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AbstractIntroductionMethodsResultsDiscussionConclusionsSodium nitrite is a potent oxidizer, which may precipitate rapidly lethal methemoglobinemia. Prompt diagnosis and treatment may salvage otherwise fatal cases. It is unclear if emergency departments are prepared for increasing cases. We describe the availability and geographic distribution of real-time methemoglobin testing and methylthioninium chloride (methylene blue) availability in three contiguous United States.This is a cross-sectional survey of hospitals served by a regional poison center in the Upper Midwestern United States. Hospitals were identified by cross-referencing poison center, health department, and state trauma databases. We queried methemoglobin testing capabilities of each site as well as immediate methylthioninium chloride availability. Resulting data are described with descriptive statistics, and predictors of testing and treatment availability are evaluated in multivariable logistic regression.We identified 320 hospitals with emergency care, analyzing 228 (71.3%) after exclusions. Real-time methemoglobin testing was available at 56 sites (30.6% of 183 respondents). Of hospitals describing methylthioninium chloride availability, 59.4% (130/219) reported having it on-site. A significant difference in real-time methemoglobin testing existed across largest and smallest population strata in adjusted analysis (OR: 64.6: 95% CI: 4.1–1,037). Similarly disparate availability of methylthioninium chloride was observed. Spatial distribution of methemoglobin testing and methylthioninium chloride availability demonstrated notable urban-rural disparities.These data demonstrate a wide disparity in the availability of real-time methemoglobin testing and methylthioninium chloride availability, suggesting that the region is ill-prepared to care for severe methemoglobinemia. Our analysis points to a disconnect between our current poison center recommendations and the capacities of our consulting institutions.We demonstrate urban-rural disparities in diagnostic and therapeutic capacity for the management of acute methemoglobinemia in this region, as well as significant geographic variations in methylthioninium chloride stocking and poisoning preparedness. Poison centers must therefore maintain an awareness of antidote availability for this emerging toxicological emergency. [ABSTRACT FROM AUTHOR]

Superoxide dismutase (SOD) and Catalase (CAT) play a crucial role as the first line of defense antioxidant enzymes in a living cell. These enzymes neutralize the superoxide anion from the autooxidation of oxyhemoglobin (Oxy-Hb) and convert hydrogen peroxides into water and molecular oxygen. In this study, we fabricated hemoglobin submicron particles (HbMPs) using the Coprecipitation Crosslinking Dissolution (CCD) technique and incorporating first-line antioxidant enzymes (CAT, SOD) and second-line antioxidant (ascorbic acid, Vit. C) to investigate a protective effect of modified HbMPs via cyclically oxygenation and deoxygenation. Thereafter, the total hemoglobin (Hb) content and Oxy-Hb content to HbMPs were determined. The results revealed that the HbMPs have a protective effect against oxidation from hydrogen peroxide and potentially neutralizing hydrogen peroxide to water over 16 times exposure cycles. No significant differences in total Hb content were found between normal HbMPs and enzyme-modified HbMPs in the absence of Vit. C. The Oxy-Hb of CAT-HbMPs showed significantly higher values than normal HbMPs. The functional Hb of normal HbMPs and enzyme-modified HbMPs was increased by 60–77% after a short time Vit. C (1:25) exposure. The co-immobilization of CAT and SOD in hemoglobin particles (CAT-SOD-HbMPs) in the presence of Vit. C provides protective effects against oxidation in cyclic Oxygenation and Deoxygenation and shows the lowest reduction of functional Hb. Our studies show that the CCD technique-modified HbMPs containing antioxidant enzymes and a reducing agent (ascorbic acid) demonstrate enhanced Hb functionality, providing protective effects and stability under oxidative conditions. [ABSTRACT FROM AUTHOR]

Jiwoong Her,1,2 Justin Roh,1 Deborah A Keys3 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; 2Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; 3Kaleidoscope Statistics, LLC Athens, GA, USACorrespondence: Jiwoong Her, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA, Email Jiwoong.her@outlook.comPurpose: To assess the agreement between pulse co-oximeter and blood co-oximeter in measuring methemoglobin (MetHb) and carboxyhemoglobin (COHb) in healthy, awake dogs.Patients and Methods: Forty-five healthy dogs were enrolled in the study. Pulse co-oximetry was performed using the Masimo Radical 7 Pulse Co-Oximeter with a Rainbow® adhesive sensor. Simultaneously, venous blood samples were collected, and MetHb and COHb were immediately measured using a Stat Profile Prime Plus VET Critical Care Analyzer. Paired measurements of MetHb and COHb were evaluated via Spearman correlation, intra-class correlation (ICC), and Bland-Altman plots to evaluate the degree of agreement between the pulse co-oximeter and the blood co-oximeter.Results: A total of 45 paired MetHb and COHb measurements were collected. There was a weak correlation between the pulse co-oximeter and the blood co-oximeter readings. The correlation coefficients for MetHb and COHb were 0.0 (95% CI, − 0.3 to 0.3) and 0.03 (95% CI, − 0.27 to 0.32), respectively. The ICC indicated poor agreement between the pulse and blood co-oximeter for MetHb (ICC = 0.00, 95% CI: − 0.12 to 0.15) and COHb (ICC = 0.03, 95% CI: − 0.27 to 0.33). Bland-Altman plots revealed low mean bias but wide limits of agreement, indicating that the pulse co-oximeter overestimated MetHb by on average of 0.7% (P < 0.0001) (95% LoA: − 0.5 to 2.0) and COHb by on average 0.2% (P = 0.59) (95% LoA: − 4.6 to 5.0).Conclusion: Obtaining MetHb and COHb measurements with the Masimo Radical 7 Pulse Co-Oximeter is straightforward in healthy, awake dogs. However, the device does not provide accurate measurements compared to the blood co-oximeter, specifically in the range of MetHb and COHb in healthy dogs, based on the wide LoA.Keywords: co-oximetry, methemoglobin, carboxyhemoglobin, dog

Cyanide poisoning poses a significant threat to burn patients exposed to smoke in residential or workplace fires, leading to central nervous system dysfunction, hemodynamic instability, cardiovascular collapse, and death. Prompt administration of an effective antidote is critical. Hydroxocobalamin, a form of vitamin B12, is the gold standard treatment for cyanide toxicity, by binding to cyanide molecules and converting them into non-toxic cyanocobalamin that is eliminated by the kidneys. This mechanism is distinct from previous cyanide antidotes, which induce the formation of methemoglobin to bind to cyanide. Recent case studies have reported elevated methemoglobin levels after hydroxocobalamin administration, raising concerns regarding its safety. The current study investigates smoke inhalation patients treated with hydroxocobalamin at a single institution Burn Unit in hopes of enhancing our understanding of the complexities surrounding cyanide antidote therapy. After Institutional Board Approval, a retrospective cohort study was conducted. Our sample comprised burn patients with inhalation injury admitted to a single institution from 2013 to 2023 and treated with hydroxocobalamin for suspected cyanide toxicity. We also analyzed a matched control cohort of similar patients with inhalation injury not treated with hydroxocobalamin. We analyzed changes and peaks in methemoglobin levels, lactate levels, blood urea nitrogen (BUN) and creatinine, ventilator days, % total body surface area (TBSA), various types of medications and dressings, and mortality. Statistical analyses included t-tests, chi-square, linear and logistic regressions, and correlation analysis. In the study, 36 patients with suspected inhalation injury were treated with hydroxocobalamin at the Los Angeles General (LAG) Burn Unit from 2013 to 2023, who were matched to 32 control patients with inhalation injury who were not treated with hydroxocobalamin. Demographic and baseline characteristics showed no statistically significant differences between the groups, including age, gender, BMI, and %TBSA. No significant differences were found in initial, final, peak, or change in methemoglobin levels. The study also revealed no significant disparities in initial lactate levels, mortality, kidney function tests, ventilator days, surgeries, or use of medications/treatments (e.g., Silvadene dressings, Vitamin C) between the two groups. When controlling for covariates, multiple linear regression analysis (age, gender, and %TBSA) indicated that hydroxocobalamin administration was not significantly associated with changes in methemoglobin or mortality. Increased %TBSA, however, was linked to elevated lactate levels. Our investigation sought to assess the potential risks associated with hydroxocobalamin administration in burn patients with concomitant inhalation injury. Contrary to our initial hypothesis, we found no statistically significant differences in methemoglobinemia, lactate levels, mortality, or kidney function. The influence of other factors, such as methemoglobinemia-inducing drugs or hydroxocobalamin's interference with co-oximetry, adds complexity. Although elevated methemoglobin levels were observed in some cases, their clinical significance was limited. However, this study's limitations, particularly the rarity of inhalation injury cases with concern for cyanide toxicity, warrant consideration. Further research is required to comprehensively elucidate the impact of hydroxocobalamin administration on burn patients' outcomes. • Hydroxocobalamin is a common antidote for suspected inhalation injury in burn patients. • Hydroxocobalamin does not lead to methemoglobinemia or increased mortality. • Hydroxocobalamin does not lead to significant changes in outcomes for burn patients. [ABSTRACT FROM AUTHOR]

