[Determination of severity of harm caused to health in depressed skull deformation by «ping-pong¼ type in an infant]. / Opredelenie stepeni tyazhesti vreda, prichinennogo zdorov'yu, pri vdavlennoi deformatsii cherepa po tipu «ping-pong¼ u mladentsa.

THE OBJECTIVE: Is to develop a differential approach to determining the severity of harm caused to health in case of depressed skull injuries in infants, depending on their morphological features and the character of required treatment. The material included data from literature sources on the study of brain injuries in infants, clinical guidelines, describing the features of clinical picture and diagnosis of depressed skull fractures in infants and legal and regulatory framework of forensic medical evaluation of harm caused to health in injury. The following methods of research were used: logical-analytical, logical-synthetic (generalization), comparative, system-analytical (analysis of relations between facts) and radiological method. An algorithm for determining the severity of harm caused to health in depressed skull deformations by «ping-pong¼ type in an infant is proposed for discussion. The algorithm is based on the data from injury imaging techniques, including X-ray computed tomography, takes into account the clinical picture and the availability of indications for surgical treatment, and will allow to objectively assess the severity of harm caused to health in such cases.

[Results of malignancy detection during prophylactic medical examinations in 2013-2014].

AIM: To analyze the efficiency of prophylactic medical examination for malignancies that considerably contributes to adult mortality. MATERIAL AND METHODS: The data of the national health statistics (Form 131/o, 7, 35) were used to make an expert analytical assessment of the results of prophylactic medical examinations for cancer in certain adult population groups in Russia in 2013-2014. RESULTS: Medical examinations covered 20.5 and 22.5 million people in 2013 and 2014, respectively. The proportion of 21-36-, 39-60-, and over 60-year olds was 36, 42, and 22%, respectively. All the age groups showed a preponderance of women with their larger proportion in the older age groups (55, 58, and 64%, respectively). In 2013 and 2014 there were 27,173 and 34,638 detected patients with malignances, including 17,095 (62.9%) and 20,944 (60.5%) women and 10,078 (37.1%) and 13,694 (39.5%) men, respectively. In these years, the breast (28 and 30.5%), prostate (13.9 and 18.5%), rectum (6.5 and 7.5%), stomach (6.3% and 7.8%), lung (6.1 and 7.3%) ranked fifth in cancer sites. There was a 17.6% increase in the detection rate of malignancy among the first identified patients during prophylactic medical examinations and and a 10.2% increase among all actively detected patients in 2014 versus 2013. The older age groups exhibited a rise in cancer detection rates, the most significant (11.8%) increase being in the women older than 60 years of age. CONCLUSION: The malignancy detection rates were noted to be on the rise, although there are defects in organizing prophylactic medical examination, ensuring the complete scope of necessary investigations, and interpreting the findings. The measures methodically supported a by regional cancer may provide a guide to solving these problems. At the same time, efforts are needed to actively attract citizens in the participation in prophylactic medical examination and in the development of behavioral attitudes associated with the higher responsibility for maintaining personal and public health.

Addiction-related genes in gambling disorders: new insights from parallel human and pre-clinical models.

Neurobiological research supports the characterization of disordered gambling (DG) as a behavioral addiction. Recently, an animal model of gambling behavior was developed (rat gambling task, rGT), expanding the available tools to investigate DG neurobiology. We investigated whether rGT performance and associated risk gene expression in the rat's brain could provide cross-translational understanding of the neuromolecular mechanisms of addiction in DG. We genotyped tagSNPs (single-nucleotide polymorphisms) in 38 addiction-related genes in 400 DG and 345 non-DG subjects. Genes with P<0.1 in the human association analyses were selected to be investigated in the animal arm to determine whether their mRNA expression in rats was associated with the rat's performance on the rGT. In humans, DG was significantly associated with tagSNPs in DRD3 (rs167771) and CAMK2D (rs3815072). Our results suggest that age and gender might moderate the association between CAMK2D and DG. Moderation effects could not be investigated due to sample power. In the animal arm, only the association between rGT performance and Drd3 expression remained significant after Bonferroni correction for 59 brain regions. As male rats were used, gender effects could not be investigated. Our results corroborate previous findings reporting the involvement of DRD3 receptor in addictions. To our knowledge, the use of human genetics, pre-clinical models and gene expression as a cross-translation paradigm has not previously been attempted in the field of addictions. The cross-validation of human findings in animal models is crucial for improving the translation of basic research into clinical treatments, which could accelerate neurobiological and pharmacological investigations in addictions.

