Activation of RAGE leads to the release of glutamate from astrocytes and stimulates calcium signal in neurons

The receptor for advanced glycation end products (RAGE) is a signal receptor first shown to be activated by advanced glycation end products, but also by a variety of signal molecules, including pathological advanced oxidation protein products and β-amyloid. However, most of the RAGE activators have multiple intracellular targets, making it difficult to unravel the exact pathway of RAGE activation. Here, we show that the cell-impermeable RAGE fragment sequence (60-76) of the V-domain of the receptor is able to activate RAGE present on the plasma membrane of neurons and, preferentially, astrocytes. This leads to the exocytosis of vesicular glutamate transporter vesicles and the release of glutamate from astrocytes, which stimulate NMDA and AMPA/kainate receptors, resulting in calcium signals predominantly in neurons. Thus, we show a specific mechanism of RAGE activation by the RAGE fragment and propose a mechanism by which RAGE activation can contribute to the neuronal-astrocytic communication in physiology and pathology

The clinical aspects ot the sulphonylurea compounds from the position of the cardioprotective approach at patient with type 2 diabetes, using glucocardiomonitoring

BACKGRAUND: Now the trend of Type 2 Diabetes Mellitus (T2DM) management from glucocentric to cardioprotective approach take place, and it especially relevant for the multiple group of patients with T2DM using Sulphonylurea (SU). Meanwhile the synchronized glucocardiomonitoring allowed to providing the accurate information about the cardiometabolic status of patients with T2DM.AIMS: Using the professional glucocardiomonitoring for T2DM-SU patients to investigate the relation between the glycemic variability, integral glycemic parameters and proarrhythmogenic cardiovascular events and the long-term cardiovascular outcomes.MATERIALS AND METHODS: In the observational (randomised for inclusion of patients) controlled trial the SU-patients with the T2DM duration 9,8±6,6 years were included, whom the professional glucocardiomonitoring had been made during 5 days and then the fatal and non-fatal cardiovascular events had been investigated during 5 years. RESULTS: From 283 patients with T2DM 154 patients (the basic group) used gliclazide (original drug Diabeton MB), 129 patients (the control group) used glibenclamide. The relation between the rising of the glycemic variability and cardiovascular events (the prolongation QT interval, the ST depression (dST), ventricular arrhythmias (VAs)) were demonstrated. At the basic and the control groups the coefficient of variation (CV) was 23,0±8,1 and 30,1±10,7% respectively (p<0,001), TIR-HYPO — 0,8±2,4 and 3,5±5,4% (p<0,001), the number of glycemia differences > 4 mmol/L/hr — 2,3±3,6 and 3,5±4,3 (p=0,010), the minimal glycemia level — 4,6±1,0 and 3,9±1,4 mmol/L (p=0,001). The followed differences of cardiovascular parameters were determined: QTc — 412±24 and 423±28 ms (p=0,001), dST — 0,052 [0; 0,275] and 0,109 [0; 0,422] (ratio, p=0,012), VAs — 2,2 [0; 5,9] and 3,5 [0; 8,3] (cases/pts, p=0,008). The long-term cardiovascular outcomes from the gliclazide and glibenclamide therapy (cases/100 pts-years): the total and cardiovascular death — 0,12 [0; 1,74] and 0,76 [0; 4,62] (p=0,062), cardiovascular death -0,12 [0; 1,74] and 0,62 [0; 4,08] (p=0,122), myocardial infarction — 1,56 [0; 6,94] and 2,00 [0; 8,02] (p=0,193), stroke — 0,78 [0; 4,66] and 0,76 [0; 4,62] (p=0,169), chronic heart failure — 0,52 [0; 3,72] and 1,24 [0; 6,06] (p=0,095), MACE — 2,46 [0; 10,1] и 2,62 [0; 9,38] (p=0,095), severe hypoglycemia at home — 2,46 [0; 9,12] и 7,24 [0; 16,68] (p<0,001).CONCLUSIONS: It was demonstrated that the gliclazide (original drug Diabeton MB) administration is characterized with the better quality of glycemia control, the lower glycemic variability, the lower frequency of the SU-associated hypoglycemia, dST, VAs, the lower prolongation QTc interval. The implementation of the synchronized glucocardiomonitoring is necessary for minimization of the cardiovascular T2DM-complications and for the choice of the personalize

Influence of temperament on educational professional аctivity of the student

The article discusses the concept of «Temperament», the main characteristic of the educationalprofessional activity, the influence of temperament on educational and professional ctivitiesВ статье рассматривается понятие «темперамент», основная характеристика учебно-профессиональной деятельности, влияние темперамента на учебно-профессиональную деятельност

Clinical and microbiological efficacy of various methods of tonsillectomy

Introduction. There is an abundance of various methods of surgical treatment in the world, which include: classical tonsillectomy (TE), shaver TE, unipolar and bipolar bilateral TE, laser TE, palatine tonsil coblation, etc. However, there is still a risk of recurrence of chronic tonsillitis after TE there is a need for a study in the late postoperative period.Purpose of the study. Improving the efficiency of surgical treatment of patients with chronic tonsillitis based on the analysis of five main methods of surgical treatment of chronic tonsillitis according to clinical and laboratory criteria.Materials and methods. Patients were divided into 5 study groups depending on the method of tonsillectomy: The first group consisted of 60 patients after classical tonsillectomy. In the second group there were 55 patients after palatine tonsil coblation. The third group included 48 patients after laser tonsillectomy. The fourth group consisted of 64 patients after tonsillectomy using the surgitron apparatus. The fifth group consisted of 58 patients after microdebrider tonsillectomy.Results. By analysis, it was found that the best results were obtained in patients of the 1st group, who underwent classical tonsillectomy. In this group, there are fewer cases of subjective and objective clinical symptoms (sore throat, signs of subatrophic pharyngitis, hypertrophy of the lateral folds of the pharynx, remnants of the lymphoid tissue of the palatine tonsils, as well as postoperative cicatricial changes). In a laboratory study, patients of the 1st group had the lowest values of the indicators (ASL-O titer, CRP and DNase B levels, negative results of the Streptatest)

