The uptake and intracellular activity of fleroxacin in murine J774.1 macrophages and human polymorphonuclear leukocytes were studied. The uptake of fleroxacin by J774.1 macrophages was rapid and reversible. The cellular to extracellular concentration ratios of fleroxacin in both types of phagocytes ranged from 5 to 6. These ratios were almost equal to those of ofloxacin and ciprofloxacin, and higher than those of the beta-lactam antibiotics, flomoxef and piperacillin. The intracellular activity of fleroxacin in J774.1 macrophages, examined with Staphylococcus aurenus as a test bacterium, showed that its bactericidal action was dependent on both the extracellular concentration and the exposure time. Fleroxacin reduced the number of viable cells of ingested S. aureus at an extracellular concentration that simulated the clinical serum levels, that is, killing more than 70% of the bacteria at 4 micrograms/ml. The bactericidal activity of fleroxacin in phagocytes was superior to that of erythromycin, flomoxef and piperacillin. These results indicate that fleroxacin is taken up well by phagocytes, reaching a concentration several fold higher than the extracellular concentration, and that it has potent activity against intracellular pathogens.

Animals↗

PubMedDate not supplied

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↗

PubMedDate not supplied

Radiotherapy with concurrent docetaxel and carboplatin for head and neck cancer.

BACKGROUND: This study was designed to evaluate the concomitant use of docetaxel and carboplatin for radiosensitization in head and neck cancer. MATERIALS AND METHODS: One dose of docetaxel at 10 mg/m2 and five doses of carboplatin at AUC of 0.4 per week were administered to patients during the first two weeks of radiotherapy. Sixteen patients were treated with this regimen. Radiotherapy was given to a total dose of 64.8 to 82.0 Gy. Altered fractionation radiotherapy was performed in 12 patients with untreated advanced tumors. RESULTS: The complete response (CR) rate was 81%, with a partial response (PR) rate of 19%. Toxicities included grade 3 mucositis in 69% of patients and grade 2 dermatitis in 56% of patients. CONCLUSION: This schedule of docetaxel and carboplatin combined with radiotherapy may become a useful approach for the management of head and neck cancer with proper management of mucositis.

Adult↗

PubMedDate not supplied

Effects of estrone with or without medroxyprogesterone acetate on the femur in aged rats.

In an attempt to define the efficacy of hormone replacement therapy in postmenopausal osteoporosis, we investigated the effects of estrone with or without medroxyprogesterone acetate on the bone mineral density of the femur of aged rats, of which plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol were markedly reduced in comparison with those of younger rats. Although additional sex hormones had little effect on the plasma levels of gonadotropins, chronic administration of estrone significantly enhanced the bone mineral density of femur in aged animals.

Aging↗

PubMedDate not supplied

Additional effects of medroxyprogesterone acetate on mammary tumors in oophorectomized, estrogenized, DMBA-treated rats.

Although hormone replacement therapy not only relieves vasomotor symptoms but also reduces cardiovascular disease and osteoporosis, long-term estrogen therapy increases the risk of endometrial and/or mammary cancer. We investigated the effects of conjugated estrogens with or without medroxyprogesterone acetate in oophorectomized, 7,12-dimethylbenz(a)anthracene-treated rats. Chemically induced mammary carcinogenesis was completely suppressed by the simultaneous oophorectomy, but conjugated estrogens replacement with or without medroxyprogesterone acetate markedly stimulated mammary carcinogenesis in the ovariectomized rats. The chronic administration of conjugated estrogens and medroxyprogesterone acetate markedly reduced the activities of thymidylate synthetase and thymidine kinase and bromodeoxyuridine-immunoreactive (S-phase) cells in mammary tumors. These results indicate that the treatment using conjugated estrogens with or without medroxyprogesterone acetate may promote the mammary carcinogenesis in postmenopausal women but the chronic administration of medroxyprogesterone acetate may alter the development of established mammary cancer.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Effects of tamoxifen on mammary tumors and bone in 7,12-dimethylbenz-(a)anthracene-treated rats.

We investigated the effects of tamoxifen on the growth of 7,12-dimethylbenz(a)anthracene induced rat mammary tumors, the activity of thymidylate synthetase and thymidine kinase (key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis), and also their gene expression. The effects on immunohistochemistry using bromodeoxyuridine in the tumors and bone mineral density of the femur in rats were also studied. Chronic administration of tamoxifen markedly reduced the expression of thymidylate synthetase mRNA, followed by a reduction in enzyme activity and S-phase cells in the mammary tumors, and significantly enhanced the bone mineral density. Tamoxifen not only attenuated bone loss in aging but also enhanced bone volume in mammary tumor-bearing rats in which tumor growth was suppressed via both the de novo and salvage pathways for pyrimidine nucleotide synthesis.

9,10-Dimethyl-1,2-benzanthracene↗