- Vom Antikörper zum Immunoassay - Nachweis und Quantifizierung des nichtsteroidalen Antirheumatikums Diclofenac in relevanten Matrices

Diclofenac, ein nichtsteroidales Antirheumatikum, wird auf Grund seiner häufigen Verwendung in der Human- und Veterinärmedizin zunehmend in der Umwelt oder in Nahrungsmitteln tierischen Ursprungs gefunden. Zu Monitoring-Zwecken sowie zur Kontrolle der Einhaltung rechtlicher Vorgaben bezüglich erlaubter Konzentrationen, wie beispielsweise in der Europäischen Wasserrahmenrichtlinie oder der Verordnung (EU) Nr. 37/2010 festgelegt, bedarf es effizienter analytischer Methoden. Im Idealfall sollten diese selektive und sensitive vor-Ort Messungen kostengünstig ermöglichen. Eine Anwendbarkeit in verschiedenen komplexen Matrices wäre zudem von großen Vorteil. Im Rahmen dieser Arbeit wurde ein optischer Biosensor zu diesem Zweck entwickelt, optimiert und etabliert. Als Nachweismethode diente hierbei die markierungsfreie zeitaufgelöste Reflektometrische Interferenzspektroskopie. Als Realmatrices wurden Kuhmilch und Flusswasser verwendet. Im Fokus standen neben der Identifizierung, Reduzierung und Vermeidung von Matrixeffekten vor allem das Erreichen möglichst geringer Nachweis- und Bestimmungsgrenzen, um im Bereich relevanter Diclofenac-Konzentrationen eine echte Alternative zu bisherigen Methoden zu bieten. Des Weitern sollte durch die Vermeidung jeglicher Probenvorbereitungsschritte eine Abgrenzung zu Standardmethoden geschaffen und eine Entwicklung zu einer vor-Ort-Messmethode ermöglicht werden. Zum Nachweis des Diclofenacs wurde als Erkennungsstruktur polyklonaler anti-Diclofenac Antikörper verwendet. Da die Erkennungsstruktur das Schlüsselreagenz jedes Immunoassays bezüglich Selektivität und Sensitivität darstellt, wurde ein polyklonaler anti-Diclofenac Antikörper selbst hergestellt und aufgereinigt. Es konnte gezeigt werden, dass die Verwendung des selbst hergestellten Antikörpers zu deutlich höheren Sensitivitäten führte

Mrgprd Enhances Excitability in Specific Populations of Cutaneous Murine Polymodal Nociceptors

The Mas-related G protein-coupled receptor D (Mrgprd) is selectively expressed in nonpeptidergic nociceptors that innervate the outer layers of mammalian skin. The function of Mrgprd in nociceptive neurons and the physiologically relevant somatosensory stimuli that activate Mrgprd^-expressing (Mrgprd^+) neurons are currently unknown. To address these issues, we studied three Mrgprd knock-in mouse lines using an ex vivo somatosensory preparation to examine the role of the Mrgprd receptor and Mrgprd+ afferents in cutaneous somatosensation. In mouse hairy skin, Mrgprd, as marked by expression of green fluorescent protein reporters, was expressed predominantly in the population of nonpeptidergic, TRPV1-negative, C-polymodal nociceptors. In mice lacking Mrgprd, this population of nociceptors exhibited decreased sensitivity to cold, heat, and mechanical stimuli. Additionally, in vitro patch-clamp studies were performed on cultured dorsal root ganglion neurons from Mrgprd^(–/–) and Mrgprd^(+/–) mice. These studies revealed a higher rheobase in neurons from Mrgprd^(–/–) mice than from Mrgprd^(+/–) mice. Furthermore, the application of the Mrgprd ligand β-alanine significantly reduced the rheobase and increased the firing rate in neurons from Mrgprd^(+/–) mice but was without effect in neurons from Mrgprd^(–/–) mice. Our results demonstrate that Mrgprd influences the excitability of polymodal nonpeptidergic nociceptors to mechanical and thermal stimuli

Using peer education to improve diabetes management and outcomes in a low-income setting: A randomized controlled trial

Background: Diabetes is an important health burden in Indonesia. However, diabetes management and treatment remain poor, with most people with diabetes in Indonesia not achieving the recommended blood glucose levels. Peer education may have particular potential in low-income settings in complementing diabetes care without being a large additional strain on the health system. Methods/design: This cluster randomized controlled trial aims to identify the effect of the implementation of peer education for patients with type 2 diabetes on diabetes-related outcomes in Aceh, Indonesia, which will complement the diabetes treatment provided at primary-care health posts (puskesmas). Altogether, 29 puskesmas were recruited in Banda Aceh and Aceh Besar, each of which was randomly assigned to either the control or the intervention group. Then, 534 people with diabetes were identified and recruited through their respective puskesmas. The intervention consists of up to two peer education groups per puskesmas, which are led by previously trained people with diabetes. Peer education sessions are held every month for 18 months, with follow-up data being collected 9 and 18 months after the first peer education session. The main objective is to improve diabetes management and the health behavior of participants receiving peer education to reduce their average blood glucose levels as measured by glycated hemoglobin (HbA1c) levels. Secondary outcomes are the effects of peer education on lipid levels, waist circumference, blood pressure, quality of life, treatment adherence, diabetes knowledge, physical activity, and dietary diversity. Data sources for the measurement of outcomes include patient and health facility surveys and biomarker measurements. An economic evaluation will be conducted to assess the cost-effectiveness of the intervention. Discussion: This trial will contribute to the evidence on the effectiveness and cost-effectiveness of peer education in improving diabetes management in a low-income setting in Indonesia and in other comparable contexts

