2,441 research outputs found
Nanoencapsulation of EPA:DHA 6:1 potentiates the endothelium-dependent relaxation of coronary artery rings compared to native form: role of NO, endothelium-dependent hyperpolarization and prostanoids
No full textIntroduction The omega 3 polyunsaturated fatty acid (PUFAs) formulation containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with a 6:1 ratio is a potent inducer of endothelium-dependent nitric oxide (NO)-mediated vasorelaxation that also improves ageing-related and angiotensin II-induced endothelial dysfunction in rats. Purpose Since PUFAs are unstable, the possibility that nanoencapsulation of EPA:DHA 6:1 followed by coating potentiates the bioactivity was evaluated. Methods EPA:DHA 6:1 was emulsified in water phase and coated with proteins and gum derivatives or used in native form. Changes in isometric tension of porcine coronary artery rings were determined using organ chambers. The role of NO was assessed using Nw-nitro-L-arginine (L-NA, NO synthase inhibitor), prostanoids using indomethacin (Indo, COX inhibitor) and endothelium-derived hyperpolarization (EDH) using TRAM-34 and UCL-1684 (Ca2 + -dependent potassium channel inhibitors). Results Coated EPA:DHA 6:1 nanoparticles (NP) caused in a concentration-dependent manner endothelium-dependent relaxations that were more sustained than those of the native form. At 0.3%, coated and native forms induced 56.6 ± 2.8% and 51.1 ± 1.5%relaxations at 10 min, and 93.8 ± 2.1% and 35.1 ± 1.7% at 60 min, respectively. The response to the coated EPA:DHA 6:1 NP was inhibited by L-NA and not affected by Indo, TRAM-34 plus UCL-1684, and by the previous incubation of rings with another oil (corn oil 0.3%). In contrast, L-NA, Indo, and TRAM-34 plus UCL-1684 inhibited the relaxation to EPA:DHA 6:1. Conclusion Nanoencapsulation of EPA:DHA 6:1 followed by coating perpetuated their ability to cause endothelium-dependent relaxation of coronary artery rings that is exclusively mediated by NO. In contrast, the relaxing activity of the native form involved NO, EDH and vasorelaxant prostanoids. Therefore, coated EPA:DHA 6:1 NP appear to be an attractive approach to enhance the vasoprotective effect of omega 3 PUFAs
Nanoencapsulation of EPA:DHA 6:1 potentiates the endothelium-dependent relaxation of coronary artery rings compared to native form: role of NO, endothelium-dependent hyperpolarization and prostanoids
No full textIntroduction The omega 3 polyunsaturated fatty acid (PUFAs) formulation containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with a 6:1 ratio is a potent inducer of endothelium-dependent nitric oxide (NO)-mediated vasorelaxation that also improves ageing-related and angiotensin II-induced endothelial dysfunction in rats. Purpose Since PUFAs are unstable, the possibility that nanoencapsulation of EPA:DHA 6:1 followed by coating potentiates the bioactivity was evaluated. Methods EPA:DHA 6:1 was emulsified in water phase and coated with proteins and gum derivatives or used in native form. Changes in isometric tension of porcine coronary artery rings were determined using organ chambers. The role of NO was assessed using Nw-nitro-L-arginine (L-NA, NO synthase inhibitor), prostanoids using indomethacin (Indo, COX inhibitor) and endothelium-derived hyperpolarization (EDH) using TRAM-34 and UCL-1684 (Ca2 + -dependent potassium channel inhibitors). Results Coated EPA:DHA 6:1 nanoparticles (NP) caused in a concentration-dependent manner endothelium-dependent relaxations that were more sustained than those of the native form. At 0.3%, coated and native forms induced 56.6 ± 2.8% and 51.1 ± 1.5%relaxations at 10 min, and 93.8 ± 2.1% and 35.1 ± 1.7% at 60 min, respectively. The response to the coated EPA:DHA 6:1 NP was inhibited by L-NA and not affected by Indo, TRAM-34 plus UCL-1684, and by the previous incubation of rings with another oil (corn oil 0.3%). In contrast, L-NA, Indo, and TRAM-34 plus UCL-1684 inhibited the relaxation to EPA:DHA 6:1. Conclusion Nanoencapsulation of EPA:DHA 6:1 followed by coating perpetuated their ability to cause endothelium-dependent relaxation of coronary artery rings that is exclusively mediated by NO. In contrast, the relaxing activity of the native form involved NO, EDH and vasorelaxant prostanoids. Therefore, coated EPA:DHA 6:1 NP appear to be an attractive approach to enhance the vasoprotective effect of omega 3 PUFAs
