The relative contribution of nmdars to excitatory postsynaptic currents is controlled by ca²⁺-induced inactivation

© 2016 Valiullina, Zakharova, Mukhtarov, Draguhn, Burnashev and Rozov.NMDA receptors (NMDARs) are important mediators of excitatory synaptic transmission and plasticity. A hallmark of these channels is their high permeability to Ca2+. At the same time, they are themselves inhibited by the elevation of intracellular Ca2+ concentration. It is unclear however, whether the Ca2+ entry associated with single NMDAR mediated synaptic events is sufficient to self-inhibit their activation. Such auto-regulation would have important effects on the dynamics of synaptic excitation in several central neuronal networks. Therefore, we studied NMDAR-mediated synaptic currents in mouse hippocampal CA1 pyramidal neurons. Postsynaptic responses to subthreshold Schaffer collateral stimulation depended strongly on the absence or presence of intracellular Ca2+ buffers. Loading of pyramidal cells with exogenous Ca2+ buffers increased the amplitude and decay time of NMDAR mediated EPSCs (EPSPs) and prolonged the time window for action potential (AP) generation. Our data indicate that the Ca2+ influx mediated by unitary synaptic events is sufficient to produce detectable self-inhibition of NMDARs even at a physiological Mg2+ concentration. Therefore, the contribution of NMDARs to synaptic excitation is strongly controlled by both previous synaptic activity as well as by the Ca2+ buffer capacity of postsynaptic neurons

The relative contribution of nmdars to excitatory postsynaptic currents is controlled by ca2+-induced inactivation

© 2016 Valiullina, Zakharova, Mukhtarov, Draguhn, Burnashev and Rozov. NMDA receptors (NMDARs) are important mediators of excitatory synaptic transmission and plasticity. A hallmark of these channels is their high permeability to Ca2+. At the same time, they are themselves inhibited by the elevation of intracellular Ca2+ concentration. It is unclear however, whether the Ca2+ entry associated with single NMDAR mediated synaptic events is sufficient to self-inhibit their activation. Such auto-regulation would have important effects on the dynamics of synaptic excitation in several central neuronal networks. Therefore, we studied NMDAR-mediated synaptic currents in mouse hippocampal CA1 pyramidal neurons. Postsynaptic responses to subthreshold Schaffer collateral stimulation depended strongly on the absence or presence of intracellular Ca2+ buffers. Loading of pyramidal cells with exogenous Ca2+ buffers increased the amplitude and decay time of NMDAR mediated EPSCs (EPSPs) and prolonged the time window for action potential (AP) generation. Our data indicate that the Ca2+ influx mediated by unitary synaptic events is sufficient to produce detectable self-inhibition of NMDARs even at a physiological Mg2+ concentration. Therefore, the contribution of NMDARs to synaptic excitation is strongly controlled by both previous synaptic activity as well as by the Ca2+ buffer capacity of postsynaptic neurons

Методы экстракорпоральной детоксикации и система гемостаза пациентов с раком яичников. Клинический случай