Nitrite/nitrate poisoning is an emerging problem, with an ongoing escalation of reported self-administration with suicidal intent in several countries. Nitrites toxicity mainly consists of their interaction with hemoglobin (Hb), causing its oxidization to methemoglobin (MetHb). In order to give support to the correct procedures for the analysis of these cases, this study aims to evaluate spontaneous sample degradation and consequent MetHb formation in the typical storage conditions of a forensic toxicology laboratory. Two different types of samples have been used in this study: the first stage of our study consisted of a retrospective analysis of blood samples obtained by judicial autopsies already stored in the toxicology laboratory, collected over four years (2018–2021), while the samples used for the second stage were appositely collected during judicial autopsies. The data obtained by the application of a derivative spectrophotometry method on these samples suggest that there seems not to be a maximum threshold for MetHb formation within which it is possible to state with a sufficient grade of certainty that the concentration of MetHb found is consistent with an ante-mortem formation and is not the result of an artifact due to sample degradation and storage conditions. On the other hand, the results suggest that MetHb formation depends on the time passed between sample collection and analysis, so that a tempestive sample processing, performed as soon as the samples are received in the laboratory, is crucial to obtain the maximum reliability and diagnostic values from the data when MetHb quantitation is necessary. [ABSTRACT FROM AUTHOR]

A knowledge of the complex phenomena that regulate T1 signal on Magnetic Resonance Imaging is essential in clinical practice for a more effective characterization of pathological processes. The authors review the physical basis of T1 Relaxation Time and the fundamental aspects of physics and chemistry that can influence this parameter. The main substances (water, fat, macromolecules, methemoglobin, melanin, Gadolinium, calcium) that influence T1 and the different MRI acquisition techniques that can be applied to enhance their presence in diagnostic images are then evaluated. An extensive case illustration of the different phenomena and techniques in the areas of CNS, abdomino-pelvic, and osteoarticular pathology is also proposed. Critical relevance statement: T1 relaxation time is strongly influenced by numerous factors related to tissue characteristics and the presence in the context of the lesions of some specific substances. An examination of these phenomena with extensive MRI exemplification is reported. Key Points: The purpose of the paper is to illustrate the chemical-physical basis of T1 Relaxation Time. MRI methods in accordance with the various clinical indications are listed. Several examples of clinical application in abdominopelvic and CNS pathology are reported. [ABSTRACT FROM AUTHOR]

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Abstract Methemoglobinemia secondary to administration of hydroxyurea is only reported in veterinary medicine as a result of accidental ingestion of high doses, and once at therapeutic dose in human medicine. A 2.5‐year‐old female spayed mixed breed dog was presented for acute signs of neurologic disease and diagnosed with severe erythrocytosis without an identified underlying cause, leading to suspicion of polycythemia vera. The dog was managed with phlebotomies, supportive care, and administration of hydroxyurea. Within 2 h of administration of hydroxyurea (37 mg/kg) administration, respiratory distress with cyanosis, and methemoglobinemia developed. Signs resolved within 24 h but recurred after a second administration of lower dosage of hydroxyurea (17 mg/kg) 20 days later. The dog remained asymptomatic except for mild cyanosis but was humanely euthanized for lack of relevant improvement of signs of neurologic disease. This case report documents the repeated occurrence of methemoglobinemia in a dog after administration of hydroxyurea at therapeutic doses.

Methemoglobinemia secondary to administration of hydroxyurea is only reported in veterinary medicine as a result of accidental ingestion of high doses, and once at therapeutic dose in human medicine. A 2.5‐year‐old female spayed mixed breed dog was presented for acute signs of neurologic disease and diagnosed with severe erythrocytosis without an identified underlying cause, leading to suspicion of polycythemia vera. The dog was managed with phlebotomies, supportive care, and administration of hydroxyurea. Within 2 h of administration of hydroxyurea (37 mg/kg) administration, respiratory distress with cyanosis, and methemoglobinemia developed. Signs resolved within 24 h but recurred after a second administration of lower dosage of hydroxyurea (17 mg/kg) 20 days later. The dog remained asymptomatic except for mild cyanosis but was humanely euthanized for lack of relevant improvement of signs of neurologic disease. This case report documents the repeated occurrence of methemoglobinemia in a dog after administration of hydroxyurea at therapeutic doses. [ABSTRACT FROM AUTHOR]

The content of membrane-bound methemoglobin (MtHb) in nucleated erythrocytes was studied in the black scorpionfish Scorpaena porcus (Linnaeus, 1758) in vitro. Spectral characteristics were determined for a whole hemolysate, a hemolysate obtained by stroma precipitation (a clarified hemolysate), and a resuspended stroma. The MtHb proportion in the erythrocyte stroma was found to exceed 80% (6.20 ± 0.59 µM). Clarified hemolysates were nearly free of MtHb (0.5 ± 0.2 µM). Membrane-bound ferric hemoglobin did not affect the erythrocyte resistance to osmotic shock. The osmotic fragility range was determined using a LaSca-TM laser microparticle analyzer (BioMedSystems, Russia) to be 102–136 mOsm/kg, much the same as in other bony fish species. A nitrite load (10 mg/L) significantly increased the MtHb content in the blood. However, the membrane-bound ferric hemoglobin content did not change significantly, amounting to 6.34 ± 1.09 µM (approximately 95%). The finding suggested a functional importance for MtHb present in the plasma membrane of nucleated erythrocytes. Membrane-bound MtHb was assumed to neutralize the external oxidative load and the toxic effect of hydrogen sulfide in bottom water layers, where the species lives. [ABSTRACT FROM AUTHOR]

In methemoglobinemia, ferrous iron in the hemoglobin is oxidized to a ferric state. Hemoglobin in this state cannot carry oxygen resulting in hypoxemia, which manifests as low peripheral oxygen saturation (SpO2). Bedside co-oximetry can identify this condition. We present here two cases of methemoglobinemia. Our experience with the first case enabled swift diagnosis of the second case. This also enabled us to prepare ourselves better in the second case if worsening of hypoxemia had occurred. Therefore, we learn here that whenever there is low SpO2 with a normal partial pressure of oxygen, methemoglobinemia should be suspected and diagnosis should be confirmed using co-oximetry.

