The combination of Ezetimibe and Statin: a new treatment for hypercholesterolemia

The combination of Simvastatin and Ezetimibe allows dual inhibition of both cholesterol production and absorption. This treatment approach allows achieving same low serum cholesterol levels with the administration of much lower doses of statins. This should reduce side effects, compared to statin only therapy, enabling more patients to achieve their LDL cholesterol treatment goals. With ezetimibe/simvastatin therapy, reductions of about 60% from baseline in LDL cholesterol have been shown. Concomitant improvement in other lipid fractions have also been demonstrated. The ezetimibe/simvastatin combination has been well tolerated, with a safety profile similar to that of statin therapy. This article will review clinical experience with ezetimibe/simvastatin combination, commenting upon its place and potential value in the prevention of cardiovascular disease

Portrait of an artist at work: exploring Max Ernst's surrealist techniques

AbstractMax Ernst was one of the most influential artists associated with both the Dada and Surrealist movements. However, until now, only few scientific studies have been devoted to his works. This paper presents the results of a multi-analytical investigation on six oil paintings, made between 1927 and 1942, belonging to the Peggy Guggenheim Collection in Venice (Solomon R. Guggenheim Foundation, New York). Through a combined art historical and scientific approach, this study aims at understanding Ernst's painting techniques, including frottage, grattage, dripping, and decalcomania, the used materials, and the state of conservation of the artworks. Non-invasive in situ investigations were performed by means of Vis–NIR multi-spectral imaging, X-ray fluorescence, external reflection FTIR and Raman spectroscopy. Imaging analysis revealed important information about Ernst's painting methods while the other techniques provided useful information about the ground layer, the painting materials and the presence of alteration products. Ernst's palette discloses great freedom in his use of materials and evolution during the time. This investigation demonstrates that an integrated, non-invasive, diagnostic approach provides a thorough analysis of materials and execution techniques of Ernst' masterworks allowing an in-depth knowledge of his highly skilled work

Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats.

Abstract Stem cells are emerging as a therapeutic option for incurable diseases, such as Amyotrophic Lateral Sclerosis (ALS). However, critical issues are related to their origin as well as to the need to deepen our knowledge of the therapeutic actions exerted by these cells. Here, we investigate the therapeutic potential of clinical-grade human neural stem cells (hNSCs) that have been successfully used in a recently concluded phase I clinical trial for ALS patients (NCT01640067). The hNSCs were transplanted bilaterally into the anterior horns of the lumbar spinal cord (four grafts each, segments L3–L4) of superoxide dismutase 1 G93A transgenic rats (SOD1 rats) at the symptomatic stage. Controls included untreated SOD1 rats (CTRL) and those treated with HBSS (HBSS). Motor symptoms and histological hallmarks of the disease were evaluated at three progressive time points: 15 and 40 days after transplant (DAT), and end stage. Animals were treated by transient immunosuppression (for 15 days, starting at time of transplantation). Under these conditions, hNSCs integrated extensively within the cord, differentiated into neural phenotypes and migrated rostro-caudally, up to 3.77 ± 0.63 cm from the injection site. The transplanted cells delayed decreases in body weight and deterioration of motor performance in the SOD1 rats. At 40DAT, the anterior horns at L3–L4 revealed a higher density of motoneurons and fewer activated astroglial and microglial cells. Accordingly, the overall survival of transplanted rats was significantly enhanced with no rejection of hNSCs observed. We demonstrated that the beneficial effects observed after stem cell transplantation arises from multiple events that counteract several aspects of the disease, a crucial feature for multifactorial diseases, such as ALS. The combination of therapeutic approaches that target different pathogenic mechanisms of the disorder, including pharmacology, molecular therapy and cell transplantation, will increase the chances of a clinically successful therapy for ALS

Non-invasive identification of paint binders in illuminated manuscripts by ER-FTIR spectroscopy: a systematic study of the influence of different pigments on the binders’ characteristic spectral features

Abstract This paper presents the results of a study of pigment-binder systems painted on parchment, both in the form of reference samples prepared in the laboratory, and of medieval and Renaissance illuminated manuscripts, by means of contactless Fourier-transform mid-infrared spectroscopy (FTIR). The research is aimed at validating external reflection FTIR (ER-FTIR) as a non-invasive method for the identification of paint binders in works of art on parchment. Based on a systematic FTIR investigation undertaken both in attenuated total reflection (ATR) and ER mode, we discuss the possibility to effectively discriminate between different binders, and the way in which the presence of a number of pigments can modify the spectral features of the pigment-binder system. The study reveals that gum Arabic can usually be discriminated from egg-based binders such as egg yolk and egg white, both in paintouts and in real artworks. Amongst all the pigments investigated, carbonates such as azurite and lead white are those that most significantly hinder the correct identification of the paint medium

Phengite megacryst quasi-exsolving phlogopite, from Sulu ultra-high pressure metamorphic terrane, Qinglongshan, Donghai County (eastern China): New data for P-T-X conditions during exhumation