Aufbruch ins sozialistische Paradies – Propagandaplakate der frühen Volksrepublik China:

Die 1950er Jahre waren eine Zeit der Kampagnen zur Industrialisierung, Modernisierung und der Verwirklichung der sozialistischen Vision. Was Realität werden sollte, zeigen die Propagandaplakate. Die Studierenden des Seminars Plakatkunst und Propaganda in der frühen Volksrepublik China haben beispielhafte Exemplare der groß angelegten Kampagnen aus der Plakatsammlung des Amsterdamer International Institute of Social History ausgewählt. Diese haben sie im Hinblick auf ihren historischen Kontext untersucht und die Ergebnisse auf zusätzlichen Infoplakaten zusammengefasst. Der Katalog zeigt die Exponate und vermittelt die entsprechenden zeit- und kunsthistorischen Hintergründe

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Development of test strategies for selective inhibition of enzymes of adrenal steroid synthesis with particular regard to species differences

Das Enzym Aldosteronsynthase (CYP11B2) ist das Schlüsselenzym der Mineralocorticoidbiosynthese und katalysiert die Umsetzung von Deoxycorticosteron zu dem hochpotenten Steroidhormon Aldosteron. Die Hemmung dieses Enzyms stellt ein vielversprechendes Therapiekonzept zur Behandlung cardiovaskulärer Erkrankungen dar, an deren Entstehung und Progression pathologisch erhöhte Aldosteronspiegel beteiligt sind. Im Rahmen dieser Arbeit wurden Strategien und Methoden zur Identifikation und Charakterisierung neuer Aldosteronsynthase-Inhibitoren entwickelt. Mit Hilfe eines miniaturisierten, auf HTRF®-Technologie basierten Testverfahrens ist es gelungen Tests im High-Throughput-Format durchzuführen. Damit können sowohl die Aktivität einer Verbindung an CYP11B2, als auch die Selektivität gegenüber CYP11B1 zuverlässig und reproduzierbar bestimmt werden. Neben der Miniaturisierung des bereits im Arbeitskreis etablierten zellulären Testsystems wurden neue, zellfreie Assays zum Screening von Substanzen entwickelt. Darüber hinaus erfolgte die biochemische Charakterisierung einer Leitverbindung. Unter anderem wurde, zur Bestimmung potentieller Spezies für nachfolgende in vivo-Studien, die inhibitorische Wirkung auf die Aldosteronsekretion an Nebennierenkulturen verschiedener Spezies untersucht. Schließlich konnte mit dieser Leitverbindung das Proof of Principle in der Ratte, nach peroraler Applikation, erbracht werden.The enzyme aldosterone synthase (CYP11B2) is the key enzyme of mineralocorticoid biosynthesis and catalyzes the conversion of deoxycorticosterone to the highly potent steroid hormone aldosterone. The inhibition of this enzyme represents a promising therapeutical approach for the treatment of cardiovascular diseases, where pathologically elevated aldosterone levels are involved in their development and progression. In this work, strategies and methods for the identification and characterization of novel aldosterone synthase inhibitors have been developed. With the help of a miniaturized test method, based on HTRF®-technology, it was managed to carry out tests in high-throughput format. Thus, both the activity of a compound to CYP11B2, as well as the selectivity for CYP11B1 can be determined in a reliable and reproducible manner. Besides the miniaturization of the already established cellular test by the working group, new cell-free assays for screening of substances have been developed. In addition, the biochemical characterization of a lead compound was carried out. Here, the inhibitory effect on the aldosterone secretion of adrenal cultures of various species was examined. This was done for determination of potential species for subsequent in vivo studies. Finally, with this lead compound the proof of principle in rat, after oral administration could be provided

Bicycle system and its development potential: the case of Pelotas / RS.

The need for mobility, in the last decades, has exponentially increased, mainly in urban areas, due to the population growth and the decentralization of residential areas. In this context, mobility is highlighted as a component of sustainability for the cities, concerning the way this circulation occurs and its relation to the urban structure. As a result, the bicycle plays an important role in the development of a sustainable urban mobility. The present work has the main objective of present the results obtained in the performance evaluation of the bike path. In order to do this, the concepts and methodological procedures of Post Occupation Evaluation (POE) to the bicycle path system, adopting the following: application of questionnaire to the people "using" the system, comprising, in this case, the bicycle riders to check their level of satisfaction resulting from using the system and the technical verification of structural conditions, related to the assumptions of the urban design.A necessidade de mobilidade, nas últimas décadas, tem aumentado exponencialmente, principalmente nas áreas urbanas, devido ao crescimento da população e da descentralização das áreas residenciais. Neste contexto, a mobilidade é destacada como um componente de sustentabilidade para as cidades, ao que diz respeito à forma como essa circulação ocorre e sua relação com a estrutura urbana. Diante disso, a bicicleta tem um papel importante no desenvolvimento de uma mobilidade urbana sustentável. O presente trabalho tem o objetivo principal de apresentar os resultados obtidos na avaliação de desempenho e um sistema cicloviário urbano. Para tanto, foram utilizados os conceitos e procedimentos metodológicos de Avaliação Pós-Ocupação (APO), adotando as seguintes etapas: aplicação de questionário para os usuários do sistema, verificando o seu nível de satisfação resultante da utilização do sistema e a verificação técnica das condições estruturais, relacionados com os pressupostos do desenho urbano