In today’s world, where stress and busyness are an integral part of everyday life, energy drinks have become not only a means of satisfying the need for energy and maintenance of vitality, but also a symbol of lifestyle, an important element of the modern culture of consumption. The speed and efficiency they promise attract the attention of consumers, especially those who are constantly on the move. Such drinks have become popular not only among young people, but also among everyone who seek to maintain their activity and efficiency during the day. The purpose of the work was to investigate the dynamics of changes in the level of total hemoglobin and its forms, in particular oxy-, carboxy-, sulf-, met-, and dyshemoglobin under the conditions of energy drink consumption. The study was conducted using male Wistar rats weighing 150–220 g kept in the vivarium under appropriate lighting conditions, temperature, humidity and standard diet. All the animals had free access to feed (based on daily requirements) and water (based on 20 ml of water per rat per day). The experiment was carried out in compliance with the requirements of the European Convention for the Protection of Vertebrate Animals used for Experimental and Scientific Purposes (Strasbourg, 1986). The animals were divided into five groups: the 1st group received drinking water (intact control); the 2nd–5th groups received daily the non-alcoholic energy drink “Burn” per os for a month. The calculation of the required amount of drink for administration per one rat was based per 1 kg of body weight. To monitor the growth and development, we weighted the rats at the beginning and at each stage of the experiment. The material (blood) was taken on the 1st (2nd group), 10th (3rd group), 20th (4th group) and 30th day (5th group) after the completion of the experiment under anesthesia (intramuscularly sodium thiopental, 60 mg/kg). The total hemoglobin level was determined with the Mythic 18 hematological analyzer. Determination of the content of oxyhemoglobin, methemoglobin, sulfhemoglobin and carboxyhemoglobin was performed spectrophotometrically. The obtained data indicate significant changes in both the total level of hemoglobin and its ligand forms, in particular, a decrease in the level of oxyhemoglobin and the accumulation of dyshemoglobins, such as methemoglobin, sulfhemoglobin, and carboxyhemoglobin. As evidenced by the obtained results, the consumption of energy drinks leads to the oxygen homeostasis violation, the development of tissue hypoxia and can cause structural and functional disorders in the body under such conditions.

Abstract Reports indicate that Plasmodium infections influence methemoglobin levels. However, findings have been inconclusive or have varied across different geographic and demographic contexts. This systematic review and meta-analysis aimed to consolidate existing data regarding the association between Plasmodium infections and alterations in methemoglobin levels related to the severity of the infection. A comprehensive literature search of several databases, including Ovid, ProQuest, Embase, Scopus, MEDLINE, and PubMed, was conducted to identify relevant studies that examined methemoglobin levels in patients with malaria. Qualitative synthesis and meta-analysis of the pooled standardized mean difference were conducted to synthesize the differences in methemoglobin levels between: (1) patients with malaria and those without malaria and (2) patients with severe malaria and those with uncomplicated malaria based on various themes including publication year, study design, study area, Plasmodium species, age group, symptomatic status, severity status, and method of malaria detection. Of the 1846 studies that were initially identified from the main databases and additional searches on Google Scholar, 10 studies met the eligibility criteria and were selected for this review. The systematic review distinctly highlighted an association between malaria and elevated methemoglobin levels, an observation consistent across diverse geographical regions and various Plasmodium species. Furthermore, the meta-analysis confirmed this by demonstrating increased methemoglobin levels in patients with malaria compared to those without malaria (P

This letter discusses a case of methemoglobinemia caused by sodium nitrite poisoning. The patient exhibited symptoms such as coma, cyanosis, desaturation, and hypotension. The blood gas analyzer used in the emergency department was unable to accurately measure hemoglobin concentration and saturation, which hindered the diagnosis and treatment of the patient. The letter also describes in vitro experiments that were conducted to understand why the analyzer failed to measure methemoglobin levels. The results suggest that the analyzer had difficulty reporting methemoglobin levels accurately, and clinicians should be aware of this issue when treating patients with methemoglobinemia. [Extracted from the article]

Superoxide dismutase (SOD) and Catalase (CAT) play a crucial role as the first line of defense antioxidant enzymes in a living cell. These enzymes neutralize the superoxide anion from the autooxidation of oxyhemoglobin (Oxy-Hb) and convert hydrogen peroxides into water and molecular oxygen. In this study, we fabricated hemoglobin submicron particles (HbMPs) using the Coprecipitation Crosslinking Dissolution (CCD) technique and incorporating first-line antioxidant enzymes (CAT, SOD) and second-line antioxidant (ascorbic acid, Vit. C) to investigate a protective effect of modified HbMPs via cyclically oxygenation and deoxygenation. Thereafter, the total hemoglobin (Hb) content and Oxy-Hb content to HbMPs were determined. The results revealed that the HbMPs have a protective effect against oxidation from hydrogen peroxide and potentially neutralizing hydrogen peroxide to water over 16 times exposure cycles. No significant differences in total Hb content were found between normal HbMPs and enzyme-modified HbMPs in the absence of Vit. C. The Oxy-Hb of CAT-HbMPs showed significantly higher values than normal HbMPs. The functional Hb of normal HbMPs and enzyme-modified HbMPs was increased by 60–77% after a short time Vit. C (1:25) exposure. The co-immobilization of CAT and SOD in hemoglobin particles (CAT-SOD-HbMPs) in the presence of Vit. C provides protective effects against oxidation in cyclic Oxygenation and Deoxygenation and shows the lowest reduction of functional Hb. Our studies show that the CCD technique-modified HbMPs containing antioxidant enzymes and a reducing agent (ascorbic acid) demonstrate enhanced Hb functionality, providing protective effects and stability under oxidative conditions.

Key Clinical Message: Treatment of congenital chyloperitoneum is a challenge. Conservative methods may be ineffective. Preoperative visualization of the site of lymphatic leakage is crucial, but radiological imaging is technically complicated and may not provide sufficient information, especially in small patients. To ease the detection of lymphatic leakage during surgery, preoperative feeding with fat‐rich formula with Sudan Black has been recommended. However, administration of Sudan Black may result in life‐threatening methemoglobinemia and liver damage without any advantage of revealing leakage during surgery. We recommend preoperative feeding with pure fat‐rich formula. [ABSTRACT FROM AUTHOR]

Introduction: Systemic toxicity of eutectic mixture of local anesthetics (EMLA) cream is rare and is most commonly observed in children, for example, upon extensive application, and rarely occurs in adults with certain dispositions. Case Report: We report the case of a 71-year-old man who developed methemoglobinemia and systemic intoxication upon topical application of EMLA cream for leg ulcer and stasis dermatitis prior to surgical debridement. Approximately 45 min after application, the patient was found to be in a somnolent state, was unable to articulate, and showed peripheral cyanosis. The blood concentration of methemoglobin (MetHb) was 15.1%, and therefore, a diagnosis of systemic toxicity of EMLA due to methemoglobinemia was established. After removal of the cream, oxygen was applied, and further observation revealed that the patient's condition rapidly improved without any residue. In the following, we also discuss literature related to systemic EMLA intoxication. Conclusion: EMLA cream may cause severe systemic toxicity even in adults under certain conditions, for example, when applied on damaged skin or in extensive amounts. [ABSTRACT FROM AUTHOR]

