Skin conductance while facing emotional pictures at day 7 helps predicting antidepressant response at three months in patients with a major depressive episode.

There are currently no reliable biological markers to identify antidepressant responders in patients suffering from major depressive disorder. In this longitudinal pilot study, we measured skin conductance response (SCR) to assess patients' emotional reactivity after antidepressant treatment initiation. Fifty-four adult patients with a major depressive episode were recruited and followed up for 3 months. After one day of antidepressant treatment (D1) and then at day 7 (D7), emotional stimuli were presented on a computer screen while SCR and subjective emotional response were recorded. Three months later, we used Montgomery and Åsberg Depression Rating Scale (MADRS) to screen patients for treatment response, and distinguished responders (N = 28) from non-responders (N = 15). While SCR at D1 did not differ between responders and non-responders, SCR at D7 was higher in responders for both positive, negative and neutral stimuli. Skin conductance rates at D7 had a relatively poor negative predictive value (38%) but a strong positive predictive value (95%). Further studies are needed to replicate in a larger sample, and validate, these preliminary results which suggest that electrodermal activity after treatment initiation could help predict antidepressant efficacy.

Salivary composition in obese vs normal-weight subjects: towards a role in postprandial lipid metabolism?

In the pathophysiological context of obesity, oral exposure to dietary fat can modulate lipid digestion and absorption, but underlying in-mouth mechanisms have not been clearly identified. Therefore, we tested the hypothesis that salivary components related to dietary fat sensitivity would differ according to body mass index (BMI) and postprandial lipid metabolism in young men. Saliva was collected from nine normal-weight (BMI=22.3±0.5 kg m(-2)) and nine non-morbid obese (BMI=31.7±0.3 kg m(-2)) men before an 8-h postprandial metabolic exploration test involving the consumption of a 40-g fat meal, in which obese subjects revealed a delayed postprandial lipid metabolism. Nine salivary characteristics (flow, protein content, lipolysis, amylase, proteolysis, total antioxidant status, lysozyme, lipocalin 1 and carbonic anhydrase-VI) were investigated. We show that, under fasting conditions, salivary lipolysis was lower in obese vs normal-weight subjects, whereas proteolysis and carbonic anhydrase VI were higher. We reveal through multivariate and Mann-Whitney analysis that differences in fasting salivary lipolysis and proteolysis between both groups are related to differences in postprandial lipid metabolism including exogenous fatty-acid absorption and ß-oxidation. These results suggest a potential role of salivary composition on postprandial lipid metabolism and bring novel causal hypotheses on the links between salivary composition, sensitivity to dietary fat oral income and postprandial lipid metabolism according to BMI.

Impact of various emulsifiers on ALA bioavailability and chylomicron synthesis through changes in gastrointestinal lipolysis.

Formulating healthy food rich in omega 3 fatty acids requires prior knowledge of the parameters influencing their bioavailability and their metabolic fate. In this context, we studied the effects of various emulsifiers widely used in the food industry, on the gastrointestinal lipolysis of flaxseed oil emulsions in an in vitro model and on the intestinal absorption and lymphatic secretion of alpha-linolenic acid (ALA) in rats. In vitro data showed that the emulsification of flaxseed oil with soya lecithin improved the gastric lipolysis of the oil (+30%), while the presence of Tween 80 or of sodium caseinate decreased it (-80% and -40%, respectively). The in vivo data demonstrated that the intestinal absorption and the lymphatic secretion of ALA were improved with soya lecithin (Cmax = 24 mg mL(-1)) and reduced in the presence of sodium caseinate (Cmax = 7 mg mL(-1)) compared to unemulsified flaxseed oil (Cmax = 16 mg mL(-1)); Tween 80 had no effect. In addition, the synthesized chylomicrons were notably larger and more numerous with soya lecithin whereas they were smaller in the presence of sodium caseinate (p < 0.05). This study shows that the intestinal bioavailability of ALA was increased by the emulsification of flaxseed oil with soya lecithin via an improved lipolysis, favouring the intestinal absorption of ALA and the secretion of many large chylomicrons in lymph.

Population kinetics and conditional assessment of the optimal dosage regimen using the P-PHARM software package.

The adjustment of individual dosage regimen is an adaptive control process based upon an individual response to a pharmacokinetic model. To attain this objective, it is very helpful to know the characteristics of the population to which the subject belongs, in terms of mean parameters and interindividual variability. Usually the available information consists of incomplete and sparse data. For this reason it is essential to employ a computational methodology based on non-linear mixed-effect procedures in order to obtain a population parameter estimate. A Bayesian methodology can then be applied from the population parameters to the specific data for the individual requiring a dosage adjustment (such data includes drug concentration(s) of the active drug, demographic data, etc). The result of the Bayesian calculation supplies the required individual pharmacokinetic parameters. An optimal dosage regimen can be defined on the basis of therapeutical criteria (concentration ranges) as well as practical constraints such as: the size of available unitary drug dosages, feasible drug intake times, penalties associated with expected concentrations falling outside the therapeutic concentration ranges. In this paper we present the methodology and results obtained using the P-Pharm software tool. P-Pharm implements a non-linear mixed-effect population parameter estimation algorithm based on the EM algorithm. This method allows the inclusion of explicit variables into the calculations, it implements an individual Bayesian parameter estimation procedure and also an algorithm for the conditional assessment of the optimal dosage regimen given a list of practical constraints.