Improvement of Possibilities of Treating Pneumonias in Patients on the Background of Acute Myeloblast Leucosis in the Aspect of Immunoresistance Mechanisms

Aim: to analyze the influence of the immunomodeling preparation glutamyl-cysteinyl-glycine disodium (glutoxim) on indices of cellular and humoral immunity in patients with pneumonias on the background of acute myeloblast leucosis to form new approaches to the improvement of treating pneumonias in patients with immunity disorders.Materials and methods. The research group - 37 patients with pneumonia on the background of acute myeloblast leucosis, who underwent the program treatment on the base of the hematological center “MI city multi-profile clinical hospital №4” Dnipro city, 2014-2015. The age of patients from 23 to 45 years old; 10 women and 27 men. The diagnosis of leucosis and pneumonia forms was verified corresponding to modern conventional clinical and morphological criteria. Patients from the main research group (n = 18) were prescribed with glutamyl-cysteinyl-glycine disodium by the scheme 2 ml of 3 % (60 mg) i/v № 10 in mornings, summary dose - 300 mg. Indications of immunograms were studied: Т-lymphocytes, В-lymphocytes and their subpopulation composition (CD3 +, CD4 +, CD8 +, CD19 +, CD19-, CD16 +, CD56+) using the flowing laser cytofluorimetry. Immunoglobulin levels were determined by the method of immunoturbometry. Indications of immunograms were assessed in the treatment dynamics. The statistical processing – using packages of applied programs «Excel» and «Statistic 10».Results. According to the analysis of indices of the cellular and humoral immunity of patients with pneumonia on the background of acute myeloblast leucosis, the process of glutamyl-cysteinyl-glycine disodium use proved the statistically reliable activation of phagocytosis and anti-infectious defense indices. The dynamics of humoral immunity indices also proved the positive influence on the state of the immune reactivity of the organism with the reliable increase of ІgА and Іg М, responsible for neutralization of infectious agents and bacterial toxins.Conclusions: The use of the ummunomodeling preparation glutamyl-cysteinyl-glycine disodium (glutoxim) in patients with pneumonia on the background of acute myeloblast leucosis results in the improvement of indices of cellular and humoral immunity and phagocytosis activation. The research results prove the possibility of optimization of approaches to treating pneumonias in patients with severe immunity disorders by using immunomedeling therapy by glutamyl-cysteinyl-glycine disodium (glutoxim)

LTD4 and TGF-β1 induce the expression of metalloproteinase-1 in chronic rhinosinusitis via a cysteinyl leukotriene receptor 1-related mechanism

A

Concentrations of Cysteinyl Leukotrienes in Various Biological Fluids of Children with Bronchial Asthma, Atopic Dermatitis and Food Protein Induced Enterocolitis

Clinical manifestation of food allergy is characterized by polymorphic cutaneous, respiratory and gastrointestinal syndromes. Leukotrienes occupy a key place in the pathogenesis of a wide range of inflammatory diseases, including bronchial asthma, allergic rhinitis, atopic dermatitis, hives, allergic conjunctivitis, atherosclerotic cardio-vascular lesions system, inflammatory bowel disease, multiple sclerosis, cancer, etc. Better understanding of general pathophysiological mechanisms of allergic realization put the focus on the studying of cysteinyl leukotrienes biological effects in infants with atopic dermatitis and food-protein induced enterocolitis important.Aim. To optimize the diagnosis of allergic lesions of the gastrointestinal tract in children.Methods. The study was conducted in the allergy center and children clinic of the «Institute Pediatrics, Obstetrics and Gynecology named after academician O. Lukyanova of NAMS of Ukraine». Children were included from September 2017 to June 2018.We examined 60 patients aged from 3 months to 3 years old, including 22 patients with atopic dermatitis, 18 children with food-protein induced enterocolitis, 8 patients with bronchial asthma in the stage of aggravation and 12 practically healthy children (control group).Medical examination have been perfomed, general IG E and specific serum IG E were defined by ImmunoCAP (Phadia, 100), as well as concentrations of cysteinyl leukotrienes (LTB4, LTC4, LTE4) in biological liquids (serum, saliva, urine) using immunoenzyme method using the production sets of the "Enzolifescience" (USA) company on the analyzer-photometer Multiskan Plus "Labsystems". The results of the received data were processed statistically. The probability of differences was estimated with Student's t-test and Tau Kendall rank correlation test. The difference was considered significant at p <0.05.Results. A significant increase in the concentrations of cysteinyl leukotrienes (C4, D4, E4) in the blood, urine and saliva was found in infants with allergic skin diseases, gastro-intestinal and respiratory tract surveyed during manifestation the disease compared with the control group.Comparison of concentrations of leukotrienes in urine and saliva of children with atopic dermatitis (AD), food-protein induced enterocolitis (FPIE) and asthma did not find credible. However, in the serum of patients with asthma, the concentration of cysteinyl leukotrienes was significantly higher (703.9±68.7) pg / ml than in children with enterocolitis induced by dietary proteins (509.3±57.4) pg / ml and significantly did not differ from patients with atopic dermatitis (695.2±46.3) pg / ml.According to the results of Kendall Tau correlation test, no significant Spearman rank correlation was found between the cysteinyl leukotrienes concentration in blood and urine – r=0.14 (p>0.05), blood and saliva r=0.07 (p>0.05), urine and saliva r=–0.52 (p>0.05).Conclusions. Increase in cysteinyl leukotrienes concentrations in serum, urine and saliva of children of early age with allergic skin diseases, respiratory and gastrointestinal tract was found. The absence of significant Spearman rank correlation between concentrations of leukotrienes in blood and urine, blood and saliva, saliva and urine shows that it is possible to select any biological fluid, saliva or urine, as a non-invasive way to determine the leukotriene concentrations for monitoring activity of allergic inflammation

