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Long-chain n-3 polyunsaturated fatty acids modulate immune cell functions. The primary objective of this study was to evaluate the impact of different lipid emulsions (LEs) with supplemented doses of fish oil (FO) on serum cytokine concentration and in vitro cytokine production in patients with intestinal failure on home parenteral nutrition (HPNPs). We hypothesized that FO supplementation would diminish lipopolysaccharide (LPS)-stimulated cytokine production. Twelve HPNPs receiving Smoflipid for at least 3 months were given FO (Omegaven) for a further 4 weeks. After this cycle, the patients were randomized to subsequently receive 1 cycle with Lipoplus and 1 cycle with ClinOleic for 6 weeks or vice versa plus 4 weeks of added Omegaven after each cycle in a crossover design. Comparison of the baseline LE regimens showed lower LPS-stimulated production of IL-1β in the HPNPs on Lipoplus than on the Smoflipid and ClinOleic regimens, as well as lower IL-8 compared to the Smoflipid regimen. Omegaven reduced IL-8 concentration in serum under the Lipoplus regimen and diminished LPS-stimulated production of IL-1β under the Smoflipid and ClinOleic. IL-6 and TNF-α production was depressed only in those on Smoflipid. Irrespective of the LE used, the HPNPs compared to the healthy controls showed higher IL-6, IL-8, and TNF-α concentrations in serum and LPS-stimulated production of IL-6 as well as lower n-6/n-3 long-chain polyunsaturated fatty acids in the erythrocyte phospholipids. LPS-stimulated production of IL-6 correlated negatively with the parenteral dose of eicosapentaenoic acid + docosahexaenoic acid. In conclusion, FO-supplemented parenteral nutrition suppresses in vitro cytokine production.

Background: Carotid endarterectomy is beneficial in symptomatic patients with ≥70% stenosis at the bifurcation of the internal carotid artery. The fact that the duplex ultrasound is widely used, inexpensive and non-invasive for examination of the carotid arteries underlines the importance of high accuracy of this method for grading internal artery stenosis. Patients and Methods: Duplex scans and arteriograms of carotid arteries of 142 patients were reviewed. Peak and end-diastolic velocities of the common and internal carotid arteries were recorded, and the percent stenosis of the internal carotid artery was determined by arteriogram. Receiver-operator characteristic curves of sensitivity, specificity, positive and negative predictive values and accuracy were determined. Results: The recommended criteria for the detection of ≥70% stenosis of the internal carotid artery were: peak systolic velocity in the internal carotid artery ≥215 cm/s, end-diastolic velocity in the internal carotid artery ≥65 cm/s, ratio of peak systolic velocities in the internal and common carotid arteries ≥2.7 and ratio of the end-diastolic velocities of the internal and common carotid arteries ≥3.7. Conclusion: These criteria allow for reliable determination of internal carotid artery stenosis ≥70% by duplex ultrasound.

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.

Markers of oxidative stress and antioxidant status in relation to inflammatory mediators in septic patients (SPs) during the course of sepsis and after recovery were analysed. Patients were 30 critically ill adults in severe sepsis/septic shock, 19 of which completed 3 samplings (S1: within 24 h after onset of sepsis, S7: 7 days after S1, R7: 7 days after clinical recovery). Comparing SPs with healthy controls (HCs), enhanced C-reactive protein, procalcitonin, bilirubin and CuZn-superoxide dismutase activity were found at S1 only. Oxidized low-density lipoprotein, conjugated dienes and nitrotyrosine were increased at S1, culminated at S7 and reverted nearly to HC levels at R7. Reduced catalase activity and serum amyloid were observed at S1 and endured until R7. Increase in IL-6, IL-10 and tumour necrosis factor alpha (TNF-α) with accompanying decrease in apolipoprotein A1, high-density lipoprotein (HDL) cholesterol, selenium, zinc, albumin, paraoxonase 1 and glutathione peroxidase 1 activity appeared at S1 and persisted until R7. TNF-α, IL-10 and markers of oxidative stress were in negative correlation with HDL cholesterol and albumin at R7. After clinical recovery, increased cytokines and decreased antioxidants were accompanied by lower albumin and HDL cholesterol levels. During this important and beneficial period of tissue repair, patients with prolonged persistence of this status are probably more vulnerable to secondary infections and should be dealt with as constituting a high-risk population.

