[Effects of cernitin pollen-extract (Cernilton) on inflammatory cytokines in sex-hormone-induced nonbacterial prostatitis rats].

Cernitin pollen-extract (Cernilton, CN) is a preparation made from eight kinds of pollen and has been used for various prostatic diseases in Japan and Europe. We reported previously that CN possessed a recovery action on the sex-hormone-induced nonbacterial prostatitis in rats. To clarify the possible mechanism of action of CN, we investigated the effects of CN on inflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha) in the same model. Aged Wistar rats were castrated and injected 17 beta-estradiol (0.25 mg/kg/day, s.c.) for 30 days. CN (630 and 1,260 mg/kg, p.o.) or testosterone (2.5 mg/kg, s.c.) was administered for the last 14 days of the treatment of 17 beta-estradiol. In control rats, prostatic IL-6 and TNF-alpha contents were increased approximately 2-3 fold, and acinar glandular inflammation and stromal proliferation were found histopathologically, as compared with those of intact rats. On the other hand, CN decreased the increased contents of cytokines in a dose-dependent manner. The histopathological changes mentioned above were restored in rats treated with 1,260 mg/kg. Testosterone also ameliorated them significantly. These results indicate that CN has an anti-inflammatory action, and that the inhibitory effect of CN on the prostatic inflammatory cytokine is an important factor in its action.

Antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines.

OBJECTIVES: To investigate the antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on human bladder cancer cell lines (KU-1 and EJ-1) and a murine bladder cancer cell line (MBT-2). METHODS: Bladder cancer cells were incubated with various concentrations of the agents. Antiproliferative activity against the bladder cancer cell lines was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diplenyl tetrazolium bromide assay. In an in vivo experiment, the mice were subcutaneously injected with MBT-2 cells, and Scutellariae radix was orally administered at a dose of 2 or 10 mg per mouse one time daily for 10 days from day 11 to day 20. RESULTS: All the drugs inhibited cell proliferation in a dose-dependent manner, but baicalin exhibited the greatest antiproliferative activity. The concentration of baicalin necessary to obtain 50% inhibition was 3.4 microg/mL for KU-1, 4.4 microg/mL for EJ-1, and 0.93 microg/mL for MBT-2. For KU-1 and MBT-2, the percentage of cell survival significantly decreased (P <0.05) at a baicalin concentration of 1 microg/mL. In an in vivo experiment, antitumor effects of Scutellariae radix on C3H/HeN mice implanted with MBT-2 were investigated. All the control mice showed a progressive increase in tumor volume, reaching 2.81 +/- 0.18 cm(3) on day 20 and 5.36 +/- 0.44 cm(3) on day 25. However, when Scutellariae radix was orally administered at a dose of 10 mg per mouse one time daily for 10 days from day 11 to day 20, the tumor volume was 1.99 +/- 0.19 cm(3) on day 20 and 3.86 +/- 0.26 cm(3) on day 25, a significant inhibition of tumor growth (P <0.05). Conclusions. These results suggest that Chinese herbal medicines may become an attractive and promising treatment for bladder cancer.

Clinical evaluation of long-term treatment using cernitin pollen extract in patients with benign prostatic hyperplasia.

Seventy-nine patients with benign prostatic hyperplasia (BPH) were treated with cernitin pollen extract. Patient ages ranged from 62 to 89 years (mean, 68 years). Mean baseline prostatic volume was 33.2 cm3. Cernitin pollen extract was administered in a dosage of 126 mg (2 tablets, 63 mg each), three times a day, for more than 12 weeks. Symptom scores, based on a modified Boyarsky scoring scale, uroflowmetry, prostatic volume, residual urine volume, and urinalysis results were examined before and after administration of cernitin pollen extract. Symptom scores significantly decreased from baseline, and the favorable results continued during the treatment period. Urine maximum flow rate and average flow rate increased significantly from 9.3 mL/s to 11 mL/s and from 5.1 mL/s to 6 mL/s, respectively. Residual urine volume decreased significantly from 54.2 mL to less than 30 mL. There was no change in prostatic volume. However, 28 patients treated for more than 1 year showed a mean decrease of prostatic volume to 26.5 cm3. No adverse reactions were observed. Clinical efficacy at 12 weeks was rated excellent, good, satisfactory, and poor in 11%, 39%, 35%, and 15% of patients, respectively. Overall clinical efficacy was 85%. In conclusion, cernitin pollen extract showed a mild beneficial effect on prostatic volume and urination variables in patients with symptomatic BPH.

