Association of serum amyloid A and oxidative stress with paraoxonase 1 in sarcoidosis patients.

BACKGROUND: It has been reported that high-density lipoprotein (HDL) particles have anti-inflammatory and antioxidant roles thanks to different enzymes such as paraoxonase 1 (PON1). Under inflammatory and oxidative stress conditions, HDL particles may lose their protective properties. Sarcoidosis is an inflammatory disease characterized by excessive oxidative stress. Serum amyloid A (SAA) is produced in liver and in granulomas, and its concentration increases in inflammatory conditions contributing to increased catabolism of HDL particles. The aim of our study was to determine PON1 activity, SAA concentration and their associations in patients with sarcoidosis. MATERIALS AND METHODS: Inflammatory [high-sensitive C-reactive protein (hsCRP), angiotensin-converting enzyme (ACE), SAA], lipid [total cholesterol (TC), HDL-cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG)] oxidative stress status parameters [total oxidant status (TOS), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), sulfhydryl (SH) groups] and PON1 activities were determined in serum of 72 patients with sarcoidosis and 62 healthy subjects. RESULTS: HsCRP (P < 0·05), TC, LDL-c, TG, SAA, TOS, MDA and PAB (P < 0·001) were significantly higher, whereas HDL-c, SH groups and PON1 activity (P < 0·001) were significantly lower in patients with sarcoidosis when compared with controls. PON1 showed significant association with SAA, MDA and PAB. It was shown that 71% of decrease in PON1 activity may be explained by increase in TOS, PAB and SAA concentration. CONCLUSIONS: We found decreased PON1 activity and increased SAA concentration in patients with sarcoidosis. Inflammatory condition presented by high SAA was implicated in impaired HDL functionality evident through dysregulated PON1 activity. Excessive oxidative stress was also involved in dysregulation of PON1 activity.

Renal transplantation promptly restores excretory function but disturbed L-arginine metabolism persists in patients during the early period after surgery.

The synthesis and whole body metabolism of L-arginine (Arg) are disturbed in renal diseases. Renal transplantation represents the best therapy in the end-stage of these diseases. In the present we compared alterations of plasma Arg and related compounds with renal excretory function in patients with end-stage renal disease, before and after kidney transplantation. Arg, asymmetric dimethylarginine (ADMA), citrulline (Cit), glutamine (Gln), ornithine (Orn), phenylalanine (Phe), tyrosine (Tyr), urea, creatinine, albumin, and nitrate were analyzed in patients before, immediately after (0-time) and 1, 2, 3, 7 and 14 days following living donors kidney transplantation. Healthy subjects were controls. Glomerular filtration rate (GFR) and amino acid molar ratios were calculated. Before transplantation creatinine, urea, Cit, Gln, ADMA, and nitrate were above, while GFR and Arg were below controls, confirming disturbed excretory and metabolic renal functions in patients with renal disease. Renal transplantation promptly normalized creatinine, urea, GFR, Cit, and nitrate. However, regardless of increased molar Phe/Tyr ratios, indicating increased net protein catabolism in peripheral tissues, low Arg and elevated ADMA concentrations persisted throughout the examined period. Alterations of other amino acids also suggest similarly disturbed Arg metabolism in patients after kidney transplantation. In conclusion, renal transplant promptly restored its excretory function, but increased net protein catabolism, disturbed Arg metabolism and endothelial dysfunction in entire body of these patients were not improved throughout the early period after the operation. That has to be considered in their therapy.

Associations of oxidative stress status parameters with traditional cardiovascular disease risk factors in patients with schizophrenia.

