Summary:The impulse response function of a radioligand is the most fundamental way to describe its pharmacokinetics and to assess its tissue uptake and retention pattern. This study investigates the impulse response function of e I Cl( +) McN5652, a radioligand used for positron emission tomogra phy (PET) imaging of the serotonin transporter (SERT) in the brain. Dynamic PET studies were performed in eight healthy volunteers injected with e 1C](+)McN5652 and subsequently with its pharmacologically inactive enantiomer [IICl( -) McN5652. The impulse response function was calculated by deconvolution &nalysis of regional time-activity curves, and its peak value (f max ), its retention value at 75 minutes (fT)' and its normalized retention (fr e l = fTlf max ) were obtained. Alterna tively, compartmental models were applied to calculate the apparent total distribution volume (DV T ) and its specific bind ing component (DVs). Both the noncompartmental (fT,het) and the compartmental parameters (DV) were investigated with and without correction for nonspecific binding by simple subtrac tion of the corresponding value obtained with [IICl(_)_ McN5652. The impulse response function obtained by decon volution analysis demonstrated high tracer extraction followed by a slow decline in the form of a monoexponential function. Statistical analysis revealed that the best compartmental model in terms of analysis of variance F and condition number of the parameter variance-covariance matrix was the one that was based on a single tissue compartment with parameters kl and k2 and that also included the parameter of regional cerebral blood Positron emission tomography (PET) imaging of the serotonin transporter (SERT) is based on the rationale that SERT is expressed by serotonergic (5-HT) neurons volume (BV).The parameter frel demonstrated low between subject variance (coefficient of variation [CV] = 19%), a mid brain to cerebellum ratio of 1.85, and high correlation with the known density of SERT (r = 0.787 where r is the coefficient of linear correlation between the parameter and the known density of SERT). After correction for nonspecific binding, fre l demonstrated further improvement in correlation (r = 0.814) and midbrain to cerebellum ratio (3.09). The variance of the distribution volumes was acceptable when the logarithmic transform InDV was used instead of DV (17% for the three parameter model), but correlation of this compartmental pa rameter was slightly less (r = 0.652 for the three-parameter model) than the correlation of the noncompartmental fre l with the known density of SERT, and the midbrain to cerebellum ratio was only 1.5 (uncorrected) and 1.8 (corrected). At the expense of increasing variance, the correlation was increased after correction for nonspecific binding using the inactive en antiomer (r = 0.694; CV = 22%). These results indicate that the kinetics of e IC]( + )McN5652 can best be described by a one-tissue compartment model with three parameters (kl, k2, and BV), and that both the noncompartmental paramete...
This animal model of ischemia causes reproducible neuronal injury primarily in cortical regions without pancellular necrosis and infarction. Damage to subcortical areas is less severe than to cortical areas, despite comparable reductions in regional cerebral blood flow. Therefore, in the presence of regionally uniform but incomplete cerebral ischemia, neocortical and hippocampal pyramidal neurons and cerebellar cortical Purkinje cells are more likely than subcortical neurons to degenerate; alternatively, pyramidal and Purkinje neurons degenerate before neostriatal neurons in this model. This neuronal degeneration may represent an intrinsic cellular mechanism without major contribution of cytotoxic pathways associated with inflammation.
Forty volunteers randomly received four intradermal injections consisting of 2% lidocaine with or without sodium bicarbonate via a 25- or 30-gauge needle. The addition of bicarbonate had a greater overall effect than needle size in decreasing the pain associated with the intradermal injection of lidocaine.
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