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1.
Front Immunol ; 15: 1407237, 2024.
Article in English | MEDLINE | ID: mdl-38947329

ABSTRACT

Introduction: Red blood cells (RBCs), also known as erythrocytes, are underestimated in their role in the immune system. In mammals, erythrocytes undergo maturation that involves the loss of nuclei, resulting in limited transcription and protein synthesis capabilities. However, the nucleated nature of non-mammalian RBCs is challenging this conventional understanding of RBCs. Notably, in bony fishes, research indicates that RBCs are not only susceptible to pathogen attacks but express immune receptors and effector molecules. However, given the abundance of RBCs and their interaction with every physiological system, we postulate that they act in surveillance as sentinels, rapid responders, and messengers. Methods: We performed a series of in vitro experiments with Cyprinus carpio RBCs exposed to Aeromonas hydrophila, as well as in vivo laboratory infections using different concentrations of bacteria. Results: qPCR revealed that RBCs express genes of several inflammatory cytokines. Using cyprinid-specific antibodies, we confirmed that RBCs secreted tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). In contrast to these indirect immune mechanisms, we observed that RBCs produce reactive oxygen species and, through transmission electron and confocal microscopy, that RBCs can engulf particles. Finally, RBCs expressed and upregulated several putative toll-like receptors, including tlr4 and tlr9, in response to A. hydrophila infection in vivo. Discussion: Overall, the RBC repertoire of pattern recognition receptors, their secretion of effector molecules, and their swift response make them immune sentinels capable of rapidly detecting and signaling the presence of foreign pathogens. By studying the interaction between a bacterium and erythrocytes, we provide novel insights into how the latter may contribute to overall innate and adaptive immune responses of teleost fishes.


Subject(s)
Aeromonas hydrophila , Carps , Cytokines , Erythrocytes , Fish Diseases , Gram-Negative Bacterial Infections , Animals , Carps/immunology , Carps/microbiology , Erythrocytes/immunology , Erythrocytes/metabolism , Cytokines/metabolism , Cytokines/immunology , Aeromonas hydrophila/immunology , Gram-Negative Bacterial Infections/immunology , Fish Diseases/immunology , Fish Diseases/microbiology , Phagocytosis/immunology , Pathogen-Associated Molecular Pattern Molecules/immunology , Immunity, Innate
2.
Aging Male ; 27(1): 2336625, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38647199

ABSTRACT

BACKGROUND: Benign prostatic hyperplasia (BPH) affects 30% of men worldwide, folate is essential for life. However, few studies have investigated the relationship between folate levels and BPH. The present study aims to explore the relationship between red blood cell (RBC) folate, a better indicator of long-term folate intake, and BPH in United States (US) men. METHODS: We used statistics from four cycles of the "National Health and Nutrition Examination Survey" (NHANES2001-2008), RBC folate data come from laboratory data and BPH date come from questionnaire data. A multivariate conditional logistic regression model and subgroup analysis were using to assess the association between RBC folate and BPH. RESULTS: 647 males from four survey cycles in the NHANES2001-2008, of which, 574 men (88.7%) had BPH. After adjusting for potential confounders, a considerable correlation was observed between RBC folate and BPH; With the first quintiles of RBC folate as the reference, multivariable-adjusted odds ratios (ORs) and confidence intervals (95% CIs) of the second, third, fourth, and the highest quintiles were 1.19 (0.58 ∼ 2.44), 1.39 (0.65 ∼ 2.97), 2.27 (0.96 ∼ 5.39), 2.26 (1.35 ∼ 3.76) and 5.37 (1.85 ∼ 15.59), respectively. CONCLUSIONS: Individuals with high levels of RBC folate were associated with an increased risk of self-reported benign prostatic hyperplasia of US men.