[Experimental study of remaxol as a drug for supportive therapy in traditional and high-dose treatment of tumors].

We have experimentally investigated the detoxifying and modifying effects of remaxol in the framework of traditional and high-dose chemotherapy in mice with transplanted tumors. The influence of remaxol in comparison with heptral was studied on the toxic and therapeutic action of cytostatic drugs gemzar, lastet (etoposide), and methotrexate during their traditional and high-dose administration in mice with transplanted P388 lympholeukosis. Remaxol demonstrated a detoxifying action with respect to these cytostatic agents, which decreased in the following series: gemzar lastet methotrexate (according to the results of lethality evaluation). Remaxol significantly increased the therapeutic efficacy of gemzar used in both traditional and high-dose regimes. This was manifested by slowing down tumor growth and increasing animal lifetime during combined administration of the drugs. This may be due to the remaxol potentiation of the antitumor effect of gemzar. In combination with lastet and methotrexate, remaxol does not alter their therapeutic efficacy. The detoxifying action of remaxol with respect to these cytostatics is more pronounced than that of heptral.

[Bicyclic furano[2,3-D] derivatives of pyrimidine nucleosides--synthesis and antiviral properties].

The methods of synthesis of furano- and pyrrolo[2,3-dlpyrimidine nucleosides as well as structure activity relationship of obtained compounds towards viruses of varicella zoster, hepatitis C, bovine viral diarrhea and some others are reviewed.

[Synthesis and biological properties of α-thymidine 5'-aryl phosphonates].

The interaction of CDI-activated diethyl phosphonoacetate with methyl 4-aminobenzoat or 3,5-difluoromethylphenylamine followed by treatment with Me3SiBr in DMF led to N-aryl aminocarbonylmethyl phosphonates and their ethyl esters. Their coupling with 3'-acetyl-α-thymidine followed by removal of the acetyl groups gave (α-D-thymidine-5'-il) N-[4-(methoxycarbonyl-, aminocarbonyl- and carboxy)phenyl]-aminocarbonylmethyl phosphonates, (α-D-thymidine-5'-il)-[3,5-bis(trifluoromethyl)phenylaminocarbonyl]methyl phosphonate and their ethyl esters. The phosphonates were stable in different conditions, low cytotoxic (in Vero and K562 cells) and were able to penetrate into K562 cells. The only ethyl ester of (α-D-thymidine-5'-il) N-[4-(methoxycarbonyl)phenyl]-aminocarbonylmethyl phosphonate in high concentration (200 µg/mL) inhibited in vitro the growth of laboratory sensitive strain of Mycobacterium tuberculosis H37Rv.

[Age-related peculiarities and determinating factors of atrial fibrillation].

The principal aim of the study was to investigate the causes and clinical features of atrial fibrillation (AF) in patients of two age groups--(1) 40-59 years and (2) 60 and elder. 454 male and female patients of the cardiology department were studied. This article discusses recent concepts of the mutual influence of AF and associated clinical cardiovascular conditions and their complications. The duration and degree of correction of cardiovascular pathology and its correlation with the incidence of AF are evaluated.

[Pathogenetic correction of metabolic disturbances in chronic liver affections].

The available drugs for the treatment of chronic liver affections (the adequate model is chronic hepatitis C) include agents of metabolic therapy, whose efficacy is not always enough, that required the search for original mitochondrial substrates on the basis of succinate. Such agents were composed as a pharmaceutical group named "Substrates of Energetic Metabolism" or "Substrate Antihypoxants". The review presents the description of the pharmacological effects of remaxole and cytoflavin, evident from lower levels of active metabolites of oxygen that increases the clinical efficacy of the therapy. Their role in the metabolic reactions in chronic liver affections is exclusive and rather actual.

[Study of detoxifying efficacy of remaxol in experimental model of cisplatin-induced toxicosis].