SHS for Space Exploration

For over past years, interest of leading space agencies (NASA, JAXA, ESA, RSA, etc.) in SHS experiments under microgravity conditions has been increasingly growing. The first SHS experiments during a parabolic flight in Russia and aboard the MIR Space station gave promising results. Similar studies are now being carried out in various countries. The obtained data and assimilated experience have shown that SHS reactions can be used for (a) synthesis of high-porosity materials and regulation of structure formation in combustion products, (b) preparation of skeleton structures by combustion of particles suspended in vacuum, (c) generation of thermal energy, (d) generation of incandescent radiation, and (e) for in-space fabrication and in-situ repair works (welding, joining, cutting, coating, near-net-shape production, etc.). However, the results of the above studies (strongly scattered in the literature) still seem insufficient for elucidating the mechanism of combustion in. Indeed, the experiments were carried out by different researchers for a dozen of systems and for strongly different duration of microgravity (drop towers, parabolic flight of a plane, parabolic flight of a spacecraft, in space stations). No correlation has been made with the available data of SHS studies (oriented largely on practical implementation) in conditions of artificial gravity. In experiments, the combustion wave has enough time to spread over the sample while the structure formation, may not have. This implies that the process of wave propagation should always be identical, irrespective of the type of experimental technique and place of experiment. SHS experiments in space are attractive because (a) of low energy requirements, (b) processing cycle is short, (c) of process simplicity, (d) of versatility (wide range of suitable materials, and (e) the use of in-situ resources possible. To date, SHS experiments has already been performed aboard the International Space Station (ISS). Space technology has been developed for frontier exploration not only around the Earth orbit environment but also to the Moon, Mars, etc

Synthetic Fragments of Receptor for Advanced Glycation End Products Bind Beta-Amyloid 1–40 and Protect Primary Brain Cells From Beta-Amyloid Toxicity

Receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of Alzheimer’s disease. We have previously revealed that RAGE fragment sequence (60–76) and its shortened analogs sequence (60–70) and (60–65) under intranasal insertion were able to restore memory and improve morphological and biochemical state of neurons in the brain of bulbectomized mice developing major AD features. In the current study, we have investigated the ability of RAGE peptide (60–76) and five shortened analogs to bind beta-amyloid (Aβ) 1–40 in an fluorescent titration test and show that all the RAGE fragments apart from one [sequence (65–76)] were able to bind Aβ in vitro. Moreover, we show that all RAGE fragments apart from the shortest one (60–62), were able to protect neuronal primary cultures from amyloid toxicity, by preventing the caspase 3 activation induced by Aβ 1–42. We have compared the data obtained in the present research with the previously published data in the animal model of AD, and offer a probable mechanism of neuroprotection of the RAGE peptide

Respiratory distress and perinatal lethality in Nedd4-2-deficient mice

The epithelial sodium channel (ENaC) is essential for sodium homoeostasis in many epithelia. ENaC activity is required for lung fluid clearance in newborn animals and for maintenance of blood volume and blood pressure in adults. In vitro studies show that the ubiquitin ligase Nedd4-2 ubiquitinates ENaC to regulate its cell surface expression. Here we show that knockout of Nedd4-2 in mice leads to increased ENaC expression and activity in embryonic lung. This increased ENaC activity is the likely reason for premature fetal lung fluid clearance in Nedd4-2−/− animals, resulting in a failure to inflate lungs and perinatal lethality. A small percentage of Nedd4-2−/− animals survive up to 22 days, and these animals also show increased ENaC expression and develop lethal sterile inflammation of the lung. Thus, we provide critical in vivo evidence that Nedd4-2 is essential for correct regulation of ENaC expression, fetal and postnatal lung function and animal survival

Analysis of critical incidents during the intrahospital transport of patients and prevention

The article deals with changes in the gas and biochemical composition of blood in patients during intrahospital transport. Changes registered in patients who were on artificial lung ventilation revealed violations of the homeostasis of the blood gas composition, in particular, a decrease in the partial oxygen tension in arterial blood during manual Ambu ventilation, which can lead to negative electrolyte shifts and clinical consequences in the form of critical incidents. Invasive monitoring of blood gas composition should reduce the risk of critical incidents during medical evacuation.В статье рассмотрены изменения газового и биохимического состава крови у пациентов при внутригоспитальной транспортировке. Изменения, зарегистрированные у пациентов, находившихся на искусственной вентиляции легких, выявили нарушения гомеостаза газового состава крови, в частности, снижение парциального напряжения кислорода в артериальной крови при ручной вентиляции мешком Амбу, что может приводить к негативным электролитным сдвигам и клиническим последствиям в виде развития критических инцидентов. Инвазивный мониторинг газового состава крови должен снизить риски развития критических инцидентов в процессе медицинской эвакуации