62 research outputs found
Endokrine Störungen verursacht durch Umweltchemikalien : Wirkungen auf Schlüsselenzyme des Steroidhormon-Metabolismus von Menschen und Tieren
No full textMany environmental chemicals are suspected of disturbing the human and animal endocrine system. These so-called endocrine disruptors can operate in many ways. The interaction of endocrine disruptive effects that eventually endanger human health is still unclear. However, one of the basic mecha-nisms of endocrine disruption is the inhibition of key enzymes in the hormone metabolism. In this study, we focused on the inhibitory potency of suspected endocrine disrupting compounds on aromatase (P450arom) and 5alpha-reductase (5alpha-Re) activities in human tissue and human cancer cells. Both enzymes are essential for the human sex steroid hormone metabolism. We were able to demonstrate that the organotin compounds tributyltin (TBT) and triphenyltin (TPT) are potent unspecific inhibitors of P450arom and 5alpha-Re activity. Prochloraz and fenarimol inhibited P450arom activity at low concentrations (IC5010 µM). While the human tissue assay proved to be more practical and sensitive as a screening tool for putative endocrine disruptors, the cell assay reflected partly the situation in vivo. In another experimental series, we investigated the inhibitory effect of TPT on P450arom, 5alpha-Re, 3beta-HSD type 2, 17beta-HSD type 1 and type 3 alone and in combination with the strong antioxidant dithioerythrithol (DTE). TPT inhibited unspecifically all enzymes that were tested. The experiments also showed that DTE is able to compensate the adverse effects of TPT, and that the effectiveness of the compensatory activity of DTE differs among the enzymes investigated. The suppressed 5alpha-Re activity could not be reactivated with DTE. Conceivably, cysteine residues that are responsible for the tertiary and quarternary structure of the enzyme are critical targets for TPT. A human sampling study was undertaken with the COMPRENDO partner in Gdansk. 60 Polish and 15 German blood samples were investigated for chemical residues and sex hormone concentrations. In addition, 15 placenta samples from Poland and Germany, respectively, were tested for chemical residues, P450arom activities and CYP19 mRNA contents. The chemical analysis was performed by the COMPRENDO partners in Milan (p,p´DDE), Orleans (TBT and TPT) and Ioannina (diuron, fenarimol, linuron und vinclozolin). The results showed that individual sex hormone concentrations in blood were not correlated with chemical body burden. The detected differences in sex hormone concentrations, specific aromatase activity and relative CYP19 mRNA content of Polish and German donors were presumably the result of other factors than the ones determined in this study. Another task of the EU-project was the investigation of the effects of chemical exposure of the aquatic model organisms Pimephales promelas, Rutilus rutilus and Xenopus laevis. We investigated the specific P450arom and 5alpha-Re activities in brain and gonads of the animals. During the qualitative investigation of the androgen metabolism in Xenopus laevis brain, 5alpha-reductase activity was discovered for the first time. In contrast to the inhibitory potency of TPT discovered in our enzyme assays, TPT exposure of aquatic model organisms had no observed effect on enzyme activity in the organs investigated, except for P450arom activities in female gonads of Pimephales promelas at 320 ng TPT/L. In this group, mean P450arom activities were elevated, possibly as a result of an overshooting upregulation due to the inhibition of P450arom by TPT. The exposure of Rutilus rutilus and Xenopus laevis to the effector substances methyltestosterone and letrozole resulted in slightly different mean enzyme activities compared to the control group. In conclusion, many of the tested pesticides are able to inhibit P450arom and 5alpha-Re, and thus might be of clinical relevance. However, results are not always coherent, and possible risks for human and wildlife health are therefore difficult to predict. Risk assessment will require large studies with an additional number of short and long term in vitro and in vivo assays. Any extrapolation to humans should be very meticulously performed.Viele Umweltchemikalien stehen im Verdacht, das endokrine System von Menschen und Tieren zu schädigen. Diese sogenannten endokrinen Disruptoren können auf verschiedene Weise wirken. Das Zusammenspiel der verschiedenen endokrinen Wirkungen, welches letztendlich zu einer Beeinträchtigung der Gesundheit führt, ist bis jetzt noch unklar. Einer der wesentlichen Faktoren für endokrine Schädigung ist jedoch die Inhibition von Schlüsselenzymen im Hormonmetabolismus, die in der vorliegenden Arbeit untersucht wird. In erster Linie wurde die inhibitorischen Wirkung potentieller endokriner Disruptoren auf die Aktivität von Aromatase (P450arom) und 5alpha-Reduktase (5alpha-Re) in menschlichen Geweben und humanen Krebszellen untersucht. Diese beiden