Mihkel Zilmer

University of Tartu, Dorpat, Tartu, Estonia

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Publications (188)359.18 Total impact

  • Kaspar Tootsi · Aare Märtson · Mihkel Zilmer · Kaido Paapstel · Jaak Kals ·

    Artery Research; 12/2015
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    Kaido Paapstel · Mihkel Zilmer · Jaan Eha · Kaspar Tootsi · Anneli Piir · Jaak Kals ·
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    ABSTRACT: BACKGROUND: Urinary liver-type fatty acid-binding protein (L-FABP) is a promising diagnostic and prognostic biomarker for both acute and chronic kidney injury (1-3). Furthermore, this protein has been shown to possess antioxidant properties and appears to provide a prognostic value for cardiovascular morbidity and mortality in different clinical settings (4-6). The aim of the current study was to evaluate its relationship to inflammation and arterial stiffness in coronary artery disease (CAD) patients without reduced kidney function and in healthy controls. METHODS: We studied 52 patients with CAD (age 63.2 ± 9.2 years) and 41 clinically healthy controls (age 60.1 ± 7.2). Urinary L-FABP, serum adiponectin and resistin levels were measured using the enzyme-linked immunosorbent assay method. The technique of applanation tonometry (Sphygmocor® system) was used for non-invasive pulse wave analysis and pulse wave velocity assessments. All statistical analysis was performed with SPSS software for Windows, version 20.0. RESULTS: Higher carotid-femoral pulse wave velocity (cf-PWV) was observed in the CAD patients as compared to the controls (9.7 ± 2.6 vs. 8.2 ± 1.7 m/s; P=0.003). The two groups also differed in WBC count (6.4 (5.2-7.9) vs. 5.1 (4.7-5.8); P=0.001), adiponectin (5701 ± 2890 vs. 7081 ± 3612; P=0.045) and resistin (3.4 (2.6-4.5) vs. 2.8 (2.4-3.5); P=0.043) levels (Table 1). No significant differences between the study groups were found with respect to markers of renal function and damage (Table 2). However, there was a positive relationship between log L-FABP and cf-PWV (r=0.46, P=0.001, Figure 1) in subjects with CAD, which remained significant after adjustment for potential confounders (Table 3). Log L-FABP also correlated with serum adiponectin levels in the patient group (r=0.35, P=0.015). CONCLUSIONS: We found independent association between urinary L-FABP and aortic stiffness for the CAD patients without 3-5 stage CKD. Because of its antioxidative properties, renal L-FABP appears to play a complex role both in inflammation and in renal damage. Further studies are required to clarify the observed relationship between cf-PWV and this urinary protein.
    Artery 15, Jagiellonian University, Krakow, Poland; 10/2015
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    ABSTRACT: Previous studies showed that a probiotic-rich diet may improve the plasma lipid profile and lower the risk of cardiovascular disease (CVD). In a randomized controlled study we tested the possibility for regulation of plasma lipid profile using a kefir that contained the antioxidative probiotic strain, Lactobacillus fermentum ME-3 (DSM14241). The trial was performed in clinically healthy adults with borderline-high serum low-density lipoprotein-cholesterol (LDL-C) and/or high serum triglyceride (TG) levels based on guidelines from the European Cardiology Society and European Atherosclerosis Society. One hundred sixty four participants meeting the inclusion criteria were included. Participants were randomised to receive 200 ml/day kefir, either with probiotic (PG; n = 71, 58 females, mean age 49.6 ± 6.5 y) or without probiotic (CG; n = 66, 58 females, mean age 49.9 ± 6.1 y). The probiotic contained 4 × 10 7 cfu/ml L. fermentum ME-3 (total 8 × 10 9 cfu/day). At 4 weeks (n = 71 PG and n = 66 CG) and at 8 weeks (n = 43 PG and n = 33 CG), we evaluated anthropologic, blood biochemical indices, and the faecal temporal persistence of the probiotic strain was assessed by real-time PCR. After 4 weeks, the lipid profiles were mostly similar between groups: only the values of oxidised LDL (ox-LDL) and TG were significantly reduced (P < 0.001 and P = 0.005, resp.). After 8 weeks, the PG group exhibited reductions in LDL-C (5 %, P = 0.001), ox-LDL (6 %, P < 0.0002), TG (17 %, P = 0.033). Next, the ratio of LDL-C to HDL-C was decreased only in the PG (P = 0.013) while in the CG it was significantly increased (P = 0.018). After completing the trial the changes in all above listed indices were significantly (P < 0.05) different between the PG and CG groups. In faeces, the prevalence of L. fermentum ME-3 increased after 4 and 8 weeks (both P < 0.001), but the counts, determined with real-time PCR, remained constant. Eight weeks of consuming kefir with the antioxidative probiotic L. fermentum ME-3, reduced serum LDL-C, ox-LDL and TG values in clinically healthy volunteers with borderline-high lipid profile indices. Thus, L. fermentum ME-3 has potential to lower the risk of CVD that is tightly associated with maintenance of plasma lipid profile. This study was registered as current controlled trial http://www.controlled-trials.com/ISRCTN49744186 as ISRCTN49744186.
