Blood Plasma Proteins Research Articles

THE INFLUENCE OF DIETARY BASIC LIMITING AMINO ACIDS AND METABOLIC ENERGY LEVELS ON PROTEIN METABOLISM INDICATORS AND PRODUCTIVITY OF PIGLETS

Data about the influence of most limiting essential amino acids (lysine, methionine, threonine) and metabolic energy (ME), provided that their level in the diet increases on the growth and content of total protein, urea and uric acid in the blood plasma of piglets are presented in the article. The stimulatory influence of these additions to the piglets' diet on the growth and protein metabolism in their body was shown. The positive effect of the introduction of essential amino acids (lysine, methionine and threonine) and sunflower oil to the diet on the taste of the mixed feed, the intensity of its eating and the growth of piglets was shown in the conducted research. The greatest gains in piglets of the 4th experimental group, where the level of ME in the diet was 13.72 MJ, lysine - 13.8 g / kg, methionine and threonine - 9.2 g / kg of the mixed feed were observed. At the same time, the safety of piglets was directly proportional to their average daily gain. The highest it was in piglets of the 4th experimental group (96.7%), and the lowest in the control group (89.7%). The increase of the content of lysine, methionine, threonine and fat in the piglets' diet led to an increase in the blood plasma of proteins level and a decrease of urea and uric acid. A clear tendency to increased total protein concentration in blood, when increasing the intensity of pre-starter mixed feed intake by piglets with the additional introduction of lysine, methionine, threonine and sunflower oil was observed. It follows from these data that if the level of the most limiting essential amino acids (lysine, methionine and threonine) increases in the diet, the synthesis of blood plasma proteins in the liver of piglets increases and this process is stimulated by the addition of fat. At the same time, feeding young piglets with amino acid and fat additions contributed to a decrease in the content of urea and uric acid in blood plasma. A significant influence of the investigated factors on the use of amino acids and metabolic energy in energy processes in the animal body indicated.

Metabolic role using a feed additive of humic nature 'humilid' on the organism of black African ostriches and broiler chickens

The study investigated the influence of the humic nature feed additive 'humilid' on physiological and biochemical parameters of blood and liver in black African ostriches and broiler chickens (Cobb 500 cross) that characterise the state of protein metabolism in agricultural poultry. Results showed that morphological and biochemical blood parameters that characterise protein metabolism state were improved in the blood of ostriches by adding 'humilid' into their diet. It was also found with 'humilid' the total content of amino acids in all types of ostriches muscles was significantly higher. It was shown that in broiler chickens 'Cobb 500' cross, to which 'humilid' was added to the water, there was an increase in the total protein of blood plasma and in the water-soluble fraction of the liver. In conclusion, additional use of the 'humilid' feed additive in poultry had increased the body's natural resistance, activated metabolic processes, and due to an increase in the muscle tissue, the content of total protein, essential amino acids and by this, it had an increase in the biological value of meat products.

Albumin-driven disassembly of lipidic nanoparticles: the specific case of the squalene-adenosine nanodrug.

In the field of nanomedicine, nanostructured nanoparticles (NPs) made of self-assembling prodrugs emerged in the recent years with promising properties. In particular, squalene-based drug nanoparticles have already shown their efficiency through in vivo experiments. However, a complete pattern of their stability and interactions in the blood stream is still lacking. In this work we assess the behavior of squalene-adenosine (SQAd) nanoparticles - whose neuroprotective effect has already been demonstrated in murine models - in the presence of fetal bovine serum (FBS) and of bovine serum albumin (BSA), the main protein of blood plasma. Extensive physicochemical characterizations were performed using Small Angle Neutron Scattering (SANS), cryogenic transmission electron microscopy (Cryo-TEM), circular dichroism (CD), steady-state fluorescence spectroscopy (SSFS) and isothermal titration calorimetry (ITC) as well as in silico by means of ensemble docking simulations with human serum albumin (HSA). Significant changes in the colloidal stability of the nanoparticles in the presence of serum albumin were observed. SANS, CD and SSFS analyses demonstrated an interaction between SQAd and BSA, with a partial disassembly of the nanoparticles in the presence of BSA and the formation of a complex between SQAd and BSA. The interaction free energy of SQAd nanoparticles with BSA derived from ITC experiments, is about -8 kcal mol-1 which is further supported in silico by ensemble docking simulations. Overall, our results show that serum albumin partially disassembles SQAd nanoparticles by extracting individual SQAd monomers from them. As a consequence, the SQAd nanoparticles would act as a circulating reservoir in the blood stream. The approach developed in this study could be extended to other soft organic nanoparticles.

