TY  - JOUR
A1  - Bousquet, J.
A1  - Farrell, J.
A1  - Crooks, G.
A1  - Hellings, P.
A1  - Bel, E. H.
A1  - Bewick, M.
A1  - Chavannes, N. H.
A1  - Correia de Sousa, J.
A1  - Cruz, A. A.
A1  - Haahtela, T.
A1  - Joos, G.
A1  - Khaltaev, N.
A1  - Malva, J.
A1  - Muraro, A.
A1  - Nogues, M.
A1  - Palkonen, S.
A1  - Pedersen, S.
A1  - Robalo-Cordeiro, C.
A1  - Samolinski, B.
A1  - Strandberg, T.
A1  - Valiulis, A.
A1  - Yorgancioglu, A.
A1  - Zuberbier, T.
A1  - Bedbrook, A.
A1  - Aberer, W.
A1  - Adachi, M.
A1  - Agusti, A.
A1  - Akdis, C. A.
A1  - Akdis, M.
A1  - Ankri, J.
A1  - Alonso, A.
A1  - Annesi-Maesano, I.
A1  - Ansotegui, I. J.
A1  - Anto, J. M.
A1  - Arnavielhe, S.
A1  - Arshad, H.
A1  - Bai, C.
A1  - Baiardini, I.
A1  - Bachert, C.
A1  - Baigenzhin, A. K.
A1  - Barbara, C.
A1  - Bateman, E. D.
A1  - Beghé, B.
A1  - Ben Kheder, A.
A1  - Bennoor, K. S.
A1  - Benson, M.
A1  - Bergmann, K. C.
A1  - Bieber, T.
A1  - Bindslev-Jensen, C.
A1  - Bjermer, L.
A1  - Blain, H.
A1  - Blasi, F.
A1  - Boner, A. L.
A1  - Bonini, M.
A1  - Bonini, S.
A1  - Bosnic-Anticevitch, S.
A1  - Boulet, L. P.
A1  - Bourret, R.
A1  - Bousquet, P. J.
A1  - Braido, F.
A1  - Briggs, A. H.
A1  - Brightling, C. E.
A1  - Brozek, J.
A1  - Buhl, R.
A1  - Burney, P. G.
A1  - Bush, A.
A1  - Caballero-Fonseca, F.
A1  - Caimmi, D.
A1  - Calderon, M. A.
A1  - Calverley, P. M.
A1  - Camargos, P. A. M.
A1  - Canonica, G. W.
A1  - Camuzat, T.
A1  - Carlsen, K. H.
A1  - Carr, W.
A1  - Carriazo, A.
A1  - Casale, T.
A1  - Cepeda Sarabia, A. M.
A1  - Chatzi, L.
A1  - Chen, Y. Z.
A1  - Chiron, R.
A1  - Chkhartishvili, E.
A1  - Chuchalin, A. G.
A1  - Chung, K. F.
A1  - Ciprandi, G.
A1  - Cirule, I.
A1  - Cox, L.
A1  - Costa, D. J.
A1  - Custovic, A.
A1  - Dahl, R.
A1  - Dahlen, S. E.
A1  - Darsow, U.
A1  - De Carlo, G.
A1  - De Blay, F.
A1  - Dedeu, T.
A1  - Deleanu, D.
A1  - De Manuel Keenoy, E.
A1  - Demoly, P.
A1  - Denburg, J. A.
A1  - Devillier, P.
A1  - Didier, A.
A1  - Dinh-Xuan, A. T.
A1  - Djukanovic, R.
A1  - Dokic, D.
A1  - Douagui, H.
A1  - Dray, G.
A1  - Dubakiene, R.
A1  - Durham, S. R.
A1  - Dykewicz, M. S.
A1  - El-Gamal, Y.
A1  - Emuzyte, R.
A1  - Fabbri, L. M.
A1  - Fletcher, M.
A1  - Fiocchi, A.
A1  - Fink Wagner, A.
A1  - Fonseca, J.
A1  - Fokkens, W. J.
A1  - Forastiere, F.
A1  - Frith, P.
A1  - Gaga, M.
