[Epithelial protective therapy in comorbid diseases. Practical Guidelines for Physicians].

This document was produced with the support of the National Medical Association for the Study of Comorbidities (NASС). In 2021 the first multidisciplinary National Consensus on the pathophysiological and clinical aspects of Increased Epithelial Permeability Syndrome was published. The proposed guidelines are developed on the basis of this Consensus, by the same team of experts. Twenty-eight Practical Guidelines for Physicians statements were adopted by the Expert Council using the "delphic" method. Such main groups of epithelial protective drugs as proton pump inhibitors, bismuth drugs and probiotics are discussed in these Guidelines from the positions of evidence-based medicine. The clinical and pharmacological characteristics of such a universal epithelial protector as rebamipide, acting at the preepithelial, epithelial and subepithelial levels, throughout gastrointestinal tract, are presented in detail.

Clonal Composition of Human Multipotent Mesenchymal Stromal Cells: Application of Genetic Barcodes in Research.

Clonal composition of human multipotent mesenchymal stromal cells (MMSCs) labeled with lentiviral vectors carrying genetic barcodes was studied. MMSCs were transduced with a cloned library of self-inactivating lentiviral vectors carrying 667 unique barcodes. At each cell culture passage, 120 cells were plated one cell per well in 96-well plates. The efficiency of cloning and labeling of the clonogenic cells was determined. DNA was extracted from the cell-derived colonies, and the barcodes were identified by Sanger sequencing. Also, DNA was extracted from the total MMSC population at each passage to analyze the diversity and representation of barcodes by deep sequencing using the Illumina platform. It was shown that the portion of MMSCs labeled with the lentiviral vectors remained stable in the passaged cells. Because of the high multiplicity of infection, the labeling procedure could decrease the proliferative potential of MMSCs. Identification of barcodes in individual cell clones confirmed the polyclonal character of the MMSC population. Clonal composition of MMSCs changed significantly with the passages due to the depletion of proliferative potential of most cells. Large clones were found at the first passage; at later passages, many small clones with a limited proliferative potential were detected in the population. The results of deep sequencing confirmed changes in the clonal composition of MMSCs. The polyclonal MMSC population contained only a small number of cells with a high proliferative potential, some of which could be stem cells. MMSCs with a high proliferative potential were detected more often in the earliest passages. In this regard, we would recommend to use MMSCs of early passages for regenerative medicine applications based on cell proliferation.

[Protective action of reactivating factor of Luteococcus japonicus subsp. casei toward cells of Escherichia coli reparation mutants inactivated with UV-light].

Reactivating factor (RF) from Luteococcus japonicus subsp. casei had a protective action on UV-irradiated cells of Escherichia coli AB1157 with a native reparation system and on cells of isogenic reparation mutants of E. coli UvrA-, RecA-, and PolA-: the effect resulted in multifold increase of survivability. Defense action of L. casei exometabolite is not connected with stimulating reparation systems in E. coli, and, probably, it is mediated by involvement of the exometabolite in the mechanism of cell division. RF did not provoke the reactivation of E. coli cells inactivated by UV-light.

[The chondroprotector mucosat in an integrated approach to the treatment of nonspecific back pain]. / Khondroprotektor mukosat v integrirovannom podkhode k lecheniiu patsientov s nespetsificheskoi bol'iu v spine.

A nonspecific back pain is in the vast majority of all possible cases of dorsopathies. The sources of back pain may be myogenic dysfunction, intervertebral disc pathology or osteoarthritis of the archicular (facet) joints of the spine, including myofascial pain syndrome. A differentiated approach to the treatment of spondylarthrosis is still an unsolved problem. The article discusses important issues of integration of non-drug treatment methods and drug therapy of nonspecific back pain in patients with facet syndrome. Special attention is paid to SYSADOA group chemicals, in particular chondroitin sulfate (mucosat). These drugs have proven analgesic and anti-inflammatory effects and also are able to improve the structure of the cartilaginous tissue, slowing the progression of the disease.

[Between depression and fibroniyalgia: the fate of the antidepressant].

