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991.
BACKGROUND AND PURPOSE
Adipocyte fatty acid-binding protein (A-FABP) is up-regulated in regenerated endothelial cells and modulates inflammatory responses in macrophages. Endothelial dysfunction accompanying regeneration is accelerated by hyperlipidaemia. Here, we investigate the contribution of A-FABP to the pathogenesis of endothelial dysfunction in the aorta of apolipoprotein E-deficient (ApoE−/−) mice and in cultured human endothelial cells.EXPERIMENTAL APPROACH
A-FABP was measured in aortae of ApoE−/−mice and human endothelial cells by RT-PCR, immunostaining and immunoblotting. Total and phosphorylated forms of endothelial nitric oxide synthase (eNOS) were measured by immunoblotting. Changes in isometric tension were measured in rings of mice aortaeKEY RESULTS
A-FABP was expressed in aortic endothelium of ApoE−/− mice aged 12 weeks and older, but not at 8 weeks or in C57 wild-type mice. Reduced endothelium-dependent relaxations to acetylcholine, UK14304 (selective α2-adrenoceptor agonist) and (calcium ionophore) and decreased protein presence of phosphorylated and total eNOS were observed in aortae of 18 week-old ApoE−/− mice compared with age-matched controls. A 6 week treatment with the A-FABP inhibitor, BMS309403, started in 12 week-old mice, improved endothelial function, phosphorylated and total eNOS and reduced plasma triglyceride levels but did not affect endothelium-independent relaxations. The beneficial effect of BMS309403 on UK14304-induced relaxations was attenuated by Pertussis toxin. In cultured human microvascular endothelial cells, lipid-induced A-FABP expression was associated with reduced phosphorylated eNOS and NO production and was reversed by BMS309403. A23187CONCLUSIONS AND IMPLICATIONS
Elevated expression of A-FABP in endothelial cells contributes to their dysfunction both in vivo and in vitro. 相似文献992.
993.
目的 分析四肢骨折患者应用渐进性肌肉放松训练治疗后精神心理状态及睡眠质量变化.方法 选取我院2018年6月至2019年9月收治的111例四肢骨折患者作为主要研究对象.采用随机数字表法分组,对照组55例给予心理治疗,在此基础上,观察组56例增加渐进性肌肉放松训练,对比两组患者治疗后抑郁自评量表(self-rating d... 相似文献
994.
Faith Wight Moffatt RN PhD Ellen Hodnett RN PhD FCAHS Mary Jane Esplen RN PhD Judy Watt‐Watson RN PhD 《分娩》2010,37(4):296-306
Abstract: Background: Hypertension occurs in nearly 10 percent of pregnancies, and is associated with higher risk of infant and maternal morbidity and mortality than in normal pregnancies. Previous studies have suggested that relaxation therapies reduce blood pressure in nonpregnant adults. The objectives of this pilot randomized trial were to provide preliminary evidence of whether relaxation by means of guided imagery would reduce blood pressure in hypertensive pregnant women, and to assess the feasibility of a larger trial. Methods: A total of 69 pregnant women with hypertension were randomized to periods of guided imagery or of quiet rest, twice daily for 4 weeks or until delivery, whichever came first. Daytime ambulatory mean arterial pressure, systolic and diastolic blood pressure, and anxiety were measured weekly for up to 4 weeks. Results: Women allocated to guided imagery had lower mean arterial pressure elevations over time than those allocated to quiet rest (guided imagery: M = 1.58 mmHg, SD = 7.63; quiet rest: M = 5.93 mmHg, SD = 6.55; t = 2.36, p = 0.02). However, when adjusted for baseline mean arterial pressure and gestation, the effect was not significant (p = 0.14). Numbers of women prescribed antihypertensive medication postrandomization were similar (guided imagery: n = 16; quiet rest: n = 13, χ2 = 0.74, p = 0.46). There was also no evidence of an effect on women’s anxiety. Nearly 90 percent (n = 26) of the guided imagery group indicated that they would use it again. Conclusions: Further rigorous study is warranted to determine effects of guided imagery on maternal blood pressure and perinatal health outcomes. (BIRTH 37:4 December 2010) 相似文献
995.