Enzyme sind für den humanen Sexualsteroid-hormon-Metabolismus unerlässlich. Die Organozinnverbindungen Tributylzinn (TBT) und Triphenylzinn (TPT) wurden als starke unspezifische Inhibitoren der P450arom und 5alpha-Re identifiziert. Prochloraz und Fenarimol hemmten die P450arom- Aktivität bereits bei niedrigen Konzentrationen (IC5010 µM). Als Screening-Test für endokrine Disruptoren erwies sich der Gewebe-Enzymtest als überaus geeignet, da er empfindlich reagiert und einfach zu handhaben ist. Dagegen spiegelt der Krebszell-Enzymtest zu einem gewissen Teil die Situation in vivo wider. In einer weiteren Studie wurde die inhibitorische Wirkung von TPT auf die Enzyme P450arom, 5alpha-Re, 3beta-HSD Typ 2, 17beta-HSD Typ 1 und Typ 3 allein und in Kombination mit dem starken Antioxidanz Dithioerythritol (DTE) untersucht. TPT hemmte unspezifisch alle getesteten Enzyme in ihrer Aktivität. Die Untersuchungen zeigten außerdem, dass DTE den schädigenden Effekt von TPT kompensieren kann und dass dieser schützende Effekt unterschiedlich stark bei den getesteten Enzymen ist. Die TPT-supprimierte 5alpha-Re-Aktivität konnte durch den Einsatz von DTE nur teilweise wiederhergestellt werden. Die Ergebnisse führen zu der Vermutung, dass Cysteinreste, die durch die Ausbildung von Disulfidbrücken entscheidend für die Tertiär- und Quartärstruktur des Enzyms sind, einen kritischen Angriffspunkt für TPT darstellen. Im Rahmen des EU-Projekts COMPRENDO wurde ein Human-Biomonitoring mit unseren Partnern in Danzig durchgeführt. Blutproben von 60 Probanden in Polen und 15 Probanden in Deutschland wurden auf Chemikalien-rückstände und Konzentrationen von Sexualhormonen getestet. Außerdem wurden je 15 Plazentaproben aus Polen und Deutschland auf Chemikalienrückstände, spezifische P450arom-Aktivität und CYP19 mRNA-Gehalt untersucht. Die Chemikalienanalyse wurde von COMPRENDO-Partnern in Mailand (p,p´DDE), Orleans (TBT und TPT) und Ioannina (Diuron, Fenarimol, Linuron und Vinclozolin) durchgeführt. Im Ergebnis zeigt sich, dass individuelle Sexualhormon-Konzentrationen im Blut mit den jeweiligen Chemikalienrückständen nicht korrelierten. Für die Unterschiede der Sexualhormon-Konzentrationen, der spezifischen P450arom-Aktivität und des relativen CYP19-Gehalts, die zwischen den beiden Gruppen in Polen und Deutschland gemessen wurden, sind daher andere Faktoren verantwortlich als die hier gemessenen. Eine weitere gemeinsam mit EU-Partnern durchgeführte Studie sollte Aufschluss über die Wirkung einer Chemikalienexposition auf die aquatischen Modellorganismen Xenopus laevis, Rutilus rutilus und Pimephales promelas geben. Es wurden die spezifischen Enzymaktivitäten in den Gehirnen und Gonaden der Tiere untersucht. Bei der qualitativen Untersuchung des Androgenmetabolismus im Gehirn von Xenopus laevis wurde zum ersten mal 5beta-Reduktase-Aktivität nachgewiesen. Im Unterschied zur starken inhibitorischen Wirkung von TPT in unseren Enzymtests fanden wir keine veränderten P450arom- oder 5alpha-Re-Aktivitäten in den untersuchten Organen, außer in den Ovarien von Pimephales promelas, die einer Konzentration von 320 ng TPT/L ausgesetzt waren. In dieser Gruppe war die mittlere P450arom-Aktivität erhöht, wahrscheinlich durch eine überschießende Hochregulierung, die durch die Inhibition durch TPT ausgelöst wurde. Die Substanzen Methyltestosteron und Letrozol führten im Vergleich zur Kontrollsubstanz Ethanol zu veränderten Enzymaktivitäten bei Rutilus rutilus und Xenopus laevis. Mehrere der getesteten Chemikalien inhibieren die P450arom- und/oder die 5alpha-Re-Aktivität und können daher von klinischer Relevanz sein. Allerdings sind die Ergebnisse der verschiedenen Experimente nicht immer einheitlich, daher lassen sich Schlussfolgerungen möglicher Gefahren für den Menschen und Tiere nur schwer ziehen. Für eine bessere Risikoabschätzung werden Studien mit verschiedenen in vitro und in vivo Kurz- und Langzeit-Testsysteme benötigt. Jede Extrapolation auf den Menschen sollte jedoch immer mit größter Sorgfalt erfolgen
Jazz: But just a sample for Expo
No full textLocations: Expo Theatre; Canada Pavilion; New York Theatre; Robson Square Cinema; Western Front off site; 86th Street. "VEJI"; "Skywalk"; "Fred Stride and the Westcoast Jazz Orchestra"; Paul Horn (sax, flute); "Phil Dwyer (sax) Quintet"; "Paul Plimley (piano, vibes) Octet"; "Dave Quarin (sax) and Gettin' Off Easy"; "Fraser MacPherson Quartet"; P.J. Perry; "Lloyd Arntzen Classic Jazz Band and Hasselbach"; "Badazjazz"; Miles Davis (tpt); Wynton Marsalis (tpt); "Dollar Brand"; "Ekaya"; "Kollektief"; Karen Young (vox); Michel Donato (bass); "Wondeur Brass"; Salome Bey (vox); Kenny Wheeler (tpt); Hugh Fraser (piano); "Bill Smith (reeds) Ensemble"; "Pat LaBarbara (ts) Quartet"; Peter Leitch (guitar) Quartet"; "UZEB"
Economics : an expert's insight on the issue in Arizona
