Simultaneous Determination of Human Plasma Levels of Citalopram, Paroxetine, Sertraline, and Their Metabolites by Gas Chromatography—Mass Spectrometry

A gas chromatography—mass spectrometry method is presented which allows the simultaneous determination of the plasma concentrations of the selective serotonin reuptake inhibitors citalopram, paroxetine, sertraline, and their pharmacologically active N-demethylated metabolites (desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline) after derivatization with the reagent N-methyl-bis(trifluoroacetamide). No interferences from endogenous compounds are observed following the extraction of plasma samples from six different human subjects. The standard curves are linear over a working range of 10-500 ng/mL for citalopram, 10-300 ng/mL for desmethylcitalopram, 5-60 ng/mL for didesmethylcitalopram, 20-400 ng/mL for sertraline and desmethylsertraline, and 10-200 ng/mL for paroxetine. Recoveries measured at three concentrations range from 81 to 118% for the tertiary amines (citalopram and the internal standard methylmaprotiline), 73 to 95% for the secondary amines (desmethylcitalopram, paroxetine and sertraline), and 39 to 66% for the primary amines (didesmethylcitalopram and desmethylsertraline). Intra- and interday coefficients of variation determined at three concentrations range from 3 to 11 % for citalopram and its metabolites, 4 to 15% for paroxetine, and 5 to 13% for sertraline and desmethylsertraline. The limits of quantitation of the method are 2 ng/mL for citalopram and paroxetine, 1 ng/mL for sertraline, and 0.5 ng/mL for desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline. No interferences are noted from 20 other psychotropic drugs. This sensitive and specific method can be used for single-dose pharmacokinetics. It is also useful for therapeutic drug monitoring of these three drugs and could possibly be adapted for the quantitation of the two other selective serotonin reuptake inhibitors on the market, namely fluoxetine and fluvoxamin

The water relations of two tropical rainforest species (Virola surinamensis and Eperua falcata): Is Virola unusual as previously reported?

HYDROInternational audienceThe objective of this study was to examine the water relations and hydraulic architecture and vulnerability to cavitation in Virola surinamensis and V. michelii and to compare to similar measurements in Eperua falcata. In several previous reports Virola was seen to have a rather narrow range of xylem pressure potentials (Ψx) near zero in the course of a wet-season day while having water fluxes quite close to Eperua. We tested the hypothesis that the narrow range of Ψx might be consistent with very high hydraulic conductivities of stems, roots and shoots and high vulnerability to cavitation in Virola compared to Eperua. When this hypothesis proved false we concluded that the previous determinations of Ψx might be wrong in Virola due to latex. We re-examined the determination of Ψx in Virola by the pressure chamber technique and compared results to determination of Ψleaf by the thermocouple psychrometer technique and found that the likely range of Ψx are more negative than previously reported. Problems concerning the determination of Ψx in species with latex are discussed

Natural history and mid-term prognosis of severe tricuspid regurgitation: A cohort study.

OBJECTIVES The objective of this study was to characterize a population of patients with severe tricuspid regurgitation (TR) evaluated at a tertiary care center, assess mid-term clinical outcomes, and identify prognostic factors. BACKGROUND The impact of TR on morbidity and mortality is increasingly recognized. Clinical characteristics and long-term outcomes of patients suffering from TR remain unclear. METHODS This is a retrospective observational single-center study from a tertiary care hospital including patients with echocardiographic diagnosis of severe TR between January 2017 and December 2018. We used the Kaplan-Meier method to estimate survival for up to 4 years. After excluding patients with tricuspid valve (TV) intervention and surgery during follow-up, a multivariate analysis was performed to assess predictors of 2-year mortality using the Cox regression model. RESULTS A total of 278 patients (mean age 74.9 ± 13.7 years, 47.8% female) with severe TR were included in the study. The majority (83.1%; n = 231) had secondary TR. Comorbidities such as atrial fibrillation (AFib) (68.0%; n = 189), severe renal failure (44.2%; n = 123), pulmonary hypertension (PHT) (80.9%; n = 225), and right ventricular (RV) dysfunction (59.7%; n = 166) were highly prevalent. More than half of patients with a cardiac implantable electronic device (CIED) (54.3%; n = 44) showed echocardiographic signs of lead-leaflet interaction causing or contributing to TR. The estimated 2- and 4-year all-cause mortality was 50 and 69%, respectively. Using multivariate analysis, age, severe renal failure, heart failure with reduced ejection fraction (HFrEF), and vena contracta width ≥14 mm were identified as predictors of 2-year mortality. Nine percent (n = 25) of the study cohort underwent transcatheter or surgical treatment for TR during follow-up. CONCLUSION Our study shows the high burden of morbidity and the dismal survival of patients with severe TR. It also highlights the extent of the therapeutic need, since the vast majority of patients were left untreated. Additionally, CIED RV lead-associated TR was prevalent suggesting a need for more attention in clinical routine and research

