[The mechanisms of anti-inflammatory action of enisamium iodide].

AIM: The role of cyclooxygenases (COX-1 and/or COX-2), transcription nuclear factor NF-κB, anti-inflammatory cytokines - TGF1b, IL-4, IL-10 and pro-inflammatory cytokines IL-1, IL-6 were studied to substantiate the expediency of antiviral agent enisamium iodide (Nobazit) using to regulate key inflammatory components in acute respiratory infections, IL-8, TNF-alpha in the realization of the pharmacological activity of this drug. MATERIALS AND METHODS: Gene expression was determined by real-time RT-PCR, the concentration of interleukins was determined by ELISA, and the viability of peripheral blood mononuclear cells (PBMC) was assessed by the MTT spectrophotometric method. The chemiluminescence method was used to assess PBMC oxidant activity. RESULTS: Enisamium iodide (10 µM) reduced mRNA levels of COX-1, COX-2, NF-κB, TGF1b, IL-1, IL-6 in stimulated PBMC of healthy donors by an average of 48% (p≤0.05). At 5 times higher concentration, 50 µM, enisamium iodide suppressed the expression of these genes by an average of 43% (p≤0.05). At a concentration of 100 µM, enisamium iodide reduced the expression of COX-2, TGF1b, IL-1, IL-6 by an average of 47% (p≤0.05). At a concentration of 10 µM, enisamium iodide stimulated the secretion of IL-10 by mononuclear cells by 1.2 times, p≤0.05. The tested drug at a concentration of 50 µM did not affected on the concentration of IL-1, IL-4, IL-8 and TNF-alpha, but significantly stimulated the production of IL-10 by 1.5 times, p≤0.05. The chemiluminescence method revealed that enisamium iodide in the entire concentration range (10-100 µM) does not reduce the viability of macrophages, but inhibits their oxidative activity (maximum value of CL intensity) by an average of 55% (p≤0.05). CONCLUSION: The anti-inflammatory effect of enisamium iodide at a concentration of 10 µM may be associated with inhibition of the expression of COX-1, 2, NF-κB, IL-1, IL-6, TGF1b and an increase in the expression and production of IL-10. An additional contribution to the anti-inflammatory activity of enisamium iodide is made by its antioxidant and antiradical activity. The absence of the effect of enisamium iodide (10-100 µM) on the viability of PBMC indicates its safety for the cells of the immune system and the expediency of using it to suppress inflammatory reactions in acute respiratory infections, restore the quality of life of patients and the possibility of using Nobazit as an effective agent for treatment of these infections of various etiologies.

[Pharmacoepidemiological research of COVID-19 in the Russian Federation EGIDA-2020].

AIM: An analysis of coronavirus infection in Russia and evaluation of different AVT regimens effectiveness. MATERIALS AND METHODS: The study involved a retrospective analysis of 1082 patient records with laboratory-confirmed COVID-19 in 17 regions of Russia. The number of men and women was equal, mean age 48.718.1 (median 50). Patients with moderate COVID-19 (85%) versus mild COVID-19 (15%) were characterized by higher age (median 54 vs 21 years; p0.001), higher body mass index (27.8 vs 23.4; p0.001), prevalence of chronic diseases (75.3% vs 8.5%; p0.001), including circulatory system diseases (37.8%). Moderate COVID-19 characterized higher intoxication (10.86.1 vs 4.22.7 days; p0.001) and catarrhal symptoms duration (10.25.4 vs 6.14.1 days; p0.001). RESULTS: During hospitalization 92% of the patients received AVT, 77% antibiotics, and 16% corticosteroids. Umifenovir therapy resulted in a significant reduction of intoxication (8.75.5 vs 11.75.5 days; p0.001) and catarrhal symptoms duration (8.85.1 vs 12.04.9 days; p0.001) compared to the group without AVT. The usage of INF reduced intoxication symptoms compared with the group without AVT (8.97.5 vs 11.75.5; p0.05). Therapy with hydroxychloroquine, imidazolylethanamide pentandioic acid, and lopinavir + ritonavir combination did not affect the course of COVID-19. Most of adverse reactions were related to antibiotics. CONCLUSION: Umifenovir therapy and inclusion of interferon in AVT regimens was associated improvement in the clinical manifestation of the disease among patients.

[NSAID enteropathy].

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used drugs in the world, and their side effects are very high. First of all, these are NSAID gastropathy, but in the long term, 5070% of NSAIDs cause damage to the small intestine (NSAID enteropathy), sometimes with serious consequences. To date, no drugs have been proposed with proven effectiveness to prevent this side effect. Apparently, this is not due to the fully clarified mechanism of pathogenesis. The most promising is the hypothesis of the participation of individual representatives of microflora in the development of enteropathy. Therefore, modulating the intestinal flora with the help of probiotics can be the basic therapeutic strategy for the prevention and treatment of such damage.

