[Intrathecal baclofen therapy: a 30-year experience]. / Intratekal'naya baklofenovaya terapiya: 30 let primeneniya.

BACKGROUND: The first pump for intrathecal administration of baclofen was implanted in 1984. Over thirty years, intrathecal prolonged infusion of muscle relaxants has occupied a worthy niche among all methods for correction of non-focal drug-resistant disabling muscle spasticity. However, this method has not become routine despite high awareness of specialists in Russia and abroad, as well as undeniable advantages for restoring the daily activity, improving the walking pattern and providing care and quality of life in people with limited mobility. This is due to scrupulous analysis of adverse events and accurate attitude towards its use.The purpose of this review was to systematize data on indications, selection criteria, pump implantation technique, subsequent patient management and treatment outcomes over a 30-year history. METHOD: A review of national and foreign literature was performed. RESULTS AND CONCLUSION: Prolonged intrathecal baclofen therapy is perspective for long-term treatment of severe spasticity interfering with quality of life and self-care if oral muscle relaxants are contraindicated or ineffective. This procedure is effective for impaired articulation, chewing and spastic pain syndrome. One can reduce the incidence of side effects via correct dosage of the drug, and tolerance to therapy can be reduced by timely elimination of problems with catheter.

[Results of the Third Congress on Functional and Stereotactic Neurosurgery]. / Itogi Tret'ego kongressa po funktsional'noi i stereotaksicheskoi neirokhirurgii.

After several years of waiting due to the "covid quarantine" and subsequent restrictions, we finally met. Epidemiological restrictions prevented the planned interim congress in 2021. The Third Congress on Functional and Stereotactic Neurosurgery was held in Moscow on March 15-17, 2023. Despite the widespread use of the online conference format, the Congress was attended by almost everyone who is in one way or another associated with functional and stereotactic neurosurgery in our country. International participation was also present despite the existing sanctions restrictions.

[Schwannoma of the parapharyngeal space]. / Shvannoma parafaringeal'nogo prostranstva.

Schwannoma is a benign neoplasm that develops from the Schwann cells of the nerve sheath. The share of neurogenic tumors of the parapharyngeal space accounts for 0.5% of all neoplasms of this localization. The article demonstrates a case from practice, presents the clinical features, diagnostics and methods of treatment for patients with pharyngeal neuromas. The peculiarity of the presented clinical observation is due to the rare occurrence of this pathology and the large size of the schwannoma in the long-term asymptomatic course of the disease.

[Giant destructive polyps of the nasal cavity (clinical case)]. / Klinicheskii sluchai gigantskikh destruktivnykh polipov polosti nosa.

Conservative therapy for chronic polyposis rhinosinusitis are well covered, and modern endoscopic rhinosurgery can effectively cope with this pathology. Clinical cases of large destructive anthrochoanal polyps are not uncommon, the pathology is well studied. However, cases with giant sinonasal polyposis, which lead to bone-destructive changes in the bones of the nose and the walls of the paranasal sinuses are very rare. We found only one case similar to the clinical observation presented in this article.

[Our first experience with endoscopic ear surgery]. / Opyt primeneniia éndoskopicheskoi tekhniki v otokhirurgii u detei.

