Correlation of neutralizing tick-borne encephalitis antibodies with the immune response to yellow fever vaccination

Due to global warming and advancing globalization, it is to be feared that flaviviruses will continue to spread. In the near future, this will result in intensified virological and infectiological research into the immune reactions to these viruses. A better understanding of the effects of pre-existing immunity on immune responses following vaccination is of great importance for translational infection research in order to develop more effective immunisation strategies. The Plaque Reduction Neutralization Test (PRNT) remains the methodological tool of choice to measure neutralizing antibody titres against Tick-Borne Encephalitis Virus (TBEV). In the present study, the neutralizing antibody titres against TBEV (NT-TBEV) before and 28 days after vaccination with the Live Attenuated Yellow Fever 17D Vaccine (YF17D) against the Yellow Fever Virus (YFV) were analyzed in comparison to the neutralizing antibody titres against YFV (NT-YFV), measured with the Fluorescence Reduction Neutralization Test (FluoRNT). In addition, the Indirect Immunofluorescence Test (IIFT) was used to test whether cross-reacting antibodies against other flaviviruses were present due to the previous TBE vaccination and how these behaved in comparison to TBE-naïve persons after the yellow fever vaccination. It was shown that the administered yellow fever vaccine YF17D had no influence on pre-existing neutralizing antibody titres against TBE. Similarly, the yellow fever vaccination induced equally strong neutralizing antibody titres against yellow fever in TBE-immunised and TBE-naïve individuals. In addition, increased panflaviviral cross-reactivity in TBE-immunised individuals and the absence of cross-reactivity in TBE-naïve individuals following yellow fever vaccination was demonstrated. This resulted in the need to investigate further specific neutralizing and/or cross-reactive epitopes of flaviviruses. The presented work is an independent part of an article submitted for publication (1), which shows that vaccination against TBE and subsequently against yellow fever do not interfere with each other's robust immune response, but can intensify immunogenicity through antibody-dependent enhancement. The data suggest that yellow fever vaccination induces non-cross-reactive antibodies in flavivirus-naïve individuals, while enhanced cross-reactivities are present in TBE vaccinated individuals due to pre-immunity

Der Weg vom Heterogenen Immunoassay zum Immunosensor: Prinzipien und Applikationen im Bereich der Klinischen Chemie

Immunosensoren sind ligandenaffinitäts-messende Sensoren, bei denen immunochemische Reaktionen über eine Transducerschaltung aufgezeichnet werden. Das fundamentale Merkmal aller Immunosensoren ist hierbei die Spezifität von Antikörpern zu geeigneten Analyten unter Ausbildung eines stabilen Immunkomplexes. Dies ist auch die Basis der Immunoassay-Methodologie. Im Vergleich beider Methoden ermöglicht die Transducer-Tech-nologie eine markierungsfreie Detektion und zugleich eine Quantifizierung des gebildeten Immunkomplexes. In den letzten Jahren wurden Immunoassays auch verstärkt zur Spurenanalyse von toxischen Substanzen in der pharmazeutischen und der Nahrungsmittelindustrie sowie in der Umweltanalytik eingesetzt. Entsprechende Mess-ungen können hierbei jedoch nur diskontinuierlich erfolgen. Um eine kontinuierliche Analytik zu ermöglichen, er-scheint der Einsatz von Immunosensoren besonders vielversprechend. Auch im Bereich der klinischen Diagnostik gibt es viele Anwendungsgebiete, für die ein kontinuierliches „Monitoring“ von verschiedenen Analyten von großem Nutzen wäre. Deshalb sollten gerade Labormediziner die Vorteile des Einsatzes von Immunosensoren in der klinische Diagnostik und Laboratoriumsmedizin bedenken. Dieser Vortrag wendet sich somit vor allem an Klinische Chemiker, Biochemiker, Physiker und Ingenieure mit Schwerpunkt Immunoassayentwicklung und Biosensortechnologie. Ziel des Vortrags ist es, die Entwicklungen in den Bereichen Immunoassay und Immunosensoren zusammenfassend darzulegen und auf das enorme Potential,wie auch auf das konkurrenzstarke Umfeld der Immunosensortechnologie in der klinischen Diagnostik hinzuweisen

Variations of Steroid Hormone Metabolites in Serum and Urine in Polycystic Ovary Syndrome after Nafarelin Stimulation: Evidence for an Altered Corticoid Excretion.