RISK MANAGEMENT OF USE DRUGS WITH NARROW THERAPEUTIC INDEX IN CLINICAL PRACTICE. Review

Relevance. Today, the pharmacotherapy of many diseases is significantly expanded. However, the amount of pathological conditions associated with the use of drugs has increased. Drug related problems in some cases can be fatal and increase health care costs. It is necessary to be able to anticipate in advance the possibility of developing such conditions, to prevent them. Therefore, the analysis of the causes and mechanisms of development of these conditions is relevant.
 Objective. To find out the most common causes of drug related problems and consider the mechanisms of such states.
 Methods. Analysis of scientific publications in PubMed by keywords for the period 2001-2018.
 Results. The therapeutic index is the ratio of the dose that causes toxic effects in 50% of patients to the dose that causes the expected therapeutic effect in 50% of patients. The therapeutic index ≤ 3 is an indicator that defines drugs with narrow (small) therapeutic index. These drugs include insulin, digoxin, warfarin, levothyroxine, aminoglycoside antibiotics, carbamazepine, lithium, phenytoin, etc.
 The risks associated with these drugs are: the use of generic drugs with insufficient bioequivalence, pharmacokinetic interaction and polymorphism of genes of drug metabolism. The main mechanisms of their pharmacokinetic interaction at the stages of absorption (alteration of digestive tract motility, influence on the activity of P-glycoprotein), distribution (competition for blood plasma proteins and tissue proteins), and biotransformation (inhibition or induction of metabolism). The role of polymorphism of genes encoding the activity of isoenzymes cytochrome P450 2C9 and 1A2 and glycoprotein P in the development of adverse drug reactions of drugs with a narrow therapeutic index is presented.
 Conclusion. Risk management of using drugs with a narrow therapeutic index should include therapeutic drug monitoring of especially generic drugs, assessment of the risks of pharmacokinetic interaction, widespread introduction pharmacogenetic tests for determine the polymorphism of the genes of metabolism enzymes and drug transporters in the clinical practice.

FAAH levels and its genetic polymorphism association with susceptibility to methamphetamine dependence

The fatty acid amide hydrolase (FAAH) gene was involved in the modulation of reward and addiction pathophysiology of illicit drugs abuse, and its polymorphisms might be associated with risk of methamphetamine (METH) dependence. This study aimed to investigate the FAAH mRNA levels in peripheral blood mononuclear cells and plasma protein levels and to analyze the 385C/A polymorphism (rs324420) between METH-dependent patients and controls. The levels of FAAH mRNA in METH dependence were significantly lower than in controls (P<0.001), however, its plasma protein underwent a significant ∼2-fold increase (P<0.001). The A allele of the 385C/A polymorphism significantly increased the METH dependence risk (P<0.001, odds ratio [OR]=1.646, 95% confidence interval [CI]=1.332-2.034). The carried A genotypes (AA, AC, and AA/AC) of 385C/A polymorphism also increased METH-dependence risks under a different genetic model (AA vs. CC: P=0.017, OR=2.454, 95%CI=1.171-2.143; AC vs. CC: P<0.001, OR=1.818, 95%CI=1.404-2.353; AC/AA vs. CC: P<0.001, OR=1.858, 95%CI=1.444-2.319). The similar results were obtained after adjusting for age and sex. Unfortunately, we failed to find that any genotype of 385C/A polymorphism affected the mRNA or plasma protein levels in controls, respectively (P>0.05). These data indicate that the FAAH may play an important role in the pathophysiological process of METH dependence, and the 385C/A polymorphism may be associated with METH dependence susceptibility in a Chinese Han population.

