Rare skin color changes in an acute pancreatitis patient undergoing maintenance hemodialysis.

BACKGROUND: Skin conditions are common in patients on maintenance hemodialysis and those with pancreatitis. However, there is a lack of research on dermatological issues in patients who have both hemodialysis and pancreatitis concurrently. CASE PRESENTATION: A 62-year-old male patient with a 4-year history of maintenance hemodialysis (MHD) presented with pain and was diagnosed with acute pancreatitis and gallbladder stones. Markedly elevated blood amylase, creatine kinase, and myoglobin were noted, alongside a purplish-red skin discoloration. Treatment included inhibition of digestive fluid secretion, anti-infection measures, blood purification, fasting, rehydration, and symptomatic care. Notably, continuous renal replacement therapy (CRRT) combined with hemoperfusion (HP) was employed. The patient's dialysis effluent initially appeared red. Upon examination of the patient's peripheral blood smear, red blood cell debris was not observed. The dialysis effluent (on Day 0) was analyzed, revealing no hemoglobin (0 g/L) but an elevated myoglobin concentration of 80.4 U/L. After the therapeutic intervention, the indicators, including the blood amylase, C-reactive protein, total bilirubin, creatine kinase, and myoglobin were improved. The patient experienced resolution of sternal and upper abdominal pain within two days. After four consecutive days of CRRT and HP treatment, the skin color returned to normal, alongside improved clarity of the dialysis effluent. Subsequently, the patient's method of blood purification was reverted to conventional hemodialysis. On the eighth day of hospitalization, the patient resumed normal diet and was discharged. CONCLUSIONS: In the case of the current patient with acute pancreatitis undergoing MHD, it is noteworthy to report the observation of a unique purplish-red skin discoloration. This phenomenon may be attributable to inflammation resulting from acute pancreatitis, and the retention of myoglobin within the body.

Facile incorporation of non-canonical heme ligands in myoglobin through chemical protein synthesis.

The incorporation of non-canonical amino acids (ncAAs) into the metal coordination environments of proteins has endowed metalloproteins with enhanced properties and novel activities, particularly in hemoproteins. In this work, we disclose a scalable synthetic strategy that enables the production of myoglobin (Mb) variants with non-canonical heme ligands, i.e., HoCys and f4Tyr. The ncAA-containing Mb* variants (with H64V/V68A mutations) were obtained through two consecutive native chemical ligations and a subsequent desulfurization step, with overall isolated yield up to 28.6 % in over 10-milligram scales. After refolding and heme b cofactor reconstitution, the synthetic Mb* variants showed typical electronic absorption bands. When subjected to the catalysis of the cyclopropanation of styrene, both synthetic variants, however, were not as competent as the His-ligated Mb*. We envisioned that the synthetic method reported herein would be useful for incorporating a variety of ncAAs with diverse structures and properties into Mb for varied purposes.

Influence of different storage atmospheres in packaging on color stability of beef.

The influence of storage atmosphere on the color development and myoglobin (Mb) redox state of beef was investigated. Beef samples were packaged in 6 different atmospheres including different degrees of vacuum, levels of oxygen, nitrogen, and a mixture with 20% CO2 and stored at 2°C for 14 days. Over this time, color and reflection of the packaged samples were measured. The used method allows quick, easy, and non-invasive measurement of the packaged samples, without using time consuming chemical assays. The method could be implemented in beef production lines, with potential for automatization. The data was used to illustrate the L*a*b* values for insights regarding qualitative color changes. Quantitative color changes were analyzed by calculation of color difference ΔE2000. Additionally, the relative levels of the deoxymyoglobin (DMb), oxymyoglobin (OMb) and metmyoglobin (MMb) were calculated from reflection spectra. The most important findings are: there is a strong correlation (rsp = 0.80 to 0.99 with one exception at rsp = 0.69 (high vacuum), p ≤ 0.05) between a* values and relative OMb levels. Storage atmospheres containing high oxygen concentrations lead to an attractive meat color, but a decreased overall color and Mb stability (ΔE = 5.02 (synthetic air) and ΔE = 2.23 (high oxygen) after 14 days of storage). Vacuum packaged samples are most stable in regards of color and Mb stability (ΔE = 1.79 (high vacuum) and ΔE = 1.63 (low vacuum) after 14 days of storage), but lack in the vibrant red color desired for sale. The experiments showed that color measurement can be a fast, non-invasive marker for meat quality. PRACTICAL APPLICATION: In this research article, six different storage atmospheres are compared regarding their influence on color stability and color quality of beef during storage in packaging. The results suggest which atmospheres to use in various sales-related scenarios. The method described can easily be applied in the meat industry to quickly monitor changes during storage and wet-aging without damaging the meat or opening the meat packages.