BACKGROUND: The purpose of this study was to assess oxidative stress status parameters and their possible associations with traditional cardiovascular risk factors in patients with schizophrenia, as well as their potential for patient-control discrimination. METHODS: Fasting glucose, lipid profile and oxidative stress status parameters were assessed in 30 schizophrenic patients with atypical antipsychotic therapy and 60 control subjects. RESULTS: Malondialdehyde (MDA), pro-oxidant/antioxidant balance (PAB) and total anti-oxidant status (TAS) were significantly higher whereas total sulfhydryl (SH) groups were significantly lower in schizophrenic patients vs. control group. Higher serum PAB values showed an independent association with schizophrenia. The addition of PAB to conventional risk factors improved discrimination between healthy control subjects and patients. CONCLUSION: Increased oxidative stress and changed lipid profile parameters are associated in schizophrenic patients and may indicate risk for atherosclerosis. The serum PAB level may reflect the levels of oxidative stress in schizophrenia and improve discrimination of patients from controls.

Association of small, dense low-density lipoprotein cholesterol and galectin-3 in patients with chronic kidney disease.

BACKGROUND: Dyslipidemia is a common feature of chronic kidney disease (CKD). Although it has been observed that the pattern of lipid abnormalities can vary according to the stage of CKD, there is lack of data concerning the distribution of lipoprotein subclasses at various stages of the disease. In addition, association of proatherogenic small, dense low-density lipoprotein (sdLDL) subclasses with markers of inflammation, such is galectin-3, is not sufficiently explored. The aim of this study was to analyze concentrations and relative proportions of sdLDL-cholesterol (sdLDL-C) and galectin-3 in patients with CKD, with respect to the stage of the disease. Also, we sought possible independent associations of galectin-3 and sdLDL-C. METHODS: The study involved 100 hemodialysis (HD) and 50 pre-dialysis patients, together with 94 healthy individuals. SdLDL-C was measured by heparin-magnesium precipitation method. Galectin-3 was measured by ELISA technique. RESULTS: Galectin-3 levels were higher in pre-dialysis and HD patients than in the control group (p < 0.01). The concentration of sdLDL-C was highest in the pre-dialysis group and lowest in HD patients (p < 0.01). CKD patients with increased galectin-3 concentrations had significantly higher relative proportions of cholesterol in sdLDL (% sdLDL-C) than their counterparts with lower galectin-3 levels (p < 0.05). Relative proportion of sdLDL-C was shown to be an independent determinant of galectin-3 concentration. CONCLUSIONS: Our results demonstrated alterations in concentrations and proportions of sdLDL-C according to the stages of CKD. The observed independent associations of % sdLDL-C and galectin-3 provide further insight into their complex interaction during the progression of atherosclerosis in CKD.

Effect of alpha-lipoic acid supplementation on oxidative stress markers and antioxidative defense in patients with schizophrenia.

BACKGROUND: The purpose of this study was to examine the effects of alpha-lipoic acid (LA) supplementation on oxidative stress markers in patients with schizophrenia. SUBJECTS AND METHODS: Eighteen (18) medicated patients with schizophrenia and 38 healthy controls received daily supplements of LA (500 mg/day) for three months. At baseline, 45th and 90th days of supplementation, venous blood collected for analysis of oxidative stress markers [superoxide anion (O2(•-)), thiobarbituric acid-reactive substances (TBARS) and advanced oxidation protein products (AOPP)] and antioxidative defense markers [superoxide dismutase (SOD), total sulfhydryl groups (-SH) and total antioxidant status (TAS)]. RESULTS: Increased plasma TBARS, TAS, SH groups levels and SOD activity were found in schizophrenic patients compared to control group. LA supplementation significantly reduced TBARS, AOPP and improved TAS levels in healthy subjects, while there were no significant differences in patients group. SH groups increased after 45 days and decreased to baseline levels after 90 days of supplementation in the control group. SOD activity decreased significantly in patients group after 45 days and 90 days of supplementation. After initial rose SOD activity in control group, decreased to baseline levels found after 90 days. CONCLUSION: LA supplementation decreased lipid peroxidation and oxidative damage of proteins and improved non-enzymatic antioxidant capacity in healthy controls. No significant changes were observed on oxidative damage in patients with schizophrenia.

Hyperlipidemia, oxidative stress, and intima media thickness in children with chronic kidney disease.

