Mineral-petrochemical wallrock alteration of rocks in Bericul gold-ore deposit (Kuznetsk Alatau)

The distribution of mineral associations in near-veined zonal propylite-beresite metasomatic columns of mesothermal Bericul gold-ore deposit was analyzed. However, the polymineral composition in the inner (axial and adjacent with it rear) zones is inconsistent to the existing metasomatic column theoretical model. According to Korzhinskii metasomatic zoning theory, implied monomineral (quartz) and binary-mineral (quartz, sericite) compositions are characteristic of axial and rear zones, respectively. In common with above-mentioned facts, the zoning formation of differential component mobility is influenced by two additional factors: counter diffusion of components from fractured fluids into pores and diffusion mechanism of mass transfer it's from pores fluids into fractured of rock-fluid systems

Clinical and pathogenetic substantiation of the use of Wobenzim in the complex treatment of generalized periodontitis.

The purpose of this study was to determine the efficacy of using Wobenzim as a general therapy in the complex treatment of generalized periodontitis. 61 patients, I-II degree of severity, with tooth safety in an amount of at least 90%, without concomitant general pathology requiring treatment for the current time were examined. Comparative effectiveness of treatment was studied in 2 groups similar in all clinical indices. The main (31 people) patients, along with the symptomatic treatment received Wobenzim; control (30 people) - polytherapy (immunocorrecting, antioxidant, antimicrobial agents). As a result of the generally accepted clinical, paraclinical, immunological and biochemical studies conducted during the treatment and at long-term follow-up, it was found that the use of systemic enzyme therapy in this category of patients ensures rapid regression of the main clinical symptoms (on days 6-7), elimination of pathogenetic links of the disease more than in 90% of treated patients and the onset of remission for at least 6-12 months. It is characteristic that during the monotherapy with Wobenzim, positive results of treatment of generalized periodontitis were achieved, similar to those with the use of complex standard therapy, including administration of a number of medications with targeted action on pathogenesis mechanisms of the disease. From the position of evidence-based medicine, the expediency of replacing a broad arsenal of medicines in the complex treatment of generalized periodontitis with certain pharmacological preparations with a systemic effect is justified

Derivative based global sensitivity measures

The method of derivative based global sensitivity measures (DGSM) has recently become popular among practitioners. It has a strong link with the Morris screening method and Sobol' sensitivity indices and has several advantages over them. DGSM are very easy to implement and evaluate numerically. The computational time required for numerical evaluation of DGSM is generally much lower than that for estimation of Sobol' sensitivity indices. This paper presents a survey of recent advances in DGSM concerning lower and upper bounds on the values of Sobol' total sensitivity indices $S\_{i}^{tot}$. Using these bounds it is possible in most cases to get a good practical estimation of the values of $S\_{i}^{tot}$. Several examples are used to illustrate an application of DGSM

