The Interplay of Dyslipidemia, Oxidative Stress, and Clinical Outcomes in Acute Ischemic Stroke Patients with and without Coronary Artery Disease.

We assessed lipid and lipoprotein profiles, along with oxidative stress (OS) parameters, in patients within the crucial 24 h period following an acute ischemic stroke (AIS), comparing those with and without coronary artery disease (CAD). We aimed to correlate these measures with clinical condition scales (NIHSS, mRS) post-AIS. This study included 27 AIS patients without CAD (AIS group) and 37 AIS patients with CAD (CAD-AIS group). Using polyacrylamide gel electrophoresis (Lipoprint system), we determined plasma LDL and HDL subfractions. Spectrophotometric methods were used to assess plasma antioxidant capacity, lipoperoxides, homocysteine (HC) levels, paraoxonase1, and catalase activities. We also measured urine isoprostanes and the activities of antioxidant enzymes (SOD, GPx) with commercial kits. CAD-AIS patients had notably higher HC levels, while there were no significant differences in lipoprotein subfractions and OS parameters between both groups. In the AIS group, mRS scores showed negative correlations with catalase, GPx activities, and total cholesterol. In the CAD-AIS group, atherogenic lipoproteins (IDLC, LDL2, LDL3-7) exhibited a significant positive correlation with mRS. This study underscores the role of dyslipidemia and OS in the development of AIS and CAD. It emphasizes the complex connections between specific biomarkers and post-stroke clinical outcomes. Our results suggest a significant impact of CAD treatment on lipid profile but not on homocysteine levels. The traditional narrative associating high cholesterol as the ultimate risk factor for cardiovascular diseases needs to be challenged, at least with respect to neurological outcomes. These insights may guide more targeted therapeutic approaches.

The effects of vitamin D on different types of cells.

Vitamin D is neccessary for regulation of calcium and phosphorus metabolism in bones, affects imunity, the cardiovascular system, muscles, skin, epithelium, extracellular matrix, the central nervous system, and plays arole in prevention of aging-associated diseases. Vitamin D receptor is expressed in almost all types of cells and its activation leads to modulation of different signaling pathways. In this review, we have analysed the current knowledge of 1,25-dihydroxyvitamin D3 or 25-hydroxyvitamin D3 effects on metabolism of cells important for the function of the cardiovascular system (endothelial cells, vascular smooth muscle cells, cardiac cells and pericytes), tissue healing (fibroblasts), epithelium (various types of epithelial cells) and the central nervous system (neurons, astrocytes and microglia). The goal of this review was to compare the effects of vitamin D on the above mentioned cells in in vitro conditions and to summarize what is known in this field of research.

Endothelial Function in Patients with Multiple Sclerosis: The Role of GLP-1 Agonists, Lipoprotein Subfractions, and Redox Balance.

INTRODUCTION: Epidemiological studies have suggested an increased vascular risk in patients with multiple sclerosis (MS). There is increasing evidence of the beneficial effects of GLP-1 agonists (GLP-1a) in preventing vascular complications and slowing the progression of neurodegeneration. Our objective was to explore the changes in the endothelial function of MS patients after 12 months of GLP-1a therapy. We also explored the role of lipoprotein subfractions and the antioxidant capacity of plasma. METHODS: MS patients were enrolled in a prospective, unicentric study. GLP-1a (dulaglutide) was administered to 13 patients. The control population consisted of 12 subjects. Endothelial function was determined by peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI). Trolox equivalent antioxidant capacity (TEAC) was used to assess the total antioxidant capacity of the plasma. The levels of lipoprotein subfractions were evaluated. RESULTS: The GLP-1a group did not have a significant change in their RHIs after 12 months (2.1 ± 0.6 vs. 2.1 ± 0.7; p = 0.807). However, a significant increase in their TEACs was observed (4.1 ± 1.4 vs. 5.2 ± 0.5 mmol/L, p = 0.010). On the contrary, the subjects in the control group had a significant worsening of their RHIs (2.1 ± 0.5 vs. 1.8 ± 0.6; p = 0.030), without significant changes in their TEACs. Except for a significant decrease in very-low-density lipoprotein (VLDL) (30.8 ± 10.2 vs. 22.6 ± 8.3 mg/dL, p = 0.043), no other significant changes in the variables were observed in the control group. VLDL levels (beta = -0.637, p = 0.001), the use of GLP-1a therapy (beta = 0.560, p = 0.003), and small LDL (beta = 0.339, p = 0.043) were the only significant variables in the model that predicted the follow-up RHI. CONCLUSION: Our results suggest that the application of additional GLP-1a therapy may have atheroprotective and antioxidant effects in MS patients with high MS activity and thus may prospectively mitigate their vascular risk. However, the lipoprotein profile may also play an important role in the atherogenic risk of MS subjects.

