Keishi-bukuryo-gan (TJ-25) is a traditional Chinese herbal remedy containing five components: bark of Cinnamomum cassia, root of Paeonia lactiflora, seed of Prunus persica or P. persiba var. davidiana, carpophores of Poria cocos and root bark of Paeonia suffruticosa. This preparation has been used in the treatment of gynecological disorders such as hypermenorrhea, dysmenorrhea and infertility. In the present study, the effects of TJ-25 on plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2), and on uterine wet weight and thymidine kinase (TK) activity were documented in immature rats. Long-term daily oral administration of TJ-25 (300 mg/kg) for 14 days decreased plasma levels of LH, FSH and E2 by 94%, 67% and 50%, respectively, compared to controls. Uterine wet weight and TK activity were reduced to 65% and 64% that of controls, respectively. Short-term effects of TJ-25 on E2 were also examined. Thirty hours after administration of E2 (1.0 micrograms/kg) alone, uterine wet weight and TK activity were elevated 2.4- and 21-fold, respectively, over controls. However, simultaneous administration of TJ-25 (three consecutive doses, every 12 h) with E2 reduced E2-induced increases in uterine wet weight and TK activity by 29% and 39%, respectively. Treatment with TJ-25 also enhanced LH-RH-induced increases in plasma LH and FSH levels 1.2- and 2.5-fold, respectively, as compared with controls. The results obtained in the present study indicate that TJ-25 may act as a LH-RH antagonist and/or as a weak anti-estrogen.

Administration, Oral↗

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How genetic defects are identified.

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Diagnosis, Differential↗

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Effects of 5-fluorouracil derivative UFT on thymidylate synthetase and thymidine kinase in rat colorectal tumors.

BACKGROUND: Thymidylate synthetase and thymidine kinase are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively. MATERIALS AND METHODS: Weekly injections of 1,2-dimethyl-hydrazine induced high incidence of colorectal adenocarcinomas in rats. RESULTS: An increased activity of thymidylate synthetase was found in the poorly differentiated adenocarcinomas of the chemically induced rat colorectal tumors. Six-week oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil (UFT) reduced the total number of colorectal tumors, with the reduction of thymidylate synthetase activity in the poorly-differentiated type, though the mRNA expression of thymidylate synthetase and thymidine kinase differed little between the groups with or without UFT treatment. CONCLUSIONS: These results indicate that the long-term oral administration using UFT suppresses colorectal carcinogenesis and the growth of the poorly-differentiated type tumors.

Animals↗

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Myocardial energy metabolism and protection of heart muscle at low temperatures.

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Adenosine Triphosphate↗

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Effects of long-term administration of UFT plus leucovorin on colorectal tumors induced with 1,2-dimethylhydrazine in rats.

Thymidylate synthase and thymidine kinase are key enzymes involved in the de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively. Thymidylate synthase is inhibited by 5-fluorodeoxyuridine monophosphate, forming an inactive ternary complex with intracellular folate. We investigated the effects of 1-(2-tetrahydrofuryl)-5-FU plus uracil (UFT) with or without leucovorin on 1,2-dimethylhydrazine-induced rat colorectal carcinomas. Thirty-week administration of UFT with or without leucovorin markedly suppressed both colorectal carcinogenesis and tumor growth, resulted in the increase of thymidylate synthase inhibition and the decrease of thymidine kinase activity in the tumor cells. These results indicate that the combination of UFT with leucovorin could be useful in the development of pre- and post-operative adjuvant chemotherapy programs.

1,2-Dimethylhydrazine↗

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Preventive effects of sulphasalazine on colorectal carcinogenesis in mice with ulcerative colitis.

Sulphasalazine has been used in the treatment of ulcerative colitis and is known to be a prodrug and split into sulphapyridine and 5-aminosalicylic acid by bacteria in the colon. An increased incidence of colorectal carcinoma is known to occur in patients with ulcerative colitis, which displays a recurrence-remission cycle on colorectal mucosa, i.e., the ulceration and regeneration periods of the colorectal mucosa. Repeated mucosal necrosis-regeneration sequence in chronic ulcerative colitis induced with 3% dextran sulfate sodium led to colorectal carcinogenesis in azoxymethane-pretreated mice. Additive treatment with sulphasalazine normalized the enlarged organs, i.e. liver, spleen and kidney and anemia and leucocytosis induced with 3% dextran sulfate sodium resulted in the reduction of tumorous regions with high-grade dysplasia.

