The in Vivo Plasma Clearance of Iron from Transferrins of Low and High Iron Saturation

1970 ◽  
Vol 38 (6) ◽  
pp. 783-793 ◽  
Author(s):  
R. S. Lane ◽  
C. A. Finch
Keyword(s):  
Iron Uptake ◽  
Plasma Clearance ◽  
High Plasma ◽  
Clearance Time ◽  
Plasma Iron ◽  
High Iron ◽  
Iron Saturation ◽  
In Vivo Release ◽  
Iron Pool

1. The rate of in vivo release of iron from plasma transferrin samples at low and high saturation was measured simultaneously in fifteen subjects with differing amounts of body iron and different rates of erythropoiesis. Iron atoms bound to transferrin at low and high plasma iron saturation were identified by using tracer labels 55Fe and 59Fe respectively. Results were expressed as the plasma 55Fe and 59Fe half-clearance time. 2. Plasma iron clearance times ranged from 15·6 to 350 min, reflecting the different amounts of available iron and marrow requirements of the patients studied. The simultaneous rates of 55Fe and 59Fe clearance from the plasma were the same in thirteen patients. Clearances in two subjects showed differences between the two isotopes, but clearances of the identical paired isotopes in two other subjects showed no difference. 3. These results confirm earlier findings of homogeneity in the plasma iron pool, extending the observations to include varying per cent saturation of transferrin and varying rates of iron uptake.

The Plasma Clearance and Liver Uptake of Iron from Transferrin of Low and High Iron Saturation

1971 ◽  
Vol 41 (5) ◽  
pp. 395-402 ◽  
Author(s):  
J. Fletcher
Keyword(s):  
Plasma Clearance ◽  
Liver Uptake ◽  
Plasma Iron ◽  
High Iron ◽  
Iron Saturation ◽  
B Uptake

1. Serum labelled with radioactive iron was adjusted to different degrees of iron saturation and clearance of the tracer from the circulation of rats and its uptake by liver and intestine were followed. 2. The results showed that: (a) plasma iron clearance did not vary according to whether labelled iron was attached to transferrin at high or low iron saturation; (b) uptake of labelled iron by the liver was greater from transferrin at high iron saturation than from transferrin at low saturation. 3. The results suggest the presence of a receptor mechanism in the liver similar to that previously shown in reticulocytes.

Heterogeneity of the plasma iron pool: explanation of the Fletcher-Huehns phenomenon

1984 ◽  
Vol 247 (2) ◽  
pp. R280-R283 ◽  
Author(s):  
H. A. Huebers ◽  
E. Huebers ◽  
E. Csiba ◽  
C. A. Finch
Keyword(s):  
Competitive Advantage ◽  
Isoelectric Focusing ◽  
Binding Sites ◽  
Iron Uptake ◽  
Iron Binding ◽  
Rabbit Plasma ◽  
Plasma Iron ◽  
Functional Differences ◽  
Iron Pool ◽  
Control Plasma

Observations on iron uptake by reticulocytes led Fletcher and Huehns to suggest differences in the behavior of the two iron-binding sites of the transferrin molecule. To clarify the continued controversy relating to this hypothesis, the original studies employing control plasma labeled with radioiron and the same plasma preincubated with reticulocytes were reexamined. Regardless of whether human or rabbit plasma was employed, there was a considerably higher uptake from the control plasma. Isoelectric focusing procedures and electrophoresis in urea gels revealed that the conspicuous difference in the amount of iron uptake is the result of differences in the proportion of di- to monoferric transferrin in the two plasmas and the competitive advantage of the diferric moiety. These studies provide an explanation for the Fletcher-Huehns phenomenon without invoking functional differences between the two sites for iron on the transferrin molecule.

Studies on Metabolism of Urokinase and Mechanism of Thrombolysis by Urokinase

1979 ◽  
Vol 42 (03) ◽  
pp. 885-894 ◽  
Author(s):  
Tatsuo Ueno ◽  
Norio Kobayashi ◽  
Tadashi Maekawa
Keyword(s):  
Molecular Weight ◽  
Plasma Clearance ◽  
Radioactive Material ◽  
Optimal Dosage ◽  
Plasma Clot ◽  
Optimal Dosage Regimen ◽  
Arterial Thrombus ◽  
Contact Experiment

