UHPLC-ESI-QqTOF Analysis and In Vitro Rumen Fermentation for Exploiting Fagus sylvatica Leaf in Ruminant Diet

In recent years, animal husbandry has aimed at improving the conditions of livestock animals useful for humans to solve environmental and health problems. The formulation of animal feeds or supplements based on antioxidant plant compounds is considered a valuable approach and an alternative for livestock productivity. Forest biomass materials are an underestimated source of polyphenolic compounds whose sustainable recovery could provide direct benefits to animals and, indirectly, human nutrition. In this context, an alcohol extract from leaves of Fagus sylvatica L. was first investigated through an untargeted ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) approach. Then, it was fractionated into a fatty acid-rich and a polyphenolic fraction, as evidenced by total lipid, phenol, and flavonoid content assays, with antiradical and reducing activity positively correlated to the latter. When tested in vitro with rumen liquor to evaluate changes in the fermentative parameters, a significant detrimental effect was exerted by the lipid-rich fraction, whereas the flavonoid-rich one positively modulated the production of volatile fatty acids (i.e., acetate, butyrate, propionate, etc.)

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

Dependence of anticonvulsant activity of 1-aryl-1, 5-dihydro-4H-pyrazole (3,4-d) pyrimidine-4-one derivatives on biopharmaceutical factors

Background: We have synthesized three 5-R-1-aryl-1,5-dihydro-4Н-pyrazole(3,4-d)pyrimidine-4-one derivatives that previously have demonstrated powerful anticonvulsant activity. A great number of physicochemical factors are known to influence on bioavailability and stability of active pharmaceutical ingredients. Therefore the purpose of research was to determine the effect of purification technology and dispersibility of 5-R-1-aryl-1, 5-dihydro-4Н-pyrazole (3,4-d) pyrimidine-4-one derivatives on their anticonvulsant activity.Methods: The anticonvulsant effect of this compounds was studied in a model of pentylenetetrazole-induced seizure in mice.Results: The results obtained revealed the optimal solvent for recrystallization of compounds to be isopropanol: compounds, purified by recrystallization from isopropanol, had higher solubility in water and tween; also, they had a tendency to increase anticonvulsant activity. It was found that there is a significant dependence of the latter on compound’s dispersion - the smaller the size of crystals the higher anticonvulsant activity.Conclusions: The dependence of anticonvulsant activity of compounds on the degree of dispersion was proved: the smaller particle size the higher anticonvulsant activity. This can be explained by fast dissolution of fine-dispersed substances, thus increasing the bioavailability if the compounds studied

Risks of osteoporosis in women with hyperthyroidism

The article deals the probability of osteoporosis in women with a history of thyrotoxicosis, as well as the correlation with risk factors such as early menopause and hypodynamy.В тексте статьи рассмотрена вероятность развития остеопороза у женщин, перенесших тиреотоксикоз в анамнезе. Также были выявлены корреляционные связи с такими факторами риска, как ранняя менопауза и гиподинамия

Технико-экономический прогноз при выборе оптимальной технологии использования биомассы и местных ископаемых топлив для производства тепловой и электрической энергии

The paper provides a technical and economic analysis pertaining to selection of optimum biomass and local fossil fuel application technology for thermal electric energy generation while using a matrix of costs and a method of minimum value. Calculation results give grounds to assert that it is expedient to burn in the boiling layer – 69 % and 31 % of wood pellets and wastes, respectively and 54 % of peat and 46 % of slate stones. A steam and gas unit (SGU) can fully operate on peat. Taking into account reorientation on decentralized power supply and increase of small power plants up to 3–5 MW the paper specifies variants of the most efficient technologies for burning biomass and local fossil fuels. Проведен технико-экономический анализ выбора оптимальной технологии использования биомассы и местных ископаемых топлив для производства тепловой и электрической энергии с использованием матрицы затрат и метода минимальной стоимости. Результаты расчетов дают основание утверждать, что в кипящем слое целесообразно сжигать 69 % древесных гранул и 31 % древесных отходов, а также 54 % торфа, 46 % сланцев. ПГУ может полностью работать на торфе.С учетом переориентации на децентрализованное энергоснабжение и увеличение количества малых энергетических установок до 3–5 МВт отмечены варианты наиболее эффективных технологий сжигания биомассы и местных ископаемых топлив

Синтез, протимікробна активність та докінгові дослідження 6-(1H-бензімідазол-2- іл)-5-метилтієно[2,3-d]піримідин-4(3H)-онів з ацетамідними та 1,2,4-оксадіазол-5- ілметильними замісниками

