A direct and simultaneous detection of zinc protoporphyrin IX, free protoporphyrin IX, and fluorescent heme degradation product in red blood cell hemolysates

2006 ◽  
Vol 40 (3) ◽  
pp. 285-294 ◽  
Author(s):  
Qiuying Chen ◽  
Rhoda Elison Hirsch
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Degradation Product ◽  
Simultaneous Detection ◽  
Protoporphyrin Ix ◽  
Zinc Protoporphyrin ◽  
Heme Degradation

scholarly journals Red blood cell regeneration induced by subcutaneous recombinant erythropoietin: iron-deficient erythropoiesis in iron-replete subjects [see comments]

Blood ◽  
1993 ◽  
Vol 81 (4) ◽  
pp. 956-964 ◽  
Author(s):  
C Brugnara ◽  
LA Chambers ◽  
E Malynn ◽  
MA Goldberg ◽  
MS Kruskall
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Treated Patient ◽  
Normal Subjects ◽  
Zinc Protoporphyrin ◽  
Recombinant Erythropoietin ◽  
Blood Donations ◽  
Iron Stores ◽  
Iron Deficient ◽  
Control Study

Limited red blood cell (RBC) regeneration often prevents collection of sufficient blood from autologous donors. We studied the effects of subcutaneous recombinant erythropoietin (rEPO) in subjects making frequent blood donations. Six healthy iron-replete male subjects took rEPO (200 U/kg) subcutaneously daily, and donated blood (450 mL) twice a week for 3 weeks. During a control study, these subjects also attempted twice-weekly blood donations without rEPO. Four other males given rEPO, including one with idiopathic hemochromatosis, waited until day 8 to begin blood donations. All healthy subjects took oral ferrous sulfate. Subcutaneous rEPO given with blood donations resulted in a marked reticulocytosis (mean peak value 568 +/- 159 x 10(9)/L v 235 +/- 77 x 10(9)/L, control study; P < .05), and enhanced RBC production at 28 days (1,208 +/- 227 mL v 719 +/- 161 mL, P < .05). rEPO in advance of blood donations was slightly less effective in normal subjects (941 +/- 139 mL, P < .05); however, the subject with hemochromatosis produced substantially more RBCs (1,764 mL) than any normal subject. rEPO-treated normal subjects (but not the rEPO-treated patient with hemochromatosis or untreated controls) produced iron-deficient RBCs with elevated zinc protoporphyrin levels and low hemoglobin content. These cells appeared within 1 week of rEPO administration and before laboratory confirmation of depleted iron stores. Thus, subcutaneous rEPO is an effective stimulant of erythropoiesis in nonanemic blood donors. However, in addition to eventual depletion of iron stores, early functional iron deficiency affects response to the drug.

scholarly journals Study protocol and pilot results of an observational cohort study evaluating effect of red blood cell transfusion on oxygenation and mitochondrial oxygen tension in critically ill patients with anaemia: the INsufficient Oxygenation in the Intensive Care Unit (INOX ICU-2) study

BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e036351 ◽  
Author(s):  
Meryem Baysan ◽  
Mendi S Arbous ◽  
Egbert G Mik ◽  
Nicole P Juffermans ◽  
Johanna G van der Bom
Keyword(s):  
Intensive Care ◽  
Blood Cell ◽  
Critically Ill ◽  
Red Blood Cell ◽  
Critically Ill Patients ◽  
Tissue Oxygenation ◽  
Protoporphyrin Ix ◽  
Oxygen Balance ◽  
Mixed Effect ◽  
Rbc Transfusion

