[The organizational aspects of security support of participants of clinical testing of vaccine "Gam-COVID-Vac"].

The COVID-19 pandemic resulted in many aftermaths, economic crisis and extra charging of health care. The development of vaccine against SARS-nCoV-2 agent turned out as the priority task of world and Russian medicine and pharmaceutics. The investigation of efficiency and safety of vaccines can be prolonged for many years that can aggravate the observed crisis. Having regard to the global scope and speed of pandemic spreading, the vaccine "Gam-COVID-Vac" was registered with special procedure by the Decree of the Government of the Russian Federation No. 441 of 03.04.2020 for accelerated access to civic turn-over. To monitor safety of vaccine on the basis of international experience, the decision was made to organize the independent Committee of monitoring data concerning efficacy and safety of vaccines applied to prevent COVID-19. The article presents rationale for necessity to create independent committee and to implement such a practice.

[Adverse drug reactions of local anesthetics used in dentistry]. / Nezhelatel'nye reaktsii na mestnye anestetiki pri ikh primenenii v stomatologii.

The aim. Study the adverse drug reactions (ADR) that occur when using local anesthetics (LA) in patients living in the Republic of Crimea and registered during the period 2010-2018. MATERIAL AND METHODS: The objects of the study were 122 notification forms about LA ADR recorded in the regional base (Register) of spontaneous reports called ARCADe (Adverse Reactions in Crimea, Autonomic Database). In most cases, ADR was associated with the use of amide LA Lidocaine - 69 cases (56.55% of the total number of cases for LA ADR), less often, ADR was caused by combinations containing Articaine (34 cases, 27.87%). Rare cases of ADR were reported for Novocaine/Procaine (9 cases, 7.38%), Bupivacaine (8 cases, 6.56%) and Mepivacaine (2 cases, 1.64%). The main clinical manifestations of reactions were hypersensitivity-like reactions (38 cases), cardiac and vascular disorders (29 cases) and central nervous system disorders (19 cases). Lack of effectiveness of LA occurred in 13 cases (10.66%). RESULTS: A study of the outcome of ADR revealed a high incidence of life-threatening conditions associated with LA use - 31 cases (25.4%), which indicates the severity of the event and the need to cancel the suspected drug and prescribe additional medications for correction. The need for hospitalization or prolongation of hospitalization was necessary in 7 cases (5.8%), and temporary disability of patients was revealed in 5 cases (4.1%). Of particular interest are 2 cases (1.6%) of the development of a fatal outcome as a result of the suspected anaphylactic shock (1 case) and disorders of the central nervous system (convulsions, development of respiratory failure). CONCLUSION: The high frequency and severity of unwanted effects resulted from the use of LA requires healthcare professionals to make rational choices and strictly monitor patient safety.

[A role of MRI-Ultrasound fusion targeted biopsy of prostate in the diagnosis of prostate cancer].

AIM: To compare the results of the MRI-ultrasound fusion targeted biopsy (MRF-TB) and systematic 12-core biopsy (SB) of the prostate and analyze the relationship between biopsy results and the prebiopsy multiparametric MRI. MATERIAL AND METHODS: The study included 380 men aged from 45 to 80 years with a total PSA level of 4 to 10 ng/ml (according to Hybritech calibration) and a negative result of digital rectal examination. All men underwent the multiparametric MRI of the prostate before biopsy. MRI results were assessed according to the PI-RADS Version 2 criterion. In all men (n=247) with PI-RADS category 2 or higher lesion were performed MRF-TB (4 targeted columns) and SB (12 standard points) of the prostate. RESULTS: There were no significant differences in the detection of all types of prostate cancer (PCa) in all patients between MRF-TB and SB (p=0.731). At the same time, significantly less low-risk PCa (Gleason 6) (p<0.001) and significantly more aggressive PCa (Gleason more or equal 7) (p<0.001) were detected in MRF-TB group in comparison with SB group. In addition, MRF-TB allowed to detect significantly more aggressive type of PCa (Gleason more or equal 4 + 3) compared to SB (p=0.025). CONCLUSION: MRF-TB allows to detect more significant PCa (Gleason more or equal 7) in comparison with SB, while limiting the detection of low-risk PCa (Gleason 6) in general population of men.

[Clinical and morphological signs of viral damage to a kidney transplant]. / Kliniko-morfologicheskie priznaki virusnogo porazheniia pochechnogo transplantata.