ВИБІР ДОПОМІЖНИХ РЕЧОВИН ДЛЯ ОТРИМАННЯ ТАБЛЕТОК L-ТРИПТОФАНУ З ТІОТРИАЗОЛІНОМ МЕТОДОМ ВОЛОГОЇ ГРАНУЛЯЦІЇ

The message 2.Influence of the excipients on pharmaco-technological parameters of L-tryptophan with thiotriazolin tablets obtained by wet granulation.The aim of the work. Creation of a new tablet with neuro psychotropic effect based on L-tryptophan and thiotriazoline. Selection of optimal excipients, study of their effect on hardness of tablets, friability, disintegration, the external appearance of coatings of L-tryptophan and thiotriazoline tablets after 6 months of storage.Materials and Methods. The active substances: L-tryptophan and thiotriazoline in a ratio of 4:1, excipients – fillers, disintegrants, binders, solubilizers). The tablets were compressed by wet granulation method. The effect of excipients on tablets containing L-tryptophan and thiotriazoline was studied according to the following parameters: hardness, friability, decomposition, external appearance of coatings after 6 months of storage.Results and Discussion. The results of analysis of variance showed that 5 % solution of HPMC have the best effect on the hardness among binders; sodium croscarmellose have the best effect among disintegrants; mixture of MCC 101+Solani amylum+ Lactose monohydrate – among fillers. Solubilizers have minimum effect on hardness of L-tryptophan with thiotriazoline.Aёrosilum have the maximum effect on friability of L-tryptophan with thiotriazoline among solubilizers; among disintegrants – Polyplasdone XL 10;The mixture of MCC 101+Solani amylum+calcium dihydrogen phosphate anhydrous have the best effect on the time of disintegration time of tablets.Sodium starch glycolate and MCC 101+Solani amylum+ basic magnesium carbonate have the best effect on the external appearance of coatings of tablets after six months of storage.Conclusions. The effect of the four groups of excipients on the hardness, friability, disintegration time, the external appearance of coatings after six months of storage of L-tryptophan with thiotriazoline tablets was studied. The following excipients were selected in order to obtain optimal composition tablets with L-tryptophan and thiotriazoline: mixture of MCC 101 + Solani amylum + basic magnesium carbonate, sodium starch glycolate, 5 % solution of HPMC 5, Aёrosilum, calcium stearate. L -tryptophan with thiotriazoline tablets were obtained in using of these excipients which meet the requirements of the SPU regarding tablets.Повідомлення 2. Вплив допоміжних речовин на фармако-технологічні показники таблеток L-триптофану з тіотриазоліном, отриманих методом вологої грануляції.Мета роботи. Cтворення нового таблеткового лікарського засобу нейропсихотропної дії на основі L-триптофану та тіотриазоліну. Підбір оптимальних допоміжних речовин (ДР), вивчення їх впливу на стійкість таблеток до роздавлювання, стираність, розпадання, зовнішній вигляд поверхні таблеток L-триптофану та тіотриазоліну після 6-ти місяців зберігання.Матеріали і методи. Діючі речовини – L-триптофан та тіотриазолін у співвідношенні 4:1, ДР (наповнювачі, розпушувачі, зв’язуючі розчини, солюбілізатори). Таблетки пресували методом вологої грануляції. Вплив ДР на таблетки, до складу яких входять L-триптофан та тіотриазолін, вивчали за такими показниками: стійкість таблеток до роздавлювання, стираність, розпадання, зовнішній вигляд поверхні таблеток після 6-ти місяців зберігання. Результати й обговорення. За результатами дисперсійного аналізу було встановлено, що на стійкість до роздавлювання серед зв’язуючих розчинів позитивний вплив має 5 % розчин ГПМЦ; серед розпушувачів – натрій кроскармелоза; серед наповнювачів – суміш МКЦ 101 + крохмаль картопляний + лактоза моногідрат. Найменший вплив на стійкість до роздавлювання таблеток L-триптофану з тіотриазоліном чинить додавання солюбілізаторів.На стираність таблеток L-триптофану з тіотриазоліном серед солюбілізаторів лідером є аеросил ; серед розпушувачів – поліплаздон ХЛ 10.При дослідженні часу розпадання таблеток найбільш значущою є суміш МКЦ 101+ крохмаль картопляний + кальцій дигідрофосфат безводний.На зовнішній вигляд поверхні таблеток після шести місяців зберігання лідерами є натрій крохмальгліколят та суміш МКЦ 101 + крохмаль картопляний + магній карбонат основний.Висновки. Вивчено вплив чотирьох груп ДР на стійкість таблеток L-триптофану з тіотриазоліном до роздавлювання, стираність, час розпадання та зовнішній вигляд поверхні через 6 місяців зберігання. З метою отримання оптимального складу таблеток з L-триптофаном та тіотриазоліном відібрано такі ДР: суміш МКЦ 101 + крохмаль картопляний + магній карбонат основний, натрій крохмальгліколят, 5 % розчин ГПМЦ 5, аеросил, кальція стеарат. При використанні саме цих ДР були отримані таблетки L-триптофану з тіотриазоліном, які відповідають вимогам ДФУ щодо таблеток

Порушення функціонування сполученої системи “відновлені тіоли – оксид азоту” при гострому порушенні мозкового кровообігу та можливі шляхи їх корекції

