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In Parkinson''s disease, the long-term use of dopamine replacing agents is associated with the development of motor complications; therefore, there is a need for non-dopaminergic drugs. This study evaluated the potential therapeutic impact of six different NR2B and A2A receptor antagonists given either alone or in combination in unilateral 6-OHDA-lesioned rats without (monotherapy) or with (add-on therapy) the co-administration of L-Dopa: Sch-58261+ Merck 22; Sch-58261+Co-101244; Preladenant + Merck 22; Preladenant + Radiprodil; Tozadenant + Radiprodil; Istradefylline + Co-101244. Animals given monotherapy were assessed on distance traveled and rearing, whereas those given add-on therapy were assessed on contralateral rotations. Three-way mixed ANOVA were conducted to assess the main effect of each drug separately and to determine whether any interaction between two drugs was additive or synergistic. Additional post hoc analyses were conducted to compare the effect of the combination with the effect of the drugs alone. Motor activity improved significantly and was sustained for longer when the drugs were given in combination than when administered separately at the same dose. Similarly, when tested as add-on treatment to L-Dopa, the combinations resulted in higher levels of contralateral rotation in comparison to the single drugs. Of special interest, the activity observed with some combinations could not be described by a simplistic additive effect and involved more subtle synergistic pharmacological interactions. The combined administration of A2A/NR2B-receptor antagonists improved motor behaviour in 6-OHDA rats. Given the proven translatability of this model such a combination may be expected to be effective in improving motor symptoms in patients. 相似文献
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Dieter Seidel Ina Pinker Klaus Richter 《Archives Of Phytopathology And Plant Protection》2013,46(6):529-535
Karl Esser: Kryptogamen 1. Cyanobacterien, Algen, Pilze, Flechten. Praktikum und Lehrbuch. Dritte, wesentlich überarbeitete Auflage. 585 S., 300 Abb., Springer‐Verlag Berlin, Heidelberg 2000. Preis: 129.00 DM, ISBN 3–540–66451–3 Jain, S. M., Gupta, R. J., Newton, R. J. (Eds.): Somatic Embryogenesis in Woody Plants. Kluwer Academic Publishers Dordrecht 1999, Vol. 2, 547 S Vanneste, J. L. (Ed.): FIRE Blight: The Disease and its Causative Agent, Erwinia amylovora. CABI Publishing, CAB International, Oxon, UK, 2000, 370 p., 16 color plates, 38 figures, 25 tables, 6 boxes, Price US$120.00, ISBN 0 85199 294 3 Heitefuss, R. Pflanzenschutz. Grundlagen der praktischen Phytomedi‐zin. 3., neubearbeitete und erweiterte Auflage. Georg Thieme Verlag Stuttgart. 2000, 399 S., 94 Abb., 22 Tab., Preis 49.90 DM, ISBN 313 5133036/650 L. Benzing, Der sachkundige Vorratsschützer. Sachkunde für Anwender und Abgebende von Vorratsschutzmitteln. Agrimedia Spithal, 2000, 158 S., 32 farbige Abb., 14 schwarz ‐ weiße Abb., 23 Tab.. Preis: 78 DM, ISBN 3–86037–115–0 相似文献
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Martin Pckert Adrien Favre Jan Schnitzler Jochen Martens Yue‐Hua Sun Dieter Thomas Tietze Frank Hailer Ingo Michalak Patrick Strutzenberger 《Ecology and evolution》2020,10(17):9283-9300
Encompassing some of the major hotspots of biodiversity on Earth, large mountain systems have long held the attention of evolutionary biologists. The region of the Qinghai‐Tibet Plateau (QTP) is considered a biogeographic source for multiple colonization events into adjacent areas including the northern Palearctic. The faunal exchange between the QTP and adjacent regions could thus represent a one‐way street (“out of” the QTP). However, immigration into the QTP region has so far received only little attention, despite its potential to shape faunal and floral communities of the QTP. In this study, we investigated centers of origin and dispersal routes between the QTP, its forested margins and adjacent regions for five clades of alpine and montane birds of the passerine superfamily Passeroidea. We performed an ancestral area reconstruction using BioGeoBEARS and inferred a time‐calibrated backbone phylogeny for 279 taxa of Passeroidea. The oldest endemic species of the QTP was dated to the early Miocene (ca. 20 Ma). Several additional QTP endemics evolved in the mid to late Miocene (12–7 Ma). The inferred centers of origin and diversification for some of our target clades matched the “out of Tibet hypothesis’ or the “out of Himalayas hypothesis” for others they matched the “into Tibet hypothesis.” Three radiations included multiple independent Pleistocene colonization events to regions as distant as the Western Palearctic and the Nearctic. We conclude that faunal exchange between the QTP and adjacent regions was bidirectional through time, and the QTP region has thus harbored both centers of diversification and centers of immigration. 相似文献
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David Pretzel Stefanie Linss Hannes Ahrem Michaela Endres Christian Kaps Dieter Klemm Raimund W Kinne 《Arthritis research & therapy》2013,15(3):R59