AIM: Тo compare morphological changes and results of immunohistochemical (IHC) identification of viruses (polyomaviruses, adenoviruses, and herpesviruses) in the biopsy specimens with their clinical manifestations in recipients of renal transplants. MATERIAL AND METHODS: Morphological and IHC studies were conducted using 71 needle renal transplant biopsy specimens from patients in the study group and 10 renal biopsy specimens from those in the control group. A number of clinical indicators were estimated. RESULTS: IHC examination revealed the expression of adenoviral antigens more commonly in patients with posttransplant nephritis than in recipients without nephritis or in control individuals (p<0.05). The association of patient age and time after kidney transplantation with the severity of viral damage was confirmed: graft loss in children occurred within the first months of surgery (p<0.05). Polyomavirus was detected by PCR in patients with the morphological patterns of polyomavirus nephropathy. Determination of HSV-1 and HSV-2 in the biopsy specimens showed no significant associations with morphological changes. CONCLUSION: By taking into account a variety of factors that influence the development of viral nephritis, morphological and IHC examinations should be combined with evaluation of clinical findings.

[The analysis of the effectiveness of the combined treatment of the patients presenting with laryngeal papillomatosis]. / Analiz éffektivnosti kombinirovannogo lecheniia bol'nykh papillomatozom gortani.

The objective of the present work was to evaluate the effectiveness of the application of the inducer of endogenous interferon synthesis in the course of the combined treatment of the adult patients presenting with laryngeal papillomatosis. A total of 50 patients with this pathology were admitted and examined at the ENT Clinics of I.M. Sechenov First Moscow State Medical University and M.F. Vladimirsky Moscow Regional Research Clinical Institute during 24 months. The patients comprising group 1 (n=25) were treated with the use of cold plasma surgery and the inducer of endogenous interferon synthesis while those included in group 2 (n=25) received only surgical treatment. It was shown that the combined treatment including the surgical step (cold plasma surgery) followed by the treatment with the inducer of endogenous interferon synthesis to prevent relapses makes it possible to reduce the number of secondary surgical interventions, increase the duration of the intervals between relapses, and decrease the content of types 6 and 11 human papilloma virus in the saliva.

[The association between the 5-HTTLPR polymorphism of the serotonin transporter gene and the efficacy and tolerability of selective serotonin reuptake inhibitors].

OBJECTIVE: To search for the association between the 5-HTTLPR polymorphism of the serotonin transporter gene and the efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs). MATERIAL AND METHODS: The complex clinical/psychopathological and genetic study of 38 patients with depression treated with SSRIs was carried out. RESULTS AND CONCLUSION: The 5-HTTLPR polymorphism was associated with the rate of achievement of remission and tolerability of treatment: carriers of the SS genotype achieved remission less frequently and more frequently experienced side-effects.

[Treatment of paracolostomic hernias using polypropylene mesh].

It was analyzed the results of treatment of 23 patients with large paracolostomic hernias. Twenty patients underwent colostomy suturing and hernial ring Onlay-plasty with polypropylene mesh without tension. Onlay-plasty of hernial ring with own tissues and polypropylene mesh and colostomy reconstruction outside of implant were performed in 3 patients. Onlay-alloplasty with polypropylene mesh "PROLENE" is effective method of treatment of postoperative paracolostomic ventral hernias with colostomy closing as well as with its reconstruction outside of implant.

[VARIANT OF HEMOSTATIC SUTURE IN MILLIGAN-MORGAN OPERATION].

On the basis of great clinical experience, the authors developed the method of choice of optimal surgical aid and suggested an original surgical method of treatment of complicated hemorrhoid. The results obtained were analyzed. There was reliably noted, that the quantity of early postoperative complications decreased, an expression of pain syndrome was lower and there were no relapses during three-year of follow-up. Given technologies allowed an introduction of them as stationary substituting operations on the basis of private medical centers with one day of hospital stay.

[Nucleosides of 1,2,4-triazole: potentialities and restrictions of chemo-enzymatic method for synthesis].

The potentialities and restrictions of chemoenzymatic approach to the synthesis of new structural analogues of antiviral drug Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) have been determined. Syntheses of various amides of 1H-1,2,4-triazole-3-carboxylic acid and its 5-substituted analogues, prospective substrates of purine nucleoside phosphorylase (PNP), have been reported. The comparative effectiveness of the methods for obtaining amides aforementioned and also the methods for introducing functional groups to the C5 position of the heterocyclic system has been studied. New Ribavirin analogues bearing various substituents in the carboxamide group have been synthesized. The biotechnological method for the preparation of 1-beta-D-ribofuranosyl- 1,2,4-triazole-3-carbonitrile used as the intermediate in the synthesis of Viramidine, a contemporary Ribavirin analogue, has been developed.

[The use of silymarin in patients with toxic and viral liver diseases].

Effective use of Silybum marianum medicines is still urgent in hepatology practice. Data about effectiveness and safety of silymarin in patients with acute and chronic toxic injuries including drug-induced ones and patients with acute and chronic viral hepatitis is reviewed in the article. An attempt of trials limitations and disadvantages systematization is made and methods of their solvation are discussed. A possibility of silymarin use as antiviral agent in patients with chronic hepatitis C is also reviewed and perspectives of this drug clinical use in future is discussed.

[Hepatoprotective properties of silymarin].

