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Free Radical Biology & Medicine Oct 2016When nitrosothiols react with excess hydrogen sulfide, HS, they form several intermediates including nitrosopersulfide (SSNO). The stability and importance of this...
When nitrosothiols react with excess hydrogen sulfide, HS, they form several intermediates including nitrosopersulfide (SSNO). The stability and importance of this species has been debated. While some data suggest SSNO can be a relatively stable source of NO activity, others suggest that the species degrades too quickly. We find the species to be relatively stable in isolation. Due to the abundance and prominence of iron-containing proteins throughout the human body, it is important to establish the interaction of ferrous- and ferric-iron containing proteins with SSNO. Study of the reactions of SSNO with heme proteins can also provide information about the potential in vivo stability and spontaneous reactivity of this species. We have used time-resolved electron paramagnetic resonance and UV-Vis absorption spectroscopy to study the reactions of SSNO with heme proteins. Iron-nitrosyl hemoglobin is formed when SSNO is reacted with deoxyhemoglobin and deoxygenated methemoglobin, suggesting NO formation from SSNO. However, the yields of nitrosyl hemoglobin in reactions of SSNO with deoxyhemoglobin are much less than when SSNO is reacted with deoxygenated methemoglobin. Very little to no nitrosyl hemoglobin is formed when SSNO is reacted carboxyhemoglobin, HbCO, and when SSNO is reacted with oxygenated hemoglobin, minimal methemoglobin is formed Taken together, these data confirm the release of NO, but indicate a vacant heme is necessary to facilitate a direct heme-SSNO reaction to form substantial NO. These data also suggest that the ferric iron in methemoglobin potentiates SSNO reactivity. These results could potentially impact NO and sulfide bioavailability and reactivity.
Topics: Carboxyhemoglobin; Heme; Hemeproteins; Hemoglobins; Humans; Hydrogen Sulfide; Iron; Kinetics; Methemoglobin; Nitric Oxide; Nitrogen Oxides; Nitroso Compounds; Oxyhemoglobins; Solutions; Sulfides
PubMed: 27609224
DOI: 10.1016/j.freeradbiomed.2016.09.005 -
BMJ Case Reports Aug 2020Methaemoglobinaemia is a rare disease that is typically caused by a medication or other exogenous agent, with dapsone being the most common. It occurs when the...
Methaemoglobinaemia is a rare disease that is typically caused by a medication or other exogenous agent, with dapsone being the most common. It occurs when the concentration of methaemoglobin rises via ferrous haeme irons becoming oxidised to the ferric state, which shifts the oxygen dissociation curve to the left. The net result of an elevated methaemoglobin concentration is functional anaemia and impaired oxygen delivery to tissues. At lower blood levels, this can cause symptoms such as cyanosis, lethargy, headache and fatigue, whereas at higher levels it can be fatal. Here we discuss a subtle case of dapsone-induced methaemoglobinaemia presenting as subacute mental status changes and apparent hypoxia, thus highlighting the association between methaemoglobinaemia and dapsone. This case demonstrates the importance of thorough medication reconciliation and maintaining a broad differential diagnosis, while also recognising the significance of conflicting data and their implications for the workup.
Topics: Aged; Anti-Infective Agents; Confusion; Dapsone; Female; Humans; Memory Disorders; Methemoglobin; Methemoglobinemia; Oxygen
PubMed: 32843412
DOI: 10.1136/bcr-2020-235403 -
Biophysical Journal Sep 2021Hemoglobin-mediated transport of dioxygen (O) critically depends on the stability of the reduced (Fe) form of the heme cofactors. Some protein mutations stabilize the...
Hemoglobin-mediated transport of dioxygen (O) critically depends on the stability of the reduced (Fe) form of the heme cofactors. Some protein mutations stabilize the oxidized (Fe) state (methemoglobin, Hb M), causing methemoglobinemia, and can be lethal above 30%. The majority of the analyses of factors influencing Hb oxidation are retrospective and give insights only for inner-sphere mutations of heme (His58, His87). Herein, we report the first all-atom molecular dynamics simulations on both redox states and calculations of the Marcus electron transfer (ET) parameters for the α chain Hb oxidation and reduction rates for Hb M. The Hb wild-type (WT) and most of the studied α chain variants maintain globin structure except the Hb M Iwate (H87Y). The mutants forming Hb M tend to have lower redox potentials and thus stabilize the oxidized (Fe) state (in particular, the Hb Miyagi variant with K61E mutation). Solvent reorganization (λ 73-96%) makes major contributions to reorganization free energy, whereas protein reorganization (λ) accounts for 27-30% except for the Miyagi and J-Buda variants (λ ∼4%). Analysis of heme-solvent H-bonding interactions among variants provide insights into the role of Lys61 residue in stabilizing the Fe state. Semiclassical Marcus ET theory-based calculations predict experimental k for the Cyt b5-Hb complex and provide insights into relative reduction rates for Hb M in Hb variants. Thus, our methodology provides a rationale for the effect of mutations on the structure, stability, and Hb oxidation reduction rates and has potential for identification of mutations that result in methemoglobinemia.
