Mihkel Zilmer

University of Tartu, Dorpat, Tartu County, Estonia

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Publications (165)384.26 Total impact

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    ABSTRACT: Childhood obesity has recently been linked to low-grade inflammation. Overweight children have slightly different processes of bone accumulation than normal weight children. The possible links between inflammation and bone accumulation have not previously been assessed in overweight children. An exploratory study to assess whether common inflammatory markers are associated with the development of obesity and bone accumulation in childhood. Thirteen different inflammatory markers in serum were measured in 38 boys with BMI >85th centile (overweight) and 38 boys with normal BMI (normal weight), aged 10-11 years. Total body (TB) and lumbar spine (LS) bone mineral density (BMD), bone mineral content (BMC) were measured by DXA. TB BMC for height, TB and LS bone mineral apparent density (BMAD) were calculated. Overweight boys had higher mean TB and LS BMD, TB BMC and TB BMC for height, but lower mean TB BMAD (all p < 0.05) than normal weight boys. Serum interferon gamma (IFNγ) concentration was significantly (p < 0.05) correlated with TB BMD (r = 0.36), TB BMC (r = 0.38) and TB BMC for height (r = 0.53) in the broader overweight group (n = 38). In obese boys (BMI > 95 centile, n = 36) IFNγ was correlated with LS BMD (r = 0.38). The positive correlation between serum INFγ concentration and BMD suggests that the inflammatory process, already involved in the early stage of obesity, may also affect bone accumulation. Further studies are needed to clarify the role of INFγ as a possible link between adipose tissue and bone health.
    Journal of endocrinological investigation 02/2014; 37(2):175-80. · 1.65 Impact Factor
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    ABSTRACT: Prevention or attenuation of diabetic vascular complications includes anti-hypertensive treatment with renin-angiotensin system inhibitors on account of their protective effects beyond blood pressure reduction. The present study aimed to investigate the effects of telmisartan, an angiotensin II type 1 receptor blocker (ARB), on blood pressure, aortic stiffening, and aortic remodelling in experimental type 1 diabetes in rats.
    Diabetology and Metabolic Syndrome 01/2014; 6:57. · 1.92 Impact Factor
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    ABSTRACT: Background. The aim was to determine the effect of heat acclimation (HA) on oxidative stress (OxS) and inflammation in resting conditions and on the response pattern of these parameters to exhausting endurance exercise. Methods. Parameters of OxS and inflammation were measured in non-heat-acclimated status (NHAS) and after a 10-day HA program (i.e., in heat-acclimated status; HAS) both at baseline and after an endurance capacity (EC) test in the heat. Results. As a result of HA, EC increased from 88.62 ± 27.51 to 161.95 ± 47.80 minutes (P < 0.001). HA increased OxS level: total peroxide concentration rose from 219.38 ± 105.18 to 272.57 ± 133.39 μ mol/L (P < 0.05) and oxidative stress index (OSI) from 14.97 ± 8.24 to 20.46 ± 11.13% (P < 0.05). In NHAS, the EC test increased OxS level: total peroxide concentration rose from 219.38 ± 105.18 to 278.51 ± 125.76 μ mol/L (P < 0.001) and OSI from 14.97 ± 8.24 to 19.31 ± 9.37% (P < 0.01). However, in HAS, the EC test reduced OSI from 20.46 ± 11.13 to 16.83 ± 8.89% (P < 0.05). The value of log high-sensitive C-reactive protein increased from -0.32 ± 0.32 to -0.12 ± 0.34 mg/L (P < 0.05) in NHAS and from -0.31 ± 0.47 to 0.28 ± 0.46 mg/L (P < 0.001) in HAS. Conclusion. HA increases OxS level. However, beneficial adaptive effects of HA on acute exhaustive exercise-induced changes in OxS and inflammation parameters occur in a hot environment.
    Oxidative medicine and cellular longevity. 01/2014; 2014:107137.