A1  - Gamkrelidze, A.
A1  - Garces, J.
A1  - Garcia-Aymerich, J.
A1  - Gemicioğlu, B.
A1  - Gereda, J. E.
A1  - González Diaz, S.
A1  - Gotua, M.
A1  - Grisle, I.
A1  - Grouse, L.
A1  - Gutter, Z.
A1  - Guzmán, M. A.
A1  - Heaney, L. G.
A1  - Hellquist-Dahl, B.
A1  - Henderson, D.
A1  - Hendry, A.
A1  - Heinrich, J.
A1  - Heve, D.
A1  - Horak, F.
A1  - Hourihane, J. O’. B.
A1  - Howarth, P.
A1  - Humbert, M.
A1  - Hyland, M. E.
A1  - Illario, M.
A1  - Ivancevich, J. C.
A1  - Jardim, J. R.
A1  - Jares, E. J.
A1  - Jeandel, C.
A1  - Jenkins, C.
A1  - Johnston, S. L.
A1  - Jonquet, O.
A1  - Julge, K.
A1  - Jung, K. S.
A1  - Just, J.
A1  - Kaidashev, I.
A1  - Kaitov, M. R.
A1  - Kalayci, O.
A1  - Kalyoncu, A. F.
A1  - Keil, T.
A1  - Keith, P. K.
A1  - Klimek, L.
A1  - Koffi N’Goran, B.
A1  - Kolek, V.
A1  - Koppelman, G. H.
A1  - Kowalski, M. L.
A1  - Kull, I.
A1  - Kuna, P.
A1  - Kvedariene, V.
A1  - Lambrecht, B.
A1  - Lau, S.
A1  - Larenas‑Linnemann, D.
A1  - Laune, D.
A1  - Le, L. T. T.
A1  - Lieberman, P.
A1  - Lipworth, B.
A1  - Li, J.
A1  - Lodrup Carlsen, K.
A1  - Louis, R.
A1  - MacNee, W.
A1  - Magard, Y.
A1  - Magnan, A.
A1  - Mahboub, B.
A1  - Mair, A.
A1  - Majer, I.
A1  - Makela, M. J.
A1  - Manning, P.
A1  - Mara, S.
A1  - Marshall, G. D.
A1  - Masjedi, M. R.
A1  - Matignon, P.
A1  - Maurer, M.
A1  - Mavale‑Manuel, S.
A1  - Melén, E.
A1  - Melo‑Gomes, E.
A1  - Meltzer, E. O.
A1  - Menzies‑Gow, A.
A1  - Merk, H.
A1  - Michel, J. P.
A1  - Miculinic, N.
A1  - Mihaltan, F.
A1  - Milenkovic, B.
A1  - Mohammad, G. M. Y.
A1  - Molimard, M.
A1  - Momas, I.
A1  - Montilla‑Santana, A.
A1  - Morais‑Almeida, M.
A1  - Morgan, M.
A1  - Mösges, R.
A1  - Mullol, J.
A1  - Nafti, S.
A1  - Namazova‑Baranova, L.
A1  - Naclerio, R.
A1  - Neou, A.
A1  - Neffen, H.
A1  - Nekam, K.
A1  - Niggemann, B.
A1  - Ninot, G.
A1  - Nyembue, T. D.
A1  - O’Hehir, R. E.
A1  - Ohta, K.
A1  - Okamoto, Y.
A1  - Okubo, K.
A1  - Ouedraogo, S.
A1  - Paggiaro, P.
A1  - Pali‑Schöll, I.
A1  - Panzner, P.
A1  - Papadopoulos, N.
A1  - Papi, A.
A1  - Park, H. S.
A1  - Passalacqua, G.
A1  - Pavord, I.
A1  - Pawankar, R.
A1  - Pengelly, R.
A1  - Pfaar, O.
A1  - Picard, R.
A1  - Pigearias, B.
A1  - Pin, I.
A1  - Plavec, D.
A1  - Poethig, D.
A1  - Pohl, W.
A1  - Popov, T. A.
A1  - Portejoie, F.
A1  - Potter, P.
A1  - Postma, D.
