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S Yoshitani

Publications and source records attributed to S Yoshitani.

11 recordsLinked to original sources

Chemoprevention of azoxymethane-induced rat aberrant crypt foci by dietary zerumbone isolated from Zingiber zerumbet.

The modifying effects of dietary feeding of zerumbone isolated from Zingiber zerumbet on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. Expression of cyclooxygenase (COX)-2 in colonic mucosa exposed to AOM and/or zerumbone was also assayed. In addition, we assessed the effects of zerumbone on cell proliferation activity of crypts by counting silver-stained nucleolar organizer regions protein (AgNORs) in colonic cryptal cell nuclei. To induce ACF rats were given three weekly subcutaneous injections of AOM (15 mg/kg body weight). They were also fed the experimental diet containing 0.01% or 0.05% zerumbone for 5 weeks, starting one week before the first dosing of AOM. AOM exposure produced 84+/-13 ACF/rat at the end of the study (week 5). Dietary administration of zerumbone caused reduction in the frequency of ACF: 72+/-17 (14% reduction) at a dose of 0.01% and 45+/-18 (46% reduction, p<0.001) at a dose of 0.05%. Feeding of zerumbone significantly reduced expression of COX-2 and prostaglandins in colonic mucosa. Zerumbone feeding significantly lowered the number of AgNORs in colonic crypt cell nuclei. These findings might suggest possible chemopreventive ability of zerumbone, through suppression of COX-2 expression, cell proliferating activity of colonic mucosa, and induction of phase II detoxification enzymes in the development of carcinogen-induced ACF.

Animals↗

Dietary administration of citrus nobiletin inhibits azoxymethane-induced colonic aberrant crypt foci in rats.

The modifying effects of dietary feeding of a polymethoxyflavonoid nobiletin isolated from Citrus unshiu on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. We also assessed the effects of nobiletin on cell proliferation activity of ACF using a monoclonal antibody MIB-5. Rats were given subcutaneous injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce ACF. They also received the experimental diet containing 0.01% or 0.05% nobiletin for 5 weeks, starting one week before the first dosing of AOM. AOM exposure produced 139 +/- 35 ACF/rat at the end of the study (week 5). Dietary administration of nobiletin caused significant reduction in the frequency of ACF: 70 +/- 15 (50% reduction, p<0.001) at a dose of 0.01% and 63 +/- 10 (55% reduction, p<0.001) at a dose of 0.05%. Nobiletin feeding significantly lowered MIB-5-index in ACF. Also, dietary administration of nobiletin significantly reduced prostaglandin E2 content in the colonic mucosa. These findings might suggest possible chemopreventive ability of nobiletin, through suppression of cell proliferating activity of ACF, in the development of ACF.

Administration, Oral↗

Ligands for peroxisome proliferator-activated receptors alpha and gamma inhibit chemically induced colitis and formation of aberrant crypt foci in rats.

The biological role of the peroxisome proliferator-activated receptors (PPARs) in various diseases, including inflammation and cancer, has been highlighted recently. Although PPARgamma ligands have been found to inhibit mammary carcinogenesis in rodents, the effects on colon tumorigenesis are controversial. In the present study, three different experiments were conducted to investigate the modifying effects of PPARs ligands (PPARalpha and PPARgamma) on colitis and an early phase of colitis-related colon carcinogenesis in male F344 rats. In the first experiment, gastric gavage of troglitazone (PPARgamma ligand, 10 or 100 mg/kg body weight) or bezafibrate (PPARalpha ligand, 10 or 100 mg/kg body weight) inhibited colitis induced by dextran sodium sulfate (DSS) and lowered trefoil factor-2 content in colonic mucosa. In the second experiment, dietary administration (0.01 or 0.05% in diet) of troglitazone and bezafibrate for 4 weeks significantly reduced azoxymethane (AOM, two weekly s.c. injections, 20 mg/kg body weight)-induced formation of aberrant crypts foci, which are precursor lesions for colon carcinoma. In the third experiment, dietary administration (0.01% in diet for 6 weeks) of pioglitazone (PPARgamma ligand), troglitazone, and bezafibrate effectively suppressed DSS/AOM-induced ACF. Administration of both ligands significantly reduced cell proliferation activity in colonic mucosa exposed to DSS and AOM. Our results suggest that synthetic PPARs ligands (PPARalpha and PPARgamma) can inhibit the early stages of colon tumorigenesis with or without colitis.