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    ABSTRACT: Objectives Arterial stiffness (AS) is increasingly recognized as an independent risk factor in different high-risk populations. Whether changes in AS can predict prognosis in patients with symptomatic peripheral arterial disease (PAD) has never been investigated. The aim of the present study was to test the hypothesis that AS is an independent predictor of all-cause and cardiovascular disease (CVD) mortality in patients with symptomatic PAD. Methods A cohort of 117 symptomatic PAD patients (aged 62.3 ± 7.7 years) were prospectively recruited from the Department of Vascular Surgery, Tartu University Hospital, between 2002 and 2010. The AS was measured using pulse wave analysis and assessment of pulse wave velocity (PWV). Results During the follow-up period (mean 4.1 ± 2.2 years) there were 32 fatal events. Kaplan–Meier analysis showed that the probability of all-cause and CVD mortality decreased with increasing small artery elasticity (SAE), as estimated by the log-rank test (p = .004; p = .005, respectively). By contrast, large artery elasticity, augmentation index, and aortic and brachial PWV were not significantly related to mortality. In a Cox proportional hazard model, SAE above the median was associated with decreased all-cause and CVD mortality after adjustment for confounding factors: relative risk (RR), 0.37; 95% confidence interval (CI), 0.17–0.81; p = .01; RR, 0.11; 95% CI, 0.01–0.86; p = .04, respectively). Conclusions This study provides the first evidence, obtained from an observational study, that decreased small artery elasticity is an independent predictor of all-cause and CVD mortality in patients with symptomatic PAD.
    European Journal of Vascular and Endovascular Surgery. 01/2014;
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    S Kaur, K Zilmer, V Leping, M Zilmer
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    ABSTRACT: Background. Research has confirmed the involvement of oxidative stress (OxS) in allergic contact dermatitis whilst other inflammation-related biomarkers have been less studied. Objective. To evaluate systemic levels of selected inflammatory markers, OxS indices and adipokines as well as their associations in allergic contact dermatitis. Methods. In 40 patients, interleukin- (IL-) 6, monocyte chemoattractant protein (MCP-1), and IL-10 levels were measured in sera with the Evidence Investigator Cytokine & Growth factors High-Sensitivity Array, total peroxide concentration (TPX) and total antioxidant capacity (TAC) by means of spectrophotometry, and the plasma concentrations of adiponectin and leptin by the quantitative sandwich enzyme immunoassay technique. Results. TNF-α level (P < 0.01) and TPX (P < 0.0001) were increased whilst IL-10 (P < 0.05) and TAC (P < 0.0001) were decreased in the patients as compared to controls. Correlation and multiple linear regression analysis identified both, TPX and TAC (inversely), as possible independent markers for evaluating allergic contact dermatitis. Adiponectin level in patients was increased (P < 0.0001), but neither adiponectin nor leptin correlated significantly with the biomarkers of inflammation or OxS. Conclusion. OxS parameters, especially TPX and OSI, reflect the degree of systemic inflammation associated with allergic contact dermatitis in the best way. The relation between OxS and adiponectin level warrants further studies.
    Dermatology Research and Practice 01/2014; 2014:415638.
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    ABSTRACT: Among the markers and targets of the early phase of Alzheimer's disease (AD) pathogenesis MnSOD (mitochondrial dysfunction) and Na-pump (disturbances in function/regulation) are often highlighted. This paper focused on comparison of the effects of three antioxidants on the activity of cerebrocortical MnSOD and Na,K-ATPase from post mortem Alzheimer's disease and age-matched normal brains. Antioxidant compounds with different origins: natural glutathione, synthetic UPF peptides (glutathione analogues) and phytoestrogen genistein were investigated. Firstly, MnSOD and Na,K-ATPase activities were found to be decreased in the post mortem AD brains compared with age-matched controls. Secondly, GSH had no effect on MnSOD activity, but decreased Na,K-ATPase activity both in the control and AD brains. Thirdly, UPF1 and UPF17 increased MnSOD activity, and UPF17 suppressed Na,K-ATPase activity. Further studies are needed to clarify, if the inhibitory effect of UPF17 on Na,KATPase could abolish the beneficial effect gained from MnSOD activation. Both the antioxidative potential of genistein and its potency to up-regulate Na,K-ATPase activity make it an attractive candidate substance to suppress the early phase of the pathogenesis of AD.