Subject(s)
Erythrocytes , Folic Acid , Nutrition Surveys , Prostatic Hyperplasia , Humans , Male , Prostatic Hyperplasia/blood , Prostatic Hyperplasia/epidemiology , Folic Acid/blood , Middle Aged , United States/epidemiology , Erythrocytes/chemistry , Erythrocytes/metabolism , Aged , Adult , Logistic Models , Risk Factors
3.
Mater Today Bio ; 24: 100913, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38188647

ABSTRACT

Cancer has become an increasingly important public health issue owing to its high morbidity and mortality rates. Although traditional treatment methods are relatively effective, they have limitations such as highly toxic side effects, easy drug resistance, and high individual variability. Meanwhile, emerging therapies remain limited, and their actual anti-tumor effects need to be improved. Nanotechnology has received considerable attention for its development and application. In particular, artificial nanocarriers have emerged as a crucial approach for tumor therapy. However, certain deficiencies persist, including immunogenicity, permeability, targeting, and biocompatibility. The application of erythrocyte-derived materials will help overcome the above problems and enhance therapeutic effects. Erythrocyte-derived materials can be acquired via the application of physical and chemical techniques from natural erythrocyte membranes, or through the integration of these membranes with synthetic inner core materials using cell membrane biomimetic technology. Their natural properties such as biocompatibility and long circulation time make them an ideal choice for drug delivery or nanoparticle biocoating. Thus, red blood cell-derived materials are widely used in the field of biomedicine. However, further studies are required to evaluate their efficacy, in vivo metabolism, preparation, design, and clinical translation. Based on the latest research reports, this review summarizes the biology, synthesis, characteristics, and distribution of red blood cell-derived materials. Furthermore, we provide a reference for further research and clinical transformation by comprehensively discussing the applications and technical challenges faced by red blood cell-derived materials in the treatment of malignant tumors.

4.
J Pak Med Assoc ; 73(9): 1921-1922, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37817717

ABSTRACT

Hepatic Haemangioma is the most common benign liver tumour. There are two types of haemangiomas: capillary haemangioma and cavernous haemangiomas. The term"giant haemangioma"isreserved for lesionslarger than 5 cm. Given the abundance of vascular structures around the liver, SPECT/CT hybrid imaging with 99mTc labelled Red Blood Cells (RBCs) constitutes an excellent modality for localization and characterization of hepatic haemangiomas.


Subject(s)
Hemangioma, Cavernous , Hemangioma , Liver Neoplasms , Humans , Hemangioma/diagnostic imaging , Hemangioma, Cavernous/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Tomography, X-Ray Computed
5.
BMC Infect Dis ; 23(1): 483, 2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37468843

ABSTRACT

BACKGROUND: Bacterial vaginosis (BV) is one of the most common infections among women of reproductive age and accounts for 15-50% of infections globally. The role played by folate in the pathogenesis and progression of BV is poorly understood. The aim of this study was to investigate the association between serum folate, red blood cell (RBC) folate, and BV in American women. METHODS: 1,954 participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) program were included in this study. Multiple logistic regression was used to analyze the association between serum folate, RBC folate, and BV, and covariates including race, age, education level, and body mass index were used to construct adjusted models. Stratified analysis was used to explore the stability of the above associations in different populations. RESULTS: In the present cross-sectional study, we found that serum folate and RBC folate were inversely associated with the risk of BV. In the fully adjusted model, the risk of BV was reduced by 35% (OR=0.65, 95% CI: 0.51~0.83, p=0.0007) in the highest serum folate group and 32% (OR=0.68, 95% CI: 0.53~0.87, p=0.0023) in the highest RBC folate group compared to the lowest group. CONCLUSIONS: The results of this study indicated that serum folate and RBC folate were inversely associated with the risk of BV folate supplementation may play an important role in the prevention and management of BV.