Reports indicate that Plasmodium infections influence methemoglobin levels. However, findings have been inconclusive or have varied across different geographic and demographic contexts. This systematic review and meta-analysis aimed to consolidate existing data regarding the association between Plasmodium infections and alterations in methemoglobin levels related to the severity of the infection. A comprehensive literature search of several databases, including Ovid, ProQuest, Embase, Scopus, MEDLINE, and PubMed, was conducted to identify relevant studies that examined methemoglobin levels in patients with malaria. Qualitative synthesis and meta-analysis of the pooled standardized mean difference were conducted to synthesize the differences in methemoglobin levels between: (1) patients with malaria and those without malaria and (2) patients with severe malaria and those with uncomplicated malaria based on various themes including publication year, study design, study area, Plasmodium species, age group, symptomatic status, severity status, and method of malaria detection. Of the 1846 studies that were initially identified from the main databases and additional searches on Google Scholar, 10 studies met the eligibility criteria and were selected for this review. The systematic review distinctly highlighted an association between malaria and elevated methemoglobin levels, an observation consistent across diverse geographical regions and various Plasmodium species. Furthermore, the meta-analysis confirmed this by demonstrating increased methemoglobin levels in patients with malaria compared to those without malaria (P < 0.001, Hedges’ g 2.32, 95% CI 1.36–3.29, I2 97.27, 8 studies). Moreover, the meta-analysis found elevated methemoglobin levels in patients with severe malaria compared to those with uncomplicated malaria (P < 0.001, Hedges’ g 2.20, 95% CI 0.82–3.58, I2 96.20, 5 studies). This systematic review and meta-analysis revealed increased methemoglobin levels in patients with P. falciparum and P. vivax infections, with a notable association between elevated methemoglobin levels and severe malaria. Future research should focus on elucidating the specific mechanisms by which changes in methemoglobin levels are related to infections by P. falciparum and P. vivax, particularly in terms of severity, and how these alterations could potentially impact patient management and treatment outcomes. [ABSTRACT FROM AUTHOR]

To demonstrate the feasibility of our previously proposed Diffuse reflectance spectral imaging (DRSI) method for in vivo monitoring of oxygenated hemoglobin, deoxygenated hemoglobin, methemoglobin, tissue oxygen saturation, and methemoglobin saturation in a rat scald burn wound model and assess whether the method could be used for differentiating the burn depth groups in rats based on the hemoglobin parameters. Superficial dermal burns (SDBs), deep dermal burns (DDBs), and deep burns (DBs) were induced in rat dorsal skin using a Walker–Mason method. An approach based on multiple regression analysis for spectral diffuse reflectance images aided by Monte Carlo simulations for light transport was used to quantify the hemoglobin parameters. Canonical discriminant analysis (CDA) was performed to discriminate SDB, DDB, and DB. CDA using the total hemoglobin concentration, tissue oxygen saturation, and methemoglobin saturation as the independent variables showed good performance for discriminating the SDB, DDB, and DB groups immediately after burn injury and the SDB group from the DDB and DB groups 24–72 h after burn injury. The DRSI method with multiple regression analysis for quantification of oxygenated hemoglobin, deoxygenated hemoglobin, and methemoglobin proved to be reliable for monitoring these hemoglobin derivatives in the rat experimental burn injury model. The parameters of tissue oxygen saturation, methemoglobin saturation, and total hemoglobin concentration are promising for the differentiating the degree of burn injury using CDA. • A scald rat burn was employed to test diffuse reflectance spectral imaging (DRSI) system. • DRSI system estimates hemoglobin derivatives and their saturations. • Canonical discriminant analysis (CDA) with hemoglobin parameters identifies superficial, dermal, and deep burns. • DRSI with CDA has potential for burn wound staging. [ABSTRACT FROM AUTHOR]

Documented cases of sodium nitrite toxicity are almost exclusively caused by accidental ingestion; however, self-poisoning with sodium nitrite represents an increasing trend in nitrate-related deaths. This systematic review summarizes the most crucial evidence regarding the fatal toxicity of sodium nitrite. It identifies gaps and differences in the diagnostic forensic approaches and the detection methods of sodium nitrite intoxication. A total of eleven research articles were selected for qualitative and quantitative data. Most of the studies (6/11) were case reports. Fifty-three cases of fatal intoxication with sodium nitrite were chosen for the review. More research is required to develop cost-effective techniques and uniform cutoffs for blood nitrite and nitrate levels in the event of deadly sodium nitrite poisoning. There is still a lack of critical information on other matrices and the impact of time since death on toxicological results in such situations. The available evidence provides useful recommendations for forensic pathologists and health practitioners engaged in instances of sodium nitrite poisoning or death. The data should also set off alarm bells in the public health system, in prosecutor's offices, and for policymakers so that they may undertake preventative measures to stop and restrict the unregulated market for these substances. [ABSTRACT FROM AUTHOR]

In methemoglobinemia, ferrous iron in the hemoglobin is oxidized to a ferric state. Hemoglobin in this state cannot carry oxygen resulting in hypoxemia, which manifests as low peripheral oxygen saturation (SpO 2). Bedside co-oximetry can identify this condition. We present here two cases of methemoglobinemia. Our experience with the first case enabled swift diagnosis of the second case. This also enabled us to prepare ourselves better in the second case if worsening of hypoxemia had occurred. Therefore, we learn here that whenever there is low SpO 2 with a normal partial pressure of oxygen, methemoglobinemia should be suspected and diagnosis should be confirmed using co-oximetry. [ABSTRACT FROM AUTHOR]

Nitrite/nitrate poisoning is an emerging problem, with an ongoing escalation of reported self-administration with suicidal intent in several countries. Nitrites toxicity mainly consists of their interaction with hemoglobin (Hb), causing its oxidization to methemoglobin (MetHb). In order to give support to the correct procedures for the analysis of these cases, this study aims to evaluate spontaneous sample degradation and consequent MetHb formation in the typical storage conditions of a forensic toxicology laboratory. Two different types of samples have been used in this study: the first stage of our study consisted of a retrospective analysis of blood samples obtained by judicial autopsies already stored in the toxicology laboratory, collected over four years (2018–2021), while the samples used for the second stage were appositely collected during judicial autopsies. The data obtained by the application of a derivative spectrophotometry method on these samples suggest that there seems not to be a maximum threshold for MetHb formation within which it is possible to state with a sufficient grade of certainty that the concentration of MetHb found is consistent with an ante-mortem formation and is not the result of an artifact due to sample degradation and storage conditions. On the other hand, the results suggest that MetHb formation depends on the time passed between sample collection and analysis, so that a tempestive sample processing, performed as soon as the samples are received in the laboratory, is crucial to obtain the maximum reliability and diagnostic values from the data when MetHb quantitation is necessary.

IntroductionThough acetaminophen overdoses are common, acetaminophen induced methemoglobinemia is rare and it is thought to be due to oxidative stress from reactive metabolites. However, few prior cases of sulfhemoglobinemia in the setting of acetaminophen overdose have been reported. We report a case of mixed methemoglobinemia and sulfhemoglobinemia in the setting of a large, isolated acetaminophen ingestion.Case reportA 30-year-old African American male presented after intentionally ingesting 50 tablets of 500 mg acetaminophen two days prior. He was cyanotic and tachypneic. Peripheral oxygen saturation was 78 % on room air and minimally improved with high-flow oxygen. He was noted to have leukocytosis, thrombocytopenia, anion gap metabolic acidosis with lactic acidemia, acute kidney injury, transaminitis, hyperbilirubinemia, and coagulopathy. Arterial partial pressure of oxygen was normal. Methemoglobin and sulfhemoglobin concentrations were 8.5 % and 5.2 %, respectively. Along with intravenous N-acetylcysteine, methylene blue was administered without clinical improvement. Hemolytic anemia was subsequently noted. Glucose-6- phosphate dehydrogenase (G6PD) deficiency was then confirmed with a quantitative assay and genetic testing. He also received one dose of intravenous metoclopramide. The patient ultimately required eight units of packed red blood cells and several weeks of hemodialysis before discharge on hospital day 43.DiscussionAcetaminophen is structurally related to compounds known to cause methemoglobinemia and sulfhemoglobinemia. We hypothesize that these dyshemoglobinemias were triggered by acetaminophen-induced oxidative stress. The role of G6PD deficiency in the formation of sulfhemoglobinemia is unclear. Acetaminophen overdoses presenting with methemoglobinemia should prompt concern for underlying G6PD deficiency. Coincidental sulfhemoglobinemia should be considered if the clinical presentation is more severe than the methemoglobin concentration alone would suggest. Use of methylene blue in this case, despite the low measured methemoglobin percentage, which likely triggered hemolytic anemia; methylene blue use in a similar circumstance should be weighed carefully against the risk of harm.