No full textabstract: The transaction privilege tax (TPT), often referred to as the sales tax, is a major source of revenue for state and local governments in Arizona. The TPT is applied to numerous categories, such as contracting and utilities. The analysis in this paper is limited to the retail category, which accounts for half of the TPT collected by state government, and the restaurant and bar category, which contributes one-tenth of the TPT revenue.Indicator insight ; v. 4, issue 2
Part 2: Starke Hathaway: Author of the Original MMPI
No full textThe video conversation was filmed at Twin Cities Public Television (TPT) in St. Paul, Minnesota in March 2016. The University of Minnesota Press has made the seven video segments available for instructors to use in assessment courses.In "A Conversation about the MMPI with Yossef Ben-Porath and Auke Tellegen" part two (of seven), authors Ben-Porath and Tellegen discuss original MMPI author Starke Hathaway's work with the test over the years and his hopes for modernizing it, as well as his pioneering vision and many talents in psychology and cognitive behavioral therapy.Ben-Porath, Yossef S.; Tellegen, Auke. (2016). Part 2: Starke Hathaway: Author of the Original MMPI. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/187608
National Evaluation Report of the Joint Assessment and Monitoring Programme of the Netherlands 1999
No full textThe Netherlands participates in the Joint Assessment and Monitoring Programme (JAMP) of the Oslo and Paris Commissions. This report gives the results of the Dutch contribution to the programme for the year 1999. An overview of the national JAMP programme is given in figure 1. This figure is a map of the Dutch part of the continental shelf showing the sampling locations. Table 1 presents the frequency of sampling and analysis of the various contaminants in the different compartments. Table 2 presents all parameters measured in the different compartments. Data on supporting parameters, nutrients, metals and organic contaminants in water and biota are presented and discussed. Tributyltin in water from inland marinas has been monitored ever since 1990. From the resultant data it is clear that there has been a decrease in TBT since the ban on the use of TBT on vessels measuring less than 25 metres. Recent data on TBT from the monitoring of sediment indicate high concentrations of tributyl and triphenyltin in all Dutch marine waters. TBT concentrations measured range between 10 and 240 ?g TBT/kg sediment normalised to 5% organic Carbon. This implies that the Dutch target value MTR (Maximum Tolerable Risk) laid down in the Fourth National Policy Document on Water Management is being exceeded by a factor 80-300. The highest TPT concentration was about 100 ?g TPT/kg sediment normalised to 5% organic Carbon, whilst the lowest values were below the detection limit (1 ?g TPT/kg). Fish disease monitoring has been included in the programme since 1991, but no results are presented in this report. The report describes the quality assurance programme of the Dutch laboratories and gives details of detection limits and participation in QUASIMEME exercises.JAM
National Evaluation Report of the Joint Assessment and Monitoring Programme of the Netherlands 2000
No full textThe Netherlands participates in the Joint Assessment and Monitoring Programme (JAMP) of the Oslo and Paris Commissions. This report gives the results of the Dutch contribution to the programme for the year 2000. An overview of the national JAMP programme is given in figure 1. This figure is a map of the Dutch part of the continental shelf showing the sampling locations. Table 1 presents the frequency of sampling and analysis of the various contaminants in the different compartments. In Table 12 the sediment sampling locations are presented (not shown in figure 1). Table 2 presents all parameters measured in the different compartments. Data on supporting parameters, nutrients, metals and organic contaminants in water and biota are presented and discussed. Tributyltin in water from inland marinas has been monitored ever since 1990. From the resultant data it is clear that there has been a decrease in TBT since the ban on the use of TBT on vessels measuring less than 25 metres. Recent data on TBT from the monitoring of sediment indicate high concentrations of tributyl and triphenyltin in all Dutch marine waters. TBT concentrations measured range between 10 and 240 ?g TBT/kg sediment normalised to 5% organic Carbon. This implies that the Dutch target value MTR (Maximum Tolerable Risk) laid down in the Fourth National Policy Document on Water Management is being exceeded by a factor 80-300. The highest TPT concentration was about 100 ?g TPT/kg sediment normalised to 5% organic Carbon, whilst the lowest values were below the detection limit (1 ?g TPT/kg). Fish disease monitoring has been included in the programme since 1991, but no results are presented in this report. The report describes the quality assurance programme of the Dutch laboratories and gives details of detection limits and participation in QUASIMEME exercises
IVT topotecan preferentially slows leptomeningeal tumor growth in brains <i>versus</i> spines.
