Search results for "Ley"
showing 10 items of 1218 documents
Synthesis and evaluation in rats of the dopamine D2/3 receptor agonist 18F-AMC20 as a potential radioligand for PET
2015
Dopamine D2/3 receptor (D2/3R) agonist PET tracers are better suited for the imaging of synaptic dopaminergic neurotransmission than D2/3R antagonists and may also offer the opportunity to study in vivo the high-affinity state of D2/3R (D2/3RHigh). With the aim to develop 18F-labeled D2/3R agonists suitable for widespread clinical application, we report here on the synthesis and in vitro and in vivo evaluation of a D2/3R agonist ligand from the aminomethyl chromane (AMC) class-(R)-2-[(4- 18Fluorobenzylamino)methyl]chroman-7-ol (18F-AMC20). Methods: In vitro affinities of AMC20 toward dopaminergic receptor subtypes were measured in membrane homogenates prepared from HEK293 cells expressing h…
The Anticonvulsant FCE 26743 is a Selective and Short-acting MAO-B Inhibitor Devoid of Inducing Properties towards Cytochrome P450-dependent Testoste…
1994
Abstract The effects of the potent anticonvulsant FCE 26743 ((S)-2-(4-(3-fluorobenzyloxy)benzylamino)propionamide) on monoamine oxidase (MAO) activity were measured in-vitro and ex-vivo using rat tissue homogenates. In-vitro, FCE 26743 showed potent and selective inhibitory properties towards liver MAO-B, with IC50 values about 10−7 m for MAO-B and higher than 10−5 m for MAO-A. When determined ex-vivo in brain, the ED50 value for the inhibition of MAO-B was 1·1 mg kg−1 (p.o.) 1 h post-dosing, whereas MAO-A remained virtually unaffected after administration of 60 mg kg−1. Similar effects were seen in liver. Following oral administration of 5 mg kg−1 FCE 26743 to rats, brain MAO-B inhibitio…
A Hydrogel Based on a Polyaspartamide: Characterization and Evaluation of In-vivo Biocompatibility and Drug Release in the Rat
1997
Abstract This paper deals with the characterization of a new microparticulate hydrogel obtained by gamma irradiation of α,β-poly[N-(2-hydroxyethyl)-dl-aspartamide] (PHEA). When enzymatic digestion of PHEA hydrogel was evaluated using various concentrations of pepsin and α-chymotrypsin no degradation occurred within 24 h. In-vivo studies showed that this new material is biocompatible after oral administration to rats. PHEA hydrogel was also studied as a system for delivery of diflunisal, an anti-inflammatory drug. In-vitro release studies in simulated gastrointestinal juice (pH 1 or 6.8) showed that most of the drug was released at pH 6.8. In-vivo studies indicated that diflunisal-loaded PHE…
Application of nano-hydroxyapatite/chitosan scaffolds on rat calvarial critical-sized defects: A pilot study
2018
Background The purpose of this pilot study was to evaluate for the first time the effect of 75/25 w/w nano-Hydroxyapatite/Chitosan (nHAp/CS) scaffolds on Guided Bone Regeneration (GBR) in rat calvarial critical-sized defects (CSDs). Material and Methods Six adult Sprague Dawley rats, 3 males and 3 females, were used. Two CSDs, full thickness and 5mm in diameter, were trephined in both sides of the parietal bone. The right CSD was filled with nHAp/CS scaffold, while the left CSD remained empty, as the control group. The wound was sutured in layers. Rats were euthanized with diethyl ether inhalation at 2, 4 and 8 weeks after surgical procedure. Histological and histomorphometric analysis was …
PEGylation of HPMA-based block copolymers enhances tumor accumulation in vivo: a quantitative study using radiolabeling and positron emission tomogra…
2013
Abstract This paper reports the body distribution of block copolymers (made by controlled radical polymerization) with N-(2-hydroxypropyl)methacrylamide (HPMA) as hydrophilic block and lauryl methacrylate (LMA) as hydrophobic block. They form micellar aggregates in aqueous solution. For this study the hydrophilic/hydrophobic balance was varied by incorporation of differing amounts of poly(ethylene glycol) (PEG) side chains into the hydrophilic block, while keeping the degree of polymerization of both blocks constant. PEGylation reduced the size of the micellar aggregates (Rh = 113 to 38 nm) and led to a minimum size of 7% PEG side chains. Polymers were labeled with the positron emitter 18F,…
[(11)C]PR04.MZ, a promising DAT ligand for low concentration imaging: Synthesis, efficient (11)C-O-methylation and initial small animal PET studies.
