Effect of propolis and N-acetylcysteine supplementation on lipoprotein subclasses distribution and paraoxonase 1 activity in subjects with acute respiratory infection.

BACKGROUND: Propolis and N-acetylcysteine have positive impact on respiratory tract health. Also, it has been suggested that they have beneficial effects on serum lipid and oxidative stress status, but the available data are limited and mostly gained from animal models. In this study we evaluated the effects of propolis and N-acetylcysteine supplementation (PropoMucil®) on lipid status, lipoprotein subclasses distribution and paraoxonase 1 activity in subjects with acute respiratory infection. METHODS: Twenty subjects with acute respiratory infection were included. PropoMucil® granules for oral solution (80 mg of dry propolis extract and 200 mg of N-acetylcysteine) were administered tree times per day for ten days. Serum lipid profile, paraoxonase 1 activity and low-density and high-density lipoprotein size and subclasses distribution were assessed at baseline and after supplementation. RESULTS: Following ten days of supplementation lipid status remained unchanged, but a significant increase of low-density lipoprotein particle size and proportion of high-density lipoprotein 3a particles were found (P<0.05). Moreover, supplementation with PropoMucil® significantly improved high-density lipoprotein particles distribution, particularly in those who smoke. There was a moderate increase of paraoxonase 1 activity, but without statistical significance. CONCLUSIONS: The presented study demonstrated that short-term supplementation with PropoMucil® has beneficial effects on low-density and high-density lipoprotein subclasses distribution and paraoxonase 1 activity in subjects with acute respiratory infection particularly in those who smoke.

Associations of cholesterol and vitamin D metabolites with the risk for development of high grade colorectal cancer.

BACKGROUND: Vitamin D deficiency is repeatedly reported in colorectal cancer (CRC). Since cholesterol and vitamin D share common precursor 7-dehydrocholesterol (7-DHC), it would be important to explore the associations of key vitamin D metabolites and serum lipid parameters in patients with high and low grade CRC. The aim of this study was to analyze relationships between serum 25(OH)D3, 24,25(OH)2D3 and 7-DHC levels and serum lipids in patients with CRC, and to evaluate their potential for prediction of risk for development of high grade CRC. METHODS: We recruited 82 patients CRC and 77 controls. 7-DHC, 25(OH)D3 and 24,25(OH)2D3 were quantified by LC-MS/MS methods. RESULTS: 7-DHC, 25(OH)D3 and vitamin D metabolic ratio (VDMR) were significantly lower in CRC patients than in control group (P<0.001, P<0.010, P<0.050 and P<0.050, respectively). 25(OH)D3 levels were higher in patients with grade I CRC when compared to grade II (P<0.050). All vitamin D metabolites positively correlated with total cholesterol (TC) concentration in CRC patients. 25(OH)D3 was significant predictor of increased CRC risk (P<0.010). After adjustment for TC concentration, 25(OH)D3 lost its predictive abilities. However, 25(OH)D3 remained significant predictor of poorly differentiated type of cancer (P<0.050). CONCLUSIONS: We found significant positive association between vitamin D status and serum total cholesterol. Although low 25(OH)D3 was found to be a significant risk factor for CRC development, the obtained results primarily suggest profound impact of cholesterol level on vitamin D status in CRC. However, our results suggest that low 25(OH)D3 might independently contribute to development of poorly differentiated tumor.

Serum Resistin, Adenylate Cyclase-Associated Protein 1 Gene Expression, and Carotid Intima-Media Thickness in Patients with End-Stage Renal Disease and Healthy Controls.

