RESUMO
HIV-1 drug resistance testing in children and adolescents in low-resource settings is both important and challenging. New (more sensitive) drug resistance testing technologies may improve clinical care, but evaluation of their added value is limited. We assessed the potential added value of using next-generation sequencing (NGS) over Sanger sequencing for detecting nucleoside reverse transcriptase inhibitor (NRTI) and nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutations (DRMs). Participants included 132 treatment-experienced Kenyan children and adolescents with diverse HIV-1 subtypes and with already high levels of drug resistance detected by Sanger sequencing. We examined overall and DRM-specific resistance and its predicted impact on antiretroviral therapy and evaluated the discrepancy between Sanger sequencing and six NGS thresholds (1%, 2%, 5%, 10%, 15%, and 20%). Depending on the NGS threshold, agreement between the two technologies was 62% to 88% for any DRM, 83% to 92% for NRTI DRMs, and 73% to 94% for NNRTI DRMs, with more DRMs detected at low NGS thresholds. NGS identified 96% to 100% of DRMs detected by Sanger sequencing, while Sanger identified 83% to 99% of DRMs detected by NGS. Higher discrepancy between technologies was associated with higher DRM prevalence. Even in this resistance-saturated cohort, 12% of participants had higher, potentially clinically relevant predicted resistance detected only by NGS. These findings, in a young, vulnerable Kenyan population with diverse HIV-1 subtypes and already high resistance levels, suggest potential benefits of more sensitive NGS over existing technology. Good agreement between technologies at high NGS thresholds supports their interchangeable use; however, the significance of DRMs identified at lower thresholds to patient care should be explored further. IMPORTANCE HIV-1 drug resistance in children and adolescents remains a significant problem in countries facing the highest burden of the HIV epidemic. Surveillance of HIV-1 drug resistance in children and adolescents is an important public health strategy, particularly in resource-limited settings, and yet, it is limited due mostly to cost and infrastructure constraints. Whether newer and more sensitive next-generation sequencing (NGS) adds substantial value beyond traditional Sanger sequencing in detecting HIV-1 drug resistance in real life settings remains an open and debatable question. In this paper, we attempt to address this issue by performing a comprehensive comparison of drug resistance identified by Sanger sequencing and six NGS thresholds. We conducted this study in a well-characterized, vulnerable cohort of children and adolescents living with diverse HIV-1 subtypes in Kenya and, importantly, failing antiretroviral therapy (ART) with already extensive drug resistance. Our findings suggest a potential added value of NGS over Sanger even in this unique cohort.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Criança , Humanos , Adolescente , HIV-1/genética , Quênia , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , Farmacorresistência Viral/genética , Genótipo , Carga Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Mutação , Sequenciamento de Nucleotídeos em Larga Escala , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêuticoRESUMO
The effects of a fluroquinolone levofloxacin on apoptosis of peripheral blood lymphocytes from patients with infiltrative pulmonary tuberculosis were studied in vitro. It was found that levofloxacin stimulated apoptotic cell death in tuberculosis. Addition of levofloxacin to cell suspension from patients with drug-susceptible form of tuberculosis led to an increase in the number of CD95+ and AnnV+ lymphocytes. In patients with drug-resistant form of tuberculosis, only the number of apoptotic lymphocytes, but not the count of CD95+ cells increased under these conditions.
Assuntos
Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Levofloxacino/farmacologia , Adulto , Apoptose/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Tuberculose Pulmonar , Receptor fas/metabolismoRESUMO
The effects levofloxacin (fluoroquinolone) and vaccinal BCG strain on cytokine production by blood mononuclear leukocytes was studied in patients with infiltrative pulmonary tuberculosis. Combined treatment with levofloxacin and vaccinal BCG strain suppressed the production of TNFα in drug-resistant pulmonary tuberculosis and production of IL-12 and IFNγ in drug-sensitive tuberculosis.
