The effect of anthracene derivatives on the state of the extracellular matrix of the periodontal connective tissue and the oral mucosa of old rats

In the experiments on 27 old female rats, the effect of the anthracene derivative preparation on the state of the intercellular matrix of the connective tissue of the periodontal and oral mucosa in intact animals, as well as on the periodontitis model, was studied

The role of polymorphic variants of arginase genes (<i>ARG1, ARG2</i>) involved in beta-2-agonist metabolism in the development and course of asthma

Asthma is a common severe disease of the respiratory tract, it leads to a significant impairment in the quality of a patient’s life unless effectively treated. Uncontrolled asthma symptoms are a cause of disease progression and development, they lead to an increase in the patient’s disability. The sensitivity to asthma therapy largely depends on the interaction of genetic and epigenetic factors, which account for about 50–60 % of variability of therapeutic response. Beta-2-agonists are some of the major class of bronchodilators used for asthma management. According to published data, allelic variants of the arginase ARG1 and ARG2 genes are associated with a risk of asthma development, spirometry measures and efficacy of bronchodilator therapy. High arginase activity results in a low level of plasma L-arginine and in a decrease in nitric oxide, and, as a result, in an increase in airway inflammation and remodeling. Arginase genetic polymorphisms (rs2781667 of the ARG1 gene, rs17249437, rs3742879, rs7140310 of the ARG2 gene) were studied in 236 children with asthma and 194 unrelated healthy individuals of Russian, Tatar and Bashkir ethnicity from the Republic of Bashkortostan. Association analysis of the studied polymorphisms with asthma development and course, the sensitivity to therapy in patients was carried out. It was found that the rs2781667*C allele of the ARG1 gene is a marker of an increased risk of asthma in Tatars. In Russians, the association of rs17249437*TT and rs3742879*GG genotypes of the ARG2 gene with a decrease in spirometry measures (FEV1, MEF25) was established. In Russians and Tatars receiving glucocorticoid monotherapy or combination therapy, the association of the rs17249437*T allele and rs17249437*TT genotype of the ARG2 gene with a partially controlled and uncontrolled course of asthma was shown

Effect of small and radical surgical injury on the level of different populations of circulating tumor cells in the blood of breast cancer patients

Circulating tumor cells (CTCs) constitute a heterogeneous population. Some tumor cells are cancer stem cells (CSCs), while others are in the process of the epithelial-mesenchymal transition (EMT); however, most CTCs are neither stem cells nor in the EMT. This prospective study of 22 patients with nonspecific-type invasive carcinoma of the breast identified different populations of CTCs by flow cytometry in the blood of patients before biopsy, after biopsy and after surgical tumor removal without neoadjuvant chemotherapy. The results showed that minor surgical injury (biopsy) was accompanied by a significant increase in the blood levels of CTCs without signs of the EMT or stemness (Epcam+CD45-CD44-CD24-Ncadh-) and CTCs with signs of stemness and without signs of the EMT (Epcam+CD45-CD44+CD24-Ncadh-). Our results suggest that minor surgical injury to a tumor contributes to the release of CTCs into the bloodstream, including a population of stem cells

Clinicopathological features of nonspecific invasive breast cancer according to its molecular subtypes

The aim of the present study was to investigate the clinical and morphological features of nonspecific invasive breast cancer according to its molecular subtypes. Materials and Methods: 163 women with nonspecific invasive breast cancer (T1–4N0–3M0) were included in the present study. Luminal A type of breast cancer was detected in 101 women, luminal B type — in 23 women, overexpression of HER2/neu was identified in 14 women and triple-negative cancer — in 25 women. Results: The study revealed that various molecular subtypes of breast cancer differ in the morphological structure, the expression characteristics of the primary tumor and the rate of lymphogenous and hematogenous metastasis. Lymphogenous metastases were more frequently (in 71%) detected in HER2/neu overexpressing breast cancer than in luminal A (41%), luminal B (39%) and triple-negative tumors (40%). Hematogenous metastasis did not depend on the morphological structure of carcinoma infiltrative component, the state of tumor stroma as well as the proliferative activity in all the investigated groups. Conclusion: The revealed clinicopathological characteristics of different molecular subtypes of invasive breast cancer allow to predict the possible outcome of the disease and select personalized treatment strategy for patients more reasonably

