Novel biochemical markers for non-invasive detection of pancreatic cancer.

To identify non-invasive biomarkers of non-metastatic pancreatic cancer (PC), the blood from 186 patients (PC n=28; DM-diabetes mellitus n=60; ChP-chronic pancreatitis n=47; healthy controls n=51) was analyzed for 58 candidate biomarkers. Their effectiveness to identify PC was compared with CA19-9. Panel defined by Random-forest (RF) analysis (CA19-9, AAT, IGFBP2, albumin, ALP, Reg3A, HSP27) outperforms CA19-9 in discrimination of PC from DM (AUC 0.92 vs. 0.82). Panel (S100A11, CA72-4, AAT, CA19-9, CB, MMP-7, S100P-s, Reg3A) is better in discrimination PC from ChP than CA19-9 (AUC 0.90 vs. 0.75). Panel (MMP-7, Reg3A, sICAM1, OPG, CB, ferritin) is better in discrimination PC from healthy controls than CA19-9 (AUC 0.89 vs. 0.78). Panel (CA19-9, S100P-pl, AAT, albumin, adiponectin, IGF-1, MMP7, S100A11) identifies PC among other groups better than CA19-9 (AUC 0.91 vs. 0.80). Panel defined by logistic regression analysis (prealbumin, IGFBP-2, DJ-1, MIC-1, CA72-4) discriminates PC from DM worse than CA19-9 (AUC 0.80 vs. 0.82). Panel (IGF-1, S100A11, Reg1alfa) outperforms CA19-9 in discrimination PC from ChP (AUC 0.76 vs. 0.75). Panel (IGF-2, S100A11, Reg3A) outperforms CA19-9 in discrimination PC from healthy controls (AUC 0.95 vs. 0.78). Panel (albumin, AAT, S100P-serum, CRP, CA19-9, TFF1, MMP-7) outperforms CA19-9 in identification PC among other groups (AUC 0.89 vs. 0.8). The combination of biomarkers identifies PC better than CA19-9 in most cases. S100A11, Reg3A, DJ-1 were to our knowledge identified for the first time as possible serum biomarkers of PC.

Statins and liver.

Statins are widely accepted hypolipidemics that work by inhibiting hydroxymethylglutaryl coenzyme A reductase and thereby inhibiting cholesterol synthesis. They significantly reduce cardiovascular risk. Their use could be associated with side effects, which are serious only in rare cases. However, an unhealthy lifestyle, obesity, and elevation of blood lipids do not only damage the cardiovascular system. The current topic not only in hepatology is non-alcoholic fatty liver disease - NAFLD. The aim of this article is, among others, to draw attention to the pleiotropic effects of statins, which could be used in the treatment of this disease in the future. Recent studies have suggested that the administration of statins to patients with NAFLD is beneficial.

Dyslipidemia in patients with chronic kidney disease: etiology and management.

The worldwide population is burdened with chronic kidney disease (CKD) from 10-13 %. Patients with CKD subsequently die to cardiovascular disease (CVD) and their complications. In the Czech population, in 2016, the number of patients with end stage renal disease (ESRD) on regular dialytic treatment was 6 739, or 674/1 000 000 inhabitants. Overall mortality in regular dialysis treatment patients was 18.4 % in 2016, of which 43 % died of cardiovascular complications. In view of this fact, a number of expert groups are concerned, among other things, with the problems of lipid metabolism disorders, with the aim of finding a common predictive marker (preferably also therapeutically qualifiable) to stratify patients dialyzed or potentially indicating hypolipidemic therapy. The aim of possible interventions is to minimize cardiovascular risk and subsequent complications resulting from cardiovascular disease (CVD), thus improving the quality of life of regular dialysis treatment patients.

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.

[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.

Omega-3 phospholipids from fish suppress hepatic steatosis by integrated inhibition of biosynthetic pathways in dietary obese mice.