Sadanori Tomiha Nachiko Iita Fumi Okada Shinya Handa Katsumi Kose 《Magnetic resonance in medicine》2008,60(2):485-488
Relaxation times (T1 and T2) of the bone marrow protons and trabecular bone volume fraction (TBVF) in the calcaneus were measured for 100 female volunteers using a compact MRI system at 0.2 T field strength. The speed of sound (SOS) through the calcaneus was measured also for the same subjects using a quantitative ultrasound system. Both relaxation times were found to have positive correlations with age (R = 0.40; P < 0.0001 and R = 0.31; P < 0.002, respectively) and negative correlations with SOS (R = ?0.38; P < 0.0001 and R = ?0.38; P < 0.0001, respectively). Although TBVF had a fairly high positive correlation with the SOS (R = 0.67), neither T1 nor T2 were correlated with TBVF (R = ?0.062 and ?0.024, respectively). These results suggest that the age dependence of both T1 and T2 is caused by the microdynamic properties of the lipid molecules in bone marrow observed using acoustic or elastic modalities. Magn Reson Med 60:485–488, 2008. © 2008 Wiley‐Liss, Inc. 相似文献
996.
Takaharu Fukuchi Yasuo Katayama Tatsushi Kamiya Ann McKee Fumihiko Kashiwagi Akiro Terashi 《Brain research》1998,792(1):502
The objective of this study was to determine whether the duration of an ischemic insult effects the activity of the mitochondrial enzyme pyruvate dehydrogenase (PDH) in relation to the recovery of metabolites and regional cerebral blood flow (rCBF) immediately after ischemia and during reperfusion in gerbil cortex. Cerebral ischemia was induced, using the bilateral carotid artery occlusion method, for 20 or 60 min, followed by reperfusion up to 120 min. Immediately after ischemia PDH activity increased threefold regardless of ischemic duration. In the 60-min ischemic group, PDH remained activated, the recovery of high energy phosphates and the clearance of lactate were poor, and the rCBF was 48% of controls after 20-min reperfusion, decreasing gradually to 26% at 120-min reperfusion. In the 20-min ischemic group, PDH activity normalized quickly, the restoration of energy phosphates was good, there was a quick reduction in lactate within the first 60 min of reperfusion, and the rCBF was 65% of control at 20-min reperfusion, and remained over 48% of control throughout reperfusion. Recovery of metabolism after reperfusion did not parallel the changes in rCBF in either group, most noticeably in the 60-min ischemic group. The slow normalization of PDH activity reflected the poor recovery of metabolites in the 60-min ischemic group, indicating that PDH activity is important in the resynthesis of energy metabolites during reperfusion. In conclusion, prolonging the ischemic insult effected PDH activity during reperfusion, impaired recovery of energy metabolites, and worsened the recovery of rCBF. 相似文献
997.
THE INHIBITION OF NITRIC OXIDE-MEDIATED RELAXATIONS IN RAT AORTA AND ANOCOCCYGEUS MUSCLE BY DIPHENYLENE IODONIUM 总被引:3,自引:0,他引:3
1. The effects of diphenylene iodonium (DPI), an inhibitor of reduced nicotinamide adenine dinucleotide phosphate-dependent oxidases (which generate superoxide anions), were studied on nitric oxide (NO)-mediated responses in isolated preparations of the rat aorta and anococcygeus muscle. 2. In aortic rings, the endothelium-dependent relaxant action of acetylcholine was reduced by DPI (0.3–10 μmol/L) in a concentration-dependent manner and abolished by the NO synthase (NOS) inhibitor L-nitro-NG-arginine methylester (l-NAME; 100 μmol/L). Relaxations induced by sodium nitroprusside (SNP) or NO were not affected by DPI or l-NAME. 3. In anococcygeus muscles, DPI (0.3–10 μmol/ L) as well as l-NAME (5–100 μmol/L) produced concentration-dependent reductions of relaxations produced by nitrergic nerve stimulation. Relaxations induced by NO and SNP were not affected by either DPI or l-NAME. l-Arginine (1 mmol/L) prevented the reduction of nitrergic relaxations by l-NAME but not by DPI. 4. Contractions of anococcygeus muscles elicited by exogenous noradrenaline (1 μmol/ L) were not affected or were inhibited by DPI (0.3–10 μmol/L), but the contractions elicited by noradrenergic nerve stimulation were significantly enhanced by DPI and l-NAME. When noradrenergic contractions had already been maximally enhanced by l-NAME (100 μmol/L), DPI produced no further enhancement. l-Arginine (1 mmol/L) prevented the enhancement of noradrenergic contractions by l-NAME but not by DPI. 5. The efflux of radioactivity induced by field stimulation from anococcygeus muscles previously incubated with [3H]-noradrenaline was not affected by either DPI or l-NAME. 6. Superoxide dismutase (SOD, 100 U/mL) had no significant effects on noradrenergic contractions, nitrergic relaxations, relaxations induced by NO or the actions of DPI in the rat anococcygeus muscle. 7. The results suggest that the effects of DPI in reducing the NO-mediated relaxations produced by acetylcholine in rat aortic rings and stimulation of nitrergic nerves in the rat anococcygeus muscle are due to the inhibition of NOS in these tissues. The effects of DPI were not sensitive to l-arginine, and thus the mechanism of inhibition of NOS differs from that of l-NAME. 相似文献
998.