Nanoencapsulation of the omega-3 EPA:DHA 6:1 formulation enhances and sustains NO-mediated endothelium-dependent relaxations in coronary artery rings and NO formation in endothelial cells
No full textInternational audienceThe eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) formulation with a ratio of 6:1 is a potent stimulator of the endothelial formation of nitric oxide (NO). The aim of the study was to investigate whether nanoencapsulation of EPA:DHA 6:1 followed by coating with gum increases its biological activity. Vascular reactivity was assessed using porcine coronary artery rings, the formation of NO in cultured endothelial cells (ECs) using DAF-FM and indirectly by platelet aggregation studies. Coated EPA:DHA 6:1 nanoparticles induced sustained relaxations of coronary artery rings that were greater in rings with than in those without endothelium, and more pronounced than with the native form. Treatment of ECs with coated EPA:DHA 6:1 nanoparticles caused greater and more sustained formation of NO and enhanced their anti-aggregatory effects. Thus, nanoencapsulation of EPA:DHA 6:1 is an attractive strategy to enhance the beneficial effect at the vascular endothelium
Potential of fluorescent nano-carriers targeting VCAM-1 for early detection of senescent endothelial cells
No full textIntroduction
Endothelial senescence has been identified as an early event promoting the development of endothelial dysfunction (ED), a hallmark of vascular ageing and major cardiovascular diseases. In vivo, senescent endothelial cells (EC) appear initially at arterial sites at risk characterized by disturbed flow and low shear stress (i.e., bifurcations and curvatures) compared to those at low risk characterized by laminar flow and a high level of shear stress (i.e., aorta).
Objective
The aim is to develop fluorescent nano-carriers (NC) to target a cell surface protein up-regulated in senescent ECs, for diagnostic purposes.
Method
NC with a lipid core containing a fluorescent probe (NR668 or Cy5.5 derivative) stabilized by a polymer scaffold and decorated with VCAM-1 antibodies (NC-VCAM-1) were applied to different models of EC senescence in cultured porcine coronary artery (premature senescence induced by angiotensin II and replicative senescence observed at passage P3). The fluorescence signal was visualized by confocal microscopy.
Results
Both models of EC senescence demonstrated higher levels of senescence-associated beta-galactosidase activity, senescence markers and VCAM-1 than healthy EC at P1. Incubation of either P3 EC or Ang II-treated P1 EC with fluorescent NC-VCAM-1 showed a higher level of fluorescence than P1 EC. The EC-related NC-VCAM-1 fluorescent signal is abolished by the previous incubation of EC with an antibody directed against VCAM-1, demonstrating the ability to target cell surface VCAM-1. The highest level of NC-VCAM-1 fluorescence was observed with NC with an average diameter below 100 nm and at 37 °C.
Conclusion
The present findings indicate that fluorescent NC-VCAM-1 allow the detection of senescent EC. Thus, using fluorescent functionalized NC targeting a senescence-associated cell surface protein appears to be an attractive strategy to evaluate the burden of EC senescence, which promotes ED and, ultimately, cardiovascular events
Potential of fluorescent nano-carriers targeting VCAM-1 for early detection of senescent endothelial cells
No full textIntroduction
Endothelial senescence has been identified as an early event promoting the development of endothelial dysfunction (ED), a hallmark of vascular ageing and major cardiovascular diseases. In vivo, senescent endothelial cells (EC) appear initially at arterial sites at risk characterized by disturbed flow and low shear stress (i.e., bifurcations and curvatures) compared to those at low risk characterized by laminar flow and a high level of shear stress (i.e., aorta).