    Current Alzheimer research 10/2013; · 4.97 Impact Factor
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    ABSTRACT: The major physiological adaptations that occur during heat acclimation (HA) are well documented. However, no studies have provided compelling evidence about the effect of HA on arterial elastic properties. The aim of this study was to examine the changes in large artery elasticity (LAE) and small artery elasticity (SAE) concomitant with HA and to determine the potential relationships among changes in arterial elasticity, baseline aerobic fitness level, and improvement in endurance capacity (EC). During 10-day HA, the subjects (n = 21) exercised daily on a treadmill for 110 min at an intensity of 55%-60% of peak oxygen uptake in a climatic chamber preset to 42 °C and 18% relative humidity. EC was tested in the heat before and after HA. Arterial elasticity was assessed by diastolic pulse wave analysis (HDI/Pulse Wave CR-2000) at baseline and after HA. Blood samples were drawn at baseline. After HA, there was a 17% increase in LAE (from 21.19 ± 4.72 mL·mm Hg(-1) × 10 to 24.77 ± 5.91 mL·mm Hg(-1) × 10, p < 0.05) and an 18% increase in SAE (from 9.32 ± 1.76 mL·mm Hg(-1) × 100 to 10.98 ± 1.75 mL·mm Hg(-1) × 100, p < 0.01). EC increased by 86% (from 88.62 ± 27.51 min to 161.95 ± 47.80 min, p < 0.001) as a result of HA. No significant associations were revealed between changes in arterial elasticity parameters and improvement in EC or baseline aerobic fitness level. We demonstrated, for the first time, that HA has a positive impact on the parameters of arterial elasticity. Further investigations are needed to determine the mechanisms underlying these changes and the potential relationships among arterial elasticity, aerobic fitness level, and EC.
    Applied Physiology Nutrition and Metabolism 09/2013; 38(9):922-7. · 2.01 Impact Factor
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    ABSTRACT: Psoriasis vulgaris (PV), a chronic inflammatory skin disease, is a condition of increased oxidative stress (OxS). However, interest related to oxidative and carbonyl stress damages to proteins, such as the formation of advanced glycation end products (AGEs) and their precursor molecule methylglyoxal (MG) has been modest. The objective of this study was to compare the systemic levels of OxS markers in patients with PV and healthy controls (Co) and to investigate their correlation with the serum level of MG. Total peroxide concentration (TPX) and total antioxidant capacity (TAC) were estimated by means of spectrophotometry. The TPX and TAC ratio was regarded as OxS index (OSI). MG level was determined using ELISA. Compared to Co, patients with PV had significantly increased blood levels of TPX (P < 0.0001), OSI (P < 0.0001), and MG (P = 0.01), and lower TAC levels (P < 0.0001). Increase in body mass index (BMI) appeared to contribute to this imbalance as TAC levels decreased with increasing BMI (r = -0.252, P < 0.01). Increased TPX concentration was associated with higher serum level of MG (r = 0.610, P = 0.004), the latter being positively correlated with psoriasis area and severity index (r = 0.577, P = 0.008). In performed multivariate regression analysis, TPX, TAC, and OSI were all significant predictors of MG level. Our study gave further proof of increased systemic psoriasis-related OxS. MG serum level, reflecting simultaneously OxS as well as carbonyl stress status, could be used as a marker of disease activity in clinical trials while looking for new systemic therapies for psoriasis.
