Toward a clinical practice guide in pharmacogenomics testing for functional polymorphisms of drug-metabolizing enzymes. Gene/drug pairs and barriers perceived in Spain

The development of clinica lpractice recommendations or guidelines for the clinical use of biomarkers is an issue of great importance withr regard to adverse drug reactions.The poten-tial of pharmacogenomicbiomarkers has been extensively investigated in recent years.However,several barriers to implementing the use of pharmacogenomics testing exist.We conducted a survey among members of the Spanish Societies of Pharmacology and Clinical Pharmacology to obtain information about the perception of such barriers and to compare the perceptions of participants about the relative importance of majorgene/drug pairs.Of 11 potential barriers,the highest importance was attributed to lack of institutional support for pharmacogenomic stesting,and to the issues related to the lack of guidelines.Of the proposed gene/drug pairs the highest importance was assigned to HLA-B/abacavir, UGT1A1/irinotecan, and CYP2D6/tamoxifen.In this perspective article,we compare the relative importance of 29 gene/drugpairs in the Spanish study with that of the same pairs in the American Society for Clinical Pharmacology and Therapeutic sstudy,and we provide suggestions and areas of focus to develop a guide for clinical practice in pharmacogenomics testingThe work in the author’s laboratory is financed by Grants PS09/00943, PS09/00469, RETICS RIRAAF RD07/0064/0016, and CIBERehd from Instituto de Salud CarlosIII,Madrid, Spain, and by Grants GR10068 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Unio

Nickel and cobalt adsorption on hydroxyapatite: a study for the de-metalation of electronic industrial wastewaters

In the present study, the Ni(II) and Co(II) adsorption efficiency and selectivity, as well adsorption mechanisms on a stoichiometric hydroxyapatite (HAP) surface have been investigated. Characterization studies (N-2 adsorption/desorption and X-ray powder diffraction (XRPD) analyses) and adsorption tests under various operative conditions provided detailed information about the use of HAP in the de-metalation of wastewaters containing Ni and Co as polluted metal species. The sorption capacity of HAP has been evaluated by static batch adsorption tests varying initial concentration of Ni(II) and Co(II) species (from ca. 0.25 to 4.3mM), contact time (from 15min to 24h), and pH (from 4 to 9) operative parameters. Proposed mechanisms of adsorption of Ni(II) and Co(II) on HAP surface are ion-exchange and surface complexation; a partial contribution of chemical precipitation from bulk solution should be considered at pH 9. In addition, adsorption isotherms of Ni(II) and Co(II) on HAP have been collected at 30 degrees C and pH 4 and modeled by employing different equations. The maximum sorption capacities have been quantified as 0.317mmolgHAP-1 (18.6mggHAP-1) and 0.382mmolgHAP-1 (22.5mggHAP-1) for Ni(II) and Co(II), respectively. Selectivity to Co and Ni in the adsorption process on HAP has also been investigated; HAP has higher affinity towards Co than Ni species (Co:Ni=2.5:1, molar ratio)

Property and activity of molybdates dispersed on silica obtained from various synthetic procedures

The synthesis and characterization of several dispersed molybdena catalysts on silica support (MoO3-SiO2) prepared from a variety of precursors (Mo(VI)-acetylacetonate, oxo-peroxo Mo-species, hydrated ammonium heptamolybdate) and preparation methods (deposition of the Mo-phase on finite SiO2 support by aqueous and methanol impregnations, by adsorption, by oxo-peroxo route-like, and by one-step synthesis of MoO3-SiO2 system with molecular precursors) are presented. The molybdena concentration on silica was comprised in a large interval (1.5 - 14 wt%) depending on the preparation method which governed the Mo-loading on silica. Convenient comparisons among samples at similar Mo-concentration have been made discussing the morphologic-structural (XRD, XPS, UV-vis-DRS, and N2-adsorption) and physicochemical (TG-DTG, TPR, and n-butylamine-TPD) sample properties. Polymeric octahedral polymolybdate aggregates predominated in the samples prepared by aqueous and methanol impregnations, which were at high Mo-concentration. On the contrary, isolated Mo(VI) species in distorted Td symmetry predominated in the sample prepared by adsorption which was at very low Mo-concentration. The sample acidity was composed of a weak acidy site population, associated with the silica support, and a strong acid site population associated with the Mo-dispersed phase. Oxidation tests of formaldehyde, an oxygen-containing VOC (Volatile Organic Compound), were performed to determine the prevalent redox or acidic function of the Mo-species at the surface of the catalysts

Tuning the sorption ability of hydroxyapatite/carbon composites for the simultaneous remediation of wastewaters containing organic-inorganic pollutants

