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Zhonghua Wei Zhong Bing Ji Jiu Yi Xue May 2024To investigate the clinical efficacy of continuous veno-venous hemodia-filtration (CVVHDF) combined with hemoperfusion (HP) HA380 in the treatment of heat stroke... (Observational Study)
Observational Study
[Observation on the efficacy of continuous veno-venous hemodia-filtration combined with hemoperfusion HA380 in the treatment of 15 cases of heat stroke with multiple organ dysfunction syndrome].
OBJECTIVE
To investigate the clinical efficacy of continuous veno-venous hemodia-filtration (CVVHDF) combined with hemoperfusion (HP) HA380 in the treatment of heat stroke patients with multiple organ dysfunction syndrome (MODS).
METHODS
A retrospective and observational study was conducted. A total of 15 patients with heat stroke combined with MODS who were admitted to the department of intensive care unit (ICU) of Suizhou Central Hospital/Hubei University of Medicine from July to September 2022 were selected as the study objects. All 15 patients were treated with CVVHDF combined with HA380 based on the comprehensive management strategy for severe illness. Organ function indicators [including total bilirubin (TBil), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), creatinine (Cr), cardiac troponin T (cTnT), myoglobin (Myo), MB isoenzyme of creatine kinase (CK-MB), sequential organ failure assessment (SOFA)] and inflammatory indicators [including white blood cell count (WBC), neutrophil count (NEU), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6)] were collected. The improvements of the above indexes at admission, after the first HP, after the second HP, after the third HP, and on the 5th day of treatment were compared. Combined with the clinical outcome of patients, the comprehensive efficacy of CVVHDF combined with HA380 in the treatment of severe heat radiation disease was evaluated.
RESULTS
There were 10 males and 5 females among the 15 patients. The average age was (64.5±11.5) years old. There were 6 cases of classical heat stroke and 9 cases of exertional heat stroke. Glasgow coma scale (GCS) was 3-8 at admission; SOFA score was 9-17 within 12 hours after admission; acute physiology and chronic health evaluation II (APACHE II) was 25-45 within 24 hours after admission. After treatment, the IL-6 level and SOFA score gradually decreased, and there were significant differences in the decrease after the second HP compared to admission [IL-6 (ng/L): 48.37 (15.36, 113.03) vs. 221.90 (85.87, 425.90), SOFA: 8.3±3.3 vs. 11.1±2.4, both P < 0.05]. The PCT level reached its peak after the first HP [12.51 (6.07, 41.65) μg/L], and then gradually decreased, and the difference was statistically significant after the third HP [1.26 (0.82, 5.40) μg/L, P < 0.05]. Compared those at admission, Cr level significantly improved after the first HP (μmol/L: 66.94±25.57 vs. 110.80±31.13, P < 0.01), Myo significantly decreased after the second HP [μg/L: 490.90 (164.98, 768.05) vs. 3 000.00 (293.00, 3 000.00), P < 0.05], After the third HP, the CK level also showed significant improvement [U/L: 476.0 (413.0, 922.0) vs. 2 107.0 (729.0, 2 449.0), P < 0.05]. After CVVHDF combined with 3 times HP treatment, the patient's inflammatory response was gradually controlled and organ function gradually recovered. On the 5th day of the disease course, WBC, PCT and IL-6 levels were significantly improved compared to admission, and AST, CK, LDH, Cr, Myo, CK-MB, and SOFA score were significantly corrected compared with those on admission. The 24-hour survival rate of 15 patients was 86.67%, and the 24-hour, 7-day and 28-day survival rates were both as high as 73.33%. The average mechanical ventilation time of 11 surviving patients was (101.8±22.0) hours, the average continuous renal replacement therapy (CRRT) time was (58.8±11.0) hours, the average length of ICU stay was (6.3±1.0) days, and the average total hospitalization was (14.6±5.2) days.
CONCLUSIONS
CVVHDF combined with HP HA380 in the treatment of heat stroke patients with MODS can effectively improve organ function and alleviate the inflammatory storm, which is an effective means to improve the rescue rate and reduce the mortality of severe heat stroke patients.
Topics: Humans; Multiple Organ Failure; Retrospective Studies; Hemoperfusion; Heat Stroke; Interleukin-6; Intensive Care Units; Continuous Renal Replacement Therapy; Male; Female; Middle Aged; Treatment Outcome
PubMed: 38845502
DOI: 10.3760/cma.j.cn121430-20230728-00561 -
Metabolic Engineering Jun 2024The development of a heme-responsive biosensor for dynamic pathway regulation in eukaryotes has never been reported, posing a challenge for achieving the efficient...
