ET-1 and NOS III gene expression regulation by plaque-free and plaque-prone hemodynamic conditions

Résumé: Les environnements hémodynamiques, favorisant ou protégeant contre la formation de la plaque, induisent tout deux une augmentation de la production d'anion superoxide dans les cellules endothéliales (ECs). Par ailleurs, une régulation différente de l'expression des gènes a été décrite dans les cellules exposées à ces différentes conditions. Dans le but d'investiguer le rôle de l'augmentation du stress oxydatif dans l'expression des gènes régulée par le flux, nous avons d'abord exposé les EC à un flux unidirectionnel, non pulsé. Dans ces conditions, l'état oxydatif des cellules endothéliales est augmenté de façon transitoire. L'expression du gène de l'endothéline 1 (ET-1) est aussi induite de façon transitoire par un tel flux, alors que l'expression du gène de la nitiric oxyde synthase endothéliale (NOS III) est stimulé de façon durable. Au contraire, un flux unidirectionnel pulsé, qui induit une augmentation durable de la production d'anion superoxide, augmente aussi de façon durable l'expression des gènes de ET-1 comme de NOS III. Un flux oscillatoire (favorisant la plaque), qui lui aussi ,a des effets à long terme sur la production d'anion superoxide, a uniquement augmenté l'expression de ET-1. De plus, l'utilisation d'un antioxydant, a seulement partiellement inhibé la stimulation de l'expression du gène NOS III par le flux unidirectionnel pulsé, alors qu'il a complètement abrogé la stimulation de l'expression du gène ET-1 par le flux unidirectionnel pulsé et oscillatoire. Ceci suggère que les forces mécaniques régulent l'expression des gènes dans les EC par un double mécanisme dépendant et indépendant du stress oxidatif des cellules. Par ailleurs, ces résultats supportent ultérieurement l'hypothèse que la balance entre la réponse oxidative et anti-oxidante dans les cellules endothéliales exposées à un environnement hémodynamique est une des clés de la prédisposition à un dysfonctionnement endothélial observé dans des régions exposées à des flux perturbés. Abstract: Both plaque-free and plaque-prone hemodynamic environments induce an increase in the oxidative state of endothelial cells (ECs), whereas differential gene expression regulation was described in cells exposed to these conditions. In order to investigate the role of the increased oxidative state in flow-regulation of gene expression, we first exposed EC to non-pulsed unidirectional shear stress. These conditions only slightly increases ECs oxidative state and endothelin-1 (ET-1) mRNA expression, whereas endothelial nitric oxide synthase (NOS III) mRNA level were significantly up-regulated. On the contrary, both ET-1 and NOS III gene expression were significantly induced in EC exposed to pulsed-unidirectional flow (plaque-free). Only ET-1 gene expression was up-regulated by oscillatory flow (plaque-prone). Moreover, use of an antioxidant only partially inhibited NOS III gene up-regulation by unidirectional flow, whereas it completely abrogated ET-1 gene up-regulation by unidirectional and oscillatory flows. Thus suggesting that mechanical forces regulate gene expression in ECs both via oxidative stress-dependent and -independent mechanisms.

Free β-human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer.

BACKGROUND: We investigated whether the free β-human chorionic gonadotropin (free β-hCG) would provide additional information to that provided by total hCG alone and thus be useful in future epidemiological studies relating hCG to maternal breast cancer risk. MATERIALS & METHODS: Cases (n = 159) and controls (n = 286) were a subset of our previous study within the Northern Sweden Maternity Cohort on total hCG during primiparous pregnancy and breast cancer risk. RESULTS: The associations between total hCG (hazard ratio: 0.79; 95% CI: 0.49-1.27), free β-hCG (hazard ratio: 0.85; 95% CI: 0.33-2.18) and maternal risk of breast cancer were very similar in all analyses and mutual adjustment for either one had minor effects on the risk estimates. CONCLUSION: In the absence of a reliable assay on intact hCG, total hCG alone can be used in epidemiological studies investigating hCG and breast cancer risk, as free β-hCG does not appear to provide any additional information.

Corne cutanée du bord libre palpébral. A propos d'une observation anatomo-clinique [A cutaneous horn of the free margin of the eyelid: an anatomical and clinical observation].

A cutaneous horn was observed close to the free margin of the inferior right eyelid in a 26-year-old-male patient. A minimal resection was primarily performed. Histopathologic study disclosed a precancerous keratosis. As the tumor had not been entirely excised, a complementary resection was performed secondarily to obtain the entire resection of the tumor.

Robust volume-targeted balanced steady-state free-precession coronary magnetic resonance angiography in a breathhold at 3.0 Tesla: a reproducibility study.