    10/2015; 1(1):1-27. DOI:10.1186/s40795-015-0020-z
  • K. Paapstel · M. Zilmer · J. Eha · K. Tootsi · A. Piir · J. Kals ·

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    ABSTRACT: Objective: The main goal of the present study was to analyze levels of cytokines of the interleukin family (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8 and IL-10), interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP1), tumor necrosis factor-alpha (TNF-α), and vascular endothelial and endothelial growth factors (VEGF and EGF), in the blood samples of first-episode psychosis (FEP) patients before and seven months after the start of antipsychotic medication use. Method: 38 anti-psychotic medication-naïve FEP patients and 37 healthy controls (HC) were recruited. Biochip array technology was used to measure cytokines and growth factors. Results: The comparison of these markers in FEP patients and HC revealed significantly higher levels of EGF, IL-4 and IL-6 and significantly lower level of IL-1β in FEP patients before the antipsychotic treatment. Multiple regression analysis demonstrated significant correlations between FEP and EGF, IL-1β and smoking. Treatment with antipsychotic drugs resulted in a statistically significant amelioration of the symptoms of psychosis, but caused a significant increase in the body mass index (BMI) of patients. Levels of EGF, IL-2, VEGF, IL-6, IFN-γ, IL-4, IL-8 and IL-1α were significantly lower in treated FEP patients compared to premedication levels. Conclusions: According to the present study, EGF and IL-1β are markers of FEP. Antipsychotic drug treatment resulted in a significant clinical improvement of FEP patients and the suppression of positive symptoms was correlated with the decreased levels of EGF, IL-2 and IL-4. EGF was the strongest marker of FEP and treatment efficiency among the measured cytokines and growth factors.
    Schizophrenia Research 09/2015; DOI:10.1016/j.schres.2015.08.027 · 3.92 Impact Factor
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    ABSTRACT: Arterial stiffness is an independent determinant of cardiovascular risk and a marker of subclinical organ damage. Metabolomics may facilitate identification of novel low-molecular cardiovascular risk factors. The aim of the present study was to compare metabolic signatures and functional-biochemical characteristics of patients with peripheral arterial disease (PAD) and clinically healthy subjects. We studied 42 men with symptomatic PAD (aged 66±7 years) and 46 healthy men (aged 66±8 years). Aortic pulse wave velocity (aPWV) was assessed by applanation tonometry using the Sphygmocor device. Metabolic profiling was performed with high-performance liquid chromatography and mass spectrometry. Serum oxidized low-density lipoprotein (oxLDL) level was measured by enzyme-linked immunosorbent assay. The aPWV as well as serum levels of lactate, free carnitine and 11 amino acids including tyrosine were higher among the patients with PAD. In contrast, serum levels of pyruvate, citrate, α-ketoglutarate, aconitate and cysteine were higher in the control group. In multiple regression models, aPWV was independently determined by log-tyrosine and log-oxLDL in the patients (R(2)=0.61; P<0.001) and by age, log-pyruvate and log-oxLDL in the controls (R(2)=0.52; P<0.001). Our study describes for the first time significant differences in metabolomic signature of patients with advanced atherosclerosis compared with clinically healthy controls. The aPWV is independently associated with serum levels of tyrosine and oxLDL in the patients with PAD and is related to pyruvate and oxLDL levels in the control group. The measurement of low-molecular metabolites, which are related to changes in vascular phenotypes, may lead to identification of novel vascular risk markers.Hypertension Research advance online publication, 2 July 2015; doi:10.1038/hr.2015.71.
