Effect of carnosine and α-lipoic acid on hepatocyte apoptosis and the cytokine profile in induced fatty liver disease in Wistar rats
Non-alcoholic fatty liver disease (NAFLD) is now a common liver disease affecting about a third of the world’s population. In this regard, the issue of studying the pathogenetic factors of the development of this disease in order to select adequate drug therapy and biologically active substances with antioxidant properties regulating the balance of pro- and anti-inflammatory cytokines is of particular relevance.
The aim of the study was to assess the effect of minor biologically active substances - carnosine and α-lipoic acid on hepatocyte apoptosis and the cytokine profile in the experimental model of the initial stage of NAFLD.
Material and methods. The studies were performed on male Wistar rats with initial body weight of 150±10 g. Animals were divided into 5 groups of 8 rats each. Within 8 weeks, rats of the 1st group (control) received a complete modified diet AIN93M, in which soybean oil was replaced with sunflower oil and lard (1:1). Rats of the experimental groups consumed high-calorie choline-deficient diet (HCCDD), in which fat content was 45%, fructose content - 20% of the energy value of the diet. Rats of the 2nd group were fed HCCDD without any supplements, the 3rd group - with the addition of carnosine (75 mg/kg body weight), the 4th group - with the addition of α-lipoic acid (75 mg/kg body weight), the 5th group - with the addition of carnosine and α-lipoic acid in a total dose of 150 mg/kg body weight. The study of rat hepatocyte apoptosis was performed by flow cytometry. Hepatocytes were stained with annexin V and vital dye 7-aminoactinomycin, followed by detection on an flow cytometer. The content of cytokines and chemokines (IL-1α, IL-10, IL-17А, M-CSF, MIP-1α, MIP-3α, RANTES) in the cytoplasmic fraction of liver tissue was determined by multiplex immunoassay.
Results and discussion. On the model of the initial stage of development of NAFLD in male Wistar rats the еnrichment of HCCDD with carnosine and α-lipoic acid had demonstrated a protective effect on hepatocytes with a decrease in apoptosis intensity to the level in control rats. Under the influence of HCCDD, an increase in the content of M-CSF and MIP-1α and a decrease in the levels of MIP-3α and RANTES, stimulating the migration and differentiation of various immunoregulatory populations to the parenchyma at an early stage of the formation of fatty hepatosis, in the cytoplasmic fraction of liver tissue were detected. Moreover, a decrease in the level of proinflammatory cytokines IL-17A and IL-1α and an increase in IL-10 produced mainly by Treg-populations indicate the absence of pronounced inflammatory changes in the liver of male Wistar rats at the initial stages of development of fatty dystrophy.
Conclusion. Enrichment of HCCDD with both carnosine and а-lipoic acid in Wistar rats had a protective effect on hepatocytes with a decrease in apoptosis to a level in control rats. The increase in the IL-10/IL-17A ratio indicates the activation of anti-inflammatory mechanisms due to the functional predominance of Treg-cells over Th1/Th17 lymphocytes.
Influence of the DAT gene knockout on exchange of essential and toxic trace elements in rats
The maintenance of energy homeostasis of the body according to modern data is carried out with the active participation of dopaminergic neurons of the central nervous system. The synthesis and metabolism of dopamine (DA) occurs both in the brain and in peripheral tissues. Violation of the synthesis and metabolism of DA is considered as a link in the vicious cycle which it formed during the development of diet-induced obesity. According to modern data, a number of essential and toxic trace elements, such as Cd, Al, As, Mn, Fe, Cu, Zn, are actively involved in the exchange of DA in the brain and peripheral organs and tissues. One way to assess this relationship is to compare changes in the microelement status of the organism when consuming hypercaloric diets in animals with normal and impaired DA transport. The latter can be animals with a knockout of the DAT transporter gene, which performs DA reabsorption with subsequent storage in the composition of secretory granules.
