Autoradiographic Mapping of 5-HT1B/1D Binding Sites in the Rhesus Monkey Brain Using [carbonyl-11C]zolmitriptan

Zolmitriptan is a serotonin 5-HT1B/1D receptor agonist that is an effective and well-tolerated drug for migraine treatment. In a human positron emission tomography study, [11C]zolmitriptan crossed the blood-brain barrier but no clear pattern of regional uptake was discernable. The objective of this study was to map the binding of [11C]zolmitriptan in Rhesus monkey brain using whole hemisphere in vitro autoradiography with [11C]zolmitriptan as a radioligand. In saturation studies, [11C]zolmitriptan showed specific (90%) binding to a population of high-affinity binding sites (Kd 0.95–5.06 nM). There was regional distribution of binding sites with the highest density in the ventral pallidum, followed by the external globus pallidus, substantia nigra, visual cortex, and nucleus accumbens. In competitive binding studies with 5-HT1 receptor antagonists, [11C]zolmitriptan binding was blocked by selective 5-HT1B and 5-HT1D ligands in all target areas. There was no appreciable change in binding with the addition of a 5-HT1A receptor antagonist

Pushing the Limits for Thiol−Ene and CuAAC Reactions: Synthesis of a 6th Generation Dendrimer in a Single Day

Dendrimer synthesis should not be tedious and time-consuming. By utilizing an AB2−CD2 approach and having orthogonal, “clickable” groups on each monomer, the time for dendrimer assembly can be drastically reduced. This was shown by preparation of a sixth generation dendrimer from starting monomer units in a single day

Cas 32: Modificació dels conceptes erronis de l’estudiantat previs a l’inici de l’adquisició de nous aprenentatges

El cas en xarxa “Modificació dels conceptes erronis de l’estudiantat previs a l’inici de l’adquisició de nous aprenentatges”, forma part del Repositori col•laboratiu de casos reals en l’àmbit educatiu (http://www.ub.edu/casosenxarxa/inici), i ha estat elaborat en el marc del projecte de recerca i d’innovació educativa Casos en xarxa per a la formació: estudi empíric, creació d'un dipòsit digital i identificació de bones pràctiques en el seu ús (REDICE 14-1478).Es proposa una estratègia per intentar modificar conceptes erronis (misconceptions) de l’estudiantat, per la correcta adquisició de nous aprenentatges. Es tracta de recollir anònimament la informació sobre els possibles errors conceptuals a l' inici de curs i retornar-la progressivament a l’ iniciar aquells continguts del temari on és necessari tenir el concepte ben assumit

Para-chloro-2-[18F]fluoroethyl-etomidate: A promising new PET radiotracer for adrenocortical imaging.

Introduction: [11C]Metomidate ([11C]MTO), the methyl ester analogue of etomidate, was developed as a positron emission tomography (PET) radiotracer for adrenocortical tumours and has also been suggested for imaging in primary aldosteronism (PA). A disadvantage of [11C]MTO is the rather high non-specific binding in the liver, which impacts both visualization and quantification of the uptake in the right adrenal gland. Furthermore, the short 20-minute half-life of carbon-11 is a logistic challenge in the clinical setting. Objectives: The aim of this study was to further evaluate the previously published fluorine-18 (T1/2=109.5 min) etomidate analogue, para-chloro-2-[18F]fluoroethyl etomidate; [18F]CETO, as an adrenal PET tracer. Methods: In vitro experiments included autoradiography on human and cynomolgus monkey (non-human primate, NHP) tissues and binding studies on adrenal tissue from NHPs. In vivo studies with [18F]CETO in mice, rats and NHP, using PET and CT/MRI, assessed biodistribution and binding specificity in comparison to [11C]MTO. Results: The binding of [18F]CETO in the normal adrenal cortex, as well as in human adrenocortical adenomas and adrenocortical carcinomas, was shown to be specific, both in vitro (in humans) and in vivo (in rats and NHP) with an in vitro Kd of 0.66 nM. Non-specific uptake of [18F]CETO in NHP liver was found to be low compared to that of [11C]MTO. Conclusions: High specificity of [18F]CETO to the adrenal cortex was demonstrated, with in vivo binding properties qualitatively surpassing those of [11C]MTO. Non-specific binding to the liver was significantly lower than that of [11C]MTO. [18F]CETO is a promising new PET tracer for imaging of adrenocortical disease and should be evaluated further in humans

De Novo Design of Bioactive Protein-Resembling Nanospheres via Dendrimer-Templated Peptide Amphiphile Assembly

Self-assembling peptide amphiphiles (PAs) have been extensively used in the development of novel biomaterials. Because of their propensity to form cylindrical micelles, their use is limited in applications where small spherical micelles are desired. Here we present a platform method for controlling the self-assembly of biofunctional PAs into spherical 50 nm particles using dendrimers as shape-directing scaffolds. This templating approach results in biocompatible, stable protein-like assemblies displaying peptides with native secondary structure and biofunctionality

Pushing the Limits for Thiol−Ene and CuAAC Reactions: Synthesis of a 6th Generation Dendrimer in a Single Day

Dendrimer synthesis should not be tedious and time-consuming. By utilizing an AB2−CD2 approach and having orthogonal, “clickable” groups on each monomer, the time for dendrimer assembly can be drastically reduced. This was shown by preparation of a sixth generation dendrimer from starting monomer units in a single day

De Novo Design of Bioactive Protein-Resembling Nanospheres via Dendrimer-Templated Peptide Amphiphile Assembly

Self-assembling peptide amphiphiles (PAs) have been extensively used in the development of novel biomaterials. Because of their propensity to form cylindrical micelles, their use is limited in applications where small spherical micelles are desired. Here we present a platform method for controlling the self-assembly of biofunctional PAs into spherical 50 nm particles using dendrimers as shape-directing scaffolds. This templating approach results in biocompatible, stable protein-like assemblies displaying peptides with native secondary structure and biofunctionality