2009
PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [{sup 11}C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [{sup 11}C]MeI mediated synthesis of [{sup 11}C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb{sub 2}CO{sub 3} in DMF in up to 95 {+-} 5% labelling yield. A preliminary {mu}PET-experim…
Distribution of nitroreductive activity toward nilutamide in rat.
2004
Abstract Nilutamide is a pneumotoxic and hepatotoxic nitroaromatic (R-NO 2 ) antiandrogen used in the treatment of prostate carcinoma in man. Previously, we established that in the rat lung, the drug is metabolized into the corresponding hydroxylamine (R-NHOH) and amine (R-NH 2 ) derivatives. These results evidenced a cytosolic oxygen-sensitive (type II) nitroreductase activity in lung. In the present studies, we extended the characterization of nilutamide metabolism in liver, brain, kidney, heart, blood, intestine (small, cecum, and large, and their respective luminal contents) of male Sprague–Dawley rats. Subcellular fractions for all tissues (except blood) examined (postmitochondrial, cy…
Effect of autologous blood transfusion on cerebral cytokine expression.
2011
BACKGROUND: Autologous blood transfusion (ABT), for example, by means of cell saver equipment, is used to reduce the need for allogenic blood transfusion in patients with high perioperative blood loss. This study investigated the effect of blood/extracorporal surface interaction during withdrawal and retransfusion of shed autologous blood on cerebral inflammation in rats. Rats subjected to hypotension with cerebral ischemia served as positive controls. METHODS: Eighty-eight male Sprague-Dawley rats were anesthetized with sevoflurane, instrumented, and randomly assigned to the following groups: sham-operation (SHAM), autologous blood withdrawal/transfusion only (ABT), or bilateral carotid ar…
Angiotensin II-Induced Mononuclear Leukocyte Interactions with Arteriolar and Venular Endothelium Are Mediated by the Release of Different CC Chemoki…
2006
Abstract Angiotensin II (Ang-II) is associated with atherogenesis and arterial subendothelial mononuclear leukocyte infiltration. We have demonstrated that Ang-II causes the initial attachment of mononuclear cells to the arteriolar endothelium. We now report on the contribution of CC chemokines to this response. Intraperitoneal administration of 1 nM Ang-II induced MCP-1, RANTES, and MIP-1α generation, maximal at 4 h, followed by mononuclear leukocyte recruitment at 8 and 24 h. Using intravital microscopy within the rat mesenteric microcirculation 4 h after exposure to 1 nM Ang-II, arteriolar mononuclear cell adhesion was 80–90% inhibited by pretreatment with Met-RANTES, a CCR1 and CCR5 ant…
Characterization of DNA adducts at the bay region of dibenz[a,h]anthracene formed in vitro
1993
Bay region diolepoxide-DNA adducts of dibenz[a,h]anthracene (DBA) formed in vitro were identified and their absolute stereochemistry was assigned. After activation of [5,12-14C]DBA with liver microsomes obtained from Aroclor 1254 treated male Sprague-Dawley rats in the presence of calf thymus DNA for 1 h, the amount of DNA adducts was found to be 9.9 +/- 2.4 pmol/mg DNA, calculated on the basis of the portion of radioactivity eluted from the HPLC reversed-phase column with a water/acetonitrile gradient. Bay region diolepoxide-DNA adducts represented 27.5% of radioactivity associated with DNA adducts. The absolute configuration of the various adducts was determined from the reaction of the (…