Effect of crystalline and amorphic phenol on characteristics of peptidases and glycosidases in chironomid larvae

The effects of crystalline and amorphous phenol (0.5 mmol/L) on the characteristics of glycosidases, as well as casein-lytic and hemoglobin-lytic peptidases, which function in the whole body of chironomid larvae Chironomus sp. were studied. Crystalline phenol decreased the activity of glycosidases in comparison to the control in the temperature range 0–50 ºС, amorphous phenol – in the temperature range 0–70 ºС. The temperature optimum of glycosidases in whole body of chironomid larvae in control and experiment corresponds to 50 ºС. The activity of glycosidases in comparison to the control decreased in the pH range 5–11 (to a greater extent in the case of the lower fraction). Amorphous phenol increased the activity of casein-lytic peptidases in comparison to the control in the temperature range of 30–50 ºС, hemoglobin-lytic peptidases – in the temperature range of 0–60 ºС. The degree of the increase of enzyme activity in the temperature optimum zone of casein-lytic and hemoglobin-lytic peptidases was different: the level of enzyme activity in the experiment was higher than in the control by 2.3 and 1.8 times, respectively. The temperature optimum of the studied peptidases of chironomid larvae, regardless of the experimental conditions, corresponds to 40 °C. Crystalline phenol did not actually affect the Q10 values of glycosidases in the temperature range 0–50 °C. Amorphous phenol decreased the Q10 values at a temperature of 40–50 °C. The Q10 values of casein-lytic peptidases increased in most cases, the Q10 values of hemoglobin-lytic peptidases decreased in the presence of amorphous phenol. The process of protein hydrolysis was characterized by a break in the Arrhenius plot at 20 °C. The values of Еact in the range 0–20 °С were lower than in the zone of higher temperatures. The Еact values of the process of casein hydrolysis by peptidases of all tissues of chironomid larvae in the presence of amorphous phenol in both temperature zones increased. The Еact values of the process of hemoglobin hydrolysis by peptidases of all tissues of chironomid larvae in the presence of amorphous phenol in both temperature zones decreased. The Еact values of the process of starch hydrolysis in the presence of crystalline phenol decreased. The amorphous phenol changed the Еact values in different directions. They slightly increased in the presence of the phenol upper fraction, but they decreased in the presence of the phenol lower fraction. The data obtained indicate a significant effect of crystalline and amorphous phenol not only on activity, but also on the characteristics of peptidases and glycosidases that function in the whole body of chironomid larvae

NMR as Used in the Russian and Foreign Pharmacopoeias for Quality Control of Medicinal Products

The ongoing development of the Pharmacopoeia of the Eurasian Economic Union and the current trend for harmonisation of the Russian Pharmacopoeia with the world leading pharmacopoeias suggest the necessity of studying how different pharmacopoeias use nuclear magnetic resonance (NMR) for quality control of medicinal products. The aim of the study was to compare the extent of medicine quality characteristics assessed by NMR in the Russian and foreign pharmacopoeias. The review summarises the experience of various national and world pharmacopoeias in using the NMR method for quality control of medicines and certification of pharmacopoeial reference materials. The comparative analysis covered the following quality parameters: active ingredient identification, determination of the composition of non-stoichiometric compounds, determination of the average polymer chain length in polymers and block copolymers, determination of the absolute content of the active ingredient, identification and quantification of impurities, polymorphism, and crystallinity. It was shown that the United States and Japanese Pharmacopoeias are leading the way in introducing the NMR method into pharmacopoeial analysis. There have been some positive trends in the introduction of the NMR method in the State Pharmacopoeia of the Russian Federation as well. It was concluded that changes are needed in the general chapters “Nuclear Magnetic Resonance Spectroscopy” and “Reference Standards” of the State Pharmacopoeia of the Russian Federation, 14th ed. in order to harmonise the texts with those of the Eurasian Pharmacopoeia and the European Pharmacopoeia and to allow for the possibility of direct identification of a substance by complex analysis of NMR spectral data, without comparing the test sample and the reference standard spectra. The NMR method should be included in the list of absolute methods used for determination of purity of primary chemical reference substances during certification

Carcinogenic and Non-Carcinogenic Health Risks Assessment of Elemental Contaminants in <I>Laminariae thalli</I>