INTRODUCTION: For the last decades endoscopic ear surgery has become a common practice. Advantages of the endoscopic technique in middle ear surgery are high definition and magnification of the endoscope with a modern camera and the ability to 'look around the corner' with the angled scope. MATERIAL AND METHODS: From March 2017 to November 2019 in NSRC PHOI named after Dmitry Rogachev in the Department of Oncology and Pediatric Surgery 53 patients (81 surgeries) have undergone endoscopic-assisted ear surgery: 3 biopsies for middle ear neoplasm with the transcanal endoscopic approach, 1 endoscopic tympanoplasty for attic retraction pocket with cholesteatoma, 2 endoscopic removal of middle ear tumors (including 1 combined approach) and 32 endoscopic myringoplasties, 22 canal wall down mastoidectomies for extensive middle ear and mastoid cholesteatoma, 21 second-look surgery with ossiculoplasty with overall good outcome. Age of the patients varied from 2 months to 16 years. Follow up period varied from 1 month to 3 years. RESULTS: Two cases of middle ear tumor removal via endoscopic transcanal approach are described. In one case endoscopic transmeatal approach was used as an addition to the middle fossa approach for removal of facial nerve neurinoma located on the upper surface of petrous bone with expansion to the middle ear cavity. In the second case endoscopic transmeatal approach was used alone for removal of benign tumor (salivary gland choristoma) of middle ear cavity with extension to pneumatic system of petrous bone. In both cases endoscopic approach allowed to biopsy the tumor first and then to remove the tumor in a less invasive way, which lead to faster patient recovery. CONCLUSION: In the majority of cases endoscopic technique is a method of assistance in otologic surgery, but sometimes could be a used a single method in middle ear surgery, allowing less traumatic approach and the implementation of high-definition camera for more precise disease control. In our preliminary experience endoscopic technique could be used in pediatric practice independently of the patient's age.

Prolactin Signaling Pathways Determining Its Direct Effects on Kidneys in the Cholestasis of Pregnancy Model.

Cholestasis of pregnancy is a pathology associated with disruptions in the bile flow and dysregulation of salt and water homeostasis. Prolactin is one of the most important regulators of salt and water balance. Changes in the expression of long and short isoforms of the prolactin receptor (PrlR) and mediators of prolactin signaling were studied by immunoblotting and RT-qPCR in the rat kidney cortex and outer medulla in the model of cholestasis of pregnancy. Both PrlR isoforms were shown to participate in the effects of prolactin in cholestasis of pregnancy. Direct impact of prolactin on the kidney has been demonstrated: (i) mRNA expression of both PrlR isoforms in the kidney depended on the physiological conditions and prolactin levels; (ii) expression of pSTAT5, a key mediator of the long PrlR isoform signaling, was increased in animals with cholestasis of pregnancy; (iii) in the case of long PrlR isoform predomination, expression of mRNAs for the prolactin signaling inhibitors SOCS3 and PIAS3 was upregulated (the genes of these regulators contain STAT-responsive elements in their promoters); (iv) expression of the mRNA for galactose-1-phosphate uridyltransferase (GALT), a molecular target of the PrlR short isoform, was decreased in the kidney outer medulla.

Agonistic and Antagonistic Effects of Progesterone Derivatives on the Transcriptional Activity of Nuclear Progesterone Receptor B in Yeast Model System.

Identification of progesterone selective agonists and antagonists that act through one of the nuclear progesterone receptor isoforms is of particular importance for the development of tissue-specific drugs in gynecology and anticancer therapy. Fourteen pregna-D'6- and pregna-D'3-pentarane progesterone derivatives with 16α,17α-cycloalkane groups and two progesterone 3-deoxyderivatives were examined for their ability to regulate transcriptional activity of human nuclear progesterone receptor isoform B (nPR-B) expressed in Saccharomyces cerevisiae yeast. Transcriptional activity of nPR-B was measured from the expression of the ß-galactosidase reporter gene with a hormone-responsible element in the promoter. Among the compounds tested, two were full progesterone agonists, four were partial agonists, one compound possessed both agonistic and antagonistic activity, one compound displayed only partial antagonistic activity, and eight compounds did not show any activity. Modifications of the pentarane structure, precisely, introduction of an additional double bound in the A or B rings and/or modification at the 6th position of progesterone, lead to a switch from the complete agonistic activity to partial agonistic or mixed activities. These modifications enable progestins to act as selective modulators of progesterone receptor. Steroids with reduced A-ring and 3-ketogroups lose their ability to regulate PR-B activity. Both 3-deoxycompounds, being selective ligands of progesterone membrane receptors, do not affect PR-B activity.

[Exoskeleton anomalies among taiga tick males from populations of the Asiatic part of Russia].