The development of a heme-responsive biosensor for dynamic pathway regulation in eukaryotes has never been reported, posing a challenge for achieving the efficient synthesis of multifunctional hemoproteins and maintaining intracellular heme homeostasis. Herein, a biosensor containing a newly identified heme-responsive promoter, CRISPR/dCas9, and a degradation tag N-degron was designed and optimized to fine-tune heme biosynthesis in the efficient heme-supplying Pichia pastoris P1H9 chassis. After identifying literature-reported promoters insensitive to heme, the endogenous heme-responsive promoters were mined by transcriptomics, and an optimal biosensor was screened from different combinations of regulatory elements. The dynamic regulation pattern of the biosensor was validated by the transcriptional fluctuations of the HEM2 gene involved in heme biosynthesis and the subsequent responsive changes in intracellular heme titers. We demonstrate the efficiency of this regulatory system by improving the production of high-active porcine myoglobin and soy hemoglobin, which can be used to develop artificial meat and artificial metalloenzymes. Moreover, these findings can offer valuable strategies for the synthesis of other hemoproteins.
PubMed: 38839038
DOI: 10.1016/j.ymben.2024.06.002 -
Meat Science Sep 2024This study aimed to develop an appropriate modified atmosphere packaging (MAP) system for displayed beef steaks following long-term superchilled (-1 °C) storage. After...
This study aimed to develop an appropriate modified atmosphere packaging (MAP) system for displayed beef steaks following long-term superchilled (-1 °C) storage. After superchilled storage for 0, 2, 8, or 16 weeks, beef loins were fabricated into steaks and displayed with 20%, 50%, or 80% O-MAP under chilled conditions. At each storage point, after display for 0, 3, 7, or 10 days, instrumental color, myoglobin redox forms percentage, lipid oxidation, total viable count (TVC), and total volatile basic nitrogen (TVB-N) were evaluated. Meat color stability decreased, with prolonged storage period and display time. When the storage period was within 8 weeks, under all the above MAP conditions, the display time for the beef steaks was up to 10 days. Considering 80% O-MAP promoted lipid oxidation, 50% and 80% O-MAP were not recommended for displaying steaks for more than 10 and 7 days respectively after 16 weeks of storage. However, 20%, 50%, or 80% O-MAP could maintain 3 days of microbial shelf-life according to TVC and TVB-N results. Additionally, after long-term superchilled storage for 16 weeks, the various O concentrations had minimal impact on microbiota succession during the MAP display period. Furthermore, beef steaks packaged under various MAP systems exhibited similar microbial compositions, with the dominant bacteria alternating between Lactobacillus and Carnobacterium. This study provided practical guidance for improving beef color stability after long-term superchilled storage.
Topics: Cattle; Food Packaging; Animals; Oxygen; Red Meat; Food Storage; Color; Food Microbiology; Myoglobin; Cold Temperature; Oxidation-Reduction; Bacteria
PubMed: 38838568
DOI: 10.1016/j.meatsci.2024.109548 -
Analytica Chimica Acta Jul 2024Carbon monoxide (CO) is an innate signaling molecule that can regulate immune responses and interact with crucial elements of the circadian clock. Moreover,...
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 F NMR spectroscopy approach to monitor the release of CO as well as quantitative evaluation of CO release. This new F 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.
Topics: Carbon Monoxide; Light; Myoglobin; Magnetic Resonance Spectroscopy; Fluorine; Animals; Photochemical Processes
PubMed: 38834263
DOI: 10.1016/j.aca.2024.342749 -
Food Chemistry: X Jun 2024Lighting conditions are an important factor affecting dry-cured products. This study investigated the effects of treatments with different light intensities (0 lx,...
Lighting conditions are an important factor affecting dry-cured products. This study investigated the effects of treatments with different light intensities (0 lx, 1000 lx, 25000 lx) and different light sources including red light, blue light, UV-light on oxidation leve and flavor change in dry-cured Wuchang fish. The results showed that dry-cured Wuchang fish exhibited an attractive brown-yellow color, the highest oxidation degree of myoglobin (Mb), the highest fat oxidation under the light conditions of 25000 lx light intensity and UV-light irradiation. This phenomenon was observed that the degree of Mb oxidation was increased, while the degree of fat oxidation was increased. At 25000 lx light intensity and UV-light irradiation, dry-cured Wuchang fish showed an ignificantly decreased fatty acid conten (especially oleic acid and linoleic acid), significantly increased characteristic volatile compound contents (22 for 25,000 lx light intensity and 27 for UV-light irradiation), which contributed to the improvement of quality stability of dry-cured Wuchang fish. Our findings provide theoretical support for the industrial application of exogenous light in dry-cured Wuchang fish.