BACKGROUND: The roles of dyslipidemia and oxidative stress in the early phases of atherosclerosis were tested in children with chronic kidney disease (CKD). Intima media thickness of common carotid arteries (cIMT) is used as a measure of early atherosclerosis. METHODS: Fifty-two pediatric CKD patients were enrolled in the study (10 with chronic renal failure [CRF], 22 with a renal transplant [RT], 20 with chronic hemodialysis (cHD) patients, and 36 healthy children (control group, CG). Lipid status, oxidative stress, and paraoxonase 1 (PON1) status were assessed. cIMT was measured by ultrasound, adjusted for age and sex, and presented as standard deviation scores (SDS). RESULTS: Children with CKD had disturbed lipid content, which was most pronounced in cHD children, with higher free cholesterol and triglycerides compared with healthy children. Oxidative stress was markedly increased (malodialdehyde [MDA, µmol/L]: CRF 1.50 ± 0.26, RT 1.55 ± 0.40, cHD 1.77 ± 0.34, CG 0.97 ± 0.33, p < 0.001) and antioxidative defense was compromised (superoxide dismutase [SOD, U/L]: CG 120 ± 21, CRF 84 ± 25, RT 93 ± 12, cHD 119 ± 37, p < 0.001). Multiple linear regression analysis showed that a model that included disease duration, blood pressure, urea, lipid, and oxidative status parameters accounted for more than 90% of the variability of cIMT-SDS. CONCLUSIONS: Early atherosclerosis in CKD children is caused, at least in part, by dyslipidemia and oxidative stress. Monitoring of vessel wall changes, along with assessment of oxidative stress status and high density lipoprotein (HDL) functionality is necessary to ensure better therapeutic strategies for delaying atherosclerotic changes in their asymptomatic phase.

Are levels of NT-proBNP and SDMA useful to determine diastolic dysfunction in chronic kidney disease and renal transplant patients?

BACKGROUND: The aim of the study was to determine the clinical usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients. METHODS: We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1. RESULTS: Independent predictors of NT-proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction. CONCLUSIONS: NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor.

Changes in LDL and HDL subclasses in normal pregnancy and associations with birth weight, birth length and head circumference.

Pregnancy is associated with alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, but the exact pattern of these variations remains controversial. This study investigates longitudinal changes of plasma LDL and HDL particles distributions during the course of normal pregnancy, as well as associations of maternal LDL and HDL subclasses distributions before delivery with parameters of newborn size. Blood samples were collected from 41 healthy pregnant women throughout entire pregnancy, before delivery and 7 weeks postpartum. LDL and HDL subclasses were determined by gradient gel electrophoresis, while other biochemical parameters were measured by standard laboratory methods. During gestation LDL size significantly decreased (P < 0.001), due to reduction in relative proportion of LDL I (P < 0.01) and increase of LDL II (P < 0.001) and IIIA (P < 0.05) subclasses. In the same time, HDL size and proportions of HDL 2a particles significantly decreased (P < 0.001), with concomitant increase of HDL 3b and 3c subclasses (P < 0.05). Observed alterations were associated with changes in serum triglyceride levels. Rearrangement in LDL subclasses distribution during gestation was transient, while postpartum HDL subclasses distribution remained shifted toward smaller particles. Higher proportion of LDL IVB in maternal plasma before delivery was an independent predictor of smaller birth weights and lengths, while higher proportions of LDL IVB and HDL 2a subclasses were independent determinants of newborns' smaller head circumferences. Routine gestational and prenatal care in otherwise normal pregnancy could be complemented with evaluation of LDL and HDL particles distribution in order to ensure an adequate size of the newborn.

Effect of astaxanthin supplementation on paraoxonase 1 activities and oxidative stress status in young soccer players.