Non-alcoholic fatty liver disease (NAFLD) accompanies obesity and insulin resistance. Recent meta-analysis suggested omega-3 polyunsaturated fatty acids DHA and EPA to decrease liver fat in NAFLD patients. Antiinflammatory, hypolipidemic, and insulin-sensitizing effects ofDHA/EPA depend on their lipid form, with marine phospholipids showing better efficacy than fish oils. We characterized the mechanisms underlying beneficial effects of DHA/EPA phospholipids, alone or combined with an antidiabetic drug, on hepatosteatosis. C57BL/6N mice were fed for 7 weeks an obesogenic high-fat diet (cHF) or cHF-based interventions: (i) cHF supplemented with phosphatidylcholine-rich concentrate from herring (replacing 10% of dietary lipids; PC), (ii) cHF containing rosiglitazone (10 mg/kg diet; R), or (iii) PC + R. Metabolic analyses, hepatic gene expression and lipidome profiling were performed. Results showed that PC and PC + R prevented cHlF-induced weight gain and glucose intolerance, while all interventions reduced abdominal fat and plasma triacylglycerols. PC and PC + R also lowered hepatic and plasma cholesterol and reduced hepatosteatosis. Microarray analysis revealed integrated downregulation of hepatic lipogenic and cholesterol biosynthesis pathways by PC, while R-induced lipogenesis was fully counteracted in PC + R Gene expression changes in PC and PC + R were associated with preferential enrichment of hepatic phosphatidylcholine and phosphatidylethanolamine fractions by DHA/EPA. The complex downregulation of hepatic lipogenic and cholesterol biosynthesis genes and the antisteatotic effects were unique to DHA/EPA-containing phospholipids, since they were absent in mice fed soy-derived phosphatidylcholine. Thus, inhibition of lipid and cholesterol biosynthesis associated with potent antisteatotic effects in the liver in response to DHA/EPA-containing phospholipids support their use in NAFLD prevention and treatment.

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.

Levels of retinol and retinoic acid in pancreatic cancer, type-2 diabetes and chronic pancreatitis.

AIMS: Retinoids participate in multiple key processes in the human body e.g., vision, cell differentiation and embryonic development. There is growing evidence of the relationship between retinol, its active metabolite- all-trans retinoic acid (ATRA) - and several pancreatic disorders. Although low levels of ATRA in pancreatic ductal adenocarcinoma (PDAC) tissue have been reported, data on serum levels of ATRA in PDAC is still limited. The aim of our work was to determine serum concentrations of retinol and ATRA in patients with PDAC, type-2 diabetes mellitus (T2DM), chronic pancreatitis (CHP) and healthy controls. METHODS: High performance liquid chromatography with UV detection (HPLC) was used to measure serum levels of retinol and ATRA in 246 patients with different stages of PDAC, T2DM, CHP and healthy controls. RESULTS: We found a significant decrease in the retinol concentration in PDAC (0.44+/-0.18 mg/L) compared to T2DM (0.65+/-0.19 mg/L, P<0.001), CHP (0.60+/-0.18 mg/L, P< 0.001) and healthy controls (0.61+/-0.15 mg/L, P<0.001), significant decrease of ATRA levels in PDAC (1.14+/-0.49 ug/L) compared to T2DM (1.37+/-0.56 ug/L, P<0.001) and healthy controls(1.43+/-0.55 ug/L, P<0.001). Differences between early stages (I+II) of PDAC and non-carcinoma groups were not significant. We describe correlations between retinol, prealbumin and transferrin, and correlation of ATRA and IGFBP-2. CONCLUSION: Significant decrease in retinol and ATRA levels in PDAC compared to T2DM, healthy individuals and/or CHP supports existing evidence of the role of retinoids in PDAC. However, neither ATRA nor retinol are suitable for detection of early PDAC. Correlation of ATRA levels and IGFBP-2 provides new information about a possible IGF and retinol relationship.

