Peroxisome proliferating activating receptor gamma-independent attenuation of interleukin 6 and interleukin 8 secretion from primary endometrial stromal cells by thiazolidinediones

To assess the effect of thiazolidinediones on the regulation of inflammatory cytokines related to endometriosis in endometrial tissue and determine whether these effects occur via activation of the peroxisome proliferating activating receptor gamma (PPAR)-γ.

Frontal areas contribute to reduced global coordination of resting-state gamma activities in drug-naïve patients with schizophrenia

Schizophrenia has been postulated to involve impaired neuronal cooperation in large-scale neural networks, including cortico-cortical circuitry. Alterations in gamma band oscillations have attracted a great deal of interest as they appear to represent a pathophysiological process of cortical dysfunction in schizophrenia. Gamma band oscillations reflect local cortical activities, and the synchronization of these activities among spatially distributed cortical areas has been suggested to play a central role in the formation of networks. To assess global coordination across spatially distributed brain regions, Omega complexity (OC) in multichannel EEG was proposed. Using OC, we investigated global coordination of resting-state EEG activities in both gamma (30–50 Hz) and below-gamma (1.5–30 Hz) bands in drug-naïve patients with schizophrenia and investigated the effects of neuroleptic treatment. We found that gamma band OC was significantly higher in drug-naïve patients with schizophrenia compared to control subjects and that a right frontal electrode (F3) contributed significantly to the higher OC. After neuroleptic treatment, reductions in the contribution of frontal electrodes to global OC in both bands correlated with the improvement of schizophrenia symptomatology. The present study suggests that frontal brain processes in schizophrenia were less coordinated with activity in the remaining brain. In addition, beneficial effects of neuroleptic treatment were accompanied by improvement of brain coordination predominantly due to changes in frontal regions. Our study provides new evidence of improper intrinsic brain integration in schizophrenia by investigating the resting-state gamma band activity.

Radiation metabolomics. 4. UPLC-ESI-QTOFMS-Based metabolomics for urinary biomarker discovery in gamma-irradiated rats

Radiation metabolomics has aided in the identification of a number of biomarkers in cells and mice by ultra-performance liquid chromatography-coupled time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) and in rats by gas chromatography-coupled mass spectrometry (GCMS). These markers have been shown to be both dose- and time-dependent. Here UPLC-ESI-QTOFMS was used to analyze rat urine samples taken from 12 rats over 7 days; they were either sham-irradiated or γ-irradiated with 3 Gy after 4 days of metabolic cage acclimatization. Using multivariate data analysis, nine urinary biomarkers of γ radiation in rats were identified, including a novel mammalian metabolite, N-acetyltaurine. These upregulated urinary biomarkers were confirmed through tandem mass spectrometry and comparisons with authentic standards. They include thymidine, 2'-deoxyuridine, 2'deoxyxanthosine, N(1)-acetylspermidine, N-acetylglucosamine/galactosamine-6-sulfate, N-acetyltaurine, N-hexanoylglycine, taurine and, tentatively, isethionic acid. Of these metabolites, 2'-deoxyuridine and thymidine were previously identified in the rat by GCMS (observed as uridine and thymine) and in the mouse by UPLC-ESI-QTOFMS. 2'Deoxyxanthosine, taurine and N-hexanoylglycine were also seen in the mouse by UPLC-ESI-QTOFMS. These are now unequivocal cross-species biomarkers for ionizing radiation exposure. Downregulated biomarkers were shown to be related to food deprivation and starvation mechanisms. The UPLC-ESI-QTOFMS approach has aided in the advance for finding common biomarkers of ionizing radiation exposure.

The production and composition of rat sebum is unaffected by 3 Gy gamma radiation

The aim of this work was to use metabolomics to evaluate sebum as a source of biomarkers for gamma-radiation exposure in the rat, and potentially in man. Proof of concept of radiation metabolomics was previously demonstrated in both mouse and rat urine, from the radiation dose- and time-dependent excretion of a set of urinary biomarkers.

