Changes in Aortic Pulse Wave Velocity in Hypertension Post-Menopausal Women: Comparison Between Calcium Channel Blocker (CCB) Vs Angiotensin Receptor Blocker (ARB) Regimen

Objective: To compare effects of a non-renin-angiotensin system (RAS) blocker, using a CCB, or a RAS blocker, using an ARB regimen on the arterial stiffness reduction in postmenopausal hypertensive women. Methods: In this prospective study, a total of 125 hypertensive women (age: 61.4_6 yrs; 98% Caucasian; BW: 71.9_14 kg; BMI: 27.3_5 kg/m2; SBP/ DBP: 158_11/92_9 mmHg) were randomized between ARB (valsartan 320mg_HCTZ) and CCB (amlodipine 10mg _ HCTZ). The primary outcome was carotid-femoral pulse wave velocity (PWV) changes after 38 weeks of treatment. Results: There were no significant differences in baseline demographic data between the two groups. Both treatments effectively lowered BP at the end of the study with similar (p>0.05) reductions in the valsartan (_22.9/_10.9 mmHg) and amlodipine based (_25.2/_11.7 mmHg) treatment groups. Despite a lower (p<0.05 for DBP) central SBP/DBP in the CCB group (_19.2/_10.3 mmHg) compared to the valsartan group (_15.7/_7.6 mmHg) at week 38, a similar reduction in carotid-femoral PWV (_1.7 vs _1.9 m/sec; p>0.05) was observed between both groups. The numerically larger BP reduction observed in the CCB group was associated with a much higher incidence of peripheral edema (77% vs 14%) than the valsartan group. Conclusion: In summary, BP lowering in postmenopausal women led to a reduction in arterial stiffness assessed by PWV measurement. Both regimens reduced PWV at 38 weeks of treatment to a similar degree, despite differences in BP lowering suggesting that the effect of RAS blockade to influence PWV may partly be independent of BP.

Direct comparison of 3D spiral vs. Cartesian gradient-echo coronary magnetic resonance angiography.

While 3D thin-slab coronary magnetic resonance angiography (MRA) has traditionally been performed using a Cartesian acquisition scheme, spiral k-space data acquisition offers several potential advantages. However, these strategies have not been directly compared in the same subjects using similar methodologies. Thus, in the present study a comparison was made between 3D coronary MRA using Cartesian segmented k-space gradient-echo and spiral k-space data acquisition schemes. In both approaches the same spatial resolution was used and data were acquired during free breathing using navigator gating and prospective slice tracking. Magnetization preparation (T(2) preparation and fat suppression) was applied to increase the contrast. For spiral imaging two different examinations were performed, using one or two spiral interleaves, during each R-R interval. Spiral acquisitions were found to be superior to the Cartesian scheme with respect to the signal-to-noise ratio (SNR) and contrast-to-noise-ratio (CNR) (both P < 0.001) and image quality. The single spiral per R-R interval acquisition had the same total scan duration as the Cartesian acquisition, but the single spiral had the best image quality and a 2.6-fold increase in SNR. The double-interleaf spiral approach showed a 50% reduction in scanning time, a 1.8-fold increase in SNR, and similar image quality when compared to the standard Cartesian approach. Spiral 3D coronary MRA appears to be preferable to the Cartesian scheme. The increase in SNR may be "traded" for either shorter scanning times using multiple consecutive spiral interleaves, or for enhanced spatial resolution.

Phosphorus burial in the ocean over glacial-interglacial time scales

The role of nutrients, such as phosphorus (P), and their impact on primary productivity and the fluctuations in atmospheric CO2 over glacial-interglacial periods are intensely debated. Suggestions as to the importance of P evolved from an earlier proposal that P actively participated in changing productivity rates and therefore climate change, to most recent ones that changes in the glacial ocean inventory of phosphorus were important but not influential if compared to other macronutrients, such as nitrate. Using new data coming from a selection of ODP sites, we analyzed the distribution of oceanic P sedimentary phases and calculate reactive P burial fluxes, and we show how P burial fluxes changed over the last glacial-interglacial period at these sites. Concentrations of reactive P are generally lower during glacial times, while mass accumulation rates (MAR) of reactive P show higher variability. If we extrapolate for the analyzed sites, we may assume that in general glacial burial fluxes of reactive P are lower than those during interglacial periods by about 8%, because the lack of burial of reactive P on the glacial shelf reduced in size, was apparently not compensated by burial in other regions of the ocean. Using the calculated changes in P burial, we evaluate their possible impact on the phosphate inventory in the world oceans. Using a simple mathematical approach, we find that these changes alone could have increased the phosphate inventory of glacial ocean waters by 17-40% compared to interglacial stages. Variations in the distribution of sedimentary P phases at the investigated sites seem to indicate that at the onset of interglacial stages, shallower sites experienced an increase in reactive P concentrations, which seems to point to P-richer waters at glacial terminations. All these findings would support the Shelf-Nutrient Hypothesis, which assumes that during glacial low stands nutrients are transferred from shallow sites to deep sea with possible feedback on the carbon cycle.

