Der neuartige (18)F-markierte Tracer, LMI1195 (N-[3-bromo-4-(3-(18)F-fluoro-propoxy)-benzyl]-guanidine) wurde für die Bildgebung des sympathischen Nervensystems entwickelt; die hohe Spezifität dieses Tracers für den neuralen Uptake-1 Mechanismus wurde bereits gezeigt in Zell-Versuchen, sowie in Studien mit Kaninchen- und nicht menschlichen Primaten zur Bestimmung des kardialen Tracer-Uptakes. Das Ziel dieser Studie war es, die Mechanismen des kardialen (18)F-LMI1195-Uptakes in der Ratte zu untersuchen, von der bekannt ist, dass es neben dem Uptake-1 Mechanismus weitere Arten der Noradrenalin-Aufnahme im Herzen gibt. / The novel PET Tracer N-[3-bromo-4-(3-18F-fluoropropoxy)-benzyl]-guanidin (LMI1195) has recently been developed for the imaging of the sympathetic nervous system. Previous studies in cell models, as well as rabbit and nonhuman primate studies have shown a high specificity for the cardiac neural uptake-1 mechanism. The aim of this study was to further assess the mechanisms of the cardiac 18-F-LMI1195 uptake in the rat heart, known to have additional, differing norepinephrine uptake mechanisms besides neural uptake-1.

The purpose of this study was to determine the effects of nonmotorized treadmill walking and motorized treadmill walking on YO, results, measured in ml•kg·'·min·•, of males and females, ages 20-30 at Utah State University, Logan, Utah, USA. The participants were required to walk at a pace of 3 miles per hour and 13% grade for a total exercise time of 9 minutes. The exercise time was broken up with 3-minute recovery periods. Oxygen uptake was measured continuously using a metabolic measurement cart. The data obtained from the metabolic cart were correlated for each treadmill to determine the degree of relationship. A 1 test for correlated means was used to determine if there was a significant difference, alpha < 0.05, when measuring YO, and metabolic (MET) results. A significantly low correlational coefficient was found when the Pro form Dual Motion Crosswalk Cross Trainer motorized treadmill (CW TM) V02 and MET results were compared with the Jane Fonda nonmotorized treadmill (Jane TM) and Voit 502 MD nonmotorized treadmill (Voit TM) YO, and MET results (r = 0.3, Q < 0.0001). These results enabled the researchers to reject the null hypotheses, which stated there would be no significant difference and a high positive correlation between nonmotorized and motorized treadmill V02 and MET results. Standard mean difference effect sizes were calculated for the nonmotorized treadmills versus the motorized treadmill. An effect size of 1.62 was found when both nonmotorized treadmills were compared with the motorized treadmill. This, combined with the significant difference, Q < 0.0001 , provided confidence that a Type I error was avoided. Therefore, the results of this research study show a significant difference in V02 and METs measured on a nonmotorized treadmill when compared with a motorized treadmill.

No description available.

TGFβ ligands, activin and myostatin have been shown to stimulate insulin production and secretion. Antagonists, Follistatin (FST) and Follistatin like 3 (FSTL3) were partially and fully ablated, respectively, creating hyperinsulinemic mice with fatty liver. Much research has surfaced on the connection between hepatic steatosis and hepatic insulin resistance. We present two different models, each with a different mechanism behind the development of fatty liver. FST288-only mice have increased synthesis of mRNA and proteins responsible for hepatic triglyceride (TG) uptake, while our double mutants have increased synthesis of mRNA and proteins responsible for TG synthesis. This alteration was likely independent of hepatic insulin resistance as livers from both mouse lines were insulin sensitive. Experiments conducted in this study to realize the causal factor of hepatic steatosis can be performed on adipose and muscle tissues in the future to better characterize the phenotype.

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No description available.

