FADS Polymorphisms Affect the Clinical and Biochemical Phenotypes of Metabolic Syndrome.

Long-chain polyunsaturated fatty acids (LC-PUFAs) play important roles in human health, from controlling inflammation to lipid and glucose homeostasis. In our previous study, which employed a cluster analysis of a plasma fatty acid (FA) pattern, we identified two clusters of metabolic syndrome (MetS) independent of clinical and biochemical parameters within the whole study group (controls together with metabolic syndrome (MetS) patients). FA desaturase (FADS) genes are the key regulators of LC-PUFA metabolism. The aim of this study was to analyze associations between FADS polymorphisms and clusters of MetS. The study group consisted of 188 controls and 166 patients with MetS. The first cluster contained 71 controls (CON1) and 109 MetS patients (MetS1). The second cluster consisted of 117 controls (CON2) and 57 MetS patients (MetS2). In comparison with MetS2, cluster MetS1 displayed a more adverse risk profile. Cluster CON1 had, in comparison with CON2, higher body weight and increased triacylglycerol levels (p < 0.05). We found that the FADS rs174537 (p < 0.001), rs174570 (p < 0.01), and rs174602 (p < 0.05) polymorphisms along with two inferred haplotypes had statistically significant genotype associations with the splitting of MetS into MetS1 and MetS2. Conversely, we observed no significant differences in the distribution of FADS polymorphisms between MetS and CON subjects, or between CON1 and CON2. These associations between FADS polymorphisms and two clusters of MetS (differing in waist circumference, HOMA-IR, lipolysis, and oxidative stress) implicate the important influence of genetic factors on the phenotypic manifestation of MetS.

Altered Indices of Fatty Acid Elongases ELOVL6, ELOVL5, and ELOVL2 Activities in Patients with Impaired Fasting Glycemia.

Background: Dysregulation of fatty acids (FA) seems to participate in the pathogenesis of disorders such as metabolic syndrome (MetS), cardiovascular diseases, or some cancers. Activities of enzymes FA desaturases and elongases [elongation of very long-chain fatty acid (ELOVL)] significantly influence FA profile in different body compartments. Although the impact of activities of desaturases on cardiometabolic diseases was broadly studied, relatively little attention was devoted to the role of elongases. Methods: Case-control study was carried out in 36 patients (18 men/18 women) with impaired fasting glycemia (IFG) without MetS and 36 age and gender-matched healthy controls. FA profiles in plasma phospholipids (PL) were assessed using gas chromatograph-flame ionization detector and indices of desaturase and elongase activities were calculated. Results: In the IFG group, we observed decreased estimated activities of ELOVL2 and ELOVL5, whereas higher estimated activities of elongase ELOVL6 were noted. IFG group was also characterized by altered composition of plasma PL FA, above all by lower percentage of cis-vaccenic acid (cVA; 18:1n-7) and of total polyunsaturated FA n-6, especially linoleic acid, and by higher proportion of stearic acid and gamma-linolenic acid. Concurrently, elevated estimated activities of desaturases delta-9-desaturase (D9D), D6D were found. Conclusions: Lower estimated activities of ELOVL2 and ELOVL5 with lowered proportion of PL cVA could be associated with disturbances of glucose homeostasis development and their corresponding indices could serve as biomarkers of such risk.

Associations of Serum Uric Acid with Endogenous Cholesterol Synthesis Indices in Men with High Cardiometabolic Risk.

Background: Patients with metabolic syndrome (MetS) have increased endogenous synthesis of cholesterol, together with lower level of intestinal cholesterol absorption. However, less is known about how individual metabolic disturbances linked to MetS correlate with dysregulated cholesterol homeostasis. Methods: We consecutively examined 178 probands (91 women/87 men) characterized by the presence of one or two components of MetS (group with an increased cardiometabolic risk [CMR]) and 42 healthy controls (24 men/18 women) of similar age, as well. In all probands, the surrogate markers for cholesterol biosynthesis (lathosterol) and absorption (campesterol and ß-sitosterol) were measured by capillary gas chromatography. In CMR group, we performed multivariate regression analysis to assess the dependence of the parameters of cholesterol biosynthesis/absorption on components of MetS including serum uric acid (SUA), apolipoprotein B (apoB), and age. Results: In CMR group, higher lathosterol to total plasma cholesterol (TC) ratio (LCR) was influenced by gender (P = 0.05, analysis of covariance [ANCOVA] for age), whereas ratios of campesterol (ß-sitosterol, respectively) to TC were lower in CMR group (P < 0.001 and P = 0.002, ANCOVA for age). In men, LCR was positively associated with SUA, apoB, and hypertension (all P < 0.05). Lathosterol to campesterol or ß-sitosterol ratios were highly dependent on SUA (both P < 0.01), the former being dependent also on apoB (P < 0.01). In women, these parameters were only weakly dependent on SUA. Conclusions: These results show that the concentration of SUA in men of CMR group is associated with the indices of de novo cholesterol biosynthesis. This association is probably influenced by interaction of arterial hypertension and apoB levels with cholesterol homeostasis.