Initiation and limitation of Ly-49A NK cell receptor acquisition by T cell factor-1.

The establishment of clonally variable expression of MHC class I-specific receptors by NK cells is not well understood. The Ly-49A receptor is used by approximately 20% of NK cells, whereby most cells express either the maternal or paternal allele and few express simultaneously both alleles. We have previously shown that NK cells expressing Ly-49A were reduced or almost absent in mice harboring a single or no functional allele of the transcription factor T cell factor-1 (TCF-1), respectively. In this study, we show that enforced expression of TCF-1 in transgenic mice yields an expanded Ly-49A subset. Even though the frequencies of Ly-49A(+) NK cells varied as a function of the TCF-1 dosage, the relative abundance of mono- and biallelic Ly-49A cells was maintained. Mono- and biallelic Ly-49A NK cells were also observed in mice expressing exclusively a transgenic TCF-1, i.e., expressing a fixed amount of TCF-1 in all NK cells. These findings suggest that Ly-49A acquisition is a stochastic event due to limiting TCF-1 availability, rather than the consequence of clonally variable expression of the endogenous TCF-1 locus. Efficient Ly-49A acquisition depended on the expression of a TCF-1 isoform, which included a domain known to associate with the TCF-1 coactivator beta-catenin. Indeed, the proximal Ly-49A promoter was beta-catenin responsive in reporter gene assays. We thus propose that Ly-49A receptor expression is induced from a single allele in occasional NK cells due to a limitation in the amount of a transcription factor complex requiring TCF-1.

Receptor occupancy vs. induction of Na+-K+-ATPase and Na+ transport by aldosterone.

In the urinary bladder of the toad Bufo marinus aldosterone (between 0.8 and 100 nM) stimulates Na+ transport [half-maximal induction concentration (K1/2) = 6.5 nM]. At low hormone concentrations (0.8-8 nM), the increase of Na+ transport between 0.75 and 2.5 h is accompanied by a fall in transepithelial resistance (R). Higher hormone concentrations (30-800 nM) induce an additional resistance-independent fraction of Na+ transport within 2.5-8 h. From 6 h on, aldosterone (between 0.2 and 20 nM) stimulates in the same tissue the biosynthesis rate of the alpha- and beta-subunits of Na+-K+-ATPase (K1/2 = 3 and 1.5 nM, respectively). New pump synthesis is thus not a prerequisite for the early mineralocorticoid response but might be linked to the late transport event. The mineralocorticoid response is usually ascribed to interaction with the higher affinity type 1 receptor. In the present study we show, however, that at least 55% of the overall Na+ transport response is linked to nuclear occupation of the lower affinity type 2 receptors [dissociation constant (Kd) = 50 nM, maximum number of binding sites (Nmax) = 315 fmol/mg protein]. Distinct aldosterone effects, such as the fall in R and the increase in Na+-K+-ATPase synthesis, are more closely related to occupation of type 1 receptors (Kd = 0.3 nM, Nmax = 23 fmol/mg protein). At maximal induction of these latter parameters, only about 20% of type 2 receptors are occupied. These results suggest that both types of aldosterone receptors are involved in the mediation of the full mineralocorticoid response: type 1 in the early and late and type 2 particularly in the late tissue response.

