[The pathophysiological role of adipokines in the development of bronchial asthma combined with obesity].

The combined course of bronchial asthma (BA) and obesity is one of the urgent medical and social problems that requires a comprehensive and careful study in connection with a decrease in the quality of life of such patients, an increase in the frequency, duration of hospitalization and a high economic burden for the state as a whole. The relationship between BA and obesity is now confirmed by numerous studies, at the same time, despite the variability of the proposed mechanisms of pathogenetic effects of obesity on asthma, metabolic aspects of the relationship of these diseases need further study. Adipose tissue hormones are responsible for the energy homeostasis of the body therefore, excessive accumulation of adipose tissue is accompanied by the development of an imbalance in metabolic processes in various organs and tissues. Due to the emergence of new scientific data on the role and function of adipokines in the body, metabolic effects of adipokines are considered in the focus of their pathophysiological association with obesity and asthma. This literary review highlights the current understanding of the role of metabolic effects of the most studied adipokines (resistin, retinol-binding protein, leptin and adiponectin) in the development of obesity and BA. Gender and age-dependent features of adipokine levels in BA and obesity are described. Data on the confirmed role of adiponectin and leptin in the progression of BA combined with obesity are presented. It has been shown that the role of resistin and retinol-binding protein in the development of BA combined with obesity has not been studied. It is demonstrated that further study of metabolic activity of adipokines in BA is an actual and perspective direction of researches which will allow to develop new diagnostic and therapeutic strategies in patients with BA with obesity.

[Plasmalogenes in the pathophysiology and therapy of age-specific diseases.]

The pathogenesis of age-related diseases such as metabolic syndrome, type 2 diabetes, Parkinson's disease and Alzheimer's disease is associated with oxidative stress and chronic inflammation. Violation of redox homeostasis is accompanied by the development of peroxisome dysfunction and impaired biosynthesis of plasmalogens, which can be closely related to the aging process and the development of age-dependent pathology. Reflecting the functional activity of peroxisomes, plasmalogens can serve not only as potential biomarkers of diseases associated with oxidative stress and aging, but also as an important therapeutic target. The purpose of this review is to analyze the current knowledge of little-studied biological and pathological aspects of plasmalogen participation in the pathophysiology of neurodegenerative and metabolic diseases of older persons. Understanding the role of plasmalogens in the pathophysiology of these diseases can lead to the development of effective diagnostic and prognostic biomarkers, as well as treatment methods for neurodegenerative and metabolic diseases of older people.

[Blood fatty acids in the development and correction of metabolic syndrome]. / Zhirnye kisloty krovi v formirovanii i korrektsii metabolicheskogo sindroma.

AIM: to investigate the composition of plasma fatty acids (FA) and red blood cells and the level of eicosanoids in patients with metabolic syndrome (MS) and to assess whether metabolic disturbances may be corrected during a cycle use of an ω-3 polyunsaturated fatty acid (PUFA). SUBJECTS AND METHODS: Examinations were made in 46 patients, including Group 1 (a control group) of 15 persons without MS components; Group 2 of 31 patients with MS, Group 3 of 16 MS patients who had taken an ω-3 PUFA for 6 months, and Group 4 of 15 MS patients who had received the drug for 12 months. The composition of plasma FA and red blood cells was analyzed on a gas-liquid chromatograph. An enzyme immunoassay was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and eicosanoids (thromboxane B2, 6-keto-prostaglandin F1α, leukotriene B4). A biologically active additive from the king crab (Paralithodes camtschatica) hepatopancreas was used as a source of ω-3 PUFA. RESULTS: Having a higher proportion of linoleic and α-linolenic acids in the plasma, the patients were found to have decreased levels of ω-3 and ω-6 PUFAs (linoleic and α-linolenic, arachidonic, and eicosapentaenoic acids) and a larger proportion of Mead acid and saturated FAs (myristic and stearic acids) in the red blood cells, suggesting that that cellular blood FA transfer was impaired and FAs were absorbed by cells. Their serum samples showed the high levels of leukotriene B4, 6-keto-prostaglandin F1α, and thromboxane A2. The long-term (6- and 12-month) use of ω-3 PUFA from the king crab hepatopancreas had a positive impact in modifying the lipid FA composition of red blood cells and in eliminating deficiencies of physiologically important ω-3 and ω-6 PUFAs in the blood cells. CONCLUSION: The findings suggest that FAs and their metabolites play an important role in the pathogenesis of MS and that dietary ω-3 PUFA should be incorporated into a package of preventive and therapeutic measures for MS.