[Review of current and future directions of antiviral therapy of influenza and acute respiratory viral infections in Russia].

AIM: to determine the perspectives for the use of drugs with combined antiviral, anti - inflammatory and immunomodulatory activity on the basis of medical studies of existing antiviral drugs for the treatment of influenza and acute respiratory viral infections in Russia. MATERIALS AND METHODS: A brief review of the antiviral drugs used in Russia for the treatment of influenza and acute respiratory viral infections was conducted on the basis of 37 articles published in Scopus, Web of Science (WoS), and RSCI databases in the period from 1997 to 2018. RESULTS: Resistance to neuraminidase inhibitors (oseltamivir, zanamivir), is slowly developing due to the mutations of the neuraminidase gene H275Y and Q136K. Most influenza A viruses remain resistant to adamantane antivirals. Repeated use of immunomodulators with indirect antiviral action leads to a hyporeactivity of the immune system and, subsequently, to a decrease in their effectiveness. Positive clinical and laboratory data in clinical trials were obtained using Enisamium iodide, a drug with combined action - direct antiviral, and immunomodulatory. CONCLUSION: According to the WHO strategy, the results of the review demonstrate the need for continued research of medications with combined antiviral and pathogenetic effects on the infectious process caused by influenza and acute respiratory viral infections.

Nephrolithiasis against type 2 diabetes mellitus: on the effect of hypoglycemic therapy on lithogenesis.

AIM: To study the effects of oral hypoglycemic agents that can affect the probability of recurrence of nephrolithiasis. MATERIALS AND METHODS: The article is based on the results of examination and treatment of 315 patients suffering from recurrent nephroli-thiasis and medically compensated type 2 diabetes mellitus treated at the N.A. Lopatkin Institute of Urology and Interventional Radio-logy - the branch of the SMRC of Radiology, Ministry of Health of Russia and D.D. Pletnev City Hospital Moscow Healthcare -Department in 2012-2017. The patients were divided into three groups according to the applied tool antidiabetic: metformin, glibenclamide, canagliflozin. The control group consisted of patients receiving insulin therapy. RESULTS: The propensity of Metformin to reduce the pH of urine, which has a negative impact in the conditions of urate nephrolithiasis, which is most common in the population of patients with type 2 diabetes mellitus. Glibenclamide, on the contrary, somewhat latches urine. But changes in the reaction of urine under the influence of the drug do not go beyond normal values and are not clinically significant. Canagliflozin increases diuresis due to medication induced glycosuria and stimulates renal excretion of uric acid and its salts. However canagliflozin does not cause significant shifts in the pH of urine that may somewhat negates the increased risk of recurrence of urate stone formation in the background of the uricosuric effect of the drug. CONCLUSION: Drug therapy of type 2 diabetes mellitus significantly affects the properties of urine from patients with nephrolithiasis.

[Effects of oral hypoglycemic drugs on lithogenic properties of urine in nephrolithiasis patients with concurrent type 2 diabetes].

AIM: To investigate the effects of oral hypoglycemic drugs on the lithogenic properties of urine in nephrolithiasis patients with concurrent type 2 diabetes. MATERIALS AND METHODS: The study comprised 376 patients with recurrent nephrolithiasis and compensated type II diabetes mellitus who attended the N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology - branch of the NMRRC of Minzdrav of Russia and D.D. Pletnev City Clinical Hospital, Moscow Health Department in 2012-2017. Patients were divided into five groups according to the administered oral hypoglycemic agent: metformin, glibenclamide, pioglitazone, canagliflozin, vildagliptin. The control group consisted of patients receiving insulin therapy. RESULTS: Metformin tended to acidify urine, thus producing a negative effect on urate nephrolithiasis, which is the most prevalent form of nephrolithiasis among patients with type II diabetes. Glibenclamide, on the contrary, alkalized the urine, but urine pH did not go beyond the ranges of normal values. Pioglitazone increased urine density with a simultaneous tendency to decrease diuresis, which is bad for any form of nephrolithiasis. Empagliflozin increased diuresis due to drug-induced glucosuria and also increased renal excretion of uric acid salts. However, at normal urine pH values, the uricosuric effect of the drug did not lead to a significantly increased risk of urate stone formation. Vildagliptin did not have a significant effect on urine output, urine pH, and renal salt excretion. CONCLUSION: Drug therapy for type II diabetes significantly affects the properties of urine in patients with nephrolithiasis, and it should be taken into account in the metaphylaxis of nephrolithiasis.

[INFLUENCE OF PROGESTERONE DERIVATIVES ON THE VIABILITY AND EXPRESSION OF ESTROGEN RECEPTOR-ALPHA MRNA IN HELA CELLS.]

