The purpose of this investigation was to evaluate the effects of smoking and gender on 1) tetrahydroisoquinolines (TIQs) and beta-carbolines (BCs) in a population of healthy subjects and 2) TIQs in an alcohol-dependent population undergoing in-patient detoxification. Comparison in plasma TIQs between the populations was additionally conducted. To support the clinical investigations, a HPLC-FD method was developed and validated to assess plasma concentrations of BCs, harman and norharman, while a HPLC-ESI-MS/MS method was validated to quantify the TIQs, R/S-salsolinol along with dopamine. Forty-one young volunteers were recruited including 19 nonsmokers (NS), 11 light smokers (LS) and 11 heavy smokers (HS), stratified by their smoking history. Each group had, at least, 5 males and females. Plasma samples were obtained for analyte measurement within 30 minutes of smoking for LS and HS groups. Two–way ANCOVA was performed on the log-transformed concentrations. Significant differences were found between HS-NS and LS-NS in analyte concentrations. A comparison to eighteen subjects (6 NS, LS and HS) abstaining from smoking for 15 hours resulted in a difference only between NS and HS, suggesting that acute tobacco smoking has a major influence on circulating TIQs and BCs between smoking status groups. In a study involving thirty-five alcohol dependent subjects (12 NS, 11 LS, and 12 HS, balanced with gender), TIQ measurements were taken on day 1, 2, 3, 8 and 15 of inpatient detoxification. A significant effect of time was observed, with TIQ concentrations slightly increasing from admission to day 15. Both factors of smoking status and gender did not have a significant effect on plasma TIQ's at any of the time points evaluated. Although, measures of acute and chronic alcohol intake had no effect on TIQ levels, liver function showed moderate correlation with plasma TIQs. Comparison of both populations showed that alcoholics had a lower average TIQ concentration than healthy subjects. The results indicate that smoking status 1) has an effect on plasma TIQs and BCs in healthy individuals and 2) does not have an effect in alcoholics during detoxification. The alcoholics possessed lower TIQ concentrations than the healthy subjects. No gender effect was observed in either study.

No description available.

In assessing and assimilating the neurodevelopmental basis of the so-called movement disorders it is probably useful to establish certain concepts that will modulate both the variation and selection of affliction, mechanisms-processes and diversity of disease states. Both genetic, developmental and degenerative aberrations are to be encompassed within such an approach, as well as all deviations from the necessary components of behaviour that are generally understood to incorporate "normal" functioning. In the present treatise, both conditions of hyperactivity/hypoactivity, akinesia and bradykinesia together with a constellation of other symptoms and syndromes are considered in conjunction with the neuropharmacological and brain morphological alterations that may or may not accompany them, e.g. following neonatal denervation. As a case in point, the neuroanatomical and neurochemical points of interaction in Attention Deficit and Hyperactivity disorder (ADHD) are examined with reference to both the perinatal metallic and organic environment and genetic backgrounds. The role of apoptosis, as opposed to necrosis, in cell death during grain development necessitates careful considerations of the current explosion of evidence for brain nerve growth factors, neurotrophins and cytokines, and the processes regulating their appearance, release and fate. Some of these processes may posses putative inherited characteristics, like asynuclein, others may to greater or lesser extents be endogenous or semi-endogenous (in food), like the tetrahydroisoquinolines, others exogenous until inhaled or injested through environmental accident, like heavy metals, e.g. mercury. Another central concept of neurodevelopment is cellular plasticity, thereby underlining the essential involvement of glutamate systems and N-methyl-D-aspartate receptor configurations. Finally, an essential assimilation of brain development in disease must delineate the relative merits of inherited as opposed to environmental risks not only for the commonly-regarded movement disorders, like Parkinson's disease, Huntington's disease and epilepsy, but also for afflictions bearing strong elements of psychosocial tragedy, like ADHD, autism and Savantism.

No description available.