[The influence of sinusoidal modulated currents on the fatty acid composition of plasma and blood erythrocytes in the patients presenting with chronic cholecystitis]. / Vliyanie sinusoidal'nykh modulirovannykh tokov na sostav zhirnykh kislot plazmy i eritrotsitov krovi u patsientov s khronicheskim kholetsistitom.

The objective of the present study was to evaluate the effectiveness of the treatment with sinusoidal modulated currents on lipid metabolism in the patients presenting with chronic cholecystitis in the state of remission. PATIENTS AND METHODS: The study included 25 patients with chronic non-calculosis cholecystitis in phase of remission and 20 healthy subjects (controls). We studied the serum lipid spectrum as well as the fatty acid composition of plasma and blood erythrocytes before and after therapy with sinusoidal modulated currents applied to the right-sided hypochondrium region. RESULTS AND DISCUSSION: The treatment of the patients with chronic cholecystitis in remission with the use of sinusoidal modulated currents produced moderate lipid-modulatory and membranotropic effects mediated through the activation of the processes of lipid metabolism that may result in the depletion of the pool of essential polyunsaturated fatty acids. CONCLUSION: The results of this study give evidence that it is advisable to treat the patients presenting with chronic cholecystitis by sinusoidal modulated currents in the combination with the oral intake of exogenous polyunsaturated fatty acids.

Effects on alimentary high-fat diet on thiol disulfide homeostasis in rats.

The effects of high-fat diet on the thiol disulfide homeostasis of rats were evaluated by activities of glutathione redox system functioning in the blood and liver. A short-term (30 days) high-fat diet inhibited activities of glutathione-dependent enzymes. High-fat loading for 90 days promoted the development of a compensatory response of the glutathione redox system and restoration of the thiol disulfide homeostasis. The compensatory processes in the glutathione system failed on day 180 of alimentary loading because of redox imbalance in the thiol disulfide metabolism.

Characteristics of heme oxygenase-1 expression in rat hepatocytes during the development of nonalcoholic steatohepatitis.

We studied heme oxygenase-1 expression in rat liver during the development of nonalcoholic steatohepatitis simulated by feeding high-fat ration for 30, 90, and 180 days. Increased number of hepatocytes synthesizing heme oxygenase-1 was demonstrated at all stages of pathology development. Herewith, the intensity of enzyme expression by individual cells was reduced on experimental day 180 during the development of liver fibrosis.

Molecular species of glycerophosphoethanolamines in obesity-associated asthma.

Bronchial asthma (BA) complicated by obesity is a progressive disease phenotype that hardly responds to standard therapy. In this regard, it is important to elucidate cellular and molecular mechanisms of development of this comorbid pathology. In recent years, lipidomics has become an active research tool, opening new opportunities not only for understanding cellular processes in health and disease, but also for providing a personalized approach to medicine. The aim of this study was to characterize the lipidome phenotype based on the study of molecular species of glycerophosphatidylethanolamines (GPEs) in blood plasma of patients with BA complicated by obesity. Molecular species of GPEs were studied in blood samples of 11 patients. Identification and quantification of GPEs was carried out using high resolution tandem mass spectrometry. For the first time in this pathology, a change in the lipidome profile of molecular species of diacyl, alkyl-acyl and alkenyl-acyl HPEs of blood plasma was shown. In BA complicated by obesity, acyl groups 18:2 and 20:4 were dominated in the sn2 position of the molecular composition of diacylphosphoethanolamines. Simultaneously with the increase in the level of GPE diacyls with the fatty acids (FA) 20:4, 22:4, and 18:2, there was a decrease in these FAs in alkyl and alkenyl molecular species of GPEs, thus indicating their redistribution between subclasses. The eicosapentaenoic acid (20:5) deficiency at the sn2 position of alkenyl GPEs in patients with BA complicated by obesity indicates a decrease in the substrate for the synthesis of anti-inflammatory mediators. The resulting imbalance in the distribution of GPE subclasses, due to a pronounced increase in the content of diacyl GPE under conditions of the deficiency of molecular species of ether forms, can probably cause chronic inflammation and the development of oxidative stress. The recognized lipidome profile characterized by the modification of the basic composition and the chemical structure of GPE molecular species in BA complicated by obesity indicates their involvement in the pathogenetic mechanisms underlying BA development. The elucidation of particular roles of individual subclasses of glycerophospholipids and their individual members may contribute to the identification of new therapeutic targets and biomarkers of bronchopulmonary pathology.