The aim is a comparative study of the content of a number of essential and toxic elements in the brain, liver, and kidneys of rats that differ in the allelic variants of the DAT gene fed balanced diet and the diet with an excess of energy value.
Material and methods. The study was carried out on 30 male rats of the DAT-KO knockout line (homozygotes DAT-/- and heterozygotes DAT+/-), 8-10 weeks old, and 13 males rats of the outbred Wistar line (DAT+/+) of the same age. For 62 days the animals (6 groups) received a semi-synthetic diet containing essential elements in the salt mixture or a similar high-fat-high-carbohydrate diet (HFCD) with 30% fat and 20% fructose solution instead of drinking water. The content of 16 trace elements (Fe, Mg, Cu, Mn, Co, Se, Zn, Cr, V, Cs, Ag, Al, Cd, As, Pb, Ni) were determined by inductively coupled plasma mass spectrometry in the liver, kidneys, and brain of rats with a knockout of the dopamine DAT transporter gene: homozygotes (DAT -/-) and heterozygotes (DAT+/-), as well as wild-type rats (DAT+/+) of the Wistar strain.
Results and discussion. In the liver, DAT knockout led to an increase in the content of As, Cd, Co, and Cs and a decrease in Fe; in the kidneys - to an increase in the levels of Pb, As, Cd and Se, in the brain - an increase in the content of most of the studied trace elements, including Pb, As, Cs, Al and Cu.
Conclusion. Against the background of consumption of HFCD, the effect of DAT knockout on the content of a number of elements was more pronounced compared with the consumption of the control diet. The revealed changes in the trace element content in DAT knockout rats are considered in terms of the effect of DA metabolism in the central nervous system and in peripheral tissues on the status of trace elements.
The comparative analysis of the spectrum of sensitization to food, pollen and fungal allergens in patients with atopic dermatitis and psoriasis
The relevance of the study of psoriatic disease is due to the insufficient effectiveness of existing etiotropic and pathogenetic methods of treatment, which confirms the necessity to search for new approaches in the research of psoriasis, including those from the standpoint of etiopathogenesis. In the literature, there is information about the combination of atopic dermatitis and psoriasis, which does not exclude a commonality of the causes and mechanisms leading to damage to the skin.
The aim of the work was to study and conduct a comparative analysis of the sensitization spectrum of patients with psoriasis and atopic dermatitis to food, pollen and fungal allergens.
Material and methods. A prospective study was conducted on patients with psoriasis (1st, n=20) and atopic dermatitis (2ndgroup, n=20) aged 18 to 57 years. A specific aller-gological examination was performed (collection of an allergological history, determination of the spectrum of sensitization to food, pollen and fungal allergens by prick testing). Statistical data processing was carried out by methods of variational analysis using the t-criterion for qualitative characteristics.
Results and discussion. No statistically significant differences in sensitization to allergens of animal origin between the examined groups were detected. The sensitization to rice and soy was statistically significantly more often noted in patients with psoriasis, in comparison with patients with atopic dermatitis: 33.3 (n=6/18) vs 5.2% (n=1/19), p=0.03 and 66.7 (n=10/15) vs 29.4% (n=5/17), p=0.04. It was determined that sensitization to plant pollen allergens was statistically significantly more often detected in patients with atopic dermatitis compared to the group with psoriasis (72.5 vs 54.4%, p=0.02). It was noted that in the group of patients with psoriasis compared to the group of patients with atopic dermatitis, sensitization to fungi of the genus Candida albicans, Alternaria alternata, Penicillium notatum was more often, however, the differences did not reach statistical significance.
Conclusion. Thus, in our study, we determined the presence of sensitization to food, pollen and fungal allergens not only in patients with atopic dermatitis, but also in psoriasis. So, sensitization to food and pollen allergens is more often determined in atopic dermatitis, and to some food and fungal allergens - in psoriasis. Preliminary prick testing guides us in further application of other methods of specific allergological diagnostics: elimination and provocative tests, and the appointment of personalized therapy.
