Effects of ABCB1 rs1045642 polymorphisms on the efficacy and safety of amlodipine therapy in caucasian patients with stage I–II hypertension
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01.01.2018 |
Sychev D.
Shikh N.
Morozova T.
Grishina E.
Ryzhikova K.
Malova E.
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Pharmacogenomics and Personalized Medicine |
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3 |
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© 2018 Sychev et al. Purpose: The aim of this study was to determine the impact of ABCB1 (MDR1) rs1045642 polymorphisms on the efficacy and safety of amlodipine in Caucasian patients. Patients and methods: The 12-week study included 100 patients. Patients with the newly diagnosed stage I–II hypertension (HT) were recruited to complete genotyping of the rs1045642 single-nucleotide polymorphism (SNP). The study design did not include a control group. Before treatment, all patients either did not undergo antihypertensive treatment at all or did not receive regular antihypertensive therapy. The initial dose was 5 mg/day. Four office blood pressure measurements, two 24-hour noninvasive ambulatory blood pressure measurements, and questionnaires of Tsvetov were used to evaluate the efficacy and safety of amlodipine. Results and conclusion: The highest antihypertensive effect in combination with the lowest incidence of adverse reactions was observed in the TT group, while patients with the CC genotype showed a low antihypertensive effect and the highest incidence of adverse effects. Patients with the CC genotype presented with adverse effects predominantly in the form of edema. A total of 33 patients reached the target blood pressure (SBP <140 mmHg; DBP <90 mmHg): two patients with the CC genotype (12%); 18 patients with the CT genotype (34%); and 13 patients with the TT genotype (43%). The intergroup differences were: CC vs CT, P=0.02; CC vs TT, P=0.02; and CT vs TT, P=0.05. The results of this study indicate the potential of pharmacogenetic testing for rs1045642 SNP when prescribing amlodipine for the first time in Caucasian patients with stage I–II arterial HT.
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Modern approaches to dietary support for patients with diabetic nephropathy
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01.01.2018 |
Sharafetdinov K.
Shekhetov A.
Plotnikova O.
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Voprosy Pitaniia |
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0 |
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© 2018 Nutritec. All Rights Reserved. The article presents modern approaches to dietary support of patients with diabetic nephropathy (DN) characterized by gradual sclerosis of the renal tissue, leading to a loss of filtration and nitrogen excretory function of the kidneys. An analysis of publications of domestic and foreign authors indicates a slowdown in the progression of chronic kidney disease against the background of low-protein diets. However, the role of protein restriction and its qualitative composition in the diet of patients with DN is the subject of comprehensive discussion. KDOQI (2007) Clinical Practice Guidelines and Clinical Practice Guidelines for Kidney Disease determine the target level of protein intake in individuals with diabetes and chronic kidney disease 1-4 stages at the level of 0.8 g/kg of body weight per day. In the recommendations on nutrition for patients with DN, along with a controlled reduction in protein content, great importance is attached to reducing sodium intake from food to 1.5-2.3 gperday. In recent years, close attention has been paid to the use of highly active natural antioxidants for the treatment and prevention of type 2 diabetes, including DN, which was determined by the results of studies demonstrating their beneficial effects on DN patterns. It has been shown that one of the ways to optimize the nutrition of patients with DN is the use of specialized foods modified by protein, fat and carbohydrate composition, including food ingredients with hypoglycemic, hypolipidemic and antioxidant effects.
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The use of the method of shadow photography for diagnosing the dispersion performance of throat sprays
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01.01.2018 |
Gobyzov O.
Ryabov M.
Yankova V.
Gribanova S.
Udyanskaya I.
Grigorieva V.