Fatty Acid Composition of Plasma Phosphatidylcholine Determines Body Fat Parameters in Subjects with Metabolic Syndrome-Related Traits.

BACKGROUND: This study examines the associations of fatty acids (FAs) in plasma phosphatidylcholine (PC) with the anthropometrical and biochemical characteristic of patients with metabolic syndrome (MetS)-related traits. METHODS: We analyzed the FA profiles of PC in 300 persons with MetS-related traits (152 M/148F, mean age 46.9 ± 9.0 years) and in 70 healthy controls of the same age using a balanced men/women ratio and gas-liquid chromatography. Multivariate linear regression analysis was performed to determine the coefficients of determination (R2) using FA proportions of the mentioned proband characteristics. RESULTS: The FA composition of PC in patients with MetS traits was only associated with waist circumference (R2 = 0.27), waist-to-hip ratio (WHR; R2 = 0.41), body fat percentage (R2 = 0.62), and fat mass (R2 = 0.29). Positive associations were found for dihomo-γ-linolenic (DGLA), palmitic, stearic (SA), α-linolenic (ALA), and eicosapentaenoic acids, whereas negative associations were found for linoleic (LA), oleic, and docosapentaenoic acids. Palmitoleic acid (POA) was positively associated with waist circumference but negatively with fat percentage. In controls, significant associations were found for waist circumference (R2 = 0.51), WHR (R2 = 0.53), body fat percentage (R2 = 0.60), and fat mass (R2 = 0.34). DGLA and saturated FA (SFA) were positively associated, whereas docosahexaenoic, adrenic, and cis-vaccenic acids were negatively associated. The study group differed from controls as follows: lower concentrations of LA and total n-6 FA, higher indices of delta-9-desaturase and delta-6 desaturase activity and higher proportions of POA, SA, ALA, DGLA, and SFA. CONCLUSIONS: We found significant associations (R2 >0.25) of FA in plasma PC with adiposity in middle-aged persons with MetS-related traits, but not with metabolic indices.

Plasma Phosphatidylcholines Fatty Acids in Men with Squamous Cell Esophageal Cancer: Chemoradiotherapy Improves Abnormal Profile.

BACKGROUND Abnormal metabolism of fatty acids (FA) is considered to play a role in human cancers, including esophageal cancer (EC). Nevertheless, there have been only a few studies dealing with the influence of the chemotherapy or radiotherapy on the plasma FA profiles. In this work we compared FA in plasma phosphatidylcholine (PC) of the patients with squamous EC and healthy subjects and investigated changes in the FA spectrum during neoadjuvant chemoradiotherapy (CRT). MATERIAL AND METHODS Forty-two men with squamous EC were compared with age-matched healthy controls. The EC group was subjected to concurrent neoadjuvant CRT. We analyzed FA in plasma PC before and after CRT. RESULTS The EC group was characterized by increased levels of both saturated and monounsaturated FA, associated with an increased index of SCD1 (stearoyl-CoA desaturase-1). Moreover, decreased levels of linoleic acid and total polyunsaturated FA (PUFA) n-6 were found in EC patients. The CRT was accompanied by increased docosahexaenoic acid and total PUFA n-3 content in plasma PC, concurrently with the decrease of estimated activity of SCD1. CONCLUSIONS We found that patients with EC had altered FA profile in plasma PC, which could be related to abnormal FA metabolism in cancer (e.g., altered synthesis de novo, b-oxidation, desaturation, and elongation). The described changes in FA profiles during CRT could be involved in favorable functioning of CRT. Further studies investigating the plasma FA compositions and their changes due to CRT in EC patients are warranted.

