Репозиторий Университета

© Copyright © 2019 Krasil’nikova, Surin, Sorokina, Fisenko, Boyarkin, Balyasin, Demchenko, Pomytkin and Pinelis. Glutamate excitotoxicity is implicated in the pathogenesis of numerous diseases, such as stroke, traumatic brain injury, and Alzheimer’s disease, for which insulin resistance is a concomitant condition, and intranasal insulin treatment is believed to be a promising therapy. Excitotoxicity is initiated primarily by the sustained stimulation of ionotropic glutamate receptors and leads to a rise in intracellular Ca2+ ([Ca2+]i), followed by a cascade of intracellular events, such as delayed calcium deregulation (DCD), mitochondrial depolarization, adenosine triphosphate (ATP) depletion that collectively end in cell death. Therefore, cross-talk between insulin and glutamate signaling in excitotoxicity is of particular interest for research. In the present study, we investigated the effects of short-term insulin exposure on the dynamics of [Ca2+]i and mitochondrial potential in cultured rat cortical neurons during glutamate excitotoxicity. We found that insulin ameliorated the glutamate-evoked rise of [Ca2+]i and prevented the onset of DCD, the postulated point-of-no-return in excitotoxicity. Additionally, insulin significantly improved the glutamate-induced drop in mitochondrial potential, ATP depletion, and depletion of brain-derived neurotrophic factor (BDNF), which is a critical neuroprotector in excitotoxicity. Also, insulin improved oxygen consumption rates, maximal respiration, and spare respiratory capacity in neurons exposed to glutamate, as well as the viability of cells in the MTT assay. In conclusion, the short-term insulin exposure in our experiments was evidently a protective treatment against excitotoxicity, in a sharp contrast to chronic insulin exposure causal to neuronal insulin resistance, the adverse factor in excitotoxicity.

© 2018 Elsevier B.V. Background: To examine efficacy of Subetta as an add-on to insulin therapy in patients with type 1 diabetes mellitus (T1DM) a multicenter, double-blind, placebo-controlled, randomized clinical trial was performed. Derived by technological treatment of antibodies to insulin receptor β-subunit and endothelial NO synthase Subetta was previously proved to activate insulin signaling pathway. Methods: A total of 144 randomized patients with poor glycemic control in basal-bolus insulin regime were included in intention-to-treat analysis in Subetta add-on therapy or placebo (n = 72 in both groups). Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), basal and prandial insulin doses, number of hypoglycemia episodes confirmed by self-monitoring of blood glucose were recorded for 36 weeks. Results: The baseline characteristics of subjects did not differ between the two groups. HbA1c mean (±standard deviation) change was −0.59 ± 0.99% (95% CI −0.84 to −0.37) after 36 weeks in Subetta (vs. −0.20 ± 1.14%; 95% CI −0.44 to 0.11 in placebo; p = 0.028). The rate of overall hypoglycemia events was 7.9 per patient year (95% CI 7.1–8.6) in Subetta group and 7.6 (95% CI 6.9–8.4) in Placebo group (p = 0.63). The basal and total insulin doses did not change at the end of 36 weeks in both groups. Conclusions: Subetta add-on therapy boosting insulin activity and improving glycemic control in patients with T1DM is proved to be beneficial. Clinical trial registration: ClinicalTrials.gov identifier: NCT01868594.

© 2018 Russian Electronic Journal of Radiology.All Rights Reserved. Thiscreatic Featuresarticlehead, ofpresentsthisthat clinicalwas theoperated clinicalcase arecasetwice, difficultiesofbut patientfirst in pre-withoperation andneuroendocrineintraoperativedid not lead tumortopicalto recovery. ofdiag-pan-nosis of small size insulinoma. The authors came to the conclusion that topical diagnostics should be complex.