The purpose of the study was to examine the effects of astaxanthin (Asx) on paraoxonase (PON1) activities and oxidative stress status in soccer players. Forty soccer players were randomly assigned in a double-blind fashion to Asx and placebo (P) group. Blood samples were obtained before, 45 and 90 days after supplementation. PON1 activity was assessed by using two substrates: paraoxon and diazoxon. The oxidative stress biomarkers were also examined: total sulphydryl group content (-SH groups), thiobarbituric acid-reactive substances (TBARS), advanced oxidation protein products and redox balance. The significant interaction effect of supplementation and training (p < 0.05) on PON1 activity toward paraoxon was observed. The PON1 activity toward diazoxon increased in Asx group after 90 days (p < 0.01), while there was no significant difference in P group. SH groups content rose from pre- to post-supplementation period only in Asx group (supplementation and training, p < 0.05; training, p < 0.01). TBARS levels decreased after 45 days and increased after 90 days of regular soccer training in both groups (training, p < 0.001). Redox balance decreased significantly in response to the regular training, regardless of treatment group (training, p < 0.001). Asx supplementation might increase total SH groups content and improve PON1 activity through protection of free thiol groups against oxidative modification.

Association of the atherogenic index of plasma and oxidative stress status with weight gain during non-complicated pregnancy.

BACKGROUND: Pregnancy is a stressful condition linked with altered lipid profile, increased oxidative stress and increased inflammation processes. The purpose of the present study was to determine the associations between those alterations with increased weight gain during pregnancy. METHODS: The atherogenic index of plasma (AIP) and oxidative stress status parameters were determinated in 50 healthy and 172 pregnant women with non-complicated pregnancy. Pregnant women were divided in four groups according to body mass index (BMI) values (BMI quartiles). RESULTS: Oxidative stress parameters were significantly lower in the control group compared with all the pregnant women quartiles. Unexpectedly, differences in oxidative stress parameters between BMI quartiles groups were not significant. The antioxidant defence parameters remained quite similar in the different BMI quartiles. Weight gain and paraoxonase-1 (PON1) activities were independently associated with increased AIP while weight gain and triglyceride concentration were found to be significant predictors of PON1 activities. CONCLUSIONS: The results of our current study indicate the association of maternal weight gain during pregnancy and altered lipid profile, elevated oxidative stress and changed antioxidative capacity of PON1. Taken together all these facts indicate possible increased risk of cardiovascular disease (CVD) development in later life if the weight gain during pregnancy is excessive.

Characteristics of low-density and high-density lipoprotein subclasses in pediatric renal transplant recipients.

Renal transplant recipients often suffer from dyslipidemia which is one of the principal risk factors for cardiovascular disease. This study sought to determine characteristics of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles and their associations with carotid intima-media thickness (cIMT) in a group of pediatric renal transplant recipients. We also examined the influence of immunosuppressive therapy on measured LDL and HDL particle characteristics. HDL size and subclass distribution were determined using gradient gel electrophoresis, while concentrations of small, dense LDL (sdLDL)-cholesterol (sdLDL-C) and sdLDL-apolipoprotein B (sdLDL-apoB) using heparin-magnesium precipitation method in 21 renal transplant recipients and 32 controls. Renal transplant recipients had less HDL 2b (P < 0.001), but more HDL 3a (P < 0.01) and 3b (P < 0.001) subclasses. They also had increased sdLDL-C (P < 0.01) and sdLDL-apoB (P < 0.05) levels. The proportion of the HDL 3b subclasses was a significant predictor of increased cIMT (P < 0.05). Patients treated with cyclosporine had significantly higher sdLDL-C and sdLDL-apoB concentrations (P < 0.05) when compared with those on tacrolimus therapy. Pediatric renal transplant recipients have impaired distribution of HDL and LDL particles. Changes in the proportion of small-sized HDL particles are significantly associated with cIMT. Advanced lipid testing might be useful in evaluating the effects of immunosuppressive therapy.

A multimarker approach for the prediction of coronary artery disease: cost-effectiveness analysis.

