1954 to 2016). Most of the 39 included studies reported solely on weight outcomes; eating and psychosocial outcomes were less common. A better early weight loss trajectory was the most consistent predictor of more successful medium-term weight outcome (≤24 months); however, its relationship to longer term weight loss maintenance is less certain. Early eating adaptation may be associated with later weight loss, but further research is needed. Evidence is lacking for associations between early adherence or early psychosocial variables and later outcome. In particular, the relationship between early post-operative depression and later weight remains unclear. Little research has considered early prediction of later eating or psychosocial outcomes. Consideration of mediating or moderating relationships is lacking. The body of evidence is limited, and synthesis is hampered by heterogeneity in the type and time at which predictors and outcomes are measured and quality of statistical reporting. Further research on prospective prediction of bariatric surgery outcome is needed to guide early post-operative intervention for those at greatest risk of poor outcomes. © 2017 World Obesity Federation.

A systematic review evaluating the role of nurses and processes for delivering early mobility interventions in the intensive care unit.

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Krupp, Anna; Steege, Linsey; King, Barbara

2018-04-19

To investigate processes for delivering early mobility interventions in adult intensive care unit patients used in research and quality improvement studies and the role of nurses in early mobility interventions. A systematic review was conducted. Electronic databases PubMED, CINAHL, PEDro, and Cochrane were searched for studies published from 2000 to June 2017 that implemented an early mobility intervention in adult intensive care units. Included studies involved progression to ambulation as a component of the intervention, included the role of the nurse in preparing for or delivering the intervention, and reported at least one patient or organisational outcome measure. The System Engineering Initiative for Patient Safety (SEIPS) model, a framework for understanding structure, processes, and healthcare outcomes, was used to evaluate studies. 25 studies were included in the final review. Studies consisted of randomised control trials, prospective, retrospective, or mixed designs. A range of processes to support the delivery of early mobility were found. These processes include forming interdisciplinary teams, increasing mobility staff, mobility protocols, interdisciplinary education, champions, communication, and feedback. Variation exists in the process of delivering early mobility in the intensive care unit. In particular, further rigorous studies are needed to better understand the role of nurses in implementing early mobility to maintain a patient's functional status. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of Need Supportive Teaching on Early Adolescents' Motivation and Engagement: A Review of the Literature

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Stroet, Kim; Opdenakker, Marie-Christine; Minnaert, Alexander

2013-01-01

In the present paper we systematically review the corpus of evidence on the effects of need supportive teaching on early adolescents' motivation and engagement for school. Based on Self-Determination Theory, we define need supportive teaching in terms of teachers' provision of autonomy support, structure, and involvement. The results of an…

Preliminary experience on early mechanical recanalization of middle cerebral artery for acute ischemic stroke and literature review

International Nuclear Information System (INIS)

Bai Weixing; Li Tianxiao; Zhu Liangfu; Xue Jiangyu; Wang Ziliang

2012-01-01

Objective: To evaluate the feasibility,efficacy and complication of early middle cerebral artery (MCA) mechanical recanalization (MER) for treatment of acute ischemic stroke. Methods: Seven cases undergone MER of MCA for the treatment of acute cerebral infarct were retrospectively reviewed and analyzed, including the etiology, mechanism, Qureshi grading scale, location and size of infarcts, NIHSS score of pre and post procedure, endovascular technique and complications. Referring to the literature, the indications of MCA recanalization were further identified. Results: A total of 7 cases with mean age of 48 yrs were reviewed, which included 3 cases of atherosclerotic thrombosis and 4 embolic cases with pre NIHSS score ranging from 3 to 22. Mechanical recanalization succeeded in 6 cases, but 2 cases of cardiogenic embolism died of intracranial hemorrhage postoperatively. Favorable clinical outcomes were achieved in 4 cases whereas 1 deteriorated. Overall complications seemed to be consistent with literatures reviewed. Conclusions: Early MER of MCA may benefit to a certain subset of acute ischemia stroke patients, however, embolic cases, elder patients and those with severe neurologic deficits are often accompanied by higher complications and unfavorable outcome. (authors)

A critical review: early life nutrition and prenatal programming for adult disease.

Science.gov (United States)

Carolan-Olah, Mary; Duarte-Gardea, Maria; Lechuga, Julia

2015-12-01

To present the evidence in relation to early life nutrition and foetal programming for adult disease. Epigenetics is a new and growing area of study investigating the impact of the intrauterine environment on the lifelong health of individuals. Discursive paper. Searches were conducted in a range of electronic health databases. Hand searches located additional articles for review. Maternal search terms included: pregnancy; nutrition; diet; obesity; over nutrition; under nutrition. Offspring related search terms included: macrosomia; intrauterine growth restriction; epigenetics; foetal programming; childhood obesity; adolescent obesity; adolescent type 2 diabetes. Results indicate that foetal programming for adult disease occurs in response to particular insults during vulnerable developmental periods. Four main areas of foetal exposure were identified in this review: (1) under nutrition; (2) over nutrition; (3) gestational diabetes mellitus; and (4) infant catch-up growth. Numerous studies also described the trans-generational nature of foetal programming. Overall, foetal exposure to excess or insufficient nutrition during vulnerable developmental periods appears to result in a lifelong predisposition to obesity and adult disease, such as type 2 diabetes and cardiac disease. For the infant who has been undernourished during early life, a predisposition to renal disease also occurs. Pregnancy is a time when women are engaged in health systems and are receptive to health messages. These factors suggest that pregnancy may be an optimal time for dietary education and intervention. There is a particular need for education on healthy diet and for interventions which aim to limit over consumption of calories. © 2015 John Wiley & Sons Ltd.

Clozapine Titration for People in Early Psychosis: A Chart Review and Treatment Guideline.

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Ballon, Jacob S; Ashfaq, Hera; Noordsy, Douglas L

2018-06-01

The use of clozapine, particularly in young people, is often limited by early treatment-emergent adverse effects including drowsiness and lethargy. Concerns about adverse effects, medication adherence, and the need for blood monitoring often impede the use of clozapine in this population, leading to repeated trials of less effective medications. Current clozapine dosing recommendations are based on people further in the course of their illness and thus reflect different responsiveness and sensitivities to antipsychotic medication. As such, there is a need for evidence-based guidelines for titration and dosing of clozapine among people in early psychosis. We performed a chart review of 14 people treated with clozapine within our early psychosis team. Data regarding dose titration, response, time to discontinuation, symptom severity, weight gain, and other adverse effects were gathered at clozapine initiation, 3 months, and last available visit on clozapine. People treated with slow titration within their first year of psychosis onset achieved sustained response at very low maintenance doses (mean dose = 81 mg/d, mean duration of treatment = 200 weeks) compared with slow titration with longer duration of illness (mean dose = 350 mg/d, mean duration of treatment = 68 weeks) or standard dose titration in early psychosis (mean dose = 112 mg/d, mean duration of treatment = 38 weeks). The most common adverse effects in all groups were weight gain and sedation, with the groups requiring higher mean doses reporting a broader range of adverse effects. There was no apparent difference in the clinical global impression for severity or improvement between the slow titration and standard titration groups in people with early psychosis. These observations are synthesized into a proposed treatment guideline for use of clozapine among people in early psychosis. We describe development of a slow titration approach to initiating clozapine among people in early psychosis. This

Searching for the structure of early American psychology: Networking Psychological Review, 1909-1923.

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Green, Christopher D; Feinerer, Ingo; Burman, Jeremy T

2015-05-01

This study continues a previous investigation of the intellectual structure of early American psychology by presenting and analyzing 3 networks that collectively include every substantive article published in Psychological Review during the 15-year period from 1909 to 1923. The networks were laid out such that articles (represented by the network's nodes) that possessed strongly correlated vocabularies were positioned closer to each other spatially than articles with weakly correlated vocabularies. We identified distinct research communities within the networks by locating and interpreting the clusters of lexically similar articles. We found that the Psychological Review was in some turmoil during this period compared with its first 15 years attributable, first, to Baldwin's unexpected departure in 1910; second, to the pressures placed on the discipline by United States entry into World War I; and, third, to the emergence of specialty psychology journals catering to research communities that had once published in the Review. The journal emerged from these challenges, however, with a better-defined mission: to serve as the chief repository of theoretical psychology in the United States. (c) 2015 APA, all rights reserved).

Chemical methods and techniques to monitor early Maillard reaction in milk products; A review.

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Aalaei, Kataneh; Rayner, Marilyn; Sjöholm, Ingegerd

2018-01-23

Maillard reaction is an extensively studied, yet unresolved chemical reaction that occurs as a result of application of the heat and during the storage of foods. The formation of advanced glycation end products (AGEs) has been the focus of several investigations recently. These molecules which are formed at the advanced stage of the Maillard reaction, are suspected to be involved in autoimmune diseases in humans. Therefore, understanding to which extent this reaction occurs in foods, is of vital significance. Because of their composition, milk products are ideal media for this reaction, especially when application of heat and prolonged storage are considered. Thus, in this work several chemical approaches to monitor this reaction in an early stage are reviewed. This is mostly done regarding available lysine blockage which takes place in the very beginning of the reaction. The most popular methods and their applications to various products are reviewed. The methods including their modifications are described in detail and their findings are discussed. The present paper provides an insight into the history of the most frequently-used methods and provides an overview on the indicators of the Maillard reaction in the early stage with its focus on milk products and especially milk powders.

Transfection of primary brain capillary endothelial cells for protein synthesis and secretion of recombinant erythropoietin: a strategy to enable protein delivery to the brain

DEFF Research Database (Denmark)

Burkhart, Annette; Andresen, Thomas Lars; Aigner, Achim

2017-01-01

, as turning BCECs into recombinant protein factories by transfection could result in protein secretion further into the brain. The present study aims to investigate the possibility of transfecting primary rat brain endothelial cells (RBECs) for recombinant protein synthesis and secretion...... of the neuroprotective protein erythropoietin (EPO). We previously showed that 4% of RBECs with BBB properties can be transfected without disrupting the BBB integrity in vitro, but it can be questioned whether this is sufficient to enable protein secretion at therapeutic levels. The present study examined various......-derived neurotropic factor (BDNF). In conclusion, non-viral gene therapy to RBECs leads to protein secretion and signifies a method for therapeutic proteins to target cells inside the CNS otherwise omitted due to the BBB....

The influence of the neighborhood physical environment on early child health and development: A review and call for research.

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Christian, Hayley; Zubrick, Stephen R; Foster, Sarah; Giles-Corti, Billie; Bull, Fiona; Wood, Lisa; Knuiman, Matthew; Brinkman, Sally; Houghton, Stephen; Boruff, Bryan

2015-05-01

This review examines evidence of the association between the neighborhood built environment, green spaces and outdoor home area, and early (0-7 years) child health and development. There was evidence that the presence of child relevant neighborhood destinations and services were positively associated with early child development domains of physical health and wellbeing and social competence. Parents׳ perceptions of neighborhood safety were positively associated with children׳s social-emotional development and general health. Population representative studies using objective measures of the built environment and valid measures of early child development are warranted to understand the impact of the built environment on early child health and development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Erythropoiesis in the aged mouse. I. Response to stimulation in vivo

International Nuclear Information System (INIS)

Udupa, K.B.; Lipschitz, D.A.

1984-01-01

Changes in erythropoiesis with age were studied by examining the hematocrit increase in response to hypoxia in aged mice and by assessing the change in erythropoiesis following the injection of erythropoietin in young and old polycythemic mice. The increase in hematocrit after exposure to hypoxia was more variable and generally lower in old mice than in young mice. When erythropoietin was injected into polycythemic animals, the increase in differentiated erythroid cells and 59 Fe incorporation into erythroid marrow and peripheral blood cells was significantly lower in old mice than in young mice. In contrast to differentiated erythroid cells, there was less evidence of a reduced response to simulation of the more primitive erythroid progenitor cells of aged animals. The early undifferentiated erythroid progenitor, burst-forming units, did not decrease when either young or aged mice were made polycythemic, and no change following erythropoietin injection was noted. Polycythemia suppressed the late-differentiated erythroid progenitor, erythroid colony-forming units, to a greater extent in aged animals, but when erythropoietin was injected, the percent increase over the subsequent 24 hours was identical to that in young mice. These observations indicate a reduced erythropoietic capacity with age, the abnormality being most obvious in the more mature erythroid precursors

Early Versus Delayed Passive Range of Motion After Rotator Cuff Repair: A Systematic Review and Meta-analysis.

