Disease relevance of EPO

• Differences among the treatment groups included a lower fetal survival percentage in UHO (vs. INT or MS) on Day 40, and higher maternal hematocrits, fetal weights, fetal hematocrits, fetal EPO levels, and liver transferrin secretion in WC vs. MS pigs [1].
• The mechanisms, however, by which EPO may cause hypertension are still unclear [2].
• Quantitative histological analysis of the ischaemic regions revealed a reduction of myocardial fibrosis (8% vs. 28%) in the EPO group [3].
• However, the hearing loss of the EPO treated animals was significantly worse than controls in trial 2 [4].
• Latency characteristics of an EPO and LLT mutant of pseudorabies virus [5].

Psychiatry related information on EPO

• In addition, the need for a more systematic longitudinal assessment of dementia in dialysis patients by standardized neuropsychologic testing, testing blood levels and glycosylated isoforms of PGD(2)S, and the effect of COX inhibition and erythropoietin administration on dialysis dementia are discussed [6].

High impact information on EPO

• Nanogram concentrations of the growth hormones potentiated erythropoietin-stimulated erythropoiesis, but not granulopoiesis, in a species-specific manner [7].
• Activity with physiologic concentrations of chloride was favored by a relatively high EPO level, a decrease in pH below neutrality and an absence of extraneous protein [8].
• When the EPO concentration of the reaction mixture was lowered, the bactericidal effect at pH 7.0 was lost first with chloride, then with bromide, and finally with iodide as the halide [8].
• Increased fetal weight, fetal liver weight, placental weight, total red blood cells, hematocrit, blood hemoglobin content, and maternal plasma erythropoietin (EPO) levels were observed as gestation advanced [1].
• CONCLUSION: Endocardial EPO injection may induce cardioprotective effects in hibernating myocardium and may attenuate the progression of ischaemic tissue damage [3].

Chemical compound and disease context of EPO

• OBJECTIVE: Recent studies have shown that erythropoietin protects neurons from glutamate toxicity and ischemia [9].
• This study tested the hypothesis that upregulation of hypoxia inducible factor and erythropoietin by preconditioning with hypoxia or the hypoxia-mimetic agents deferoxamine and cobalt chloride would be neuroprotective in a piglet model of deep hypothermic circulatory arrest [10].

Biological context of EPO

• BACKGROUND: Apart from its well-known stimulation of erythropoiesis, erythropoietin (EPO) exhibits angiogenic and anti-apoptotic effects [3].
• A rise in blood pressure is the main side effect of erythropoietin (EPO) treatment in patients with renal anemia [2].
• In a second study at day 35 of gestation, embryonic liver EPO mRNA expression was measured in the same three pig models and in two embryos of divergent weights from each gilt [11].
• There was no apparent relationship between embryonic development, measured as embryonic and placental size, and plasma EPO concentrations or liver EPO mRNA expression [11].
• EPO administration may alter the blood flow dynamics of the cochlear vascular bed during or after noise exposure, by a potential induction of vasoconstriction [4].

Anatomical context of EPO

• The testes showed a higher ratio of EPO mRNA to total RNA than the liver [12].
• Spleen showed very low levels of expression, while no expression of erythropoietin mRNA was detected in brain tissue, bone marrow, lung, lymph nodes, and ovaries [12].
• We therefore investigated the effects of EPO on endothelin (ET) synthesis and cytosolic free calcium concentration ([Ca2+]i) in vascular endothelial cells [2].
• An erythropoietin (EPO) assay showed that all nine transgenic lines carrying the 8.8 kb construct expressed recombinant human erythropoietin (rhEPO) only in their urethra and bladder, whereas two transgenic lines carrying the 2.1 kb pUPII promoter displayed hEPO expression in several organs including bladder, kidney, spleen, heart, and brain [13].
• We hypothesize on the existence of a local paracrine system and that EPO treatment may be feasible following inner ear damage [14].

Associations of EPO with chemical compounds

• EPO (12 to 200 U/mL) stimulated ET release time- and dose-dependently by up to 83.2% (P < .01) within 12 h in the absence of fetal calf serum and heparin [2].
• The tyrosine kinase inhibitor genistein suppressed the EPO-induced rise in [Ca2+]i and cellular ET synthesis [2].
• 70% ethanol caused an irreversible, plateauing decline in EPO, while 35% ethanol caused a reversible decline in EP [15].
• The erythropoietin group had higher vascular resistance and mean arterial pressure values, lower intracerebral concentrations of glutamate and glycerol, higher brain tissue oxygen tension, and lower apoptotic index [9].
• Growth stimulation effects of erythropoietin on cultured gastric mucosal cells were determined by ELISA using bromodeoxyuridine (BrdU) [16].

Regulatory relationships of EPO

• We conclude, that EPO is expressed by spiral ganglion neurons and that the EPO receptor is widely expressed by several cell types within the guinea pig cochlea [14].

Other interactions of EPO

• Accordingly, this study determines expression of EPO and EPOR in the inner ear of the guinea pig [14].
• Adaptation to hypoxic stress provokes activation of the hypoxia-inducible-factor-1 (HIF-1) which mediates gene expression of, e.g., erythropoietin or vascular endothelial growth factor [17].
• Brain hypoxia inducible factor and erythropoietin contents were assessed by means of Western blotting at 3, 8, and 24 hours after treatment (n = 3 per time point) [10].

Analytical, diagnostic and therapeutic context of EPO

• Expression analyses using a competitive RT-PCR assay showed that the kidneys contain about ten times more erythropoietin mRNA than the liver in five-week-old piglets, thus indicating that the shift from mainly hepatic to mainly renal EPO production has taken place at this age [12].
• RESULTS: Endocardial electromechanical mapping showed an increase of mean unipolar voltage (UV) amplitude in the ischaemic myocardial segments in the EPO-treated animals (8.5 mV pre and 10.6 mV post treatment) and a significantly reduced ischaemic surface area compared to the control group (19% vs. 41%) suggesting a decline in ischaemic injury [3].
• A partial cDNA for porcine EPO, developed via reverse transcription and polymerase chain reaction procedures was used to generate a 32P-labeled probe for use in Northern analyses [11].
• Normal guinea pig inner ears were processed for immunohistochemistry, using poly-clonal antibodies against EPO and the EPO receptor [14].
• Liver EPO mRNA expression did not differ among animal models, nor did plasma EPO or tissue EPO mRNA expression differ between large and small embryos [11].

References