To evaluate the clinical relevance of testing pituitary-ovarian responses in patients suffering from polycystic ovary syndrome (PCOS) with the GnRH agonist nafarelin, a 1.2-mg dose of nafarelin was given intranasally to 19 women with PCOS and 15 healthy premenopausal women. The subsequent analysis of steroids in both serum and urine during the test was carried out at several time points for up to 24 h. Serum levels of 17 alpha-hydroxyprogesterone were elevated at all time points of the test in PCOS patients vs. controls [at baseline, 3.5 +/- 0.2 vs. 1.8 +/- 0.1 nmol/L (P < 0.001); at 24 h, 9.9 +/- 0.9 vs. 4.9 +/- 0.3 nmol/L (P < 0.001)]. Basal levels of androstenedione were higher in the patient group, but there was no significant change during the test in either group. Serum testosterone levels were also found to differ in PCOS patients compared with the control values at baseline (2.2 +/- 0.2 vs. 1.5 +/- 0.1 nmol/L; P < 0.05) and after nafarelin treatment (at 24 h, 3.2 +/- 0.4 vs. 1.8 +/- 0.2 nmol/L; P < 0.05). Serum estradiol levels rose significantly in both groups during the test; the posttest levels were significantly higher in PCOS than in controls. The PCOS patients displayed a significant increase in androgen and gestagen metabolites as well as in glucocorticoid metabolites excreted in the urine during the 24 h. In the control subjects, except for 17 alpha-hydroxypregnanolone, which rose significantly, none of the urinary steroids investigated showed relevant changes during the nafarelin test. The posttest excretion of allo-tetrahydrocortisol (1.4 +/- 0.2 vs. 0.3 +/- 0.1 mumol/g creatinine; P < 0.001) and the increase in 17 alpha-hydroxypregnanolone excretion (1.4 +/- 0.2 vs. 0.3 +/- 0.1 mumol/g creatinine; P < 0.001) were distinctly higher in PCOS patients than in the controls; the diagnostic sensitivity of the combination of both parameters was 89% at a 93% specificity. Thus, measurements of 17 alpha-hydroxyprogesterone levels in serum and of urinary allo-tetrahydrocortisol and 17 alpha-hydroxypregnanolone after nafarelin treatment make this stimulation test a valuable diagnostic tool for identifying PCOS patients. The significant changes in the excretion of urinary androgen and gestagen metabolites, unmasked by GnRH agonist stimulation, suggest a functional alteration of the pituitary-ovarian axis. The reason for the increased excretion of glucocorticoid metabolites after nafarelin stimulation remains to be clarified

Quality assessment of glucose measurement with regard to epidemiology and clinical management of diabetes mellitus in Germany

Background:During the last decade, Germany has seen an increased prevalence and a redistribution from undetected to diagnosed diabetes mellitus. Due to this substantial epidemiological development, the number of people with documented type 2 diabetes was 8.7 million in 2022. An estimated two million undiagnosed subjects are to be added. Beyond that, the life expectancy of diabetic subjects is increasing due to more responsive health systems in terms of care. Possible reasons include improved screening of at-risk individuals, the introduction of HbA1c for diagnosis in 2010, and the higher use of risk scores. Additionally, quality aspects of the laboratory methodology should be taken into consideration.Methods:Epidemiology and clinical management of diabetes in Germany are presented in the light of publications retrieved by a selective search of the PubMed database. Additionally, the data from German external quality assessment (EQA) surveys for the measurands glucose in plasma and HbA1c in whole blood, reviewed from 2010 until 2022, were evaluated. Above this, data concerning the analytical performance of near-patient glucometer devices, according to the ISO norm 15197:2013, were analyzed.Results:Two laboratory aspects are in good accordance with the observation of an increase in the diabetes mellitus prevalence when retrospectively reviewing the period 2010 to 2022: First, the analytical performance according to the ISO norm 15197:2013 of the glucometer devices widely used by patients with diabetes for the glucose self-testing, has improved during this period. Secondly, concerning the EQA program of INSTAND, the number of participating laboratories raised significantly in Germany. The spreads of variations of the specified results for plasma glucose remained unchanged between 2010 and 2022, whereas for HbA1c a significant decrease of the result scattering could be observed.Conclusion:These retrospectively established findings testify to an excellent analytical quality of laboratory diagnostics for glucose and HbA1c throughout Germany which may be involved in a better diagnosis and therapy of previously undetected diabetes mellitus

Publicações de teatro em 2013

O texto procede ao levantamento bibliográfico, selecção da tipologia e listagem das edições de / sobre teatro no ano indicado, inclui adenda aos anos anterioresinfo:eu-repo/semantics/publishedVersio

Selective Attenuation of Norepinephrine Release and Stress-Induced Heart Rate Increase by Partial Adenosine A1 Agonism

