32 research outputs found
Evaluation of inter-departmental variability of ejection fraction and cardiac volumes in myocardial perfusion scintigraphy using simulated data
Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress
In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse
Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene GRIN2A as a Parkinson's Disease Modifier Gene via Interaction with Coffee
Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P2df = 10−6, GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10−7) but not in light coffee-drinkers. The a priori Replication hypothesis that “Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers” was confirmed: ORReplication = 0.59, PReplication = 10−3; ORPooled = 0.51, PPooled = 7×10−8. Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10−3), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10−13). Imputation revealed a block of SNPs that achieved P2df<5×10−8 in GWAIS, and OR = 0.41, P = 3×10−8 in heavy coffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify genes that are missed in GWAS. Both adenosine antagonists (caffeine-like) and glutamate antagonists (GRIN2A-related) are being tested in clinical trials for treatment of PD. GRIN2A may be a useful pharmacogenetic marker for subdividing individuals in clinical trials to determine which medications might work best for which patients
Modular structure of web-based decision support systems for integrated pest management. A review
Estimating the biological half-life for radionuclides in homoeothermic vertebrates: a simplified allometric approach
The application of allometric, or mass-dependent,
relationships within radioecology has increased with the
evolution of models to predict the exposure of organisms
other than man. Allometry presents a method of addressing
the lack of empirical data on radionuclide transfer and
metabolism for the many radionuclide–species combinations
which may need to be considered. However, sufficient data
across a range of species with different masses are required to
establish allometric relationships and this is not always
available. Here, an alternative allometric approach to predict
the biological half-life of radionuclides in homoeothermic
vertebrates which does not require such data is derived.
Biological half-life values are predicted for four radionuclides
and compared to available data for a range of species.
All predictions were within a factor of five of the observed
values when the model was parameterised appropriate to the
feeding strategy of each species. This is an encouraging level
of agreement given that the allometric models are intended to
provide broad approximations rather than exact values.
However, reasons why some radionuclides deviate from what
would be anticipated from Kleiber’s law need to be determined
to allow a more complete exploitation of the potential
of allometric extrapolation within radioecological models
Transfer parameters for ICRP reference animals and plants collected from a forest ecosystem
The International Commission on Radiological
Protection (ICRP) have suggested the identification of a
series of terrestrial, marine and freshwater sites from which
samples of each Reference animal and plant (RAP) could
be systematically collected and analysed. We describe the
first such study in which six of the eight terrestrial RAPs,
and associated soil samples, were collected from a site
located in a managed coniferous forestry plantation in
north-west England. Adult life stages of species representing
six of the terrestrial RAPs (Wild grass, Pine tree,
Deer, Rat, Earthworm and Bee) were sampled and analysed
to determine concentrations of 60 elements and gammaemitting
radionuclides. The resultant data have been used
to derive concentration ratios (CRwo-soil) relating element/
radionuclide concentrations in the RAPs to those in soil.
This paper presents the first-reported transfer parameters
for a number of the RAP–element combinations. Where
possible, the derived CRwo-soil values are compared with
the ICRPs-recommended values and any appreciable differences
discussed