In Vitro Metabolism of Six C-Glycosidic Flavonoids from Passiflora incarnata L.

Several medical plants, such as Passiflora incarnata L., contain C-glycosylated flavonoids, which may contribute to their efficacy. Information regarding the bioavailability and metabolism of these compounds is essential, but not sufficiently available. Therefore, the metabolism of the C-glycosylated flavones orientin, isoorientin, schaftoside, isoschaftoside, vitexin, and isovitexin was investigated using the Caco-2 cell line as an in vitro intestinal and epithelial metabolism model. Isovitexin, orientin, and isoorientin showed broad ranges of phase I and II metabolites containing hydroxylated, methoxylated, and sulfated compounds, whereas schaftoside, isoschaftoside, and vitexin underwent poor metabolism. All metabolites were identified via UHPLC-MS or UHPLC-MS/MS using compound libraries containing all conceivable metabolites. Some structures were confirmed via UHPLC-MS experiments with reference compounds after a cleavage reaction using glucuronidase and sulfatase. Of particular interest is the observed cleavage of the C–C bonds between sugar and aglycone residues in isovitexin, orientin, and isoorientin, resulting in unexpected glucuronidated or sulfated luteolin and apigenin derivatives. These findings indicate that C-glycosidic flavones can be highly metabolized in the intestine. In particular, flavonoids with ortho-dihydroxy groups showed sulfated metabolites. The identified glucuronidated or sulfated aglycones demonstrate that enzymes expressed by Caco-2 cells are able to potentially cleave C–C bonds in vitro

Novel selective butyrylcholinesterase inhibitors incorporating antioxidant functionalities as potential bimodal therapeutics for Alzheimer’s Disease

Isosorbide-2-carbamates-5-aryl esters are highly potent and very selective butyrylcholinesterase inhibitors. The objective of the present work was to address the hypothesis that the isosorbide-aryl-5-ester group could be replaced with an antioxidant functionality while maintaining inhibitor effects and selectivity. We successfully incorporated ferulic acid or lipoic acid groups producing potent selective inhibitors of butyrylcholinesterase (BuChE). The hybrid compounds were non-toxic to the murine hippocampal cell line HT-22 and lipoate esters were neuroprotective at 10 and 25 mu M when the cells were challenged with glutamate (5 mM) in a similar manner to the positive control quercetin. The benzyl carbamate 7a was a potent inhibitor of BuChE (IC50 150 nM) and it was effective in reducing glutamate toxicity to neuronal cells at >5 mu M. Representative compounds exhibited an antioxidant effect in the oxygen radical absorbance capacity assay as the lipoate 7d was not active, whereas the ferulate 8a showed a weak, but significant, activity with 0.635 +/- 0.020 Trolox Equivalent

Grenzüberschreitender Öffentlicher Verkehr - immer noch Barrieren trotz EU

Der Beitrag befasst sich mit dem Ausbau des grenzüberschreitenden Verkehrs innerhalb der EU. Trotz jahrelanger Bestrebungen im Bereich des grenzüberschreitenden Verkehrs durch die Verkehrs- und Kohäsionspolitik bestehen nach wie vor in vielen Grenzregionen Herausforderungen in Bezug auf Verkehrsinfrastruktur und Öffentlichen Verkehr. Diese werden im ersten Teil des Beitrags beleuchtet. Danach werden die verkehrspolitischen Ziele und Instrumente auf EU-Ebene präsentiert, die anschließend anhand von Fallbeispielen im Grenzraum auf ihren Einfluss überprüft werden. Die EU-Politik und die Förderinstrumente sind wenig konkret und verbindlich, sodass in der nationalen Politik der Mitgliedsstaaten nach wie vor große Unterschiede herrschen. Wichtig für die Umsetzung sind ein starker politischer Wille und eine gesicherte Finanzierung. Verkehr ist eine wichtige Basis für andere Bereiche in der grenzüberschreitenden Zusammenarbeit. Es sollte daher nachhaltig in dieses Schlüsselfeld investiert werden.This paper is concerned with the extension of cross-border transport within the EU. Despite the longstanding efforts of transport and cohesion policies to improve cross-border transport, many border regions still face challenges related to transport infrastructure and local public transportation. These are discussed in the first part of the paper. Transport policy goals and instruments on the EU level are then presented and their impact is assessed using case studies in the border area. EU policy and funding instruments are neither particularly concrete nor binding, so that there are still great variations between the national policies of member states. Implementation requires strong political will and secure finance. Transport is an important foundation for other fields of cross-border cooperation. Sustained investment in this key area is therefore necessary