The detoxifying efficacy of remaxol in the experimental model of cisplatin-induced toxicosis has been studied and the possibility of using this drug in cancer patients therapy is evaluated. Remaxol exhibited pronounced dose-dependent detoxifying effect in the model of toxicosis induced by cisplatin in a toxic dose (LD50). It reduced the death rate in test animals about three times when used at a 130 ml/kg dose, and prevented lethal outcome at a 500 ml/kg dose. Remaxol also normalized biochemical blood indices that characterized liver and kidney functions in survived animals. Remaxol did not stimulate growth of experimental carcinoma, sarcoma, melanoma, and lympholeukosis. The drug did not interfere with the anti-tumor efficacy of cisplatin in the schemes with combined treatment of animals bearing tumors of various histogenesis. Remaxol can be recommended for clinical study as a detoxifying preparation for cancer patients with various malignancies.

[4'-C-modified nucleosides: synthesis and antiviral properties].

The synthetic methods for 4'-C-modified nucleosides as well as structure activity relationship of obtained compounds towards hepatitis C virus are reviewed.

[The use of laser-assisted scanning confocal microscopy for the detection of foreign particles in internal organ tissues].

The objective of this study was to evaluate the possibility and effectiveness of using laser-assisted scanning confocal microscopy for the detection of foreign particles in internal organ tissues for the purpose of forensic medical diagnosis of fatal cases of acute and chronic drug intoxication. Lung tissue samples stained with hematoxylin and eosin exhibited autofluorescent foreign particles localized in vascular lumen. Microphotographs and autofluorescence spectral profiles of the examined tissues are presented.

[New furano- and pyrrolo[2,3-d]pyrimidine nucleosides and their 5'-triphosphates: synthesis and biological properties].

Bicyclic furano[2,3-d]pyrimidine ribonucleosides were synthesized by Pd(0)- and CuI-catalyzed coupling of 5-iodouridine with terminal alkynes. The treatment of the resulting nucleosides with ammonia or methylamine solution in aqueous alcohol resulted in pyrrolo- and N(7)-methylpyrrolo[2,3-d]pyrimidine nucleosides. 5'-O-Triphosphates of bicyclic nucleosides were obtained by the treatment of the nucleosides with POCl3 in the presence of a "proton sponge." The 5'-O-triphosphates are not substrates for HCV RNA-dependent RNA polymerase, but are effective substrates for HCV RNA helicase/NTPase and did not inhibit ATP hydrolysis. Only 3-(beta-D-ribofuranosyl)-6-decyl-2,3-dihydrofuro-[2,3-d]pyrimidin-2-one showed a moderate anti-HCV activity in the HCV replicon system and efficiently inhibited replication of bovine viral diarrhea virus (BVDV) in KCT-cells, other compounds being inactive. None of the compounds were cytotoxic within the tested range of concentrations.

[Synthesis and antiviral activity of new 5-substituted 2'-deoxyuridine derivatives].

New 5-azole- and 5-oxime-substituted analogues of 2'-deoxyuridine are synthesized. The analogues with azole ring manifest low toxicities and antiherpetic activities on Vero cell culture, the imidazole derivative being the most active. The inhibitory effects of oximes of 5-formyl-deoxyuridine are comparable with those of the azole-containing nucleoside analogues, although their cytotoxicities are found to be higher; oxime of 5-formyldeoxyuridine is particularly toxic. The nucleoside analogues synthesized exhibit no marked activity on cell cultures infected with various variants of poxvirus. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 6; see also http://www.maik.ru.

Protective effect of carnosine on excitable structures of the auditory apparatus in albino rats with acute acoustic trauma.

We studied the effect of natural antioxidant carnosine on Wistar rats with experimental acoustic trauma of the auditory apparatus. Repeated intraperitoneal injection of carnosine in a dose of 200 mg/kg 12 and 0.5 h before modeling of acute acoustic trauma decreased the severity of degenerative and atrophic changes in the nuclei of hair cells in the cochleae. Carnosine compensated the deficiency of tissue antioxidant systems and suppressed generation of lipid peroxidation products in tissues of the membranous cochlea and auditory cortex of the temporal lobes. Carnosine holds much promise as a nonspecific otoprotector.