A Series of Eight Cases of Pigment Nephropathy: An Obscured Aspect of Acute Kidney Injury.

Pigment-induced acute kidney injury (AKI) is an important and preventable complication of rhabdomyolysis or hemolysis. It is characterized by the release of free heme pigment (myoglobin or hemoglobin) in the circulation, leading to direct injury of the proximal tubule and distal tubule obstruction by pigment cast. We are reporting eight cases of pigment-induced AKI, including six cases of myoglobin cast nephropathy and two cases of hemoglobin cast nephropathy. The causes of rhabdomyolysis were strenuous exercise, infection/febrile illness, and drug-induced neuroleptic malignant syndrome. Paroxysmal nocturnal hemoglobinuria and anti-tuberculosis treatment (rifampicin and isoniazid) had led to hemoglobin cast nephropathy each in one case. Seven cases had severe renal failure requiring dialysis. Short-term renal outcome was favorable. However, long-term follow-up is necessary to determine whether pigment-induced AKI has delayed sequelae. Therefore, clinicians should consider rhabdomyolysis or hemolysis as potential hidden causes of AKI in diverse clinical conditions, especially those of non-traumatic origin, to achieve an accurate diagnosis.

The influence of fixing condition on myoglobin stainability of striated muscle as a tool for forensic diagnosis.

It is reported that immunostaining of Myoglobin (Mb) is useful for forensic diagnosis. In this study, we investigated the condition of fixation of striated muscle in 10 % neutral-buffered formalin to obtain appropriate stationarity of Mb in immunostaining. Firstly, criteria for staining intensity and definition of the stainability of examined were determined for sheep muscle tissue. Sheep myocardial tissue was fixed using 10 % neutral-buffered formalin under the 21 different conditions based on combinations of the following: three ratios of volume of formalin (mL) to weight of myocardium (g) (RFM) of 1, 4 or 9, 7 durations of fixation (DF) of 0.5, 3 or 6 h, and 1, 2, 5 or 7 days. Secondly, detection of Mb diffused form skeletal muscle from autopsy cases into formalin during fixation were confirmed by ELISA. Finally, the evaluation of stainability of Mb of striated muscle in routine autopsy examinations was confirmed using sheep staining intensity standards. From this experimental investigation, it has been demonstrated that the most suitable formalin fixation condition for using Mb staining in forensic diagnosis is RFM4 with a fixation time of at least DF 3 h up to 1 day. It was evident that staining intensity decreases with fixation durations exceeding 2 days, irrespective of the RFM. Thus, the fixation time was deemed the most influential factor affecting the staining properties of Mb staining in skeletal muscle tissue. When conducting Mb staining using striated muscle as an evaluation sample, particular attention should be paid to the fixation time.

Myoglobin saturation as an intracellular indicator for transfusion need in oncology patients.

