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Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. Although opioid sensitivity is well known to vary widely among individual subjects, several candidate genetic polymorphisms reported so far are not sufficient for fully understanding the wide range of interindividual differences in human opioid sensitivity. By conducting a multistage genome-wide association study (GWAS) in healthy subjects, we found that genetic polymorphisms within a linkage disequilibrium block that spans 2q33.3-2q34 were strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery. The C allele of the best candidate single-nucleotide polymorphism (SNP), rs2952768, was associated with more analgesic requirements, and consistent results were obtained in patients who underwent abdominal surgery. In addition, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence in patients with methamphetamine dependence, alcohol dependence, and eating disorders and a lower 'Reward Dependence' score on a personality questionnaire in healthy subjects. Furthermore, the C/C genotype of this SNP was significantly associated with the elevated expression of a neighboring gene, CREB1. These results show that SNPs in this locus are the most potent genetic factors associated with human opioid sensitivity known to date, affecting both the efficacy of opioid analgesics and liability to severe substance dependence. Our findings provide valuable information for the personalized treatment of pain and drug dependence. [ABSTRACT FROM AUTHOR]

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) in combination with scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) is used for the determination of elemental spatial distribution in ceramic multi-layer systems such as those found in intermediate-temperature solid oxide fuel cells (IT-SOFCs). Because layer sintering occurs at high temperature (usually well over 1000 °C), there may be mutual diffusion of ions from one layer to another, with dramatic consequences on cell performances. In this work, two model materials have been used to test LA-ICP-MS: LaSrGaMgO (LSGM), one of the most promising electrolytes for IT-SOFCs, and LaSrMnO (LSM), a highly representative perovskite material, which are amply used to design electrode materials. A two-layer system screen printed onto an LSM pellet (LSM-LSGM-LSM pellet) was successively sintered at a typical processing temperature, i.e. 1300 °C, for a short time (1 h). Elemental spatial distribution was determined by line profile analyses carried out on fracture surfaces; for comparison SEM-EDS line profiles were tested on the same surface. LA-ICP-MS line profile analysis evidenced that, notwithstanding the relatively low sintering temperature and short firing time (1 h per sintering), manganese cation diffusion into LSGM is relatively abundant, in agreement with previous literature reports and present EDS results. While line scan EDS analyses are not as conclusive for Ga and Mg diffusion, LA-ICP-MS shows that both ions diffuse across both interfaces, and Ga diffuses even over very long distances into the LSM pellet; on the contrary, only trace amounts of Mg can be found far from the LSGM/LSM interface. [ABSTRACT FROM AUTHOR]

Several studies indicate that the μ-opioid receptor plays a role in addiction not only to opiate drugs but also to alcohol and non-opiate addictive drugs. Our studies aim to reveal the associations between gene polymorphisms and methamphetamine (MAP) dependence/psychosis. We newly identified several polymorphisms and four substantial linkage disequilibrium (LD) blocks in the μ-opioid receptor (OPRM1) gene. We found significant differences in both genotype and allele frequencies of the single-nucleotide polymorphism (SNP) IVS2+G691C between control (n=232) and MAP-dependent/psychotic patients (n=128). There was also a significant association between IVS2+G691C and patients with transient psychosis. These results suggest that the OPRM1 gene variations may be a factor in development and prognosis of MAP psychosis.The Pharmacogenomics Journal (2006) 6, 179–188. doi:10.1038/sj.tpj.6500355; published online 10 January 2006 [ABSTRACT FROM AUTHOR]

Psychostimulant use disorder and schizophrenia have a substantial genetic basis. Evidence from human and animal studies on the involvement of the?-aminobutyric acid (GABA) system in methamphetamine (METH) use disorder and schizophrenia is mounting. As we tested for the association of the human GABAA receptor gamma 2 subunit gene (GABRG2) with each diagnostic group, we used a case-control design with a set of 178 subjects with METH use disorder, 288 schizophrenics and 288 controls. First, we screened 96 controls and identified six SNPs in GABRG2, three of whom we newly reported. Next, we selected two SNPs, 315C>T and 1128+99C>A, as representatives of the linkage disequilibrium blocks for further case-control association analysis. Although no associations were found in either allelic or genotypic frequencies, we detected a haplotypic association in GABRG2 with METH use disorder, but not with schizophrenia. This finding partly replicates a recent case-control study of GABRG2 in METH use disorder, and thus indicates that GABRG2 may be one of the susceptibility genes of METH use disorder.The Pharmacogenomics Journal (2005) 5, 89-95. doi:10.1038/sj.tpj.6500292 [ABSTRACT FROM AUTHOR]

The recent interest in the (Sr, Mg) doped LaGaO3 family compounds as electrolyte for Intermediate Temperature Solid Oxide Fuel Cells (IT-SOFCs) has suggested the study of the system α-Al2O3/La0.8Sr0.2Ga0.8Mg0.2O3–δ as a possible new ionic conductor composite. The studies concerning the electrical and microstructural characterization of the system α-Al2O3/La0.8Sr0.2Ga0.8Mg0.2O3–δ, in a wide compositions range, are reported and discussed. [ABSTRACT FROM AUTHOR]

Deals with a study which investigated the association between methamphetamine (METH) dependence/psychosis and the hDAT1 gene encoding the dopamine transporter, which is the primary site of METH activity in the brain. Introduction to the study; Subjects and methods.

