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The values for flow and rate constants for a kinetic model of [99mTc]-hexamethylpropyleneamine oxime (HM-PAO) distribution in the human brain were determined. The single-pass extraction ratio of HM-PAO was also determined in the rat brain by the indicator diffusion method; a value of 0.90 +/- 0.02 (mean +/- SEM, n = 5) was obtained. Time course data of brain activity and arterial blood activity of the tracer were fitted to a four compartment model: Values of blood flow and the first-order rate constants for backdiffusion of the diffusible tracer from brain to blood (k2), conversion of the lipophilic tracer to the hydrophilic one in brain (k3), and conversion of the diffusible tracer to the nondiffusible one in blood (k5) were determined. Conversion of hydrophilic tracer back to a lipophilic form in both blood and brain was assumed to be negligible during the course of the experiment. The values obtained for blood flow, k2, and k3 were, respectively, 0.40 +/- 0.03 ml/g/min, 0.38 +/- 0.04 min-1, and 0.92 +/- 0.05 min-1 in the gray matter (n = 4), and 0.23 +/- 0.01 ml/g/min, 0.17 +/- 0.01 min-1, and 1.01 +/- 0.05 min-1 in the white matter (n = 2) in patients with cerebrovascular disorder. The k5 value was 1.14 +/- 0.06 min-1 (n = 4). These experimentally determined values agree well with the theoretical ones previously reported by Lassen et al. The results suggest the relative constancy of the k3 and k5 values and the more prominent initial backdiffusion of the lipophilic HM-PAO from brain to blood in high flow regions compared to low flow regions.
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PMID:Determination of flow and rate constants in a kinetic model of [99mTc]-hexamethyl-propylene amine oxime in the human brain. 319 43

The uptake and retention in a 2 cm thick brain section was recorded serially by SPECT after i.v. injection of [99mTc]-d,l-HM-PAO (HM-PAO). In 16 patients, the fraction of the administered dose retained by the brain was 5.2 +/- 1%, showing a peak after 40-50s, then decreasing by 10% within the first 10 min and then by only 0.4% per hour. The image contrast was measured in each patient as the regional hemispheric asymmetry difference in percent of the highest value of the two regions. It decreased from 31% at 30-40 s to 25% at 10 min. At 24 h, a value of 19% was reached. Using the images obtained at 10 min after injection, a region to region comparison of the original and corrected HM-PAO images to the xenon-133 regional cerebral blood flow (rCBF) images was performed. Forty-four patients with stroke, epilepsy, dementia, basal ganglia disease, and tumors and control subjects were included in this comparison. The algorithm proposed by Lassen et al. was used to correct the original images for back diffusion of tracer (brain to blood); a good correlation very close to the line of identity between the corrected HM-PAO and xenon-133 data was obtained when using a conversion/clearance ratio of 1.5 and when the noninvolved hemisphere was used as a reference region (r = 0.86, p less than 0.0001). Serial arterial and cerebral venous blood sampling was performed over 10 min following i.v. injection of HM-PAO in six patients. An overall brain retention fraction of 0.37 +/- 0.03 (mean +/- SEM) was calculated from the data. An average CBF of 0.62 +/- 0.12 ml/g/min was determined on the basis of the Fick principle; this compared to a value of 0.59 +/- 0.09 ml/g/min (mean +/- SEM) measured by the xenon-133 inhalation method. The two sets of CBF values correlated linearly with a correlation coefficient of 0.97 (p less than 0.01). Inserting the average CBF value for the hemisphere as measured by the Fick principle into the algorithm described by Lassen et al. yields absolute rCBF values (ml/g/min) directly from the corrected HM-PAO images.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Quantitative measurements of cerebral blood flow using SPECT and [99mTc]-d,l-HM-PAO compared to xenon-133. 326 80

