Inhibition of aromatase activity by green tea extract catechins and their endocrinological effects of oral administration in rats.

We orally administered polyphenone-60 (P-60), green tea extract catechins, in the diet (0, 1.25 and 5%) to male rats for 2, 4 and 8 weeks initiated at 5 weeks old. It was found that a 5% dose to male rats for 2-8 weeks induced goiters and decreased weights of the body, testis and prostate gland. Endocrinologically, elevating plasma thyroid stimulating hormone (TSH), luteinizing hormone (LH) and testosterone levels and decreasing tri-iodothyronine (T(3)) and thyroxine (T(4)) levels were induced by this treatment. We also found that P-60 as a whole and some of its constituents exhibited inhibitory effects on human placental aromatase activity by in vitro assay. The concentration of P-60 that required producing 50% inhibition of the aromatase activity (IC(50) value) was 28 microg/ml. The IC(50) values of (-)-catechin gallate (Cg), (-)-epigallocatechin (EGC), (-)-epigallocatechin gallate (EGCg) and (-)-gallocatechin gallate (GCg) were 5.5 x 10(-6), 1.0 x 10(-4), 6.0 x 10(-5) and 1.5 x 10(-5) M, respectively. (-)- Epicatechin gallate (ECg) at 1.0 x 10(-4) M produced 20% inhibition. (-)-Epicatechin (EC) and (+)-catechin (CT) exhibited no effects on aromatase activity. The endocrinological changes observed in vivo were in conformity with antithyroid effects and aromatase inhibition effects of P-60 and its constituents.

[Adenomatoid tumor of testicular tunica albuginea: a case report].

Adenomatoid tumors are uncommon neoplasms of the paratesticular tissues. We report a case of an adenomatoid tumor of the testicular tunica albuginea. A 54-year-old man presented with a painless right intrascrotal mass. Serum levels of HCG-beta and AFP were within normal limits. Scrotal ultrasonography showed an oval-shaped low echoic lesion located on the surface of the testis. The patient underwent right partial orchiectomy. Histological examination revealed adenomatoid tumor of the tunica alubuginea testis. Adenomatoid tumors of the testicular tunica alubuginea are rare. Examination of tumor markers, ultrasound studies and diagnoses of frozen sections can prevent needless orchiectomy.

Goitrogenic effects of green tea extract catechins by dietary administration in rats.

The effects of green tea extract catechins on the rat thyroid were examined in a 13-week feeding study and subsequent 2-,4- and 8-week studies. Commercially available polyphenon-60 (P-60) which contains green tea extract catechins at 66.2% was used as a source of catechins. A basic diet containing different concentrations of P-60 was used for experiments. In the 13-week study, 10 rats of each sex were administered diets containing P-60 at 0 (control), 0.625, 1.25, 2.5 and 5.0%. Goiters were observed in the 13-week test. The mean thyroid weight of rats fed a diet containing 5.0% of P-60 (5.0% group) significantly increased to 444% of the control in males and to 304% of the control in females. Histological examinations of the thyroid of the 5.0% group revealed marked hypertrophy and/or hyperplasia of the follicles, some with depletion of colloid and some with rich colloid, and formation of a fibrous capsule. Slight hypertrophy of follicular cells was observed in male rats fed a diet containing 1.25% of P-60 (1.25% group) and female rats fed a diet containing 2.5% of P-60 (2.5% group). Degree and incidence of thyroid lesions were higher in males than in females in the 1.25, 2.5 and 5.0% groups. In the 2-8-week studies, five rats of each sex were given diets containing 0 (control) and 5.0% of P-60. In the 5.0% group, the mean thyroid weight in males significantly increased to 161% of the control as early as 2 weeks and increased to 357% of the control at 8 weeks. Histologically, these goiters were also associated with follicular cell hypertrophy/hyperplasia as in the 13-week study. The degree and incidence of thyroid lesions were higher in males than in females. These results indicate that dietary administration of the green tea extract catechins at high doses induced goiters in rats, and this may be due to antithyroid effects of catechins. In the 13-week study, the no-observed effect level (NOEL) of green tea extract catechins for F344 rats based on histological changes of the thyroid was considered to be 0.625% in males and 1.25% in females in the diet, respectively.

Chronic oral toxicity and carcinogenicity study of thiabendazole in rats.