A1  - Price, D.
A1  - Rabe, K. F.
A1  - Raciborski, F.
A1  - Radier Pontal, F.
A1  - Repka‑Ramirez, S.
A1  - Reitamo, S.
A1  - Rennard, S.
A1  - Rodenas, F.
A1  - Roberts, J.
A1  - Roca, J.
A1  - Rodriguez Mañas, L.
A1  - et al, 
T1  - Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)
JF  - Clinical and Translational Allergy
N2  - Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
KW  - EIP on AHA
KW  - European Innovation Partnership on Active and Healthy Ageing
KW  - AIRWAYS ICPs
KW  - MACVIA
KW  - Scaling up
KW  - Chronic respiratory diseases
KW  - ARIA
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166874
VL  - 6
IS  - 29
ER  - 
TY  - JOUR
A1  - Bousquet, J.
A1  - Anto, J. M.
A1  - Akdis, M.
A1  - Auffray, C.
A1  - Keil, T.
A1  - Momas, I.
A1  - Postma, D. S.
A1  - Valenta, R.
A1  - Wickman, M.
A1  - Cambon-Thomsen, A.
A1  - Haahtela, T.
A1  - Lambrecht, B. N.
A1  - Lodrup Carlsen, K. C.
A1  - Koppelman, G. H.
A1  - Sunyer, J.
A1  - Zuberbier, T.
A1  - Annesi-Maesano, I.
A1  - Arno, A.
A1  - Bindslev-Jensen, C.
A1  - De Carlo, G.
A1  - Forastiere, F.
A1  - Heinrich, J.
A1  - Kowalski, M. L.
A1  - Maier, D.
A1  - Melen, E.
A1  - Palkonen, S.
A1  - Smit, H. A.
A1  - Standl, M.
A1  - Wright, J.
A1  - Asarnoj, A.
A1  - Benet, M.
A1  - Ballardini, N.
A1  - Garcia-Aymerich, J.
A1  - Gehring, U.
A1  - Guerra, S.
A1  - Hohman, C.
A1  - Kull, I.
A1  - Lupinek, C.
A1  - Pinart, M.
A1  - Skrindo, I.
A1  - Westman, M.
A1  - Smagghe, D.
A1  - Akdis, C.
A1  - Albang, R.
A1  - Anastasova, V.
A1  - Anderson, N.
A1  - Bachert, C.
A1  - Ballereau, S.
A1  - Ballester, F.
A1  - Basagana, X.
A1  - Bedbrook, A.
A1  - Bergstrom, A.
A1  - von Berg, A.
A1  - Brunekreef, B.
A1  - Burte, E.
A1  - Carlsen, K.H.
A1  - Chatzi, L.
A1  - Coquet, J.M.
A1  - Curin, M.
A1  - Demoly, P.
A1  - Eller, E.
A1  - Fantini, M.P.
A1  - Gerhard, B.
A1  - Hammad, H.
A1  - von Hertzen, L.
A1  - Hovland, V.
A1  - Jacquemin, B.
A1  - Just, J.
A1  - Keller, T.
A1  - Kerkhof, M.
A1  - Kiss, R.
A1  - Kogevinas, M.
A1  - Koletzko, S.
A1  - Lau, S.
A1  - Lehmann, I.
A1  - Lemonnier, N.
A1  - McEachan, R.
A1  - Makela, M.
A1  - Mestres, J.
A1  - Minina, E.
A1  - Mowinckel, P.
A1  - Nadif, R.
A1  - Nawijn, M.
A1  - Oddie, S.
A1  - Pellet, J.
A1  - Pin, I.
A1  - Porta, D.
A1  - Rancière, F.
A1  - Rial-Sebbag, A.
A1  - Schuijs, M.J.
A1  - Siroux, V.
A1  - Tischer, C.G.
A1  - Torrent, M.
A1  - Varraso, R.
A1  - De Vocht, J.
A1  - Wenger, K.
A1  - Wieser, S.
A1  - Xu, C.
T1  - Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story 
Mechanisms of the Development of ALLergy; EUFP7-CP-IP; Project No: 261357; 2010-2015
JF  - Allergy
N2  - MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.