Effect of salinity on water relations of wild barley plants differing in salt tolerance

Root hydraulic conductivity was decreased by salinity in barley plants in parallel with slower transpiration rates and a down-regulation of aquaporin expression in the roots. The effects were larger and faster in a more salinity-tolerant line

Crack-Like Processes Governing the Onset of Frictional Slip

We perform real-time measurements of the net contact area between two blocks of like material at the onset of frictional slip. We show that the process of interface detachment, which immediately precedes the inception of frictional sliding, is governed by three different types of detachment fronts. These crack-like detachment fronts differ by both their propagation velocities and by the amount of net contact surface reduction caused by their passage. The most rapid fronts propagate at intersonic velocities but generate a negligible reduction in contact area across the interface. Sub-Rayleigh fronts are crack-like modes which propagate at velocities up to the Rayleigh wave speed, VR, and give rise to an approximate 10% reduction in net contact area. The most efficient contact area reduction (~20%) is precipitated by the passage of slow detachment fronts. These fronts propagate at anomalously slow velocities, which are over an order of magnitude lower than VR yet orders of magnitude higher than other characteristic velocity scales such as either slip or loading velocities. Slow fronts are generated, in conjunction with intersonic fronts, by the sudden arrest of sub-Rayleigh fronts. No overall sliding of the interface occurs until either of the slower two fronts traverses the entire interface, and motion at the leading edge of the interface is initiated. Slip at the trailing edge of the interface accompanies the motion of both the slow and sub-Rayleigh fronts. We might expect these modes to be important in both fault nucleation and earthquake dynamics.Comment: 19 page, 5 figures, to appear in International Journal of Fractur

Uniform Selection as a Primary Force Reducing Population Genetic Differentiation of Cavitation Resistance across a Species Range

Background: Cavitation resistance to water stress-induced embolism determines plant survival during drought. This adaptive trait has been described as highly variable in a wide range of tree species, but little is known about the extent of genetic and phenotypic variability within species. This information is essential to our understanding of the evolutionary forces that have shaped this trait, and for evaluation of its inclusion in breeding programs. Methodology: We assessed cavitation resistance (P 50), growth and carbon isotope composition in six Pinus pinaster populations in a provenance and progeny trial. We estimated the heritability of cavitation resistance and compared the distribution of neutral markers (FST) and quantitative genetic differentiation (QST), for retrospective identification of the evolutionary forces acting on these traits. Results/Discussion: In contrast to growth and carbon isotope composition, no population differentiation was found for cavitation resistance. Heritability was higher than for the other traits, with a low additive genetic variance (h 2 ns = 0.4360.18, CVA = 4.4%). QST was significantly lower than FST, indicating uniform selection for P50, rather than genetic drift. Putativ

Photon-Photon Physics in Very Peripheral Collisions of Relativistic Heavy Ions

In central collisions at relativistic heavy ion colliders like the Relativistic Heavy Ion Collider RHIC/Brookhaven and the Large Hadron Collider LHC (in its heavy ion mode) at CERN/Geneva, one aims at detecting a new form of hadronic matter - the Quark Gluon Plasma. It is the purpose of this review to discuss a complementary aspect of these collisions, the very peripheral ones. Due to coherence, there are strong electromagnetic fields of short duration in such collisions. They give rise to photon-photon and photon-nucleus collisions with high flux up to an invariant mass region hitherto unexplored experimentally. After a general survey photon-photon luminosities in relativistic heavy ion collisions are discussed. Special care is taken to include the effects of strong interactions and nuclear size. Then photon-photon physics at various gamma-gamma-invariant mass scales is discussed. The region of several GeV, relevant for RHIC is dominated by QCD phenomena (meson and vector meson pair production). Invariant masses of up to about 100 GeV can be reached at LHC, and the potential for new physics is discussed. Photonuclear reactions and other important background effects, especially diffractive processes are also discussed. A special chapter is devoted to lepton-pair production, especially electron-positron pair production; due to the strong fields new phenomena, especially multiple e+-e- pair production, will occur there.Comment: 40 pages, 19 figures, Topical Review, to appear in Journal of Physics G, revised text, updated text/references, one figure replace