Simulation of nonalcoholic steatohepatitis in rats.

The new model of nonalcoholic steatohepatitis in rats is based on alimentary effects of hypercaloric diet including much cholesterol and beef fat. This model reproduces structural and functional disorders in the liver, including hepatocyte fatty degeneration, parenchymatous necrosis and fibrosis paralleled by dyslipidemia and is intended for studies of the mechanisms of formation, progress, and therapy of liver diseases of noninfectious origin.

[Fatty acid epoxides in the regulation of the inflammation]. / Époksidy polinenasyshchennykh zhirnykh kislot v reguliatsii vospaleniia.

Cyclooxygenase and lipoxygenase derived lipid metabolites of polyunsaturated fatty acids (PUFAs), as well as their role in the inflammation, have been studied quite thoroughly. However, cytochrome P450 derived lipid mediators, as well as their participation in the regulation of the inflammation, need deeper understanding. In recent years, it has become known that PUFAs are oxidized by cytochrome P450 epoxygenases to epoxy fatty acids, which act as the extremely powerful lipid mediators involved in resolving inflammation. Recent studies have shown that the anti-inflammatory mechanisms of ω-3 PUFAs are also mediated by their conversion to the endocannabinoid epoxides. Thus, it is clear that a number of therapeutically relevant functions of PUFAs are due to their conversion to PUFA epoxides. However, with the participation of cytochrome P450 epoxygenases, not only PUFA epoxides, but also other metabolites are formed. They are further are converted by epoxide hydrolases into pro-inflammatory dihydroxy fatty acids and anti-inflammatory dihydroxyeicosatrienoic acids. The study of the role of PUFA epoxides in the regulation of the inflammation and pharmacological modeling of the activity of epoxide hydrolases are the promising strategies for the treatment of the inflammatory diseases. This review systematizes the current literature data of the fatty acid epoxides, in particular, the endocannabinoid epoxides. Their role in the regulation of inflammation is discussed.

Phospholipid composition of erythrocytes and glutathione redox system in rats during adaptation to cholesterol load.

We studied phospholipid composition of erythrocytes and the state of the glutathione redox system in rats during adaptation to cholesterol load for 180 days. The adaptive response is formed during the period from day 30 to day 90 of cholesterol load and is associated with increased relative content of phosphatidylethanolamine and phosphatidylinositol, activation of glutathione redox system enzymes (glutathione reductase and glutathione peroxidase), and enhanced production of glutathione.

[Influence high-fat ration on plasma and erythrocyte lipids fatty acids of rats].

Study character of the redistribution of fatty acids between the lipid fraction of plasma and erythrocytes in rats with prolonged high-fat diet (30, 90, 180 days). Shown that at long high-fat rations in the lipids of erythrocytes decreasing pool polyunsaturated fatty acids (oleic, dihomo-gamma-linoleic, eicosapentaenoic, arachidonic), increases of saturated fatty acids (myristic, stearic) levels. In lipids fractions of plasma revealed the opposite direction of changes in the level of the fatty acids: the accumulation of essential polyunsaturated fatty acids, reduction of saturated fatty acids. Supposedly, that high-fat diet promotes de novo compensatory synthesis of polyunsaturated fatty acids, but disturbed apoB-100 receptor-mediated active transport of fatty acids with low-density lipoproteins (LDL), synthesized in the liver fatty acids is not captured by the cells peripheral organs. Marker of the apoB-100 receptor breach of transfer low-density lipoprotein, transporting polyunsaturated fatty acids was to increase LDL cholesterol in serum.

