Effects of 1,3,4-thiadiazine compound with antidepressant properties in ligation model of acute pancreatitis

Based on hypotheses concerning the role of stress in acute pancreatitis development, the experimental approach for the decrease stress damage via the use the compound with proven antistress/neuroleptic action was conducted. The study was aimed to discover 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine hydrobromide (compound L-17) therapeutic action in experimental acute pancreatitis. The experimental model used was the ligation model. The trial was carried out on 50 male Wistar rats with average body weight 180-240g. Histological picture of the pancreas was studied and biochemical and enzyme-immunoassays were carried out on the first and seventh days. The significant reduction in mortality on the background of L-17 compound administration was observed. While levels of all cytokines increased in induced experimental acute pancreatitis groups, the cytokine level rise was decreased when compound L-17 was administered. On the cellular level, the study revealed L-17’s ability to prevent granulocytosis and decrease granulocytes infiltration to inflammatory foci. The decrease in inflammatory reaction magnitude and prevention of abscess formation in experimental acute pancreatitis accompanied by sistemic inflamamtion was due to L-17’s ability to reduce neutrophilia and neutrophil entry into the injury zone. © 2018, Slovak Academy of Sciences. All rights reserved.Government Council on Grants, Russian FederationMinistry of Education and Science of the Russian Federation, Minobrnauka: 17.7255.2017/8.9AAAA-A18-118020690020-1Funding information. Partly the study was supported by the Act 211 of the Government of Russian Federation, contract No 02.A03.21.0006; Government contract of Russian Federation with Institute of Immunology and Physiology (AAAA-A18-118020690020-1) and the Ministry of Education and Science of the Russian Federation (# 17.7255.2017/8.9)

Prognostic value of leukocyte indices in acute severe pancreatitis

The article analyzed the results of laboratory blood tests obtained in patients on the day of entry into the body and calculated for various leukocyte indices in patients with acute severe pancreatitis. The study based on the case reports of the MAI “City Clinical Hospital” No. 40 of Yekaterinburg in the period 2015-2020. The study aim is to identify the informative value of leukocyte indicators in relation to predicting the severity of acute pancreatitis and mortality. Some leukocyte indices have sufficient information in predicting the severity, course of acute pancreatitis and mortality, taking into account the incidence.В статье были проанализированы результаты лабораторных исследований крови, полученных у пациентов в день поступления в приемный покой и рассчитаны различные лейкоцитарные индексы у пациентов с острым тяжелым панкреатитом. Исследование проведено по материалам историй болезни МАУ «Городская клиническая больница» №40 г. Екатеринбурга в период 2015-2020 гг. Проведенное исследование было направлено на выявление информативности лейкоцитарных индексов в отношении прогнозирования тяжести течения острого панкреатита и летальности. Некоторые лейкоцитарные индексы обладают достаточной информативностью в прогнозировании тяжести течения острого панкреатита и летальности, связанной с данным заболеванием

Combined in Silico, Ex Vivo, and in Vivo Assessment of L-17, a Thiadiazine Derivative with Putative Neuro-and Cardioprotective and Antidepressant Effects

Depression associated with poor general medical condition, such as post-stroke (PSD) or post-myocardial infarction (PMID) depression, is characterized by resistance to classical antidepres-sants. Special treatment strategies should thus be developed for these conditions. Our study aims to investigate the mechanism of action of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobro-mide (L-17), a recently designed thiadiazine derivative with putative neuro-and cardioprotective and antidepressant-like effects, using combined in silico (for prediction of the molecular binding mechanisms), ex vivo (for assessment of the neural excitability using c-Fos immunocytochemistry), and in vivo (for direct examination of the neuronal excitability) methodological approaches. We found that the predicted binding affinities of L-17 to serotonin (5-HT) transporter (SERT) and 5-HT3 and 5-HT1A receptors are compatible with selective 5-HT serotonin reuptake inhibitors (SSRIs) and antagonists of 5-HT3 and 5-HT1A receptors, respectively. L-17 robustly increased c-Fos immunoreac-tivity in the amygdala and decreased it in the hippocampus. L-17 dose-dependently inhibited 5-HT neurons of the dorsal raphe nucleus; this inhibition was partially reversed by the 5-HT1A antagonist WAY100135. We suggest that L-17 is a potent 5-HT reuptake inhibitor and partial antagonist of 5-HT3 and 5-HT1A receptors; the effects of L-17 on amygdaloid and hippocampal excitability might be mediated via 5-HT, and putatively mediate the antidepressant-like effects of this drug. Since L-17 also possesses neuro-and cardioprotective properties, it can be beneficial in PSD and PMID. Combined in silico predictions with ex vivo neurochemical and in vivo electrophysiological assessments might be a useful strategy for early assessment of the efficacy and neural mechanism of action of novel CNS drugs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Funding: The work of the authors of this study was supported by the Slovak Research and Development Agency (contract APVV-19-0435), Scientific Grant Agency of the Ministry of Education of the Slovak Republic, the Slovak Academy of Sciences (grant VEGA 2/0046/18), and a Government Contract of the Russian Federation with the Institute of Immunology and Physiology (AAAA-A18-118020690020-1)