   Introduction. Malignant tumors dominate in the picture of disability and mortality worldwide. One of the most frequent and dangerous comorbid conditions is kidney injury. At the same time, the most unfavorable incidence of acute kidney injury is recorded in multiple myeloma, leukemia, lymphoma and kidney and/or liver cancer and malignant ovarian neoplasms. In this regard, of vital importance is the choice of tactics in the prevention of thrombosis and thromboembolic complications, as well as the individual approach to of the anticoagulant therapy regimen during renal replacement therapy sessions, depending on the underlying disease and the state of the hemostatic system.   Aim. To evaluate the effect of calcium citrate veno-venous hemodiafi ltration sessions on the hemostatic system of a patient with progressive organ dysfunctions associated with malignant ovarian neoplasm.   Materials and methods. The methodology involved literature review and a case study to assess the effect of veno-venous hemodiafi ltration on hemostasis.   Results and discussion. The clinical case was assessed in terms of P-selectin (CD62), which characterizes platelet activation processes. It should be noted that in this patient, the expression of P-selectin increased with each session of renal replacement therapy, while the platelet aggregation values remained at the level of the lower thresholds, which indicates a low probability of coagulation initiation. However, due to aggressive regulation of ovarian cancer by the hemostatic system in the form of production of inflammatory mediators, microvesicles, tissue factor expression and endothelial activation, attention should be paid to the molecular aspects of platelet activation in renal replacement therapy with regional citrate coagulation.   Conclusion. The widespread use of extracorporeal detoxification methods is an independent risk factor not only for bleeding events, but may potentially contribute to thrombosis and thromboembolic complications, which requires a further detailed study of molecular mechanisms of hemostasis regulation by tumor and clinical evaluation of various anticoagulation methods.   Введение. Злокачественные новообразования занимают лидирующую позицию в общей структуре инвалидности и смертности во всем мире. Одним из наиболее частых и грозных сопутствующих состояний является повреждение почек. При этом наиболее неблагоприятная частота развития острого повреждения почек регистрируется при множественной миеломе, лейкемии, лимфоме и раке почки и / или печени и злокачественных новообразованиях яичников. В связи с этим жизненно важным становится выбор тактики при профилактике тромбозов и тромбоэмболических осложнений, а также обеспечение индивидуального подбора режима антикоагулянтной терапии при сеансах почечно-заместительной терапии в зависимости от основного заболевания и состояния системы гемостаза.   Целью демонстрации данного клинического случая является оценка влияния сеансов кальций-цитратной вено-венозной гемодиафильтрации на показатели системы гемостаза пациентки с прогрессированием органных дисфункций, развившихся на фоне злокачественного новообразования яичников.   Материалы и методы. Анализ доступной литературы и представленного клинического случая для оценки влияния вено-венозной гемодиафильтрации на показатели системы гемостаза.   Результаты и обсуждение. В приведенном клиническом случае мы оценили экспрессию P-селектина (CD62), который характеризует процессы активации тромбоцитов. Следует отметить, что у данной пациентки с каждым сеансом заместительной почечной терапии возрастала экспрессия Р-селектина, при этом значения агрегации тромбоцитов оставались на уровне нижних пороговых показателей, что свидетельствует о низкой вероятности инициации свертывания крови. Однако, принимая во внимание факт агрессивного регулирования рака яичника системой гемостаза в виде продукции медиаторов воспаления, микровезикул, экспрессии тканевого фактора и активации эндотелия, следует обратить внимание на молекулярные аспекты активации тромбоцитов при почечно-заместительной терапии с регионарной цитратной коагуляцией.   Выводы. Таким образом, широкое распространение методов экстракорпоральной детоксикации является самостоятельным фактором риска не только развития кровотечений, но может и потенциально способствовать развитию тромбозов и тромбоэмболических осложнений, что требует детального дальнейшего изучения молекулярных механизмов регулирования системы гемостаза опухолью и клинической оценкой различных методов антикоагуляции

Current status of nuclear cardiology in the Russian Federation

The article is devoted to the analysis of the current status of nuclear cardiology in the Russian Federation. The data on the number of facilities performing radionuclide investigations for the diagnosis and monitoring of the treatment of cardiovascular diseases, their staffing and equipment are given. The statistics of the conducted nuclear cardiology tests for 2018-2020 are given, as well as their methods, features and diagnostic significance are described

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

The use of thermal imaging survey to identify defects building envelope constructions and energy eqipment

Meeting the challenges of evaluating technical condition of building envelope constructions and energy equipment is largely connected to the introduction of effective methods of instrumental monitoring and, in particular, thermal nondestructive testing method - IR diagnostics. The following are the main points for thermal imaging diagnostics and main factors influencing measurement accuracy. The results are providedfor IR diagnosis of various objects

The relative contribution of nmdars to excitatory postsynaptic currents is controlled by ca2+-induced inactivation

© 2016 Valiullina, Zakharova, Mukhtarov, Draguhn, Burnashev and Rozov. NMDA receptors (NMDARs) are important mediators of excitatory synaptic transmission and plasticity. A hallmark of these channels is their high permeability to Ca2+. At the same time, they are themselves inhibited by the elevation of intracellular Ca2+ concentration. It is unclear however, whether the Ca2+ entry associated with single NMDAR mediated synaptic events is sufficient to self-inhibit their activation. Such auto-regulation would have important effects on the dynamics of synaptic excitation in several central neuronal networks. Therefore, we studied NMDAR-mediated synaptic currents in mouse hippocampal CA1 pyramidal neurons. Postsynaptic responses to subthreshold Schaffer collateral stimulation depended strongly on the absence or presence of intracellular Ca2+ buffers. Loading of pyramidal cells with exogenous Ca2+ buffers increased the amplitude and decay time of NMDAR mediated EPSCs (EPSPs) and prolonged the time window for action potential (AP) generation. Our data indicate that the Ca2+ influx mediated by unitary synaptic events is sufficient to produce detectable self-inhibition of NMDARs even at a physiological Mg2+ concentration. Therefore, the contribution of NMDARs to synaptic excitation is strongly controlled by both previous synaptic activity as well as by the Ca2+ buffer capacity of postsynaptic neurons

