Effects of edaravone, a free-radical scavenger, on bleomycin-induced lung injury in mice.

Reactive oxygen species play an important role in the pathogenesis of acute lung injury and pulmonary fibrosis. The present authors hypothesise that edaravone, a free-radical scavenger, is able to attenuate bleomycin (BLM)-induced lung injury in mice by decreasing oxidative stress. Lung injury was induced in female ICR mice by intratracheal instillation of 5 mg x kg(-1) of BLM. Edaravone (300 mg x kg(-1)) was administered by intraperitoneal administration 1 h before BLM challenge. Edaravone significantly improved the survival rate of mice treated with BLM from 25 to 90%, reduced the number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) on day 7, and attenuated the concentrations of lipid hydroperoxide in BALF and serum on day 2. The fibrotic change in the lung on day 28 was ameliorated by edaravone, as evaluated by histological examination and measurement of hydroxyproline contents. In addition, edaravone significantly increased the prostaglandin E(2) concentration in BALF on day 2. In summary, edaravone was shown to inhibit lung injury and fibrosis via the repression of lipid hydroperoxide production and the elevation of prostaglandin E(2) production in the present experimental murine system.

[Cytokine production by peripheral blood mononuclear cells in bronchial asthma treated with suplatast tosilate].

Supratast tosilate is a newly developed 'anti-allergic' drug and it has been shown to suppress cytokine production by type-2 helper T cells (Th2) in vitro. However, it is unclear whether a similar inhibitory effect on Th2 cytokines production is produced iv vivo. To elucidate the actions of the in vivo mechanisms of this drug, we isolated peripheral blood mononuclear cells (PBMCs) from 10 atopic asthmatics treated with supratast tosilate and investigated the capacity for cytokine production ex vivo. Interleukin (IL)-5 production by PBMCs stimulated with the combination of phorbol myristate acetate and ionomycin were reduced significantly 6 or 12 weeks after the treatment with supratast tosilate. In contrast, no significant reduction was seen in IL-4 or Interferon (IFN)-gamma production. The peripheral blood eosinophil count and weeks, but no significant difference was sees in total IgE levels. Both morning and evening peak expiratory flow were significantly elevated after 6 weeks. These results suggest that supratast tosilate improves the disease status of bronchial asthma through its ability to inhibit the production Th2 cytokines, at least IL-5, in vivo.

Development of a new device for recording condylar head movement.

Several excellent devices have recently been developed to precisely record mandibular movement. However, these devices are not always suitable for use under certain conditions, such as during sleep, because they incorporate a face bow unit. We report here a newly developed, easy and convenient recording device that does not require the use of an instrument within the mouth. Instead, a subminiature pressure transducer is inserted between the outer surface of a fixation device in the external auditory meatus and the anterior cutaneous surface of the external auditory meatus. The fixation device was made using silicone impression material in the shape of the inner external auditory meatus. Following moulding, the material was cut in half and the parts were reconnected using a coiled spring. This method is based on a routine clinical method for palpating the external auditory meatus to observe condylar head movement. By comparing the results obtained using this device with those obtained using CADIAX, we confirmed that it is useful for recording the movement of the condylar head in routine clinical examinations.

Concurrence of sarcoidosis and lung cancer. A report of four cases.

Although sarcoidosis and lung cancer are both frequently encountered conditions, their simultaneous occurrence in the same patient is unusual. In this report, we describe 4 cases of their concurrence and discuss the possible pathogenic mechanisms of their concurrent appearance. In particular, in 2 of the cases, both diseases had coexisted for a long period (more than 6 and 4 years, respectively), showing a surprisingly slow growth of cancers. Although the chest computed tomography showed hilar and mediastinal lymphadenopathy, the histopathological findings of the excised lymph nodes of both cases revealed no metastasis. The causal relationship between sarcoidosis and lung cancer remains uncertain, but cases such as these may be helpful in elucidating its precise nature.

Cytokine-induced neutrophil chemoattractant in a rat model of lipopolysaccharide-induced acute lung injury.

To elucidate the role of major chemotactic factors, cytokine-induced neutrophil chemoattractant (CINC), leukotriene B4 (LTB4) and C5a in lipopolysaccharide (LPS)-induced acute lung injury in rat, we employed three reagents: anti-CINC-1 antibody, an LTB4 receptor antagonist (ONO-4057) and an anti-complementary agent (K-76COONa). Rats were divided into five groups: (1)control group; (2) LPS group, which received intratracheal instillation of LPS (100 microg/kg); (3) Anti-CINC group, which received intratracheal coinstillation of LPS with anti-CINC-1 antibody (1 mg/kg); (4) LTB4-Ra group, which received intravenous ONO-4057 (10 mg/kg) prior to intratracheal LPS; (5) Anti-C5a group, which received intravenous K-76COONa (100 mg/kg) prior to intratracheal LPS. The number of neutrophils in bronchoalveolar lavage (BAL) fluids 6 h after LPS instillation was significantly reduced in the Anti-CINC group, however, no reduction was found in either the LTB4-Ra group or Anti-C5a group. The levels of CINC-1, CINC-2alpha and CINC-3 in BAL fluids were significantly higher in the LPS group than in the saline-instilled control group. In vitro, the production of CINC-1 and CINC-3 from LPS-stimulated macrophages was significantly elevated compared to unstimulated macrophages 6 h later. The increase in CINC-2alpha production was markedly less than that of CINC-1 or CINC-3. These results indicate that CINCs, especially CINC-1 and CINC-3 play an important role in the recruitment of neutrophils to the lung in LPS-induced acute lung injury.

[Electromyographic power spectral analysis of sternocleidomastoid muscle during sustained voluntary clenching].

The purpose of this study was to investigate the changes of the activity of the sternocleidomastoid (SCM) muscles during sustained voluntary clenching. Ten healthy male subjects without any occlusal functional problems were asked to clench as long as possible in the intercuspal position while keeping the electromyographic activity of the masseter muscle at the 50% maximum voluntary contraction. Frequency analysis was carried out by computer using a fast Fourier transform algorithm to obtain the power spectrum of the SCM muscle during the fatiguing process and the recovery process. The results were as follows: 1. Sustained activities of the SCM muscles were observed during sustained voluntary clenching. 2. The power spectra of the SCM muscles significantly shifted to a lower frequency as time elapsed. 3. The power spectra of the SCM muscles obtained three minutes after relaxation recovered to those of the beginning of clenching. These findings indicated that muscle fatigue may be induced in the SCM muscle during sustained voluntary clenching and that electromyographic power spectral analysis can be used as a noninvasive, objective, and quantitative index of SCM muscle fatigue.

[Role of oxidants in adhesion molecule expression and cytokine production].

Reactive oxygen intermediates such as hydrogen peroxide play an important role in the pathophysiology of acute lung injury, not only as terminal effectors, but also as second messengers in signal transduction; we studied their role in adhesion molecule expression and cytokine production. N-acetylcysteine, an antioxidant, decreased the TNF alpha-induced expression of intercellular adhesion molecule-1 on cultured epithelial cells from human bronchi (BEAS-2A), and inhibited IL-8 production by those cells. In vivo, N-acetylcysteine attenuated the sequestration of polymorphonuclear neutrophils in rat lungs caused by intratracheal lipopolysaccharide. These findings suggest that adhesion molecule expression and cytokine production in the lung are mediated by the production of reactive oxygen intermediates. Because adhesion molecules and cytokines play a crucial role in the pathophysiology of neutrophil-mediated acute lung injury, the inhibition of adhesion molecule expression and cytokine production with anti-oxidants such as N-acetylcysteine may be a useful therapeutic strategy.