[The role of phytates in human nutrition].

Claims that consumption of phytate-rich grains, by definition, worsens mineral status needs to be clarified as new evidence emerges about the role of phytic acids (FA) from whole grains in improving population health outcomes. In this regard, it seems appropriate to draw the attention of practitioners to the need to correct patient's diet in order to prevent non-communicable diseases. The aim of this review was to generalize and analyze the modern data on the role of phytates in human nutrition. Material and methods. A search for domestic and foreign literature in the bibliographic databases of articles on medical sciences was carried out using the PubMed, MEDLINE and eLibrary search engines. Results. Deficit of minerals and trace elements in the diet, especially deficiency of iron, calcium, selenium, zinc, iodine, is an urgent public health problem in many countries. Calcium, magnesium, zinc, selenium, and iron deficiencies are associated with impaired immune function and an increased risk of both acute and chronic diseases. Vegan and vegetarian behavior styles with the restriction and exclusion of animal sources of bioavailable minerals and trace elements are gaining more and more popularity in our country. FA is the main storage form of phosphorus in nuts, grains, legumes, and seeds, which satisfies the biosynthesis needs of growing tissues during germination. FA is known as a dietary inhibitor that chelates minerals and trace elements, limiting their bioavailability and reducing their absorption. Pre-treatment methods to reduce phytate levels and increase the nutritional value of diets are fermentation, soaking, and sprouting. Reducing phytate content in plant foods by processing leads to a measurable improvement in mineral status, however, the chelating and antioxidant properties of phytates may be beneficial and their potential in the prevention of cancer, cardiovascular disease, diabetes mellitus and kidney stone formation is currently being studied. Conclusion. Essential components of a healthy diet are whole whole grains, legumes, vegetables, seeds and nuts, despite the fact that most of them are relatively high in FA. Despite some antinutrient properties, FAs have preventive effects on public health.

[Social jetlag: possibilities of micronutrient support].

The concept of social jetlag refers to asynchronous communication of a person's biological clock with tempo of modern living, which occurs mainly as a result of intensive work. At the core of social jetlag is sleep deprivation or chronic sleep restriction caused by social factors: pervasive use of electronic solutions and networks, intensive round the clock operation, chronic diseases. The aim of the work was to determine vitamins, minerals, and other micronutrients, the availability of which is important for supporting the organism in case of circadian rhythm sleep disorders and sleep restrictions, the so-called social jetlag. Material and methods. The analysis of 78 sources from PubMed and Google Scholar bibliographic bases was carried out with a detailed analysis of data from the published studies. Results. Circadian rhythm sleep disorders and sleep restrictions affects cognitive functions, increasing risk of anxiety and depressive disorders, enhances processes of chronic inflammation, oxidative stress, cardiometabolic disorders. Scientific evidence has been collected that lack of such elements as magnesium, folates, omega-3 polyunsaturated fatty acids and probiotics in diet can worsening effects of social jetlag and increase the risk of chronic diseases. Preventive course intake of this micronutrients is reasonable in people predisposed to social jetlag. Conclusion. In risk groups of people predisposed to social jetlag, along with diverse diet and adequate nutrition, sleep hygiene, it is necessary to provide targeted supplementation with magnesium, folates, omega-3 polyunsaturated fatty acids and probiotic products.

[Prospects of probiotic strains of bifidobacteria and enterococcus in treatment and prevention of diseases in gastroenterology].

Variability of the intestinal microbiota has been under close scientific study in recent years; more and more studies confirm specific changes in microbiota under certain pathologies. Enterococcus faecium and Bifidobacterium longum strains are naturally occurring symbiotic bacteria that inhabit the gastrointestinal tract. The safety and efficacy profile of bifidobacteria, widely used as probiotics, has been thoroughly studied. Deviations in species composition, diversity, and relative abundance have been reported for some diseases. The aim of the research was to substantiate the need and to study the prospects for the inclusion of probiotics strains of bifidobacteria and enterococci in the complex therapy of gastroenterological diseases. Material and methods. The data from MEDLINE and PubMed-NCBI bibliographic databases have been analyzed in this review. Results and discussion. The published data indicate the positive effect of bifidobacteria on human health, starting from a direct effect inside the gastrointestinal tract, moving to modulating the immune system and, in general, the systemic effect of probiotics on the organism by changing the level of various mediators. Probiotic strains of Enterococcus faecium contribute to the preservation and growth of endogenous species of bifidobacteria and lactobacilli. Additional intake, as well as stimulation of the growth and activity of probiotic strains in the intestine can be considered as a potential approach to combating foodborne intestinal pathogens, to the treatment of lactase deficiency and irritable bowel syndrome. Conclusion. The inclusion of probiotics in the complex therapy of lactase deficiency, irritable bowel syndrome, as well as antibiotic-associated diarrhea is pathogenetically substantiated.