Lipoprotein Subfractions Associated with Endothelial Function in Previously Healthy Subjects with Newly Diagnosed Sleep Apnea-A Pilot Study.

BACKGROUND: Obstructive sleep apnea (OSA) activates several pathophysiological mechanisms which can lead to the development of vascular diseases. Endothelial dysfunction (ED) is an initial step in the development of atherosclerosis. The association between ED and OSA has been described in several studies, even in previously healthy subjects. High-density lipoproteins (HDL) were generally considered to be atheroprotective, and low-density lipoprotein (LDL) to be an atherogenic component of lipoproteins. However, recent findings suggest a pro-atherogenic role of small HDL subfractions (8-10) and LDL subfractions (3-7). This study aimed to evaluate the relationship between endothelial function and lipid subfractions in previously healthy OSA subjects. MATERIAL AND METHODS: We prospectively enrolled 205 subjects with sleep monitoring. Plasma levels of triacylglycerols, total cholesterol, LDL, HDL, and their subfractions were assessed. Endothelial function was determined using peripheral arterial tonometry, and reperfusion hyperemia index (RHI) was assessed. RESULTS: Plasma levels of small and intermediate HDL subfractions have statistically significant pro-atherogenic correlations with endothelial function (p = 0.015 and p = 0.019). In other lipoprotein levels, no other significant correlation was found with RHI. In stepwise multiple linear regression analysis, small HDL (beta = -0.507, p = 0.032) was the only significant contributor in the model predicting RHI. CONCLUSIONS: In our studied sample, a pro-atherogenic role of small HDL subfractions in previously healthy subjects with moderate-to-severe OSA was proven.

Assessment of the Potential Health Risk of Gold Nanoparticles Used in Nanomedicine.

Due to unique properties, nanoparticles (NPs) have become a preferred material in biomedicine. The benefits of their use are indisputable, but their safety and potential toxicity are becoming more and more important. Especially, excessive production of reactive oxygen species (ROS) induced by the strong oxidation potential of metal NPs could evoke adverse effects associated with damage to nucleic acids, proteins and lipids. Our study gives a view on the potential cytotoxicity of gold NPs (Au NPs) of different size from the perspective of the redox state of healthy (HEK 293 T) and cancer (A375 and A594) cell lines. These cells were incubated in the presence of two concentrations of Au NPs for 24 h or 72 h and total antioxidant capacity, 8-isoprostane, and protein carbonyl levels were determined. Furthermore, the activity of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase was detected in cell lysates. Our results compared to the results of other laboratories are very contradictory. The outcomes also differ between healthy and cancer cell lines. However, there are certainly changes in the activities of antioxidant enzymes, as well as the damage to biological molecules due to increased NP-induced oxidative stress. But the final decision of the effect of Au NPs on the oxidative state of selected cell lines requires further research.

Preliminary Findings on the Effect of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles and Acute Stress on Selected Markers of Oxidative Stress in Normotensive and Hypertensive Rats.