Animals↗

Troglitazone, a ligand for peroxisome proliferator-activated receptor gamma, inhibits chemically-induced aberrant crypt foci in rats.

The biological roles of peroxisome proliferator-activated receptors (PPARs) in various diseases, including inflammation and cancer, have been highlighted recently. Although PPARgamma ligand is suspected to play an important role in carcinogenesis, its effects on colon tumorigenesis remain undetermined. The present time-course study was conducted to investigate possible modifying effects of a PPARgamma ligand, troglitazone, on the development and growth of aberrant crypt foci (ACF), putative precursor lesions for colon carcinoma, induced by azoxymethane (AOM) or dextran sodium sulfate (DSS) in male F344 rats. Oral troglitazone (10 or 30 mg / kg body weight (b.w.)) significantly reduced AOM (two weekly subcutaneous injections, 20 mg / kg b.w.)-induced ACF. Treatment with troglitazone increased apoptosis and decreased polyamine content and ornithine decarboxylase (ODC) activity in the colonic mucosa of rats treated with AOM. Gastric gavage of troglitazone also inhibited colitis and ACF induced by DSS (1% in drinking water), in conjunction with increased apoptosis and reduced colonic mucosal polyamine level and ODC activity. Our results suggest that troglitazone, a synthetic PPARgamma ligand, can inhibit the early stage of colon tumorigenesis with or without colitis.

Animals↗

[Clinical study on dosage schedule of tobramycin: controlled comparison between 180 mg b.i.d. and t.i.d].

The efficacy and safety of tobramycin (TOB) administration at 90 mg twice a day (90 mg group) to patients with respiratory tract infections (RTI) were objectively investigated by means of a well-controlled comparative study. The results in this 90 mg group were compared with the case of administering 3 times a day of 60 mg each (60 mg group) as the control. In both of these patient groups, TOB was administered by intramuscular injection for 10 consecutive days. This study included 85 patients (90 mg group: 43 patients; 60 mg group: 42 patients). The Committee, however, excluded 19 patients consisting of 13 cases of infection other than RTI and 6 cases of out of protocol drug administration. Thus, 66 patients (90 mg group: 32 patients; 60 mg group: 34 patients) were used for the efficacy analysis. All 85 patients were used, however, for the evaluation of the safety of TOB and for the usefulness of TOB as judged by the physicians in charge. A brief summary of the results is presented below. The cases employed by the Committee consisted of 8 and 17 cases in the 90 mg and 60 mg groups, respectively, with bacterial pneumonia and lung abscess, and 24 and 17 cases in the 90 mg and 60 mg groups, respectively, with chronic RTI. There was a tendency for the distribution of disease cases in the 2 drug groups to be significant. Within the chronic RTI disease classification, the number of patients with chronic bronchitis was almost equal in the 2 drug groups; 16 cases in the 90 mg group and 15 cases in the 60 mg group. However, secondary infections were diagnosed in 8 cases in the 90 mg group and 2 cases in the 60 mg group. The clinical efficacy judged for all cases investigated by the Committee showed efficacy ratios of 56.3% for the 90 mg group and 70.6% for the 60 mg group. The difference between the 2 drug groups was not statistically significant. In the treatment of bacterial pneumonia and lung abscess, the efficacy rate in the 90 mg group was 87.5%, while it was 88.2% in the 60 mg group; these high values were practically identical. Against chronic RTI, the efficacy rates were 45.8% in the 90 mg group and 52.9% in the 60 mg group; within that disease classification, the efficacy rates against the chronic bronchitis cases were nearly the same at 43.8% and 46.7%, respectively. These data showed no statistically significant differences between the 2 drug administration groups. (ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