Deep phenotyping of 34,128 patients hospitalised with COVID-19 and a comparison with 81,596 influenza patients in America, Europe and Asia: an international network study.

Background In this study we phenotyped individuals hospitalised with coronavirus disease 2019 (COVID-19) in depth, summarising entire medical histories, including medications, as captured in routinely collected data drawn from databases across three continents. We then compared individuals hospitalised with COVID-19 to those previously hospitalised with influenza. Methods We report demographics, previously recorded conditions and medication use of patients hospitalised with COVID-19 in the US (Columbia University Irving Medical Center [CUIMC], Premier Healthcare Database [PHD], UCHealth System Health Data Compass Database [UC HDC], and the Department of Veterans Affairs [VA OMOP]), in South Korea (Health Insurance Review & Assessment [HIRA]), and Spain (The Information System for Research in Primary Care [SIDIAP] and HM Hospitales [HM]).

Mutagenesis testing using the LacZ reporter activity of the reparation gene mus209 in Drosophila melanogaster.

We studied a set of Drosophila melanogaster strains that could be potentially suitable for testing a variety of mutagenic factors. Their genomes contained insertions of the enhancer trap P{lacW} in which the activity of the LacZ reporter is under the control of the reparation genes’ regulatory region. We demonstrated that the beta-galactosidase reporter, which is encoded by insertion of P{lacW} element in the gene mus209, is induced by irradiation in the cells of the salivary glands and wing imaginal discs.

Pituitary tumor transforming gene as a novel regulatory factor of liver fibrosis.

Aims: Pituitary tumor-transforming gene (PTTG) is involved in multiple cellular pathways. We studied the development of liver fibrosis induced by thioacetamide (TAA) in knockout (PTTG-/-) and wildtype (PTTG+/+) mice.

Main Methods: Liver fibrosis in PTTG+/+ and PTTG-/- mice was induced by escalating dose TAA treatment (50-400mg/kg, i.

Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice.

The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues.

DNA methylation in Drosophila melanogaster may depend on lineage heterogeneity.

DNA methylation has been discovered in Drosophila only recently. Current evidence indicates that de novo methylation patterns in drosophila are maintained in a different way compared to vertebrates and plants. As the genomic role and determinants of DNA methylation are poorly understood in invertebrates, its link with several factors has been suggested.

Elimination kinetics of the novel prodrug cinazepam possessing psychotropic activity in mice.

The kinetics of excretion of the novel tranquilizer cinazepam (3-hydroxy-7-bromo-5-(ortho-chlorophenyl)-1,2-dihydro-3H-1,4-benzdiazepin-2-one hemisuccinate (I)) in mice after a single administration and different schemes of multiple administration were determined. Mass balance was studied daily in excretions of mice (feces and urine) for 5-10 days. We observed that monoexponential renal excretion of (14)C-cinazepam and its metabolites predominated with all dosage regimens.

[Effects of plasminogen and streptokinase on the vital functions of nervous tissue cells in culture].

In the protein-deficient media plasminogen stimulated the vital functions of cells and in concentrations 10(-7)-10(-10) M it protected cells of sympathetic ganglia, neocortex and continues cell lines under damaging actions of H2O2 (0.0001 M), NH4CI (0.01 M) and cooling.

Pharmacokinetics of a synthetic interferon inducer amixin in mice.

Pharmacokinetics of amixin, a synthetic interferon inducer, has been studied in mice under intravenous and oral routes of administration. Following oral administration, 80% of the drug was eliminated in the unchanged form. Its absolute biological availability comprised 0.

Effects of streptokinase on the development of rat cerebral cortical cells in vitro.

The aim of the present work was to study the effects of streptokinase (SK) on the ultrastructure of the cellular elements of the cerebral cortex of neonatal rats in vitro. Three series of cultures were used: cultures maintained in DMEM enriched with 15% fetal calf serum (control 1), some transferred to minimal nutritive medium containing only 0.5% serum (control 2), and some supplemented with SK (2000 MU/ml) (experimental).

[The effect of streptokinase on the development of rat cerebral cortex cells in vitro].

The aim of this study was to determine the effect of streptokinase (SK) on the ultrastructure of cellular elements in the cerebral cortex of newborn rats in vitro. Three series of cell cultures grown on DMEM were used, including those grown on the medium enriched with 15% fetal calf serum (control 1), cultures transferred to the depleted medium containing only 0.5% of this serum (control 2), and the experimental cultures, to which SK (2000 IU/ml) was added.

Pharmacokinetics of ethanol in mice with different alcohol motivation.

We studied the pharmacokinetics of (14)C-ethanol administered in various doses and via different routes to CBA, C57Bl/6, and (CBAxC57Bl/6)F1 mice. Kinetic scheme of ethanol distribution included its elimination by enzymatic (80-90% C(0)) and exponential (10-20% C(0)) mechanisms. Ethanol pharmacokinetics did not depend on the administration route and mouse strain.

Modulation of GABAA receptor-mediated currents by phenazepam and its metabolites.