    Archives for Dermatological Research 05/2013; · 2.71 Impact Factor
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    ABSTRACT: AIMS: Vitamin D may have an important role in reducing the risk of cardiovascular disease. Advanced glycation end-products (AGEs) such as Ne-(carboxymethyl)lysine (CML), have been implicated in diabetic vascular complications via oxidative stress-mediated pathways. We investigated the potential protective effect of vitamin D on CML accumulation in the diabetic aortic wall. To test the effects of vitamin D on systemic oxidative stress we also assessed liver oxidative stress index (OSI) and serum total antioxidant capacity (TAC). METHODS: Male Wistar rats were assigned to three groups: control, untreated diabetes, and diabetes+cholecalciferol. Diabetes was induced by streptozotocin, followed by oral administration of cholecalciferol (500IU/kg) for 10 weeks in the treatment group. Aortic CML accumulation was determined by ELISA and immunohistochemical assays. OSI was assessed by measuring TAC and the level of total peroxides in the liver and serum using colorimetric assays. RESULTS: Untreated diabetes was associated with significantly elevated CML levels in the aortic wall (19.5±3.3 vs 10.2±4.7ng/mL), increased liver OSI (6.8±1.9 vs 3.1±0.7), and reduced serum TAC (0.4±0.1 vs 0.8±0.3mmol Trolox/L), in comparison with the control group. Cholecalciferol significantly blocked the accumulation of CML in the aortic wall (10.4±8.4 vs 19.5±3.3ng/mL), decreased liver OSI (4.2±1.4 vs 6.8±1.9), and improved serum TAC (1.0±0.2 vs 0.4±0.1mmol Trolox/L), compared with the untreated diabetic group. CONCLUSIONS: Streptozotocin-diabetes resulted in increased deposition of AGEs and increased oxidative stress in the serum and liver. Vitamin D supplementation may provide significant protection against oxidative stress-mediated vascular complications in diabetes.
    Diabetes research and clinical practice 03/2013; · 2.74 Impact Factor
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    ABSTRACT: Abstract Background/Aims: Some markers of inflammation have been found to be associated with cardiorespiratory fitness levels, but only few studies have studied this in overweight children. The aim of this study was to investigate associations between markers of inflammation and the fitness levels measured by peak oxygen consumption (VO2peak and VO2peak/kg) in boys with increased body mass index (BMI) and with normal BMI. Participants/Methods: Subjects were 38 boys with BMI above 85th percentile (OWB) and 38 boys with normal BMI (NWB) at the age of 10 to 11 years. Serum concentrations of IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFNγ, TNF-α, IL-1α, IL-1β, MCP-1, EGF, CRP and associations with measured cardiorespiratory fitness levels were studied. High-sensitive chips were used to measure 13 markers of inflammation. Results: Mean VO2peak was significantly higher (2.1±0.3 vs. 1.8±0.3 L/min; p<0.05) and mean VO2peak/kg significantly lower (33.7±4.7 vs. 48.9±6.4 mL/min/kg; p<0.05) in OWB than in NWB group. Out of 13 measured biochemical markers IL-6 correlated with VO2peak/kg (r=-0.37; p<0.05) and TNF-α with VO2peak (r=0.41; p<0.01) in OWB. BMI and IL-6 together explained 44.5% of the variability of VO2peak/kg in the OWB group. Conclusions: Overweight boys had lower cardiorespiratory fitness level measured by VO2peak/kg and this was negatively correlated with serum IL-6 level. Measurement of serum IL-6 level in overweight boys may help to identify subjects who need specific exercise formats to achieve maximal beneficial health effects and to reduce their risk for the development of type 2 diabetes and atherosclerosis later in life.
    Journal of pediatric endocrinology & metabolism: JPEM 03/2013; · 0.75 Impact Factor
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    ABSTRACT: The aim of the study was to determine the roles of intrafollicular and systemic oxidative stress and antioxidant response in ovarian stimulation and intracytoplasmic sperm injection (ICSI) outcomes. For this purpose, 102 ICSI patients undergoing controlled ovarian stimulation were enrolled and samples were collected on the day of follicle puncture. Total peroxide (TPX) concentrations and total antioxidant response (TAR) were measured in follicular fluid and blood plasma, and an oxidative stress index (OSI) was calculated based on these two parameters. Urinary concentrations of 8-iso-prostaglandin F(2a) (F(2)IsoP) were measured. Elevated intrafollicular oxidative stress was positively correlated with ovarian stimulation outcome: less FSH per retrieved oocyte was used, more oocytes were collected and higher serum oestradiol concentrations were measured in patients with higher follicular OSI. However, high urinary F(2)IsoP related to lower embryo quality and F(2)IsoP was also elevated in smoking patients. Patients with endometriosis had lower follicular antioxidant status. Most importantly, higher systemic blood TAR was significantly favourable for achieving clinical pregnancy (P=0.03). In conclusion, the findings suggest clear associations between oxidative stress, antioxidant status and several aspects of ovarian stimulation and IVF/ICSI outcome, including pregnancy rate. Several oxygen-dependent biochemical reactions produce reactive oxygen species as by-products that may eventually lead to oxidative stress, which is detrimental to cells and tissues. Total antioxidant status, on the other hand, comprises several agents that balance the excess of these reactive oxygen species and reduce potential damage to the body. The aim of the current work was to study this balance in 102 patients participating in an ICSI programme and to examine the degree to which total peroxide content and antioxidant status influence infertility and pregnancy outcome. During the study, several tests were performed to characterize oxidative stress levels in ovarian follicular fluid, blood plasma and urine. We found a significantly higher oxidative stress environment in the ovary when compared with blood plasma. This suggests a prominent role of oxidative stress in the ovaries of these patients. The elevated oxidative stress levels were correlated to a higher number of oocytes that could be obtained via the procedure and to a lower amount of FSH needed to mature the oocytes, suggesting that oxidative stress, to some degree, is favourable for hormone stimulation outcome. A high level of lipid peroxidation products in the urine, another marker of oxidative stress, was observed in smokers and this marker was elevated in patients with embryos that had lower developmental potential. A higher overall antioxidant status in blood plasma was advantageous for achieving pregnancy.