Objective
The aim is to develop fluorescent nano-carriers (NC) to target a cell surface protein up-regulated in senescent ECs, for diagnostic purposes.
Method
NC with a lipid core containing a fluorescent probe (NR668 or Cy5.5 derivative) stabilized by a polymer scaffold and decorated with VCAM-1 antibodies (NC-VCAM-1) were applied to different models of EC senescence in cultured porcine coronary artery (premature senescence induced by angiotensin II and replicative senescence observed at passage P3). The fluorescence signal was visualized by confocal microscopy.
Results
Both models of EC senescence demonstrated higher levels of senescence-associated beta-galactosidase activity, senescence markers and VCAM-1 than healthy EC at P1. Incubation of either P3 EC or Ang II-treated P1 EC with fluorescent NC-VCAM-1 showed a higher level of fluorescence than P1 EC. The EC-related NC-VCAM-1 fluorescent signal is abolished by the previous incubation of EC with an antibody directed against VCAM-1, demonstrating the ability to target cell surface VCAM-1. The highest level of NC-VCAM-1 fluorescence was observed with NC with an average diameter below 100 nm and at 37 °C.
Conclusion
The present findings indicate that fluorescent NC-VCAM-1 allow the detection of senescent EC. Thus, using fluorescent functionalized NC targeting a senescence-associated cell surface protein appears to be an attractive strategy to evaluate the burden of EC senescence, which promotes ED and, ultimately, cardiovascular events
Scientific and medical evidence informing expansion of hepatitis B treatment guidelines
No full text: Chronic hepatitis B treatment relies on nucleoside or nucleotide analogue drugs that suppress hepatitis B virus (HBV) replication, normalise liver enzymes, and slow disease progression with excellent safety profiles. Treatment is not curative, and patients remain at risk of cirrhosis and hepatocellular carcinoma. Treatment guidelines have generally restricted antiviral therapy to individuals with high HBV DNA and elevated ALT or hepatic fibrosis, often requiring longitudinal testing that can be scarcely available in resource-limited settings. Consequently, fewer than 3% of people living with HBV infection are receiving antiviral therapy. Guidelines from China and WHO recently broadened access criteria to antiviral therapy, but there are people who fall outside these guidelines who could still benefit from treatment initiation. The pathological processes induced by HBV infection are still active in these patients. We present the benefits and risks of expanding treatment eligibility. We believe that the benefits of reduced hepatic damage and carcinogenic stimuli greatly outweigh the risks
Search for the rare decays B ---> K l+ l- and B ---> K* l+ l-
No full textWe present results from a search for the flavor-changing neutral current decays B --> Kl(+)l(-) and B --> K*l(+)l(-), where l(+)l(-) is either an e(+)e(-) or mu(+)mu(-) pair. The data sample comprises 22.7 x 10(6) Y (4S) --> BB decays collected with the BABAR detector at the PEP-II B Factory. We obtain the 90% C. L. upper limits B (B --> Kl(+)l(-)) K*l(+)l(-)) Ke(+/-) mu(-/+) and B --> K* e(+/-) mu(-/+)
Search for lepton-number violating B + → X -l + l ′ + decays
No full textWe report on a search for eleven lepton-number violating processes B+→X-l+l′+ with X-=K-, π-, ρ-, K*-, or D- and l+/l′+=e+ or μ+, using a sample of 471±3 million BB̄ events collected with the BABAR detector at the PEP-II e+e- collider at the SLAC National Accelerator Laboratory. We find no evidence for any of these modes and place 90% confidence level upper limits on their branching fractions in the range (1.5-26)×10-7. © 2014 American Physical Society
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