Olanzapine versus risperidone in the treatment of post-psychotic depression in schizophrenic patients

OBJECTIVE: To compare the efficacy of two atypical antipsychotic drugs, olanzapine and risperidone, in schizophrenic patients with post-psychotic depression. RESULTS: A clinically significant decrease of MADRS scores occurred in patients treated with both drugs for 8 weeks. CONCLUSION: Atypical antipsychotic drugs may be particularly appropriate when treating schizophrenic patients with depression.     

Calculation of absolute protein-ligand binding free energy from computer simulations

A general methodology for calculating the equilibrium binding constant of a flexible ligand to a protein receptor is formulated on the basis of potentials of mean force. The overall process is decomposed into several stages that can be computed separately: the free ligand in the bulk is first restrained into the conformation it adopts in the bound state, position, and orientation by applying biasing potentials, then it is translated into the binding site, where it is released completely. The conformational restraining potential is based on the root-mean-square deviation of the peptide coordinates relative to its average conformation in the bound complex. Free energy contributions from each stage are calculated by means of free energy perturbation potential of mean force techniques by using appropriate order parameters. The present approach avoids the need to decouple the ligand from its surrounding (bulk solvent and receptor protein) as is traditionally performed in the double-decoupling scheme. It is believed that the present formulation will be particularly useful when the solvation free energy of the ligand is very large. As an application, the equilibrium binding constant of the phosphotyrosine peptide pYEEI to the Src homology 2 domain of human Lck has been calculated. The results are in good agreement with experimental values.     

Effect of a nutritional intervention promoting the Mediterranean food pattern on electrophoretic characteristics of low-density lipoprotein particles in healthy women from the Québec City metropolitan area

The objective of the present study was to evaluate the effect of a nutritional intervention promoting the Mediterranean food pattern in free-living conditions on LDL electrophoretic characteristics in a group of seventy-one healthy women, aged between 30 and 65 years. The 12-week nutritional intervention consisted of two courses on nutrition and seven individual sessions with a dietitian. The first course provided information on the Mediterranean food pattern and the second was a cooking lesson. LDL peak particle diameter (LDL-PPD) and cholesterol levels in small (LDL-cholesterol<255 A) and large LDL fractions (LDL-cholesterol>260 A) were obtained by 2-16 % polyacrylamide gel electrophoresis of whole plasma. The sample was divided on the basis of baseline LDL-PPD using tertiles of the distribution (258.4 A and 260.0 A). Among the total sample of women, no significant change in LDL-PPD was observed in response to the nutritional intervention. However, subjects who at baseline were in the first tertile of the LDL-PPD distribution (<258.4 A) showed a significant increase in LDL-PPD and in the proportion of LDL %>260 A in response to the 12-week nutritional intervention (P<0.05). In contrast, LDL-PPD decreased significantly (P=0.007) among women with large LDL particles at baseline (LDL-PPD >260 A) while the proportion of LDL %<255 A and of LDL %>260 A remained unchanged. To conclude, changes in the food pattern, in response to a nutritional intervention promoting the Mediterranean food pattern, were accompanied by beneficial modifications in LDL electrophoretic characteristics in women who were characterised at baseline by smaller LDL particles.     

Synchronous lesions detected by autofluorescence bronchoscopy in patients with high-grade preinvasive lesions and occult invasive squamous cell carcinoma of the proximal airways

The cancerization field concept implies that lung cancer multicentricity may be a frequent event and primary studies using white-light bronchoscopy (WLB) have reported a high prevalence of multicentricity in patients with roentgenographically occult lung cancer. We have used autofluorescence bronchoscopy (AFB) to reassess the prevalence of synchronous lesions in patients referred for the staging and/or treatment of occult lesions initially detected during WLB. All the patients referred with high-grade preinvasive lesions (severe dysplasia, DYS S and carcinoma in situ, CIS) and occult invasive squamous cell carcinoma (CIV) of the bronchus initially detected during WLB at other centers, underwent AFB. Data were prospectively collected and retrospectively analyzed to assess the prevalence of synchronous occult lesions. From January 1996 to December 2001, 28 patients (26 males, 2 females; mean age: 65 +/- 11) were assessed. After re-evaluation, in two cases, the referred lesions corresponded only to metaplasia and were discarded from analysis. The 26 other patients were referred for 28 lesions (3 DYS S, 19 CIS and 6 CIV; 2 patients were referred with two synchronous lesions). AFB revealed, in these 26 patients, six additional lesions (1 DYS S, 4 CIS and 1 CIV). Multicentricity in this group, initially estimated to amount to 7% with WLB alone, raised to 23% by using AFB. The high prevalence of synchronous lesions in this series of patients with occult DYS S, CIS and occult CIV suggests that AFB may be a useful adjunct in the pretreatment evaluation.     

Memantine enhances autonomy in moderate to severe Alzheimer's disease

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia and its course renders patients functionally disabled. Memantine is the first drug to demonstrate a clinical benefit in the treatment of patients with moderately-severe to severe AD. OBJECTIVES: Our objective was to illustrate the benefits of memantine on functional disability. METHODS: We classified 252 patients from a randomised 28-week clinical trial of memantine vs placebo according to their Activities of Daily Living capabilities measured by the ADCS-ADLsev scale. The scale was divided into two sub-scores: basic and instrumental. The relevance of this classification was validated by comparing clinical and socio-demographic parameters between the different autonomy classes (autonomous and dependent). The effect of memantine was estimated by using a logistic regression model on the autonomy status of patients at week 28, controlling for confounding factors (Observed Cases analysis). RESULTS: Our results showed that dependent patients (n = 106) had significantly longer disease duration, poorer cognition, greater severity, more behavioural alterations and higher total societal costs compared with autonomous patients (n = 146). When controlling for autonomy and severity at baseline, memantine-treated patients were three times more likely [Odds Ratio (OR) = 3.03; 95% Confidence Intervals (CI) = (1.38, 6.66)] to remain autonomous after 28 weeks. Analysis of the Treated Per Protocol set and the use of Last Observation Carried Forward analyses confirmed this finding. CONCLUSIONS: Memantine enhances autonomy in patients with moderately-severe to severe AD by increasing the probability of their remaining autonomous, therefore delaying transition to the dependent stage.     

Nuclear expression of S100B in oligodendrocyte progenitor cells correlates with differentiation toward the oligodendroglial lineage and modulates oligodendrocytes maturation

The S100B protein belongs to the S100 family of EF-hand calcium binding proteins implicated in cell growth and differentiation. Here, we show that in the developing and the adult mouse brain, S100B is expressed in oligodendroglial progenitor cells (OPC) committed to differentiate into the oligodendrocyte (OL) lineage. Nuclear S100B accumulation in OPC correlates with the transition from the fast dividing multipotent stage to the morphological differentiated, slow proliferating, pro-OL differentiation stage. In the adult, S100B expression is down-regulated in mature OLs that have established contacts with their axonal targets, suggesting a nuclear S100B function during oligodendroglial cells maturation. In vitro, the morphological transformation and maturation of pro-OL cells are delayed in the absence of S100B. Moreover, mice lacking S100B show an apparent delay in OPC maturation in response to demyelinating insult. We propose that nuclear S100B participates in the regulation of oligodendroglial cell maturation.