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 β-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.

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. Anti-inflammatory, hypolipidemic, and insulin-sensitizing effects of DHA/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 cHF-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 down-regulation 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 down-regulation 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.

OBJECTIVES Oxidative stress has been implicated in the pathogenesis of chronic pancreatitis (CP) and pancreatic cancer (PC). The study aim was to assess the oxidative stress markers and antioxidant defense system in patients with CP and those with PC. METHODS Activities of superoxide dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), arylesterase (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1) and concentrations of reduced glutathione, conjugated dienes in low-density lipoprotein (CD/LDL) and oxidized LDL (ox-LDL/LDL) were assessed in 50 PC and 50 CP patients and 50 age and sex-matched controls. RESULTS Comparison of PC and CP groups to controls found the following changes: glutathione peroxidase 1 (GPX1) (-20.2%, -25.5%; P < 0.001), glutathione reductase (GR) (-9.5%, -11.9%; P < 0.05), SOD1 (+22.9%; P < 0.01), CAT (-10.6%; P < 0.05), PON1-A (-34.3%, -16.0%; P < 0.001), PON1-L (-44.2%; -17.0%; P < 0.01), conjugated dienes in LDL (CD/LDL) (+20%, +33.3%; P < 0.05) and ox-LDL/LDL (+42.2%, +14.4%; P < 0.05). The patients with PC had changed activities and levels of SOD1 (+24.2%), CAT (-10.4); P < 0.01), PON1-A (-21.7%), PON1-L (-32.9%), and ox-LDL/LDL (+24.3%); (all P < 0.01) compared with the patients with CP. CONCLUSIONS Reduced antioxidant defense system capacity and increased markers of oxidative stress were found in PC and CP. PON1-L and CAT activities, along with ox-LDL/LDL levels, were the independent factors differentiating the patients with PC from the patients with CP.

This study analyzes fatty acid (FA) composition in plasma lipids and erythrocyte phospholipids while comparing septic and non-septic critically ill patients. The aim was to describe impacts of infection and the inflammatory process. Patients with severe sepsis (SP, n = 13); age-, sex- and APACHE II score-matched non-septic critically ill with systemic inflammatory response syndrome (NSP, n = 13); and age-/sex-matched healthy controls (HC, n = 13) were included in a prospective case–control study during the first 24 h after admission to the intensive care unit. In both SP and NSP, lower n-6 polyunsaturated FA (PUFA) accompanied by higher proportions of monounsaturated FA (MUFA) in plasma phospholipids (PPL) was observed relative to HC. MUFA proportion was negatively correlated with n-6 PUFA, high density lipoprotein cholesterol (HDL-C), and albumin. MUFA was positively correlated with C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-6, IL-10), oxidized low density lipoproteins (ox-LDL), and conjugated dienes (CD). In both SP and NSP, inflammatory and lipid peroxidation markers were significantly higher—CRP (p

Background: This is the second of two review parts aiming at describing the major physiological roles of fatty acids, as well as their applications in specific conditions related to human health. Results: The review included the current literature published in Pubmed up to March 2011. In humans, fatty acids are a principle energy substrate and structural components of cell membranes (phospholipids) and second messengers. Fatty acids are also ligands of nuclear receptors affecting gene expression. Longer-chain (LC) polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid are precursors of lipid mediators such as eicosanoids (prostaglandins, leukotrienes, thromboxanes), resolvins and neuroprotectins. Lipid mediators produced by EPA and DHA (LC n-3 PUFA; mainly found in oily fish) are considered as inflammation-resolving, and thus, fish oil has been characterised as antiinflammatory. Recommendations for EPA plus DHA intake from oily fish vary between 250-450 mg/day. Dietary reference values for fat vary between nutrition bodies, but mainly agree on a low total and saturated fat intake. The existing literature supports the protective effects of LC n-3 PUFA (as opposed to n-6 PUFA and saturated fat) in maternal and offspring health, cardiovascular health, insulin sensitivity, the metabolic syndrome, cancer, critically ill patients, and immune system disorders. Conclusion: Fatty acids are involved in multiple pathways and play a major role in health. Further investigation and a nutrigenomics approach to the effects of these biocompounds on health and disease development are imperative and highlight the importance of environmental modifications on disease outcome.

