Publications by authors named "Thomas Pekar"

10 Publications

  • Page 1 of 1

Rubella and tick-borne encephalitis vaccination rates among staff and students at Austrian University of Applied Sciences.

Cent Eur J Public Health 2021 Mar;29(1):18-22

University of Applied Sciences Wiener Neustadt, Wiener Neustadt, Austria.

Objectives: Rubella and tick-borne encephalitis (TBE) are infectious diseases caused by viruses. Rubella is an air-borne infection. TBE, on the other hand, is transmitted by virus-infected ticks. Both diseases show specific symptoms after an incubation period of approximately 10 days. The Austrian vaccination plan recommends vaccinations against both viruses, as only these can protect against both infectious diseases. Because of both, an increase in measles infections and the high endemic rate of TBE in Austria, our goal was to evaluate the vaccination rate, antibody titre and general level of knowledge with respect to these two infections amongst adults in order to identify possible nescience regarding booster vaccination and general titre rates.

Methods: One hundred ninety-nine people participated in the study of the TBE and rubella titre determination. We used indirect ELISA and asked the volunteers to complete a questionnaire.

Results: The analysis of the results showed a vaccination coverage rate of over 90% for both diseases.

Conclusion: Our findings lead to the conclusion that the protection through immunization is very high and the vaccines used are extremely effective, particularly as some individuals do not adhere to the recommended vaccination schedule.
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http://dx.doi.org/10.21101/cejph.a6014DOI Listing
March 2021

The positive effect of spermidine in older adults suffering from dementia : First results of a 3-month trial.

Wien Klin Wochenschr 2021 May 19;133(9-10):484-491. Epub 2020 Nov 19.

FAZ Floridsdorfer Allergiezentrum, Pius-Parsch-Platz 1/3, 1210, Vienna, Austria.

The worldwide prevalence of dementia is estimated at 35.6 million and will rise to 115 million by 2050. There is therefore an urgent need for well-founded dementia diagnostics and well-researched therapeutic options. Previous studies have highlighted that spermidine has the ability to trigger the important process of dissolving amyloid-beta plaques by autophagy. They also confirmed that nutritional intervention with the natural polyamine spermidine can prevent memory loss in aging model organisms. This multicentric double-blind preliminary study focused on the effect of oral spermidine supplementation on older adults' cognitive performance. Memory tests were carried out on 85 subjects aged between 60 and 96 years in 6 nursing homes in Styria. Blood samples were taken for the determination of spermidine concentration and measurement of metabolic parameters. The results demonstrated a clear correlation between the intake of spermidine and the improvement in cognitive performance in subjects with mild and moderate dementia in the group treated with the higher spermidine dosage. The most substantial improvement in test performance was found in the group of subjects with mild dementia with an increase of 2.23 points (p = 0.026) in the mini mental state examination (MMSE) and 1.99 (p = 0.47) in phonematic fluidity. By comparison, the group which had a lower spermidine intake showed consistent or declining cognitive performance.
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http://dx.doi.org/10.1007/s00508-020-01758-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116233PMC
May 2021

Brain Distribution of Dual ABCB1/ABCG2 Substrates Is Unaltered in a Beta-Amyloidosis Mouse Model.

Int J Mol Sci 2020 Nov 3;21(21). Epub 2020 Nov 3.

Preclinical Molecular Imaging, AIT Austrian Institute of Technology GmbH, 2444 Seibersdorf, Austria.

Background: ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) are co-localized at the blood-brain barrier (BBB), where they restrict the brain distribution of many different drugs. Moreover, ABCB1 and possibly ABCG2 play a role in Alzheimer's disease (AD) by mediating the brain clearance of beta-amyloid (Aβ) across the BBB. This study aimed to compare the abundance and activity of ABCG2 in a commonly used β-amyloidosis mouse model (APP/PS1-21) with age-matched wild-type mice.

Methods: The abundance of ABCG2 was assessed by semi-quantitative immunohistochemical analysis of brain slices of APP/PS1-21 and wild-type mice aged 6 months. Moreover, the brain distribution of two dual ABCB1/ABCG2 substrate radiotracers ([C]tariquidar and [C]erlotinib) was assessed in APP/PS1-21 and wild-type mice with positron emission tomography (PET). [C]Tariquidar PET scans were performed without and with partial inhibition of ABCG2 with Ko143, while [C]erlotinib PET scans were only performed under baseline conditions.

Results: Immunohistochemical analysis revealed a significant reduction (by 29-37%) in the number of ABCG2-stained microvessels in the brains of APP/PS1-21 mice. Partial ABCG2 inhibition significantly increased the brain distribution of [C]tariquidar in APP/PS1-21 and wild-type mice, but the brain distribution of [C]tariquidar did not differ under both conditions between the two mouse strains. Similar results were obtained with [C]erlotinib.