    Hypertension Research 07/2015; 8(4). DOI:10.1038/hr.2015.71 · 2.66 Impact Factor
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    ABSTRACT: Juvenile idiopathic arthritis (JIA) is a frequent childhood rheumatic disease characterized by chronic inflammation. The latter has been related to impairment of arterial functional-structural properties, atherogenesis and later cardiovascular events. The objective of this study was to examine intima-media thickness (IMT) and the parameters of arterial stiffness in children with JIA at diagnosis and their correlation with JIA subtype and markers of inflammation and atherosclerosis. Thirty-nine newly diagnosed patients with JIA (26 girls; mean age, 13.2 ± 2.6 years) and 27 healthy controls (9 girls; mean age, 13.6 ± 3.4 years) were included in the study. Twelve patients had oligoarthritis, fifteen had extended oligoarthritis and twelve had rheumatoid factor-negative polyarthritis. IMT of the common carotid artery was determined by ultrasonography, carotid-femoral pulse wave velocity (cfPWV) and augmentation index adjusted to a heart rate of 75 beats/min (AIx@75) were determined by applanation tonometry. The serum levels of atherosclerosis-related biomarkers, such as asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and adiponectin, were measured by enzyme-linked immunosorbent assay. Mean IMT (0.46 ± 0.04 vs. 0.42 ± 0.04 mm; p = 0.0003) and MPO concentration (115.2 [95 % confidence interval {95 % CI}, 97.4-136.3] vs. 57.6 [95 % CI, 47.1-70.3] ng/ml; p < 0.0001) were higher in the patients with JIA than in the control subjects. The cfPWV, AIx@75 and serum ADMA and adiponectin levels did not significantly differ between the groups and JIA subtypes. Serum adiponectin level correlated negatively with AIx@75 in patients with JIA (r = -0.38; p < 0.05). Patients with JIA have increased mean IMT and elevated MPO levels at early stages of the disease. AIx@75 was inversely independently associated with adiponectin level in the patients, suggesting that lower adiponectin levels might influence arterial subclinical stiffening in patients with newly diagnosed JIA.
    Arthritis research & therapy 07/2015; 17(1):180. DOI:10.1186/s13075-015-0699-x · 3.75 Impact Factor
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    M. Zagura · J. Kals · K. Kilk · K. Paapstel · M. Serg · P. Kampus · J. Eha · U. Soomets · M. Zilmer ·
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    ABSTRACT: Background: Arterial stiffness is an independent determinant of cardiovascular risk. Metabolomics is the comprehensive analysis of low-molecular-weight metabolites, which could provide additional information regarding the pathogenesis of atherosclerosis. The aim of the current study was to compare metabolic signatures and functional-biochemical characteristics of patients with peripheral arterial disease (PAD) and clinically healthy subjects. Methods: We studied 42 men with symptomatic PAD (66±7 years) and 46 healthy men (66±8 years). Aortic pulse wave velocity (aPWV) was assessed by applanation tonometry using the Sphygmocor device. Metabolic profiling was performed with high-performance liquid chromatography and mass-spectrometry. Serum oxLDL level was measured by ELISA. Results: The aPWV as well as serum levels of lactate, free carnitine and 11 amino acids including tyrosine were higher among the patients with PAD. The aPWV correlated significantly with severeal amino acids: log-phenylalanine, log-tyrosine and log-serine for the patients with PAD. In the control group, aortic PWV was correlated to log-pyruvate. In multiple regression models, aPWV was independently determined by log-tyrosine and log-oxLDL in the patients (R2=0.61; p<0.001) and by age, log-pyruvate and log-oxLDL in the controls (R2=0.52; p<0.001). Conclusion: Metabolomic signature of patients with advanced atherosclerosis differs compared to clinically healthy controls. The aPWV is independently associated with serum levels of Tyr and oxLDL in the patients with PAD and is related to pyruvate and oxLDL levels in the control group. The measurement of low-molecular metabolites, which are related to changes in vascular phenotypes, may lead to identification of novel vascular risk markers.
