Aspects chimiques et physiologiques du transfert trophique du méthylmercure et du tributylétain chez deux prédateurs benthiques

Cet article discute des aspects chimiques et physiologiques du devenir des composés organométalliques chez les organismes aquatiques et est basé sur les résultats de travaux ayant porté sur la pharmacocinétique et l'organotropisme du tributylétain (TBT) et du méthylmercure (MeHg) ingérés avec la nourriture chez deux prédateurs benthiques : la plie canadienne (Hippoglossoides platessoides) et le crabe des neiges (Chionoecetes opilio). Les principales observations ont été les suivantes; - 1o l'efficacité d'assimilation (EA) du MeHg est élevée (ca. 90 %) et il est lentement (t0.95 " 40 d) et uniformément distribué dans l'organisme de la plie et du crabe,- 2o la demie-vie biologique du MeHg est beaucoup plus longue que celle du TBT (t0.5 " 600 d et 50 d, respectivement), et ce pour les deux espèces,- 3o la plie canadienne assimile moins efficacement le TBT que le crabe des neiges (EA=47 % et 92 %, respectivement),- 4o le TBT est rapidement (t0.95=7 d) et uniformément distribué dans l'organisme de la plie canadienne, alors que chez le crabe des neiges une faible fraction de la dose de TBT administrée avec la nourriture est retrouvée dans les tissus autres que l'hépatopancréas.Certaines de ces observations peuvent être conciliées en tenant compte des propriétés physiques et chimiques du TBT et du MeHg, tels que l'encombrement stérique, la stabilité en milieu biologique, et l'affinité pour certains ligands biologiques. Cependant, des facteurs physiologiques doivent être invoqués pour concilier d'autres observations, comme l'étendue et la vitesse de la distribution du TBT chez la plie canadienne comparativement au crabe des neiges. Par exemple, bien que le TBT soit métabolisé au niveau hépatique chez les deux espèces, la structure du système dans lequel le TBT est distribué diffère fondamentalement. Ainsi, chez la plie canadienne, une importante proportion du TBT absorbé est distribuée à l'ensemble de l'organisme sans être capté par le foie, site de métabolisation, alors que chez le crabe la totalité du TBT absorbé doit d'abord traverser le site de métabolisation, l'hépatopancréas, avant d'être distribué au reste de l'organisme. Dans ce dernier cas, ceci peut avoir pour résultat de limiter le transfert du TBT vers les tissus autres que l'hépatopancréas. Ces résultats montrent que les facteurs ayant une influence dominante sur le transfert trophique et le devenir des organométaux chez les prédateurs benthiques peuvent différer selon le composé considéré; du fait de sa stabilité, le devenir du MeHg semble être presqu'exclusivement contrôlé par ses propriétés chimiques, alors que dans le cas du TBT ce sont les 'propriétés physiologiques' des organismes considérés qui ont une plus grande influence sur son devenir.It is well known that the physical and chemical characteristics of an organometal determine its fate within a given aquatic organism. The extent of uptake and the body distribution of a given organometal can vary greatly from one animal species to another. However, the effects of both chemical and physiological factors have rarely been considered simultaneously. This