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Vol 23, No 5 (2020)

Articles

Preparation and properties of fulvic acids of low-mineralized peloids

Avvakumova N.P., Krivopalova M.A., Glubokova M.N., Katunina E.E., Zhdanova A.V.

Abstract

Low-mineralized sulphide silt muds have high biological activity; they produce both local and general effects on the body. Fulvic acids (FA) are less understood components of peloids; they are difficult to study due to their high mineralization when isolated by classical methods. In this regard, it is relevant to find new methods for obtaining FA and determine their constitutional parameters. The aim of the work was to obtain fulvic acids of peloids with a low degree of mineralization and to determine some physical and chemical parameters. FA were isolated from low-mineralized sulphide silt muds using reprecipitation. Elemental analysis of FA samples was carried out with a Evro 300 CHN analyzer; IR spectra were recorded with an FSM 1201 IR Fourier spectrophotometer; molecular mass distribution was carried out by gel filtration, self-diffusion coefficients were determined with NMR with a magnetic field pulsed gradient; adsorption isotherms of water vapor were obtained in a vacuum adsorption unit. The IR spectra of the obtained FA sample contain a wide passband with a frequency of 3453 cm-1, which corresponds to vibrations of aliphatic groups, as well as stretching vibrations of hydroxyl groups. The transmission maximum with a frequency of 1634 cm-1 may reflect the stretching vibrations of the conjugated carbon - carbon and carbon - oxygen bonds of the carboxylate type.The molecular weight distribution revealed two fractions in the group of fulvic acids. The established adsorption characteristics show the high adsorption ability of FA of peloids. The proposed method helps to obtain a low-ash preparation with preservation of all structural components of the natural substance. The obtained characteristics of FA of peloids allow identification of natural substances; it contributes to the formation of the data and analytical base, which is necessary to shift fulvic acids to the category of standardized pharmaceutical preparations.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(5):3-9
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Analysis of level of leptin circulating in blood in the yakut population

Nikanorova A.A., Barashkov N.A., Nakhodkin S.S., Pshennikova V.G., Solovyev A.V., Romanov G.P., Kuzmina S.S., Sazonov N.N., Fedorova S.A.

Abstract

Relevance. Adipose tissue is considered an endocrine organ that produces several hormonally active substances, including the hormone leptin. This hormone plays a key role in regulating energy homeostasis and thermoregulation and may be involved in microevolutionary mechanisms of human adaptation to cold climates. The purpose of this work is to analyze the levels of leptin in the blood of young Yakut people living in the Republic of Sakha (Yakutia). Material and methods. The sample included Yakuts 18-30 years old with a total population of 281 people (186 women and 95 men). For each participant, the body mass index (BMI) was calculated, and the level of leptin in the blood serum was determined. Results. The average leptin level in women was 18.95±0.9 ng/ml, in men 6.57±0.88 ng/ml. In the Yakut population, previously known leptin sexual dimorphism (p<0.001) was confirmed, where women have higher levels of leptin in contrast to men. The previously known dependence of blood leptin level on BMI was also confirmed in both women (r=0.4588; p=0.0000) and men (r=0.4385; p=0.00001). Conclusions. The results complement the available data on leptin levels and their relationship to gender and BMI in various human populations.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(5):10-14
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The differential scanning calorimetry of binary systems with participation of some antifungal substances; аntifungal activity of eutectic structures

Seryakova A.N., Tkachenko M.L., Lyamin A.V., Zhnyakina L.E.

Abstract

The parameters of the invariant equilibrium points of binary systems (for a total of 19 pairs of substances) of some antimycotic substances obtained using differential scanning calorimetry and the results of preclinical testing of eutectic dispersions with respect to N. Candida albicans (ATCC 90028) and a culture resistant to antifungal azoles are presented R. Candida albicans isolated from clinical material. The belonging of the investigated binary systems to simple eutectics is established. It was found that the antifungal activity of eutectic dispersions is significantly higher than the activities of the initial components from 4 to 4 thousand times both in relation to the N. Candida albicans and in relation to its resistant form. The noted features may be useful in the clinical use of eutectic dispersions of antifungal substances as an antifungal drug delivery system for more effective achievement of therapeutic goals.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(5):15-22
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Relationship between serum metal and metalloid levels with metabolic risk markers in overweight and obese women

Tinkov A.A., Ajsuvakova O.P., Skalnaya M.G., Skalny A.V.

