Biomedical subjects

S Kubodera

Publications and source records attributed to S Kubodera.

11 recordsLinked to original sources

PubMed2001

Inhibition of nitric oxide synthase induces intestinal mucosal damage and increases mortality in rats treated by FK506.

INTRODUCTION: Despite the beneficial immunosuppressive effects of FK506 during small intestine transplantation, FK506 appears to have direct toxic effects on the intestine. The mechanisms of FK506-induced intestinal damage is unclear, and whether nitric oxide (NO) is involved in the mechanism has not been well defined. This study was designed to evaluate the effects of NG-Nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, on small intestinal damage in rats treated with FK506. MATERIALS AND METHODS: Wistar rats weighing 240-260 g, aged 11 weeks, were administered FK506 (5 mg/kg/day i.m) and/or L-NAME (5 mg/dl in drinking water) for 10 days. Body weight gain, diarrhoea and mortality were observed during experiment. At the end of experiment, the intestinal specimens were excised for histological evaluation. In addition, the effects of L-aginine treatment (1 g/dl in drinking water) were evaluated in this study. RESULTS: L-NAME administration time-dependently induced diarrhoea and high mortality in the rats treated with FK506. At the end of 10 days treatment, 7 of 12 rats (58.3%) suffered from diarrhoea and 5 of 12 rats (41.7%) died in the FK506 + L-NAME group (vs. FK506 group, p = 0.05). A significant loss of body weight was also found in the rats treated with FK506 + L-NAME (-52.2 +/- 28.8 g, in FK506 + L-NAME group vs. -14.3 +/- 8.7 g in FK506 group, p = 0.001). In parallel with the severe diarrhoea and high mortality, the loss of villi, hemorrhage and necrosis (grade 5 of pathological damage) was seen in the small intestinal mucosa of rats treated with FK506 + L-NAME. L-arginine treatment in part prevented diarrhoea, mortality and pathological damage of small intestinal mucosa induced by L-NAME. CONCLUSIONS: Inhibition of NOS induces intestinal mucosal damage and increases mortality in rats treated with FK506. L-arginine treatment can in part prevent the injury induced L-NAME. The present study suggests that NO, as an important protective factor, may be involved in the FK506-induced intestinal damage.

Administration, Oral↗

PubMed2001

Effects of nitric oxide synthesis inhibition on FK506-induced nephrotoxicity in rats.

This study was designed to evaluate the role of nitric oxide (NO) in FK506-induced nephrotoxicity by administering an inhibitor of NO synthesis, N omega-nitro-L-arginine methyl ester (L-NAME) to rats treated with FK506. After one week of treatment with FK506 (3.2 mg/kg/day, intramuscularly) and/or L-NAME (5 mg/100 mL of L-NAME in the drinking water), the arterial pressure, urinary NOx, and parameters for renal function were measured, and histological analysis of the kidney was made. In the L-NAME without FK506 group, L-NAME administration effectively inhibited urinary NOx excretion and increased mean arterial pressure (MAP) without any change in renal function. In the FK506 without L-NAME group, FK506 treatment showed increase in urinary NOx excretion and mild renal dysfunction. In the FK506 with L-NAME group, urinary NOx excretion was decreased by L-NAME administration and renal function was significantly worsened than FK506 without L-NAME group. The plasma creatinine, BUN and urinary N-acetyl-beta-D-glucosaminidase increased 2-, 3-, and 3-fold, respectively and the creatinine clearance was reduced by 50% as compared with that in the FK506 without L-NAME group. Histological analysis revealed severe interstitial fibrosis and tubular atrophy in the FK506 + L-NAME treatment group. Thus, results suggest that NO synthesis is enhanced in the kidney during FK506-induced nephrotoxicity and that NO synthesis inhibition aggravates FK506-induced nephrotoxicity. NO may play a protective role attributable to the balance of vasoactive substances in FK506-induced nephrotoxicity.

Animals↗

PubMed2000

Distribution of phenolic yeasts and production of phenolic off-flavors in wine fermentation.

The activity of wine yeasts to decarboxylate ferulic and p-coumaric acids is one of their biological properties related to the production of phenolic off-flavors (POF) in wine-making. We examined POF productivity in 116 strains of wine yeast, 74 strains of wild yeast (Saccharomyces cerevisiae) and 23 strains of non-Saccharomyces yeast, and found that a majority of these yeasts were POF-producing strains. The frequency distribution of POF-producing strains was 81 to 95% in wine yeasts, 85 to 97% in wild yeasts and 78 to 83% in non-Saccharomyces yeasts based on the POF test with addition of ferulic and p-coumaric acids to grape juice medium. The Rhodotorula, Candida, Cryptococcus, Pichia, Hansenula, and Brettanomyces strains had high or moderate POF productivity among the 20 non-Saccharomyces species. The decomposition rate of ferulic acid correlated with POF production and the critical concentration of phenolic acid (free form) in grape must was estimated to be more than 10 mg/l. Segregation of POF phenotype and Southern blot analysis of phenolic wine yeasts suggest that POF production is controlled by the POF gene (PAD1). The results showed the frequent distribution of phenolic yeasts in the wine-making environment. These suggest the importance of controlling POF production by using wine yeast strains of low POF productivity. The grapes must be prepared by a suitable process to prevent the increase in phenolic acid content.

Journal Article↗

PubMed1997

The role of lymphadenectomy in the treatment of transitional cell carcinoma of the upper urinary tract.

PURPOSE: We evaluated the efficacy of lymphadenectomy in conjunction with nephroureterectomy in patients with transitional cell carcinoma of the upper urinary tract. MATERIALS AND METHODS: Data were evaluated retrospectively in 21 consecutive men and 15 women (mean age 67 years) who underwent total nephroureterectomy with lymphadenectomy between January 1985 and December 1993. RESULTS: Of the 36 patients 11 (31%) had lymph node metastases. Of 20 patients with stages pT3 to 4 or pN+ tumors 12 received cisplatin based chemotherapy (11 postoperatively and 1 preoperatively). Followup ranged from 3 to 135 months (mean 55). Among 13 patients who died by May 1996 tumor was the cause of death in 8, while 5 died of unrelated causes. The probability of a cause specific survival at 5 years was 100% in patients with stages pTa to 1, 80% with stage pT2, 59% with stage pT3 and 0% with stage pT4 cancer. The probability of a cause specific survival at 5 years in patients with nodal metastasis was 21%. No patient without nodal metastasis died of tumor related causes. CONCLUSIONS: Lymphadenectomy may provide therapeutic benefit in select patients with lymph node metastasis. It also may be a useful indicator of candidates for adjuvant chemotherapy if an effective regimen is established because lymph node metastasis is common in patients with carcinoma of the upper urinary tract and is critical in establishing the prognosis.

Adult↗

PubMed1997