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Voprosy Prakticheskoi Pediatrii |
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0 |
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© 2018, Dynasty Publishing House. All rights reserved. The objective. A comparative diagnosis of dispersion performance by the dynamic characteristics and dispersion composition of aerosol-spray forms of drugs for treatment of inflammatory disease of the throat in children (from the age of 3 years) and adults. Materials and methods. The objects of the study were 10 medications for treatment of inflammatory diseases of the throat, 9 of which have the drug form of a metered-dose spray and 1 drug has the form of undosed aerosol. A comparative diagnostics of the drugs was performed by the following dynamic spray characteristics: total length and length of particular spray phases, spray cone angle and a form of droplet population of the cone. The dispersion composition of spray was characterised by the mean and mass-median diameters of particles, particle size distribution. These characteristics were measured by a direct observation method – shadow photography – with digital processing of images using the «Actual Flow» software. Results. Diagnostics of spray dispersion by dynamic characteristics has shown that the most effective dispersion in the shape of a wide hollow cone was obtained in the drugs Tantum® Verde and Grammidin®. Diagnostics of sprays by their dispersion composition has confirmed the correspondence of all the examined preparations to pharmaceutical sprays for local treatment of the upper respiratory tract. Practically in all sprays, the maximal portion of the drug content is transferred by droplets of the optimal for spray sizes from 10 to 100 μm. The mass content of «hazardous» small droplets with sizes less than 10 μm is insignificant and amounts to less than 1%. Conclusion. Based on diagnostics of 10 sprays by the method of shadow photography on the basis of all examined parameters of the dynamics and fineness of dispersion the most effective dispersion from the viewpoint of drug delivery to throat mucous membranes is achieved in the drug Tantum® Verde.
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The impact of the lipid a structure on lipopolysaccharide (LPS) interactions with serum LPS-binding protein (LBP) and activation of white blood cells
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01.01.2018 |
Kabanov D.
Radzyukevich Y.
Grachev S.
Prokhorenko I.
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Biologicheskie Membrany |
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1 |
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© 2018 Russian Academy of Sciences. All rights reserved. The current theoretical and experimental data about the impact of the lipid A structure on interactions of lipopolysaccharide (LPS) with serum lipid-binding protein (LBP) are presented. LBP interacts more efficiently with the LPS lipid A from Rhizobium, Escherichia, and Neisseria spp. than with the LPS lipid from Francisella, Porphyromonas, Helicobacter, Chlamydophila, as well as with the lipid A synthetic analogue-compound E5564. It is shown that the lipid A hydrocarbon chain of 14 carbon atoms is most favorable, while that of 16 carbon atoms is ultimate for interaction of LBP with lipid A. A high content of unusually long chains and branched-chain acyl residues in lipid A will further complicate the interaction of LBP with LPS. The reviewed data provide a deeper insight into the mechanisms of the LPS delivery and cell activation accomplished by serum cationic proteins such as LBP. A direct relation between the efficiency of the LBP interaction with a particular lipid A of LPS and the development of the fulminant acute inflammation is proposed.
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Clinical and interferon-modulating efficacy of a combination of rectal and topical dosage forms of interferon-α2b in acute respiratory infections
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01.01.2018 |
Kalyuzhin O.
Ponezheva Z.
Kupchenko A.
Shuvalov A.
Guseva T.
Parshina O.
Malinovskaya V.
Akimkin V.
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Terapevticheskii Arkhiv |
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0 |
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© 2018 Media Sphera Publishing Group.All Rights Reserved. The aim of the study was to evaluate the clinical and interferon-modulating efficacy of a combination of rectal and topical dosage forms of IFN-α2b with antioxidants in the treatment of acute respiratory infections (ARIs) in comparison with other variants of antiviral therapy. Materials and methods. A total of 90 servicemen aged 19.2±0.9 years with uncomplicated forms of ARI were hospitalized not later than 48 hours after the onset of the disease. Patients were randomized into 3 groups of 30 people each. In the first group, patients received rectal suppositories containing IFN-α2b (1 million IU) and antioxidants (alpha-tocopherol acetate and ascorbic acid) twice a day for 5 days. In the second group, patients received intranasally a gel formulation containing IFN-α2b (36 000 IU/1 g) and antioxidants 3 times a day in addition to the above suppositories. In the third group, patients were prescribed umifenovir (reference drug) at dose of 200 mg 4 times a day for 5 days. The dynamics of regression of clinical manifestations of ARI in different groups, changes in concentrations of IFN-α and IFN-γ in blood plasma, as well as spontaneous and induced production of these cytokines by blood cells ex vivo were evaluated. After that, the patients were observed for another 3 months to register repeated cases of hospitalization for ARI. Results. Marked tendency to accelerate the regression of symptoms of intoxication and fever was observed when intranasal dosage form of IFN-α2b was administered to patients receiving the rectal form of this cytokine. The combination of rectal and topical dosage forms of IFN-α2b with antioxidants was more effective than monotherapy with the rectal suppositories in preventing repeated hospitalization for ARI. The above combination caused the most complete correction of induced production of IFN-α by blood cells ex vivo at its initial deviation from the norm. Conclusion. The obtained data indicate the expediency of using the combination of rectal and topical dosage forms of IFN-α2b with antioxidants for treatment of ARI.