IntroductionThe recently developed protoporphyrin IX-triple state lifetime technique measures mitochondrial oxygenation tension (mitoPO2) in vivo at the bedside. MitoPO2might be an early indicator of oxygen disbalance in cells of critically ill patients and therefore may support clinical decisions regarding red blood cell (RBC) transfusion. We aim to investigate the effect of RBC transfusion and the associated changes in haemoglobin concentration on mitoPO2 and other physiological measures of tissue oxygenation and oxygen balance in critically ill patients with anaemia. We present the protocol and pilot results for this study.Methods and analysisWe perform a prospective multicentre observational study in three mixed intensive care units in the Netherlands with critically ill patients with anaemia in whom an RBC transfusion is planned. The skin of the anterior chest wall of the patients is primed with a 5-aminolevulinic acid patch for 4 hours for induction of mitochondrial protoporphyrin-IX to enable measurements of mitoPO2, which is done with the COMET monitoring device. At multiple predefined moments, before and after RBC transfusion, we assess mitoPO2 and other physiological parameters of oxygen balance and tissue oxygenation. Descriptive statistics will be used to describe the data. A linear mixed-effect model will be used to study the association between RBC transfusion and mitoPO2 and other traditional parameters of oxygenation, oxygen delivery and oxygen balance. Missing data will be imputed using multiple imputation methods.Ethics and disseminationThe institutional ethics committee of each participating centre approved the study (reference P16.303), which will be conducted according to the 1964 Helsinki declaration and its later amendments. The results will be submitted for publication in peer-reviewed journals and presented at scientific conferences.Trial registration numberNCT03092297.

scholarly journals Ferroptosis as a target for protection against cardiomyopathy

2019 ◽  
Vol 116 (7) ◽  
pp. 2672-2680 ◽  
Author(s):  
Xuexian Fang ◽  
Hao Wang ◽  
Dan Han ◽  
Enjun Xie ◽  
Xiang Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Death ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Protoporphyrin Ix ◽  
Iron Chelation ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Free Iron ◽  
Heme Degradation

Heart disease is the leading cause of death worldwide. A key pathogenic factor in the development of lethal heart failure is loss of terminally differentiated cardiomyocytes. However, mechanisms of cardiomyocyte death remain unclear. Here, we discovered and demonstrated that ferroptosis, a programmed iron-dependent cell death, as a mechanism in murine models of doxorubicin (DOX)- and ischemia/reperfusion (I/R)-induced cardiomyopathy. In canonical apoptosis and/or necroptosis-defective Ripk3−/−, Mlkl−/−, or Fadd−/−Mlkl−/− mice, DOX-treated cardiomyocytes showed features of typical ferroptotic cell death. Consistently, compared with dexrazoxane, the only FDA-approved drug for treating DOX-induced cardiotoxicity, inhibition of ferroptosis by ferrostatin-1 significantly reduced DOX cardiomyopathy. RNA-sequencing results revealed that heme oxygenase-1 (Hmox1) was significantly up-regulated in DOX-treated murine hearts. Administering DOX to mice induced cardiomyopathy with a rapid, systemic accumulation of nonheme iron via heme degradation by Nrf2-mediated up-regulation of Hmox1, which effect was abolished in Nrf2-deficent mice. Conversely, zinc protoporphyrin IX, an Hmox1 antagonist, protected the DOX-treated mice, suggesting free iron released on heme degradation is necessary and sufficient to induce cardiac injury. Given that ferroptosis is driven by damage to lipid membranes, we further investigated and found that excess free iron accumulated in mitochondria and caused lipid peroxidation on its membrane. Mitochondria-targeted antioxidant MitoTEMPO significantly rescued DOX cardiomyopathy, supporting oxidative damage of mitochondria as a major mechanism in ferroptosis-induced heart damage. Importantly, ferrostatin-1 and iron chelation also ameliorated heart failure induced by both acute and chronic I/R in mice. These findings highlight that targeting ferroptosis serves as a cardioprotective strategy for cardiomyopathy prevention.

scholarly journals Red blood cell regeneration induced by subcutaneous recombinant erythropoietin: iron-deficient erythropoiesis in iron-replete subjects [see comments]

Blood ◽  
1993 ◽  
Vol 81 (4) ◽  
pp. 956-964 ◽  
Author(s):  
C Brugnara ◽  
LA Chambers ◽  
E Malynn ◽  
MA Goldberg ◽  
MS Kruskall
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Treated Patient ◽  
Normal Subjects ◽  
Zinc Protoporphyrin ◽  
Recombinant Erythropoietin ◽  
Blood Donations ◽  
Iron Stores ◽  
Iron Deficient ◽  
Control Study