[Formation of the compensation answer in the system "lipid peroxidation - antioxidant protection" in rats with alimentary dislipidemia].

It is investigated conditions of system "lipid peroksidation - antioxidant protection" at rats of the line Wistar at prolonged formation alimentary dyslipidemia (DLP). It is established, that at formation DLP during 46 days in cells there was no increase in resistance and capacity of processes antioxidant protection. In prolonged DLP (90 days) was characterized by occurrence of the compensation-adaptive answer in the system "lipid peroksidation - antioxidant protection".

[The role of modification of fatty acid composition of erythrocyte lipids in pathogenesis of arterial hypertension].

We used liquid chromatography for analysis of fatty acids (FA) in lipids of erythrocytes of patients with hypertensive disease (HD) with normo- (group 1) and hyperlipidemia (group 2). Abnormalities of FA composition of erythrocyte lipids were revealed in both groups. In group 1 we found deficit of polyenic acids of omega-6 family, accumulation of Mead acid - prostanoid precursor with pronounced vasoconstrictor and pro inflammatory properties. In group 2 we noted more profound rearrangement of lipid matrix of erythrocyte membrane manifested as deficiency of omega-3 polyenic acids, accumulation of palmitinic and arachidonic acids. Preponderance of saturated FA in erythrocytes and deficiency of polyenic acids might evidence for pathology of their ligand-receptor transport into the cell. Blockade of active FA transport initiates formation of HD, promotes accumulation of atherogenic fractions of lipoproteins in blood. These results evidence for important pathogenetic role of FA in development of hypertension.

[Effect utilize of food biologically active additive on base the lipid marine hydrobions under experimental cardiovascular pathology rats].

The impact of different doses of food biologically active additive (BAA) on base lipid sea-hydrobions on the condition of water-electrolyte and nitrogen metabolism, proteinosynthesis and hepatobiliary functions of liver has been studied for rats with the experimental cardio-vascular pathology. BAA is the lipid fraction from schoolmaster gonate squid Berryteuthis magister liver, containing 10% of polyunsaturated fatty acids (PUFA) and 50% of alkyldiacylglycerides. In relation to organism's emunctory systems in conditions of experimental cardio-vascular pathology the biotropic dose makes 1 g/kg daily. BAA acts negatively in dose 2 g/kg daily. It is conditioned by aggravation of electrolyte imbalance, lowering of excretion and reabsorption of sodium, potassium, magnesium, metabolites of purine and nitrogen metabolism, stimulation of intoxication and calcification processes, load effect on proteinosynthesis function of rats liver.

[The composition of blood fatty acids and the level of oxylipins in patients with metabolic syndrome].

Gas liquid chromatography was used to analyze the composition of plasma free fatty acids (FA) and erythrocyte lipid FAs in patients with metabolic syndrome (MS) in various glucose-insulin homeostasis. The serum lipids of oxylipins were studied in patients with MS, by applying enzyme immunoassay. The patients with MS in the absence of glucose-insulin homeostatic disorders and those with significant insulin resistance (IR) were found to have accumulation of polyenic FA (18:2 omega6), 18:p omega3, 22:4 omega6) and a decreased pool of saturated FA (12:0, 14:0, 16:0, 17:0) in the plasma with simultaneous polyunsaturated FA (18:3 omega3, 20:4 omega6) with a preponderance of fatty FA (14:0, 18:0) in the red blood cells. The high serum concentrations of leukotriene B, and 6-keto-prostaglandine-F1a, were detectable in the examinees with MS. Increased thromboxane A2 synthesis was observed when the patients with MS developed IR. The findings suggest that there are impairments in the composition of plasma free FA and erythrocyte lipid FA and in the synthesis of oxylipins in patients with MS.