[Iatrogenic deficits of micronutrients].

Long-term use of certain drugs causes subclinical and clinically significant micronutrient deficiencies, which can affect the course of the disease, its prognosis, quality of life, and patient compliance with therapy. The aim of the study was to single out groups of drugs, which long-term use leads to micronutrient deficiency, and to determine vitamins, minerals and trace elements, which supply can be reduced as a result of pharmacotherapy, basing on the analysis of data published in the scientific literature. Material and methods. This review analyzes articles on medical sciences from MEDLINE and PubMed-NCBI bibliographic databases. Results. Combined oral contraceptives reduce woman's supply with B vitamins (B6, B12, B9), can cause hypomagnesemia, affect the calcium/magnesium blood ratio, reduce the amount of vitamin E circulating in blood. Proton pump inhibitors reduce the absorption of vitamin B12, calcium, magnesium, iron, zinc. Aspirin increases ascorbic acid metabolism. Loop diuretics increase urinary excretion of calcium, magnesium, thiamine, thiazide ones elevate zinc and vitamin B9 excretion. Loss of taste when taking captopril is associated with a decrease in zinc supply. The use of calcium channel blockers interfere with the absorption of folic acid by gingival fibroblasts. Conclusion. Given the growing prevalence of long-term drug use, it is necessary to be able to predict and prevent potential consequences of interactions with micronutrients. It is advisable, along with a varied and healthy diet, to provide patients with supplementation in order to prevent micronutrient deficiencies. Optimization of vitamin status of the population in terms of its significance for public health is comparable to drug therapy and is one of the technologies for reducing losses from chronic diseases.

[Role of tomatoes and products thereof in human healthy diet].

Tomatoes are an essential part of the diet. Epidemiological studies have established a link between the consumption of tomatoes, which contain carotenoids, and a reduction in the risk of diseases such as cancer and cardiovascular diseases. Ripe tomato fruits are dark red in color due to the carotenoid lycopene, which is synthesized during fruit ripening. The aim of this review was to summarize and analyze modern data on the role of tomatoes and their processed products in healthy human nutrition. Results. The beneficial effects of this vegetable on bone health, cognitive function, and the cardiovascular system have been studied. However, large intervention studies are needed to confirm a real causal relationship between tomato consumption and the risk of these diseases. Given the presence of various useful bioactive components in tomatoes, the results of most studies provide a reason to include more tomatoes and their processed products in the diet. However, both excessive and regular consumption of this vegetable can cause some side effects in the human body. Conclusion. Recent studies highlight the relationship between tomato consumption and a reduced risk of various diseases such as obesity, hypercholesterolemia, cardiovascular disease and cancer. Tomatoes, thanks to the bioactive substances they contain, with an adequate level of consumption, can become effective component of a healthy diet.

[The importance of nuts in the prevention of various diseases].

Nuts are rich in unsaturated fatty acids, protein, dietary fiber, a number of micronutrients and biologically active substances. The aim of this review is to summarize and analyze current data on the role of nuts in human nutrition. Results. Large prospective cohort studies show an association between regular consumption of nuts (>= 140 g per week) and a reduced risk of coronary heart disease. In randomized controlled trials, strong evidence has been obtained that consuming nuts lowers blood cholesterol and improves glycemic control in patients with type 2 diabetes. Recent epidemiological studies show that high nut consumption does not increase body weight; rather, the inclusion of nuts in the hypocaloric diet can help to control or reduce body weight and waist circumference. A meta-analysis of prospective cohort studies shows that nut consumption is associated with a reduced risk of death from all causes and from chronic diseases. "Nut snack" is a good strategy to avoid weight gain and improve chemical composition of the diet. Conclusion. Adequate replacement of some foods in the diet with nuts does not cause body weight increase and helps to prevent a number of diseases.

Significance of L-carnitine in internal medicine.