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Kluczynski, Melissa A; Nayyar, Samir; Marzo, John M; Bisson, Leslie J

2015-08-01

Postoperative rehabilitation has been shown to affect healing of the rotator cuff after surgical repair. However, it is unknown whether an early or delayed rehabilitation protocol is most beneficial for healing. To determine whether early versus delayed passive range of motion (PROM) affects rotator cuff (RC) retear rates after surgery. Systematic review and meta-analysis. A systematic review of the literature published between January 2003 and February 2014 was conducted. Retear rates were compared for early (within 1 week after surgery) versus delayed (3-6 weeks after surgery) PROM using χ(2) or Fisher exact tests as well as relative risks (RR) and 95% CIs. In the first analysis, data from evidence level 1 studies that directly compared early versus delayed PROM were pooled; and in the second analysis, data from level 1 to 4 studies that did not directly compare early versus delayed PROM were pooled. The second analysis was stratified by tear size and repair method. Twenty-eight studies (1729 repairs) were included. The first analysis of level 1 studies did not reveal a significant difference in retear rates for early (13.7%) versus delayed (10.5%) PROM (P = .36; RR = 1.30 [95% CI, 0.74-2.30]). The second analysis revealed that for ≤3 cm tears, the risk of retear was lower for early versus delayed PROM for transosseous (TO) plus single-row anchor (SA) repairs (18.7% vs 28.2%, P = .02; RR = 0.66 [95% CI, 0.47-0.95]). For >5 cm tears, the risk of retear was greater for early versus delayed PROM for double-row anchor (DA) repairs (56.4% vs 20%, P = .002; RR = 2.82 [95% CI, 1.31-6.07]) and for all repair methods combined (52.2% vs 22.6%, P = .01; RR = 2.31 [95% CI, 1.16-4.61]). There were no statistically significant associations for tears measuring 3 cm. Evidence is lacking with regard to the optimal timing of PROM after RC repair; however, this study suggests that tear size may be influential. © 2014 The Author(s).

Early prediction of outcome of activities of daily living after stroke: a systematic review

OpenAIRE

Veerbeek, J.M.; Kwakkel, G.; Wegen, van, E.E.H.; Ket, J.C.F.; Heijmans, M.W.

2011-01-01

BACKGROUND AND PURPOSE-Knowledge about robust and unbiased factors that predict outcome of activities of daily living (ADL) is paramount in stroke management. This review investigates the methodological quality of prognostic studies in the early poststroke phase for final ADL to identify variables that are predictive or not predictive for outcome of ADL after stroke. METHODS-PubMed, Ebsco/Cinahl and Embase were systematically searched for prognostic studies in which stroke patients were inclu...

A Review of Early Sport Specialization in Relation to the Development of a Young Athlete

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Jonathan Michael Normand

2017-04-01

Full Text Available Background: The overall physical and psychological development of a young athlete is crucial for the enjoyment of physical activity for a lifetime. Children, as well as parents, tend to focus on individual accomplishment in sport despite any other aspect of physical development or appropriate training. Objective: the pressure to excel in sport has all too often brought about negative consequences through specialization at an early age. Method: A review and commentary report on the impact of early sport specialization on the physical and psychological development of a young athlete. Conclusion: A long-term, activity and age-appropriate developmental model is essential to those involved in training young athletes. Sport specialization may be appropriate in unique situations but only after the development of specific skills, abilities, and psychological maturity. As sport professionals, parents and coaches should be educated the pros/cons of early sport specialization. Ultimately, the focus on sport participation should be to increase physical activity, psychological development, and appreciation for a lifetime.

A Systematic Review of Early Prognostic Factors for Persistent Pain Following Acute Orthopedic Trauma

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Fiona J Clay

2012-01-01

Full Text Available Persistent or chronic pain is prevalent in many developed countries, with estimates ranging from 10% to higher than 50%, and is a major economic burden to individuals and societies. However, the variation in pain outcomes after acute orthopedic trauma and treatment confronts treating physicians with uncertainty in providing prognostic advice regarding long-term recovery. Although several previous reviews have addressed the determinants of chronic pain outcomes secondary to acute trauma, they have primarily focused on specific injury samples and, furthermore, lack consistency with respect to the important prognostic factors, which limits the generalizability of findings. This review, however, aimed specifically to identify the early prognostic factors associated with variation in persistent pain outcomes following acute orthopedic trauma presenting with a spectrum of pathologies.

Fostering and Sustaining Diverse Literacy Practices in the Early Childhood Classroom: Reviewing the Literature in Three Areas

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Machado, Emily

2017-01-01

In this article, I synthesize extant research that documents how teachers foster and sustain children's diverse literacy practices within the early childhood classroom. Framing this review with Bakhtin's heteroglossia, I draw on theoretical and empirical scholarship in the fields of biliteracy, translanguaging, and culturally sustaining pedagogy.…

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.

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

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Morawin, B; Turowski, D; Naczk, M; Siatkowski, I; Zembron-Lacny, A

2014-08-01

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

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.

Early diagnosis and early intervention in cerebral palsy

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Mijna eHadders-Algra

2014-09-01

Full Text Available This paper reviews the opportunities and challenges for early diagnosis and early intervention in cerebral palsy (CP. CP describes a group of disorders of the development of movement and posture, causing activity limitation, that are attributed to disturbances that occurred in the fetal or infant brain. Therefore the paper starts with a summary of relevant information from developmental neuroscience. Most lesions underlying CP occur in the second half of gestation, when developmental activity in the brain reaches its summit. Variations in timing of the damage not only result in different lesions, but also in different neuroplastic reactions and different associated neuropathologies. This turns CP into a heterogeneous entity. This may mean that the best early diagnostics and the best intervention methods may differ for various subgroups of children with CP. Next, the paper addresses possibilities for early diagnosis. It discusses the predictive value of neuromotor and neurological exams, neuro-imaging techniques and neurophysiological assessments. Prediction is best when complementary techniques are used in longitudinal series. Possibilities for early prediction of CP differ for infants admitted to neonatal intensive care and other infants. In the former group best prediction is achieved with the combination of neuro-imaging and the assessment of general movements, in the latter group best prediction is based on carefully documented milestones and neurological assessment. The last part reviews early intervention in infants developing CP. Most knowledge on early intervention is based on studies in high risk infants without CP. In these infants early intervention programs promote cognitive development until preschool age; motor development profits less. The few studies on early intervention in infants developing CP suggest that programs that stimulate all aspects of infant development by means of family coaching are most promising. More research is

Key components of a service model providing early childhood support for women attending opioid treatment clinics: an Australian state health service review.

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Harvey, Susan R; Schmied, Virginia; Nicholls, Daniel; Dahlen, Hannah

2012-09-01

To report the findings of a service review--specifically the strategy to provide early childhood services 'on site' at opioid treatment clinics to address access difficulties. Child and family health nurses are skilled in the assessment and support of families during early childhood. However, women with a history of substance abuse are often cautious when engaging with universal and other health services, with the result that the infant may miss recommended developmental screening and early referral to improve health outcomes. In 2006, an internal review was undertaken of the integration of early childhood and parenting services at opioid treatment clinics in a large Area Health Service of New South Wales, Australia. A qualitative study design, using semi-structured interview questions was used. Data were collected via six focus groups (4-15 participants in each group) and individual interview of child and family health nurses, nurse unit managers and clinical staff (n=58). Three key components of a model for providing early childhood support in collaboration with opioid treatment services were identified. First, the importance of building a trusting relationship between the woman and the child and family health nurses, second, maintaining continuity of care and a multidisciplinary/multiagency approach, and finally the importance of staff education, support and professional development. The provision of early childhood and parenting services on site, as part of a multidisciplinary 'one stop shop' approach to service delivery was a clear recommendation of the review. Reduction of access difficulties to specialised early childhood support is of benefit to clients, community health services attempting to provide a service to this difficult to reach population and to drug and alcohol services seeking to provide a high level of holistic care for clients. © 2012 Blackwell Publishing Ltd.

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

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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.

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

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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.

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

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Zhao Zhong Chong

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

DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD DC:0-5: SELECTIVE REVIEWS FROM A NEW NOSOLOGY FOR EARLY CHILDHOOD PSYCHOPATHOLOGY.

Science.gov (United States)

Zeanah, Charles H; Carter, Alice S; Cohen, Julie; Egger, Helen; Gleason, Mary Margaret; Keren, Miri; Lieberman, Alicia; Mulrooney, Kathleen; Oser, Cindy

2016-09-01

The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-5; ZERO TO THREE) is scheduled to be published in 2016. The articles in this section are selective reviews that have been undertaken as part of the process of refining and updating the nosology. They provide the rationales for new disorders, for disorders that had not been included previously in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-3R; ZERO TO THREE, 2005), and for changes in how certain types of disorders are conceptualized. © 2016 Michigan Association for Infant Mental Health.

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

Prognostic Impact of Erythropoietin Expression and Erythropoietin Receptor Expression on Locoregional Control and Survival of Patients Irradiated for Stage II/III Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Rades, Dirk; Setter, Cornelia; Dahl, Olav; Schild, Steven E.; Noack, Frank

2011-01-01

Purpose: Prognostic factors can guide the physician in selecting the optimal treatment for an individual patient. This study investigates the prognostic value of erythropoietin (EPO) and EPO receptor (EPO-R) expression of tumor cells for locoregional control and survival in non-small-cell lung cancer (NSCLC) patients. Methods and Materials: Fourteen factors were investigated in 62 patients irradiated for stage II/III NSCLC, as follows: age, gender, Karnofsky performance score (KPS), histology, grading, TNM/American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, pack years (average number of packages of cigarettes smoked per day multiplied by the number of years smoked), smoking during radiotherapy, hemoglobin levels during radiotherapy, EPO expression, and EPO-R expression. Additionally, patients with tumors expressing both EPO and EPO-R were compared to those expressing either EPO or EPO-R and to those expressing neither EPO nor EPO-R. Results: On univariate analysis, improved locoregional control was associated with AJCC stage II cancer (p 70 (p = 0.08), an N stage of 0 to 1 (p = 0.07), and no EPO-R expression (p = 0.10). On multivariate analysis, AJCC stage II and no EPO expression remained significant. No smoking during radiotherapy was almost significant. On univariate analysis, improved survival was associated with N stage 0 to 1 (p = 0.009), surgery (p = 0.039), hemoglobin levels of ≥12 g/d (p = 0.016), and no EPO expression (p = 0.001). On multivariate analysis, N stage 0 to 1 and no EPO expression maintained significance. Hemoglobin levels of ≥12 g/d were almost significant. On subgroup analyses, patients with tumors expressing both EPO and EPO-R had worse outcomes than those expressing either EPO or EPO-R and those expressing neither EPO nor RPO-R. Conclusions: EPO expression of tumor cells was an independent prognostic factor for locoregional control and survival in patients irradiated for NSCLC. EPO-R expression showed a trend

Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review.

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Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia; Andersen, Anne-Marie Nybo

2015-01-01

After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating

A review of neighborhood effects and early child development: How, where, and for whom, do neighborhoods matter?

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Minh, Anita; Muhajarine, Nazeem; Janus, Magdalena; Brownell, Marni; Guhn, Martin

2017-07-01

This paper describes a scoping review of 42 studies of neighborhood effects on developmental health for children ages 0-6, published between 2009 and 2014. It focuses on three themes: (1) theoretical mechanisms that drive early childhood development, i.e. how neighborhoods matter for early childhood development; (2) dependence of such mechanisms on place-based characteristics i.e. where neighborhood effects occur; (3) dependence of such mechanisms on child characteristics, i.e. for whom is development most affected. Given that ecological systems theories postulate diverse mechanisms via which neighborhood characteristics affect early child development, we specifically examine evidence on mediation and/or moderation effects. We conclude by discussing future challenges, and proposing recommendations for analyses that utilize ecological longitudinal population-based databases. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

A literature review of the relationship between breastfeeding and early childhood caries

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Narjes Amiri TehraniZadeh

2012-01-01

Full Text Available Background and Aims: Improper feeding is one of the most important etiologic factors in early childhood caries (ECC. In some clinical trials, breast feeding (BF is mentioned as a causing factor in ECC. Results in this topic are different or even controversial. It is vital that all general advices given out are consistent with general health education messages. The aim of this study was to conduct a systematic review on the relationship between breast feeding and early childhood caries. Materials and Methods: Articles, guidelines, related books, and specific databases such as SID, PubMed, Scirus, Elsevier, American Association of Pediatric Dentistry (AAPD, American Association of Pediatrics (AAP and American Dental Association (ADA were searched for related topics cited since 1990. Early childhood caries definition, breast feeding and other variables such as sample size, study location and study design were analyzed.Results: According to data analysis, there was a lack of methodological consistency and inconsistent definitions of ECC and BF in the literature making it difficult to draw conclusions. Results about relationship between prolonged BF and ECC were inconclusive. There was a positive relationship between nocturnal BF and ECC. A history of BF did not have any effect on the caries incidence.Conclusion: Because of the role of breast feeding in children's health, it is important to inform the parents about the possibility of dental caries due to nocturnal breast feeding.

Scoping the evidence for EarlyBird and EarlyBird Plus, two United Kingdom-developed parent education training programmes for autism spectrum disorder.

