RESUMO
We revealed some features of the neurohumoral and immune profile in preschool children with functional disorders of the autonomic nervous system (ANS) associated with the polymorphism of the SIRT1 gene (rs7069102) responsible for stability of the cell cycle, energy and plastic metabolism of organic substances, and Ca2+ exchange. The neurohumoral profile of the surveyed children is characterized by excessive content of glutamic acid and serotonin, which leads to excessive synaptic activation and disorders of ANS inhibition (p<0.05). The cell immune profile is characterized by a reduced immunoregulatory index CD4+/CD8+ with a simultaneous deficiency of CD3+CD4+ and excess of CD3+CD8+ lymphocytes (p<0.05). These etiopathogenetic disorders of the neurohumoral and immune profile are associated with variant G-allele of the SIRT1 gene (rs7069102) and the corresponding homozygous GG-genotype (p<0.05), which leads to disturbances in the control of the cell cycle stability, including apoptosis, cytochrome deacetylation, inhibition of the glutamate dehydrogenase enzyme activity with excessive glutamate accumulation, energy metabolism in mitochondria, and Ca2+ exchange. The revealed features of neurotransmitters content (excess of serotonin and glutamic acid) and indicators of cell immunity (reduced proportion of CD4+/CD8+ cells) associated with the variant G allele and GG genotype of the SIRT1 gene (rs7069102) form a complex of neurohumoral, immune, and genetic markers in children with functional disorders of ANS (G90.8). This allows recommending them as indicators for early diagnosis and prevention of autonomic disorders in children.
Assuntos
Doenças do Sistema Nervoso Autônomo , Sirtuína 1 , Doenças do Sistema Nervoso Autônomo/imunologia , Pré-Escolar , Humanos , Neurotransmissores/genética , Polimorfismo de Nucleotídeo Único , Sirtuína 1/genéticaRESUMO
The study examined peculiarities of immune regulation and associated polymorphic variants of candidate genes in men with atherosclerosis in Perm region. The revealed deficiency of CD127 lymphocytes and Annexin V-FITC+7AAD- cells, as well as enhanced level of CD3+CD4+ lymphocytes against the background of variant alleles of candidate genes FAS (rs1159120), CPOX (rs1131857) and wild-type alleles SULT1A1 (rs9282861), MMP9 (rs17576) are responsible for peculiar features of hereditary determination and pathogenesis of atherosclerosis in examined sample (p<0.05). The genetically determined degradation of extracellular matrix in vascular wall and implication of regulated Fas/APO1 apoptosis in the development of progressive atherosclerotic lesions indicate important role of immune system in atherogenesis. The revealed immunological and genetic features are recommended as the markers for early diagnosis of atherosclerosis and its prevention in men of Perm region.
Assuntos
Aterosclerose/genética , Polimorfismo Genético/genética , Adulto , Alelos , Arilsulfotransferase/genética , Arilsulfotransferase/metabolismo , Aterosclerose/imunologia , Complexo CD3/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Humanos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
We studied the immunological status and polymorphic variants of candidate genes in men with disturbances of autonomic nervous regulation under conditions of aerogenic exposure to benzene. The group of men with pathology of the autonomic nervous system (autonomic dysfunction syndrome) living under conditions of aerogenic exposure to benzene is characterized by increased blood contamination with benzene, which 1.5-fold surpassed this parameter in the group of conventionally healthy men (p<0.05). The immune profile of the surveyed men is characterized by increased specific sensitization (IgG to benzene) and activation of apoptosis (TNFR, p53) and phagocytosis. The production of serum IgA was also increased (p<0.05) in men of this group. The content of CD127- lymphocytes significantly (p<0.05) exceeded the reference level against the background of a significantly reduced (p<0.05) level of CD3+CD95+ lymphocytes irrespective of the presence or absence of autonomic nervous system pathology in men with excessive haptenic load with benzene. The revealed features of the immune status of men with autonomic regulation disorders were significantly associated (OR>1; p<0.05) with the variant allele of the FOXP3 immune regulation gene (rs3761547) and with wild-type allele of the SOD2 superoxide dismutase gene (rs2758330) and the corresponding homozygous genotypes. The established features of immune regulation (hyperproduction of IgG to benzene, imbalance of apoptosis markers (CD127-, CD3+CD95+, p53, and TNFR) against the background of altered polymorphism of candidate genes (FOXP3, SOD2) form a complex of genetic and immunological markers of autonomic regulation disorders in men living under conditions of aerogenic exposure to benzene.
Assuntos
Doenças do Sistema Nervoso Autônomo/genética , Doenças do Sistema Nervoso Autônomo/imunologia , Benzeno/toxicidade , Exposição Ambiental/efeitos adversos , Imunidade Inata/efeitos dos fármacos , Adulto , Poluentes Atmosféricos/toxicidade , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/epidemiologia , Estudos de Casos e Controles , Exposição Ambiental/análise , Exposição Ambiental/estatística & dados numéricos , Fatores de Transcrição Forkhead/genética , Frequência do Gene , Interação Gene-Ambiente , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Imunidade Inata/genética , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Federação Russa/epidemiologia , Superóxido Dismutase/genéticaRESUMO
The study employed in vitro assay to examine the peculiarities of immune status in children with functional disorders of the autonomic nervous system diagnosticated as asthenoneurotic syndrome. In contrast to control children without asthenoneurotic syndrome, the examined group was characterized by significantly (p<0.05) elevated hapten-specific immunological sensitization (indicated by anti-Al IgG), induction of inflammatory reactions (IL-1), activation of apoptosis (CD3+CD95+ and Ñ53) observed against the background inhibition of adaptive immune response (CD3+, CD3+CD4+, CD3+CD8+, CD16+56+, and CD19+), as well as hyperexpression of glutamic acid, NO, and VEGF combined with deficiency of serotonin. In cultured immunocompetent cells derived from children with hapten-modified immune status, the combined application of cytokine stimulator IL-1 with hapten sensitizer aluminum or with endocrine stimulator cortisol significantly (p<0.05) up-regulated expression of IL-8 and IL-10, but down-regulated production of IL-17 in a dose-dependent manner.
Assuntos
Haptenos/toxicidade , Neurastenia/diagnóstico , Neurastenia/metabolismo , Antígenos CD19/metabolismo , Complexo CD3/metabolismo , Antígenos CD4/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Criança , Humanos , Receptores de IgG/metabolismo , Serotonina/metabolismoRESUMO
The study covered influence of combined toxic chemicals on fire extinguishers. Acute exposure of respiratory and peripheral nervous systems was demonstrated. Consequences of the exposure were proved to include polyneuropathies, neuroses and other health disorders.
Assuntos
Incêndios , Substâncias Perigosas/efeitos adversos , Doenças do Sistema Nervoso/induzido quimicamente , Transtornos Neuróticos/induzido quimicamente , Doenças Profissionais/induzido quimicamente , Ocupações , Doenças Respiratórias/induzido quimicamente , Adulto , Humanos , Masculino , Doenças do Sistema Nervoso/diagnóstico , Transtornos Neuróticos/diagnóstico , Doenças Profissionais/diagnóstico , Doenças Respiratórias/diagnóstico , Fatores de TempoRESUMO
Treatments results of 22 cases of atypical generalized and local carcinoma of the prostate involving different cells and tissues and accompanied by persistent neuropathic pain are described in the paper. The method of continuous epidural analgesia by an opioid agonist ((a 2% morphine hydrochloride solution and a local anesthetic) and by a 0.5% anekain solution provides for a smaller single dose of the preparation and for a less number of injections that should be used; it also eliminates the pain stress and improves the life quality of patients.