The aim of this study was to investigate the effect of the microsomal triglyceride transfer protein (MTP) −493G/T polymorphism on clinical and biochemical parameters in relation to the presence of metabolic syndrome (MS). A group of 270 participants, 143 men and 127 women [50 men/36 women fulfilled the International Diabetes Federation (IDF) criteria of MS], was categorized on the basis of the MTP −493G/T polymorphism: GG homozygotes (Group GG) and carriers of the T allele (Group TT+TG). In men with MS, the presence of the T allele was associated with elevated concentrations of plasma insulin (by 48%, P

Fourteen pairs of obese female monozygotic twins were recruited for a study of genetic influences on serum and adipose fatty acid (FA) composition. Following 1 wk of inpatient stabilization, fasting serum and adipose tissue obtained by surgical excision were analyzed by thin-layer and gas chromatography. Intrapair resemblances (IPR) for individual FA were assessed by Spearman rank correlation and by analysis of variance and were found in serum cholesteryl esters (CF), triglycerides (TG), and adipose TG. With two exceptions (CE linoleate and adipose eicosapentaenoate), these IPR were limited to the nonessential FA. Palmitate had significant IPR in four lipid fractions; in serum CE and adipose TG palmitate was strongly correlated with multiple measures of adiposity. In contrast to other lipid fractions, serum phosphatidylcholine (PC) FA had 12 [PR, of which 6 were essential FA including arachidonate (r = 0.76, P < 0.0005), eicosapentaenoate (r = 0.78, P < 0.0005), and docosahexaenoate (r = 0.86, P< 0.0001). The PC [PR could not be explained by analysis of preadmission 7-d food records. After dividing the pairs into two groups differing and nondiffering according to fat intake of individuals in the pair, there was no evidence of a gene-environment interaction between fat intake and FA composition. The IPR for nonessential FA indicate that there is active genetic control of either food choices or postabsorptive metabolic processing. The high level of IPR in the PC fraction in contrast to the other lipid fractions suggests strong genetic influence over selection of specific FA for this membrane fraction independent of diet.

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.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.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.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.

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.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.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 p0.05) in CE were found, while in PC increased proportion of saturated FA was observed (p0.05). Moreover, index of D6D activity was significantly increased in PC and CE (p0.05). Concomitantly, in depressive patients higher levels of plasma triacylglycerols (p0.05), conjugated dienes in LDL (p0.001) and HOMA index of IR (p0.05) were found.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.

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.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).Treatment with n-3 PUFA caused a decrease in plasma triacylglycerols (28%, p0.001), and VLDL (-27%, p0.001), an increase in HDL-C (+4%, p0.01), and a decrease in sdLDL cholesterol (-16%, p0.05). These changes were accompanied by a decrease in microalbuminuria (-30%, p0.05), 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.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.

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.

Summary 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.

Objective. The aim of the study was to determine the optimum cut-off value of the quantitative immunochemical test (q-FIT) OC-Sensor® for colorectal cancer and advanced adenomatous polyps in a particular population. Methods. 815 patients were referred for colonoscopy and were offered two q-FIT examinations at two different colonoscopy centers. The patients were classified according to the colonoscopic findings. Test sensitivity, specificity, and accuracy were statistically evaluated using one test and two tests at the levels of 50, 75, 100, 125, and 150 ng/mL of faecal hemoglobin in those patients with advanced polyps and colorectal cancer. The optimum cut-off test level for clinically significant neoplasia was determined using one test. Results. The optimum cut-off value of q-FIT OC-Sensor ® for the detection of clinically significant neoplasia in our particular population was determined as 75 ng/mL using one test. This value provides an optimum proportion of 73% sensitivity (±95% CI 60.3% – 83.4%) and 90% specificity (±95% CI 86.8% – 92.8%), PPV and NPV were determined as 54.76% and 95.43% respectively. Conclusions. The first step in the implementation of q-FIT test in the screening program in our country is to determine the optimum cut-off level for a population, and to estimate the number of tests performed with respect to the optimum cost effectiveness and economical climate. Using one test, the optimum level of q-FIT OC-Sensor® in the Czech Republic was determined as 75 ng/mL. This study could serve as a model for further studies in other countries, where screening does not yet exist.