La clause de limitation des bénéfices dans la convention de double imposition entre la Suisse et les Etats-Unis

AVANT PROPOS L'abus des conventions de double imposition (treaty shopping) est une des problématiques les plus riches de la fiscalité internationale contemporaine. L'utilisation d'une telle convention (ci-après : CDI) par des personnes ne résidant effectivement dans aucun des Etats contractants à la convention constitue pour une majorité de la doctrine internationale un abus de droit. La problématique de l'abus des CDI a été identifiée de longue date en Suisse. Elle a suivi une évolution partiellement différente aux Etats-Unis. Les deux approches se sont rencontrées une première fois lors de la conclusion de la CDI CH-US de 1951 (art. XI). Longtemps évoquée, la révision de cette convention a été finalisée en 1996. Cette deuxième rencontre a fait entrer dans l'ordre juridique suisse une disposition d'un type complètement nouveau, qui aura des répercussions jusque dans la pratique anti-abus au plan interne en Suisse. La présente étude s'attachera à examiner l'évolution comparée de la lutte contre l'abus des CDI en Suisse tout d'abord (première partie), et aux Etats-Unis ensuite (IIe partie), ainsi que les relations entre les normes internes anti-abus et celles découlant d'une convention dans chacun des deux Etats. La clause spécifique de limitation des avantages de la Convention actuelle (art. 22 CDI-US) sera analysée dans la IIIe partie. La dernière partie (IVe partie) sera consacrée à une comparaison entre cette disposition et les mesures anti-abus contenues dans le Modèle de convention de l'OCDE afin de déterminer si cette clause constitue réellement l'instrument optimal pour lutter contre l'utilisation indue des conventions de double imposition.

Effects of 2 different prior endurance exercises on whole-body fat oxidation kinetics: light vs. heavy exercise.

This study aimed to compare the effects of 2 different prior endurance exercises on subsequent whole-body fat oxidation kinetics. Fifteen men performed 2 identical submaximal incremental tests (Incr2) on a cycle ergometer after (i) a ∼40-min submaximal incremental test (Incr1) followed by a 90-min continuous exercise performed at 50% of maximal aerobic power-output and a 1-h rest period (Heavy); and (ii) Incr1 followed by a 2.5-h rest period (Light). Fat oxidation was measured using indirect calorimetry and plotted as a function of exercise intensity during Incr1 and Incr2. A sinusoidal equation, including 3 independent variables (dilatation, symmetry and translation), was used to characterize the fat oxidation kinetics and to determine the intensity (Fat(max)) that elicited the maximal fat oxidation (MFO) during Incr. After the Heavy and Light trials, Fat(max), MFO, and fat oxidation rates were significantly greater during Incr2 than Incr1 (p < 0.001). However, Δ (i.e., Incr2-Incr1) Fat(max), MFO, and fat oxidation rates were greater in the Heavy compared with the Light trial (p < 0.05). The fat oxidation kinetics during Incr2(Heavy) showed a greater dilatation and rightward asymmetry than Incr1(Heavy), whereas only a greater dilatation was observed in Incr2(Light) (p < 0.05). This study showed that although to a lesser extent in the Light trial, both prior exercise sessions led to an increase in Fat(max), MFO, and absolute fat oxidation rates during Incr2, inducing significant changes in the shape of the fat oxidation kinetics.

Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon-gamma release assay vs. tuberculin skin test.

BACKGROUND: Antitumour necrosis factor (anti-TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon-gamma release assays (IGRA) have been shown to be more sensitive and specific than TST. OBJECTIVE: To compare the TST and the T-SPOT.TB IGRA for identifying LTBI in patients with psoriasis before anti-TNF treatment. METHODS: A retrospective study was carried out over a 4-year period on patients with psoriasis requiring anti-TNF treatment. All were subjected to the TST, T-SPOT.TB and chest X-ray. Risk factors for LTBI and history of bacillus Calmette-Guérin (BCG) vaccination were recorded. The association of T-SPOT.TB and TST results with risk factors for LTBI was tested through univariate logistic regression models. Agreement between tests was quantified using kappa statistics. Treatment for LTBI was started 1 month before anti-TNF therapy when indicated. RESULTS: Fifty patients were included; 90% had prior BCG vaccination. A positive T-SPOT.TB was strongly associated with a presumptive diagnosis of LTBI (odds ratio 7.43; 95% confidence interval 1.38-39.9), which was not the case for the TST. Agreement between the T-SPOT.TB and TST was poor, kappa = 0.33 (SD 0.13). LTBI was detected and treated in 20% of the patients. In 20% of the cases, LTBI was not retained in spite of a positive TST but a negative T-SPOT.TB. All patients received an anti-TNF agent for a median of 56 weeks (range 20-188); among patients with a positive TST/negative T-SPOT.TB, no tuberculosis was detected with a median follow-up of 64 weeks (44-188). One case of disseminated tuberculosis occurred after 28 weeks of adalimumab treatment in a patient with LTBI in spite of treatment with rifampicin. CONCLUSION: This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti-TNF therapy, even if LTBI is correctly diagnosed and treated.