Conclusions: Despite a reduction in the abundance of cerebral ABCG2 and ABCB1 in APP/PS1-21 mice, the brain distribution of two dual ABCB1/ABCG2 substrates was unaltered. Our results suggest that the brain distribution of clinically used ABCB1/ABCG2 substrate drugs may not differ between AD patients and healthy people.
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http://dx.doi.org/10.3390/ijms21218245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663372PMC
November 2020

Spermidine in dementia : Relation to age and memory performance.

Wien Klin Wochenschr 2020 Jan 12;132(1-2):42-46. Epub 2019 Dec 12.

FAZ Floridsdorfer Allergiezentrum, Pius-Parsch-Platz 1/3, 1210, Vienna, Austria.

Previous studies have highlighted that spermidine has the ability to trigger the important process of dissolving amyloid-beta plaques by autophagy. This manuscript focuses on the correlation of serum spermidine levels between age and between performance in mini-mental state examinations. It will serve as a premise for an ongoing multicentric placebo-controlled study, which focuses on the effect of oral spermidine supplementation on memory performance. Memory tests were carried out on 80 subjects aged 60-96 years old in 6 nursing homes in Styria. Blood samples were taken for the determination of spermidine concentration. The results showed a significant correlation between the spermidine concentration and the mini-mental state examination score (p = 0.025). On the basis of the dependence demonstrated it can be concluded that spermidine might be suitable as a biomarker for the diagnosis of neurocognitive changes (senile dementia or Alzheimer's disease).
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http://dx.doi.org/10.1007/s00508-019-01588-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978435PMC
January 2020

Protein measurements in venous plasma, earlobe capillary plasma and in plasma stored on filter paper.

Anal Biochem 2019 02 22;566:146-150. Epub 2018 Nov 22.

Department of Behavioural Biology, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria.

In this study, levels of inflammatory protein biomarkers in venous plasma, plasma derived from capillary blood from the earlobe, and capillary plasma stored as dried plasma spots (DPS) were compared. Samples from 12 male individuals were assessed with a panel of 92 inflammation-related proteins using multiplex proximity extension assay. Correlations between sample types varied greatly between analytes. A high correlation of ρ > 0.8 was observed between capillary plasma and DPS for 32 analytes. At this level of correlation, 13 analytes correlated between venous and capillary plasma and 5 analytes in the comparison of venous blood with DPS.
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http://dx.doi.org/10.1016/j.ab.2018.11.016DOI Listing
February 2019

Age dependency of cerebral P-glycoprotein function in wild-type and APPPS1 mice measured with PET.

J Cereb Blood Flow Metab 2020 01 24;40(1):150-162. Epub 2018 Oct 24.

Center for Health & Bioresources, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.

P-glycoprotein (P-gp, ABCB1) is an efflux transporter at the blood-brain barrier (BBB), which mediates clearance of beta-amyloid (Aβ) from brain into blood. We used ()-[C]verapamil PET in combination with partial P-gp inhibition with tariquidar to measure cerebral P-gp function in a beta-amyloidosis mouse model (APPtg) and in control mice at three different ages (50, 200 and 380 days). Following tariquidar pre-treatment (4 mg/kg), whole brain-to-plasma radioactivity concentration ratios () were significantly higher in APPtg than in wild-type mice aged 50 days, pointing to decreased cerebral P-gp function. Moreover, we found an age-dependent decrease in cerebral P-gp function in both wild-type and APPtg mice of up to -50%. Alterations in P-gp function were more pronounced in Aβ-rich brain regions (hippocampus, cortex) than in a control region with negligible Aβ load (cerebellum). PET results were confirmed by immunohistochemical staining of P-gp in brain microvessels. Our results confirm previous findings of reduced P-gp function in Alzheimer's disease mouse models and show that our PET protocol possesses adequate sensitivity to measure these functional changes in vivo. Our PET protocol may find use in clinical studies to test the efficacy of drugs to induce P-gp function at the human BBB to enhance Aβ clearance.
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http://dx.doi.org/10.1177/0271678X18806640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928546PMC
January 2020

Lipocalin-2 as an Infection-Related Biomarker to Predict Clinical Outcome in Ischemic Stroke.

PLoS One 2016 6;11(5):e0154797. Epub 2016 May 6.

Department of Neurology, Medical University of Graz, Graz, Austria.

Objectives: From previous data in animal models of cerebral ischemia, lipocalin-2 (LCN2), a protein related to neutrophil function and cellular iron homeostasis, is supposed to have a value as a biomarker in ischemic stroke patients. Therefore, we examined LCN2 expression in the ischemic brain in an animal model and measured plasma levels of LCN2 in ischemic stroke patients.

Methods: In the mouse model of transient middle cerebral artery occlusion (tMCAO), LCN2 expression in the brain was analyzed by immunohistochemistry and correlated to cellular nonheme iron deposition up to 42 days after tMCAO. In human stroke patients, plasma levels of LCN2 were determined one week after ischemic stroke. In addition to established predictive parameters such as age, National Institutes of Health Stroke Scale and thrombolytic therapy, LCN2 was included into linear logistic regression modeling to predict clinical outcome at 90 days after stroke.

