Lobbyen: Blijspel of Grieks drama?

Op 18 oktober werd door de BIL een groots forum georganiseerd ter gelegenheid van haar tweede lustrum. Titel van het forum was “Lobbyen; Blijspel of Grieks drama” voor de democratie. Voor het forum was dit keer niet gekozen voor een opzet met referaten en co-referaten, maar er waren verschillende debatrondes

Ervaringen met verzelfstandiging: Symposiumverslag

Op woensdag 10 mei jl. vond ter gelegenheid van het tweede lustrum van de Bestuurskundige Interfacultaire vereniging Leiden (BIL) een symposium plaats onder de titel "Ervaring met verzelfstandiging". Om optimaal voorbereid aan dit symposium deel te kunnen nemen verstrekte de BIL een inleidende leesbundel "Verzelfstandigen: hoe, wat en waarom?", met daarin enkele recente artikelen uit allerlei bladen die betrekking hadden op verzelfstandigen

Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity

The study of rare families with inherited pain insensitivity can identify new human-validated analgesic drug targets. Here, a 66-yr-old female presented with nil requirement for postoperative analgesia after a normally painful orthopaedic hand surgery (trapeziectomy). Further investigations revealed a lifelong history of painless injuries, such as frequent cuts and burns, which were observed to heal quickly. We report the causative mutations for this new pain insensitivity disorder: the co-inheritance of (i) a microdeletion in dorsal root ganglia and brain-expressed pseudogene, FAAH-OUT, which we cloned from the fatty-acid amide hydrolase (FAAH) chromosomal region; and (ii) a common functional single-nucleotide polymorphism in FAAH conferring reduced expression and activity. Circulating concentrations of anandamide and related fatty-acid amides (palmitoylethanolamide and oleoylethanolamine) that are all normally degraded by FAAH were significantly elevated in peripheral blood compared with normal control carriers of the hypomorphic single-nucleotide polymorphism. The genetic findings and elevated circulating fatty-acid amides are consistent with a phenotype resulting from enhanced endocannabinoid signalling and a loss of function of FAAH. Our results highlight previously unknown complexity at the FAAH genomic locus involving the expression of FAAH-OUT, a novel pseudogene and long non-coding RNA. These data suggest new routes to develop FAAH-based analgesia by targeting of FAAH-OUT, which could significantly improve the treatment of postoperative pain and potentially chronic pain and anxiety disorders. - 2019 The Author(s)Medical Research Council (Career Development Award G1100340 to JJC); Wellcome Trust ( 200183/Z/15/Z to JJC, 095698Z/11/Z and 202747/Z/16/Z to DLHB); Alzheimer's Society (research fellowship to JTB), University of Cambridge Academic Foundation Programme (to MCL); Molecular Nociception Group (to MCL); National Institutes of Health (Bethesda, MD, USA) Ruth L. Kirschstein Institutional National Research Service Award (to MCL); Wellcome Trust funded London Pain Consortium (to JDR); Colciencias through a Francisco Jose de Caldas Scholarship (LASPAU, Harvard University) (to JDR); Canadian Institutes of Health Research (CIHR; to MNH); CIHR (postdoctoral funding to MM)

Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity

The study of rare families with inherited pain insensitivity can identify new human-validated analgesic drug targets. Here, a 66-yr-old female presented with nil requirement for postoperative analgesia after a normally painful orthopaedic hand surgery (trapeziectomy). Further investigations revealed a lifelong history of painless injuries, such as frequent cuts and burns, which were observed to heal quickly. We report the causative mutations for this new pain insensitivity disorder: the co-inheritance of (i) a microdeletion in dorsal root ganglia and brain-expressed pseudogene, FAAH-OUT, which we cloned from the fatty-acid amide hydrolase (FAAH) chromosomal region; and (ii) a common functional single-nucleotide polymorphism in FAAH conferring reduced expression and activity. Circulating concentrations of anandamide and related fatty-acid amides (palmitoylethanolamide and oleoylethanolamine) that are all normally degraded by FAAH were significantly elevated in peripheral blood compared with normal control carriers of the hypomorphic single-nucleotide polymorphism. The genetic findings and elevated circulating fatty-acid amides are consistent with a phenotype resulting from enhanced endocannabinoid signalling and a loss of function of FAAH. Our results highlight previously unknown complexity at the FAAH genomic locus involving the expression of FAAH-OUT, a novel pseudogene and long non-coding RNA. These data suggest new routes to develop FAAH-based analgesia by targeting of FAAH-OUT, which could significantly improve the treatment of postoperative pain and potentially chronic pain and anxiety disorders

De waterbestendige stad: Meerlaagsveiligheidbenadering toegepast op de regio Amsterdam

De waterbestendige stad is een van de zes gebiedspilots in het deltaprogramma veiligheid, waarin de noodzaak en consequenties van nieuwe waterveiligheidsnormen en de toepasbaarheid van de zogenaamde meerlaagsveiligheidsbenadering is onderzocht. In de regio Amsterdam is de veiligheidsopgave complex. Het betreft een dichtbevolkt stedelijk gebied dicht bij een industrieel havengebied, gelegen in driie dijkringen met verschillende beschermingsniveaus, er zijn overstromingsdreigingen vanuit verschillende bronnen (Noordzee, Lek, Markermeer en het regionaal watersysteem) en twee primaire keringen lopen dwars door de stad, en zijn volledig gebouwd. Hoe veilig is de stad Amsterdam? Deze pilot komt met conclusies en aanbevelingen, ondanks het complexe watersysteem van de regio Amsterdam

A novel highly selective 5-HT6 receptor antagonist attenuates ethanol and nicotine seeking but does not affect inhibitory response control in Wistar rats

Recent studies suggest a potential role for 5-hydroxytryptamine(6) (5-HT6) receptors in the regulation of addictive behavior. In the present study, our aim was to investigate whether the novel highly selective 5-HT6 receptor antagonist compound (CMP) 42 affected nicotine and ethanol seeking behavior in Wistar rats. We have also studied whether CMP 42 had beneficial effects in a model of impulse control, as measured in the 5-choice serial reaction time task (5-CSRTT). Rats were trained to nose poke to receive intravenous infusions of nicotine or an ethanol drop. CMP 42 (3-30 mg/kg intraperitoneally, i.p.) was administered to investigate the effects on nicotine self-administration. Rats were also tested for cue-induced reinstatement of nicotine and ethanol seeking. In addition, the effects of CMP 42 were studied on the number of anticipatory responses in the 5-CSRTT. CMP 42 was effective in reducing nicotine self-administration and reinstatement of nicotine seeking at a dose of 30 mg/kg (i.p.). CMP 42 was also effective in reducing reinstatement of ethanol seeking (30 mg/kg i.p.). In contrast, CMP 42 did not affect anticipatory responding at doses tested, indicating no effects on impulse control. These results add to a body of evidence implicating the 5-HT6 receptor as a viable target for the control of drug abuse. Specifically, we demonstrated for the first time effects on nicotine self-administration and on nicotine and ethanol reinstatement. Further, these effects are probably not mediated by effects on impulse control

SLV330, a cannabinoid CB(1) receptor antagonist, attenuates ethanol and nicotine seeking and improves inhibitory response control in rats

Cannabinoid C