Modifier le comportement alimentaire : mission impossibles ?

Is it possible to modify intake behaviors for body weight control purposes? Over the last 40 years, dozens of international, peer-reviewed articles have described behavior modification approaches aiming at body weight reduction. The present article first presents a historical account of behavioral methods and their results. From the early therapies exclusively addressing behaviors (excluding restrictive diets) until the recent cognitive-behavioral treatments, published studies have reported modest weight losses associated with numerous metabolic, nutritional and psychological benefits whose maintenance, beyond the treatment duration, appear reasonably good. Recent studies specifically address the conditions of long-term maintenance. The main elements of behavioral-cognitive treatments are described briefly. Finally, the particular problems associated with these approaches in the French context are underlined.     

Les onze propositions issues des 3es États généraux des malades du cancer et de leurs proches de la Ligue contre le cancer

Sans résumé     

Singlet oxygen-induced arrhythmias. Dose- and light-response studies for photoactivation of rose bengal in the rat heart

In a study of aerobically perfused rat hearts, the in situ photoactivation (530-590 nm) of rose bengal (a process that leads to the production of singlet oxygen and superoxide) has been shown to lead to the rapid development of electrocardiographic abnormalities and arrhythmias. With rose bengal concentrations of 1,000, 500, 250, 100, and 50 nmol/l (n = 6/group), photoactivation (3,600 lx) led to electrocardiographic changes (inversion of the T wave, Q-T prolongation, or both) after 3.8 +/- 0.9, 4.5 +/- 0.7, 11.8 +/- 2.1, 24.8 +/- 3.9, and 65.3 +/- 6.0 seconds), respectively; ventricular premature beats occurred in 100% of hearts after 0.5 +/- 0.2, 1.1 +/- 0.3, 2.2 +/- 0.7, 4.4 +/- 0.8, and 6.6 +/- 1.2 minutes, respectively. Ventricular tachycardia occurred in 83%, 83%, 83%, 67%, and 50% of hearts after 2.1 +/- 0.2, 2.1 +/- 0.4, 2.8 +/- 0.7, 5.7 +/- 2.0, and 11.2 +/- 1.9 minutes, respectively, and complete atrioventricular block in 100%, 100%, 100%, 100%, and 67% of hearts after 3.8 +/- 0.7, 6.5 +/- 1.0, 5.5 +/- 0.9, 13.8 +/- 1.0, and 14.1 +/- 0.9 minutes, respectively. With a fixed concentration (250 nmol/l) of rose bengal, similar light-response relations were observed. Photoactivation of rose bengal had no effect on heart rate but caused a transient (0-4 minutes) vasodilation followed by a progressive vasoconstriction. In further studies in which rose bengal was washed out for 10 minutes before photoactivation, several arrhythmias still developed, indicating that rose bengal binds strongly to tissue and acts as a cellular level rather than in the vascular compartment. To assess the reversibility of rose bengal-induced effects, hearts (n = 6/group) were perfused with rose bengal (250 nmol/l) for 1, 2, 4, 6, and 20 minutes followed by perfusion in the dark for 19, 18, 16, 14, and 0 minutes, respectively. During dark perfusion, the incidence of arrhythmias declined and any decrease in coronary flow was reversed. However, analysis of contents of adenosine triphosphate, creatine phosphate, lactate, and creatine kinase leakage indicated the occurrence of severe injury that did not abate on termination of photoactivation. Finally, although many arrhythmias developed before the onset of vasoconstriction, the reduction in flow with consequent ischemia was shown to exacerbate vulnerability to arrhythmias. In conclusion, short-lived reactive oxygen intermediates such as singlet oxygen and superoxide, which are produced during the photoactivation of rose bengal, can cause rapid and major damage to the heart and its function.     

Fisher information matrix for nonlinear mixed effects multiple response models: Evaluation of the appropriateness of the first order linearization using a pharmacokinetic/pharmacodynamic model

We focus on the Fisher information matrix used for design evaluation and optimization in nonlinear mixed effects multiple response models. We evaluate the appropriateness of its expression computed by linearization as proposed for a single response model. Using a pharmacokinetic–pharmacodynamic (PKPD) example, we first compare the computation of the Fisher information matrix with approximation to one derived from the observed matrix on a large simulation using the stochastic approximation expectation–maximization algorithm (SAEM). The expression of the Fisher information matrix for multiple responses is also evaluated by comparison with the empirical information obtained through a replicated simulation study using the first‐order linearization estimation methods implemented in the NONMEM software (first‐order (FO), first‐order conditional estimate (FOCE)) and the SAEM algorithm in the MONOLIX software. The predicted errors given by the approximated information matrix are close to those given by the information matrix obtained without linearization using SAEM and to the empirical ones obtained with FOCE and SAEM. The simulation study also illustrates the accuracy of both FOCE and SAEM estimation algorithms when jointly modelling multiple responses and the major limitations of the FO method. This study highlights the appropriateness of the approximated Fisher information matrix for multiple responses, which is implemented in PFIM 3.0, an extension of the R function PFIM dedicated to design evaluation and optimization. It also emphasizes the use of this computing tool for designing population multiple response studies, as for instance in PKPD studies or in PK studies including the modelling of the PK of a drug and its active metabolite. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis, phencyclidine-like pharmacology, and antiischemic potential of meta-substituted 1-(1-phenylcyclohexyl)-1,2,3,6-tetrahydropyridines

A series of 1-[1-arylcyclohexyl]-1,2,3,6-tetrahydropyridines were prepared by the reaction between 1-(1-cyanocyclohexyl)-1,2,3,6-tetrahydropyridine (1) and an appropriately substituted Grignard reagent. The resulting compounds were tested for their phencyclidine binding site affinities. Selected compounds were then tested for their ability to produce ketamine appropriate responding in monkeys and/or to show neuroprotective effects in a baby rat hypoxia/ischemia model. While it was found that binding site affinity correlated well with discriminative stimulus effects, it was found to be a poor indicator of neuroprotective efficacy within this series.     

Onset of spermatozoal degeneration in low-fertility Delaware roosters and test for autoimmune basis

The objectives of this study were 1) to determine the onset of a heritable reproductive disorder in the rooster that is characterized by extensive spermatozoal degeneration within the ductus deferens, and 2) to determine if autoimmunity was associated with spermatozoal degeneration. Seventy-five percent of the affected roosters did not ejaculate large percentages of degenerate spermatozoa at 20 wk of age, approximately the age of sexual maturity. Rather, seminal quality gradually declined over the next 6 wk, as both ejaculate volume and number of spermatozoa ejaculated increased. The evaluation of testicular and excurrent duct tissues via immunofluorescence failed to reveal either IgY or IgA associated with spermatozoa. While histological examination revealed greater lymphocyte numbers (P less than .05) in the proximal ductus deferens, these cells were not associated with spermatozoa nor spermatozoal clumping. While spermatozoal degeneration tends to be latent at the onset of semen production, it does not appear to be due to spermatozoal autoimmunity.     

Découverte d’une nouvelle cellule tueuse de tumeurs*

Une équipe labellisée par la Ligue vient de démasquer une cellule aux propriétés extraordinaires: elle se faufile auprès des tumeurs et les détruit en un temps record. Une première mondiale. *Article publié dans le magazine Vivre n˚ 329 écrit par la journaliste S. Delage/Sequoia ETC. Pour vous abonner, téléphoner au 0 810 111 101 (prix d’un appel local)