Assuntos
Antibacterianos/farmacologia , Vacina BCG/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Levofloxacino/farmacologia , Tuberculose Pulmonar/imunologia , Adulto , Estudos de Casos e Controles , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Interferon gama/biossíntese , Interferon gama/imunologia , Interleucina-12/biossíntese , Interleucina-12/imunologia , Interleucina-2/biossíntese , Interleucina-2/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium bovis/citologia , Mycobacterium bovis/imunologia , Mycobacterium tuberculosis/citologia , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Cultura Primária de Células , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologiaRESUMO
We compared changes in the redox status and intensity of oxidative modification of proteins in intact Jurkat tumor cells and cells cultured with buthionine sulfoximine, an inhibitor of the key enzyme of glutathione synthesis γ-glutamylcysteine synthetase. The glutathione system components play a role in modulation of the content of protein-bound glutathione, protein carbonyl derivatives, bityrosine, and oxidized tryptophan, and in dysregulation of apoptosis in Jurkat tumor cells. Inhibition of de novo synthesis of glutathione in Jurkat tumor cells was followed by accumulation of hydroxyl radical, a reduction in the level of protein-bound glutathione and oxidized tryptophan, and a rise in the concentration of protein carbonyl derivatives. These changes were accompanied by activation of programmed cell death.
Assuntos
Apoptose/efeitos dos fármacos , Butionina Sulfoximina/farmacologia , Inibidores Enzimáticos/farmacologia , Glutamato-Cisteína Ligase/genética , Glutationa/antagonistas & inibidores , Expressão Gênica , Glutamato-Cisteína Ligase/antagonistas & inibidores , Glutamato-Cisteína Ligase/metabolismo , Glutationa/metabolismo , Humanos , Radical Hidroxila/agonistas , Radical Hidroxila/metabolismo , Células Jurkat , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Triptofano/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
Activation of free radical oxidation in different cell types, including breast epithelial cells, may result in damage to macromolecules, in particular, proteins taking part in regulation of cell proliferation and apoptosis. The glutathione, glutaredoxin and thioredoxin systems play an essential role in maintaining intracellular redox homeostasis. Due to this fact, modulation of cellular redox status under the effect of an SH group inhibitor and an SH group protector may be used as a model for studying the role of redox proteins and glutathione in regulating cell proliferation in different pathological processes. In this study we have evaluated the state of the thioredoxin, glutaredoxin and glutathione systems as well as their role in regulating proliferation of HBL-100 breast epithelial cells under redox status modulation with N-ethylmaleimide (NEM) and 1,4-dithioerythriol (DTE). Modulating the redox status of breast epithelial cells under the effect of NEM and DTE influences the functional activity of glutathione-dependent enzymes, glutaredoxin, thioredoxin, and thioredoxin reductase through changes in the GSH and GSSG concentrations. In HBL-100 cells under redox-status modulation, we have found an increase in the number of cells in the S-phase of the cell cycle and a decrease in the number of cells in the G0/G1 and G2/Ð phases, as opposed to the values in the intact culture. The proposed model of proliferative activity of cells under redox status modulation may be used for development of new therapeutic approaches for treatment of diseases accompanied by oxidative stress generation.
Assuntos
Ditioeritritol/farmacologia , Inibidores Enzimáticos/farmacologia , Células Epiteliais/efeitos dos fármacos , Etilmaleimida/farmacologia , Substâncias Protetoras/farmacologia , Catalase/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Etilmaleimida/antagonistas & inibidores , Citometria de Fluxo , Glutarredoxinas/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Humanos , Glândulas Mamárias Humanas/citologia , Glândulas Mamárias Humanas/efeitos dos fármacos , Glândulas Mamárias Humanas/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Tiorredoxina Dissulfeto Redutase/metabolismo , Tiorredoxinas/metabolismoRESUMO
The effects of the SH-group blocker N-ethylmaleimide (NEM) and thiol group protector 1,4-dithioerythritol (DTE) on the redox status of cells HBL-100 cells, oxidative modification of their proteins and the state of glutathione and thioredoxin systems have been investigated. Breast epithelial cells cultivated in the presence of NEM were characterized by decreased redox status, increased glutathione reductase activity, and increased concentrations of products of irreversible oxidative modification of protein and amino acids. Cultivation of HBL-100 cells in the presence of DTE resulted in a shift of the redox status towards reduction processes and increased reversible protein modification by glutathionylation. The proposed model of intracellular redox modulation may be used in the development of new therapeutic approaches to treat diseases accompanied by impaired redox homeostasis (e.g. oncologic, inflammatory, cardiovascular and neurodegenerative disease).
