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21.
Ad F. Roffel Willy G. in't Hout Rokus A. de Zeeuw Johan Zaagsma 《Naunyn-Schmiedeberg's archives of pharmacology》1987,335(5):593-595
Summary We have characterized the muscarine receptors in bovine tracheal and left ventricular membranes using 3H-dexetimide/pirenzepine and 3H-dexetimide/AF-DX 116 competition studies. Pirenzepinc exhibited low (M2) affinity binding to both preparations; K
d was 590 nM in left ventricle and 463 nM in trachea. AF-DX 116 exhibited high (M2) affinity binding to left ventricle (K
d = 95.6 nM); in tracheal membranes it bound with high (M2) affinity (K
d = 40.7 nM) to 74% of the receptors and with low (M3) affinity (K
d = 2.26 M) to 26% of the receptors. It is concluded that bovine tracheal muscle membranes contain a heterogeneous population of muscarine binding sites, the majority having M2 (heart) subtype characteristics and being located on the smooth muscle membranes; a minority having M3 (exocrine gland) subtype characteristics and presumed to be located in submucosal glands. This is the first report of high affinity binding of AF-DX 116 to non-cardiac peripheral muscarine receptors.
Send offprint requests to A. F. Roffel at the above address 相似文献
22.
Willy Palm Erin Webb Cristina Hernández-Quevedo Giada Scarpetti Suszy Lessof Luigi Siciliani Ewout van Ginneken 《Health policy (Amsterdam, Netherlands)》2021,125(3):341-350
This study identifies gaps in universal health coverage in the European Union, using a questionnaire sent to the Health Systems and Policy Monitor network of the European Observatory on Health Systems and Policies. The questionnaire was based on a conceptual framework with four access dimensions: population coverage, service coverage, cost coverage, and service access. With respect to population coverage, groups often excluded from statutory coverage include asylum seekers and irregular residents. Some countries exclude certain social-professional groups (e.g. civil servants) from statutory coverage but cover these groups under alternative schemes. In terms of service coverage, excluded or restricted services include optical treatments, dental care, physiotherapy, reproductive health services, and psychotherapy. Early access to new and expensive pharmaceuticals is a concern, especially for rare diseases and cancers. As to cost coverage, some countries introduced protective measures for vulnerable patients in the form of exemptions or ceilings from user chargers, especially for deprived groups or patients with accumulation of out-of-pocket spending. For service access, common issues are low perceived quality and long waiting times, which are exacerbated for rural residents who also face barriers from physical distance. Some groups may lack physical or mental ability to properly formulate their request for care. Currently, available indicators fail to capture the underlying causes of gaps in coverage and access. 相似文献
23.
The interaction of phenylbutazone with the enantiomers and racemic [
3
H]phenprocoumon was studied in male inbred Wistar-Lewis rats following a single i.v. dose of the three forms of phenprocoumon and chronic oral treatment with phenylbutazone (average plasma concentration of about 60 g/ml). Phenylbutazone augmented the anticoagulant effect of R(+), S(–), and R, S (±) phenprocoumon to a similar extent. The free fraction of drug in the plasma of the enantiomers and racemic phenprocoumon increased in the presence of phenylbutazone. However, the rate of elimination of total drug from plasma and liver and the distribution between liver and plasma of all three forms of phenprocoumon remained nearly unaffected by phenylbutazone. Thus there is no evidence for a stereoselective drug interaction between phenprocoumon and phenyl-butazone. For racemic [
3
H]phenprocoumon it was possible to follow the kinetics of free drug in plasma and liver along with the time course of anticoagulant activity. In these studies, free drug concentrations in plasma and liver increased during treatment with phenylbutazone, but the elimination rate constant of free racemic phenprocoumon in plasma and liver remained essentially unchanged. Phenylbutazone markedly decreased the volume of distribution referenced to free drug and the clearance of free phenprocoumon (i.e., intrinsic metabolic clearance). Whereas the total (bound and unbound) drug concentration-effect relationship in plasma and liver was shifted to the left in rats treated with phenylbutazone, such shift was not seen in the free drug concentration-response relationship. In conclusion, the increase in the free concentration of phenprocoumon in plasma and liver and the concomitant decrease in the clearance of free drug are the mechanisms responsible for the marked and sustained enhancement of the anticoagulant effect which follows treatment with phenbutazone.This work was supported by the Deutsche Forschungsgemeinschaft. 相似文献
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25.
