Search

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two efflux transporters which are expressed in the apical (i.e. airway lumen-facing) membranes of lung epithelial cells. To assess the influence of P-gp and BCRP on the pulmonary disposition of inhaled drugs, we performed positron emission tomography (PET) imaging in rats after intratracheal aerosolization of two model P-gp/BCRP substrate radiotracers (i.e. [

Several drugs approved for inhalation for the treatment of pulmonary diseases are substrates of the adenosine triphosphate-binding cassette (ABC) transporter P-glycoprotein (P-gp). P-gp is expressed in the apical membrane of pulmonary epithelial cells and could play a role in modulating the pulmonary absorption and distribution of inhaled drugs, thereby potentially contributing to variability in therapeutic response and/or systemic side effects. We developed a new in vivo experimental approach to assess the functional impact of P-gp on the pulmonary delivery of inhaled drugs in rats. By using positron emission tomography (PET) imaging, we measured the intrapulmonary pharmacokinetics of the model P-gp substrates (R)-[

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged at the end of 2019, causing the coronavirus disease (COVID-19). The main sources of infections are infected and asymptomatic persons. One major problem of the pandemic are the diverse symptoms and the varying manifestations of the illness. In this study, the IgG level recognizing the RBD of SARS-CoV-2 was determined within 336 volunteers from the environment of the University of Applied Sciences Wiener Neustadt. The aims of this study were to identify the estimated number of undiscovered COVID-19 infections and the corresponding antibody levels. In total, 11.3% of the nonvaccinated probands had a positive IgG antibody titer against SARS-CoV-2, whereas 4.0% did not test positive for SARS-CoV-2 or had never been tested at the time of sampling. Probands in this study reported tiredness (57,5%), ageusia/anosmia (55%) and headache (47,5%) as most frequent symptoms.

Es ist bekannt, dass es in Deutschland nach der Kriegsniederlage 1918 einflussreiche Kreise in Militär, Wirtschaft, Gesellschaft und Politik gab, die an einer Strategie arbeiteten1, die aus dieser Niederlage Lehren ziehen sollte, um in einem zukünftigen Krieg siegreich sein zu können2 – ein amerikanischer Militärstratege hat das treffend ,,Preparing for the War of the Future in the Wake of Defeat“3 genannt, also den Krieg der Zukunft im Aufschwung der Niederlage vorbereiten.4 Dieser zukünftige Krieg wurde als ein ,totaler‘ konzipiert5, obwohl sich der Erste Weltkrieg in seiner Endphase schon ,,in Richtung des totalen Krieges entwickelt“6 hatte.

SummaryPrevious 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).

Thomas Manns Mythos-Verstandnis, welches fur seine Roman-Tetralogie Joseph und seine Bruder (1933-1943) grundlegend ist, wird in diesem Aufsatz als Gegenentwurf zum faschistischen Einheitsmythos von Volk und Rasse verstanden. Dieser faschistische Mythos wurde vor allem von Alfred Baeumler (1926) entworfen und spater von Alfred Rosenberg in dem Standardwerk der NS-Ideologie, Der Mythus des 20. Jahrhunderts (1930), ausgefuhrt. Auf diese beiden Ideologen bezieht sich Thomas Mann explizit und kritisch. Der Schriftsteller und Begrunder der Paneuropa-Union, Richard Nikolaus Graf Coudenhove-Kalergi (1894-1972), dem Thomas Mann 1926, als er gerade mit der Konzeption und anfanglichen Niederschrift seines Josephsromans beschaftigt war, in Paris erstmalig begegnete, bedeutete, so meine These, eine Verkorperung seines hybriden, anti-faschistischen Mythos-Verstandnisses, welches zudem von einer erotischen Faszination gespeist war. Damit sind die beiden grundlegenden Prinzipien, Hybridisierung und Erotisierung, genannt, die fur Thomas Manns Mythos-Verstandnis und damit fur seinen Josephsroman als grundlegend angesehen werden.

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&rsquo, s disease (AD) by mediating the brain clearance of beta-amyloid (A&beta, ) across the BBB. This study aimed to compare the abundance and activity of ABCG2 in a commonly used &beta, 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 ([11C]tariquidar and [11C]erlotinib) was assessed in APP/PS1-21 and wild-type mice with positron emission tomography (PET). [11C]Tariquidar PET scans were performed without and with partial inhibition of ABCG2 with Ko143, while [11C]erlotinib PET scans were only performed under baseline conditions. Results: Immunohistochemical analysis revealed a significant reduction (by 29&ndash, 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 [11C]tariquidar in APP/PS1-21 and wild-type mice, but the brain distribution of [11C]tariquidar did not differ under both conditions between the two mouse strains. Similar results were obtained with [11C]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.