Several studies have reported that the administration of various nanoparticles in vivo can cause oxidative stress. The combination of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) and acute stress was selected because, during intravenous application of a contrast agent, patients are exposed to psycho-emotional stress. This study was designed to investigate the effect of acute stress and USPIONs on selected markers of oxidative stress (antioxidant capacity, superoxide dismutase, glutathione peroxidase and catalase activities, levels of advanced oxidation protein products, protein carbonyls, lipoperoxides and 8-isoprostanes) in plasma and erythrocytes in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In the WKY and SHR groups, there was a significant main effect of genotype between groups on studied markers except protein carbonyls and lipoperoxides. In SHR, the combination of acute stress and USPIONs increased the antioxidant capacity of plasma and the selected enzyme activities of erythrocytes. In WKY, the combination of acute stress and USPIONs decreased the antioxidant capacity of erythrocytes and reduced levels of advanced oxidation protein products in plasma. Our study points to the fact that, when hypertensive subjects are treated with iron oxide nanoparticles, caution should be taken, especially in stress conditions, since they seem to be more vulnerable to oxidative stress produced by USPIONs.

The impact of sleep apnea syndrome on the altered lipid metabolism and the redox balance.

BACKGROUND: Obstructive sleep apnea (OSA) is a disorder with a significant risk for cardiovascular diseases. Dyslipidemia and redox imbalance belong to potential mechanisms linking OSA with the development of vascular diseases. The main aim of this study was the evaluation of the presence of lipid abnormalities in OSA patients, focusing on small dense low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions and determination of the redox imbalance by evaluating the marker of oxidative damage to plasma lipids - lipoperoxides. METHODS: The study included 15 male subjects with polysomnographically confirmed OSA and 16 male healthy controls. Plasma levels of total cholesterol, LDL and HDL and their subfractions, triacylglycerols and lipoperoxides were determined in all study individuals. Plasma LDL and HDL subfractions were separated by the Lipoprint system which is a polyacrylamide gel electrophoresis. Lipoperoxide levels were determined spectrophotometrically. RESULTS: OSA patients had significantly higher triacylglycerols, total cholesterol and LDL-cholesterol compared to healthy controls. HDL cholesterol was not significantly different. Of the LDL and HDL subfractions, OSA patients had significantly lower levels of atheroprotective LDL1 and large HDL subfractions and significantly higher levels of atherogenic small dense LDL3-7 and HDL8-10 subfractions. Lipoperoxide levels in patients with OSA were significantly elevated compared to healthy individuals. CONCLUSION: The lipoprotein pro-atherogenic phenotype was found in individuals with OSA characterized by increased levels of atherogenic lipoprotein subfractions and reduced levels of atheroprotective subfractions. In addition, a plasma redox imbalance was found in patients with OSA compared to controls by detecting higher oxidative damage to lipids. Abnormalities in lipoprotein levels in patients with OSA, as well as the redox imbalance, could lead to an acceleration of the atherosclerotic process in predisposed individuals and thus represent a significant risk factor for vasular diseases.

γ- and δ-Tocotrienols interfere with senescence leading to decreased viability of cells.

Senescence is an irreversible permanent cell cycle arrest accompanied by changes in cell morphology and physiology. Bioactive compounds including tocotrienols (vitamin E) can affect important biological functions. The aim of this study was to investigate how γ- and δ-tocotrienols can affect stress-induced premature senescence. We established two different models of premature stress senescence by induction of senescence with either hydrogen peroxide or etoposide in human lung fibroblasts MRC-5 (ECACC, England). We observed increased percentage of cells with increased SA-ß-galactosidase activity, decreased cell viability/proliferation and increased level of p21 in both models. In addition, γ-tocotrienol or δ-tocotrienol (both at concentrations of 150, 200 and 300 µM) were added to the cells along with the inductor of senescence (cotreatment). We have found that this cotreatment led to the decrease of cell viability/proliferation in both models of premature stress senescence, but did not change the percentage of senescent cells. Moreover, we detected no expression of caspase-3 or apoptotic DNA fragmentation in any models of premature stress senescence after the cotreatment with γ- as well as δ-tocotrienols. However, an increased level of autophagic protein LC-3 II was detected in cells with hydrogen peroxide-induced senescence after the cotreatment with γ-tocotrienol as well as δ-tocotrienol. In case of etoposide-induced senescence only δ-tocotrienol cotreatment led to an increased level of LC-3 II protein in cells. According to our work δ-tocotrienol is more effective compound than γ-tocotrienol.

Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?

BACKGROUND: Inflammatory cytokines contribute to proatherogenic changes in lipid metabolism by reduction of HDL-cholesterol (HDL-C) levels, impairment of its antiinflammatory and antioxidant functions. Therefore, the protective actions of HDL-C can be limited in chronic inflammatory diseases such as multiple sclerosis (MS). The aim of this study was to assess the association between lipoprotein subfractions and inflammatory status in early stages of multiple sclerosis. METHODS: Polyacrylamide gel electrophoresis Lipoprint© System was used for lipoprotein profile analysis in 19 newly diagnosed MS patients, and in matched 19 healthy controls. Serum levels of interleukin (IL) 1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, interferon-γ and TNF-α were measured by multiplex bead assay. RESULTS: Concentrations of the measured cytokines and lipoprotein subclasses were comparable between MS patients and controls. Male, but not female MS patients had significantly higher total HDL-C and small HDL-C subfraction than healthy controls. Large HDL-C negatively correlated with all measured cytokines except IL-17 in MS but not in controls. Intermediate HDL-C subfractions correlated positively with all measured cytokines except G-CSF in MS females but not in MS males or controls. CONCLUSION: Our results of higher HDL-C and mainly its small HDL-C subfraction suggest that male MS patients are at higher risk of atherosclerosis and the subtle dyslipidemia is present in early stages of the disease. The correlations between specific HDL-C subfractions and the inflammatory cytokines demonstrate mutual links between systemic inflammation and lipid metabolism in MS. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03052595 Registered on Feb 14, 2017.

Gender differences in LDL and HDL subfractions in atherogenic and nonatherogenic phenotypes.

OBJECTIVES: The aim of our study was to examine the role of low density lipoprotein (LDL)-subfractions in individuals with the atherogenic and non-atherogenic phenotype and the gender differences in lipoprotein subfractions including small dense LDL (sdLDL) and small high density lipoprotein (sHDL) subfractions representing the most atherogenic lipoprotein subfractions. DESIGN & METHODS: 35 persons in the atherogenic group (AG) (with sdLDL3-7 subfractions ≥6 mg/dl) and 104 individuals in the non-atherogenic group (NAG) (sdLDL3-7 subfractions <6 mg/dl) were included in our study. To analyze plasma lipoprotein subfractions, a polyacrylamide gel electrophoresis-the Lipoprint system was used. RESULTS: Males compared to females in the AG had significantly higher levels of atherogenic lipoprotein subfractions such as HDL8, HDL9 and HDL10. All participants in AG had significantly lower levels of intermediate density lipoprotein IDL-A than those in NAG but significantly higher levels of IDL-B and IDL-C. Males in the AG compared to NAG had significantly lower levels of LDL1 and higher levels of LDL2 and LDL3-7 subfractions. In the NAG LDL2 positively correlated with sHDL subfractions while in the AG with the large HDL subfraction. CONCLUSION: Results of our study demonstrate more atherogenic profile in males compared to females and a double role of LDL2 subfraction in the atherogenic process depending on the phenotype (atherogenic/non-atherogenic) of individuals.

Oxidative stress in patients with newly diagnosed multiple sclerosis: any association with subclinical atherosclerosis?

OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory autoimmune and neurodegenerative disease of the central nervous system (CNS) typically affecting young adults. Although the pathogenesis of MS is not fully understood, there is evidence to suggest that inflammation-induced oxidative stress can play a role in demyelination and axonal damage. Oxidative stress also participates in the pathogenesis of endothelial dysfunction and atherogenesis. Data from large epidemiological studies showed a higher risk of vascular events in MS patients. The aim of our study was to analyse the presence of oxidative stress and its association with the parameters of subclinical atherosclerosis in the early stages of MS. MATERIAL AND METHODS: We compared 13 newly diagnosed MS patients with a group of 13 healthy age- and BMI-matched controls. Blood samples were measured for total antioxidant activity using TEAC assay. Endothelial function, expressed as reperfusion hyperaemia index (RHI) and arterial stiffness, expressed as augmentation index standardized to a pulse of 75/min (AI@75) were assessed using peripheral arterial tonometry. RESULTS: MS patients had significantly lower TEAC compared to controls [0.8 (0.4-2.4) vs. 1.2 (0.6-3.8) mmol/l; p=0.004]. The frequency of increased arterial stiffness (61.6% vs. 30.8%) and endothelial dysfunction (46.2% vs. 38.5%) was comparable in MS patients and in controls. There was no significant association between TEAC, increased arterial stiffness or endothelial dysfunction in patients and controls. CONCLUSION: Our study showed decreased antioxidant capacity in newly diagnosed MS patients compared to controls. We failed to find association of subclinical atherosclerosis with oxidative stress in newly diagnosed MS.

Effect of 8-weeks intensive lifestyle intervention on LDL and HDL subfractions.

OBJECTIVE: Atherogenic dyslipidemia is a cardinal feature of obesity and the metabolic syndrome, which increases the risk of cardiovascular diseases. Many interventional studies, describing the influence of weight loss on cardiometabolic risks, are bariatric surgery studies. The aim of our study was to analyze the effect of intensive lifestyle changes on LDL- and HDL-cholesterol subfractions and cardiometabolic risk factors in obese subjects. METHODS: A group of 41 patients with obesity (11M/30F; 44.1±12.4 years; BMI 30.2±6.3kg/m2) participated in an 8-week weight loss interventional program (NCT02325804), consisting of caloric intake reduced by 30% and physical activity (150min/week). Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) and physical fitness was measured using bicycle ergometry. Lipid subfractions were measured using the Lipoprint system (Quantimetrix Corp., CA, USA). RESULTS: After the intervention, body weight was reduced by 5.4±4.5kg, as well as body fat mass and waist circumference. Physical fitness improved, systolic and diastolic blood pressure as well as heart rate decreased after the intervention. Insulin sensitivity improved after the intervention. Total, LDL, HDL cholesterol, as well as triglycerides decreased after the intervention. Regarding the lipoprotein subfractions, LDL2 and small HDL subfractions decreased, while others have not changed. CONCLUSION: Eight weeks of diet and physical activity intervention led to weight and fat mass loss and induced improvement of insulin sensitivity, as well as atheroprotective changes of lipid profile. However, the weight loss associated changes in cholesterol subfractions as cardiovascular risk biomarkers deserve further studies.

Self-Reported Exposure to ETS (Environmental Tobacco Smoke), Urinary Cotinine, and Oxidative Stress Parameters in Pregnant Women-The Pilot Study.

BACKGROUND: Exposure to ETS (environmental tobacco smoke) is one of the most toxic environmental exposures. OBJECTIVE: To investigate the association of ETS with physiological, biochemical, and psychological indicators, as well as with urine antioxidant capacity (AC) and oxidative damage to lipids in a pilot sample of healthy pregnant women. METHODS: Exposure to ETS was investigated via a validated questionnaire, and urine cotinine and the marker of oxidative damage to lipids via 8-isoprostane concentrations using an ELISA kit. Urine AC was determined by the spectrophotometric Trolox-equivalent antioxidant capacity (TEAC) method. From a sample of pregnant women (n = 319, average age 30.84 ± 5.09 years) in 80, the levels of cotinine and oxidative stress markers were analyzed. RESULTS: Among the 80 pregnant women, 5% (7.4% confirmed by cotinine) reported being current smokers and 25% reported passive smoking in the household (18.8% confirmed by cotinine). The Kappa was 0.78 for smokers and 0.22 for ETS-exposed nonsmokers. Pregnant women in the ETS-exposed group had significantly reduced AC compared to both the nonsmoker (ETS-) and the smoker groups (p < 0.05). Nonsmokers had significantly lower levels of 8-isoprostane than smokers (p < 0.01) and ETS-exposed nonsmokers (p < 0.05). Correlations between urine levels of cotinine and AC were positive in ETS-exposed nonsmokers. CONCLUSION: A harmful association of active and passive smoking and oxidative stress parameters among pregnant women has been indicated.

