A new paradigm for high‐sensitivity 19F magnetic resonance imaging of perfluorooctylbromide

In the present work, the NMR properties of perfluorooctylbromide are revisited to derive a high‐sensitivity fluorine MRI strategy. It is shown that the harmful effects of J‐coupling can be eliminated by carefully choosing the bandwidth of the 180° pulses in a spin‐echo sequence. The T₂ of the CF₃ resonance of the molecule is measured using a multispin‐echo sequence and shown to dramatically depend on the interpulse delay. Following these observations, an optimized multispin‐echo imaging sequence is derived and compared with short TE/pulse repetition time gradient echo and chemical shift imaging sequences. The unparalleled sensitivity yielded by the multispin‐echo sequence is promising for future applications, in particular for targeted contrast agents such as perfluorooctylbromide nanoparticles. Magn Reson Med 63:1119–1124, 2010. © 2010 Wiley‐Liss, Inc.     

Automated segmentation of myocardial scar in late enhancement MRI using combined intensity and spatial information

Accurate assessment of the size and distribution of a myocardial infarction (MI) from late gadolinium enhancement (LGE) MRI is of significant prognostic value for postinfarction patients. In this paper, an automatic MI identification method combining both intensity and spatial information is presented in a clear framework of (i) initialization, (ii) false acceptance removal, and (iii) false rejection removal. The method was validated on LGE MR images of 20 chronic postinfarction patients, using manually traced MI contours from two independent observers as reference. Good agreement was observed between automatic and manual MI identification. Validation results showed that the average Dice indices, which describe the percentage of overlap between two regions, were 0.83 ± 0.07 and 0.79 ± 0.08 between the automatic identification and the manual tracing from observer 1 and observer 2, and the errors in estimated infarct percentage were 0.0 ± 1.9% and 3.8 ± 4.7% compared with observer 1 and observer 2. The difference between the automatic method and manual tracing is in the order of interobserver variation. In conclusion, the developed automatic method is accurate and robust in MI delineation, providing an objective tool for quantitative assessment of MI in LGE MR imaging. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Pratique du contrôle glycémique en réanimation et charge de travail infirmier

Following the publication of the spectacular effects of tight glucose control by intensive insulin therapy in 2001, the glycemic targets have been lowered. The practical aspects of this policy are reviewed here. The effects of tight glucose control on the risks of hypoglycaemia and on the nursing workload are discussed as well. These latter issues, and the lack of confirmation of the external validity of the landmark 2001 study, lead to the adoption of an intermediate glucose target by the majority of intensivists.     

Chromosome 9p and 10q losses predict unfavorable outcome in low-grade gliomas

The loss of chromosomes 1p–19q is the only prognostic molecular alteration identified in low-grade gliomas (LGGs) to date. Search for loss of heterozygosity (LOH) on chromosomes 1p, 9p, 10q, and 19q was performed in a series of 231 LGGs. Loss of chromosomes 1p–19q was strongly correlated with prolonged progression-free survival (PFS) and overall survival (OS) in univariate and multivariate analyses. LOH on 9p and 10q were associated with shortened PFS (P = .01 and .03, respectively) on univariate analysis. On multivariate analysis, LOH on 9p remained significant for PFS (P = .05), whereas LOH on 10q had a significant effect on OS (P = .02). Search for LOH 9p and 10q appears to be a useful complement to analysis of chromosomes 1p–19q in LGGs.     

Alteration of neuromuscular function in squash

The alteration in neuromuscular function of knee extensor muscles was characterised after a squash match in 10 trained players. Maximal voluntary contraction (MVC) and surface EMG activity of vastus lateralis (VL) and vastus medialis (VM) muscles were measured before and immediately after a 1-h squash match. M-wave and twitch contractile properties were analysed following single stimuli. MVC declined (280.5 ± 46.8 vs. 233.6 ± 35.4 N m, ?16%; P < 0.001) after the exercise and this was accompanied by an impairment of central activation, as attested by decline in voluntary activation (76.7 ± 10.4 vs. 71.3 ± 9.6%, ?7%; P < 0.05) and raw EMG activity of the two vastii (?17%; P < 0.05), whereas RMS/M decrease was lesser (VL: ?5%; NS and VM: ?12%; P = 0.10). In the fatigued state, no significant changes in M-wave amplitude (VL: ?9%; VM: ?5%) or duration were observed. Following exercise, the single twitch was characterised by lower peak torque (?20%; P < 0.001) as well as shorter half-relaxation time (?13%; P < 0.001) and reduced maximal rate of twitch tension development (?23%; P < 0.001) and relaxation (?17%; P < 0.05). A 1-h squash match play caused peripheral fatigue by impairing excitation–contraction coupling, whereas sarcolemmal excitability seems well preserved. Our results also emphasise the role of central activation failure as a possible mechanism contributing to the torque loss observed in knee extensors. Physical conditioners should consider these effects when defining their training programs for squash players.     