The taiga tick (Icodes persulcatus, Schulze, 1930) is the main and most epidemiologically dangerous vector of tick-born encephalitis virus (TBEV) and Borrelia in most parts of Russia's territory (Alekseev et al., 2008). The purpose of this article is to describe the incidence rate of I. persulcatus males with exoskeleton anomalies in populations of the Asiatic part of Russia. A total of 2630 taiga tick males were morphologically analyzed. They were collected in Far Eastern, Siberian and Ural Federal Districts (respectively, FEFD, SFD, UFD) in 15 geographically remote locations. It is shown that in all populations there are adult ticks with impaired exoskeleton, among which two types dominate: twin dents at the back of conscutum (P11), and uneven surface of conscutum - a "shagreen skin" (P9). The frequency of abnormalities in males from the areas with temperate monsoon and temperate continental climate (FEFD) was definitely lower (6.5 ± 1.05 %), than in individuals from the territories of SFD (29.7 ± 1.03 %) and UFD (25.8 ± 3.93 %) with continental and sharply continental climate. FEFD territory is also characterized by a less number of males having two simultaneous exoskeleton anomalies. Similar district-preconditioned differences in the frequency of recorded body distortions are also typical of females, with a higher percentage of deviant individuals in comparison with males. Thus, the identified polymorphism of exoskeleton structure of the taiga tick may reflect the natural phenogeographical variability of this trait and might not be the result of human impact.

[Progestins and Carcinogenesis].

Progesterone and its analogs may exert opposite effects on cell proliferation, apoptosis, and epithelial-mesenchymal transition, leading to higher cell motility and metastasis. Their ultimate effect is determined by a number of factors: the structure and concentration of the steroid, its affinity for various forms of steroid hormone receptors, activation of nongenomic mechanisms, the composition and proportion of different progesterone receptors and sensors, activity of various signaling pathways, the set of transcription factor coregulators, DNA accessibility in chromatin, activity of steroid-metabolizing enzymes, intercellular interactions within tissues, the hormonal status of the body, disease stage, and species-specific features. The review considers the factors that determine the role progestins play in proliferation and apoptosis of human tumor cells of various origins.

Simulation of Viral Hepatitis E in Marmosets.

We developed a model of hepatitis E virus infection in common marmosets (Callithrix jacchus) and determined optimal route of infection, duration, clinical and virological characteristics of infection in laboratory animals. Using this model, we demonstrated that replication of hepatitis E virus primarily occurs in the liver, while virus replication presumed to take place in the intestine was not confirmed in this experiment.

[EFFECT OF MEDIATOR-TYPE DRUGS ON HUMAN PSYCHOPHYSIOLOGICAL STATUS DURING MODEL OPERATOR ACTIVITY].

In a placebo-controlled study, changes in psychophysiological status of operators (38 healthy male volunteers aged 23-35 years) performing 4-hour model operator activity were evaluated after a single oral administration of typical representatives of the different classes of drugs (haloperidol, proroxan, yohimbine hydrochloride, propranolol, mesocarb, isoprenaline, Belladonna extract, anabasine hydrochloride, valproate sodium, and phenazepam), which are used for the treatment, rehabilitation and prophylaxis of common diseases. It was found that all the drugs modified to a greater or lesser extent some components of the model operator activity. Isoprenaline and phenazepam had the most negative effect on the psychophysiological indicators and quality of the modeled operator activity. The results should be considered before administration of such drugs to working operators.

[EXOSKELETON ABNORMALITIES IN TAIGA TICK FEMALES FROM POPULATIONS OF THE ASIATIC PART OF RUSSIA].

