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The effects of lung water compartments (WCs) on the fast nuclear magnetic resonance (NMR) transverse relaxation time (T2f) and T2 slow (T2s) decay curves were analyzed in peripheral lung tissues. Analysis of multiexponential NMR T2 decay curves in peripheral lung tissues indicated the direct relationship of alveolar wall WCs to T2f NMR components compared to T2s. The relationship between alveolar WCs and T2f was also exhibited by the effects of intravascular osmotic pressure on pulmonary intracellular water.

Tsuji, Chizuko, Sumie Shioya, Yuki Hirota, Naoto Fukuyama, Daisaku Kurita, Toshimori Tanigaki, Yasuyo Ohta, and Hiroe Nakazawa. Increased production of nitrotyrosine in lung tissue of rats with radiation-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol 278: L719-L725, 2000.--The purposes of this study were 1) to identify the nitric oxide (NO) synthase (NOS) isoform responsible for NO-mediated radiation-induced lung injury, 2) to examine the formation of nitrotyrosine, and 3) to see whether nitrotyrosine formation and lung injury are reduced by an inducible NOS (iNOS) inhibitor, aminoguanidine. The left hemithorax of rats was irradiated (20 Gy), and the degree of lung injury, the expression of NOS isoforms, and the formation of nitrotyrosine and superoxide were examined after 2 wk. iNOS mRNA was induced, and endothelial NOS mRNA was markedly increased in the irradiated lung. Nitrotyrosine was detected biochemically and immunohistochemically. Aminoguanidine prevented acute lung injury as indicated by decreased protein concentration and lactate dehydrogenase activity in bronchoalveolar lavage fluid and improved NMR parameters and histology. Furthermore, the formation of nitrotyrosine was significantly reduced in the aminoguanidine group. We conclude that iNOS induction is a major factor in radiation-induced lung injury and that nitrotyrosine formation may participate in the NO-induced pathogenesis. nitric oxide; nitric oxide synthase; aminoguanidine

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., (© The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

In most clinical laboratories, low density lipoprotein (LDL) cholesterol is usually estimated indirectly with the Friedewald equation or directly with the N-geneous assay. We assessed LDL-cholesterol values obtained by both methods to find an appropriate fasting period and to assess the influence of the energy content of the last meal. Blood samples were taken from 28 healthy volunteers who had consumed a standard meal (107 g of carbohydrate, 658 kcal) followed by a fasting period of 12 and 18 h, or a high-energy meal (190 g of carbohydrate, 1011 kcal) with a fasting period of 12 h. Prolongation of the fasting period from 12 h to 18 h decreased glucose level, but did not decrease triacylglycerol, total cholesterol, or high density lipoprotein (HDL) cholesterol. LDL-cholesterol levels measured with the N-geneous assay did not change (94.0 +/- 21.5 to 96.3 +/- 19.1 mg/dl). LDL-cholesterol levels calculated with the Friedewald equation were also similar after fasting periods of 12 h (98.5 +/- 21.4 mg/dl) and 18 h (99.7 +/- 20.2 mg/dl). The high-energy meal did not change the level of LDL-cholesterol measured with the N-geneous assay (96.1 +/- 21.2 mg/dl), or the glucose, triacylglycerol, total cholesterol, or HDL-cholesterol level, but LDL-cholesterol levels evaluated from the Friedewald equation (92.6 +/- 20.3 mg/dl) became significantly lower. A fasting time longer than 12 h is not necessary to obtain reasonable blood lipid levels. The Friedewald equation gave higher LDL-cholesterol levels than N-geneous assay in young Japanese females who had eaten a low-energy meal, and lower values when they had eaten a high-energy meal. Thus, it may be necessary to pay attention to energy of nigh meal prior to blood withdrawal.

Objectives: Atheroma with reduced collagen content becomes fragile, but the underlying mechanisms have not been established. We investigated the influence of inducible nitric oxide synthase (iNOS) induction upon matrix metalloproteinases (MMP)s and collagen content in atheroma., Methods and Results: ApoE-/- x iNOS-/- double knockout and ApoE-/- x iNOS+/+ mice were fed a high-cholesterol diet for 15 weeks. Large atheromatous lesions of comparable size appeared in the roof of the aorta in both strains. Induction of iNOS mRNA was observed only in the atheroma of the ApoE-/-/iNOS+/+ mice. Collagen content was sparse and fat droplets were increased. Gelatin zymography and in situ zymography showed that pro- and active forms of MMP-2 and MMP-9 were more strongly expressed in ApoE-/-/iNOS+/+ than in ApoE-/-/iNOS-/- mice, nitrotyrosine and MMP-9 were co-expressed in the atheroma., Conclusion: We conclude that induction of iNOS in atheroma of high-cholesterol-fed ApoE-/-/iNOS+/+ mice leads to increased production and activation of MMPs, with a subsequent decrease in collagen content, affording fragile plaque.

Unlabelled: Chronic obstructive pulmonary disease (COPD) is characterized by obstructive bronchiolitis and parenchymal destruction. In animal models, air space enlargement induced by intratracheal elastase is augmented by prior depletion of lung hyaluronan by hyaluronisase. Recently our colleagues reported that intravenous hyaluronisaein in the absence of elastase produced emphysema-like alveolar dilation [1]. In this study we measured functional residual capacity (FRC) and airway resistance (Raw) in the rats with hyaluronidaseinduced experimental COPD., Materials and Methods: Hyaruonidase (20 mg/kg) was administered from the caudal vein of 19 male Wistar rats (COPD rats). Two weeks after the injection, FRC and Raw were measured with bodyplethysmogarph., Results: Thickness or inflammatory cell infiltrations were not apparent in the bronchus of the COPD rat while alveolar distension was obvious. The mean FRC of the COPD rats (6.22 ± 1.00 ml, mean ± SD) was significantly larger than that of Control rats (5.48 ± 0.85 ml). There was no statistical significance between the mean Raw of the COPD rats (0.28 ± 0.08 cmH2O/ml/s) and that of the control rats (0.28 ± 0.13 cmH2O/ml/s)., Conclusion: Systemic administration of hyaluronidase produced pulmonary overinflation but did not bronchial constriction. We speculate that hyaluonidase-induced COPD simulates panlobular emphysema.

The role of inducible nitric oxide synthase (iNOS) in the progression of fibrosis during nonalcoholic steatohepatitis remains to be elucidated. This study examined the role of iNOS in the progression of fibrosis during steatohepatitis by comparing iNOS knockout (iNOS(-/-)) and wild-type (iNOS(+/+)) mice that were fed a high-fat diet. Severe fatty metamorphosis developed in the liver of iNOS(+/+) and iNOS(-/-) mice. Fibrotic changes were marked in iNOS(-/-) mice. Gelatin zymography showed that pro MMP-2 and pro MMP-9 protein expressions were more highly induced in iNOS(+/+) mice than in iNOS(-/-) mice. Active forms of MMP-2 and MMP-9 were clearly present only in the liver tissue of iNOS(+/+) mice. In situ zymography showed strong gelatinolytic activities in the liver tissue of iNOS(+/+) mice, but only spotty activity in iNOS(-/-)mice. iNOS may attenuate the progression of liver fibrosis in steatohepatitis, in part by inducing MMP-2 and MMP-9 expression and augmenting their activity.