36 research outputs found
PPAR beta/delta Agonists Modulate Platelet Function via a Mechanism Involving PPAR Receptors and Specific Association/Repression of PKC alpha-Brief Report
Objectives-Peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) is a nuclear receptor found in platelets. PPAR beta/delta agonists acutely inhibit platelet function within a few minutes of addition. As platelets are anucleated, the effects of PPAR beta/delta agonists on platelets must be nongenomic. Currently, the particular role of PPAR beta/delta receptors and their intracellular signaling pathways in platelets are not known.
Methods and Results-We have used mice lacking PPAR beta/delta (PPAR beta/delta(-/-)) to show the effects of the PPAR beta/delta agonist GW501516 on platelet adhesion and cAMP levels are mediated specifically by PPAR beta/delta, however GW501516 had no PPAR beta/delta-specific effect on platelet aggregation. Studies in human platelets showed that PKC alpha, which can mediate platelet activation, was bound and repressed by PPAR beta/delta after platelets were treated with GW501516.
Conclusions-These data provide evidence of a novel mechanism by which PPAR receptors influence platelet activity and thereby thrombotic risk. (Arterioscler Thromb Vasc Biol. 2009; 29: 1871-1873.
146 ACUTE KIDNEY INJURY RELATED TO TRADITIONAL/COMPLEMENTARY MEDICINES OR SUPPLEMENTS IN MALAYSIA
Making anti-thrombotic bypass vessels from selected populations of vascular smooth muscle cells
Objectives: Vein grafts are commonly used for coronary artery bypass surgery but poor long-term patency and high failure rate make the idea of ‘designer’ bypass vessels attractive. Here we have investigated the possibility of forming bypass vessels from populations of vascular smooth muscle cells (VSMCs) selected for their anti-thrombotic potential. Methods: Clonal populations of rat VSMCs were derived and characterised for their morphology, protein expression and mediator production. Selected cells were also seeded into vascular scaffolds derived by decellularising rat aortae and cultured for periods of up to 40 days. Results: Clone 5 was found to be the optimal clone due to its ability to produce the anti-platelet hormone prostaglandin (PG) I2 and inhibit platelet activation. In experiments combining the synthetic vessels with platelets, a notable inhibition of platelet activation was seen with a reduction in platelet aggregation (72±4% to 31±9%) (Abstract 024 Figure 1), adhesion (43±2% to 19±6%) (Abstract 024 Figure 2), decreased production of thromboxane A2 (58±8 ng/ml to 31±3 ng/ml) and increased prostaglandin I2 production (0.6±0.5 ng/ml to 5.5±0.8 ng/ml), in response to collagen (3 µg/ml). Conclusions: These results demonstrate that clonal VSMC populations with favourable characteristics, such as the production of anti-thrombotic PGI2 can be isolated and used to produce anti-thrombotic vessels. This raises the possibility of producing vessels for bypass surgery by the simple seeding of selected VSMC populations into inert vascular scaffolds. Keywords: anti-thrombotic; bypass; smooth muscleNon peer reviewedSubmitted Versio
Role of prostacyclin versus peroxisome proliferator-activated receptor beta receptors in prostacyclin sensing by lung fibroblasts.
Prostacyclin and its mimetics are used therapeutically for the treatment of pulmonary hypertension. These drugs act via cell surface prostacyclin receptors (IP receptors); however, some of them can also activate the nuclear receptor peroxisome proliferator-activated receptor beta (PPARbeta). We examined the possibility that PPARbeta is a therapeutic target for the treatment of pulmonary hypertension. Using the newly approved (for pulmonary hypertension) prostacyclin mimetic treprostinil sodium, reporter gene assays for PPARbeta activation and measurement of lung fibroblast proliferation were analyzed. Treprostinil sodium was found to activate PPARbeta in reporter gene assays and to inhibit proliferation of human lung fibroblasts at concentrations consistent with an effect on PPARs but not on IP receptors. The effects of treprostinil sodium on human lung cell proliferation are mimicked by those of the highly selective PPARbeta ligand GW0742. There are no receptor antagonists for PPARbeta or for IP receptors, but by using lung fibroblasts cultured from mice lacking PPARbeta (PPARbeta-/-) or IP (IP-/-), we demonstrate that the antiproliferative effects of treprostinil sodium are mediated by PPARbeta and not IP in lung fibroblasts. These observations suggest that some of the local, longer-term benefits of treprostinil sodium on reducing the remodeling associated with pulmonary hypertension may be mediated by PPARbeta. This study is the first to identify PPARbeta as a potential therapeutic target for the treatment of pulmonary hypertension, which is important because orally active PPARbeta ligands have been developed for the treatment of dyslipidemia
The Activity of Fosfomycin Against Extended-Spectrum Beta-Lactamase-Producing Isolates of Enterobacteriaceae Recovered from Urinary Tract Infections: A Single-Center Study Over a Period of 12 Years
Rapid investigation of α-glucosidase inhibitory activity of Phaleria macrocarpa extracts using FTIR-ATR based fingerprinting
Phaleria macrocarpa, known as “Mahkota Dewa”, is a widely used medicinal plant in Malaysia. This study focused on the characterization of α-glucosidase inhibitory activity of P. macrocarpa extracts using Fourier transform infrared spectroscopy (FTIR)-based metabolomics. P. macrocarpa and its extracts contain thousands of compounds having synergistic effect. Generally, their variability exists, and there are many active components in meager amounts. Thus, the conventional measurement methods of a single component for the quality control are time consuming, laborious, expensive, and unreliable. It is of great interest to develop a rapid prediction method for herbal quality control to investigate the α-glucosidase inhibitory activity of P. macrocarpa by multicomponent analyses. In this study, a rapid and simple analytical method was developed using FTIR spectroscopy-based fingerprinting. A total of 36 extracts of different ethanol concentrations were prepared and tested on inhibitory potential and fingerprinted using FTIR spectroscopy, coupled with chemometrics of orthogonal partial least square (OPLS) at the 4000–400 cm−1 frequency region and resolution of 4 cm−1. The OPLS model generated the highest regression coefficient with R2Y = 0.98 and Q2Y = 0.70, lowest root mean square error estimation = 17.17, and root mean square error of cross validation = 57.29. A five-component (1+4+0) predictive model was build up to correlate FTIR spectra with activity, and the responsible functional groups, such as –CH, –NH, –COOH, and –OH, were identified for the bioactivity. A successful multivariate model was constructed using FTIR-attenuated total reflection as a simple and rapid technique to predict the inhibitory activity
Silicon photonics
In this talk, silicon photonics is introduced together with its opportunities in producing highly efficient optical interconnects. An overview of recent advancements in the building block component development and the integration of these components both with each other and electronic devices to form functional photonic circuits is given.The paper then presents some of the remaining challenges for silicon photonics researchers worldwide and some approaches which can answer these needs