[Herpangina. Clinical case]. / Gerpeticheskaya angina ­ aktual'naya problema otorinolaringologicheskoi praktiki.

Enterovirus infections are a group of acute infectious diseases caused by enteroviruses (including Coxsackie A and B viruses, ECHO viruses), which clinically present symptoms of damage to the central nervous system, cardiovascular system, gastrointestinal tract, muscular system, mucous membranes and skin, fever. This article presents a clinical case of patient L., 12 years old, who admitted to an otorhinolaryngologist with clinical manifestations of herpangina. The diagnosis was confirmed by PCR. The patient was prescribed, adequate rehydration, diet with the exclusion of salty, spicy and fried foods, restriction of physical activity, exclusion of thermal procedures, Benzydamine Spray (Oralsept) 0.255 mg/dose, 6 doses 3 times/day, topically, on demand and inosine pranobex (Groprinosin) in a daily dose of 50 mg/kg of body weight: 1 tablet 500 mg 4 times a day for 7 days (at the rate of 1 tablet of 500 mg per 10 kg of body weight; for a patient weighing 41 kg - 4 tablets per day). On the 10th day from the onset of the disease, the docter noted a complete regression of clinical symptoms and the patient was discharged with recovery.

Prevalence and risk factors of potentially prescribing omissions in elderly and senile patients: clinical practice in Russian hospitals.

A retrospective pharmacoepidemiological study (included data from medical records of 401 patients ≥65 years of age who received treatment in hospitals) was aimed to measure prevalence of potentially prescribing omissions (PPOs) among older people using Screening Tool to Alert doctors to Right Treatment 2 (START-2) criteria (2015) and to investigate associated risk factors. Statistical analysis includes methods of parametric and nonparametric statistics. We compared patients who had PPOs with those had not PPOs. It was found that hypertension, diabetes mellitus and high levels of concomitant diseases were more characteristic for people with PPOs, and they received more medications. There were no significantly differences in terms of age and gender. Polypharmacy was observed in 36,7% of patients. Using the START-2 criteria, 633 episodes of PPOs were indicated (67,3% of patients). 94,7% PPOs were mainly associated with under-use of statins, aspirin, b-blockers and angiotensin-converting enzyme inhibitors. Multivariate analyses revealed strong association of PPOs prevalence with the number of prescribed medications and comorbidities, especially, ischaemic heart disease and hypertension. Cardiovascular medications were the most common among PPOs.

[Treatment of chronic heart failure: is deprescribing possible?]

Deprescribing is a scheduled withdrawal, dose reduction, or replacement of a medicine with a safer one. Several groups of medicinal products (MPs) are used simultaneously in the treatment of chronic heart failure. This increases the risk of adverse drug reactions, particularly in elderly and senile patients. A systematic search for literature allowed evaluating possibilities of deprescribing for the following pharmaceutic groups: 1) MPs influencing the renin-angiotensin-aldosterone system; 2) beta-blockers; 3) digoxin; and 4) diuretics. Three systematic reviews and several studies were analyzed to determine the most feasible and potentially optimal regimens of deprescribing in CHF. It was established that in CHF, deprescribing has a very limited potential for use due to the documented, obvious effect of some MP groups on prediction and severity of clinical symptoms in CHF patients.

[Drug-induced insomnia in old and very old patients]. / Lekarstvenno-indutsirovannaia insomniia u patsientov pozhilogo i starcheskogo vozrasta.

According to modern concepts, sleep disorders are considered as a common geriatric syndrome, which also emphasizes their polyfactorial genesis. One of the important factors inducing sleep disorders is the intake of various drugs, which becomes especially significant with the problems of polymorbidity and polypharmacy occurring in older age groups. The article provides a classification of drug-induced sleep disorders, which presents a wide range of conditions associated with a disturbance of the sleep-wake cycle. The authors present the frequency of insomnia associated with taking drugs from different pharmacological groups according to the literature, and consider mechanisms of insomnia development due to the effect on various receptors and neurotransmitter systems, as well as data on their effect on sleep structure. The article presents risk factors for drug-induced insomnia and discusses preventive measures and management of patients.

