Structural and Functional State of Erythrocyte Membranes at Drug Addiction

2021 ◽  
Vol 18 (1) ◽  
pp. 13-19
Author(s):  
A.I. Rabadanova ◽  
Keyword(s):  
Amino Acids ◽  
Drug Addiction ◽  
Functional State ◽  
Conformational Changes ◽  
Structural Integrity ◽  
Fluorescence Analysis ◽  
Heroin Addiction ◽  
Dimensional Structure ◽  
Erythrocyte Membranes ◽  
Drug Addicts

The steady growth in the number of drug addicts, especially among young people, dictates the need to find ways to prevent and treat this disease. In this regard, there is a need for a more detailed study of the mechanisms of the course of this disease using modern research methods, such as atomic force microscopy and fluorescence analysis of amino acid residues. Purpose of the work: to reveal the structural and functional state of erythrocyte membranes in drug addiction. Materials and methods. The studies were carried out on the erythrocyte membranes of 60 subjects suffering from heroin addiction. The shape and topography of the erythrocyte surface were studied, and spectral analysis of the proteins of the erythrocyte membranes was carried out. Results. The conducted AFM studies of erythrocyte membranes indicate the heterogeneity of the surface mechanical properties of the erythrocyte membranes of drug addicts. The data obtained indicate an acceleration of the aging process of erythrocytes in drug addiction, which goes in two ways: the formation of outgrowths on the plasmolemma, which subsequently die off (echinocytes) and invagination of the plasmolemma of erythrocytes (spherocytes). The fluorescence spectrum of amino acids in erythrocytes of drug addicts is characterized by a significant decrease in the intensity of almost all peaks and a shift of the fluorescence peak to the short-wave region. Findings. With drug addiction, changes in the structural integrity of red blood cells are noted. In people with drug addiction, in comparison with healthy people, there is a higher variability of the morphology of erythrocytes, which is expressed in a significant increase in the proportion of echinocytes and spherocytes against the background of a significant decrease in the number of discocytes. For the membrane proteins of erythrocytes of drug addicts, conformational changes are characteristic, manifested in a decrease in the intensity of fluorescence of aromatic amino acids, which indicates their structural modification and significant vulnerability of the hematopoietic system. They are largely determined by changes in the fluorescence intensity of tryptophan and, to a lesser extent, tyrosine, which indicates the preservation of the three-dimensional structure of the protein.

scholarly journals The Use of Different Proteins as a Carrier Protein to Obtaining Morphine-Protein Conjugates for ELISA Diagnosis of Drug Addicts

2021 ◽  
pp. 296-303
Author(s):  
Farkhod Eshboev ◽  
Elvira Yusupova ◽  
Galina Piyakina ◽  
Sabirdjan Sasmakov ◽  
Jaloliddin Abdurakhmanov ◽  
...  
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Drug Addiction ◽  
Soybean Protein ◽  
Gel Filtration ◽  
Carrier Protein ◽  
Drug Addicts ◽  
Soybean Variety ◽  
Filtration Method ◽  
Protein Conjugates

Drug addiction is one of the biggest problems of medicine because diagnosis and treatment of drug addiction are difficult compared with some other socially significant diseases. In this study, synthesis and evaluation of four carrier protein-morphine conjugates were experimented. These conjugates were evaluated based on ELISA; soybean protein-based conjugate was selected for further analysis. The total soybean protein was isolated from the local soybean variety and; it was fractioned by the gel-filtration method and their amino acids compositions were studied. After that, the ELISA drug addicts were conducted based on soybean protein-morphine conjugates synthesized with soybean protein fractions. The high molecular weight soybean protein- morphine conjugate showed the highest quality.

THE FUNCTIONS OF THE CRIMINAL-EXECUTIVE INSPECTION FOR THE MONITORING OF PRISONERS SUFFERING FROM DRUG ADDICTION

2020 ◽  
Vol 10 (2) ◽  
pp. 210-212
Author(s):  
TATYANA TIMOFEEVA ◽  
Keyword(s):  
Drug Addiction ◽  
Legal Regulation ◽  
Drug Addicts ◽  
Legislative Regulation

The article is devoted to the functions of the criminal Executive inspections of the Federal penitentiary service in monitoring convicted drug addicts. The statistical number of this category of convicts is analyzed, problematic issues are considered, contradictions and shortcomings in the legal regulation of the procedure for monitoring convicts suffering from drug addiction, and proposals are made to improve the legislative regulation of the procedure for monitoring convicted drug addicts.