Aim. To synthesize, study the antimicrobial activity and suggest antimicrobial activity mechanism for the novel derivatives of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-one. Results and discussion. As the result of the targeted modification of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]-pyrimidin-4(3H)-one in position 3 with acetamide and 1,2,4-oxadiazol-5-ylmethyl substituents, the compounds, which demonstrated better antimicrobial activity in the agar well diffusion assay than the reference drug Streptomycin, were obtained. To elucidate the mechanism of action of the novel compounds, the docking studies were con-ducted to the active site of the 16S subunit of ribosomal RNA, the proven target for aminoglycoside antibiotics, as well as tRNA (Guanine37-N1)-methyltransferase (TrmD), which inhibitors were considered as a new potential class of antibiotics. Experimental part. By the interaction of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-one with a series of N-arylchloroacetamides and 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles in DMF in the presence of K2CO3 the target compounds were obtained. The antimicrobial activity was assessed by the agar well diffusion method. The concentration of microbial cells was determined by the McFarland standard; the value was 107 cells in 1 mL of the media. The 18 – 24 hour culture of microorganisms was used for tests. For the bacteria cultivation, Müller-Hinton agar was used, Sabouraud agar was applied for C. albicans cultivation. The compounds were tested as the DMSO solution with the concentration of 100 µg/mL; the volume of the solution was 0.3 mL, the same volume was used for Streptomycin (the concentration 30 µg/mL). The docking studies were performed using Autodock Vina. Crystallographic data for the complexes of Streptomycin with the 16S subunit of ribosomal RNA (1NTB) and its active site, as well as for tRNA (Guanine37-N1)-methyltransferase (EC 2.1.1.228; TrmD) (5ZHN) and its active site were obtained from the Protein Data Bank.Conclusions. It has been determined that 2-[6-(1H-benzimidazol-2-yl)-5-methyl-4-oxothieno[2,3-d]pyrimidin-3(4H)-yl]-N-[4-(ethoxy)phenyl]acetamide, which is the most active as an antimicrobial agent among the compounds tested, also shows the best binding activity towards the active site of tRNA (guanine37-N1)-methyltransferase.Мета. Синтезувати й дослідити протимікробну активність нових похідних 6-(1H-бензімідазол-2-іл)-5-метилтієно[2,3-d]піримідин-4(3H)-онів та запропонувати механізм протимікробної активності.Результати та їх обговорення. У результаті цілеспрямованої модифікації положення 3 6-(1H-бензімідазол-2-іл)-5-метилтієно[2,3-d]піримідин-4(3H)-ону ацетамідним та 1,2,4-оксадіазол-5-ілметильним замісниками було одержано сполуки з визначеною методом дифузії в агар протимікробною активністю, що є більшою за активність препарату порівняння Стрептоміцину. З метою з’ясування механізму дії синтезованих сполук було проведено докінгові дослідження щодо активного сайту субодиниці 16S рибосомальної РНК, яка є підтвердженою мішенню для аміноглікозидних антибіотиків, а також тРНК (Гуанін-37-N1)-метилтрансферази (TrmD), інгібітори якої розглядаються як новий потенційний клас антибіотиків. Експериментальна частина. Шляхом взаємодії 6-(1H-бензімідазол-2-іл)-5-метилтієно[2,3-d]піримідин-4(3H)-ону з рядом N-арилхлороацетамідів та 3-арил-5-(хлорометил)-1,2,4-оксадіазолів в умовах ДМФА-K2CO3 було одержано цільові сполуки. Антимікробну активність визначали методом дифузії в агар. Концентрацію мікробних клітин визначали за МакФарландом; мікробне навантаження склало 107 мікробних одиниць в 1 мл середовища. Для тестів використовували 18 – 24 годинну культуру мікроорганізмів. Для культивування бактерій використовували агар Мюллера-Гінтона; для культивування C. albicans використовували агар Сабуро. Сполуки вводили методом дифузії в агар (лунками) у вигляді розчину у ДМСО в концентрації 100 мкг/мл в об’ємі 0,3 мл; аналогічний об’єм використовували для Стрептоміцину (конц. 30 мкг/мл). Докінгові дослідження проводили за допомогою програми Autodock Vina. Кристалографічні дані для комплексів стрептоміцину з 16S субодиницею рибосомальної РНК (1NTB) та її активного сайту і для тРНК (Гуанін-37-N1)-метилтрансферази (EC 2.1.1.228; TrmD) (5ZHN) та її активного сайту було отримано з Protein Data Bank.Висновки. Виявлено, що сполука 2-[6-(1H-бензімідазол-2-іл)-5-метил-4-оксотієно[2,3-d]піримідин-3(4H)-іл]-N-[4-(етокси)феніл]ацетамід, яка характеризується найбільшою протимікробною активністю, у докінгових розрахунках є також найбільш ефективним інгібітором тРНК (Гуанін-37-N1)-метилтрансферази

Molecular docking studies of N-substituted 4-methoxy-6-oxo-1-aryl-pyridazine-3-carboxamide derivatives as potential modulators of glutamate receptors

In the present study, the affinity of pyridazine derivatives for the most promising antiparkinsonian biotargets - I-III groups of metabotropic and ionotropic NMDA-glutamate receptors - was evaluate

Simultaneous pancreas‐kidney transplantation in type 1 diabetes mellitus. Clinical options

Simultaneous pancreas-kidney transplantation (SPKT) is the most promising treatment option for patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease (ESRD) due to diabetic nephropathy (DN). Successful SPKT eliminates uremic intoxication and hyperglycemia – the leading trigger of vascular diabetic complications. Therefore, euglycemia is an important metabolic change in patients after surgery and remains only one of the factors for the saved renal allograft functioning. In the case of resuming renal replacement therapy by dialysis after SPKT, the management and monitoring of the pancreatic graft remains open. Special attention to the pancreatic graft’s function is due to both the potential risk of surgical complications, and some probability of T1DM relapse with the need to resume insulin therapy. In patients with saved function of both transplants, the assessment of the dynamics of diabetic complications in general becomes more important. The results of few studies in this regard remain contradictory. Thus, clinical options can be unpredictably diverse and require not only search for the root cause, but also optimization of rehabilitation tactics, even if the expected results are achieved