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Dawson-Squibb, John-Joe; Davids, Eugene Lee; de Vries, Petrus J

2018-03-01

EarlyBird and EarlyBird Plus are parent education and training programmes designed by the UK National Autistic Society in 1997 and 2003, having been delivered to more than 27,000 families in 14 countries. These group-based programmes aim to (1) support parents immediately after diagnosis of autism spectrum disorder, (2) empower parents, encouraging a positive perception of their child's autism spectrum disorder and (3) help parents establish good practice. In the absence of any previous comprehensive review, we performed a scoping review of all peer-reviewed publications on EarlyBird/EarlyBird Plus. A search was conducted between February and June 2016 using EbscoHost, Sabinet, SAGE Journals, Directory of Open Access Journals, BioMed Central, Scopus, ScienceDirect and grey literature. Two reviewers independently screened titles and abstracts for inclusion. In total, 18 articles were identified: 16 from the United Kingdom and 2 from New Zealand. We reviewed the context, study populations, design, outcome measures, whether focus was on parental perception, parental change or child changes and programme feasibility. Strong parental support for the acceptability but lower level evidence of efficacy of EarlyBird/EarlyBird Plus was found. Future research should consider randomised controlled trials. There is no research on EarlyBird/EarlyBird Plus in low-resource settings; therefore, we recommend broader feasibility evaluation of EarlyBird/EarlyBird Plus including accessibility, cultural appropriateness and scalability.

Healthy eating in early years settings: a review of current national to local guidance for North West England.

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Bristow, Katie; Capewell, Simon; Abba, Katharine; Goodall, Mark; Lloyd-Williams, Ffion

2011-06-01

To determine the extent to which national and local UK guidelines for the early years sector address key recommendations for encouraging healthy eating based on best available evidence. Phase 1 comprised a literature review to identify new evidence to assess current relevance of the Caroline Walker Trust (CWT) 'Eating well for under-5 s in child care' guidelines. Phase 2 assessed the completeness of seven local to national-level government guidelines by comparison with the 'gold standard' CWT guidelines. Desk-based review using secondary data. Research literature and statutory guidelines on healthy eating in early years settings. Phase 1 retrieved seventy-five papers, of which sixty were excluded as they addressed compliance with nutritional and food-based standards only. One report examined a social marketing tool and was deemed too narrow. The remaining fourteen documents assessed interventions to encourage healthy eating in early years settings. Following quality assessment, seven documents were included. Nine key recommendations were identified: (i) role of government; (ii) early years setting policy/guidelines; (iii) training; (iv) menu planning; (v) parents; (vi) atmosphere and encouragement; (vii) learning through food; (viii) sustainability; and (ix) equal opportunities. Phase 2 identified that all seven guidelines included the nine key recommendations but sporadic cover of sub-key recommendations. More detail is needed on how early years settings can encourage children to eat healthily. Research is required to develop second-layer guidance for interactive materials. Clear processes of communication and support for parents are required. Ways food relates to children's wider learning and social development need further thought, requiring collaboration between the Department of Health and the Department for Education.

Oral Zinc Supplementation Reduces the Erythropoietin Responsiveness Index in Patients on Hemodialysis

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Hiroki Kobayashi

2015-05-01

Full Text Available Background: In hemodialysis (HD patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI. Methods: Patients on HD with low serum zinc levels (<65 μg/dL were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc (n = 35 and the control group (no supplementation (n = 35 for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units/dry weight (kg/hemoglobin (g/dL. Results: There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI. Conclusions: Zinc supplementation reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for patients with renal anemia and low serum zinc levels.

A Systematic Review of Non-Invasive Pharmacologic Neuroprotective Treatments for Acute Spinal Cord Injury

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Okon, Elena; Hillyer, Jessica; Mann, Cody; Baptiste, Darryl; Weaver, Lynne C.; Fehlings, Michael G.; Tetzlaff, Wolfram

2011-01-01

Abstract An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically review the available pre-clinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we review treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications, or are available in a form that could be administered to humans. These include: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in-vivo animal model was utilized to assess the efficacy of the therapy in a traumatic SCI paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the pre-clinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation. PMID:20146558

Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin

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Yun Seong-Jo

2012-01-01

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

Early intervention for post-traumatic stress disorder.

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Bryant, Richard A

2007-02-01

The potentially debilitating effect of posttraumatic stress disorder (PTSD) has created much interest in early intervention strategies that can reduce PTSD. This review critiques the evidence for psychological debriefing approaches and alternate early intervention strategies. The review critiques the randomized controlled trials of psychological debriefing, and early provision of cognitive behavior therapy. The latter approach involves therapy attention on acutely traumatized individuals who are high risk for PTSD development, and particularly in people with acute stress disorder (ASD). Psychological debriefing does not prevent PTSD. Cognitive behaviour therapy strategies have proven efficacy in reducing subsequent PTSD in ASD populations. Despite the promising evidence for early provision of CBT, many people do not benefit from CBT. This review concludes with consideration of major challenges facing early intervention approaches in the context of terrorist attacks and mass disasters.

Parents' early healthcare transition experiences with preterm and acutely ill infants: a scoping review.

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Ballantyne, M; Orava, T; Bernardo, S; McPherson, A C; Church, P; Fehlings, D

2017-11-01

Parents undergo multiple transitions following the birth of an ill infant: their infant's illness-health trajectory, neonatal intensive care unit hospitalization and transfers from one healthcare setting to another, while also transitioning to parenthood. The objective of this review was to map and synthesize evidence on the experiences and needs of parents of preterm or ill infants as they transition within and between healthcare settings following birth. The scoping review followed Arskey and O'Malley's () framework, enhanced by Levac et al. (). Relevant studies were identified through a comprehensive search strategy of scientific and grey literature databases, online networks, Web of Science and citation lists of relevant articles. Inclusion criteria encompassed a focus on infants undergoing a healthcare transition, and the experiences and needs of parents during transition. Studies were appraised for design quality, and data relevant to parent experiences were extracted and underwent thematic analysis. A total of 7773 records were retrieved, 90 full texts reviewed and 11 articles synthesized that represented a total sample of 435 parents of preterm or ill infants. Parents reported on their experiences in response to their infant's transition within and between hospitals and across levels of neonatal intensive care unit, intermediate and community hospital care. Ten studies used qualitative research methods, while one employed quantitative survey methods. Four key themes were identified: that of parent distress throughout transition, parenting at a distance, sources of stress and sources of support. Parents' stress resulted from not being informed or involved in the transition decision, inadequate communication and perceived differences in cultures of care across healthcare settings. Opportunities to improve parents' early transition experiences include enhanced engagement, communication, information-sharing and shared decision-making between health care

Understanding the Early Years (UEY) Initiative

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Human Resources and Social Development Canada, 2007

2007-01-01

Internal Audit Services conducted an Early Implementation Review of the Understanding the Early Years (UEY) Initiative in 2006-07. This review is intended to provide assurance to senior management that program delivery has been established appropriately in order to meet its objectives and highlight any areas that require focused management…

A protocol of a cross-sectional study evaluating an online tool for early career peer reviewers assessing reports of randomised controlled trials.

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Chauvin, Anthony; Moher, David; Altman, Doug; Schriger, David L; Alam, Sabina; Hopewell, Sally; Shanahan, Daniel R; Recchioni, Alessandro; Ravaud, Philippe; Boutron, Isabelle

2017-09-15

Systematic reviews evaluating the impact of interventions to improve the quality of peer review for biomedical publications highlighted that interventions were limited and have little impact. This study aims to compare the accuracy of early career peer reviewers who use an innovative online tool to the usual peer reviewer process in evaluating the completeness of reporting and switched primary outcomes in completed reports. This is a cross-sectional study of individual two-arm parallel-group randomised controlled trials (RCTs) published in the BioMed Central series medical journals, BMJ , BMJ Open and Annals of Emergency Medicine and indexed with the publication type 'Randomised Controlled Trial'. First, we will develop an online tool and training module based (a) on the Consolidated Standards of Reporting Trials (CONSORT) 2010 checklist and the Explanation and Elaboration document that would be dedicated to junior peer reviewers for assessing the completeness of reporting of key items and (b) the Centre for Evidence-Based Medicine Outcome Monitoring Project process used to identify switched outcomes in completed reports of the primary results of RCTs when initially submitted. Then, we will compare the performance of early career peer reviewers who use the online tool to the usual peer review process in identifying inadequate reporting and switched outcomes in completed reports of RCTs at initial journal submission. The primary outcome will be the mean number of items accurately classified per manuscript. The secondary outcomes will be the mean number of items accurately classified per manuscript for the CONSORT items and the sensitivity, specificity and likelihood ratio to detect the item as adequately reported and to identify a switch in outcomes. We aim to include 120 RCTs and 120 early career peer reviewers. The research protocol was approved by the ethics committee of the INSERM Institutional Review Board (21 January 2016). The study is based on voluntary

Aberrant expression of erythropoietin in uterine leiomyoma: implications in tumor growth.

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Asano, Ryoko; Asai-Sato, Mikiko; Miyagi, Yohei; Mizushima, Taichi; Koyama-Sato, Makiko; Nagashima, Yoji; Taguri, Masataka; Sakakibara, Hideya; Hirahara, Fumiki; Miyagi, Etsuko

2015-08-01

Myomatous erythrocytosis syndrome is a rare complication of uterine leiomyoma caused by erythropoietin (EPO) that is produced by tumor cells. We assessed the EPO expression in leiomyomas and investigated the effects of EPO on the tumor growth. Tissue samples were collected from 114 patients with uterine leiomyomas who underwent myomectomy or hysterectomy in Yokohama City University Hospital. From 17 patients, the corresponding normal myometrium was also collected. All samples were analyzed for EPO messenger RNA (mRNA) expression by real-time reverse transcription-polymerase chain reaction. EPO protein expression was determined by an enzyme-linked immunosorbent assay. The relationships between EPO expression and clinicopathological features were retrospectively analyzed using the patients' charts. Blood vessel density and maturity were assessed using hematoxylin-eosin staining and CD34 immunohistochemistry. EPO mRNA expression was detected in 108 of 114, or 95%, of the leiomyomas. The mean EPO mRNA expression in the leiomyoma was higher than the corresponding normal myometrium (3836 ± 4122 vs 1455 ± 2141; P = .025 by Wilcoxon rank test). The EPO mRNA expression in the leiomyomas varied extensively among samples, ranging from undetectable levels to 18-fold above the mean EPO mRNA of normal myometrium. EPO protein production was observed concomitant with mRNA expression. A positive correlation of leiomyoma size and EPO mRNA expression was shown by Spearman rank correlation coefficient (ρ = 0.294; P = .001), suggesting the involvement of EPO in leiomyoma growth. The blood vessel maturity was also significantly increased in EPO-producing leiomyomas (high vessel maturity in high vs low EPO group: 67% vs 20%; P = .013 by Fisher exact test). This report demonstrates that EPO is produced in most of conventional leiomyomas and supports a model in which EPO accelerates tumor growth, possibly by inducing vessel maturity. Our study suggests one possible mechanism by which

Routine culture-based screening versus risk-based management for the prevention of early-onset group B streptococcus disease in the neonate: a systematic review.

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Kurz, Ella; Davis, Deborah

2015-04-17

Early-onset group B streptococcus disease, recognized as the most common cause of early onset neonatal sepsis in developed countries, is transmitted vertically from the group B streptococcus carrier mother to the neonate in the peripartum. Accordingly, early-onset group B streptococcus disease is prevented by halting the transmission of the microorganism from the mother to the infant. Two main methods, routine culture-based screening and risk-based management, may be used in the identification of mothers requiring intrapartum antibiotic prophylaxis in labor. While there are advantages and disadvantages to each, there is limited high level evidence available as to which method is superior. To identify the effectiveness of risk-based management versus routine culture-based screening in the prevention of early-onset group B streptococcus disease in the neonate. This review considered studies which treated pregnant women with intrapartum antibiotic prophylaxis following risk- and culture-based protocols for the prevention of early-onset group B streptococcus disease in the neonate. Types of intervention: This review considered studies that evaluated risk-based management against routine culture-based screening for the prevention of early-onset group B streptococcus disease in the neonate. Types of studies: This review looked for highest evidence available which in this case consisted of one quasi experimental study and eight comparative cohort studies with historical or concurrent control groups. Types of outcomes: Incidence of early-onset group B streptococcus disease in neonates as measured by positive group B streptococcus culture from an otherwise sterile site. Secondary outcomes include neonatal death due to group B streptococcus sepsis and percentage of women who received intrapartum antibiotic prophylaxis. A multi-step search strategy was used to find studies which were limited to the English language and published between January 2000 and June 2013. The quality

Epobis is a Nonerythropoietic and Neuroprotective Agonist of the Erythropoietin Receptor with Anti-Inflammatory and Memory Enhancing Effects

Directory of Open Access Journals (Sweden)

Oksana Dmytriyeva

2016-01-01

Full Text Available The cytokine erythropoietin (EPO stimulates proliferation and differentiation of erythroid progenitor cells. Moreover, EPO has neuroprotective, anti-inflammatory, and antioxidative effects, but the use of EPO as a neuroprotective agent is hampered by its erythropoietic activity. We have recently designed the synthetic, dendrimeric peptide, Epobis, derived from the sequence of human EPO. This peptide binds the EPO receptor and promotes neuritogenesis and neuronal cell survival. Here we demonstrate that Epobis in vitro promotes neuritogenesis in primary motoneurons and has anti-inflammatory effects as demonstrated by its ability to decrease TNF release from activated AMJ2-C8 macrophages and rat primary microglia. When administered systemically Epobis is detectable in both plasma and cerebrospinal fluid, demonstrating that the peptide crosses the blood-brain barrier. Importantly, Epobis is not erythropoietic, but systemic administration of Epobis in rats delays the clinical signs of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, and the peptide has long-term, but not short-term, effects on working memory, detected as an improved social memory 3 days after administration. These data reveal Epobis to be a nonerythropoietic and neuroprotective EPO receptor agonist with anti-inflammatory and memory enhancing properties.

