1.Development of a new alternative method to inhalation exposure: intratracheal instillation studies using molecular dispersion.
Toshiki MORIMOTO ; Chinatsu NISHIDA ; Hiroto IZUMI ; Taisuke TOMONAGA ; Kazuma SATO ; Yasuyuki HIGASHI ; Ke-Yong WANG ; Takuma KOJIMA ; Kazuo SAKURAI ; Akihiro MORIYAMA ; Jun-Ichi TAKESHITA ; Kei YAMASAKI ; Hidenori HIGASHI ; Kazuhiro YATERA ; Yasuo MORIMOTO
Environmental Health and Preventive Medicine 2025;30():69-69
BACKGROUND:
Organic chemicals have been known to cause allergic diseases such as bronchial asthma and hypersensitivity pneumonitis; however, the possibility that they do not cause irreversible pulmonary fibrosis has not been considered. Polyacrylic acid (PAA), an organic chemical, has caused irreversible progressive pulmonary fibrosis in exposed workers, indicating its potential to induce pulmonary inflammation and fibrosis. Although intratracheal instillation studies are commonly used for evaluating lung pathology, traditional methods face challenges with chemical substances, particularly nanoparticles, which tend to aggregate in suspension and prevent uniform pulmonary distribution. Such aggregation alters the qualitative and quantitative responses to lung injury, limiting accurate assessment of lung pathology. To overcome this limitation, we developed a 'molecular dispersion method' that uses pH modification to negative charges to PAA particles, maintaining their dispersion. Using this method, we investigated the effects of PAA on pulmonary inflammation and fibrosis in a rat model.
METHODS:
F344 rats were intratracheally instilled with PAA using molecular dispersion (0.1 mg/rat, 1.0 mg/rat), PAA without molecular dispersion (1.0 mg/rat), and normal saline (control group). Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after exposure to examine inflammatory and fibrotic responses.
RESULTS:
PAA caused persistent increases in neutrophil influx in the bronchoalveolar lavage fluid (BALF) from 3 days to 1 month following instillation. In histopathological findings, the group with molecular dispersion had almost no inflammatory masses in the lung tissue compared to the group without molecular dispersion, and exhibited relatively uniform dispersion.
CONCLUSION
Intratracheal instillation of dispersed PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA might have pulmonary inflammogenicity and fibrogenicity. Intrapulmonary dispersion of PAA particles following intratracheal instillation studies using the molecular dispersion method was similar to that following inhalation studies.
Animals
;
Rats, Inbred F344
;
Acrylic Resins/adverse effects*
;
Rats
;
Inhalation Exposure/adverse effects*
;
Male
;
Pulmonary Fibrosis/pathology*
;
Pneumonia/pathology*
;
Lung/pathology*
;
Bronchoalveolar Lavage Fluid/cytology*
2.Clinical significance of the level of fibrin degradation products in drowning patients without cardiac arrest
Ken-ichi MURAMATSU ; Kazuhiko OMORI ; Yoshihiro KUSHIDA ; Hiroki NAGASAWA ; Ikuto TAKEUCHI ; Kei JITSUIKI ; Jun SHITARA ; Hiromichi OHSAKA ; Yasumasa OODE ; Youichi YANAGAWA
Journal of Rural Medicine 2020;15(4):201-203
Objective: This study aimed to retrospectively investigate the clinical significance of the level of fibrin degradation products in drowning patients without cardiac arrest.Patients and Methods: All drowning patients who were transported to our department from January 2011 to December 2019 were retrospectively investigated through a medical chart review and included as subjects in the present study. The exclusion criteria were the occurrence of cardiac arrest before patient arrival to our department and lack of measurement of the fibrin degradation product level on arrival. The subjects were divided into two groups: early discharge group, which included patients who were discharged within 3 days, and late discharge group, which included patients who were discharged after 3 days.Results: The early discharge group included 10 subjects and the late discharge group included 39 subjects. No significant differences were observed in age, sex, proportion of freshwater drowning cases, proportion of alcohol drinkers, vital signs, blood gas analysis findings, proportion of lung lesions, or survival rate between the two groups. The levels of glucose and fibrin degradation products on arrival were significantly greater in the early discharge group than in the late discharge group. A multivariate analysis showed that the only significant predictor of early discharge was the fibrin degradation product level among variables identified in a univariate analysis.Conclusion: This is the first study to show that the level of fibrin degradation products on arrival can predict early or late discharge in drowning patients without cardiac arrest before arriving to the hospital.