The authors present the information about one of the least studied antidepressants- milnacipran. Recommendations of its clinical use have been long based on incorrect conceptions of its pharmacological properties. Currently, milnacipran is considered as ancirepinephrine and serotonin (to a lesser degree) reuptake inhibitor and NMDA receptor blocker. Milnacipran can be successfully used in apatic, asthenic, adynamic and anhedonic depressions as well as in fibromyalgia in patients with marked fatigability and pain. However the recommendations for the latter are not registered in Russia (maybe due to the differences in the diagnosis of fibromyalgia which is traditionally more often diagnosed as neurasthenia).

[Pharmacotherapy and dementia]. / Farmakoterapiia i dementsiia.

The review considers treatment aspects of dementia in Alzheimer's disease (DAD), vascular dementia (VD) and some other forms of dementia. Pathogenetic pharmacotherapy of DAD aims to maintain the activity of cholinergic neurons with anticholinesterase drugs including donepezil, which is used most often. The main objective of VD treatment is prevention of new cerebral infarctions using cardiotropic medications, antiaggregants, anticoagulants, hypotensive drugs and statins. In Russia, patients with DAD and VD receive polymodal drugs as well. These drugs have been included in the list of antidementia medications due to their wide use in treatment of discirculatory encephalopathy and chronic brain ischemia.

[A psychoneurophysiological evaluation of non-specific cerebral systems in patients with permanent autonomic disorders of psychogenic etiology during therapy]. / Psikhoneirofiziologicheskaia otsenka sostoianiia nespetsificheskikh sistem mozga u bol'nykh s permanentnymi vegetativnymi rasstroistvami psikhogennogo kharaktera v protsesse lecheniia.

Fifteen patients with permanent vegetative disorders combined with a pronounced anxiety were examined before and after treatment by the Nott drug. The clinical-and-neurological technique, psychometric evaluation of cognitive functions and the neurophysiological method of acoustic cognitive induced potentials P300 were made use of. Before treatment, pronounced vegetative anxiety-related and cognitive disorders were observed in patients. A reliably decreased amplitude of the P300 peak was noted in patients versus healthy subjects while registering the cognitive induced potentials. After treatment, there was a reliably decreased severity of vegetative, anxious and cognitive disorders in patients; the P300 amplitude went up reliably. Supposedly, the changed P300 amplitude, as observed in patients with permanent vegetative disorders; denotes the malfunction in non-specific limbic-reticular brain structures. A growing P300-peak amplitude combined with the arrest of psychovegetative and anxious disorders and with an improvement of cognitive functions in patients due to therapy are indicative of a lower degree of the functional disintegration in the non-specific limbic-reticular brain structures. Finally, the method of endogenous induced P300 potentials can be used as a diagnostic tool in the objective evaluation of a condition of non-specific brain systems in patients with the psychovegetative syndrome; it can also be an objective criterion in the efficiency assessment of a conducted therapy.

[Features of daily rhythm of arterial pressure in patients with primary arterial hypertension and neurogenic syncope conditions]. / Osobennosti sutochnogo ritma arterial'nogo davleniia u patsientov s pervichnoi arterial'noi gipotoniei i neirogennymi sinokopal'nymi sostoianiiami.

AIM: A comparative analysis of parameters of systemic BP in patients with primary arterial hypotension (PAH) and in patients with neurogenic syncopes (NS) in the cycle sleep-awake. MATERIALS AND METHODS: Blood pressure was investigated in 20 patients with PAH aged 16-44 years and 18 patients with NS aged 16-49 years. 24-h ambulatory monitoring of BP was made on the monitor ABPM-02/M (Meditech, Hungary). RESULTS: Rhythm indices of BP in NS patients corresponded to age normal criteria. 24-h arrhythmia of BP in PAH patients manifests with excessive drop of diastolic BP in sleep (55% patients were overdippers). PAH and NS patients differ maximally by hypotonic load in sleep: 1.0 +/- 0.7% in NS vs 15.4 +/- 3.2% in PAH. Hypotonia episodes in awake PAH patients were registered at each 4th-5th measurement of BP, in NS patients--at each 11th-13th. Heart rate in awake PAH patients is higher than in healthy subjects. CONCLUSION: Hypotonic load in sleep carries the highest differentially-diagnostic importance. This makes more perspective examinations of such patients in the cycle sleep-awake. The changes observed in PAH patients evidence for activation of cerebral sympathico-adrenal systems participating in baroreflex regulation.

[Rationale for the choice of medication based on the conception of the pathogenesis of mental disorder and mechanism of drug action]. / Ratsional'nyi vybor preparata na osnove predstavlenii o patogeneze psikhicheskogo rasstroistva i mekhanizme ego deistviia.

