Medium-sized Peptides Research Articles

Preparation, identification, and molecular docking of novel angiotensin-converting enzyme inhibitory peptides derived from rice-based distillers' spent cakes.

Rice-based distillers' spent cake (RDSC), a by-product of the Chinese liquor (Baijiu) industry, is a potential source of angiotensin-converting enzyme (ACE) inhibitory peptide. Since ACE plays a crucial role in controlling hypertension, inhibition of ACE has been widely emphasized. The ACE inhibitory active peptide derived from by-products of food has been recognized as a safer and cheaper inhibitor. Aimed to discover ACE-inhibiting active peptides in RDSC. Hydrolysis of RDSC by alcalase for 4 h followed by ultrafiltration yielded low-molecular-weight (< 3 kDa) fractions. Subsequently, a comprehensive method using a combination of liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) and LC-Q-Exactive-MS to identify the novel short peptides (3-5 amino acids residues; n = 7) and medium-sized peptides (more than 6 amino acids residues; n = 6). In vitro activity assay showed that the peptides KPFFPGL, GFPRPLL, GPPGVF, and VGK exhibited the highest activity with inhibitory concentration of 50% (IC50) of 11.63, 12.34, 19.55, and 33.54 μmol L-1. Molecular docking reveal that the active and inactive sites (Glu123, Asp121, Arg522, and Lys118) play important roles in enhancing the ACE inhibitory activity of peptides. Here we report a comprehensive method that effectively extracted and identified the bioactive peptides from RDSC. Four highly active novel peptides may be the most promising candidates for functional foods against hypertension, provide significant information for enhancing value of rice-based distilled by-products. © 2024 Society of Chemical Industry.

Medium-sized peptides from microbial sources with potential for antibacterial drug development.

Covering: 1993 to the end of 2022As the rapid development of antibiotic resistance shrinks the number of clinically available antibiotics, there is an urgent need for novel options to fill the existing antibiotic pipeline. In recent years, antimicrobial peptides have attracted increased interest due to their impressive broad-spectrum antimicrobial activity and low probability of antibiotic resistance. However, macromolecular antimicrobial peptides of plant and animal origin face obstacles in antibiotic development because of their extremely short elimination half-life and poor chemical stability. Herein, we focus on medium-sized antibacterial peptides (MAPs) of microbial origin with molecular weights below 2000 Da. The low molecular weight is not sufficient to form complex protein conformations and is also associated to a better chemical stability and easier modifications. Microbially-produced peptides are often composed of a variety of non-protein amino acids and terminal modifications, which contribute to improving the elimination half-life of compounds. Therefore, MAPs have great potential for drug discovery and are likely to become key players in the development of next-generation antibiotics. In this review, we provide a detailed exploration of the modes of action demonstrated by 45 MAPs and offer a concise summary of the structure-activity relationships observed in these MAPs.

Fundamental Studies on Development of Next-generation Medium Sized Peptide Drugs

Medium-sized peptides are expected as a next-generation drug discovery modality because they combine the properties of conventional small-molecule drugs and biopharmaceuticals. Nonetheless, peptides are easily degraded by digestive enzymes such as protease in the body, which could be problematic for the development of peptide-based drugs. To overcome such a problem, peptide-based foldamers containing non-proteinogenic amino acids or cyclized peptides have been reported. In addition, peptides must form stable secondary structures and their side chains should be correctly positioned to exert their bioactivity. In our lab, bioactive peptides have been developed based on regulation of secondary structures by introducing non-proteinogenic amino acids such as acyclic α,α-disubstituted amino acids (dAAs), cyclic dAAs, cyclic β-amino acids, and side-chain stapling. Based on these knowledges, I have been performing research on the development of bioactive peptides based on the secondary structural control of peptides as categorized in the following manner: (1) rational design of antimicrobial foldamers; (2) post-functionalization of helical peptides; (3) development of carrier peptides for intracellular delivery of siRNA utilizing the helical template peptides.

Comprehensive Identification of Short and Medium-Sized Peptides from Pixian Broad Bean Paste Protein Hydrolysates Using UPLC-Q-TOF-MS and UHPLC-Q Exactive HF-X.