Development of reference methods of measurements mass (molar) concentration of proteins in the field of physical and chemical analysis of blood

The work is devoted to the development of reference methods for measuring the mass concentration of proteins in blood plasma that would meet modern metrological requirements (high accuracy of reference values, metrological traceability, etc.), which will allow the use of modern high-tech methods of physicochemical analysis.

Platelet-derived- Extracellular Vesicles Promote Hemostasis and Prevent the Development of Hemorrhagic Shock

Every year more than 500,000 deaths are attributed to trauma worldwide and severe hemorrhage is present in most of them. Transfused platelets have been shown to improve survival in trauma patients, although its mechanism is only partially known. Platelet derived-extracellular vesicles (PEVs) are small vesicles released from platelets upon activation and/or mechanical stimulation and many of the benefits attributed to platelets could be mediated through PEVs. Based on the available literature, we hypothesized that transfusion of human PEVs would promote hemostasis, reduce blood loss and attenuate the progression to hemorrhagic shock following severe trauma. In this study, platelet units from four different donors were centrifuged to separate platelets and PEVs. The pellets were washed to obtain plasma-free platelets to use in the rodent model. The supernatant was subjected to tangential flow filtration for isolation and purification of PEVs. PEVs were assessed by total count and particle size distribution by Nanoparticle Tracking Analysis (NTA) and characterized for cells of origin and expression of EV specific-surface and cytosolic markers by flow cytometry. The coagulation profile from PEVs was assessed by calibrated automated thrombography (CAT) and thromboelastography (TEG). A rat model of uncontrolled hemorrhage was used to compare the therapeutic effects of 8.7 × 108 fresh platelets (FPLT group, n = 8), 7.8 × 109 PEVs (PEV group, n = 8) or Vehicle (Control, n = 16) following severe trauma. The obtained pool of PEVs from 4 donors had a mean size of 101 ± 47 nm and expressed the platelet-specific surface marker CD41 and the EV specific markers CD9, CD61, CD63, CD81 and HSP90. All PEV isolates demonstrated a dose-dependent increase in the rate and amount of thrombin generated and overall clot strength. In vivo experiments demonstrated a 24% reduction in abdominal blood loss following liver trauma in the PEVs group when compared with the control group (9.9 ± 0.4 vs. 7.5 ± 0.5 mL, p < 0.001>). The PEV group also exhibited improved outcomes in blood pressure, lactate level, base excess and plasma protein concentration compared to the Control group. Fresh platelets failed to improve these endpoints when compared to Controls. Altogether, these results indicate that human PEVs provide pro-hemostatic support following uncontrolled bleeding. As an additional therapeutic effect, PEVs improve the outcome following severe trauma by maintaining hemodynamic stability and attenuating the development of ischemia, base deficit, and cardiovascular shock.

Role of glutathione redox system on the susceptibility to deoxynivalenol of pheasant (Phasianus colchicus)

There are only a few reports on the effects of mycotoxins on pheasant (Phasianus colchicus) and the susceptibility to deoxynivalenol of these birds have never been reported before. The present experiment focuses to investigate the effects of different dietary concentrations of deoxynivalenol on blood plasma protein content, some parameters of lipid peroxidation and glutathione redox system and on the performance of pheasant chicks. A total of 320 1-day-old female pheasants were randomly assigned to four treatment groups fed with a diet contaminated with deoxynivalenol (control, 5.11 mg/kg, 11.68 mg/kg and 16.89 mg/kg). Birds were sacrificed at early (12, 24 and 72 h) and late (1, 2 and 3 weeks) stages of the experiment to demonstrate the oxidative stress-inducing effect of deoxynivalenol. Feed refusal was dose dependent, especially in the last third of the trial, but only minor body weight gain decrease was found. Lipid-peroxidation parameters did not show dose-dependent effect, except in blood plasma during the early stage of the trial. The glutathione redox system, reduced glutathione content and glutathione peroxidase activity, was activated in the liver, but primarily in the blood plasma. Glutathione peroxidase activity has changed parallel with reduced glutathione concentration in all tissues. Comparing our results with literature data, pheasants seem to have the same or higher tolerance to deoxynivalenol than other avian species, and glutathione redox system might contribute in some extent to this tolerance, as effective antioxidant defence against oxidative stress.

