Enzyme-catalyzed uridine phosphorolysis: SN2 mechanism with phosphate activation by desolvation

AbstractThe rate of uridine phosphorolysis catalyzed by uridine phosphorylase from Escherichia coli decreases with increasing ionic strength. In contrast, the rate was increased about twofold after preincubation of uridine phosphorylase with 60% acetonitrile. These data correlate with known effects of polar and bipolar aprotic solvents on SN2 nucleophilic substitution reactions. The enzyme modified with fluorescein-5′-isothiocyanate (fluorescein residue occupies an uridine-binding subsite [Komissarov et al., (1994) Biochim. Biophys. Acta 1205, 54–58]) was selectively modified with irreversible inhibitor SA-423, which reacts near the phosphate-binding subsite. The double-modified uridine phosphorylase is assumed to imitate the enzyme—substrate complex. Modification with SA-423 was accompanied with dramatic changes in the absorption spectrum of active site-linked fluorescein, which were identical to those for fluorescein in a hydrophobic medium, namely 80% acetonitrile. The data obtained suggest that an increase in active site hydrophobicity leads to phosphate desolvation and facilitates the enzymatic SN2 uridine phosphorolysis reaction

Information Technologies for the Analyzing of Kamchatka and the Kuril Islands Volcanoes Activity in 2019-2020

The work is devoted to the activity analysis of Kamchatka and the Kuril Islands volcanoes in 2019-2020.The activity of the volcanoes was estimated based on the processing of data from daily satellite monitoring carried out using the information system “Remote monitoring of Kamchatkan and the Kuriles volcanoes activity (VolSatView)”. The activity of the Kamchatka and the Kuril Islands volcanoes considered based on the analysis of their thermal anomalies. Analysis of the characteristics of thermal anomalies over volcanoes was carried out in KVERT IS. Analysis of the temperature of thermal anomalies of volcanoes in the Kuril - Kamchatka region in 2019-2020 shows a significantly higher activity of the Kamchatka volcanoes in comparison with the Kuril volcanoes

The results of the scientific and practical conference 'The topical problems of forensic medicine and medical law', Moscow, 23.12. 2016 [O rabote nauchno-prakticheskoĭ konferentsii 'Aktual'nye voprosy sudebnoĭ meditsiny i meditsinskogo prava'. Moskva, 23.12.2016]

[No abstract available

Assessment of lung morphological changes in acute intoxications with clozapine, ethanol and their combination

Objective: to detect lung morphological changes in acute intoxications with clozapine, ethanol, and their combination 3 and 24 hours after poisoning. Materials and methods. Experiments were carried out in outbred male rats weighing 270–300 g. Clozapine was given in a dose of 250 mg per kg animal body weight under chloralose anesthesia. Following 3 and 24 hours, the animals were withdrawn from the experiment by decapitation. Lung histological sections from 6 rats that had received oral clozapine 250 mg/kg, 6 rats that had oral ethanol 8.6 ml/kg, and 6 rats that had a combination of ethanol and clozapine orally in the above doses were examined 3 hours after intoxication. Those from 18 rats that had been orally given the similar agents in the above doses and withdrawn from the experiment were also investigated 24 hours after drug administration. The sections were compared with those from 6 rats that had not received the above agents. Nonparametric methods (χ2 test) were used for statistical processing. The investigators assessed the following morphological signs: circulatory disorders (plethora, hemorrhages), interstitial and alveolar edema, damage to the bronchial and alveolar epithelium and to the endothelium, and a cell reaction. The differences were considered significant at p<0.05. Results. In the control animal group, histological examination did not reveal any circulatory disorders and damage to the bronchial and alveolar epithelium and to the endothelium. Three hours after its administration, the animals that had received clozapine were observed to have acute pulmonary circulatory disorders (plethora in the pulmonary artery system, focal plethora of the capillaries of interalveolar septa and that of veins) that increased 24 hours after its ingestion. If death occurred 3 hours after ethanol intake, there was obvious perivascular edema, plethora, and hemorrhage; some alveoli contained transudate. Moderate venous plethora was seen 24 hours following ethanol administration. The secretory activity of the bronchial mucosa decreased. Three hours after coadministration of clozapine and ethanol, there were acute pulmonary circulatory disorders (marked plethora, multiple hemorrhages, and alveolar edema), bronchial epithelial lesion (desquamation), and no staining of endothelial cell nuclei. Lymphocyte accumulation was observed around the veins and arteriovenous anastomoses. Perivascular edema was absent. The lesions increased 24 hours after coadministration of clozapine and ethanol. Conclusion. The changes found at lung histological examination of the animals receiving clozapine alone and its combination with ethanol in conjunction with the results of forensic chemical analysis may be used to diagnose relevant intoxications and to establish their duration. © 2015 AVES Ibrahim Kara. All rights reserved

