Risks of pyrrolizidine alkaloids in tea and herbal infusions

Pyrrolizidinalkaloide (PA) sind sekundäre Pflanzeninhaltsstoffe, die von einer Vielzahl von Pflanzen gebildet werden und u. a. zur Abwehr von Fraßfeinden dienen. Toxikologisch bedeutsam sind die PA, die eine Doppelbindung in 1,2-Position aufweisen. Diese können zu gesundheitlichen Schäden bei Mensch und Tier führen, wobei die Leber das Hauptzielorgan darstellt. Neben den bekannten hepatotoxischen Effekten können 1,2-ungesättigte PA auch die DNA schädigen und krebserzeugend wirken. Die Verbindungen gelangen in erster Linie über Wild- und Beikräuter in die Lebensmittelkette. In der im Jahr 2016 durch das Bundes­institut für Risikobewertung (BfR) veröffentlichten Bewertung stellte der Verzehr von kontaminiertem Tee und Kräutertee die wesentliche Expositionsquelle für die Bevölkerung gegenüber 1,2-ungesättigten PA in Deutschland dar; aber auch andere Lebensmittel können zur Aufnahme beitragen. In der vorliegenden Arbeit, in der ausschließlich Tee und Kräutertee berücksichtigt werden, zeigt sich, dass die Gehalte an 1,2-ungesättigten PA in dieser Lebensmittelgruppe im Vergleich zu 2016 deutlich gesunken sind. Dennoch kann es insbesondere bei Personen, die langfristig hohe Mengen Kräutertee bzw. Rooibostee verzehren, auch gegenwärtig noch zu Aufnahmemengen kommen, die in einem Margin of Exposure von unter 10.000 resultieren, weshalb es auch weiterhin angezeigt scheint, Maßnahmen zur Senkung der Gehalte durchzuführen.Pyrrolizidine alkaloids (PA) are secondary plant metabolites which are produced by a large number of plants, e. g. to ward off herbivores. PA with a double bond in the 1,2-position are of toxicological relevance. These derivatives can cause adverse health effects in humans and animals, with the liver being the major target organ. Besides the known hepatotoxic effects, 1,2-unsaturated PA may also damage DNA and may be carcinogenic. The occurrence of these compounds in foods is primarily caused by contamination with wild herbs. In the assessment published in 2016 by the German Federal Institute for Risk Assessment (BfR), consumption of contaminated tea and herbal tea was the main source of exposure for the population to 1.2-unsaturated PA in Germany; however, other foods can also contribute to intake. The present study, which focuses exclusively on tea and herbal tea, shows that levels of 1,2-unsaturated PA in this food group have decreased significantly compared to 2016. Nevertheless, persons who consume high amounts of herbal tea or rooibos tea in the long term may still be exposed to intakes that result in a margin of exposure of less than 10,000, which is why it still seems appropriate to implement measures to reduce the levels

Novel Whole-Cell Antibiotic Biosensors for Compound Discovery▿

Cells containing reporters which are specifically induced via selected promoters are used in pharmaceutical drug discovery and in environmental biology. They are used in screening for novel drug candidates and in the detection of bioactive compounds in environmental samples. In this study, we generated and validated a set of five Bacillus subtilis promoters fused to the firefly luciferase reporter gene suitable for cell-based screening, enabling the as yet most-comprehensive high-throughput diagnosis of antibiotic interference in the major biosynthetic pathways of bacteria: the biosynthesis of DNA by the yorB promoter, of RNA by the yvgS promoter, of proteins by the yheI promoter, of the cell wall by the ypuA promoter, and of fatty acids by the fabHB promoter. The reporter cells mainly represent novel antibiotic biosensors compatible with high-throughput screening. We validated the strains by developing screens with a set of 14,000 pure natural products, representing a source of highly diverse chemical entities, many of them with antibiotic activity (6% with anti-Bacillus subtilis activity of ≤25 μg/ml]). Our screening approach is exemplified by the discovery of classical and novel DNA synthesis and translation inhibitors. For instance, we show that the mechanistically underexplored antibiotic ferrimycin A1 selectively inhibits protein biosynthesis

Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

AIM: To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells

CT or Invasive Coronary Angiography in Stable Chest Pain.

Background: In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain. Methods: We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris. Results: Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P = 0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48). Conclusions: Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229.)