In modern medicine, when prescribing drugs it is customary to take into account the pathogenesis of the disease and the mechanism of action of drugs. On the example of buspirone, authors have shown that in psychiatry recommendations for administration of drugs should also consider the pathogenesis of diseases (disorders) and the mechanism of drug action. These data will contribute to the rapprochement of neurology and psychiatry with other medical specialties.

[Treatment of asthenic syndrome in patients with chronic brain ischemia: results of the non-interventional observational program TRIUMPH].

OBJECTIVE: To assess the severity of asthenic syndrome (AS) in chronic brain ischemia (CBI) in primary health care settings. MATERIAL AND METHODS: The study included 1170 patients with brain ischemia, aged 45-65 years, treated with phenotropil in dose 100 mg during 2 and 3 months. Clinical examination and MFI-20 subscales were administered. RESULTS AND СONCLUSION: The high incidence of asthenic syndrome was observed across all MFI-20 subscales. The decrease in asthenic syndrome severity was significant already in the end of the first month of treatment with phenotropil. Such dynamics maintained to the end of the second and third month of treatment. More than 2-fold decrease in the severity of asthenia symptoms was achieved in all subgroups 3 months after treatment. More rapid and apparent decrease in asthenic syndrome was observed in younger patients.

[L-carnitine treatment patients with chronic cerebral ischemia].

The purpose of this study is to investigate the effectiveness of L-carnitine treatment in patients with dodementia stage chronic cerebral ischemia. In parallel comparative clinical study included 60 patients (22 men and 38 women aged 42 to 74 years), the average age of the patients was 61.2±8.2 years. All patients received basic treatment, including antihypertensive and antiplatelet drugs. The first group consisted of 20 patients who received 1000 mg of L-carnitine per day (bilology supplement karniton). In the second group (20 patients), the drug was administered to 2000 mg per day. In the third (the control group) was carried out only basic therapy. The course of treatment was 60 days. After treatment significantly reduced the frequency of complaints of weakness, decreased performance, memory loss, headache, dizziness, unsteadiness of gait. Statistically significant differences after treatment revealed in the MMSE total score and subtests "focus" and "memory", compared to the baseline reduced the running time with all 5-tables in the test Schulte. According to questionnaire fatigue MFI-20 the main group level decreased overall, physical and mental asthenia, increased activity and the level of motivation. Revealed a dose-dependent effect of the drug.

[Filterable microbial forms in the Rybinsk water reservoir].

Molecular identification of the filterable forms of microorganisms in the water of the Rybinsk reservoir, one of the largest open water bodies in European Russia, was carried out. The number of ultrasmall microbial cells passing through 0.22 µm filters was 10(4) cells/mL. These were represented by both bacteria and archaea. Most bacterial 16S rRNA gene sequences retrieved from filtered water belonged to the Betaproteobacteria and exhibited high similarity (99.0-99.5%) to thos of bacteria of the genus Polynucleobacter. The archaeal 16S rRNA gene clone library was composed of the sequences of members of the Euryarchaeota, including the orders Methanobacteriales and Methanomicrobiales, as well as of two archaeal groups (LDS and RC-V) with no characterized representatives. The species composition of filterable bacteria from reservoir water wast different from that revealed previously in bogs and small lakes at catchment areas; The pool of filterable archaea in the reservoir exhibited, however, significant similarity to that for boggy catchment areas and was characterized by perdominance of the clade LDS. Available data indicate that this archaeal group is typical of the northern freshwater ecosystems, and the organisms of this group are represented by ultrasmall cells.

Psychoneurophysiological assessment of recovery of cognitive function in patients with asthenia during rehabilitation.

Forty patients with severe asthenia were subjected to clinical, neurological, psychometric, and neurophysiologic examination before and after Enerion therapy. Psychoneurophysiological assessment with cognitive evoked potentials P300 and psychometric tests revealed serious impairment of cognitive functions in patients before therapy (compared to healthy individuals). Enerion therapy decreased the degree of psychoautonomic syndrome and asthenia and improved cognitive functions.

[Use of enerion in psychovegetative syndrome with pronounced asthenia]. / Primenenie éneriona pri psikhovegetativnom sindrome v sochetanii s vyrazhennoi asteniei.