Subject(s)
Folic Acid , Vaginosis, Bacterial , Humans , Female , United States/epidemiology , Vaginosis, Bacterial/epidemiology , Nutrition Surveys , Cross-Sectional Studies , Logistic Models
6.
Cells ; 12(12)2023 06 19.
Article in English | MEDLINE | ID: mdl-37371132

ABSTRACT

BACKGROUND: The soluble form of receptor for advanced glycation end products (sRAGE) have been implicated in the prevention of numerous pathologic states, and highlights as an attractive therapeutic target. Because diets rich in monounsaturated fatty acids (MUFA) reduce postprandial oxidative stress and inflammation that is related to better health during aging, we investigated the association between red blood cell (RBC) fatty acids with circulatory AGE biomarkers and further stratified this correlation based on GG and GA + AA genotype. METHODS: A total of 172 healthy participants (median age = 53.74 ± 0.61 years) were recruited for the study. RBC fatty acid was analysed using gas chromatography and sRAGE was measured using a commercial ELISA kit. RESULTS: The result showed a non-significant correlation between total MUFA with sRAGE however oleic acid (C18:1) exhibited a positive correlation (r = 0.178, p = 0.01) that remained statistically significant (ß = 0.178, p = 0.02) after a stepwise multivariate regression analysis after adjusting for age, BMI and gender. In a univariate analysis, a positive significant correlation between C18:1 and sRAGE in GG genotype (r = 0.169, p = 0.02) and a non-significant correlation with GA + AA genotype (r = 0.192, p = 0.21) was evident. When C18:1 was stratified, a significant difference was observed for oleic acid and G82S polymorphism: low C18:1/GA + AA versus high C18:1/GG (p = 0.015) and high C18:1/GA + AA versus high C18:1/GG (p = 0.02). CONCLUSION: Our study suggests that increased levels of C18:1 may be a potential therapeutic approach in increasing sRAGE in those with GG genotype and play a role in modulating AGE metabolism.


Subject(s)
Erythrocytes , Maillard Reaction , Oleic Acid , Receptor for Advanced Glycation End Products , Humans , Middle Aged , Alleles , Oleic Acid/analysis , Oleic Acid/blood , Oleic Acid/metabolism , Polymorphism, Genetic , Receptor for Advanced Glycation End Products/genetics , Receptor for Advanced Glycation End Products/metabolism , Erythrocytes/chemistry
7.
Am J Physiol Lung Cell Mol Physiol ; 324(6): L825-L835, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37014821

ABSTRACT

Band 3 protein is a Cl-/[Formula: see text] transporter on the red blood cell (RBC) surface with an important role in CO2 excretion. Greater band 3 expression by roughly 20% is found in people with the GP.Mur blood type. Intriguingly, a disproportional percentage of those with GP.Mur excel in field-and-track sports. Could higher band 3 activity benefit an individual's physical performance? This study explored the impact of GP.Mur/higher band 3 expression on ventilation and gas exchange during exhaustive exercise. We recruited 36 nonsmoking, elite male athletes (36.1% GP.Mur) from top sports universities to perform incremental exhaustive treadmill cardiopulmonary exercise testing (CPET). We analyzed CPET data with respect to absolute running time and to individual's %running time and %maximal O2 uptake. We found persistently higher respiratory frequencies and slightly lower tidal volume in GP.Mur athletes, resulting in a slightly larger increase of ventilation as the workload intensified. The expiratory duty cycle (Te/Ttot) was persistently longer and inspiratory duty cycle (Ti/Ttot) was persistently shorter for GP.Mur subjects throughout the run. Consequently, end-tidal pressure of carbon dioxide ([Formula: see text], a surrogate marker for alveolar and arterial CO2 tension-[Formula: see text] and [Formula: see text]) was lower in the GP.Mur athletes during the early stages of exercise. In conclusion, athletes with GP.Mur and higher band 3 expression hyperventilate more during exercise in a pattern that uses a greater fraction of time for expiration than inspiration to increase the rate of CO2 excretion than increased tidal volume. This greater ventilation response reduced Pco2 and may help to extend exercise capacity in high-level sports.NEW & NOTEWORTHY Higher expression of the Cl-/[Formula: see text] transporter band 3 anion exchanger-1 (AE1) on the red blood cell membrane, as in people with the GP.Mur blood type, increases the rate of CO2 excretion during exercise.


