Репозиторий Университета

© 2018 2018 Walter de Gruyter GmbH, Berlin/Boston. Calcium drugs are analogs of endogenous substances. The baseline concentration of endogenous substances in the body and homeostasis mechanisms of regulation make the bioavailability and bioequivalence (BE) evaluation of these drugs very difficult. The aim of the study was to assess the pharmacokinetic parameters of calcium in the studies of comparative bioavailability combined with the assessment of homeostatic regulation mechanisms. The study included 42 healthy male volunteers. We studied the composition of 1000 and 1200 mg of calcium, and 800 and 1000 IU of cholecalciferol. Blood sampling was carried out at 8 a.m. and 0.5, 1, 2, 3, 4, 6, 8 h after administering the drugs. Calcium pharmacokinetic parameters were measured: the area under the curve (AUC) "concentration-time", and maximum concentration (Cmax) in volunteers. The excretion of calcium in urine in terms of creatinine clearance and parathyroid hormone (PTH) levels was assessed. The maximum excretion of calcium was converted to creatinine (calcium/creatinine). Enzyme-linked immunosorbent assay (ELISA) was used to determine the PTH and the o-cresolphthalein method to quantitatively measure the total calcium serum and urine. Results indicated that both the AUC and the excretion of calcium are comparable, and the differences are not statistically significant, p>0.05 (the ratio of calcium and creatinine in the urine maintained within physiological levels). The comparable dynamics of PTH concentration is an indirect measure of the amount of absorbed calcium. The study demonstrates that, along with the standard way of calculating the area under the curve "concentration-time" (total calcium in serum), it is important to assess the calcium excretion in urine in terms of creatinine excretion, as well as focusing on the changes in the PTH levels in volunteers, which could be considered as a marker of the calcium level in the blood.

© 2018 Elsevier Ltd  Rod cell membranes contain cholesterol-rich detergent-resistant membrane (DRM) rafts, which accumulate visual cascade proteins as well as proteins involved in regulation of phototransduction such as rhodopsin kinase and guanylate cyclases. Caveolin-1 is the major integral component of DRMs, possessing scaffolding and regulatory activities towards various signaling proteins. In this study, photoreceptor Ca 2+ -binding proteins recoverin, NCS1, GCAP1, and GCAP2, belonging to neuronal calcium sensor (NCS) family, were recognized as novel caveolin-1 interacting partners. All four NCS proteins co-fractionate with caveolin-1 in DRMs, isolated from illuminated bovine rod outer segments. According to pull-down assay, surface plasmon resonance spectroscopy and isothermal titration calorimetry data, they are capable of high-affinity binding to either N-terminal fragment of caveolin-1 (1–101), or its short scaffolding domain (81–101) via a novel structural site. In recoverin this site is localized in C-terminal domain in proximity to the third EF-hand motif and composed of aromatic amino acids conserved among NCS proteins. Remarkably, the binding of NCS proteins to caveolin-1 occurs only in the absence of calcium, which is in agreement with higher accessibility of the caveolin-1 binding site in their Ca 2+ -free forms. Consistently, the presence of caveolin-1 produces no effect on regulatory activity of Ca 2+ -saturated recoverin or NCS1 towards rhodopsin kinase, but upregulates GCAP2, which potentiates guanylate cyclase activity being in Ca 2+ -free conformation. In addition, the interaction with caveolin-1 decreases cooperativity and augments affinity of Ca2 + binding to recoverin apparently by facilitating exposure of its myristoyl group. We suggest that at low calcium NCS proteins are compartmentalized in photoreceptor rafts via binding to caveolin-1, which may enhance their activity or ensure their faster responses on Ca 2+ -signals thereby maintaining efficient phototransduction recovery and light adaptation.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Issues pertaining to determination of the pharmacokinetic parameters of calcium preparations are examined using their comparative bioavailability as an example. Pharmacokinetic parameters of calcium such as area under the concentration—time curve (AUC) and maximum concentration (Cmax) are calculated considering the background calcium contents in volunteers. Calcium excretion with urine is assessed as clearance of creatinine, a calcium elimination factor. The dynamics of the content of parathormone (PTH), the main hormone regulating calcium homeostasis, are studied. The results can be used to plan clinical trials for assessing the pharmacokinetics of drug analogs of endogenous compounds.