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Oxidative and carbonyl stress as a factors of the modification of proteins and DNA destruction in diabetes
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01.01.2018 |
Lankin V.
Tikhaze A.
Konovalova G.
Odinokova O.
Doroshchuk N.
Chazova I.
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Terapevticheskii Arkhiv |
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0 |
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© 2018 Media Sphera Publishing Group.All Rights Reserved. Aim. To study the oxidative damage of biopolymers (proteins and nucleic acids) in blood of patients with type 2 diabetes mellitus (DM). Materials and methods. In the blood of 50 patients with DM and 25 patients without disorders of carbohydrate metabolism were estimated: the level of oxidized low-density lipoprotein (oxLDL) by immunochemical method, the content of SH-groups in plasma proteins, the activity of Cu, Zn-superoxide dismutase (SOD) in erythrocytes, the length of telomere in leukocyte DNA, the level of 8-hydroxy-2'-deoxy-gunosine (8-oxo-dG) in plasma and urine. Results and discussion. It is shown that in DM patients the level of oxLDL increases and the content of SH-groups in proteins and peptides of the blood plasma decreases, which indicates the development of oxidative stress. In addition, a carbonyl-dependent modification of erythrocyte SOD was detected in DM patients, as well as oxidative DNA destruction (decrease in telomere length in leukocytes and an increase in the level of 8-oxo-dG in blood plasma and urine). Conclusion. On the basis of the definition of a complex of correct indicators, a multiple oxidative modification of biopolymers of blood (proteins and DNA) was detected in patients with DM.
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Cognitive impairment in patients with type 2 diabetes mellitus: prevalence, pathogenetic mechanisms, the effect of antidiabetic drugs
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01.01.2018 |
Ostroumova O.
Surkova E.
Chikh E.
Rebrova E.
Borisov M.
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Diabetes Mellitus |
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3 |
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© 2018 Russian Association of Endocrinologists. All rights reserved. In recent years, a large amount of data has been accumulated on the relationship between cognitive impairment, dementia and diabetes mellitus. This article presents an overview of modern literature, including the definition of cognitive functions, the modern classification of cognitive impairment, pathogenetic mechanisms of diabetes mellitus influence on the development of cognitive impairment and dementia (neurogenesis, integrity of the blood-brain barrier, systemic inflammatory reactions, hyper- And hypoglycemia, insulin resistance, vascular dysfunction of the microvasculature and increase in glucocorticosteroids). The influence of anti-diabetic medications on cognitive functions has been examined in detail: insulin preparations, oral hypoglycemic agents of the biguanide group (metformin), thiazolidinediones (rosiglitazone and pioglitazone), sulfonylurea derivatives (glycazide, glipizide), a-glucosidase (acarbose) inhibitors, incretin-directed therapy (receptor agonists glucan-like peptide (exenatide and liraglutide) and inhibitors of dipeptidylpeptidase type 4 (sitagliptin, vildagliptin and alogliptin)), sodium glucose inhibitors cotransporter type 2. The data demonstrating a multidirectional effect on the cognitive functions of various antidiabetic drugs is presented, the possible influence on the rate of progression of cognitive impairment and the risk of dementia of intensive control of plasma glucose level in comparison with the standard decrease in patients with type 2 diabetes is analyzed.
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The impact of optical radiation of femtosecond duration on human glial cells
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01.01.2018 |
Ilatovskaia D.
Porozov Y.
Demchenko P.
Meglinski I.
Khodzitsky M.