In this paper, we report on the rational design, synthesis, characterization, and application of eco-friendly hydroxyapatite/carbon (HAP/C) composites as effective sorbents for the simultaneous remediation of organic-inorganic pollution in wastewaters. Carbon content in composites ranged from ca. 4 to ca. 20 wt%. Structural and morphological features of the composites were studied by N2 adsorption/desorption analyses, electron microscopy (TEM and HAADF-STEM/EDX) and X-ray powder diffraction (XRPD). These features were correlated with the composition and the exposure of surface functional groups. Surface acid-base groups were assessed by liquid-solid acid/base titrations and results depended on the composition ratio of the two components. Batch adsorption tests, performed with various initial concentrations of pollutant species and dosages, proved that composites merged the sorption properties of the two moieties, being able to simultaneously adsorb organic (methylene blue) and inorganic (Cu(II) and Ni(II)) pollutants. On the optimal carbonaceous scaffold content (ca. 8 wt% carbon), kinetic tests revealed that this composite could almost completely remove high concentrations of co-present pollutants, namely, Cu(II), Ni(II), (300 ppm) and methylene blue (250 ppm) in ca. 1 h, with sorbent dosage of 10 g L−1. In addition, leaching tests proved the permanent retention of the hazardous species on the composites

Influence of the Nb/P ratio of acidic Nb-P-Si oxides on surface and catalytic properties

In this work, two acidic Nb-P-Si mixed oxide gel-derived materials characterized by Nb/P molar ratios equal to 2 (5Nb2.5 P) and 1 (2.5NbP) were investigated for their surface and bulk properties in relation with the catalytic performances in the fructose dehydration reaction. The structural characteristics of the studied samples and the changes occurring after water treatment and after reaction were investigated by 29Si and 31P solid state nuclear magnetic resonance (MAS-NMR) and X-ray photoelectron (XPS) spectroscopies, while the characterization of their acidic properties was performed by base (2-phenylethylamine) adsorption in liquid phase. MAS-NMR showed that the phosphorus remains firmly anchored into the siloxane matrix after exposure to cold water for 5Nb2.5 P sample and XPS confirmed the homogeneity of the sample composition. Both samples exhibited good intrinsic acidity and maintained significant effective acidity in polar-protic liquids; 2.5NbP manifested a double amount of acid sites compared to 5Nb2.5 P, when 2-phenylethylamine is used as probe. Fructose dehydration to 5-(hydroxymethyl)furfural (HMF) on the two gel-derived catalysts was performed in water and in water-isopropanol solution under mild conditions (130 °C) working in a recirculation reaction line comprising a tubular catalytic reactor. In water-isopropanol solution, the samples displayed good performances, as expected thanks to the lively effective acidity. Around 45-50% fructose conversion was attained on both samples, with selectivity to HMF equal to about 50% on 2.5NbP gel-derived catalyst. Recycling tests showed satisfactorily stable activity during three consecutive runs

Tuning the Cu/SiO2 wettability features for bio-derived platform molecules valorization

A simple organosilane-grafting protocol has been used for the preparation of a copper heterogeneous catalyst with tunable wettability properties. A series of Cu/SiO2 trietoxyoctylsilane-modified systems with gradually reduced alcoholphilicity has been used in the hydrogenation of the platform molecule gamma-valerolactone into 1,4-pentandiol, a valuable biobased monomer. The surface modification obtained with the proposed procedure allows to significantly increase the selectivity (99%) of the process and therefore the yield (80%) in the desired diol. Several characterization techniques (static contact angle, ATR, CP-MAS solid state NMR, pyridine and ammonia adsorption) put in light the modification of the surface while preserving the hydrogenation activity of the metallic phase. The results obtained show the opportunity given by this simple catalytic system in combining the activity of the copper phase and the modified polarity of the surface

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate

Spontaneous chromosomal instability in peripheral blood lymphocytes from two molecularly confirmed italian patients with hereditary fibrosis poikiloderma: Insights into cancer predisposition

Two Italian patients with the initial clinical diagnosis of Rothmund-Thomson syndrome were negative for RECQL4 mutations but showed in peripheral blood cells a spontaneous chromosomal instability significantly higher than controls. Revisiting after time their clinical phenotype, the suggestive matching with the autosomal dominant syndrome Poikiloderma, Hereditary Fibrosing with Tendon Contracture, Myopathy and Pulmonary fibrosis (POIKTMP) was confirmed by identification of the c.1879A>G (p.Arg627Gly) alteration in FAM111B. We compare the overall clinical signs of our patients with those of reported carriers of the same mutation and present the up-to-date mutational repertoire of FAM111B and the related phenotypic spectrum. Our snapshot highlights the age-dependent clinical expressivity of POIKTMP and the need to follow-up patients to monitor the multi-tissue impairment caused by FAM111B alterations. We link our chromosomal instability data to the role of FAM111B in cancer predisposition, pointed out by its implication in DNA-repair pathways and the outcome of pancreatic cancer in 2 out of 17 adult POIKTMP patients. The chromosomal instability herein highlighted well connects POIKTMP to cancer-predisposing syndromes, such as Rothmund-Thomson which represents the first hereditary poikiloderma entering in differential diagnosis with POIKTMP