Small dense LDL - an important part of the atherogenic lipoprotein profile in individuals with impaired metabolism of lipoproteins. Comparison of two analytical procedures.

OBJECTIVES: To compare two different analytical methods for determination of small dense LDL and to determine a share of corresponding and non-corresponding (inconsistent) results METHODS: In the group of 104 hyperlipidemic patients and 20 healthy individuals of the control group we analysed the total cholesterol and triglycerides by enzymatic CHOD PAP method (Roche Diagnostics, Germany) in EDTA-K2 plasma. Small dense LDL (sdLDL) were quantified by the electrophoretic method for lipoprotein analysis on polyacrylamide gel (PAG) (Lipoprint LDL System, Quantimetrix, CA, USA) and simultaneously, the small dense LDL concentrations in the indentical samples were analysed by an enzymatic method LDL-EX ´Seiken´(Randox, England). RESULTS: In 31 patients we found the discrepancy in the sdLDL levels using the two different procedures. Out of them, 24 patients tested by enzymatic method ´SEIKEN´ had higher sdLDL values (more than 0.9 mmol/l) compared to the Lipoprint LDL results, which identified normal sdLDL values in the same samples (in 23% of tested patients). In 7 patients out of the 31 tested patients with discrepant sdLDL values, the Lipoprint LDL identified increased values of plasma sdLDL (more than 0.155 mmol/l), while the enzymatic LDL-EX Seiken did not find an increased concentration of sdLDL (in 7% of tested patients). In the control group a discrepancy in the sdLDL results between the two tested analytical methods was not found. CONCLUSION: The concentration of sdLDL in plasma lipoprotein spectrum obtained by two different laboratory procedures was analysed, compared, evaluated and 70% identical corresponding results have been confirmed.

Gender differences in LDL- and HDL-cholesterol subfractions in patients after the acute ischemic stroke and their association with oxidative stress markers.

The aim of our study was to examine gender differences of LDL- and HDL-cholesterol subfractions in patients after the acute ischemic stroke with focus on small LDL and HDL subfractions, and their association with oxidative stress markers. In addition, we have monitored the 7-day effect of cholesterol-lowering drugs administered to patients after the acute ischemic stroke, on these subfractions. Eighty two stroke patients and 81 age matched controls were included in this study. Blood was collected from patients within 24 h after the stroke (group A) and re-examined at the 7-day follow-up (group B). We have found gender differences in LDL- and HDL-subfractions in stroke patients, lipid-lowering drugs administered to acute ischemic stroke patients significantly reduced all measured parameters of lipoprotein profile. In the group A LDL1 subfraction positively correlated with activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) indicating a protective role of this subfraction. On the contrary, small HDL subfractions positively correlated with lipoperoxide levels and negatively with trolox equivalent antioxidant capacity in plasma suggesting a negative role of these subfractions. In this work we have confirmed the hypothesis of atherogenic properties of small HDL subfractions and anti-atherogenic properties of large LDL1-subfractions.

Chronic Stress Produces Persistent Increases in Plasma Corticosterone, Reductions in Brain and Cardiac Nitric Oxide Production, and Delayed Alterations in Endothelial Function in Young Prehypertensive Rats.