Pleiotropic effects of niacin: Current possibilities for its clinical use.

Niacin was the first hypolipidemic drug to significantly reduce both major cardiovascular events and mortality in patients with cardiovascular disease. Niacin favorably influences all lipoprotein classes, including lipoprotein[a],and belongs to the most potent hypolipidemic drugs for increasing HDL-C. Moreover, niacin causes favorable changes to the qualitative composition of lipoprotein HDL. In addition to its pronounced hypolipidemic action, niacin exerts many other, non-hypolipidemic effects (e.g., antioxidative, anti-inflammatory, antithrombotic), which favorably influence the development and progression of atherosclerosis. These effects are dependent on activation of the specific receptor HCA2. Recent results published by the two large clinical studies, AIM-HIGH and HPS2-THRIVE, have led to the impugnation of niacin's role in future clinical practice. However, due to several methodological flaws in the AIM-HIGH and HPS2-THRIVE studies, the pleiotropic effects of niacin now deserve thorough evaluation. This review summarizes the present and possible future use of niacin in clinical practice in light of its newly recognized pleiotropic effects.

Osteopontin as a discriminating marker for pancreatic cancer and chronic pancreatitis.

INTRODUCTION: We analyzed concentrations of osteopontin (OPN) in patients with pancreatic ductal adenocarcinoma (PDAC) in order to determine firstly whether it is useful to distinguish between PDAC patients and those with chronic non-hereditary pancreatitis (CP) and type 2 diabetes mellitus (T2DM), and secondly whether OPN concentrations depend on the PDAC stage. METHODS: Groups consisting of 64 patients with PDAC, 71 with CP, 67 with T2DM and 48 healthy controls (CON) were enrolled in the study. Controls were compared with regard to levels of OPN, oxidative stress markers, conventional tumor markers and other biochemical parameters. RESULTS: Levels of OPN were higher in patients with PDAC compared with CP patients (P< 0.001), T2DM (P< 0.001) and CON (P< 0.001). There were increased OPN levels in CP patients in comparison with T2DM (P< 0.001) and CON (P< 0.001). Patients with PDAC in stage IV had higher OPN levels than PDAC patients in stage III (P< 0.01). There was no difference in OPN levels of PDAC patients in stage III compared to patients in stage II. CONCLUSION: Our pilot study demonstrates the usefulness of estimating OPN levels to differentiate between pancreatic cancer and chronic pancreatitis. Higher OPN levels over 102 ng/ml could be a potential diagnostic biomarker for pancreatic cancer.

Chronic pancreatitis and the composition of plasma phosphatidylcholine fatty acids.

Chronic pancreatitis (CP) is an irreversible inflammatory disorder characterized by the destruction of both exocrine and endocrine tissue. There is growing evidence that dysregulation of fatty acid (FA) metabolism is connected with many diseases; however, there are few data concerning FA composition in CP. Therefore, we analyzed FA profiles in plasma phosphatidylcholines in 96 patients with CP and in 108 control subjects (CON). The patients with CP had, in comparison with CON, increased sum of monounsaturated FA (ΣMUFA) and decreased content of polyunsaturated FA (PUFA) in both n-6 and n-3 families. Moreover, CP patients had increased indexes for delta-9, delta-6 desaturases, and fall in activity of delta-5 desaturase. Increased ratio of 16:1n-7/18:2n-6 (marker of essential n-6 FA deficiency), was more prevalent among CP patients. These changes implicated decreased fat intake, including n-3 as well as n-6 PUFA, and intrinsic changes in FA metabolism due to the alteration of delta desaturase activities.

[Desaturases of fatty acids (FADS) and their physiological and clinical implication]. / Desaturázy mastných kyselin: patofyziologie a klinický význam.