[Transurethral hyperthermic treatment in patients with benign prostatic hypertrophy].

Transurethral hyperthermic treatment was performed on 30 patients with benign prostatic hypertrophy (BPH). Two patients had a urethral catheter because of urinary retention. The prostate was heated transurethrally. The treatment consisted of 3-8 sessions of 60 min. each. To evaluate this treatment, the following parameters were determined before and 1-5 weeks after the last hyperthermia session; subjective symptoms score, and as objective data residual urine volume and uroflowmetry. The symptoms score improved in 25 (83%) patients. Of 2 patients with a catheter, the catheter could be removed from 1 patient. Although there was no change in prostatic volume, significant decreases in residual urine volume, and increases of maximum flow rate and mean flow rate were observed. No adverse reactions were seen. Judging from the above results, this treatment is considered to be useful for patients with BPH.

[Transrectal hyperthermia for benign prostatic hyperplasia].

Transrectal hyperthermia was performed on 30 patients with benign prostatic hyperplasia twice a week for a total of ten times with the temperature of the prostatic tissue set at 43.0 degrees C. In our in vitro experiment using an agar phantom, the highest temperature was observed at approx. 1.5 cm from the point where the 915-MHz microwave was generated. Our histopathological study of the prostatic tissue, resected at open surgery after three days of hyperthermia, indicated that the effect of hyperthermia first occurred in the interstitial tissues, and then extended to the epithelial cells. Subjective symptoms and objective findings were evaluated. In almost all cases, improvement was observed in subjective symptoms after completion of the treatment. The residual urine volume improved significantly. Also, significant improvement was observed in our urodynamics study. In 16 out of 30 cases (53%), both subjective symptoms and objective findings were still improved after six months.

[Hyperthermic treatment in patients with benign prostatic hypertrophy].

Hyperthermic treatment was performed in 31 patients with benign prostatic hypertrophy (BPH). Eight patients of them had a urethral catheter because of urinary retention. The prostate was heated trans-rectally to 43-45 degrees C. The treatment consisted of 10 sessions of 60 min. each. To evaluate this treatment, the following parameters were determined before, during and one week after the last hyperthermia session: subjective symptoms score, and residual urine volume, uroflowmetry and transrectal ultrasound of the prostate as objective data. Symptoms score improve in all patients. Of 8 patients with a catheter, the catheter could be removed from 4 patients. There was no significant change in prostate volume, but significant decreases of residual urine volume, and increases of maximum flow rate and mean flow rate were observed. No adverse reactions were seen. Judging from the above results, this treatment is considered to be useful for patients with BPH.

Multidisciplinary treatment for bladder carcinoma--biological response modifiers and kampo medicines.

Authors studied the effects of several biological response modifiers (BRMs) on bladder carcinoma. On carcinogenesis in BBN-induced bladder carcinoma rats, Schizophyllan (SPG) showed inhibition of body weight loss and thymus weight loss. Bladder weight increase was also inhibited. SPG prolonged cancer-bearing survival time, and postponed malignant changes of bladder mucosa. On thymocytes of SPG-treated cancer-bearing rats, rosette-forming thymocytes increased. In clinical study, SPG, OK-432, ubenimex and kampo medicine were used as BRMs. As a result, the number of suppressor-inducer T cells increased, and in cytotoxic T cells a slow fall was observed. On helper-inducer T cells, a slow rise and decrease were noticed in the SPG group, and the reverse tendency was seen in the ubenimex and OK-432 group.