OBJECTIVES: Coronary artery disease (CAD), as the leading cause of death, poses a huge economic burden on health-care systems. We used a multi-marker approach to explore discriminative abilities of several lipid, inflammatory, and oxidative stress/antioxidative defense markers as CAD predictors. We assessed their cost-effectiveness compared with the Framingham risk score (FRS). METHODS: Using a decision model, we evaluated the costs, accuracy, and cost-effectiveness of each model. The FRS was used as the baseline model. Other models were formed with the consecutive addition of selected markers: apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), apolipoprotein (a) [apo(a)] isoform, lipoprotein (a), high-sensitivity C-reactive protein, malondialdehyde, superoxide dismutase (SOD), sulfhydryl, and superoxide anion (O(2) (-) ). A best-case model was formed from a combination of diagnostic markers to yield the best patient stratification algorithm. All models were assessed by their predictive probabilities using receiver operating characteristic curves. To accomplish our goals, we recruited 188 CAD patients (verified by coronary angiography) and 197 asymptomatic CAD-free subjects for comparison. The analysis was performed from a third-party payer perspective. RESULTS: Only two strategies had outstanding discriminative abilities: the best-case model (FRS, SOD, and O(2) (-) ) and FRS plus SOD with area under the curve (AUC) values of 0.924 and 0.906, respectively. The cost-effectiveness ratio varied between €593 per AUC for the baseline model to €2425 per AUC for FRS plus apo(a) isoform. Strategies involving oxidative stress/antioxidative defense markers were more cost-effective than strategies involving lipid or inflammatory markers. All results were robust. CONCLUSION: Our results support the feasibility of a multimarker approach for CAD screening. The introduction of oxidative stress/antioxidative defense markers in the clinical laboratory would be convenient and cost-effective.

Evaluation of different formulas for LDL-C calculation.

BACKGROUND: Friedewald's formula for the estimation of LDL-C concentration is the most often used formula in clinical practice. A recent formula by Anandaraja and colleagues for LDL-C estimation still needs to be evaluated before it is extensively applied in diagnosis. In the present study we validated existing formulas and derived a more accurate formula to determine LDL-C in a Serbian population. METHODS: Our study included 2053 patients with TG < or = 4.52 mmol/L. In an initial group of 1010 patients, Friedewald's and Anandaraja's formulas were compared to a direct homogenous method for LDL-C determination. The obtained results allowed us to modify Friedewald's formula and apply it in a second group of patients. RESULTS: The mean LDL-C concentrations were 3.9 +/- 1.09 mmol/L, 3.63 +/- 1.06 mmol/L and 3.72 +/- 1.04 mmol/L measured by a direct homogenous assay (D-LDL-C), calculated by Friedewald's formula (F-LDL-C) and calculated by Anandaraja's formula (A-LDL-C), respectively in the 1010 patients. The Student's paired t-test showed that D-LDL-C values were significantly higher than F-LDL-C and A-LDL-C values (p < 0.001). The Passing-Bablok regression analysis indicated good correlation between calculated and measured LDL-Cs (r > 0.89). Using lipoprotein values from the initial group we modified Friedewald's formula by replacing the term 2.2 with 3. The new modified formula for LDL-C estimation (S-LDL-C) showed no statistically significant difference compared to D-LDL-C. The absolute bias between these two methods was -0.06 +/- 0.37 mmol/L with a high correlation coefficient (r = 0.96). CONCLUSIONS: Our modified formula for LDL-C estimation appears to be more accurate than both Friedewald's and Anandaraja's formulas when applied to a Serbian population.

Paraoxonase 1 and atherosclerosis-related diseases.

A direct and an indirect relationship between paraoxonase 1 (PON1) and atherosclerosis exists. Given PON1's physical location within high-density lipoprotein (HDL) particles and its recognized enzyme activity, it is certainly reasonable to suggest that PON1 facilitates the antiatherogenic nature of HDL particles. PON1 also plays a role in regulating reverse cholesterol transport, antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities and several endothelial cell functions. HDL dysfunctionality is a more recent issue and seems to be centered on pathological conditions affecting HDL structure and size profiles. This review is focused on the role of PON1 status in different atherosclerosis-related diseases that we have studied over the last twenty years (coronary heart disease, acute ischemic stroke, diabetes mellitus type 2, end-stage renal disease, chronic obstructive pulmonary disease, and sarcoidosis) with the aim to determine the true value of PON1 as a biomarker. The role of PON1 in cancer is also covered, as risk factors and mechanisms underlying both atherosclerosis and cancer share common features.

