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排序方式: 共有91条查询结果,搜索用时 31 毫秒
1.
Screening methods for thyroid hormone disruptors 总被引:15,自引:0,他引:15
DeVito M Biegel L Brouwer A Brown S Brucker-Davis F Cheek AO Christensen R Colborn T Cooke P Crissman J Crofton K Doerge D Gray E Hauser P Hurley P Kohn M Lazar J McMaster S McClain M McConnell E Meier C Miller R Tietge J Tyl R 《Environmental health perspectives》1999,107(5):407-415
The U.S. Congress has passed legislation requiring the EPA to implement screening tests for identifying endocrine-disrupting chemicals. A series of workshops was sponsored by the EPA, the Chemical Manufacturers Association, and the World Wildlife Fund; one workshop focused on screens for chemicals that alter thyroid hormone function and homeostasis. Participants at this meeting identified and examined methods to detect alterations in thyroid hormone synthesis, transport, and catabolism. In addition, some methods to detect chemicals that bind to the thyroid hormone receptors acting as either agonists or antagonists were also identified. Screening methods used in mammals as well as other vertebrate classes were examined. There was a general consensus that all known chemicals which interfere with thyroid hormone function and homeostasis act by either inhibiting synthesis, altering serum transport proteins, or by increasing catabolism of thyroid hormones. There are no direct data to support the assertion that certain environmental chemicals bind and activate the thyroid hormone receptors; further research is indicated. In light of this, screening methods should reflect known mechanisms of action. Most methods examined, albeit useful for mechanistic studies, were thought to be too specific and therefore would not be applicable for broad-based screening. Determination of serum thyroid hormone concentrations following chemical exposure in rodents was thought to be a reasonable initial screen. Concurrent histologic evaluation of the thyroid would strengthen this screen. Similar methods in teleosts may be useful as screens, but would require indicators of tissue production of thyroid hormones. The use of tadpole metamorphosis as a screen may also be useful; however, this method requires validation and standardization prior to use as a broad-based screen. 相似文献
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Robin P.F. Dullaart Uwe J.F. Tietge Arjan J. Kwakernaak Bert D. Dikkeschei Frank Perton René A. Tio 《Atherosclerosis》2014
Background
The cholesterol esterifying enzyme, lecithin:cholesterol acyltransferase (LCAT), plays a key role in HDL maturation and remodeling. Myeloperoxidase (MPO) may compromise LCAT enzymatic activity. We tested the extent to which plasma LCAT activity is altered in acute myocardial infarction (MI) in conjunction with abnormal MPO levels. We also assessed the impact of LCAT and MPO on newly developed major adverse cardiovascular events (MACE).Methods
Two-hundred one consecutive patients referred for acute chest pain of whom 134 had MI (95 with ST-elevation) participated. Forty-five new MACE were ascertained during 1203 (range 13–1745) days of follow-up among 185 patients. Plasma LCAT activity was measured using an exogenous substrate assay. MPO mass was assayed by chemiluminescent microparticle immunoassay.Results
Plasma LCAT activity was decreased by 15%, coinciding with 7-fold increased MPO levels in acute MI patients vs. patients with non-cardiac chest pain (p < 0.001 for both; correlation: r = −0.343, p < 0.001). MI at admission was associated independently with both lower plasma LCAT activity and higher MPO (age- and sex-adjusted odds ratio per 1 SD increment: 0.46 (95% CI, 0.31–0.68), p < 0.001 and 7.58 (95% CI, 3.34–17.11), p < 0.001, respectively). In an analysis with LCAT and MPO together these associations were modestly attenuated. MPO mass (hazard ratio: 1.59 (95% CI, 1.15–2.19), p = 0.004), but not LCAT activity (hazard ratio: 0.87 (95% CI, 0.65–1.19), p = 0.39), predicted newly manifest MACE.Conclusion
In acute MI patients, plasma LCAT activity is decreased coinciding with increased MPO levels. Higher MPO but not lower LCAT activity prospectively predicts adverse cardiac outcome. 相似文献6.