In the present work the influence of hypoxia on black scorpionfish (Scorpaena porcus) nucleated red blood cells has been studied at in vivo (whole blood) and in vitro (cell suspension) experiments. Experiments were conducted in the range of oxygen concentration 0,3-8,5 mg О2 l-1, water temperature 14-16 оС, and the duration of exposure period was 4 h. Deep hypoxia (less than 2 mgО2 l-1) caused hemoglobin transition to a ferry-form (MtHb), and the most substantial increase of MtHb concentration was observed at severe hypoxic conditions (less than 1 mg О2 l-1). The highest MtHb level observed was 19-32 %. The results of in vivo and in vitro experimental series were similar, indicating that mechanisms involved in MtHb formation occur within cells and are not associated with organismic responses to oxygen deficiency. Moderate hypoxia (oxygen concentration more than 2 mg О2 l-1) did not cause hemoglobin transformation. MtHb formation did not influence the level of reactive oxygen species (DCF-DA fluorescence) and the integrity of cellular membrane (double staining with SYBR Green I and Propidium iodide) in red blood cells. The level of dead cells in control and experimental groups did not differ, indicating that responses observed were in the range of physiological norm.

Background: Decreased systemic oxygen delivery derived from gas exchange abnormalities in severe hemolysis complicates patients requiring mechanical circulatory support devices. Severe hemolysis releases free hemoglobin in plasma causing elevation of carboxyhemoglobin and methemoglobin levels. Hemolysis-induced decline in hemoglobin and oxyhemoglobin saturation significantly reduces the arterial oxygen content in blood, reducing systemic oxygen delivery. These patients develop hypoxemia with misleadingly normal oxygen saturation measured by standard pulse oximetry. Methods: Retrospective review of 2 clinical cases reaching carboxyhemoglobin and methemoglobin levels > 2% while supported with an Impella device. Results: Case 1. Patient with cardiogenic shock refractory to maximal medical therapy required insertion of Impella device achieving improvement in cardiac output, pulse oximetry, arterial oxygen saturation and systemic oxygen delivery. The device caused significant hemolytic anemia with severe decline in hemoglobin and arterial oxygen saturation with elevation of carboxyhemoglobin and methemoglobin levels, causing drastic reduction in systemic oxygen delivery despite adequate cardiac output. Device removal reversed severe hemolytic anemia, causing increased arterial oxygen saturation and systemic oxygen delivery despite borderline cardiac output.Case 2. Patient with refractory cardiogenic shock improved after insertion of Impella device. Initial improvement cardiac output and systemic oxygen delivery was negated by hemolytic anemia associated with elevation of carboxyhemoglobin and methemoglobin levels. Hemolysis decreased by reducing the Impella power output. Carboxyhemoglobin and methemoglobin levels correlated precisely with degree of hemolysis allowing to titrate therapy to best systemic oxygen delivery. Conclusions: Monitoring carboxyhemoglobin and methemoglobin levels readily identifies patients with ongoing hemolysis secondary to invasive supportive devices.

Methemoglobinemia (MET) is a life-threatening condition resulting from the development of methemoglobin (MetHb), which binds oxygen irreversibly, causing refractory hypoxia and so-called "functional anemia". MET can be caused by hereditary or acquired processes. Acquired forms are the most common. Symptoms correlate with the MetHb level and range from cyanosis and dyspnea to dysrhythmias, metabolic acidosis, coma, and cardiac arrest. MetHb levels above 70% are fatal. Methylene blue (MB) is the specific antidote. In all cases, supportive treatment, including intravenous hydration, glucose correction, and oxygen supplementation, must be started immediately. Exchange transfusion has been used successfully to treat MET and may be appropriate in patients for whom MB is ineffective. We report the case of a 54-year-old woman who presented to our emergency department for the acute and sudden development of chest pain, shortness of breath, and severe cyanosis after drinking a significant amount of boiled courgette water. Arterial blood gas analysis revealed a MetHb level of 26%. She was treated immediately with MB, oxygen supplementation, and hydration with normalization of her MetHb in 12 hours. Our recommendation is to always investigate MET in patients with unexplained cyanosis and refractory hypoxia. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to assess the impact of hydroxocobalamin (OHCbl) infusion on arterial blood gas and oximetry values in patients with vasoplegic syndrome. Methods Blood samples collected from 95 patients receiving OHCbl infusion were assayed using the ABL90 FLEX Plus blood gas analyzer for the concentration of methemoglobin (MetHb), total hemoglobin (tHb), carboxyhemoglobin (COHb), arterial oxygen saturation (SaO2), arterial oxygen partial pressure (PaO2), and arterial carbon dioxide partial pressure (PaCO2). Interference of OHCbl on these variables was evaluated using the measured difference between the preinfusion and postinfusion samples. Results Blood MetHb (%) measured after the infusion of OHCbl (5g) were significantly higher than the baseline levels, with a median of 4.8 (IQR, 3.0−6.5) versus 1.0 (IQR, 1.0−1.2) (P <.001). Blood COHb (%) increased from a median of 1.3 (IQR, 1.0−1.8) to 1.7 (IQR, 1.3−2.2) (P <.001) following the OHCbl infusion. No differences were seen in median levels of tHb, PaO2, PaCO2, and SaO2 between pre- and post-OHCbl treatment. Conclusion The presence of OHCbl in blood clearly interfered with the oximetry measurements of the hemoglobin component fractions by falsely increasing the levels of MetHb and COHb. Blood levels of MetHb and COHb cannot be reliably determined by the co-oximetry when OHCbl is known or suspected. [ABSTRACT FROM AUTHOR]

Introduction: During their lifespan in the bloodstream, red blood cells (RBCs) are exposed to multiple stressors, including increased oxidative stress, which can affect their morphology and function, thereby contributing to disease. Aim: This investigation aimed to explore the cellular and molecular mechanisms related to oxidative stress underlying anion exchanger 1 activity (band 3, SLC4A1/AE1) in human RBCs. To achieve this aim, the relationship between RBC morphology and functional and metabolic activity has been explored. Moreover, the potential protective effect of an anthocyanin-enriched fraction extracted from Callistemon citrinus flowers was studied. Methods: Cellular morphology, parameters of oxidative stress, as well as the anion exchange capability of band 3 have been analyzed in RBCs treated for 1 h with 50 mM of the pro-oxidant 2,2'-azobis (2-methylpropionamide)-dihydrochloride (AAPH). Before or after the oxidative insult, subsets of cells were exposed to 0.01 µg/mL of an anthocyanin-enriched fraction for 1 h. Results: Exposure to AAPH caused oxidative stress, exhaustion of reduced glutathione, and over-activation of the endogenous antioxidant machinery, resulting in morphological alterations of RBCs, specifically the formation of acanthocytes, increased lipid peroxidation and oxidation of proteins, as well as abnormal distribution and hyper-phosphorylation of band 3. Expected, oxidative stress was also associated with a decreased band 3 ion transport activity and an increase of oxidized haemoglobin, which led to abnormal clustering of band 3. Exposure of cells to the anthocyanin-enriched fraction prior to, but not after, oxidative stress efficiently counteracted oxidative stress-related alterations. Importantly, protection of band3 function from oxidative stress could only be achieved in intact cells and not in RBC ghosts. Conclusion: These findings contribute a) to clarify oxidative stress-related physiological and biochemical alterations in human RBCs, b) propose anthocyanins as natural antioxidants to neutralize oxidative stress-related modifications, and 3) suggest that cell integrity, and therefore a cytosolic component, is required to reverse oxidative stress-related pathophysiological derangements in human mature RBCs. [ABSTRACT FROM AUTHOR]

