Neurotoxicity of drugs

Neurotoxicity is not uncommon in use of the drugs in many therapeutic classes. Manifestations of neurotoxicity vary from ototoxicity, visceral neuropathy and neuromuscular blockade (defeat of the peripheral nervous system) to impaired consciousness, nonspecific encephalopathy, seizures and non-convulsive epileptic status (central nervous system damage). The article presents predisposing factors of neurotoxicity, as well as the mechanisms of its development. On the example of neuroactive drugs (anticonvulsants, anesthetics and psychotropic drugs) their effect in the antenatal period and during lactation is examined. In the post-neonatal period antibiotics play an important role in the neurotoxic effect, in particular, ß-lactams and fluoroquinolones

Pharmacotherapy in a Multidisciplinary Paediatric Hospital: Polypharmacy and Drug–Drug Interaction Risk Illustrated with a Clinical Case

Nowadays, the problems caused by polypharmacy are recognised and widely discussed in the medical community. Multimorbidity, which is not uncommon in paediatric practice, comes with an increase in the number of prescriptions and necessitates an active search for tools to reduce the potential risk and frequency of adverse drug–drug interactions in paediatric patients.The aim of the study was to use a clinical case to illustrate the need for monitoring, including laboratory monitoring of pharmacokinetic parameters, during concomitant therapy in paediatric practice.Materials and methods: the study consisted in a retrospective analysis of the archived medical records of an 11-year-old child with nephrotic syndrome associated with a concomitant tuberculous process who had been receiving inpatient treatment with immunosuppressants at the Russian Children’s Clinical Hospital from May to July 2018.Results: the prescription of cyclosporine for nephrotic syndrome entailed monitoring of plasma drug levels for potential pharmacokinetic interactions with the medicinal products used to treat the concomitant disease. The monitoring revealed an interaction between cyclosporine and rifampicin at the level of biotransformation. An adjustment of the concomitant therapy (discontinuation of rifampicin) allowed for achieving the target blood cyclosporine concentration, decreasing proteinuria and hypercholesterolemia, and increasing the blood total protein level in the child, which indicated the effectiveness of the ongoing treatment for the chief complaint.Conclusions: the data obtained suggest that laboratory monitoring of pharmacokinetic parameters in paediatric polypharmacy can increase the effectiveness of therapy and prevent adverse reactions and irrational combination of medicinal products

INTERSTICIAL PNEUMONITIS, CAUSED BY PEGYLATED INTERFERON ALFA-2A IN A 4 MONTHS CHILD WITH GIGANTIC KAPOSI'S HAEMANGIOEPITHELIOM AND KASABACH – MERRIT PHENOMENON: A CASE REPORT

The article presents the description of a case of drug-induced lung impairment in a child

Experimental Substantiation of New Presentation Form of Cholera Diagnostic Sera

Objective of the study is experimental substantiation of possibility to produce new presentation form of cholera diagnostic sera – lyophilizate in bottles. Materials and methods. Cholera diagnostic sera. Liophylization was performed in Martin Christ Epsilon 2-6D. Residual moisture of dry sera was determined using humidity meter Sartorius MA 150. Solubility of experimental samples was assessed visually. pH was evaluated by potentiometry with the help of PK SevenExcellence-475 Mettler Toledo device, measuring pH/ORP/Ion content/conductivity/concentration. Specific activity and specificity was analyzed through expanded agglutination reaction, using relevant control strains of cholera vibrio. Results and conclusions. Experimentally justified is the possibility to lyophilize cholera diagnostic sera in flasks. Specified are the optimum parameters of lyophilization. It is determined that lyophilization does not result in deterioration of properties, as judging by the quality indicators they meet the requirements of regulatory documentation. Using accelerated aging test, it is demonstrated that the new presentation form of cholera diagnostic sera – lyophilizate in flasks – maintains their specific activity within five years term (the set out shelf life), which fully conform to normative standards

Folding of poly-amino acids and intrinsically disordered proteins in overcrowded milieu induced by pH change

pH-induced structural changes of the synthetic homopolypeptides poly-E, poly-K, poly-R, and intrinsically disordered proteins (IDPs) prothymosin alpha (ProT alpha) and linker histone H1, in concentrated PEG solutions simulating macromolecular crowding conditions within the membrane-less organelles, were characterized. The conformational transitions of the studied poly-amino acids in the concentrated PEG solutions depend on the polymerization degree of these homopolypeptides, the size of their side chains, the charge distribution of the side chains, and the crowding agent concentration. The results obtained for poly-amino acids are valid for IDPs having a significant total charge. The overcrowded conditions promote a significant increase in the cooperativity of the pH-induced coil-alpha-helix transition of ProTa and provoke histone H1 aggregation. The most favorable conditions for the pH-induced structural transitions in concentrated PEG solutions are realized when the charged residues are grouped in blocks, and when the distance between the end of the side group carrying charge and the backbone is small. Therefore, the block-wise distribution of charged residues within the IDPs not only plays an important role in the liquid-liquid phase transitions, but may also define the expressivity of structural transitions of these proteins in the overcrowded conditions of the membrane-less organelles. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Оценка безопасности лекарственной терапии в клинической практике Костылева М.Н.1,2, Белоусов Ю.Б.2, Грацианская А.Н.1,2,