    Reproductive biomedicine online 01/2013; · 2.68 Impact Factor
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    ABSTRACT: Background. Vascular endothelial growth factors are important mediators for neovascularization of chronically ischemic adult heart, but their elevated values have also been connected with acute ischemia. Coronary artery bypass grafting (CABG) is associated with activation of inflammatory processes. We aimed to clarify whether the latter is also accompanied with acute changes in concentrations of vascular growth factors. Methods. Concentrations of growth factors VEGF and EGF, monocyte chemoattractant protein-1 (MCP-1), and a set of cytokines of 39 patients with stable coronary artery disease (CAD) were evaluated before and after CABG. Preoperative values were compared with data of healthy volunteers. Results. In comparison with CAD patients, healthy controls had significantly higher values of VEGF (15.5 (10.05-35.3) and 119.4 (55.7-136.9) pg/mL, resp.), EGF (1.70 (1.14-3.18) and 37.3 (27.1-51.9) pg/mL, resp.), and MCP-1 (111.6 (81.75-171.9) and 156.9 (134.7-241.3) pg/mL, resp.). MCP-1, but not others, demonstrated a significant rise throughout the postoperative period. Proinflammatory interleukin-6 was significantly higher and anti-inflammatory IL-4 and IL-10 lower in patients with CAD. Conclusions. Patients with stable CAD have lower serum levels of growth factors than healthy volunteers. MCP-1, but not VEGF and EGF, becomes elevated immediately after CABG. Inflammatory status of CAD patients was drifted towards proinflammatory state.
    BioMed research international. 01/2013; 2013:985404.
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    ABSTRACT: Objective: Previous epidemiological studies together with animal studies have suggested an association between adiponectin, and oxidative stress and inflammation, but community-based studies are lacking. Our objective was to investigate the relative importance of oxidative stress and inflammatory markers, representing different pathways in relation to adiponectin. Design and Methods: In a cross-sectional sample of 929 70-year-old individuals (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors study, relations between serum adiponectin and oxidative stress [conjugated dienes (CD), homocysteine, total antioxidant capacity, oxidized low-density lipoprotein (OxLDL), OxLDL antibodies, baseline CD of LDL, glutathione (GSH), total glutathione (TGSH), glutathione disulfide], circulation interleukins (IL-6, IL-8), other cytokines [tumor necrosis factor α, monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor], cell adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, P-selectin, L-selectin), and systemic inflammatory markers [C-reactive protein (CRP), leukocyte count] in separate models were investigated. Results: In age- and sex-adjusted, as well as multivariable-adjusted models, adiponectin was significantly and positively associated with GSH, log TGSH, whereas an inverse association was observed for CD and log EGF. An inverse association between adiponectin and MCP-1, log E-selectin, and log CRP was significant in age- and sex-adjusted models, but not in multivariable-adjusted models. Conclusions: Our results imply that higher levels of adiponectin are associated with a more beneficial oxidative stress profile, with higher levels of principal anti-oxidative GSH and total GSH together with lower levels of lipid peroxidation, possibly through shared pathways. Further studies are needed to investigate whether changes in the oxidative stress profile may be a mechanism linking adiponectin with type 2 diabetes and/or cardiovascular disease.
