The striatal dopamine transporter in first-episode, drug-naive schizophrenic patients: evaluation by the new SPECT-ligand[99mTc]TRODAT-1

Following the current hypothesis that acute schizophrenic psychotic illness is associated with a triatal ‘hyperdopaminergic state’, presynaptic integrity and dopamine transporter (DAT) density in first-episode, neuroleptic-naive schizophrenic patients was measured by single-photonemission- tomography (SPECT) and compared with that in healthy control subjects. A new SPECT-ligand for assessment of the striatal DAT, the Technetium-99m-labelled tropane TRODAT-1 ([99mTc]TRODAT-1), was used. Ten inpatients suffering from a first acute schizophrenic episode and 10 age- and sex-matched healthy control subjects underwent SPECT with [99mTc]TRODAT-1. On the day of SPECT, psychopathological ratings were performed with the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and Schedule for Assessment of Negative Symptoms (SANS). Patients had not previously received any neuroleptic or antidepressant medication. Mean specific TRODAT-1 binding in the striatum did not differ significantly between the patient and the age- and sex-matched control group (1.25 vs. 1.28). Variance was significantly higher in the patient group. The data obtained with the new ligand in first-episode, drug-naive schizophrenic patients are in line with the PET results from the group of Laakso et al. in a comparable patient sample. [99mTc]TRODAT-1 seems to be a valuable new SPECTligand in the evaluation of the presynaptic site of the striatal dopaminergic synapse in schizophrenia

Striatal dopamine D2 receptor binding of risperidone in schizophrenic patients as assessed by 123I-iodobenzamide SPECT: a comparative study with olanzapine

The aim of this investigation was to compare the degree of striatal dopamine-(D2) receptor blockade by two atypical antipsychotic drugs, risperidone and olanzapine. The percentage of D2 receptor occupancy during treatment was calculated by comparing the results of 123I-iodobenzamide SPECT with those from healthy control subjects. Twenty inpatients suffering from schizophrenia or schizoaffective psychosis according to DSM IV/ICD-10 criteria were treated with clinically recommended doses of risperidone and compared with 13 inpatients treated with up to 20 mg olanzapine. Neuroleptic dose and D2 receptor blockade correlated strongly for both risperidone (Pearson r = –0.86, p = 0.0001) and olanzapine (Pearson r = –0.77, p = 0.002). There was no significant difference between the D2 receptor occupancy of the two substances when given in the clinically recommended dose range (unpaired t-test, t= –0.112, p=0.911)

Translational Modeling in Schizophrenia:Predicting Human Dopamine D2 Receptor Occupancy

OBJECTIVES: To assess the ability of a previously developed hybrid physiology-based pharmacokinetic-pharmacodynamic (PBPKPD) model in rats to predict the dopamine D2 receptor occupancy (D2RO) in human striatum following administration of antipsychotic drugs.METHODS: A hybrid PBPKPD model, previously developed using information on plasma concentrations, brain exposure and D2RO in rats, was used as the basis for the prediction of D2RO in human. The rat pharmacokinetic and brain physiology parameters were substituted with human population pharmacokinetic parameters and human physiological information. To predict the passive transport across the human blood-brain barrier, apparent permeability values were scaled based on rat and human brain endothelial surface area. Active efflux clearance in brain was scaled from rat to human using both human brain endothelial surface area and MDR1 expression. Binding constants at the D2 receptor were scaled based on the differences between in vitro and in vivo systems of the same species. The predictive power of this physiology-based approach was determined by comparing the D2RO predictions with the observed human D2RO of six antipsychotics at clinically relevant doses.RESULTS: Predicted human D2RO was in good agreement with clinically observed D2RO for five antipsychotics. Models using in vitro information predicted human D2RO well for most of the compounds evaluated in this analysis. However, human D2RO was under-predicted for haloperidol.CONCLUSIONS: The rat hybrid PBPKPD model structure, integrated with in vitro information and human pharmacokinetic and physiological information, constitutes a scientific basis to predict the time course of D2RO in man.</p

Pranolium

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72226/1/j.1527-3466.1983.tb00447.x.pd

Is teacher happiness contagious? A study of the link between perceptions of language teacher happiness and student attitudes

There remains a dearth of research on the effects of student perception of teacher happiness and the ramifications of those perceptions on student feelings and attitudes. Using an online questionnaire, data were collected from 129 adult students of ESL/EFL across the world who were enrolled in formal English classes of intermediate to advanced level proficiency. Participants were asked about their perception of various aspects of their teachers’ happiness, and about their own attitudes and motivation to learn English. Statistical analyses revealed that student perception of teacher happiness was significantly (and positively) linked with students’ Overall attitude and motivation, as well as students’ Attitude towards the teacher. This is interpreted as an illustration of the process of positive emotional contagion between teachers and students. Pedagogical implications of the results are discussed

Geochemical and Strontium Isotope Characterization of Produced Waters from Marcellus Shale Natural Gas Extraction

Extraction of natural gas by hydraulic fracturing of the Middle Devonian Marcellus Shale, a major gas-bearing unit in the Appalachian Basin, results in significant quantities of produced water containing high total dissolved solids (TDS). We carried out a strontium (Sr) isotope investigation to determine the utility of Sr isotopes in identifying and quantifying the interaction of Marcellus Formation produced waters with other waters in the Appalachian Basin in the event of an accidental release, and to provide information about the source of the dissolved solids. Strontium isotopic ratios of Marcellus produced waters collected over a geographic range of ∼375 km from southwestern to northeastern Pennsylvania define a relatively narrow set of values (εSr SW = +13.8 to +41.6, where εSr SW is the deviation of the 87Sr/86Sr ratio from that of seawater in parts per 104); this isotopic range falls above that of Middle Devonian seawater, and is distinct from most western Pennsylvania acid mine drainage and Upper Devonian Venango Group oil and gas brines. The uniformity of the isotope ratios suggests a basin-wide source of dissolved solids with a component that is more radiogenic than seawater. Mixing models indicate that Sr isotope ratios can be used to sensitively differentiate between Marcellus Formation produced water and other potential sources of TDS into ground or surface waters