Scientific relevance. Laminariae thalli are a native herbal preparation used to prevent or treat multiple diseases. To achieve the optimal effect, this herbal preparation is usually taken for several weeks or months. The control of Laminariae thalli should extend beyond the element content in the herbal drug limited by specifications; additionally, it is important to assess the health risks of ingesting heavy metals with the medicinal product during the exposure period.Aim. The study aimed to assess the carcinogenic and non-carcinogenic risks of consuming elemental contaminants with therapeutic doses of herbal medicinal products based on Laminariae thalli.Materials and methods. The study investigated the content of elemental contaminants (Al, As, Cd, Cr, Co, Cu, Fe, Hg, Mn, Mo, Ni, Se, Pb, Sr, V, and Zn) in Laminaria saccharina and Laminaria japonica. The content of inorganic arsenic was determined by solid-phase extraction using inductively coupled plasma mass spectrometry (ICP-MS).Results. When averaged at the 90th percentile level, the mean concentrations of the specified elements did not exceed the limits for seaweed and seagrass foods. The total hazard index from exposure to all analysed elements amounted to 0.173 at the median level and 0.616 at the 90th percentile level. The leading contributors to the total hazard index were As, Fe, Cd, and Sr. The individual carcinogenic risk (CR) values for the potential carcinogens (As, Cd, Pb, and Cr) fell within the range of 1×10-6&lt;CR&lt;1×10-4.Conclusions. If the elements analysed are ingested with a daily therapeutic dose of Laminariae thalli for the exposure period, their total negative effect will not cause harm to the human body. To eliminate the risk of developing neoplasms when the studied medicinal product (Laminariae thalli) is taken at its maximum recommended therapeutic dose for a month or more, the Cr content should be controlled along with the elements limited by specifications for herbal medicines

Determination of Heavy Metals, Arsenic, and Aluminum Content in Pumpkin Seed Herbal Substance and Native Products, by Inductively Coupled Plasma Mass Spectrometry

Pumpkin seeds belong to the so-called native products. Their characteristic feature is that they can be consumed directly, without prior extraction of the starting material. All elemental toxicants contained in pumpkin seeds are transferred in full to the native product. Therefore, it is important to study specific aspects of elemental toxicant accumulation by pumpkin seeds.The aim of the study was to determine the content of heavy metals, As, and Al in pumpkin seed herbal substance and native products, and to assess the degree of accumulation of these elements, depending on the vegetation area.Materials and methods: the study evaluated pumpkin seed native products by Russian manufacturers as well as pumpkin seeds harvested in areas with different anthropogenic load. The sample preparation was performed by microwave digestion, and the determination of the elemental toxicants was perfomed by inductively coupled plasma mass spectrometry.Results: the pumpkin seeds were shown to contain essential, probably essential, potentially toxic, and toxic elements. The authors performed comparative analysis of the elemental composition of pumpkin seeds as well as seeds, grains, and beans of various oil-bearing, grain, and leguminous crops.Conclusions: the content of the specified elemental toxicants (As, Cd, Hg, Pb) in the tested samples of pumpkin seed herbal substance and herbal medicinal products did not exceed the limits established by the Russian Pharmacopoeia. The unspecified toxic elements were either absent in pumpkin seeds (Tl) or found in trace amounts (Al). The content of a number of essential elements (Zn, Fe, Mn, Cu, Mo, Cr) in pumpkin seeds was higher than in the seeds of many oil-bearing crops. The vegetation area had no significant influence on the content of the tested elements in the pumpkin seeds. Pumpkin seeds are capable of accumulating abnormally high amounts of Cd, Co, and Ni in areas with high environmental pollution

Diffusion-Ordered NMR Spectroscopy Application for Analysis of Polysaccharides

Diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY) is a molecular transport method in analytical chemistry, based on experimental recording of the molecules’ translational mobility at thermodinamic equilibrium in a solution. The translational mobility is characterised quantitatively by a self-diffusion coefficient. The aim of the study was to summarise the main trends in application of DOSY for the analysis of natural and modified natural polysaccharides used in pharmaceuticals and pharmaceutical biotechnology. The review shows that this method is an effective instrument for monitoring fractionation during isolation of polysaccharides from a natural mixture, for estimating their average molecular weight and molecular weight distribution, and for studying the formation of supramolecular systems based on polysaccharides. The paper describes main issues of the precise measurement of polysaccharide macromolecules self-diffusion coefficients and provides the correction factors to compensate for errors caused by fluctuations in temperature and viscosity of solutions. The observed scatter of self-diffusion coefficients of narrowly dispersed polymer macromolecules nuclei is explained using the polyphase concept. The paper illustrates ways of describing translational mobility of a polyphase polymer macromolecule as a whole. The authors summarise values of the gradient pulse sequence parameters used in quantitative measurements of self-diffusion coefficients of linear, low-branched, and branched polysaccharides