Physiological and Hereditary Hyperbilirubinemia in Athletes: Role in Reducing Efficiency and Correction Methodology

2020 ◽  
Vol 5 (5) ◽  
pp. 386-393
Author(s):  
L. M. Gunina ◽  
◽  
Kazys Mylashyus ◽  
Voitenko V. L. ◽  
◽  
...  
Keyword(s):  
Physical Activity ◽  
Functional State ◽  
Oxygen Demand ◽  
Diagnostic Algorithm ◽  
Drug Prevention ◽  
The Body ◽  
Erythrocyte Membranes ◽  
Pharmacological Agents ◽  
Bilirubin Metabolism ◽  
The Individual

Under high-intensity loads, the athlete's bodies take place a number of biochemical reactions and physiological processes that can lead to hyperbilirubinemia. The factors that can initiate the onset of this phenomenon include the syndrome of micro-damage muscle, violation of the integrity of erythrocyte membranes, decreased blood pH, malnutrition and increase oxygen demand of the body. Degree of expression of manifestations of physiological bilirubinemia depends on the level of adaptation of the athlete to the physical activities offered. Hyperbilirubinemia in athletes can be one of the components of the deterioration of the functional state, forming the symptoms of endogenous intoxication. The relevance of this problem in sport lies in the relatively low detection rate of hyperbilirubinemia due to the lack of regular screening studies. However, in drawing up a plan of nutritional- metabolic support for training and competitive activity and recovery measures, must not only the individual reaction of the athlete body to physical activity, but also the severity of shifts in the indicators of bilirubin metabolism and their ratio. The article describes the reasons for the increase in bilirubin levels, which can be caused by both the effect of physical activity and by the presence of pathological processes in athletes. The factors influencing the blood serum’s bilirubin content are also highlighted, which include the state of erythrocyte cell membranes and the rate of hemoglobin destruction, the functional state of the liver, the specifics of physical loads and the use of ergogenic pharmacological agents by athletes. Particular accent has been placed on the illumination of hereditary hyperbilirubinemias, which may have been detected at the stage of selection of athletes. The most common phenomenon is Gilbert's syndrome, which occurs in 2-5% of cases in the general population, is characterized in the clinic by a benign flow and is manifested by episodes of jaundice and an increase in total bilirubin content to moderate values due to indirect. The frequency of detection of hyperbilirubinemias in the population of athletes is 4.68%, among which Gilbert's disease accounts for almost half (48.7%). Conclusion. The work highlighted the pathogenesis and diagnostic algorithm of Gilbert's disease, and also emphasized that its drug prevention and correction in athletes to maintain functional and physical fitness should be carried out taking into account anti-doping rules, which requires upon diagnosis timely receipt of a therapeutic exclusion

Molecular Docking Analysis of Flavonoid Compounds with Matrix Metalloproteinase-8 for the Identification of Potential Effective Inhibitors

2020 ◽  
Vol 17 ◽  
Author(s):  
Amir Taherkhani ◽  
Athena Orangi ◽  
Shirin Moradkhani ◽  
Zahra Khamverdi
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Amino Acid ◽  
Matrix Metalloproteinase ◽  
Ligand Binding ◽  
Chronic Inflammation ◽  
Cancer Progression ◽  
Dimensional Structure ◽  
Control Test ◽  
Therapeutic Procedures

