Effects of Deoxycholylglycine, a Conjugated Secondary Bile Acid, on Myogenic Tone and Agonist-Induced Contraction in Rat Resistance Arteries

Bile acids (BAs) regulate cardiovascular function via diverse mechanisms. Although in both health and disease serum glycine-conjugated BAs are more abundant than taurine-conjugated BAs, their effects on myogenic tone (MT), a key determinant of systemic vascular resistance (SVR), have not been examined.Fourth-order mesenteric arteries (170-250 µm) isolated from Sprague-Dawley rats were pressurized at 70 mmHg and allowed to develop spontaneous constriction, i.e., MT. Deoxycholylglycine (DCG; 0.1-100 µM), a glycine-conjugated major secondary BA, induced reversible, concentration-dependent reduction of MT that was similar in endothelium-intact and -denuded arteries. DCG reduced the myogenic response to stepwise increase in pressure (20 to 100 mmHg). Neither atropine nor the combination of L-NAME (a NOS inhibitor) plus indomethacin altered DCG-mediated reduction of MT. K(+) channel blockade with glibenclamide (K(ATP)), 4-aminopyradine (K(V)), BaCl(2) (K(IR)) or tetraethylammonium (TEA, K(Ca)) were also ineffective. In Fluo-2-loaded arteries, DCG markedly reduced vascular smooth muscle cell (VSM) Ca(2+) fluorescence (∼50%). In arteries incubated with DCG, physiological salt solution (PSS) with high Ca(2+) (4 mM) restored myogenic response. DCG reduced vascular tone and VSM cytoplasmic Ca(2+) responses (∼50%) of phenylephrine (PE)- and Ang II-treated arteries, but did not affect KCl-induced vasoconstriction.In rat mesenteric resistance arteries DCG reduces pressure- and agonist-induced vasoconstriction and VSM cytoplasmic Ca(2+) responses, independent of muscarinic receptor, NO or K(+) channel activation. We conclude that BAs alter vasomotor responses, an effect favoring reduced SVR. These findings are likely pertinent to vascular dysfunction in cirrhosis and other conditions associated with elevated serum BAs

Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements

A considerable number of genes that code for AU-rich mRNAs including cytokines, growth factors, transcriptional factors, and certain receptors are involved in both chronic inflammation and cancer. Overexpression of these genes is affected by aberrations or by prolonged activation of several signaling pathways. AU-rich elements (ARE) are important cis-acting short sequences in the 3′UTR that mediate recognition of an array of RNA-binding proteins and affect mRNA stability and translation. This review addresses the cellular and molecular mechanisms that are common between inflammation and cancer and that also govern ARE-mediated post-transcriptional control. The first part examines the role of the ARE-genes in inflammation and cancer and sequence characteristics of AU-rich elements. The second part addresses the common signaling pathways in inflammation and cancer that regulate the ARE-mediated pathways and how their deregulations affect ARE-gene regulation and disease outcome

Implementation of focused beam reflectance measurement (FBRM) in antisolvent crystallization to achieve consistent product quality

10.1021/cg100533nCrystal Growth and Design1083668-367

Adaptive concentration control of cooling and antisolvent crystallization with laser backscattering measurement

10.1021/cg800131rCrystal Growth and Design91182-19

Amphiphilic Properties of Dumbbell-Shaped Inorganic–Organic–Inorganic Molecular Hybrid Materials in Solution and at an Interface

Five novel dumbbell-shaped polyoxometalate (POM)-based inorganic-organic-inorganic molecular hybrids are investigated both in polar solvents and at interfaces for potential amphiphilic properties, which are compared with those of conventional surfactants. These hybrids with the general formula {P(2)V(3)W(15)}(2)-bis(TRIS)-linker are formed by linking two Wells Dawson-type clusters, [P(2)V(3)W(15)O(62)](9-), with different linear bis(TRIS) linker ligands between the two TRIS moieties. Laser light scattering (LLS) studies reveal the presence of self-assembled vesicular structures in water/acetone mixed solvents, and the vesicle size increases with increasing acetone content, suggesting a charge-regulated process. The elastic constants, which are used to calculate the bending energy during vesicle formation, reveal that the organic ligands play an important role in determining the self-assembly process and that the hybrids do demonstrate amphiphilic behavior at the water/air interface. Furthermore, it is shown that some of the hybrids form monolayers at the interface, with an average molecular area that can be correlated with their organic linkers, as determined from their pi-A isotherms. Finally, the hybrids not only display amphiphilic behavior akin to that of a surfactant but also exhibit an unusually high entropy contribution to vesicle formation as a result of their unique large, polar head groups, complex organic linkers, and their special molecular architectures as well as because of the involvement of the amphiphilic tetrabutylammonium (TBA) counterions