Animals↗

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Preventive effects of a Chinese herbal medicine, hochu-ekki-to, on bone loss in ovariectomized rats.

To evaluate the effects of a traditional Chinese herbal medicine, Hochu-ekki-to [Bu-zong-yi-qi-tang], on the bone loss induced by ovariectomy in rats, ovariectomized female rats of the Sprague-Dawley strain at age 35 weeks were daily given Hochu-ekki-to and/or 17 alpha-ethynylestradiol for 8 weeks by gastric tube and, subsequently, the serum hormone levels and the tibial bone mineral density were measured. Hochu-ekki-to treatment suppressed the ovariectomy-induced reduction of the bone mineral density in the whole and metaphysis of tibia with a slight increase of serum levels of estradiol and progesterone, maintaining bone mineral density values similar to that in the estradiol treated ovariectomized rats, as well as the intact control rats. Hochu-ekki-to is suggested to elevate the serum levels of ovarian hormones slightly and prevent bone loss in ovariectomized rats.

Alkaline Phosphatase↗

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Lead poisoning from art restoration and pottery work: unusual exposure source and household risk.

Two cases of lead poisoning following exposures in the arts and crafts environment are presented. The first illustrates the impact of an unusual exposure source experienced by a female art conservator while restoring an antique Peruvian tapestry from the Chancay Period (A.D. 1000-1500). The second demonstrates the extension to the artist's family members of a lead hazard associated with pottery work. Noted were a wide spectrum of clinical and biochemical abnormalities, ranging from severe neurological and gastrointestinal symptoms to subtle alterations in the biosynthetic pathway of heme. Marked elevation of the blood lead level (up to 130 mcg/100 mL) was found in the most severe case of lead poisoning. The cases illustrate the need for industrial hygiene measures in this type of work in order to prevent lead intoxication, both in the adult artist and children in the household. However, in some instances of increased lead absorption in persons with lead-related hobbies, sources other than those associated with arts and crafts should be investigated. This alternative is illustrated by a third case, in which firearms training was the more likely source of excessive exposure. Multiple occupational factors must occasionally be considered in evaluating increased lead absorption.

Adult↗

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Inhibition of carbon monoxide production by tin-protoporphyrin.

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Bilirubin↗

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Effects of danazol on proliferation and viability of 7,12-dimethylbenz(a)anthracene-induced mammary tumours in rats.

The suppressive effects of danazol, an isoxazol derivative of a synthetic steroid 17 alpha-ethinyltestosterone, on cellular viability and DNA synthesis in 7,12-dimethylbenz(a)anthracene induced mammary tumours were investigated in adult female rats by enzyme assays and immunohistochemistry with bromodeoxyuridine (BrdU). Rats treated with danazol for 30 days showed a decrease of plasma levels of luteinizing hormone and estradiol associated with a dysfunction in hypothalamo-hypophysial-gonadal axis, resulting in lower activities in succinate dehydrogenase and thymidine kinase, and a reduction of BrdU-immunoreactive cells in mammary tumours compared with the control, i.e., decreases of viability and pyrimidine nucleotide synthesis in tumour cells in danazol-treated rats.

9,10-Dimethyl-1,2-benzanthracene↗

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Effects of luteinizing hormone-releasing hormone analogue on DNA synthesis in rat prostate and uterus.

Buserelin, a potent LH-RH agonist, has been used for the treatment of hormonal disorders such as precocious puberty, endometriosis, cystic mastitis and prostatic carcinoma. Prolonged treatment with buserelin has been known to induce a refractory phase of pituitary desensitization. In the present study, we found that two-week treatment with buserelin strongly suppressed the activities of thymidylate synthetase and thymidine kinase, and markedly reduced the appearance of BrdU-immunoreactive (S-phase) cells in both prostate glands and uteri in male and female adult rats, respectively.

Animals↗