paper presents the results of a study on the pharmacokinetics and tissue distribution of dietary [113Sn]tributyltin (TBT), and [203Hg]methylmercury (MeHg) in a coastal benthic fish, the American plaice (Hippoglossoides platessoides), and a coastal benthic crustacean, the snow crab (Chionoecetes opilio). The main observations were: - the assimilation efficiencies (AE) of MeHg for the plaice and the snowcrab were high (88% ± 8 and 94% ± 4, respectively), and it was slowly and uniformly distributed within the body of both American plaice and snow crab (t0.95=35 ± 4 d and 42 ± 38 d, respectively);- the biological half-life of MeHg was longer than that of TBT (t0.5 " 600 d and 50 d, respectively) for both species;- the assimilation efficiency of TBT was lower for the plaice than for the crab (47% ± 7 and 92% ± 12, respectively);- TBT was rapidly (t0.95=7 ± 2 d) and uniformly distributed in the American plaice, whereas only a minor fraction of the dose administered to snow crab reached tissues other than the hepatopancreas.These observations can be explained if physical and chemical properties of TBT and MeHg are taken into account, as well as the physiological properties of the two organisms. Chemical factors can explain some of the differences observed. For example, the lower AE values of TBT compared to MeHg in the American plaice may be due to steric factors. The much longer half-life of MeHg is due to its higher stability in biological media compared to TBT. The high affinity of MeHg for sulfhydryl groups, that are ubiquitous in living tissues, is most likely responsible for its uniform distribution in the body of both American plaice and snow crab. However, physiological factors must be considered to explain the more uniform and faster rate of distribution of TBT in the American plaice, when compared to the snow crab. Though hepatic metabolism of TBT occurs in both species, the physiological systems of the plaice and the snowcrab are fundamentally different. Fish are characterised by a mammillary structure (peripheral compartments connected in parallel to a central one), whereas crustaceans are characterised by a caternary structure (compartments connected in series only to their nearest neighbours) (see below). In the American plaice, binding of TBT to plasmatic proteins likely prevents its efficient removal from blood by the liver, resulting in a large proportion of the TBT dose being distributed throughout the body.In the snow crab, TBT must first go through the site of metabolism before diffusing into the hemolymph for subsequent distribution to other tissues. This may limit the transfer of TBT or its metabolites to tissues other than the hepatopancreas. These results suggest that there are different factors influencing the fate of organometals ingested by benthic predators. Because of its stability, it appears that the fate of MeHg is almost exclusively controlled by its chemical properties (i.e., its exceptional affinity for SH groups). In contrast, the physiological properties of the organisms appear to be a more important determinant of the fate of TBT. These observations illustrate the need to consider the trophic transfer of organometals from a multidisciplinary point of view