ВОСПАЛЕНИЕ КАК ТЕРАПЕВТИЧЕСКАЯ МИШЕНЬ ПРИ КОМПЛЕКСНОМ ЛЕЧЕНИИ ЗЛОКАЧЕСТВЕННЫХ ОПУХОЛЕЙ

In this review, we analyzed the role of inflammation in carcinogenesis, tumor development, and metastasis. In addition, the mechanisms of non-steroidal anti-inflammatory drugs (NSAIDs) and the reasons of their contradictory influence on cancers were discussed. We summarized the numerous data about effectiveness of anti-inflammatory drugs for the prevention and additional therapy of tumor diseases. In particular, divergent effects of NSAIDs may be due to the peculiarities of immune-inflammatory responses that are realized in carcinogenesis and tumor development that have yet to be studied. We also discussed the selectivity of NSAID effects on different cancers and opposite effects of anticancer drugs with similar mechanisms of action. Apparently, the unsuccessful use of NSAIDs in cancer prevention and therapy are more specific for squamous cell carcinomas. Based on the literature, we provided significant clinical findings regarding the need of NSAID use in the current therapy of certain cancers and the determination of molecular predictors of the drug effect. In fact, anti-inflammatory therapy could eliminate the factors that contribute to the appearance of invasive and metastatic tumor cells, cancer and premetastatic niches and thus prevent metastasis and recurrence. At present, some non-selective (aspirin) and selective (celecoxib) NSAIDs are highly promising in the therapy of solid tumors. В обзоре анализируется роль воспаления в канцерогенезе, развитии опухоли и метастазировании. Обобщены многочисленные данные об эффективности противовоспалительных препаратов с целью профилактики и вспомогательной терапии опухолевой болезни. Обсуждены механизмы действия и причины противоречивости результатов использования нестероидных противовоспалительных препаратов (НПВП). Разнонаправленность эффектов может быть обусловлена особенностями иммуновоспалительных реакций, реализующихся в процессе канцерогенеза и развития опухолей, которые еще предстоит изучить. Обращается внимание на избирательность эффектов НПВП в отношении разных нозологических форм опухолей и противоположный характер противоопухолевых эффектов препаратов, относящихся по механизму действия к одной группе. Сделано заключение, что неудачи применения НПВП с профилактической и лечебной целью чаще возникают при карциномах, происходящих из плоского эпителия. Анализ литературы позволяет прийти к заключению, что имеются неоспоримые данные, позволяющие включать противовоспалительные препараты в существующие схемы противоопухолевого лечения при некоторых нозологических формах с определением молекулярных предикторов эффекта. Противовоспалительная терапия позволит устранить факторы, способствующие приобретению опухолевыми клетками инвазивных и метастатических свойств и формированию опухолевых и преметастатических ниш, а значит, развитию метастазов и рецидивов опухоли. Особенно перспективны при солидных опухолях определенные неселективные (аспирин) и селективные (целекоксиб) НПВП.

Падения у коморбидных пациентов старческого возраста при сочетанном применении психотропных и кардиологических лекарственных средств

The article discusses aspects of drug-induced falls in elderly comorbid patients against the background of polypragmasy and also assesses the role of drug interactions that are highly dangerous according to the risk of falling. A drug audit of the obtained pharmacotherapy database was performed in patients with comorbid pathology older than 75 years, in order to identify fall-risk-increasing drugs, ranked according to the degree of risk of falling, their significant interactions and with using the traffic light classification. The data on the analysis of the contribution of psychotropic, cardiological drugs and their combination on the risk of developing a fall in the hospital in comorbid patients of old age against polypragmasy are presented. В статье рассмотрены аспекты лекарственно-индуцированных падений у коморбидных пациентов старческого возраста на фоне полипрагмазии, а также оценена роль сочетанного применения лекарственных средств, отнесенных к высокоопасным по риску падения. Проведен лекарственный аудит базы данных получаемой фармакотерапии у пациентов старше 75 лет с коморбидной патологией на предмет выявления лекарственных средств, отнесенных к высокоопасным по риску падения, ранжированных по степени этого риска согласно светофорной классификации, и их значимых взаимодействий. Представлены данные по анализу исследования вклада психотропных, кардиологических лекарственных средств и их сочетания на риск развития падения в стационаре у коморбидных пациентов старческого возраста на фоне полипрагмазии

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

Background and purpose: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3&nbsp;years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0&nbsp;years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013