Evidence map›Paper›PMID 35171971›Full record

ArticlePloS one2022

Scalable manufacturing platform for the production of methemoglobin as a non-oxygen carrying control material in studies of cell-free hemoglobin solutions.

Xiangming Gu, Richard Hickey, Antara Rath, Andre F Palmer

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 41% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
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  5. Facile synthesis of Ag@FeScientific reports · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Xiangming GuWilliam G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, United States of America.ORCID 0000-0001-9096-5911
Richard HickeyWilliam G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, United States of America.
Antara RathWilliam G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, United States of America.
Andre F PalmerWilliam G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, United States of America.ORCID 0000-0002-3378-3772
The Ohio State University · US

Funding

PEGylated megahemoglobin for use as a red blood cell substituteR01HL138116 · NHLBI · OHIO STATE UNIVERSITY · PI CABRALES, PEDRO, KAUMAYA, PRAVIN T. P. · 2017 to 2020
$2.9M
Fractionation of Aged RBCs Based on Hemoglobin ContentR01HL131720 · NHLBI · OHIO STATE UNIVERSITY · PI CHALMERS, JEFFREY JOHN, PALMER, ANDRE FRANCIS · 2017 to 2020
$2.7M
Bioengineering a Dual Function Protein Construct to Detoxify Heme and HemoglobinR01HL159862 · NHLBI · OHIO STATE UNIVERSITY · PI BUEHLER, PAUL WERNER, CABRALES, PEDRO · 2021 to 2024
$2.6M
Engineering a novel biomaterial for oxygen transport applicationsR01HL156526 · NHLBI · OHIO STATE UNIVERSITY · PI BUEHLER, PAUL WERNER, PALMER, ANDRE FRANCIS · 2021 to 2024
$2.5M
Attenuating the Oxidative and Myocardial Side-Effects of Acellular HemoglobinR01HL126945 · NHLBI · OHIO STATE UNIVERSITY · PI CABRALES, PEDRO, PALMER, ANDRE FRANCIS · 2016 to 2019
$1.7M
Polymerized Hemoglobins for Facilitated Oxygen Transport in Hepatic BioreactorsR01EB021926 · NIBIB · OHIO STATE UNIVERSITY · PI BERTHIAUME, FRANCOIS, PALMER, ANDRE FRANCIS · 2016 to 2019
$1.4M
NHLBI NIH HHS R01 HL126945NHLBI NIH HHS R01 HL131720NHLBI NIH HHS R01 HL138116NHLBI NIH HHS R01 HL156526NHLBI NIH HHS R01 HL159862NIBIB NIH HHS R01 EB021926
6 · The paper itself

Abstract

Methemoglobin (metHb) arises from the oxidation of ferrous hemoglobin (HbFe2+, Hb) to ferric hemoglobin (HbFe3+, metHb), which is unable to bind gaseous ligands such as oxygen (O2) and carbon monoxide (CO), and binds to nitric oxide (NO) significantly slower compared to Hb. Therefore, metHb does not elicit vasoconstriction and systemic hypertension in vivo due to its extremely slow NO scavenging rate in comparison to cell-free Hb, but will induce oxidative tissue injury, demonstrating the potential of using metHb as a control material when studying the toxicity of cell-free Hb. Hence, the goal of this work was to develop a novel manufacturing strategy for production of metHb that is amenable to scale-up. In this study, small scale (e.g. 1 mL reaction volume) screening experiments were initially conducted to determine the optimal molar ratio of Hb to the oxidization agents hydrogen peroxide (H2O2) or sodium nitrite (NaNO2) to achieve the highest conversion of Hb into metHb. A spectral deconvolution program was employed to determine the molar fraction of various species (hemichrome, metHb, oxyHb, metHb-[Formula: see text], and NaNO2) in solution during the oxidation reaction. From this analysis, either a 1:1 or 1:5 molar ratio was identified as optimal molar ratios of Hb:NaNO2 (heme basis) that yielded the highest conversion of Hb into metHb with negligible amounts of side products. Hence in order to reduce the reaction time, a 1:5 molar ratio was chosen for large scale (i.e. 1.5 L reaction volume) synthesis of bovine metHb (metbHb) and human metHb (methHb). The biophysical properties of metHb were then characterized to elucidate the potential of using the synthesized metHb as a non-O2 carrying control material. The haptoglobin binding kinetics of metHb were found to be similar to Hb. Additionally, the synthesized metHb was stable in phosphate buffered saline (PBS, 50 mM, pH 7.4) at 4°C for approximately one week, indicating the high stability of the material.

Indexed as

AnimalsCattleHemoglobinsHumansHydrogen PeroxideMethemoglobinNitric OxideOxidantsOxidation-ReductionOxygenSodium NitriteHemoglobinsHydrogen PeroxideMethemoglobinNitric OxideOxidantsOxygenSodium Nitrite

Identifiers

PMID35171971
PMCPMC8849478
OpenAlexW4213063397

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.