Ferritin as an independent mortality predictor in patients with pancreas cancer. Results of a pilot study.

Prognosis of patients with pancreas cancer is very poor. The aim of the study was to test the significance of laboratory parameters in the prognosis of patients with pancreas cancer. The studied group included 57 patients (31 men, 26 women, mean age 65 ± 9 years). Blood was collected at the time of diagnosis of pancreas cancer and basic laboratory parameters, including nutritional and inflammatory markers and tumour markers were measured. Patients were followed up until death (median survival 147 days). Ferritin, iron, albumin, prealbumin, cholinesterase, haemoglobin, C-reactive protein, alkaline phosphatase and carcinoembryonic antigen were significant for patients' prognosis in univariate analysis while CA 19-9, bilirubin, liver, pancreas and kidney tests and lipids were not. Multivariate Cox regression demonstrated ferritin, iron and albumin as independent mortality predictors (RR (95%CI), per standard deviation: ferritin 1.497(1.215-2.241), p = 0.002; albumin, 0.716(0.521-0.977), p = 0.035; iron, 0.678(0.504-0.915), p = 0.010). Iron correlated significantly with albumin (r = 0.397, p = 0.002) but neither iron nor albumin correlated with ferritin. Patients who survived 100 days had significantly lower ferritin (median 239 µg/l vs. non-survivors 435 µg/l, p = 0.014), significantly higher albumin but the difference in serum iron was not quite significant. ROC analysis for ferritin revealed AUC for 100 days survival of 0.710, p = 0.007 (and 0.725, p = 0.004 for 200 days survival). AUC for albumin for 100 days survival was not significant (p = 0.073). This study points out ferritin as an independent mortality predictor in patients with pancreas cancer. High serum levels of ferritin at the time of diagnosis of pancreas cancer indicate bad prognosis of the patient.

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.

Lipid-lowering effect of fluvastatin in relation to cytochrome P450 2C9 variant alleles frequently distributed in the Czech population.

BACKGROUND: CYP2C9*3 allele has been reported to correlate with increased plasma concentration of fluvastatin active form in healthy volunteers. We analyzed the correlation between the CYP2C9 genotype and cholesterol-lowering effect of fluvastatin in human hypercholesterolemic patients. MATERIAL/METHODS: The study was prospective, without any interventions to standard procedures of hypolipidemic treatment. CYP2C9 genotype was determined by PCR-RFLP assay in 87 patients on concomitant fluvastatin therapy, in 48 patients on monotherapy, and in a control group of 254 healthy volunteers of Czech nationality. Biochemical and clinical data were collected before the initiation of fluvastatin treatment and 12 weeks later. RESULTS: The frequency of CYP2C9 alleles did not differ significantly among groups of patients and volunteers. The most frequently observed allele was CYP2C9*2. Treatment with 80 mg of fluvastatin daily of 48 patients on monotherapy for 12 weeks resulted in mean low-density lipoprotein cholesterol (LDL-C) reduction by 25%, mean serum total cholesterol (TC) reduction by 21%, and mean triglyceride (TG) reduction by 28%. The CYP2C9*1/*3 genotype was associated with a decrease in LDL-C levels (by 40.0% for CYP2C9*1/*3, but only by 22.4% for CYP2C9*1/*1), and with the reduction of TC (by 28.6% in CYP2C9*1/*3 versus 20.2% in CYP2C9*1/*1). CONCLUSIONS: In hypercholesterolemic patients, LDL-C serum concentration was decreased more significantly in fluvastatin-treated subjects bearing the CYP2C9*1/*3 genotype compared to CYP2C9*1/*1 genotype. However, due to rare occurrence of some CYP genotypes, it was impossible to report a definitive positive genotype-fluvastatin effect association.

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.

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.

[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.