Topics: Electrons; Heme; Hemoglobins; Methemoglobin; Oxidation-Reduction; Retrospective Studies
PubMed: 34265263
DOI: 10.1016/j.bpj.2021.07.007 -
International Journal of Molecular... Feb 2021Cyanosis is a pathological condition that is characterized by a bluish discoloration of the skin or mucous membranes. It may result from a number of medical conditions,...
Cyanosis is a pathological condition that is characterized by a bluish discoloration of the skin or mucous membranes. It may result from a number of medical conditions, including disorders of the respiratory system and central nervous system, cardiovascular diseases, peripheral vascular diseases, deep vein thrombosis, and regional ischemia. Cyanosis can also be elicited from methemoglobin. Therefore, a simple, rapid, and simultaneous monitoring of changes in oxygenated hemoglobin and deoxygenated hemoglobin is useful for protective strategies against organ ischemic injury. We previously developed a red-green-blue camera-based spectral imaging method for the measurements of melanin concentration, oxygenated hemoglobin concentration (), deoxygenated hemoglobin concentration (), total hemoglobin concentration () and tissue oxygen saturation () in skin tissues. We leveraged this approach in this study and extended it to the simultaneous quantifications of methemoglobin concentration (), , , and . The aim of the study was to confirm the feasibility of the method to monitor , , , , and . We performed in vivo experiments using rat dorsal skin during methemoglobinemia induced by the administration of sodium nitrite (NaNO) and changing the fraction of inspired oxygen (FiO), including normoxia, hypoxia, and anoxia. Spectral diffuse reflectance images were estimated from an RGB image by the Wiener estimation method. Multiple regression analysis based on Monte Carlo simulations of light transport was used to estimate , , , , and . rapidly increased with a half-maximum time of less than 30 min and reached maximal values nearly 60 min after the administration of NaNO, whereas dramatically dropped after the administration of NaNO, indicating the temporary production of methemoglobin and severe hypoxemia during methemoglobinemia. Time courses of and , while changing the FiO, coincided with well-known physiological responses to hyperoxia, normoxia, and hypoxia. The results indicated the potential of this method to evaluate changes in skin hemodynamics due to loss of tissue viability and vitality.
Topics: Algorithms; Animals; Cyanosis; Data Analysis; Diagnostic Imaging; Hemoglobins; Male; Methemoglobin; Monte Carlo Method; Oxygen; Oxyhemoglobins; Rats; Regression Analysis; Spectrum Analysis
PubMed: 33546389
DOI: 10.3390/ijms22041528 -
The American Journal of Clinical... Jul 2009
Topics: Animals; Diet; Food; Food Analysis; Fruit; Humans; Infant; Meat; Methemoglobin; Methemoglobinemia; Nitrates; Nitrites; Vegetables; World Health Organization
PubMed: 19458015
DOI: 10.3945/ajcn.2009.28014 -
Journal of Biomedical Optics Mar 2015Due to the various causes of methemoglobinemia and its potential to be confused with other diseases, in vivo measurements of methemoglobin have significant applications...
Due to the various causes of methemoglobinemia and its potential to be confused with other diseases, in vivo measurements of methemoglobin have significant applications in the clinic. Using photoacoustic microscopy (PAM), we quantified the average and the distributed percentage of methemoglobin both in vitro and in vivo. Based on the absorption spectra of methemoglobin, oxyhemoglobin, and deoxyhemoglobin, three wavelengths were chosen to differentiate methemoglobin from the others. The methemoglobin concentrations calculated from the photoacoustic signals agreed well with the preset concentrations. Then we imaged the methemoglobin percentage in microtubes that mimicked blood vessels. Average percentages calculated for five samples with different methemoglobin concentrations also agreed well with the preset values. Finally, we demonstrated the ability of PAM to detect methemoglobin in vivo in a mouse ear. Our results show that PAM can quantitatively image methemoglobin distribution in vivo.