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Proceedings of SPIE - The International Society for Optical Engineering |
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0 |
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© 2018 Copyright SPIE. The paper presents the results of the studies of influence of optical radiation with wavelengths of 520 and 780 nm on human glial cells (U251) at the range of exposure times ∼ 1-15 min. It was found that after the first minute of irradiation at the wavelength of 780 nm, the relative number of apoptotic cells significantly increased. The result corroborates the concept of biological hazard of optical radiation for tumor cells, and suggests that the approach has a great potential in clinical application for the treatment of human glioma.
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<sup>18</sup>F-FDG PET/CT in the diagnostics of endometrial cancer
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01.01.2018 |
Aretinskiy A.
Ternovoy S.
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Russian Electronic Journal of Radiology |
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0 |
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© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: This article is dedicated to analysis of use PET-CT with 18F-FDG for the last 10 years. Determining the presence of metastasis in regional lymph nodes and distant sites in endometrial cancer is an important diagnostic step aimed at the choice of treatment tactics and improvement of surgical treatment results. If the process is beyond the uterus itself, it significantly worsens the prognosis of survival. In addition, in these cases, it is necessary to change the treatment and surgical tactics. Determination of stage 1 and 2 of the process gives an optimistic prognosis for the survival of patients. Currently, ultrasound, magnetic resonance imaging and, to a much lesser extent, computed tomography are used to assess the prevalence of the process. The diagnostic value of these methods according to some authors does not exceed 66-73%. In this regard, it is justified to work on finding more reliable methods that will more accurately determine the presence of metastatic disease in, both regional lymph nodes and distant organs. One of such promising methods is the use of positron emission tomography combined with computed tomography (PET/CT), using as radiotracer 18 - fluorodeoxyglucose. This article is a review of the scientific literature on this problem over the past 10 years and is devoted to the evaluation of the diagnostic accuracy of PET/CT with 18F-FDG.
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Genetic factors of the development of chronic pancreatitis
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01.01.2018 |
Litvinova М.
Khafizov K.
Shipulin G.
Аyginin А.
Vinokurova L.
Nikolskaya K.
Dubtsova E.
Bordin D.
Asanov A.
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Voprosy Prakticheskoi Pediatrii |
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0 |
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© 2018, Dynasty Publishing House. All rights reserved. Chronic pancreatitis, being a complex multifactor clinico-genetic phenomenon, is a significant medical, social and economic problem. Study of pancreatitis remains a topical theme also for the paediatric cohort, especially taking into account practically similar morbidity rates in adults and children. The review presents information and analyzes main genetic risk factors of the development of pancreatitis. Mutations and polymorphisms of the CFTR, CTRC, SPINK1, CPA1, PRSS1, PRSS2 genes that are significant for functioning of the pancreas are discussed in detail. Examples of genetic variants associated with increased or decreased risks of developing disease are given. Special attention is paid to difficulties of interpreting the results of molecular-genetic testing associated with certain gene homology, presence of pseudogenes and disease cases conditioned by spontaneous mutation. Detection of genetic risk factors of chronic pancreatitis allows to early prevent the development of disease in the proband’s relatives, and also to take a more personalized approach to the patient’s treatment.
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Differences between cerebrovascular effects of 5-hydroxyadamantane-2-one, nimodipine and S-amlodipine nicotinate in the hemorrhagic and ischemic model damage of rat brain
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01.01.2018 |
Mirzoyan R.
Gan'shina T.
Kim G.
Kurdyumov I.
Maslennikov D.
Kurza E.
Gorbunov A.
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Eksperimental'naya i Klinicheskaya Farmakologiya |
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1 |
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© 2018 Izdatel'stvo Meditsina. All rights reserved. The cerebrovascular effects of 5-hydroxyadamantane-2-one (100 mg/kg, i.v.), nimodipine (0.03 mg/kg, i.v.), and S-amlodi- pine nicotinate (0.1 rag/kg, i.v.) were compared and found to differ significantly. While G ABA-ergic 5-hydroxyadaman- tan-2-one and slow calcium channels blocker nimodipine cause a pronounced increase in cerebral blood supply under conditions of global transient ischemia of the brain, their activity in modeling hemorrhagic stroke is significantly lower. At the same time, S-amlodipine nicotinate equally improves cerebral circulation in both hemorrhagic and ischemic brain damage, i.e., the cerebrovascular effect of S-amlodipine nicotinate in the hemorrhagic stroke model is superior to that of nimodipine and 5-hydroxyadamantan-2-one. This is due to a distinguishing feature of the of S-amlodipine nicotinate action, which, in contrast to 5-hydroxyadamantan-2-one and nimodipine, has a binary vasodilating effect on cerebral vessels: (i) blocking slow calcium channels and (ii) stimulating GABAA-receptors.