We have studied the effect of new ligands of progesterone receptors, including pregna-D'-pentaran 6-methoxyimino-16a,17a-cyclohexanopregn-4-en-3,20-dio-ne (K1047), 17a-acetoxy-3b-butanoyloxy-6-methylpregna-4,6-dien-20-one (buterol), progesterone (P4), and medroxyprogesterone acetate on the viability of HeLa cells and expression of estrogen receptor-alpha (Era) mRNA gene in these cells. K1I047 and buterol exhibited high cytostatic activity, which exceeded the activity of reference compounds on the average by 15% (p < 0.05). Both buterol and K-1047 (at 10(-6)M) effectively suppressed ERa mRNA gene expression in HeLa cell culture by 83.4 - 9 8.6%.

[EMPIRICAL ANTIBACTERIAL PROPHYLAXIS IN EMERGENCY SURGERY].

The main principles of selecting antibacterial drugs for prophylactic therapy of patients prior to surgery of gastrointestinal tract, vessels, skin, and soft tissues are considered. Special attention is devoted to antibacterial prophylaxis in co-morbid patients, in particular those with chronic renal insufficiency, chronic liver disorder, decompensated diabetes mellitus, and allergy to beta-lactam antibiotics. All proposed schemes are optimized with respect to three criteria: clinical effectiveness, economic feasibility, and epidemiologic safety (stopping the selection of poly-resistant microbial families).

[Modern combined oral contraceptive pills].

Hormonal contraceptives possess unique additional (non-contraceptive) properties that offer potential health benefits and help maintaining good quality of life. This review presents the existing notions about molecular mechanisms of the direct and side effects of combined oral contraceptive pills (COCPs), and gives a generalized classification of synthetic progestins. A new illustrative scheme, showing the androgen and corticoid properties of synthetic progestins, is presented. Main principles of the individual selection of hormonal COCPs are discussed.

[Relative binding activity of dydrogesterone with blood mononuclear cells progesterone receptors of women included in the IVF program].

It has been shown that specific binding of dydrogesterone with progesterone receptors in blood mononuclear cells of the patients included in the programs of in vitro fertilization, varies from 0 to 298%, thus at 38% of women dydrogesterone concedes to a progesterone in the competition for receptors of a progesterone, and 62%--exceed. The revealed variations of specific binding dydrogesterone with receptors of a progesterone are a reserve of increase of efficiency of auxiliary reproductive technology at the expense of individual selection of hormonal agents.

[Estrogens and brain].

Recent data upon molecular mechanisms of pleiotropic action of estrogens in human brain is presented in the article. Given detailed descriptions of properties of classical and membrane bound estradiol receptors, that maintain gene expression regulation, modulation of neurotransmittent systems and signal cascade activation in neuronal cells. Data upon regional distribution of estradiol receptor subtypes in the brain, their participation in main cell population function control (including progenitor cells) is given. Special attention is paid to estrogen participation in neurogenesis, inflammation and apoptosis regulation in central nervous system; in the control of formation and functioning of cerebral vessels.

[Empiric treatment of pyelonephritis].

The article analyses the most typical clinical situations in empirical treatment of pyelonephritis including situations with comorbid severe diseases: decompensated diabetes mellitus, chronic renal failure, HIV-infection. Choice of antibacterial medicines for empiric treatment of pyelonephritis is based on the results of the latest studies of antibioticoresistance of pyelonephritis pathogens as well as on specific features of pharmacokinetics and pharmacodynamics of antibacterial drugs.

[Gestagens and the brain].

Modern data on molecular mechanisms underlying intracerebral pleutropic action ofgestagens (progesterone, its metabolites, and synthetic gestagens) are reviewed. Properties of classical and membrane-bound progesterone receptors involved in regulation of gene expression, modulation of neurotransmitter systems, and activation of signal cascades in neurons are described along with data of regional distribution of progesterone receptor subtypes in brain, metabolism, functional activity, and mechanisms of action of progesterone metabolites. Special attention is given to analysis of progesterone and metabolite neuroprotective activity in CNS, such as anti-inflammatory and antiapoptotic effects, and participation in neurogenesis regulation. Clinical application of progesterone-based drugs is discussed with reference to the treatment of brain injuries and prospects for extension of indications for their use in neurologic practice.

[Current status of antibiotic resistance of pyelonephritis causing pathogens].

The article gives the analysis of frequent clinical situations arising in empiric therapy of pyelonephritis alone and accompanied with other severe diseases such as decompensated diabetes mellitus, chronic renal insufficiency, HIV infection. The choice of antibacterial drugs for empiric therapy of pyelonephritis is based on the results of the tests for antibiotic resistance of pyelonephritis causing agents, pharmacokinetic and pharmacodynamic studies. Present-day standards and recommendations of leading centers of pyelonephritis empiric therapy are reviewed.