The Content of Heavy Metals, Arsenic, and Aluminum in Mint Leaves and Products

Mint is a medicinal herbal drug; and its leaves are also widely used in the food and cosmetic industries. Medical literature states that mint is naturally resistant to toxic elements and capable of accumulating them in significant amounts. The aim of the study was to compare heavy metals, arsenic, and aluminum contents in mint leaves and products. Materials and methods: the study covered peppermint leaves, tinctures, and oils, as well as teas and dietary supplements made of different varieties of mint. Elemental analysis was performed according to the procedure of inductively coupled plasma mass spectrometry (ICP-MS) developed by the authors. Results: the authors studied the compliance of the experimentally established contents of heavy metals, arsenic, and aluminum in peppermint leaves and products to the requirements of Russian and foreign regulatory documentation. Nonparametric Spearman correlation coefficients were calculated to characterise the interaction between chemical elements. Conclusions: arsenic contents in mint leaves may exceed the limit given in the State Pharmacopoeia of the Russian Federation, 14th ed. It is supposed that the increased contents are not a result of the anthropogenic factor, but a specific characteristic of this plant. The study demonstrated synergistic absorption of aluminum, iron, and vanadium, as well as copper and zinc by mint. It was established that manganese had an antagonistic effect on the absorption of nickel, lead, and cobalt by mint

Determination of zinc content in insulin products by inductively coupled plasma mass spectrometry

Scientific relevance. Zinc content is a quality attribute of insulin products. The State Pharmacopoeia of the Russian Federation requires that it should be determined by flame atomic absorption spectrometry (FAAS). However, many pharmaceutical manufacturers currently prefer inductively coupled plasma mass spectrometry (ICP-MS), which is considered the most promising method for pharmaceutical and biomedical elemental analysis.Aim. The study aimed to develop and validate an ICP-MS-based analytical procedure for zinc content determination in insulin products.Materials and methods. The study focused on human insulin, insulin lispro, insulin aspart, and insulin glargine in the form of active substances, suspensions for subcutaneous injection, and solutions for injection from different manufacturers. Zinc content was determined on an Agilent 7900 ICP-MS; the analysis included 66Zn signal intensity registration.Results. The study compared the results of zinc content determination in test samples with either hydrochloric or nitric acid used as the solvent for sample preparation. The authors selected the experimental conditions to achieve relative standard deviations (RSDs) of not more than 2.5% for the measurements. The ICP-MSbased analytical procedure was validated for its specificity, linearity, accuracy, and precision in the range of 0.4–1.6 mg/L. The authors compared the measurements of zinc content made using FAAS and ICP-MS.Conclusions. The ICP-MS-based analytical procedure for zinc content determination in insulin products meets the validation criteria. This analytical procedure, as developed and validated, may be used in the quality control of medicinal products in the Russian healthcare system and at the batch release stage of pharmaceutical manufacturing

Temperature characteristics of peptidase in chironomid larvae, potential fish prey, at various pH values

The temperature dependence of casein- and hemoglobinlytic peptidases functioning in the whole organism of chironomid larvae Chironomus plumosus, food objects of adult benthophages and juvenile fish of various ecological groups, was studied within the temperature range of 0–70 ºС at different рН values (3.0, 5.0 and 7.4). The method of mixed samples was used to determine the activity and characteristics of enzymes. Homogenates of previously crushed and carefully mixed dozens of larvae were used as enzymatically active preparations. Activity of peptidases was assayed by the increase in tyrosine concentration using the Folin-Ciocalteu reagent. It is shown that the activity of peptidases that function in the tissues of chironomid larvae depends to a considerable extent on temperature and рН, but the pH has a smaller effect on the activity and the temperature dependence of casein- and hemoglobin-lytic peptidases than temperature. The temperature optimum of the studied peptidases of chironomid larvae corresponds to 40 ºС. The Q10 values in the zone of vital temperatures are slightly changed. They are, as a rule, increased in the zone of 30–40 ºС, and are sharply decreased in the zone of high temperatures. The values of activation energy of the process of hydrolysis of casein and hemoglobin in the zone of low and high temperatures are different. The Еact values of the process of hydrolysis of casein and hemoglobin at a temperature not exceeding 20 ºС are usually below those in the zone of higher temperatures (except for hemoglobin-lytic peptidases at pH 5.0). The data obtained indicate a significant effect of pH not only on the activity, but also on the temperature characteristics of peptidases that function in the body of chironomid larvae. Differences in the characteristics of casein- and hemoglobin-lytic peptidases in chironomid larvae at different temperatures and pH can influence the digestion in benthophages and fry of all fish species

