Search results for "amines"
showing 10 items of 664 documents
Contrasting coping styles meet the wall: A dopamine driven dichotomy in behavior and cognition
2017
Individual variation in the ability to modify previously learned behaviour is an important dimension of trait correlations referred to as coping styles, behavioral syndromes or personality. These trait clusters have been shaped by natural selection, and underlying control mechanisms are often conserved throughout vertebrate evolution. In teleost fishes, behavioral flexibility and coping style have been studied in the high (HR) and low-responsive (LR) rainbow trout lines. Generally, proactive LR trout show a behaviour guided by previously learned routines, while HR trout show a more flexible behaviour relying on environmental cues. In mammals, routine dependent vs flexible behavior has been …
Hypothesis: Etiologic and Molecular Mechanistic Leads for Sporadic Neurodegenerative Diseases Based on Experience With Western Pacific ALS/PDC
2019
Seventy years of research on Western Pacific amyotrophic lateral sclerosis and Parkinsonism-dementia Complex (ALS/PDC) have provided invaluable data on the etiology, molecular pathogenesis and latency of this disappearing, largely environmental neurodegenerative disease. ALS/PDC is linked to genotoxic chemicals (notably methylazoxymethanol, MAM) derived from seed of the cycad plant (Cycas spp.) that were used as a traditional food and/or medicine in all three disease-affected Western Pacific populations. MAM, nitrosamines and hydrazines generate methyl free radicals that damage DNA (in the form of O6-methylguanine lesions) that can induce mutations in cycling cells and degenerative changes …
Genetic inactivation of the sigma-1 chaperone protein results in decreased expression of the R2 subunit of the GABA-B receptor and increased suscepti…
2021
There is a growing body of evidence demonstrating the significant involvement of the sigma-1 chaperone protein in the modulation of seizures. Several sigma-1 receptor (Sig1R) ligands have been demonstrated to regulate the seizure threshold in acute and chronic seizure models. However, the mechanism by which Sig1R modulates the excitatory and inhibitory pathways in the brain has not been elucidated. The aim of this study was to compare the susceptibility to seizures of wild type (WT) and Sig1R knockout (Sig1R−/−) mice in intravenous pentylenetetrazol (PTZ) and (+)-bicuculline (BIC) infusion-induced acute seizure and Sig1R antagonist NE-100-induced seizure models. To determine pos…
Synthesis and antiproliferative mechanism of action of pyrrolo[3′,2′:6,7] cyclohepta[1,2-d]pyrimidin-2-amines as singlet oxygen photosensitizers
2016
A new series of pyrrolo[3′,2′:6,7]cyclohepta[1,2-d]pyrimidin-2-amines, was conveniently prepared using a versatile and high yielding multistep sequence. A good number of derivatives was obtained and the cellular photocytotoxicity was evaluated in vitro against three different human tumor cell lines with EC50 (0.08–4.96 μM) values reaching the nanomolar level. Selected compounds were investigated by laser flash photolysis. The most photocytotoxic derivative, exhibiting a fairly long-lived triplet state (τ ∼ 7 μs) and absorbance in the UV–Vis, was tested in the photo-oxidations of 9,10-anthracenedipropionic acid (ADPA) by singlet oxygen. The photosentizing properties are responsible for the c…
The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes.
2020
The vitamin D receptor (VDR) must be relevant to liver lipid metabolism because VDR deficient mice are protected from hepatosteatosis. Therefore, our objective was to define the role of VDR on the overall lipid metabolism in human hepatocytes. We developed an adenoviral vector for human VDR and performed transcriptomic and metabolomic analyses of cultured human hepatocytes upon VDR activation by vitamin D (VitD). Twenty percent of the VDR responsive genes were related to lipid metabolism, including MOGAT1, LPGAT1, AGPAT2, and DGAT1 (glycerolipid metabolism)
Spontaneous domain formation of phospholipase A2 at interfaces: fluorescence microscopy of the interaction of phospholipase A2 with mixed monolayers …
1992
Abstract Fluorescence microscopy has recently been proven to be an ideal tool to investigated the specific interaction of phospholipase A 2 with oriented substrate monolayers. Using a dual labeling technique, it could be shown that phospholipase A 2 can specifically attack and hydrolyze solid analogous l -α-DPPC domains. After a critical extent of monolayer hydrolysis the enzyme itself starts to aggregate forming regular shaped protein domains (Grainger et al. (1990) Biochim. Biophys. Acta 1023. 365–379). In order to confirm that the existence of hydrolysis products in the mononlayer is necessary for the observed aggregation of phospholipase A 2 , mixed monolayers of d - and l -α-DPPC, l -α…
Chiral Serum Pharmacokinetics of 4-Fluoroamphetamine after Controlled Oral Administration
2021
Abstract Over the last two decades, misuse of 4-fluoroamphetamine (4-FA) became an emerging issue in many European countries. Stimulating effects last for 4–6 hours and can impact psychomotor performance. The metabolism of amphetamine-type stimulants is stereoselective and quantification of (R)- and (S)-enantiomers has been suggested for assessing time of use. To date, no data on enantioselective pharmacokinetics is available for 4-FA in serum samples. An enantioselective liquid chromatography−tandem mass spectrometry (LC–MS-MS) method was developed using a chiral Phenomenex® Lux 3 μm AMP column. Validation of the method showed satisfactory selectivity, sensitivity, linearity (0.5–250 ng/mL…
Diastereoselective synthesis of 6-functionalized 4-aryl-1,3-oxazinan-2-ones and their application in the synthesis of 3-aryl-1,3-aminoalcohols and 6-…
2010
Abstract Halocyclocarbamation of benzyl N -(1-phenyl-3-butenyl)carbamates afforded 6-functionalized 4-aryl-1,3-oxazinan-2-ones with moderate to excellent diastereoselectivity depending on the N -substituent. Importantly, in contrast to reported cyclocarbamations of homoallylic carbamates, which are generally trans -diastereoselective, cyclization of N -unsubstituted Cbz-protected homoallylamines led to cis -1,3-oxazinan-2-ones, predominantly. The use of N -benzylated and in situ prepared N -silylated derivatives resulted however in trans -selectivity. Transition states are proposed to explain the stereochemical influence of the N -substituent on the cyclocarbamations. The functionalized 1,3…
Smart inulin-based polycationic nanodevices for siRNA delivery
2017
The advances of short interfering RNA (siRNA) mediated therapy provide a powerful option for the treatment of many diseases by silencing the expression of targeted genes including cancer development and progression. Inulin is a very simple and biocompatible polysaccharide proposed by our groups to produce interesting delivery systems for Nucleic Acid Based Drugs (NABDs), such as siRNA, either as polycations able to give polyplexes and polymeric coatings for nanosystems having a metallic core. In this research field, different functionalizing groups were linked to the inulin backbone with specific aims including oligoamine such as Ethylendiammine (EDA), Diethylediamine (DETA), Spermine, (SPM…
Development of a simple, biocompatible and cost-effective Inulin-Diethylenetriamine based siRNA delivery system
2015
Small interfering RNAs (siRNAs) have the potential to be of therapeutic value for many human diseases. So far, however, a serious obstacle to their therapeutic use is represented by the absence of appropriate delivery systems able to protect them from degradation and to allow an efficient cellular uptake. In this work we developed a siRNA delivery system based on inulin (Inu), an abundant and natural polysaccharide. Inu was functionalized via the conjugation with diethylenetriamine (DETA) residues to form the complex Inu-DETA. We studied the size, surface charge and the shape of the Inu-DETA/siRNA complexes; additionally, the cytotoxicity, the silencing efficacy and the cell uptake-mechanis…