BACKGROUND: Transient balanced steady-state free-precession (bSSFP) has shown substantial promise for noninvasive assessment of coronary arteries but its utilization at 3.0 T and above has been hampered by susceptibility to field inhomogeneities that degrade image quality. The purpose of this work was to refine, implement, and test a robust, practical single-breathhold bSSFP coronary MRA sequence at 3.0 T and to test the reproducibility of the technique. METHODS: A 3D, volume-targeted, high-resolution bSSFP sequence was implemented. Localized image-based shimming was performed to minimize inhomogeneities of both the static magnetic field and the radio frequency excitation field. Fifteen healthy volunteers and three patients with coronary artery disease underwent examination with the bSSFP sequence (scan time = 20.5 ± 2.0 seconds), and acquisitions were repeated in nine subjects. The images were quantitatively analyzed using a semi-automated software tool, and the repeatability and reproducibility of measurements were determined using regression analysis and intra-class correlation coefficient (ICC), in a blinded manner. RESULTS: The 3D bSSFP sequence provided uniform, high-quality depiction of coronary arteries (n = 20). The average visible vessel length of 100.5 ± 6.3 mm and sharpness of 55 ± 2% compared favorably with earlier reported navigator-gated bSSFP and gradient echo sequences at 3.0 T. Length measurements demonstrated a highly statistically significant degree of inter-observer (r = 0.994, ICC = 0.993), intra-observer (r = 0.894, ICC = 0.896), and inter-scan concordance (r = 0.980, ICC = 0.974). Furthermore, ICC values demonstrated excellent intra-observer, inter-observer, and inter-scan agreement for vessel diameter measurements (ICC = 0.987, 0.976, and 0.961, respectively), and vessel sharpness values (ICC = 0.989, 0.938, and 0.904, respectively). CONCLUSIONS: The 3D bSSFP acquisition, using a state-of-the-art MR scanner equipped with recently available technologies such as multi-transmit, 32-channel cardiac coil, and localized B0 and B1+ shimming, allows accelerated and reproducible multi-segment assessment of the major coronary arteries at 3.0 T in a single breathhold. This rapid sequence may be especially useful for functional imaging of the coronaries where the acquisition time is limited by the stress duration and in cases where low navigator-gating efficiency prohibits acquisition of a free breathing scan in a reasonable time period.

Reproducibility of 3D free-breathing magnetic resonance coronary vessel wall imaging.

AIMS: Although the coronary artery vessel wall can be imaged non-invasively using magnetic resonance imaging (MRI), the in vivo reproducibility of wall thickness measures has not been previously investigated. Using a refined magnetization preparation scheme, we sought to assess the reproducibility of three-dimensional (3D) free-breathing black-blood coronary MRI in vivo. METHODS AND RESULTS: MRI vessel wall scans parallel to the right coronary artery (RCA) were obtained in 18 healthy individuals (age range 25-43, six women), with no known history of coronary artery disease, using a 3D dual-inversion navigator-gated black-blood spiral imaging sequence. Vessel wall scans were repeated 1 month later in eight subjects. The visible vessel wall segment and the wall thickness were quantitatively assessed using a semi-automatic tool and the intra-observer, inter-observer, and inter-scan reproducibilities were determined. The average imaged length of the RCA vessel wall was 44.5+/-7 mm. The average wall thickness was 1.6+/-0.2 mm. There was a highly significant intra-observer (r=0.97), inter-observer (r=0.94), and inter-scan (r=0.90) correlation for wall thickness (all P<0.001). There was also a significant agreement for intra-observer, inter-observer, and inter-scan measurements on Bland-Altman analysis. The intra-class correlation coefficients for intra-observer (r=0.97), inter-observer (r=0.92), and inter-scan (r=0.86) analyses were also excellent. CONCLUSION: The use of black-blood free-breathing 3D MRI in conjunction with semi-automated analysis software allows for reproducible measurements of right coronary arterial vessel-wall thickness. This technique may be well-suited for non-invasive longitudinal studies of coronary atherosclerosis.

Consumer Advisory Bulletin; Beware of “Free Trial Offers”, July 2010

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Aortic vessel wall magnetic resonance imaging at 3.0 Tesla: a reproducibility study of respiratory navigator gated free-breathing 3D black blood magnetic resonance imaging.

