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The purpose of this work is to develop a material capable of detecting neutrons produced by photodisintegration in a linear accelerator for its medical use. In this study, we have developed a gel-like material doped with fluorescent organic particles. PPO at 1 wt% is used as primary dopant and POPOP as secondary one at 0.03 wt%. A set of four samples is produced, with boric acid concentrations of 0, 400, 800 and 1200 ppm. The viscoelastic properties of the material are characterized with rheological measurements, finding a gel-like behavior, i.e., a material that can keep its original shape if no stresses are applied, but can also be deformed by applying a moderate shear rate. Furthermore, the material was irradiated with gamma, electron, and neutron emission sources from 137Cs, 22Na, 60Co, 210Po, 90Sr and 241AmBe, and its response was measured in two different experimental settings, in two different institutions, for comparative purposes. From these measurements, one can clearly establish that the new material detects neutrons, electrons, and gammas within the MeV regions and below. Thus, our findings show that the developed material and its properties make it a promising technology for its use in a neutron detector.

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INTRODUCTION: Determination of the intrinsic efficacy of ligands at the A2A receptor is important for selecting drug candidates, e.g. in the case of inflammatory diseases where agonists are searched for or in Parkinson disease (antagonists). METHODS: Three functional binding assays were compared with up to seven ligands with different efficacies: the GTP-shift method based on the decrease of affinity observed with agonists when GTP is added to the competition binding assay; the Ki ratio method based on the different affinity states of the receptor when using an agonist or antagonist radioligand and the Na+-shift assay based on the difference of affinity of agonists when tested in a medium containing a divalent cation (50mM MgCl2) favoring the G protein coupled agonist-receptor complex or sodium (100mM NaCl) as negative allosteric modulator. RESULTS: The Na+-shift assay proposed herein successfully discriminated the full agonists CGS21680, NECA and adenosine (IC50 ratio=13-14) from the weak inverse agonists ZM241385 and IBMX (IC50 ratio=0.85) and the partial agonists LUF5834 and regadenoson (IC50 ratios equal to 3 and 10, respectively). DISCUSSION: We conclude that the Na+-shift assay proposed herein for the A2A receptors has been validated and represents a rapid, economic and efficient functional binding assay to be used in a drug development program for early estimation of the intrinsic efficacy of hits.

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Piracetam is a cyclic derivative of γ-aminobutyric acid (GABA). It was the first nootropic drug approved for clinical use. However, mechanism of its action is still not clear. In present paper, I investigated effects of piracetam on neurotransmitter release, plasma membrane potential monitored by fluorescent dye DiSC3(5) and chloride transport monitored by fluorescent dye SPQ in rat brain synaptosomes. It was shown that piracetam (1 mM) induces slow weak plasma membrane depolarization. This effect was decreased on 43% and 58% by both AMPA/kainate receptor blockers NBQX (10 µM) and CNQX (100 µM), respectively, on 84% by GABA ionotropic receptor blocker picrotoxin (50 µM) and on 91% upon withdrawal of HCO(3-) ions from incubation medium. GABA (1 mM) and kainate (100 µM) were found not to produce changes of plasma membrane potential. Also, it was found that piracetam induces chloride efflux which seems to be the reason of depolarization. Thereby, piracetam induces depolarization of plasma membrane of isolated neuronal presynaptic endings by picrotoxin-sensitive way.

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The incomplete inhibition of platelet function by acetylsalicylic acid (ASA), despite the patients are receiving therapeutic doses of the drug ('aspirin-resistance'), is caused by numbers of risk factors. In this study we verified the idea that plasma homocysteine (Hcy) contributes to 'aspirin-resistance' in patients with coronary artery disease (CAD) and with or without type 2 diabetes mellitus (T2DM). A cross-designed randomized controlled intervention study has been performed (126 CAD pts incl. 26 with T2DM) to determine whether increasing ASA dose from 75mg to 150mg daily may result in the increased antiplatelet effect, in the course of four-week treatment. Platelet response to collagen (coll) or arachidonic acid (AA) was monitored with whole blood aggregometry, plasma thromboxane (Tx), and Hcy levels were determined immunochemically. The ASA-mediated reductions in platelet response to coll (by 12±3%) or AA (by 10±3%) and in plasma Tx (by 20±9%; p<0.02 or less) were significantly greater for higher ASA dose and significantly correlated with plasma Hcy, which was significantly lower in "good" ASA responders compared to "poor" responders (p<0.001). Higher plasma Hcy appeared a significant risk factor for blood platelet refractoriness to low ASA dose (OR=1.11; ±95%CI: 1.02-1.20, p<0.02, adjusted to age, sex and CAD risk factors). Hcy diminished in vitro antiplatelet effect of low ASA concentration and augmented platelet aggregation (by up to 62% (p<0.005) for coll and up to 15% (p<0.005) for AA), whereas its acetyl derivative acted oppositely. Otherwise, Hcy intensified antiplatelet action of high ASA. Hyperhomocysteinaemia may be a novel risk factor for the suppressed blood platelet response to ASA, and homocysteine may act as a specific sensitizer of blood platelets to some agonists. While homocysteine per se acts as a proaggregatory agent to blood platelets, its acetylated form is able to reverse this effect. Thus, these findings reveal a possibly new challenging potential of the acetylating properties of ASA therapy.

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