Экономический механизм и моделирование денежных потоков при обратном ипотечном кредитовании

The research is devoted to the economic mechanism of reverse mortgage —  a credit product aimed at improving the standard of living of senior citizens, owners of real estate. The idea of the reverse mortgage has been given, as well as the mechanisms of use of real estate owned by senior citizens in order to provide them with additional income. The examples of reverse mortgage in the uS, the uK, Spain and Australia have been given. The authors have also described the methods of reverse mortgage lending in Russia. Based on the analysis of international experience, the economic expediency of investing in this credit tool has been assessed. Considering consumer demand factor, it is possible to calculate the equilibrium rate and, therefore, to find the coordinates of the market equilibrium point. The authors have developed a mathematical model of reverse mortgage for the case of lifetime annuity payments. This model allows to calculate the expected benefits of borrowers and lenders. There have been done (and implemented) two notes that significantly distinguish reverse mortgage modeling from other loan products: 1) a lifetime reverse mortgage does not have a fixed expiration date; 2) when taking a loan of this type, borrowers consider not only consumption, but also accumulation of inheritance. The model allows to calculate the position of break-even points and market equilibrium (relative to the interest rate). This will help economically interested agents to assess the potential of the reverse mortgage market in Russia.Исследуется экономический механизм обратной ипотеки —  кредитного продукта, направленного на повышение уровня жизни граждан преклонного возраста, являющихся владельцами недвижимости. Изложена суть операции обратного ипотечного кредитования, принципы действия механизмов использования принадлежащих пожилым людям объектов недвижимости для обеспечения им дополнительного дохода. Приведены примеры использования системы обратного ипотечного кредитования в США, Великобритании, Испании и Австралии. Авторы описывают существующие методики обратного ипотечного кредитования в России. На основе анализа опыта зарубежных стран дана оценка экономической целесообразности вложения денежных средств в данный кредитный инструмент. С учетом фактора потребительского спроса имеется возможность рассчитать равновесную ставку —  следовательно, найти координаты точки рыночного равновесия. Разработана математическая модель обратной ипотеки для случая с пожизненными аннуитетными платежами. Данная модель позволяет рассчитать ожидаемые выгоды заемщиков и кредиторов. Сделано (и реализовано в модели) два примечания, которые значительно отличают моделирование обратной ипотеки от других кредитных продуктов: 1) пожизненный обратный ипотечный кредит не имеет фиксированного срока окончания; 2) при взятии кредита такого типа заемщики рассматривают мотив не только потребления, но и накопления наследства. В результате построена модель, позволяющая рассчитать положение точек безубыточности и рыночного равновесия (относительно процентной ставки). Это поможет экономически заинтересованным агентам оценить потенциал рынка обратного ипотечного кредитования в России

NMR Spectroscopy Study of the Effect of the Molecular Mass of Hypromellose Phthalate on Its Solubility

Scientific relevance. Hypromellose phthalate is used in enteric coatings for oral medicinal products. The proportion of phthalate groups in the polymer is standardised because it has a significant effect on solubility. Whereas, the molecular mass of hypromellose phthalate is not controlled, and its impact on solubility in media with different pH values is understudied.Aim. The study aimed to employ NMR spectroscopy to investigate the effect the molecular mass of hypromellose phthalate may have on the dissolution kinetics at the pH value declared by the polymer manufacturer.Materials and methods. The study analysed hypromellose phthalate isolated from proton-pump inhibitor enteric coatings and the hypromellose phthalate reference standard. The molecular mass of the polymer was estimated by diffusion-ordered NMR spectroscopy (DOSY) with polyethylene glycols of known molecular masses for calibration. The authors studied the dissolution profiles of hypromellose phthalates of different molecular masses using 1H NMR spectra.Results. The authors developed a procedure for estimating the average molecular mass of hypromellose phthalate by DOSY. The procedure showed variations in the molecular mass of the polymer in the test samples; the molecular mass scatter amounted to 10 kDa. The dissolution profile of the test samples in an aqueous buffer solution (pH 5.59) was described by a linear function during the first hour. The slope characterising the dissolution rate varied from 10° to 36°.Conclusions. The variation in the molecular mass of hypromellose phthalate significantly affects the dissolution rate of the test samples. The function of the dissolution rate against the molecular mass of hypromellose phthalate is non-linear. The article provides a compelling reason for further research to derive a correlation equation for the dissolution rate of hypromellose phthalate as a function of two variables (molecular mass and proportion of phthalate groups in the polymer)