Niveau de contamination par le mercure des sédiments de surface et des crevettes du fjord du Saguenay

De 1947 à 1976, plusieurs dizaines de tonnes de mercure d'origine industrielle ont été déversées dans les eaux de la rivière Saguenay et une grande partie de ce métal toxique se retrouve aujourd'hui dans les sédiments du Fjord. Les sédiments de surface (0-2 cm) de 17 stations réparties sur tout le bassin intérieur du fjord ont été prélevés et analysés pour le mercure total. De plus, environ 150 crevettes (Pandalus borealis) ont été capturées à Sainte-Rose-du-Nord pour fins d'analyse du mercure et pour une expérience de bioaccumulation à partir d'une diète contaminée. L'analyse des données disponibles pour les sédiments de surface montre que les teneurs moyennes (0,93 ± 0,11 µg.g-1 poids sec) en mercure n'ont pas varié de façon significative au cours des dix dernières années dans la région de Sainte-Rose-du-Nord, située dans la moitié amont du bassin intérieur. Les concentrations de mercure dans le muscle comestible des crevettes varient de 0,13 à 0,58 µg.g-1 (poids humide) selon la taille avec une valeur moyenne de 0,36 ± 0,11 µg.g-1. On trouve une concentration moyenne de 0,26 ± 0,09 µg.g-1 dans le céphalothorax et la cuticule. Un accroissement rapide et important du mercure dans, l'appareil digestif a été observé chez tes crevettes adultes soumises à une diète de chair de moules préalablement contaminée (6,0 ± 1,0 µg.g-1). Un taux de bioaccumulation de 0,09 µg.g-1 par jour dans le muscle comestible a été estimé pour les 14 premiers jours de diète contaminée.From 1947 to 1976, many tons of industrial mercury were tipped into the Saguenay River and a large amount of this toxic heavy metal is now in the sediments of the Saguenay Fjord. Surface sediments (0-2 cm) were collected at seventeen stations along the inner basin of the Saguenay Fjord and analysed for total mercury content. About 150 shrimps (Pandalus borealis) fished in the Sainte-Rose-du-Nord area were also used for mercury analyses and the determination of mercury uptake rate from contaminated food. The mercury concentrations in surface sediments ranged from 0.18 to 0.20 µg.g-1 (dry weight) with a mean value of 0.63 µg.g-1. This mean level is about one order of magnitude higher than the background level found in deep sediments. The examination of available data for surface sediments in the Sainte-Rose-du-Nord vicinity, located in the first half of the inner basin, shows the "steady state" of the mercury contamination over the last 10 years. Indeed, the mercury concentrations observed in surface sediments ranged from 0.75 to 1.20 µg.g-1, with a mean value of 0.93 µg.g-1 since 1976. The steady state of mercury contamination can be explained by two hypothesis : (1) an unexpected highly active bioturbation mechanism contributes to the mercury remobilisation from lower sediment layers (10-20 cm) and its vertical transportation up to the surface, or (2) the anthropogenic upstream discharge of mercury was not really stopped in 1976 and one or many unidentified sources are still active along the Saguenay River. The mercury concentrations in the edible part of shrimps (fished in November 1985) ranged from 0.13 to 0.58 µg.g-l (wet weight) with an average value of 0.36 ± 0.11 µg.g-1. A positive and significative linear relationship (r = 0.786) is observed between the Hg concentration in the edible part and the total wet weight of the shrimp. The mean Hg in the edible part found in 1985 is not significantly different from the mean value reported in 1932. The mean concentration found in the cephalothorax and the cuticle (taken together) of shrimps was 0.26 ± 0.09 µg.g-1. In order to estimate the mercury uptake rate by shrimps from contaminated food, a number of adult shrimps were fed with pre-contaminated mussel tissues (0.6 ± 1.0 µg.g-1) for three weeks. A high and rapid increase of mercury concentration was observed in the digestive organs after only 24 hours. The uptake rate in the edible part was estimated at 0.09 µg.g-1 per day during the first fourteen days of the bioassay. These findings clearly indicate the fragility of the balance between the biota and the physical environment and how fast major changes can occur when the level of contamination of the diet is modified

Sequential Adaptive Detection for In-Situ Transmission Electron Microscopy (TEM)

We develop new efficient online algorithms for detecting transient sparse signals in TEM video sequences, by adopting the recently developed framework for sequential detection jointly with online convex optimization [1]. We cast the problem as detecting an unknown sparse mean shift of Gaussian observations, and develop adaptive CUSUM and adaptive SSRS procedures, which are based on likelihood ratio statistics with post-change mean vector being online maximum likelihood estimators with $\ell_1$. We demonstrate the meritorious performance of our algorithms for TEM imaging using real data

Superconducting magnesium diboride films with Tc \approx 24K grown by pulsed laser deposition with in-situ anneal

Thin superconducting films of magnesium diboride (MgB2) with Tc \approx 24K were prepared on various oxide substrates by pulsed laser deposition (PLD) followed by an in-situ anneal. A systematic study of the influence of various in-situ annealing parameters shows an optimum temperature of about 600C in a background of 0.7 atm. of Ar/4%H2 for layers consisting of a mixture of magnesium and boron. Contrary to ex-situ approaches (e.g. reacting boron films with magnesium vapor at 900C), these films are processed below the decomposition temperature of MgB2. This may prove enabling in the formation of multilayers, junctions, and epitaxial films in future work. Issues related to the improvement of these films and to the possible in-situ growth of MgB2 at elevated temperature are discussed.Comment: 5 pages, 4 figure

An improved continuous compositional-spread technique based on pulsed-laser deposition and applicable to large substrate areas