Topics: Animals; Ear Auricle; Hemoglobins; Methemoglobin; Methemoglobinemia; Mice; Microscopy, Acoustic; Oxyhemoglobins; Phantoms, Imaging; Photoacoustic Techniques; Spectrum Analysis
PubMed: 25760655
DOI: 10.1117/1.JBO.20.3.036007 -
Medical Archives (Sarajevo, Bosnia and... Jun 2017Surgery is supposed to modulate the production of carbon monoxide by the reduction of heme oxygenase activity or transcriptional regulation of inducible heme oxygenase....
INTRODUCTION
Surgery is supposed to modulate the production of carbon monoxide by the reduction of heme oxygenase activity or transcriptional regulation of inducible heme oxygenase. On the other hand, the inhalation of tobacco smoke can substantially raise the level of carboxyhemoglobin in the blood. Furthermore, methemoglobin is maintained at a constant level. However, excessive production of methemoglobin relative to total methemoglobin reductase activity results in methemoglobin increase.
AIM
The aim of our study was to investigate the perioperative variations of carboxyhemoglobin and methemoglobin during urologic surgeries, and at the same time to evaluate the changes in methemoglobin as a possible indicator of nitric oxide generation. Our second aim was to evaluate the effect of preoxygenation on the level of carboxyhemoglobin and methemoglobin and the influence of blood transfusion on their changes.
MATERIAL AND METHODS
The study included 30 patients scheduled for urologic surgery under general endotracheal anesthesia, aged 18-60 years without any history of respiratory disease, divided into two groups. The study group comprised patients who were smoking cigarettes or tobacco pipe, while the control group included non-smokers. In both groups carboxyhemoglobin (COHb) and methemoglobin (MetHb) levels were determined preoperatively, after preoxygenation, and postoperatively.
RESULTS
COHb levels were decreased postoperatively in both groups. The average values of COHb between the two groups were statistically significantly different (p=0.00). MetHb levels increased postoperatively in the group of smokers and decreased in the group of non-smokers. There were no statistically significant differences in the average postoperative MetHb levels between the two groups.
CONCLUSION
Changes in carboxyhemoglobin and methemoglobin concentrations in arterial blood occur during urologic surgery, although these amplitudes are small when compared with carbon monoxide intoxication and methemoglobinemia. It is likely that organ perfusion and functions are affected by these monoxide gas mediators during urologic surgery.
Topics: Adolescent; Adult; Blood Transfusion; Carbon Dioxide; Carboxyhemoglobin; Cigarette Smoking; Humans; Intraoperative Care; Methemoglobin; Middle Aged; Oxygen; Partial Pressure; Pipe Smoking; Prospective Studies; Urologic Surgical Procedures; Young Adult
PubMed: 28974829
DOI: 10.5455/medarh.2017.71.178-182 -
Journal of Biomedical Optics Dec 2021For optical methods to accurately assess hemoglobin oxygen saturation in vivo, an independently verifiable tissue-like standard is required for validation. For this...
SIGNIFICANCE
For optical methods to accurately assess hemoglobin oxygen saturation in vivo, an independently verifiable tissue-like standard is required for validation. For this purpose, we propose three hemoglobin preparations and evaluate methods to characterize them.
AIM
To spectrally characterize three different hemoglobin preparations using multiple spectroscopic methods and to compare their absorption spectra to commonly used reference spectra.
APPROACH
Absorption spectra of three hemoglobin preparations in solution were characterized using spectroscopic collimated transmission: whole blood, lysed blood, and ferrous-stabilized hemoglobin. Tissue-mimicking phantoms composed of Intralipid, and the hemoglobin solutions were characterized using spatial frequency-domain spectroscopy (SFDS) and enhanced perfusion and oxygen saturation (EPOS) techniques while using yeast to deplete oxygen.
RESULTS
All hemoglobin preparations exhibited similar absorption spectra when accounting for methemoglobin and scattering in their oxyhemoglobin and deoxyhemoglobin forms, respectively. However, systematic differences were observed in the fitting depending on the reference spectra used. For the tissue-mimicking phantoms, SFDS measurements at the surface of the phantom were affected by oxygen diffusion at the interface with air, associated with higher values than for the EPOS system.
CONCLUSIONS
We show the validity of different blood phantoms and what considerations need to be addressed in each case to utilize them equivalently.