BACKGROUND: Human resistin is a proinflammatory cytokine with significant proatherogenic effects which acts through adenylyl cyclase-associated protein 1 (CAP1). Chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients have increased cardiovascular risk and resistin levels. Previous studies indicated resistin significance as a predictor of mortality in CKD. AIMS: We sought to investigate plasma resistin levels, peripheral blood mononuclear cell (PBMC) resistin mRNA, and for the first time CAP1 mRNA levels in ESRD patients and healthy controls. We also sought to investigate the relation of resistin and CAP1 to carotid intima media thickness (CIMT), CD36 gene expression, and matrix metalloproteinase 9 (MMP-9) circulating levels in ESRD patients and healthy controls. METHODS: This study included 33 patients with ESRD and 27 healthy controls. Resistin and MMP-9 levels were measured by ELISA. Resistin, CAP1, and CD36 PBMC mRNA were measured by quantitative PCR. RESULTS: Our study showed that ESRD patients have significantly higher levels of circulatory resistin compared to healthy controls (p < 0.001), while there was no significant difference in resistin mRNA. A significant upregulation of CAP1 and CD36 was observed in the ESRD group (p < 0.001; p < 0.001). Resistin concentration correlated with CIMT in healthy controls (r = 0.512, p = 0.036), and with MMP-9 concentration in ESRD (r = 0.353, p = 0.044) and healthy controls (r = 0.463, p = 0.026). CAP1 correlated positively with CIMT (r = 0.464, p = 0.008) in ESRD, and with CD36 in healthy controls (r = 0.447, p = 0.022) and ESRD (r = 0.824, p < 0.001). CONCLUSION: The obtained data suggest that high levels of circulating resistin acting upon cells with an upregulated CAP1 gene could contribute to the increased inflammation and accelerated atherosclerosis seen in CKD patients.

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.

Association among resistin, adenylate cyclase-associated protein 1 and high-density lipoprotein cholesterol in patients with colorectal cancer: a multi-marker approach, as a hallmark of innovative predictive, preventive, and personalized medicine.

BACKGROUND: Elevated concentrations of resistin have been reported in colorectal cancer (CRC), but its interactions with adenylate cyclase-associated protein 1 (CAP-1) are largely unexplored. We investigated resistin plasma concentration, peripheral blood mononuclear cells (PBMCs) resistin messenger ribonucleic acid (mRNA), and CAP-1 mRNA levels in CRC patients, as well as the impact of resistin gene polymorphism rs1862513 on the examined markers. We also explored associations of resistin with high-density lipoprotein cholesterol (HDL-C) and predictive potential of our parameters for CRC. METHODS: Eighty-six patients with CRC and 75 healthy adults were included. Commercial ELISA kit was used for obtaining resistin's concentrations, while polymerase chain reaction (PCR) method was applied for evaluation of resistin and CAP-1 mRNA levels and rs1862513 polymorphism. RESULTS: Plasma resistin and CAP-1 mRNA levels were higher in CRC patients (p < 0.001 and p < 0.05, respectively), while resistin mRNA levels were lower (p < 0.001). Negative association existed among plasma resistin and HDL-C concentrations (ρ = - 0.280; p < 0.05). A model including age, body-mass index, HDL-C, low-density lipoprotein cholesterol (LDL-C), and plasma resistin concentrations as independent predictors of CRC showed very good diagnostic accuracy (AUC = 0.898). We found no associations of rs1862513 with the examined markers. CONCLUSIONS: Our study demonstrated increased plasma resistin and CAP-1 mRNA levels, implying their possible interaction in CRC. The association among plasma resistin and HDL-C might indicate that HDL-C is involved in alterations of resistin's secretion process. As a hallmark of personalized medicine, multi-marker approach in determination of resistin-related parameters might be useful for prediction and prevention of CRC development.

Changes in lecithin: cholesterol acyltransferase, cholesteryl ester transfer protein and paraoxonase-1 activities in patients with colorectal cancer.

