169 research outputs found

    Role of protein kinase C in inhibition of renin release caused by vasoconstrictors

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    It was the aim of the present study to get insight into some of the intracellular mechanisms by which the vasoconstrictor hormones angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine (NE) inhibit renin release from renal juxtaglomerular cells. To this end a primary cell culture from rat renal cortex was established that consisted of 50% juxtaglomerular cells. The cultured juxtaglomerular cells contained prominent renin granules closely resembling those in the intact kidney and responded to a number of stimuli of renin release. By using these cultures, we found that ANG II (10(-7) M), AVP (10(-6) M), and NE (10(-5) M) inhibited renin release and increased the calcium permeability of the plasma membrane of the cultured cells. Both the effects on renin release and on calcium permeability could be diminished or even be abolished by the calcium channel blocker verapamil (Vp) (10(-5) M). ANG II, AVP, and NE led to an increased formation of diacylglycerol (DAG), a well-known stimulator of protein kinase C (PKC). Moreover, a direct stimulation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) (10(-8)-10(-6) M) also inhibited renin release and increased the calcium permeability of the cell membrane. Similar to ANG II, AVP, and NE, the effects of TPA on calcium permeability and renin release could be diminished by Vp. In conclusion, these results point toward a common mechanism by which vasoconstrictors inhibit renin release from renal juxtaglomerular cells: ANG II, AVP, and NE activate a phospholipase C, which generates DAG.(ABSTRACT TRUNCATED AT 250 WORDS

    Heme oxygenase-1 and its metabolites affect pancreatic tumor growth in vivo

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    <p>Abstract</p> <p>Background</p> <p>Pancreatic cancer (PaCa) is a fatal human cancer due to its exceptional resistance to all current anticancer therapies. The cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly overexpressed in PaCa and seems to play an important role in cancer resistance to anticancer treatment. The inhibition of HO-1 sensitized PaCa cells to chemo- and radiotherapy <it>in vitro</it>.</p> <p>Therefore, we investigated the effects of HO-1 and its metabolites biliverdin, carbon monoxide and iron on PaCa cells.</p> <p>PaCa cell lines with divergent HO-1 expression patterns were used in a murine orthotopic cancer model. HO-1 expression and activity was regulated by zinc (inhibition) and cobalt (induction) protoporphyrin. Furthermore, the influence of cellular HO-1 levels and its metabolites on effects of standard chemotherapy with gemcitabine was tested <it>in vivo </it>and <it>in vitro</it>.</p> <p>Results</p> <p>High HO-1 expression in PaCa cell lines was associated with increased chemoresistance <it>in vitro</it>. Chemoresistance to gemcitabine was increased during HO-1 induction in PaCa cells expressing low levels of HO-1. The inhibition of HO-1 activity in pancreatic tumors with high HO-1 boosted chemotherapeutic effects <it>in vivo </it>significantly. Furthermore, biliverdin and iron promoted PaCa resistance to chemotherapy. Consequently, specific iron chelation by desferrioxamine revealed profound anticancerous effects.</p> <p>Conclusion</p> <p>In summary, the inhibition of HO-1 and the chelation of iron in PaCa cells were associated with increased sensitivity and susceptibility of pancreatic tumors to chemotherapy <it>in vivo</it>. The metabolites biliverdin and iron seem to be involved in HO-1-mediated resistance to anticancer treatment. Therefore, HO-1 inhibition or direct interference with its metabolites may evolve new PaCa treatment strategies.</p

    Functional implications of ontogenetically and sexually dimorphic dentition in the eastern shovelnose ray, Aptychotrema rostrata

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    Unlike other elasmobranchs, batoids exhibit sexually dimorphic dentition. The functional implications of such dentition, however, remain understudied. For the present study, ontogenetic and sexual dimorphism in tooth and jaw structure, together with the functional implications of this dimorphism, were determined in the eastern shovelnose ray, Aptychotrema rostrata. Sexually dimorphic dentition and jaw structure was first observed in sub-adult age classes, with males developing a pronounced lower jaw at the symphysis. Monognathic heterodonty was prominent in mature males, with teeth in the symphyseal region developing significantly greater heights and sharpness ratios in comparison to females. Ex vivo mechanical grip strength tests were used to determine simulated bite-grip tenacity. The mean peak pull-out forces required to withdraw a section of a dissected pectoral fin from between jaws closed with a constant occlusal force was highest for mature males, intermediate for mature females and lowest for immature females and males. Although the species exhibits ontogenetic variations in diet, these were unrelated to sex. Rather, the larger and highly cuspidate teeth of mature males increased the bite-grip tenacity, which likely aids in copulation

    Oskar Nobiling an Hugo Schuchardt (01-07923)

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    Oskar Nobiling an Hugo Schuchardt (02-07924)

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    Ausstellungen als Medium für die Gesundheitsförderung? - Eine Darstellung am Beispiel der Ausstellung Riesenküche zum Thema Kindersicherheit

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    Noch immer gelten 60% der Kinderunfälle als vermeidbar (vgl. Schriever 1997). Dennoch fehlt der Thematik Kindersicherheit bisher auf der gesundheitspoli-tischen Tagesordnung in Deutschland eine entsprechende Lobby. Die BAG hat sich des Themas Kindersicherheit angenommen und hat damit eine bundesweit anerkannte Institution geschaffen, die seit knapp zehn Jahren erfolgreich auf dem Gebiet der Kindersicherheit und Unfallprävention im Bereich Heim und Freizeit tätig ist. Ebenso ist das Thema Kindersicherheit und Familie für die TK von großer Relevanz, da sie für ihre Versicherten primärpräventive Maßnahmen sowie Setting-Maßnahmen nach §20 SGB V anbietet. Ausstellungen sind ein Medium, das die Gesundheitsaufklärung und -förderung etwa seit Beginn des 20. Jahrhunderts nutzt, um der Bevölkerung Botschaften und Informationen zu verschiedenen Gesundheitsthemen zu vermitteln. Mit einfachen, aber damals innovativen Darstellungsmöglichkeiten, z.B. anhand von gezeichneten Bildern, Graphen und Diagrammen, wurden der Bevölkerung die demographische Entwicklung der Bevölkerung, Zahlen der Säuglingssterblichkeit oder umfassende Hygieneausstellungen demonstriert. Die vorliegende Arbeit beschäftigt sich mit der Frage, ob Ausstellungen ein geeignetes Medium für die moderne Gesundheitsförderung sind. Um einen Themenbezug zu einem Gesundheitsthema herzustellen, wird diese Arbeit auf dem Hintergrund der Wanderausstellung Riesenküche zum Thema Kindersicherheit geschrieben, die 2004 im Rahmen einer Kooperation zwischen der TK und der BAG durchgeführt wurde

    Oskar Nobiling an Hugo Schuchardt (03-07925)

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