Molecular docking, ADMET study and in vivo pharmacological research of N-(3,4-dimetoxyphenyl)-2-{[2-methyl-6-(pyridine-2-yl)-pyrimidin-4-yl]thio}acetamide as a promising anticonvulsant

The search for new anticonvulsants for epilepsy treatment with higher efficacy and better tolerability remains important. The aim of the present research was an in silico and in vivo pharmacological study of N-(3,4-dimethoxyphenyl)-2-((2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)thio)acetamide (Epirimil) as a promising anticonvulsan

The structure of mineral and bone disorders in patients with сhronic kidney disease of the 5th dialysis stage, taking into account the presence or absence of a diagnosis of type 1 diabetes mellitus

BACKGROUND: In patients with end-stage CKD, receiving renal replacement therapy (RRT) with programmed hemodialysis (HD), the severity of complications is associated with metabolic disturbances: accumulation of uremic toxins, nephrogenic anemia, secondary hyperparathyroidism (SHPT), extraskeletal calcification, impaired clearance and rhythm of hormone secretion.AIM: To evaluate the main biochemical and hormonal parameters, and manifestations of mineral bone disease (MBD) in patients receiving RRT with HD, before and after hemodialysis, taking into account the presence or absence of diabetes mellitus.MATERIALS AND METHODS: We divided all patients receiving RRT with HD in two groups: #1 (n=24) — patients with DM, #2 (n=16) — patients without DM. All of them had their blood analyzed before and immediately after the HD. Data analysis was performed with the Statistica 13 (StatSoft, USA). A prognostically significant model was considered at p<0.05.RESULTS: The level of iPTH, both at baseline and after HD, was lower in group #1 (p<0.001). The level of alkaline phosphatase (AP) was significantly higher in group #2 (p=0.012). In both groups before HD, a high incidence of hypocalcemia was detected (according to albumin-corrected calcium in group #1 in 58.3%, in group #2 in 43.7% of cases, p = 0.366) and hyperphosphatemia (in 66.7% and in 43 .7% of cases, respectively, p=0.151). Hypocalcemia after HD in group #1 persisted in 14%, in group #2 — in 20% of cases (p>0.05); hyperphosphatemia in group #1 was completely leveled, in group #2 it persisted in 7% of cases (p=0.417). Prior to the HD session, group #1 had significantly higher levels of RAGE, glucagon, immunoreactive insulin (IRI), cortisol, and glucose than after the HD session (p<0.05). In group #2, after HD, the levels of glucagon, IRI and cortisol significantly decreased (p<0.05), and the level of 3-nitrotyrosine (3-HT) increased significantly (p=0.026). In group #1, fibrocalcinosis of the heart valves according to ECHO and calcification of the arteries of the lower extremities according to ultrasonic doplerography were more common than in group #2 (42% vs 25%, p<0.001 and 75% vs 37.5%, p=0.018, respectively). (χ2)). Compression fractures occurred with the same frequency in both groups (60%). A decrease in bone mineral density (BMD) to the level of osteopenia was noted more often in group #1 (50% vs 18.8%), and osteoporosis was more common in group #2 (68.8% vs 33.3%) (p<0.001, χ2).CONCLUSION: The low level of PTH in group #1 may reflect the effect of diabetes on calcium-phosphorus metabolism. Patients with DM have an increased risk of renal osteodystrophy with a low bone turnover because of a number of metabolic factors inherent in diabetes. At the same time, the dynamics of phosphorus and calcium indicators during the HD procedure were similar

Factores de Risco para Náuseas e Vómitos no Pós-Operatório de Cirurgia Oftalmológica

Fundamentação: As náuseas e vómitos no pós-operatório são frequentes em cirurgia oftalmológica e podem ter repercussões graves. Não estão identificados os factores de risco para a sua ocorrência e desconhece-se qual a estratégia profilática mais eficaz. Objectivo: Identificar os factores de risco para náuseas e vómitos no pós-operatório em cirurgia oftalmológica e comparar a eficácia profilática das associações droperidol-metoclopramida e dexametasona-metoclopramida. Metodologia: Estudo prospectivo unicêntrico de 80 doentes sem história prévia de náuseas e vómitos no pós-operatório, propostos para cirurgia oftalmológica sob anestesia geral. Aplicou-se um questionário para caracterização demográfica, clínica e laboratorial. Todos os doentes foram submetidos a profilaxia com droperidol-metoclopramida (1,25+20mg) ou dexametasona-metoclopramida (5+20mg), segundo distribuição aleatorizada por blocos e assegurando dupla-ocultação. Resultados: Ocorreram náuseas e vómitos no pós-operatório em 17,5% dos doentes. O sistema de estratificação de risco de Apfel não identificou os doentes que desenvolveram náuseas e vómitos no pós-operatório. O risco de náuseas e vómitos no pós-operatório foi significativamente maior entre os adultos nos extremos etários (<40 anos e ≥60 anos), naqueles com menor classe de peso e nos doentes com classe ASA-I (OR: 3,36). As náuseas e vómitos no pós-operatório foram menos frequentes entre os doentes medicados com dexametasona-metoclopramida (12,8%) do que naqueles submetidos a profilaxia com droperidol-metoclopramida (22%), mas a diferença não atingiu significado estatístico. Conclusões: Os sistemas de estratificação do risco de náuseas e vómitos no pós-operatório não são aplicáveis em cirurgia oftalmológica, sendo necessários estudos em maior escala neste âmbito. É possível que a associação dexametasona-metoclopramida seja não apenas tão eficaz quanto a droperidol-metoclopramida, como eventualmente superior