Studies of the phenotypic structure of Ixodes persulcatus (Schulze, 1930) populations in relation to their exoskeleton abnormalities are important in both theoretical and practical respects. The data on the species' population structure in Asiatic part of Russia are fragmentary. The goal of the study was to describe taiga tick population structure based on the pattern of females' exoskeleton abnormalities revealed in Asiatic part of Russia. A total of 3872 I. persulcatus females from 16 geographically remote sites of Far Eastern, Siberian, and Ural Federal Districts (FEFD, SFD, and UFD accordingly) were studied. It was demonstrated that all the populations possessed specimens with exoskeleton abnormalities. The «shagreen skin¼ abnormality was dominant in all these areas. At the same time, the percentage of abnormalities among the specimens collected to the north of 55°N is considerably higher (63.4 ± 3.39 %) than that of samples from the SFD southward territories (33.1 ± 3.43 %). The frequency of abnormalities in its turn is lower (24.4 ± 1.93 %) in the females from the territories with moderate monsoon and moderate continental climate (FEFD) than that in specimens from SFD and UFD areas with sharp continental climate. Thus, such polymorphism of the females' exoskeleton structure may reflect the natural phenogeographical variability of the character rather than the result of the anthropogenic impact. 403

[Molecular basis and tissue specificity of the progestins action].

The review considers the effect of progestins on the function, proliferation, and apoptosis of cells of various organs in health and noncancerous disorders. Data are summarized to describe the mechanism of progestin action through various progesterone receptors and sensors and the regulation of their levels. The effects of progestins depend on the cell phenotype, including the composition and proportion of different receptors, activity of signaling pathways, and expression of transcription factor coregulators and steroid metabolism enzymes. The role paracrine regulation plays in the progestin effect is described. Particular attention is paid to the progestin effect on the tissues where progestins are thought or known to affect carcinogenesis or to stimulate or suppress the tumor growth, that is, to modulate cell proliferation, apoptosis, and the epithelial-mesenchymal transition.

[POLYMORPHISM IN THE PHENOTYPIC STRUCTURE OF A POPULATION OF TAIGA TICK AND ITS EPIDEMIOLOGICAL SIGNIFICANCE].

The paper presents the results of 10-year (2005-2014) observations of an Ixodespersulcatus Schulze population. The purpose of this investigation was to trace long-term changes in the structure of the taiga tick population from the proportion of specimens with external skeletal anomalies and to assess a relationship between the pattern of imago phenotypic variation and the virus percentage of a carrier. There were a total of reports of the external skeletal structure of 1123 females gathered from plants to a flag in an area at 43 km from the Baikal Road connecting Irkutsk and the settlement of Listvyanka (Irkutsk Region). The proportion of specimens with anomalies averaged 37.8 +/- 1.88%. Four-to-seven varying anomalies were annually recorded. There was a preponderance of scutum impairment (an average of 17.0 +/- 3.08% of all females) that was a conglomerate of prominences and indentations along the entire clypeus surface and that was denoted P9. The nature of a change in the proportion of ticks with two anomalies (average monthly registration rate, 2.5 +/- 0.66%) is exhibited by three-year high-frequency oscillations whereas the specimens with P9 anomalies fail to show so clear cycling. The percentage of virus-containing taiga ticks was individually determined estimating the level of tick-borne encephalitis virus antigen by an enzyme immunoassay. A total of 4022 ticks were examined. The male and female data were pooled. There was a positive correlation between the change in the proportion of females with P9 anomaly and the infection of ticks in the examined population (Spearman's correlation coefficient, 0.88; P < 0.01). This supports the earlier observation of the greater epidemiological significance of the imago of a taiga tick with external skeletal anomalies particularly with considerably marked ones.

[GENUS ANELLOVIRIDAE VIRUSES IN CHRONIC LIVER DISEASE].