Abstract

The objective of the present study was to assess serum metal and metalloid levels in patients with overweight and obesity, as well as evaluation of its association with metabolic risk markers. Material and methods. A total of 82 adult women with overweight and obesity (BMI > 25), as well as 88 lean (18.5 < BMI < 25) controls were examined. Assessment of serum metal levels was performed using inductively-coupled plasma mass-spectrometry. Serum was also used for evaluation of markers of lipid and carbohydrate metabolism, as well as inflammation and oxidative stress. Results. The obtained data demonstrate that patients with obesity were characterized by at herogenic dyslipidemia, insulin resistance, systemic inflammation, as well as oxidative stress. A significant increase in alanine aminotransferase, Y-glutamyl transferase, and cholinesterase activity was observed. Serum copper and aluminium levels in overweight and obese subjects exceeded the control values by 12% and 17%, respectively. Copper concentration was also considered as a positive predictor of increased BMI (ß=0.391; p=0.008) in regression models, being also negatively interrelated with total antioxidant activity (ß=-0.322; p=0.032) and high-density lipoprotein cholesterol (ß=-0.241; p=0.024) after adjustment for anthropometric parameters. At the same time, serum vanadium (ß=-0.576; p=0.027) and chromium (ß=-0.682; p=0.036) were inversely associated with fasting glucose concentration. Zinc level was considered as the most significant predictor of total antioxidant activity (ß=0.643; p=0.003). Conclusion. Therefore, serum metal and metalloid levels in patients with obesity are associated with pathogenetic mechanisms of metabolic syndrome including insulinresistance, at herogenic dyslipidemia, inflammation, and oxidative stress.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(5):23-29
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Content of control points of the immunity sPD-1 and sPD-L1 in the blood plasma of ovarian cancer patients

Utkin D.O., Korotkova E.A., Petrikova N.A., Ermilova V.D., Khulamkhanova M.M., Kushlinsky D.N., Sokolov N.Y., Zhordania K.I., Gerstein E.S.

Abstract

Relevance. In recent years, close attention has been paid to the study of the expression of the PD-1 / PD-L1 signaling pathway in malignant tumors, including ovarian cancer (OC). The low effectiveness of the treatment of OC can be associated with various factors, including the mechanisms of the tumor escaping from the immune response through the PD-1 / PD-L1 immunity checkpoint system. Relatively recently, studies have appeared on the study of soluble forms of PD-1 and its ligands (sPD-1, sPD-L1 / 2) in the blood of cancer patients. These data are beginning to be actively used in an oncology clinic in the treatment of melanoma, renal cell carcinoma, non-small cell lung cancer. Purpose of the study. Analysis of the content of sPD-1 and sPD-L1 in the blood plasma of patients with OC, taking into account the main clinical and morphological characteristics of the disease. Material and methods. We examined 93 patients with OC, 22 with benign ovarian neoplasms, 10 with borderline ovarian tumors, and 35 with healthy women in the control group. In all, an ovarian tumor was detected for the first time and confirmed by histological examination. The concentrations of sPD-L1 and sPD-1 were determined in the blood plasma of patients and healthy women before the start of specific treatment using standard reagent kits for direct enzyme immunoassay Human PD-L1 Platinum ELISA and Human PD-1 ELISA kit (Affymetrix, eBioscience, USA) in accordance with the manufacturer's instructions. The reliability of the differences was evaluated using nonparametric tests (Mann-Whitney U-test, Kolmogorov-Smirnov type test). For all statistical tests, p values <0.05 were considered statistically significant. Results. Isolated indicators of sPD-1 and sPD-L1 in blood plasma cannot be used as diagnostic markers of OC. The sPD-1 and sPD-L1 indices are closely related to the main clinical and morphological characteristics of OC: elevated plasma concentrations of sPD-L1 in patients with OC show a statistically significant stage of the disease, are associated with criteria T and M, the presence of metastases in the greater omentum and tumor cells in swabs from the abdominal cavity. Moreover, the degree of differentiation and the histological variant of the tumor structure are not associated with the concentrations of sPD-1 and sPD-L1 in the blood plasma of patients with OC. Unlike sPD-1, sPD-L1 concentrations are directly correlated with the levels of tumor markers CA-125 and HE-4 in the blood plasma of patients with OC. Conclusion. The data presented indicate a close relationship between the levels of sPD-1 and sPD-L1 in the blood plasma of patients with OC with adverse clinical and morphological factors of the disease. Further study of the soluble forms of sPD-1 and sPD-L1 of the PD-1 / PD-L1 signaling pathway in patients with ovarian cancer will reveal their potential role as biomarkers in assessing the prognosis of the disease.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(5):30-36
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Analysis of the range of soft dosage forms for oral administration containing substances of plant origin

Zvereva V.I., Semkina O.A., Dzhavakhyan M.A.