The review presents the results of a number of experimental and clinical studies proving the prospects of using L-carnitine in the clinic of internal diseases. Due to the antioxidant and antihypoxant properties, the additional use of L-carnitine in addition to the main etiopathogenetic therapy is prescribed by cardiologists, nephrologists, neurologists, gerontologists. Experimental studies we conducted earlier showed no effect of L-carnitine on the activity of the P450 CYP 3A4 system, which reduces the likelihood of drug-drug interaction at the level of metabolism of drugs metabolized by P450 3A4. When using L-carnitine as part of complex pharmacotherapy, the drug has an increased safety profile in comorbid patients taking L-carnitine. Keywords: L-carnitine, P450 CYP 3А4, chronic heart failure, myocardial infarction, chronic renal failure, inter-drug interaction, antioxidant, antihypoxant.

[Long-chain ω-3 polyunsaturated fatty acids in the prevention of diseases in adults and children: a view of the clinical pharmacologist].

Adequate and balanced intake of ω-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) is important throughout life, and directly affects health status: from preconception and pregnancy to the prevention of various diseases. Russia geographically belongs to regions with a low level of consumption of eicosapentaenoic and docosahexaenoic acids. In addition, gender characteristics and genetic polymorphisms underlie the variability of the synthesis of ω-3 LCPUFA in the human organism from alpha-linolenic acid. ω-3 LCPUFA play one of the key roles in the human organism: they regulate lipid metabolism, have a positive effect on cognitive functions, have anti-inflammatory activity, and contribute to the prolongation of pregnancy. ω-3 LCPUFA should be ingested in sufficient quantities, since they are essential nutrients, be in the form of release, provide high compliance for admission and be balanced in content of EPA and DHA.

[Enzymatic activity of recombinant metallopeptidase for further using in meat industry].

Enzymatic modification of meat with a high content of connective tissue is an effective mean, allowing to improve its properties and expand its use. Microbial enzymes have been extensively investigated as meat tenderizers. Compliance with safety requirements in terms of forecasting the development of various risks is essential for the use of these enzymes in food industry. The method of producing recombinant protease as a potential candidate for applications on meat tenderization was described in the article. The aim of this study was the production of recombinant Pichia pastoris with M9 peptidase gene from Aeromonas salmonicida. Material and methods. Objects: peptidase gene M9 (GenBank: CP000644.1 ASA_3723) Aeromonas salmonicida (strain of laboratory collection, isolated from the surface of raw meat), the vector plasmid pPic9K, competent E. coli DH5α cells, competent Pichia pastoris GS115 cells, culture fluid (QOL) from recombinant Pichia pastoris clones, beef shank samples. To obtain a recombinant strain, genetic engineering methods, the PCR method, and the bacteriological method were used. Polyacrylamide gel electrophoresis was used to separate and analyze the components of the supernatant. Enzyme activity was evaluated by HPLC-MS/MS using synthesized peptides. The impact of the supernatant from recombinant clones on the connective tissue of raw meat was assessed by histological method. Results and discussion. A metalloprotease M9 gene was cloned from the Aeromonas salmonicida (2748 bp) and expressed in Pichia pastoris. The molecular mass of the recombinant protein was estimated to be 120 kDa by SDS-PAGE. Histological analyses of the control and enzyme treated beef samples showed degradation intramuscular connective tissue, suggesting its effectiveness on meat tenderization. Conclusion. The recombinant strain Pichia pastoris, which produces the recombinant M9 peptide of Aeromonas salmonicida, has a specific enzymatic activity against collagen, the main component of the connective tissue of meat. The obtained recombinant peptidase M9 can be used as an enzyme softener of raw meat with a high content of connective tissue.

[Lipoic acid: physiological role and prospects for clinical application].

α-Lipoic acid (also known as thioctic acid) is a natural vitamin-like compound. Lipoic acid contains asymmetrical carbon, which causes the presence of two possible optical isomers (enantiomers): R-lipoic acid (levogyrate isomer) and S-lipoic acid (rightspinning isomer). Lipoic acid functions as a cofactor for several important mitochondrial multienzyme complexes, enhances the uptake of glucose by the cells, and modulates the activity of various signaling molecules and transcription factors. It was shown that α-lipoic acid and its derivative, dihydrolipoic acid, have a direct antioxidant effect due to the neutralization of reactive oxygen species that are destructive to DNA, proteins and lipids of cells. Dihydrolipoic acid enhances the antioxidant properties of ascorbic acid, glutathione and ubiquinone. Available evidence suggests that supplementation with lipoic acid reduces the symptoms of peripheral diabetic neuropathy. Results from randomized controlled trials show that high doses of lipoic acid can improve the glycemic profile of subjects with metabolic disorders. Lipoic acid can be used to control body weight in people with obesity. R-Lipoic acid is synthesized in the human body and is contained in foods in a form covalently associated with lysine (lipoyllysine). Its dose in dietary supplements significantly exceeds the amount in the diet. Most dietary supplements contain a racemic mixture of R- and S-lipoic acid.