Improved sensitivity of an interferon-gamma release assay (T-SPOT.TB™) in combination with tuberculin skin test for the diagnosis of latent tuberculosis in the presence of HIV co-infection

Background Interferon-gamma release assays (IGRA) are more specific than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis infection. Data on sensitivity are controversial in HIV infection. Methods IGRA (T-SPOT.TB) was performed using lymphocytes stored within 6 months before culture-confirmed tuberculosis was diagnosed in HIV-infected individuals in the Swiss HIV Cohort Study. Results 64 individuals (69% males, 45% of non-white ethnicity, median age 35 years (interquartile range [IQR] 31-42), 28% with prior AIDS) were analysed. Median CD4 cell count was 223 cells/μl (IQR 103-339), HIV-RNA was 4.7 log10 copies/mL (IQR 4.3-5.2). T-SPOT.TB resulted positive in 25 patients (39%), negative in 18 (28%) and indeterminate in 21 (33%), corresponding to a sensitivity of 39% (95% CI 27-51%) if all test results were considered, and 58% (95% CI 43-74%) if indeterminate results were excluded. Sensitivity of IGRA was independent of CD4 cell count (p = 0.698). Among 44 individuals with available TST, 22 (50%) had a positive TST. Agreement between TST and IGRA was 57% (kappa = 0.14, p = 0.177), and in 34% (10/29) both tests were positive. Combining TST and IGRA (at least one test positive) resulted in an improved sensitivity of 67% (95% CI 52-81%). In multivariate analysis, older age was associated with negative results of TST and T-SPOT.TB (OR 3.07, 95% CI 1,22-7.74, p = 0.017, per 10 years older). Conclusions T-SPOT.TB and TST have similar sensitivity to detect latent TB in HIV-infected individuals. Combining TST and IGRA may help clinicians to better select HIV-infected individuals with latent tuberculosis who qualify for preventive treatment.

Characterisation and optimisation of the new Prompt Gamma-ray Activation Analysis (PGAA) facility at FRM II

At the research reactor Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II) a new Prompt Gamma-ray Activation Analysis (PGAA) facility was installed. The instrument was originally built and operating at the spallation source at the Paul Scherrer Institute in Switzerland. After a careful re-design in 2004–2006, the new PGAA instrument was ready for operation at FRM II. In this paper the main characteristics and the current operation conditions of the facility are described. The neutron flux at the sample position can reach up 6.07×1010 [cm−2 s−1], thus the optimisation of some parameters, e.g. the beam background, was necessary in order to achieve a satisfactory analytical sensitivity for routine measurements. Once the optimal conditions were reached, detection limits and sensitivities for some elements, like for example H, B, C, Si, or Pb, were calculated and compared with other PGAA facilities. A standard reference material was also measured in order to show the reliability of the analysis under different conditions at this instrument.

Is gamma band EEG synchronization reduced during auditory driving in schizophrenia patients with auditory verbal hallucinations?

Auditory verbal hallucinations (AVH) in schizophrenia patients assumingly result from a state inadequate activation of the primary auditory system. We tested brain responsiveness to auditory stimulation in healthy controls (n=26), and in schizophrenia patients that frequently (n=18) or never (n=11) experienced AVH. Responsiveness was assessed by driving the EEG with click-tones at 20, 30 and 40Hz. We compared stimulus induced EEG changes between groups using spectral amplitude maps and a global measure of phase-locking (GFS). As expected, the 40Hz stimulation elicited the strongest changes. However, while controls and non-hallucinators increased 40Hz EEG activity during stimulation, a left-lateralized decrease was observed in the hallucinators. These differences were significant (p=.02). As expected, GFS increased during stimulation in controls (p=.08) and non-hallucinating patients (p=.06), which was significant when combining the two groups (p=.01). In contrast, GFS decreased with stimulation in hallucinating patients (p=0.13), resulting in a significantly different GFS response when comparing subjects with and without AVH (p<.01). Our data suggests that normally, 40Hz stimulation leads to the activation of a synchronized network representing the sensory input, but in hallucinating patients, the same stimulation partly disrupts ongoing activity in this network.