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
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Rats, Inbred F344
;
Acrylic Resins/adverse effects*
;
Rats
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Inhalation Exposure/adverse effects*
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Male
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Pulmonary Fibrosis/pathology*
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Pneumonia/pathology*
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Lung/pathology*
;
Bronchoalveolar Lavage Fluid/cytology*
2."Acupuncture Treatment on the Local Area versus the Distal Area"-Physical ConditionsII-Definition of the Local and Distal Area Treatment
Takayoshi OGAWA ; Akihiro OZAKI ; Shuiti KATAI ; Shoji SHINOHARA ; Takemasa SHIRAISHI ; Tomomasa MORIYAMA
Journal of the Japan Society of Acupuncture and Moxibustion 2004;54(1):2-13
This symposium was held as the second in a three part series at Kagawa Conference (June 6-8, 2003). During the Tsukuba conference (2002), distal area treatment was the topic of focus. The criteria and evidence for the effectiveness of distal area treatments were presented. Three symposists and one minor speaker reported on the effectiveness of distal area treatments from clinical and basic viewpoints. However, another symposist showed the superiority of local area treatments and denied the effectiveness of distal area treatments. There fore, we decided that a succinct and definitive discussion on distal area treatments (etc) should be presented during the second symposium. To this end, long time members of JSAM were given a questionnaire survey prior to the conference. Respondents were asked to define their own use of local and distal treatment, to hypothesize on the curing mechanism involved and to state which practice methods they use most.
Mr. Ogawa reported that, as a result of analyzing the questionnaire survey no distinct differences were found in the definitions stated by respondents from several different schools. The standard images of “the local area” were the area where pains were felt when pressure is applied, the areas which transmit special sensitivity or the area where a disorder is found. Also, the images of “the distal area” were the areas which have some relationship to the local area, such as meridians and collaterals, nerves, reflex points, tender points, or related points which induce a clearly recognizable physical reaction.
Mr.Shinohara showed the superiority of distal area treatments according to the muscle meridian theory by utilizing the 3 arm crossover examination. Furthermore, he established the delayed myalgia as a model of the illness on a specific muscle meridian region. He investigated the effect of intradermal needling. He observed that after a weight bearing exercise on the biceps brachii, the threshold of tenderness on the Lung meridian decreases. He proposed the possibility of using the points in extremities which had selectively responded by manifesting of the delayed myalgia.
Mr. Moriyama, one of the minor speakes, explained, using the theory of biomechanics, the possibility of in-fluences of distal area disharmony on the local area. He introduced the Meridian Test as one clinically useful method for finding disharmony which is typically difficult to discern and may contribute to the disorder. He proposed that a microscopic “eye” to be used to see the local area and the macroscopic “eye” b used to see the whole body in medical examination and treatment. Using the “eyes” in synthesis and not separately, he concluded, must be the basic state for treatment.
Another minor speaker, Mr.Shiraishi reported on analyzed results of the experiments on lumbago patients. Applying Yuandaoci (distant needling) reduced a response on points of the trunk (BL 23, Shenshu, Jinyu) in stimulating points, i.e, BL 40 (Weizhong, Ichu), BL 57 (Chengshan, Shozan) BL 58 (Feiyang, Hiyo) BL 60 (Kunlun, Konron) GB 34 (Yanglingquan, Yoryosen) varying in many ways and confirming the peculiarity of each point, meridian and collateral. Based on these findings he supports the effectiveness of distal meridian area treatments.
Mr. Ozaki, also, another minor speaker proposed, from the outcome of animal experiments. Stimulation by acupuncture at either adjacent or distal areas can affect motor reflex. So from this point of view, insertion at adjacent and distal area has some recordable effect. He added that stimulation given either at adjacent or distal areas would converge to the same neuron and the same modification would occur. From this point of view, the difference in processing information at the neuron level would control the manifestation of the effect and thus investigations on these treatments should be discussed as a synthesis, including, not


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