A sensitive liquid chromatographic assay for plasma aspirin and salicylate concentrations after low doses of aspirin

An original, highly sensitive and specific high performance liquid chromatographic method has been developed for the measurement of aspirin and salicylate in plasma. Minimum concentrations of 10 xg/L (aspirin) and 0.5 mg/L (salicylate) can be measured using 1 ml of plasma. After collection, plasma is first treated with physostigmine sulfate to inhibit enzymatic hydrolysis of aspirin to salicylate. Maximal recovery is achieved using an acid extraction into anhydrous diethyl ether with a subsequent drying-down step in an iced water bath. Aspirin and salicylate are separated by elution with a mixture of methanol, 1-butanol, orthophosphoric acid, and water on a reversed-phase octadecyl silane column at 47°C and detected at 234 nm by ultraviolet absorption. Quantitation is achieved using the peak height ratio of aspirin and salicylate to internal standard (m-anisic acid). The assay has been used for the study of simultaneous aspirin and salicylate pharmacokinetics after a single oral dose of 100 mg soluble glycinated aspirin for platelet antiaggregatory therapy in six subjects, one of whom was also studied after receiving a 600 mg dose

RE-ORGANIZING THE PHARMACEUTICAL SUPPLY CHAIN DOWNSTREAM: IMPLEMENTATION A NEW PHARMACY

International audienceCroix-Rousse hospital launched a variety of projects on how best to organize and/or re-organize the flow of pharmaceutical products from the suppliers to there cares units. Among these projects was the reconfiguration and arrangement of the establishment's pharmacy. In this article, an analyse of the pharmaceutical products consumption in the hospital, which identify the scale and the activities required across supply chain, is presented, which is followed by an explanation of the process modelling in order to identify the best practices. Finally, the different reengineering solutions as well as the method of classification and evaluation of these solutions are developed

A multichronometer approach for unravelling the exhumation history of an active orogen: the example of the Northern Apennines (Italy)

In active orogens spatial variations in exhumation rates are reflected by different cooling ages of single thermochronometers across the range, whereas temporal variations in exhumation rate are recorded in the age-elevation relationship (AER) of vertical transects. To a first order, slopes of the AER for each thermochronometer record the vertical velocity of samples relative to the relevant closure isotherm. Here we focus on the Northern Apennine chain, a tectonically active bimodal orogen characterized by paired contractional and extensional domains. We used fission-track and (U-Th)/He analysis on apatite to study vertical profiles sampled in the foredeep turbidite deposits of Oligocene-Miocene age at Mt. Cimone, Mt. Falterona and the Pratomagno ridge. The Mt. Falterona profile has been extended by using some samples from a nearby exploration well. The Pratomagno and Falterona profiles yield comparable exhumation rates, both showing an increase from values lower than 0.5 km/m.y. to values higher than 1 km/m.y. Maximum rates were reached at 3-4 Ma with subsequent exhumation apparently decreasing to rates lower than 1 km/m.y. The Cimone profile shows a significantly different exhumation history, with rates in the range of 0.3-0.4 km/m.y. at least until 3 Ma, followed by an apparent moderate increase in rates. These different exhumation histories can be explained in the light of the different structural setting of the sampled profiles. While the Pratomagno and Falterona profiles are located along the ridges of two of the Plio-Pleistocene intramontane basins that characterize the hinterland of the chain, the Cimone profile is close to the watershed and is not noticeably affected by extensional tectonics. Therefore, we propose that extensional tectonics was the likely cause of the pulse of the exhumation rates at 3-4 Ma detected in the Pratomagno and Falterona profiles. At present, a complete data set is available only for these three vertical transects, but we argue that an increase of exhumation rates is recorded in the AER from the ridges bordering all the intramontane basins and it is linked to the extensional tectonics of the basins themselves

Exhumation of the Northern Apennines core: new thermochronological data from the Alpi Apuane

The metamorphic core of the Northern Apennines is exposed in the Alpi Apuane which form a topographic high located to the west of the axial zone of the range. The metamorphic rocks of the Alpi Apuane are bordered by a tectonic contact which separates a footwall affected by maximum P and T conditions ranging between 0.6-0.8 Gpa and 420-500\ub0C (Massa unit) and 0.4-0.6 Gpa and 350-420\ub0C (Apuane unit), from a hangingwall of unmetamorphosed Macigno sandstone. The metamorphic rocks of the Alpi Apuane have long been interpreted as an example of tectonic exhumation formed during active convergence in the Apennines. Here we report 53 new zircon and apatite (U-Th)/He (ZHe and AHe, respectively) ages on rocks from the Alpi Apuane and the Macigno sandstones to provide a much more detailed understanding of when the Apuane fault was active and how much section was cut out. The ZHe and AHe systems provide cooling ages corresponding to closure temperatures of 180\ub0C and 70\ub0C, respectively. ZHe ages in the crystalline core of the Alpi Apuane are all reset and vary around an average of 5.7 Ma (std deviation 1.2 Ma). In the hangingwall, the Macigno sandstones have ZHe ages which vary between 47.1 and 9.3 Ma, indicating partial resetting. This result indicates that the hangingwall saw a temperature no greater than 160-190 \ub0C, followed by cooling around 9 Ma. AHe ages in the Alpi Apuane and in the Macigno sandstone show no differences and vary around a mean of 4.9 Ma (std deviation 1.2 Ma). Our data clearly constrain different exhumation paths for the Alpi Apuane and the Macigno sandtones between 180\ub0C and 70\ub0C, whereas their paths are similar from 70\ub0C to the surface. The different thermal histories from 180\ub0C to 70\ub0C suggest that between 6 and 4 Ma, 4\ub11 km have been removed along the contact between the Macigno sandstones and the Alpi Apuane. The amount of crustal section removed has been determined assuming a geothermal gradient of 25\ub1\ub0C/km, and a cooling age of 8\ub11 Ma at 110\ub0C for the Macigno sandstones. The geometry of the major Apuane boundary and the different exhumation times suggest that extension under brittle conditions played a major role in the exhumation of the metamorphic core of the Apennines

Thermochronologic evidence for the exhumational history of the Alpi Apuane metamorphic core complex, northern Apennines, Italy

The Apennine Range is a young convergent orogen that formed over a retreating subduction zone. The Alpi Apuane massif in the northern Apennines exposes synorogenic metamorphic rocks, and provides information about exhumation processes associated with accretion and retreat. (U-Th)/He and fission-track ages on zircon and apatite are used to resolve exhumational histories for the Apuane metamorphic rocks and the structurally overlying, very low grade Macigno Formation. Stratigraphic, metamorphic, and thermochronologic data indicate that the Apuane rocks were structurally buried to 15–30 km and 400C at about 20 Ma. Exhumation to 240C and 9 km depth (below sea level) occurred at 10–13 Ma. By 5 Ma the Apuane rocks were exhumed to 70C and 2 km. The Macigno and associated Tuscan nappe were also structurally buried and the Macigno reached its maximum depth of 7 km at 15 to 20 Ma. Stratigraphic evidence indicates that the Apennine wedge was submarine at this time. Thus we infer that initial exhumation of the Apuane was coeval with tectonic thickening higher in the wedge, as indicated by synchronous structural burial of the Tuscan nappe. From 6 to 4 Ma, thinning at shallow depth is indicated by continued differential exhumation between the Apuane and the Tuscan nappe at high rates. After 4 Ma, differential exhumation ceased and the Apuane and the Tuscan nappe were exhumed at similar rates (0.8 km/Ma), which we attribute to erosion of the Apennines, following their emergence above sea level