Solvent mediated forces in critical fluids

The effective interaction between two planar walls immersed in a fluid is investigated by use of Density Functional Theory in the super-critical region of the phase diagram. A hard core Yukawa model of fluid is studied with special attention to the critical region. To achieve this goal a new formulation of the Weighted Density Approximation coupled with the Hierarchical Reference Theory, able to deal with critical long wavelength fluctuations, is put forward and compared with other approaches. The effective interaction between the walls is seen to change character on lowering the temperature: The strong oscillations induced by layering of the molecules, typical of the depletion mechanism in hard core systems, are gradually smoothed and, close to the critical point, a long range attractive tail emerges leading to a scaling form which agrees with the expectations based on the critical Casimir effect. Strong corrections to scaling are seen to affect the results up to very small reduced temperatures. By use of Derjaguin approximation, this investigation has natural implications for the aggregation of colloidal particles in critical solvents.Comment: 15 pages, 16 figure

Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and improved cyclooxygenase-2/cyclooxygenase-1 selectivity.

he important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new compounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diarylpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3- acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain

Synthesis, in vitro, and in vivo biological evaluation and molecular docking simulations of chiral alcohol and ether derivatives of the 1,5-diarylpyrrole scaffold as novel anti-inflammatory and analgesic agents.

Following our previous research on anti-inflammatory drugs (NSAIDs), we report here the synthesis of chiral 1,5-diarylpyrroles derivatives that were characterized for their in vitro inhibitory effects toward cyclooxygenase (COX) isozymes. Analysis of enzymatic affinity and COX-2 selectivity led us to the selection of one compound (+/-)-10b that was further tested in vitro in the human whole blood (HWB) and in vivo for its anti-inflammatory activity in mice. The affinity data have been rationalized through docking simulations

Antropofagia in “Crisis”: Oswald de Andrade’s Third Dentition

info:eu-repo/semantics/publishedVersio

Fluids at interfaces: Casimir effect, depletion and thermo-osmosis.

The critical Casimir effect is the long-range interaction between two planar walls in a critical fluid due to the confinement, achieved by the wall interfaces, of the critical density fluctuations. In this Thesis we provide a microscopic description of the critical Casimir force, introducing a novel density functional approximation coupled to the hierarchical reference theory of fluids. The depletion interaction is an effective attractive force arising between colloidal particles immersed in a solvent: The first prediction of this effect dates back to the seminal work by Asakura and Oosawa and has been obtained assuming that the colloidal particles were perfectly smooth spheres immersed in an ideal gas. In this Thesis we address the study of the interaction potential mediated by an ideal gas between two rough colloidal particles, as a function of the geometry, the dimension and the spatial configuration of the corrugations. When a thermal gradient is applied to a fluid at contact with a surface a stationary flow develops. This effect, referred to as thermo-osmosis, has been discovered in the late nineteenth century but successful theoretical descriptions have been up to now devised only when the fluid is a rarefied gas. In this thesis we presents a microscopic theory of thermo-osmosis based on a generalisation of linear response theory to inhomogeneous and anisotropic environments and to thermal disturbances

Was Whitman “Betrayed” in Brazil?: Geir Campos, Ana Cristina Cesar, and the 1983 Chopping Up of Leaves of Grass

info:eu-repo/semantics/publishedVersio

Persistent recovery of normal left ventricular function and dimension in idiopathic dilated cardiomyopathy during long\u2010term follow\u2010up: does real healing exist?

