Comparison of in vitro assays in selecting radiotracers for in vivo P-glycoprotein PET imaging

Positron emission tomography (PET) imaging of P-glycoprotein (P-gp) in the blood-brain barrier can be important in neurological diseases where P-gp is affected, such as Alzheimer’s disease. Radiotracers used in the imaging studies are present at very small, nanomolar, concentration, whereas in vitro assays where these tracers are characterized,...

Human apolipoprotein C-I expression in mice impairs learning and memory functions

The H2 allele of APOC1, giving rise to increased gene expression of apolipoprotein C-I (apoC-I), is in genetic disequilibrium with the APOE4 allele and may provide a major risk factor for Alzheimer's disease (AD). We found that apoC-I protein is present in astrocytes and endothelial cells within hippocampal regions in both human control and AD...

Neuroprotective effects of modafinil in a marmoset Parkinson model: Behavioral and neurochemical aspects

The vigilance-enhancing agent modafinil has neuroprotective properties: it prevents striatal ischemic injury, nigrostriatal pathway deterioration after partial transsection and intoxication with 1-methyl-1,2,3,6-tetrahydropyridine. The present study determines the protective effects of modafinil in the marmoset 1-methyl-1,2,3,6...

Neurobehavioural evaluation and kinetics of inhalation of constant or fluctuating toluene concentrations in human volunteers

The health risks of inhalation exposure to volatile organic solvents may not only depend on the total external dose, but also on the pattern of exposure. It has been suggested that exposure to regularly occurring peak concentrations may have a stronger impact on the brain than constant exposure at the same average level. Recent animal...

Behavioural effects and kinetics in brain in response to inhalation of constant or fluctuating toluene concentrations in the rat

The toxicity of exposure by inhalation to organic solvents may not only be related to the total external dose, but also to the pattern of exposure. In this study the impact of the exposure scenario on the behavioural effects of the model solvent toluene in rats was investigated. Rats were exposed for 7.5 h to either a constant concentration or...

Bioavailability of tryptophan from a single oral dose of a trytophan-enriched peptide mixture in healthy men

The aim of the study was to investigate the bioavailability of tryptophan (Trp) from a Trp-enriched peptide mixture in healthy men. A second objective was to investigate the effect of this Trp-enriched protein hydrolysate on potential parameters of serotonergic activity. serum serotonim melatonin and prolactin and urinary 5-hydroxyindol-acetic...

Moderate whisky consumption in combination with an evening meal reduces tryptophan availability to the brain but does not influence performance in healthy volunteers

Brain serotonin (5-HT) synthesis is controlled by nutrients that influence the availability of plasma tryptophan (Trp) as compared with the sum of the other large neutral amino acids (LNAA; Trp:LNAA). Alcohol consumption is found to change mood and performance and this might well be due to alterations in the plasma Trp:LNAA ratio and brain 5-HT....

Application of physiologically based toxicokinetic modelling to study the impact of the exposure scenario on the toxicokinetics and the behavioural effects of toluene in rats

The toxicity of inhalatory exposure to organic solvents may not only be related to the total external dose, but also to the pattern of exposure. In this study physiologically based toxicokinetic (PBTK) modelling has been used to study the impact of the exposure scenario on the toxicokinetics and the behavioural effects of the model solvent...

Effects of food on cortisol and mood in vulnerable subjects under controllable and uncontrollable stress

The aim of this study was to investigate whether in stress-prone subjects, carbohydrate-rich, protein-poor food (CR/PP) diminished depressive mood and a cortisol response under controllable as well as uncontrollable laboratory stress. Twenty-two subjects with high stress proneness (HS) and 23 subjects with low stress proneness (LS) participated...

Carbohydrate intake improves cognitive performance of stress-prone individuals under controllable laboratory stress

Cognitive performance has been found to decline after exposure to stress, particularly in stress-prone subjects. The present study investigated whether a carbohydrate-rich, protein-poor (CR/PP) diet, which may enhance cerebral serotonin function in stress-prone subjects due to increases in the available tryptophan, improves the performance of...

Selective lesions by manganese and extensive damage by iron after local injection into rat striatum or hippocampus

Regional 45Ca2+ accumulation and analysis of monoamines and metabolites in dissected tissues were used to localize, quantify, and characterize brain damage after intracerebral injections of Mn2+ into striatum and hippocampus. The specificity of Mn2+-induced lesions is described in relation to brain damage produced by local Fe2+ or 6-...

Kinetic profile in blood and brain of the cholinesterase reactivating oxime HI-6 after intravenous administration to the rat

The kinetic profile of the oxime HI-6, a potent cholinesterase reactivator, after iv administration of 0.1325 mmol/kg (50 mg/kg) to rats is described. The blood concentrations measured over a period of 300 min can be described by a two-compartment open model. Excretion occurred only by the kidney. Approximately 60% was excreted in unmetabolized...

The influence of triorthocresylphosphate on the distribution of 32P in the body of the rat after the injection of 32P-sarin

The ChE- and AE- activities and the 32P-concentration of the plasma from rats 1 and 24 hr after s.c. injection of 32P-sarin (200 μg kg) were measured. One hr after the injection the ChE was inhibited to approx. 10 per cent and the AE to 40-50 per cent; 23 hr later 50 per cent of the ChE activity was found to be restored and the AE had recovered...