OBJECTIVES: This study aims to demonstrate the potential of myoglobin saturation as an indicator of oxygen delivery adequacy to help determine the need for red cell transfusion. BACKGROUND: Modern blood management approaches have been established to optimise use of red blood cells for transfusions in patients with anaemia. However, most approaches make recommendations to transfuse based on haemoglobin or haematocrit levels and do not directly address adequacy of oxygen delivery. Intracellular oxygen determined by myoglobin saturation directly measures oxygen delivery at the tissue level. METHODS/MATERIALS: A custom built spectrometer system with an optical fibre probe was used in this pilot study to measure muscle cell myoglobin saturation noninvasively from the first digital interosseous muscles in patients undergoing planned red blood cell transfusion. Patients were recruited from both the in-patient and out-patient oncology service at a major university medical centre. Measurements were made immediately before, immediately after, and 24 h following transfusion. Clinical data and tissue oxygen values from the Somanetics INVOS system were also collected. RESULTS: Myoglobin saturation, and thus cellular oxygen increased in some, but not all patients receiving a transfusion, and was most pronounced in patients who initially had low myoglobin saturation compared with the group as a whole. CONCLUSION: Clinical decisions to transfuse based on haemoglobin or haematocrit thresholds alone are likely insufficient to optimise use of red blood cell transfusions. The combination of haemoglobin or haematocrit with myoglobin saturation may optimally determine who will benefit physiologically from a transfusion.

Clinical characteristics and biomarkers feature analysis using a proteomics platform in young patients with acute coronary syndrome.

Background: Acute coronary syndrome (ACS) is a leading cause of morbidity and mortality worldwide. In recent years, ACS has been reported to be associated with age, and the incidence has become more common in younger patients. Previous studies have identified various risk factors that contribute to the stratification of ACS patients. However, it remains unclear whether these risk factors, along with proteomic and clinical characteristics, are applicable to young ACS patients, as they are for middle-aged and elderly patients. This study aimed to investigate the proteomics, risk factors, and clinical characteristics of young ACS patients, as well as the differences between them and middle-aged and elderly ACS patients. By comparing these findings with those of middle-aged and elderly patients, we aimed to identify any discrepancies and these findings possibly may have implications for future management strategies of this specific population. Methods: This observational study included a total of 187 participants diagnosed with ACS and 17 young healthy individuals as the control group. ACS patients were divided into three age groups: <45 years old, 45-60 years old, and 61-75 years old. The control group consisted of healthy individuals under the age of 45 who underwent coronary angiography and were excluded from CAD. We collected clinical characteristics, laboratory data, and echocardiographic results from each participant. Additionally, blood samples were collected for further analysis of relevant proteomic and arteriosclerosis marker data using proteomics analysis. Results: Our findings revealed that the presence of certain key factors was associated with a significantly difference in patients with ACS aged younger than 45 years, and this association differed from that of traditional cardiovascular risk factors in patients older than 45 years. Specifically, a higher body mass index and hyperlipidemia were found to be associated with an increased risk of ACS morbidity in young adults (<45 years old) compared to middle-aged and elderly individuals. Furthermore, our findings indicated that the expression levels of growth differentiation factor 15, osteopontin, and NT-proBNP were significantly different among the groups. Conclusion: In summary, our study revealed that the main pathogenic factors of ACS patients under 45 years of age differed from those of middle-aged and elderly patients. These findings may contribute to the prevention and treatment strategies for young patients with ACS.

Haptoglobin Administration for Intravascular Hemolysis: A Systematic Review.

INTRODUCTION: Exogenous haptoglobin administration may enhance plasma-free hemoglobin (pfHb) clearance during hemolysis and reduce its end-organ damage: we systematically reviewed and summarized available evidence on the use of haptoglobin as a treatment for hemolysis of any cause. METHODS: We included studies describing haptoglobin administration as treatment or prevention of hemolysis-related complications. Only studies with a control group reporting at least one of the outcomes of interest were included in the quantitative synthesis. Primary outcome was the change in pfHb concentration 1 h after haptoglobin infusion. RESULTS: Among 573 articles, 13 studies were included in the review (677 patients, 52.8% received haptoglobin). Median initial haptoglobin intravenous bolus was 4,000 (2,000, 4,000) IU. Haptoglobin was associated with lower pfHb 1 h (SMD -11.28; 95% CI: -15.80 to -6.75; p < 0.001) and 24 h (SMD -2.65; 95% CI: -4.73 to -0.57; p = 0.001) after infusion. There was no difference in all-cause mortality between haptoglobin-treated patients and control group (OR 1.41; 95% CI: 0.49-4.95; p = 0.520). Haptoglobin was associated with a lower incidence of acute kidney injury (OR 0.64; 95% CI: 0.44-0.93; p = 0.020). No adverse events or side effects associated with haptoglobin use were reported. CONCLUSIONS: Haptoglobin administration has been used in patients with hemolysis from any cause to treat or prevent hemolysis-associated adverse events. Haptoglobin may reduce levels of pfHb and preserve kidney function without increase in adverse events.