Different approaches to liver-specific medicines, particularly silymarin, which exist in russian and foreign hepatology leads to formation of some difficulties in their medical usage. There is a necessity to discuss classification and terminology aspects and to study study present evidence about silymarin medicines content, pharmacokinetic and mechanisms of action, clinical efficacy and safety in patients with hepatic disorders. We had performed search in medical databases and analysed articles about silymarin. The results of clinical trials and systematic reviews of silymarin use show high efficacy of the drug in patients with amanitine, drugs, and other toxic injuries of liver, viral hepatitis, NASH. In patients with carcinoma and primarily biliary cirrhosis efficacy of silymarin is ambiguous.

[Diclofenac sodium in osteoarthritis. Is there risk of hepatotoxicity? A systematic review].

Diclofenac sodium is one of the most prescribed NSAIDs in the world which is frequently used in therapy of musculosceletal diseases. Therefore it is important to justify clinical and literary data about diclofenac hepatotoxicity. We searched for diclofenac versus placebo investigations performed in patients with osteoarthrosis. A method of the search included international databases such as EMBASE, Cochrane Database, databases of medical publishers and search engines. Total amount of patients in all trials was 1121. 583 patients took diclofenac and 538 ones took placebo. Meta-analysis was performed in StatsDirect software. We estimated 95% confidence interval, Q and 12 criteria, Mantel-Haenszel and DerSimonian-Laird statistics and relative risk of adverse reactions. Relative risk of hepatitis in diclofenac group did not differ from placebo. Hereby the fact of diclofenac hepatotoxicity needs more detailed study and genetic factors of risk should be taken into account.

The NMR microimaging studies of the interplay of mass transport and chemical reaction in porous media.

PFG NMR is employed to perform a comparative study of the filtration of water and propane through model porous media. It is shown that the dispersion coefficients for water are dominated by the holdup effects even in a bed of nonporous glass beads. It is demonstrated that correlation experiments such as VEXSY are applicable to gas flow despite the large diffusivity values of gases. The PFG NMR technique is applied to study the gravity driven flow of liquid-containing fine solid particles through a porous bed. The NMR imaging technique is employed to visualize the propagation of autocatalytic waves for the Belousov-Zhabotinsky reaction which is carried out in a model porous medium. It is demonstrated that the wave propagation velocity decreases as the wave crosses the boundary between the bulk liquid and the flooded bead pack. The images detected during the catalytic hydrogenation of alpha-methylstyrene on a single catalyst pellet at elevated temperatures have revealed that the reaction and the accompanying phase transition alter the distribution of the liquid phase within the pellet.

The effect of oxidative stress on structural transitions of human erythrocyte ghost membranes.

Differential scanning microcalorimetry was used to study the effect of oxidative stress induced by cumene hydroperoxide (CHP) and Fe2+ on structural transitions of membranes of human erythrocyte ghosts. The CHP homolysis was shown to cause: (a) reduction of the intensity of all structural transitions with the disappearance of B1- and D-transitions; (b) decrease in the enthalpy of oxidized membrane denaturation; (c) negative slope of thermograms; (d) anomalous growth of heat absorption by membranes above 72 degreesC. All these changes occurred until the ratio Fe2+/CHP/membranes<0.02:0.05:1 was reached, i.e., prior to the moment of maximal level of TBA-RS in membrane ghosts. We interpret changes in the character of heat absorption by oxidized membranes as perturbations in the structural organization and interactions inside the spectrin-actin-protein 4.1 domains, the spectrin-protein 4.2 domain, as well as inside the domain of spectrin-ankyrin-cdB3 and the domain formed by the msdB3. These perturbations are associated mainly with the decrease in the concentration of native protein in the domains because of oxidative aggregation of proteins, as evidenced by SDS electrophoresis of oxidized membranes. Preincubation of membranes with tocopherol did not block the aggregation of proteins in electrophoresis and the decrease in the intensity of structural transitions, whereas it blocked completely the formation of TBA-RS, changes in the thermogram slope and the sharp rise in the heat absorption above 72 degreesC. This proves that these processes are determined by the thermotropic properties of the oxidized lipid bilayer of membranes and also provides evidence that the degradation of PUFA of phospholipids modifies both the structure of protein domains and the physical properties of the lipid bilayer of membranes.

[Thrombosis and thrombophlebitis after catheterization of the subclavian vein]. / Trombozy i tromboflebity pri kateterizatsii podkliuchichnoi veny.

The authors analysed 685 catheterizations of the subclavian vein. Thrombophlebitic complications were diagnosed in 13 patients--phlebothrombosis in 9 of them and thrombophlebitis in 4. The complications developed mostly in cases with a severe general disease, in ++pyo-septic conditions. In 19 patients the catheter was displaced into the internal jugular vein during phlebography. Catheterization had to be repeated in 73 patients, thrombophlebitic complications occurred in 4 of them. A conclusion is drawn on the expediency of the principle of unilateral manipulations in catheterization repeated many times.