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Features of the myometrial status during cesarean section with regard to amniorrhea and birth activity: A clinical and morphological study
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01.01.2018 |
Prikhodko A.
Baev O.
Karapetyan A.
Demura T.
Kogan E.
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Akusherstvo i Ginekologiya (Russian Federation) |
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0 |
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© Bionika Media Ltd. Different factors caused by both equipment and the course of surgery (conditions under which the operation is performed, the location of incision, the characteristics of suture material, the type of surgical suture, and the amount of blood loss), by the course of the postoperative period, and the peculiarities of repair of damaged tissues influence wound healing of the uterus during cesarean section. Objective. To establish the value of premature amniorrhea and uterine inertia as predictors of impaired myometrial repair after cesarean section, by using clinical and morphological analyses. Subjects and methods. The investigation enrolled 129 patients who had given birth via cesarean section. Of them, 44 patients had delivery before birth activity, 85 during the first stage of labor. 49 and 80 women delivered before and after amniorrhea, respectively. During cesarean section, uterine tissue was taken from the upper edge of the wound after uterine incision. The myometrial biopsy specimens obtained during cesarean section were morphologically and immunohistochemically examined. The patients were divided into 4 groups according to the level of birth activity and the preservation of amniotic fluid at the time of cesarean section. Group 1 included patients with regular labor activity and amniorrhea at the time of caesarean section; Group 2 consisted of those with labor activity in the presence of whole amniotic fluid; Group 3 comprised those without birth activity in the presence of whole amniotic fluid; Group 4 included patients with premature amniorrhea without uterine contractions. 36 cases (9 in each group) were selected by random sampling for morphological and immunohistochemical examinations. The biopsy specimens were fixed in 10% neutral formalin and embedded in paraffin. The serial paraffin-embedded sections underwent histological examination and immunohistochemical tests for the following markers: TGF-β, VEGF, MMP2, TIMP1, types I and III collagen, TNF, and PDGF. Results. The morphological and immunohistochemical analyses revealed the most pronounced signs of myometrial damage during cesarean section in Group 4 patients having premature amniorrhea without uterine contractions. There were decreased VEGF, PDGF, MMP2, and TIMP levels and simultaneously increased TNF-α expression in leiomyocytes, vascular endothelium, and myometrial stromal cells. The findings may indicate the relatively lower reparative potential of the myometrium and the increased readiness for an inflammatory response in the group of women undergoing cesarean section in the presence of premature amniorrhea without uterine contractions. Conclusion. Clinical, morphological, and immunohistochemical analyses have revealed differences in the myometrial status in relation to typical clinical factors, such as amniorrhea and birth activity. Wound healing occurs under the influence of growth factors and the ratio of expression levels for growth factors can vary in different pathological conditions. The reduced expression of VEGF, MMP2, TIMP, and PDGF and the increased expression of TNF in the group having amniorrhea without uterine contractions (P-B+) suggest that there are pronounced inflammatory processes and impaired myometrial repair with the longer latency period in the absence of labor activity, which may refer these women to a group at risk for incompetent scar formation.
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Somatostatin receptors as potentialtherapeutic targets in the treatment of advanced adrenocortical cancer. a case report
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01.01.2018 |
Kolomeytseva A.
Delektorskaya V.
Orel N.
Emelianova G.
Bokhian V.
Fedenko A.