Abstract

The purpose of the study: to study the range of soft dosage forms for oral medications administration containing substances of plant origin. Material and methods. This study used methods of content analysis, data aggregation, and comparative analysis. Data from the State register of medicinal products (GRLS) and the Russian register of medicinal products (RLS) as of February 28, 2020 were used as information bases for the study. Statistical data processing was performed using MSExcel 2016. The results of a study of the current state of pharmaceutical science in the field of creating alternative tablets and capsules for oral dosage forms showed that gels are promising for the delivery of various groups of biologically active substances for the prevention and treatment of a wide range of nosological forms. According to the State Register of Medicinal Products on the territory of the Russian Federation, two foreign-made medicines are registered in the form of a soft dosage form for oral administration: paste and paste for the preparation of a suspension for oral administration. The main group of dietary supplements for food in this category is used as a source of vitamins, micro and macro elements, as well as drugs used in the complex treatment of diseases of the urinary system, nervous system, and cardiovascular system. As the active substance of such dietary supplements to food, a complex of plant extracts is mainly used. Structuring agents that ensure the stability of the dosage form, mainly of natural and semi-synthetic origin. The leading position among the manufacturing countries of dietary supplements and drugs is Russia. Conclusion. The above information indicates the need to expand the range and increase the number of domestic drugs in the form of gels for oral administration and the undoubted relevance of this area.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(5):37-44
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Study of chemical composition of volatile substances of Podophyllum peltatum cellular culture

Kitaeva M.P., Kopytko Y.F., Fedotcheva T.A.

Abstract

Podophyllum peltatum L. is used in modern medicine as a source of obtaining podophyllin. Podophyllin is a mixture of resinous substances, lignans such as aryl tetralin, the cytostatic compound of podophyllotoxin, which is the main active component of podophyllin, as well as flavonoids (quercetin and campferol). GC-MS is an optimal tool for studying the volatile compounds that make up the P. peltatum medicinal plant material. The purpose of the research was to study the chemical composition of podophyllin resin obtained from the cell culture of P. peltatum. The objective of the study is to conduct a chemical analysis of podophyllin resin by GC-MS. The object of the study was suspension cell cultures of Podophyllum peltatum L., obtained from the fetus, kidney, and root of the plant, which are in the collection of All-Russian Scientific Research Institute of Medicinal and Aromatic Plants. GC-MS analysis of the extracts was carried out on a Varian GC-220MS chromatograph-mass spectrometer with an ion trap mass analyzer. Quantification was carried out by the method of normalization by peak area. During methanol extraction of P. peltatum, the proportion of podophyllin in % of the dry weight of the cell culture was 15.98 ± 4.82% for the kidney cell line, 12.50 ± 3.32% for the fetus, and 18.38 ± 3.16% for the root. GC-MS analysis of the extract revealed a large number of volatile compounds (233-490): nitrogen-containing substances, alkaloids, esters of fatty acids, steroids, carbohydrates, glycosides, hydrocarbons, ketones, etc.
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(5):45-53
pages 45-53 views

Cytotoxicity and toxicological characteristics of the new leukocytar polypeptide

Grishina T.A., Volkov A.G., Volkova L.V.

Abstract

The aim of the study is to assess the safety of a low molecular weight leukocyte protein-peptide complex (LPPC) at the stage of preclinical studies. The object of the study was an experimental sample of a new leukocyte protein-peptide complex (LPPK) obtained by ultrasonic treatment of human leukocytes in vitro. LPPK cytotoxicity was assessed on the cell line of pig embryonic kidney epithelial cells (SPEV) and in vitro MTT test on human tumor cell lines HCT 116 (colorectal carcinoma) and MS (melanoma). A proliferation index was used to assess the effect on the growth of cells of the leukocyte protein-peptide complex (LBPC). Experiments on the study of acute toxicity of LPPK were performed on white nonlinear mice, which were injected intraperitoneally. To assess the results used the method of determining the average lethal dose according to V. Prozorovsky. When studying cytotoxicity, it was found that the addition of an experimental sample of the leukocyte protein-peptide complex to the growth medium for culturing the SPEV cell line favorably affects cell growth. The proliferation index increased from the first to the fourth passage by 1.09 times, while in the control sample the increase in PI occurred by 1.03 times. A study of the cytotoxicity of LPPK showed that the sample did not exhibit a cytotoxic effect on tumor cells HCT 116 and MS, since the IC50 concentrations calculated for them in all cases were significantly lower than the reference drug Doxorubicin. The results of the assessment of acute toxicity in experimental animals showed that the test sample with intraperitoneal administration is low toxic according to the classification of GOST 12.1.007.-76 (LD50 3500.0 mg / kg). The article demonstrates the results of determining the toxicological and cytotoxic characteristics of the protein-peptide complex obtained from human leukocytes. It was shown that the studied protein-peptide complex did not exhibit toxic effects on the studied cell lines, as well as laboratory animals (mice).
Problems of Biological Medical and Pharmaceutical Chemistry. 2020;23(5):54-58
pages 54-58 views

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