Pre-exercise cryotherapy reduces myoglobin and creatine kinase levels after eccentric muscle stress in young women.

Introduction: The aim of this study was to investigate the effect of pre-exercise whole-body cryotherapy (WBC) on muscle damage indicators following eccentric treadmill exercise in young women. Methods: Twenty-seven participants underwent two 1-h downhill treadmill runs, replicating 60% of their maximal oxygen uptake, with a 4-week intermission for recovery and treatment application. In this intermission, one group underwent 20 sessions of WBC, delivered five times a week at -120°C for 3 min each, while the comparison group received no such treatment. Markers of muscle injury-serum myoglobin concentration, creatine kinase and lactate dehydrogenase activity and also uric acid, and cell-free DNA concentration-were measured before and after downhill runs. Results: The study observed a notable reduction in post-exercise myoglobin and CK levels in the WBC group after the second running session. Discussion: The results suggest that WBC can have a protective effects against muscle damage resulting from eccentric exercise.

The Implication of Elevated Serum Myoglobin Level in Acute Diabetic Complications of Ketoacidosis and Hyperglycemic Hyperosmolar State: A Real-World Study.

Objective: To investigate the implications of elevated myoglobin (MYO) in acute diabetic conditions of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). Materials and methods: This study integrates in-patient data from Shanghai Pudong Hospital from 2019 to 2023. Laboratory data were compared between stable T2D patients (without acute diabetic complications), DKA, and HHS patients. The multilinear regression explored variables relevant to the elevated MYO in DKA and HHS. The dynamics of MYO, the survival rate, and associated risk factors in HHS were determined. Results: Except for triglyceride, procalcitonin, low-density lipoprotein, islet cell autoimmune antibodies, N-terminal Pro-brain natriuretic peptide (NT-ProBNP), and brain natriuretic peptide (BNP), there were significant differences in age, gender distribution, duration of diabetes, type of diabetes, and other referred laboratory data (p<0.05). The age, gender, creatine kinase (CK), estimated glomerular filtration rate (eGFR), and free triiodothyronine (FT3) in DKA, whereas osmolar, uric acid (UA), and cardiac troponin I (cTNI) in the HHS, were significant determinants of elevated MYO, respectively (p<0.05). The dynamic of MYO in HHS was in line with the survival trend, where the percentage of death was 29.73%, and aging with higher procalcitonin levels was a key risk factor. Besides, the cumulative survival rates between patients with or without bone fracture or muscle injury were substantially different. Conclusion: This real-world study demonstrated DKA and HHS potentially have unique causes for increased MYO. By utilizing the appropriate regression parameters, we could forecast the progression of increased MYO in groups of DKA and HHS, while based on risk factors of aging, severity of infection, and different MYO sources, we could predict the prognosis of HHS.

Methylglyoxal-induced modification of myoglobin: An insight into glycation mediated protein aggregation.

Post-translational modification of proteins by Maillard reaction, known as glycation, is thought to be the root cause of different complications, particularly in diabetes mellitus and age-related disorders. Methylglyoxal (MG), a reactive α-oxoaldehyde, increases in diabetic condition and reacts with the proteins to form advanced glycation end products (AGEs) following a Maillard-like reaction. In a time-dependent reaction study of MG with the heme protein myoglobin (Mb), MG was found to induce significant structural alterations of the heme protein, such as heme loss, changes in tryptophan fluorescence, and decrease of α-helicity with increased ß-sheet content. These changes were found to occur gradually with increasing period of incubation. Incubation of Mb with MG induced the formation of several AGE adducts, including, carboxyethyllysine at Lys-16, carboxymethyllysine at Lys-87, carboxyethyllysine or pyrraline-carboxymethyllysine at Lys-133, carboxyethyllysine at Lys-42 and hydroimidazolone or argpyrimidine at Arg-31 and Arg-139. MG induced amyloid-like aggregation of Mb was detected at a longer period of incubation. MG-derived AGEs, therefore, appear to have an important role as the precursors of protein aggregation, which, in turn, may be associated with pathophysiological complications.