States associated with insulin resistance, as overweight/obesity, type 2 diabetes mellitus (DM2), cardiovascular diseases (CVD), some cancers and neuropsychiatric diseases are characterized with a decrease of long-chain polyunsaturated fatty acids (LC-PUFA) levels. Amounts of LC-PUFA depend on the exogenous intake of their precursors [linoleic (LA) and α-linolenic acid (ALA)] and by rate of their metabolism, which is influenced by activities of enzymes, such as Δ6-desaturase (D6D, FADS2), D5D, FADS1, elongases (Elovl2, -5, 6).Altered activities of D5D/D6D were described in plenty of diseases, e.g. neuropsychiatric (depressive disorders, bipolar disorder, dementia), metabolic (obesity, metabolic syndrome, DM2) and cardiovascular diseases (arterial hypertension, coronary heart disease), inflammatory states and allergy (Crohns disease, atopic eczema) or some malignancies. Similar results were obtained in studies dealing with the associations between genotypes/haplotypes of FADS1/FADS2 and above mentioned diseases, or interactions of dietary intake of LA and ALA on one hand and of the polymorphisms of minor allels of FADS1/FADS2, usually characterized by lower activities, on the other hand.The decrease of the desaturases activities leads to decreased concentrations of products with concomitant increased concentrations of substrates. Associations of some SNP FADS with coronary heart disease, concentrations of plasma lipids, oxidative stress, glucose homeostasis, and inflammatory reaction, were described. Experimental studies on animal models and occurrence of rare diseases, associated with missing or with marked fall activities of D5D/D6D emphasized the significance of desaturases for healthy development of organism as well as for pathogenesis of some disease.

Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place?

Niacin is considered to be a powerful drug for the treatment of lipid and lipoprotein abnormalities connected with "residual cardiovascular risk", which persist in high-risk patients even when the target goals of LDL-C are achieved with statin therapy. Recent large randomized clinical studies - AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides) and HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) - delivered some disappointing results, leading to the conclusion that no further benefit (decreased parameters of cardiovascular risk) is achieved by adding niacin to existing statin therapy in patients with high cardiovascular risk. Moreover, in these studies, several adverse effects of the treatment were observed; therefore, niacin treatment for hypolipidemias is not recommended. In this paper, we analyze the mechanisms underlying the hypolipidemic and antiatherogenic effects of niacin as well as some limitations of the designs of the AIM HIGH and HP2-THRIVE studies. We also provide the possibilities of rational usage of niacin for specific types of dyslipidemias.

The prevalence of nonalcoholic liver steatosis in patients with type 2 diabetes mellitus in the Czech Republic.

AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with components of the metabolic syndrome (MS) but the prevalence of NAFLD in the Czech Republic is unknown. The aim of this study was to assess the latter in patients with type 2 diabetes (DM2) and to compare the noninvasive fibrosis scores with ultrasound findings in those patients. METHODS: 180 consecutive patients with DM2 (mean age 64.2±9.3 years, 63% men) were examined for liver biochemistry, MS parameters and had liver ultrasound. MS was diagnosed according to the International Diabetes Federation. The diagnosis of NAFLD was based on liver ultrasound. Other aetiology of liver lesion was ruled out. Additionally, AST/ALT ratio, APRI, NAFLD fibrosis score, FIB4 and BARD scores were calculated. RESULTS: 93% of patients met the MS criteria, 79% had NAFLD and 13% had ultrasound signs of fibrosis/cirrhosis. NAFLD patients had greater weight (96.9±19.3 vs 84.7±14.7 kg; P=0.003), BMI (32.6±5.2 vs 29.4±5.4 kg/m(2); P=0.007), waist circumference (113.8±12.8 vs 107.1±10.3 cm; P=0.033), ALT (0.73±0.57 vs 0.55±0.53 µkat/L, P=0.007) and triglyceridaemia (1.9±1.4 vs 1.4±1 mmol/L; P=0.005) than patients without NAFLD. There were no significant differences in age, sex, cholesterol, fasting glycaemia or glycated haemoglobin. Of calculated scores only the NAFLD fibrosis score revealed significant differences between patients with and without ultrasound signs of fibrosis/cirrhosis (1.027±2.228 vs -0.118±1.402, P=0.026). CONCLUSION: Patients with DM2 had in the majority of cases NAFLD which was related to weight, BMI, waist circumference and serum triglycerides. The validity of the liver fibrosis scoring system has to be assessed in those patients in the future.

Serum adiponectin relates to shortened overall survival in men with squamous cell esophageal cancer treated with preoperative concurrent chemoradiotherapy: a pilot study.

