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*

Rikkunshito is comprised of 8 crude drugs and is used for the treatment of gastrointestinal dysfunctions such as anorexia and heavy stomach feeling. These symptoms are often caused by delay in gastric emptying. Cisplatin is a representative cancer chemotherapeutic drug with severe adverse effects such as anorexia and nausea, that gives rise to a delay in gastric emptying. However, it is still unknown whether rikkunshito has effects on improving the delayed gastric emptying induced by cisplatin. In the present study, we examined the effects of rikkunshito (an Atractylodis rhizoma-containing formula) on cisplatin-induced delay in gastric emptying in the rat. Rikkunshito improved this. Among the crude drugs that comprise rikkunshito, Atractylodis rhizoma, Ginseng radix, Poria and Aurantii nobilis pericarpium individually improved the delay in gastric emptying, suggesting that they all contribute to the action of rikkunshito. Moreover, the effects of these 4 crude drugs in combinations were also examined, and as a result, tended to be stronger when Atractylodis rhizoma was included. On the other hand, when Atractylodis rhizoma was excluded from rikkunshito, the effects were weaker. Meanwhile, atractylenolide III, a specific chemical constituent of Atractylodis rhizoma, improved delay in gastric emptying in a manner similar to that of rikkunshito with Atractylodis rhizoma. These results, taken together, suggest that Atractylodis rhizoma likely contributes greatly to the improving effect of rikkunshito on cisplatin-induced delay in gastric emptying.

The effects of four Kampo medicines, Ninjin-to, Hange-shashin-to, Rikkunshi-to and Sho-hange-ka-bukuryo-to, were investigated in a rat model of postoperative ileus. The postoperative ileus model was made by incising the abdomen and exposing the small intestine and caecum for five minutes under ether anesthesia. The gastrointestinal transit was estimated by the migration of a charcoal marker. In contrast to the animals anesthetized only, the gastrointestinal transit was markedly decreased in control animals. First, we studied the gastrointestinal prokinetic drugs (cisapride, mosapride and metoclopramide), the anti-inflammatory drug indomethacin, and the Kampo medicine Dai-kenchu-to in this model. They significantly increased the transit as compared with the control. Using the same method, Rikkunshi-to and Sho-hange-ka-bukuryo-to were demon-strated to be almost inactive. However, Ninjin-to and Hange-shashin-to not only significantly improved the gastrointestinal mobility compared to the control, but also showed stronger effects than those of Dai-kenchu-to. These results suggest that in addition to Dai-kenchu-to, Ninjin-to and Hange-shashin-to are also effective Kampo medicines for postoperative ileus.

At institutions in 9 areas of all over Japan, epidemiological and clinical surveys and investigations have been performed on the relationship between alcohol drinking and health for inhabitants in agricultural and fishing villages. The ethanol cutaneous patch test showed about 40% ALDH2 defficiency in these subjects. There were remarkable defferences in the drinking behavior between these positive and negative 2 groups. Various factors affecting the drinking behavior of subjects are there congenital diathesis, sexual difference, natural and social differences as well as age and occupation. By drinking, various abnomalities have been observed in various indexes such as medical examinations namely, hepatic functions (γ-GTP, GOT, GTP, etc), lipids (HDL-C, TG, etc), circulating functions (blood pressure, pulse, etc), metabolisms (uric acid, blood sugar, etc), and pancreatic functions. Most of them are risk factors in adult diseases. Accordingly, through collective education for drinking, its effect can be observed earlier and it will be very important to educate individuals for health control.