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.

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.

Background. Fatty acids are substantial components of lipids and cell membranes in the form of phospholipids. This review consists of two parts. The present part aims at describing fatty acid classification, dietary sources and biological functions. The second part will focus on fatty acid physiological roles and applications in human health and disease. Results. In humans, not all fatty acids can be produced endogenously due to the absence of certain desaturases. Thus, specific fatty acids termed essential (linoleic, alpha-linolenic) need to be taken from the diet. Other fatty acids whose synthesis depends on essential fatty acid intake include eicosapentaenoic acid and docosahexaenoic acid, found in oily fish. Dietary sources of saturated fatty acids are animal products (butter, lard) and tropical plant oils (coconut, palm), whereas sources of unsaturated fatty acids are vegetable oils (such as olive, sunflower, and soybean oils) and marine products (algae and fish oils). Saturated fatty acids have been related to adverse health effects, whereas unsaturated fatty acids, especially monounsaturated and n-3 polyunsaturated, are thought to be protective. In addition, trans fatty acids have been shown to have negative effects on health, whereas conjugated fatty acids might be beneficial. Lastly, fatty acids are the main components of lipid classes (triacylglycerols, phospholipids, cholesteryl esters, non-esterified fatty acids). Conclusion. Fatty acids are important biocompounds which take part in complex metabolic pathways, thus having major biological roles. They are obtained from various dietary sources which determine the type of fat consumed and consequently health outcome.

UNLABELLED The aim of this study was to analyze the relationship of serum leptin as well as adiponectin and the manifestation of pancreatic cancer (PC). Serum leptin, adiponectin, glucose homeostasis and insulin resistance (expressed as HOMA-IR) were investigated in 64 patients with newly diagnosed PC and compared with 64 healthy controls (CON group) and 75 patients with type 2 diabetes (DM2). Seventy percent of newly diagnosed PC patients had DM2. The levels of leptin were lower, whilst adiponectin/leptin ratio was higher in PC patients (both with and without DM2), in comparison with CON and DM2 groups (P < 0.001) independently of age, BMI and waist circumference. Newly diagnosed PC is characterized with lower leptin concentrations and higher adiponectin/leptin ratio in comparison with CON or DM2 individuals. Analysis of these parameters could help in the screening of persons in high risk for PC, especially in those with DM2. KEYWORDS adiponectin, leptin, pancreatic cancer, type 2 diabetes mellitus.

The receptor for advanced glycation end-products (RAGE) takes part in the pathogenesis of many diseases, including diabetes mellitus and cancer. AGE-precursors are detoxified by glyoxalase (GLO). sRAGE, soluble RAGE, is an inhibitor of pathological effects mediated via RAGE. The aim was to study sRAGE and polymorphisms of RAGE (AGER) and GLO genes in patients with pancreas cancer (PC).The studied group consisted of 51 patients with PC (34 with impaired glucose tolerance-IGT, 17 without IGT), 34 type 2 DM and 154 controls. For genetic analysis, the number of patients was increased to 170. Serum sRAGE was measured by ELISA and all polymorphisms (RAGE -429T/C, -374T/A, 2184A/G, Gly82Ser and GLO A419C) were determined by PCR-RFLP and confirmed by sequencing.Soluble RAGE is decreased in patients with PC compared to patients with DM and controls (975+/-532 vs. 1416+/-868 vs. 1723+/-643pg/mL, p0.001). Patients with PC and IGT have lower sRAGE levels compared to patients with PC without IGT (886+/-470 vs. 1153+/-616pg/mL, p0.05). No relationship of sRAGE to the stage was found. We did not show any difference in allelic and genotype frequencies in all RAGE and GLO polymorphisms among the studied groups.This is the first study demonstrating decreased sRAGE in patients with pancreas cancer. Its levels are even lower than in diabetics and are lowest in patients with PC and IGT. Our study supports the role of glucose metabolism disorder in cancerogenesis. Further studies are clearly warranted, especially with respect to potential preventive and therapeutic implications.