Development of HPLC Method for Quantitative Determination of Epimidin - New Perspective АPhI with Anticonvulsive Activity

The aim. Development of optimal, high-precision and reproducible methods for quantitative determination of the main substance in the substance Epimidin - 1-(4-methoxyphenyl)-5-[2-[4-(4-methoxyphenyl)piperazin-1-yl]-2-oxo-ethyl]pyrazolo[3,4-d]pyrimidin-4-one by high performance liquid chromatography.Materials and methods. High performance liquid chromatography (HPLC) was performed using a ShimadzuNexeraX2 LC-30AD system (Shimadzu, Japan) equipped with a SPD-M20A diode array detector (DAD). ACE C18 column, size 250 x 4.6 mm, YMC with pre-column, particle size 5 μm, filled with octylsilyl silica gel for chromatography P. During the work acetonitrile and trifluoroacetic acid of HPLC class (Sigma-AldrichGmbH, Switzerland) were used, other chemicals and solvents were of analytical grade. In the study an analytical ware class A were used that meet the requirements of SPhU.Results. The following optimal conditions of chromatographic distribution are established: column C18 (250*4.6 mm); the speed of the mobile phase 1 ml / min; column thermostat temperature 35 °С; injection volume 10 μl; mobile phase A - 0.1 % trifluoroacetic acid; mobile phase B - acetonitrile P; the detection wavelength is 270 nm, the retention time of the test compound is 7.22 minutes. The performance of the column was determined for its main indicators, such as the number of theoretical plates (more than 25410) and the coefficient of symmetry (about 1.00). The technique was tested for the influence of various factors, such as flow rate, mobile phase composition and column thermostat temperature. It was established that the influence of these factors is insignificant and does not affect the results obtained by this method. The method was validated in accordance with the recommendations of SPhU on the parameters of specificity, linearity, correctness, precision, robustness (stability).Conclusions. For the first time, a high-precision and reproducible method for quantitative determination of the main substance in the substance Epimidin with anticonvulsant activity by high-performance liquid chromatography was developed. Conditions for chromatographic analysis (HPLC) were standardized. The requirements for the test “System suitability test criteria for chromatographic methods” are set. Statistical processing of the experimental results shows that the relative uncertainty of the average result is within acceptable limits. The correctness of the method was confirmed by validation studies. The developed technique will be used for pharmaceutical development and standardization of dosage for

Accumulation of lipophilic dications by mitochondria and cells

Lipophilic monocations can pass through phospholipid bilayers and accumulate in negatively-charged compartments such as the mitochondrial matrix, driven by the membrane potential. This property is used to visualize mitochondria, to deliver therapeutic molecules to mitochondria and to measure the membrane potential. In theory, lipophilic dications have a number of advantages over monocations for these tasks, as the double charge should lead to a far greater and more selective uptake by mitochondria, increasing their therapeutic potential. However, the double charge might also limit the movement of lipophilic dications through phospholipid bilayers and little is known about their interaction with mitochondria. To see whether lipophilic dications could be taken up by mitochondria and cells, we made a series of bistriphenylphosphonium cations comprising two triphenylphosphonium moieties linked by a 2-, 4-, 5-, 6- or 10-carbon methylene bridge. The 5-, 6- and 10-carbon dications were taken up by energized mitochondria, whereas the 2- and 4-carbon dications were not. The accumulation of the dication was greater than that of the monocation methyltriphenylphosphonium. However, the uptake of dications was only described by the Nernst equation at low levels of accumulation, and beyond a threshold membrane potential of 90–100 mV there was negligible increase in dication uptake. Interestingly, the 5- and 6-carbon dications were not accumulated by cells, due to lack of permeation through the plasma membrane. These findings indicate that conjugating compounds to dications offers only a minor increase over monocations in delivery to mitochondria. Instead, this suggests that it may be possible to form dications within mitochondria that then remain within the cell