BACKGROUND: An important number of patients with idiopathic dilated cardiomyopathy have dramatically improved left ventricular function with optimal treatment; however, little is known about the evolution and long-term outcome of this subgroup, which shows apparent healing. This study assesses whether real healing actually exists in dilated cardiomyopathy. METHODS AND RESULTS: Persistent apparent healing was evaluated among 408 patients with dilated cardiomyopathy receiving tailored medical treatment and followed over the very long-term. Persistent apparent healing was defined as left ventricular ejection fraction 6550% and indexed left ventricular end-diastolic diameter 6433 mm/m(2) at both mid-term (19\ub14 months) and long-term (103\ub19 months) follow-up. At mid-term, 63 of 408 patients (15%) were apparently healed; 38 (60%; 9%of the whole population) showed persistent apparent healing at long-term evaluation. No predictors of persistent apparent healing were found. Patients with persistent apparent healing showed better heart transplant\u2013free survival at very long-term follow-up (95% versus 71%; P=0.014) compared with nonpersistently normalized patients. Nevertheless, in the very longterm, 37% of this subgroup experienced deterioration of left ventricular systolic function, and 5% died or had heart transplantation. CONCLUSIONS: Persistent long-term apparent healing was evident in a remarkable proportion of dilated cardiomyopathy patients receiving optimal medical treatment and was associated with stable normalization of main clinical and laboratory features. This condition can be characterized by a decline of left ventricular function over the very long term, highlighting the relevance of serial nd individualized follow-up in all patients with dilated cardiomyopathy, especially considering the absence of predictors for longterm apparent healing

Fluids at interfaces: Casimir effect, depletion and thermo-osmosis.

The critical Casimir effect is the long-range interaction between two planar walls in a critical fluid due to the confinement, achieved by the wall interfaces, of the critical density fluctuations. In this Thesis we provide a microscopic description of the critical Casimir force, introducing a novel density functional approximation coupled to the hierarchical reference theory of fluids. The depletion interaction is an effective attractive force arising between colloidal particles immersed in a solvent: The first prediction of this effect dates back to the seminal work by Asakura and Oosawa and has been obtained assuming that the colloidal particles were perfectly smooth spheres immersed in an ideal gas. In this Thesis we address the study of the interaction potential mediated by an ideal gas between two rough colloidal particles, as a function of the geometry, the dimension and the spatial configuration of the corrugations. When a thermal gradient is applied to a fluid at contact with a surface a stationary flow develops. This effect, referred to as thermo-osmosis, has been discovered in the late nineteenth century but successful theoretical descriptions have been up to now devised only when the fluid is a rarefied gas. In this thesis we presents a microscopic theory of thermo-osmosis based on a generalisation of linear response theory to inhomogeneous and anisotropic environments and to thermal disturbances

Improving the solubility of a new class of antiinflammatory pharmacodynamic hybrids, that release nitric oxide and inhibit cycloxygenase-2 isoenzyme

The development of a novel class of pharmacodynamic hybrids that inhibits COX-2 isoform is reported. These molecules display enhanced nitric oxide releasing properties due to the presence of an ionisable moiety. The in vivo analgesic/anti-inflammatory activity was maintained in relation to the parent compounds

Novel ester and acid derivatives of the 1,5-diarylpyrrole scaffold as anti-inflammatory and analgesic agents. Synthesis and in vitro and in vivo biological evaluation.

A new generation of selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) was developed to circumvent the major side effects of cyclooxygenase-1 (COX-1) and COX-2 inhibitors (stomach ulceration and nephrotoxicity). As a consequence, coxibs are extremely valuable in treating acute and chronic inflammatory conditions. However, the use of coxibs, such as rofecoxib (Vioxx), was discontinued because of the high risk of cardiovascular adverse events. More recent clinical findings highlighted how the cardiovascular toxicity of coxibs could be mitigated by an appropriate COX-1 versus COX-2 selectivity. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, selective for COX-2. Here, we describe the synthesis of new1,5-diarylpyrroles along with their inhibitory effects in vitro, ex vivo, and in vivo toward COX isoenzymes and their analgesic activity. Isopropyl-2-methyl-5-[4- (methylsulfonyl)phenyl]-1-phenyl-1H-pyrrole-3-acetate (10a), a representative member of the series, was selected for pharmacokinetic and metabolic studies