Natural antioxidant L-carnosine inhibits LPO intensification in structures of the auditory analyzer under conditions of chronic exposure to aminoglycoside antibiotics.

Intragastric administration of L-carnosine suspension to Wistar-Kyoto rats 3 days before and after 7-day course of intraperitoneal injections of ototoxic aminoglycoside antibiotic kanamycin compensated expenditures of tissue antioxidant systems and significantly eliminated kanamycin-induced intensification of MDA production in tissues of the membrane part of the cochlea and in the auditory cortex of the temporal lobe. L-NAME (competitive NO synthase inhibitor) also inhibited LPO, increased total antioxidant activity, and decreased ototoxicity of kanamycin, which confirms the contribution of NO into LPO intensification under conditions of aminoglycoside treatment. Inhibition of pathological intensification of LPO processes and increase in total antioxidant activity under conditions of induced acute aminoglycoside ototoxicity characterizes L-carnosine as a highly effective otoprotector.

[Efficacy of 4'-thio-5-ethyl-2'-deoxyuridine (TEDU) and its derivatives in experimental infection in mice caused by herpes simplex virus]. / Izuchenie éffektivnosti 4'-tio-5-étil-2'-deoksiuridina (TEDU) i ego proizvodnykh, vyzvannoi virusom gerpesa prostogo.

It was demonstrated that several 5'-phosphonates of 4'-thio-5-ethyl-2'-deoxyuridine possessed antiviral activity in vitro and in the murine model of herpes simplex virus type 1 infection. It was shown that the derivatives after intraabdominal administration penetrated effectively into the brain tissue. The agents provided statistically significant increase of the average life span, lower virus titre in the brain and lower lethality when compared to the control group of the animals. It is emphasized that the derivatives were less toxic than the original compound.

[4'-Thio-5-ethyl-2'-deoxyuridine 5'-phosphonates: synthesis and antiviral activity]. / 5'-Fosfonaty 4'-tio-5-étil-2'-dezoksiuridina: sintez i antivirusnye svoistva.

A number of new 5'-phosphonate derivatives of 4'-thio-5-ethyl-2'-deoxyuridine (TEDU) were synthesized. These compounds displayed a low cytotoxicity and, except for TEDU 5'-fluorophosphate, antiherpes activity similar to that of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir) and 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (pencyclovir). 5'-Ethoxycarbonylphosphonate and 5'-aminocarbonylphosphonate of TEDU were also found to suppress the reproduction of herpes simplex type 1 virus, which is resistant to acyclovir.

[Complications high frequency catheter destruction of heart conduction pathways]. / Oslozhneniia vysokochastotnoi kateternoi destruktsii provodiashchikh putei serdtsa.

An analysis of 490 operations in 442 patients with different variants of supraventricular and ventricular tachycardia was made. Complications developed in 23 cases (4.7%). The least (0.8%) risk of complications was noted in patients after destruction of the atrioventricular junction, the greatest (9.6%) in patients with abnormal junctions. Measures of treatment depended on the degree and severity of the complication and the character of concomitant disease. The division of complications into biogenic and technogenic allows the possible factors influencing their development to be differentiated. The frequency of complications is determined by complexity of the methods used and the necessary experience on the one hand, and by the severity of the patient's state and coexistent diseases on the other hand.

[Complications after angioplasty and stenting of coronary arteries in ischemic heart disease patients]. / Oslozhneniia angioplastiki i stentirovaniia koronarnykh arterii u bol'nykh s ishemicheskoi bolezn'iu serdtsa.

The authors have made an analysis of most frequent complications of angioplasty and stenting of coronary arteries in 1900 patients with various forms of ischemic heart disease. The mechanisms, pathomorphology, angiographic and clinical manifestations of such complications as dissection of the coronary artery intima, acute occlusion of the coronary artery, "no-reflow" syndrome, perforation and rupture of the coronary artery, acute thrombosis in the stent area and other complications are considered in detail. Special medical strategy, both therapeutic and surgical, is proposed for each case. The authors propose a number of prophylactic measures allowing to avoid the complications described or to minimize them. Intraoperative lethality in this group of patients was 0.5% (10 patients), during the first week after endovascular intervention 26 patients died (1.4%).