The effect on Ni^2+ uptake of human serum albumin (HSA), sodium diethyldithiocarbamate (DOC), D-penicillamine (O-Pen) , ethylenediaminetetra-acetic acid [di sodiurn salt] (EDTA) , L-aspartic acid (L-Asp) , L-Lysine (L-Lys) , and L-histidine (L-His) was examined in three cell lines: (1) human red blood cells (RBCs), (2) cultured human B-lymphoblasts and (3) rabbit alveolar macrophages. It was found that EDTA, L-His, HSA, and O-Pen were good inhibitors of ^63Ni^2+ uptake by cells and each was able to remove ^63Ni^2+ previously associated with the cells. In contrast L-Lys and L-Asp, which do not bind Ni^2+ well, were both poor inhibitors of Ni uptake and poor sequestering agents for cell-associated Ni^2 +. Thus it seems that at physiological concentrations , L-His and HSA play a major role in regulating the association of Ni^2+ with cells. DOC enhanced cellular uptake of ^63Ni^2+, but was not very effective in removing ^63Ni^2+ from cells. An increase in pH enhanced ^63Ni^2+ uptake in the lymphoblasts, macrophages and human peripheral lymphocytes. This dependence was interpreted to indicate the existence of either: (1) an increase in membrane permeability with an increase in pH; (2) the development of a proton gradient across the cell membrane favouring the antiport transport of H^+ and Ni^2+; or (3) Ni^2+;proton competition for cellular binding groups. The cellular uptake of Ni^2+ is interpreted in terms of an "equilbrium" model of metal-ion transport. It is concluded that since HSA and L-His can control cellular uptake and removal of Ni^2+, they may play a role in regulating the cellular toxicity of this ion. It was found that L-His and O-Pen acted similarly such that at various concentrations both inhibited cellular uptake of ^63Ni^2+ but did not change the normal distribution of Ni^2+ within the cell. Conversely, DOC enhanced Ni^2+ uptake by cells while simultaneously shifting the distribution of Ni^2+ from the cell lysate to the cellular membranous pellet. Furthermore, DOC caused Ni^2+ to become more lipophilic as shown by the increase of ^63Ni^2+ in a chloroform extract. DOC also caused a change in Ni^2+ distribution in whole blood by enhancing Ni^2+ association with RBCs and lymphocytes and decreasing serum-associated Ni^2+. The different responses produced by O-Pen, L-His and DOC are ascribed to the hydrophilicity of the [Ni(D-Pen)_2]^2- and Ni(His)_2 complexes and the lipophilicity of the Ni(DDC)_2 complex, and allow a rationalization of the contrasting therapeutic effects of O-Pen and DDC. / Thesis / Master of Science (MS)

京都大学 / 新制・課程博士 / 博士(人間・環境学) / 甲第23533号 / 人博第1012号 / 新制||人||239(附属図書館) / 2021||人博||1012(吉田南総合図書館) / 京都大学大学院人間・環境学研究科相関環境学専攻 / (主査)教授 小松 直樹, 教授 津江 広人, 准教授 土屋 徹 / 学位規則第4条第1項該当 / Doctor of Human and Environmental Studies / Kyoto University / DFAM

Isoxaben is a preemergence herbicide used for broadleaf weed control in turf and ornamentals. Although isoxaben can be used on a number of ornamentals, certain species are injured by isoxaben applications. The objectives of this research were: a) to evaluate the tolerance of ajuga, wintercreeper and dwarf burning bush to isoxaben applications, b) to compare the absorption, translocation and metabolism of isoxaben following root and shoot application in these ornamentals, and c) to examine the effect of isoxaben on glucose incorporation in the roots of these species. Greenhouse and lathhouse studies demonstrated that ajuga was the most sensitive species compared to wintercreeper and dwarf burning bush following root and shoot exposure to isoxaben at 0.84, 1.69 and 3.39 kg ai/ha. Following root and shoot application, isoxaben at 3.39 kg/ha caused approximately 50% shoot injury in ajuga at 2 months after treatment compared to approximately 30% in dwarf burning bush in sand culture. Wintercreeper was not visually injured by any isoxaben rate. Isoxaben at 3.39 kg/ha reduced wintercreeper root weight by 15% following root application and shoot weight by 10% following shoot application. Field studies showed that isoxaben applications made one month after bud-break caused 30 to 45% injury to dwarf burning bush. However, the plants outgrew the injury in the following year. Dwarf burning bush was not injured from applications of isoxaben made at the dormant stage or two months after the bud-break stage. Studies with root-applied radiolabeled isoxaben showed that ajuga and dwarf burning bush had absorbed 34 and 41% of the applied radioactivity, respectively, while wintercreeper had absorbed only 21% at 14 days after treatment (DAT). The percent of absorbed radioactivity which translocated was greater in ajuga (58%) and wintercreeper (50%) than in dwarf burning bush (28%). In the root extracts, metabolism of isoxaben was greater in ajuga than wintercreeper or dwarf burning bush at 3, 7 and 14 DAT. Most of the radioactivity recovered from the shoots of the three species appeared to be polar metabolites of isoxaben, possibly conjugates. In studies with shoot-applied radiolabeled isoxaben, radioactivity recovered from the treated leaf of ajuga increased from 46% of applied at 3 days to 64% at 14 days after treatment. In wintercreeper, the most tolerant species, approximately 40% of the applied radioactivity was recovered in the treated leaf at each harvest date. Radioactivity recovered from the treated leaflet increased from 45 at 3 DAT to 70% at 14 DAT in both growth stages of dwarf burning bush. Ajuga and wintercreeper metabolized isoxaben faster than dwarf burning bush. There was no difference in the metabolism of isoxaben between the two growth stages of dwarf burning bush. Incorporation of glucose in the roots of wintercreeper and dwarf burning bush was not inhibited by isoxaben (1 mM). Approximately 10% inhibition of glucose incorporation by isoxaben was observed in the roots of the sensitive species ajuga. / Ph. D.