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Siberian Journal of Oncology |
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0 |
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© 2018 Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved. background. Adrenocortical cancer (ACC) is a rare malignancy of the adrenal cortex. Therapeutic options for advanced ACC are limited. It is necessary to study new and more effective drug combinations and tumor biological targets. the purpose of the study was to determine the expression of somatostatin receptor subtypes 2A and (SSTR 2A and SSTR 5) using immunohistochemical (IHC) analysis of tumor tissue samples in patients with ACC, as well as to study the feasibility of using prolonged analogues of somatostatin in the treatment of advanced ACC. material and methods. The expression of SSTR 2A and SSTR 5 was analyzed using imunohistochemistry of tumor tissue samples from 20 patients with advanced ACC. results. The negative (0) IHC status of SSTR 2A and SSTR 5 was determined in 10 patients (50 %). A different staining intensity of SSTR 2A and SSTR 5 expression was found in tumor cells of 10 patients (50 %). The low SSTR expression was associated with low membrane immunoreactivity and high SSTR expression was associated with moderate and strong immunoreactivity. High level of somatostatin receptor expression was detected in 7 patients (35 %). Conclusion. The detection of SSTR 2A and SSTR 5 expression in tumor tissue of patients with advanced ACC, as well as the study of feasibility of using prolonged somatostatin analogs are promising in the treatment of patients with high receptor expression, however, further research is required.
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Ultrasonic elastography of shear wave with elastometry in defining normative values of Young's modulus of elasticity of the ovaries in women of reproductive age
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01.01.2018 |
Diomidova V.
Zakharova O.
Siordiya A.
Chameeva T.
Vinogradova V.
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Voprosy Ginekologii, Akusherstva i Perinatologii |
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0 |
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© 2018 Dynasty Publishing House. All rights reserved. The objective: to study the diagnostic efficiency and to establish normative values of stiffness of ovaries in healthy women of reproductive age, using multiparametric ultrasound (MPUS), advanced with the 2DSWE mode. Patients and methods: In order to establish stiffness of structures of normal ovaries, MPUS with measurement of Jung's modulus in kPa of right and left ovary were held in 25 healthy women of reproductive age between the 5th-7thday of menstrual cycle. For more precise quantitative parameter of Jung's modulus, measurements were repeated at least in two menstrual cycles in every woman. Results: At ovarian MPUS with the 2DSWE technology, determination of stiffness of ovaries in healthy women of reproductive age was carried out at the average volume of ovary 4,9 ± 0,5 cm3(minimum is 3.7 cm3maximum of 6.9 cm3). In addition, in healthy women of reproductive age, quantitative indicators of Jung's modulus of stiffness of structures of ovary (2,5 - 97,5 percentile - 95% interval) were as follows: median Emean is 8.7 kPa (2,1 - 16,9), the SD of 2.6 kPa (0,7 - 4,1). Qualitative analysis of color elastomers obtained showed a uniform homogeneous blue background of intact ovaries in all cases of the study. Conclusion: When extending the algorithm of MPUS with the 2DSWE technology, the effectiveness of the method in the study of normative values of Jung's modulus of stiffness of ovaries in healthy women of reproductive age was 100%.
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Immune checkpoint inhibition and autoimmunity: Rheumatological problems
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01.01.2018 |
Nasonov E.
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Nauchno-Prakticheskaya Revmatologiya |
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1 |
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The paper deals with the mechanisms of a T-cell immune response, which depends on the balance between costimula-tory and coinhibitory signals that have been called as immune checkpoints (ICP). The imbalance of T-cell activation within ICTs (CTLA4/CD28 and PD1/PD1L) is considered to be a fundamental mechanism not only of autoimmune disease, but also impaired antitumor immunity underlying the development of malignant tumors. The use of monoclonal antibodies against negative regulatory ICTs (CTLA4, PD1, and PD1L) is a major achievement in the treatment of malignant neoplasms in the early 21st century. However, since CTLA4 and PD1 control the activation of auto-reactive T cells, the inhibition of these ICTs is associated with the development of autoimmune disease that is defined as immune-mediated adverse even. The paper considers the clinical manifestations of IMAR, primarily rheumatic ones and discusses the prospects of pharmacotherapy from the standpoint of achievements of modern rheumatology.
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Giant ovarian mucinous cystadenoma in a 54-year-old woman
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01.01.2018 |
Chuprynin V.
Buralkina N.
Chursin V.
Asaturova A.
Katkova A.
Zhurba A.