BACKGROUND: The convergence of nutritional, genetic, and inflammatory factors plays a significant role in the pathophysiology of squamous cell esophageal cancer (SCEC). The parameters of inflammation, indices of nutritional status, and adipocyte-derived hormones such as leptin, adiponectin, and resistin have been shown to be prognostic factors in some gastrointestinal and pancreatic cancers. MATERIAL/METHODS: Forty-two patients with SCEC were subjected to a multimodal regimen of concurrent neoadjuvant chemoradiotherapy (CRT) followed by surgery. We retrospectively analyzed the impact of pretreatment values of serum leptin, adiponectin, resistin, soluble leptin receptor, C-reactive protein, TNF alpha, leukocytes, and indices of nutritional status (BMI, plasma total protein, albumin, cholesterol, and triacylglycerols) on overall survival (OS). RESULTS: Univariate analysis revealed significant a negative correlation between OS and serum adiponectin (p=0.027), and a positive relationship was found between serum albumin (p=0.002), cholesterol (p=0.049) level, and OS. In multivariate analysis, only the trend (p=0.086) for negative serum adiponectin association with the OS was observed. CONCLUSIONS: In men with SCEC treated by neoadjuvant concurrent CRT and esophagectomy, high pretreatment level of serum adiponectin was associated with shorter OS while the serum albumin and cholesterol were associated with longer OS.

Xanthomas: clinical and pathophysiological relations.

BACKGROUND: Xanthomas are well circumscribed lesions in the connective tissue of the skin, tendons or fasciae that predominantly consist of foam cells; these specific cells are formed from macrophages as a result of an excessive uptake of low density lipoprotein (LDL) particles and their oxidative modification. RESULTS: Until recently, xanthelasma was considered to be only a cosmetic lesion; however, according to the results of recent prospective studies it is connected with an increased cardiovascular risk and reduced average lifespan. Pathogenetic mechanisms involved in the development of xanthomas resemble early stages of atherogenesis. In clinical practice, xanthomas can signalise various congenital or acquired dyslipidemias. The most prevalent form of xanthomas is xanthelasma palpebrarum. Tendinous and tuberous xanthomas are typical for autosomal dominant hypercholesterolemia, as well as for some rare conditions, such as cerebrotendinous xanthomatosis and familial ß-sitosterolemia. In patients with familial hypercholesterolemia, the presence of tendinous xanthomas has been shown to be associated with a two to four times higher risk for cardiovascular disease. Eruptive xanthomas are skin manifestations of a severe hypertriglyceridemia and implicate an elevated risk for acute pancreatitis or type 2 diabetes mellitus. Xanthoma striatum palmare is pathognomic for primary dysbetalipoproteinemia, whereas diffuse plane xanthomas are frequently associated with paraproteinemia and lymphoproliferative disorders. CONCLUSION: Thorough familiarity with the clinical presentation of xanthomas helps in the diagnosis and follow-up of different forms of dyslipidemia. Moreover, xanthelasma palpebrarum, the most prevalent form of xanthomas, is connected with increased risk of atherothrombotic disease independently of conventional cardiovascular risk factors. To fully understand the pathogenesis, further experimental and clinical research is required.

Altered activities of antioxidant enzymes in patients with metabolic syndrome.

OBJECTIVE: In the pathogenesis of the metabolic syndrome (MetS), an increase of oxidative stress could play an important role which is closely linked with insulin resistance, endothelial dysfunction, and chronic inflammation. The aim of our study was to assess several parameters of the antioxidant status in MetS. METHODS: 40 subjects with MetS and 40 age- and sex-matched volunteers without MetS were examined for activities of superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), paraoxonase1 (PON1), concentrations of reduced glutathione (GSH), and conjugated dienes in low-density lipoprotein (CD-LDL). RESULTS: Subjects with MetS had higher activities of CuZnSOD (p < 0.05) and GR (p < 0.001), higher concentrations of CD-LDL (p < 0.001), lower activities of CAT (p < 0.05) and PON1 (p < 0.05), and lower concentrations of GSH (p < 0.05), as compared with controls. Activity of GPX1 was not significantly changed. CONCLUSIONS: Our results implicated an increased oxidative stress in MetS and a decreased antioxidative defense that correlated with some laboratory (triglycerides, high-density lipoprotein cholesterol (HDL-C)) and clinical (waist circumference, blood pressure) components of MetS.

Plasma fatty acid profile in depressive disorder resembles insulin resistance state.

