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- Varnäs, K., et al.
(författare)
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Integrated strategy for use of positron emission tomography in nonhuman primates to confirm multitarget occupancy of novel psychotropic drugs : An example with AZD3676
- 2016
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology and Experimental Therapy. - 0022-3565 .- 1521-0103. ; 358:3, s. 464-471
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Tidskriftsartikel (refereegranskat)abstract
- Positron emission tomography (PET) is widely applied in central nervous system (CNS) drug development for assessment of target engagement in vivo. As the majority of PET investigations have addressed drug interaction at a single binding site, findings of multitarget engagement have been less frequently reported and have often been inconsistent with results obtained in vitro. AZD3676 [N,N-dimethyl-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl) benzofuran-2-carboxamide] is a novel combined serotonin (5- hydroxytryptamine) 5-HT1A and 5-HT1B receptor antagonist that was developed for the treatment of cognitive impairment in Alzheimer's disease. Here, we evaluated the properties of AZD3676 as a CNS drug by combining in vitro and ex vivo radioligand binding techniques, behavioral pharmacology in rodents, and PET imaging in nonhuman primates. Target engagement in the nonhuman primate brain was assessed in PET studies by determination of drug-induced occupancy using receptorselective radioligands. AZD3676 showed preclinical properties consistent with CNS drug potential, including nanomolar receptor affinity and efficacy in rodent models of learning and memory. In PET studies of the monkey brain, AZD3676 inhibited radioligand binding in a dose-dependent manner with similar affinity at both receptors. The equally high affinity at 5-HT1A and 5-HT1B receptors as determined in vivo was not predicted from corresponding estimates obtained in vitro, suggestingmore than 10-fold selectivity for 5-HT1A versus 5-HT1B receptors. These findings support the further integrated use of PET for confirmation of multitarget occupancy of CNS drugs. Importantly, earlier introduction of PET studies in nonhuman primates may reduce future development costs and the requirement for animal experiments in preclinical CNS drug development programs.
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- Mellander, S, et al.
(författare)
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Neural beta-adrenergic dilatation of the facial vein in man. Possible mechanism in emotional blushing
- 1982
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 114:3, s. 393-399
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Tidskriftsartikel (refereegranskat)abstract
- Ring preparations of the superficial buccal segment of the human facial vein, taken from extirpated tissue in 12 patients during neck surgery, were studied in vitro. The vein developed a maintained intrinsic myogenic tone in response to passive stretch and was supplied with alpha- as well as beta-adrenoceptors, both of which could be influenced by transmural nerve stimulation (TNS) and noradrenaline. These unusual characteristics for a vein are basically similar to the ones described for the rabbit facial vein by Pegram, Bevan & Bevan (1976). In man there seemed to be an inter-individual difference with regard to the abundance of 'innervated' alpha- and beta-adrenoceptors. Facial vein specimens from some subjects thus responded with prompt and pronounced net dilatation to TNS with maximum at 4 Hz and those from others with net constriction with maximum at 16 Hz. The latter showed a reversal into neural beta-adrenergic dilatation after alpha-adrenergic blockade. The human external jugular vein was devoid of intrinsic tone and beta-adrenoceptors. It is tentatively proposed that a beta-adrenergic neuro-effector mechanism in superficial ramifications of the facial vein in man might be involved in the emotional blushing reaction.
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- Strömsöe, Anneli, 1969-, et al.
(författare)
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Improvements in logistics could increase survival after out-of-hospital cardiac arrest in Sweden
- 2013
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 273:6, s. 622-627
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. In a review based on estimations and assumptions, to report the estimated number of survivors after out-of-hospital cardiac arrest (OHCA) in whom cardiopulmonary resuscitation (CPR) was started and to speculate about possible future improvements in Sweden.Design. An observational study. Setting All ambulance organisations in Sweden. Subjects Patients included in the Swedish Cardiac Arrest Registry who suffered an OHCA between January 1, 2008 and December 31, 2010. Approximately 80% of OHCA cases in Sweden in which CPR was started are included. Interventions NoneResults. In 11005 patients, the 1-month survival rate was 9.4%. There are approximately 5000 OHCA cases annually in which CPR is started and 30-day survival is achieved in up to 500 patients yearly (6 per 100000 inhabitants). Based on findings on survival in relation to the time to calling for the Emergency Medical Service (EMS) and the start of CPR and defibrillation, it was estimated that, if the delay from collapse to (i) calling EMS, (ii) the start of CPR, and (iii) the time to defibrillation were reduced to <2min, <2min, and <8min, respectively, 300400 additional lives could be saved.Conclusion. Based on findings relating to the delay to calling for the EMS and the start of CPR and defibrillation, we speculate that 300400 additional OHCA patients yearly (4 per 100000 inhabitants) could be saved in Sweden.
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- Tittel, Wolfgang, et al.
(författare)
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Photon-echo quantum memory in solid state systems
- 2010
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Ingår i: Laser & Photonics Reviews. - : Wiley. - 1863-8880 .- 1863-8899. ; 4:2, s. 244-267
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Forskningsöversikt (refereegranskat)abstract
- Many applications of quantum communication crucially depend oil reversible transfer of quantum states between light and matter Motivated by rapid recent developments in theory and experiment, we review research related to quantum memory based oil a photon-echo approach in solid state material with emphasis on use in a quantum repeater After introducing quantum communication, the quantum repeater concept. and properties of a quantum memory required to be useful in a quantum repeater, we describe the historical development from spin echoes, discovered in 1950. to photon-echo quantum memory We present a simple theoretical description of the ideal protocol, and comment oil the impact of a non-ideal realization Oil Its quantum nature We extensively discuss rare-earth-ion doped crystals and glasses as material candidates, elaborate oil traditional photon-echo experiments as a test-bed for quantum State storage, and describe the current state-of-the-art of photon-echo quantum memory Finally, we give a brief outlook On Current research.
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