    Atherosclerosis; 07/2015
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    ABSTRACT: Mutations in the WFS1 gene, which encodes the endoplasmic reticulum (ER) glycoprotein, cause Wolfram syndrome, a disease characterized by juvenile-onset diabetes mellitus, optic atrophy, deafness, and different psychiatric abnormalities. Loss of neuronal cells and pancreatic β-cells in Wolfram syndrome patients is probably related to the dysfunction of ER stress regulation, which leads to cell apoptosis. The present study shows that Wfs1-deficient mice have brain-region-specific changes in Na(+) ,K(+) -ATPase activity and in the expression of the α1 and β1 subunits. We found a significant (1.6-fold) increase of Na-pump activity and β1 subunit mRNA expression in mice lacking the Wfs1 gene in the temporal lobe compared with their wild-type littermates. By contrast, exposure of mice to the elevated plus maze (EPM) model of anxiety decreased Na-pump activity 1.3-fold in the midbrain and dorsal striatum and 2.0-fold in the ventral striatum of homozygous animals compared with the nonexposed group. Na-pump α1 -subunit mRNA was significantly decreased in the dorsal striatum and midbrain of Wfs1-deficient homozygous animals compared with wild-type littermates. In the temporal lobe, an increase in the activity of the Na-pump is probably related to increased anxiety established in Wfs1-deficient mice, whereas the blunted dopamine function in the forebrain of Wfs1-deficient mice may be associated with a decrease of Na-pump activity in the dorsal and ventral striatum and in the midbrain after exposure to the EPM. © 2014 Wiley Periodicals, Inc.
    Journal of Neuroscience Research 03/2015; 93(3). DOI:10.1002/jnr.23508 · 2.59 Impact Factor
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    ABSTRACT: Lactobacillus fermentum ME-3 (LfME-3) has been proven to synthesize and secrete glutathione. A regular use of the foods fermented by it has shown a favourable influence on human lipid profiles and several antioxidant parameters. We administered the LfME-3-fermented kefir for 14 days to 43 human subjects and evaluated their serum with MALDI-TOF mass spectrometer at the beginning and end of the test period. We found an increase of the peak at m/z 308 (corresponding to glutathione) and a new peak at m/z 1467.