Myoglobin as a molecular biomarker for meat authentication and traceability.

The global incidence of economically motivated meat adulteration represents a crucial issue for the food industry. Undeclared addition of cheaper or low-quality species to meat products of high commercial value has become a common practice that needs to be countered with specific measures. In this framework, myoglobin (Mb) is a sarcoplasmic haemoprotein, primarily responsible for meat colour and has been successfully used in meat fraud authentication. Mb is highly soluble in water, easily monitored at 409 nm and species-specific. Knowing that various analytical DNA-based and protein-based methods, as well as spectroscopic techniques have been developed over the years for the detection of meat fraud, the aim of the present review is to take stock of the situation regarding the possible use of Mb as a molecular biomarker for the easy and rapid detection of undeclared species in meat products, avoiding the need of sophisticated or expensive equipment and specialised operators.

Unique myoglobin adaptation to endothermy and flight since the origin of birds.

Myoglobin (Mb) mediates oxygen diffusion and storage in muscle tissue and thus is important for the energy utilization and activity of animals. Birds generally have a high body temperature, and most species also possess the capability of powered flight. Both of these require high levels of aerobic metabolism. Within endothermic mammals, bats also independently evolved flight. Although the functional evolution of myoglobins in deep-diving amniote vertebrates has been well-studied, the functional evolution of myoglobin since the origins of both birds and bats is unclear. Here, with Mb-coding sequences from >200 extant amniote species, we reconstructed ancestral sequences to estimate the functional properties of myoglobin through amniote evolution. A dramatic change in net surface charge on myoglobin occurred during the origin of Aves, which might have been driven by positively selected amino acid substitutions that occurred on the lineage leading to all birds. However, in bats, no change in net surface charge occurred and instead, the Mb genes show evidence of strong purifying selection. The increased net surface charge on bird myoglobins implies an adaptation to flight-related endothermic and higher body temperatures, possibly by reducing harmful protein aggregations. Different from the findings of net surface charge, myoglobins of extant birds show lower stability compared with other amniotes, which probably accelerates the rate of oxygen utilization in muscles. In bats and other mammals, higher stability of Mb may be an alternative pathway for adaptation to endothermy, indicating divergent evolution of myoglobin in birds and bats.

Effects of dapagliflozin on myoglobin efflux from cardiomyocyte during myocardial ischemia/reperfusion in anesthetized rats.

It has been suggested that sodium-glucose cotransporter 2 (SGLT2) inhibitors have cardioprotective effects during myocardial ischemia/reperfusion (I/R) independent of glucose-lowering action. However, the effects of SGLT2 inhibitors on structural damage to cardiomyocytes in the ischemic region during I/R remain unknown. We applied a microdialysis technique to the heart of anesthetized rats and investigated the effects of an SGLT2 inhibitor, dapagliflozin, on myocardial interstitial myoglobin levels in the ischemic region during coronary occlusion followed by reperfusion. Dapagliflozin was administered systemically (40 µg/body iv) or locally via a dialysis probe (100 µM and 1 mM) 30 min before coronary occlusion. In the vehicle group, coronary occlusion increased the dialysate myoglobin concentration in the ischemic region. Reperfusion further increased the dialysate myoglobin concentration. Intravenous administration of dapagliflozin reduced dialysate myoglobin concentration during ischemia and at 0-15 min after reperfusion, but local administration (100 µM and 1 mM) did not. Therefore, acute systemic administration of dapagliflozin prior to ischemia has cardioprotective effects on structural damage during I/R.

Exploring structural and computational contrasts in Myoglobins: Implications for thermal treatment-induced Sulfmyoglobin formation.