Paraoxonase 1 is believed to play a role in preventing lipid oxidation and, thus, limiting production of proinflammatory mediators. Systemic inflammatory response in sepsis increases oxidative stress and decreases high-density lipoprotein (HDL) concentrations. The objective of this study was to investigate serum paraoxonase 1 activities in critically ill patients with sepsis and after recovery. Serum paraoxonase 1 arylesterase/paraoxonase activities, concentration of total cholesterol, HDL cholesterol (HDL-C) and serum C-reactive protein (CRP) in septic patients of a medical intensive care unit (n = 30) and age/sex-matched outpatient controls without sepsis (n = 30) were analyzed. Paired convalescent samples were also taken 1 week after recovery (n = 11). In septic patients, both arylesterase (88.3 +/- 36.5 vs. 162.1 +/- 44.8 kU/l, P < 0.001) and paraoxonase (75.2 +/- 50.0 vs. 125.2 +/- 69.4 U/l, P < 0.01) paraoxonase 1 activities decreased as compared to controls. Both activities normalized after recovery. Negative correlation was found between CRP and both arylesterase (r = -0.676, P < 0.001) and paraoxonase (r = -0.401, P < 0.01) as well as positive correlation between HDL-C and both arylesterase (r = 0.585, P < 0.001) and paraoxonase (r = 0.405, P < 0.01) paraoxonase 1 activities. The decreased activity of paraoxonase 1 in negative correlation with CRP offers a potentially useful marker of sepsis progress and recovery in critically ill patients.

Although most of us are more or less familiar with the term "cholesterol", the world of sterols is far more complicated and interesting. Apart from cholesterol, many non-cholesterol sterols can be found in human plasma and these sterols serve many important functions in human organism. They are either derived from endogenous biosynthesis of cholesterol or they come from dietary sources (phytosterols). The sole cholesterol molecule is used for keeping our cell membranes fit, for signalization purposes as well as a precursor for bile acids and steroid hormones. The compounds prior to cholesterol in its biosynthetic pathway were identified as vitamin D3 precursor, meiosis activating sterols and nowadays it seems that they could play a role in cholesterol homeostasis. The sterols from ingested vegetable sources, the phytosterols, are expelled from enterocytes and thus indirectly help our gut in coping with abundant cholesterol in the lumen. Higher plants synthesize many phytosterols, but in marine organisms, we can find other innumerous sterol molecules. The diversity of sterol molecules produced and resistance of their tetracyclic core to enzymatic activities implies crucial importance of sterols during the ontogenesis of multicellular organisms. First oxygen appeared on the Earth app. 2.7 billion years ago and since that time, every new life form took the advantage of oxygen needed also for build-up of sterol molecules. The last decades changed our view to the sterol molecules on almost at all levels of their appearance in human body. In the gut, the absorption of sterols was proven to be protein dependent and the quest for the transporter was successful. The general concepts of intracellular homeostasis of cholesterol have been described including the covalent interaction unbelievable so far - cholesterol and a protein. The clinical importance of non-cholesterol sterols rises with the effort to discover underlying facts about the causes of atherosclerosis. The compound in question, cholesterol, seems to be involved, but it sounds not to be crucial per se. The fact that the accumulation of phytosterols in sitosterolemia enhances the probability of early atherosclerosis onset further supports the hypothesis about some sterol (or steroid) compound being responsible on the molecular level for triggering the pathobiochemical cascade of events leading to atherosclerosis. Understanding the processes taking place in the enterocyte during the absorption of sterols resulted in synthesis of selective inhibitors at the level of sterol translocation into the enterocyte, sterol esterification and chylomicron packing, which are in different phases of clinical testing. The studies in the last part of the monograph represent the clinical potential of the analyses of non-cholesterol sterols. In well-defined groups, these analytes enables us to assess the changes in the homeostasis of cholesterol, which can be reflected in the concentration of total cholesterol. Furthermore, the high concentrations of some plasma sterols could point to the inborn errors of cholesterol biosynthesis (Smith-Laemli-Opitz syndrome), transport (sitosterolemia) or metabolization (cerebrotendinous xanthomatosis). Some issues concerning the research on the non-cholesterol sterols still remain unanswered - it is not known why some of the enzymes of the cholesterol biosynthesis (seladin-1, sterol D14 reductase) have other functions, qualitative aspects of sterol absorption are not satisfactorily explained and exact reason for expulsion of phytosterols from human body is not clear. Nevertheless, the authors hope that the presented facts can broaden the reader's perspective about the area, which is usually hidden beneath the cholesterol molecule.