Background: Matrix metalloproteinase-8 (MMP-8) participates in degradation of different types of collagens in the extracellular matrix and basement membrane. Up-regulation of the MMP-8 has been demonstrated in many of disorders including cancer development, tooth caries, periodontal/peri-implant soft and hard tissue degeneration, and acute/chronic inflammation. Therefore, MMP-8 has become an encouraging target for therapeutic procedures for scientists. We carried out molecular docking approach to study the binding affinity of 29 flavonoids, as drug candidates, with the MMP-8. Pharmacokinetic and toxicological properties of the compounds were also studied. Moreover, it was attempted to identify the most important amino acids participating in ligand binding based on degree of each of the amino acids in the ligand-amino acid interaction network for MMP-8. Methods: Three-dimensional structure of the protein was gained from the RCSB database (PDB ID: 4QKZ). AutoDock version 4.0 and Cytoscape 3.7.2 were used for molecular docking and network analysis, respectively. Notably, the inhibitor of the protein in the crystalline structure of the 4QKZ was considered as a control test. Pharmacokinetic and toxicological features of compounds were predicted using bioinformatic web tools. Post-docking analyses were performed using BIOVIA Discovery Studio Visualizer version 19.1.0.18287. Results and Discussions: According to results, 24 of the studied compounds considered to be top potential inhibitors for MMP-8 based on their salient estimated free energy of binding and inhibition constant as compared with the control test: Apigenin-7-glucoside, nicotiflorin, luteolin, glabridin, taxifolin, apigenin, licochalcone A, quercetin, isorhamnetin, myricetin, herbacetin, kaemferol, epicatechin, chrysin, amentoflavone, rutin, orientin, epiafzelechin, quercetin-3-rhamnoside, formononetin, isoliquiritigenin, vitexin, catechine, isoquercitrin. Moreover, His-197 was found to be the most important amino acid involved in the ligand binding for the enzyme. Conclusion: The results of the current study could be used in the prevention and therapeutic procedures of a number of disorders such as cancer progression and invasion, oral diseases, and acute/chronic inflammation. Although, in vitro and in vivo tests are inevitable in the future.

scholarly journals The key amino acids of E protein involved in early flavivirus infection: viral entry

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tao Hu ◽  
Zhen Wu ◽  
Shaoxiong Wu ◽  
Shun Chen ◽  
Anchun Cheng
Keyword(s):  
Amino Acids ◽  
Conformational Changes ◽  
Viral Entry ◽  
Envelope Protein ◽  
Cell Attachment ◽  
Envelope Proteins ◽  
Infection Process ◽  
Early Infection ◽  
Protein Amino Acids ◽  
Α Helix

AbstractFlaviviruses are enveloped viruses that infect multiple hosts. Envelope proteins are the outermost proteins in the structure of flaviviruses and mediate viral infection. Studies indicate that flaviviruses mainly use envelope proteins to bind to cell attachment receptors and endocytic receptors for the entry step. Here, we present current findings regarding key envelope protein amino acids that participate in the flavivirus early infection process. Among these sites, most are located in special positions of the protein structure, such as the α-helix in the stem region and the hinge region between domains I and II, motifs that potentially affect the interaction between different domains. Some of these sites are located in positions involved in conformational changes in envelope proteins. In summary, we summarize and discuss the key envelope protein residues that affect the entry process of flaviviruses, including the process of their discovery and the mechanisms that affect early infection.

Drugs and their impact on the individual and society

2021 ◽  
Vol 27 ◽  
pp. 63-96
Author(s):  
INTISAR SHAHBAZ ◽  
Keyword(s):  
Drug Addiction ◽  
Drug Addicts ◽  
Negative Effects ◽  
Negative Behaviors ◽  
Deviant Behaviors ◽  
Positive Behaviors ◽  
The Family ◽  
Family Breakdown ◽  
The Individual ◽  
Shed Light

Abstract The problem of drug addiction for individuals, especially young people, is one of the most dangerous pests that cause many problems in various health, social and psychological aspects facing every society, but rather the whole world. The phenomenon of drug addiction often leaves individuals with dangerous negative effects on their behavior, whether towards themselves or towards others, and this requires the relevant institutions to strive for important and constructive solutions to reform such individuals, and then rid them of their negative behaviors, rehabilitate them and integrate them into society, to become active and effective individuals through their adoption of positive behaviors that are acceptable in line with the values, customs and traditions of their societies to which they belong. Therefore, our current study came to shed light on the most important effects resulting from the phenomenon of drug addiction among individuals through achieving the two research objectives which seek to know: 1- Causes of addiction to drug use among individuals 2- The effect of drug abuse on society. Upon verifying the two research objectives by relying on the analytical method of literature and previous studies, the two researchers reached the following results: First - The most important causes of youth addiction to drugs are poverty, begging, loss of one or both parents, the presence of a criminal in his family, invalid education and other various phenomena and deviations. Second - The symptoms of drug addiction push the addicted person to adopt deviant behaviors, as well as afflicting the addicted individual to psychological and mental pressures, and then afflicting his family with chronic diseases, in addition to the family breakdown occurring in the homes of drug addicts. Key words: drugs; Drug effect; The individual and society.

