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Assessment of dietary and genetic factors influencing serum and adipose fatty acid composition in obese female identical twins

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 (CE), 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 IPR, 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 IPR 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.

Antioxidant status and oxidative stress markers in pancreatic cancer and chronic pancreatitis.

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.

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 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.

Effect of 4-wk treatment of obesity by very-low-calorie diet on anthropometric, metabolic, and hormonal indexes

One-month treatment of obese 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 mobilization was depressed at the thigh region where a substantially lower percent decrement of thigh skinfold thickness was demonstrated 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 unchanged after the treatment.

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

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.

Body-fat distribution and serum lipids during the long-term follow-up of obese patients treated initially with a very-low-calorie diet

To evaluate a long-term efficacy of very-low-calorie-diet (VLCD) treatment, 42 obese patients were reexamined 1 y after the initiation of the weight reduction by VLCD treatment for 1 mo. All the subjects participating in the long-term outpatient weight-reduction regime were divided into weight losers and regainers according to the weight change achieved at the end of 1-y follow-up. A final body weight decrease in weight losers was followed by a significant decline of total cholesterol-high-density-lipoprotein (HDL) cholesterol ratio together with significant rise of serum HDL cholesterol whereas almost all skinfold thicknesses declined. In weight regainers the sum of 10 skinfold thicknesses was the same at the end of follow-up as at the beginning of VLCD treatment, but body fat distribution was shifted towards the gynoid type when individual skinfold thicknesses were assessed. However, among the generally employed indexes of body fat distribution only waist-thigh ratio significantly decreased in weight losers. Nonsignificant differences in serum concentrations of total cholesterol, HDL cholesterol, and triglycerides between weight regainers and weight losers at the end of long-term follow-up suggest that some kind of adherence to weight reduction regime including physical exercise may favorably affect the lipid profile as well as body fat distribution independently on the body weight regained.

Improvements in colorectal cancer screening programmes – quantitative immunochemical faecal occult blood testing – how to set the cut-off for a particular population

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.

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.