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P.1.g.016 Immunity system state in liquidators of consequences of Chernobyl atomic power station accident
P.1.g Basic neuroscience – Other secretion of neurotransmitters, proteins, etc. Indeed, the physiological mechanisms which are involved in the natural regulation of store-operated Ca2+ entry are poorly understood. Recently, the involvement of mitochondria in the regulation of Ca2+ release from the intracellular Ca2+ stores was shown for several cell types. In addition, it was shown that mitochondria are localized strikingly close to the plasma membrane. Thus they could be able to mediate effective calcium buffering upon activation of calcium entry. Methods: We utilized several imaging methods to measure free calcium concentration in the cytoplasm and intracellular calcium stores, such as mitochondria and endoplasmic reticulum. Calcium concentration in the cytosol ([Ca2+ ]i ), inside the mitochondria ([Ca2+ ]mit ) and in the endoplasmic reticulum ([Ca2+ ]ER ) were measured using fura-2/AM, rhod-2/AM and mag-fura-2/AM dyes correspondingly. Results: To activate store-operated calcium entry and visualize calcium influx we first empted the intracellular calcium stores by cell’s stimulation with neurotransmitters in calcium free extracellular media and then added calcium to the media. We showed that application of acetylcholine induced store-operated Ca2+ influx and subsequent store-operated [Ca2+ ]i transients which kinetics were depended on the potency of stimulation. It was shown that the inhibition of mitochondria mediated Ca2+ uptake by protonophore FCCP resulted in the marked decrease of amplitude and initial slope of the store-operated [Ca2+ ]i transients. In addition, the peak of the differentiated [Ca2+ ]i transient’s signal, which is an indicator of the number of open store-operated Ca2+ channels, was also significantly reduced by mitochondrial Ca2+ uptake inhibition. Since the Ca2+ sequestration mediated by mitochondria reflects the effectiveness of two interdependent processes such as Ca2+ uptake by Ca2+ uniporter and subsequent Ca2+ release via mitochondrial Na/Ca exchanger, we were interested to find out the effect of Na/Ca exchanger inhibition on the spatial-temporal parameters of neurotransmitters-induced store-operated Ca2+ transients. We found that the inhibition of the mitochondrial Na/Ca exchanger by its selective antagonist CGP 37157 caused significant decrease in the amplitude and the initial slope of store-operated [Ca2+ ]i transient. The marked reduction of the peak amplitude of the differentiated [Ca2+ ]i transient’s signal caused by CGP was also shown. Conclusions: Ca2+ uptake by mitochondria prevents Ca2+ dependent inactivation of store-operated Ca2+ channels. Inhibition of mitochondrial Ca2+ buffering caused almost complete inhibition of calcium entry when cells were continuously stimulated by neurotransmitters, whereas the suppression was much smaller when neurotransmitter was removed before mitochondria blocking. Our data indicate that mitochondria play a crucial role for maintaining of store-operated Ca2+ influx under physiological conditions. Due to their specific localization mitochondria regulate intracellular calcium recycling that represent the physiological intracellular mechanism for the regulation of store-operated calcium entry.
P.1.g.016 Immunity system state in liquidators of consequences of Chernobyl atomic power station accident V. Nikitina ° , T. Vetlugina. Mental Health Research Institute, department of psychoneuroimmunology, Tomsk, Russia Comparative catamnestic clinical-immunological examination of 248 patients (liquidators of consequences of the Chernobyl
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Atomic Power Station accident (ChAPS) accident) with borderline neuro-mental disorders formed in result of prolonged postradiation stress has been conducted. According to time period passing after the accident patients have been divided by us into two groups: 10−11 years after the accident at ChAPS (the first period) and 16−20 years after the accident (the second period). Clinical signs of secondary immune deficiency have been revealed in 93.4% of liquidators of the first period and in 100.0% of liquidators of the second period. The leading clinical syndrome in both groups was an infectious one (70.7% and 59.5%). Allergic (8.7% and 8.3%) and autoimmune (10.7% and 15.2%) syndromes were observed more seldom. Combination of two and more syndromes of immune deficiency was noticed in 3.3% of patients examined in the first period and 20.0% of patients examined in the second period. Comparative analysis of immunopathological syndromes in two groups has shown that in liquidators 16−20 years after accident at ChAPS infectious syndrome is found more seldom and autoimmune syndrome is diagnosed more frequently, incidence of combination of two and more syndromes is higher almost sevenfold. Presence of these signs results in lingered course of borderline neuro-mental disorders (BNMD) and polymorphism of clinical symptoms. In addition, in liquidators distinct trend to deterioration of somatic health with high degree of disability is followed up. So, in liquidators 10−11 years after accident at ChAPS with