BackgroundExhaled 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.MethodsBreath 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.ResultsThe 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).ConclusionMeasurements of exhaled VOCs by a double cold-trap method may help diagnose lung cancer and monitor its progression and regression.
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.
Abstract. Serotonin 2C receptor (5-HT2CR) mRNA receives editing at 5 nucleotide positions (sites A -E) located in the sequence encoding the second intracellular loop of 5-HT2CR. 5-HT2CR mRNA without editing and with editing at sites AB, ABD, ABC, ABCD, and C are translated to 6 isoforms of 5-HT2CR: INI(non-edited), VNI(AB), VNV(ABD), VSI(ABC), VSV(ABCD), and ISI(C), respectively. In this study, we investigated electrophysiologically the ability of these isoforms to couple with the G protein / phospholipase C (PLC) system using Xenopus oocytes injected with edited 5-HT2CR RNAs and muscarinic M 1 receptor (M1R) RNA. The efficacy with which 5-HT stimulated each isoform was calculated by comparing 5-HT-induced current with 100 μ M acetylcholine-induced M1R current. Stimulation with 5-HT of INI(non-edited), VNI(AB), VNV(ABD), VSI(ABC), VSV(ABCD), and ISI(C) expressed in Xenopus oocytes showed concentration-dependent responses with EC 50 values of 8.6, 17.2, 76,5, 22.0, 91.2, and 20.3 nM, respectively. No significant difference in the ability of 5-HT to induce currents among the oocytes expressing these isoforms was detected, but in the oocytes expressing VSI(ABC) or VSV(ABCD), 5-HT had a significantly reduced ability to induce currents. These results suggest that editing at site C together with sites A and B and/or D markedly reduces 5-HT2CR function by generating isoforms with reduced ability to activate PLC.
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.
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.
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