AIM: Viruses from genus Anelloviridae (TTV, TTMDV and TTMV) are small DNA viruses that are widespread in human popu- lation. Data on tissue tropism, cell localization and morphometry of anelloviruses are scarce. The purpose of this study was to determine the prevalence of TTV, TTMDV and TTMV in persons with liver disease and in healthy individuals, as well as electron-microscopic verification of Anelloviridae species. METHODS: Detection of anelloviral DNA was performed in serum samples from 203 patients with liver diseases of various etiology and 115 voluntary blood donors using PCR with primers allowing to differentiate TTV, TTMDV TTMV based on the length of amplified fragment. Histopathological and electron microscopic studies were performed for liver biopsy specimens from 203 patients with liver disease. RESULTS: High prevalence (70-90%) of all three anelloviruses in healthy individuals and patients with liver disease was demonstrated, with high frequency of triple TTV, TTMDV and TTMV infection (52.2-55.7%). Electron-microscopic study of liver biopsy specimens from TTMDV monoinfected patients gave a submicroscopic image of TTMDV virions with diameter 35.86 ± 2.04 nm. Electron microscopic studies confirmed the nature of liver damage in TTMDV monoinfection: accumulation of virus in the hepatocytes, significant cyropathy with enlightenment matrix of the cytoplasm and reduction of intracellula organelles involved in protein synthesis, portal and perivascular perisinusoidal fibrosis. TTV, TTMDV and TTMV virions were dentified in hepatocytes, confirming these viruses to be hepatotropic. CONCLUSION: Our results demonstrate that anelloviruses are lymphotropic viruses, individual genotypes of those might be hepatotropic and pathogenic to liver.

Kinetics and mechanism of the reaction of fluorine atoms with pentafluoropropionic acid.

The kinetics of the reaction between fluorine atoms and pentafluoropropionic acid has been studied experimentally at T = 262-343 K. The overall reaction rate constant decreases with temperature: k1(T) = 6.1 × 10(-13) exp(+1166 K)/T) cm(3) molecule(-1) s(-1). The potential energy surface of the reaction has been studied using quantum chemistry. The results were used in transition state theory calculations of the temperature dependences of the rate constants of the two channels of the reaction. The abstraction channel ultimately producing HF, C2F5, and CO2 is dominant at the experimental temperatures; the addition-elimination channel producing C2F5 and CF(O)OH becomes important above 1000 K.

[Vesicular intracellular transport in the digestive organs. Membrane vesicle--the universal mechanism of the functional transport].

On the basis of long-term research of the morpho-functional characteristics of the cells of the stomach, small intestine and gallbladder the mechanism and function of membrane vesicles in the implementation of the main functions of these organs sets out in this article: the secretion of hydrochloric acid by parietal cells, the absorption of nutrients in the small intestine and the fluid at a concentration of bile epitheliocytes of gallbladder. Proofs of the intracellular formation of hydrochloric acid in tubulovesicles of the parietal cells and turnover of its secretory membranes in the process of secretory cycle, that has ensured the re-use and explained the extraordinary life of these unique cells are presented. The credible mechanism of HCl output oppression by H(+)-K(+)-ATPase activity blockers has set out on this basis. The article provides detailed endocytosis mechanism of the ions and nutrients absorption by enterocytes. The mechanism of participation of the apical contractile complex of brush border of epithelial cells in the initiation of endocytosis and cytoplasmic microtubules in transport of membrane vesicles in the cytoplasm was analyzed. Based on our research and numerous of the world scientific proceedings the conclusion was done about the existence of two energy dependent types of transport in the absorptive epithelium of the digestive--transmembrane (ionic and nutritive) homeostatic type which is realized by the ATP-system of the basal plasmalemma, and vesicular (endocytosis) type which is impltmented by apical contractile complex of brush border and cytoplasmic microtubules. Both types of transport are interrelated and are under constant cellular control. This observation is relevant to the majority of cells, including those involved in the secretion of various substances: hydrochloric acid by parietal cells, enzymes by main cells of the gastric glands and exocrinocytes of the pancreas, hormone by endocrine cells of the APUD system and, finally, mediators by nerve cells. To clarify the problem of cell transport two types: homeostatic and functional transport should be distinguished. The first type is carried out mainly in relation to ions on basolateral membrane with the help of its ATPase systems and provides intracellular homeostasis and nutritive co- transportation, the second (functional) type defines the basic specific function by means of membrane vesicles.

Approaches to the design of selective ligands for membrane progesterone receptor alpha.