Causes of mortality in early infantile epileptic encephalopathy: A systematic review.

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Radaelli, Graciane; de Souza Santos, Francisco; Borelli, Wyllians Vendramini; Pisani, Leonardo; Nunes, Magda Lahorgue; Scorza, Fulvio Alexandre; da Costa, Jaderson Costa

2018-06-12

Early infantile epileptic encephalopathy syndrome (EIEE), also known as Ohtahara syndrome, is an age-dependent epileptic encephalopathy syndrome defined by clinical features and electroencephalographic findings. Epileptic disorders with refractory seizures beginning in the neonatal period and/or early infancy have a potential risk of premature mortality, including sudden death. We aimed to identify the causes of death in EIEE and conducted a literature survey of fatal outcomes. We performed a literature search in MEDLINE, EMBASE, and Web of Science for data from inception until September 2017. The terms "death sudden," "unexplained death," "SUDEP," "lethal," and "fatal" and the medical subject heading terms "epileptic encephalopathy," "mortality," "death," "sudden infant death syndrome," and "human" were used in the search strategy. The EIEE case report studies reporting mortality were included. The search yielded 1360 articles. After screening for titles and abstracts and removing duplicate entries, full texts of 15 articles were reviewed. After reading full texts, 11 articles met the inclusion criteria (9 articles in English and 2 in Japanese, dated from 1976 to 2015). The review comprised 38 unique cases of EIEE, 17 of which had death as an outcome. In all cases, the suppression-burst pattern on electroencephalographies (EEGs) was common. Most cases (55%) involved male infants. The mean (standard deviation [SD]) age at onset of seizure was 19.6 ± 33 days. The mean (SD) age at death was 12.9 ± 14.1 months. Most infants (58.8%) survived less than one year. The cause of death was described only in eight (47%) patients; the cause was pneumonia/respiratory illness or sudden unexpected death in epilepsy (SUDEP). The results show EIEE as a severe disease associated with a premature mortality, evidenced by a very young age at death. Increasing interest in the detection of new molecular bases of EIEE is leading us to a better understanding of this severe

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

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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.

Medieval and early modern approaches to fractures of the proximal humerus: an historical review

DEFF Research Database (Denmark)

Brorson, S.

2010-01-01

The diagnosis and management of complex fractures of the proximal humerus have challenged surgical practitioners and medical writers since the earliest recorded surgical texts. Current knowledge of fractures of the proximal humerus has been obtained through pathoanatomical and biomechanical studies...... within the last two centuries. However, the historical preconditions for this development have not been studied. This paper reviews written sources from the fall of the Roman Empire to the late eighteenth century. Medieval and early modern writers mainly rely on the Hippocratic writings De Fracturis...

A review of early influences on physical activity and sedentary behaviors of preschool-age children in high-income countries.

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Lindsay, Ana Cristina; Greaney, Mary L; Wallington, Sherrie F; Mesa, Tatiana; Salas, Carlos F

2017-07-01

Promoting physical activity (PA) is a key component of preventing and controlling childhood obesity. Despite well-documented benefits of PA, globally, rates of PA among young children have declined over the past decades, and most children are not accruing sufficient PA daily. Helping children develop the foundation for PA habits early in life is critical for the promotion of health in childhood and prevention of chronic diseases later in life, and will ultimately promote longer and healthier lives for individuals and the general population. The purpose of this review is to provide a synthesis of current evidence on influences on PA and sedentary behaviors of preschool-age children in high-income countries. A systematic review of three databases was performed. Studies conducted in high-income countries and published from 2000 onward that addressed influences on PA and sedentary behaviors of preschool-age children were identified and reviewed. Additionally, reference lists of identified articles and relevant published reviews were reviewed. Studies that met the following inclusion criteria were considered: (a) sample included preschoolers (age ≤5 years); (b) PA and/or sedentary behaviors or factors associated with PA and/or sedentary behaviors was assessed; (c) published in English; (d) used either quantitative or qualitative methods; and (e) conducted in a high-income country. Data were extracted from selected studies to identify influences on PA and sedentary behaviors of preschool-age children and organized using the social-ecological model according to multiple levels of influence. Results from included studies identify multiple factors that influence PA and sedentary behaviors of young children in high-income countries at the various levels of the social-ecological model including intrapersonal, interpersonal, environmental, organizational, and policy. Given pediatric nurses' role as primary care providers, and their frequent and continued contact with parents

Early versus late surgical intervention or medical management for infective endocarditis: a systematic review and meta-analysis.

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Anantha Narayanan, Mahesh; Mahfood Haddad, Toufik; Kalil, Andre C; Kanmanthareddy, Arun; Suri, Rakesh M; Mansour, George; Destache, Christopher J; Baskaran, Janani; Mooss, Aryan N; Wichman, Tammy; Morrow, Lee; Vivekanandan, Renuga

2016-06-15

Infective endocarditis is associated with high morbidity and mortality and optimal timing for surgical intervention is unclear. We performed a systematic review and meta-analysis to compare early surgical intervention with conservative therapy in patients with infective endocarditis. PubMed, Cochrane, EMBASE, CINAHL and Google-scholar databases were searched from January 1960 to April 2015. Randomised controlled trials, retrospective cohorts and prospective observational studies comparing outcomes between early surgery at 20 days or less and conservative management for infective endocarditis were analysed. A total of 21 studies were included. OR of all-cause mortality for early surgery was 0.61 (95% CI 0.50 to 0.74, pendocarditis between the overall unmatched cohorts. The results of our meta-analysis suggest that early surgical intervention is associated with significantly lower risk of mortality in patients with infective endocarditis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Mood and anxiety disorders as early manifestations of medical illness: a systematic review.

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Cosci, Fiammetta; Fava, Giovanni A; Sonino, Nicoletta

2015-01-01

Affective disturbances involving alterations of mood, anxiety and irritability may be early symptoms of medical illnesses. The aim of this paper was to provide a systematic review of the literature with qualitative data synthesis. MEDLINE, PsycINFO, EMBASE, Cochrane, and ISI Web of Science were systematically searched from inception to February 2014. Search terms were 'prodrome/early symptom', combined using the Boolean 'AND' operator with 'anxiety/depression/mania/hypomania/irritability/irritable mood/hostility', combined with the Boolean 'AND' operator with 'medical illness/medical disorder'. PRISMA guidelines were followed. A total of 21 studies met the inclusion criteria and were analyzed. Depression was found to be the most common affective prodrome of medical disorders and was consistently reported in Cushing's syndrome, hypothyroidism, hyperparathyroidism, pancreatic and lung cancer, myocardial infarction, Wilson's disease, and AIDS. Mania, anxiety and irritability were less frequent. Physicians may not pursue medical workup of cases that appear to be psychiatric in nature. They should be alerted that disturbances in mood, anxiety and irritability may antedate the appearance of a medical disorder.

Antibody-based enzyme-linked lectin assay (ABELLA) for the sialylated recombinant human erythropoietin present in culture supernatant.

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Kim, Hyoung Jin; Lee, Seung Jae; Kim, Hong-Jin

2008-11-04

The terminal sialic acid of human erythropoietin (hEPO) is essential for in vivo activity. The current resorcinol and HPLC methods for analyzing alpha2,3-linked sialic acid require more than a microgram of purified rhEPO, and purification takes a great deal of time and labor. In this study, we assessed the use of an antibody-based enzyme-linked lectin assay (ABELLA) for analyzing non-purified recombinant hEPO (rhEPO). The major problem of this method was the high background due to terminal sialylation of components of the assay (antibody and bovine serum albumin) other than rhEPO. To solve this problem, we used a monoclonal antibody (Mab 287) to capture the rhEPO, and oxidized the bovine serum albumin used for blocking with meta-periodate. The sialic acid content of non-purified rhEPO measured by ABELLA was similar to that obtained by the resorcinol method on purified rhEPO. ABELLA has advantages such as adaptability and need for minimal amounts of rhEPO (40 ng/ml). Our observations suggest that ABELLA should reduce the time and labor needed to improve culture conditions so as to increase protein sialylation, and also facilitate the study of sialylation mechanisms.

Social networks, support and early psychosis: a systematic review.

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Gayer-Anderson, C; Morgan, C

2013-06-01

Background. There is strong evidence that those with a long-standing psychotic disorder have fewer social contacts and less social support than comparison groups. There is less research on the extent of social contacts and support prior to or at the onset of psychosis. In the light of recent evidence implicating a range of social experiences and contexts at the onset of psychosis, it is relevant to establish whether social networks and support diminished before or at the time of onset and whether the absence of such supports might contribute to risk, either directly or indirectly. We, therefore, conducted a systematic review of this literature to establish what is currently known about the relationship between social networks, support and early psychosis. Methods. We identified all studies investigating social networks and support in first episode psychosis samples and in general population samples with measures of psychotic experiences or schizotype by conducting systematic searches of electronic databases using pre-defined search terms and criteria. Findings were synthesized using non-quantitative approaches. Results. Thirty-eight papers were identified that met inclusion criteria. There was marked methodological heterogeneity, which limits the capacity to draw direct comparisons. Nonetheless, the existing literature suggests social networks (particularly close friends) and support diminished both among first episode samples and among non-clinical samples reporting psychotic experiences or with schizotype traits, compared with varying comparison groups. These differences may be more marked for men and for those from minority ethnic populations. Conclusions. Tentatively, reduced social networks and support appear to pre-date onset of psychotic disorder. However, the substantial methodological heterogeneity among the existing studies makes comparisons difficult and suggests a need for more robust and comparable studies on networks, support and early psychosis.

History of early atomic clocks

International Nuclear Information System (INIS)

Ramsey, N.F.

2005-01-01

This review of the history of early atomic clocks includes early atomic beam magnetic resonance, methods of separated and successive oscillatory fields, microwave absorption, optical pumping and atomic masers. (author)

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

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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.

Does Early Versus Delayed Active Range of Motion Affect Rotator Cuff Healing After Surgical Repair? A Systematic Review and Meta-analysis.

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Kluczynski, Melissa A; Isenburg, Maureen M; Marzo, John M; Bisson, Leslie J

2016-03-01

The timing of passive range of motion (ROM) after surgical repair of the rotator cuff (RC) has been shown to affect healing. However, it is unknown if early or delayed active ROM affects healing. To determine whether early versus delayed active ROM affects structural results of RC repair surgery. Systematic review and meta-analysis. A systematic review of articles published between January 2004 and April 2014 was conducted. Structural results were compared for early (repair method. A total of 37 studies (2251 repairs) were included in the analysis, with 10 (649 repairs) in the early group and 27 (1602 repairs) in the delayed group. For tears ≤3 cm, the risk of a structural tendon defect was higher in the early versus delayed group for transosseous plus single-row suture anchor repairs (39.7% vs 24.3%; RR, 1.63 [95% CI, 1.28-2.08]). For tears >3 cm, the risk of a structural tendon defect was higher in the early versus delayed group for suture bridge repairs (48% vs 17.5%; RR, 2.74 [95% CI, 1.59-4.73]) and all repair methods combined (40.5% vs 26.7%; RR, 1.52 [95% CI, 1.17-1.97]). For tears >5 cm, the risk of structural tendon defect was higher in the early versus delayed group for suture bridge repairs (100% vs 16.7%; RR, 6.00 [95% CI, 1.69-21.26]). There were no statistically significant associations for tears measuring ≤1, 1-3, or 3-5 cm. Early active ROM was associated with increased risk of a structural defect for small and large RC tears, and thus might not be advisable after RC repair. © 2015 The Author(s).

Clinical outcomes of immediate/early loading of dental implants. A literature review of recent controlled prospective clinical studies.