Assuntos
Ditioeritritol/farmacologia , Células Epiteliais/metabolismo , Glutationa/metabolismo , Glândulas Mamárias Humanas/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Linhagem Celular , Feminino , Humanos , Oxirredução/efeitos dos fármacosRESUMO
The aim of this study was to establish the role of redox modification of proteins and redox status in the realization of apoptosis of MCF-7 breast adenocarcinoma cells du-ing cultivation with the SH-group blocker N-ethylmaleimide (NEM) and the SH-group protector 1,4-dithioerythritol (DTE). The activation of apoptosis in MCF-7 breast adenocarcinoma cells was shown to be due to the irreversible modification of redox sensitive protein molecules. The presence of DTE in the culture medium of cancer.cells caused reversible glutathionylation of protein molecules and did not change the: number of apoptotic MCF-7 cells.
Assuntos
Adenocarcinoma/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Processamento de Proteína Pós-Traducional , Ditioeritritol/farmacologia , Etilmaleimida/farmacologia , Glutationa/metabolismo , Humanos , Células MCF-7 , Oxirredução , Reagentes de Sulfidrila/farmacologiaRESUMO
There were studied distribution of polymorphic variants of gene of repair of DNA XPD A751C in lung cancer depending on histological type of tumor (small cell / non-small cell lung cancer) and the prevalence of tumor process (with foci / without foci of metastasis). It was found a significant increase in the incidence of minor allele C, CC and AC genotypes of the polymorphic site of gene XPD A751C in patients with lung cancer. We estimated relative risks of lung cancer development in carriers of polymorphic variants of gene XPD A751C. The heterozygous genotype AC polymorphism of gene XPD A751C is characterized by the greatest risk of developing lung cancer with small cell histological type. Homozygous CC genotype of the polymorphic site of gene XPD A751C is associated with non-small cell lung cancer development. Statistically significant differences in the distribution of polymorphic variants of gene A751C XPD depending on spread of cancer were not received.
Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Alelos , Reparo do DNA/genética , Feminino , Genótipo , Heterozigoto , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de RiscoRESUMO
The review provides information on current literature on structural and functional features of eosinophilic granulocytes and their role in the pathogenesis of cancer. There are examined data of clinical and experimental studies about an influence of hemic and tissue eosinophilia on the course and prognosis of malignant tumors. Molecular mechanisms of action of eosinophils in tumor pathology are discussed.
Assuntos
Eosinofilia/patologia , Granuloma Eosinófilo/patologia , Granulócitos/patologia , Eosinofilia/genética , Granuloma Eosinófilo/complicações , Granuloma Eosinófilo/genética , Eosinófilos/patologia , Humanos , Interleucinas/genéticaRESUMO
Spontaneous lipolysis was found to be increased in adipocytes of rats with alloxan-induced diabetes. In addition, isoproterenol-stimulated hydrolysis of triacylglycerols was inhibited against the background of oxidative stress and decreased redox-status of cells. A decrease in the ability of insulin to inhibit isoproterenol-stimulated lipolysis in adipocytes that were isolated from adipose tissue of rats with experimental diabetes was found, which shows a disorder in regulation of lipolysis in adipocytes by the hormone in alloxan-induced diabetes. Based on these findings, we concluded that there is an influence of reactive oxygen species, superoxide anion radical in particular, and redox potential of the glutathione system on molecular mechanisms of change in lipolysis intensity in rat adipocytes in alloxan-induced oxidative stress. Activation of spontaneous lipolysis under conditions of oxidative stress might be a reason for the high concentration of free fatty acids in blood plasma in experimental diabetes, and this may play a significant role in development of insulin resistance and appearance of complications of diabetes.
Assuntos
Adipócitos/metabolismo , Diabetes Mellitus Experimental/metabolismo , Glutationa/metabolismo , Insulina/farmacologia , Lipólise , Estresse Oxidativo/fisiologia , Superóxidos/metabolismo , Animais , Células Cultivadas , Resistência à Insulina , Masculino , Ratos , Ratos WistarRESUMO
CD4(+) T cells orchestrate the immune response by differentiating into T helper (Th) or regulatory (Treg) cell subsets that secrete distinct sets of cytokines. They also play a critical role in the pathogenesis of autoimmunity, asthma, allergy and, likely, cancer. The mechanisms involved in the regulation of CD4(+) T cell homeostasis by galectin-1 remain poorly characterized. To investigate whether galectin-1 modulates the differentiation of CD4(+) T cells, the effects of galectin-1 on the mRNA expression levels of TBX21, GATA-3, FOXP3 and RORC in activated peripheral blood mononuclear cells were examined. The expression levels of GATA-3 and FOXP3 mRNA were up-regulated after treatment with 1.0 µg/ml galectin-1 and were unchanged (for GATA-3) or slightly elevated (for FOXP3) compared with untreated cells when 2.0 µg/ml galectin-1 was added. At the same time, at both concentrations of galectin-1, we observed reduced TBX21 and RORC mRNA expression levels. These findings support the concept that galectin-1 skews the differentiation of CD4(+) T cells towards Th2 and Treg cells.