[S-methylmethionin (vitamin U): experimental studies and clinical perspective].

Vitamin-like compound S-methyl-L-methionine (SMM, historically called vitamin U) is a metabolic agent, affects metabolic processes, which causes a wide variety of effects. The data of the studies demonstrating gastroprotective effect, hypolipidemic and antioxidant effect, participation in regulation of adipocyte function, homocysteine exchange are presented. SMM is involved in all methylation reactions in which another activated form of methionine, S-adenosylmethionine, normally participates. The results of the observed studies indicate a possible expansion of the clinical use of S-methylmethionine.

Taurine modulates catalytic activity of cytochrome P450 3A4.

The influence of the biologically active compound taurine on the stability and catalytic properties of the hemoprotein cytochrome P450 3A4 has been investigated. The catalytic properties were analyzed by electrochemical methods (cyclic and square-wave voltammetry) using cytochrome P450 3A4 immobilized on the electrode. Taurine at concentrations in the range 10-70 µM stimulated the electrochemical reduction of cytochrome P450 3A4, and the reduction was the highest (115 ± 3%) in the presence of 50 µM taurine. Taurine pronouncedly attenuated the itraconazol-caused inhibition of the P450 isoenzyme P450 3A4. Taurine protected cytochrome P450 3A4 due to stabilizing it during electrolysis at controlled voltage in the presence of erythromycin as a substrate. This protection was manifested by an increase in the amount of the "residual" reduced form of the hemoprotein (52 ± 5 and 71 ± 8%, respectively).

[Role of ascorbic acid and tocopherol in the prevention and treatment of diseases from the standpoint of evidence-based medicine].

The role of vitamin C and vitamin E in the prevention and treatment of diseases is analyzed from the standpoint of evidence-based medicine. The high provision of a patient with the vitamins has a therapeutic and preventive impact on the development and course of a number of diseases. Furthermore, when additionally prescribing the vitamins as part of combination therapy, it is necessary to take into account possible drug interactions, including those due to the inducing effect of the above antioxidants on cytochrome P450 3A4.

[A relationship between analgesic and neurotropic effects by the example of milgamma].

Combined vitamin preparations containing thiamine (vitamin B1), pyridoxine (vitamin B6), and cyanocobalamin (vitamin B12) are widely used in medical practice. The results of investigations have confirmed that it is expedient to potentiate an analgesic effect due to the concurrent use of vitamin B group and nonsteroidal anti-inflammatory drugs given to relieve significant neuropathic pain. Milgamma compositum (Wörwag Pharma, Germany) is one of the most studied drugs on the Russian market, which contains a combination of vitamin B group (including benfotiamin).

[Modeling of drug-drug interactions between omeprazole and erythromycin with cytochrome P450 3A4 in vitro assay]. / Modelirovanie mezhlekarstvennogo vzaimodeistviia omeprazola i éritromitsina s ispol'zovaniem tsitokhrom R450-zavisimoi sistemy in vitro.

In the present study the electrochemical system based on recombinant cytochrome P450 3A4 (CYP3A4) was used for the investigation of potential drug-drug interaction between medicinal preparations employed for Helicobacter pylori eradication therapy. Drug interactions were demonstrated in association of omeprazole as a proton pump inhibitor (PPI) and macrolide antibiotic erythromycin during cytochrome P450 3A4-mediated metabolism. It was shown that in the presence of omeprazole the rate of N-demethylase activity of CYP3A4 to erythromycin measured by means of product (formaldehyde) formation decreased. Mass-spectrometry analysis of omeprazole sulfone as a CYP3A4-mediated metabolite demonstrated the absence of erythromycin influence on CYP3A4-dependent omeprazole metabolism. This phenomenon may be explained by lower spectral dissociation constant of CYP3A4-omeprazole complex (Kd = 18±2 µM) than that of CYP3A4-erythromycin complex (Kd = 52 µM). Using the electrochemical model of electrochemically-driven drug metabolism it is possible to register CYP3A4-mediated catalytic conversion of certain drugs. In vitro experiments of potential CYP3A4-mediated drug-drug interactions are in accordance with in silico modeling with program PASS and PoSMNA descriptors in the case of omeprazole/erythromycin combinations.

