Raloxifene reduces fractures in postmenopausal women with osteoporosis

in Clinical Orthopaedics & Related Research (2006), 443

Recently, selective estrogen receptor modulators have been developed for the management of osteoporosis based on antiosteoclastic properties similar to that of estrogens but with a safety profile ... [more ▼]

Recently, selective estrogen receptor modulators have been developed for the management of osteoporosis based on antiosteoclastic properties similar to that of estrogens but with a safety profile including potential benefits on the breast, heart, and cognitive function. Raloxifene, the first selective estrogen receptor modulator to be marketed for the treatment of osteoporosis has shown reduction in spinal fracture risk in patients with low bone mineral density with (48%) or without (35%) prevalent vertebral fracture. Raloxifene also reduces nonvertebral fractures in high risk patients (47%). The decrease in Type I procollagen N-terminal propeptide at 1 year accounts for 28% of the total reduction in vertebral fracture risk. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84%. Among subjects with increased cardiovascular risk at baseline, those assigned to raloxifene had a 40% decrease in the risk of cardiovascular events compared with placebo. The definite anti-fracture efficacy of raloxifene at the spine, its plausible effect on non-spine fracture in high-risk patients and its beneficial effect on breast and heart make this compound an interesting approach for women presenting with osteoporosis. LEVEL OF EVIDENCE: Therapeutic study, level II (lesser quality randomized controlled trial [eg, < 80% followup, no blinding, or improper randomization]). See the Guidelines for Authors for a complete description of the levels of evidence. [less ▲]

Raloxifene-induced myeloma cell apoptosis: a study of nuclear factor-kappaB inhibition and gene expression signature.

in Molecular Pharmacology (2006), 69(5), 1615-1623

Because multiple myeloma remains associated with a poor prognosis, novel drugs targeting specific signaling pathways are needed. The efficacy of selective estrogen receptor modulators for the treatment of ... [more ▼]

Because multiple myeloma remains associated with a poor prognosis, novel drugs targeting specific signaling pathways are needed. The efficacy of selective estrogen receptor modulators for the treatment of multiple myeloma is not well documented. In the present report, we studied the antitumor activity of raloxifene, a selective estrogen receptor modulator, on multiple myeloma cell lines. Raloxifene effects were assessed by tetrazolium salt reduction assay, cell cycle analysis, and Western blotting. Mobility shift assay, immunoprecipitation, chromatin immunoprecipitation assay, and gene expression profiling were performed to characterize the mechanisms of raloxifene-induced activity. Indeed, raloxifene, as well as tamoxifen, decreased JJN-3 and U266 myeloma cell viability and induced caspase-dependent apoptosis. Raloxifene and tamoxifen also increased the cytotoxic response to vincristine and arsenic trioxide. Moreover, raloxifene inhibited constitutive nuclear factor-kappaB (NF-kappaB) activity in myeloma cells by removing p65 from its binding sites through estrogen receptor alpha interaction with p65. It is noteworthy that microarray analysis showed that raloxifene treatment decreased the expression of known NF-kappaB-regulated genes involved in myeloma cell survival and myeloma-induced bone lesions (e.g., c-myc, mip-1alpha, hgf, pac1,...) and induced the expression of a subset of genes regulating cellular cycle (e.g., p21, gadd34, cyclin G2,...). In conclusion, raloxifene induces myeloma cell cycle arrest and apoptosis partly through NF-kappaB-dependent mechanisms. These findings also provide a transcriptional profile of raloxifene treatment on multiple myeloma cells, offering the framework for future studies of selective estrogen receptor modulators therapy in multiple myeloma. [less ▲]

The Ramachandran Plots Of Glycine And Pre-Proline

in Bmc Structural Biology (2005), 5

BACKGROUND: The Ramachandran plot is a fundamental tool in the analysis of protein structures. Of the 4 basic types of Ramachandran plots, the interactions that determine the generic and proline ... [more ▼]

BACKGROUND: The Ramachandran plot is a fundamental tool in the analysis of protein structures. Of the 4 basic types of Ramachandran plots, the interactions that determine the generic and proline Ramachandran plots are well understood. The interactions of the glycine and pre-proline Ramachandran plots are not. RESULTS: In glycine, the psi angle is typically clustered at psi = 180 degrees and psi = 0 degrees. We show that these clusters correspond to conformations where either the N(i+1) or O atom is sandwiched between the two Halpha atoms of glycine. We show that the shape of the 5 distinct regions of density (the alpha, alphaL, betaS, betaP and betaPR regions) can be reproduced with electrostatic dipole-dipole interactions. In pre-proline, we analyse the origin of the zeta region of the Ramachandran plot, a region unique to pre-proline. We show that it is stabilized by a CO(i-1)...CdeltaHdelta(i+1) weak hydrogen bond. This is analogous to the CO(i-1)...NH(i+1) hydrogen bond that stabilizes the gamma region in the generic Ramachandran plot. CONCLUSION: We have identified the specific interactions that affect the backbone of glycine and pre-proline. Knowledge of these interactions will improve current force-fields, and help understand structural motifs containing these residues. [less ▲]

Raman scattering in crystalline oligothiophenes: A comparison between density functional theory and bond polarizability model

in Journal of Physical Chemistry B (2006), 110(49), 24869-24875

Raman intensity of intramolecular and lattice modes of crystalline alpha-bithiophene (alpha-2T) are investigated within density functional theory using a nonlinear response formalism. First, comparison ... [more ▼]

