STEPHEN JOHN KISH

..Our data suggest that chronic heroin exposure might produce a modest reduction in dopaminergic and serotonergic activity that could affect motivational state and impulse control, respectively...

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..There is no medication approved for the treatment of relapses of methamphetamine addiction; however, potential therapeutic agents targeted to dopamine and nondopamine (e.g., opioid) systems are in clinical testing...

..However, there has been no consistency in the selection of a "SERT-free" reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed...

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..Until these issues are resolved, it cannot be assumed that ecstasy exposure represents a chronic serotonin deficiency condition...

..We suggest that pharmacotherapies which augment this compensatory response might have utility as a treatment for Parkinson's disease...

..We conclude that dopamine stimulated AC can be measured in cerebral cortex of human brain allowing for the possibility that this process can be examined in human brain disorders in which dopaminergic abnormalities are suspected...

..The data expand the clinical spectrum of TH deficiency and suggest that TH mutations may account for some patients with DRD simulating spastic paraplegia...

..Our data suggest that the DYT1 mutation is not associated with significant damage to the nigrostriatal DA system, in keeping with the absence of parkinsonism and levodopa response in this disorder...

..g., phosphorylation/accessory binding protein) or caused by the existence of multiple molecular forms of the DA transporter is currently unknown...

..In conclusion our data indicate different regulatory properties of PE and PC synthesis in human brain, and suggest that the rate of PE synthesis may be more dependent upon substrate (ethanolamine) availability than that of PC synthesis...

..Our data demonstrate a new phenotype of GCH deficiency associated with compound heterozygosity for GCH gene mutations and suggest the usefulness of combined BH4 and levodopa therapy for this disorder...

..Further investigation will be required to establish whether SERT binding is more or less decreased in those patients with PD who also have major depressive disorder...

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..Studies of cognitive and brain cholinergic status in high dose users of MA are warranted...

..Nevertheless, reduced levels of this rate-limiting enzyme of the Krebs cycle could contribute to the brain neurodegenerative mechanisms of AD...

..Increased quinolinic acid phosphoribosyltransferase activity may represent a mechanism, in the degenerating cerebellum, to protect quinolinic acid-sensitive granule cells in patients with olivopontocerebellar atrophy...

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..Our finding suggests a beneficial effect of amantadine on this type of dyskinesia frequently observed in relatively severe dopamine-deficient metabolic disorders...

..This provides evidence for involvement of oxygen-based free radicals in the action of MA in both dopamine-rich (caudate) and -poor (cerebral cortex) areas of human brain...

..Experimental findings using animal models of Parkinson disease (PD) suggest that noradrenaline might protect dopamine neurons from damage...

..This suggests that noradrenaline signalling is much less spatially and temporally restricted in the caudomedial accumbens than in other noradrenaline-rich brain areas...

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..Our postmortem brain data suggest involvement of striatal dynorphin systems in human cocaine users and should add to the interest in the testing of new dynorphin-related therapeutics for the treatment of cocaine addiction...

..If correct, (+)[(11)C]DTBZ might be a useful imaging probe to correlate changes in brain dopamine stores and behavior in users of methamphetamine...

..The presence of very high, localized noradrenaline concentrations in the caudomedial nucleus accumbens implies a special biological role for this neurotransmitter in human brain motivational processes...

..Increased CuZnSOD and uric acid might reflect compensatory responses to oxidative stress. Future studies are necessary to establish whether these changes are associated with oxidative brain damage in human methamphetamine users...

..This possibility should be taken into account when utilizing VAChT as a neuroimaging outcome marker for cholinergic neuron number in human studies...

..Decreased striatal Ca-PLA(2) and/or PCCT activity in cocaine users might also help to explain why CDP choline, which enhances phospholipid synthesis, reduces craving in some users of the drug cocaine...

..Our data suggest that the extent of striatal tyrosine hydroxylase protein loss may be critical in determining dopa-responsive dystonia symptomatology...

..Decreased dopamine D(1) receptor function might underlie part of the known (drug withdrawal syndrome) or expected (drug tolerance) consequences of methamphetamine exposure in humans...

..Our brain data suggest that a systemic, global disturbance in the catalytic activity and degradation ability of the proteasome itself is unlikely to explain the cause of Parkinson's disease...

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..This suggests that declines in DA-related function during adulthood and senescence may be explained by losses in DA per se as opposed to DAergic neuropil...

..g. levodopa) during drug rehabilitation might be helpful...

..The supersensitive dopamine D(1) receptors in both striatum and cerebral cortex in PD might compensate for dopamine deficiency, but could also contribute to long-term complications of levodopa therapy...

..Drug users and investigators examining possible brain neurotoxic effects of MDMA need to consider that "ecstasy" tablets can contain MDA and methamphetamine despite no demand for the drugs...

..Surgical treatment is an option for a defined patient population...

..Taken together, these observations suggest that elevations of alpha(s) in BD brain are more likely related to factors affecting the disposition or availability of alpha(s) to this posttranslational enzymatic modification...

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..More broadly, our data will help define the contribution of different neuroanatomical components of the brain serotonin system to human behavior. ..

..Results might also help in assessing the validity of a brain imaging tool that has been proposed for use in testing whether new neuroprotective drugs slow down the progression of Parkinson's disease. ..