The relative contribution of nmdars to excitatory postsynaptic currents is controlled by ca2+-induced inactivation

© 2016 Valiullina, Zakharova, Mukhtarov, Draguhn, Burnashev and Rozov. NMDA receptors (NMDARs) are important mediators of excitatory synaptic transmission and plasticity. A hallmark of these channels is their high permeability to Ca2+. At the same time, they are themselves inhibited by the elevation of intracellular Ca2+ concentration. It is unclear however, whether the Ca2+ entry associated with single NMDAR mediated synaptic events is sufficient to self-inhibit their activation. Such auto-regulation would have important effects on the dynamics of synaptic excitation in several central neuronal networks. Therefore, we studied NMDAR-mediated synaptic currents in mouse hippocampal CA1 pyramidal neurons. Postsynaptic responses to subthreshold Schaffer collateral stimulation depended strongly on the absence or presence of intracellular Ca2+ buffers. Loading of pyramidal cells with exogenous Ca2+ buffers increased the amplitude and decay time of NMDAR mediated EPSCs (EPSPs) and prolonged the time window for action potential (AP) generation. Our data indicate that the Ca2+ influx mediated by unitary synaptic events is sufficient to produce detectable self-inhibition of NMDARs even at a physiological Mg2+ concentration. Therefore, the contribution of NMDARs to synaptic excitation is strongly controlled by both previous synaptic activity as well as by the Ca2+ buffer capacity of postsynaptic neurons

The relative contribution of nmdars to excitatory postsynaptic currents is controlled by ca²⁺-induced inactivation

© 2016 Valiullina, Zakharova, Mukhtarov, Draguhn, Burnashev and Rozov.NMDA receptors (NMDARs) are important mediators of excitatory synaptic transmission and plasticity. A hallmark of these channels is their high permeability to Ca2+. At the same time, they are themselves inhibited by the elevation of intracellular Ca2+ concentration. It is unclear however, whether the Ca2+ entry associated with single NMDAR mediated synaptic events is sufficient to self-inhibit their activation. Such auto-regulation would have important effects on the dynamics of synaptic excitation in several central neuronal networks. Therefore, we studied NMDAR-mediated synaptic currents in mouse hippocampal CA1 pyramidal neurons. Postsynaptic responses to subthreshold Schaffer collateral stimulation depended strongly on the absence or presence of intracellular Ca2+ buffers. Loading of pyramidal cells with exogenous Ca2+ buffers increased the amplitude and decay time of NMDAR mediated EPSCs (EPSPs) and prolonged the time window for action potential (AP) generation. Our data indicate that the Ca2+ influx mediated by unitary synaptic events is sufficient to produce detectable self-inhibition of NMDARs even at a physiological Mg2+ concentration. Therefore, the contribution of NMDARs to synaptic excitation is strongly controlled by both previous synaptic activity as well as by the Ca2+ buffer capacity of postsynaptic neurons

The relative contribution of nmdars to excitatory postsynaptic currents is controlled by ca2+-induced inactivation

© 2016 Valiullina, Zakharova, Mukhtarov, Draguhn, Burnashev and Rozov. NMDA receptors (NMDARs) are important mediators of excitatory synaptic transmission and plasticity. A hallmark of these channels is their high permeability to Ca2+. At the same time, they are themselves inhibited by the elevation of intracellular Ca2+ concentration. It is unclear however, whether the Ca2+ entry associated with single NMDAR mediated synaptic events is sufficient to self-inhibit their activation. Such auto-regulation would have important effects on the dynamics of synaptic excitation in several central neuronal networks. Therefore, we studied NMDAR-mediated synaptic currents in mouse hippocampal CA1 pyramidal neurons. Postsynaptic responses to subthreshold Schaffer collateral stimulation depended strongly on the absence or presence of intracellular Ca2+ buffers. Loading of pyramidal cells with exogenous Ca2+ buffers increased the amplitude and decay time of NMDAR mediated EPSCs (EPSPs) and prolonged the time window for action potential (AP) generation. Our data indicate that the Ca2+ influx mediated by unitary synaptic events is sufficient to produce detectable self-inhibition of NMDARs even at a physiological Mg2+ concentration. Therefore, the contribution of NMDARs to synaptic excitation is strongly controlled by both previous synaptic activity as well as by the Ca2+ buffer capacity of postsynaptic neurons