Lebendige Gemeinde am Rande der Großstadt: die Kölner Pfarrei St. Hedwig 1967-2007

Auch im Buchhandel erhältlich: Lebendige Gemeinde am Rande der Großstadt : die Kölner Pfarrei Sankt Hedwig 1967-2007 / von Marcel Albert; Markus Eckstein. - Münster : Monsenstein und Vannerdat, 2007 105 S. (Forschungen zur Volkskunde ; 55 : Abteilung Kirchen- und Ordensgeschichte ; 2) ISBN 978-3-86582-430-1 Preis: 13,90 €Die elektronische Fassung ist mit dem gedruckten Buch vollkommen identisch

Ist die Expression des GP88-Proteins (Progranulin) ein klinisch relevanter Prognosefaktor für Prostatakarzinompatienten?

Progranulin (GP88), an autocrine growth factor, has been recognized as a biomarker in several tumor entities. GP88 can be detected in the tumor tissue and serum of patients, which enables its detection in a minimally invasive (liquid biopsy) test. In prostate cancer (PCa), studies on this marker have been only preliminary as yet. The authors’ own studies analyzed the protein level of GP88 protein in the serum (enzyme-linked immunosorbent assay) and tumor tissue (immunohistochemistry) in two PCa patient cohorts separately. The detection of increased GP88 protein in both tumor tissue and serum appeared to be a negative prognostic biomarker. Interestingly, this result related only to younger PCa patients. Further studies are needed to confirm these results and to estimate the eligibility of GP88 for diagnosis and treatment monitoring in PCa patients.Progranulin (GP88), ein autokriner Wachstumsfaktor, stellt einen für zahlreiche Tumorentitäten vielversprechenden Biomarker dar. Da sich GP88 sowohl im Tumorgewebe als auch im Serum von Tumorpatienten nachweisen lässt, ist ein minimal-invasiver Test („liquid biopsy“) zum Nachweis von GP88 möglich. Im Prostatakarzinom (PCa) wurde dieser Marker bisher nur in wenigen Voruntersuchungen auf seine diagnostische Aussagekraft hin charakterisiert. In unseren eigenen Arbeiten analysierten wir die Proteinlevel von GP88 im Serum (ELISA-Test) und im Tumorgewebe (Immunhistochemie) in 2 Prostatakarzinompatientenkohorten. Dabei erwies sich der verstärkte Proteinnachweis sowohl im Serum als auch im Tumorgewebe als negativer Prognosefaktor. Interessanterweise traf dies nur auf die jüngeren PCa-Patienten zu. Es sind weitere Untersuchungen erforderlich, um diese Ergebnisse zu bestätigen bzw. eine Eignung von GP88 auch für die Diagnose und das Therapiemonitoring von PCa-Patienten einzuschätzen

The metabolic fate of two new psychoactive substances - 2-aminoindane and N-methyl-2-aminoindane - studied in vitro and in vivo to support drug testing

The aim of this study was to characterize the in vitro and in vivo metabolism of 2-aminoindane (2,3-dihydro-1H-inden-2-amine, 2-AI), and N-methyl-2-aminoindane (N-methyl-2,3-dihydro-1H-inden-2-amine, NM-2-AI) after incubations using pooled human liver microsomes (pHLMs), pooled human liver S9 fraction (pS9), and rat urine after oral administration. After analysis using liquid chromatography coupled to high-resolution mass spectrometry, pHLM incubations revealed that 2-AI was left unmetabolized, while NM-2-AI formed a hydroxylamine and diastereomers of a metabolite formed after hydroxylation in beta position. Incubations using pS9 led to the formation of an acetyl conjugation in the case of 2-AI and merely a hydroxylamine for NM-2-AI. Investigations on rat urine showed that 2-AI was hydroxylated also forming diasteromers as described for NM-2-AI or acetylated similar to incubations using pS9. All hydroxylated metabolites of NM-2-AI except the hydroxylamine were found in rat urine as additional sulfates. Assuming similar patterns in humans, urine screening procedures might be focused on the parent compounds but should also include their metabolites. An activity screening using human recombinant N-acetyl transferase (NAT) isoforms 1 and 2 revealed that 2-AI was acetylated exclusively by NAT2, which is polymorphically expressed

Trions, Exciton Dynamics and Spectral Modifications in Doped Carbon Nanotubes: A Singular Defect-Driven Mechanism

Doping substantially influences the electronic and photophysical properties of semiconducting single-wall carbon nanotubes (s-SWNTs). Although prior studies have noted that surplus charge carriers modify optical spectra and accelerate non-radiative exciton decay in doped s-SWNTs, a direct mechanistic correlation of trion formation, exciton dynamics and energetics remains elusive. This work examines the influence of doping-induced non-radiative decay and exciton confinement on s-SWNT photophysics. Using photoluminescence, continuous-wave absorption, and pump-probe spectroscopy, we show that localization of and barrier formation by trapped charges can be jointly quantified using diffusive exciton transport- and particle-in-the-box models, yielding a one-to-one correlation between charge carrier concentrations derived from these models. The study highlights the multifaceted role of exohedral counterions, which trap charges to create quenching sites, form barriers to exciton movement, and host trion states. This contributes significantly to understanding and optimizing the photophysical properties of doped SWNTs