Determinants of Hemodialysis Performance: Modeling Fluid and Solute Transport in Hollow-Fiber Dialyzers.

Hemodialysis constitutes the lifeline of patients with end stage renal disease, yet the parameters that affect hemodialyzer performance remain incompletely understood. We developed a computational model of mass transfer and solute transport in a hollow-fiber dialyzer to gain greater insight into the determinant factors. The model predicts fluid velocity, pressure, and solute concentration profiles for given geometric characteristics, membrane transport properties, and inlet conditions. We examined the impact of transport and structural parameters on uremic solute clearance by varying parameter values within the constraints of standard clinical practice. The model was validated by comparison with published experimental data. Our results suggest solute clearance can be significantly altered by changes in blood and dialysate flow rates, fiber radius and length, and net ultrafiltration rate. Our model further suggests that the main determinant of the clearance of unreactive solutes is their diffusive permeability. The clearance of protein-bound toxins is also strongly determined by blood hematocrit and plasma protein concentrations. Results from this model may serve to optimize hemodialyzer operating conditions in clinical practice to achieve better clearance of pathogenic uremic solutes.

Bioavailability Study of Recombinant Plasmid DNA Nerve Growth Factor after Intramuscular Injection by Electroporation

Comparative analysis of plasmid DNA delivery into cells efficiency (with effective agent concentration 250 μg/kg), ensuring accumulation of nerve growth factor (NGF) after intramuscular injection and intramuscular administration using electroporation method on rats was performed. Application of electroporation method ensured over 4 times increase of DNA plasmid concentration in muscle tissue within the first hour after its injection and increased the duration of its determination. Higher bioavailability parameters were confirmed by 3 times increase in gene expression level, encoding NGF accumulation and 3 times increase in concentration of the target NGF protein in blood plasma. The results obtained allow us to recommend this method for introduction of NGF plDNA in its biological activity and effectiveness in models of nerve damage investigation.

Cadmium-binding proteins in human blood plasma

Blood is the transmission medium for metal contaminants to and from bodily organs; as such, it can provide useful and reliable information about their bio-kinetics as they're distributed throughout the body. Metals can interact with endogenous proteins present in the blood, and these metal-protein complexes often dictate the fates of the introduced metals. The aim of this study was to investigate cadmium-binding protein characteristics in normal human plasma. Cadmium-binding plasma proteins in two different groups: normal human plasma (n = 29), and normal paired maternal and fetal umbilical cord plasmas (n = 3), were analyzed. In order to detect cadmium-binding plasma proteins present in low concentrations, blood plasma samples were first depleted of their two most abundant proteins - albumin and immunoglobulin G. Both the crude and depleted plasma samples were analyzed using column gel electrophoresis in conjunction with Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). One cadmium-binding protein was detected in 11 of 29 normal plasma samples and all three paired maternal and cord plasma samples. This protein was further identified as apolipoprotein A-I by high-resolution mass spectrometry. To the best of our knowledge, this is the first study to reveal cadmium-binding proteins in real human blood plasma, which is extremely critical to our understanding of cadmium transportation and accumulation in human blood.

Application of Mass Spectrometry in Analysis of Non-Enzymatic Glycation Proteins in Diabetic Blood

Abstract Diabetes mellitus (DM) is a metabolic disorder disease characterized by hyperglycemia. Long-term physiological hyperglycemia will aggravate the degree of non-enzymatic glycation (NEG) proteins. Because the abnormal changes of non-enzymatic process can cause a series of pathological variation, NEG proteins have attracted more and more attention. Mass spectrometry (MS) is an indispensable and powerful analytical tool for the qualitative and quantitative analysis of proteins due to its ultra-high sensitivity, excellent detection limits, and multi-component simultaneous analysis, and has been applied to the identification and qualification of NEG proteins. Herein, the principle of NEG proteins and the application of MS in the identification and quantitation of NEG plasma proteins and hemoglobin (Hb) in blood are reviewed. The forecast in the analysis of NEG proteins based on MS is also provided.

