Dielectric dispersion study of binary mixtures of methyl ethers with water at 298.15 K using frequency domain technique

448-454A precision LCR meter along with a liquid dielectric cell have been used to measure the capacitance and resistance of the binary mixtures of methyl ethers with water at 298.15 K in the frequency range of 20 Hz to 2 MHz. The measured values are used to compute the complex dielectric permittivity ε*(ω). The parameters like complex electrical modulus M*(ω), complex electrical conductivity σ*(ω) and loss tangent (tan δ) are obtained from the complex dielectric permittivity values of the samples. The values of excess dielectric permittivity of the samples are calculated using the respective static dielectric permittivity values. The refractive indices of all the samples were measured using Abbe’s refractometer at 298.15 K. All these parameters are used to gain insight into the concentration dependent variation in dielectric and electrical properties of the binary mixtures. A dominance of electrode polarization effect in the lower frequency region is observed for all the samples studied here

Dielectric dispersion study of binary mixtures of methyl ethers with water at 298.15 K using frequency domain technique

A precision LCR meter along with a liquid dielectric cell have been used to measure the capacitance and resistance of the binary mixtures of methyl ethers with water at 298.15 K in the frequency range of 20 Hz to 2 MHz. The measured values are used to compute the complex dielectric permittivity ε*(ω). The parameters like complex electrical modulus M*(ω), complex electrical conductivity σ*(ω) and loss tangent (tan δ) are obtained from the complex dielectric permittivity values of the samples. The values of excess dielectric permittivity of the samples are calculated using the respective static dielectric permittivity values. The refractive indices of all the samples were measured using Abbe’s refractometer at 298.15 K. All these parameters are used to gain insight into the concentration dependent variation in dielectric and electrical properties of the binary mixtures. A dominance of electrode polarization effect in the lower frequency region is observed for all the samples studied here

Vitronectin Increases Vascular Permeability by Promoting VE-Cadherin Internalization at Cell Junctions

Cross-talk between integrins and cadherins regulates cell function. We tested the hypothesis that vitronectin (VN), a multi-functional adhesion molecule present in the extracellular matrix and plasma, regulates vascular permeability via effects on VE-cadherin, a critical regulator of endothelial cell (EC) adhesion.Addition of multimeric VN (mult VN) significantly increased VE-cadherin internalization in human umbilical vein EC (HUVEC) monolayers. This effect was blocked by the anti-α(V)β(3) antibody, pharmacological inhibition and knockdown of Src kinase. In contrast to mult VN, monomeric VN did not trigger VE-cadherin internalization. In a modified Miles assay, VN deficiency impaired vascular endothelial growth factor-induced permeability. Furthermore, ischemia-induced enhancement of vascular permeability, expressed as the ratio of FITC-dextran leakage from the circulation into the ischemic and non-ischemic hindlimb muscle, was significantly greater in the WT mice than in the Vn(-/-) mice. Similarly, ischemia-mediated macrophage infiltration was significantly reduced in the Vn(-/-) mice vs. the WT controls. We evaluated changes in the multimerization of VN in ischemic tissue in a mouse hindlimb ischemia model. VN plays a previously unrecognized role in regulating endothelial permeability via conformational- and integrin-dependent effects on VE-cadherin trafficking.These results have important implications for the regulation of endothelial function and angiogenesis by VN under normal and pathological conditions

Absence of Host Plasminogen Activator Inhibitor 1 Prevents Cancer Invasion and Vascularization

Acquisition of invasive/metastatic potential through protease expression is an essential event in tumor progression. High levels of components of the plasminogen activation system, including urokinase, but paradoxically also its inhibitor, plasminogen activator inhibitor 1 (PAI1), have been correlated with a poor prognosis for some cancers. We report here that deficient PAI1 expression in host mice prevented local invasion and tumor vascularization of transplanted malignant keratinocytes. When this PAI1 deficiency was circumvented by intravenous injection of a replication-defective adenoviral vector expressing human PAI1, invasion and associated angiogenesis were restored. This experimental evidence demonstrates that host-produced PAI is essential for cancer cell invasion and angiogenesis