KW  - asthma
KW  - birth cohort
KW  - atopic-dermatitis
KW  - immune-responses
KW  - IgE
KW  - multimorbidity
KW  - polysensitization
KW  - rhinitis
KW  - chronic respiratory-diseases
KW  - childhood asthma
KW  - immunological reactivity
KW  - IgE sensitazion
KW  - immunoglobulin-e
KW  - integraed care
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186858
VL  - 71
IS  - 11
ER  - 
TY  - JOUR
A1  - Eltze, M.
A1  - Ullrich, B.
A1  - Mutschler, E.
A1  - Moser, U.
A1  - Bungardt, E.
A1  - Friebe, T.
A1  - Gubitz, C.
A1  - Tacke, Reinhold
A1  - Lambrecht, G.
T1  - Characterization of muscarinic receptors mediating vasodilation in rat perfused kidney
N2  - The muscarinic receptor mediating vasodilation of resistance vessels in the rat isolated, constant-pressure perfused kidney (preconstriction by w- 7 M cirazoline) was characterized by subtype-preferring agonists and se]ective antagonists. The agonists produced vasodi1ation with the fol1owing rank order of potency: arecaidine propargy] ester (APE) > 5-methylfurtrethonium = methacholine = oxotremorine > (S)-aceclidine > arecaidine 2-butyne-1,4-diyl bisester > 4-Cl-McN-A-343 = (R)-nipecotic acid ethyl ester = N-ethyl-guvacine propargyl ester- (R)-aceclidine = (S)-nipecotic acid ethyl ester > McN-A-343. Agonist-induced vasodilation disappeared after destruction of the endothelium with detergent. Highly significant correlations of agonist potencies for vasodilation were found between rat kidney and guinea-pig ileum submucosal arterioles as weH as agonist potencies at smooth muscle muscarinic M\(_3\) receptors of the guinea-pig ileum. The rank order of antagonist potencies (4-diphenylacetoxy-Nmethylpiperidine methiodide (4-DAMP) > (R)-hexahydro-difenidol - hexahydro-sila-difenidol > pirenzepine - p-fluorohexahydro- sila-difenidol- himbacine- AF-DX 384- AQ-RA 741 > (S)-hexahydro-difenidol) to attenuate vasodilation to APE in rat kidney, correlated significantly with affinities at M\(_3\) receptors in submucosal arterioles and in smooth muscle of the guinea-pig ileum, but differed from those at M\(_1\) and M\(_2\) receptors in rabbit vas deferens. The agonist and antagonist potencies suggest that vasodilation elicited by muscarinic stimuli in endothelium-intact rat renal vasculature is mediated by functional muscarinic M\(_3\) receptors.
KW  - Anorganische Chemie
KW  - Kidney (perfused
KW  - rat)
KW  - Muscarinic receptor agonists
KW  - Muscarinic receptor antagonists
KW  - Arterioles (submucosal)
KW  - Ileum; Atrium
KW  - Vas deferens
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64283
ER  - 
TY  - JOUR
A1  - Tacke, Reinhold
A1  - Mahner, K.
A1  - Strohmann, C.
A1  - Forth, B.
A1  - Mutschler, E.
A1  - Friebe, T.
A1  - Lambrecht, G.