SummaryPharmacokinetics of intravenously injected 125I-labeled urokinase (125I-UK) of a molecular weight of 33,000 daltons in normal rabbits and patients with various diseases were investigated. The plasma clearance of 125I-UK in rabbits was described by a biexponential curve within six hours with a half-life of 8 minutes, 2.3 hours, respectively. The radioactivity in the liver and kidneys 15 minutes after iv injection with 125I-UK was 9.6% and 14.0% of the radioactivity injected, respectively. Approximately 80% of the total radioactive material injected was excreted in the urine in 18 hours. No increase in activator activity in the urine was observed after a large amount of UK injection. Activity uptake of 125I-UK by experimentally induced arterial thrombus was little. Lysis of the stasis thrombus was produced by injecting 7.5 × 104 IU of UK in only one out of 8 rabbits. In vitro contact experiment revealed that transfer of 125I-UK to plasma clot is slow (24 hours for 10% of 125I-UK by plasma clot). In 4 patients plasma clearance of 125I-UK was essentially similar to that in rabbits. From the results obtained optimal dosage regimen of UK administration for complete thrombolysis in vivo was discussed.

Clearance and In Vivo Release by Heparin of Human Platelet Factor 4 (PF4) in the Rabbit

1984 ◽  
Vol 52 (02) ◽  
pp. 157-159 ◽  
Author(s):  
M Prosdocimi ◽  
N Scattolo ◽  
A Zatta ◽  
F Fabris ◽  
F Stevanato ◽  
...  
Keyword(s):  
Half Life ◽  
Human Platelet ◽  
Slow Component ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
In Vivo Release ◽  
Partial Release ◽  
Different Doses ◽  
New Zealand Rabbits

Summary13 male New Zealand rabbits were injected with two different doses (25 μg/Kg and 100 μg/Kg) of human platelet factor 4 antigen (PF4). The disappearance of the protein was extremely fast with an half-life for the fast component of 1.07 ± 0.16 and 1.76 ± 0.11 min respectively. The half-life for the slow component, detectable only with the highest dosage, was 18.8 min.The administration of 2500 I.U. of heparin 30 min after PF4 administration induced a partial release of the injected protein and its clearance from plasma was slow, with half-life of 23.3 ± 5.9 min and 30.9 ± 2.19 min respectively.

scholarly journals CBIO-10. REDUCED IRON EXPORT FUNCTIONS IN A CELL INTRINSIC MANNER TO DRIVE GLIOBLASTOMA GROWTH

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii17-ii17
Author(s):  
Katie Troike ◽  
Erin Mulkearns-Hubert ◽  
Daniel Silver ◽  
James Connor ◽  
Justin Lathia
Keyword(s):  
Tumor Cells ◽  
Iron Uptake ◽  
Iron Homeostasis ◽  
Iron Status ◽  
Tumor Grade ◽  
Hfe Gene ◽  
Iron Release ◽  
Female Patients ◽  
Cellular Iron

Abstract Glioblastoma (GBM), the most common primary malignant brain tumor in adults, is characterized by invasive growth and poor prognosis. Iron is a critical regulator of many cellular processes, and GBM tumor cells have been shown to modulate expression of iron-associated proteins to enhance iron uptake from the surrounding microenvironment, driving tumor initiation and growth. While iron uptake has been the central focus of previous investigations, additional mechanisms of iron regulation, such as compensatory iron efflux, have not been explored in the context of GBM. The hemochromatosis (HFE) gene encodes a transmembrane glycoprotein that aids in iron homeostasis by limiting cellular iron release, resulting in a sequestration phenotype. We find that HFE is upregulated in GBM tumors compared to non-tumor brain and that expression of HFE increases with tumor grade. Furthermore, HFE mRNA expression is associated with significantly reduced survival specifically in female patients with GBM. Based on these findings, we hypothesize that GBM tumor cells upregulate HFE expression to augment cellular iron loading and drive proliferation, ultimately leading to reduced survival of female patients. To test this hypothesis, we generated Hfe knockdown and overexpressing mouse glioma cell lines. We observed significant alterations in the expression of several iron handling genes with Hfe knockdown or overexpression, suggesting global disruption of iron homeostasis. Additionally, we show that knockdown of Hfe in these cells increases apoptosis and leads to a significant impairment of tumor growth in vivo. These findings support the hypothesis that Hfe is a critical regulator of cellular iron status and contributes to tumor aggression. Future work will include further exploration of the mechanisms that contribute to these phenotypes as well as interactions with the tumor microenvironment. Elucidating the mechanisms by which iron effulx contributes to GBM may inform the development of next-generation targeted therapies.

scholarly journals The Insulin Receptor Mediates Insulin’s Early Plasma Clearance by Liver, Muscle, and Kidney