Pathogenetic aspects of magnesium deficiency in connective tissue dysplasia syndrome
The problem of connective tissue dysplasia is currently becoming particularly relevant because of significant increase of individuals with characteristic abnormalities in the structure of connective tissue. The lack of some micronutrients, arising during ontogenesis in the organism, can determine a high risk of worsening connective tissue homeostasis. Recently, the decisive role of magnesium deficiency in the progression of this disease has been demonstrated.
The aim of the study was to substantiate the need for magnesium diet therapy in individuals with connective tissue dysplasia basing on the study of the pathogenetic significance of magnesium deficiency in this pathology.
Material and methods. The electronic resources of the portals PubMed-NCBI, MEDLINE, the Scientific Electronic Library eLIBRARY.RU, CyberLeninka and the Google Academy were used.
Results and discussion. The analysis of the obtained data made it possible to identify fundamentally new provisions on the main mechanisms of the magnesium influence on the metabolic state of all components of connective tissue. It was proved that magnesium deficiency is a predictor of worsening connective tissue homeostasis, increasing in the number of dysplastic symptoms and their severity. This pathogenetically justifies prescribing a balanced diet to patients with connective tissue dysplasia, including products rich in magnesium, taking into account its recommended daily intake, depending on age of patients.
Conclusion. Adequate daily intake of magnesium will increase the mechanical properties and functionality of the connective tissue, and should be recommended for patients with connective tissue dysplasia to prevent the development of complications, maintain the quality of life and improve the prognosis for this disease.
Comparative analysis of enteral feeding practices for prevention of gastrointestinal complications in infants with ductus-dependent congenital heart diseases
Mesenterial hypoperfusion is one of the main pathogenetic factors of necrotizing enterocolitis (NEC) in infants with ductus-dependent congenital heart diseases. NEC in infants undergoing congenital heart surgery increases mortality and length of hospital stay. NEC is also associated with adverse neurodevelopmental outcome. Optimization of enteral feeding can reduce the risk of gastrointestinal complications. NEC risk factors in infants with congenital heart are of special interest in the literature. This article discusses criteria for enteral feeding initiation and increasing preoperatively and after heart surgery. Enteral feeding protocols of leading cardiac surgical centers are reviewed. Practices to provide high energy and nutrient consumption in infants with congenital heart disease are described.
Key problems of nutritional support in patients with ischemic stroke and nontraumatic intracranial hemorrhage
The presented systematic literature review is focused on the main problems of nutritional support as a complex treatment of patients with ischemic stroke and non-traumatic intracranial hemorrhage. Nutritional support is one of the main points of intensive care in patients with stroke with a neurological deficit. Conducting rational nutritional therapy in this category of patients requires taking into account the characteristics of both the main and concomitant pathologies, in particular diabetes mellitus, cardiovascular pathology. Deep analysis of recent data shows that a number of questions for assessing the severity of hypermetabolic syndrome and differentiated correction of protein and energy metabolic disorders in various clinical forms (ischemic, hemorrhagic) of cerebral stroke with or without comorbid pathology has not been studied enough and are waiting to be resolved. The search continues for new techniques and optimal algorithms for nutritional support with the subsequent development of appropriate clinical recommendations for use in this category of patients. Controversial issues remain regarding the timing of the start of nutritional support, protein and energy requirements, ways to control the adequacy and effectiveness of clinical nutrition.
Traditional nutrition and demography in the Arctic zone of Western Siberia
High requirements for macro- and micronutrients of the organism of a pregnant woman living in the Far North are associated with the influence of extreme factors of high latitudes, and the needs of the mother and the growing fetus. Only the products of the unique food culture of the Arctic people - the Nenets, make it possible to meet the emerging needs. The aim of the work was to study the impact of traditional nutrition on the reproductive health of Nenets women living in the Arctic zone of Western Siberia.