To investigate the activities of the main antioxidative enzymes and oxidative stress in women with depressive disorder (DD).In 35 drug-naive women with DD and 35 age matched healthy women enzymes superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPX1), glutathione reductase (GR) and paraoxonase (PON1), concentrations of conjugated dienes (CD), reduced glutathione (GSH) and anthropometric and clinical data were investigated.Women with DD were found to have decreased activities of GPX1 (p0.05), decreased concentrations of GSH (p0.05), and increased activities of GR (p0.05), CuZnSOD (p0.001), and concentrations of CD (p0.05). Activity of GPX1 was positively correlated with concentration of GSH (p0.05). Concentrations of CD were positively correlated with TG (p0.01).Our set of depressive women was characterized by changes indicating an increased oxidative stress, as well as by certain features of metabolic syndrome.

Depressive disorder (DD) is associated with an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). It was suggested, that metabolic syndrome (MetS), cluster of metabolic and hormonal changes, such as insulin resistence (IR), abdominal obesity, dyslipidemia, arterial hypertension and elevated fasting glycaemia, could stand behind the connection. Recent findings have shown, that adipocytokines leptin and adiponectin might play a role in both depression and MetS.The aim of this pilot study was to observe the plasma concentrations of leptin, adiponectin, leptin-to-adiponectin ratio and indices of IR in women with depressive disorder.The plasma leptin, adiponectin, parameters of lipid and glucose homeostasis and indices of IR were investigated in a group of 38 women with DD. The results were compared with those of 38 healthy women of the control group, matched for age.Depressive women differed significantly from the controls in higher concentrations of plasma leptin (p0.05), insulin (p0.01), C-peptide (p0.01), value of HOMA-IR (p0.01), and the leptin-to-adiponectin ratio (p0.05).The QUICKI index of insulin sensitivity was lower (p0.01). HAM-D score of DD cases correlated negatively with adiponectin (r = - 0.3505; p0.05), independently of HOMA-IR. We have not found in DD group any differences between the drug free patients and those treated either with escitaloprame alone or in the combination with mirtazapine.The results of the pilot study presented support the hypothesis that at least part of DD cases has increased leptin serum levels and certain features of MetS. It could be the factor connecting depression with an increased risk of either DM2 or CVD.

Metabolic syndrome (MS) is defined by the clustering of several components (MSC), which include abdominal fat accumulation, impaired glucose homeostasis, hypertriglyceridemia, lowered high-density lipoprotein cholesterol, increased blood pressure, and hyperuricemia. Metabolic syndrome is also accompanied by increased oxidative stress and inflammation as well as by altered composition of esterified fatty acids (FA). Therefore, we have investigated 210 men (categorized into six groups with increasing number of MSC) to find trends in the extent of oxidative stress, FA pattern and frequency of pathological alleles of the selected candidate genes for lipid metabolism. Increasing number of MSC was connected with the raised serum glucose and insulin, increased concentrations of conjugated dienes in low-density lipoprotein (all p < 0.0001), and high frequency of e2 and e4 alleles of the apolipoprotein E gene (p < 0.005). However, the last significance was lost after the adjustment for age. The incidence of 54Thr allele for intestinal isoform of the fatty acid-binding protein (FABP-2) gene was comparable in all groups. The most important findings were the raised content of saturated FA and the increased activities of Delta9 and Delta6 desaturases (all p < 0.0001), and the decreased content of polyunsaturated FA n-6 family and the decreased activity of Delta5 desaturase (both p < 0.001) in connection with increasing number of MSC. In conclusion, the severity of MS is connected with the progression of oxidative stress and the unfavorable changes in the FA composition. These changes are independent of the studied gene polymorphisms.