Subject(s)
Carbon Dioxide , Pulmonary Gas Exchange , Humans , Male , Carbon Dioxide/metabolism , Pulmonary Gas Exchange/physiology , Respiration , Lung/metabolism , Exhalation
8.
Life (Basel) ; 13(2)2023 Feb 02.
Article in English | MEDLINE | ID: mdl-36836774

ABSTRACT

Molecular hydrogen has an anti-inflammatory and cardioprotective effect, which is associated with its antioxidant properties. Erythrocytes are subjected to oxidative stress in pathologies of the cardiovascular system, which is the cause of a violation of the gas transport function of blood and microcirculation. Therefore, our aim was to investigate the effects of H2 inhalation on the functional states of red blood cells (RBCs) in chronic heart failure (CHF) in rats. The markers of lipid peroxidation, antioxidant capacity, electrophoretic mobility of erythrocytes (EPM), aggregation, levels of adenosine triphosphate (ATP) and 2,3-diphosphoglyceric acid (2,3-DPG), hematological parameters were estimated in RBCs. An increase in EPM and a decrease in the level of aggregation were observed in groups with multiple and single H2 application. The orientation of lipoperoxidation processes in erythrocytes was combined with the dynamics of changes in oxidative processes in blood plasma, it was observed with both single and multiple exposures, although the severity of the changes was greater with multiple H2 inhalations. Probably, the antioxidant effects of molecular hydrogen mediate its metabolic action. Based on these data, we conclude the use of H2 improves microcirculation and oxygen transport function of blood and can be effective in the treatment of CHF.

9.
Clin Hemorheol Microcirc ; 83(3): 231-245, 2023.
Article in English | MEDLINE | ID: mdl-36565107

ABSTRACT

BACKGROUND AND OBJECTIVE: Microfluidics is a useful tool for investigating blood microrheology. The study aimed to present the development of a microfluidic device for assessing the microrheological properties of blood cells' suspensions and its application in patients with diabetes mellitus type 2 (T2DM). METHODS: A new microfluidic device was elaborated, connected to a system, including a microscope with a digital camera, a pump with a manometer and a computer with specially developed software. Blood cells' suspensions were investigated in a microchamber between two parallel optical slides within a 100µm distance. The motion of the blood cells in the microchamber was observed by the microscope and it was recorded and visualized by a digital camera. A method for evaluating the deformability of blood cells and a device for its implementation were used [1]. RESULTS: The pressure and flow rate ranges in the microfluidic device were specified by model suspensions of beta-ferroxy-hydroxide and red blood cells (RBC) suspensions. The pressure changes, realized by a pump (micropipette), connected to a manometer were established and the corresponding shear rates in the microfluidic device were determined. Data about the blood microrheological properties like RBC aggregation and deformability, leukocyte adhesion from a group of healthy volunteers and from patients with T2DM were obtained. CONCLUSIONS: The developed device and experimental system is a promising tool for the study of blood microrheology.


Subject(s)
Diabetes Mellitus, Type 2 , Microfluidics , Humans , Erythrocyte Deformability , Suspensions , Erythrocytes , Lab-On-A-Chip Devices
10.
Vox Sang ; 118(2): 147-152, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36510386

ABSTRACT

BACKGROUND AND OBJECTIVES: Early studies indicate that red cell A and B antigens are attached primarily onto band 3 and GLUT1 on the erythrocyte membrane and little onto glycophorin A (GPA) and glycophorin B (GPB). But as GPA and band 3 form stable protein complexes and GPA is much more heavily glycosylated than band 3, this study re-examined the association between ABO antigens and GPA/GPB. MATERIALS AND METHODS: Band 3/GPA-associated protein complexes were first immunoprecipitated, followed by differential enzymatic deglycosylation that removed sialic acids, N-glycans and O-glycans. Serological anti-A (BIRMA 1) and anti-B IgM (GAMA 110) could be used for western blot (WB); however, only the anti-B IgM showed significant reactivity for the immunoprecipitates isolated by anti-band 3. The expression of the B antigen in un-deglycosylated and differentially deglycosylated band 3 immunoprecipitates was thus compared. RESULTS: Besides attachment to band 3, red cell B antigen expressed substantially on GPA monomer and homodimer, GPA*GPB heterodimer, and GPB monomer and dimer via attachments through the N- and O-glycans. CONCLUSION: Immunoprecipitation (IP), as a means of protein separation and concentration, was used in combination with a WB to differentiate glycosylation on different proteins and oligomers. This study implemented differential enzymatic deglycosylation during IP of the band 3 complexes. This combined approach allowed separate identification of the B antigen on GPA/GPB monomer and dimer and GPA*GPB heterodimer, and band 3 on the WB and verified non-trivial expression of the B antigen on GPA and GPB on the erythrocyte surface.


