Dynamic Stability of Volatile Organic Compounds in Respiratory Air in Schizophrenic Patients and Its Potential Predicting Efficacy of TAAR Agonists.

OBJECTIVES: Volatile organic compounds (VOCs) in the breathing air were found to be altered in schizophrenia patients compared to healthy participants. The aim of this study was to confirm these findings and to examine for the first time whether these VOCs are stable or change in concentration during the early treatment course. Moreover, it was investigated whether there is a correlation of the VOCs with the existing psychopathology of schizophrenia patients, i.e., whether the concentration of masses detected in the breath gas changes when the psychopathology of the participants changes. METHODS: The breath of a total of 22 patients with schizophrenia disorder was examined regarding the concentration of VOCs using proton transfer reaction mass spectrometry. The measurements were carried out at baseline and after two weeks at three different time points, the first time immediately after waking up in the morning, after 30 min, and then after 60 min. Furthermore, 22 healthy participants were investigated once as a control group. RESULTS: Using bootstrap mixed model analyses, significant concentration differences were found between schizophrenia patients and healthy control participants (m/z 19, 33, 42, 59, 60, 69, 74, 89, and 93). Moreover, concentration differences were detected between the sexes for masses m/z 42, 45, 57, 69, and 91. Mass m/z 67 and 95 showed significant temporal changes with decreasing concentration during awakening. Significant temporal change over two weeks of treatment could not be detected for any mass. Masses m/z 61, 71, 73, and 79 showed a significant relationship to the respective olanzapine equivalents. The length of hospital stay showed no significant relationship to the masses studied. CONCLUSION: Breath gas analysis is an easy-to-use method to detect differences in VOCs in the breath of schizophrenia patients with high temporal stability. m/z 60 corresponding to trimethylamine might be of potential interest because of its natural affinity to TAAR receptors, currently a novel therapeutic target under investigation. Overall, breath signatures seemed to stable over time in patients with schizophrenia. In the future, the development of a biomarker could potentially have an impact on the early detection of the disease, treatment, and, thus, patient outcome.

Nobiletin acts anti-inflammatory on murine IL-10-/- colitis and human intestinal fibroblasts.

PURPOSE: Inflammatory bowel disease (IBD) shows increasing prevalence over the last years. We propose that anti-inflammatory plant substances could be used as additional or alternative agents with good compliance in prevention and/or therapy of IBD and its complication intestinal fibrosis. We could recently show that the citrus flavonoid nobiletin acts anti-inflammatory on activation of intestinal mast cells. Here, we analysed the effects of nobiletin on inflammation and fibrosis in IL-10-/- colitis. METHODS: IL-10-/- and wild-type (WT) mice were orally treated with/without vehicle or nobiletin. Clinical symptoms of colitis and disease activity index (DAI) were assessed, and colon tissue was analysed for tissue damage, cellular infiltration, bowel wall thickness, mast cell number and degranulation, as well as collagen deposition as marker for fibrosis. Human intestinal fibroblasts (hiFB) were treated with nobiletin and the expression of collagen and pro-inflammatory cytokines was measured. RESULTS: Nobiletin treatment of IL-10-/- mice resulted in a reduction of clinical colitis symptoms and a longer survival time. In addition, histological scores of colitis were reduced compared to control groups. Mast cell number and degranulation was lower in nobiletin treated IL-10-/- mice, and correlated positively with DAI. As well, fibrotic marker of collagen deposition was reduced by nobiletin. In hiFB, the expression of collagen as well as of pro-inflammatory cytokines IL-6, TNF and CCL2 was down-regulated by nobiletin treatment. CONCLUSIONS: Nobiletin decreases inflammatory symptoms and markers in murine colitis as well as fibrotic collagen deposition and expression. Thus, nobiletin could be a potential new agent in therapy of chronic colitis.

Ranking the effectiveness of autologous blood conservation measures through validated modeling of independent clinical data.

BACKGROUND: Future supply with allogeneic blood transfusions faces several crucial challenges that warrant thorough (re-)evaluation of existing alternatives. Meta-analyses have indicated a significant potential for autologous blood conservation (ABC) measures to reduce the need for allogeneic blood transfusions. The quality of currently available studies, however, prohibits definite conclusions. Under these circumstances, mathematical modeling offers unique opportunities to compare various ABC measures and to test the impact of different variables on efficacy and effectiveness. STUDY DESIGN AND METHODS: We performed an extensive search for clinical ABC studies, focusing on acute normovolemic hemodilution (ANH), intraoperative blood salvage (IBS), or preoperative autologous deposit (PAD). Only ABC studies providing a minimum set of clinical variables were included. Using a clinically validated mathematical model, we then calculated maximal allowable blood loss (efficacy) and increase in red blood cell (RBC) mass (effectiveness) to rank the three techniques. RESULTS: We identified 21 clinical ABC studies, including 3926 patients, as suitable for our model. Our model shows that IBS with high recovery rates is the most efficacious and effective ABC measure. PAD will reveal nearly similar efficacy and effectiveness, only if sufficient time for RBC regeneration has passed and if 4 PAD units or more are available. Our model further demonstrates that ANH as well as IBS with low recovery rates are the least efficacious and effective alternatives. CONCLUSIONS: IBS appears to be the most efficacious and effective ABC measure. PAD can only reduce the need for allogeneic blood transfusions under certain circumstances. ANH does not appear to play an important role in ABC.