Diagnostic performance of the urinary canine calgranulins in dogs with lower urinary or urogenital tract carcinoma

Abstract Background Onset of canine transitional cell carcinoma (TCC) and prostatic carcinoma (PCA) is usually insidious with dogs presenting at an advanced stage of the disease. A biomarker that can facilitate early detection of TCC/PCA and improve patient survival would be useful. S100A8/A9 (calgranulin A/B or calprotectin) and S100A12 (calgranulin C) are expressed by cells of the innate immune system and are associated with several inflammatory disorders. S100A8/A9 is also expressed by epithelial cells after malignant transformation and is involved in the regulation of cell proliferation and metastasis. S100A8/A9 is up-regulated in human PCA and TCC, whereas the results for S100A12 have been ambiguous. Also, the urine S100A8/A9-to-S100A12 ratio (uCalR) may have potential as a marker for canine TCC/PCA. Aim of the study was to evaluate the diagnostic accuracy of the urinary S100/calgranulins to detect TCC/PCA in dogs by using data and urine samples from 164 dogs with TCC/PCA, non-neoplastic urinary tract disease, other neoplasms, or urinary tract infections, and 75 healthy controls (nested case-control study). Urine S100A8/A9 and S100A12 (measured by species-specific radioimmunoassays and normalized against urine specific gravity [S100A8/A9USG; S100A12USG], urine creatinine concentration, and urine protein concentration and the uCalR were compared among the groups of dogs. Results S100A8/A9USG had the highest sensitivity (96%) and specificity (66%) to detect TCC/PCA, with specificity reaching 75% after excluding dogs with a urinary tract infection. The uCalR best distinguished dogs with TCC/PCA from dogs with a urinary tract infection (sensitivity: 91%, specificity: 60%). Using a S100A8/A9USG ≥ 109.9 to screen dogs ≥6 years of age for TCC/PCA yielded a negative predictive value of 100%. Conclusions S100A8/A9USG and uCalR may have utility for diagnosing TCC/PCA in dogs, and S100A8/A9USG may be a good screening test for canine TCC/PCA

Essential Oils as Multicomponent Mixtures and Their Potential for Human Health and Well-Being

Essential oils (EOs) and their individual volatile organic constituents have been an inherent part of our civilization for thousands of years. They are widely used as fragrances in perfumes and cosmetics and contribute to a healthy diet, but also act as active ingredients of pharmaceutical products. Their antibacterial, antiviral, and anti-inflammatory properties have qualified EOs early on for both, the causal and symptomatic therapy of a number of diseases, but also for prevention. Obtained from natural, mostly plant materials, EOs constitute a typical example of a multicomponent mixture (more than one constituent substances, MOCS) with up to several hundreds of individual compounds, which in a sophisticated composition make up the property of a particular complete EO. The integrative use of EOs as MOCS will play a major role in human and veterinary medicine now and in the future and is already widely used in some cases, e.g., in aromatherapy for the treatment of psychosomatic complaints, for inhalation in the treatment of respiratory diseases, or topically administered to manage adverse skin diseases. The diversity of molecules with different functionalities exhibits a broad range of multiple physical and chemical properties, which are the base of their multi-target activity as opposed to single isolated compounds. Whether and how such a broad-spectrum effect is reflected in natural mixtures and which kind of pharmacological potential they provide will be considered in the context of ONE Health in more detail in this review

S100A12 concentrations and myeloperoxidase activity in the intestinal mucosa of healthy dogs