© 2018 Izdatel'stvo Meditsina. All rights reserved. Results of studying the comparative bioavailability of pharmaceutical preparations - alternative analogs of endogenous compounds containing calcium and colecalciferol are presented. The drug concentrations were recalculated with allowance for the endogenous calcium level, in accordance with the relevant normative guidelines. The standard methodology of bioequivalence studies can be used to evaluate the quality of reproduced calcium preparations, taking into account low values of intra-individual variability of pharmacokinetic parameters.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: Arterial hypertension (AH) is one of the most common and socially significant diseases worldwide. Despite years of experience gained in studying hypertension, the problems concerning selection of antihypertensive therapy with pleiotropic organ-protecting effects are still of current importance. The purpose of the study was to assess therapeutic efficacy and pleiotropic organ-protective capability of third-generation calcium antagonist lercanidipine in patients with stage 2-3 hypertension. Method: Our study enrolled a total of ninety-two 31-to-84-year-old patients. Of these, 72 patients diagnosed as having stage 2 or 3 AH composed the Study Group and 20 apparently healthy subjects were included into the Control Group. At baseline and after 6 months, all patients of the Study Group underwent examinations consisting in measuring biochemical parameters [total cholesterol (TCH), triglycerides (TG), low-density lipoprotein cholesterol (LDL CH), uric acid, urea, creatinine, glucose], 24-hour ambulatory BP monitoring, echocardiography (EchoCG) in order to assess the dimensions and volume of the cardiac chambers, thickness of the left ventricular posterior wall (LVPW) and left-ventricular myocardium mass index (LVMMI), studying microalbuminuria (MAU), a known marker of endothelial dysfunction and early renal lesion; assessing the state of the vascular wall by the ankle-brachial index (ABI) and pulse pressure (PP). Antihypertensive therapy consisted in lercanidipine alone taken at a dose of 10-20 mg/day, failure to thereby achieve the target BP level was followed by additionally prescribing an angiotensin converting enzyme (ACE) inhibitor, enalapril, given at a dose of 5-20 mg twice daily. Results: All patients by the end of the study achieved the target level of AP (p<0.05), also demonstrating significantly improved (p<0.01) parameters of endothelial dysfunction and an early marker of renal damage (MAU), indices of elastic properties of the vascular wall ABI (p<0.05) and PP (p=0.01). Significantly positive dynamics was observed for the following parameters: decreased creatinine concentration (p<0.001), increased GFR (p<0.001), decreased levels of TCH (p<0.01) and LDL CH (p<0.001). Conclusion: Lercanidipine therapy of patients with stage 2-3 AH proved highly efficient, well tolerated, metabolically neutral with pleiotropic organ-protecting properties in the form of improved condition of the vascular wall, correction of endothelial dysfunction, nephroprotective action.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. A calcium deficiency is detected in more than 80% of children. This is the result of inadequate consumption of milk and dairy products which are the main food sources of calcium. There is a correlation between deficiency of calcium intake with food in childhood and the risk of osteopenia and osteoporosis in subsequent life periods. With insufficient exogenous intake of calcium, its concentration in the blood decreases which stimulates bone resorption. The factors that further limit the consumption of dairy products are lactase deficiency and cow's milk protein allergy. In order to ensure the intake of the necessary amount of calcium, it is advisable to use vitaminmineral complexes in children that contain not only a sufficient amount of calcium and Vitamin D but also other micronutrients required for bone formation.

© 2018 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved. Aim. To evaluate the prevalence of arterial hypertension (AH) in heart transplant recipients, and its influence on the risk of adverse events, as the efficacy and safety of antihypertension medications (AHM). Material and methods. To the study, were consequently included all heart transplant recipients operated in the Shumakov Centre during the years 2013 to 2016 and survived 90 days after orthotopic heart transplantation. Results. Totally, 353 recipients included, with AH or AHM intake in anamnesis in 62 (17,6%). Within 90 days post surgery, AH that demanded for medication therapy was found in 151 (42,8%) patients. In posttransplant AH patients there were the following specific parameters in preoperational period: higher body mass index - 25,7±4,1 vs 24,9±4,4 (р=0,026), blood creatinine concentration - 100,6±62,6 vs 68,8±4,8 (р<0,001), donor heart posterior wall thickness - 11,9±0,8 vs 11,3±0,7 (р=0,034), creatinine concentration in 3 month after operation - 131,7±101,6 vs 94,1±46,5 (p<0,001). There was relation revealed, of AH development risk with anamnesis of AH and renal failure, as a necessity for renal replacement therapy within 30 days post surgery and episodes of acute antibody-mediated reaction on transplant. In the recipients taking angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEi/ARB) before operation, the survival rate free from adverse events was better than in those taking calcium channel blockers (CCB) (plog-rank=0,042). Conclusion. The results of the study point on high prevalence of AH in heart recipients. Presence of AH in anamnesis, renal failure, episodes of humoral, but not cellular, reaction to the transplant, and donor heart hypertrophy do significantly increase the probability of AH development after transplantation. Comparison revealed significant benefit of ACEi/ ARB versus CCB as antihypertension medications in either monotherapy or in combination with diuretics.