© 2018, SPb RAACI. The aim of this prospective randomized clinical study was to investigate the role of preoperative carbohydrate admnistration in surgery-induced metabolic, immune and inflammatory reactions after thoracoabdominal operations. At the Surgical department I (B.V. Petrovsky National Research Center of Surgery), we investigated a modulatory role of carbohydrate preload upon surgical stress observed after major thoracoabdominal operations (thoracoscopic and open esophagectomy, retrosternal colonic esophagoplasty) followed by the enhanced recovery protocol. The study was performed in 2014-2017, it included 30 patients, divided into 2 groups. Group A patients (n = 16) received carbohydrates preload (12.5% maltodextrin solution per os or enterally). In patients with dysphagia, the 12.5% dextrose solution was used intravenously in equal volumes. Group B patients didn’t receive any additional preload with carbohydrates. The groups were age- and gender-matched, similar for disease and surgery types. Glucose and insulin levels (with HOMA insulin resistance index, HOMA-IR) were measured before surgery and on day +1, interleukin levels (IL-6, IL-10, IL-8) and index IL-8/IL-10 were assessed before surgery, and on days +1 and +5 after surgery. Cell-mediated immunity was investigated before surgery and on day +5. The stress-induced hyperglycemia (> 7.8 mmol/L) was detected more frequently in group B (50%), than in group A (6%), p = 0.012. Insulin resistance measured by HOMA-IR in group B was detected in 71% of patients and in 25% patients of group A only, p = 0.027. Individual analysis of immune response demonstrated that a trend for immune recovery was detected by the day +5 post-op in the group A. Postoperative levels of IL-6 and IL-10 were lower on day +1 and +5 in group A. Morbidity rates and the terms of hospitalization were similar in both groups. Local postsurgical infections in group A were developed in 6% of the patients vs 35.6% in group B (p = 0.072). In conclusion, a complex study of surgical stress, i.e., metabolic, immune and inflammatory reactions after esophageal surgery has shown that the carbohydrate preload decreased the incidence of postoperative insulin resistance and stress-induced hyperglycemia, being accompanied by lower release of proinflammatory cytokines and provides positive effects upon the patient’s immune system.

© 2018 Dynasty Publishing House. All rights reserved. The article presents a clinical case of a patient with genetically confirmed Alagille syndrome (ALGS) with marked delay of physical development that did not correspond to the severity of liver damage. Alagille syndrome (ALGS) is a rare hereditary disease with underlying hypoplasia of the intrahepatic bile ducts manifested by cholestasis syndrome in the first weeks of life. Developmental delay is characteristic for cholestatic diseases of the liver, including ALGS, which is conditioned by impaired absorption of fats and fat-soluble vitamins in the intestines. But growth delay and underweight in this syndrome often do not correlate with the severity of cholestatis syndrome, and causes of their development remain unstudied. Cholestatis syndrome was moderate, and clinical signs of liver cirrhosis were absent. Intense skin itching, greatly disturbing not only the baby's wake period but also sleep, along with marked height and weight deficit were indications for liver transplantation at the age of 4 years, after which a fast normalisation of the parameters of physical development was noted. This clinical case study permits to hypothesize that developmental delay in children with ALGS is conditioned by chronic cholestatic liver damage, irrespective of the severity of its clinical presentation.