The purpose of this study was to evaluate a free-breathing three-dimensional (3D) dual inversion-recovery (DIR) segmented k-space gradient-echo (turbo field echo [TFE]) imaging sequence at 3T for the quantification of aortic vessel wall dimensions. The effect of respiratory motion suppression on image quality was tested. Furthermore, the reproducibility of the aortic vessel wall measurements was investigated. Seven healthy subjects underwent 3D DIR TFE imaging of the aortic vessel wall with and without respiratory navigator. Subsequently, this sequence with respiratory navigator was performed twice in 10 healthy subjects to test its reproducibility. The signal-to-noise (SNR), contrast-to-noise ratio (CNR), vessel wall sharpness, and vessel wall volume (VWV) were assessed. Data were compared using the paired t-test, and the reproducibility of VWV measurements was evaluated using intraclass correlation coefficients (ICCs). SNR, CNR, and vessel wall sharpness were superior in scans performed with respiratory navigator compared to scans performed without. The ICCs concerning intraobserver, interobserver, and interscan reproducibility were excellent (0.99, 0.94, and 0.95, respectively). In conclusion, respiratory motion suppression substantially improves image quality of 3D DIR TFE imaging of the aortic vessel wall at 3T. Furthermore, this optimized technique with respiratory motion suppression enables assessment of aortic vessel wall dimensions with high reproducibility.

The effects of added glycerol or unprotected free fatty acids or a combination of the two on silage intake, milk production, rumen fermentation and diet digestibility in cows given grass silage based diets

Selostus: Väkirehuun lisätyn glyserolin tai vapaiden rasvahappojen tai näiden yhdistelmän vaikutus maidontuotantoon ja pötsifermentaatioon ruokittaessa lypsylehmiä säilörehuun perustuvalla ruokinnalla

Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction between Wy14643 and fasting. Numerous genes were commonly regulated in liver between the two treatments, including many classical PPARalpha target genes, such as Aldh3a2 and Cpt2. Remarkably, several genes induced by Wy14643 were upregulated by fasting independently of PPARalpha, including Lpin2 and St3gal5, suggesting involvement of another transcription factor. Using chromatin immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets of PPARbeta/delta during fasting, whereas Aldh3a2 and Cpt2 were exclusive targets of PPARalpha. Binding of PPARbeta/delta to the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA) concentration, consistent with activation of PPARbeta/delta by plasma FFAs. Subsequent experiments using transgenic and knockout mice for Angptl4, a potent stimulant of adipose tissue lipolysis, confirmed the stimulatory effect of plasma FFAs on Lpin2 and St3gal5 expression levels via PPARbeta/delta. In contrast, the data did not support activation of PPARalpha by plasma FFAs. The results identify Lpin2 and St3gal5 as novel PPARbeta/delta target genes and show that upregulation of gene expression by PPARbeta/delta is sensitive to plasma FFA levels. In contrast, this is not the case for PPARalpha, revealing a novel mechanism for functional differentiation between PPARs.

Impact of free-range pigs on mountain pastures in the Swiss Jura

The consequences of foraging by free-range pigs on the vegetation of mountain pastures was investigated. 25 pigs (15 week-old, mean weight 50 kg) were enclosed from June to mid-September in a 2 ha-enclosure in Jura Mountains (Switzerland), fed with a mixture of lactoserum and cereals. The enclosure contained five different plant communities. Eutrophic pastures on deep soil were strongly overturned, but the recolonisation was quick and dominated by the original species. Mesotrophic pastures were less damaged on stony soil but completely destroyed on deep soil, and the recovery was slow, characterised by a shift of plant species in a more eutrophic direction. Four years were not sufficient for complete recovery. Oligotrophic calcareous pastures on shallow stony soil were not damaged. Extensive breeding of pigs in mountain pastures might be harmful to plant species and vegetation, and ought to be restricted to the less sensitive plant communities, with a rotation on two to three different sites.

Application of a floating well concept to a latch-up-free, low-cost, smart power high-side switch technology

The aim of this brief is to present an original design methodology that permits implementing latch-up-free smart power circuits on a very simple, cost-effective technology. The basic concept used for this purpose is letting float the wells of the MOS transistors most susceptible to initiate latch-up.

Non-constant discounting in finite horizon: The free terminal time case

This paper derives the HJB (Hamilton-Jacobi-Bellman) equation for sophisticated agents in a finite horizon dynamic optimization problem with non-constant discounting in a continuous setting, by using a dynamic programming approach. A simple example is used in order to illustrate the applicability of this HJB equation, by suggesting a method for constructing the subgame perfect equilibrium solution to the problem.Conditions for the observational equivalence with an associated problem with constantdiscounting are analyzed. Special attention is paid to the case of free terminal time. Strotz¿s model (an eating cake problem of a nonrenewable resource with non-constant discounting) is revisited.