[Drug-induced hearing loss as a manifestation of drug-induced ototoxicity]. / Lekarstvenno-indutsirovannaia tugoukhost' kak proiavlenie lekarstvenno-indutsirovannoi ototoksichnosti.

The ability of drugs to have an ototoxic effect has been studied for a long time, however, the true prevalence of this undesirable phenomenon is unknown, which is due to the use of various audiological protocols, a wide range of reactions to drugs in different ethnic groups, and most importantly, the lack of caution with regard to otological symptoms due to their reversibility or lack of immediate threat to life. Drug-induced ototoxicity is a functional disorder of the inner ear (cochlea and/or vestibular apparatus) or eighth pair of cranial nerves. Pharmacotherapy, associated with the development of ototoxic drug reactions, may remain undervalued for a long time, often until irreversible hearing impairment is formed. The most frequently prescribed drugs that cause ototoxic phenomena include anticancer drugs, antibacterial drugs of the aminoglycoside group, loop diuretics, calcium channel blockers, non-steroidal anti-inflammatory drugs, antimalarial drugs, salicylates, etc. Monitoring the degree of hearing impairment before and during therapy is important in preventing the development of drug-induced ototoxicity and makes it possible to consider alternative treatment regimens in a timely manner. It is in this connection that the role of participation in the appointment of rational pharmacotherapy to patients with a potential risk of developing otological phenomena of a clinical pharmacologist and audiologist undoubtedly increases.

[Drug-induced delirium in elderly and senile patients]. / Lekarstvenno-indutsirovannyi delirii u patsientov pozhilogo i starcheskogo vozrasta.

Drug-induced delirium is an urgent challenge of modern healthcare, especially in elderly patients, due to the widespread prevalence, associated complications, longer hospitalization period, higher mortality rate. The exact pathogenesis of delirium is unknown, however, a number of studies suggest that it is based on neurotransmitter dysfunction. Thus, drugs that affect the metabolism of these neurotransmitters can lead to the onset of delirium. The Delirium Drug Scale (DDS) and the Anticholinergic Burden scale (ACB) are used to assess the risk of delirium. For patients with an increased risk of delirium, it is recommended to avoid prescribing benzodiazepines, use with caution opiates, dihydropyridines and antagonists of H1-histamine receptors. Non-pharmacological methods are recommended as a first-line treatment of delirium (behavioral approaches, placing the patient in specially equipped delirious rooms, etc.). If non-pharmacological methods have shown to be ineffective or the patient's behavior represents a danger to the life and health of himself and / or others, it is possible to administer antipsychotic drugs.

[Antipsychotics: features of undesirable adverse reactions in elderly and senile age]. / Antipsikhotiki: osobennosti nezhelatel'nykh pobochnykh reaktsii u lits pozhilogo i starcheskogo vozrasta.

This review summarizes and systematizes currently available literature on antipsychotics as one of the most frequently prescribed group of psychotropic drugs. Based on published data from clinical studies and meta-analyzes, the authors consider unwanted adverse reactions in patients taking antipsychotic medications. Mechanisms of development of undesirable drug reactions are discussed. Special attention is paid to those adverse reactions of antipsychotics that most often occur in old and very old age (increased risk of adverse cardiovascular and cerebrovascular events, sudden death, prolonged QTc interval, falls, fractures, orthostatic hypotension, extrapyramidal disorders, pneumonia, urinary tract infections, etc.).

[The relationship between the combined use of various proton pump inhibitors with antiplatelet drugs and the risk of cardiovascular complications].