This manuscript describes a novel approach for treating patients with long‐term sequelae from hemoglobin Evans (Hb Evans). After instituting conservative therapies for approximately 2 years, our patient's symptoms continually worsened. Therefore, we performed red blood cell exchange (RBCx) to reduce his Hb Evans percentage and his co‐existing elevation of methemoglobin. Our assumptions of clinical benefit were based on our collective experience performing RBCx for patients with sickle cell disease. After the first exchange, pre‐ and post‐laboratory results supported our approach and the patient experienced marked improvement in his clinical signs and symptoms. This report provides preliminary proof of principle for the use of RBCx to treat Hb Evans and other non‐Hb S hemoglobinopathies. [ABSTRACT FROM AUTHOR]

The acute toxicity and sublethal effects of ammonia and nitrite on the air-beathing Siamese fighting fish, betta (Betta splendens) was studied for 96 h. The LC50 (50% Lethal Concentration) for 96 h for adult bettas to ammonia-N and nitrite-N was 123.4 mM (1.7 g/L, 95% confidence limits: 114.7–130.0 mM) and 24.6 mM (343.6 mg/L, 95% confidence limits: 22.7–26.4 mM) respectively. Exposure to 90 mM ammonia did not affect ammonia and urea excretion rates in bettas. There was no significant difference in values between control and ammonia-loaded (90 mM ammonia) individuals in either brain or liver activities of glutamine synthase, while plasma ammonia levels slightly increased. It appears unlikely that ammonia was converted to urea or amino acids for detoxification. Sublethal nitrite (24.6 mM nitrite) affected plasma nitrite, methemoglobin and hemoglobin. Plasma nitrite values remained much lower than ambient concentrations. Betta has a labyrinth organ and can breathe air. Bettas may temporarily reduce the entry of ammonia and nitrite into the body by increasing the rate of air respiration and reducing the contribution of the gill epithelium, which is highly permeable to these nitrogenous pollutants. [ABSTRACT FROM AUTHOR]

Alternative contrast agents for MRI are needed for individuals who may respond adversely to gadolinium, and need an intravascular agent for specific indications. One potential contrast agent is intracellular methemoglobin, a paramagnetic molecule that is normally present in small amounts in red blood cells. An animal model was used to determine whether methemoglobin modulation with intravenous sodium nitrite transiently changes the T1 relaxation of blood. Four adult New Zealand white rabbits were treated with 30 mg intravenous sodium nitrite. 3D TOF and 3D MPRAGE images were acquired before (baseline) and after methemoglobin modulation. T1 of blood was measured with 2D ss EPl acquisitions with inversion recovery preparation performed at two-minute intervals up to 30 min. T1 maps were calculated by fitting the signal recovery curve within major blood vessels. Baseline T1 was 1758 ± 53 ms in carotid arteries and 1716 ± 41 ms in jugular veins. Sodium nitrite significantly changed intravascular T1 relaxation. The mean minimum value of T1 was 1126 ± 28 ms in carotid arteries 8 to 10 min after the injection of sodium nitrite. The mean minimum value of T1 was 1171 ± 52 ms in jugular veins 10 to 14 min after the injection of sodium nitrite. Arterial and venous T1 recovered to baseline after a period of 30 min. Methemoglobin modulation produces intravascular contrast on T1-weighted MRI in vivo. Additional studies are needed to safely optimize methemoglobin modulation and sequence parameters for maximal tissue contrast. [ABSTRACT FROM AUTHOR]

The hemoglobin concentration of 35 g/dl of human red blood cells is close to the solubility threshold. Using microwave dielectric spectroscopy, we have assessed the amount of water associated with hydration shells of methemoglobin as a function of its concentration in the presence or absence of ions. We estimated water–hemoglobin interactions to interpret the obtained data. Within the concentration range of 5–10 g/dl of methemoglobin, ions play an important role in defining the free-to-bound water ratio competing with hemoglobin to recruit water molecules for the hydration shell. At higher concentrations, hemoglobin is a major contributor to the recruitment of water to its hydration shell. Furthermore, the amount of bound water does not change as the hemoglobin concentration is increased from 15 to 30 g/dl, remaining at the level of ∼20% of the total intracellular water pool. The theoretical evaluation of the ratio of free and bound water for the hemoglobin concentration in the absence of ions corresponds with the experimental results and shows that the methemoglobin molecule binds about 1400 water molecules. These observations suggest that within the concentration range close to the physiological one, hemoglobin molecules are so close to each other that their hydration shells interact. In this case, the orientation of the hemoglobin molecules is most likely not stochastic, but rather supports partial neutralization of positive and negative charges at the protein surface. Furthermore, deformation of the red blood cell shape results in the rearrangement of these structures. [ABSTRACT FROM AUTHOR]

SIGNIFICANCE: Noninvasive diffuse optical spectroscopy (DOS) is a promising adjunct diagnostic imaging technique for distinguishing benign and malignant breast lesions. Most DOS approaches require normalizing lesion biomarkers to healthy tissue since major tissue constituents exhibit large interpatient variations. However, absolute optical biomarkers are desirable as it avoids reference measurements which may be difficult or impractical to acquire. AIM: Our goal is to determine whether absolute measurements of minor absorbers such as collagen and methemoglobin (metHb) can successfully distinguish lesions. We hypothesize that metHb would exhibit less interpatient variability and be more suitable as an absolute metric for malignancy. However, we would expect collagen to exhibit more variability, because unlike metHb, collagen is also present in the healthy tissue. APPROACH: In this retrospective clinical study, 30 lesions with breast imaging reporting and database system score   (  BIRADS  )    >    =  3 (12 benign and 18 malignant) measured with broadband quantitative DOS were analyzed for their oxyhemoglobin (HbO), deoxyhemoglobin (HHb), water, lipids, collagen, metHb concentrations, and optical scattering characteristics. Wilcoxon rank sum test was used to compare benign and malignant lesions for all variables in both normalized and absolute forms. RESULTS: Among all absolute DOS parameters considered, only absolute metHb was observed to be significant for lesion discrimination (0.43  ±  0.18  μM for benign versus 0.87  ±  0.32  μM for malignant, p  =  0.0002). Absolute metHb concentration was also determined to be the best predictor of malignancy with an area under the curve of 0.89. CONCLUSIONS: Our findings demonstrate that lesion metHb concentration measured by DOS can improve noninvasive optical diagnosis of breast malignancies. Since metHb concentration found in normal breast tissue is extremely low, metHb may be a more direct indicator of malignancy that does not depend on other biomarkers found in healthy tissue with significant variability. Furthermore, absolute parameters require reduced measurement time and can be utilized in cases where healthy reference tissue is not available.