Assuntos
Fatores de Transcrição Forkhead/genética , Fator de Transcrição GATA3/genética , Galectina 1/farmacologia , Expressão Gênica/efeitos dos fármacos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Proteínas com Domínio T/genética , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Mitochondrial permeabilisation after NO donor application did not activate caspase-9. We have studied the X-linked apoptosis inhibitor (XIAP) and Aven protein content in NO-treated Jurkat cells. The level of both proteins increased in NO-treated cells. Thus the increase in XIAP and Aven content could be the cause of the lack of caspase-9 activity after mitochondrial permeabilisation in NO-treated Jurkat cells.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Triazenos/farmacologia , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Apoptose/efeitos dos fármacos , Caspase 9/metabolismo , Humanos , Células Jurkat , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Permeabilidade/efeitos dos fármacosRESUMO
In review the possibility of biomaterials osseointegration improvement with help of bisphosphonates or strontium ranelate is discussed. For this purpose, they are added to hydroxyapatite used for implants coating, or are included as a component of bulk calcium phosphate materials. Strontium is employed as a compound of biodegradable metal alloys, also. Combined use of carrier (implant) with bisphosphonates or strontium ranelate promotes controlling local delivery of pharmaceutical molecules into lesion, enhances the therapy efficiency, and decreases a dose and systemic toxicity of the drugs. Bisphosphonates and strontium ranelate increase the mass, a count and thickness of bone trabeculas, improve the bone biomechanical properties in the place of implants fixation, and diminish the bone fracture risk. Main studies are devoted to pharmacologic mechanisms of implants osseointegration improvement. Bisphosphonates as isoprenoid lipids chemical analogues diminish by concurrent principle the osteoclastsfarnesylpyrophosphate synthase activity and inhibit the prenylation. Unprenylated small GTPases don't fasten onto osteoclasts membrane that weakens cellular resorptive activity and accelerates their apoptosis. Strontium ranelate enhances osteoblasts replicative activity and suppresses their apoptosis, also retards osteoclasts resorptive function and accelerates their apoptosis. Its effects are conditioned by activating Wnt-signaling pathway by means of calcium-sensing receptor and by changing the RANKL/RANK/OPG system.
Assuntos
Doenças Ósseas/terapia , Substitutos Ósseos/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas Ósseas/terapia , Tiofenos/uso terapêutico , Implantes Absorvíveis , Conservadores da Densidade Óssea/uso terapêutico , HumanosRESUMO
Analysis of modern literature data as well as the results of personal research on development of oxidative stress in adipose tissue in diabetes is presented. Mechanisms of modulation of spontaneous and induced lipolysis in adipocytes in conditions of oxidative stress are discussed. Participation of adipose tissue in forming insulin resistance in types 1 and 2 diabetes is considered.
Assuntos
Tecido Adiposo/metabolismo , Diabetes Mellitus/metabolismo , Resistência à Insulina/fisiologia , Lipólise/fisiologia , Estresse Oxidativo , Adipócitos/metabolismo , Ácidos Graxos não Esterificados/sangue , Humanos , Peroxidação de Lipídeos , Peróxidos Lipídicos/sangueRESUMO
Modern immunological studies showed that eosinophilic granulocytes producing the key mediators of cellular and humoral immune response contribute to the common cytokine imbalance developing in tuberculous infection. A significant increase in BCG-induced secretion of IL-2, IL-5, and TNF-α by eosinophils in patients with pulmonary tuberculosis indicated high reserve reactivity of eosinophilic cells realizing their functional potential in regulation of the specific resistance reactions of the microorganism under conditions of M. tuberculosis infection.