One-month treatment ofobese patients (body mass index, 39.44 ± 0.94, measured in kg/m2) with a very-low- calorie diet (VLCD) resulted in a significant weight loss, which was higher in men than in women. In contrast, the decrease of percent fat content was higher in gynoid obese women than in men or women with android fat distribution. In females fat mo- bilization was depressed at the thigh region where a substantially lower percent decrement of thigh skinfold thickness was dem- onstrated in comparison with males. VLCD treatment positively affected blood pressure and concentrations of total cholesterol, triglyceride, insulin, and cortisol. Total cholesterol-high-density- lipoprotein (HDL) cholesterol ratio remained unchanged and HDL cholesterol in serum significantly declined. Indexes of body fat distribution were not significantly influenced by the short- term treatment by VLCD except waist-hip ratio, which declined in android obese females. VLCD does not decrease a tolerance of physical exercise, as the metabolic response to submaximal workload on a cycle ergometer as well as the responses of cortisol, growth hormone, and prolactin remained unchangedafter the treatment. .4m J C/in Nutr 1992;56:281S-2S.

BACKGROUND Oxidative stress can potentiate atherogenesis via modification of biological structures and formation of new compounds, e.g. advanced glycation end products (AGEs) and advanced oxidation protein products (AOPP). The aim of the study was to determine AGEs and AOPP in patients with atherosclerosis, effect of statin therapy and relationship to parameters of lipid metabolism. METHODS AND RESULTS AGEs (carboxymethyllysine - ELISA and fluorescent AGEs - spectrofluorimetry) and AOPP (spectrophotometry) were assessed in 42 patients with atherosclerosis and 21 healthy controls. AGEs are significantly elevated in patients with atherosclerosis in comparison with healthy subjects (carboxymethyllysine 9.02+/-1.66 microg/g prot. vs 7.52+/-1.18 microg/g prot., p

The composition of polyunsaturated fatty acids (PUFAs) in cell membranes and body tissues is altered in metabolic syndrome (MetS) and depressive disorder (DD). Within the cell, fatty acid coenzyme A (CoA) ligases (FACLs) activate PUFAs by esterifying with CoA. The FACL4 isoform prefers PUFAs (arachidonic and eicosapentaenoic acid) as substrates, and the FACL4 gene is mapped to Xq23. We have analyzed the association between the common single nucleotide polymorphism (SNP) (rs1324805, C to T substitution) in the first intron of the FACL4 gene and MetS or DD. The study included 113 healthy subjects (54Males/59Females), 56 MetS patients (34M/22F) and 41 DD patients (7M/34F). In MetS group, T-carriers and patients with CC or C0 (CC/C0) genotype did not differ in the values of metabolic indices of MetS and M/F ratio. Nevertheless, in comparison with CC/C0, the T-allele carriers were characterized by enhanced unfavorable changes in fatty acid metabolism typical for MetS: higher content of dihomogammalinolenic acid (P < 0.05) and lower content of arachidonic acid in plasma phosphatidylcholine (PC) (P = 0.052), lower index of Δ5 desaturation (P < 0.01) and unsaturation index (UI) (P < 0.001). In contrast, DD patients had higher concentrations of plasma glucose, insulin, conjugated dienes and index of insulin resistance, but showed no significant association with the studied SNP. The present study shows that the common SNP (C to T substitution) in the first intron of the FACL4 gene is associated with altered FA composition of plasma phosphatidylcholines in patients with MetS.