Real-Life Peak and Trough Dabigatran Plasma Measurements over Time in Hospitalized Geriatric Patients with Atrial Fibrillation.

BACKGROUND: Few geriatric patients were included in studies on direct oral anticoagulants and data on dabigatran concentration and safety are needed in this population. Our objectives were to evaluate peak and trough dabigatran plasma concentrations over time in a geriatric population and to identify factors associated with dabigatran plasma concentrations and to assess the relationship with bleeding events. METHODS: Peak and trough dabigatran plasma concentration were performed 4,8,15,30,45 days after inception of dabigatran treatment in 68 consecutive patients ≥75 years old hospitalized in a geriatric hospital with atrial fibrillation. Bleeding events were monitored for 1 year. RESULTS: Mean age was 85.8(5.1) years old and 76.5% were women. Overall, 541 dabigatran plasma measurements (270 peak, 271 trough) were performed. Mean dabigatran concentrations of the 5 sequential measurements ranged 106-146ng/mL for peak and 66-84ng/mL for trough. Renal failure was associated with high peak and trough dabigatran concentration. Inter- and intra-individual coefficients of variation were 59.5% and 44.7% for peak and 74.5% and 44.6% for trough. Participants in the lower two tertiles of dabigatran concentration at day 8 (D8) remained below the 90th percentile (243.9ng/ml) on the next measurements. Bleeding events were associated with high trough dabigatran concentrations. Trough dabigatran concentration at D8>243.9ng/mL significantly predicted bleeding. CONCLUSION: In this geriatric population, renal function and low albumin were associated with dabigatran concentrations. Despite large variability, participants in the lower two tertiles of dabigatran concentration at D8 remained below the 90th percentile on the following measurements. D8 dabigatran trough concentration≥243.9ng/mL identified patients at risk of bleeding.

Static and dynamic electronic characterization of organic monolayers grafted on a silicon surface.

Organic layers chemically grafted on silicon offer excellent interfaces that may open up the way for new organic-inorganic hybrid nanoelectronic devices. However, technological achievements rely on the precise electronic characterization of such organic layers. We have prepared ordered grafted organic monolayers (GOMs) on Si(111), sometimes termed self-assembled monolayers (SAMs), by a hydrosilylation reaction with either a 7-carbon or an 11-carbon alkyl chain, with further modification to obtain amine-terminated surfaces. X-ray photoelectron spectroscopy (XPS) is used to determine the band bending (∼ 0.3 eV), and ultraviolet photoelectron spectroscopy (UPS) to measure the work function (∼ 3.4 eV) and the HOMO edge. Scanning tunneling microscopy (STM) confirms that the GOM surface is clean and smooth. Finally, conductive AFM is used to measure electron transport through the monolayer and to identify transition between the tunneling and the field emission regimes. These organic monolayers offer a promising alternative to silicon dioxide thin films for fabricating metal-insulator-semiconductor (MIS) junctions. We show that gold nanoparticles can be covalently attached to mimic metallic nano-electrodes and that the electrical quality of the GOMs is completely preserved in the process.

Controlling the reproducibility of Coulomb blockade phenomena for gold nanoparticles on an organic monolayer/silicon system.

Two types of highly ordered organic layers were prepared on silicon modified with an amine termination for binding gold nanoparticles (AuNPs). These two grafted organic monolayers (GOMs), consisting of alkyl chains with seven or 11 carbon atoms, were grafted on oxide-free Si(111) surfaces as tunnel barriers between the silicon electrode and the AuNPs. Three kinds of colloidal AuNPs were prepared by reducing HAuCl4 with three different reactants: citrate (Turkevich synthesis, diameter ∼16 nm), ascorbic acid (diameter ∼9 nm), or NaBH4 (Natan synthesis, diameter ∼7 nm). Scanning tunnel spectroscopy (STS) was performed in a UHV STM at 40 K, and Coulomb blockade behaviour was observed. The reproducibility of the Coulomb behavior was analysed as a function of several chemical and physical parameters: size, crystallinity of the AuNPs, influence of surrounding surfactant molecules, and quality of the GOM/Si interface (degree of oxidation after the full processing). Samples were characterized with scanning tunneling microscope, STS, atomic force microscope, Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy (XPS), and high resolution transmission electronic microscope. We show that the reproducibility in observing Coulomb behavior can be as high as ∼80% with the Natan synthesis of AuNPs and GOMs with short alkyl chains.