[Influence of the structure of synthetic gestagens on their binding to progesteron receptors in the endometrium].

Chemical modification of progesterone molecule leads to changes both in the gestagenic activity of new derivatives and in their specific binding with progesterone receptors. The passage from esters (acetomepregenole, butagest) to the corresponding OH-forms such as 17a-acetoxy-3b-hydroxy-6-methyl-pregna-4,6-dien-20-one (ABMP)is accompanied by an increase in the binding with progesterone receptors in vitro. The translocation of a double bond from endocyclic (N6-N7) to exocyclic position (methylene group at N6 in ABMP) has no significant effect on the ability to binding with progesterone receptors.

[An analysis of 3H-tamoxifen binding with the cell plasma membranes of the rat uterus]. / Analiz sviazyvaniia 3H-tamoksifena s plazmaticheskimi membranami kletok matki krys.

The effect of phencarol, ranitidine, propranolol, atropine, and diethylstilbestrol (known as modulators of the tamoxifen-binding sites in plasma membranes) on the 3H-tamoxifen binding to the plasma membrane fraction of white rat uterine cells was studied by determining the amounts of estradiol and H1- and H2-receptors. The interaction of tamoxifen with various receptors of uterine cells may be significant for evaluation of the tumor activity of this compound.

[The effect of pregna-D'-pentarans on myometrial contractile activity in pregnant rats]. / Vliianie pregna-D'-pentaranov na sokratitel'nuiu aktivnost' miometriia beremennykh krys.

The authors studied the effect of synthetic gestagens on spontaneous contractility of the myometrium in pregnant rats. The direction of the effect of progesterone and its analogs on the contractility is determined by stereochemistry of the linkage of rings A and B of the steroid molecule. Compounds possessing translinkage (5 beta-steroids) increase the amplitude of myometrium contraction, whereas their analogs with cms-coupling of rings A and B (5 alpha-steroids), and 4,5-unsaturated steroids reduce it.

[Effect of gestagen therapy on clinical and biochemical parameters in patients with atypical endometrial hyperplasia]. / Vliianie gestagenoterapii na klinicheskie i biokhimicheskie parametry u bol'nykh s atipicheskoi giperplaziei éndometriia.

The investigation involved 22 reproductive and menopausal women (aged 30-48) with atypical endometrial hyperplasia. In addition to general clinical examination, all the patients underwent ultrasound scanning of the organs of the small pelvis, hysteroscopy and diagnostic curettage for morphological examination both before and after treatment. All tissue samples taken before and after treatment were assayed for cytoplasmic and plasma-membrane receptor levels and a number of biochemical parameters of plasma membranes. Hormone therapy with prolonged-release gestagen-based drugs pointed to changes which occurred in: (1) sex steroid reception at cytosol and plasma-membrane levels; (2) the lipids profile of plasma membranes, and (3) activity of membrane-related enzymes. Among the beneficial results of gestagen treatment was coming most of lipid profile parameters and plasma-membrane enzymes back to normal. However, a decrease in the progesterone reception level in target tissue after 3-6 month treatment may suggest a likelihood of development of tolerance to gestagen. The data also suggest that further research continue in this area of endometrial precancer.

[Concentrations of urine 6-sulfatoxymelatonin during the treatment of patients with epilepsy: a pilot clinical trial].

The effect of the epiphysis hormone melatonin on the brain bioelectrical activity is understudied: the data of experimental and clinical studies of melatonin effects are inconclusive and related mostly to exogenous administration. We studied 43 patients with focal epilepsy, 25 patients with cryptogenic epilepsy and 18 with symptomatic epilepsy. Carbamazepine and valproate were used as anticonvulsive drugs. Morning and evening urine concentrations of 6-sulfatoxymelatonin (6-COM), the main melatonin metabolite, were determined twice using immunoassay method: in autumn at the inclusion in the study and beginning of the anticonvulsant treatment and after 6 months, in spring, when anticonvulsant doses had been adjusted. The presence of epileptic seizures was associated with the reduction of melatonin concentration in the body that was supported by the decrease of urine 6-COM, in particular in the morning, in non-treated patients. Prescription of anticonvulsant treatment resulted in the increase of 6-COM. The concentration of the morning urine 6-COM was higher in patients with focal epilepsy receiving anticonvulsant treatment with valproate compared to those receiving carbamazepine: 49.28±6.71 and 37.09±5.43 ng/ml versus 20.00±3.6 and 13.11±2.08 ng/ml in patients treated with valproate and carbamazepine, respectively, before and after the adjustment.