The effects of 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (phenazepam, PNZ), a 1,4-benzodiazepine derivative, and its physiological metabolites on GABA-activated whole-cell currents were studied in enzymatically isolated rat Purkinje neurones. PNZ, its hydroxylated metabolite (HPNZ) and a reference benzodiazepine, diazepam, potently enhanced (up to 200% of control) peak amplitude of currents activated by 10 microM GABA with EC50s of 6.1 +/- 0.

[Use of the acoustic startle response in the mouse to evaluate the pharmacodynamic action of ethanol].

A method of the pharmacological screening of psychotropic drugs that is based on the estimation of the peak amplitude and latency of the acoustic startle response (ASR) is suggested. A linear relationship between the changes of the ASR parameters induced by acute i.p.

The pharmacodynamics of anticonvulsant and subconvulsant effects of ethanol in CBA and C57BL/6 mice.

A method of determination of minimal effective doses (MEDs) of bicuculline causing clonic-tonic convulsions (CTC) and tonic extension (TE) was used to investigate ethanol pharmacodynamics in C57BL/6 and CBA mice, differing in levels of alcohol predisposition. It is observed that ethanol produces a powerful anticonvulsant action antagonizing convulsant effects of bicuculline. On a long-term scale, the pharmacological action of alcohol had two phases in both strains of mice: anticonvulsant (in the interval 5 min to 4 h after ethanol administration) and subconvulsant (4-24 h after ethanol administration).

Biokinetics of gidazepam, derivatives of peptideaminobenzophenones and their metabolites.

Results of a comparative study of biokinetics of two prodrugs gidazepam (I) and the derivative of peptideaminobenzophenone, 2-N-carbobenzylglycyl-glycylamido-5-bromobenzophenone (II) and their main physiologically active metabolite-7-brom-5-phenyl-dihydro-3H-1,4-benzodiazepine (III) were investigated in mice. It was shown earlier that I undergoes intensive N1-desalkylation with the formation of a metabolite: (III) and products of its further oxidation. Metabolism of II is characterized by hydrolysis of the peptide fragment and subsequent intramolecular condensation resulting in the formation of III, its oxi- and metoxylated derivatives and other minor metabolites.

[The effect of nerve growth factor on regeneration of the fibers in the rat sciatic nerve].

Exogenic nerve growth factor in the crushed nerve of rat promotes the development of reparative-regenerative processes. This was established by electron microscopy and electrophysiological method and is expressed through the activation of phagocytosis in the remained crushed axons in distal segments, relatively more early and vast penetration of the growing fibres to the outside of the traumatic zone, a single supramaximum stimulation of proximal region above the appearance and growth of action potential amplitude and also its spreading to the periphery as compared to control animals, treated with equal amounts of isotonic natrium chloride.

[Biokinetics of a new prodrug gidazepam and its metabolite].

Pharmacodynamics and pharmacokinetics of a novel tranquilizing agent--gidazepam (I), a prodrug, and its physiologically active metabolite--7-bromo-5-phenyl-1,2-di-hydro-3H-1,4- benzodiazepine-2-one (II) in mice organism were studied. The form of relationship was determined between the dynamics of the anticonvulsant effect of labelled (2-14C-) I and II and the kinetics of the content of 14C-compounds in the experimental animals brain. It was noted that the biophase of the effect and the effector fragment of the scheme of biokinetics for I and II are identical.

[The effect of nerve tissue growth factor on the structural-functional state of the sympathetic neurons after cutting their axons].

Under study was the influence of the nerve growth factor on morpho-functional and cytometrical characteristics of sympathetic neurons after cutting their axons. The work was carried out in albino rats which were subjected to dissection of the external and internal carotid nerves of the cranial cervical ganglion. This operation resulted in death of about 50% of the neurons of the node in question, in 30 and 60% in reduction of the intensity of fluorescence of the neuron body catecholamines within 7 and 14 days.

[Effector modeling of the action of ligands of the GABA receptor complex: functional interactions of muscimol and exogenous modulators of the complex].

In comparison with the literature data the pharmacological effects of muscimol (MS) on mice organism were studied under the condition of administration of the exogenic ligands of GABA-receptor complex GABA antagonist bicuculline (BC), chloride ionophor blocking agent pentylenetetrazole (PZ), phenazepam (BD), sodium barbital (BB) and GABA synthesis antagonist--thiosemicarbazide (TS). Antagonism of MS to the anticonvulsant effect of BB and BD at the administration of BC to the animal was observed, while no effect was observed at the administration of PZ. However at the administration of TS to the experimental animals MS exhibits anticonvulsant effect.

[Effector modeling of the action of ligands of GABA-receptor complex. Functional interaction of the hypothetic alcohol receptor with other subunits of the complex].

The types of the interaction of the pharmacological effects of ethanol and barbiturate antagonists--picrotoxin, bemegride and corasol--were determined. The effect of ethanol was determined as competitive--for the convulsant effects of bicuculline, and non-competitive--for the effects of thiosemicarbazide. The indices of the anticonvulsant effects of n-aliphatic alcohols were compared.