Stacy Schantz Wilkins PhD Rebecca J. Melrose PhD Katherine S. Hall PhD Erin Blanchard MS Steven C. Castle MD Teresa Kopp PT MBA Leslie I. Katzel MD PhD Alice Holder MHS PT Neil Alexander MD Michelle K.S. McDonald BA OT Arti Tayade MD CMD HMDC Daniel E. Forman MD Lauren M. Abbate MD PhD Rebekah Harris PT DPT PhDc Willy M. Valencia MD Miriam C. Morey PhD Cathy C. Lee MD 《Journal of the American Geriatrics Society》2021,69(4):1045-1050
26.
Christoph Josef Spindelegger Konstantinos Papageorgiou Renate Grohmann Rolf Engel Waldemar Greil Anastasios Konstantinidis Marcus Willy Agelink Stefan Bleich Eckart Ruether Sermin Toto Siegfried Kasper 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2015,18(4)
27.
MacAndrew and Edgerton's seminal Drunken Comportment revealed that normative expectations to drunken behaviour differ greatly across cultures. Such variation also exists within cultures, where different drinking contexts may be associated with great normative variation. However, why social regulation of drunken comportment varies has largely been left unexplored. To examine the basis of such differences, two Norwegian drinking contexts are compared: (i) the high school graduation celebration and (ii) the two introduction weeks at university. Data comprise 71 qualitative interviews and field notes from participant observation. The two practices take place within a time span of only four months and involve many of the same participants. Alcohol plays a key role in both contexts. However, while the first context allows for heavy intoxication, sexual explorations and violating norms that ordinarily regulate behaviour in public, the second context is associated with much more control. We argue that the basis of this difference may be found in the differing value priorities of these practices, with participants' behaviour being guided primarily by hedonism and social integration, respectively. When applied to drinking practices in general this conceptual apparatus might elucidate the basis of context-specific norms and intra-cultural variation in drunken comportment. 相似文献
28.
β-Chemokines and neutralizing antibody titers correlate with sterilizing immunity generated in HIV-1 vaccinated macaques 下载免费PDF全文
Jonathan L. Heeney Vera J. P. Teeuwsen Marille van Gils Willy M. J. M. Bogers Carlo De Giuli Morghen Antonia Radaelli Susan Barnett Bror Morein Lennart kerblom Yufei Wang Thomas Lehner David Davis 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(18):10803-10808
One of the obstacles to AIDS vaccine development is the variability of HIV-1 within individuals and within infected populations, enabling viral escape from highly specific vaccine induced immune responses. An understanding of the different immune mechanisms capable of inhibiting HIV infection may be of benefit in the eventual design of vaccines effective against HIV-1 variants. To study this we first compared the immune responses induced in Rhesus monkeys by using two different immunization strategies based on the same vaccine strain of HIV-1. We then utilized a chimeric simian/HIV that expressed the envelope of a dual tropic HIV-1 escape variant isolated from a later time point from the same patient from which the vaccine strain was isolated. Upon challenge, one vaccine group was completely protected from infection, whereas all of the other vaccinees and controls became infected. Protected macaques developed highest titers of heterologous neutralizing antibodies, and consistently elevated HIV-1-specific T helper responses. Furthermore, only protected animals had markedly increased concentrations of RANTES, macrophage inflammatory proteins 1α and 1β produced by circulating CD8+ T cells. These results suggest that vaccine strategies that induce multiple effector mechanisms in concert with β-chemokines may be desired in the generation of protective immune responses by HIV-1 vaccines. 相似文献
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