Hsp70 Trap Assay for Detection of Misfolded Subproteome Related to Myelodysplastic Syndromes.

The onset and progression of numerous serious diseases (e.g., various types of malignancies, neurodegenerative diseases, and cardiac diseases) are, on a molecular level, associated with protein modifications and misfolding. Current methods for the detection of misfolded proteins are not able to detect the whole misfolded subproteome and, moreover, are rather laborious and time consuming. Herein, we report on a novel simple method for the detection of misfolded proteins employing a surface plasmon resonance (SPR) biosensor and heat shock protein 70 (Hsp70) that recognizes and traps misfolded proteins in a nucleotide-dependent manner. We use this method for the detection of misfolded proteins in blood plasma of patients with various subtypes of myelodysplastic syndromes (MDS) and healthy donors. Our results reveal significantly elevated levels of misfolded proteins in the two stages of MDS that are most affected by oxidative stress: low-risk (RARS) and intermediate-risk (RCMD) patients. This approach can be extended to a variety of diseases and provides unique insights into the thus far unexplored area of blood proteome.

Effects of hydrophobicity, tethering and size on flow-induced activation of von Willebrand factor multimers

Von Willebrand factor (VWF) is a multimeric protein of blood plasma that mediates platelet adhesion to injury under strong hemodynamic flows in arterias and microvasvulature. We present a 3D coarse-grained computer model of VWF multimers in flowing viscous fluid that explicitely grasps the dynamics, the conformational changes and the hydrodynamics-induced activation of adhesivity of these protein concatamers to GPIb receptor of blood platelets. The model is based on the fluctuating Lattice Boltzmann method for modelling the hydrodynamics in the simulation box and the Lagrangian particle dynamics coupled to the fluid by a viscous drag force. The model has been validated by the comparison with the experimental data found in literature. We studied the effect of hydrophobic interactions on the conformational dynamics of VWF multimers. The simulations suggest that the contour length is an important parameter that controls the functionality of VWF multimers in blood. We also demonstrate that tethering to the surface of a vessel wall promoted the flow-induced activation of VWF, while those multimers that remain untethered and move freely in the blood plasma require a stronger shearing to get activated.

Effects of lavender (Lavandula angustifolia) extract inclusion in diet on growth performance, innate immunity, immune-related gene expression, and stress response of common carp, Cyprinus carpio

In the present study, the effects of dietary lavender (Lavandula angustifolia) extract (LE) on growth performance and immune, antioxidant, and stress responses in common carp, Cyprinus carpio were investigated. For this, four diets containing 0, 0.5, 1.0 and 1.5% LE were offered to triplicate groups of fish (25.8 ± 1.66 g) for 70 days, and then the fish were exposed to a 3-h crowding stress. Growth performance, blood leukocyte count, plasma proteins and innate immune parameters, and head kidney cytokines’ gene expression were studied after the 70-day feeding trial (before the crowding stress). Plasma cortisol, glucose, superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were measured before and after the crowding stress. Results showed that dietary LE had no significant effects on the fish growth performance, blood leukocyte differential count, plasma albumin and total protein, and head kidney interferon gamma-1 gene expression. Blood leukocyte and plasma globulin, alternative complement and total immunoglobulin significantly increased in the fish fed with 1.0–1.5% LE diets compared to the fish fed with the control diet (0% LE). The plasma lysozyme activity significantly increased along with dietary LE supplemental levels. The lowest expression of interlukin-1 beta gene was related to the 1.0% LE treatment. Tumor necrosis factor-alpha gene expression significantly decreased along with increase in dietary LE levels and the lowest expression was related to the fish fed with 1.5% LE diet. The LE administration led to significant increase in interlukine-10 gene expression and the highest expression was related to the fish fed with 1.0% and 1.5% LE diets. The fish fed with 1.5% LE diet had significantly higher transforming growth factor-beta gene expression compared to the control group. Liver SOD and CAT activities showed significant increases along with dietary LE supplementation levels. After the crowding stress, hepatic SOD decreased in the control group, but not the LE-supplemented groups. Stress led to significant decrease in hepatic CAT activities in all treatments, but CAT activity increased along with the LE levels with highest activity in the fish fed with 1.5% LE. The stress led to significant increase in hepatic MDA in the treatments control and 0.5% LE, but not 1.0–1.5% LE groups. The stress led to significant increase in plasma cortisol and glucose levels in all treatments but dietary LE levels significantly decreased these parameters. Dietary LE supplementation at levels of 1.0–1.5% is recommended for common carp to suppress stress, inflammation and oxidative conditions and augment immune responses in the fish.