Greening of tuna metmyoglobin (MetMb) by thermal treatment (TT) and free cysteine is associated with sulfmyoglobin (SulfMb) production. This greening reaction (GR) was once thought to occur only in tuna species. However, recent research has revealed that not all tuna species exhibit this behavior, and it can also occur in horse MetMb. Thus, the present study aimed to compare the GR-reactive (Katsuwonus pelamis and Equus caballus) and GR-unreactive (Sarda chiliensis and Euthynnus lineatus) MetMb using UV-vis spectrometry during TT (60 °C/30 min and free cysteine) to monitor the GR. We used molecular dynamics (MD) simulation to assess the stability of the heme group during TT. We discovered that using GR-unreactive MetMb resulted in an incomplete GR without producing SulfMb. Additionally, our MD simulations indicated that Met85 presence in the heme cavity from GR-unreactive is responsible for the heme group instability and displacement of distal His during TT.

Structural Phylogenetics with Protein Mass Spectrometry: A Proof-of-Concept.

It is demonstrated, for the first time, that a mass spectrometry approach (known as phylonumerics) can be successfully implemented for structural phylogenetics investigations to chart the evolution of a protein's structure and function. Illustrated for the compact globular protein myoglobin, peptide masses produced from the proteolytic digestion of the protein across animal species generate trees congruent to the sequence tree counterparts. Single point mutations calculated during the same mass tree building step can be followed along interconnected branches of the tree and represent a viable structural metric. A mass tree built for 15 diverse animal species, easily resolve the birds from mammal species, and the ruminant mammals from the remainder of the animals. Mutations within helix-spanning peptide segments alter both the mass and structure of the protein in these segments. Greater evolution is found in the B-helix over the A, E, F, G and H helices. A further mass tree study, of six more closely related primate species, resolves gorilla from the other primates based on a P22S mutation within the B-helix. The remaining five primates are resolved into two groups based on whether they contain a glycine or serine at position 23 in the same helix. The orangutan is resolved from the gibbon and siamang by its G-helix C110S mutation, while homo sapiens are resolved from chimpanzee based on the Q116H mutation. All are associated with structural perturbations in such helices. These structure altering mutations can be tracked along interconnecting branches of a mass tree, to follow the protein's structure and evolution, and ultimately the evolution of the species in which the proteins are expressed. Those that have the greatest impact on a protein's structure, its function, and ultimately the evolution of the species, can be selectively tracked or monitored.

Nitric Oxide Binding Geometry in Heme-Proteins: Relevance for Signal Transduction.

Nitric oxide (NO) synthesis, signaling, and scavenging is associated to relevant physiological and pathological events. In all tissues and organs, NO levels and related functions are regulated at different levels, with heme proteins playing pivotal roles. Here, we focus on the structural changes related to the different binding modes of NO to heme-Fe(II), as well as the modulatory effects of this diatomic messenger on heme-protein functions. Specifically, the ability of heme proteins to bind NO at either the distal or proximal side of the heme and the transient interchanging of the binding site is reported. This sheds light on the regulation of O2 supply to tissues with high metabolic activity, such as the retina, where a precise regulation of blood flow is necessary to meet the demand of nutrients.

Comparative proteomic analyses to investigate premature browning in high­oxygen modified atmosphere packaged beef patties.

This study compared the proteomics of beef patties under high­oxygen modified atmosphere packaging (HiOx-MAP) and vacuum packaging (VP) during heating. The color and oxidation stability of fresh patties, and myoglobin denaturation of cooked patties were also measured. The results suggested that HiOx-MAP patties contained more oxymyoglobin in fresh meat and had higher myoglobin denaturation during heating than VP patties, resulting in premature browning (PMB) during cooking. Proteomic analysis found that the overabundance of proteasome subunit beta type-2 (PSMB2) and peroxiredoxin-2 (PRDX2) in HiOx-55 °C, which can remove the damaged proteins and inhibit oxidation respectively, are of benefit to meat color stability during storage, however, this was still insufficient to inhibit the occurrence of PMB during cooking. The high abundance of lamin B1 (LMNB1) in VP-55 °C can maintain the stability of meat color. This research provides greater understanding, based on proteomic perspectives, of the molecular mechanism of PMB.