To develop a new reactivator of inhibited acetylcholinesterase (AChE) that can easily penetrate the blood-brain barrier (BBB), BBB penetration of 6 known and novel pyridinealdoxime methiodide (PAM)-type oximes (alkylPAMs) with relatively high reactivation activities was examined by in vivo rat brain microdialysis with liquid chromatography-mass spectrometry (LC-MS/MS). The 50% lethal dose (LD(50)) of alkylPAMs was intravenously determined for Wistar rats, then the limit of detection, quantification range and linearity of the calibration curve of the alkylPAMs in dialysate and blood were determined by LC-MS/MS. Following 10% LD(50) intravenous administration of the alkylPAMs, 4-[(hydroxyimino) methyl]-1-(2-phenylethyl) pyridinium bromide (4-PAPE) and 4-[(hydroxyimino) methyl]-1-octylpyridinium bromide (4-PAO) appeared in the dialysate. Striatal extracellular fluid/blood concentration ratios were 0.039+/-0.018 and 0.301+/-0.183 (mean+/-SEM), respectively, 1 h after treatment. This is the first report of BBB penetration of 4-PAPE, and the concentration ratio was smaller than that of 2-PAM. The mean BBB penetration of 4-PAO was approximately 30%, indicating that intravenous administration of 4-PAO may be effective for the reactivation of blocked cholinesterase in the brain. However, the toxicity of 4-PAO (LD(50); 8.89 mg/kg) was greater than that of 2-PAM. Further investigation is required to determine the effects of these alkylPAMs in organophosphate poisoning.
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PMID:Blood-brain barrier penetration of novel pyridinealdoxime methiodide (PAM)-type oximes examined by brain microdialysis with LC-MS/MS. 1796 25

The amidoximated chitosan-grafted polyacrylonitrile (CTS-g-PAO) was prepared for the adsorption of uranium from water. The effects of pH, concentration of uranium and the solid-liquid ratio on the adsorption of uranium by CTS-g-PAO were optimized using Doehlert design of response surface methodology (RSM). The adsorption capacity and removal efficiency achieved 312.06 mg/g and 86.02%, respectively. The adsorption process attained equilibrium only in 120 min. More than 80% of the absorbed uranium could be desorbed by 0.1 mol/l HCl or EDTA-Na, and CTS-g-PAO could be reused at least 3 times. The CTS-g-PAO and U(VI) ions formed a chelate complex due to FTIR spectral analysis. The surface morphology of CTS-g-PAO was also investigated by SEM. The adsorption process was better described by Langmuir isotherm and pseudo second order kinetic model. Results obtained indicated that CTS-g-PAO was very promising in adsorption of uranium from water.
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PMID:Adsorption of uranium by amidoximated chitosan-grafted polyacrylonitrile, using response surface methodology. 2565 74

The individual cellular level and quantitative Polyphosphate (PolyP)-metal compositions in EBPR (enhanced biological phosphorus removal) systems have hardly been investigated and its potential link to EBPR performance therefore remain largely unknown. In this study, we applied scanning electron microscopy combined with energy dispersive X-ray spectroscopy (SEM/EDX) method that enabled detection and semiquantification of metal elemental compositions in intact intracellular PolyP granules in individual PAO (polyphosphate accumulating organism) cells. We, for the first time, revealed diverse and dynamic distributions of different metals ions in the PolyP-metal granules in different EBPR systems operated with the same influent metal composition but varying SRT of 5-30 days. We further demonstrated that the PolyP-metal composition diversity correlated with 16S rRNA gene based PAO phylogenetic diversity, suggesting the possible phylogeny-dependent PolyP-metal composition variation. The impact of PolyP metal composition in EBPR system, especially the Mg content in PolyP granules, was evidenced by the significant and strong positive correlation between PolyP-Mg content and the long-term stability of the four EBPR systems with varying SRTs. The PolyP-Mg content can therefore possibly serve as an indicator for EBPR performance monitoring. The results demonstrated that phenotyping techniques, such as PolyP-metal-based profiling, in compliment, or combined with genotyping techniques such as phylogenetic and functional gene sequencing, can provide more insights into the mechanisms and performance prediction of this important microbial ecosystem.
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PMID:The Composition and Implications of Polyphosphate-Metal in Enhanced Biological Phosphorus Removal Systems. 3058 45