A new method for continuous compositional-spread (CCS) thin-film fabrication based on pulsed-laser deposition (PLD) is introduced. This approach is based on a translation of the substrate heater and the synchronized firing of the excimer laser, with the deposition occurring through a slit-shaped aperture. Alloying is achieved during film growth (possible at elevated temperature) by the repeated sequential deposition of sub-monolayer amounts. Our approach overcomes serious shortcomings in previous in-situ implementations of CCS based on sputtering or PLD, in particular the variations of thickness across the compositional spread and the differing deposition energetics as function of position. While moving-shutter techniques are appropriate for PLD-approaches yielding complete spreads on small substrates (i.e. small as compared to distances over which the deposition parameters in PLD vary, typically about 1 cm), our method can be used to fabricate samples that are large enough for individual compositions to be analyzed by conventional techniques, including temperature-dependent measurements of resistivity and dielectric and magnetic and properties (i.e. SQUID magnetometry). Initial results are shown for spreads of (Sr,Ca)RuO$_3$.Comment: 6 pages, 8 figures, accepted for publication in Rev. Sci. Instru

Effects of sacubitril/valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) according to background therapy

Background—In the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan was more effective than the angiotensin-converting enzyme inhibitor enalapril in patients with heart failure and reduced ejection fraction. We examined whether this benefit was consistent irrespective of background therapy. Methods and Results—We examined the effect of study treatment in the following subgroups: diuretics (yes/no), digitalis glycoside (yes/no), mineralocorticoid receptor antagonist (yes/no), and defibrillating device (implanted defibrillating device, yes/no). We also examined the effect of study drug according to β-blocker dose (≥50% and <50% of target dose) and according to whether patients had undergone previous coronary revascularization. We analyzed the primary composite end point of cardiovascular death or heart failure hospitalization, as well as cardiovascular death. Most randomized patients (n=8399) were treated with a diuretic (80%) and β-blocker (93%); 47% of those taking a β-blocker were treated with ≥50% of the recommended dose. In addition, 4671 (56%) were treated with a mineralocorticoid receptor antagonist, 2539 (30%) with digoxin, and 1243 (15%) had a defibrillating device; 2640 (31%) had undergone coronary revascularization. Overall, the sacubitril/valsartan versus enalapril hazard ratio for the primary composite end point was 0.80 (95% confidence interval, 0.73–0.87; P<0.001) and for cardiovascular death was 0.80 (0.71–0.89; P<0.001). The effect of sacubitril/valsartan was consistent across all subgroups examined. The hazard ratio for primary end point ranged from 0.74 to 0.85 and for cardiovascular death ranged from 0.75 to 0.89, with no treatment-by-subgroup interaction. Conclusions—The benefit of sacubitril/valsartan, over an angiotensin-converting enzyme inhibitor, was consistent regardless of background therapy and irrespective of previous coronary revascularization or β-blocker dose

Baseline characteristics and treatment of patients in prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF)

Aim<p></p> To describe the baseline characteristics and treatment of the patients randomized in the PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and morbidity in Heart Failure) trial, testing the hypothesis that the strategy of simultaneously blocking the renin–angiotensin–aldosterone system and augmenting natriuretic peptides with LCZ696 200 mg b.i.d. is superior to enalapril 10 mg b.i.d. in reducing mortality and morbidity in patients with heart failure and reduced ejection fraction.<p></p> Methods<p></p> Key demographic, clinical and laboratory findings, along with baseline treatment, are reported and compared with those of patients in the treatment arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) and more contemporary drug and device trials in heart failure and reduced ejection fraction.<p></p> Results<p></p> The mean age of the 8442 patients in PARADIGM-HF is 64 (SD 11) years and 78% are male, which is similar to SOLVD-T and more recent trials. Despite extensive background therapy with beta-blockers (93% patients) and mineralocorticoid receptor antagonists (60%), patients in PARADIGM-HF have persisting symptoms and signs, reduced health related quality of life, a low LVEF (mean 29 ± SD 6%) and elevated N-terminal-proB type-natriuretic peptide levels (median 1608 inter-quartile range 886–3221 pg/mL).<p></p> Conclusion<p></p> PARADIGM-HF will determine whether LCZ696 is more beneficial than enalapril when added to other disease-modifying therapies and if further augmentation of endogenous natriuretic peptides will reduce morbidity and mortality in heart failure and reduced ejection fractio