Mechanostability of the Fibrinogen Bridge between Staphylococcal Surface Protein ClfA and Endothelial Cell Integrin αVβ3.

Binding of the Staphylococcus aureus surface protein clumping factor A (ClfA) to endothelial cell integrin αVβ3 plays a crucial role during sepsis, by causing endothelial cell apoptosis and loss of barrier integrity. ClfA uses the blood plasma protein fibrinogen (Fg) to bind to αVβ3 but how this is achieved at the molecular level is not known. Here we investigate the mechanical strength of the three-component ClfA-Fg-αVβ3 interaction on living bacteria, by means of single-molecule experiments. We find that the ClfA-Fg-αVβ3 ternary complex is extremely stable, being able to sustain forces (∼800 pN) that are much stronger than those of classical bonds between integrins and the Arg-Gly-Asp (RGD) tripeptide sequence (∼100 pN). Adhesion forces between single bacteria and αVβ3 are strongly inhibited by an anti-αVβ3 antibody, the RGD peptide, and the cyclic RGD peptide cilengitide, showing that formation of the complex involves RGD-dependent binding sites and can be efficiently inhibited by αVβ3 blockers. Collectively, our experiments favor a binding mechanism involving the extraordinary elasticity of Fg. In the absence of mechanical stress, RGD572-574 sequences in the Aα chains mediate weak binding to αVβ3, whereas under high mechanical stress exposure of cryptic Aα chain RGD95-97 sequences leads to extremely strong binding to the integrin. Our results identify an unexpected and previously undescribed force-dependent binding mechanism between ClfA and αVβ3 on endothelial cells, which could represent a potential target to fight staphylococcal bloodstream infections.

Tuning of salt separation efficiency by flow rate control in microfluidic dynamic dialysis

Microliter-scale separation processes are important for biomedical research and point-of-care diagnostics with small-volume clinical samples. Analytical assays such as mass spectrometry and field effect sensing necessitate sample desalting, but too low a salt concentration can disrupt protein structures and biomolecular interactions. In this work, we investigated whether salt extraction from a protein solution can be controlled by dynamic dialysis parameters. A microfluidic counter-flow dialyzer with a 5 kDa molecular weight cut-off cellulose membrane was fabricated by laser cutting and operated with a wide range of feed and dialysis flow rates. It was found that with the appropriate flow conditions, most notably the feed flow rate, retentate salt concentrations from 0.1 to 99% of the input NaCl concentration can be achieved. The experimental data were in good agreement with a theoretical diffusion-based mass transfer model. The salt dialysis performance was similar in the presence of 50 mg/mL albumin, approximating blood plasma protein content, and did not deteriorate with overnight continuous dialysis, indicating minimal membrane fouling. The dialyzer construction method is compatible with all planar membranes, enabling implementation of tuneable dynamic dialysis for a wide range of on-line microfluidic biomolecular separations.

A multiscale model of protein adsorption on a nanoparticle surface

We present a methodology to quantify the essential interactions at the interface between inorganic solid nanoparticles (NPs) and biological molecules. Our model is based on pre-calculation of the repetitive contributions to the interaction from molecular segments, which allows us to efficiently scan a multitude of molecules and rank them by their adsorption affinity. The interaction between the biomolecular fragments and the nanomaterial are evaluated using a systematic coarse-graining scheme starting from all-atom molecular dynamics simulations. The NPs are modelled using a two-layer representation, where the outer layer is parameterized at the atomistic level and the core is treated at the continuum level using Lifshitz theory of dispersion forces. We demonstrate that the scheme reproduces the experimentally observed features of the NP protein coronas. To illustrate the use of the methodology, we compute the adsorption energies for human blood plasma proteins on gold NPs of different sizes as well as the preferred orientation of the molecules upon adsorption. The computed energies can be used for predicting the composition of the NP-protein corona for the corresponding material.