BACKGROUND: Depressive disorder is related to an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). Insulin resistance (IR), connected with altered fatty acid (FA) composition, namely with decreased proportion of polyunsaturated FA could participate in these associations. The aim of the study was to investigate the composition of FA in plasma cholesterol esters (CE) and phosphatidylcholine (PC) as well as indices of insulin resistance and oxidative stress in the patients with depressive disorder. MATERIALS AND METHODS: Parameters of lipid and glucose homeostasis, concentrations of FA in plasma cholesteryl esters (CE) and phosphatidylcholine (PC) and conjugated dienes in LDL were investigated in a group of 47 patients (9M/38F) with depression and compared with 47 control persons (16M/31F). Delta-9 desaturase (D9D) and D6D desaturase were estimated as product to precursor fatty acid ratios. RESULTS: In depressive patients increased concentrations of palmitoleic acid and total monounsaturated FA with decreased proportion of total polyunsaturated FA n-6 (PUFA n-6) (all p<0.05) in CE were found, while in PC increased proportion of saturated FA was observed (p<0.05). Moreover, index of D6D activity was significantly increased in PC and CE (p<0.05). Concomitantly, in depressive patients higher levels of plasma triacylglycerols (p<0.05), conjugated dienes in LDL (p<0.001) and HOMA index of IR (p<0.05) were found. CONCLUSIONS: Esterified FA composition of depressive patients revealed changes, similar to those, usually observed in insulin resistance. Dysregulation of FA could participate in the pathogenesis of depression and be associated with an increased risk of CVD and DM2.

N-3 polyunsaturated fatty acids in the treatment of atherogenic dyslipidemia.

BACKGROUND: Atherogenic dyslipidemia contributes substantially to the residual cardiovascular risk. The aim of this study was to examine the effects of therapeutic doses of n-3 polyunsaturated fatty acids on the three major lipid abnormalities of atherogenic dyslipidemia, i.e. hypertriacylglycerolemia, low HDL cholesterol, and increased levels of small dense LDL particles, as well as on some new risk factors. MATERIALS AND METHODS: A total of 60 hypertriacylglycerolemic patients were included in the study. Group S consisted of 36 patients who were already treated with statins, Group N of 24 patients not yet treated. Each patient was examined after six weeks on placebo and six weeks of treatment with n-3 PUFA (eicosapentaenoic and docosahexaenoic acid ethyl esters, 3.0 g/d). RESULTS: Treatment with n-3 PUFA caused a decrease in plasma triacylglycerols (28%, p<0.001), and VLDL (-27%, p<0.001), an increase in HDL-C (+4%, p<0.01), and a decrease in sdLDL cholesterol (-16%, p<0.05). These changes were accompanied by a decrease in microalbuminuria (-30%, p<0.05), as well as in several parameters of oxidative stress. Analysis of the fatty acids composition of plasma phospholipids showed a significant increase in all n-3 PUFAs examined, accompanied by a decrease in n-6 PUFAs, as well as in monounsaturated acids. No significant differences in the effects of n-3 PUFA were found between the Groups S and N. CONCLUSION: Our results support the opinion that hypertriacylglycerolemic patients benefit from the treatment with n-3 PUFA which improves several important metabolic factors of cardiovascular risk.

Plasma fatty acid composition in patients with pancreatic cancer: correlations to clinical parameters.

Pancreatic cancer (PC) ranks as the fourth cause of cancer-related deaths in the Czech Republic. Evidence exists that deregulation of fatty acid (FA) metabolism is connected with some malignancies; therefore, we decided to analyze FA profile in plasma lipid classes in patients with PC with relation to tumor staging, nutritional status, and survival. The study included 84 patients (47 males, 37 females) with PC and 68 controls (36 males, 32 females). FA patterns were analyzed in plasma lipid classes by gas-chromatography. We observed increased proportion of total monounsaturated FA (MUFA) in PC group in all plasma lipid classes. These changes were connected with increased Δ9-desaturase (SCD1) and Δ5-desaturase indices. Correlations of dihomo-γ-linolenic acid (DHGLA) with these variables were opposite. Longer survival of patients was connected with higher content of EPA, DHA, and with lower SCD1 index, respectively. Plasma phospholipid proportions of α-linolenic acid, DHGLA, EPA, and n-3 polyunsaturated fatty acids displayed negative trend with tumor staging. Plasma lipid FA pattern in PC patients resulted from decreased dietary fat intake and increased de novo synthesis of FA with transformation into MUFA. Changes in FA profile implicated some pathophysiological mechanisms responsible for disturbed FA metabolism in PC and importance of appropriate nutritional support.