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This study was undertaken to determine the effectiveness of two types of educational interventions on child safety seat usage among new mothers at the time of discharge from a hospital setting. Ninety-three women included in this study were divided into three groups consisting of a control group, a video teaching intervention, and a video and face-to-face intervention. All women were given a demographic questionnaire during their hospital stay and observed for actual car seat usage at the time of discharge. Results, based on a 1 x 3 Analysis of Variance (ANOVA), showed no statistically significant difference in child safety seat usage between control and experimental groups. Factors which may have influenced the findings were the unusually high overall compliance rate of this population (83.9%) and the socio-economic make-up; the majority being white, well-educated, and above average income. Good maternal seat belt use may have predisposed this group toward high child restraint device (CRD) compliance,aas well as the widespread diffusion of information on child safety seats and awareness of the California CRD law. Supplementary analyses indicated that video plus face-to-face instruction may be more effective with first-time mothers who have performance scores below 80, are themselves not seat belt users and who are members of minority groups. 相似文献
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Luchtefeld M Schunkert H Stoll M Selle T Lorier R Grote K Sagebiel C Jagavelu K Tietge UJ Assmus U Streetz K Hengstenberg C Fischer M Mayer B Maresso K El Mokhtari NE Schreiber S Müller W Bavendiek U Grothusen C Drexler H Trautwein C Broeckel U Schieffer B 《The Journal of experimental medicine》2007,204(8):1935-1944
Liver-derived acute phase proteins (APPs) emerged as powerful predictors of cardiovascular disease and cardiovascular events, but their functional role in atherosclerosis remains enigmatic. We report that the gp130 receptor, which is a key component of the inflammatory signaling pathway within hepatocytes, influences the risk of atherosclerosis in a hepatocyte-specific gp130 knockout. Mice on an atherosclerosis-prone genetic background exhibit less aortic atherosclerosis (P < 0.05) with decreased plaque macrophages (P < 0.01). Translating these findings into humans, we show that genetic variation within the human gp130 homologue, interleukin 6 signal transducer (IL6ST), is significantly associated with coronary artery disease (CAD; P < 0.05). We further show a significant association of atherosclerotic disease at the ostium of the coronary arteries (P < 0.005) as a clinically important and heritable subphenotype in a large sample of families with myocardial infarction (MI) and a second independent population-based cohort. Our results reveal a central role of a hepatocyte-specific, gp130-dependent acute phase reaction for plaque development in a murine model of atherosclerosis, and further implicate IL6ST as a genetic susceptibility factor for CAD and MI in humans. Thus, the acute phase reaction should be considered an important target for future drug development in the management of CAD. 相似文献
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Tietge UJ Cichon G Büttner C Genschel J Heeren J Gielow P Grewe N Dogar M Beisiegel U Manns MP Lochs H Burchert W Schmidt HH 《Gene therapy》2004,11(7):574-580
Noninvasive tools to quantitate transgene expression directly are a prerequisite for clinical gene therapy. We established a method to determine location, magnitude, and duration of low-density lipoprotein (LDL) receptor (LDLR) transgene expression after adenoviral gene transfer into LDLR-deficient Watanabe hypercholesterolemic rabbits by following tissue uptake of intravenously injected (111)In-labeled LDL using a scintillation camera. Liver-specific tracer uptake was calculated by normalizing the counts measured over the liver to counts measured over the heart that represent the circulating blood pool of the tracer (liver/heart (L/H) ratio). Our results indicate that the optimal time point for transgene imaging is 4 h after the tracer injection. Compared with control virus-injected rabbits, animals treated with the LDLR-expressing adenovirus showed seven-fold higher L/H ratios on day 6 after gene transfer, and had still 4.5-fold higher L/H ratios on day 30. This imaging method might be a useful strategy to obtain reliable data on functional transgene expression in clinical gene therapy trials of familial hypercholesterolemia. 相似文献
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