[Clinical evaluation of Cernilton on benign prostatic hypertrophy--a multiple center double-blind study with Paraprost].

A multiple center double blind study was performed to study the effectiveness of Cernilton (CN) on benign prostatic hypertrophy in comparison to Paraprost (PP). Among a total of 192 patients, overall effect was studied on 159 patients, overall safety rate on 178 patients and rate of effectiveness on 159 patients. There were no differences between the two groups in the selected patients, criteria for exclusion and drop out cases or background data of the patients. Impression of patients and overall effect by committee and physician judgment were slightly higher in the CN group compared to the PP group, but there was no significant difference between the two groups. For the improvement in subjective symptoms, the rate of moderate improvement or more after 4 weeks by committee judgement was higher in the CN group compared to the PP group. The rate of improvement in protracted miction, which is an effective marker of urinary disturbance, was also higher in the CN group compared to the PP group. An analysis of objective symptoms showed a significant improvement in residual urinary volume, average flow rate, maximum flow rate and prostatic weight in the CN group. A significant improvement in the phased change of residual urinary volume was also seen in the CN group. No side effects or abnormalities in clinical test levels were noted in the CN group. By committee judgement, the rate of more than moderate effectiveness was 49.1% in the CN group compared to 41.2% in the PP group, but there was no significant difference between the two groups. By physician's judgment, the rate of more than moderate effectiveness was 49.4% in the CN group compared to 46.3% in the PP group, but there was also no significant difference between the two groups. These results suggested that Cernilton was an effective drug for benign prostatic hypertrophy.

Red blood cell aluminum in patients with renal failure and effect of desferrioxamine infusion.

Red blood cell (RBC) aluminum (Al) in patients with renal failure on different treatments was studied. Nondialyzed renal failure patients had high levels of RBC Al, but low serum Al levels. However, their RBC Al levels were lower than those of patients on hemodialysis (HD) and continuous ambulatory peritoneal dialysis. In addition, HD patients who were not given Al-containing medications showed high levels of RBC Al, which suggests that there may be a source of Al other than medications. When desferrioxamine (DFO) was administered to these HD patients, the changes in RBC Al levels after DFO infusion were independent of those in serum Al levels and blood hemoglobin levels. In an in vitro study, RBC Al was removed using an ultrafiltration membrane, which showed that RBC Al exists in a bound form. These results suggest that Al accumulates in RBCs of renal failure patients independently of serum Al levels, and that the improvement of anemia by DFO may not be due to the direct removal of RBC Al.

[Study on effectiveness of carmofur (Mifurol) in urogenital carcinoma, especially bladder cancer, as a post-operative adjuvant chemotherapeutic agent].

This study was carried out to evaluate the effects of carmofur (Mifurol), a masked compound of 5-fluorouracil (5-FU), in preventing postoperative recurrence of urogenital carcinoma (especially in bladder cancer). Carmofur was given orally at the dose of 300 approximately 600 mg/day to 134 patients (90 males and 44 females) after the resection. Out of 134 patients, 121 patients were evaluable and the rate of their recurrence was 10.7%. The rate of cumulative nonrecurrence for 65 patients it was 96.0, 73.0 and 60.8% in 1, 2 and 3 years, respectively. The group of curative resection demonstrated a higher cumulative nonrecurrence rate than that of noncurative or palliative resection group. In considering the resection methods, transurethral resection of bladder tumor group demonstrated a higher rate than partial or total cystectomy. The average concentration of 5-FU in serum was 0.65 microgram/ml at 120 minutes after oral administration of 200 mg of carmofur. Moreover, the concentration of 5-FU (15 approximately 35 micrograms/ml) in urine was higher than that of carmofur. The rate of side effects that appeared was 19.6%. The side effects were hot feeling (12.2%), pollakisuria (4.3%), anorexia (4.3%), an antabuse-like reaction by drinking (3.8%) and so on. These results were similar to those already reported.