Material and methods. 619 indigenous inhabitants (Nenets) of the Yamal, Nadym and Taz districts of the Yamal-Nenets Autonomous Okrug at the age of 18-65 years were examined. The influence of the type of nutrition (traditional or imported products) on reproductive health indicators (the number of pregnancies, the number of children, the number of spontaneous abortions, frequency of gestosis, threats of termination of pregnancy, operative deliveries) for the period 2013-2018 was studied by analyzing official statistics and by questioning of the female population in own research.
Results. The consumption of traditional products (venison, local fishery products, at least 3 times a week) by Nenets women was more often accompanied by a normal physiological course of pregnancy and childbirth (75.2 versus 64.2%,x2=8.7; p=0.003). It led to a 1.5-fold decrease in the frequency of complications during pregnancy (gestosis, the threat of abortion) (x2=5.8; p=0.01) and a 20% decrease in the frequency of delivery by cesarean section (x2 = 16.6; p<0.001). As a result, a family whose diet was dominated by traditional products had a statistically significantly larger number of children (per child). Conclusion. The preservation of the consumption of reindeer and river fishery products by indigenous women will contribute to the sufficient intake of macro - and micronutrients, that will make it possible to gestate and give birth to a healthier generation of the Nenets society.
Maternal vitamin D status and association with neonatal anthropometric measures
Pregnant women are at risk of developing vitamin D insufficiency or deficiency. Vitamin D status has a great impact on both pregnancy and the fetus.
The aim of the study was to evaluate the maternal serum vitamin D level and its impact on the neonatal anthropometric measures.
Material and methods. A prospective study among 71 pregnant women aged 19 to 40 years was carried out. Women with a gestation period of 12-15 weeks between October to April were included in this study. A survey of pregnant women was conducted and the maternal serum total vitamin D [25 (OH) D2 and D3] level was determined by enzyme immunoassay. Neonatal anthropometric parameters (weight, body length, weigjht-length ratio) were measured.
Results and discussion. Vitamin D deficiency was observed in 41 (57.7%) of pregnant women, insufficiency - in 7 (9.9%), and the optimal level - in 23 (32.4%) of examined women. Women with vitamin D deficiency were more likely to have a miscarriage in anamnesis than women with optimal D status (OR - 9.06; 95% CI: 1.11-73.86, р=0.0396). We have not established the influence of other factors (age, social status, body mass index, number of pregnancies) on the maternal D-status. There were no significant differences between indicators of weight by age, body length of a child by age, and Apgar scores depending on the vitamin-D status of pregnant women.
Conclusion. The study showed that the optimal vitamin D level is observed only in 32.4%, and its deficiency or insufficiency occurs in 67.6% of pregnant women. The study did not reveal the correlation between maternal vitamin-D status and neonatal anthropometric measures. Taking into account the trend towards lower weight-length ratio to gestational age of the newborns from mothers with vitamin D deficiency/insufficiency, further studies are needed.
The effect of administration of dietary supplement with calcium and vitamins D3 and B6 on calcium homeostasis and falls incidence in patients with high fracture risk undergoing medical rehabilitation
Elimination of vitamin D and calcium deficiencies is of particular importance in older patients undergoing medical rehabilitation after a serious illness, surgery or injury and having a high risk of fractures. Preventing falls and fractures, including during the course of rehabilitation, is an important challenge that can be addressed in these patients, in particular through improved nutrition and vitamin D and calcium supplementation.
The aim of the study was to evaluate the effect of long-term intake of a complex dietary supplement with calcium and vitamins D3 and B6 on calcium homeostasis and the frequency of falls in patients with high fracture risk undergoing medical rehabilitation. Material and methods. The study enrolled 109 women and 10 men (mean age 65.5±7.9 years) with high fracture risk who were undergoing medical rehabilitation. After baseline examination, 41 patients have been receiving antiresorptive therapy already comprised group 1, and patients who didn’t receive osteoporotic therapy were randomized into groups 2 (n=39) and3 (control, n=39). Patients in groups 1 and 2 for 12 months were prescribed a dietary supplement containing calcium in a daily dose of 200 mg (in the form of citrate 1000 mg), 600IU of vitamin D3 and 2 mg of vitamin B6. Allpatients underwent assessment of bone mineral density (BMD), calculation of absolute 10-year fracture risk according to FRAX, assessment of food calcium intake, etermination of biochemical parameters of calcium-phosphorus metabolism and bone remodeling (total calcium, inorganic phosphorus, alkaline phosphatase activity - by colorimetric method in blood serum; immunoreactive parathyroid hormone (PTH) and osteocalcin - by electrochemiluminescence immunoassay in blood serum; β-isomer of C-terminal telopeptide of type I collagen (CTx) and 25(OH)D in blood plasma - by immu-nochemiluminescence analysis), cases of falls and fractures were fixed.