© Russian Association of Endocrinologists, 2018. BACKGROUND. Intensive glycaemic control in patients with type 1 diabetes may lead to hypoglycaemia and thus increase the risk of cardiovascular and cerebrovascular events. Platelet activation and/or decreased activity of physiological anticoagulants during hypoglycaemia may play a role in the development of cardiovascular or cerebrovascular complications. AIMS. To investigate induced platelet activity, the activity of physiological anticoagulants, and the von Wil-lebrand factor in patients with type 1 diabetes with the hyperinsulinaemic-hypoglycaemic clamp. MATERIALS AND METHODS. We examined 11 patients with type 1 diabetes without macro- and micro-vascular complications (6 males, 5 females, mean age 23.7 ± 5.6 years, A1C 9.7 ± 2.3%). Induced platelet aggregation, physiological anticoagulants (Protein S, Protein C, AT III) and the von Willebrand factor were studied at hyperglycaemic, euglycaemic, and hypoglycaemic stages during use of a hyperinsulinaemic (1 mU/kg/min) hypoglycaemic clamp. RESULTS. Platelet aggregation to all agonists increased significantly during the hypoglycaemic stage, compared with the euglycaemic or hyperglycaemic stages. There was no difference in platelet aggregation between the euglycaemic and hyperglycaemic stages. Platelet aggregation to all agonists increased during the hypoglycaemic stage compared with the hyperglycaemic period: thrombin-23.9%, ADP-30.6%, arachidonic acid-30.9%, collagen-69.4% and ristocetin-70.8%. During hypoglycaemia aggregation to ADP, arachidonic acid and collagen remained within normal limits (upper quartile); aggregation to thrombin was significantly above normal limits and aggregation to ristocetin remained significantly below lower limits. Protein S activity was significantly increased during hypoglycaemia compared with euglycaemia (p = 0.046) and hyperglycaemia (p = 0.046). Antithrombin-III activity decreased significantly at the euglycaemic and hypoglycaemic stages, compared with the hyperglycaemic period, but still remained significantly elevated above the upper threshold. Protein C and vWf activity did not change significantly. CONCLUSIONS. In patients with type 1 diabetes platelet aggregation and protein S activity increases significantly at the hypoglycaemic stage of the hyperinsulinaemic-hypoglycaemic clamp. Platelet activation is directly caused by hypoglycaemia and not by decreasing glucose levels. Increased protein S activity is a compensatory response to platelet activation.

© 2018 Stavropol State Medical University. All Rights Reserved. Type I Diabetes mellitus (DM), or insulin-dependent diabetes, is the most common endocrine pathology among children and teenagers. The purpose of this study is to research the content of 1A melatonin receptor and antibodies to it in blood serum of children and teenagers. We examined 71 children and teenagers aged 1.9 to 17 years. We measured the content of 1A melatonin receptor and antibodies to it in hemolymph using an immunofluorescence assay test system (IFA). We found that the lowest levels of the 1A melatonin receptor were prevailing in children with a serious condition at the DM decompensation stage, median values were diagnosed in children in a state of moderate severity, and the maximum quantities are fixed in children against the background of the compensation of DM. The obtained data confirm the hypothesis about the possible involvement of the corpus pineale (epiphysis) in the pathogenesis of Type I Diabetes mellitus.

© 2018 John Wiley  &  Sons Ltd. While the insulin receptor (IR) was found in the CNS decades ago, the brain was long considered to be an insulin-insensitive organ. This view is currently revisited, given emerging evidence of critical roles of IR-mediated signaling in development, neuroprotection, metabolism, and plasticity in the brain. These diverse cellular and physiological IR activities are distinct from metabolic IR functions in peripheral tissues, thus highlighting region specificity of IR properties. This particularly concerns the fact that two IR isoforms, A and B, are predominantly expressed in either the brain or peripheral tissues, respectively, and neurons express exclusively IR-A. Intriguingly, in comparison with IR-B, IR-A displays high binding affinity and is also activated by low concentrations of insulin-like growth factor-2 (IGF-2), a regulator of neuronal plasticity, whose dysregulation is associated with neuropathologic processes. Deficiencies in IR activation, insulin availability, and downstream IR-related mechanisms may result in aberrant IR-mediated functions and, subsequently, a broad range of brain disorders, including neurodevelopmental syndromes, neoplasms, neurodegenerative conditions, and depression. Here, we discuss findings on the brain-specific features of IR-mediated signaling with focus on mechanisms of primary receptor activation and their roles in the neuropathology. We aimed to uncover the remaining gaps in current knowledge on IR physiology and highlight new therapies targeting IR, such as IR sensitizers.