Abstract Introduction Methemoglobinemia is a condition in which methemoglobin is increased and the oxygen carrying capacity of tissues is decreased, causing a lack of oxygen to the whole body. RNA (ribonucleic acid) sequencing technologies have made it possible to systematically examine how the human transcriptome responds to invasive pathologies. To our knowledge, no previous studies have reported the results of RNA sequencing in a patient with methemoglobinemia. We describe the analysis of RNAs from the whole blood of a patient with methemoglobinemia. Case presentation A 31-year-old Japanese man was brought to our hospital with symptoms of dyspnea due to inhalation of gas from an acetic acid phosphonitrate storage tank at a factory. The nitrogen oxide concentration measured around the storage tank was over 2500 ppm, and he witnessed orange–brown smoke at that time. After entering the area and taking a few breaths, he suddenly became unwell, with dyspnea and numbness in his extremities. He was evacuated from the area within a few minutes, at which time he was suffering from whole-body cyanosis and was still aware of the above symptoms. On arrival at the hospital, his respiration rate was 18 breaths/minute, and his SpO2 ranged from 80% to 85% on 15 L/minute of oxygen by mask (2.5 hours postexposure). Arterial blood gas testing revealed a methemoglobin level of 23.1%. After the administration of methylene blue, the patient’s methemoglobin level normalized and his symptoms improved. Chest X-ray and chest computed tomography showed no evidence of pulmonary edema or interstitial pneumonia, and no other abnormal findings were observed. RNA sequencing was performed on the blood samples obtained at the time of the visit, with the blood sample collected on day 5 used as a control. To our knowledge, the present study is the first to describe the analysis of RNAs from the whole blood of a patient with methemoglobinemia. The RNA sequencing analysis showed that an activated “hydrogen peroxide catabolic process” may be associated with the pathogenesis of methemoglobinemia. Conclusion The results reported in the present study may explain the pathogenesis of methemoglobinemia.

Introduction: During their lifespan in the bloodstream, red blood cells (RBCs) are exposed to multiple stressors, including increased oxidative stress, which can affect their morphology and function, thereby contributing to disease.Aim: This investigation aimed to explore the cellular and molecular mechanisms related to oxidative stress underlying anion exchanger 1 activity (band 3, SLC4A1/AE1) in human RBCs. To achieve this aim, the relationship between RBC morphology and functional and metabolic activity has been explored. Moreover, the potential protective effect of an anthocyanin-enriched fraction extracted from Callistemon citrinus flowers was studied.Methods: Cellular morphology, parameters of oxidative stress, as well as the anion exchange capability of band 3 have been analyzed in RBCs treated for 1 h with 50 mM of the pro-oxidant 2,2′-azobis (2-methylpropionamide)-dihydrochloride (AAPH). Before or after the oxidative insult, subsets of cells were exposed to 0.01 μg/mL of an anthocyanin-enriched fraction for 1 h.Results: Exposure to AAPH caused oxidative stress, exhaustion of reduced glutathione, and over-activation of the endogenous antioxidant machinery, resulting in morphological alterations of RBCs, specifically the formation of acanthocytes, increased lipid peroxidation and oxidation of proteins, as well as abnormal distribution and hyper-phosphorylation of band 3. Expected, oxidative stress was also associated with a decreased band 3 ion transport activity and an increase of oxidized haemoglobin, which led to abnormal clustering of band 3. Exposure of cells to the anthocyanin-enriched fraction prior to, but not after, oxidative stress efficiently counteracted oxidative stress-related alterations. Importantly, protection of band3 function from oxidative stress could only be achieved in intact cells and not in RBC ghosts.Conclusion: These findings contribute a) to clarify oxidative stress-related physiological and biochemical alterations in human RBCs, b) propose anthocyanins as natural antioxidants to neutralize oxidative stress-related modifications, and 3) suggest that cell integrity, and therefore a cytosolic component, is required to reverse oxidative stress-related pathophysiological derangements in human mature RBCs.

Objective: To assess serial methemoglobin (MetHb) levels in preterm infants as a possible diagnostic method for late-onset sepsis (LOS). Methods: Preterm infants were assigned into two groups: those with culture-proven LOS and controls. Serial MetHb levels were measured. Results: The MetHb values of the LOS group were found to be significantly increased (p < 0.001). The cutoff value for the detection of LOS was calculated as MetHb > 1.75%, optimized for a sensitivity of 81.9% and specificity of 90%. After antimicrobial therapy, MetHb values were found to decrease significantly (p < 0.001). MetHb had an AUC of 0.810 for mortality using the calculated cutoff of >2% (p < 0.005). Conclusions: MetHb levels increase at the onset of LOS and decrease following treatment. MetHb can be added to other sepsis biomarkers as a rapid infectious process indicator for preterm neonates. MetHb > 2% is associated with LOS mortality. [ABSTRACT FROM AUTHOR]

Amide proton transfer (APT) and semi-solid magnetization transfer (ssMT) imaging can predict clinical outcomes in patients with glioma. However, the treatment of brain tumors is accompanied by the deposition of blood products within the tumor area in most cases. For this reason, the objective was to assess whether the diagnostic interpretation of the APT and ssMT is affected by methemoglobin (mHb) and hemosiderin (Hs) depositions at the first follow-up MRI 4 to 6 weeks after the completion of radiotherapy. A total of 34 participants underwent APT and ssMT imaging by applying reconstruction methods described by Zhou et al. (APTwasym), Goerke et al. (MTRRexAPT and MTRRexMT) and Mehrabian et al. (MTconst). Contrast-enhancing tumor (CE), whole tumor (WT), mHb and Hs were segmented on contrast-enhanced T1wCE, T2w-FLAIR, T1w and T2*w images. ROC-analysis, Kaplan–Meier analysis and the log rank test were used to test for the association of mean contrast values with therapy response and overall survival (OS) before (WT and CE) and after correcting tumor volumes for mHb and Hs (CEC and WTC). CEC showed higher associations of the MTRRexMT with therapy response (CE: AUC = 0.677, p = 0.081; CEC: AUC = 0.705, p = 0.044) and of the APTwasym with OS (CE: HR = 2.634, p = 0.040; CEC: HR = 2.240, p = 0.095). In contrast, WTC showed a lower association of the APTwasym with survival (WT: HR = 2.304, p = 0.0849; WTC: HR = 2.990, p = 0.020). Overall, a sophisticated correction for blood products did not substantially influence the clinical performance of APT and ssMT imaging in patients with glioma early after radiotherapy. [ABSTRACT FROM AUTHOR]

Nitroxides are stable, low molecular-weight radicals containing a nitroxide group that has an unpaired electron. The presence of a nitroxide group determines their redox properties. The effect of the piperidine nitroxides, Tempo, Tempol, and Tempamine, on metalloproteins (hemoglobin, superoxide dismutase, catalase) and lactate dehydrogenase in red blood cells was investigated in this research. In addition, the level of lipid peroxidation and the level of protein carbonyl groups were examined as indicators of the effect of oxidative stress. Nitroxides increased superoxide dismutase activity and oxidized hemoglobin to methemoglobin, and also slightly decreased the catalase activity of red blood cells treated with nitroxides. Tempol significantly decreased lactate dehydrogenase activity. All three nitroxides had no effect on membrane lipid peroxidation and protein oxidation. Our results confirm that nitroxides have both antioxidant and prooxidative effects in human red blood cells. The piperidine nitroxides do not initiate the oxidation of proteins and lipids in the membranes of human red blood cells. [ABSTRACT FROM AUTHOR]

The efficiency of food irradiation depends on the accuracy of the irradiation dose range that is sufficient for inhibiting microbiological growth without causing an irreversible change to the physical and chemical properties of foods. This study suggests that the concentration of hemoglobin derivatives can be used as a criterion for establishing the limit for chilled beef irradiation at which irradiation-induced oxidation becomes irreversible. The express spectrophotometry method for estimating the hemoglobin derivative concentration shows a nonlinear increase in methemoglobin concentration from 15% to 50% in beef irradiated by accelerated electrons with the doses ranging from 250 Gy to 10,000 Gy. The monitoring of the hemoglobin derivative concentration for three days after irradiation shows nonmonotonous dependencies of methemoglobin concentration in beef in the storage time since the oxidation of hemoglobin occur as a result of irradiation and biochemical processes in beef during storage. The proposed method based on the quantitative analysis of the hemoglobin derivative concentration can be used to estimate the oxidation level for irradiation of foods containing red blood cells. The study proposes a model that describes the change in hemoglobin derivative concentration in beef after irradiation considering that oxidation of hemoglobin can be triggered by the direct ionization caused by accelerated electrons, biochemical processes as a result of bacterial activity, and reactive oxygen species appearing during irradiation and storage. This research throws light on the mechanisms behind food irradiation during storage that should be taken into account for selecting the optimal parameters of irradiation. [ABSTRACT FROM AUTHOR]