BACKGROUND: Previous studies revealed decreased level of high-density lipoprotein cholesterol (HDLC) as important factor for development of colorectal cancer (CRC). Quantity and structure of HDL particles depend on activities of lipid transfer proteins lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP), but this topic is largely unexplored in CRC. The main objective of this study was to investigate activities of LCAT and CETP in patients with CRC. Additionally, we analyzed activity of paraoxonase-1 (PON-1), as a main carrier of HDL-antioxidant function. MATERIALS AND METHODS: Ninety-nine CRC patients and 101 healthy individuals were included. LCAT and CETP activities were assessed by measuring rates of formation and transfer of cholesteryl esters. PON-1 paraoxonase and arylesterase activities were measured. RESULTS: Lower levels of HDL-C (p < .001) were observed in cohort of patients, alongside with decreased LCAT (p < .050) and increased CETP activity (p < .050). Both PON-1 activities were diminished in CRC (p < .050 and p < .001 respectively). Univariate logistic regression singled out HDL-C level (OR = 0.218, p < .001), CETP activity (OR = 1.010, p < .01) and mass (OR = 0.994, p < .001) as possible markers of elevated CRC risk. CETP mass maintained its predictive significance when adjusted for traditional risk factors and level of oxidative stress (OR = 0.993, p < .001; OR = 0.982, p < .050, respectively). CONCLUSION: Our results demonstrated increased CETP and decreased LCAT and PON-1 activities in CRC patients. In preliminary analysis CETP mass was identified as potential significant predictor of CRC development, suggesting that alterations in HDL-C levels, alongside with changes in HDL structure might have a role in carcinogenesis.

Prostate Cancer Probability Prediction By Machine Learning Technique.

The main goal of the study was to explore possibility of prostate cancer prediction by machine learning techniques. In order to improve the survival probability of the prostate cancer patients it is essential to make suitable prediction models of the prostate cancer. If one make relevant prediction of the prostate cancer it is easy to create suitable treatment based on the prediction results. Machine learning techniques are the most common techniques for the creation of the predictive models. Therefore in this study several machine techniques were applied and compared. The obtained results were analyzed and discussed. It was concluded that the machine learning techniques could be used for the relevant prediction of prostate cancer.

Copeptin Levels Do Not Correlate With Cross-Clamping Time in Patients Undergoing Carotid Endarterectomy Under General Anesthesia.

Copeptin is a sensitive and more stable surrogate marker for arginine vasopressin. In this study, we evaluated copeptin levels in carotid endarterectomy (CEA) patients, perioperatively, to determine whether copeptin levels can be related to carotid artery cross clamping (CC) time and to postoperative neurological outcomes. Copeptin, interleukin 6, C-reactive protein, cortisol, and brain natriuretic peptide were measured preoperatively (T1) and 3 hours postoperatively (T3) as well as intraoperatively (T2). We recruited 77 patients. Values of copeptin rose gradually over the observed times: T1 = 7.9 (6.4-9.6), T2 = 12.6 (9.3-16.8), and T3 = 72.3 (49.1-111.2) pmol/L. There was a significant difference for repeated measurement ( P = .000, P = .000, and P = .000). Duration of carotid artery CC during CEA does not affect postoperative copeptin level (CC ≤ 13 minutes: 106.8 ± 93.6 pmol/L, CC > 13 minutes: 96.7 ± 89.1 pmol/L; P = .634). Preoperative copeptin level was significantly higher in patients with ulcerated plaque morphology. Activation of the stress axis in patients undergoing CEA results in copeptin elevation. Duration of CC during CEA does not affect postoperative copeptin levels.

Effects of polyphenol-rich chokeberry juice on antioxidant/pro-oxidant status in healthy subjects.

Berry fruits are a rich source of polyphenols, especially anthocyanins: well-known potent anti-oxidant phytochemicals. The purpose of this study was to evaluate beneficial effects of long-term consumption of polyphenol-rich organic chokeberry juice on different markers of antioxidant/pro-oxidant status in healthy female volunteers. Twenty-nine women, aged 25-49, were included in the study. Serological markers of oxidative stress and antioxidant defence, blood pressure, routine biochemical, and anthropometric parameters were analyzed at baseline and after twelve weeks of regular chokeberry juice consumption. Significant decrease in thiobarbituric acid-reactive substances level (TBARS; P<.001) and pro-oxidant-antioxidant balance (PAB; P<.05), as well as increase in paroxonase-1 activity toward diazoxon (P<.01) were found. Total oxidative status and sulphydryl groups levels were not significantly influenced by the intervention. Anthropometric, biochemical parameters, and blood pressure values were within the referent values for all subjects and were not influenced by the chokeberry juice consumption. However, we found positive correlation between age, body mass index, waist circumference, body fat percent, blood pressure, and analyzed marker of lipid peroxidation, which was influenced by the consumption. In conclusion, the fine modulation of several antioxidant/pro-oxidant status biomarkers observed in healthy subjects indicates putative prophylactic effects of polyphenol-rich chokeberry juice and supports its importance as part of an optimal diet.