Capillary Electrophoresis of Free Amino Acids in Physiological Fluids Without Derivatization Employing Direct or Indirect Absorbance Detection.

Whole blood and/or plasma amino acids are useful for monitoring whole-body protein and amino acid metabolism in an organism under various physiological and pathophysiological conditions. Various methodological procedures are in use for their measurement in biological fluids. From the time when capillary electrophoresis was introduced as a technology offering rapid separation of various ionic and/or ionizable compounds with low sample and solvent consumption, there were many attempts to use it for the measurement of amino acids present in physiological fluids. As a rule, these methods require derivatization procedures for detection purposes.Here, we present two protocols for the analysis of free amino acids employing free zone capillary electrophoresis. Main advantage of both methods is an absence of any derivatization procedures that permits the analysis of free amino acid in physiological fluids. The method using direct detection and carrier electrolyte consisting of disodium monophosphate (10 mM at pH 2.90) permits determination of compounds that absorb in UV region (aromatic and sulfur containing amino acids, as well as some peptides such as carnosine, reduced, and oxidized glutathione). The other method use indirect absorbance detection, employing 8 mM p-amino salicylic acid buffered with sodium carbonate at pH 10.2 as running electrolyte. It permits quantification of 30 underivatized physiological amino acids and peptides. In our experience factorial design represents a useful tool for final optimization of the electrophoretic conditions if it is necessary.

Capillary electrophoresis method optimized with a factorial design for the determination of glutathione and amino acid status using human capillary blood.

Plasma aromatic and sulfur containing amino acids are good indicators of protein anabolism/catabolism, while blood reduced and oxidized glutathione reflect oxidative status in an organism. Using a full factorial design for screening important variables (pH, concentration, temperature) we developed a capillary zone electrophoresis method permitting their measurements in the single run, without any derivatization procedures. The best separations were obtained within less than 30 min employing a 10 mmol/l phosphate buffer, pH 2.8, 18 degrees C, 15 kV voltage. Fairly good precision with a linear relationship between peak area and concentrations (r=0.995-0.999) were obtained. The method was used to analyze human capillary blood.

Does simultaneous determination of LDL and HDL particle size improve prediction of coronary artery disease risk?

BACKGROUND: Alterations in plasma lipoprotein subclass distribution affect the risk for coronary artery disease (CAD). However, it is unclear whether the determination of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) phenotypes may or may not improve the ability to predict CAD development. METHODS: Polyacrylamide gradient (3-31%) gel electrophoresis was used to simultaneously determine size and distribution of lipoprotein subclasses in 181 CAD patients and 178 controls. RESULTS: Mean LDL and HDL subclass sizes were significantly smaller in patients than in controls (p < 0.001). Multivariate logistic regression analysis showed that small dense LDL particles were independent CAD risk predictors (OR = 2.867, p < 0.01), even when adjusted for other traditional risk factors, while small HDL particles lost their significance after adjustment (OR = 2.071, p = 0.054). The area under the ROC curve for LDL (0.671) and HDL (0.643) particle size measurement demonstrated low clinical accuracy when compared to the combination of traditional lipid risk factor measurements. CONCLUSIONS: CAD is associated with the predominance of smaller LDL and HDL particles. However, simultaneous determination of these two lipoprotein phenotypes provides no additional power in discriminating CAD and non-CAD subjects, beyond that obtained by the traditional risk factors.

Cytotoxic effects of the Viscum album L. extract on Ehrlich tumour cells in vivo.