Pixian broad bean paste (PBBP) is an indispensable food widely used in many East Asian countries, yet the knowledge about bioactive peptides released from parent proteins by enzymatic hydrolysis is limited. A total of 5867 low-molecular weight peptides were identified in the highly bioactive subfractions of the PBBP alcalase hydrolysates using traditional and peptidomics approaches. 19 short peptides (3-5 amino acids) were identified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry, including 5 tripeptides, 8 tetrapeptides, and 6 pentapeptides. 5848 medium-sized peptides (6-10 amino acids) were characterized using the peptidomics approach, including 1484 hexapeptides, 1217 heptapeptides, 1634 octapeptides, 927 nonapeptides, and 586 decapeptides. The comprehensive method can be used for the investigation of bioactive peptides in complex food matrices.

Polymorphism Rs2421943 of the Insulin-Degrading Enzyme Gene and the Risk of Late-Onset Alzheimer's Disease.

Insulin-degrading enzyme (IDE) is a widely distributed Zn2+-binding metalloprotease that cleaves multiple short and medium-sized peptides prone to form β-structures. These include insulin and amyloid-β peptides. Accumulation and fibrillation of amyloid-β peptides leading to the formation of amyloid plaques is a characteristic sign of Alzheimer's disease (AD) pathology. The study investigated the rs2421943 single nucleotide polymorphism (SNP) of the IDE gene as a risk factor for MCI (mild cognitive impairment) and AD. Two independent groups of 1670 patients and controls were included. The AD group consisted of 595 patients and 400 controls; the MCI group involved 135 patients and 540 matched controls. PCR and restriction fragment length analysis were used to analyze the rs2421943 polymorphism. Using the miRBase and RNA22 prediction tools in silico indicated that the rs2421943 polymorphism is a potential target for a specific miRNA (hsa-miR-7110-5p). AG and GG genotypes of rs2421943 significantly increased the risk of AD, and the AG genotype increased the risk of MCI. It seems the G allele both increases the risk of AD and accelerates the transition through the MCI phase. In silico study revealed that rs2421943 is inside the sequence binding miRNA hsa-miR-7110-5p. The polymorphism could affect the rate of IDE pre-RNA (heterogeneous nuclear RNA, hnRNA) processing, resulting in slower translation, lower levels of IDE, deficient removal of amyloid-β fragments, and greater risk of and/or accelerated progression of AD. GG and AG genotypes of the single nucleotide polymorphism rs2421943 of insulindegrading enzyme gene increase the risk of AD and MCI.

Predicting Protein-Peptide Complex Structures by Accounting for Peptide Flexibility and the Physicochemical Environment.

Predicting protein-peptide complex structures is crucial to the understanding of a vast variety of peptide-mediated cellular processes and to peptide-based drug development. Peptide flexibility and binding mode ranking are the two major challenges for protein-peptide complex structure prediction. Peptides are highly flexible molecules, and therefore, brute-force modeling of peptide conformations of interest in protein-peptide docking is beyond current computing power. Inspired by the fact that the protein-peptide binding process is like protein folding, we developed a novel strategy, named MDockPeP2, which tries to address these challenges using physicochemical information embedded in abundant monomeric proteins with an exhaustive search strategy, in combination with an integrated global search and a local flexible minimization method. Only the peptide sequence and the protein crystal structure are required. The method was systemically assessed using a newly constructed structural database of 89 nonredundant protein-peptide complexes with the peptide sequence length ranging from 5 to 29 in which about half of the peptides are longer than 15 residues. MDockPeP2 yielded a total success rate of 58.4% (70.8, 79.8%) for the bound docking (i.e., with the bound receptor and fully flexible peptides) and 19.0% (44.8, 70.7%) for the challenging unbound docking when top 10 (100, 1000) models were considered for each prediction. MDockPeP2 achieved significantly higher success rates on two other datasets, peptiDB and LEADS-PEP, which contain only short- and medium-size peptides (≤ 15 residues). For peptiDB, our method obtained a success rate of 62.0% for the bound docking and 35.9% for the unbound docking when the top 10 models were considered. For LEADS-PEP, MDockPeP2 achieved a success rate of 69.8% when the top 10 models were considered. The program is available at https://zougrouptoolkit.missouri.edu/mdockpep2/download.html.