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 37
Author(s):  
Rick I. Meijer ◽  
Eugene J. Barrett
Keyword(s):  
Insulin Receptor ◽  
Plasma Clearance ◽  
Plasma Insulin ◽  
Insulin Clearance ◽  
Initial Plasma ◽  
Liver And Kidney ◽  
Pre Treatment ◽  
Initial Clearance

The role of the insulin receptor in mediating tissue-specific insulin clearance in vivo has not been reported. Using physiologic insulin doses, we measured the initial clearance rate (first 5 min) of intravenously injected ([125I]TyrA14)-insulin by muscle, liver, and kidney in healthy rats in the presence and absence of the insulin receptor blocker S961. We also tested whether 4 weeks of high-fat diet (HFD) affected the initial rate of insulin clearance. Pre-treatment with S961 for 60 min prior to administering labeled insulin raised plasma ([125I]TyrA14)insulin concentration approximately 5-fold (p < 0.001), demonstrating receptor dependency for plasma insulin clearance. Uptake by muscle (p < 0.01), liver (p < 0.05), and kidney (p < 0.001) were each inhibited by receptor blockade, undoubtedly contributing to the reduced plasma clearance. The initial plasma insulin clearance was not significantly affected by HFD, nor was muscle-specific clearance. However, HFD modestly decreased liver clearance (p = 0.056) while increasing renal clearance by >50% (p < 0.01), suggesting a significant role for renal insulin clearance in limiting the hyperinsulinemia that accompanies HFD. We conclude that the insulin receptor is a major mediator of initial insulin clearance from plasma and for its clearance by liver, kidney, and muscle. HFD feeding increases renal insulin clearance to limit systemic hyperinsulinemia.

scholarly journals Relation of Oxidative Metabolism to the Incorporation of Plasma Iron into Ferritin in Vivo

1961 ◽  
Vol 236 (4) ◽  
pp. 1109-1116
Author(s):  
Abraham Mazur ◽  
Anne Carleton ◽  
Ann Carlsen
Keyword(s):  
Oxidative Metabolism ◽  
Plasma Iron

The in vivo release of 90Y from cyclic and acyclic ligand-antibody conjugates

1991 ◽  
Vol 18 (5) ◽  
pp. 469-476 ◽  
Author(s):  
A. Harrison ◽  
C.A. Walker ◽  
D. Parker ◽  
K.J. Jankowski ◽  
J.P.L. Cox ◽  
...  
Keyword(s):  
In Vivo Release ◽  
Antibody Conjugates

scholarly journals Catalytic activity and stereoselectivity of engineered phosphotriesterases towards structurally different nerve agents in vitro

2021 ◽  
Author(s):  
Anja Köhler ◽  
Benjamin Escher ◽  
Laura Job ◽  
Marianne Koller ◽  
Horst Thiermann ◽  
...  
Keyword(s):  
Plasma Clearance ◽  
Nerve Agents ◽  
Inhibition Assay ◽  
Ache Inhibition ◽  
Catalytic Activities ◽  
Chiral Lc ◽  
Hydrolysis Of ◽  
Medical Countermeasures

AbstractHighly toxic organophosphorus nerve agents, especially the extremely stable and persistent V-type agents such as VX, still pose a threat to the human population and require effective medical countermeasures. Engineered mutants of the Brevundimonas diminuta phosphotriesterase (BdPTE) exhibit enhanced catalytic activities and have demonstrated detoxification in animal models, however, substrate specificity and fast plasma clearance limit their medical applicability. To allow better assessment of their substrate profiles, we have thoroughly investigated the catalytic efficacies of five BdPTE mutants with 17 different nerve agents using an AChE inhibition assay. In addition, we studied one BdPTE version that was fused with structurally disordered PAS polypeptides to enable delayed plasma clearance and one bispecific BdPTE with broadened substrate spectrum composed of two functionally distinct subunits connected by a PAS linker. Measured kcat/KM values were as high as 6.5 and 1.5 × 108 M−1 min−1 with G- and V-agents, respectively. Furthermore, the stereoselective degradation of VX enantiomers by the PASylated BdPTE-4 and the bispecific BdPTE-7 were investigated by chiral LC–MS/MS, resulting in a several fold faster hydrolysis of the more toxic P(−) VX stereoisomer compared to P(+) VX. In conclusion, the newly developed enzymes BdPTE-4 and BdPTE-7 have shown high catalytic efficacy towards structurally different nerve agents and stereoselectivity towards the toxic P(−) VX enantiomer in vitro and offer promise for use as bioscavengers in vivo.

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