    Obesity 10/2012; · 3.92 Impact Factor
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    ABSTRACT: Ischemic preconditioning induces tolerance against ischemia-reperfusion injury prior a sustained ischemic insult. In experimental studies, exposure to hyperoxia for a limited time before ischemia induces a low-grade systemic oxidative stress and evokes an (ischemic) preconditioning-like effect of the myocardium. We hypothesised that pre-treatment by hyperoxia favours enchanced myocardial protection described by decreased release of cTn T in the 1st postoperative morning and reduces the release of inflammatory cytokines. Forty patients with stable coronary artery disease underwent coronary artery bypass grafting with cardiopulmonary bypass. They were ventilated with 40 or >96% oxygen for 60 minutes followed by by 33 (18-59) min normoxia before cardioplegia. In the 1st postoperative morning concentrations of cTnT did not differ between groups ((0.44 (0.26-0.55) ng/mL in control and 0.45 (0.37-0.71) ng/mL in hyperoxia group). Sixty minutes after declamping the aorta, ratios of IL-10/IL-6 (0.73 in controls and 1.47 in hyperoxia, p = 0.03) and IL-10/TNF-α (2.91 and 8.81, resp., p = 0.015) were significantly drifted towards anti-inflammatory, whereas interleukins 6, 8and TNF-α and interferon-γ showed marked postoperative rise, but no intergroup differences were found. Pre-treatment by 60 minutes of hyperoxia did not reduce postoperative leak of cTn T in patients undergoing coronary artery bypass surgery. In the hyperoxia group higher release of anti-inflammatory IL-10 caused drifting of IL-10/IL-6 and IL-10/TNF-α towards anti-inflammatory.
    Journal of Negative Results in BioMedicine 09/2012; 11:14. · 1.47 Impact Factor
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    ABSTRACT: Efficient function of the mitochondrial respiratory chain and the citric acid cycle (CAC) enzymes is required for the maintenance of human brain function. A conception of oxidative stress (OxS) was recently advanced as a disruption of redox signalling and control. Mitochondrial OxS (MOxS) is implicated in the development of Alzheimer's disease (AD). Thus, both pro- and anti-oxidants of the human body and MOxS target primarily the redox-regulated CAC enzymes, like mitochondrial aconitase (MAc). We investigated the specific activity of the MAc and MOxS index (MOSI) in an age-matched control (Co), AD and Swedish Familial AD (SFAD) post-mortem autopsies collected from frontal cortex (FC) and occipital primary cortex (OC) regions of the brain. We also examined whether the mitochondrial neuroprotective signalling molecules glutathione, melatonin and 17-β-estradiol (17βE) and mitochondrially active pro-oxidant neurotoxic amyloid-β peptide can modulate the activity of the MAc isolated from FC and OC regions similarly or differently in the case of Co, AD and SFAD. The activity of redox-sensitive MAc may directly depend on the mitochondrial oxidant/antioxidant balance in age-matched Co, AD and SFAD brain regions.
    Free Radical Research 09/2012; · 3.28 Impact Factor
  • S Kaur, K Zilmer, V Leping, M Zilmer
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    ABSTRACT: Background: Psoriasis vulgaris (PV) is associated with low-grade systemic inflammation. Objective: Cytokines' and growth factors' serum patterns in patients with PV, allergic contact dermatitis (ACD) and healthy subjects were investigated to describe and compare systemic inflammatory responses in these diseases. Methods: A total of 12 inflammation-sensitive biomarkers were analyzed simultaneously by means of the Evidence Investigator™ biochip technology. Results: In PV, proinflammatory tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukins (IL)-1β, -2, -6, -8, and monocyte chemoattractant protein (MCP)-1 were elevated. In ACD, 2 markers, TNF-α and MCP-1, were increased, and regulatory cytokine IL-10 was decreased. Proinflammatory IL-2 had the strongest correlations with other pro- as well as anti-inflammatory cytokines in PV and ACD, whilst IL-6 correlated positively with the Psoriasis Area and Severity Index. Growth factors' levels correlated with MCP-1, but only in PV. Conclusion: Although psoriasis induces a more variegated proinflammatory systemic response, ACD is likewise associated with a systemic increase in inflammatory mediators.
