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排序方式: 共有803条查询结果,搜索用时 31 毫秒
71.
Artwohl M Muth K Kosulin K de Martin R Hölzenbein T Rainer G Freudenthaler A Huttary N Schmetterer L Waldhäusl WK Baumgartner-Parzer SM 《American journal of physiology. Endocrinology and metabolism》2007,293(3):E681-E689
Lipoic acid was recently demonstrated to improve endothelial dysfunction or retinopathy not only in rats but also in diabetic patients. We tested the hypothesis that R-(+)-alpha-lipoic acid (LA) directly affects human endothelial cell (EC) function (e.g., apoptosis, proliferation, and protein expression), independent of the cells' vascular origin. Macrovascular EC (macEC), isolated from umbilical (HUVEC) and adult saphenous veins and from aortae, as well as microvascular EC (micEC) from retinae, skin, and uterus, were exposed to LA (1 mumol/l-1 mmol/l) with/without different stimuli (high glucose, TNF-alpha, VEGF, wortmannin, LY-294002). Apoptosis, proliferation, cell cycle distribution, and protein expression were determined by DNA fragmentation assays, [(3)H]thymidine incorporation, FACS, and Western blot analyses, respectively. In macro- and microvascular EC, LA (1 mmol/l) reduced (P < 0.05) basal (macEC, -36 +/- 4%; micEC, -46 +/- 6%) and stimulus-induced (TNF-alpha: macEC, -75 +/- 11%; micEC, -68 +/- 13%) apoptosis. In HUVEC, inhibition of apoptosis by LA (500 mumol/l) was paralleled by reduction of NF-kappaB. LA's antiapoptotic activity was reduced by PI 3-kinase inhibitors (wortmannin, LY-294002), being in line with LA-induced Akt phosphorylation (Ser(437), +159 +/- 43%; Thr(308), +98 +/- 25%; P < 0.01). LA (500 mumol/l) inhibited (P < 0.001) proliferation of macEC (-29 +/- 3%) and micEC (-29 +/- 3%) by arresting the cells at the G(1)/S transition due to an increased ratio of cyclin E/p27(Kip) (4.2-fold), upregulation of p21(WAF-1/Cip1) (+104 +/- 21%), and reduction of cyclin A (-32 +/- 11%), of hyperphosphorylated retinoblastoma protein (macEC: -51 +/- 7%; micEC: -50 +/- 15%), and of E2F-1 (macEC: -48 +/- 3%; micEC: -31 +/- 10%). LA's ability to inhibit apoptosis and proliferation of ECs could beneficially affect endothelial dysfunction, which precedes manifestation of late diabetic vascular complications. 相似文献
72.
Cui W Paglialunga S Kalant D Lu H Roy C Laplante M Deshaies Y Cianflone K 《American journal of physiology. Endocrinology and metabolism》2007,293(6):E1482-E1491
Acylation-stimulating protein (ASP), a lipogenic hormone, stimulates triglyceride (TG) synthesis and glucose transport upon activation of C5L2, a G protein-coupled receptor. ASP-deficient mice have reduced adipose tissue mass due to increased energy expenditure despite increased food intake. The objective of this study was to evaluate the blocking of ASP-C5L2 interaction via neutralizing antibodies (anti-ASP and anti-C5L2-L1 against C5L2 extracellular loop 1). In vitro, anti-ASP and anti-C5L2-L1 blocked ASP binding to C5L2 and efficiently inhibited ASP stimulation of TG synthesis and glucose transport. In vivo, neither anti-ASP nor anti-C5L2-L1 altered body weight, adipose tissue mass, food intake, or hormone levels (insulin, leptin, and adiponectin), but they did induce a significant delay in TG clearance [P < 0.0001, 2-way repeated-measures (RM) ANOVA] and NEFA clearance (P < 0.0001, 2-way RM ANOVA) after a fat load. After treatment with either anti-ASP or anti-C5L2-L1 antibody there was no change in adipose tissue AMPK activity, but neutralizing antibodies decreased perirenal TG mass (-38.4% anti-ASP, -18.8% anti-C5L2, P < 0.01-0.001) and perirenal LPL activity (-75.6% anti-ASP, -72.5% anti-C5L2, P < 0.05). In liver, anti-C5L2-L1 decreased TG mass (-42.8%, P < 0.05), whereas anti-ASP increased AMPK activity (+34.6%, P < 0.001). In the muscle, anti-C5L2-L1 significantly increased TG mass (+128.0%, P < 0.05), LPL activity (+226.1%, P < 0.001), and AMPK activity (+71.1%, P < 0.01). In addition, anti-ASP increased LPL activity (+164.4, P < 0.05) and AMPK activity (+53.9%, P < 0.05) in muscle. ASP/C5L2-neutralizing antibodies effectively block ASP-C5L2 interaction, altering lipid distribution and energy utilization. 相似文献
73.