Subject(s)
Blood Group Antigens , Glycophorins , Humans , Glycophorins/metabolism , Anion Exchange Protein 1, Erythrocyte/metabolism , Erythrocytes , Blood Group Antigens/metabolism , Carbohydrates , Immunoglobulin M
11.
Front Bioeng Biotechnol ; 10: 1049878, 2022.
Article in English | MEDLINE | ID: mdl-36561046

ABSTRACT

Red blood cells (RBCs) clump together under low flow conditions in a process called RBC aggregation, which can alter RBC perfusion in a microvascular network. As elevated RBC aggregation is commonly associated with cardiovascular and inflammatory diseases, a better understanding of aggregation is essential. Unlike RBC aggregation in polymer solutions which can be well explained by polymer depletion theory, plasma-mediated RBC aggregation has features that best match explanations with cross-bridging mechanisms. Previous studies have demonstrated the dominant role of fibrinogen (Fg) in promoting aggregate formation and recent cell-force spectroscopy (CFS) experiments on interacting RBC doublets in plasma have reported an inverse relationship between disaggregation force and the adhesive contact area between RBCs. This has led investigators to revisit the hypothesis of inter-RBC cross-bridging which involves cross-bridge migration under interfacial tension during the forced disaggregation of RBC aggregates. In this study, we developed the cross-bridge migration model (CBMM) in plasma that mechanistically represents the migrating cross-bridge hypothesis. Transport of mobile Fg cross-bridges (mFg) was calculated using a convection-diffusion transport equation with our novel introduction of convective cross-bridge drift that arises due to intercellular friction. By parametrically transforming the diffusivity of mFg in the CBMM, we were able to match experimental observations of both RBC doublet formation kinematics and RBC doublet disaggregation forces under optical tweezers tension. We found that non-specific cross-bridging promotes spontaneous growth of adhesion area between RBC doublets whereas specific cross-bridging tends to prevent adhesion area growth. Our CBMM was also able to correlate Fg concentration shifts from healthy population blood plasma to SLE (lupus) condition blood plasma with the observed increase in doublet disaggregation forces for the RBC doublets in SLE plasma.

12.
Am J Kidney Dis ; 80(3): 383-392, 2022 09.
Article in English | MEDLINE | ID: mdl-35777984

ABSTRACT

Evaluation of hematuria and microscopic examination of urine sediment are commonly used tools by nephrologists in their assessment of glomerular diseases. Certain morphological aspects of urine red blood cells (RBCs) seen by microscopy may help in identifying the source of hematuria as glomerular or not. Recognized signs of glomerular injury are RBC casts or dysmorphic RBCs, in particular acanthocytes (ring-shaped RBCs with protruding blebs). Despite being a highly operator-dependent test, urine sediment examination revealing these signs of glomerular hematuria has demonstrated specificities and positive predictive values ranging between 90%-100% for diagnosing glomerular disease, although sensitivity can be quite variable. Hematuria is a commonly used tool for diagnosing patients with proliferative glomerulonephritis such as IgA nephropathy, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and lupus nephritis, sometimes even as a surrogate for kidney involvement. Studies examining the role for hematuria in monitoring and predicting adverse outcomes in these diseases have shown inconsistent results, possibly due to inconsistent definitions that often fail to consider specific markers of glomerular hematuria such as dysmorphic RBCs, acanthocytes, or RBC casts. A consensus definition of what constitutes glomerular hematuria would help standardize use in future studies and likely improve the diagnostic and prognostic value of hematuria as a marker of glomerulonephritis.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Glomerulonephritis, IGA , Glomerulonephritis , Biomarkers , Glomerulonephritis/complications , Glomerulonephritis/diagnosis , Hematuria/diagnosis , Hematuria/etiology , Humans , Kidney Glomerulus , Microscopy
13.
Indian J Hematol Blood Transfus ; 38(2): 373-380, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35496977