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Dielectric relaxation and molecular interaction study of aqueous amides

621-628Dielectric permittivity spectra of amides (DMF and DMA) over entire concentrations with aqueous solution have been measured with different frequency ranges at 25 °C. The permittivity spectra of amide-water mixtures at lower frequencies (20 Hz to 2 MHz) have been measured using Agilent Precision LCR meter E4980A and the same have been measured at higher frequencies using time domain reflectometry technique in the frequency range of 10 MHz to 30 GHz. The permittivity spectra have been fitted in Cole-Davidson model in order to evaluate the dielectric parameters. Further the Excess permittivity, Kirkwood correlation factor, Bruggeman factor have been calculated to study the molecular interactions in amides with water molecules. The study has been extended to confirm the molecular interactions among the unlike molecules using the volumetric properties

Factor VII activating protease (FSAP) regulates the expression of inflammatory genes in vascular smooth muscle and endothelial cells

Background and aims: The factor VII activating protease (FSAP) knockout mice have a bigger neointima after vascular injury and a larger infarct volume after stroke. The Marburg I (MI) single nucleotide polymorphism (SNP) in the FSAP-encoding gene is associated with an increased risk of stroke and carotid stenosis in humans. We hypothesize that the regulation of gene expression by FSAP in vascular cells accounts for its vasculo-regulatory properties. Methods: Vascular smooth muscle cells (VSMC) and endothelial cells (EC) were stimulated with FSAP and a microarray-based expression analysis was performed. Selected genes were further investigated by qPCR. Receptor- and pathway-inhibitors were used to elucidate the mechanisms involved. Results: Pathways significantly activated by FSAP include those related to inflammation, apoptosis and cell growth in VSMC and inflammation in EC. The key upregulated genes in VSMC were AREG, PTGS2 and IL6; and in EC these were SELE, VCAM1, and IL8. Secretion of IL6 in VSMC and IL8 in EC was also stimulated by FSAP. Recombinant wild type protease domain of FSAP, but not the MI-isoform, could recapitulate most of these effects. In VSMC, but not EC, gene expression by FSAP was impaired by PAR1 (protease-activated receptor1) receptor antagonists. In VSMC, FSAP-induced expression of AREG and IL6 was blocked by cAMP and MAPK pathway inhibitors indicating that multiple signalling pathways are likely to be involved. Conclusions: The stimulation of inflammation- and proliferative/apoptosis-related genes in VSMC and EC provides a comprehensive basis for understanding the role of FSAP in vascular diseases

Dielectric relaxation of poly ethylene glycol-water mixtures using time domain technique

476-481Complex dielectric measurements in the frequency range 10 MHz-20 GHz have been carried out in poly ethylene glycol- water mixtures with various concentrations using Time Domain Reflectometry (TDR) method at 25ºC. The dielectric dispersion spectra could be fitted with a single relaxation time with Davidson-Cole behaviour at low volume fraction of water. However, at higher volume fraction of water in poly ethylene glycol dielectric dispersion spectra can be fitted with the Debye behaviour. The values of static dielectric constant, relaxation time, distribution parameter, Bruggeman factor and Kirkwood correlation factor have been determined for the poly ethylene glycol-water system. The study confirms that the intermolecular homogeneous and heterogeneous hydrogen bonding vary significantly with the increase in concentration of poly ethylene glycols in aqueous solutions

Study of dielectric relaxation and hydrogen bonding interaction in binary mixtures of methoxy polyethylene glycol and water

282-287The complex permittivity spectra of binary mixtures of methoxy polyethylene glycol (Polyethylene glycol monomethylether 350) and water over entire concentrations and at different temperatures have been measured using time domain technique in the frequency range of 10 MHz to 30 GHz. The spectra have been fitted to Cole-Davidson model using non linear least square fit method to obtain the dielectric parameters. The non linear behaviour of dielectric parameters suggest intermolecular interaction among the unlike molecules. Excess properties and Bruggeman factor confirm the contribution of hydrogen bonding interactions among the solute-solvent mixtures. Thermodynamic properties of these binary mixtures are also discussed