PubMed: 38817983
DOI: 10.1016/j.fochx.2024.101464 -
Biophysical Chemistry Aug 2024Reverse micelles (RMs) are spontaneously organizing nanobubbles composed of an organic solvent, surfactants, and an aqueous phase that can encapsulate biological...
Reverse micelles (RMs) are spontaneously organizing nanobubbles composed of an organic solvent, surfactants, and an aqueous phase that can encapsulate biological macromolecules for various biophysical studies. Unlike other RM systems, the 1-decanoyl-rac-glycerol (10MAG) and lauryldimethylamine-N-oxide (LDAO) surfactant system has proven to house proteins with higher stability than other RM mixtures with little sensitivity to the water loading (W, defined by the ratio of water to surfactant). We investigated this unique property by encapsulating three model proteins - cytochrome c, myoglobin, and flavodoxin - in 10MAG/LDAO RMs and applying a variety of experimental methods to characterize this system's behavior. We found that this surfactant system differs greatly from the traditional, spherical, monodisperse RM population model. 10MAG/LDAO RMs were discovered to be oblate ellipsoids at all conditions, and as W was increased, surfactants redistributed to form a greater number of increasingly spherical ellipsoidal particles with pools of more bulk-like water. Proteins distinctively influence the thermodynamics of the mixture, encapsulating at their optimal RM size and driving protein-free RM sizes to scale accordingly. These findings inform the future development of similarly malleable encapsulation systems and build a foundation for application of 10MAG/LDAO RMs to analyze biological and chemical processes under nanoscale confinement.
Topics: Micelles; Myoglobin; Surface-Active Agents; Glycerol; Cytochromes c; Flavodoxin; Laurates; Thermodynamics; Water; Dimethylamines
PubMed: 38815545
DOI: 10.1016/j.bpc.2024.107269 -
Journal of Inorganic Biochemistry Sep 2024Antioxidant assays are typically based on non-physiologically relevant reagents. We describe here a quantitative assay based on the inhibition of the liposome...
Antioxidant assays are typically based on non-physiologically relevant reagents. We describe here a quantitative assay based on the inhibition of the liposome autooxidation in the presence of myoglobin (ILA-Mb), an oxidative process with direct biomedical relevance. Additional advantages of the assay include the use of standard and readily available reagents (lecithin and myoglobin) and the applicability to lipophilic antioxidants. The ILA-Mb assay is based on previously reported qualitative or semi-quantitative ones that employed cytochrome c instead of myoglobin. A number of antioxidants are tested, and their IC parameters are discussed and interpreted to involve direct interaction with both myoglobin and the liposomes.
Topics: Myoglobin; Liposomes; Antioxidants; Oxidation-Reduction; Biomimetics; Animals; Horses
PubMed: 38815361
DOI: 10.1016/j.jinorgbio.2024.112613 -
Food Chemistry Oct 2024This study explored the effect of constant-current pulsed electric field thawing (CC-T) on the proteins and water-holding capacity of pork. Fresh meat (FM), and frozen...
This study explored the effect of constant-current pulsed electric field thawing (CC-T) on the proteins and water-holding capacity of pork. Fresh meat (FM), and frozen meat after constant-voltage thawing (CV-T), air thawing (AT) and water immersion thawing (WT) were considered as controls. The results indicated that CC-T had a higher thawing rate than conventional thawing during ice-crystal melting stage (-5 to -1 °C). It also showed a lower water migration and thawing loss, maintaining pH and shear force closer to FM. Meanwhile, CC-T decreased myoglobin oxidation, resulting in a favorable surface color. The results of protein solubility, differential scanning calorimetry, total sulfhydryl, carbonyl and surface hydrophobicity demonstrated that CC-T reduced myofibrillar protein oxidative denaturation by suppressing the formation of disulfide and carbonyl bonds, thus enhancing solubility and thermal stability. Additionally, microstructural observation found that CC-T maintained a relatively intact muscle fiber structure by reducing muscle damage and myosin filament denaturation.