The dynamics of the content of erythrocyte number and concentration of methemoglobin in the blood of the thermophilic mullet (Chelon auratus Risso, 1810) and the cold-loving flounder (Platichthys flesus L., 1758) during the annual cycle has been studied. The degree of maturity of the circulating erythrocyte mass is judged on the basis of construction of acid erythrograms. A pronounced negative relationship is found between the number of red blood cells and the concentration of methemoglobin in the blood of both types (r = –0.681; –0.778). It has been shown that the youngest generation of red blood cells appears in the peripheral bed of both species in the postspawning period (1.5–2.0 months), which reflects the active production of erythrocytes by hematopoietic tissue. The rest of the time, there is a gradual aging of the circulating erythrocyte mass. This leads to a decrease in the number of red blood cells in the blood and is accompanied by an increase in the concentration of methemoglobin. The latter, apparently, determines the production of erythropoietins in the kidneys and activates the processes of erythropoiesis in hematopoietic tissue (prespawning period). [ABSTRACT FROM AUTHOR]

Abstract Background Topical anesthetics are commonly used over the counter, and one of the adverse effects of these medications is methemoglobinemia, which is a serious and life-threatening condition. Case presentation We describe a 25-year-old Persian male presenting with generalized weakness, dizziness, headache, and cyanosis. In addition, he had genital warts starting 3 weeks ago, which were self-treated with podophyllin, resulting in itching and pain. He used over-the-counter topical anesthetics, including benzocaine and lidocaine, to reduce the symptoms. According to the lab data, signs and symptoms of methemoglobinemia and hemolysis were diagnosed. Considering the hemolysis, ascorbic acid was used for treatment. The patient was discharged after 5 days with normal arterial blood gas and pulse oximetry and no signs and symptoms. Conclusion This case highlights that self-administration of some topical anesthetics may lead to potentially fatal conditions.

Methemoglobinemia is a dyshemoglobinemia characterized by cyanosis and reduced oxygen saturation with increased methemoglobin values. The etiology may be congenital or acquired, with the latter being more common. We report a case of a full-term neonate who presented with transient cyanosis and methemoglobinemia caused by a mutation in the gamma chain of fetal hemoglobin.

Methemoglobinemia is a potentially life-threatening disease resulting from high blood levels of methemoglobin resulting in failure of binding and delivery of oxygen to tissues. The most common causes of methemoglobinemia are oxidizing toxins, such as butamirate citrate, which is a commonly used liquid antitussive, especially in pediatric patients. Herein, we present the case of a 3-year-old girl who accidentally ingested excessive amounts of butamirate citrate. She presented with mild lip cyanosis with high methemoglobin levels (6.5%) and normal oxygen saturation (98%), and was managed by prompt gut decontamination with activated charcoal, followed by monitoring and intravenous glucose administration. Therefore, methemoglobinemia should be considered a differential diagnosis in a patient presenting with cyanosis without any underlying lung or heart disease.

In the present work the influence of hypoxia on black scorpionfish (Scorpaena porcus) nucleated red blood cells has been studied at in vivo (whole blood) and in vitro (cell suspension) experiments. Experiments were conducted in the range of oxygen concentration 0,3-8,5 mg О2 l-1, water temperature 14-16 оС, and the duration of exposure period was 4 h. Deep hypoxia (less than 2 mgО2 l-1) caused hemoglobin transition to a ferry-form (MtHb), and the most substantial increase of MtHb concentration was observed at severe hypoxic conditions (less than 1 mg О2 l-1 ). The highest MtHb level observed was 19-32 %. The results of in vivo and in vitro experimental series were similar, indicating that mechanisms involved in MtHb formation occur within cells and are not associated with organismic responses to oxygen deficiency. Moderate hypoxia (oxygen concentration more than 2 mg О2 l-1) did not cause hemoglobin transformation. MtHb formation did not influence the level of reactive oxygen species (DCF-DA fluorescence) and the integrity of cellular membrane (double staining with SYBR Green I and Propidium iodide) in red blood cells. The level of dead cells in control and experimental groups did not differ, indicating that responses observed were in the range of physiological norm. [ABSTRACT FROM AUTHOR]

Methemoglobinemia (MetHb, Fe3+) is a chronic disease arising from the unequal distribution of oxyhemoglobin (HbFe2+, OHb) in the blood circulatory system. The oxidation of standard oxyhemoglobin forms methemoglobin, causing cyanosis (skin bluish staining). Methemoglobin cannot bind the pulmonary gaseous ligands such as oxygen (O2) and carbon monoxide (CO). As an oxidizing agent, the biochemical approach (MetHb, Fe3+) is modified in vitro by sodium nitrite (NaNO2). The silver-doped iron zinc oxide (Ag@Fe3O4/ZnO) is hydrothermally synthesized and characterized by analytical and spectroscopic techniques for the electrochemical sensing of methemoglobin via cyclic voltammetry (CV). Detection parameters such as concentration, pH, scan rate, electrochemical active surface area (ECSA), and electrochemical impedance spectroscopy (EIS) are optimized. The linear limit of detection for Ag@Fe3O4/ZnO is 0.17 µM. The stability is determined by 100 cycles of CV and chronoamperometry for 40 h. The serum samples of anemia patients with different hemoglobin levels (Hb) are analyzed using Ag@Fe3O4/ZnO modified biosensor. The sensor's stability, selectivity, and response suggest its use in methemoglobinemia monitoring. [ABSTRACT FROM AUTHOR]

Introduction: Methemoglobinemia is a condition in which methemoglobin is increased and the oxygen carrying capacity of tissues is decreased, causing a lack of oxygen to the whole body. RNA (ribonucleic acid) sequencing technologies have made it possible to systematically examine how the human transcriptome responds to invasive pathologies. To our knowledge, no previous studies have reported the results of RNA sequencing in a patient with methemoglobinemia. We describe the analysis of RNAs from the whole blood of a patient with methemoglobinemia. Case presentation: A 31-year-old Japanese man was brought to our hospital with symptoms of dyspnea due to inhalation of gas from an acetic acid phosphonitrate storage tank at a factory. The nitrogen oxide concentration measured around the storage tank was over 2500 ppm, and he witnessed orange–brown smoke at that time. After entering the area and taking a few breaths, he suddenly became unwell, with dyspnea and numbness in his extremities. He was evacuated from the area within a few minutes, at which time he was suffering from whole-body cyanosis and was still aware of the above symptoms. On arrival at the hospital, his respiration rate was 18 breaths/minute, and his SpO2 ranged from 80% to 85% on 15 L/minute of oxygen by mask (2.5 hours postexposure). Arterial blood gas testing revealed a methemoglobin level of 23.1%. After the administration of methylene blue, the patient's methemoglobin level normalized and his symptoms improved. Chest X-ray and chest computed tomography showed no evidence of pulmonary edema or interstitial pneumonia, and no other abnormal findings were observed. RNA sequencing was performed on the blood samples obtained at the time of the visit, with the blood sample collected on day 5 used as a control. To our knowledge, the present study is the first to describe the analysis of RNAs from the whole blood of a patient with methemoglobinemia. The RNA sequencing analysis showed that an activated "hydrogen peroxide catabolic process" may be associated with the pathogenesis of methemoglobinemia. Conclusion: The results reported in the present study may explain the pathogenesis of methemoglobinemia. [ABSTRACT FROM AUTHOR]