    Dermatology 08/2012; 225(1):54-61. · 2.02 Impact Factor
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    ABSTRACT: Many inflammation parameters are associated with obesity, but few comparable data are found in youth. This study aims to characterize the differences in serum levels of 13 biochemical inflammatory markers between boys with increased BMI and boys with normal BMI, and examine the relationships between inflammation markers, skinfold thicknesses, and body composition. The participants were 38 boys (BMI above 85th percentile) and 38 boys (normal BMI) at the age of 10-11 years. Measurements included BMI, 9 skinfold thicknesses, waist and hip circumferences, and total body and trunk fat mass and percentage as indices of obesity, fasting insulin, glucose, and serum concentrations of IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFN-γ, TNF-α, IL-1α, IL-1β, monocyte chemoattractant protein-1 (MCP-1), epidermal growth factor, and CRP. Overweight boys (OWB) were taller and more frequently in puberty than normal-weight boys (NWB). Skinfold thicknesses and body composition parameters were higher in OWB. They had significantly higher serum IL-6, IL-8, IFN-γ, MCP-1, and CRP values compared to NWB. Six of 13 measured biochemical markers were significantly increased in OWB, indicating that many low-grade inflammatory processes are already involved in the development of obesity in childhood.
    Hormone Research in Paediatrics 07/2012; 78(1):31-9. · 1.55 Impact Factor
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    ABSTRACT: Arterial stiffness is an independent predictor of vascular morbidity and mortality in patients with atherosclerosis. Angiographic score (ASc) reflects severity of atherosclerosis in patients with peripheral arterial disease (PAD). Osteopontin (OPN) and oxidized low-density lipoprotein (oxLDL) are involved in the pathogenesis of atherosclerosis. The aim of the present study was to evaluate the association between arterial stiffness, ASc, serum OPN and oxLDL in patients with symptomatic PAD, and in clinically healthy subjects. We studied 79 men with symptomatic PAD (mean age 64±7 years) and 84 healthy men (mean age 63±8 years). Calculation of the ASc was based on severity and location of atherosclerotic lesions in the arteries of the lower extremities. Aortic pulse wave velocity (aPWV) was evaluated by applanation tonometry using the Sphygmocor device. Serum OPN and oxLDL levels were determined by enzyme-linked immunosorbent assay. The aPWV (10±2.4 VS. 8.4±1.7 (m s(-1)); P<0.001), OPN (75 (62.3-85.8) VS. 54.8 (47.7-67.9) (ng ml(-1)); P<0.001) and oxLDL (67 (52.5-93.5) VS. 47.5 (37-65.5); P<0.001) were different for the patients and for the controls. In multiple regression models, aPWV was independently determined by ASc, log-OPN, log-oxLDL and estimated glomerular filtration rate in the patients (R(2)=0.44; P<0.001) and by log-OPN, log-oxLDL, age and heart rate in the controls (R(2)=0.38; P<0.001). The independent relationship of a PWV with serum levels of OPN and oxLDL in the patients with PAD and in the controls indicates that OPN and oxLDL might influence arterial stiffening in patients with atherosclerosis and in clinically healthy subjects.
    Hypertension Research 06/2012; 35(10):1032-7. · 2.79 Impact Factor
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    ABSTRACT: Arterial hypertension is characterised by increased oxidative stress and inflammation, which are associated with further cardiovascular risk. The aim of our study was to investigate the long-term effects of nebivolol and metoprolol succinate on oxidative stress, and on inflammatory and pro-inflammatory markers in patients with hypertension. Eighty patients with never-treated mild-to-moderate essential hypertension, aged 30-65 years, were randomised to a 5 mg daily dose of nebivolol or a 50-100 mg daily dose of metoprolol succinate. Brachial blood pressure, plasma oxidized LDL (oxLDL), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), fibrinogen, intercellular adhesion molecule-1 (ICAM-1), asymmetric dimethylarginine (ADMA), and urine 8-isoprostane levels were measured before and after 1 year of treatment. Nebivolol and metoprolol reduced equally significantly brachial blood pressure. The oxLDL was significantly reduced in both groups (p < 0.01 and for both drugs), but only nebivolol reduced 8-isoprostanes (p = 0.01). In the metoprolol group, change in oxLDL levels correlated with change in systolic blood pressure (r = 0.45; p < 0.01) and pulse pressure (r = 0.47; p < 0.01). Both metoprolol and nebivolol reduced ICAM-1 (p < 0.01). There was no change in IL-6, hsCRP, fibrinogen, or ADMA levels in either group. These data suggest that in long-term antihypertensive treatment both the cardioselective beta blocker metoprolol succinate and the vasodilating beta blocker nebivolol have inflammation-related effects but only nebivolol has a favourable blood pressure-independent effect on oxidative stress.