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Akusherstvo i Ginekologiya (Russian Federation) |
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0 |
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© Bionika Media Ltd. Background. Ovarian cancer develops from benign tumors in 80% of cases during long-term follow-up. According to the literature, the incidence of giant ovarian cystadenoma is extremely low. There are difficulties in verifying these ovarian tumors. Description. The paper describes a rare clinical case of a 54-year-old patient with giant ovarian cystadenoma. It depicts the patient’s clinical, medical history, laboratory, and instrumental data and demonstrates the technical complexities of surgery and the features of postoperative management. Conclusion. The early diagnosis and timely treatment of ovarian tumors will be able to avoid technically difficult surgical interventions and to minimize postoperative complications, which will substantially improve the prognosis of the disease. Such operations should be performed by a surgeon having extensive surgical experience and high qualification.
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Thromboxane a synthase: A new target for the treatment of cardiovascular diseases
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01.01.2018 |
Mesitskaya D.
Syrkin A.
Aksenova M.
Zhang Y.
Zamyatnin A.
Kopylov P.
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Cardiovascular and Hematological Agents in Medicinal Chemistry |
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1 |
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© 2018 Bentham Science Publishers. Atherothrombosis-related diseases are one of the world’s leading causes of mortality, and thus the search for new therapeutic approaches in this area remains a very urgent task. Modern pharmacogenomic technologies make it possible to obtain valuable data on disease pathogenesis and optimal therapeutic approaches. One promising research direction is the study of the thromboxane A2 - thromboxane A synthase - thromboxane A2 receptor axis. This review summarizes the recent evidence and suggests that systematic works in this area are creating new and promising opportunities in the treatment of patients with cardiovascular diseases.
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The role of DNA-methyltransferases in the life cycle of hepatitis b virus and pathogenesis of chronic hepatitis b
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01.01.2018 |
Kostyushev D.
Zueva A.
Brezgin S.
Lipatnikov A.
Volchkova E.
Maleyev V.
Chulanov V.
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Voprosy Virusologii |
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0 |
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© 2017 Izdatel'stvo Meditsina. All rights reserved. Chronic hepatitis B is caused by a persistent form of hepatitis B virus, covalentiy closed circular DNA (cccDNA). Stability of cccDNA is associated with intracellular localization of cccDNA and formation of minichromosome, regu-lated by epigenetic mechanisms. One of the key mechanisms in epigenetics is methylation of DNA on CpG islands. Expression levels of DNA-methyltransferases (DNMTs) in chronic hepatitis B patients were shown to be upregu-lated. Nevertheless, the role of DNMTs in the life cycle of HBV and their effects on the cell remain elusive. In this review, we discuss latest achievements on the role of DNMTs in chronic hepatitis B and HBV in vitro models.
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Influence of CYP3A activity on the efficacy and safety of fluvoxamine in patients depressive disorders and comorbid alcohol use disorder
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01.01.2018 |
Zastrozhin M.
Smirnov V.
Sorokin A.
Grishina E.
Ryzhikova K.
Bedina I.
Shipitsyn V.
Savchenko L.
Buzik O.
Koporov S.
Bryun E.
Sychev D.
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Vestnik Rossiiskoi Akademii Meditsinskikh Nauk |
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© 2018 Izdatel'stvo Meditsina. All rights reserved. BACKGROUND: Alcohol dependence is often combined with affective disorders, in particular, depressive disorder (DD), which worsens adversely affects the prognosis of the course of both diseases and their outcomes. For the treatment of DD, drugs from the group of selective serotonin reuptake inhibitors, whose representative is fluvoxamine, are used. Fluvoxamine therapy is often associated with a risk of development is shown to be ineffective, and a part of patients develop dose-dependent adverse drug reactions (ADR) and pharmacoresistance. OBJECTIVE: To study the effects of CYPD6 isoenzyme activity on the efficacy and safety of fluvoxamine therapy in patients with depressive disorders, comorbid with alcoholism. METHODS: The study was conducted on 117 Russian patients with DD, alcohol-dependent comorbid. For the purpose of correction of depressive disorders within the framework of cyclothymia, fluvoxamine (Fevarin) was