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Sennerby, L; Gottlow, J

2008-06-01

Two previous reviews have evaluated the clinical outcomes of immediate/early loading of dental implants based on studies published until 2005.(1,2) The aim of the present paper was to review controlled clinical studies on the subject published since 2005 including at least 10 patients in each group followed for at least one year in function. Six comparative studies were found and none of these showed any differences in survival rates or marginal bone loss after one to five years. Most authors used specified inclusion criteria to avoid known risk factors such as soft bone, short implants and bruxism. Data from one randomized study in the edentulous maxilla showed no differences between early and delayed loading in consecutive clinical routine cases including short implants and soft bone. Three additional studies comparing different surfaces or implant designs under immediate loading were reviewed. No differences between implants with a moderately rough or smooth surface topography were observed. The data add to the previous bulk of evidence that various designs of implants can be loaded shortly after their placement in both the mandible and the maxilla. However, one study reported on marginal bone loss around a novel one-piece implant design leading to implant failure which was not seen for control two-piece implants.(3).

Influence of Erythropoietin Dose and Albumin Level on the Plasma Brain Natriuretic Peptide in Hemodialysis Patients

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Alsuwaida Abdulkareem

2006-01-01

Full Text Available Brain natriuretic peptide (BNP levels increase in patients with congestive heart failure. Theoretically, BNP levels can be helpful in the determination of the "dry weight" of hemodialysis patients. To evaluate the effect of hemodialysis on the plasma concentration of BNP and to determine the factors that affect BNP levels during hemodialysis in patients with chronic renal failure, we studied five stable patients with chronic renal failure. A total of 15 blood samples were obtained for BNP levels at 24, 48 and 72 hours after the last hemodialysis session. The plasma BNP levels did not change significantly either with ultrafiltration volume or with time since last dialysis. However, the BNP levels correlated positively with the erythropoietin (EPO dose (r=0.98, P< 0.001 and negatively with the serum albumin levels (r = 0.94, P=0.02. Univariate analysis showed that the EPO dose (P=0.001 and the albumin level (P=0.02 were significant predictors of BNP level. Adjusted multivariate analysis showed significant interaction between the EPO dose and the albumin level (P=0.01, P=0.03 respectively. In conclusion: the plasma BNP levels were not significantly influenced by ultrafiltration volume or time since last dialysis. However, the BNP levels may be a useful prognostic parameter for assessing the risk of cardiovascular morbidity and mortality in hemodialysis patients.

The flora of Early Permian coal measures from the Parana Basin in Brazil: A review

International Nuclear Information System (INIS)

Iannuzzi, Roberto

2010-01-01

This paper presents an updated overview integrating both previous and newly published data on the most important floras found associated with Early Permian coal seams in the Parana Basin, Brazil. These floras occur within the Rio Bonito Formation and correspond to the Gondwana ''Glossopteris Flora.'' For this review, five floras are selected, in ascending stratigraphic order: the ''Sao Joao do Triunfo,'' ''Figueira,'' ''Quiteria,'' ''Morro do Papaleo'' and ''Irapua Bed'' floras. They are the best-known floras of the basin in terms of taxonomic composition, paleoecology and environments of deposition. An early-mid Sakmarian to earliest Artinskian age is indicated for the Rio Bonito Formation based on absolute radiometric and relative biostratigraphic ages. Integration of available information about the selected floras allows evaluation of taphonomic and paleoecological factors to provide a more comprehensive understanding of the Early Permian floral record in the Parana Basin. The variation observed in both the taxonomic composition of individual floras and in the frequency of occurrence of different plant groups is due to the broad range of environmental/edaphic conditions that prevailed in the many different depositional settings represented in the Rio Bonito Formation. A more precise age determination obtained for the plant-bearing deposits permits the establishment of a more confident correlation between the Early Permian floral succession in the Parana Basin and other Early Permian floral successions in other basins. The Sakmarian global warming favored the appearance of pecopterid and sphenopterid ferns amongst the spore-producing plants, and the glossopterids amongst the pollen-producing plants. (author)

Barriers and facilitators to implementing family support and education in Early Psychosis Intervention programmes: A systematic review.

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Selick, Avra; Durbin, Janet; Vu, Nhi; O'Connor, Karen; Volpe, Tiziana; Lin, Elizabeth

2017-10-01

Family support is a core component of the Early Psychosis Intervention (EPI) model, yet it continues to have relatively low rates of implementation in practice. This paper reports results of a literature review on facilitators and barriers to delivering family interventions in EPI programmes. A search was conducted of 4 electronic databases, Medline, EMBASE, PsycINFO and Joanna Briggs, from 2000 to 2015 using terms related to early onset psychosis, family work and implementation. Four thousand four hundred and two unique studies were identified, 7 of which met inclusion criteria. Barriers and facilitators were coded and aggregated to higher-level themes using a consensus approach. Five of 7 studies examined structured multifamily psychoeducation. Uptake by families was affected by: family/client interest and readiness to participate; ability to access supports; and support needs/preferences. Implementation by programmes was affected by staff access to training and resources to provide family support. A key finding across the identified studies was that families have different needs and preferences regarding the timing, length, intensity and content of the intervention. One size does not fit all and many families do not require the intensive psychoeducational programmes typically provided. The reviewed literature suggests that flexible, tiered approaches to care may better meet family needs and increase rates of uptake of family support. However, more research is needed on the effectiveness of different models of family support in early psychosis and how they can be successfully implemented. © 2017 John Wiley & Sons Australia, Ltd.

Early versus Late Decompression for Traumatic Spinal Cord Injuries; a Systematic Review and Meta-analysis

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Mahmoud Yousefifard

2017-01-01

Full Text Available Introduction: Despite the vast number of surveys, no consensus has been reached on the optimum timing of spinal decompression surgery. This systematic review and meta-analysis aimed to compare the effects of early and late spinal decompression surgery on neurologic improvement and post-surgical complications in patients with traumatic spinal cord injuries.Methods: Two independent reviewers carried out an extended search in electronic databases. Data of neurological outcome and post-surgery complication were extracted. Finally, pooled relative risk (RR with a 95% confidence interval (CI was reported for comparing of efficacy of early and late surgical decompression.Results: Eventually 22 studies were included. The pooled RR was 0.77 (95% CI: 0.68-0.89 for at least one grade neurological improvement, and 0.84 (95% CI: 0.77-0.92 for at least two grade improvement. Pooled RR for surgical decompression performed within 12 hours after the injury was 0.26 (95% CI: 0.13-0.52; p<0.001, while it was 0.75 (95% CI: 0.63-0.90; p=0.002 when the procedure was performed within 24 hours, and 0.93 (95% CI: 0.76-1.14; p=0.48 when it was carried out in the first 72 hours after the injury. Surgical decompression performed within 24 hours after injury was found to be associated with significantly lower rates of post-surgical complications (RR=0.77; 95% CI: 0.68-0.86; p<0.001.Conclusion: The findings of this study indicate that early spinal decompression surgery can improve neurologic recovery and is associated with less post-surgical complications. The optimum efficacy is observed when the procedure is performed within 12 hours of the injury.

How to get started with a systematic review in epidemiology: an introductory guide for early career researchers.

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Denison, Hayley J; Dodds, Richard M; Ntani, Georgia; Cooper, Rachel; Cooper, Cyrus; Sayer, Avan Aihie; Baird, Janis

2013-08-07

Systematic review is a powerful research tool which aims to identify and synthesize all evidence relevant to a research question. The approach taken is much like that used in a scientific experiment, with high priority given to the transparency and reproducibility of the methods used and to handling all evidence in a consistent manner.Early career researchers may find themselves in a position where they decide to undertake a systematic review, for example it may form part or all of a PhD thesis. Those with no prior experience of systematic review may need considerable support and direction getting started with such a project. Here we set out in simple terms how to get started with a systematic review. Advice is given on matters such as developing a review protocol, searching using databases and other methods, data extraction, risk of bias assessment and data synthesis including meta-analysis. Signposts to further information and useful resources are also given. A well-conducted systematic review benefits the scientific field by providing a summary of existing evidence and highlighting unanswered questions. For the individual, undertaking a systematic review is also a great opportunity to improve skills in critical appraisal and in synthesising evidence.

Review of Factors Influencing Women's Choice of Mastectomy Versus Breast Conserving Therapy in Early Stage Breast Cancer: A Systematic Review.

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Gu, Jeffrey; Groot, Gary; Boden, Catherine; Busch, Angela; Holtslander, Lorraine; Lim, Hyun

2018-01-03

We have performed a narrative synthesis. A literature search was conducted between January 2000 and June 2014 in 7 databases. The initial search identified 2717 articles; 319 underwent abstract screening, 67 underwent full-text screening, and 25 final articles were included. This review looked at early stage breast cancer in women only, excluding ductal carcinoma in situ and advanced breast cancer. A conceptual framework was created to organize the central constructs underlying women's choices: clinicopathologic factors, physician factors, and individual factors with subgroups of sociodemographic, geographic, and personal beliefs and preferences. This framework guided our review's synthesis and analysis. We found that larger tumor size and increasing stage was associated with increased rates of mastectomy. The results for age varied, but suggested that old and young extremes of diagnostic age were associated with an increased likelihood of mastectomy. Higher socioeconomic status was associated with higher breast conservation therapy (BCT) rates. Resident rural location and increasing distance from radiation treatment facilities were associated with lower rates of BCT. Individual belief factors influencing women's choice of mastectomy (mastectomy being reassuring, avoiding radiation, an expedient treatment) differed from factors influencing choice of BCT (body image and femininity, physician recommendation, survival equivalence, less surgery). Surgeon factors, including female gender, higher case numbers, and individual surgeon practice, were associated with increased BCT rates. The decision-making process for women with early stage breast cancer is complicated and affected by multiple factors. Organizing these factors into central constructs of clinicopathologic, individual, and physician factors may aid health-care professionals to better understand this process. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

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B. Morawin

2014-08-01

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

Erythropoietin and its receptors in the brainstem of adults with fatal falciparum malaria

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White Nicholas J

2009-11-01

Full Text Available Abstract Background Facilitation of endogenous neuroprotective pathways, such as the erythropoietin (Epo pathway, has been proposed as adjuvant treatment strategies in cerebral malaria. Whether different endogenous protein expression levels of Epo or differences in the abundance of its receptor components could account for the extent of structural neuropathological changes or neurological complications in adults with severe malaria was investigated. Methods High sensitivity immunohistochemistry was used to assess the frequency, distribution and concordance of Epo and components of its homodimeric and heteromeric receptors, Epo receptor and CD131, within the brainstem of adults who died of severe malaria. The following relationships with Epo and its receptor components were also defined: (i sequestration and indicators of hypoxia; (ii vascular damage in the form of plasma protein leakage and haemorrhage; (iii clinical complications and neuropathological features of severe malaria disease. Brainstems of patients dying in the UK from unrelated non-infectious causes were examined for comparison. Results The incidence of endogenous Epo in parenchymal brain cells did not greatly differ between severe malaria and non-neurological UK controls at the time of death. However, EpoR and CD131 labelling of neurons was greater in severe malaria compared with non-neurological controls (P = .009. EpoR labelling of vessels was positively correlated with admission peripheral parasite count (P = .01 and cerebral sequestration (P P = .001. There were no significant correlations with indicators of vascular damage, neuronal chromatolysis, axonal swelling or vital organ failure. Conclusion Cells within the brainstem of severe malaria patients showed protein expression of Epo and its receptor components. However, the incidence of endogeneous expression did not reflect protection from vascular or neuronal injury, and/or clinical manifestations, such as coma. These

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

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

2000-07-01

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

Comparison the effects of poor health and low income on early retirement: a systematic review and meta-analysis.

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Homaie Rad, Enayatollah; Rashidian, Arash; Arab, Mohamad; Souri, Ali

2017-08-08

The main aim of this study was to estimate the effects of poor health and low income on early retirement. For this purpose systematic review and meta-analysis were conducted. Web of Science, PUBMED and Scopus databases were searched systematically. Finally 17 surveys were added in meta-analysis. These studies were conducted in 13 countries. At the end a Meta regression was done to show the effects of welfare system type on effect sizes of poor health and low income. The results of this study showed that poor health had effect on the risk of early retirement. (Poor health pooled effect sizes: 1.279 CI: (1.15 1.41), low income pooled effect sizes: 1.042 CI: (0.92 1.17), (poor health pooled marginal effects: 0.046 CI: (-0.03 0.12), low income pooled marginal effects: -0.002 CI: (-0.003 0.000). The results of this study showed that association between poor health and early retirement was stronger in comparison with low income and early retirement.

[Pediatrician-parent interaction and early prevention : A review about the limits in addressing psychosocial risks during well-child visits].

