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.     

Antemortem MRI based STructural Abnormality iNDex (STAND)-scores correlate with postmortem Braak neurofibrillary tangle stage

The clinical diagnosis of Alzheimer's disease (AD) does not exactly match the pathological findings at autopsy in every subject. Therefore, in-vivo imaging measures, such as Magnetic Resonance Imaging (MRI) that reflect underlying pathology, would be clinically useful independent supplementary measures of disease stage. We have developed an algorithm that extracts atrophy information from individual patient's 3D MRI scans and assigns a STructural Abnormality iNDex (STAND)-score to the scan based on the degree of atrophy in comparison to patterns extracted from a large library of clinically well characterized AD and CN (cognitively normal) subject's MRI scans. STAND-scores can be adjusted for demographics to give adjusted-STAND (aSTAND)-scores which are >0 for subjects with brains identified as abnormal by the algorithm. Since histopathological findings are considered to represent the "ground truth", our objective was to assess the sensitivity of aSTAND-scores to pathological AD staging. This was done by comparing antemortem MRI based aSTAND-scores with postmortem grading of disease severity in 101 subjects who had both antemortem MRI and postmortem Braak neurofibrillary tangle (NFT) staging. We found a rank correlation of 0.62 (p<0.0001) between Braak NFT stage and aSTAND-scores. The results show that optimally extracted information from MRI scans such as STAND-scores accurately capture the severity of neuronal pathology and can be used as an independent approximate surrogate marker for in-vivo pathological staging as well as for early identification of AD in individual subjects.     

Alzheimer's disease diagnosis in individual subjects using structural MR images: validation studies

OBJECTIVE: To develop and validate a tool for Alzheimer's disease (AD) diagnosis in individual subjects using support vector machine (SVM)-based classification of structural MR (sMR) images. BACKGROUND: Libraries of sMR scans of clinically well characterized subjects can be harnessed for the purpose of diagnosing new incoming subjects. METHODS: One hundred ninety patients with probable AD were age- and gender-matched with 190 cognitively normal (CN) subjects. Three different classification models were implemented: Model I uses tissue densities obtained from sMR scans to give STructural Abnormality iNDex (STAND)-score; and Models II and III use tissue densities as well as covariates (demographics and Apolipoprotein E genotype) to give adjusted-STAND (aSTAND)-score. Data from 140 AD and 140 CN were used for training. The SVM parameter optimization and training were done by four-fold cross validation (CV). The remaining independent sample of 50 AD and 50 CN was used to obtain a minimally biased estimate of the generalization error of the algorithm. RESULTS: The CV accuracy of Model II and Model III aSTAND-scores was 88.5% and 89.3%, respectively, and the developed models generalized well on the independent test data sets. Anatomic patterns best differentiating the groups were consistent with the known distribution of neurofibrillary AD pathology. CONCLUSIONS: This paper presents preliminary evidence that application of SVM-based classification of an individual sMR scan relative to a library of scans can provide useful information in individual subjects for diagnosis of AD. Including demographic and genetic information in the classification algorithm slightly improves diagnostic accuracy.     

The role of androgens on periodontal repair in female rats

1 Background

Testosterone replacement enhances cognitive function and musculoskeletal health in postmenopausal women. However, the biological role of testosterone on inflammation and bone metabolism in females is not well understood. Our objective was to measure the impact of androgens and their receptors on periodontal tissues during periodontal repair in female rats.

2 Methods

Seventy female Holtzman rats were divided into seven groups (n = 10/group): negative control; repair control; androgen receptor antagonist (flutamide, 50 mg/kg, every other day); estrogen receptor antagonist (fulvestrant, 1.5 mg/kg/day); testosterone supplementation (durateston, 250 mg/kg, weekly); aromatase inhibitor (anastrozole, 0.2 mg /kg/day); testosterone plus anastrozole. Cotton ligatures were kept for 13 days, when pharmacological treatment was initiated. On day 14, the ligatures were removed. The rats were euthanized on the 17^th or the 28^th day (n = 5/group/period) for the evaluation of markers related to inflammation and bone. The tissue and serum samples were evaluated using a multiplexed immunoassay for the inflammatory targets. Radiographic and histologic analyses were performed to assess changes in tissues.

3 Results

Blockage of androgen receptors had little effect on inflammatory cell count, although it tended to increase interleukin (IL)‐4, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) as well as decrease IL‐1β, tumor necrosis factor (TNF)‐α, and IL‐6. Flutamide also significantly impaired bone repair (P < 0.05) and had greater osteoclast count, although this last difference was not statistically significant. Testosterone supplementation significantly increased the inflammatory cell count, decreased the levels of IL‐4, IL‐10, IL‐1β, IL‐6, and TNF‐α; and increased VEGF and EGF.

4 Conclusion

The blockage of androgen receptors significantly impair bone repair in females through mechanisms that are different from those related to estrogen receptors.