    01/2015; 10(1). DOI:10.1515/biol-2015-0021
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    K. Paapstel · M. Zilmer · J. Eha · J. Kals ·
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    ABSTRACT: Introduction: Contrast-induced nephropathy (CIN) is widely recognized as the third most common type of hospital-acquired acute kidney injury. Despite the impact of CIN on adverse cardiovascular events, little is known about the effects of contrast media on arterial functional properties. However, much emphasis has been placed on seeking novel biomarkers that enable earlier identification of patients at higher risk for CIN. The objective of this study was to evaluate effects on central hemodynamics, arterial stiffness as well as changes in biomarkers of inflammation and kidney injury after contrast media administration. Methods: The cohort comprised 36 symptomatic peripheral arterial disease (PAD) patients with GFR ≥ 60ml/min/1.73² undergoing a lower extremities digital subtraction angiography (DSA) with intra-arterial iso-osmolar iodinated contrast media. Central hemodynamics and arterial stiffness parameters were determined by applanation tonometry (on admission, 8h, 24h after DSA). Serum samples (on admission, 2h, 8h, 24h after DSA) and urine samples (on admission, 24h after DSA) were collected. All samples underwent ELISA testing for biomarkers. Statistically significant differences were calculated by one-way ANOVA and paired t-test. Results: Augmentation pressure (AP) decreased and pulse pressure amplification (pPP/cPP) increased significantly (p=0.01 ; p=0.02, respectively) compared to baseline, but there were no changes in augmentation index (AIx) and aortic pulse wave velocity (aPWV). Increase in the levels of serum neutrophil gelatinase lipocalin (sNGAL, p=0.00003), urinary kidney injury molecule-1 (uKIM-1, p=0.02), beta-2 microglobulin (B2M, p=0.03), high-sensitivity CRP (hsCRP, p=0.001), myeloperoxidase (MPO, p=0.01) and interleukin-6 (IL-6, p=0.001) were observed compared to baseline. Conclusions: To our knowledge, this is the first clinical study to evaluate the complex effects of contrast media on arterial stiffness, central hemodynamics and several biomarkers. The results suggest that in PAD patients without impaired renal function contrast media may induce acute inflammation, moderate tubular injury and changes in central hemodynamics.
    Artery Research; 12/2014
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    ABSTRACT: Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.
    PLoS Genetics 12/2014; 10(12):e1004801. DOI:10.1371/journal.pgen.1004801 · 7.53 Impact Factor
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    ABSTRACT: AIMS: Estimated central systolic blood pressure (cSBP) and amplification (Brachial SBP-cSBP) are non-invasive measures potentially prognostic of cardiovascular (CV) disease. No worldwide, multiple-device reference values are available. We aimed to establish reference values for a worldwide general population standardizing between the different available methods of measurement. How these values were significantly altered by cardiovascular risk factors (CVRFs) was then investigated. METHODS AND RESULTS: Existing data from population surveys and clinical trials were combined, whether published or not. Reference values of cSBP and amplification were calculated as percentiles for 'Normal' (no CVRFs) and 'Reference' (any CVRFs) populations. We included 45,436 subjects out of 82,930 that were gathered from 77 studies of 53 centres. Included subjects were apparently healthy, not treated for hypertension or dyslipidaemia, and free from overt CV disease and diabetes. Values of cSBP and amplification were stratified by brachial blood pressure categories and age decade in turn, both being stratified by sex. Amplification decreased with age and more so in males than in females. Sex was the most powerful factor associated with amplification with 6.6 mmHg (5.8-7.4) higher amplification in males than in females. Amplification was marginally but significantly influenced by CVRFs, with smoking and dyslipidaemia decreasing amplification, but increased with increasing levels of blood glucose. CONCLUSION: Typical values of cSBP and amplification in a healthy population and a population free of traditional CVRFs are now available according to age, sex, and brachial BP, providing values included from different devices with a wide geographical representation. Amplification is significantly influenced by CVRFs, but differently in men and women.