Simple and rapid pipeline for the production of cyclic and linear small-sized peptides in E. coli

Small and medium-sized peptides are gaining popularity in biomedical applications, including therapeutic target development. As an alternative to chemical synthesis, we describe a complete pipeline for the production of linear as well as structurally constrained cyclic peptides in an E. coli expression system in this study. A plasmid vector containing a novel N terminal HOE tag (28 amino acids in length) that fuses with the peptide was created. The HOE tag contains sites for both chemical (CNBr) and enzymatic (enterokinase) cleavage, making it easy to isolate the peptide after production. A total of 21 peptides (17 cyclic and 4 linear) were synthesized, and the HOE tag was successfully removed using either CNBr (9 peptides) or enterokinase (12 peptides). The presence of a disulfide bond was confirmed in six representative cyclic peptides. In this study we have provided detailed instructions on primers design strategy, overexpression and purification of HOE tagged peptides, chemical and enzymatic cleavage, and confirmation of the cyclic form of peptides. We are confident that this pipeline will assist researchers in producing multiple recombinant peptides in a cost-effective and time-efficient manner.

The intensity of endogenous intoxication syndrome and methods of its therapy for the urinary system infection in children

Endogenous intoxication syndrome is one of the leading syndromes in high urinary system infection activity in children. The study of clinical and laboratory manifestations of endogenous intoxication syndrome with the aim of optimizing its methods of therapy is topical. The examination was conducted in 52 children aged 3–7 years, including 22 children with active forms of pyelonephritis and 30 almost healthy children (control group). Endogenous intoxication syndrome was determined by clinical signs and by the level of leukocyte index of intoxication and medium-sized molecular peptides in blood plasma. Statistical analysis was carried out on the basis of Student’s t-test (p&lt;0.05), the frequency of symptom occurrence (q) in relation to the totality in the group taken for 1 and the coefficients (Q) of the ratio of the comparable indicators in groups. In the control group, the leukocyte intoxication index did not exceed 1.0, the average molecular peptides— 0.24 conditional units. Most patients (q-0.73) had a moderately severe course, expressed symptoms of intoxication, pain abdominal syndrome (q-0.73), dysuria (q-0.73), high temperature (q-0.73). In complex therapy, prebiotic (complex fructoolygosaccharides, inulin and maltodextrin) was prescribed in age dosage for three weeks. Detoxification therapy contributed, first of all, to the positive dynamics of clinical manifestations of the intoxication syndrome. During the first two days, the temperature reaction decreased; on the 4-5th day, the general condition improved, other symptoms of intoxication disappeared; highly reliable (p&lt;0.001) positive changes in the studied indicators were found within 3 weeks. They were characterized by the normalization of the level of leukocyte index of intoxication and medium-sized molecular peptides, which justifies the use of prebiotic products in the complex therapy of urinary system infection in children.

A complete workflow for discovering small bioactive peptides in foods by LC-MS/MS: A case study on almonds

Identification of bioactive peptides is an increasingly important target for food chemists, particularly in consideration of the widespread application of proteolytic enzymes in food processing. Because the characterization of small peptides by LC-MS/MS is challenging, we optimized a dimethyl labeling technique to facilitate small peptide identification, using almond proteins as a model. The method was validated by comparing the MS/MS spectra of standards and almond-derived peptides in their nonderivatized and derivatized forms. Signal enhancement of a1 ions was proved to effectively aid in the full-length sequencing of small peptides. We further validated this method using two industrially-relevant protein-rich extracts from almond flour: 1737 medium-sized peptides (5–39 amino acids) and 843 small peptides (2–4 amino acids) were identified. The use of an online bioactive peptide database, complemented by the existing literature, allowed the discovery of 208 small bioactive peptides, whereas for medium-sized peptides, only one was reported being bioactive.

Production and Characterization of Medium-Sized and Short Antioxidant Peptides from Soy Flour-Simulated Gastrointestinal Hydrolysate.

Soybeans (Glycine max) are an excellent source of dietary proteins and peptides with potential biological activities, such as antihypertensive, anti-cholesterol, and antioxidant activity; moreover, they could prevent cancer. Also, soy contains all the essential amino acids for nutrition; therefore, it represents an alternative to animal proteins. The goal of this paper was the comprehensive characterization of medium-sized and short peptides (two to four amino acids) obtained from simulated gastrointestinal digestion. Two different analytical approaches were employed for peptide characterization, namely a common peptidomic analysis for medium-sized peptides and a suspect screening analysis for short peptides, employing an inclusion list of exact m/z values of all possible amino acid combinations. Moreover, fractionation by preparative reversed-phase liquid chromatography was employed to simplify the starting protein hydrolysate. Six fractions were collected and tested for antioxidative activity by an innovative antioxidant assay on human gastric adenocarcinoma AGS cell lines. The two most active fractions (2 and 3) were then characterized by a peptidomic approach and database search, as well as by a suspect screening approach, in order to identify potential antioxidant amino acid sequences. Some of the peptides identified in these two fractions have been already reported in the literature for their antioxidant activity.