ABSTRACT

The present study aims to investigate the changes in different parameters related to the storage time of red blood cell (RBC) units. Microscopic, flow cytometric, and electrophoretic assessments were employed every few days for 60 days to investigate the alterations in morphology, size, phosphatidylserine (PS) externalization, and membrane proteins over time. Morphological transformation from discocytes to spherocytes progressed as the storage time increased, which was accompanied by an increment of cellular size. However, this storage period did not result in the externalization of significant amounts of PS (p > 0.05). Mean Fluorescence Intensity (MFI) values increased by 11% to 23% between days 21 and 35 compared to the day 1 sample (p < 0.001). By day 60, the MFI decreased to about 70% of the day 1 sample. The analysis of membrane proteins' distribution showed a significant drop in band 3 expression after 35 days (p < 0.05 and 0.001 on days 42 and 60, respectively); however, no significant change was observed up to five weeks (p > 0.05). The inconsistency observed between Eosin-5-Maleimide (5-EMA) binding and the relative band 3 content could be due to additional accessibility of 5-EMA to hidden domains of other membrane proteins on RBCs as a result of increased mean corpuscular volume (MCV) and changes in morphology. Overall, our present study represents a step-wise and time-dependent series of events that progressively affects stored RBCs.

14.
Clin Hemorheol Microcirc ; 81(4): 325-341, 2022.
Article in English | MEDLINE | ID: mdl-35527542

ABSTRACT

BACKGROUND: In the blood vessels the impaired hemorheological parameters in patients with type 2 diabetes mellitus (T2DM) could lead to elevated flow resistance, increased forces at the endothelial wall and to microvascular disturbances. OBJECTIVE: The aim of the study is to investigate the hemorheological variables and the changes of the skin blood flow responses to cold stress in T2DM patients. METHODS: The basic hemorheological parameters: hematocrit (Ht), fibrinogen (Fib), whole blood viscosity (WBV) and plasma viscosity (PV) were examined in 20 patients with T2DM and a control group of 10 healthy age and sex matched controls. The mechanisms of vascular tone regulation were investigated using the wavelet analysis of the skin temperature oscillations (WAST). The degrees of the microvascular tone changes were determined during a cold test in the endothelial (0.02-0.0095 Hz), neurogenic (0.05- 0.02 Hz) and myogenic (0.05- 0.14 Hz) frequency ranges. RESULTS: Significant increase of Fib and WBV in the patients in comparison to controls was found. The mean values of the amplitudes of the skin temperature (ST) pulsations decreased significantly during the cold stress only in the endothelial frequency range for the diabetic patients. CONCLUSIONS: The results of our study reveal parallel impairment of the blood rheological parameters and the cutaneous microcirculation in T2DM patients.


Subject(s)
Diabetes Mellitus, Type 2 , Blood Viscosity/physiology , Erythrocyte Aggregation , Erythrocyte Deformability , Fibrinogen , Hematocrit , Hemorheology , Humans , Microcirculation
15.
Front Physiol ; 13: 838138, 2022.
Article in English | MEDLINE | ID: mdl-35283784