Eighty-nine samples of grey wolf (Canis lupus L.) faeces were collected between 2002 and 2004 from two areas in the western Beskidy Mts (south Poland). Helminth eggs were observed in 56.2% of faeces examined. These included: Alaria alata (2.2%), taeniid eggs (11.2%), Toxocara canis (5.6%), Toxascaris leonina (1.1%), Eucoleus aerophilus (14.6%), Ancylostoma caninum (12.3%), Uncinaria stenocephala (37%) and unidentified roundworm eggs of the family Strongyloididae (1.1%). Eucoleus aerophilus is recorded for the first time from Poland. The results are compared with the helminth fauna of other wolf populations in Europe. 相似文献
74.
Thermodynamic benchmark study using Biacore technology 总被引:1,自引:0,他引:1
Navratilova I Papalia GA Rich RL Bedinger D Brophy S Condon B Deng T Emerick AW Guan HW Hayden T Heutmekers T Hoorelbeke B McCroskey MC Murphy MM Nakagawa T Parmeggiani F Qin X Rebe S Tomasevic N Tsang T Waddell MB Zhang FF Leavitt S Myszka DG 《Analytical biochemistry》2007,364(1):67-77
A total of 22 individuals participated in this benchmark study to characterize the thermodynamics of small-molecule inhibitor-enzyme interactions using Biacore instruments. Participants were provided with reagents (the enzyme carbonic anhydrase II, which was immobilized onto the sensor surface, and four sulfonamide-based inhibitors) and were instructed to collect response data from 6 to 36 degrees C. van't Hoff enthalpies and entropies were calculated from the temperature dependence of the binding constants. The equilibrium dissociation and thermodynamic constants determined from the Biacore analysis matched the values determined using isothermal titration calorimetry. These results demonstrate that immobilization of the enzyme onto the sensor surface did not alter the thermodynamics of these interactions. This benchmark study also provides insights into the opportunities and challenges in carrying out thermodynamic studies using optical biosensors. 相似文献
75.
76.
Pandozi C Galeazzi M Lavalle C Ficili S Russo M Santini M 《Indian pacing and electrophysiology journal》2011,10(12):556-561
Radiofrequency ablation procedures inside the left atrial appendage (LAA) are likely to involve dangerous complications because of a high thrombogenic effect. Cryoablation procedures are supposed to be safer. We describe two cases of successful cryoablation procedures. Two NavX-guided cryoablations of permanent focal atrial arrhythmias arising from the LAA were performed. Left atrial reconstruction and mapping allowed the zone of the earliest atrial potential to be recorded; the entire course of the ablation catheter was monitored. The arrhythmias were successfully ablated; no thrombotic complications were observed. 相似文献
77.
78.
Diffusion through the extracellular matrix (ECM) is a critical step for the delivery of nanoparticles and genes. Gene delivery requires a carrier that protects the nucleic acid from degradation and facilitates transport. Chitosan is a promising carrier. To increase the circulation time, PEGylation of the carrier is performed. However, the effect of PEGylation on the transport and stability of gene delivery systems in the ECM has only been studied in solutions containing ECM components. We used polymerized collagen and collagen-hyaluronic acid (HA) gels to study the effects of PEGylation on the diffusion and stability of chitosan-DNA polyplexes. We found that PEGylation of the polyplexes was required for diffusion to occur, and PEGylation increased the dissociation between DNA and chitosan to some extent. The presence of HA had a contradictory role: it decreased the penetration depth of PEGylated polyplexes into the gels and increased the diffusion of the polyplexes being mixed into the gels. 相似文献
79.
80.
Glesner J Wünschmann S Li M Gustchina A Wlodawer A Himly M Chapman MD Pomés A 《PloS one》2011,6(7):e22223