Alpine tectonic evolution and thermal water circulations of the Argentera Massif (South-Western Alps)

Three groups of thermal springs with temperatures close to 70 °c discharge both in the core (at bagni di Vinadio and terme di Valdieri) and on the external margin (at Berthemont-Les-Bains) of the Argentera Massif. Detailed structural field analysis carried out on the hydrothermal sites allows us to delineate both a model of Alpine tectonic evolution of the Argentera Massif and the patterns of hydrothermal circulation that were active during its final exhumation. the observed fault rock assemblages provide information relative to deformation that occurred in viscous, frictional-to-viscous and frictional crustal regimes. During the Early Miocene, the bersezio Fault Zone and the Fremamorta shear Zone, two main mylonitic shear zones, mainly accommodated regional transpression and provided pathways for fluid flow promoting mineral reactions in greenschist facies. During the Late Miocene-Early Pliocene, frictional-to-viscous deformation affected the massif, which underwent predominant transpression in the internal sectors and extension on the external margin. During the Plio-Pleistocene, deformation in frictional condition accompanied the final exhumation of the massif in a transpressive regime and resulted in the development of the NW-SE striking cataclastic zones. The hydraulic properties of these structures mainly influence the patterns of the active thermal circulations and the localization of the recharge and discharge zones. At Berthemont these faults represent conduits, whereas at Vinadio and Valdieri they form complex systems of conduits and barriers. In these two latter sites, the cataclastic faults compose flower structures that constrain laterally the thermal fluid flows while intensely fractured granites sited at depth constitute a highly-transmissive geothermal reservoir. Less permeable migmatitic gneisses overlaying the granites prevent a massive infiltration of the cold fluids at depth. This context favours within the high-ermeability fractures granites the development of buoyancy-driven flows which combined with topographically-driven flows, provided the conditions for the pflow of the high-temperature waters. © Birkhäuser Verlag, Basel, 2009

A 30-years Review on Pharmacokinetics of Antibiotics: Is the Right Time for Pharmacogenetics?

Drug bioavailability may vary greatly amongst individuals, affecting both efficacy and toxicity: in humans, genetic variations account for a relevant proportion of such variability. In the last decade the use of pharmacogenetics in clinical practice, as a tool to individualize treatment, has shown a different degree of diffusion in various clinical fields. In the field of infectious diseases, several studies identified a great number of associations between host genetic polymor-phisms and responses to antiretroviral therapy. For example, in patients treated with abacavir the screening for HLA-B*5701 before starting treatment is routine clinical practice and standard of care for all patients; efavirenz plasma levels are influenced by single nucleotide polymorphism (SNP) CYP2B6-516G> T (rs3745274). Regarding antibiotics, many studies investigated drug transporters involved in antibiotic bioavailability, especially for fluoroquinolones, cephalosporins, and antituberculars. To date, few data are available about pharmacogenetics of recently developed antibiotics such as tigecycline, daptomycin or linezolid. Considering the effect of SNPs in gene coding for proteins involved in antibiotics bioavailability, few data have been published. Increasing knowledge in the field of antibiotic pharmacogenetics could be useful to explain the high drug inter-patients variability and to individualize therapy. In this paper we reported an overview of pharmacokinetics, pharmacodynamics, and pharmacogenetics of antibiotics to underline the importance of an integrated approach in choosing the right dosage in clinical practice

Plasma concentrations of boosted and unboosted atazanavir are predicted by 63396C>T SNP in the PXR gene

Purpose of the study Atazanavir (ATV) is administered at the usual adult dose of 300 mg with 100 mg of ritonavir (RTV) once a day (boosted). However, 400 mg once a day (unboosted) is also used in some settings. ATV plasma concentrations are influenced by efflux transporters, influx transporters and metabolism enzymes. The expression of many of these proteins is regulated by nuclear receptors such as PXR. Recently polymorphisms in the regulatory region of the PXR gene have been reported to influence its expression and the activity of downstream genes, such as CYP3A4 and ABCB1. The aim of this study was to investigate whether polymorphisms in PXR influence trough concentrations (Ctrough) of boosted or unboosted ATV