3.A Case of Unexpected Tracheal Stenosis in Marfan Syndrome after Surgical Repair for Acute Type A Aortic Dissection
Shuji Moriyama ; Jun-ichi Kei ; Masahiko Hara
Japanese Journal of Cardiovascular Surgery 2014;43(2):53-57
A 29-year-old woman with severe chest and back pain was referred to our hospital. She exhibited the following physical symptoms of Marfan syndrome : arachnodactyly, wrist sign, thumb sign, pectus excavatum, pes planus, scoliosis, and myopia. Computed tomography revealed a Stanford type A aortic dissection with dilatation of the aortic root, therefore, emergency surgery was performed. Total arch replacement, including an elephant trunk procedure, was performed, followed by valve-sparing aortic root replacement using the reimplantation technique. Following an initially uneventful postoperative course, she was reintubated on the third postoperative day due to laryngeal edema and aspiration. On the sixth postoperative day, it was difficult to ventilate her due to severe tracheal stenosis. Although we managed to return her to spontaneous breathing under proper sedation, it was difficult to maintain stable ventilation. She developed a recurrent respiratory distress following physical irritation such as intratracheal aspiration or a postural change. We believe that during the perioperative management of patients with Marfan syndrome with thoracic deformities, such as pectus excavatum and scoliosis, the possibility of postoperative tracheal stenosis due to tracheal fragility, tracheal edema, and compression of the surrounding tissues must be considered.
4.Peri-orbital electrodes as a supplemental recording for detection of ictal discharges in medial temporal lobe epilepsy
Hiroshi Shigeto ; Ayumi Sakata ; Takato Morioka ; Kei-ichiro Takase ; Ko-ichi Hagiwara ; Takashi Kamada ; Yuji Kanamori ; Kimiaki Hashiguchi ; Shozo Tobimatsu ; Natsumi Yamashita ; Jun-ichi Kira
Neurology Asia 2011;16(4):303-307
Objective: The feasibility of peri-orbital electrodes, which are not invasive and do not induce pain, as a
supplemental electrode for detection of ictal discharges in medial temporal lobe epilepsy (MTLE) was
examined. Methods: Patients with MTLE, who underwent video-EEG monitoring with simultaneous
peri-orbital and sphenoidal electrodes and obtained good outcome following standard anterior temporal
lobectomy, were subjects in this study. Initial ictal discharge amplitudes were compared between
sphenoidal (Sp1/ 2), standard anterior temporal in 10-20 system (F7/ 8), peri-orbital (superior orbital
lateral: SOL, inferior orbital medial: IOM), frontopolar (Fp1/ 2), frontal (F3/4) and ear (A1/ 2) electrodes.
Results: A total of 34 consecutive seizures from 20 patients were analyzed, with a maximum amplitude
observed at Sp1/2 (57.57±5.59), followed by F7/8 (54.89±5.59), SOL (50.97±5.59), IOM (46.95±5.59),
A1/2 (45.07±5.69), Fp1/2 (44.78±5.62), and F3/4 (37.75±5.66) (mean±standard error, μV). There was
no statistical difference between Sp1/2, F7/8, SOL, and IOM values. When the sphenoidal electrode
was omitted, 13 seizures (13/34, 38.2%) resulted in the highest amplitude at peri-orbital electrodes
and 10 seizures (10/ 34, 29.4%) at F7/8.
Conclusions: Peri-orbital electrodes could detect ictal discharges in MTLE as well as sphenoidal and
standard anterior temporal electrodes in 10-20 system and are useful for supplemental recording for
detecting ictal epileptiform discharges in MTLE.


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