    European Heart Journal 11/2014; 35(44):3122-33. · 15.20 Impact Factor
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    ABSTRACT: Background: Essential hypertension is characterised by alterations in haemodynamics. Hence haemodynamic profiling could lead to improved blood pressure (BP) control in these patients. We tested if baseline haemodynamic indices predict the BP lowering effects of different classes of antihypertensive drugs in hypertensive patients. Methods: In this double-blind placebo-controlled crossover study we randomised 53 hypertensive patients to receive doxazosin 4mg, candesartan 16mg, bisoprolol 5mg, isosorbide mononitrate (ISMN) 50mg, and placebo daily for 6 weeks. Brachial and central BP, augmentation index (AIx), aortic pulse wave velocity (aPWV), stroke volume (SV), cardiac output (CO), peripheral vascular resistance (PVR), and pulse pressure amplification (PPA) were measured at baseline and after each drug. Results: Baseline AIx and PPA determined BP reduction with antihypertensive therapy, particularly with bisoprolol. In patients with low baseline AIx (1.7-28.9%) and high PPA (1.22-1.87), bisoprolol had a weak antihypertensive effect, while the opposite was observed in patients with high AIx (36.3-48.2%) and low PPA (1.05-1.11). With candesartan, BP reduction was the largest, regardless of baseline AIx or PPA levels. Conclusions: Our study suggests that ARBs reduce BP the most irrespective of the underlying haemodynamic profile. Antihypertensive therapy guided by AIx and PPA may have some merit in the guidance of antihypertensive drug treatment, particularly if beta-blockers are considered for treatment. However, larger studies are needed to confirm these results. Clinical Trials Registry number: EudraCT 2006-006981-40. © 2014 Association for Research into Arterial Structure and Physiology.
    Artery Research 09/2014; 8(4). DOI:10.1016/j.artres.2014.07.004
  • J. Kals · J. Lieberg · P. Kampus · M. Zagura · J. Eha · M. Zilmer ·
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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.
    Journal of Vascular Surgery 09/2014; 48(3). DOI:10.1016/j.ejvs.2014.05.018 · 3.02 Impact Factor
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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 08/2014; 2014:415638. DOI:10.1155/2014/415638
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    ABSTRACT: Background 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. Methods Diabetes was induced by streptozotocin (STZ) (65 mg/kg) in male Wistar rats. One diabetic group was treated for 10 weeks with telmisartan (10 mg/kg/day p/o). Pressure-independent aortic pulse wave velocity (PWV) was measured under anaesthesia after intravenous infusion of phenylephrine and nitroglycerine. Aortic wall samples were collected for histomorphometrical analysis. Results Untreated diabetes imposed differential effects on aortic stiffening, as demonstrated by increased isobaric PWV over a range of high blood pressures, but not at lower blood pressures. This was associated with loss and disruption of elastin fibres and an increase in collagen fibres in the aortic media. Treatment with telmisartan decreased resting blood pressure, reduced aortic stiffness, and partially prevented the degradation of elastin network within the aortic wall. Conclusions Telmisartan improved the structural and functional indices of aortic stiffening induced by untreated STZ-diabetes, demonstrating the importance of ARBs in the therapeutic approach to diabetic vascular complications.
    Diabetology and Metabolic Syndrome 05/2014; 6(1):57. DOI:10.1186/1758-5996-6-57 · 2.17 Impact Factor
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    Triin Kaldur · Jaak Kals · Vahur Oöpik · Mihkel Zilmer · Kersti Zilmer · Jaan Eha · Eve Unt ·
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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 μmol/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 μmol/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 05/2014; 2014:107137. DOI:10.1155/2014/107137 · 3.36 Impact Factor
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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. DOI:10.1007/s40618-013-0029-6 · 1.45 Impact Factor
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    C Kairane · R Mahlapuu · K Ehrlich · M Zilmer · U Soomets ·
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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; 11(1). DOI:10.2174/15672050113106660179 · 3.89 Impact Factor

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3k Citations
359.18 Total Impact Points


  • 1994-2015
    • University of Tartu
      • • Institute of Biomedicine and Translational Medicine
      • • Department of Biochemistry (ARBK)
      • • Institute of Chemistry
      • • Faculty of Medicine
      Dorpat, Tartu, Estonia
  • 2007
    • University of Kuopio
      Kuopio, Northern Savo, Finland
  • 2001-2003
    • Uppsala University Hospital
      Uppsala, Uppsala, Sweden
  • 2000-2003
    • Karolinska University Hospital
      • Department of Thoracic Surgery
      Tukholma, Stockholm, Sweden
  • 1997
    • University of Ljubljana
      • Division of Biochemistry
      Lubliano, Ljubljana, Slovenia