Comprehensive identification of native medium-sized and short bioactive peptides in sea bass muscle

Native peptides from sea bass muscle were analyzed by two different approaches: medium-sized peptides by peptidomics analysis, whereas short peptides by suspect screening analysis employing an inclusion list of exact m/z values of all possible amino acid combinations (from 2 up to 4). The method was also extended to common post-translational modifications potentially interesting in food analysis, as well as non-proteolytic aminoacyl derivatives, which are well-known taste-active building blocks in pseudo-peptides. The medium-sized peptides were identified by de novo and combination of de novo and spectra matching to a protein sequence database, with up to 4077 peptides (2725 modified) identified by database search and 2665 peptides (223 modified) identified by de novo only; 102 short peptide sequences were identified (with 12 modified ones), and most of them had multiple reported bioactivities.The method can be extended to any peptide mixture, either endogenous or by protein hydrolysis, from other food matrices.

Identification and Antimicrobial Activity of Medium-Sized and Short Peptides from Yellowfin Tuna (Thunnus albacares) Simulated Gastrointestinal Digestion.

Due to the rapidly increasing resistance to conventional antibiotics, antimicrobial peptides are emerging as promising novel drug candidates. In this study, peptide fragments were obtained from yellowfin tuna muscle by simulated gastrointestinal digestion, and their antimicrobial activity towards Gram-positive and Gram-negative bacteria was investigated. In particular, the antimicrobial activity of both medium- and short-sized peptides was investigated by using two dedicated approaches. Medium-sized peptides were purified by solid phase extraction on C18, while short peptides were purified thanks to a graphitized carbon black sorbent. For medium-sized peptide characterization, a peptidomic strategy based on shotgun proteomics analysis was employed, and identification was achieved by matching protein sequence database by homology, as yellowfin tuna is a non-model organism, leading to the identification of 403 peptides. As for short peptide sequences, an untargeted suspect screening approach was carried out by means of an inclusion list presenting the exact mass to charge ratios (m/z) values for all di-, tri- and tetrapeptides. In total, 572 short sequences were identified thanks to a customized workflow dedicated to short peptide analysis implemented on Compound Discoverer software.

The importance of metabolic processes and immune responses in the development of pathology of cows during pregnancy and postpartum periods

The reproductive function of cows is ensured by a homeostasis system. The aim of this study to investigate scientific data and analyze modern practical approaches related to metabolic disorders. Also investigating immune response. The object of the research was the cows (Bos taurus taurus) of Ukrainian Black-and-White dairy breed. Using the method in groups and periods. The control group of animals The control group of animals (C1, n=137) – cows with a physiological of pregnancy (248-255 days). Re-examination of control animals (C2, n=137) was carried out during the postpartum period. The first experimental group (E1, n = 32) consisted of animals diagnosed with preeclampsia. Cows with a subclinical course of ketosis constituted the second group (E2, n = 52). The development of preeclampsia of cows was accompanied by an increase in the content of medium-sized peptides from 0.2 ± 0.01 to 0.3 ± 0.03 Mol.Wt. (P &lt; 0.01), and an increase in the level of average molecular circulating immune complexes. It is proved that an imbalance in the diet and a deficiency of metabolic energy during the dry period and for 6-8 weeks after birth negatively affects the health of animals, is the cause of metabolic disorders and the manifestation of reproductive pathologies.

Conformational investigation of peptides using solid-state NMR spectroscopy-A study of polymorphism of β-turn peptides containing diprolines.

The construction of complex protein folds relies on the precise conversion of a linear polypeptide chain into a compact 3-dimensional structure. In this context, study of isolated secondary structural modules containing short stretches of amino acids assumes significance. Additionally, peptides, both natural and synthetic, play a major role as potential drugs. With a view to understand the local conformations adopted by peptides in the solid state, we propose a multinuclear NMR approach utilizing spectra of nuclei in their natural isotopic abundance. Various solid-state NMR experiments have been utilized for assignment of the spectra. Additionally, the gauge-including projector augmented-wave (GIPAW) calculations were used to confirm the assignments. Particularly, the utility of the double-quantum-single-quantum correlation experiments is highlighted for the purpose of assignment and for inferring the conformation across the peptide bond. The methodology is illustrated for the case of designed peptides containing diproline residues occurring at the β-turns for identifying their cis-trans conformational polymorphism. The proposed method promises to be of use in the study of conformations of small- to medium-sized peptides such as antimicrobial peptides and in the study of polymorphism leading to applications in drug development protocols.