The potential toxicity and carcinogenicity of thiabendazole (TBZ) was investigated in F344 rats. TBZ was given in pelleted diets at different dietary levels (0, 0.05, 0.1, 0.2 or 0.4%) to groups of 30 rats of each sex for 104 wk. Throughout the study, a marked decrease in body-weight gain was observed in males and females fed 0.4% TBZ. Transitional cell hyperplasia of the renal pelvis and/or papilla was observed in dosed groups of each sex with significant positive trends. Low incidence of transitional cell papilloma or carcinoma of the urinary system was recorded in the dosed groups. Preputial gland adenoma occurred in males treated with 0.4% TBZ, and the incidence was significantly higher than in controls. There was no clear-cut evidence of the carcinogenic activity of TBZ in the urinary system of male and female rats.

[The male reproductive function in patients with spinal cord injury].

Seminal findings and blood hormone levels were studied for evaluating the male reproductive function in patients with spinal cord injury. The patients were divided into 3 groups, namely, 18 patients with complete injury, 5 patients with incomplete injury and 3 patients with dyspermatism. The number of sperms, the rate of movement and rate of deformation were measured for semen obtained by forced ejaculation. The number of sperms was kept at a relatively high level in the three groups, while the rate of movement fell off in all of the three groups. The rate of deformation was highest in the patients with complete injury and lowest in the patients with dyspermatism. As for blood hormone levels, LH, FSH and Testosterone (hereinafter referred to as TES) were determined by the RIA. The cases were classified into those in the acute stage and those in the chronic stage 3 months after sustaining injury for a comparative study. The subjects consisted of 27 cases in the acute stage and 47 cases in the chronic stage. For 8 patients in the acute stage, the blood hormone levels were determined even in the chronic stage and follow-up observations were made on the changes in the levels. The FSH level was low in both stages, while LH and TES tended to increase in the chronic stage. Particularly, the TES level was elevated in all the cases in the follow-up observations made in 8 patients. From the results mentioned above, transient disturbance of the interstitial function is suggested as the mechanism of male gonadal disturbance due to spinal cord injury.

[A case of squamous cell carcinoma of the renal pelvis accompanying an ectopic opening with vesicoureteral reflux of complete duplication of uretero pelvis].

Squamous cell carcinoma of the renal pelvis is a relatively rare disease. Recently, we observed a case of squamous cell carcinoma of the renal pelvis with vesicoureteral reflux in a 49-year-old female patient. Her main symptom was abdominal pain on the left side. The complete duplications of uretero-pelvis on both sides, and vesicoureteral reflux in the upper left part of the kidney were recognized by means of various examinations. During the operation, a tumor was found in the upper left renal pelvis, and in the ureter belonging to the upper left renal pelvis. Pathologically, it was diagnosed as a squamous cell carcinoma. After the extraction of the left uretero-pelvis, 50 Gy of radiotherapy was administered to the patient. However, she died four months after the operation.

Enhancing effect of thiabendazole on urinary bladder carcinogenesis induced by sodium o-phenylphenate in F344 rats.

Sodium o-phenylphenate (OPP-Na), a urinary bladder carcinogen in rats, and another fungicide, thiabendazole (TBZ) were fed separately or simultaneously to F344/DuCrj rats of both sexes. The rats were fed one of six diets, either the basal (control) diet or basal diet containing 0.2% TBZ (group T), 1% OPP-Na (1% SO), 2% OPP-Na (2% SO), 1% OPP-Na plus 0.2% TBZ (1% SO-T) or 2% OPP-Na plus 0.2% TBZ (2% SO-T) for 13 or 65 wk. In the 13-wk study, in which groups of ten rats of each sex were used, urinary bladder tumours appeared in 8/10 males in each of three groups--the 2% SO, 1% SO-T and 2% SO-T groups--but not in the remaining animals. Of these tumours, carcinoma accounted for 3/8 tumours in the 2% SO group, 2/8 in the 1% SO-T group and 8/8 in the 2% SO-T group. In the 65-wk study, in which groups of 15 rats were used, the tumour incidence in males was 1/15 in the T group and 15/15, 12/15 and 14/15 in the 2% SO, 1% SO-T and 2% SO-T groups, respectively, while in the females, tumours were found in 2/15, 1/15 and 12/15 animals in the 2% SO, 1% SO-T and 2% SO-T groups, respectively. Of these tumours, carcinoma accounted for 10/15, 11/12 and 10/14 in the males of the 2% SO, 1% SO-T and 2% SO-T groups, respectively, and for 1/2 and 6/12 in the 2% SO and 2% SO-T females, respectively. The tumour incidences in the 1% SO-T males in the two studies and in the 2% SO-T females in the 65-wk study showed a statistically significant increase over those in the 1% SO males or the 2% SO females. Thus, TBZ apparently enhanced the carcinogenic effects of OPP-Na in the rat urinary bladder.