Topics: Hemoglobins; Methemoglobin; Oxygen; Oxygen Saturation; Oxyhemoglobins
PubMed: 34850613
DOI: 10.1117/1.JBO.27.7.074708 -
PloS One 2018Detecting life-threatening common dyshemoglobins such as carboxyhemoglobin (COHb, resulting from carbon monoxide poisoning) or methemoglobin (MetHb, caused by exposure...
Detecting life-threatening common dyshemoglobins such as carboxyhemoglobin (COHb, resulting from carbon monoxide poisoning) or methemoglobin (MetHb, caused by exposure to nitrates) typically requires a laboratory CO-oximeter. Because of cost, these spectrophotometer-based instrument are often inaccessible in resource-poor settings. The aim of this study was to determine if an inexpensive pocket infrared spectrometer and smartphone (SCiO®Pocket Molecular Sensor, Consumer Physics Ltd., Israel) accurately detects COHb and MetHb in single drops of blood. COHb was created by adding carbon monoxide gas to syringes of heparinized blood human or cow blood. In separate syringes, MetHb was produced by addition of sodium nitrite solution. After incubation and mixing, fractional concentrations of COHb or MetHb were measured using a Radiometer ABL-90 Flex® CO-oximeter. Fifty microliters of the sample were then placed on a microscope slide, a cover slip applied and scanned with the SCiO spectrometer. The spectrograms were used to create simple linear models predicting [COHb] or [MetHb] based on spectrogram maxima, minima and isobestic wavelengths. Our model predicted clinically significant carbon monoxide poisoning (COHb ≥15%) with a sensitivity of 93% and specificity of 88% (regression r2 = 0.63, slope P<0.0001), with a mean bias of 0.11% and an RMS error of 21%. Methemoglobinemia severe enough to cause symptoms (>20% MetHb) was detected with a sensitivity of 100% and specificity of 71% (regression r2 = 0.92, slope P<0.001) mean bias 2.7% and RMS error 21%. Although not as precise as a laboratory CO-oximeter, an inexpensive pocket-sized infrared scanner/smartphone detects >15% COHb or >20% MetHb on a single drop of blood with enough accuracy to be useful as an initial clinical screening. The SCiO and similar relatively low cost spectrometers could be developed as inexpensive diagnostic tools for developing countries.
Topics: Algorithms; Animals; Carbon Monoxide Poisoning; Carboxyhemoglobin; Cattle; Equipment Design; Hemoglobinometry; Humans; Internet; Methemoglobin; Methemoglobinemia; Mobile Applications; Oximetry; Sensitivity and Specificity; Smartphone; Spectrophotometry, Infrared
PubMed: 29513738
DOI: 10.1371/journal.pone.0193891 -
Anesthesiology Nov 2006A new eight-wavelength pulse oximeter is designed to measure methemoglobin and carboxyhemoglobin, in addition to the usual measurements of hemoglobin oxygen saturation... (Comparative Study)
Comparative Study
BACKGROUND
A new eight-wavelength pulse oximeter is designed to measure methemoglobin and carboxyhemoglobin, in addition to the usual measurements of hemoglobin oxygen saturation and pulse rate. This study examines this device's ability to measure dyshemoglobins in human volunteers in whom controlled levels of methemoglobin and carboxyhemoglobin are induced.
METHODS
Ten volunteers breathed 500 ppm carbon monoxide until their carboxyhemoglobin levels reached 15%, and 10 different volunteers received intravenous sodium nitrite, 300 mg, to induce methemoglobin. All were instrumented with arterial cannulas and six Masimo Rad-57 (Masimo Inc., Irvine, CA) pulse oximeter sensors. Arterial blood was analyzed by three laboratory CO-oximeters, and the resulting carboxyhemoglobin and methemoglobin measurements were compared with the corresponding pulse oximeter readings.
RESULTS
The Rad-57 measured carboxyhemoglobin with an uncertainty of +/-2% within the range of 0-15%, and it measured methemoglobin with an uncertainty of 0.5% within the range of 0-12%.
CONCLUSION
The Masimo Rad-57 is the first commercially available pulse oximeter that can measure methemoglobin and carboxyhemoglobin, and it therefore represents an expansion of our oxygenation monitoring capability.
Topics: Bias; Blood Chemical Analysis; Carboxyhemoglobin; Humans; Methemoglobin; Methemoglobinemia; Oximetry
PubMed: 17065881
DOI: 10.1097/00000542-200611000-00008