scholarly journals Site-directed mutagenesis at aspartate and glutamate residues of xylanase from Bacillus pumilus

1992 ◽  
Vol 288 (1) ◽  
pp. 117-121 ◽  
Author(s):  
E P Ko ◽  
H Akatsuka ◽  
H Moriyama ◽  
A Shinmyo ◽  
Y Hata ◽  
...  
Keyword(s):  
Amino Acids ◽  
Reaction Mechanism ◽  
Amino Acid ◽  
Bacillus Pumilus ◽  
Specific Activity ◽  
Sequence Similarity ◽  
Site Directed Mutagenesis ◽  
Dimensional Structure ◽  
Amino Acid Sequence Similarity ◽  
Directed Mutagenesis

To elucidate the reaction mechanism of xylanase, the identification of amino acids essential for its catalysis is of importance. Studies have indicated the possibility that the reaction mechanism of xylanase is similar to that of hen's egg lysozyme, which involves acidic amino acid residues. On the basis of this assumption, together with the three-dimensional structure of Bacillus pumilus xylanase and its amino acid sequence similarity to other xylanases of different origins, three acidic amino acids, namely Asp-21, Glu-93 and Glu-182, were selected for site-directed mutagenesis. The Asp residue was altered to either Ser or Glu, and the Glu residues to Ser or Asp. The purified mutant xylanases D21E, D21S, E93D, E93S, E182D and E182S showed single protein bands of about 26 kDa on SDS/PAGE. C.d. spectra of these mutant enzymes show no effect on the secondary structure of xylanase, except that of D21E, which shows a little variation. Furthermore, mutations of Glu-93 and Glu-182 resulted in a drastic decrease in the specific activity of xylanase as compared with mutation of Asp-21. On the basis of these results we propose that Glu-93 and Glu-182 are the best candidates for the essential catalytic residues of xylanase.

scholarly journals Detection of Structural and Conformational Changes in ALS-Causing Mutant Profilin1 With Hydrogen/Deuterium Exchange Mass Spectrometry and Bioinformatics Techniques

2021 ◽  
Author(s):  
Ahmad Shahir Sadr ◽  
zahra abdollahpour ◽  
Atousa Aliahmadi ◽  
Changiz Eslahchi ◽  
Mina Nekouei ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Amino Acid ◽  
Conformational Changes ◽  
Docking Simulation ◽  
Hydrogen Deuterium Exchange ◽  
Maldi Tof Ms ◽  
Maldi Tof ◽  
Hydrogen Deuterium ◽  
Tof Ms

Abstract The hydrogen/deuterium exchange (HDX) is a reliable method to survey the dynamic behavior of proteins and epitope mapping. Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) is a quantifying tool to assay for HDX in the protein of interest. We combined HDX-MALDI-TOF MS and molecular docking/MD simulation to identify accessible amino acids and analyze their contribution in the structural changes of profilin1 (PFN1). The molecular docking/MD simulations are computational tools for enabling the analysis of the type of amino acids that may be involved via HDX identified under the lowest binding energy condition. Glycine to Valine amino acid (G117V) substitution mutation is linked to amyotrophic lateral sclerosis (ALS). This mutation is found to be in the actin-binding site of PFN1 and prevents the dimerization/polymerization of actin and invokes a pathologic toxicity that leads to ALS. In this study, we sought to understand the PFN1 protein dynamic behavior using purified wild type and mutant PFN1 proteins. The data obtained from HDX-MALDI-TOF MS for PFN1WT and PFN1G117V at various time intervals, from seconds to hours, revealed multiple peaks corresponding to molecular weights from monomers to multimers. PFN1/Benzaldehyde complexes identified 20 accessible amino acids to HDX that participate in the docking simulation in the surface of WT and mutant PFN1. Consistent results from HDX-MALDI-TOF MS and docking simulation predict candidate amino acid(s) involved in the dimerization/polymerization of PFNG117V. This information may shed critical light on the structural and conformational changes with details of amino acid epitopes for mutant PFN1s’ dimerization, oligomerization, and aggregation.

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