ВСЕРОССИЙСКАЯ НАУЧНО-ПРАКТИЧЕСКАЯ КОНФЕРЕНЦИЯ “ДЕКАБРЬСКИЕ ЧТЕНИЯ ПО СУДЕБНОЙ МЕДИЦИНЕ В РУДН: АКТУАЛЬНЫЕ ВОПРОСЫ СУДЕБНОЙ МЕДИЦИНЫ И АНЕСТЕЗИОЛОГИИ-РЕАНИМАТОЛОГИИ”

This article contains information on the Scientific Conference, brief content of the reports.В статье приводится информация о проведенной научно-практической конференции, дано краткое содержание представленных докладов

ХАРАКТЕРИСТИКА ГИСТОМОРФОЛОГИЧЕСКИХ ИЗМЕНЕНИЙ В СЕРДЦЕ ПРИ ОТРАВЛЕНИИ КЛОЗАПИНОМ

The article deals with the features of histomorphological changes in the heart in poisoning with atypical neuroleptic - clozapine. The relevance of the topic is caused by the large number of poisoning by this substance. The authors conducted a study of heart histological sections of 10 rats treated with clozapine at a dosage of 150 mg / kg in order to assess changes in them. The sections were compared with histological sections of the heart of intact animals (5). The hidtomorphological changes revealed in heart along with the hismimorphological changes in other organs and the results of chemical analysis will hallow to diagnose clozapine poisonings.В статье рассмотрены особенности гистоморфологических изменений в сердце при отравлении атипичным нейролептиком - клозапином. Актуальность темы обусловлена большим количеством отравлений этим веществом. Авторы провели исследование гистологических препаратов сердца 10 подопытных крыс, получавших клозапин в дозе 150 мг/кг с целью оценки изменений в них. Сравнение проводилось с гистологическими срезами сердца интактных животных. Выявлен- ные гистоморфологические изменения в сердце вместе с изменениями в других органах и результатами судебно-химического исследования позволят диагностировать отравления клозапином

Assessment of lung morphological changes in acute intoxications with clozapine, ethanol and their combination

Objective: to detect lung morphological changes in acute intoxications with clozapine, ethanol, and their combination 3 and 24 hours after poisoning. Materials and methods. Experiments were carried out in outbred male rats weighing 270–300 g. Clozapine was given in a dose of 250 mg per kg animal body weight under chloralose anesthesia. Following 3 and 24 hours, the animals were withdrawn from the experiment by decapitation. Lung histological sections from 6 rats that had received oral clozapine 250 mg/kg, 6 rats that had oral ethanol 8.6 ml/kg, and 6 rats that had a combination of ethanol and clozapine orally in the above doses were examined 3 hours after intoxication. Those from 18 rats that had been orally given the similar agents in the above doses and withdrawn from the experiment were also investigated 24 hours after drug administration. The sections were compared with those from 6 rats that had not received the above agents. Nonparametric methods (χ2 test) were used for statistical processing. The investigators assessed the following morphological signs: circulatory disorders (plethora, hemorrhages), interstitial and alveolar edema, damage to the bronchial and alveolar epithelium and to the endothelium, and a cell reaction. The differences were considered significant at p<0.05. Results. In the control animal group, histological examination did not reveal any circulatory disorders and damage to the bronchial and alveolar epithelium and to the endothelium. Three hours after its administration, the animals that had received clozapine were observed to have acute pulmonary circulatory disorders (plethora in the pulmonary artery system, focal plethora of the capillaries of interalveolar septa and that of veins) that increased 24 hours after its ingestion. If death occurred 3 hours after ethanol intake, there was obvious perivascular edema, plethora, and hemorrhage; some alveoli contained transudate. Moderate venous plethora was seen 24 hours following ethanol administration. The secretory activity of the bronchial mucosa decreased. Three hours after coadministration of clozapine and ethanol, there were acute pulmonary circulatory disorders (marked plethora, multiple hemorrhages, and alveolar edema), bronchial epithelial lesion (desquamation), and no staining of endothelial cell nuclei. Lymphocyte accumulation was observed around the veins and arteriovenous anastomoses. Perivascular edema was absent. The lesions increased 24 hours after coadministration of clozapine and ethanol. Conclusion. The changes found at lung histological examination of the animals receiving clozapine alone and its combination with ethanol in conjunction with the results of forensic chemical analysis may be used to diagnose relevant intoxications and to establish their duration. © 2015 AVES Ibrahim Kara. All rights reserved