Raman intensity of intramolecular and lattice modes of crystalline alpha-bithiophene (alpha-2T) are investigated within density functional theory using a nonlinear response formalism. First, comparison between the calculated Raman spectrum and the experimental data allows the assignment of the main Raman lines over the whole frequency range. Then, a bond polarizability (BP) model, limited to first neighbors, is built. We show that, although the BP model cannot reproduce the changes of dielectric susceptibility under individual atomic displacements, it is accurate enough to reproduce the profile of the unpolarized nonresonant Raman spectrum of alpha-2T powder. Finally, the BP model, fitted on our first-principles results on alpha-2T, is applied with success to the alpha-quaterthiophene polymorph phases and alpha-sexithiophene, demonstrating on practical examples that first-principles and BP approaches are powerful complementary tools to calculate the nonresonant Raman spectrum of alpha-2T and make reasonable predictions on larger oligothiophenes. [less ▲]

Raman spectroscopic study of complex formation between major calixarene derivatives and three pharmaceutical substances

Poster (2010, November)

Complex formation of six calix[n]arene derivatives – tert-butyl-calix[4]arene (C4), tert-butyl-calix[6]arene (C6), tert-butyl-calix[8]arene (C8) and their ethyl-acetic-ester derivatives (C4Es4, C6Es6 ... [more ▼]

Complex formation of six calix[n]arene derivatives – tert-butyl-calix[4]arene (C4), tert-butyl-calix[6]arene (C6), tert-butyl-calix[8]arene (C8) and their ethyl-acetic-ester derivatives (C4Es4, C6Es6, C8Es8) – has been the subject for our Raman spectroscopic study. Substances taken in study for complexation were the two widely used anticoagulants – warfarin and its 5-nitro- derivative, acenocoumarol – and their antidote, phytomenadione (also known as phylloquinone or vitamin K1). For each standard substance, Raman spectra were studied between 3620 and 90 cm-1. In order to obtain the complexes, a mixture of solutions of each calixarene and each analyte was prepared, in a stoichiometric ratio of 1:1 and then the solvents were evaporated. Spectra of solid residues obtained were compared with those of initial molecules. In all cases, there was observed a Raman band shifting or even the disappearance of some bands, indicating that calixarene derivatives interact with the studied molecules. In conclusion, the six calixarene derivatives taken in study seem to be able to form complexes with the molecules of warfarin, acenocoumarol and phylloquinone. [less ▲]

Raman spectroscopy of dye mixtures on cotton fibres

Conference (2011, June 17)

Raman spectroscopy is becoming a routine technique in numerous forensic labs since it is fast and non-destructive. Recent work has shown that Raman spectra of dyes depend on the excitation laser ... [more ▼]

Raman spectroscopy is becoming a routine technique in numerous forensic labs since it is fast and non-destructive. Recent work has shown that Raman spectra of dyes depend on the excitation laser wavelength used (resonance effects) and on the scattering ability of the dye molecule itself. Both factors together with fluorescence emission may affect the detection of a dye, especially within a mixture. In order to obtain a better understanding of their Raman behavior binary mixtures at various ratios have been prepared using five known dyes showing different scattering and fluorescent abilities. Their Raman investigation at 514 and 785 nm highlights the complementarity of these two resonant and non-resonant sources and the limitations of the Raman technique in the detection of both major and minor components of a dye mixture. Other investigations have been performed on binary and ternary known dye mixtures on cotton fibres by Raman spectroscopy and MSP-Vis. The combination of two laser sources leads in most cases to the detection of both or two out of three dye components. This Raman information reinforces clearly the confidence in MSP-Vis results. Indeed the contribution of the minor dye component is sometimes very small in the MSP spectrum and a visual inspection of the spectra in addition to inhomogeneous dyeing on cotton may result in difficult interpretation. For these reasons Raman spectroscopy is a very convenient technique to confirm or maybe specify the MSP results, especially for fibre types with common MSP spectra. Furthermore, MSP-Vis also showed some limitations with very light or very dark colored fibres whereas Raman spectroscopy could still discriminate between fibre types. [less ▲]

Rambus déclare forfait. La Commission dans un fauteuil.

in Revue du Droit des Technologies de l'Information [= RDTI] (2010), 41

The present contribution comments the undertaking decision of the European Commission in the Rambus case. We put the case into context and introduce the economic notions needed to understand patent ambush ... [more ▼]

The present contribution comments the undertaking decision of the European Commission in the Rambus case. We put the case into context and introduce the economic notions needed to understand patent ambush issues. We then explain how such strategies may harm the economy. Second, we present the various legal tools which may be invoked to fight patent ambushes, with a specific emphasis on competition law tools. Third, we discuss whether such tools provide an efficient answer to the patent ambush issue. If the intervention of the Commission seems legally possible, by offering commitments, Rambus gets the Commission out of a difficult situation. [less ▲]

The Ramesside Triumph Scene: monumental transmission in the Theban temple context

Book published by Presses Universitaires de Liège (in press)

The Ramses Project. Linguistic annotation and corpus mark-up in Late Egyptian: Theoretical and methodological issues

Conference (2011, December 12)

Ramses. A New Research Tool in Philology and Linguistics

in Strudwick, Nigel (Ed.) Information Technology and Egyptology in 2008. Proceedings of the meeting of the Computer Working Group of the International Association of Egyptologists (Informatique et Egyptologie), Vienna, 8–11 July 2008 (2009)

This paper introduces Ramses, a database of Late Egyptian texts, currently under development at the University of Liège (Belgium). Ramses sets out to be a new and powerful research tool. Its main ... [more ▼]

This paper introduces Ramses, a database of Late Egyptian texts, currently under development at the University of Liège (Belgium). Ramses sets out to be a new and powerful research tool. Its main applications are linguistically and philologically orientated. After a general overview of the structure of the database, the search engines are described with some detail. [less ▲]