Asian German Studies“ haben sich seit etwa 2006 als interdisziplinäre Forschung etabliert1, um besonders den asiatischen Einfluss auf die Literatur- und Kulturentwicklung in den deutschsprachigen Ländern2, die Repräsentationen Asiens (vor allem Ostasiens) in der deutschen Gesellschaft und Kultur und die wechselseitigen (,,transnationalen“)3 Kulturkontakte und Durchdringungen in Hinsicht auf eine globale bzw. transkulturelle Geschichtsschreibung zu erforschen.4 Asian German Studies erheben den Anspruch, eine ganz neue Disziplin zu sein.5 Dies mag partiell berechtigt sein, beispielsweise in Hinsicht auf die Erforschung konkreter kultureller Kontaktzonen6, verkennt bzw. ignoriert in wesentlichen Teilen aber die Forschungen, die in umfangreicher Weise seit den 1970er Jahren in diesem Feld der asiatisch-westlichen Literatur- und Kulturkontakte geleistet worden sind. Es soll an dieser Stelle keine systematische Vorgeschichte der Asian German Studies gegeben werden7 (die gleichwohl noch aussteht), sondern lediglich festgestellt sein, dass es insbesondere die Exilforschung war, die spätestens seit den 1980er Jahren diese europäisch-asiatischen Kulturverflechtungen in den Blick nahmen, jedenfalls soweit sie mit Flüchtlingen aus Nazi-Deutschland bzw. den von Deutschland im Zweiten Weltkrieg besetzten Gebieten in Europa, die sich in das asiatische Exil retten konnten, zu tun haben.

Das Rahmenthema LV des Jahrbuchs für internationale Germanistik, ,,Deutsch-Japanische Komparatistik im weltkulturellen Kontext“, ergänzt die laufenden Rahmenthemen XLII: ,,Deutsch-französische Literaturbeziehungen“, XLIII: ,,Deutsch-italienische Literaturbeziehungen“, XLIX: ,,Von Spanien nach Deutschland und umgekehrt: Transkulturelle Beziehungen im 18. Jahrhundert“, L: ,,Deutsch-chinesische Literaturbeziehungen“ und LVI: ,,Deutsch-polnische Literaturbeziehungen“. Das neue Rahmenthema geht auf den 2. Deutsch-Asiatischen Studientag Literaturwissenschaft zurück, der am 2. November 2016 unter dem Titel ,,Deutsch-Japanische Komparatistik im weltkulturellen Kontext“ an der Friedrich Schlegel Graduiertenschule für literaturwissenschaftliche Studien der Freien Universität Berlin stattgefunden hat. 2015 an der Friedrich Schlegel Graduiertenschule gegründet, wird der Deutsch-Asiatische Studientag Literaturwissenschaft seit 2017 in Kooperation mit der Mori-Ôgai-Gedenkstätte der Humboldt-Universität zu Berlin durchgeführt. Er schließt grundsätzlich an das an, was seit 2006 vorwiegend in den USA als ,,Asian German Studies“ verhandelt wird.

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 ( R)-[11C]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 ( Kp,brain) 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.

SummaryThe 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.

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.

Background Netrin-1, a secreted laminin-related protein, is known to regulate not only axonal guidance and neuronal cell migration, but also blood–brain barrier integrity and inflammation. Two preliminary studies reported altered serum netrin-1 levels in multiple sclerosis; however, associations with longitudinal clinical and magnetic resonance imaging activity have not been investigated. Objectives We aimed to assess serum netrin-1 in multiple sclerosis and controls with respect to disease activity and its temporal dynamics. Methods Serum netrin-1 was assessed by enzyme-linked immunosorbent assay in 79 patients with clinically isolated syndrome or multiple sclerosis, and 30 non-inflammatory neurological disease controls. In patients, serum samples were collected immediately prior to gadolinium-enhanced 3 T magnetic resonance imaging at two time points (initial contrast-enhancing gadolinium+ n = 47, non-enhancing gadolinium– n = 32; reference gadolinium– n = 70; median time-lag 1.4, interquartile range 1.0–2.3 years). Results Serum netrin-1 levels were similar in clinically isolated syndrome, multiple sclerosis and controls, and gadolinium+ and gadolinium– patients. Among gadolinium+ patients, serum netrin-1 was decreased in clinically active ( n = 8) vs non-active patients ( n = 39; p = 0.041). Serum netrin-1 showed no temporal dynamics in multiple sclerosis and was unrelated to clinical data. Conclusions Serum netrin-1 levels show no multiple sclerosis specific changes and are not sensitive for detection of subclinical disease activity. Netrin-1 changes during relapses may deserve further examination.

UnlabelledNeurofascin 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.ResultsImmunohistochemistry 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.ConclusionsWe 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.