In vitro effect of organic and inorganic mercury on the serotonergic system.

Interactions of organic (methyl mercury) and mineral (acetate, chloride, nitrate: Hg2+) mercury salts with the serotonergic systems were studied in vitro using synaptosomal fractions prepared from rat brain cortex preloaded with [3H]5-HT. In the absence of calcium, mercury salts induced a spontaneous release of the amine corresponding to a total depletion of the synaptosomal content. EC50 for the organic and mineral forms of the ion were 66 +/- 2 microM and 107 +/- 16 microM respectively. In the presence of calcium (2.4 mM) a similar pattern of release was observed except that an additional release was induced by mineral mercury at low concentration (EC50 = 8.4 +/- 1.3 microM) which corresponded to a maximal release of 18.6 +/- 3.5% of the synaptosomal content. Therefore, the latter release appears calcium-dependent. Parallelly, the effects of mercury salts have been examined on the binding of [3H]5-HT to its high affinity 5-HT1 sites; organic and mineral mercury inhibited the binding with IC50 of 27.8 +/- 3.2 microM respectively. These results show that mercury ions interact with the serotonergic system by different mechanisms depending on their concentrations and their ionic forms.

The effects of inorganic lead on the spontaneous and potassium-evoked release of 3H-5-HT from rat cortical synaptosome interaction with calcium.

Interaction of lead with the serotonergic system has been studied in vitro in rat brain synaptosomal fraction prepared from cortical tissue. Synaptosomes were loaded with 3H-5-HT and spontaneous and K+-evoked release of the amine was examined in the presence and the absence of calcium. It was shown that lead itself induced the release of 3H-5-HT (EC50 = 27 microM). This effect decreased (40%) in the presence of calcium without modification of the EC50. Moreover, lead markedly inhibited the K+-evoked release of 3H-5-HT observed in the presence of calcium. This effect was obtained either in the presence of lead or using synaptosomes pretreated with lead and washed. These results indicate that lead interferes with neuronal 5-HT release by mechanism(s) involving calcium.

Evaluation of the cutaneous-irritation potential of 56 compounds.

The primary cutaneous irritation of 56 chemicals was tested in the rabbit using three different procedures. The three protocols selected for the tests were the method published by the French authorities for the testing of cosmetics and toiletries (Journal Officiel 21 April 1973, p. 3862; ibid 5 June 1973, p. 3953) and the methods proposed for the testing of chemicals by the Association Française de Normalisation (AFNOR) and, in 1979, by the Organisation for Economic Co-operation and Development. The results of the three sets of tests were compared and the effects of differences in procedure and numbers of animals were studied, together with the possible relation between irritancy and the pH of the test material. It was concluded that the AFNOR protocol best met the requirements for such tests and that gloves should be worn for the handling of all substances classified as moderately or severely irritant on that scale.

Evaluation of the ocular-irritation potential of 56 compounds.

The ocular irritancy of 56 chemicals was tested in the rabbit eye, with and without rinsing, using a procedure that complied with the main requirements of three protocols, namely those proposed by the Association Française de Normalisation (AFNOR) in 1982 and by the Organisation for Economic Co-operation and Development in 1979 for the testing of chemicals and that published by the French authorities (Journal Officiel 21 April 1971, p. 3862; ibid 5 June 1973, p. 3953) for the testing of cosmetics and toiletries. The results obtained were used to establish the extent to which the assessment of a chemical's irritation potential was affected by the differences between the three protocols in respect of the observation times prescribed, the inclusion and timing of rinsing, the number of animals used and the interpretation procedure. Conclusions were also drawn about the influence of the physical state and pH of a material on its potential irritancy and about the level of irritancy that necessitates the use of eye protection.