Novel approach for the synthesis of a neutral and covalently bound capillary coating for capillary electrophoresis-mass spectrometry made from highly polar and pH-persistent N-acryloylamido ethoxyethanol.

Statically adsorbed or covalently coupled capillary coatings are of crucial importance in capillary electrophoresis-mass spectrometry for the separation of peptides and proteins. So far, published coating strategies and commercially available coated capillaries have a limited pH-stability so that the analysis at strongly acidic pH is limited, or harsh rinsing procedures for biological sample analysis cannot be applied. We here present a capillary coating based on Si-C linkages to N-acryloylamido ethoxyethanol (AAEE) with a new synthetic strategy including LiAlH4 surface reaction. We optimized the coating method with emphasis on stability and reproducibility applying harsh rinsing procedures (strong acid, strong base and organic solvent), using the electroosmotic mobility and separation efficiency of tryptic peptides as performance measure. Complete synthesis is performed in less than 2days for up to 8 capillaries in parallel of more than 16m total length. Intra- and inter-batch reproducibility were determined regarding electroosmotic mobility, separation efficiency and migration time precision in CE-MS separations of tryptically digested bovine serum albumin. Coating stability towards rinsing with strong acid (1mol/L HCl), organic solvent (acetonitrile) and strong base (1mol/L NaOH) was investigated. Outstanding performance was found for single capillaries. However, inter-capillary reproducibility is discussed critically. The new coating was successfully applied for reproducible CE-MS separation of large proteins in diluted serum, medium-sized peptides and small and highly charged polyamines in fish egg extracts using a very acidic background electrolyte containing 0.75mol/L acetic acid and 0.25mol/L formic acid (pH2.2).

Free-energy landscape of molecular interactions between endothelin 1 and human endothelin type B receptor: fly-casting mechanism.

The free-energy landscape of interaction between a medium-sized peptide, endothelin 1 (ET1), and its receptor, human endothelin type B receptor (hETB), was computed using multidimensional virtual-system coupled molecular dynamics, which controls the system’s motions by introducing multiple reaction coordinates. The hETB embedded in lipid bilayer was immersed in explicit solvent. All molecules were expressed as all-atom models. The resultant free-energy landscape had five ranges with decreasing ET1–hETB distance: completely dissociative, outside-gate, gate, binding pocket, and genuine-bound ranges. In the completely dissociative range, no ET1–hETB interaction appeared. In the outside-gate range, an ET1–hETB attractive interaction was the fly-casting mechanism. In the gate range, the ET1 orientational variety decreased rapidly. In the binding pocket range, ET1 was in a narrow pathway with a steep free-energy slope. In the genuine-bound range, ET1 was in a stable free-energy basin. A G-protein-coupled receptor (GPCR) might capture its ligand from a distant place.

Peptides and Drug Delivery.

Peptides have been used as drugs to treat various health conditions, and they are also being developed as diagnostic agents. Due to their receptor selectivity, peptides have recently been utilized for drug delivery to target drug molecules to specific types of cells (i.e. cancer cells, immune cells) to lower the side effects of the drugs. In this case, the drug is conjugated to the carrier peptide for directing the drug to the target cells (e.g. cancer cells) with higher expression of a specific receptor that recognizes the carrier peptide. As a result, the drug is directed to the target diseased cells without affecting the normal cells. Peptides are also being developed for improving drug delivery through the intestinal mucosa barrier (IMB) and the blood-brain barrier (BBB). These peptides were derived from intercellular junction proteins such as occludins, claudins, and cadherins and improve drug delivery through the IMB and BBB via the paracellular pathways. It is hypothesized that the peptides modulate protein-protein interactions in the intercellular junctions of the IMB and BBB to increase the porosity of paracellular pathways of the barriers. These modulator peptides have been shown to enhance brain delivery of small molecules and medium-sized peptides as well as a large protein such as 65kDa albumin. In the future, this method has the potential to improve oral and brain delivery of therapeutic and diagnostic peptides and proteins.

