Oblique coronal view of computerized tomography myelography visualizing the dorsal rootlets

<p><b>Copyright information:</b></p><p>Taken from "Computerized tomography myelography with coronal and oblique coronal view for diagnosis of nerve root avulsion in brachial plexus injury"</p><p>http://www.JBPPNI.com/content/2/1/16</p><p>Journal of Brachial Plexus and Peripheral Nerve Injury 2007;2():16-16.</p><p>Published online 25 Jul 2007</p><p>PMCID:PMC1947985.</p><p></p

Coronal view of computerized tomography myelography visualizing the ventral rootlets

<p><b>Copyright information:</b></p><p>Taken from "Computerized tomography myelography with coronal and oblique coronal view for diagnosis of nerve root avulsion in brachial plexus injury"</p><p>http://www.JBPPNI.com/content/2/1/16</p><p>Journal of Brachial Plexus and Peripheral Nerve Injury 2007;2():16-16.</p><p>Published online 25 Jul 2007</p><p>PMCID:PMC1947985.</p><p></p> The number or size of rootlets and the connection with the cord are well visualized

Intramolecular H/D Exchange of Ethanol Catalyzed by Acidic OH Groups on H‑ZSM‑5 Zeolite

IR observation of ethanol adsorption clarified the presence of the apparent intramolecular isotope exchange from CD₃CH₂OH to CHD₂CH₂OD on acidic OH groups of H-ZSM-5 zeolite. This reaction did not proceed with CD₃OH nor CH₃CD₂OH, implying that the β-hydrogen of alcohol had interaction with the lattice oxygen adjacent to Al and that the reaction was mediated by isotope exchange of CD₃ groups of ethanol and OH groups on zeolite

Combining Chimeric Mice with Humanized Liver, Mass Spectrometry, and Physiologically-Based Pharmacokinetic Modeling in Toxicology

Species differences exist in terms of drug oxidation activities, which are mediated mainly by cytochrome P450 (P450) enzymes. To overcome the problem of species extrapolation, transchromosomic mice containing a human P450 3A cluster or chimeric mice transplanted with human hepatocytes have been introduced into the human toxicology research area. In this review, drug metabolism and disposition mediated by humanized livers in chimeric mice are summarized in terms of biliary/urinary excretions of phthalate and bisphenol A and plasma clearances of the human cocktail probe drugs caffeine, warfarin, omeprazole, metoprolol, and midazolam. Simulation of human plasma concentrations of the teratogen thalidomide and its human metabolites is possible with a simplified physiologically based pharmacokinetic model based on data obtained in chimeric mice, in accordance with reported clinical thalidomide concentrations. In addition, <i>in vivo</i> nonspecific hepatic protein binding parameters of metabolically activated ¹⁴C-drug candidate and hepatotoxic medicines in humanized liver mice can be analyzed by accelerator mass spectrometry and are useful for predictions in humans

Simulation of Human Plasma Concentrations of Thalidomide and Primary 5‑Hydroxylated Metabolites Explored with Pharmacokinetic Data in Humanized TK-NOG Mice

Plasma concentrations of thalidomide and primary 5-hydroxylated metabolites including 5,6-dihydroxythalidomide and glutathione (GSH) conjugate(s) were investigated in chimeric mice with highly “humanized” liver cells harboring cytochrome <i>P450 3A5*1</i>. Following oral administration of thalidomide (100 mg/kg), plasma concentrations of GSH conjugate(s) of 5-hydroxythalidomide were higher in humanized mice than in controls. Simulation of human plasma concentrations of thalidomide were achieved with a simplified physiologically based pharmacokinetic model in accordance with reported thalidomide concentrations. The results indicate that the pharmacokinetics in humans of GSH conjugate and/or catechol primary 5-hydroxylated thalidomide contributing <i>in vivo</i> activation can be estimated for the first time

<i>In vitro</i> inhibition and enhancement of liver microsomal S-777469 metabolism by long-chain fatty acids and serum albumin: insight into <i>in vitro</i> and <i>in vivo</i> discrepancy of metabolite formation in humans

<p>1. It was previously demonstrated that 10% of S-777469, a cannabinoid receptor 2 selective agonist, is metabolized to its carboxylic acid metabolite (S-777469 5-carboxylic acid, 5-CA) in humans <i>in vivo</i>, while the formation of 5-CA is extremely low in human cryopreserved hepatocytes and liver microsomes (HLMs). In this study, factors causing the different metabolite formation rates of S-777469 <i>in vitro</i> and <i>in vivo</i> were investigated.</p> <p>2. Formation of 5-CA and S-777469 5-hydroxymethyl (5-HM), a precursor metabolite of 5-CA, was catalyzed by CYP2C9. Arachidonic acid, α-linolenic acid, oleic acid and myristic acid, which have been reported to exist in liver microsomes, inhibited S-777469 oxidation by CYP2C9, but serum albumin enhanced this reactions.</p> <p>3. The IC₅₀ values of these fatty acids for 5-CA formation from 5-HM were lower than those of 5-HM formation from S-777469. Serum albumin extensively enhanced 5-CA formation from 5-HM in comparison to 5-HM formation from S-777469.</p> <p>4. CYP2C9 was the enzyme responsible for S-777469 oxidation in human livers. The suppressive effects of several fatty acids and enhancing action of serum albumin <i>in vitro</i> are likely to be the causal factors for the apparently different rates of <i>in vitro</i> and <i>in vivo</i> metabolite formation of S-777469.</p