[The role of free and esterified fatty acids in pathogenesis of metabolic syndrome].

Patients with insulin resistance and those with metabolic syndrome (MS) in the absence of alteration of glucose-insulin homeostasis were found to have abnormal composition of plasma free fatty acids (FA) and lipid FA in erythrocytes. Patients with metabolic syndrome and different glucose-insulin homeostasis accumulated polyenic FA and lost saturated FA in plasma; saturated FA in their erythrocytes increased while polyunsaturated FA decreased. These findings suggest disturbed receptor-mediated active transport of FA and the predominance of passive absorption of free FA by cells as a cause of insulin resistance and hyperinsulinism.

[Effect of 1-O-alkyl-glyceride ethers isolated from lipids of the squid Berrytteuthis magister liver on lipid metabolism and hematological parameters of rats with experimental dislipidemia].

On the white Wistar rats with alimentary dyslipidemia investigated influence 1-O-alkyl-glycerides ethers (AGE), received by a method of hydrolysis 1-O-alkyl-diacylglycerides from lipids of the squid Berryteuthis magister liver, on a lipid metabolism, hepatobiliary functions of liver, antioxidant systems and parameters of blood. Are revealed antioxidant, antianemia and immunoactive properties of AGE. AGE raise a level of glucose and activity of enzymes hepatobiliary systems in blood, interfere the decrease of a cholesterol in blood.

[The composition of nonesterified fatty acids in patients with metabolic syndrome].

The blood composition of non-etherized fatty acids (NEFA) was studied in 22 patients with metabolic syndrome (MS) and 11 healthy individuals. The qualitative NEFA composition presented by 31 components of individual fatty acids was analyzed, by taking into account of glucose-insulin homeostatic changes in MS patients: those without insulin resistance (IR) (Group 1) and those with diagnosed IR (Group 2). MS patients with normal insulinemia were ascertained to have lower levels of lauric, myristic, palmitic, C24:0, C16:0i acids. With a decrease in the relative quantity of saturated NEFA, the levels of polyunsaturated fatty acids (FA) increased. The proportions of linoleic (C18:2 omega 6) and linolenic (C18:3 omega 3) acids doubled (p < 0.01), arachidonic acid (C20:4 omega 6) was observed to tend to rise. The cumulative FA index sigma omega 6 increased twofold. In Group 1, the integrated index of changes in the FA series (unsaturation index) was 41% higher than that in the control group (p < 0.05). In Group 2, the vector of changes in the relative quantity of NEFA was similar, but impairments were less marked than that in Group 1. The findings suggest that the development of insulin resistance is preceded by impaired blood cell transfer and absorption of NEFA.

[Application of food supplement on the base of potassium and magnesium at experimental cardiopathology].

The data of research have shown that the biologically active additive of food "Algilosa potassium-magnesium" possess the favorable action on the "lipid peroxidation-antioxidant protection" system, normalized parameters of immunity, action of erythrocytes and platelet aggregation properties of blood. The leaded research recommend to use of "Algilosa potassium-magnesium" for preventive and treatment of diseases of cardiovascular system and other pathological conditions at which infringements mention investigated systems.

[Membrane lipids in patients with chronic bronchitis concurrent with urolithiasis in the phase of clinical remission].

The composition of erythrocytic lipids was studied in patients with chronic nonobstructive bronchitis in the phase of clinical remission concurrent with urolithiasis. There was a significant increase in the proportion of phosphatidylserine with the decreased levels of sphingomyelin and phosphatidylcholine, a reduction in the relative quantity of fatty acids of iso- and anteisometric structure, an impairment in the relations between fatty acids that are precursors of the synthesis of eicosanoids of different series, as well as a decrease in the total unsaturation of erythrocytic lipids. The impairments found in the composition of erythrocytic lipids are markers of membrane destruction and they may serve as diagnostic criteria for concomitant pulmonary and renal lesions.