The change in plasma GABA,glutamine and glutamate levels in fluoxetine- or S-citalopram-treated female patients with major depression

Objective  The aim of this study was to investigate the relationship between plasma glutamate, glutamine and γ-aminobutyric acid (GABA) levels in female patients with major depression treated with S-citalopram or fluoxetine. Methods  The patients were assigned into S-citalopram (10 mg/day) or fluoxetine (20 mg/day) groups (n = 15 per group). The Hamilton and Beck Depression Inventory Scales were performed on all study participants, and blood samples were collected. The same procedures were repeated 10 days following the onset of therapy. Fifteen female healthy volunteers were also included in the study for the evaluation of normal plasma levels. Results  The plasma GABA levels of the healthy volunteers were higher whereas those for glutamate and glutamine were lower than the day zero samples of the patients. An increase in plasma GABA levels and a decrease in glutamate and glutamine levels were observed on the 10th day of treatment. No difference was detected between the drug treatments. Conclusion  Our findings may suggest that GABA, glutamate and glutamine play a role in depression and that plasma GABA may be used as a biomarker for treatment control.     

TMC–MCC (N-trimethyl chitosan–mono-N-carboxymethyl chitosan) nanocomplexes for mucosal delivery of vaccines

In this study, for the first time, TMC/MCC complex nanoparticles as a delivery system and as an adjuvant were developed and evaluated to obtain systemic and mucosal immune responses against nasally administered tetanus toxoid (TT). Nanoparticles were developed by complexation between the oppositely charged chitosan derivatives, N-trimethyl chitosan (TMC, polycationic) and mono-N-carboxymethyl chitosan (MCC, polyampholytic) without using any crosslinker for mucosal vaccination. The cellular viability was found to be higher with TMC/MCC complex compared to that of MCC and TMC alone. Size, zeta potential and morphology of the nanoparticles were investigated as a function of preparation method. Nanoparticles with high loading efficacy (95%) and positively charged surface were obtained with an average particle size of 283 ± 2.5 nm. The structural integrity of the TT in the nanoparticles was confirmed by SDS–PAGE electrophoresis analysis. Cellular uptake studies indicated that FITC-BSA loaded nanoparticles were effectively taken up into the mouse Balb/c monocyte macrophages. Mice were nasally immunized with TT loaded TMC/MCC complex nanoparticles and compared to that of TMC and MCC nanoparticles. TMC/MCC complex nanoparticles were shown to induce both the mucosal and systemic immune response indicating that this newly developed system has potential for mucosal administration of vaccines.     

Acute sleep deprivation is associated with increased QT dispersion in healthy young adults

Background: Sleep deprivation (SD) is known to be associated with worse cardiovascular outcome including mortality. We investigated the association between acute SD and electrocardiographic maximum QT interval (QTmax), QT, and corrected QT dispersion (QTd/cQTd), which are known to be among predictors of ventricular arrhythmias and sudden death.
Methods: We obtained electrocardiograms of 37 healthy young volunteers (age: 28.45 ± 7.97 years; 11 women) after a night with regular sleep and repeated after a night with sleep debt. We measured minimum QT interval (QTmin), QTmax, QTd, and cQTd in milliseconds.
Results: Average sleep time of the subjects were 7.7 ± 0.8 hours during regular sleep and 1.7 ± 1.6 hours during a night with sleep debt (P < 0.001). Subjects had similar values of QTmin in milliseconds after a night of sleep debt when compared to after regular sleep (347.56 ± 29.75 vs 344.59 ± 20.89; P = 0.51), whereas they had significantly higher values of QTmax, QTd, and cQTd (396.48 ± 30.11 vs 378.10 ± 23.90; P = 0.001, 49.45 ± 9.11 vs 33.51 ± 10.05; P < 0.001 and 54.92 ± 10.42 vs 37.23 ± 10.81; P < 0.001, respectively). In Pearson's correlation analysis, QTmax, QTd, and cQTd were inversely correlated with sleep time (P = 0.012, r =–0.291; P < 0.001, r =–0.625 and P < 0.001, r =–0.616, respectively)
Conclusions: In conclusion, we clearly demonstrated that even one night of SD is associated with significant increase in QTmax, QTd, and cQTd in healthy young adults despite remaining within normal limits. These electrocardiographic changes in acute SD might contribute to development and/or recurrence of arrhythmias. This implication deserves further studies for clarifying the possible linkage between SD and arrhythmias.     

Assessment of Endothelial Function in Alzheimer's Disease: Is Alzheimer's Disease a Vascular Disease?

OBJECTIVES: To compare endothelial function of people with Alzheimer's disease (AD) with that of people without. DESIGN: Case-control study. SETTING: Geriatric medicine outpatient clinic of a university hospital. PARTICIPANTS: Twenty-five patients with AD who were free of vascular risk factors and 24 healthy elderly controls were enrolled. Exclusion criteria were diabetes mellitus, hypertension, dyslipidemia, evident stroke, smoking, documented coronary artery disease, history of myocardial infarction, heart failure, acute or chronic infection, malignancy, peripheral artery disease, renal disease, rheumatologic diseases, alcohol abuse, and certain drugs that may affect endothelial function. Both groups underwent comprehensive geriatric assessment and neuropsychiatric assessment. MEASUREMENTS: Endothelial function was evaluated according to flow-mediated dilation (FMD) from the brachial artery. RESULTS: Mean age +/- standard deviation was 78 +/- 5.9 in the group with AD (11 female and 14 male) and 72.1 +/- 5.8 in the control group (9 female and 11 male). Multiple linear regression analysis revealed that FMD was significantly lower in patients with AD (median 3.45, range 0-7) than controls (median 8.41, range 1-14) (P < .001), independent of age. It was also found that FMD values were inversely correlated with the stage of the disease as determined according to the Clinical Dementia Rating scale (r=-0.603, P < .001). CONCLUSION: Endothelial function is impaired in patients with AD. Endothelial function was worse in patients with severe AD. These findings provide evidence that vascular factors have a role in the pathogenesis of AD.