Concentrations of Cysteinyl Leukotrienes in Various Biological Fluids of Children with Bronchial Asthma, Atopic Dermatitis and Food Protein Induced Enterocolitis

Clinical manifestation of food allergy is characterized by polymorphic cutaneous, respiratory and gastrointestinal syndromes. Leukotrienes occupy a key place in the pathogenesis of a wide range of inflammatory diseases, including bronchial asthma, allergic rhinitis, atopic dermatitis, hives, allergic conjunctivitis, atherosclerotic cardio-vascular lesions system, inflammatory bowel disease, multiple sclerosis, cancer, etc. Better understanding of general pathophysiological mechanisms of allergic realization put the focus on the studying of cysteinyl leukotrienes biological effects in infants with atopic dermatitis and food-protein induced enterocolitis important.Aim. To optimize the diagnosis of allergic lesions of the gastrointestinal tract in children.Methods. The study was conducted in the allergy center and children clinic of the «Institute Pediatrics, Obstetrics and Gynecology named after academician O. Lukyanova of NAMS of Ukraine». Children were included from September 2017 to June 2018.We examined 60 patients aged from 3 months to 3 years old, including 22 patients with atopic dermatitis, 18 children with food-protein induced enterocolitis, 8 patients with bronchial asthma in the stage of aggravation and 12 practically healthy children (control group).Medical examination have been perfomed, general IG E and specific serum IG E were defined by ImmunoCAP (Phadia, 100), as well as concentrations of cysteinyl leukotrienes (LTB4, LTC4, LTE4) in biological liquids (serum, saliva, urine) using immunoenzyme method using the production sets of the "Enzolifescience" (USA) company on the analyzer-photometer Multiskan Plus "Labsystems". The results of the received data were processed statistically. The probability of differences was estimated with Student's t-test and Tau Kendall rank correlation test. The difference was considered significant at p <0.05.Results. A significant increase in the concentrations of cysteinyl leukotrienes (C4, D4, E4) in the blood, urine and saliva was found in infants with allergic skin diseases, gastro-intestinal and respiratory tract surveyed during manifestation the disease compared with the control group.Comparison of concentrations of leukotrienes in urine and saliva of children with atopic dermatitis (AD), food-protein induced enterocolitis (FPIE) and asthma did not find credible. However, in the serum of patients with asthma, the concentration of cysteinyl leukotrienes was significantly higher (703.9±68.7) pg / ml than in children with enterocolitis induced by dietary proteins (509.3±57.4) pg / ml and significantly did not differ from patients with atopic dermatitis (695.2±46.3) pg / ml.According to the results of Kendall Tau correlation test, no significant Spearman rank correlation was found between the cysteinyl leukotrienes concentration in blood and urine – r=0.14 (p>0.05), blood and saliva r=0.07 (p>0.05), urine and saliva r=–0.52 (p>0.05).Conclusions. Increase in cysteinyl leukotrienes concentrations in serum, urine and saliva of children of early age with allergic skin diseases, respiratory and gastrointestinal tract was found. The absence of significant Spearman rank correlation between concentrations of leukotrienes in blood and urine, blood and saliva, saliva and urine shows that it is possible to select any biological fluid, saliva or urine, as a non-invasive way to determine the leukotriene concentrations for monitoring activity of allergic inflammation

The treatment of asthma with leukotriene receptor antagonists

Over the past three decades the pharmacotherapy of asthma has been based on glucocorticoids, ß2 agonists and theophyllines. Research conducted over the past 10 years has led to greater understanding of the cellular and molecular basis of asthma, particularly the role of the underlying inflammatory process.peer-reviewe

Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s.