This study was designed to investigate whether oxidative stress, nitric oxide (NO) deficiency and/or endothelial dysfunction (ED) are present in young borderline hypertensive rats (BHR) and whether these pathologies can be causally involved in the initiation of blood pressure (BP) increases. Additionally, we tested the hypothesis that crowding stress, experienced during the peripubertal period, may produce persistent or delayed disorders in corticosterone release, NO synthesis, oxidative status and/or endothelial function that could accelerate BP increases. To test these hypotheses, 5-week-old male BHR and normotensive Wistar-Kyoto rats (WKY) were either kept in control conditions (for 2 and 4 weeks, respectively) or exposed to social stress produced by crowding for 2 weeks (stress). After cessation of crowding, a group of rats of each phenotype was kept in control conditions for the next 2 weeks (post-stress). Systolic BP of 5-week-old BHR was significantly increased vs. age-matched WKY (127 ± 3 vs. 104 ± 3 mmHg, p < 0.01) and remained significantly higher throughout the course of the experiment. Despite elevated BP, no signs of oxidative damage to plasma lipids, NO deficiency or ED were observed in control BHR vs. age-matched WKY. Crowding stress elevated plasma corticosterone and accelerated BP increases only in BHR; these effects persisted 2 weeks post-stress. Crowding failed to induce oxidative damage to plasma lipids in either phenotype, but it produced persistent decreases in NO production in the hypothalamus and brainstem of both strains of rats, as well as in the hearts of BHR. In contrast, crowding failed to reduce NO production in the aortae or acetylcholine-induced relaxations of the femoral arteries in both strains investigated. However, significantly reduced aortic NO production was observed in BHR 2 weeks post-stress vs. age-matched controls, which was in agreement with reduced NO-dependent components of vasorelaxation. In conclusion, this study's data showed that oxidative stress, NO deficiency and ED are not causally involved in initiation of blood pressure increase in BHR. However, exposure to stressful environments produced persistent increases in plasma corticosterone and reductions of brain and cardiac NO production followed by a delayed decrease in the NO-dependent component of endothelium-dependent relaxation-changes that collectively accelerated BP increases only in BHR.

LDL and HDL lipoprotein subfractions in multiple sclerosis patients with decreased insulin sensitivity.

OBJECTIVES: Increased metabolic and cardiovascular morbidity has been reported in multiple sclerosis (MS) patients. Previously, we have found decreased insulin sensitivity and hyperinsulinemia in a group of newly diagnosed MS patients. We hypothesize that these features may be associated with an altered lipid profile and low, intermediate, or high density lipoprotein (LDL, IDL, HDL) subclasses accelerating atherosclerosis and thus contributing to the cardiovascular risk increase in these patients. SUBJECTS AND METHODS: In a group of 19 newly diagnosed untreated MS patients with previously found hyperinsulinemia and insulin resistance and a matched group of 19 healthy controls, the lipoprotein subclasses profile was determined. Polyacrylamide gel electrophoresis was used to separate and measure the LDL (large LDL and small dense LDL), HDL (large, intermediate and small), and IDL (A, B and C) subclasses with the Lipoprint© System (Quantimetrix Corporation, Redondo Beach, CA, USA). RESULTS: No difference was found either in the conventional lipid or lipoprotein subclasses profile between the MS patients and healthy controls. We found an inverse association between the level of IDL-B with fasting insulin (r=-0.504, p=0.032), the insulin resistance estimated by homeo-static model assessment - insulin resistance (HOMA-IR) (r=-0.498, p=0.035), insulin response expressed as area under the curve (AUC; r=-0.519, p=0.027), and area above the baseline (AAB; r=-0.476, p=0.045) and positive association with insulin sensitivity estimated by insulin sensitivity index (ISI) Matsuda (r=0.470, 0.048) in MS patients, but not in healthy controls suggesting the first signs in lipoprotein subclasses profile change. CONCLUSIONS: Our data indicate that changes in lipoprotein profile and subclasses are preceded by insulin resistance and hyperinsulinemia in patients with newly diagnosed MS.

Effect of Neonatal Exposure to Poly(Ethylene Glycol)-block-Poly(Lactic Acid) Nanoparticles on Oxidative State in Infantile and Adult Female Rats.