Myoglobin adsorption and saturation kinetics of the cytokine adsorber Cytosorb® in patients with severe rhabdomyolysis: a prospective trial.

BACKGROUND: Rhabdomyolysis is a serious condition that can lead to acute kidney injury with the need of renal replacement therapy (RRT). The cytokine adsorber Cytosorb® (CS) can be used for extracorporeal myoglobin elimination in patients with rhabdomyolysis. However, data on adsorption capacity and saturation kinetics are still missing. METHODS: The prospective Cyto-SOLVE study (NCT04913298) included 20 intensive care unit patients with severe rhabdomyolysis (plasma myoglobin > 5000 ng/ml), RRT due to acute kidney injury and the use of CS for myoglobin elimination. Myoglobin and creatine kinase (CK) were measured in the patient´s blood and pre- and post-CS at defined time points (ten minutes, one, three, six, and twelve hours after initiation). We calculated Relative Change (RC, %) with: [Formula: see text]. Myoglobin plasma clearances (ml/min) were calculated with: [Formula: see text] RESULTS: There was a significant decrease of the myoglobin plasma concentration six hours after installation of CS (median (IQR) 56,894 ng/ml (11,544; 102,737 ng/ml) vs. 40,125 ng/ml (7879; 75,638 ng/ml) (p < 0.001). No significant change was observed after twelve hours. Significant extracorporeal adsorption of myoglobin can be seen at all time points (p < 0.05) (ten minutes, one, three, six, and twelve hours after initiation). The median (IQR) RC of myoglobin at the above-mentioned time points was - 79.2% (-85.1; -47.1%), -34.7% (-42.7;-18.4%), -16.1% (-22.1; -9.4%), -8.3% (-7.5; -1.3%), and - 3.9% (-3.9; -1.3%), respectively. The median myoglobin plasma clearance ten minutes after starting CS treatment was 64.0 ml/min (58.6; 73.5 ml/min), decreasing rapidly to 29.1 ml/min (26.5; 36.1 ml/min), 16.1 ml/min (11.9; 22.5 ml/min), 7.9 ml/min (5.5; 12.5 ml/min), and 3.7 ml/min (2.4; 6.4 ml/min) after one, three, six, and twelve hours, respectively. CONCLUSION: The Cytosorb® adsorber effectively eliminates myoglobin. However, the adsorption capacity decreased rapidly after about three hours, resulting in reduced effectiveness. Early change of the adsorber in patients with severe rhabdomyolysis might increase the efficacy. The clinical benefit should be investigated in further clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04913298. Registered 07 May 2021, https//clinicaltrials.gov/study/NCT04913298.

Quantifying CO-release from a photo-CORM using 19F NMR: An investigation into light-induced CO delivery.

Carbon monoxide (CO) is an innate signaling molecule that can regulate immune responses and interact with crucial elements of the circadian clock. Moreover, pharmacologically, CO has been substantiated for its therapeutic advantages in animal models of diverse pathological conditions. Given that an excessive level of CO can be toxic, it is imperative to quantify the necessary amount for therapeutic use accurately. However, estimating gaseous CO is notably challenging. Therefore, novel techniques are essential to quantify CO in therapeutic applications and overcome this obstacle precisely. The classical Myoglobin (Mb) assay technique has been extensively used to determine the amount of CO-release from CO-releasing molecules (CORMs) within therapeutic contexts. Nevertheless, specific challenges arise when applying the Mb assay to evaluate CORMs featuring innovative molecular architectures. Here, we report a fluorinated photo-CORM (CORM-FBS) for the photo-induced CO-release. We employed the 19F NMR spectroscopy approach to monitor the release of CO as well as quantitative evaluation of CO release. This new 19F NMR approach opens immense opportunities for researchers to develop reliable techniques for identifying molecular structures, quantitative studies of drug metabolism, and monitoring the reaction process.