the present review is devoted to an actual problem of safety of pharmacotherapy in clinical practice; the particular attention is paid to the state of this problem in pediatrics. Information about pharmacovigilance is proposed; criteria of definition, methods of collecting (their advantages and limitations), account and analysis of the adverse reactions of drugs in post-marketing period are described. The off label use of drugs in children and a role of clinical pharmacologist in the adverse reactions of drugs monitoring in a hospital is discussed.настоящий обзор посвящен актуальной проблеме безопасности фармакотерапии в клинической практике, отдельное внимание уделено состоянию проблемы в педиатрии. Предлагаются сведения о фармаконадзоре: описаны критерии определения, методы сбора (их преимущества и недостатки), учета и анализа нежелательных явлений лекарств на пострегистрационном этапе. Обсуждается проблема off label назначений лекарств у детей и роль врача-клинического фармаколога в организации мониторинга нежелательных явлений в условиях стационара

The era of Belousov Yuri: continuing the tradition. To the 80th birthday

The article is dedicated to the outstanding scientist, doctor, teacher, public figure, corresponding member of the Russian Academy of Sciences, professor, doctor of medical sciences Belousov Yuri, who would have turned 80 on September 23, 2022. The presented materials make it possible to recall the main milestones in the biography of this remarkable person. The article is based on materials collected by relatives, friends, colleagues and students of Yuri Belousov

OPTIMIZATION OF PRESENTATION AND CONSUMER CONTAINER OF ANTI-RABIES IMMUNOGLOBULIN OBTAINED FROM HORSE SERUM

We presented the data concerning optimization of presentation and consumer container of anti-rabies immunoglobulin obtained, from horse serum.. During the experiments, ampoules and. flasks were used for primary packaging. They were filled within 5 ml of the preparation of freeze-drying. Comparative analysis of physical, chemical and. biological properties and. molecular parameters of freeze-dried and initial forms of the immunoglobulin. was carried out. Freeze-drying was demonstrated to promote stabilization of its properties and. prevent emergence of fragments and. aggregates during anti-rabies immunoglobulin storage

The 6^{6}H states studied in the d(8He,α)d(^8\text{He},\alpha) reaction and evidence of extremely correlated character of the 5^{5}H ground state

The extremely neutron-rich system $^{6}$H was studied in the direct $^2\text{H}(^8\text{He},{^4\text{He}})^{6}$H transfer reaction with a 26 $A$ MeV secondary $^{8}$He beam. The measured missing mass spectrum shows a resonant state in $^{6}$H at $6.8(3)$ MeV relative to the $^3$H+$3n$ threshold. The population cross section of the presumably $p$-wave states in the energy range from 4 to 8 MeV is $d\sigma/d\Omega_{\text{c.m.}} \simeq 190(40)$ $\mu$b/sr in the angular range $5^{\circ}<\theta_{\text{c.m.}}<16^{\circ}$. The obtained missing mass spectrum is free of the $^{6}$H events below 3.5 MeV ($d\sigma/d\Omega_{\text{c.m.}} \lesssim 3$ $\mu$b/sr in the same angular range). The steep rise of the $^{6}$H missing mass spectrum at 3 MeV allows to show that $4.5(3)$ MeV is the lower limit for the possible resonant state energy in $^{6}$H tolerated by our data. According to paring energy estimates, such a $4.5(3)$ MeV resonance is a realistic candidate for the $^{6}$H ground state (g.s.). The obtained results confirm that the decay mechanism of the $^{7}$H g.s.\ (located at 2.2 MeV above the $^{3}$H+$4n$ threshold) is the ``true'' (or simultaneous) $4n$ emission. The resonance energy profiles and the momentum distributions of the sequential $^{6}$H \,\rightarrow \, ^5H(g.s.)+n\, \rightarrow \, ^3H+$3n$ decay fragments were analyzed by the theoretically-updated direct four-body-decay and sequential-emission mechanisms. The measured momentum distributions of the $^{3}$H fragments in the $^{6}$H rest frame indicate very strong ``dineutron-type'' correlations in the $^{5}$H ground state decay.Comment: 9 pages, 11 figure