[Statin-ezetimibe combination in hyperlipidemia treatment]. / Kombinace statin-ezetimib v lécbe hyperlipidémie.

BACKGROUND: Statin monotherapy for dyslipidemia only rarely achieves recommended target values of plasma lipids. Statin plus ezetimibe is a feasible treatment option. The aim of the present study was to test efficacy and safety of statin plus ezetimibe combination in the treatment of severe dyslipidemia in patients coming to an ordinary lipid and diabetology department. METHODS AND RESULTS: A retrospective evaluation of 3 months treatment in 82 dyslipidemia patients (25 male, 57 female) with unsatisfactory statin monotherapy results (average equivalent of 30 mg atorvastatin) was performed. Ezetimibe 10 mg per day was added to preceding treatment. The group included 26 diabetics type 2. The addition of ezetimibe resulted in statistically significant decrease of plasma total cholesterol (TC) (-21%), LDL-C (-28%), triacylglyceroles (TAG) (-26%) and HDL-C (-6%). The recommended values of LDL-C were achieved in 42% of patients. In the diabetic subgroup a significant decrease of TC (24%), LDL-C (33%) and TAG (18%) was observed. There was no significant decrease of HDL-C. The recommended value of LDL-C was achieved in 48% of diabetics. There were no unfavourable side effects. CONCLUSIONS: The addition of ezetimib in a dose of 10 mg in hyperlipidaemia patients who had not achieved the recommended target values of LDL-C resulted in a subsequent significant decrease of both TC and LDL-C. It also enabled to increase the number of patients achieving the recommended target plasma lipid values. The treatment was safe and was not associated with adverse effects.

N-3 polyunsaturated fatty acids in psychiatric diseases: mechanisms and clinical data.

The lipids constitute majority of dry weight of mature human brain. From lipids, 35% is comprised of PUFA with long chain (LC-PUFA), especially docosahexaenoic acid (DHA) of n-3 family and arachidonic acid (AA) of n-6 family. Humans are dependent on dietary intake of both AA and DHA. Interestingly, the dietary n-6/n-3 ratio increased considerably during last century. LC-PUFAs play numerous roles in the brain, including structural (forming the physico-chemical properties in the lipid bilayer of cellular membranes) and signaling ones. Moreover, they influence neurogenesis and neurotransmission within the nervous tissue. The metabolites of PUFA modulate immune and inflammatory processes in the brain, oxidative stress as well as its consequences. Of high importance is also their connection with several metabolic factors involved in the proper function of the brain and/or were discovered to play a role in the pathogenesis of neuropsychiatric diseases - melatonin, homocysteine, leptin, and adiponectin. This review gives short view of the metabolism and possible mechanisms of PUFA n-3 action in the brain, and their role in the pathogenesis of psychiatric diseases.

[Reactive oxygen and nitrogen species in the clinical medicine]. / Reaktivní kyslíkové a dusíkové slouceniny v klinické medicíne.

Vast knowledge has accumulated recently on the role of reactive oxygen and nitrogen species (RONS) in clinical medicine. Strong evidence was disclosed on their important role in the pathogenesis of several diseases. Free radicals have unpaired electron and this is the reason for extreme reactivity causing propagation reactions that lead to the multiple damage to cells. Oxidizing agents belong to the family of reactive species. Reactive oxygen species are produced during biochemical processes such as oxidative phosphorylation, phagocytosis and metabolism of purins. Overproduction of reactive oxygen species can cause the tissue damage. Reactive nitrogen species are produced by inhibition of nitric oxide synthase by the action of asymmetric dimethylarginine. Peroxisomal oxidases, NAD(P) oxidase, xanthinoxidase, nitric oxide synthase, myeloperoxidase and lipooxygenase catalyze biochemical reactions producing reactive oxygen and nitrogen species. Biochemical and molecular processes in cells are negatively influenced by chemical modification of DNA, proteins and lipids caused by the action of reactive oxygen and nitrogen species. Antioxidant metabolites and enzymes work together to stop and to prevent oxidative modification of biomolecules. Reactive oxygen and nitrogen species play an important role in the pathogenesis of many diseases such as atherosclerosis, diabetes, hyperlipidaemia and neurodegenerative diseases.