[Oxidative stress after anthracycline therapy in patients with solid tumors]. / Oxidacní stres u nemocných po lécbe antracyklíny pro solidní nádorová onemocnení

BACKGROUND: Anthracyclines are regarded as some of the most potent oxidative stress inductors. Despite the fact that oxidative stress induction by anthracyclines is believed to be the key factor in anthracycline-related cardiotoxicity, the precise timeline of oxidative stress changes after anthracycline treatment remains unknown. The aim of the present study is to assess the level of oxidative stress after anthracycline therapy in patients with solid tumors. PATIENTS: The study population consists of 128 adult patients (14 males, 114 females, mean age 56 ± 10 years) receiving anthracycline chemotherapy for solid tumors. The control group consists of 38 patients (4 males, 34 females, mean age 59 ± 11 years) receiving anthracycline-free chemotherapy for solid tumors. METHODS: The main activities of antioxidant enzymes (catalase, glutathione peroxidase-1, superoxide dismutase, and paraoxonase-1) and concentrations of conjugated dienes, surrogate markers of oxidative stress level, were established at the baseline and after anthracycline therapy (median 45; IQR 27-69 days after the end of anthracycline therapy) in all patients. By comparing the activities of antioxidant enzymes and the concentrations of conjugated dienes, before and after therapy, changes in oxidative stress level within the time period were established for both study groups. Differences between the study groups, with regard to changes in the activities of antioxidant enzymes and the concentrations of conjugated dienes, were also evaluated. CONCLUSIONS: An increase in oxidative stress was observed after the end of anthracycline therapy in patients with solid tumors. However, our study shows that this persistent elevation of oxidative stress after the end of anthracycline therapy is probably not caused by anthracyclines.

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.

[Current status of pancreatic cancer diagnosis]. / Soucasný stav diagnostiky karcinomu pankreatu.

Pancreatic cancer still remains one of the tumors with the worst prognosis. The five-year survival rate ranges between 0.4 to 2 per cent. In most cases the tumor is diagnosed at an advanced stage, which does not allow a radical surgical treatment. Currently, the diagnosis of pancreatic cancer is based on dynamically developing imaging methods that allow detecting even small lesions. The basic testing method is the contrast computed tomography which is, in most cases, linked up to the endoscopic ultrasonography. In most patients results of the cytopathological and histological examinations are obtained before surgical or oncological therapy. The decisive factor for further therapeutic approach is the tumor staging. Despite the apparent progress in diagnostic techniques, the early diagnosis of pancreatic cancer remains unsatisfactory.

[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.

A Matched Case-Control Study of Noncholesterol Sterols and Fatty Acids in Chronic Hemodialysis Patients.

Dyslipidemia is common among patients on hemodialysis, but its etiology is not fully understood. Although changes in cholesterol homeostasis and fatty acid metabolism play an important role during dialysis, the interaction of these metabolic pathways has yet to be studied in sufficient detail. In this study, we enrolled 26 patients on maintenance hemodialysis treatment (high-volume hemodiafiltration, HV HDF) without statin therapy (17 men/9 women) and an age/gender-matched group of 26 individuals without signs of nephropathy. The HV-HDF group exhibited more frequent signs of cardiovascular disease, disturbed saccharide metabolism, and altered lipoprotein profiles, manifesting in lower HDL-C, and raised concentrations of IDL-C and apoB-48 (all p < 0.01). HV-HDF patients had higher levels of campesterol (p < 0.01) and ß-sitosterol (p = 0.06), both surrogate markers of cholesterol absorption and unchanged lathosterol concentrations. Fatty acid (FA) profiles were changed mostly in cholesteryl esters, with a higher content of saturated and n-3 polyunsaturated fatty acids (PUFA) in the HV-HDF group. However, n-6 PUFA in cholesteryl esters were less abundant (p < 0.001) in the HV-HDF group. Hemodialysis during end-stage kidney disease induces changes associated with higher absorption of cholesterol and disturbed lipoprotein metabolism. Changes in fatty acid metabolism reflect the combined effect of renal insufficiency and its comorbidities, mostly insulin resistance.