J. W. de Vos J. G. R. Ufkes H. van Wilgenburg P. J. Geerlings W. van den Brink 《European journal of clinical pharmacology》1995,48(5):361-366
In a closed metabolic ward the pharmacokinetics of methadone and its primary metabolite (EDDP) were studied in 20 long-term opiate addicts. After administration of the daily oral dose of methadone HCl (mean 60 mg, range 10–225 mg) blood samples were taken and analysed, using a newly developed high-performance liquid chromatography (HPLC) method. The steady-state plasma concentrations of the 20 subjects varied from 65–630 ng·ml–1 and from 5 to 55 ng·ml–1, whereas the peak concentrations were 124–1255 ng·ml–1 and 10 – 301 ng·ml–1 for methadone and EDDP, respectively. The calculated ratios between the area under the curve (AUC(0–24 h)) for methadone and the AUC(0–24 h) for EDDP varied from 5.9 to 44.6, indicating interindividual differences in metabolic activity. In 19 out of 20 subjects the pharmacokinetics of methadone are best described using a two-compartment model. The mean body clearance was 1.64 ml·min–1·kg–1, whereas the mean elimination rate constant () and plasma half-life (t
1/2) were 0.026·h–1 (range 0.013–0.053·h–1) and 31.2 h (range 13–53 h), respectively. Differences of gender were also found. A poor correlation was found between the methadone dose and the steady-state level. A much better correlation was found between the normalized steady-state level and the body clearance. 相似文献
999.
Russell Jones Michaela Marschmann Michael Keller Na Hong Qiu Stephen Fowler Thomas Singer 《Xenobiotica; the fate of foreign compounds in biological systems》2016,46(6):483-494
1.?In recent years, the minipig is increasingly used as a test species in non-clinical assessment of drug candidates. While there is good scientific evidence available concerning cytochrome P450-mediated metabolism in minipig, the knowledge of other metabolic pathways is more limited.2.?The aim of this study was to provide an understanding of when, why, and how drug metabolism in minipig differs from other species commonly used in non-clinical studies. In-house cross-species metabolite profile comparisons in hepatocytes and microsomes of 38 Roche development compounds were retrospectively analyzed to compare the metabolism among minipig, human, rat, dog, monkey, rabbit and mouse.3.?A significant contributor to the elevated metabolism observed for certain compounds in minipig was identified as amide hydrolysis. The hepatic amide hydrolysis activity in minipig was further investigated in subcellular liver fractions and a structure–activity relationship was established. When structural motifs according to the established SAR are excluded, coverage of major human metabolic pathways was shown to be higher in minipig than in dog, and only slightly lower than in cynomolgus monkey.4.?A strategy is presented for early identification of drug compounds which might not be suited to further investigation in minipig due to excessive hydrolytic metabolism. 相似文献
1000.
MV Wenzl G W?lkart H Stessel M Beretta K Schmidt B Mayer 《British journal of pharmacology》2009,156(8):1248-1255