In the article the problem of the combined use of clopidogrel and various proton pump inhibitors (PPIs) in terms of cardiovascular complications risk and stent thrombosis is considered. The results of meta - analyses and a systematic reviews affecting this issue are represented in detail. The inter - drug interactions mechanisms of various PPIs with clopidogrel based on the characteristics of the metabolism in the liver cytochromes system are discussed. The authors conducted a search, systematization and analysis of studies regarding the association between cardiovascular risk and combined use of individual medications from PPI class with clopidogrel, and these results are presented in the review. Currently available data do not allow to answer the question about the differences between individual PPIs in their impact on the risk of adverse cardiovascular events due to the small number of such studies, design heterogeneity, differences in the inclusion criteria and end points as well as in the rate of administration of individual PPIs.

Analysis of Nonsense-Mediated mRNA Decay at the Single-Cell Level Using Two Fluorescent Proteins.

Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved mechanism of specific degradation of transcripts with a premature stop codon. NMD eliminates aberrant mRNAs arising from mutations, alternative splicing, and other events in cells. In addition, many normal transcripts undergo NMD. Recent studies demonstrated that NMD activity is specifically regulated and that NMD can play a role of global regulator of gene expression. Recently, we developed dual-color fluorescent protein-based reporters for quantification of NMD activity using fluorescence microscopy and flow cytometry (Pereverzev, Gurskaya, et al., 2015). Due to ratiometric fluorescence response, these reporters make it possible to assess NMD activity in live cells at the single-cell level and to reveal otherwise hidden heterogeneity of cells in respect of NMD activity. Here we provide a detailed description of applications of the NMD reporters in mammalian cell lines.

[Differences of Nonsense-Mediated mRNA Degradation Activity in Mammalian Cell Lines Revealed by a Fluorescence Reporter].

Activity of nonsense-mediated mRNA degradation (NMD) was studied in several mammalian cell cultures using recently developed genetically encoded fluorescence sensor [Pereverzev et al., Sci. Rep., 2015, vol. 5, p. 7729]. This NMD reporter enables measurement of NMD activity in single live cells using ratio of green and red fluorescent proteins signals. The following cell lines were analyzed: mouse colon carcinoma CT26, mouse Lewis lung carcinoma LLC, human T-cell leukemia Jurkat, and spontaneously immortalized human keratinocytes HaCaT. These cell lines demonstrated very different NMD activities. In CT26, NMD activity was low, whereas in LLC it was high (8.5-fold higher than in CT26). Jurkat and HaCaT cells possessed strong heterogeneity and consisted of two cell subpopulations with high and low NMD activities. In addition, we detected high NMD activity in primary culture of mouse embryonic hippocampal neurons.

[Intron 2 of human beta-globin in 3'-untranslated region enhances expression of chimeric genes].

Possibility to enhance heterologous gene expression in mammalian cells by introduction of an intron in 3' untranslated region (UTR) was investigated. To this end, a fragment of human beta-globin gene with intron 2 and flanked exon regions was introduced into vector encoding green fluorescent protein TagGFP2 after the TagGFP2 stop-codon (Int+). The distance between the stop-codon and the exonjunction was 35 nucleotides. It ensured that Int+ mRNA was resistant to degradation by nonsense mediated decay (NMD) machinery. A control vector Int- contained corresponding intronless sequence of the beta-globin mRNA. On the same plasmid, the second gene encoded far-red fluorescent protein Katushka was used to normalize fluorescence for transfection efficiency and expression level in individual cells. Transiently transfected HEK293T cells were analysed by flow cytometry. It was shown that cells transfected with plasmid carrying the Int+ gene possess 1.8 ± 0.2 fold higher green fluorescence compared to Int- cells. The observed effect was used to enhance expression of destabilized variants of yellow fluorescent protein TurboYFP-dest with high degradation rate in mammalian cells. We believe that introduction of beta-globin intron in the 3'-UTR of the chimeric gene can be used to enhance its expression and may be advantageous in some cases when usage of 5'-UTR intron is inappropriate.