Enerion was used in the treatment of 40 patients with psychovegetative syndrome and asthenia. Before treatment, the patients have pronounced asthenia appearances, anxiety disorders, relevant autonomic disorders, mild depression and decrease of working capacity, attention concentration and memory. The treatment was conducted as monotherapy during 28 days with enerion dosage 400 mg/day. After treatment, expression of autonomic and asthenic disorders was reduced significantly, along with improvement of psychometric and neurophysiological indices. High efficacy of the medication was detected in 75% of the patients and moderate one--in 25%. The drug was well-tolerated.

[Use of citrulline malate (stimol) in patients with autonomic dystonia associated with arterial hypotension]. / Primenenie malata tsitrullina (stimola) u lits s vegetativnoi distoniei v sochetanii s arterial'noi gipotenziei.

To study possibilities of a therapeutic correction of asthenic syndrome in individuals with chronic arterial hypotension with malate citrulline, the study was made of 12 women and 3 men with psychoautonomic syndrome (autonomic dystonia), combined with chronic constitutional arterial hypotension. Their age was from 27 to 45 years (mean age--37.6). A control group comprised 14 healthy individuals. Both a state of autonomic nervous system and manifestations of arterial hyportension were analyzed by means of complex scored questionnaires. Mental condition was assessed by the tests of Spilberger (evaluation of reactive and personal anxiety) and of Beck (estimation of depressive manifestations). In all the examined individuals with chronic arterial hypotension, there was psychoautonomic syndrome combined with complaints to asthenic manifestations, namely, to low performance and fatigue. Stimol was prescribed in the form of 50% solution in daily dose of 6 g (3 administrations). The therapy resulted in regression of clinical manifestations of both psychoautonomic syndrome and asthenic symptoms. A mechanism of the drug's action works through favourable changes in cerebral and muscular cells, that, in turn, had an influence on other manifestations of psychoautonomic syndrome.

[State of autonomic regulation mechanisms in arterial hypotension]. / Sostoianie mekhanizmov vegetatibnoi reguliatsii pri arterial'noi gipotenzii.

To investigate the role of suprasegmental and segmental parts of autonomic nervous systems (ANS) in genesis of arterial hypotension (AH) 75 individuals with arterial hypotension as well as 30 healthy persons were examined using clinical and psychological methods, evaluation of the state of ANS segmental part by means of evoked skin sympathetic potentials, spectral analysis of the variability of the heart rhythm, 5 standard cardiovascular tests according to Ewing. The conclusion was made that individuals with AH had combination of alterations of both emotional-personality sphere and autonomic functions in all systems of organism tested. Exactly they had psychoautonomic syndrome presenting as combination of asthenic manifestations, elements of Reynaud phenomenon and headaches pronounced differently (headaches of tension more frequently). Clinical alterations were combined with changes of indices of functional testing, that reflected disorders in some link of sympathetic regulation including baroreflex one. Decompensation in individuals with AH and change for the worse of the indices of functional testing were due both to the increase of psychoautonomic disorders, growing of desintegrational processes in ANS and the decrease of adaptive mechanisms in its sympathetic part.

[Indices of 24-hour monitoring of arterial blood pressure in patients with neurogenic syncope and patients with chronic constitution- dependent hypotension]. / Pokazateli sutochnogo monitoringa arterial'nogo davleniia u bol'nykh sinkopal'nymi sostoianiiami neirogennoi prirody i bol'nykh khronicheskoi konstitutsional'noi gipotenziei.

Clinical-psychologic study, spectral analysis of heart rate variability, 24-h monitoring of arterial pressure (AP) were performed in 20 patients with chronic constitutional arterial hypotension and in 18 patients with neurogenic syncopal states. Both groups were characterised by considerable manifestations of the syndrome of autonomic dystonia, by emotional-personal disorders that correlated with elevated level of slow-waves of the second order in heart rhythms' spectrum. That testified activation of supersegmental sympathetic-adrenal systems. Disorders in sympathetic-parasympathetic correlations were specific in each group. In patients with arterial hypotension disorder of circadian rhythm was observed in the form of superfluous decrease of diastolic AP during sleep. Circadian rhythms in patients with neurogenic syncopes have parameters characteristic for normals showing a preverved chronobiologic AP regulation. A role of the alterations revealed in pathogenesis of arterial hypotensionis discussed.