Assuntos
Citocinas/metabolismo , Eosinófilos/metabolismo , Tuberculose Pulmonar/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Interleucina-2/metabolismo , Interleucina-5/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
Hemopoietic islets, associations of stromal (macrophages, fibroblasts) and blood (including stem) cells, are structural and functional units of the bone marrow. We studied cellular and molecular processes developing following short-term (1 h) contact of hemopoietic islets with ferromagnetic nanoparticles in a multicellular system of the bone marrow in vitro. It was established that nanodispersions of magnetite (Fe(3)O(4), mean particle diameter 18 nm) and iron coated with carbon (Fe(C), particle diameter 5-10 nm) in a dose of 3 mg/liter had a minor effect on processes of necrotic and apoptotic cell death. Nanodispersion of carbon-coated iron (Fe(C)) most mildly stimulated oxidizing processes recorded by intracellular levels of reactive oxygen species. These nanoparticles, in contrast to magnetite, did not reduce the amount of hemopoietic islets in the bone marrow cell suspension.
Assuntos
Células da Medula Óssea/fisiologia , Ferro/química , Magnetismo , Nanopartículas Metálicas , Animais , Células da Medula Óssea/metabolismo , Citometria de Fluxo , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de OxigênioRESUMO
In vitro experiments on cultured adipocytes from epididymal adipose tissue showed that addition of alloxan (0.5-10.0 mmol/liter) to the incubation medium induced the development of oxidative stress accompanied by an increase in the concentration of reactive oxygen species, TBA-reactive substances, and lipid hydroperoxides in cells. The redox state of adipocytes changed significantly under these conditions, which was associated with a decrease in the amount of reduced tripeptide, an increase in the content of glutathione disulfide, and a decrease in the reduced/oxidized glutathione ratio. The development of oxidative stress in adipocytes was accompanied by activation of spontaneous lipolysis, which probably plays an important role in the mechanisms of insulin resistance.
Assuntos
Adipócitos/metabolismo , Aloxano/farmacologia , Glutationa/biossíntese , Lipólise/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Animais , Células Cultivadas , Diabetes Mellitus/metabolismo , Dissulfeto de Glutationa/biossíntese , Resistência à Insulina , Masculino , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
We studied the effect of a gas transmitter hydrogen sulfide (H(2)S) on the realization of apoptosis in Jurkat cells and mononuclear leukocytes from healthy donors. Treatment with H(2)S donor NaHS was accompanied by a dose-dependent intensification of cell death via apoptosis and necrosis. T-cell leukemia cells were more sensitive to H2S than mononuclear leukocytes from healthy donors. H(2)S-induced cell apoptosis was accompanied by activation of caspase-3 and caspase-9.
Assuntos
Apoptose/efeitos dos fármacos , Sulfeto de Hidrogênio/metabolismo , Sulfetos/farmacologia , Caspases/metabolismo , Células Cultivadas , HumanosRESUMO
Psychoimmune interactions were studied in women of reproductive age with endometriosis. Pronounced immunological shifts manifested in a shift of the T-cellular immunity, resulting in imbalanced production of pro- (IL-1ß, IL-2, IFN-γ) and anti-inflammatory (IL-4) cytokines. Significant correlations between the severity of mental shifts and immunopathogenetic factors in the studied patient population demonstrated the psychoneuroimmune nature of endometriosis.
Assuntos
Endometriose/imunologia , Endometriose/psicologia , Adolescente , Adulto , Antígenos CD/metabolismo , Ansiedade/sangue , Ansiedade/epidemiologia , Ansiedade/imunologia , Estudos de Casos e Controles , Comorbidade , Citocinas/sangue , Depressão/sangue , Depressão/epidemiologia , Depressão/imunologia , Endometriose/sangue , Endometriose/epidemiologia , Feminino , Humanos , Contagem de Linfócitos , Linfócitos/imunologia , Linfócitos/metabolismo , Pessoa de Meia-Idade , Estresse Psicológico/sangue , Estresse Psicológico/epidemiologia , Estresse Psicológico/imunologia , Adulto JovemRESUMO
We studied the state of the thiol-disulfide system (contents of reduced and oxidized glutathione, their ratio, and concentrations of protein SH-groups and protein-bound glutathione) and functional properties of neutrophils (production of hydroxyl radicals, IL-8, and TNF-α and myeloperoxidase activity) from healthy donors under conditions of oxidative stress in vitro induced by H(2)O(2)in a final concentration of 200 µM and from patients with community-acquired pneumonia. We evaluated the role of reduced and protein-bound glutathione in the regulation of functional state of blood neutrophils from patients with community-acquired pneumonia and during oxidative stress in vitro under conditions cell incubation with N-ethylmaleimide or 1,4-dithioerythritolsulfhydryl, the blocker and protector of sulfhydryl groups, respectively.