A large crystal of trigonal phengite (Phe-3T; K0.96Na0.02Ba0.01)(Al1.35Mg0.40Fe2+0.11Fe3+0.13Ti0.02)Σ=2.02[Si3.44Al0.56]O10(OH)2), sampled from a phengite+quartz metamorphic vein in the eclogites-bearing rocks of Sulu UHP metamorphic terrane, exhibits unusual thin lamellae of ferrian-aluminian trigonal/monoclinic phlogopite polytypes (Phl-3T: (K0.78Na0.01)(Mg1.48Fe2+0.39Fe3+0.45Al0.30Ti0.06)Σ=2.68[Si2.98Al1.02]O10((OH)1.77F0.23); Phl-1M: (K0.85Ca0.01)(Mg1.43Fe2+0.45Fe3+0.54Al0.21Ti0.06)Σ=2.69[Si2.88Al1.12]O10((OH)1.99F0.01)). This assemblage is rarely observed in UHP eclogite-bearing rocks, and has never been reported before in the Sulu UHP metamorphic terrane. A detailed crystal-chemical characterisation of Phe-3T, Phl-3T and Phl-1M allowed the development of a thermodynamic model that estimates the P-T conditions of formation of such an assemblage and helps to understand the relationship between mica polytypes and a quartz dominated (silica oversaturated) system, which characterised the Sulu vein. Phe-3T varies in composition upon approaching Phl-3T/1M, showing a decrease of Si and Al and an increase of Fe and Mg contents. Observed phlogopites cannot be ascribed to bare exsolving processes, and require the involvement of a non-isochemical reaction, dominated by exsolution (quasi-exsolution process) in combination with a contribution from an “external chemical supplier” (most probably provided by circulating fluids). Mass balance calculations between the mineralogical assemblage of Sulu vein and the solute components of alkali-alumino-silicate high pressure fluids demonstrate that a silicic-type major element composition accounts for a phengite-quartz based rock. The occurrence of phlogopite micas can be explained as an effect of disproportion in combination with supply components, i.e. Mg, Al and K, from alkali-alumino-silicate high pressure fluids. On the basis of energy modelling of the reaction process from phengite to phlogopite in presence of quartz and a matter exchanger, we determined that such a transformation is weakly dependent on T over the 500–930 °C thermal range. The intersection of the calculated P-T assemblage equilibrium curve with the country rock P-T metamorphic path occurs at P ~ 2.4 ± 0.2 GPa and T ~ 700 °C, thus reflecting an early stage of exhumation, close to the metamorphic peak of the Sulu UHP terrane

Shades of black: Production technology of the black slip ware from Barikot, north-western Pakistan

The archaeometric analysis of a set of potsherds of black slip ware found at the site of Barikot (SwatValley, north-western Pakistan), dated between the Indo-Greek and the Kushan phases (middle 2nd century BCE–middle 2nd century CE), was addressed to define the provenance of this pottery and to constrain the production technology of both the ceramic body and the black external slip in terms of raw materials used and firing conditions. A multidisciplinary approach, consisting in the petrographic, mineralogical, chemical and spectroscopic (Mössbauer) analyses, was used to define possible differences between sherds archaeologically classified as grey ware, northern black polished ware and black gloss ware. The composition of this ceramic class resulted quite homogeneous, indicating the use of similar clay materials (low-calcium and both potassium- and iron-rich) and preparation procedures, with one exception represented by the only black gloss ware analysed. When samples are considered in diachronic terms, a progressive change can be observed, mainly related to a progressive intensification of the clay levigation. The petrographic nature of medium and fine sand-sized inclusions indicates that the pottery was produced within the region and possibly in Barikot. As for its production technology, the miner-alogical associations indicate that the firing temperature was in the thermal interval between 650◦C and950◦C, while the presence of spinel-like minerals, maghemite and wustite suggests that the firing was in reducing conditions. Important differences were observed in terms of paste and slip preparation for the black gloss ware with respect to the grey ware and northern black polished ware, which were interpreted also under an archaeological viewpoint

Fe3+ reduction during biotite melting in graphitic metapelites: another origin of CO2 in granulites

The Fe(3+)/ Fe(tot) of all Fe-bearing minerals has been analysed by Mossbauer spectroscopy in a suite of biotite-rich to biotite-free graphitic metapelite xenoliths, proxies of an amphibolite-granulite transition through progressive biotite melting. Biotite contains 9 to 16% Fe(3+)/Fe(tot), whereas garnet, cordierite and ilmenite are virtually Fe(3+) - free (0 - 1% Fe(3+)/Fe(tot)) in all samples, regardless of biotite presence. Under relatively reducing conditions (graphite-bearing assemblages), biotite is the only carrier of Fe(3+) during high-temperature metamorphism; therefore, its disappearance by melting represents an important event of iron reduction during granulite formation, because haplogranitic melts usually incorporate small amounts of ferric iron. Iron reduction is accompanied by the oxidation of carbon and the production of CO(2), according to the redox reaction: 2Fe(2)O(3)((Bt)) 3+ C((Gr)) double right arrow 4FeO((Crd, Grt, Ilm, Opx)) + CO(2)((fluid, melt, Crd)). Depending on the nature of the peritectic Fe-Mg mineral produced ( garnet, cordierite, orthopyroxene), the CO(2) can either be present as a free fluid component, or be completely stored within melt and cordierite. The oxidation of graphite by iron reduction can account for the in situ generation of CO(2), implying a consequential rather than causal role of CO(2) in some granulites and migmatites. This genetic model is relevant to graphitic rocks more generally and may explain why CO(2) is present in some granulites although it is not required for their formation