Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The brain mechanisms underlying the cause of nicotine dependence are unknown, however, hostility traits are associated with increased susceptibility to nicotine dependence. We used FDG PET to measure brain metabolic response to nicotine administered by patch while the subject performed the Bushman aggression task in 86 high- and low-hostility subjects. Low-hostility trait subjects demonstrated no significant change in brain metabolic response to nicotine. In marked contrast, high-hostility non-smokers subjects demonstrated dramatic metabolic changes to low dose (3.5 mg patch) as did high-hostility smokers to high dose nicotine (21 mg patch) throughout the brain bilaterally (p<0.025). Correlational analyses demonstrated greater metabolic changes in response to nicotine in subjects with greatest hostility trait measures. The observed differences were not a consequence of plasma nicotine or cotinine levels. These metabolic changes were not observed when subjects performed a sustained attentional task (continuous performance task; CPT). Behaviorally, high-hostility subjects had higher ratings of anger, impatience, irritability and nervousness, and lower ratings of happiness, relaxation and curiosity than low-hostility subjects. Smokers had significantly greater scores on impatience and restlessness than non-smokers. This PET study demonstrates a conspicuous lack of the brain metabolic response to nicotine in low-hostility non-smokers in contrast to a dramatic brain response to nicotine in high hostility subjects. This biological difference in brain metabolic response to nicotine between high and low hostility trait subjects may explain differences in susceptibility to nicotine dependence.
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PMID:Hostility differentiates the brain metabolic effects of nicotine. 1473 73

We examined the benefit of gene expression analysis on peripheral blood cellular subsets of different radiosensitivity to elucidate their utility as biodosimeters for estimation of dose in irradiated individuals. Peripheral mononucleated cells were isolated from 18 healthy volunteers employing density separation in a CPT-NH tube. Peripheral mononucleated cells were cultured in RPMI 1640 medium containing 10% autologous serum and were irradiated with 0.1-1 Gy (240 kV, 13 mA, X rays at 1 Gy/min). A low-dose study was performed with isolated peripheral mononucleated cells from one healthy donor in three independent experiments. Peripheral mononucleated cells were irradiated at 0 (sham), 1, 2.5 and 5 cGy (70 kV, 13 mA X rays at 1 cGy/min) and gene expression was measured 24 and 48 h after irradiation. After irradiation, CD4(+) or CD8(+) cells were isolated by magnetic beads in independent experiments. RNA from lymphocyte subsets and peripheral mononucleated cells was isolated after 24 and 48 h and converted into cDNA. Gene expression of GADD45, CDKN1A, DDB2, PCNA, BAX and ATF3 were determined using RTQ-PCR. Data were analyzed employing linear and logistic regression analysis. The same examinations were performed in 5 individuals either diagnosed using CT scans (up to 4.3 cGy) or by administering (F-18)-fluoro-2-deoxy-d-glucose (F-18 FDG, 0.6 cGy). Methodological, intra- and inter-individual variability in 90-95% of measurements did not exceed the introduced twofold change over sham-irradiated control values in peripheral mononucleated cells and CD4(+) cells, and therefore no false positive results were observed. Dose reconstruction in peripheral mononucleated cells in opposite to CD4(+) lymphocytes required fewer genes and appeared more efficient (R-square = 84.8% compared to 51.8%). In vitro samples exposed to 10 cGy could be completely discriminated from sham-irradiated samples without individual pre-exposure controls, which coincided with our preliminary in vivo results. However, in vitro differential gene expression was measured relative to control values and did not differ significantly at 24 and 48 h after irradiation in contrast to our preliminary in vivo data. In addition, below 5 cGy in vitro data did not show reproducible significant changes in gene expression, which was opposite to our preliminary in vivo data. Therefore a twofold change in gene expression over control sufficiently controls for different sources of variance, and measuring gene expression in peripheral mononucleated cell for biological dosimetry purposes appears superior over measurements in lymphocyte subsets. The increased gene expression measured after low absorbed doses in vivo and in vitro might indicate a particular applicability of this method for a low-level radiation scenario in the absence of individual pre-exposure controls. However, the constant gene expression values measured up to 48 h in our in vitro model at doses >10 cGy, and the absence of reproducible and statistically significant gene expression changes below 5 cGy contrast to the preliminary in vivo results performed at similar doses. Therefore, measurements with our in vitro models should be interpreted cautiously.
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PMID:Gene expression comparisons performed for biodosimetry purposes on in vitro peripheral blood cellular subsets and irradiated individuals. 2276 26

The ability of heart and skeletal muscle (SM) to switch between fat and carbohydrate oxidation is of high interest in the study of metabolic diseases and exercise physiology. Positron emission tomography (PET) imaging with the glucose analog 2-[18F]fluoro-2-deoxy-glucose (18F-FDG) provides a noninvasive means to quantitate glucose metabolic rates. However, evaluation of fatty acid oxidation (FAO) rates by PET has been limited by the lack of a suitable FAO probe. We have developed a metabolically trapped oleate analog, ( Z)-18-[18F]fluoro-4-thia-octadec-9-enoate (18F-FTO), and investigated the feasibility of using 18F-FTO and 18F-FDG to measure FAO and glucose uptake, respectively, in heart and SM of rats in vivo. To enhance the metabolic rates in SM, the vastus lateralis (VL) muscle was electrically stimulated in fasted rats for 30 min before and 30 min following radiotracer injection. The responses of radiotracer uptake patterns to pharmacological inhibition of FAO were assessed by pretreatment of the rats with the carnitine palmitoyl-transferase-1 (CPT-1) inhibitor sodium 2-[5-(4-chlorophenyl)-pentyl]oxirane-2-carboxylate (POCA). Small-animal PET images and biodistribution data with 18F-FTO and 18F-FDG demonstrated profound metabolic switching for energy provision in the myocardium from exogenous fatty acids to glucose in control and CPT-1-inhibited rats, respectively. Uptake of both radiotracers was low in unstimulated SM. In stimulated VL muscle, 18F-FTO and 18F-FDG uptakes were increased 4.4- and 28-fold, respectively, and CPT-1 inhibition only affected 18F-FTO uptake (66% decrease). 18F-FTO is a FAO-dependent PET probe that may allow assessment of energy substrate metabolic switching in conjunction with 18F-FDG and other metabolic probes.
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PMID:Noninvasive evaluation of fat-carbohydrate metabolic switching in heart and contracting skeletal muscle. 3051 88