© 2018 Ima-Press Publishing House. All rights reserved. Rheumatoid arthritis (RA) and the use of glucocorticoids (GCs) are proven risk factors for osteoporosis (OP) and osteoporotic fractures (OPF). There are also other reasons for increased fracture risk in RA. Objective: to determine the rate of RA in an epidemiological sample of persons aged 50 years and older and to identify those in need of antiosteoporotic therapy among the patients with RA in order to prevent OPF. Subjects and methods. The epidemiological sample included 18,018 people aged 50 years and older (13,941 women and 4,077 men; mean age, 62±10 years). The survey consisted of a unified questionnaire, measurement of daily dietary calcium intake, and calculation of a 10-year fracture risk using the FRAX® algorithm. Results and discussion. The prevalence of RA in the epidemiological population sample aged 50 years and older was 1.7% (1.9% in women and 1.2% in men; p=0.0047). The mean FRAX® values for major OPF in RA patients were significantly higher than those in non-RA individuals: 18.4±10 and 13.2±7.9%, respectively (p=0.0001) for women and 8.9±6.4 and 6.2±3.7%, respectively (p=0.0001) for men. 42% of the patients with RA were at high risk for OPF. Thus, 48% of the women with RA had FRAX® values above the therapeutic intervention threshold; and the non-RA group needed antiosteoporotic therapy significantly less (31%; p=0.00001). At the same time, the detection rate of high-risk OPF in men with and without RA did not differ significantly (8 and 5%, respectively; p>0.05). The most common risk factors (RFs) for OP and OPF in RA patients included previous fractures (33%), secondary causes of OP (30%), GC use (18%), and, additionally, smoking (33%) in male patients with RA. The female patients with RA significantly more frequently took GCs (17%) and had other secondary causes of OP and OPF (33%) than those without RA (7.7% (p=0.0001) and 23% (p=0.0004, respectively). The male patients with RA versus to the population-based control showed significant differences when they only used GCs (20 and 5%, respectively; p = 0.0001); the remaining RFs were encountered at the same frequency. Less than half of the normal daily calcium intake was observed in 20% of men and 16% of women (p=0.53). Conclusion. 42% of the RA patients aged 50 years and older were at high risk for OPF and needed antiosteoporotic therapy. Every third woman with RA had at least one other comorbidity or condition associated with the increased risk of OPF. In the male patients with RA, the FRAX® algorithm could reveal only 8% of persons at high risk for fractures, while 58% of them had two or more additional RFs that can negatively affect bone mineral density and increase the risk of fracture. To identify those who require prevention and treatment of OP and OPF, it is preferable to perform bone densitometry of the axial skeleton among male patients with RA.