administered to patients at a dosage of 50−150 mg/day. Genotyping was carried out by the method of polymerase chain reaction in Real-time mode with allele-specific hybridization. Efficacy and safety were assessed using validated psychometric scales and an assessment of the severity of ADR. To evaluate the activity of CYP2D6, the method of high performance liquid chromatography with mass spectrometry was used to measure the urinary content of the endogenous substrate of this isoenzyme and its metabolite, the ratio of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline. RESULTS: By the 9th day of the study, the severity of depressive symptoms on the HAMD scale was statistically significantly different in patients with different genotypes: (GG) 7.0 [6.0; 8.0], (GA) 4.0 [3.0; 5.0] (p<0.001); safety indicator, estimated on a UKU scale: 3.0 [2.0; 4.0], (GA) 4.0 [4.0; 4.2] (p<0.001). The presence of differences persisted on the 16th day: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.0] (p<0.001); safety indicator, estimated on a UKU scale: (GG) 9.0 [9.0; 10.0], (GA) 6.0 [6.0; 7.0] (p<0.001). The calculation of the correlation coefficients between the difference in the number of scores on psychometric scales and the metabolic ratio showed a statistically significant inverse correlation of the average power degree between the efficiency index estimated by the HAMD scale (r=-0.467, p<0.05). There was no connection with the difference on the UKU scale (r=0.173, p>0.05). CONCLUSION: In a study of a group of 117 patients with DD, comorbid with alcohol dependence, the effect of CYP2D6 activity, estimated by the ratio of the endogenous substrate concentrations of pinolin and its metabolite 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline, on the efficacy of fluvoxamine therapy. This effect was also shown using the results of genotyping. The results of genotyping also showed the existence of a difference in the safety index in patients with different genotypes from the polymorphic marker CYP2D6 1846G>A.
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Effect of indapamide/perindopril fixed-dose combination on 24-hour blood pressure and cognitive functions in treatment-naive middle-aged patients with essential arterial hypertension
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01.01.2018 |
Ostroumova T.
Parfenov V.
Ostroumova O.
Borisova E.
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Nevrologiya, Neiropsikhiatriya, Psikhosomatika |
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© Ima-Press Publishing House. All rights reserved. Objective: to investigate the effect of indapamide/perindopril fixed-dose combination (FC) on 24-hour blood pressure (BP) and cognitive functions in antihypertensive treatment-naive middle-aged patients with uncomplicated grade 1-2 essential arterial hypertension (EAH). Patients and methods. The open prospective study enrolled 25 patients (9 men and 16 women) aged 40-59 years with a diastolic BP of 90-109 mm Hg and/or a systolic BP of 140-179 mm Hg, as evidenced by routine measurements. As starting antihypertensive therapy, the patients received indapamide 1.25/perindopril 5 mg FC once daily in the morning; if necessary, after 2 weeks (if the routine blood pressure was ≥140/90 mm Hg) they took indapamide 2.5/perindopril 10 mg once daily in the morning. The follow-up period was 14-16 weeks. Before and at the end of the follow-up, the patients underwent 24-hour ambulatory BP monitoring (ABPM) and evaluation of cognitive functions using the Montreal Cognitive Assessment (MoCA), ten-words test (immediate and delayed word recall), verbal association test (literal and categorical associations), number connecting test (Trail making test (TMT), part A and numbers and letters connecting test (TMT) part B), and Stroop test. Results. At the end of the follow-up period, treatment with indapamide/perindopril fixed-dose combination showed a statistically significant reduction in BPs, as evidenced by routine measurements and ABPM (during 24-hour, and awake and sleep periods); a statistically significant cognitive improvement: an increase in the number of the so-called words in the ten-words test during both immediate (from 5.5±1.6 6.5±1.5 words; p=0.02 vs baseline) and delayed (from 6.2±1.7 to 7.4±1.4 words; p=vs baseline) recalls, a decrease in the performance time of TMT-B (from 112.6±42.5 to 90.4±28.4 sec; p=0.02) and Stroop test Part 3 (from 135.5±50.1 to 112.6±19.6 sec; p=0.02), and a larger number of called words in the categorical associations test (from 6.5±2.4 to 8.1±2.9 words; p=0.02). Conclusion. The results obtained indicate that in treatment-naive middle-aged patients with EAH, indapamide/perindopril fixed-dose combination assures an effective reduction in BPs, as evidenced by routine measurements and ABPM, also improves cognitive functions, particularly attention, information processing speed, semantic memory, cognitive flexibility, and short-term and long-term memory.
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