Acute Effects of a Fungal Volatile Compound

Objective: 3-Methylfuran (3-MF) is a common fungal volatile product with active biologic properties, and previous studies have indicated a contribution to airway disease. The aim of the present study was to assess the acute health effects of this compound in humans. Design: Acute effects were assessed via chamber exposure to (1 mg/m(3)) 3-MF. Participants and measurements: Twenty-nine volunteers provided symptom reports, ocular electromyograms, measurement of eye tear film break-up time, vital staining of the eye, nasal lavage, acoustic rhinometry, transfer tests, and dynamic spirometry. Results: No subjective ratings were significantly increased during exposure. Blinking frequency and the lavage biomarkers myeloperoxidase and lysozyme were significantly increased, and forced vital capacity was significantly decreased during exposure to 3-MF compared with air control. Conclusions and relevance to clinical practice: Acute effects in the eyes, nose, and airways were detected and might be the result of the biologically active properties of 3-MF. Thus, 3-MF may contribute to building-related illness

Chronic Citalopram Administration Causes a Sustained Suppression of Serotonin Synthesis in the Mouse Forebrain

BACKGROUND:Serotonin (5-HT) is a neurotransmitter with important roles in the regulation of neurobehavioral processes, particularly those regulating affect in humans. Drugs that potentiate serotonergic neurotransmission by selectively inhibiting the reuptake of serotonin (SSRIs) are widely used for the treatment of psychiatric disorders. Although the regulation of serotonin synthesis may be an factor in SSRI efficacy, the effect of chronic SSRI administration on 5-HT synthesis is not well understood. Here, we describe effects of chronic administration of the SSRI citalopram (CIT) on 5-HT synthesis and content in the mouse forebrain. METHODOLOGY/PRINCIPAL FINDINGS:Citalopram was administered continuously to adult male C57BL/6J mice via osmotic minipump for 2 days, 14 days or 28 days. Plasma citalopram levels were found to be within the clinical range. 5-HT synthesis was assessed using the decarboxylase inhibition method. Citalopram administration caused a suppression of 5-HT synthesis at all time points. CIT treatment also caused a reduction in forebrain 5-HIAA content. Following chronic CIT treatment, forebrain 5-HT stores were more sensitive to the depleting effects of acute decarboxylase inhibition. CONCLUSIONS/SIGNIFICANCE:Taken together, these results demonstrate that chronic citalopram administration causes a sustained suppression of serotonin synthesis in the mouse forebrain. Furthermore, our results indicate that chronic 5-HT reuptake inhibition renders 5-HT brain stores more sensitive to alterations in serotonin synthesis. These results suggest that the regulation of 5-HT synthesis warrants consideration in efforts to develop novel antidepressant strategies