Infections with gastrointestinal parasitic helminths indigenous to Japan and their treatment historically studied in an attempt to control the diseases in countries where they are still rampant: (1) the Jomon to Edo periods.

Infections with gastrointestinal parasitic helminthes were historically surveyed from the Jomon period to the end of the Edo period in Japan. The parasitic helminthes whose eggs or symptoms were shown in the remains and bibliographies are the roundworm, whipworm, liver fluke, Yokogawa's fluke and the cestode, Diphyllobothrium sp. The first two are soil-transmitted nematodes and the other three parasitic helminths are those with which people are infected following eating raw fish. The infection routes provide valuable information on the environments, life-style and customs in those days. The eggs of the soil-transmitted parasites have the thick shells resistant to the environments. Humans are infected with the parasites after the eggs are orally ingested with soil, dust, vegetables grown with night soil or manure. When the custom of the night soil was started in the history of Japan was discussed with this infection route. In ancient times, feces are thought to have been discarded. In the Medieval Period, they were started to be used as a fertilizer. No mature types of manure were used until the modern times (already in the Edo period). To our idea, no recoveries of eggs of hookworms causing severe anemia do not necessarily mean that people were not infected with the parasites in those days because the eggs are covered with thin shells liable to rupture. The latter fact of the eggs of the platihelminths, C. sinensis, M. yokogawai and D. latum has something to do with Japanese traditional eating customs, unequivocally demonstrating that they ate raw fish from the Nara Period, at latest, until today. Whether eggs of the cestode (D. latum) are found in Jomon remains, Momijiyama Iseki, Hokkaido should be investigated. If no eggs of the cestode are found in their toilet site or elsewhere, it could be concluded that they did not have the custom of eating raw salmon. Such a conclusion would be itself a new fact. One of the effective treatments for the cestode (D. latum) sometimes still carried out in the 21st century in Japan, is binding worms from the anus using chopsticks. This method can be traced back to the Edo period as far as this investigation is concerned. Though the historical studies on anthelmintics are in progress, there seem to be no effective anthelmintics leaving nothing to be desired to the present authors' knowledge.

Construction of the curriculum and lectures for the subject, "History of pharmacy" in Matsuyama University School of Pharmacy.

Matsuyama University School of Clinical Pharmacy started in the academic year of 2006. After an obligatory subject, "The Outline of Pharmacy" in the spring semester, the elective course on pharmaceutical history is held with a 90-minute lecture a week for 15 weeks in the autumn semester of the first year for the students. The course consists of 4 parts as follows. The 15 consecutive lectures are carried out in the order of (1), (2), (3) and (4) and they are; (1) Pharmaceutical History in Japan, (2) Pharmaceutical History in the World, (3) The Specific Lectures:Infectious diseases and their treatment from the viewpoint of history, and (4) Introducing English Articles: "Highlights from the History of Medicine". However, in the present authors' opinion, pharmaceutical history from the beginning through the present days might fall roughly into 3 phases, namely the ages of superstition, experience and science with the occasional humanitarianism activities. We have been looking for a possible similar idea published elsewhere.

A chronological research on parasitic endemic disease, "Katayama-disease" (Schistosomiasis japonica) in Hiroshima Prefecture in the 20th century (the 3rd communication on the historical research on Schistosomiasis japonica in Hiroshima Prefecture).

A chronological research on the parasitic endemic disease, "Katayama Disease" in Hiroshima Prefecture was carried out. The present study was concerned mainly with the documents in the 20th century. It was confirmed that the development of excellent chemotherapeutic agents were not pivotal as a result. The eradication of the vector snails was clearly shown to be responsible for that of the infectious disease.

Study of neonatal exposure to androgenic endocrine disruptors, testosterone and dihydrotestosterone by normal-phase HPLC.

Neonatal exposure to androgen induces developmental abnormalities in the male reproductive system. To investigate whether neonatal exposure affects spermatogenesis in juvenile and pubertal testis, Sprague-Dawley rat pups were given androgen or various androgenic endocrine disruptors by a single injection on the day of birth at concentrations ranging between 4 mm to 200 mm, and sacrificed on day 21 (juvenile) or 50 (puberty). The testes were weighed and examined histologically at each stage. Further, the metabolites of steroidogenesis were analyzed using normal-phase high-performance liquid chromatography. Neonatal exposure significantly reduced testis weights and steroidogenesis of juveniles. Neonatal exposure to testosterone and dihydrotestosterone still suppressed pubertal steroidogenesis, although testis weight was completely restored during puberty.

