Brain whole, studies

Davatzikos C, Shen D, Gur RC, Wu X, Liu D, et al. 2005. Whole-brain morphometric study of schizophrenia revealing a spatially complex set of focal abnormalities. Arch Gen Psychiatry 62 1218-1227. 

Fig. 1.18. Whole brain perfusion study on a Siemens SOMATOM Definition AS+ Using a detector configuration of 128x0.6mm and a detector coverage of 38.4mm, whole brain perfusion studies can be carried out by using a special spiral shuttle mode that uses a sinosoi-dal motion of the patient table to cover the whole brain for a period of 30 s...

Warach S, Gaa J, Siewert B, Wielopolski P, Edelman RR. Acute human stroke studied by whole brain echo planar diffusion-weighted magnetic resonance imaging. Ann Neurol 1995 37 231-241. 

PBPK models have also been used to explain the rate of excretion of inhaled trichloroethylene and its major metabolites (Bogen 1988 Fisher et al. 1989, 1990, 1991 Ikeda et al. 1972 Ramsey and Anderson 1984 Sato et al. 1977). One model was based on the results of trichloroethylene inhalation studies using volunteers who inhaled 100 ppm trichloroethylene for 4 horns (Sato et al. 1977). The model used first-order kinetics to describe the major metabolic pathways for trichloroethylene in vessel-rich tissues (brain, liver, kidney), low perfused muscle tissue, and poorly perfused fat tissue and assumed that the compartments were at equilibrium. A value of 104 L/hour for whole-body metabolic clearance of trichloroethylene was predicted. Another PBPK model was developed to fit human metabolism data to urinary metabolites measured in chronically exposed workers (Bogen 1988). This model assumed that pulmonary uptake is continuous, so that the alveolar concentration is in equilibrium with that in the blood and all tissue compartments, and was an expansion of a model developed to predict the behavior of styrene (another volatile organic compound) in four tissue groups (Ramsey and Andersen 1984). 

ACh is widely distributed throughout the brain and parts of the spinal cord (ventral horn and dorsal columns). Whole brain concentrations of lOnmolg" tissue have been reported with highest concentrations in the interpeduncular, caudate and dorsal raphe nuclei. Turnover figures of 0.15-2.0 nmol g min vary with the area studied and the method of measurement, e.g. synthesis of labelled ACh from [ " C]-choline uptake or rundown of ACh after inhibition of choline uptake by hemicholinium. They are all sufficiently high, however, to suggest that in the absence of synthesis depletion could occur within minutes. 

The localisation of a particular peptide to a particular brain area and possibly associated with a particular transmitter (e.g. CCK with dopamine in mesolimbic pathways) has often prompted a prediction of function (e.g. CCK may have a role in schizophrenia). Animal studies in which the peptide has been injected into the appropriate brain area or tested on slices taken from the brain area have sometimes been taken to confirm such hypotheses. These approaches have lined up the peptides for a whole range of potential roles, some of which are listed in Table 12.4. Whether these predictions are realities will depend on the availability of chemical agents and their evaluation, not only in animals but also in humans. 

Surgery followed by whole-brain radiotherapy (WBRT) is best indicated for patients with an accessible single brain lesion and controlled or limited systemic MM.62 Two randomized studies reported improved survival in patients treated with combination surgery and WBRT compared with WBRT alone.62,63 For those patients with multiple metastatic brain... 

Quinolinyl compounds were first reported by Chan et al. as potent orexin receptor antagonists with excellent selectivity for OX1, good brain permeability and in vivo activity following i.p. dosing [62,63]. In fact, compounds SB-334867 (21), SB-408124 (22) and SB-410220 (23) displayed high affinity for the OX1 receptor in both whole cell (Ki — 99, 57 and 19nM, respectively) and membrane formats (X = 38, 27 and 4.5 nM, respectively). Meanwhile, native orexin peptides A and B display affinities for the OX1 receptor with K values of 318 and 1516 nM, respectively. In addition, calcium mobilization studies showed that all three are functional antagonists of the OX1 receptor, with potencies in line with their affinities, and with 50-fold... 

In whole blood, phosphatase activity is associated primarily with red blood cells, but it is recognized that blood has a low phosphatase activity compared to other tissues such as the kidney, brain, liver, lung, and heart ([87] [88] and refs. cit. therein). Thus, studies with blood preparations should underestimate the in vivo rate of hydrolysis of phosphoric acid esters, a point of significance in the development of phosphate prodrugs. 

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