Background: Relatively few laboratory markers have been evaluated for the detection or monitoring of intestinal inflammation in canine chronic enteropathies, including inflammatory bowel disease (IBD). Previous research found that the intestinal mucosal levels of S100A12 and myeloperoxidase (MPO), as biomarkers of gut inflammation, were elevated in human patients with IBD. To date, the S100A12 and MPO levels in intestinal mucosal samples from either healthy dogs or from dogs suffering from IBD remain unreported. Therefore, this study aimed to evaluate the mucosal S100A12 and MPO levels in four different parts of the intestine (duodenum, jejunum, ileum and colon) in 12 healthy laboratory Beagle dogs using the ELISA and spectrophotometric methods, respectively. Results: Based on histological examinations, the recorded findings for all the samples were considered normal. The mucosal concentration of S100A12 in the ileum was significantly higher than in all other segments of the intestine (p <0.05). MPO activity was significantly higher in the ileal, jejunal and duodenal than in colonic mucosal samples (p <0.05). Moreover, its concentration was higher in the jejunum than in the duodenum. Conclusions: This study showed that S100A12 and MPO are reliably detectable in canine intestinal mucosa. The assays used appeared to be sufficient to further evaluate the role of S100A12 and MPO in the pathogenesis of canine chronic enteropathies, including IBD. These biomarkers may play a role in the initial detection of gut inflammation suggesting the need for further investigations to confirm IBD or to differentiate between IBD subtypes. Understanding the role of S100A12 and MPO in the pathogenesis of chronic intestinal inflammation in future may result in an improved understanding of canine chronic intestinal inflammation.Peer reviewe

Managing spatial sustainability trade-offs: The case of wind power

The deployment of onshore wind power involves spatial sustainability trade-offs, e.g., between the minimization of energy system costs, the mitigation of impacts on humans and biodiversity, and equity concerns. We analyze challenges arising for decision-making if wind power generation capacity has to be allocated spatially in the presence of such trade-offs. The analysis is based on a game developed for and played by stakeholders in Germany. The results of the game illustrate that there is no unanimously agreed ranking of sustainability criteria among the participating stakeholders. They disagreed not only on the weights of different criteria but also their definition and measurement. Group discussions further revealed that equity concerns mattered for spatial allocation. Yet, stakeholders used quite different concepts of equity. The results support the importance of transparent, multi-level and participatory approaches to take decisions on the spatial allocation of wind power generation capacity

Flächenpolitische Ziele unter Schrumpfungsbedingungen in der Kernregion Mitteldeutschland: normative überörtliche Aussagen im Spiegel der Fachdiskussion

Die derzeit in der Planungspraxis vorzufindende Ausweisung von Siedlungsflächen führt zu einer erheblichen Änderung der bisherigen Siedlungsstrukturen. Weiterhin tritt verstärkt das Problem des Bevölkerungsrückgangs und der Alterung auf. Sowohl im bundesdeutschen Durchschnitt, insbesondere aber in Ostdeutschland, sinkt damit die Nutzungsdichte. Die höhere Inanspruchnahme von Flächen für Siedlungs- und Verkehrszwecke führt außerdem zu einem Verlust einer nicht erneuerbaren Gutes und verändert das Landschaftsbild. Sowohl im Wohn- als auch im gewerblichen Bereich werden die vorhandenen Potenziale zu wenig genutzt. Während innerstädtische Flächen brachfallen, erfolgt die Ausweisung neuer Baugebiete im Außenbereich. Mit einem nachhaltigen regionalen Flächenmanagement sollen der Flächenverbrauch reduziert und eine zukunftsfähige Raumstruktur entwickelt werden. Vor der Diskussion geeigneter Instrumente ist eine kritische Auseinandersetzung mit den gegenwärtigen flächenpolitischen Zielen und deren Optimierung erforderlich. In diesem fünften Band der KoReMi-Schriftenreihe werden daher die flächenpolitischen Ziele unter Schrumpfungsbedingungen diskutiert. Dabei wird zunächst ein theoretischer flächenpolitischer Zielkatalog erarbeitet, der Handlungsziele und Maßnahmen enthält und eine Ableitung flächenpolitischer Strategien ermöglicht. Diesem Katalog werden die gegenwärtigen normativen Aussagen der Landes- und Regionalplanung in der Kernregion Mitteldeutschland gegenübergestellt. Die gewonnenen Erkenntnisse liefern eine wertvolle Grundlage für die Auseinandersetzung mit den gemeindlichen Entwicklungsperspektiven, die als Band 06 dieser Schriftenreihe veröffentlicht werden