Rescue from dwarfism by thyroid function compensation in rdw rats.

The rdw rat was initially reported as having hereditary dwarfism caused by pituitary dysfunction. Subsequent studies on the rdw rat, however, have demonstrated that the primary cause of rdw dwarfism is present in the thyroid gland but not in the pituitary gland. The primary cause of rdw rat disorders is a missense mutation of the thyroglobulin (Tg) gene by a one-point mutation. In the present study, we attempted to rescue the dwarfism of the rdw rats using a diet supplemented with thyroid powder (T-powder) and a thyroid graft (T-graft). The infants of the rdw rat were successfully raised to a mature stage body weight, accompanied by elevation of serum growth hormone (GH) and prolactin (PRL), by the T-powder. Furthermore, the T-graft successfully increased the body weight with fertility. The serum GH and PRL levels in the T-graft rdw rat significantly increased. The serum thyroid-stimulating hormone (TSH) levels in the T-graft rdw rat were significantly decreased but were significantly higher than those in the control rat. The GH and PRL mRNA expression in the rdw rat with the T-graft was virtually the same as that of the control, but the TSH beta mRNA differed from that of the control rats. Thus, the dwarfism in the rdw rat is rescued by thyroid function compensation, such as that afforded by T-powder and T-graft.

Delayed persistent estrus induced by continuous lighting after inadequate acclimation in rats.

While the normal estrous cycle of adequately acclimated female rats was replaced by a persistent estrus (PE) under continuous lighting, the onset of PE was delayed following several irregular cycles without acclimation or after acclimation for one week, suggesting that transportation induces a significant critical stress.

Kinetic study on conformational change in a single molecular species, beta3, of beta-conglycinin in an acidic ethanol solution.

The conformational change in a single molecular species, beta3, of beta-conglycinin in an acidic ethanol solution was kinetically studied by the stopped-flow technique, utilizing the intrinsic fluorescence of proteins and the fluorescence of 1-anilinonaphthalene-8-sulfonic acid (ANS) bound to the proteins. The time-course of the intrinsic fluorescence changes clearly showed the rate of conformational change below and above 25% ethanol to be quite different from each other. ANS could bind well to the protein in an ethanol concentration range of 15-25%. However, the rate of conformational change of the protein corresponding to that for ANS binding could not be obtained at less than 25% ethanol, while the rate of conformational change agreed well with that for ANS binding at more than 25% ethanol. In addition, the process showing the greatest and slowest ANS binding was not apparent in the denaturation of beta-conglycinin under the conditions employed. These results lead to the conclusions that the beta-conglycinin structure could be maintained in the mild molten globule-like denaturation state, and that various tertiary structural changes could take place without any significant effect on the high sensitivity of intrinsic fluorescence after the secondary structural changes.

One-step analysis of testis steroidogenesis from neonatal exposure to synthetic estrogen by normal-phase HPLC.

Neonatal exposure to synthetic estrogen endocrine disruptors or estrogen-receptor inhibitors induces developmental abnormalities in the male reproductive system. To investigate whether neonatal exposure affects spermatogenesis in juvenile and pubertal testis, Sprague-Dawley rat pups were given synthetic estrogen endocrine disruptors or estrogen-receptor inhibitors by a single injection on the day of birth at concentrations ranging between 2 to 40 mm, and sacrificed on day 21 (juvenile), 35 (prepuberty) or 50 (puberty). The testes were weighed and examined histologically at each stage. Further, the metabolites of steroidogenesis were analyzed using normal-phase high performance liquid chromatography. Neonatal exposure significantly reduced testis weights and steroidogenesis to one- fifth to one-half of that of the juvenile control, and further suppressed irreversible steroidogenesis and spermatogenesis during puberty.

Neonatal exposure to endocrine disruptors suppresses juvenile testis weight and steroidogenesis but spermatogenesis is considerably restored during puberty.

Neonatal exposure to endocrine disruptors induces developmental abnormalities in the male reproductive system. As to investigate whether neonatal exposure affects spermatogenesis in juvenile and pubertal testes, Sprague-Dawley rat pups were given various endocrine disruptors by a single injection on the day of birth at concentrations ranging between 4 microM and 40 mM and sacrificed on day 21 (juvenile) or 50 (puberty). The testes were weighed and examined histologically at each stage. Further, the metabolites of steroidogenesis were analyzed using normal-phase high performance liquid chromatography. Neonatal exposure significantly reduced testis weights and steroid biosynthesis of juveniles, but they were highly restored at puberty.