Various volatile organic compounds (VOCs) are known to be toxic. Although exhaled VOC patterns change in obstructive sleep apnea (OSA) patients, individual VOC profiles are not fully determined. The primary outcome was VOC characterizations; secondary outcomes included their relationships with sleep and clinical parameters in OSA patients. We prospectively examined 32 OSA patients with an apnea-hypopnea index (AHI) ≥ 15 by full polysomnography, and 33 age- and sex-matched controls without obvious OSA symptoms. Nine severe OSA patients were examined before and after continuous positive airway pressure (CPAP) treatment. By applying a method which eliminates environmental VOC influences, exhaled VOCs were identified by gas chromatography (GC)-mass spectrometry, and their concentrations were determined by GC. Exhaled aromatic hydrocarbon concentrations (toluene, ethylbenzene, p-xylene, and phenylacetic acid) in the severe OSA groups (AHI ≥ 30) and exhaled saturated hydrocarbon concentrations (hexane, heptane, octane, nonane, and decane) in the most severe OSA group (AHI ≥ 60) were higher than those in the control group. Exhaled isoprene concentrations were increased in all OSA groups (AHI ≥ 15); acetone concentration was increased in the most severe OSA group. Ethylbenzene, p-xylene, phenylacetic acid, and nonane concentrations were increased according to OSA severity, and correlated with AHI, arousal index, and duration of percutaneous oxygen saturation (SpO2) ≤ 90%. Multiple regression analyses revealed these 4 VOC levels were associated with the duration of SpO2 ≤ 90%. Isoprene and acetone decreased after CPAP treatment. OSA increased some toxic VOCs, and some correlated with OSA severity. CPAP treatment possibly ameliorates these productions.
An electrophysiological bioassay was used to isolate the active compound from Hochuekkito (HET), which the current authors previously described as having potent agonist action against serotonin 2C receptors (5-HT2CR). Synthetic 5-HT2CR mRNA was injected into Xenopus oocytes to specifically express these receptors. Crude extracts and purified products were subjected to an electrophysiological bioassay using the voltage clamp method. HET stimulated a 5-HT2CR-induced current response, whereas Juzentaohoto (JTT), which has anti-depressive action similar to that of HET, did not. Current responses were not observed with an extract mixed with five types of herbal medicines common to HET and JTT but were detected with an extract with the five types of herbal medicines found in HET alone (Hoc5). When the responses to each of the five types of Hoc5 were examined, current responses were noted with Cimicifugae rhizoma (CR) and Citrus unshiu Markovich extracts. Since efficacy and the EC50 value were higher for CR, its constituents were separated using three-dimensional high-performance liquid chromatography and the current response at each of the isolated peaks was examined. One constituent displayed a strong response and was identified as a single substance with a molecular weight of 283.1393 based on liquid chromatography/mass spectrometry. These results will contribute to the isolation of 5-HT2CR-stimulating constituents in HET and the identification of trace constituents with agonist action.
Exhaled volatile organic compounds (VOC) are being considered as biomarkers for various lungs diseases, including cancer. However, the accurate measurement of extremely low concentrations of VOC in expired air is technically challenging. We evaluated the clinical contribution of exhaled VOC measured with a new, double cold-trap method in the diagnosis of lung cancer.Breath samples were collected from 116 patients with histologically confirmed lung cancer and 37 healthy volunteers (controls) after inspiration of purified air, synthesized through a cold-trap system. The exhaled VOC, trapped in the same system, were heat extracted. We analyzed 14 VOC with gas chromatography.The concentrations of exhaled cyclohexane and xylene were significantly higher in patients with lung cancer than in controls (p = 0.002 and 0.0001, respectively), increased significantly with the progression of the clinical stage of cancer (both p < 0.001), and decreased significantly after successful treatment of 6 patients with small cell lung cancer (p = 0.06 and 0.03, respectively).Measurements of exhaled VOCs by a double cold-trap method may help diagnose lung cancer and monitor its progression and regression.
A new concept expired gas measurement system used double cold-trap method was developed. The system could detect selectively volatile organic compound (VOC) derived from the human body. The gas chromatography (GC) profiles of healthy volunteer's expired gas collected by our system were analyzed. As a result, 60 VOCs were detected from the healthy volunteer's expired gas. We examined 14 VOCs among them further, which could be converted to the concentration from the GC profiles. The concentration of almost VOCs decreased when the subjects inspired purified air compared with the atmosphere. On the other hand, isoprene was almost the same. It was strongly suggested that these VOCs were derived from the human body because the concentration of these VOCs in the atmosphere were nearly zero. Expired gas of two sleep apnea syndrome (SAS) patients were analyzed as preliminary study. As a result of the study, the concentration of some VOCs contained in the expired gas of the SAS patients showed higher value than a healthy controls.
Volatile organic compounds (VOCs) are organic chemical substances that volatilize easily in ambient air at normal temperature and pressure.VOCs in human expired gas have been reported to be useful in the diagnosis of various diseases, but measurement of VOCs in human expired gas is technically dif cult because the concentrations in expired gas are extremely low and almost the same as the concentrations in ambient air.Accurate VOC measurement usually requires a large system, and no VOC measuring systems suitable for clinical practice are available.We developed a compact, simple, double cold trap system that can measure the concentrations of VOCs originating in humans.Our system detects a limited number of VOCs with very high sensitivity at concentrations as low as 0.05 ppb.We evaluated the reproducibility of our system and measured VOCs in ambient air, puri ed air, and human expired gas from smokers, non-smokers, and patients.Errors of ±10% seem unavoidable in our system.Our veri cation experiment using human expired gas strongly suggests that the reproducibility and detection sensitivity of our system allow the detection of most VOCs in human expired gas.
Diverse biological activities of 7 healthy foods [powdered pine needle, citrate-fermented sesame, powdered coffee, royal jelly, propolis, pollen and white sesame oil (extracted by super critical state (40 degrees C, 350 atmospheric pressure))] were investigated. The pine needle, sesame and powdered coffee was also extracted successively by ethanol and hot water, and lyophilized. The pine needle and coffee extracts, and propolis showed higher in vitro cytotoxic, bactericidal and oxidation activity, as compared with other 4 lipophilic healthy foods. However, propolis showed slightly lower, but significant cytotoxic and bactericidal activity with much reduced oxidation potential. ESR spectroscopy demonstrated that the cytotoxic activity of these extracts was closely related to their radical generation and O2- scavenging activities. Healthy food components may have both pro-oxidant and anti-oxidant properties. Pre-treatment of mice with pine needle, sesame or powdered coffee extract significantly reduced the lethality of bacterial infection, possibly due to their host-mediated action. These extracts failed to reduce the cytophatic effect of HIV-1 (human immunodeficiency virus) infection in MT-4 cells. No apparent acute toxicity was detected in mice by oral administration of 10 g/kg of these extracts. This data suggest the medicinal efficacy of healthy foods.