    Scandinavian journal of clinical and laboratory investigation 06/2012; 72(5):427-32. · 1.38 Impact Factor
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    ABSTRACT: Diabetes mellitus is associated with micro- and macrovascular complications and increased cardiovascular risk. Elevated levels of serum asymmetric dimethylarginine (ADMA) may be responsible for endothelial dysfunction associated with diabetes-induced vascular impairment. Vitamin D may have potential protective effects against arterial stiffening. This study aimed to examine both the effects of diabetes on the functional/structural properties of the aorta and the endothelial function and the effects of vitamin D supplementation. Male Wistar rats (n = 30) were randomly assigned to control untreated, diabetic untreated, and diabetic + cholecalciferol groups. Diabetes was induced by intraperitoneal injection of streptozotocin, followed by oral administration of cholecalciferol (500 IU/kg) for 10 weeks in the treatment group. Aortic pulse wave velocity (PWV) was recorded over a mean arterial pressure (MAP) range of 50 to 200 mmHg using a dual pressure sensor catheter. Intravenous infusion of phenylephrine and nitroglycerine was used to increase and decrease MAP, respectively. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using a radioimmune assay. ADMA levels in serum were measured by enzyme-linked immunoassay. Aortic samples were collected for histomorphometrical analysis. PWV up to MAP 170 mmHg did not reveal any significant differences between all groups, but in diabetic rats, PWV was significantly elevated across MAP range between 170 and 200 mmHg. Isobaric PWV was similar between the treated and untreated diabetic groups, despite significant differences in the levels of serum 25(OH)D (493 ± 125 nmol/L vs 108 ± 38 nmol/L, respectively). Serum levels of ADMA were similarly increased in the treated and untreated diabetic groups, compared to the control group. The concentration and integrity of the elastic lamellae in the medial layer of the aorta was impaired in untreated diabetic rats and improved by vitamin D supplementation. PWV profile determined under isobaric conditions demonstrated differential effects of uncontrolled diabetes on aortic stiffness. Diabetes was also associated with elevated serum levels of ADMA. Vitamin D supplementation did not improve the functional indices of aortic stiffness or endothelial function, but prevented the fragmentation of elastic fibers in the aortic media.
    Cardiovascular Diabetology 05/2012; 11:58. · 4.21 Impact Factor

Publication Stats

2k Citations
384.26 Total Impact Points


  • 1988–2014
    • University of Tartu
      • • Institute of Biomedicine and Translational Medicine
      • • Department of Cardiology (ARKA)
      • • Faculty of Medicine
      • • Department of Biochemistry (ARBK)
      • • Department of Microbiology (ARMB)
      Dorpat, Tartu County, Estonia
  • 2009–2012
    • North Estonia Medical Centre Foundation
      • Anesthesiology Clinic
      Kolyvan, Harju, Estonia
  • 2003–2008
    • Uppsala University Hospital
      • Department of Hospital School
      Uppsala, Uppsala, Sweden
  • 2005–2007
    • Uppsala University
      • Department of Medical Sciences
      Uppsala, Uppsala, Sweden
    • Tallinn University of Technology
      Kolyvan, Harju, Estonia
  • 1998–2003
    • Karolinska University Hospital
      • Department of Thoracic Surgery
      Tukholma, Stockholm, Sweden
  • 2000
    • Stockholm University
      • Department of Neurochemistry
      Stockholm, Stockholm, Sweden