Immunoglobulins and predicted mortality in clinical course of concomitant HIV and TB infection

A search for prognostic markers of HIV and tuberculosis coinfection (HIV/TB), especially in case of Mycobacterium tuberculosis multidrug resistance (MDR MBT) associated with low rates of TB eradication, is of relevance in connection with the problem of choosing adequate anti-TB therapy which is able to decrease mortality. 113 HIV/TB patients aged 24 to 58 years were examined: 70 males and 43 females hospitalized at the Novokuznetsk TB Clinic during the 2017—2019 period. MDR MBT (concomitant resistance to Isoniazid and Rifampicin) was found in 50 patients (12 patients with MDR MBT had additional resistance to Fluoroquinolones) aged 24 to 54 years — 31 males and 19 females. The control group consisted of 49 healthy individuals aged 27 to 72 years (26 females and 23 males) lacking focal and systemic infections with moderately pronounced age-related changes. In plasma samples, concentration of total (non-specific) immunoglobulins of classes E, M, G, A (including secretory immunoglobulin A, sIgA) were measured by using enzyme-linked immunosorbent assay. Data statistical processing was performed by using licensed software packages InStatII, Microsoft Excel, IBM SPSS Statistics 22. An extended range of individual variability in count of peripheral blood CD4 lymphocytes was revealed both among non-survivor and survivor patients with HIV/TB examined, being a drawback of using such parameter as lethality predictor. It was found that the serum level of total IgE, IgM, IgG, IgA and sIgA in patients with HIV/ TB was higher than that one in control group, whereas in non-survivor vs. survivor patients the concentration of IgE and sIgA was elevated. The coefficient of disease outcome prediction (CP) for patients with HIV/TB and MDR MBT was calculated being equal to the ratio of the multiplication of serum concentration of IgE, IgM, IgA and secretory IgA to CD4 lymphocyte count (CP = IgE x IgM x IgA x sIgA/CD4). CP higher than 200 was detected in 77% non-survivor and 6% of survivor patients. The relative risk of death with CP > 200 was very high (OR = 56.7, p < 0.0001) being 8.5 times higher than that one upon CD4 < 200 (OR = 6.7, p = 0.0237). A positive correlation between CP and lethal outcome was more valuable than that of CD4. The data presented allow us to propose CP for clinical use as an effective prognostic criterion for HIV/TB with MDR MBT

The relationship between self-organization and membrane effects of aqueous dispersion systems of the thyroliberin oligopeptide

© 2017, Pleiades Publishing, Ltd. The relationship between rearrangement of the dispersed phase inducing considerable changes in the pH and nonmonotonic concentration dependences of membrane effects in aqueous systems of the endogenous regulatory peptide, thyroliberin (thyrotropin-releasing hormone), in 10 –3 –10 –16 mol/L concentration range was demonstrated for the first time. The membrane structure modification in the 10 –13 –10 –16 mol/L range was found to be due to accumulation of nanoassociates, while the oppositely directed pronounced structural changes in the 10 –6 –10 –12 mol/L range may be associated with the coexistence and rearrangement of dispersed phases of various nature (domains and associates) whose action on membrane lipid components is regulated in this concentration range by the correlated changes in the dispersed phase parameters and pH

Real-Time PCR Detection of <i>Bacillus anthracis</i> by Lambda_Ba03 Prophage Genes

The aim of the study was to develop a set of primers and fluorescent probes for the detection of two chromosomal targets of Bacillus anthracis using real-time PCR based on the lambda_Ba03 prophage genes.Materials and methods. BLAST analysis of B. anthracis chromosomal DNA identified two target genes in the region of lambdaBa03 prophage, BA_5358 (AE016879.1: 4852332..4853642) and BA_5361 (AE016879.1: 4855298..4856278). The designed primers and fluorescent hydrolysable TaqMan probes for simultaneous detection of B. anthracis chromosomal DNA by two stated genes were tested in qPCR for sensitivity and specificity.Results and discussion. Studies performed on chromosomal DNA samples of closely related bacteria (B. cereus, B. thuringiensis, B. subtilis, B. clausii) have shown 100 % specificity of the developed sets of primers/probes. The sensitivity of the devised multiplex kit, tested on DNA samples of the m55-VNIIVViM vaccine strain and archival DNA samples of B. anthracis, reached 100 fg of bacterial DNA, which sets the limit of sensitivity at 17 genomes per reaction. The developed multiplex kit can be used as a separate tool for research laboratories studying anthrax

Modulation of the Functional State of Mouse Neutrophils by Selenium Nanoparticles In Vivo