Science.gov (United States)

Barth, Michael

2016-10-01

Pediatricians can be a door opener to early prevention for families at risk. The German well-child program is well-established, but there is a gap between the structural possibilities and the observed placements. The aim of this review is to show how pediatricians and parents talk about psychosocial risks under the very structured conditions of well-child visits. The challenges and traps of the framed interactions will be described and options for early prevention will be shown. The review is primarily based on the work of conversational and ethnomethodological studies reconstructing the pediatrician's discussion with parents about psychosocial issues in the family. Well-child visits are a highly routinized practice. Talking about family issues for both partners is a difficult task. Discussions about psychosocial issues are seldom and vague . Predominantly, they work cooperatively on reciprocal normalization of the child's development. Based on this shared orientation, pediatricians make an early, mostly general, prescription of parental tasks, supporting the child in the next developmental step. This kind of routine anticipatory counselling puts some pressure on the parents. Parents under unknown stress could be overburdened with this advice. In the script of well-child visits, there are no slots that indicate to pediatricians and parents when, which, how and for what purpose psychosocial issues can be discussed and negotiated. For implementing such slots in well-child visits, three steps are necessary: a structured and regular assessment of psychosocial issues, a trained pediatrician in motivational interviewing and a social worker guiding the family in the network of early prevention.

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

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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.

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

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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.

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

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Nordsborg, N B; Robach, P; Boushel, R; Calbet, J A L; Lundby, C

2015-12-01

It is investigated if recombinant human erythropoietin (rHuEPO) treatment for 15 weeks (n = 8) reduces extracellular accumulation of metabolic stress markers such as lactate, H(+) , and K(+) during incremental exhaustive exercise. After rHuEPO treatment, normalization of blood volume and composition by hemodilution preceded an additional incremental test. Group averages were calculated for an exercise intensity ∼80% of pre-rHuEPO peak power output. After rHuEPO treatment, leg lactate release to the plasma compartment was similar to before (4.3 ± 1.6 vs 3.9 ± 2.5 mmol/min) and remained similar after hemodilution. Venous lactate concentration was higher (P release to the plasma compartment after rHuEPO was similar to before (19.6 ± 5.4 vs 17.6 ± 6.0 mmol/min) and remained similar after hemodilution. Nevertheless, venous pH was lower (P release to the plasma compartment after rHuEPO treatment was similar to before (0.8 ± 0.5 vs 0.7 ± 0.7 mmol/min) and remained similar after hemodilution. Additionally, venous K(+) concentrations were similar after vs before rHuEPO (5.3 ± 0.3 vs 5.1 ± 0.4 mM). In conclusion, rHuEPO does not reduce plasma accumulation of lactate, H(+) , and K(+) at work rates corresponding to ∼80% of peak power output. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Integrating Early Child Development and Violence Prevention Programs: A Systematic Review.

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Efevbera, Yvette; McCoy, Dana C; Wuermli, Alice J; Betancourt, Theresa S

2018-03-01

Limited evidence describes promoting development and reducing violence in low- and middle-income countries (LMICs), a missed opportunity to protect children and promote development and human capital. This study presents a systematic literature review of integrated early childhood development plus violence prevention (ECD+VP) interventions in LMICs. The search yielded 5,244 unique records, of which N = 6 studies met inclusion criteria. Interventions were in Chile, Jamaica, Lebanon, Mexico, Mozambique, and Turkey. Five interventions were parent education programs, including center-based sessions (n = 3) and home visiting (n = 2), while one intervention was a teacher education program. All but one study reported improvements in both child development and maltreatment outcomes. The dearth of evidence on ECD+VP interventions suggests additional research is needed. Integrated ECD+VP interventions may improve multiple child outcome domains while leveraging limited resources in LMICs. © 2018 Wiley Periodicals, Inc.

Anemia, tumor hypoxemia, and the cancer patient

International Nuclear Information System (INIS)

Varlotto, John; Stevenson, Mary Ann

2005-01-01

Purpose: To review the impact of anemia/tumor hypoxemia on the quality of life and survival in cancer patients, and to assess the problems associated with the correction of this difficulty. Methods: MEDLINE searches were performed to find relevant literature regarding anemia and/or tumor hypoxia in cancer patients. Articles were evaluated in order to assess the epidemiology, adverse patient effects, anemia correction guidelines, and mechanisms of hypoxia-induced cancer cell growth and/or therapeutic resistance. Past and current clinical studies of radiosensitization via tumor oxygenation/hypoxic cell sensitization were reviewed. All clinical studies using multi-variate analysis were analyzed to show whether or not anemia and/or tumor hypoxemia affected tumor control and patient survival. Articles dealing with the correction of anemia via transfusion and/or erythropoietin were reviewed in order to show the impact of the rectification on the quality of life and survival of cancer patients. Results: Approximately 40-64% of patients presenting for cancer therapy are anemic. The rate of anemia rises with the use of chemotherapy, radiotherapy, and hormonal therapy for prostate cancer. Anemia is associated with reductions both in quality of life and survival. Tumor hypoxemia has been hypothesized to lead to tumor growth and resistance to therapy because it leads to angiogenesis, genetic mutations, resistance to apoptosis, and a resistance to free radicals from chemotherapy and radiotherapy. Nineteen clinical studies of anemia and eight clinical studies of tumor hypoxemia were found that used multi-variate analysis to determine the effect of these conditions on the local control and/or survival of cancer patients. Despite differing definitions of anemia and hypoxemia, all studies have shown a correlation between low hemoglobin levels and/or higher amounts of tumor hypoxia with poorer prognosis. Radiosensitization through improvements in tumor oxygenation/hypoxic cell

A Systematic Literature Review and Meta-Regression Analysis on Early-Life Energy Restriction and Cancer Risk in Humans.

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Elands, Rachel J J; Simons, Colinda C J M; Dongen, Martien van; Schouten, Leo J; Verhage, Bas A J; van den Brandt, Piet A; Weijenberg, Matty P

2016-01-01

In animal models, long-term moderate energy restriction (ER) is reported to decelerate carcinogenesis, whereas the effect of severe ER is inconsistent. The impact of early-life ER on cancer risk has never been reviewed systematically and quantitatively based on observational studies in humans. We conducted a systematic review of observational studies and a meta-(regression) analysis on cohort studies to clarify the association between early-life ER and organ site-specific cancer risk. PubMed and EMBASE (1982 -August 2015) were searched for observational studies. Summary relative risks (RRs) were estimated using a random effects model when available ≥3 studies. Twenty-four studies were included. Eleven publications, emanating from seven prospective cohort studies and some reporting on multiple cancer endpoints, met the inclusion criteria for quantitative analysis. Women exposed to early-life ER (ranging from 220-1660 kcal/day) had a higher breast cancer risk than those not exposed (RRRE all ages = 1.28, 95% CI: 1.05-1.56; RRRE for 10-20 years of age = 1.21, 95% CI: 1.09-1.34). Men exposed to early-life ER (ranging from 220-800kcal/day) had a higher prostate cancer risk than those not exposed (RRRE = 1.16, 95% CI: 1.03-1.30). Summary relative risks were not computed for colorectal cancer, because of heterogeneity, and for stomach-, pancreas-, ovarian-, and respiratory cancer because there were <3 available studies. Longer duration of exposure to ER, after adjustment for severity, was positively associated with overall cancer risk in women (p = 0.02). Ecological studies suggest that less severe ER is generally associated with a reduced risk of cancer. Early-life transient severe ER seems to be associated with increased cancer risk in the breast (particularly ER exposure at adolescent age) and prostate. The duration, rather than severity of exposure to ER, seems to positively influence relative risk estimates. This result should be interpreted with caution due to the

The early universe

International Nuclear Information System (INIS)

Steigman, G.

1989-01-01

The author discusses the physics of the early universe: the production and survival of relics from the big bang. The author comments on relic WIMPs as the dark matter in the universe. The remainder of this discussion is devoted to a review of the status of the only predictions from the early evolution of the universe that are accessible to astronomical observation: primordial nucleosynthesis

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

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Jérôme Pineault

2017-11-01

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

Serum proteomic changes after randomized prolonged erythropoietin treatment and/or endurance training: detection of novel biomarkers.

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Britt Christensen

Full Text Available Despite implementation of the biological passport to detect erythropoietin abuse, a need for additional biomarkers remains. We used a proteomic approach to identify novel serum biomarkers of prolonged erythropoiesis-stimulating agent (ESA exposure (Darbepoietin-α and/or aerobic training.Thirty-six healthy young males were randomly assigned to the following groups: Sedentary-placebo (n = 9, Sedentary-ESA (n = 9, Training-placebo (n = 10, or Training-ESA (n = 8. They were treated with placebo/Darbepoietin-α subcutaneously once/week for 10 weeks followed by a 3-week washout period. Training consisted of supervised biking 3/week for 13 weeks at the highest possible intensity. Serum was collected at baseline, week 3 (high dose Darbepoietin-α, week 10 (reduced dose Darbepoietin-α, and after a 3-week washout period.Serum proteins were separated according to charge and molecular mass (2D-gel electrophoresis. The identity of proteins from spots exhibiting altered intensity was determined by mass spectrometry.Six protein spots changed in response to Darbepoietin-α treatment. Comparing all 4 experimental groups, two protein spots (serotransferrin and haptoglobin/haptoglobin related protein showed a significant response to Darbepoietin-α treatment. The haptoglobin/haptoglobin related protein spot showed a significantly lower intensity in all subjects in the training-ESA group during the treatment period and increased during the washout period.An isoform of haptoglobin/haptoglobin related protein could be a new anti-doping marker and merits further research.ClinicalTrials.gov NCT01320449.

Systematic review and meta-analysis of early life exposure to di(2-ethylhexyl) phthalate and obesity related outcomes in rodents

NARCIS (Netherlands)

Wassenaar, Pim Nicolaas Hubertus; Legler, Juliette

Background It has been suggested that the plasticizer di(2-ethylhexyl) phthalate (DEHP) exerts obesogenic effects after pre- or perinatal exposure. Objective A systematic review with meta-analyses was conducted of early life exposure to DEHP, or its biologically active metabolite mono(2-ethylhexyl)

Towards a better understanding of caregiver distress in early psychosis: a systematic review of the psychological factors involved.

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Jansen, Jens Einar; Gleeson, John; Cotton, Sue

2015-02-01

We sought to review empirical studies of psychological factors accounting for distress in caregivers of young people with early psychosis. Following the PRISMA guidelines, we included studies that empirically tested psychological models of caregiver distress in early psychosis by searching the following databases up until March 2014: PsycINFO, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL). This was followed by additional manual searches of reference lists and relevant journals. The search identified 15 papers describing 13 studies together comprising 1056 caregivers of persons with early psychosis. The mean age of caregivers was 47.2years (SD=9.8), of whom 71.5% were female and 74.4% were parents. Nine different psychological variables were examined in the included studies, which were categorised in the following non-mutually exclusive groups: coping, appraisal/attribution and interpersonal response. There was considerable data to support the link between distress and psychological factors such as avoidant coping, appraisal and emotional over-involvement. However, the possibilities of drawing conclusions were limited by a number of methodological issues, including cross-sectional data, small sample sizes, confounding variables not being accounted for, and a wide variation in outcome measures. The strengths of the review were the systematic approach, the exclusion of non-empirical papers and the rating of methodological quality by two independent raters. Limitations were that we excluded studies published in languages other than English, that data extraction forms were developed for this study and hence not tested for validity, and that there was a potential publication bias in favour of significant findings. A better grasp of the psychological factors accounting for caregiver distress early in the course of illness may help us understand the trajectory of distress. This is an important step in preventing long-term distress in caregivers and

Early determinants of mental health

NARCIS (Netherlands)

Räikkönen, Katri; Pesonen, Anu-Katriina; Roseboom, Tessa J.; Eriksson, Johan G.

2012-01-01

Environmental adversities in pre- and early postnatal life may have life-long consequences. Based upon a series of epidemiological and clinical studies and natural experiments, this review describes how the early life environment may affect psychological functions and mental disorders later in life.

Early Child Development and Nutrition: A Review of the Benefits and Challenges of Implementing Integrated Interventions.

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Hurley, Kristen M; Yousafzai, Aisha K; Lopez-Boo, Florencia

2016-03-01

Poor nutrition (substandard diet quantity and/or quality resulting in under- or overnutrition) and the lack of early learning opportunities contribute to the loss of developmental potential and life-long health and economic disparities among millions of children aged early child development (ECD) or nutrition have been linked to positive child development and/or nutritional status, and recommendations currently advocate for the development and testing of integrated interventions. We reviewed the theoretical and practical benefits and challenges of implementing integrated nutrition and ECD interventions along with the evidence for best practice and benefit-cost and concluded that the strong theoretical rationale for integration is more nuanced than the questions that the published empirical evidence have addressed. For example, further research is needed to 1) answer questions related to how integrated messaging influences caregiver characteristics such as well-being, knowledge, and behavior and how these influence early child nutrition and development outcomes; 2) understand population and nutritional contexts in which integrated interventions are beneficial; and 3) explore how varying implementation processes influence the efficacy, uptake, and cost-benefit of integrated nutrition and ECD interventions. © 2016 American Society for Nutrition.