Essential Oils as Multicomponent Mixtures and Their Potential for Human Health and Well-Being

Essential oils (EOs) and their individual volatile organic constituents have been an inherent part of our civilization for thousands of years. They are widely used as fragrances in perfumes and cosmetics and contribute to a healthy diet, but also act as active ingredients of pharmaceutical products. Their antibacterial, antiviral, and anti-inflammatory properties have qualified EOs early on for both, the causal and symptomatic therapy of a number of diseases, but also for prevention. Obtained from natural, mostly plant materials, EOs constitute a typical example of a multicomponent mixture (more than one constituent substances, MOCS) with up to several hundreds of individual compounds, which in a sophisticated composition make up the property of a particular complete EO. The integrative use of EOs as MOCS will play a major role in human and veterinary medicine now and in the future and is already widely used in some cases, e.g. , in aromatherapy for the treatment of psychosomatic complaints, for inhalation in the treatment of respiratory diseases, or topically administered to manage adverse skin diseases. The diversity of molecules with different functionalities exhibits a broad range of multiple physical and chemical properties, which are the base of their multi-target activity as opposed to single isolated compounds. Whether and how such a broad-spectrum effect is reflected in natural mixtures and which kind of pharmacological potential they provide will be considered in the context of ONE Health in more detail in this review

Hyperhomocysteinemia in greyhounds and its association with hypofolatemia and other clinicopathologic variables

Background: Folate and cobalamin are essential cofactors for homocysteine (HCY) metabolism. Hyperhomocysteinemia, a multifactorial condition, may reflect B vitamin deficiency and is associated with increased risk of cardiovascular disease, thrombosis, and neurodegenerative and chronic gastrointestinal diseases in humans. Hyperhomocysteinemia has been reported in Greyhounds with suspected chronic enteropathy. Objectives: To evaluate the frequencies of and the association between hypofolatemia and hyperhomocysteinemia in Greyhounds. Animals: Data and serum samples from 559 Greyhounds. Methods: Nested case-control study. The frequency of hypofolatemia in Greyhounds was determined by a laboratory database search. The relationship between hyperhomocysteinemia (measured by gas chromatography-mass spectrometry) and hypocobalaminemia and hypofolatemia was evaluated, and its frequency compared between healthy Greyhounds and Greyhounds with thrombosis or chronic diarrhea. Results: Hypofolatemia was identified in 172 of 423 (41%) Greyhounds and was more common in hypo- than in normocobalaminemic dogs (49% vs. 35%; P = .0064). Hyperhomocysteinemia was detected in 53 of 78 (68%) of Greyhounds, being more common in hypo- than in normofolatemic dogs (88% vs. 59%; P = .0175). All healthy Greyhounds, 21 of 30 (70%) of dogs with chronic diarrhea and 6 of 8 (75%) of those with thrombosis, were hyperhomocysteinemic. Serum HCY concentrations were inversely correlated with serum folate concentration (q = -0.28; P = .0386) and were positively associated with serum albumin concentration (q = 0.66; P = .0022). Conclusions and Clinical Relevance: Hyperhomocysteinemia occurs frequently in the Greyhound population. Its association with hypofolatemia suggests decreased intracellular availability of B vitamins, but the functional implications warrant further investigation. Hyperhomocysteinemia in Greyhounds potentially may serve as a spontaneous canine model to further investigate hyperhomocysteinemia in humans