ABSTRACT

Refrigerated storage of red cell concentrates before transfusion is associated with progressive alterations of red blood cells (RBC). Small RBC (type III echinocytes, sphero-echinocytes, and spherocytes) defined as storage-induced micro-erythrocytes (SME) appear during pretransfusion storage. SME accumulate with variable intensity from donor to donor, are cleared rapidly after transfusion, and their proportion correlates with transfusion recovery. They can be rapidly and objectively quantified using imaging flow cytometry (IFC). Quantifying SME using flow cytometry would further facilitate a physiologically relevant quality control of red cell concentrates. RBC stored in blood bank conditions were stained with a carboxyfluorescein succinimidyl ester (CFSE) dye and incubated at 37°C. CFSE intensity was assessed by flow cytometry and RBC morphology evaluated by IFC. We observed the accumulation of a CFSE high RBC subpopulation by flow cytometry that accounted for 3.3 and 47.2% at day 3 and 42 of storage, respectively. IFC brightfield images showed that this CFSE high subpopulation mostly contains SME while the CFSE low subpopulation mostly contains type I and II echinocytes and discocytes. Similar numbers of SME were quantified by IFC (based on projected surface area) and by flow cytometry (based on CFSE intensity). IFC and scanning electron microscopy showed that ≥95% pure subpopulations of CFSE high and CFSE low RBC were obtained by flow cytometry-based sorting. SME can now be quantified using a common fluorescent dye and a standard flow cytometer. The staining protocol enables specific sorting of SME, a useful tool to further characterize this RBC subpopulation targeted for premature clearance after transfusion.

16.
Arch Toxicol ; 96(5): 1387-1409, 2022 05.
Article in English | MEDLINE | ID: mdl-35294598

ABSTRACT

The present study compares two approaches to evaluate the effects of inter-individual differences in the biotransformation of chlorpyrifos (CPF) on the sensitivity towards in vivo red blood cell (RBC) acetylcholinesterase (AChE) inhibition and to calculate a chemical-specific adjustment factor (CSAF) to account for inter-individual differences in kinetics (HKAF). These approaches included use of a Supersome™ cytochromes P450 (CYP)-based and a human liver microsome (HLM)-based physiologically based kinetic (PBK) model, both combined with Monte Carlo simulations. The results revealed that bioactivation of CPF exhibits biphasic kinetics caused by distinct differences in the Km of CYPs involved, which was elucidated by Supersome™ CYP rather than by HLM. Use of Supersome™ CYP-derived kinetic data was influenced by the accuracy of the intersystem extrapolation factors (ISEFs) required to scale CYP isoform activity of Supersome™ to HLMs. The predicted dose-response curves for average, 99th percentile and 1st percentile sensitive individuals were found to be similar in the two approaches when biphasic kinetics was included in the HLM-based approach, resulting in similar benchmark dose lower confidence limits for 10% inhibition (BMDL10) and HKAF values. The variation in metabolism-related kinetic parameters resulted in HKAF values at the 99th percentile that were slightly higher than the default uncertainty factor of 3.16. While HKAF values up to 6.9 were obtained when including also the variability in other influential PBK model parameters. It is concluded that the Supersome™ CYP-based approach appeared most adequate for identifying inter-individual variation in biotransformation of CPF and its resulting RBC AChE inhibition.


Subject(s)
Chlorpyrifos , Acetylcholinesterase/metabolism , Chlorpyrifos/toxicity , Cytochrome P-450 Enzyme System/metabolism , Humans , Kinetics , Liver/metabolism , Microsomes, Liver/metabolism , Models, Biological , Monte Carlo Method , Toxicokinetics
18.
Ann Med Surg (Lond) ; 75: 103383, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35198198

ABSTRACT

A red blood cell (RBC) transfusion can be fatal if an acute hemolytic transfusion reaction (AHTR) occurs. In the past, ABO-incompatible blood transfusions were the most common cause of hemolysis-associated acute kidney injury (AKI); however, these are now rare due to improving blood banking practices. A 29-year- old obstetric female of blood group A positive was admitted due to anuric AKI and intravascular hemolysis after receiving an incompatible transfusion of blood group AB positive. The patient displayed a classic triad of symptoms a few minutes after the transfusion and fortunately, the infant was saved by the performance of an immediate cesarean section. The patient required four sessions of hemodialysis during their hospital stay due to severe uremia and acute pulmonary edema. Kidney function improved very slowly and returned to near normal after six weeks. This case was the second obstetric patient; admitted to our hospital; in the past few months with prolonged AKI induced by an ABO-incompatible blood transfusion. Complications arising from a RBC transfusion can be exhausting for the patient and medical staff and require a long hospital stay and high costs. This demonstrates the need for medical staff to reserve blood transfusions for obvious indications, to repeat the blood type, and to confirm the recorded compatibility of the patient and the blood unit before transfusion. Also, medical staff should always monitor the patient's symptoms during the transfusion process, to recognize these severe conditions and to administer effective treatments as soon as possible.