T1  - Cyclohexyl(4-fluorophenyl)(3-piperidinopropyl)silanol (p-fluoro-hexahydro-sila-difenidol, p-F-HHSiD) and derivatives: synthesis and antimuscarinic properties
N2  - Four different syntheses of the potent and selective muscanruc antagonist cyclohexyl( 4- fluorophenyl)(3-piperidinopropyl)silanol ( p-fluoro-hexahydro-sila-difenidol, p-F-HHSiD (2b); isolated as hydrochloride 2b· HCl) are described (starting materials: (CH\(_3\)O)\(_2\)SiCH\(_2\)CH\(_2\)CH\(_2\)Cl and Si(OCH\(_3\))\(_4\) ). In addition, the synthesis of the corresponding carbon analogue p-fluoro-hexahydro-difenidol ( p-F-HHD (2a); isolated as 2a· HCI) and the syntheses of three p-F-HHSiD derivatives (3-5), with a modified cyclic amino group, are reported (3: piperidinojpyrrolidino exchange, isolated as 3· HCI; 4: piperidinoj hexamethylenimino exchange, isolated as 4 · HCl; 5: quaternization of 2b with methyl iodide). The chiral compounds 2a, 2b, 3, 4 and 5 were prepared as racemates. In functional pharmacological studies, 3-5 behaved as simple competitive antagonists at musearlnie Ml receptors in rabbit vas deferens, M2 receptors in guinea-pig atria, and M3 receptors in guinea-pig ileal smooth rnuscle. The pyrrolidino (3) and hexamethylenimino (4) analogues of the parent drug p-F-HHSiD (2b) displayed the highest affinity for Ml and M3 receptors (pA\(_2\) values: 7.0-7.4) but exhibited lower affinity for cardiac M2 receptors (pA\(_2\) : 5.9 and 6.0). Their affinity profile (Ml- M3 > M2) is different from that of p-F-HHSiD (2b) (M3 > Ml > M2), but qualitatively very similar tothat of p-F-HHD (2a). The methiodide 5 exhibited the highest affinity for Ml receptors (pA\(_2\) : 8.5) but lower affinity for M2 and M3 receptors by factors of 5.6 and 3.6, respectively.
KW  - Anorganische Chemie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64162
ER  - 
TY  - JOUR
A1  - Lambrecht, G.
A1  - Feifel, R.
A1  - Forth, B.
A1  - Strohmann, C.
A1  - Tacke, Reinhold
A1  - Mutschler, E.
T1  - p-Fluoro-hexahydro-sila-difenidol: the first M\(_{2\beta}\)-selective muscarinic antagonist
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63872
ER  - 
TY  - JOUR
A1  - Pfeiffer, A.
A1  - Rochlitz, H.
A1  - Noelke, B.
A1  - Tacke, R.
A1  - Moser, U.
A1  - Mutschler, E.
A1  - Lambrecht, G.
T1  - Muscarinic receptors mediating acid secretion in isolated rat gastric parietal cells are of M3 type
JF  - Gastroenterology
N2  - Five subtypes of muscarinic receptors have been identified by pharmacological and molecular biological methods. The muscarinic receptor subtype mediating acid secretion at the level of the parietal cell was unknown. Therefore, this study was performed to characterize muscarinic receptors on rat gastric parietal cells using the 3 subtype-selective antagonists hexahydrosiladifenidol and silahexocyclium, which have high affinity for glandular M3 subtypes, and AF-DX 116, which has high affinity to cardiac M2 receptors. The affinity of these antagonists was determined by radioligand binding experiments. In addition, their inhibitory potency on carbachol-stimulated inositol phosphate production was investigated. Inhibition of carbachol-stimulated aminopyrine uptake was used as an indirect measure of proton production. Both M3 antagonists, hexahydrosiladifenidol and silahexocyclium, had nanomolar affinities for parietal cell muscarinic receptors and potently antagonized inositol phosphate production with nanomolar Ki values. Silahexocyclium similarly antagonized aminopyrine accumulation while hexahydrosiladifenidol behaved as a noncompetitive antagonist. AF-DX 116 was a low-affinity ligand and a weak competitive antagonist at parietal-cell muscarinic receptors. It was concluded that muscarinic M3 receptors mediate acid secretion probably by activation of the phosphoinositide second messenger system in rat gastric parietal cells.
KW  - hexahydrosiladifenidol
KW  - muscarinic receptors
KW  - parasympatholytics
KW  - radioligand assay
KW  - parasympatholytics/pharmacology
KW  - gastric acid/secretion
KW  - animals
KW  - piperidines/pharmacology
KW  - piperazines/pharmacology
KW  - gastric/secretion parietal cells
KW  - muscarinic/physiology receptors
KW  - muscarinic/drug effects receptors
KW  - rats
KW  - piperidines
KW  - piperazines
KW  - silahexocyclium
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128337
VL  - 98
IS  - 1
ER  -