The release of the neurotransmitter norepinephrine (NE) is modulated by presynaptic adenosine receptors. In the present study we investigated the effect of a partial activation of this feedback mechanism. We hypothesized that partial agonism would have differential effects on NE release in isolated hearts as well as on heart rate in vivo depending on the genetic background and baseline sympathetic activity. In isolated perfused hearts of Wistar and Spontaneously Hypertensive Rats (SHR), NE release was induced by electrical stimulation under control conditions (S1), and with capadenoson 6 · 10−8 M (30 µg/l), 6 · 10−7 M (300 µg/l) or 2-chloro-N6-cyclopentyladenosine (CCPA) 10−6 M (S2). Under control conditions (S1), NE release was significantly higher in SHR hearts compared to Wistar (766+/−87 pmol/g vs. 173+/−18 pmol/g, p<0.01). Capadenoson led to a concentration-dependent decrease of the stimulation–induced NE release in SHR (S2/S1 = 0.90±0.08 with capadenoson 6 · 10−8 M, 0.54±0.02 with 6 · 10−7 M), but not in Wistar hearts (S2/S1 = 1.05±0.12 with 6 · 10−8 M, 1.03±0.09 with 6 · 10−7 M). CCPA reduced NE release to a similar degree in hearts from both strains. In vivo capadenoson did not alter resting heart rate in Wistar rats or SHR. Restraint stress induced a significantly greater increase of heart rate in SHR than in Wistar rats. Capadenoson blunted this stress-induced tachycardia by 45% in SHR, but not in Wistar rats. Using a [35S]GTPγS assay we demonstrated that capadenoson is a partial agonist compared to the full agonist CCPA (74+/−2% A1-receptor stimulation). These results suggest that partial adenosine A1-agonism dampens stress-induced tachycardia selectively in rats susceptible to strong increases in sympathetic activity, most likely due to a presynaptic attenuation of NE release

Hyaluronan Export through Plasma Membranes Depends on Concurrent K+ Efflux by Kir Channels

Hyaluronan is synthesized within the cytoplasm and exported into the extracellular matrix through the cell membrane of fibroblasts by the MRP5 transporter. In order to meet the law of electroneutrality, a cation is required to neutralize the emerging negative hyaluronan charges. As we previously observed an inhibiting of hyaluronan export by inhibitors of K+ channels, hyaluronan export was now analysed by simultaneously measuring membrane potential in the presence of drugs. This was done by both hyaluronan import into inside-out vesicles and by inhibition with antisense siRNA. Hyaluronan export from fibroblast was particularly inhibited by glibenclamide, ropivacain and BaCl2 which all belong to ATP-sensitive inwardly-rectifying Kir channel inhibitors. Import of hyaluronan into vesicles was activated by 150 mM KCl and this activation was abolished by ATP. siRNA for the K+ channels Kir3.4 and Kir6.2 inhibited hyaluronan export. Collectively, these results indicated that hyaluronan export depends on concurrent K+ efflux

Behavioural activation by mental health nurses for late-life depression in primary care: a randomized controlled trial

Background: Depressive symptoms are common in older adults. The effectiveness of pharmacological treatments and the availability of psychological treatments in primary care are limited. A behavioural approach to depression treatment might be beneficial to many older adults but such care is still largely unavailable. Behavioural Activation (BA) protocols are less complicated and more easy to train than other psychological therapies, making them very suitable for delivery by less specialised therapists. The recent introduction of the mental health nurse in primary care centres in the Netherlands has created major opportunities for improving the accessibility of psychological treatments for late-life depression in primary care. BA may thus address the needs of older patients while improving treatment outcome and lowering costs.The primary objective of this study is to compare the effectiveness and cost-effectiveness of BA in comparison with treatment as usual (TAU) for late-life depression in Dutch primary care. A secondary goal is to explore several potential mechanisms of change, as well as predictors and moderators of treatment outcome of BA for late-life depression. Methods/design: Cluster-randomised controlled multicentre trial with two parallel groups: a) behavioural activation, and b) treatment as usual, conducted in primary care centres with a follow-up of 52 weeks. The main inclusion criterion is a PHQ-9 score > 9. Patients are excluded from the trial in case of severe mental illness that requires specialized treatment, high suicide risk, drug and/or alcohol abuse, prior psychotherapy, change in dosage or type of prescribed antidepressants in the previous 12 weeks, or moderate to severe cognitive impairment. The intervention consists of 8 weekly 30-min BA sessions delivered by a trained mental health nurse. Discussion: We expect BA to be an effective and cost-effective treatment for late-life depression compared to TAU. BA delivered by mental health nurses could increase the availability and accessibility of non-pharmacological treatments for late-life depression in primary care. Trial registration: This study is retrospectively registered in the Dutch Clinical Trial Register NTR6013on August 25th 2016. © 2017 The Author(s)