Biomarkers of acute kidney injury in pediatric cardiac surgery.

OBJECTIVES: Acute kidney injury (AKI) is a significant problem in children undergoing cardiopulmonary bypass (CPB). The aims of this study were to assess the diagnostic validity of serum CysC (sCysC), serum neutrophil gelatinase lipocalin (sNGAL), urine neutrophil gelatinase lipocalin (uNGAL), urine kidney injury molecule (uKIM)-1, and urine liver fatty acid-binding protein (uL-FABP) to predict AKI presence and severity in children undergoing CPB. DESIGN AND METHODS: We performed a prospective single-center evaluation of sCysC, sNGAL, uNGAL, uKIM-1 and uL-FABP at 0, 2, 6, 24 and 48 h postoperatively in children undergoing CPB during cardiac surgery. AKI was defined as ≥25% decrease in the estimated creatinine clearance (eCCl) from pre-operative baseline at 48h after surgery. RESULTS: Of the 112 patients, 18 patients (16.1%) developed AKI; four of them needed acute dialysis treatment and three AKI patients died. In the AKI compared to the non-AKI group, sCysC at 2h, and uNGAL and uL-FABP at 2-48 h were significantly increased, as well as CPB, aortic cross clamp time and length of hospital stay. Biomarkers increased with worsening AKI severity. At 2h after CPB the best accuracy for diagnosis of AKI had uL-FABP and sCysC with area under the receiver operator curve (AUC) of 0.89 and 0.73, respectively. At 6 and 24h after CPB the best AUC was found for uL-FABP (0.75 and 0.87 respectively) and for uNGAL (0.70 and 0.93, respectively). CONCLUSIONS: sCysC, uNGAL and uL-FABP are reliable early predictors for AKI after CPB. By allowing earlier timing of injury and earlier intervention, they could improve AKI outcome.

Route-dependent effects of cadmium/cadmium and magnesium acute treatment on parameters of oxidative stress in rat liver.

The study was designed to evaluate and compare the effects of single oral (or) and intraperitoneal (i.p.) cadmium (Cd) administration on parameters of oxidative stress in liver of rats. Furthermore, investigation on protective effects of magnesium (Mg) or and i.p. pretreatment on the same parameters was performed. Wistar rats were administrated oral dose of Cd (30 mg Cd/kg b.w.)/Cd+Mg (30 mg Cd/kg b.w., 50 mg Mg/kg b.w.) or i.p. dose of Cd (1.5 mg Cd/kg b.w.)/Cd+Mg (1.5 mg Cd/kg b.w., 3 mg Mg/kg b.w.) and sacrificed after 24 h. In liver homogenates superoxide anion, malondialdehyde, non-protein sulfhydryl groups, total sulfhydryl groups content, and superoxide dismutase activity were determined. Cadmium intoxication caused the increase of superoxide anion and malondialdehyde levels and had negative effect on investigated parameters of antioxidant defense system, except on total sulfhydryl groups. The negative effect was more emphasized after i.p. Cd administration. Oral Mg pretreatment induced more pronounced positive effect than Mg given intraperitoneally that can be attributed, at least partly, to Cd and Mg interactions on the level of GIT. On the basis of the obtained results it can be concluded that both Cd and Cd+Mg effects on parameters of oxidative stress in rats liver are route-dependent.