[Prospects of application of acetyl-L-carnitine in neurology and psychiatry (the treatment of polyneuropathy and depressive states)]. / Perspektivy primeneniia atsetil-L-karnitina v nevrologii i psikhiatrii (terapiia polineiropatii i depressivnykh sostoianii).

Acetyl-L-carnitine (ALA) is a biologically active form of L-carnitine, which is a readily available substrate for triggering energy-dependent metabolic processes in the mitochondria. The mechanism of the protective effect of ALA on brain tissue is a significant reduction in the amount of oxygen consumed for energy supply of the needs of the nervous system. ALA also has antioxidant and antiapoptotic activity. In addition, ALK plays a neuromodulating effect on both synaptic morphology and synaptic transmission. The similarity in structure with acetylcholine allows to have a cholinomimetic effect, as well as to show neuroprotective and neurotrophic properties. ALK has an antidepressant and analgesic effect in painful neuropathies. Therefore, ALA is a promising drug for the treatment of polyneuropathy of various origins. Compared with antidepressants efficacy and a minimum of side effects open up wide possibilities of using ALA in the treatment of depression with a low risk of developing NLR.

[Role of antioxidants in electro catalytic activity of cytochrome P450 3A4].

The electrochemical analysis of cytochrome Р450 3А4 catalytic activity has shown that vitamins C, A and Е influence on electron transfer and Fe3+/Fe2+ reduction process of cytochrome Р450 3А4. These data allow to assume possibility of cross effects and interference of vitamins-antioxidants with drugs metabolised by cytochrome Р450 3А4, at carrying out of complex therapy. This class of vitamins shows antioxidant properties that lead to increase of the cathodic current corresponding to heme reduction of this functionally significant haemoprotein. Ascorbic acid of 0.028-0.56 mM concentration stimulates cathodic peak (an electrochemical signal) of cytochrome Р450 3А4. At the presence of diclofenac (Voltaren) - a typical substrate of cytochrome Р450 3А4 - the increase growth of a catalytic current testifying to an electrocatalysis and stimulating action of ascorbic acid is observed. In the presence of vitamins A and Е also is registered dose-dependent (in a range of 10-100 M) increase in a catalytic current of cytochrome Р450 3А4: the maximum increase corresponds to 229 ± 20% for 100 M of vitamin A, and 162±10% for 100 M of vitamin E. Vitamin E in the presence of P450's inhibitor itraconazole doesn't give essential increase in a reductive current, unlike retinol (vitamin A). This effect can manifest substrate properties of tocopherol (vitamin E). The electrochemical approach for the analysis of catalytic activity of cytochrome Р450 3А4 and studies of influence of biologically active compounds on an electrocatalysis is the sensitive and effective sensor approach, allowing to use low concentration of protein on an electrode (till 10-15 mol/electrode), to carry out the analysis without participation of protein redox partners, and to reveal drug-drug or drug-vitamins interaction in pre-clinical experiments.

[The influence of vitamin B group on monooxygenase activity of cytochrome P450 3A4: pharmacokinetics and electro analysis of catalytic properties].

It was shown that vitamin B group permit to shorten the longitude of diclofenak therapy and to reduce the daytime dose of this drug. All three schemes of diclofenac treatment - only diclofenac, diclofenac plus 2 tablets of Gitagamp (mixture of vitamin B group), and diclofenac plus 4 tablets of Gitagamp--gave maximum value of diclofenal in blood through 1 hour after treatment. In the case of diclofenak treatment without vitamins Cmax corresponds to 1137.2 +/- 82.4 ng/ml, with 2 tablets of Gitagamp--Cmax 1326.7 +/- 122.5 ng/ml, and with 4 tablets--Cmax 2200.4 +/- 111.3 ng/ml. Positive influence of vitamin B group on the decrease of pain syndrome was shown. Pharmacodynamics and pharmacokinetics data were confirmed in electrochemical experiments with cytochrome P450 3A4. For enzyme immobilization screen printed graphite electrodes modified with gold nanoparticles and synthetic membrane-like compound didodecyldimethylammonium bromide (DDAB/Au) were used. Electrochemical analysis reviled the influence of vitamin B group on metabolism of non steroid anti inflammation drug diclofenac catalyzed by cytochrome P450 3A4. Riboflavin was the most effective inhibitor of diclofenac hydroxylation by cytochrome P450 3A4 as was compared at 300 M concentration of vitamin B group (B1, B2, B6). These data confirmed the opportunity of pharmacokinetic parameters regulation and the level of pharmacodynamic effects by the influence of vitamin B group on the catalytic activity of cytochrome P450 3A4.