Experimental acute ischemic stroke was modeled by bilateral occlusion of the common carotid arteries in rats. Antioxidant system in the brain tissue was evaluated by the activity of key enzymes of thiol and disulfide indicators nitrosative stress. Simulation of acute ischemic accompanied by violation of the thiol-disulfide balance and increased nitrotyrosine levels, indicating that the development of oxidative and nitrosative stress in brain tissue. It is established that the use of thiol-containing antioxidants – Thiotriazoline and Angiolin set the highest possible ratio between the levels of reduced and oxidized thiol groups and glutathione, which indicates that the active mobilization of thioldisulfide system in the neutralization products of free-radical oxidation. Identified effects of the drugs used due to the presence in their structure of the thiol group, which contributes to the normalization of the glutathione system in conditions of oxidative stress.Экспериментальное острое нарушение мозгового кровообращения моделировали путем двусторонней окклюзии общих сонных артерий у крыс. Состояние антиоксидантной системы в мозговой ткани оценивали по активности ключевых ферментов тиол-дисульфидной системы и показателям нитрозативного стресса. Моделирование острого ишемического поражения головного мозга сопровождалось нарушением тиол-дисульфидного равновесия, повышением активности NO-синтазы и уровня нитротирозина, что свидетельствует о развитии оксидативного и нитрозативного стресса. Использование модуляторов тиол-дисульфидной системы – тиотриазолина и ангиолина позволяет установить наиболее оптимальное соотношение между уровнями восстановленной и окисленной тиольных групп и глутатиона. Это указывает на активное участие тиол-дисульфидной системы в нейтрализации продуктов свободнорадикального окисления. Выявленные эффекты препаратов объясняются наличием в их структуре тиольной группы, которая играет роль скавенджера NO и способствует ограничению цитотоксического действия нитрозативного стресса.Експериментальне гостре порушення мозкового кровообігу моделювали шляхом двосторонньої оклюзії загальних сонних артерій у щурів. Стан антиоксидантної системи в мозковій тканині оцінювали за активністю ключових ферментів тіол-дисульфідної системи та показниками нітрозативного стресу. Моделювання гострого ішемічного ураження головного мозку супроводжувалося порушенням тіолдисульфідної рівноваги, підвищенням активності NO-синтази і рівня нітротирозину, що свідчить про розвиток оксидативного та нітрозативного стресу. Використання модуляторів тіол-дисульфідної системи – тіотриазоліну й ангіоліну дозволяє встановити найбільш оптимальне співвідношення між рівнями відновленої та окисненої тіольних груп і глутатіону. Це вказує на активну участь тіол-дисульфідної системи в нейтралізації продуктів вільнорадикального окиснення. Виявлені ефекти препаратів можна пояснити наявністю в їх структурі тіольної групи, яка відіграє роль скавенджеру NO та сприяє обмеженню цитотоксичної дії нітрозативного стресу.ітрозативного стресу

REGARDING L-LYSINE 3-METHYL-1.2.4-TRIAZOLE-5-THIOACETATE STANDARDIZATION

The aim of the work. Developing the methods of standardization, including identi cation and quantitative assay, of L-lysine 3-methyl-1.2.4-triazole-5-thioacetate an active pharmaceutical ingredient (API) by physico-chemical methods. Research Methods. For identi cation of L-lysine 3-methyl-1.2.4-triazole-5-thioacetate we invited and conducted method of spectroscopic studies. During of operation we selected optimal condition for the analyses of L-lysine 3-methyl-1.2.4-triazole-5-thioacetate in different concentration. We picked up concentration for our results that absorption line must be in the UV area 238 nm. Results and Discussion. The results of the studies show that the absorption characteristic in UV area of L-lysine 3-methyl-1.2.4-triazolyl-5-thioacetate an shoulder of 238 nm. Conclusions. We developed methods to identi cation and quantitative during operation of substance. In further time we have plan to introduce methods of qualitative and quantitative analysis substance to MCQ drugs L-lysine 3-methyl-1.2.4-triazolyl-5-thioacetate

Theoretical study about L-arginine complexes formation with thiotriazolin

Brain vascular diseases are one of the leading causes of morbidity, mortality and disability of population in the industrialized countries of the world. An important element of this problem’s solution is the creation of new highly effective and safe drugs, which would lead to mortality reduction, to increase in life expectancy and quality of life. Therefore it is interesting to create a new combined drug based on L-arginine and thiotriazolin. Purpose of the study: to consider the possible structure and energy characteristics of complexes formed by L-arginine, 3-methyl-1,2,4-triazolyl-5-thioacetate (MTTA) and morpholine. Calculation method. The initial approximation to the complex geometry was obtained using molecular docking with the help of AutoDock Vina program. The obtained ternary complexes were pre-optimized by semi-empirical PM7 method with modeling the impact of the environment by COSMO method. The calculations were carried out using MOPAC2012 program. Then they were optimized by B97-D3/SVP + COSMO (Water) dispersion-corrected DFT-D with geometrical spreading correction on insufficiency of gCP basis set. A more accurate calculation of the solvation energy was conducted by SMD. The calculations by density functional method were carried out using the ORCA 3.0.3 software. Energy complex formation in solution was calculated as the difference of the Gibbs free energy of the solvated complex and its individual components. Results. Quantum chemical calculations show, that thiotriazolin and L-arginine are able to form ternary complexes, where molecules are linked by multiple hydrogen bonds. The calculation data suggest, that studied complexes are thermodynamically unstable in solution. The energies of them are positive, but rather low despite charge gain of a number of intermolecular hydrogen bonds. Finding. Based on the results of the conducted quantum-chemical study of a three components system (MTTA, morpholine, and L-arginine) it is possible to show the possibility to form ternary complexes with low stability in infinite dilute solutions. It should be noted that two negative charges are always localized in formed complexes on the deprotonated carboxyl groups. The positive charges are located either on the guanidine moiety and the a-amino group of L-arginine, or on the guanidine moiety of L-arginine and protonated molecule of morpholine. It can be expected that the strengthening of intermolecular interactions in the real solutions may result in increased stability of the complexes