Cadmium Alters the Biotransformation of Carcinogenic Aromatic Amines by Arylamine N-Acetyltransferase Xenobiotic-Metabolizing Enzymes: Molecular,Cellular, and in Vivo Studies

Background

Cadmium (Cd) is a carcinogenic heavy metal of environmental concern. Exposure to both Cd and carcinogenic organic compounds, such as polycyclic aromatic hydrocarbons or aromatic amines (AAs), is a common environmental problem. Human arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that play a key role in the biotransformation of AA carcinogens. Changes in NAT activity have long been associated with variations in susceptibility to different cancers in relation with exposure to certain AAs.

Objective

We explored the possible interactions between Cd and the NAT-dependent biotransformation of carcinogenic AAs.

Methods

We exposed purified enzymes, lung epithelial cells, and mouse models to Cd and subsequently analyzed NAT-dependent metabolism of AAs.

Results

We found that Cd, at biologically relevant concentrations, impairs the NAT-dependent acetylation of carcinogenic AAs such as 2-aminofluorene (2-AF) in lung epithelial cells. NAT activity was strongly impaired in the tissues of mice exposed to Cd. Accordingly, mice exposed to Cd and 2-AF displayed altered in vivo toxicokinetics with a significant decrease (~ 50%) in acetylated 2-AF in plasma. We found that human NAT1 was rapidly and irreversibly inhibited by Cd [median inhibitory concentration (IC₅₀) ≈ 55 nM; rate inhibition constant (k_inact) = 5 × 10⁴ M⁻¹ · sec⁻¹], with results of acetyl coenzyme A (acetyl-CoA) protection assays indicating that Cd-mediated inhibition was due to the reaction of metal with the active-site cysteine residue of the enzyme. We found similar results for human NAT2, although this isoform was less sensitive to inactivation (IC₅₀ ≈ 1 μM; k_inact = 1 × 10⁴ M⁻¹ · sec⁻¹).

Conclusions

Our data suggest that Cd can alter the metabolism of carcinogenic AAs through the impairment of the NAT-dependent pathway, which may have important toxicological consequences.     

Influence of sildenafil on micturition and urethral tone in ovariectomized and non-ovariectomized mice

IntroductionNitric oxide synthases (NOSs) and estrogen receptors are expressed in the female urethra.AimWe aimed to assess the impact of sildenafil on micturition behavior, urethral tone according to the hormonal status and to determine the implications of the neuronal isoform of NOS (nNOS).MethodsFour‐week‐old C57/BL6 female mice were sham‐operated or ovariectomized. Six weeks later, they were injected intraperitoneally by any combination of sildenafil, 7‐nitroindazole (7‐NI)—a potent selective nNOS inhibitor—or the corresponding vehicles. The mice were then subjected to micturition behavior and leak point pressure studies. Urethral histomorphometry was performed.Main Outcome MeasuresThe main outcome measures were micturition behavior, leak point pressure, and histomorphometry.ResultsIn sham‐operated and ovariectomized animals, sildenafil did not impact micturition, although it decreased urethral resistance 10‐fold. nNOS inhibition by 7‐NI reduced the number of micturitions and increased residual volume and leak point pressure. It abrogated sildenafil‐induced drop in urethral resistances. Hormonal status did not influence the structure of the urethral layers.Conclusions.Irrespective of the hormonal status, sildenafil decreased leak point pressure by a nNOS‐mediated mechanism. Gamé X, Bouali O, Allard J, Gourdy P, Escourrou G, Tack I, Rischmann P, Arnal J‐F, and Malavaud B. Influence of sildenafil on micturition and urethral tone in ovariectomized and non‐ovariectomized mice. J Sex Med 2012;9:466–471.