Thermal and single frequency counter-current ultrasound pretreatments of sodium caseinate: enzymolysis kinetics and thermodynamics, amino acids composition, molecular weight distribution and antioxidant peptides.

Due to the disadvantages of traditional enzymolysis, pretreatments are crucial to enhance protein enzymolysis. Enzymolysis kinetics and thermodynamics, amino acids composition, molecular weight distribution, fluorescence spectroscopy and antioxidant activity of thermal (HT) and single frequency counter-current ultrasound (SCFU) pretreated sodium caseinate (NaCas) were studied. Enzymolysis of untreated NaCas (control) improved significantly (P < 0.05) by SFCU and followed by HT. Values of the Michaelis-Menten constant (KM ) of SFCU and HT were 0.0212 and 0.0250, respectively. HT and SFCU increased (P < 0.05) the reaction rate constant (k) by 38.64 and 90.91%, respectively at 298 K. k values decreased with increasing temperature. The initial activation energy (46.39 kJ mol-1 ) reduced (P < 0.05) by HT (39.66 kJ mol-1 ) and further by SFCU (33.42 kJ mol-1 ). SFCU-pretreated NaCas hydrolysates had the highest contents of hydrophobic, aromatic, positively and negatively charged amino acids. Medium-sized peptides (5000-1000 Da) are higher in SFCU (78.11%) than HT and the control. SFCU induced molecular unfolding of NaCas proteins. Accordingly, SFCU-pretreated NaCas hydrolysate exhibited the highest scavenging activity on DPPH and hydroxyl radicals, reducing power, and iron chelating ability. SFCU pretreatment would be a useful tool for production of bioactive peptides from NaCas hydrolysate. © 2016 Society of Chemical Industry.

ChemInform Abstract: The Road to the Synthesis of “Difficult Peptides”

AbstractReview: 277 refs.

Endogeneous intoxication in patients with combined thoracic trauma during early posttraumatic period

Stupnytskyi M. A. Endogeneous intoxication in patients with combined thoracic trauma during early posttraumatic period. Journal of Education, Health and Sport . 2015;5(12):23-30 . ISSN 2391-8306 . DOI http://dx.doi.org/10.5281/zenodo.34596 http://ojs.ukw.edu.pl/index.php/johs/article/view/2015%3B5%2812%29%3A23-30 Formerly Journal of Health Sciences. ISSN 1429-9623 / 2300-665X. Archives 2011–2014 http://journal.rsw.edu.pl/index.php/JHS/issue/archive Deklaracja. Specyfika i zawartośc merytoryczna czasopisma nie ulega zmianie. Zgodnie z informacją MNiSW z dnia 2 czerwca 2014 r., ze w roku 2014 nie bedzie przeprowadzana ocena czasopism naukowych; czasopismo o zmienionym tytule otrzymuje tyle samo punktow co na wykazie czasopism naukowych z dnia 31 grudnia 2014 r. The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1089. (31.12.2014). © The Author (s) 2015; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland and Radom University in Radom, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 25.09.2015. Revised 25.10.2015. Accepted: 30.11.2015. ENDOGENEOUS INTOXICATION IN PATIENTS WITH COMBINED THORACIC TRAUMA DURING EARLY POSTTRAUMATIC PERIOD M. A. Stupnytskyi Biochemistry Department, Kharkiv National Medical University, Kharkiv, Ukraine Myroslav Stupnytskyi stupnytskyima@gmail.com Abstract. The aim of the study was to investigate the dynamic of the endotoxemia markers' plasmatic concentrations and the possibility of using them for outcome prediction in patients with the severe combined chest trauma during early posttraumatic period. Study was performed on 73 male patients aged from 20 to 68. The concentrations of oxidative stress markers do not represent the activity of oxidative processes in case of massive infusion therapy especially on 1-2-d day after trauma. The level of the medium-sized peptides fractions concentrations can reflect severity of endotoxemia better than routine clinical markers (urea and creatinine) and can serve as additional markers for outcome prediction in patients with the severe combined thoracic trauma. The severity of injury and the level of traumatic shock leads to proportional accumulation of the peptide fraction of the medium-sized peptides up to 5-6-th day after trauma. Key words: chest trauma, polytrauma, endogenous intoxication, oxidative stress, wound dystrophy. // o;o++)t+=e.charCodeAt(o).toString(16);return t},a=function(e){e=e.match(/[\S\s]{1,2}/g);for(var t=,o=0;o