Results. Average daily intake of calcium in the studied sample (n=119) was 782.9±243.4 mg, and 67.2% of patients consumed less than 800 mg of calcium daily. Vitamin D deficit was detected in 38.4% of the examined, its insufficiency - in 32.8%. An increase in 25(OH)D concentration was noted in groups 1 and 2 after 6 and 12 months (p<0.01), while in group 3 there was no dynamics of 25(OH)D (p>0.05). Patients in group 1 showed an increase in the level of osteocalcin and total calcium after 6 and 12 months, as well as alkaline phosphatase activity after 6 months (p<0.05). In group 3, there was an increase of PTH levels after 6 (p<0.05) and 12 months (p<0.01), CTx and alkaline phosphatase activity after 12 months (p<0.05). In group 1, there was an increase in BMD in the spine (+4.2%, p=0.024), femoral neck (+3.0%, p=0.041), and total femur (+2.7%, p=0.045), in patients of group 2 -an increase in BMD in the spine (+1.8%, p=0.048). In group 1, there was also a decrease in proportion of patients who fell after 6 months (x2=4.97, p=0.026) and a decrease in the total number of falls after 12 months (x2=4.89, p=0.027). Group 2 showed a decrease in the number of patients who fell after 6 and 12 months (x2=48.58, p=0.0034 at both stages of the study) and the number of falls in general after 6 months (x2=6.02, p=0.0142).
Conclusion. The obtained data allow us to recommend prescription of dietary supplements containing calcium and vitamin D3 as a part of complex rehabilitation of patients with high fracture risk.
Influence of antioxidants in native and micelled forms on the shelf life of the emulsion fat product
Emulsion fat products due to the presence of the aqueous phase are more prone to oxidative damage than pure oils and fats, which requires the use of antioxidants. Based on a social request for the use of natural antioxidants in the food industry, tocopherols, their mixtures, as well as ascorbic acid are widespread. However, most natural antioxidants (vitamins, plant extracts) have lower antioxidant activity in fats than synthetic ones and require more incorporation into the product, which can negatively affect its organoleptic properties and the cost of the finished emulsion fat product. One way to solve this problem is to use new micellized forms of antioxidants. The micellization of various types of water-and fat-soluble antioxidants can increase their specific activity, which is apparently associated with an increase in the relative interaction surface in the product. The development of emulsion fat products using new technological forms of natural antioxidants in order to increase their shelf life is relevant and practically significant for the food industry.
The aim of the study was a comparative assessment of the effectiveness of natural antioxidants in native and micellized forms in the margarine formulation.
Material and methods. Antioxidants (tocopherols, rosemary extract and ascorbic acid) in the native and micellized forms were selected as objects of the study for their introduction into margarine with a mass fraction of fat of 82%. Peroxide Value and p-anizidin Value were determined in dynamics during storage of margarine in its fatty phase.
Results. Experimental data have been obtained on the action of the studied antioxidants in various technological forms on the formation of primary and secondary oxidation products in margarine during storage at the temperature 23±3 °С. It was determined that the introduction of micellized forms of various antioxidants into margarine at a concentration of 0.015-0.03% most effectively slows down the formation of oxidation products compared to using their native forms in an amount equivalent to the active substances.