This study aimed to discover the immunomodulatory effect of selenium nanoparticles (SeNPs) on the functional state of neutrophils in vivo. Intraperitoneal injections of SeNPs (size 100 nm) 2.5 mg/kg/daily to BALB/c mice for a duration of 7–28 days led to the development of an inflammatory reaction, which was registered by a significant increase in the number of neutrophils released from the peritoneal cavity, as well as their activated state, without additional effects. At the same time, subcutaneous injections of the same SeNPs preparations at concentrations of 0.1, 0.5, and 2.5 mg/kg, on the contrary, modulated the functional state of neutrophils depending on the concentration and duration of SeNPs administration. With the use of fluorescence spectroscopy, chemiluminescence, biochemical methods, and PCR analysis, it was found that subcutaneous administration of SeNPs (0.1, 0.5, and 2.5 mg/kg) to mice for a short period of time (7–14 days) leads to modification of important neutrophil functions (adhesion, the number of migrating cells into the peritoneal cell cavity, ROS production, and NET formation). The obtained results indicated the immunostimulatory and antioxidant effects of SeNPs in vivo during short-term administration, while the most pronounced immunomodulatory effects of SeNPs were observed with the introduction of a low concentration of SeNPs (0.1 mg/kg). Increase in the administration time of SeNPs (0.1 mg/kg or 2.5 mg/kg) up to 28 days led to a decrease in the adhesive abilities of neutrophils and suppression of the expression of mRNA of adhesive molecules, as well as proteins involved in the generation of ROS, with the exception of NOX2; there was a tendency to suppress gene expression pro-inflammatory factors, which indicates the possible manifestation of immunosuppressive and anti-inflammatory effects of SeNPs during their long-term administration. Changes in the expression of selenoproteins also had features depending on the concentration and duration of the administered SeNPs. Selenoprotein P, selenoprotein M, selenoprotein S, selenoprotein K, and selenoprotein T were the most sensitive to the introduction of SeNPs into the mouse organism, which indicates their participation in maintaining the functional status of neutrophils, and possibly mediated the immunomodulatory effect of SeNPs

HE DEPENDENCE OF IMMUNOGLOBULIN IGA AND IGE TEAR LEVELS FROM GLUTATHIONES-TRANSFERASE P1 GENE POLYMORPHISMS IN STEELWORKERS WITH OPHTHALMOPATHY

Abstract.  Associations  between  I105V  and  A114V gene  polymorphisms  of  glutathione-S-transferase P1  and  levels  of  IgE  and  secretory  IgA  in  tear  fluid were  studied  in  steelworkers  with  or  without  ocular diseases,  as  compared  with  healthy  office  employees. Genotyping was performed by means of allele-specific polymerase chain reaction, whereas ELISA technique was used for immune testing. We have found that IgE levels in tear fluid was increased in steelworkers with dystrophic eye diseases, pinguecula/pterygium, and healthy steelworkers, in comparison with control group. This increase correlates with pinguecula/pterygium size and with their industrial employment terms. Secretory IgА levels in tears were decreased in these groups of workers, as compared with controls. Concentrations of both  immunoglobulins  in  tear  samples  depended  on  I105V  and  А114V  glutathione-S-transferase  P1  gene polymorphisms. I105V polymorphism correlated with lower concentrations of tear IgЕ in steelworkers with ocular  dystrophic  diseases  and  healthy  metallurgists.  А114V  polymorphism  is  connected  with  decreased quantities of tear IgЕ in steelworkers with ocular dystrophic diseases, as well as with the lower amounts of secretory  IgА  in  healthy  workers  and  administrative  staff.  Hence,  polymorphic  loci  I105V  and  А114V  of glutathione-S-transferase P1 gene may exert a modulatory effect upon biosynthesis of both Ig types. (Med. Immunol., 2011, vol. 13, N 6, pp 609-616

SERUM SECRETORY IMMUNOGLOBULIN A AND Gln223Arg POLYMORPHISM OF THE LEPR GENE IN ALCOHOLIC AND NON-ALCOHOLIC FATTY LIVER DISEASES

Level of serum secretory immunoglobulin A was investigated in alcoholic liver disease (ALD, 59 men and 23 women) and non-alcoholic fatty liver disease (NAFLD, 17 men and 93 women).The data were compared with those of persons without liver pathology (control group, 43 men and 73 women). Moreover, we studied possible associations between ssIgA level and Gln223Arg polymorphism of the LEPR gene. Immunological and DNA diagnostics was performed by means of, respectively, ELISA and allele-specific polymerase chain reaction. We have found that the average level of ssIgA was three times higher in ALD group (11.45±0.82 mg/l), than in the NAFLD group (4.35±0.35 mg/l) or in controls (3,60±0,29 mg/l). SsIgА concentration did not depend on adiposity and gender. The ssIgА concentration proved to be increased in Gln223Arg heterozygotes with NAFLD, when compared with controls. However, the frequency of 223Arg and 223Gln alleles was virtually equal in all observed groups with above-normal concentration of ssIgА, as compared to a sub-group with normal ssIgА concentration. Hence, we have not revealed any significant association between Gln223Arg polymorphism of LEPR and ssIgA level. The data obtained will be useful for studying genetic risk factors in development of infectious mucosаl lesions

Immunomodulatory and Anti-Inflammatory Properties of Selenium-Containing Agents: Their Role in the Regulation of Defense Mechanisms against COVID-19

The review presents the latest data on the role of selenium-containing agents in the regulation of diseases of the immune system. We mainly considered the contributions of selenium-containing compounds such as sodium selenite, methylseleninic acid, selenomethionine, and methylselenocysteine, as well as selenoproteins and selenium nanoparticles in the regulation of defense mechanisms against various viral infections, including coronavirus infection (COVID-19). A complete description of the available data for each of the above selenium compounds and the mechanisms underlying the regulation of immune processes with the active participation of these selenium agents, as well as their therapeutic and pharmacological potential, is presented. The main purpose of this review is to systematize the available information, supplemented by data obtained in our laboratory, on the important role of selenium compounds in all of these processes. In addition, the presented information makes it possible to understand the key differences in the mechanisms of action of these compounds, depending on their chemical and physical properties, which is important for obtaining a holistic picture and prospects for creating drugs based on them