19.
J Theor Biol ; 539: 110982, 2022 04 21.
Article in English | MEDLINE | ID: mdl-35051431

ABSTRACT

This paper develops a detailed model of human and bovine erythrocytes quantifying the dependence of total cell volume upon composition of an aqueous solution in which it is immersed. The cytoplasm is represented as an aqueous solution of hemoglobin and salt (KCl or NaCl). Model-based analysis of literature data on human erythrocytes, and of new experiments with bovine erythrocytes, leads to two findings. First, the Boyle-van't Hoff plot for human erythrocytes is found to be well described based on a solid volume fraction of âˆ¼0.3 in complete agreement with desiccation experiments. The linear portion of the calculated curve turns out to be numerically indistinguishable from the commonly used ideal model parameterized with an apparent osmotically inactive volume fraction of âˆ¼0.5. This mathematical outcome explains the longstanding perceived (but actually nonexistent) disconnect between the aforementioned fractions âˆ¼0.3 and âˆ¼0.5. A corollarial implication is that the actual volume fraction of osmotically nonparticipant (vicinal) water is very small (∼0.035). Second, an initial crenation of bovine erythrocytes (which occurs in classical techniques for measuring membrane permeability) is found to increase their fragility to an extent which correlates well with the crenated cell volume, and would affect the permeability determination.


Subject(s)
Erythrocytes , Hemoglobins , Animals , Cattle , Cell Membrane Permeability , Cell Size , Hemoglobins/metabolism , Humans , Osmotic Fragility
20.
J Cardiothorac Vasc Anesth ; 36(7): 1908-1918, 2022 07.
Article in English | MEDLINE | ID: mdl-34969561

ABSTRACT

OBJECTIVE: To evaluate racial and/or ethnic and sex disparities in allogeneic and autologous red blood cell (RBC) transfusions in cardiac surgery. DESIGN: A retrospective observational study. SETTING: 2007 to 2018 data from FL, MD, KY, WA, NY, and CA from the State Inpatient Databases (SID), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality. PARTICIPANTS: A total of 710,296 inpatients who underwent elective or emergency coronary artery bypass grafting (CABG), cardiac valve surgery,or combination CABG and/or valve surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were cohorted by race and/or ethnicity and sex, as defined by SID-HCUP. Demographic characteristics and comorbidities were compared. Rates and risk-adjusted odds ratios (aOR) were calculated for allogeneic and autologous RBC transfusion (primary outcomes). Additional secondary analyses were conducted for in-hospital mortality, 30-day readmission, 90-day readmission, hospital length of stay, and total charges to examine the effect of RBC transfusion status. Effect modification between race and sex was assessed. When controlling for patient demographics, comorbidities, and hospital characteristics, non-White patients were more likely to receive an allogeneic RBC transfusion during cardiac surgery than White patients (Black: aOR 1.17, 99% CI 1.13-1.20, p < 0.001, Hispanic: aOR 1.22, 99% CI 1.19-1.22, p < 0.001). Women were more likely to receive allogeneic RBC than men (aOR 1.69, 99% CI 1.66-1.72, p < 0.001). In interaction models, non-White women had the highest odds of allogeneic blood transfusion as compared to White men (reference category; Black women: aOR 2.04, 99% CI 1.91-2.17, p < 0.001, Hispanic women: aOR 2.03, 99% CI 1.90-2.16, p < 0.001). CONCLUSION: These findings highlighted the differences in the rates of allogeneic RBC transfusion for non-White and female patients undergoing cardiac surgery, which is a well-established marker of poorer outcomes.


Subject(s)
Cardiac Surgical Procedures , Hematopoietic Stem Cell Transplantation , Female , Humans , Male , Blood Transfusion , Erythrocyte Transfusion , Ethnicity , Retrospective Studies
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