Abstract Limited red blood cell (RBC) regeneration often prevents collection of sufficient blood from autologous donors. We studied the effects of subcutaneous recombinant erythropoietin (rEPO) in subjects making frequent blood donations. Six healthy iron-replete male subjects took rEPO (200 U/kg) subcutaneously daily, and donated blood (450 mL) twice a week for 3 weeks. During a control study, these subjects also attempted twice-weekly blood donations without rEPO. Four other males given rEPO, including one with idiopathic hemochromatosis, waited until day 8 to begin blood donations. All healthy subjects took oral ferrous sulfate. Subcutaneous rEPO given with blood donations resulted in a marked reticulocytosis (mean peak value 568 +/- 159 x 10(9)/L v 235 +/- 77 x 10(9)/L, control study; P < .05), and enhanced RBC production at 28 days (1,208 +/- 227 mL v 719 +/- 161 mL, P < .05). rEPO in advance of blood donations was slightly less effective in normal subjects (941 +/- 139 mL, P < .05); however, the subject with hemochromatosis produced substantially more RBCs (1,764 mL) than any normal subject. rEPO-treated normal subjects (but not the rEPO-treated patient with hemochromatosis or untreated controls) produced iron-deficient RBCs with elevated zinc protoporphyrin levels and low hemoglobin content. These cells appeared within 1 week of rEPO administration and before laboratory confirmation of depleted iron stores. Thus, subcutaneous rEPO is an effective stimulant of erythropoiesis in nonanemic blood donors. However, in addition to eventual depletion of iron stores, early functional iron deficiency affects response to the drug.

scholarly journals Application of innovative hemocytometric parameters and algorithms for improvement of microcytic anemia discrimination

2015 ◽  
Vol 7 (2) ◽  
Author(s):  
Margreet Schoorl ◽  
Marianne Schoorl ◽  
Johannes Van Pelt ◽  
Piet C.M. Bartels
Keyword(s):  
Iron Deficiency ◽  
Blood Cell ◽  
Iron Deficiency Anemia ◽  
Red Blood Cell ◽  
Hematological Parameters ◽  
Deficiency Anemia ◽  
Zinc Protoporphyrin ◽  
Distribution Width ◽  
New Algorithms ◽  
Rbc Count

Hemocytometric parameters like red blood cell (RBC) count, mean red blood cell volume (MCV), reticulocyte count, red blood cell distribution width (RDW-SD) and zinc protoporphyrin (ZPP) are frequently established for discrimination between iron-deficiency anemia and thalassemia in subjects with microcytic erythropoiesis. However, no single marker or combination of tests is optimal for discrimination between iron-deficiency anemia and thalassemia. This is the reason why many algorithms have been introduced. However, application of conventional algorithms, only resulted in appropriate classification of 30-40% of subjects. In this mini-review the efficacy of innovative hematological parameters for detection of alterations in RBCs has been considered. It refers to parameters concerning hemoglobinization of RBCs and reticulocytes and the percentages microcytic and hypochromic RBCs, for discrimination between subjects with iron-deficiency anemia (IDA) or thalassemia as well as a combination of both. A new discriminating tool including the above mentioned parameters was developed, based on two precondition steps and discriminating algorithms. The percentage microcytic RBCs is considered in the first pre-condition step. MCV, RDW-SD and RBC count are applied in the second precondition step. Subsequently, new algorithms, including conventional as well as innovative hematological parameters, were assessed for subgroups with microcytic erythropoiesis. The new algorithms for IDA discrimination yielded results for sensitivity of 79%, specificity of 97%, positive and negative predictive values of 74% and 98% respectively. The algorithms for beta-thalassemia discrimination revealed similar results (74%, 98%, 75% and 99% respectively). We advocate that innovative algorithms, including parameters reflecting hemoglobinization of RBCs and reticulocytes, are integrated in an easily accessible software program linked to the hematology equipment to improve the discrimination between IDA and thalassemia.

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