Conclusion. It has been experimentally established that the use of micellized forms of tocopherols, ascorbic acid and rosemary extract allows more efficient creation of emulsion fat products with an extended shelf life.
Ways of nutritional value increasing of distillary grain fiber
In the process of grain processing for ethyl alcohol, practically only carbohydrates are consumed, which are presented mainly in the form of starch. The remaining components (protein, fats, fiber, minerals) in transit pass into the grain fiber remaining after distillation of the alcohol from the mash. Distillery grain fiber surpasses wheat bran in its indicators, since during the processing it is enriched with biomass of alcohol yeast. In addition, there is a technological possibility of its additional enrichment with protein, amino acids, and vitamins due to changes in the modes of alcoholic fermentation.
The aim of the work was to assess the influence of the mode and conditions of alcoholic fermentation on the composition of distillery grain fiber.
Material and methods. Under laboratory conditions, samples of grain fiber of alcohol production were obtained by the method of fermentation samples from wheat under various fermentation conditions. In the obtained samples, the following parameters were determined: protein according to Barnstein, crude protein, vitamins B1, B2, B6, E, as well as the amino acid composition. The volume fraction of ethyl alcohol, the mass concentration of fermentable carbohydrates, and the concentration of yeast cells were determined in intermediate products of alcohol production.
Results and discussion. Studies on the effect of yeast from various manufacturers on fermentation rates, biomass growth and grain fiber composition showed the advantage of race Y-717 in terms of alcohol accumulation (11.5% vol.), Fermentation rate (56 hours) and yeast cell concentration (260 million/cm3), which was 15-30% more than in other options. However, from the point of view of increasing the content of protein according to Barnstein and crude protein in samples of grain fiber with yeast Y-717, an increase of only 3-4% was noted compared with other options. This was associated with a decrease in the concentration of yeast by 72 h of fermentation due to autolysis. Studies on the influence of the initial yeast concentration on the growth of biomass, the fermentation rate and grain fiber indices showed that with an increase in the initial yeast concentration from 15 to 45 million/cm3, the fermentation time reduced to 48 h, the biomass growth at the end of fermentation was 20%, the protein in grain fiber increased by 15%, the content of vitamins B1, B2, B6 and E as well as amino acids increased by 13-17%.
Conclusion. According to the results of the studies, the technological possibility of enriching distillery grain fiber with protein, amino acids, and vitamins due to a change in the fermentation process during the processing of grain raw materials to alcohol is shown. In particular, this could be achieved through the use of yeast with a high growth rate, by increasing the concentration of yeast biomass, shortening the fermentation period and preventing yeast autolysis at the maturation stage.
The identification of the primal wine production with the protected designation of origin with the appliance of cluster metrics
The article considers the guidelines of the choice of identification criteria, allowing to verify and confirm the geographical name of the origin of domestic primal wine production, thereby confirming their legal status. A priori the production of wine with protected designation of origin includes the use of certain raw materials with predetermined organoleptic and physical-chemical characteristics, which can be confirmed by respective tests.
The aim of the work was to develop a robust differentiating criterion that allows one to determine the authenticity and origin of wine materials relative to the standard.
Material and methods. The authors presented a clustering technique, which allows on the basis of test results and developed digital identification criteria to verify the origin of wine materials from Krasnodar and Rostov-on-Don regions. As a criterion, the data from the analysis of mineral and trace element composition of primal wine production in these regions have been used.
Results. The article postulates following: the main concern of clustering, methods of identification from the perspective of food production using food regression model, information on fundamental clustering metrics, fields of appliance according to the approach of the identification of the product with indication of geographic place of origin. Based on the results of the analysis of the content of 21 mineral substances (10 in μg/l and 11 in mg/l), a regressive model of the primal wine production was built. Based on this model, cluster centers were identified. The resultant model allows us to distinguish the two mentioned wine regions and form a spatial digital discrimination criterion based on the proximity to one of the established cluster centers.
Conclusion. The proposed model can be adapted to identify the production of different branches of the food industry.