Functional nitric oxide conjugate systems state/restored heart thiols of rats in modeling isadrine-pituitrin’s myocardial infarction using metabolite-tropic cardioprotector “Angiolin”

Background: According to modern researches, endothelial dysfunction (ED) is one of the primary pathogenetic elements of cardiovascular diseases (myocardial infarction [MI], ischemic heart diseases, cerebral ischemic stroke, atherosclerosis, arterial hypertension, pulmonary hypertension, heart failure, and dilated cardiomyopathy) as well as obesity, hyperlipidemia, diabetes and hyperhomocysteinemia. The aim of this work was to study the influence of potential metabolitotropic cardioprotector “Angiolin” on the parameters of conjugate systems nitric oxide (NO)/restored thiols in heart under isadrine-pituitrin MI.Methods: This study was performed on Wistar white rats weighing 190-210 g. Biochemical, immune-enzyme analysis and histoimmunechemical study were performed.Results: In histological sections of hearts of the rats receiving Angiolin in parenteral dosing 50 mg/kg 30 mins before each pituitrin injection the density of endothelial NO-synthase (NOS)-positive cells increased by 29% and the density of inducible NOS-positive cells decreased by 23.3%. In cytosolic fraction of myocardium homogenate NOS activity increased by 27%, the concentration of NO stable metabolites increased by 70% and the content of nitrosative stress marker nitrotyrosine decreased by 42% when compared with control group. At the same time in similar samples of heart homogenate the increase of restored thiol groups’ level by 53.3%, methionine - by 35.1%, cysteine - by 170% and activity of glutathione reductase - by 186% was noted. The administration of reference drug mildronate to the animals with MI in dose 100 mg/kg did not result in significant changes of the studied parameters of thiol-disulfide system and NO system of the heart when compared with control group.Conclusions: Angiolin does not influence directly on NOS in MI, but at the same time protects NO from nitrosative stress increasing restored equivalents of thiol-disulfide system

Optimization of L-tryptophan and thiotriazoline compound analysis by high-performance liquid chromatography

Introduction. An actual task of modern medicine is the development of treatment methods of the central nervous system diseases. The solution of this problem was the creation of new, more effective neuropsychotropic drug that shows pronounced antidepressant, nootropic, neuroprotective and antioxidant effects based on the fixed combination of L-tryptophan with thiotriazoline. One of the steps in creating a new drug is the standardization of active ingredients. Today, much attention is being paid to new physical-chemical methods of drugs study, including high-performance liquid chromatography (HPLC). Increasingly, the HPLC method is used for the determination of active ingredients of organic nature, both in mono-preparations and in combined dosage forms. Therefore, we have proposed the HPLC method for new combined L-tryptophan and thiotriazoline drug in order to determine active substances based on their effects. The purpose of our study is to develop a method for the simultaneous standardization of L-tryptophan and thiotriazoline in an artificial compound by high-performance liquid chromatography, in particular the selection of the mobile and stationary phase. Materials and methods. In the first stage of our work, a selection of phase and eluents was carried out for L-tryptophan and thiotriazoline model compound in a ratio of 1:1. The analysis method of thiotriazoline in the reverse phase (C 18) using the eluents, which are water-methanol compounds, was taken as a basis. Results. In the course of study, it was found that the retention volume of both tryptophan and thiotriazoline decreased, and the peak distribution coefficient increased with the number of theoretical plates with increasing content of methanol in phosphate buffer compound. Therefore, as an eluent, attention was drawn to a solution of 20% methanol with 80 % phosphate buffer. Under these conditions, the tryptophan retention volume was 15.11 ml, thiotriazoline – about 6.05 ml, the efficacy of the chromatographic column, calculated on the tryptophan peak of about 3300 theoretical plates. Findings: A highly sensitive technic was developed as part of the study for the simultaneous determination of L-tryptophan and thiotriazoline in a model mixture by HPLC (high performance liquid chromatography method, that is planned to be used in further study, was developed as a part of the study. The method is developed not only for L-tryptophan and thiotriazoline standardization in the combined drug, but also for their determination in biological fluids