A number of progesterone derivatives were assayed in terms of their affinity for recombinant human membrane progesterone receptor alpha (mPRα) in comparison with nuclear progesterone receptor (nPR). The 16α,17α-cycloalkane group diminished an affinity of steroids for mPRα without significant influence on affinity for nPR, thus rendering a prominent selectivity of ligands for nPR. On the contrary, substitution of methyl at C10 for ethyl or methoxy group moderately increased the affinity for mPRα and significantly lowered the affinity for nPR. A similar but even more prominent effect was observed upon substitution of the 3-oxo group for the 3-O-methoxyimino group. A significant preference towards mPRα was also rendered by the 17α-hydroxy group and additional C6-C7-double bond. The data suggest that the modes of ligand interaction with mPRα and nPR in the C3 region of the steroid molecule are different. One can speculate that combination of the above substitutions at C17, C10, C6, and C3 may give ligand(s) with high specificity towards mPRα over nPR.

Changes in levels of gene expression in human aortal intima during atherogenesis.

Changes in the contents of 36 mRNAs species related to lipid turnover, inflammation, metabolism and the action of sex hormones in samples of aortal intima along the "intact tissue - lesions of type I - lesions of type II - lesions of type Va" sequence were analyzed using quantitative PCR. The expression of several mRNAs coding for components of the vesicular transfer and lipid turnover machinery was found to be resistant to atherogenesis or even decline in the course of atherogenesis. Decrease in expression was also recorded for steroid sulfatase, androgen receptor, and low density lipoprotein receptor mRNAs. However, the contents of the majority of other mRNA species increased gradually during disease progression. The earliest changes found as early as in lesions of type I were characteristic for estrogen sulfotransferase, apolipoprotein E, scavenger receptor SR-BI, collagen COL1A2, as well as chemokine CCL18 mRNAs. The contents of several mRNAs in intact tissue and atherosclerotic injuries had gender differences. Additionally, responses of two mRNAs, for aromatase and sterol regulatory element binding protein 2, to atherosclerotic lesion were also sex-differentiated. The contents of the majority of analyzed mRNAs in peripheral blood monocyte-derived macrophages were higher than in intact aorta. The correlations found in atherosclerotic lesions between mRNA species that predominant in macrophages and those expressed at comparable levels in macrophages and intact aorta or mainly in aorta suggest that the observed rise in the content of the majority of mRNAs during atherogenesis is determined by increase in expression in resident cells. The data suggest that the revealed absence of homeostatic regulation of expression of a number of genes associated with vesicular transfer and lipid turnover can serve as one of the reasons for lysosomal function insufficiency that leads to foam cell formation in atheroma. The observed sex differences in expression of a number of mRNAs suggest that estrogens in women perform their atheroprotective effects starting with predisposition to the disease and finishing with advanced stages of the pathologic process.

Coordination in gene expression during atherogenesis.

General tendencies in the regulation of gene expression during atherogenesis were investigated using correlation analysis for 34 mRNA species of several functional groups. The contents of mRNA were measured by quantitative PCR in samples of human aortal intima containing no lesions or atherosclerotic lesions of types I (initial lesions), II (fatty streaks), and Va (fibroatheromas). The coupling between mRNA contents in lesions and the same mRNAs in intact tissue was found to descend in the course of the disease progression. The data are in accordance with the opinion that successive morphologic types of atherosclerotic lesions correspond to steps of atherogenesis. In addition, the contents of individual mRNA species could correlate with each other within the given sample type, the extent of this coupling rising along with the disease progression. The exception from this rule was a collapse in coupling for several functional groups of mRNA in lesions of type I. This collapse could indicate special position of these lesions in pathogenesis. Statistically significant correlations between mRNAs found in samples of all four types comprised in total about 50% of all possible correlations. 66% of these correlations were conservative, i.e. observed in at least two sample types. By coupling-strength, the studied mRNAs could be divided into four clusters whose composition significantly varied along with the disease progression. The disease progression was also associated with decline in number of regulatory factors that determine coordination in expression of the analyzed genes.