No full textBioluminescence of brains and spines calculated at each time point up to the first death in each group. Shown: mean ± SEM for each group. (A) Ratios of spine-to-brain radiance measurements illustrate the relatively-faster increase in spine radiance compared to brain radiance in IVT TPT groups compared to the non-IVT groups. (B) Brain radiance measurements reveal more effective suppression of tumor growth in brains of TPT IP mice compared to saline IP in brains of TPT IVT (bolus or pump) mice compared to TPT IP and in brains of TPT IVT bolus mice compared to TPT IVT pump. (C) Spine radiance measurements reveal more effective tumor growth suppression in spines of TPT IVT bolus mice compared to TPT IP mice. There was a trend toward significance in spines of mice treated with TPT IVT bolus compared to TPT IVT pump, but it did not reach significance levels. p-values were calculated for each two groups using unpaired t-tests at each of the time points.</p
Contrasts between maximum power transfer and maximum efficiency
No full textProfessor Lawrence Hmurcik's article discussing power transfer and efficiency published in "The Physics Teacher".Copyright 1986 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics.The following article appeared in The Physics Teacher volume 24 issue 8 and may be found at http://scitation.aip.org/content/aapt/journal/tpt/24/8/10.1119/1.2342101http://scitation.aip.org/content/aapt/journal/tpt/24/8/10.1119/1.234210
Triptolide regulates T cell-mediated immunity via induction of CD11c(low) dendritic cell differentiation
No full textTriptolide(TPT) isolated from one of the Chinese herbs, Tripterygium wilfordii Hook. F. (TWHF), are known to have a variety of immunomodulatory activities. This study was performed to investigate the effect of TPT on the differentiation of splenic DCs and its influence on T cell-mediated immunity regarding to DC subsets CD11c(low)I-a/e(low)CD45RB(+)(CD11c(low) DCs) and CD11c(high)I-a/e(high)CD45RB(-) (CD11c(high) DCs) in male C57BL/6 mice spleens in vitro. The percentage of CD11c(low) DCs was significantly increased after treatment with TPT compared to their counterparts (CD11c(high) DCs). It was found that unlike the gradually decreasing interleukin (IL)-12 secretion of CD11c(high) DCs induced by TPT, CD11c(low) DCs showed a obvious dose-dependent response between the increasing of IL-10 production and TPT stimulation. After treatment with anti-IL-12R or anti-IL-10 monoclonal antibody in CD4(+) T cells + CD11c(high) DCs or CD11c(low) DCs mixed lymphocyte reaction, the induction of these DCs on T cells was inhibited dramatically. These data demonstrated that TPT might induce the differentiation of splenic DCs to CD11c(low) DCs followed by shifting of Th1 to Th2 with enhancement of T lymphocyte immune function in vitro. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.Food Science & TechnologyToxicologySCI(E)0ARTICLE72560-25645
Highly crystalline covalent organic frameworks from flexible building blocks
No full textTwo novel 2D covalent organic frameworks (TPT-COF-1 and TPT-COF-2) were synthesized from the flexible 2,4,6-triaryloxy-1,3,5-triazine building blocks on a gram scale, which show high crystallinity and large surface area. The controllable formation of highly ordered frameworks is mainly attributed to the self-assembly Piedfort unit of 2,4,6-triaryloxy-1,3,5-triazine.MOST of China [2011CB932501, 2013CB834504]SCI(E)[email protected]; [email protected]; [email protected]; [email protected]
- …
