Mononuclear cell migration into the vascular subendothelium constitutes an early event of the atherogenic process. Because the effect of retinoid X receptor (RXR)α on arterial mononuclear leukocyte recruitment is poorly understood, this study investigated whether RXR agonists can affect this response and the underlying mechanisms involved. Decreased RXRα expression was detected after 4 h stimulation of human umbilical arterial endothelial cells with TNF-α. Interestingly, under physiological flow conditions, TNF-α–induced endothelial adhesion of human mononuclear cells was concentration-dependently inhibited by preincubation of the human umbilical arterial endothelial cells with RXR agonists such as bexarotene or 9-cis-retinoid acid. RXR agonists also prevented TNF-α–induced VCAM-1 and ICAM-1 expression, as well as endothelial growth-related oncogene-α and MCP-1 release. Suppression of RXRα expression with a small interfering RNA abrogated these responses. Furthermore, inhibition of MAPKs and NF-κB pathways were involved in these events. RXR agonist-induced antileukocyte adhesive effects seemed to be mediated via RXRα/peroxisome proliferator-activated receptor (PPAR)γ interaction, since endothelial PPARγ silencing abolished their inhibitory responses. Furthermore, RXR agonists increased RXR/PPARγ interaction, and combinations of suboptimal concentrations of both nuclear receptor ligands inhibited TNF-α–induced mononuclear leukocyte arrest by 60–65%. In vivo, bexarotene dose-dependently inhibited TNF-α–induced leukocyte adhesion to the murine cremasteric arterioles and decreased VCAM-1 and ICAM-1 expression. Therefore, these results reveal that RXR agonists can inhibit the initial inflammatory response that precedes the atherogenic process by targeting different steps of the mononuclear recruitment cascade. Thus, RXR agonists may constitute a new therapeutic tool in the control of the inflammatory process associated with cardiovascular disease.

Objective-Angiotensin-II (Ang-II) promotes the interaction of mononuclear cells with arterioles and neutrophils with postcapillary venules. To investigate the mechanisms underlying this dissimilar response, the involvement of fractalkine (CX 3 CL1) was explored. Methods and Results-Enhanced CX 3 CL1 expression was detected in both cremasteric arterioles and postcapillary venules 24 hours after Ang-II intrascrotal injection. Arteriolar leukocyte adhesion was the unique parameter significantly reduced (83%) in animals lacking CX 3 CL1 receptor (CX 3 CR1). Human umbilical arterial and venous endothelial cell stimulation with 1 μmol/L Ang-II increased CX 3 CL1 expression, yet neutralization of CX 3 CL1 activity only significantly inhibited Ang-II-induced mononuclear cell-human umbilical arterial endothelial cell interactions (73%) but not with human umbilical venous endothelial cells. The use of small interfering RNA revealed the involvement of tumor necrosis factor-α in Ang-II-induced CX 3 CL1 upregulation and mononuclear cell arrest. Nox5 knockdown with small interfering RNA or pharmacological inhibition of extracellular signal-regulated kinases1/2, p38 mitogen-activated protein kinase, and nuclear factor-κB also abolished these responses. Finally, when human umbilical arterial endothelial cells were costimulated with Ang-II, tumor necrosis factor-α, and interferon-γ, CX 3 CL1 expression and mononuclear cell adhesiveness were more pronounced than when each stimulus was provided alone. Conclusion-These

In Europe there is a continuous increase in the demand for diesel fuel. Also, regulations to reduce tail pipe emissions to the atmosphere impose new and more stringent specifications; for diesel transportation fuel, main pressure being on the reduction of sulphur and polyaromatic concentration, reduction of density and decrease of final boiling point. For example, maximum sulphur level allowed now is 350 ppm, with reductions to levels of around 50 ppm foreseen in the short term. Further reductions (even to less than 10 ppm) are also on the horizon. Hydrotreatment (HDT), as a variety of processes, is the main tool available to the refinery industry to improve diesel quality. This paper deals with the reach of hydrotreatment (HDT) technologies to adapt diesel fuel to the new regulations. The discussion is centred on three aspects: feed processability, process conditions and catalysts employed. Feed processability is studied in terms of how somefeed properties such as sulphur content and specific gravity have an effect on the HDS conversion. Correlations are shown that explain the effect of such variables. Mainprocess conditions such as space velocity and hydrogen partial pressure are studied, and their effect on theproduct sulphur level is shown. Typical CoMo and NiMo hydrotreatment catalysts are compared upon on the perspective of actual and future specifications. Changes in product properties occurring during hydrotreatment (aromatic content, cetane index and specific gravity) are also shown. This comprehensive study of the HDT process allows us to estimate hydrotreatment requirements to adapt our refineries to future specifications of the diesel fuel. Introduction In Europe, estimates are that oil fuels demand for transportation will increase by less than 1% per year, during the next 20 years. In the same period, demand for diesel oil is expected to increase at a rate of 2–2,5% per year. This increase in diesel demand will be accompanied by an important severe in specifications, aimed at the reduction of tail pipe emissions. Table 1 shows some of these specifications and the trend that they are likely to follow in the near future. The refiners in several ways will face this new demand and quality situation:Increase in conversion installed.Increase in conversion process selectivity towards products boiling in the diesel range.New sources for diesel will have to be considered: oxygenates, bio diesel, oligomerization process, GTL processes etc.Increase in HDT capacity. Out of these possibilities, installation of further HDT capacity is the most straight forward solution to improve diesel quality for a number of reasons: it is a known and proven technology, makes use of hydrogen selectively and requires moderate investments. Feed Processability It is well known that not all feeds respond similarly to a given HDS process. Reasons are many, but they can be resumed in two groups:those related to the type and concentration of different sulfur compounds with different reactivity present in the feed, andthose related the presence of inhibitors or poisons that modify catalyst activity. Since many of these factors are difficult to measure, and in any case, impractical from the refiner, a try has been done to corelate some feed properties to its reactivity towards HDS.

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