Liquid Chromatography-High-Resolution Mass Spectrometry-Based In Vitro Toxicometabolomics of the Synthetic Cathinones 4-MPD and 4-MEAP in Pooled Human Liver Microsomes

Synthetic cathinones belong to the most often seized new psychoactive substances on an international level. This study investigated the toxicometabolomics, particularly the in vitro metabolism of 2-(methylamino)-1-(4-methylphenyl)-1-pentanone (4-MPD) and 2-(ethylamino)-1-(4- methylphenyl)-1-pentanone (4-MEAP) in pooled human liver microsomes (pHLM) using untargeted metabolomics techniques. Incubations were performed with the substrates in concentrations ranging from 0, 12.5, and 25 µM. Analysis was done by means of high-performance liquid chromatography coupled to high-resolution mass spectrometry (HPLC-HRMS/MS) in full scan only and the obtained data was evaluated using XCMS Online and MetaboAnalyst. Significant features were putatively identified using a separate parallel reaction monitoring method. Statistical analysis was performed using Kruskal-Wallis test for prefiltering significant features and subsequent hierarchical clustering, as well as principal component analysis (PCA). Hierarchical clustering or PCA showed a distinct clustering of all concentrations with most of the features z-scores rising with the concentration of the investigated substances. Identification of significant features left many of them unidentified but revealed metabolites of both 4-MPD and 4-MEAP. Both substances formed carboxylic acids, were hydroxylated at the alkyl chain, and formed metabolites after combined hydroxylation and reduction of the cathinone oxo group. 4-MPD additionally formed a dihydroxy metabolite and a hydroxylamine. 4-MEAP was additionally found reduced at the cathinone oxo group, N-dealkylated, and formed an oxo metabolite. These findings are the first to describe the metabolic pathways of 4-MPD and to extend our knowledge about the metabolism of 4-MEAP. Findings, particularly the MS data of the metabolites, are essential for setting up metabolite-based toxicological (urine) screening procedures

Immune Checkpoint Inhibitors in Urothelial Carcinoma: Recommendations for Practical Approaches to PD-L1 and Other Potential Predictive Biomarker Testing

Immuno-oncology (IO) agents (anti–programmed cell death 1 (PD-1) and anti–programmed cell death-ligand 1 (PD-L1)) are approved as first- and second-line treatments for metastatic UC. PD-L1 expression levels in UC tumors help clinicians determine which patients are more likely to respond to IO therapies. Assays for approved IO agents use different antibodies, immunohistochemical protocols, cutoffs (defining “high” vs. “low” PD-L1 expression), and scoring algorithms. The robust control of pre-analytical and analytical standards is needed to obtain high-quality PD-L1 results. To better understand the status and perspectives of biomarker-guided patient selection for anti–PD-1 and anti–PD-L1 agents in UC, three workshops were held from December 2018 to December 2019 in Italy, Malaysia, and Spain. The primary goal was to develop recommendations for best practice approaches to PD-L1 testing in UC. Recommendations pertaining to the interpretation and reporting of the results of PD-L1 assays from experienced pathologists and oncologists from around the globe are included. A test request form for pathology laboratories was developed as a critical first step for oncologists/urologists to encourage communication between clinicians and pathologists, ensuring fast and high-quality test results. In this era of personalized medicine, we briefly discuss novel biomarkers being evaluated for IO agents in UC

Toxicokinetic studies of the four new psychoactive substances 4-chloroethcathinone, N-ethylnorpentylone, N-ethylhexedrone, and 4-fluoro-alpha-pyrrolidinohexiophenone

Purpose The presented study aimed to elucidate the toxicokinetics of the four synthetic cathinones 4-chloroethcathinone (4-CEC), N-ethylnorpentylone (N-ethylpentylone, ephylone), N-ethylhexedrone (NEH), and 4-fluoro-alpha-pyrrolidinohexiophenone (4-fluoro-alpha-pyrrolidinohexanophenone, 4-F-α-PHP, 4F-alpha-PHP, 4F-PHP). Methods First, their metabolism was studied using human urine and blood samples. Analysis of specimens was performed by liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) and gas chromatography–mass spectrometry (GC–MS). LC-HRMS/MS was also used to analyze in vitro incubations of the new psychoactive substances using pooled human liver S9 fraction (pS9), to identify the monooxygenases involved in the initial metabolic steps, and determination of plasma concentrations after a standard addition method. Metabolic stability was tested in pooled human liver microsomes incubations analyzed by LC-ion trap MS. Results Using LC-HRMS/MS, 47 metabolites in total were found in patient samples and pS9 incubations. Using GC–MS, 4-CEC, ephylone, NEH, and five of their metabolites were detectable in urine. The following main phase I reactions were observed: carbonyl group reduction, N-deethylation, hydroxylation, lactam formation (4F-PHP), and demethylenation (ephylone). Mainly glucuronidations were observed as phase II reactions besides conjugates with the dicarboxylic acids malonic, succinic, and glutaric acid (4-CEC), sulfation, methylation (both ephylone), and N-acetylation (NEH). A broad range of monooxygenases was involved in the initial steps with exception of NEH (only CYP1A2 and CYP2C19). 4F-PHP had the shortest in vitro half-life (38 min) and highest intrinsic clearance (15.7 mL/min/kg). Plasma concentrations ranged from 0.8 to 8.5 ng/mL. Conclusions Our results are expected to help toxicologists to reliably identify these substances in case of suspected abuse and allow them a thorough risk assessment