Our goal was to evaluate the potential health risk of the polymeric NP, poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA), from the view of redox imbalance of the organism in two different life stages. Female Wistar rats were neonatally administered intraperitoneally with PEG-b-PLA NPs [20 mg/kg of b.w. (PEG20) or 40 (PEG40) mg/kg of b.w.] from postnatal day 4 (PND4) to PND7. We measured antioxidant capacity (TEAC), level of protein carbonyls and lipoperoxides in plasma, activities of catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD) in hemolysates of infantile (sacrificed on PND17) and adult (sacrificed after PND176) rats. Compared to controls, neonatal PEG40 exposure induced a significant TEAC reduction in the infantile rats. Protein carbonyls and lipoperoxide levels were not affected after any dose of PEG-b-PLA NP administration. In adult rats, PEG20 administration caused a significant decrease of protein carbonyl levels compared to controls. In infantile rats, both doses of PEG-b-PLA NP administration increased catalase, Gpx, and SOD activities compared to controls. Surprisingly, in adult rats, the activities of Gpx and SOD decreased significantly after administration of both doses of PEG-b-PLA NPs. Obtained data indicate a possible age-related association between the oxidative status and neonatal PEG-b-PLA NP administration in female rats.

Fish oil emulsion supplementation might improve quality of life of diabetic patients due to its antioxidant and anti-inflammatory properties.

Diabetes-related complications, including cardiovascular disease, retinopathy, nephropathy, and neuropathy, are a significant cause of increased morbidity and mortality among people with diabetes. Previous studies have confirmed that hyperglycemia has pro-oxidative and proinflammatory properties which cause diabetic complications. We hypothesized that supplementation of fish oil emulsion (FOE), rich in omega-3 polyunsaturated fatty acids, to diabetic patients might reduce hyperglycemia-induced pathological changes due to specific properties of FOE. Omega-3 polyunsaturated fatty acids have a wide range of biological effects. In this project, we have examined the potential protective effect of the FOE on hyperglycemia-induced oxidative stress and cytokine generation in monocytes/macrophages U937 system in vitro. The monocytes/macrophages U937 were cultivated under normal or hyperglycemic (35 mmol/L glucose) conditions with/without FOE for 72 hours. We have focused on specific markers of oxidative stress (antioxidant capacity; superoxide dismutase activity; oxidative damage to DNA, proteins, and lipids) and inflammation (tumor necrosis factor, interleukin-6, interleukin-8, monocytic chemotactic protein-1). Hyperglycemia caused reduction of antioxidant capacity, induction of DNA damage, and proinflammatory cytokine secretion. FOE significantly increased antioxidant capacity of cells as well as superoxide dismutase activity and significantly reduced tumor necrosis factor, interleukin-6, interleukin-8, and monocytic chemotactic protein-1 release. No effect was observed on oxidative damage to DNA, proteins, and lipids. Our results indicate that FOE can reduce hyperglycemia-induced pathological mechanisms by its antioxidant and anti-inflammatory properties.

Association of lipoprotein subfractions with endothelial function and arterial stiffness in acute ischemic stroke.

Hypercholesterolemia represents a risk factor for the development of atherosclerosis. Lipoprotein research has recently been focused on the phenomenon of atherogenic and non-atherogenic lipoproteins. The aim of this study was to explore the association of lipoprotein subfractions with a measure for endothelial function (represented by reactive hyperemia index [RHI]) and arterial stiffness (represented by augmentation index [AI]) in patients with acute ischemic stroke. We enrolled 51 patients with acute ischemic stroke. Blood samples were obtained within 24 h after the stroke onset in a fasting condition. Electrophoresis method on polyacrylamide gel was used for the analysis of plasma lipoproteins. RHI and AI was measured by peripheral arterial tonometry (EndoPAT2000 device). We failed to find any significant correlation between RHI and baseline characteristics of the population. Significant correlation was found between AI and age, hypertension, low density lipoprotein cholesterol (LDL) 1, LDL 3-7, score for anti-atherogenic risk and atherogenic profile. Age (beta = .362, p = .006) and LDL1 (beta = -0.283, p = .031) were the only independent variables significantly associated with AI in regression analysis. Significantly higher AI was found in an atherogenic lipoprotein profile compared to a non-atherogenic profile population (median 25% vs. median 11.5%, p = .043). In conclusion, our results suggest significant inverse correlation between levels of LDL 1 subfraction and measures of AI in patients with acute ischemic stroke. Significantly higher values of AI were observed in the population with an atherogenic lipoprotein profile.