To date most pharmacological studies on mistletoe (Viscum album L.) have focused on the therapeutic properties of its polar extracts. This study examined the non-polar constituents of Viscum album and their biological activities. Supercritical CO(2) extraction coupled with gas chromatography/mass spectrometry (GC/MS) was used to selectively extract and identify compounds in Viscum album leaves. Several non-polar classes of compounds were identified in the extract. In addition, a volatile fraction was identified that contained several novel terpene molecules. The hypothesis was tested that the Viscum album extract exhibits cytotoxic properties in Ehrlich carcinoma (EAC) cells in vivo due to the induction of oxidative stress. A significant reduction in the incidence of cancer was observed in all groups that received the Viscum album extract compared with the EAC control group. The largest decrease was observed in mice pretreated with the Viscum album extract, although significantly reduced numbers of EAC cells were also observed in animals with developed carcinoma. The activities of antioxidative enzymes in the EAC cells suggested the absence of oxidative stress. However, changes in the antioxidative enzymes activities observed after administration of the Viscum album extract might be due to the induction of oxidative stress in the EAC cells.

Associations of lipoprotein subclasses and oxidative stress status in pulmonary and pulmonary plus extrapulmonary sarcoidosis.

Background: Sarcoidosis is an inflammatory disease with pulmonary and extrapulmonary manifestations. In such pathologic conditions, increased oxidative stress and rearrangement of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) may occur. Objective: This study evaluated association of oxidative stress and lipoprotein subclasses in severe forms of pulmonary and pulmonary plus extrapulmonary sarcoidosis. Methods: Lipid parameters, LDL and HDL subclass distributions, high-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), paraoxonase 1 (PON1), malondialdehyde (MDA), total-oxidant status (TOS), sulfhydryl (SH) groups, pro-oxidant anti-oxidant balance (PAB) were determined in 77 patients (53 isolated pulmonary and 24 pulmonary plus extrapulmonary) and 139 controls. Results: Both pulmonary and extrapulmonary sarcoidosis patients had significantly higher levels of triglycerides and TOS (P<0.05) and more LDL II, LDL III, LDL IVA particles (P<0.01), but lower HDL size, SH groups (P<0.001), PON1 activity and less LDL I subclasses (P<0.05) than controls. In isolated pulmonary disease, HDL-cholesterol (P<0.01) was significantly lower whereas proportions of HDL 3a and PAB were significantly higher (P<0.05) when compared with the control group. PON1 was significantly higher in pulmonary than in combined pulmonary-extrapulmonary disease (P<0.05). In pulmonary sarcoidosis, TOS and PON1 correlated significantly with small-sized HDL particles (P<0.05). Conclusions: Both patient groups were characterized by adverse lipoprotein profile and elevated oxidative stress. In isolated pulmonary group significant associations of oxidative stress and HDL particles distribution was demonstrated. Pulmonary sarcoidosis was associated with higher PON1 activity and rearrangement of LDL particles did not depend on disease localization. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 198-205).

Cost-effectiveness analysis in diagnosis of coronary artery disease: choice of laboratory markers.

OBJECTIVES: The aim of our study was to determine the cost-effectiveness of coronary artery disease (CAD) diagnostic parameters in a clinical laboratory setting. DESIGN AND METHODS: The effectiveness of apolipoproteins, lipoproteins and high sensitivity C-reactive protein (hs-CRP) supplementary to Framingham scoring data within a CAD risk assessment procedure was established in 221 CAD patients and 289 controls. The total costs of diagnostic procedures were calculated and incremental cost-effectiveness analysis was applied. RESULTS: A diagnostic strategy employing Framingham calculation followed by apolipoprotein A-I (apoA-I) had the lowest cost per additional successfully diagnosed patient than the same strategy followed by hs-CRP in the low (2.63 vs. 24.47 euros) and intermediate-risk groups (2.96 vs. 122.85 euros). In the high-risk group the diagnostic strategy employing apoA-I saved 9.14 euros in comparison to the strategy employing hs-CRP. CONCLUSION: Cost-effectiveness analysis of different diagnostic markers results in improved identification of at-risk patients at a lower health cost for society.