[The study of the content of short-chain fatty acids in the intestine of people with lipid metabolism disorders].

Dyslipidemias are a risk factor for cardiovascular diseases, especially at a young age. It is known from modern sources that shortchain fatty acids (SCFA) synthesized in the intestine are actively involved in the genesis of dyslipidemia, the spectrum and ratio of which depends on the consumed food substrates. In particular, it has been found that food components such as dietary fiber can affect the lowering of blood lipids by affecting the intestinal microbiota. Therefore, dietary correction can be an important step in the prevention and treatment of dyslipidemia, and as a result, help reduce the risk of developing cardiovascular disease (CD). The aim of the research was to study the content of the main SCFAs (acetate, propionate, butyrate) in the feces of people with dyslipidemia, including taking into account the actual nutrition and consumption of the carbohydrate fraction of the diet (starch, mono- and disaccharides, dietary fiber) as precursors of SCFAs. Material and methods. 70 patients aged 18 to 45 years with dyslipidemia were selected as stool donors. All subjects were divided into 2 groups: the main group with the risk of CD (the risk was determined by the risk scale for CD) and the comparison group with established cardiovascular pathology (CVP). SCFAs in stool samples collected after natural defecation and subjected to immediate freezing at -70 °C were determined by gas chromatography. The diet was analyzed by the 24-hour food recall method. Results. The frequency of occurrence of the optimal ratio acetate - acetic acid : propionate - propionic acid : butyrate - butyric acid (60:20:20) in all groups was no more than 25%. At the same time, in persons at risk of CD, in the SCFA pool there was a pronounced decrease in the proportion of butyrate, which is characterized by cardioprotective properties, up to 15% (with an optimal proportion of 20%) compared with the levels for healthy people noted in the works of M.D. Ardatskaya et al. and A.A. Kurmangulov. And in persons with CVP, the levels of fecal acetate, which is a regulator of metabolic processes, namely lipogenesis, differed insignificantly compared with the values obtained in the studies of the above authors. In all examined individuals, the content of acetate in feces depended on the carbohydrate component of the diet, primarily on the total amount of carbohydrates consumed. And increasing the amount of dietary fiber intake contributed to the elevation of this SCFA. In individuals at risk of CD a significant correlation was found between the content of acetate and the atherogenic index (r=0,695). And in persons with CVP, there was a high negative correlation between the level of acetate in the feces and the amount of mono- and disaccharides in the diet (r=-0,934). Conclusion. In individuals with dyslipidemia and CVD risk factors, the results obtained in this study confirm the need for targeted correction of diets in order to increase the proportion of food substrates, which are potential precursors of butyrate.

[The role of the gut microbiome in health and diet-related diseases].

In recent years, new data have been obtained on the participation of the organism-associated microbiota in the pathogenesis of many non-communicable diseases. However, these data are mostly multidirectional and require interpretation. The aim - to highlight the role of the intestinal microbiome in the human body in health and some nutritional-dependent pathologies, taking into account modern scientific knowledge. Material and methods. The analysis of domestic and foreign scientific literature in the field of studying the intestinal microbiome in humans and practical measures for its correction in the most common diet-related non-communicable diseases, using the Scopus, Web of Science, PubMed, Google Schoolar, eLibrary, Cyberleninka databases has been held. Results. The data on the significance and function of the intestinal microbiome for the human body in health and in nutrient-dependent diseases, with attention to publications containing information that meets the criteria of scientific evidence have been summarized. It has been shown that the intestinal microbiome plays a biologically significant role not only in digestion processes, but also in many metabolic processes and in the adaptive potential of the human organism. The role of the microbiome in the metabolism of lipids supplied with food, as well as its participation in the mechanisms of development of dyslipidemias and metabolic syndrome in the case of dysbiotic disorders in the intestine, have been described. Conclusion. Nowadays the importance of the intestinal microbiome as an integral factor in the vital functions of the organism that determines the development and maintenance of the immune system, digestive processes, and biochemical balance in humans in norm has been convincingly proven at all levels of numerous studies. However, the study of the effect of dysbiotic changes in the gut microbiota as a direct cause of the development of non-communicable diseases requires further research with a high level of evidence.

A pharmacokinetic and pharmacodynamic study of intravenous vs oral artesunate in uncomplicated falciparum malaria.

AIMS: To obtain comprehensive pharmacokinetic and pharmacodynamic data for artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) following i.v. and oral administration of ARTS to patients with acute, uncomplicated falciparum malaria. METHODS: Twenty-six Vietnamese patients with falciparum malaria were randomized to receive either i.v. ARTS (120 mg; group 1) or oral ARTS (100 mg; group 2), with the alternative preparation given 8 h later in an open crossover design. Mefloquine (750 mg) was administered at 24 h. Plasma concentrations of ARTS and DHA were determined by h.p.l.c. assay. Pharmacokinetic parameters were calculated by non-compartmental methods. The time to 50% parasite clearance (PCT50) was calculated by linear interpolation of parasite density determinations. Linear least squares and multiple linear regression analyses were used to evaluate pharmacokinetic-pharmacodynamic relationships. RESULTS: Following i.v. bolus, ARTS had a peak concentration of 29.5 microM (11 mg l[-1]), elimination t1/2 = 2.7 min, CL = 2.33 l h(-1) kg(-1) and V = 0.14 l kg(-1). The Cmax for DHA was 9.3 microM (2.64 mg l[-1]), t1/2 = 40 min, CL =0.75 l h(-1) kg(-1) and V = 0.76 l kg(-1). Following oral ARTS, relative bioavailability of DHA was 82%, Cmax was 2.6 microM (0.74 mg l[-1]), t1/2 = 39 min, and MAT = 67 min. Overall, the PCT50 and fever clearance time (FCT) were 6.5 h and 24 h, respectively. There was no correlation between PCT50 or FCT and AUC, Cmax or MRT for DHA. CONCLUSIONS: Despite rapid clearance of ARTS and DHA in patients with uncomplicated falciparum malaria, prompt parasite and fever clearance were achieved. High relative bioavailability of DHA following oral ARTS administration, and clinical outcomes comparable with those after i.v. ARTS, support the use of the oral formulation in the primary care setting.