Topics: Animals; Swine; Water; Freezing; Muscle, Skeletal; Solubility; Muscle Proteins; Electricity; Meat; Oxidation-Reduction; Food Handling
PubMed: 38815321
DOI: 10.1016/j.foodchem.2024.139784 -
Clinical Toxicology (Philadelphia, Pa.) May 2024Myotoxicity is an important toxidrome that can occur with envenoming from multiple Australian snake types. Early antivenom administration is an important strategy to...
INTRODUCTION
Myotoxicity is an important toxidrome that can occur with envenoming from multiple Australian snake types. Early antivenom administration is an important strategy to reduce the incidence and severity of myotoxicity. The current gold standard biomarker, serum creatine kinase activity, does not rise early enough to facilitate early antivenom administration. Several other skeletal muscle biomarkers have shown promise in other animal models and scenarios. The aim of this study was to examine the predictive values of six skeletal muscle biomarkers in a rat model of Australian snake myotoxicity.
METHODS
Sprague-Dawley rats were anaesthetised and administered either (red-bellied black snake) or (tiger snake) venom, or normal saline via intramuscular injection. Blood samples were collected. Assays were performed for serum creatine kinase skeletal muscle troponin-I concentration, skeletal muscle troponin-C concentration, myoglobin activity, skeletal muscle myosin light chain-1 concentration, and creatine kinase-MM activity. Serum markers were plotted against time, with comparison of area under the concentration (or activity)-time curve. The predictive values of six skeletal muscle biomarkers were examined using receiver operating characteristic curves.
RESULTS
There was no difference in area under the serum creatine kinase activity-time curve between venom and control groups. Serum creatine kinase-MM activity rose early in the venom treated rats, which had a significantly greater area under the serum activity-time curve. No difference in area under the serum concentration-time curve was demonstrated for the other biomarkers. Creatine kinase-MM activity had a superior predictive values than creatine kinase activity at 0-4 hours and 0-10 hours after venom administration, as indicated by area under the receiver operating characteristic curves (95 per cent confidence intervals) of 0.91 (0.78-1.00) and 0.88 (0.73-1.00) versus 0.79 (0.63-0.95) and 0.66 (0.51-0.80).
DISCUSSION
The limitations of serum creatine kinase activity in early detection of myotoxicity were demonstrated in this rat model.
CONCLUSION
Serum creatine kinase-MM activity was superior for early detection of Australian myotoxic snake envenoming.
Topics: Animals; Biomarkers; Muscle, Skeletal; Rats, Sprague-Dawley; Pilot Projects; Snake Bites; Rats; Australia; Male; Disease Models, Animal; Elapid Venoms; Myotoxicity; Elapidae; Antivenins; Myoglobin; Myosin Light Chains; Creatine Kinase; Early Diagnosis; Creatine Kinase, MM Form
PubMed: 38804832
DOI: 10.1080/15563650.2024.2349690 -
Clinical Chemistry and Laboratory... May 2024This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of...
OBJECTIVES
This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of detection (LoD), precision, linearity, analytical specificity and sex-specific 99th percentile upper reference limits.
METHODS
LoB, LoD, precision, linearity and analytical specificity were studied according to Clinical and Laboratory Standards Institute. We used one reagent lot and one CL1200i analyzer. Skeletal troponin I and T, cardiac troponin T, troponin C, actin, tropomyosin, myosin light chain, myoglobin and creatine kinase (CK-MB) were studied for cross-reactivity. Interference with biotin was examined. Lithium heparin samples (one freeze thaw cycle) from healthy males and females were measured to determine the 99th percentiles by using the non-parametric method. Analyses were performed before and after excluding subjects with clinical conditions and/or increased surrogate biomarkers.
RESULTS
The Mindray hs-cTnI assay met criteria to be considered as a hs-cTn assay. LoB and LoD was <0.1 ng/L and 0.1 ng/L, respectively. Repeatability had a coefficient of variation 1.2-3.8 %, and within-laboratory imprecision 1.7-5.0 %. The measuring interval ranged from 1.1 to 28,180 ng/L. The analytical specificity was clinically acceptable for the interferents studied. After exclusions, the 99th percentile URLs obtained were 10 ng/L overall, 5 ng/L for females and 12 ng/L for males.
CONCLUSIONS
Analytical observations of the Mindray hs-cTnI assay demonstrated excellent LoB, LoD, precision, linearity and analytical specificity, that were in alignment with the manufacturer's claims and regulatory guidelines for hs-cTnI. The assay is suitable for clinical investigation for patient-oriented studies.
PubMed: 38801528
DOI: 10.1515/cclm-2024-0352