maximum frequency diseases of gastrointestinal tract (37.3%), thyroid gland (16.0%), bronchial-pulmonary system (8.7%) are found. Great percent of cases falls on combined pathology (32.0%). In liquidators 16−19 years after the accident at ChAPS incidence of diseases of thyroid gland (22.8%) is heightening. Also high frequency of incidence of mixed pathology has been noticed (presence in one patient simultaneously of 2−3 and more diseases) – 58.4% (that exceeds this index during observation in the first period 1.8-fold). In laboratory investigations of the first period the secondary immunodeficit is confirmed in 74.7% of liquidators, the second one – 98.3%. It has been identified that in liquidators 16−20 years after the accident at ChAPS a stable immunodeficit remains that is characterized by steady decrease (as compared with healthy persons) of total number of T-lymphocytes – CD2+ and CD3+-phenotypes (p < 0.01 and p < 0.001, respectively), helpers/inductors CD4+phenotype (p < 0.001), cytotoxic suppressors of CD8+-phenotype (p < 0.01), phagocytic activity of neutrophiles: total number of phagocyting cells has been decreased (p < 0.01) and so phagocytic number has been (p < 0.001). Background activity of oxidant systems of neutrophiles compatible with indices of stimulated variant of HCT-test of healthy people has been decreased (p < 0.001). Activation of humoral immunity has been recognized: level of circulating immune complexes – CIC has been heightened (p < 0.001) and so concentration of serum immunoglobulins IgG (p < 0.001) and IgA (p < 0.01) has been. In liquidators, reinforcement of expression of CD95 receptor – receptor of preparedness to apoptosis (p < 0.001) – has been detected.
P.1.g.016 Immunity system state in liquidators of consequences of Chernobyl atomic power station accident V. Nikitina ° , T. Vetlugina. Mental Health Research Institute, department of psychoneuroimmunology, Tomsk, Russia Comparative catamnestic clinical-immunological examination of 248 patients (liquidators of consequences of the Chernobyl
S311
Atomic Power Station accident (ChAPS) accident) with borderline neuro-mental disorders formed in result of prolonged postradiation stress has been conducted. According to time period passing after the accident patients have been divided by us into two groups: 10−11 years after the accident at ChAPS (the first period) and 16−20 years after the accident (the second period). Clinical signs of secondary immune deficiency have been revealed in 93.4% of liquidators of the first period and in 100.0% of liquidators of the second period. The leading clinical syndrome in both groups was an infectious one (70.7% and 59.5%). Allergic (8.7% and 8.3%) and autoimmune (10.7% and 15.2%) syndromes were observed more seldom. Combination of two and more syndromes of immune deficiency was noticed in 3.3% of patients examined in the first period and 20.0% of patients examined in the second period. Comparative analysis of immunopathological syndromes in two groups has shown that in liquidators 16−20 years after accident at ChAPS infectious syndrome is found more seldom and autoimmune syndrome is diagnosed more frequently, incidence of combination of two and more syndromes is higher almost sevenfold. Presence of these signs results in lingered course of borderline neuro-mental disorders (BNMD) and polymorphism of clinical symptoms. In addition, in liquidators distinct trend to deterioration of somatic health with high degree of disability is followed up. So, in liquidators 10−11 years after accident at ChAPS with maximum frequency diseases of gastrointestinal tract (37.3%), thyroid gland (16.0%), bronchial-pulmonary system (8.7%) are found. Great percent of cases falls on combined pathology (32.0%). In liquidators 16−19 years after the accident at ChAPS incidence of diseases of thyroid gland (22.8%) is heightening. Also high frequency of incidence of mixed pathology has been noticed (presence in one patient simultaneously of 2−3 and more diseases) – 58.4% (that exceeds this index during observation in the first period 1.8-fold). In laboratory investigations of the first period the secondary immunodeficit is confirmed in 74.7% of liquidators, the second one – 98.3%. It has been identified that in liquidators 16−20 years after the accident at ChAPS a stable immunodeficit remains that is characterized by steady decrease (as compared with healthy persons) of total number of T-lymphocytes – CD2+ and CD3+-phenotypes (p < 0.01 and p < 0.001, respectively), helpers/inductors CD4+phenotype (p < 0.001), cytotoxic suppressors of CD8+-phenotype (p < 0.01), phagocytic activity of neutrophiles: total number of phagocyting cells has been decreased (p < 0.01) and so phagocytic number has been (p < 0.001). Background activity of oxidant systems of neutrophiles compatible with indices of stimulated variant of HCT-test of healthy people has been decreased (p < 0.001). Activation of humoral immunity has been recognized: level of circulating immune complexes – CIC has been heightened (p < 0.001) and so concentration of serum immunoglobulins IgG (p < 0.001) and IgA (p < 0.01) has been. In liquidators, reinforcement of expression of CD95 receptor – receptor of preparedness to apoptosis (p < 0.001) – has been detected.