Prediction of human pharmacokinetics of typical compounds by a physiologically based method using chimeric mice with humanized liver

<p></p><p>In this study, total body clearance (CL_t), volume of distribution at steady state (<i>V</i>_ss) and plasma concentration–time profiles in humans of model compounds were predicted using chimeric mice with humanized livers.</p><p>On the basis of assumption that unbound intrinsic clearance (CL_Uint) per liver weight in chimeric mice was equal to those in humans, CL_t were predicted by substituting human liver blood flow and liver weights in well-stirred model. <i>V</i>_ss were predicted by Rodgers equation using scaling factors of tissue-plasma concentration ratios (SF_Kp) in chimeric mice estimated from a difference between the observed and predicted <i>V</i>_ss. These physiological approaches showed high prediction accuracy for CL_t and <i>V</i>_ss values in humans.</p><p>We compared the predictability of CL_t and <i>V</i>_ss determined by the physiologically based predictive approach using chimeric mice with those from predictive methods reported by Pharmaceutical Research Manufacturers of America. The physiological approach using chimeric mice indicated the best prediction accuracy in each predictive method.</p><p>Simulation of human plasma concentration–time profiles were generally successful with physiologically based pharmacokinetic (PBPK) model incorporating CL_Uint and SF_Kp obtained from chimeric mice.</p><p>Combined application of chimeric mice and PBPK modeling is effective for prediction of human PK in various compounds.</p><p></p> <p>In this study, total body clearance (CL_t), volume of distribution at steady state (<i>V</i>_ss) and plasma concentration–time profiles in humans of model compounds were predicted using chimeric mice with humanized livers.</p> <p>On the basis of assumption that unbound intrinsic clearance (CL_Uint) per liver weight in chimeric mice was equal to those in humans, CL_t were predicted by substituting human liver blood flow and liver weights in well-stirred model. <i>V</i>_ss were predicted by Rodgers equation using scaling factors of tissue-plasma concentration ratios (SF_Kp) in chimeric mice estimated from a difference between the observed and predicted <i>V</i>_ss. These physiological approaches showed high prediction accuracy for CL_t and <i>V</i>_ss values in humans.</p> <p>We compared the predictability of CL_t and <i>V</i>_ss determined by the physiologically based predictive approach using chimeric mice with those from predictive methods reported by Pharmaceutical Research Manufacturers of America. The physiological approach using chimeric mice indicated the best prediction accuracy in each predictive method.</p> <p>Simulation of human plasma concentration–time profiles were generally successful with physiologically based pharmacokinetic (PBPK) model incorporating CL_Uint and SF_Kp obtained from chimeric mice.</p> <p>Combined application of chimeric mice and PBPK modeling is effective for prediction of human PK in various compounds.</p

Mean accuracy (SD) for the letter and fingerspelling conditions during fMRI.

<p>Mean accuracy (SD) for the letter and fingerspelling conditions during fMRI.</p

Modality-specific neural components for converting letter and fingerspelling inputs into phonological STM during verbal learning.

<p>The left IOG involved in letter perception is known to have fast and direct connections with the left IFG involved in speech production and lexical learning. This ventral occpitofrontal connection constitutes a specific neural pathway involved in verbal learning via letter inputs (white line). The dorsal parietofrontal connection linking the left SPL with the left IFG serves as a visuomotor pathway for verbal learning via sign language learning (gray line). The left PMd selectively activated by fingerspelling inputs is also known to have structural and functional coupling with the posterior parietal and inferior frontal regions [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0177599#pone.0177599.ref023" target="_blank">23</a>] and thus likely to operate with this dorsal neural system (dotted line).</p

Heterogeneous Ni Catalyst for Direct Synthesis of Primary Amines from Alcohols and Ammonia

This paper reports the synthesis of primary amines from alcohols and NH₃ by an Al₂O₃-supported Ni nanoparticle catalyst as the first example of heterogeneous and noble-metal-free catalytic system for this reaction without additional hydrogen sources under relatively mild conditions. Various aliphatic alcohols are tolerated, and turnover numbers were higher than those of Ru-based homogeneous catalysts. The catalyst was recoverable and was reused. The effects of the Ni oxidation states and the acid–base nature of support oxides on the catalytic activity are studied. It is clarified that the surface metallic Ni sites are the catalytically active species, and the copresence of acidic and basic sites on the support surface is also indispensable for this catalytic system