Results: Immunohistochemistry revealed expression of LCN2 in the mouse brain already at one day following tMCAO, and the amount of LCN2 subsequently increased with a maximum at 2 weeks after tMCAO. Accumulation of cellular nonheme iron was detectable one week post tMCAO and continued to increase. In ischemic stroke patients, higher plasma levels of LCN2 were associated with a worse clinical outcome at 90 days and with the occurrence of post-stroke infections.

Conclusions: LCN2 is expressed in the ischemic brain after temporary experimental ischemia and paralleled by the accumulation of cellular nonheme iron. Plasma levels of LCN2 measured in patients one week after ischemic stroke contribute to the prediction of clinical outcome at 90 days and reflect the systemic response to post-stroke infections.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154797PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859492PMC
July 2017

Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat.

PLoS One 2014 20;9(1):e85393. Epub 2014 Jan 20.

University of Glasgow, Institute of Infection, Immunity and Inflammation, Glasgow, United Kingdom.

Unlabelled: Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum.

Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody.

Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085393PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896359PMC
December 2014

Plasma midregional pro-adrenomedullin improves prediction of functional outcome in ischemic stroke.

PLoS One 2013 22;8(7):e68768. Epub 2013 Jul 22.

Department of Neurology, Medical University of Graz, Graz, Austria.

Background: To evaluate if plasma levels of midregional pro-adrenomedullin (MR-proADM) improve prediction of functional outcome in ischemic stroke.

Methods: In 168 consecutive ischemic stroke patients, plasma levels of MR-proADM were measured within 24 hours from symptom onset. Functional outcome was assessed by the modified Rankin Scale (mRS) at 90 days following stroke. Logistic regression, receiver operating characteristics (ROC) curve analysis, net reclassification improvement (NRI), and Kaplan-Meier survival analysis were applied.

Results: Plasma MR-proADM levels were found significantly higher in patients with unfavourable (mRS 3-6) compared to favourable (mRS 0-2) outcomes. MR-proADM levels were entered into a predictive model including the patients' age, National Institutes of Health Stroke Scale (NIHSS), and the use of recanalization therapy. The area under the ROC curve did not increase significantly. However, category-free NRI of 0.577 (p<0.001) indicated a significant improvement in reclassification of patients. Furthermore, MR-proADM levels significantly improved reclassification of patients in the prediction of outcome by the Stroke Prognostication using Age and NIHSS-100 (SPAN-100; NRI = 0.175; p = 0.04). Kaplan-Meier survival analysis showed a rising risk of death with increasing MR-proADM quintiles.

Conclusions: Plasma MR-proADM levels improve prediction of functional outcome in ischemic stroke when added to the patients' age, NIHSS on admission, and the use of recanalization therapy. Levels of MR-proADM in peripheral blood improve reclassification of patients when the SPAN-100 is used to predict the patients' functional outcome.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0068768PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718829PMC
February 2014

Circulating Dickkopf-1 in acute ischemic stroke and clinically stable cerebrovascular disease.

Atherosclerosis 2011 Sep 23;218(1):233-7. Epub 2011 May 23.

Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria.

Objectives: Previous data suggest that Dickkopf-1 (Dkk-1), an inhibitor of the canonical/β-catenin cascade of the Wnt pathway, is upregulated in carotid atherosclerosis and acute myocardial ischemia. It is currently unclear if such upregulation also occurs in cerebral ischemia.

Methods: We measured plasma levels of Dkk-1 in patients with acute ischemic stroke (n=57) within 24h from symptom onset, in patients with clinically stable cerebrovascular disease (n=29) and in healthy controls (n=29). Stroke severity on admission was determined by the National Institutes of Stroke Scale (NIHSS). The modified Rankin Scale (mRS) served to define outcome at day 90. Ischemic stroke subtype and cause was determined by the Oxfordshire Community Stroke Project (OCSP) criteria and the Causative Classification of Stroke System (CCS).

Results: Dkk-1 plasma levels were significantly higher in acute stroke patients (median 727.1 pg/ml) as compared to patients with stable cerebrovascular disease (median 534.2 pg/ml; p=0.017) or healthy controls (median 371.3 pg/ml; p<0.001). The difference of Dkk-1 levels between patients with stable cerebrovascular disease and healthy controls was also significant (p=0.005). No significant differences in Dkk-1 plasma levels were found between different causes or subtypes of ischemic stroke. No correlation of Dkk-1 levels was found with stroke severity on admission and outcome at day 90.

Conclusion: Our study provides for the first time evidence for a release of Dkk-1 into the circulation in patients with acute ischemic stroke and also in patients with clinically stable cerebrovascular disease.
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http://dx.doi.org/10.1016/j.atherosclerosis.2011.05.015DOI Listing
September 2011