Antibiotic Exposure in Early Life Increases Risk of Childhood Obesity: A Systematic Review and Meta-Analysis

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Xiaoqing Shao

2017-07-01

Full Text Available A number of studies have previously assessed the impact of antibiotic exposure in early life on the risk of childhood obesity, but no systematic assessment is currently available. A systematic review and meta-analysis was performed to comprehensively and quantitatively elucidate the risk of childhood obesity caused by antibiotic exposure in early life. Literature search was performed in PubMed, Embase, and Web of Science. Random-effect meta-analysis was used to pool the statistical estimates. Fifteen cohort studies involving 445,880 participants were finally included, and all those studies were performed in developed countries. Antibiotic exposure in early life significantly increased risk of childhood overweight [relative risk (RR = 1.23, 95% confidence interval (CI 1.13–1.35, P < 0.001] and childhood obesity (RR = 1.21, 95% CI 1.13–1.30, P < 0.001. Antibiotic exposure in early life also significantly increased the z-score of childhood body mass index (mean difference: 0.07, 95% CI 0.05–0.09, P < 0.00001. Importantly, there was an obvious dose–response relationship between antibiotic exposure in early life and childhood adiposity, with a 7% increment in the risk of overweight (RR = 1.07, 95% CI 1.01–1.15, P = 0.03 and a 6% increment in the risk of obesity (RR = 1.06, 95% CI 1.02–1.09, P < 0.001 for each additional course of antibiotic exposure. In conclusion, antibiotic exposure in early life significantly increases risk of childhood obesity. Moreover, current analyses are mainly taken from developed countries, and therefore the impact of antibiotic exposure on risk of childhood obesity in vulnerable populations or developing countries still needs to be evaluated in future studies.

Economic evaluation of medical tests at the early phases of development: a systematic review of empirical studies.

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Frempong, Samuel N; Sutton, Andrew J; Davenport, Clare; Barton, Pelham

2018-02-01

There is little specific guidance on the implementation of cost-effectiveness modelling at the early stage of test development. The aim of this study was to review the literature in this field to examine the methodologies and tools that have been employed to date. Areas Covered: A systematic review to identify relevant studies in established literature databases. Five studies were identified and included for narrative synthesis. These studies revealed that there is no consistent approach in this growing field. The perspective of patients and the potential for value of information (VOI) to provide information on the value of future research is often overlooked. Test accuracy is an essential consideration, with most studies having described and included all possible test results in their analysis, and conducted extensive sensitivity analyses on important parameters. Headroom analysis was considered in some instances but at the early development stage (not the concept stage). Expert commentary: The techniques available to modellers that can demonstrate the value of conducting further research and product development (i.e. VOI analysis, headroom analysis) should be better utilized. There is the need for concerted efforts to develop rigorous methodology in this growing field to maximize the value and quality of such analysis.

The use of telehealth in early autism training for parents: a scoping review

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Boisvert M

2014-03-01

Full Text Available Michelle Boisvert,1 Nerissa Hall2 1WorldTide, Inc., Williamsburg, MA, USA; 2Communicare, LLC, Ludlow, MA, USA Abstract: Telehealth involves the application of technology to deliver services over a geographical distance. Studies in which telehealth procedures were used in the training or coaching of parents with young children (aged 6 years and under who were diagnosed with autism were reviewed. Scoping searches identified two studies that met the inclusion criteria. These studies were evaluated in terms of the: 1 characteristics of the participants; 2 technology utilized; 3 services delivered via telehealth; 4 research methodology; and 5 results and conclusions of the study. Telehealth was used by speech–language pathologists and university researchers to provide training to parents on specific intervention approaches to facilitate targeted communication initiations and responses by gestures, picture pointing, or verbalizations, as well as the delivery and evaluation of the Early Start Denver Model. While the available literature is limited on this topic, this review suggests that the use of telehealth is a viable means to provide training to parents with young children diagnosed with autism. Keywords: autism spectrum disorder, telehealth, training, education, caregivers, parents

Review of early assessment models of innovative medical technologies

DEFF Research Database (Denmark)

Fasterholdt, Iben; Krahn, Murray D; Kidholm, Kristian

2017-01-01

INTRODUCTION: Hospitals increasingly make decisions regarding the early development of and investment in technologies, but a formal evaluation model for assisting hospitals early on in assessing the potential of innovative medical technologies is lacking. This article provides an overview of models...

Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group.

Science.gov (United States)

Remacha, A F; Arrizabalaga, B; Villegas, A; Manteiga, R; Calvo, T; Julià, A; Fernández Fuertes, I; González, F A; Font, L; Juncà, J; del Arco, A; Malcorra, J J; Equiza, E P; de Mendiguren, B P; Romero, M

1999-12-01

Anemia leading to transfusion is probably the most important problem in patients with myelodysplastic syndromes (MDS). Human recombinant erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) have been used to treat patients with anemia of MDS, but fewer than 50% respond. The aim of this work was to evaluate the benefit of rHuEpo +/- G-CSF treatment and to isolate the response predictive variables in a group of selected patients with MDS. A non-randomized multicenter trial was carried out in 32 patients with MDS. The inclusion criteria were age >= 18 years, refractory anemia (RA) or refractory anemia with ringed sideroblasts, Hb +1 (77% of cases responded). In contrast, when this score was <= 1 only 15 % of the cases responded. Use of the Scandinavian-American response score is to be recommended in a patient-oriented approach to treating MDS cases with the Epo and G-CSF. Treatment with rHuEpo and G-CSF is safe, its main drawback being its cost. However, a long-term study evaluating the regimen's cost-benefit ratio is warranted.

Bipolar Disorder and Early Affective Trauma.

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de Codt, Aloise; Monhonval, Pauline; Bongaerts, Xavier; Belkacemi, Ikram; Tecco, Juan Martin

2016-09-01

Bipolar disorder is a chronic psychiatric disease with a high prevalence and is a major psychosocial and medical burden. The exact etiological pathways of bipolar disorder are not fully understood. Genetic factors are known to play an important role in the etiology of bipolar disorder. However, high rates of discordance among identical twins and a growing body of evidence that environmental factors such as early stress can influence the onset and course of psychiatric diseases underline the importance of additional etiological mechanisms of bipolar disorders. There has been little investigation about early trauma in bipolar disorder. The aim of this study was to review the literature on the association between early traumatic interactions like child neglect, mistreatment, abuse or early parental separation and the occurrence of bipolar disorder in adulthood or impact on the course of the disease. Studies investigating associations between child neglect, mistreatment, abuse or early parental separation and occurrence of bipolar disorder in adulthood or impact on the course of the disease were searched in the Pubmed database. More than 700 articles were sorted independently by two of the authors using predefined criteria. Only research articles, reviews and meta-analyses were selected for this review. 53 articles met the inclusion criteria. To date, four systematic reviews partially addressed our research question. Early trauma is more frequently found in the past of bipolar patients than in the general population. Studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a worse prognosis. Early trauma is more often found in the past of bipolar adult patients than the general population and studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a

Systematic review of surveillance systems and methods for early detection of exotic, new and re-emerging diseases in animal populations.

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Rodríguez-Prieto, V; Vicente-Rubiano, M; Sánchez-Matamoros, A; Rubio-Guerri, C; Melero, M; Martínez-López, B; Martínez-Avilés, M; Hoinville, L; Vergne, T; Comin, A; Schauer, B; Dórea, F; Pfeiffer, D U; Sánchez-Vizcaíno, J M

2015-07-01

In this globalized world, the spread of new, exotic and re-emerging diseases has become one of the most important threats to animal production and public health. This systematic review analyses conventional and novel early detection methods applied to surveillance. In all, 125 scientific documents were considered for this study. Exotic (n = 49) and re-emerging (n = 27) diseases constituted the most frequently represented health threats. In addition, the majority of studies were related to zoonoses (n = 66). The approaches found in the review could be divided in surveillance modalities, both active (n = 23) and passive (n = 5); and tools and methodologies that support surveillance activities (n = 57). Combinations of surveillance modalities and tools (n = 40) were also found. Risk-based approaches were very common (n = 60), especially in the papers describing tools and methodologies (n = 50). The main applications, benefits and limitations of each approach were extracted from the papers. This information will be very useful for informing the development of tools to facilitate the design of cost-effective surveillance strategies. Thus, the current literature review provides key information about the advantages, disadvantages, limitations and potential application of methodologies for the early detection of new, exotic and re-emerging diseases.

Techniques for Abdominal Wall Closure after Damage Control Laparotomy: From Temporary Abdominal Closure to Early/Delayed Fascial Closure—A Review

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Qian Huang

2016-01-01

Full Text Available Open abdomen (OA has been an effective treatment for abdominal catastrophes in traumatic and general surgery. However, management of patients with OA remains a formidable task for surgeons. The central goal of OA is closure of fascial defect as early as is clinically feasible without precipitating abdominal compartment syndrome. Historically, techniques such as packing, mesh, and vacuum-assisted closure have been developed to assist temporary abdominal closure, and techniques such as components separation, mesh-mediated traction, bridging fascial defect with permanent synthetic mesh, or biologic mesh have also been attempted to achieve early primary fascial closure, either alone or in combined use. The objective of this review is to present the challenges of these techniques for OA with a goal of early primary fascial closure, when the patient’s physiological condition allows.

Early identification and intervention in cerebral palsy

DEFF Research Database (Denmark)

Herskind, Anna; Greisen, Gorm; Nielsen, Jens Bo

2015-01-01

Infants with possible cerebral palsy (CP) are commonly assumed to benefit from early diagnosis and early intervention, but substantial evidence for this is lacking. There is no consensus in the literature on a definition of 'early', but this review focuses on interventions initiated within...

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.

Shift working in the Chilean Andes (> 3,600 m) and its influence on erythropoietin and the low-pressure system.

Science.gov (United States)

Gunga, H C; Röcker, L; Behn, C; Hildebrandt, W; Koralewski, E; Rich, I; Schobersberger, W; Kirsch, K

1996-08-01

It was hypothesized that, in shift workers with a history of intermittent hypoxic stress (working 10 days at > 3,600 m, then resting for 4 days at sea level) for > 5 yr, the initial erythropoietin (EPO) response and the changes in central venous pressure (CVP) are different from those in Caucasian lowlanders. We studied the kitchen personnel (n = 11) of a mine (3,600 m) and a group of Caucasian lowlanders (n = 5). Blood samples were taken, and CVP was determined several times before, during, and after a typical shift. At baseline data collection (BDC) before transition, the shift workers had EPO concentrations of 5.2 +/- 2.4 mU/ml, which increased at altitude (P < 0.01) and returned to BDC values on the recovery (day 16). The Caucasians showed the same time course. Serum transferrin receptor concentrations did not change in either group. CVP values were generally higher in the shift workers than in the Caucasians. In conclusion, the hypothesis that the initial EPO response to a hypoxic stimulus is altered in these shift workers has to be refuted. Higher hemoglobin concentrations and/or CVP values in shift workers might be responsible for the rather low EPO concentrations in shift workers at BDC.

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

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Paulson Olaf B

2010-10-01

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

[Advances and strategies in gene doping detection].

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He, Jiangang; Liu, Zhen; Liu, Jing; Dou, Peng; Chen, Hong-Yuan

2008-07-01

This review surveys the recent status of gene doping detection and the strategies for anti-gene doping. The main gene doping candidates for athletes are summarized, and the advances in the detection of the proteins expressed by these genes such as erythropoietin (EPO) and human growth hormone (hGH) are reviewed. The potential detection strategies for further gene doping analysis are also discussed.

A review on early gut maturation and colonization in pigs, including biological and dietary factors affecting gut homeostasis

DEFF Research Database (Denmark)

Everaert, Nadia; Van Cruchten, Steven; Weström, Björn

2017-01-01

During the prenatal, neonatal and post-weaning periods, the mammalian gastrointestinal tract undergoes various morphological and physiological changes alongside with an expansion of the immune system and microbial ecosystem. This review focuses on the time period before weaning and summarizes...... in digestive function coincides with development in both the adaptive and innate immune system. This secures a balanced immune response to the ingested milk-derived macromolecules, and colonizing bacteria. Husbandry and dietary interventions in early life appear to affect the development of multiple components...... and immunological maturation, as influenced by early microbial colonization and ingestion of dietary factors, is of utmost importance to identify management and feeding strategies to optimize intestinal health. We discuss some possible implications related to intrauterine growth restriction, and preterm delivery...

An early-stage epidemic: a systematic review of correlates of smoking among Chinese women.