Group 2 innate lymphoid cells (ILC2s) and type 2 helper T cells (Th2 cells) are the primary source of interleukin 5 (IL-5) and IL-13 during type 2 (allergic) inflammation in the lung. In Th2 cells, T cell receptor (TCR) signaling activates the transcription factors nuclear factor of activated T cells (NFAT), nuclear factor κB (NF-κB), and activator protein 1 (AP-1) to induce type 2 cytokines. ILC2s lack a TCR and respond instead to locally produced cytokines such as IL-33. Although IL-33 induces AP-1 and NF-κB, NFAT signaling has not been described in ILC2s. In this study, we report a nonredundant NFAT-dependent role for lipid-derived leukotrienes (LTs) in the activation of lung ILC2s. Using cytokine reporter and LT-deficient mice, we find that complete disruption of LT signaling markedly diminishes ILC2 activation and downstream responses during type 2 inflammation. Type 2 responses are equivalently attenuated in IL-33- and LT-deficient mice, and optimal ILC2 activation reflects potent synergy between these pathways. These findings expand our understanding of ILC2 regulation and may have important implications for the treatment of airways disease

Involvement of leukotriene pathway in the pathogenesis of ischemia-reperfusion injury and septic and non-septic shock.

The 5-lipoxygenase (5-LO) pathway is responsible for the production of leukotrienes (LTs), inflammatory lipid mediators which play a role in innate immunity. More recently, a pivotal role of LTs in ischemia-reperfusion and shock injury has been suggested. In fact, these pathological conditions are characterized by a severe neutrophil infiltration that gives rise to tissue injury and 5-LO metabolites control neutrophil recruitment in injured tissue by the modulation of adhesion molecule expression. The aim of this review is to analyze the results reported in the literature on the role of 5-LO pathway, with particular regard to LTs, in these pathological conditions. A better understanding of the mechanisms underlying the role of the 5-LO enzyme and/or its metabolites in the regulation of neutrophil trafficking, might open new perspectives in the therapy of organ dysfunction and/or injury associated with shock and ischemia-reperfusion injury

Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease

BACKGROUND: The recent growing evidence that the proximal tubule underlies the early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and promising perspectives. This pathophysiological concept links tubulointerstitial oxidative stress, inflammation, hypoxia, and fibrosis with the progression of DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal tubular cells emerge as an innovative opportunity for prevention and management of DKD as well as to improve diabetic dysmetabolism. SUMMARY: The mercapturate pathway (MAP) is a classical metabolic detoxification route for xenobiotics that is emerging as an integrative circuitry detrimental to resolve tubular inflammation caused by endogenous electrophilic species. Herein we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of proximal tubular cell function, and cysteine-S-conjugates might represent targets for early intervention in DKD. Moreover, the biomonitoring of urinary mercapturates from metabolic inflammation products might be relevant for the implementation of preventive/management strategies in DKD.info:eu-repo/semantics/publishedVersio

Review

The chalcogen elements oxygen, sulfur, and selenium are essential constituents of side chain functions of natural amino acids. Conversely, no structural and biological function has been discovered so far for the heavier and more metallic tellurium element. In the methionine series, only the sulfur-containing methionine is a proteinogenic amino acid, while selenomethionine and telluromethionine are natural amino acids that are incorporated into proteins most probably because of the tolerance of the methionyl-tRNA synthetase; so far, methoxinine the oxygen analogue has not been discovered in natural compounds. Similarly, the chalcogen analogues of tryptophan and phenylalanine in which the benzene ring has been replaced by the largely isosteric thiophene, selenophene, and more recently, even tellurophene are fully synthetic mimics that are incorporated with more or less efficiency into proteins via the related tryptophanyl- and phenylalanyl-tRNA synthetases, respectively. In the serine/cysteine series, also selenocysteine is a proteinogenic amino acid that is inserted into proteins by a special translation mechanism, while the tellurocysteine is again most probably incorporated into proteins by the tolerance of the cysteinyl-tRNA synthetase. For research purposes, all of these natural and synthetic chalcogen amino acids have been extensively applied in peptide and protein research to exploit their different physicochemical properties for modulating structural and functional properties in synthetic peptides and rDNA expressed proteins as discussed in the following review

Phase 2 trial of montelukast for prevention of pain in sickle cell disease.

Cysteinyl leukotrienes (CysLTs) are lipid mediators of inflammation. In patients with sickle cell disease (SCD), levels of CysLTs are increased compared with controls and associated with a higher rate of hospitalization for pain. We tested the hypothesis that administration of the CysLT receptor antagonist montelukast would improve SCD-related comorbidities, including pain, in adolescents and adults with SCD. In a phase 2 randomized trial, we administered montelukast or placebo for 8 weeks. The primary outcome measure was a >30% reduction in soluble vascular cell adhesion molecule 1 (sVCAM), a marker of vascular injury. Secondary outcome measures were reduction in daily pain, improvement in pulmonary function, and improvement in microvascular blood flow, as measured by laser Doppler velocimetry. Forty-two participants with SCD were randomized to receive montelukast or placebo for 8 weeks. We found no difference between the montelukast and placebo groups with regard to the levels of sVCAM, reported pain, pulmonary function, or microvascular blood flow. Although montelukast is an effective treatment for asthma, we did not find benefit for SCD-related outcomes. This clinical trial was registered at www.clinicaltrials.gov as #NCT01960413