© 2018 Ima-Press Publishing House. Objective: to compare the efficacy of methotrexate (MTX) and colchicine in patients with chronic arthritis in calcium pyrophosphate crystal deposition disease (CPPDD). Subjects and methods. Data from a controlled prospective cross-sectional study of 10 patients (8 women and 2 men) with chronic arthritis in CPPDD are presented. In the initial period of treatment, all the patients were given colchicine 1 mg/day for 3 months, followed by a wash-out period for 1 month and then subcutaneous MTX 20 mg/week for 3 months. The diagnosis of CPPDD was made if there were calcium pyrophosphate crystals in synovial fluid and signs of chondrocalcinosis, as evidenced by joint X-ray and/or ultrasonography. DAS44, the swollen joint count (SJC) and tender joint count (TJC), pain intensity on a visual analog scale (VAS), the Health Assessment Questionnaire (HAQ) index, and serum C-reactive protein (CRP) levels were determined in all the patients at baseline, 3 months after the beginning of treatment with colchicine, after a wash-out period, and 3 months after the beginning of MTX treatment. Results and discussion. At baseline, mean DAS44 value was 2.47}0.27; SJC and TJC were 2.0}0.6 and 2.4}1.1, respectively; pain intensity was 55.2}12.3 mm; serum CRP level-3.89}3.82 mg/l; HAQ-1.1}0.3. Three months after colchicine therapy initiation, mean DAS44 value decreased to 1.76}0.28 (p = 0.004), SJC-to 1.4}0.5 (p = 0.048), TJC-to 1.6}1.35 (p = 0.023), pain intensity-to 42.0}13.2 mm (p = 0.023), CRP level-to 3.13}2.85 mg/l (p = 0.75), HAQ-to 0.95}0.3 (p = 0.041). Good response was achieved in 7 patients after 3 months of colchicine therapy. After the wash-out period, the mean DAS44 value was 2.08}0.26; SJC and TJC-1.6}0.5 and 1.7}1.4, respectively; pain intensity-46.5}9.8 mm; CRP level-3.38}1.74 mg/l; HAQ-1.3}0.34. Following 3 months of MTX therapy, mean DAS44 value decreased to 1.39}0.45 (p = 0.027), SJC-to 0.7}0.5 (p = 0.023), TJC-to 0.6}0.5 (p = 0.007), pain intensity-to 26.0}18.97 mm (p = 0.045), CRP level-to 2.87}2.06 mg/l (p = 0.75), HAQ-to 0.8}0.6 (p = 0.045). Two of the 3 patients with an insufficient effect of colchicine achieved DAS44 remission after MTX treatment; two patients attained remission after therapy with colchicine and developed an exacerbation of the disease when this drug was replaced by MTX. Conclusion. MTX 20 mg/week is as effective as colchicine in most cases and can be the drug of choice in patients with chronic arthritis in CPPDD if colchicine therapy is ineffective.

© 2018, Nizhny Novgorod State Medical Academy. All rights reserved. The aim of the study was to investigate the morphological and metabolic features of primary hippocampal cultures formation on hydrogel films and scaffolds based on hyaluronic acid glycidyl methacrylate. Materials and Methods. Hydrogel films and scaffolds with certain architectonics were developed by micromolding technique on the basis of hyaluronic acid glycidyl methacrylate. Primary hippocampal cells obtained from C57BL/6 mouse embryos (E18) were cultured on the created constructs more than 14 days. Testing cell viability, morphometric assessment, and analysis of spontaneous calcium activity of primary hippocampal cultures were performed on day 14 of cultures development in vitro. Results. This study revealed that the material for the development of scaffolds with given architectonics is non-toxic for the nervous system cells. Dissociated hippocampal cells were actively attached to the scaffold surface and were assembled into cell conglomerates, which exhibited spontaneous calcium activity. Conclusion. Scaffolds designed on the basis of hyaluronic acid glycidyl methacrylate have a high biocompatibility with the nervous system cells. Architectonics and adhesive properties of scaffold contribute to the formation of functionally active cell conglomerates.

Проведен анализ научной литературы за период с 1991 по 2016 г., посвященной хирургической подготовке костной ткани челюстей к дентальной имплантации путем применения синтетических остеопластических материалов. Подбор научной литературы проводился в Центральной научной медицинской библиотеке, электронной медицинской библиотеке eLIBRARY.RU, а также по базе данных медицинских публикаций PubMed. В обзоре проанализированы результаты экспериментальных и клинических исследований особенностей и эффективности применения таких материалов, сроки их замещения на новообразованную костную ткань, а также эффективность применения синтетических заменителей и других видов остеопластических материалов.

Проведен анализ научной литературы за период с 1991 по 2016 г., посвященной хирургической подготовке костной ткани челюстей к дентальной имплантации путем применения синтетических остеопластических материалов. Подбор научной литературы проводился в Центральной научной медицинской библиотеке, электронной медицинской библиотеке eLIBRARY.RU, а также по базе данных медицинских публикаций PubMed. В обзоре проанализированы результаты экспериментальных и клинических исследований особенностей и эффективности применения таких материалов, сроки их замещения на новообразованную костную ткань, а также эффективность применения синтетических заменителей и других видов остеопластических материалов.