Several lines of evidence suggest that monoaminergic systems, especially dopaminergic and serotoninergic systems, modulate ethanol consumption. Humans display significant differences in expression of the vesicular and plasma membrane monoamine transporters important for monoaminergic functions, including the vesicular monoamine transporter (VMAT2, SLC18A2) and dopamine transporter (DAT, SLC6A3). In addition, many ethanol effects differ by sex in both humans and animal models. Therefore, ethanol consumption and preference were compared in male and female wild-type mice, and knockout (KO) mice with deletions of genes for DAT and VMAT2. Voluntary ethanol (2-32% v/v) and water consumption were compared in two-bottle preference tests in wild-type (+/+) vs heterozygous VMAT2 KO mice (+/-) and in wild-type (+/+) vs heterozygous (+/-) or homozygous (-/-) DAT KO mice. Deletions of either the DAT or VMAT2 genes increased ethanol consumption in male KO mice, although these effects were highly dependent on ethanol concentration, while female DAT KO mice had higher ethanol preferences. Thus, lifetime reductions in the expression of either DAT or VMAT2 increase ethanol consumption, dependent on sex. [ABSTRACT FROM AUTHOR]

Focuses on the molecular sites of action of cocaine reward and locomotor stimulation. Role of dopamine transporter blockade by cocaine in cocaine-induced locomotion; Differences in locomotion without drug stimulation; Multitransporter involvement of dopamine with the rewarding and aversive actions of cocaine.

Abstract Rationale: Differences in p-opiate receptor (MOR) gene expression may modulate the rewarding effects of ethanol. Objective: The effects of MOR gene knockout (KO) were examined in wild-type (+/+), heterozygote MOR KO (+/-), and homozygote MOR KO (-/-) mice on voluntary ethanol consumption, conditioned place preference produced by ethanol, and locomotor responses to ethanol in separate groups of mice. Methods: Voluntary ethanol consumption (2-32% v/v) was examined in a two-bottle home-cage consumption test. The conditioned place preference paradigm was a biased design. Mice received four pairings of ethanol (2.0 g/kg IP) on the initially preferred side and four pairings on the initially non-preferred side with saline. The difference in time spent on the initially non-preferred side (pre- versus post-conditioning) was the measure of drug-induced preference. After habituation to a novel locomotor test chamber mice were tested, on subsequent sessions, for ethanol induced locomotion (0.0, 0.5, 1.0, and 2.0 g/kg IP). Results: Heterozygous and homozygous MOR KO mice consumed less ethanol than wildtype mice. These effects appeared to be greater in female KO mice than in male KO mice. MOR KO mice, especially females, exhibited less ethanol reward in a conditioned place preference paradigm. These effects on ethanol reward were produced by reductions in MOR expression levels as small as 50%. MOR KO mice exhibited less ethanol-stimulated locomotion than did wild-type mice, an effect that was also largest in females. Conclusions: These data fit with the reported therapeutic effica-... [ABSTRACT FROM AUTHOR]

The crystal structure of YCaCuO has been determined by neutron powder diffraction at room temperature. The compound crystallizes with the symmetry of the hexagonal space group P6/m and lattice parameters a=6.1991(2), c=11.2059(3) Å. The configuration of the atoms in the unit cell may be alternatively described as an AgFeO-type structure with extra oxygen atoms in the copper plane, or as an oxygen-deficient perovskite of general formula ABO (x=0.46) chemically and structurally related to the '123' superconductor oxide. In the unit cell the sequence of layers is ...[(YO )( CuO+Cu )( YO )( CuO+Cu )]... . The yttrium and calcium atoms are mixed over three symmetrically independent sites. The coordination number of Y/Ca atoms is seven. The defective layer can be derived from a defective perovskite layer BO in which rows of oxygen atoms are interleaved with double rows of oxygen vacancies, giving an oxygen stoichiometry of O. The shifts of the oxygen atoms from their original perovskite positions and the hexagonal distortion of the lattice result in tetrahedral coordination around each Cu atom. The additional oxygen vacancies in the copper layers necessary to reduce the oxygen stoichiometry to O are assumed to be randomly distributed. [ABSTRACT FROM AUTHOR]