Effect of Primary and Secondary Beads of Carbon Enterosorbent on Haematological Parameters and Oxidative Stress Development Caused by Melphalan in Rats.

Background and Objectives: Side effects of anti-cancer drugs are usually accompanied by oxidative stress, including myelotoxicity. We evaluated the potential of oral highly activated micro-/macroporous carbon adsorbents (bulk density of 0.16 g/cm3, surface area calculation by Brunauer–Emmett–Teller model (SBET) > 2200 m2/g, derived from proprietary phenolic resin beads) to alleviate oxidative stress and myelotoxicity in rats. Materials and Methods: A single injection of cytostatic melphalan (L-PAM) at a dose of 4 mg/kg was used for modelling. Two forms of activated carbon were used: AC1—primary beads with the particle size range of 125–250 µm, and AC2—micronized AC1 with a mean particle size of ~1 µm. We measured haematological parameters white blood cells, red blood cells, platelet count, and haemoglobin level. Oxidative stress intensity was evaluated using the following markers: total levels of reactive oxygen species (ROS) in blood plasma; catalase activity (CAT) and pro-oxidant/antioxidant ratio in blood haemolysate samples; level of reduced glutathione (GSH) in liver tissues; oxidative modification of proteins, OPM (APHD, aldehyde–dinitrophenylhydrazone derivatives and KPHD, ketone dinitrophenylhydrazone derivatives) and malonic dialdehyde (MDA) in blood plasma and liver samples. Results: AC2 administration promoted significant myeloprotective effect: 1.5-fold increase in leukocytes, 2-fold in neutrophils, 1.5-fold in lymphocytes, and 1.23-fold in platelet count compared to the experimental Melphalan Group. At the same time, AC1 administration resulted in a slight increase in haematological parameters. Both ACs positively corrected important, but diverse, components of oxidative stress. They significantly reduced oxidative modification of blood and liver proteins (especially the AC1 form), normalized the level of reduced glutathione, pro-oxidant/antioxidant ratio and other markers. For some markers, such as ROS production in blood plasma, the use of enterosorbents resulted in non-significant a shift towards normal parameters. Conclusions: Oral activated carbon adsorbents reduce oxidative stress intensity and myelotoxicity; they can be promising means to combat the adverse effects of chemotherapy in clinical practice.

Pilot-Scale Study Of Human Plasma Proteomics Identifies ApoE And IL33 As Markers In Atopic Asthma.

BackgroundThe pathobiology of atopic asthma is complex and the symptoms similar to other respiratory diseases. As such, identification of biomarkers of atopic asthma is of prime importance for better diagnosis and control of the disease.ObjectivesWe sought to study the changes in plasma proteome and cytokine-expression profile across healthy and atopic asthmatics for identifying biomarkers and exploring aberrant pathways for atopic asthma.MethodsA pilot-scale study in humans was performed to identify differentially expressed proteins in blood plasma of healthy controls (n=5) and treatment-naïve atopic asthma patients (n=5) using quantitative label-free liquid chromatography–tandem mass spectrometry proteomics and ELISA.ResultsMass spectrometry–based proteomic analysis revealed ApoE to be significantly downregulated in atopic asthmatics compared to healthy volunteers. Decreased expression of ApoE in atopic asthmatics was validated by immunoblotting (50.74% decrease). Comparison with atopic asthmatics and COPD patients showed that ApoE was decreased (36.33%) in atopic asthma compared to COPD. IL33 was significantly upregulated in atopic asthmatics compared to healthy subjects (3.84-fold).ConclusionApoE was downregulated and IL33 upregulated in atopic asthma patients compared to healthy volunteers. These two proteins' profiles were distinct in atopic asthma from healthy and COPD plasma samples. Differential expression of these proteins could serve as a probable candidate for a two-protein classifier–based prognostic biomarker of atopic asthma.