The Impact of Superior Labral Anterior to Posterior Lesions on Functional Status in Shoulder Instability: A Multicenter Cohort Study

BACKGROUND: Type IV superior labral anterior to posterior (SLAP) lesions, which are superior labral detachments associated with Bankart tears, are reported to occur in up to 25% of recurrent shoulder instability patients. However, the clinical implications of this finding are debatable. PURPOSE: To determine whether there are any functional differences between anterior instability patients with and without type IV SLAP lesions at the time of presentation and at short-term follow-up after surgical intervention. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A prospective, multicenter database was established to follow the clinical evolution of patients with shoulder instability. Patients were diagnosed as having a type IV SLAP lesion at the time of arthroscopic Bankart surgery (SLAP+). These patients were compared with a group of patients who simply had a Bankart lesion (SLAP-). The 2 groups had their functional outcomes (Western Ontario Shoulder Instability Index [WOSI]; Disability of the Arm, Shoulder, and Hand [QuickDASH]; and Walch-Duplay) compared prior to surgery and 1 year postoperatively. RESULTS: A total of 103 subjects were included in the study; of these, 56 (43 men, 13 women) completed 1-year follow-up. Twenty-three subjects had a type IV SLAP tear, and most had this repaired along with their Bankart lesion. At baseline, SLAP+ subjects had inferior QuickDASH scores compared with SLAP- subjects (37.8 vs 29.0) as well as poorer pain subscores on both the WOSI and QuickDASH. At 1-year follow-up, however, there were no significant differences in any of the outcome measures. CONCLUSION: A type IV SLAP lesion can be expected in 22% of patients with recurrent shoulder instability. This finding implies that at baseline, the patient will have slightly worse functional scores related to pain. However, following surgical management of the labral pathology, these patients will have equivalent functional outcomes at short-term follow-up. CLINICAL RELEVANCE: With surgical management of the superior and anteroinferior labrum, patients with type IV SLAP lesions will do as well as those with only Bankart tears. Thus, the presence of SLAP lesions should not alter the decision to provide surgical management and should not change the prognosis for a specific patient

Systolic blood pressure, cardiovascular outcomes and efficacy and safety of sacubitril/valsartan (LCZ696) in patients with chronic heart failure and reduced ejection fraction: results from PARADIGM-HF

Background: Compared to heart failure patients with higher systolic blood pressure (SBP), those with lower SBP have a worse prognosis. To make matters worse, the latter patients often do not receive treatment with life-saving therapies that might lower blood pressure further. We examined the association between SBP and outcomes in the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with an angiotensin-converting enzyme (ACE) inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF), as well as the effect of sacubitril/valsartan, compared with enalapril, according to baseline SBP. Methods: We analysed the effect of treatment on SBP and on the primary composite outcome (cardiovascular death or heart failure hospitalization), its components and all-cause death. We examined baseline SBP as a categorical (<110, 110 to < 120, 120 to < 130, 130 to < 140 and ≥140 mmHg) and continuous variable, as well as average in-trial SBP and time-updated SBP. Findings: All-cause and cardiovascular mortality rates were highest in patients with the lowest SBP whereas there was a U-shaped relationship between SBP and the rate of heart failure hospitalization. The benefit of sacubitril/valsartan over enalapril was consistent across all baseline SBP categories for all outcomes. For example, the sacubitril/valsartan versus enalapril hazard ratio for the primary endpoint was 0.88 (95%CI 0.74–1.06) in patients with a baseline SBP <110 mmHg and 0.81 (0.65–1.02) for those with a SBP ≥140 mmHg (P for interaction = 0.55). Symptomatic hypotension, study drug dose-reduction and discontinuation were more frequent in patients with a lower SBP. Interpretation: In PARADIGM-HF, patients with lower SBP at randomization, notably after tolerating full doses of both study drugs during a run-in period, were at higher risk but generally tolerated sacubitril/valsartan and had the same relative benefit over enalapril as patients with higher baseline SBP