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Ding, Ding; Gebel, Klaus; Oldenburg, Brian F; Wan, Xia; Zhong, Xuefeng; Novotny, Thomas E

2014-08-01

Despite the historically low smoking prevalence among Chinese women, there is a trend of future increase. We systematically reviewed the correlates of smoking among Chinese girls and women. We conducted a systematic review of literature on correlates of smoking among Chinese women using Medline and China Academic Journals databases. Following the PRISMA statement, two investigators independently searched for literature, identified and reviewed papers, assessed the quality of the papers, and extracted information. The characteristics of studies and correlates of smoking were synthesized separately for youth and adults. A total of 15 articles (11 on adults, 4 on youth) met the inclusion criteria. Based on these studies, peer smoking was the most consistent correlate of smoking among Chinese girls. Among Chinese women, partner smoking, job-related stress, and exposure to cigarettes made for women were consistent correlates of smoking. Knowledge of harms and negative attitudes towards smoking were found to be negatively associated with smoking. Overall, the evidence base for smoking among Chinese women is limited. Although smoking among Chinese women is still at an early stage, it is becoming more prevalent among specific population subgroups, such as rural-to-urban migrant workers. Although further research is needed, findings from the current study provide a roadmap for research and policy on prevention of smoking among Chinese girls and women.

Advances in understanding the pathogenesis of primary familial and congenital polycythemia

Science.gov (United States)

Huang, Lily Jun-shen; Shen, Yu-Min; Bulut, Gamze B.

2010-01-01

Summary Primary familial and congenital polycythemia (PFCP) is an autosomal-dominant proliferative disorder characterized by erythrocytosis and hypersensitivity of erythroid progenitors to erythropoietin (Epo). Several lines of evidence suggest a causal role of truncated erythropoietin receptor (EpoR) in this disease. In this review, we discuss PFCP in the context of erythrocytosis and EpoR signaling. We focus on recent studies describing mechanisms underlying Epo-dependent EpoR down-regulation. One mechanism depends on internalization mediated through the p85 regulatory subunit of the Phosphoinositide 3-Kinase, and the other utilizes ubiquitin-based proteasomal degradation. Truncated PFCP EpoRs are not properly down-regulated upon stimulation, underscoring the importance of these mechanisms in the pathogenesis of PFCP. PMID:20096014

Influence of hypothermia combined with erythropoietin on serum neurological function indexes in newborns with severe hypoxic ischemic encephalopathy

Directory of Open Access Journals (Sweden)

Hua Tian

2017-05-01

Full Text Available Objective: To study the influence of hypothermia combined with erythropoietin (EPO on serum neurological function indexes in newborns with severe hypoxic ischemic encephalopathy (HIE. Methods: A total of 48 cases of newborns with severe hypoxic ischemic encephalopathy in our hospital were enrolled and divided into control group and observation group according to random number table, 24 cases in each group. On the basis of conventional treatment, patients in control group were treated with mild hypothermia, and those in observation group were treated with mild hypothermia combined with EPO. Serum nerve injury indexes, neurological function indexes and nerve apoptosis indexes were compared between two groups before and after treatment. Results: Before treatment, differences in the levels of nerve injury indexes, neurological function indexes and nerve apoptosis indexes were not statistically significant between two groups. After treatment, serum nerve injury indexes NSE and S-100B levels of observation group were lower than those of control group, neurolocial function indexes BDNF, NGF, IGF-1 and GH levels of observation group were higher than those of control group, and nerve apoptosis indexes sFas and sFasL levels of observation group were lower than those of control group. Conclusion: Mild hypothermia combined with EPO can reduce the neurological damage and inhibit neuronal apoptosis in children with severe HIE.

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

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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.

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

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Shi YN

2012-12-01

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

Late Jurassic–Early Cretaceous oysters from Siberia: A systematic review

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Igor N. Kosenko

2017-11-01

Full Text Available The present study reviews the taxonomy of Late Jurassic–Early Cretaceous oysters from the Northern and the Subpolar Urals (Western Siberia and northern East Siberia. Previous studies have documented 10 species from the genus Liostrea (L. delta, L. cucurbita, L. praeanabarensis, L. anabarensis, L. plastica, L. gibberosa, L. planoconvexa, L. siberica, L. uralensis, L. lyapinensis, and 3 species from the genus Gryphaea (G. borealis and 2 species in open nomenclature. Liostrea gibberosa, L. planoconvexa, L. uralensis, and L. cucurbita are transferred in this study to the genus Pernostrea. Furthermore, two new species of Pernostrea are described: P. mesezhnikovi sp. nov. and P.? robusta sp. nov. Liostrea siberica is transferred to the genus Praeexogyra. Liostrea praeanabarensis and L. anabarensis are attributed to the subgenus Boreiodeltoideum (genus Deltoideum as well as L. delta sensu Zakharov (1966 which is described here as new species Deltoideum (Boreiodeltoideum borealis sp. nov. The similar shell morphology of the genera Deltoideum and Pernostrea provides a basis to establish the new tribe Pernostreini trib. nov. in the subfamily Gryphaeinae. Three species are recorded for the first time from Siberia: Nanogyra? cf. thurmanni, “Ostrea” cf. moreana and Gryphaea (Gryphaea curva.

Early subsidence of shape-closed hip arthroplasty stems is associated with late revision. A systematic review and meta-analysis of 24 RSA studies and 56 survival studies.

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van der Voort, Paul; Pijls, Bart G; Nieuwenhuijse, Marc J; Jasper, Jorrit; Fiocco, Marta; Plevier, Josepha W M; Middeldorp, Saskia; Valstar, Edward R; Nelissen, Rob G H H

2015-01-01

Few studies have addressed the association between early migration of femoral stems and late aseptic revision in total hip arthroplasty. We performed a meta-regression analysis on 2 parallel systematic reviews and meta-analyses to determine the association between early migration and late aseptic revision of femoral stems. Of the 2 reviews, one covered early migration data obtained from radiostereometric analysis (RSA) studies and the other covered long-term aseptic revision rates obtained from survival studies with endpoint revision for aseptic loosening. Stems were stratified according to the design concept: cemented shape-closed, cemented force-closed, and uncemented. A weighted regression model was used to assess the association between early migration and late aseptic revision, and to correct for confounders. Thresholds for acceptable and unacceptable migration were determined in accordance with the national joint registries (≤ 5% revision at 10 years) and the NICE criteria (≤ 10% revision at 10 years). 24 studies (731 stems) were included in the RSA review and 56 studies (20,599 stems) were included in the survival analysis review. Combining both reviews for the 3 design concepts showed that for every 0.1-mm increase in 2-year subsidence, as measured with RSA, there was a 4% increase in revision rate for the shape-closed stem designs. This association remained after correction for age, sex, diagnosis, hospital type, continent, and study quality. The threshold for acceptable migration of shape-closed designs was defined at 0.15 mm; stems subsiding less than 0.15 mm in 2 years had revision rates of less than 5% at 10 years, while stems exceeding 0.15 mm subsidence had revision rates of more than 5%. There was a clinically relevant association between early subsidence of shape-closed femoral stems and late revision for aseptic loosening. This association can be used to assess the safety of shape-closed stem designs. The published research is not sufficient

Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

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Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina

2017-04-01

Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O 2 , 6 h; postnatal day 7 , P7) at P14. Exposure to hypoxia led to reduced body weight ( P controls and was associated with significantly reduced plasma levels of mouse GH ( P controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain. Copyright © 2017 the American Physiological Society.

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

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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.

The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants.

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Dubois, J; Dehaene-Lambertz, G; Kulikova, S; Poupon, C; Hüppi, P S; Hertz-Pannier, L

2014-09-12

Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. Although the baby's brain is organized early on, it is not a miniature adult brain: regional brain changes are asynchronous and protracted, i.e. sensory-motor regions develop early and quickly, whereas associative regions develop later and slowly over decades. Concurrently, the infant/child gradually achieves new performances, but how brain maturation relates to changes in behavior is poorly understood, requiring non-invasive in vivo imaging studies such as magnetic resonance imaging (MRI). Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Reviewing the current evidence supporting early B-cells as the cellular origin of Merkel cell carcinoma.

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Sauer, C M; Haugg, A M; Chteinberg, E; Rennspiess, D; Winnepenninckx, V; Speel, E-J; Becker, J C; Kurz, A K; Zur Hausen, A

2017-08-01

Merkel cell carcinoma (MCC) is a highly malignant skin cancer characterized by early metastases and poor survival. Although MCC is a rare malignancy, its incidence is rapidly increasing in the U.S. and Europe. The discovery of the Merkel cell polyomavirus (MCPyV) has enormously impacted our understanding of its etiopathogenesis and biology. MCCs are characterized by trilinear differentiation, comprising the expression of neuroendocrine, epithelial and B-lymphoid lineage markers. To date, it is generally accepted that the initial assumption of MCC originating from Merkel cells (MCs) is unlikely. This is owed to their post-mitotic character, absence of MCPyV in MCs and discrepant protein expression pattern in comparison to MCC. Evidence from mouse models suggests that epidermal/dermal stem cells might be of cellular origin in MCC. The recently formulated hypothesis of MCC originating from early B-cells is based on morphology, the consistent expression of early B-cell lineage markers and the finding of clonal immunoglobulin chain rearrangement in MCC cells. In this review we elaborate on the cellular ancestry of MCC, the identification of which could pave the way for novel and more effective therapeutic regimens. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A Review on Hot-IP Finding Methods and Its Application in Early DDoS Target Detection

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Xuan Dau Hoang

2016-10-01

Full Text Available On the high-speed connections of the Internet or computer networks, the IP (Internet Protocol packet traffic passing through the network is extremely high, and that makes it difficult for network monitoring and attack detection applications. This paper reviews methods to find the high-occurrence-frequency elements in the data stream and applies the most efficient methods to find Hot-IPs that are high-frequency IP addresses of IP packets passing through the network. Fast finding of Hot-IPs in the IP packet stream can be effectively used in early detection of DDoS (Distributed Denial of Service attack targets and spreading sources of network worms. Research results show that the Count-Min method gives the best overall performance for Hot-IP detection thanks to its low computational complexity, low space requirement and fast processing speed. We also propose an early detection model of DDoS attack targets based on Hot-IP finding, which can be deployed on the target network routers.

Early endoscopic realignment of traumatic anterior and posterior urethral disruptions under caudal anaesthesia - a 5-year review.

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Olapade-Olaopa, E O; Atalabi, O M; Adekanye, A O; Adebayo, S A; Onawola, K A

2010-01-01

We recently described early rigid retrograde endoscopic realignment of the disrupted urethra under caudal anaesthesia in the outpatient setting. This retrospective study was performed to evaluate our medium-term results. A retrospective review of patients who had early rigid retrograde endoscopic realignment of traumatic urethral disruptions in our institution over a 5-year period was done and the relevant data extracted and analyzed. Fourteen acutely ruptured urethras (10 posterior and four anterior) were endoscopically realigned early in the study period. Nine (90%) of the posterior disruptions occurred at bulbo-membranous urethra (distal to the external sphincter mechanism). Thirteen of the ruptured urethras (93%) were successfully realigned (nine posterior and four anterior) and postoperative clean intermittent self-calibration (CIC) was instituted in 10 patients. The mean follow-up period was 36.6 months (range 18-54 months). The mean operating time and the median hospital stay were 22 min (range 8-68 min) and 3 days (range 1-10 days), respectively, and were shorter in patients with injuries of the anterior urethra than those with posterior urethral tears (p < or = 0.0001). Post-realignment, all 13 patients were potent and continent. Two patients required additional procedures (direct vision internal urethrotomy or urethral dilation) and one patient has remained on CIC i.e. a stricture rate of 21%. Early retrograde endoscopic realignment under caudal analgesia is suitable and cost-effective for patients with acute traumatic urethral disruptions and has good medium-term results. In addition, an early postoperative regimen of CIC significantly reduced stricture-formation in our series.

Superimposition of carbon dioxide on acute isobaric hypoxia: plasma erythropoietin, acid-base status, and P/sub 50/ in the unanesthetized rabbit

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Wolf-Priessnitz, J.

1978-06-01

Major factors affecting changes of the arterial Hb--O/sub 2/ affinity (P/sub 50/) were examined in relation to the initiation of erythropoietin (ESF) production in unanesthetized New Zealand white male rabbits. They were exposed to an isobaric hypoxic environment (8.8 percent O/sub 2/) with and without CO/sub 2/ (5.6 percent or 10 percent). During 5 hrs exposure, samples of arterial blood were collected for measurements of plasma ESF titers; whole-blood pH, P/sub CO2/, S/sub O2/, lactate, pyruvate, and P/sub 50/; and intraerythrocytic 2,3-DPG, ATP and ADP. Exposure to 8.8 percent oxygen alone stimulated ESF production and caused a leftward shift in the in vivo P/sub 50/; the addition of CO/sub 2/ significantly inhibited ESF production and blocked the shift in P/sub 50//sub (i.v.)/. The data suggest that increased oxygenation of the whole-body tissues occurs with exposure to 8.8 percent O/sub 2/ + CO/sub 2/ as reflected by lower whole-blood excess lactate accumulation. In keeping with the prevailing theory, the suppression of ESF production is probably a result of this increased oxygenation.

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

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

2015-09-15

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