Biomedical subjects

Bunzo Kashiwagi

Publications and source records attributed to Bunzo Kashiwagi.

14 recordsLinked to original sources

PubMed2006

Positive effect of prostaglandin on regulation of prostatic blood flow.

OBJECTIVES: To investigate the effects of prostaglandin E2 (PGE2) and its antireceptor antibody on prostatic blood flow regulation using a rat model. We estimated that PGE2 participated in the signaling pathway of hormonal regulation of the prostatic blood flow. METHODS: The rats were castrated and injected locally with dihydrotestosterone (200 ng/head) or PGE2 (250 ng/head) directly into the prostatic membrane. After local dihydrotestosterone or PGE2 administration, anti-PGE2 receptor antibody (200 ng/head) was injected locally to investigate interruption of the signaling pathway. After administration, we evaluated the relative prostatic blood flow using a laser blood flow meter. The change in cyclooxgenase-2 mRNA expression and the changes in PGE2 concentration in response to androgen stimulation were also examined. RESULTS: PGE2 was involved in blood flow regulation with activity equal to that of androgen. The effect of dihydrotestosterone was abolished by coadministration with anti-PGE2 receptor antibody. Cyclooxgenase-2 gene expression was upregulated in response to androgen stimulation. The PGE2 concentration also increased in response to androgen stimulation. CONCLUSIONS: Our finding of PGE2 participation in androgen regulation of prostatic blood flow might lead to pathophysiologic elucidation of prostatic diseases.

Animals↗

PubMed2006

Participation of adrenomedullin and its relation with vascular endothelial growth factor in androgen regulation of prostatic blood flow in vivo.

OBJECTIVES: We had previously reported that androgen-regulated prostatic blood flow and vascular endothelial growth factor (VEGF) were involved in the signal transduction pathway. Adrenomedullin (ADM) is a multifunctional regulatory peptide with mitogenic and angiogenic capabilities that are regulated by androgen. ADM is abundantly expressed in the prostate. We focused on ADM and evaluated its participation and relation with VEGF in androgen prostatic blood flow regulation using a castrated rat model. METHODS: We examined the effect of locally injected dihydrotestosterone (DHT) and ADM, and the co-administration of DHT with an ADM receptor antagonist (ADM 22-52) on prostatic blood flow. Furthermore, prostatic blood flow was evaluated after ADM and VEGF administration with each other's antagonist, VEGF neutralizing antibody and ADM 22-52, respectively. Changes in the mRNA expression levels of ADM in the prostate after castration and successive androgen stimulation were also evaluated. RESULTS: The administration of ADM promptly increased prostatic blood flow in a dose-dependent manner within 30 minutes. The DHT-induced increase in prostatic blood flow was completely abolished by co-administration with anti-ADM. Anti-ADM inhibited the VEGF-induced prostatic blood flow elevation, but a VEGF neutralizing antibody did not affect the ADM-mediated blood flow elevation. Furthermore, upregulation of the ADM gene induced by DHT was inhibited by co-administration with a VEGF-neutralizing antibody. CONCLUSIONS: These results have clearly demonstrated the direct regulation of prostatic blood flow by ADM and its involvement in androgenic prostatic blood flow regulation. Furthermore, ADM was estimated to be a downstream mediator of VEGF action in the signal transduction pathway.

Adrenomedullin↗

PubMed2005

Acute genitourinary toxicity after high dose rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: Second analysis to determine the correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity.

PURPOSE: We have been treating localized prostate cancer with high-dose-rate (HDR) brachytherapy combined with hypofractionated external beam radiation therapy (EBRT) at our institution. We recently reported the existence of a correlation between the severity of acute genitourinary (GU) toxicity and the urethral radiation dose in HDR brachytherapy by using different fractionation schema. The purpose of this study was to evaluate the role of the urethral dose in the development of acute GU toxicity more closely than in previous studies. For this purpose, we conducted an analysis of patients who had undergone HDR brachytherapy with a fixed fractionation schema combined with hypofractionated EBRT. METHODS AND MATERIALS: Among the patients with localized prostate cancer who were treated by 192-iridium HDR brachytherapy combined with hypofractionated EBRT at Gunma University Hospital between August 2000 and November 2004, we analyzed 67 patients who were treated by HDR brachytherapy with the fractionation schema of 9 Gy x two times combined with hypofractionated EBRT. Hypofractionated EBRT was administered at a fraction dose of 3 Gy three times weekly, and a total dose of 51 Gy was delivered to the prostate gland and seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography-guided HDR brachytherapy. The planning target volume was defined as the prostate gland with a 5-mm margin all around, and the planning was conducted based on computed tomography images. The tumor stage was T1c in 13 patients, T2 in 31 patients, and T3 in 23 patients. The Gleason score was 2-6 in 12 patients, 7 in 34 patients, and 8-10 in 21 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 11 months (range 3-24 months). The toxicities were graded based on the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer toxicity criteria. RESULTS: The main symptoms of acute GU toxicity were dysuria and increase in the urinary frequency or nocturia. The grade distribution of acute GU toxicity in the patients was as follows: Grade 0-1, 42 patients (63%); Grade 2-3, 25 patients (37%). The urethral dose in HDR brachytherapy was determined using the following dose-volume histogram (DVH) parameters: V30 (percentage of the urethral volume receiving 30% of the prescribed radiation dose), V80, V90, V100, V110, V120, V130, and V150. In addition, the D5 (dose covering 5% of the urethral volume), D10, D20, and D50 of the urethra were also estimated. The V30-V150 values in the patients with Grade 2-3 acute GU toxicity were significantly higher than those in patients with Grade 0-1 toxicity. The D10 and D20, but not D5 and D50, values were also significantly higher in the patients with Grade 2-3 acute GU toxicity than in those with Grade 0-1 toxicity. Regarding the influence of the number of needles implanted, there was no correlation between the number of needles implanted and the severity of acute GU toxicity or the V30-V150 values and D5-D50 values. CONCLUSIONS: It was concluded that HDR brachytherapy combined with hypofractionated EBRT is feasible for localized prostate cancer, when considered from the viewpoint of acute toxicity. However, because the urethral dose was closely associated with the grade of severity of the acute GU toxicity, the urethral dose in HDR brachytherapy must be kept low to reduce the severity of acute GU toxicity.

Aged↗

PubMed2005

Effect of androgen concentration on seminal vesicle blood flow in rats-establishment of new highly sensitive simultaneous androgen measurement method.

OBJECTIVES: To clarify the effect of androgen concentration on blood flow regulation in seminal vesicles and to identify the androgen most responsible for this effect. METHODS: The androgen concentrations in the seminal vesicles and the seminal vesicle blood flow were measured at 0, 3, 6, 12, 24, 48, and 72 hours after castration. The androgen concentration was measured with a newly developed highly sensitive simultaneous androgen quantification method that uses liquid chromatography-tandem mass spectrometry. The blood flow was measured with the radioactive microsphere injection method. The change in seminal vesicle blood flow in 6-hour castrated rats after administration of 3 mg/kg testosterone, 3 mg/kg dihydrotestosterone (DHT), 3 mg/kg dehydroepiandrosterone, or 3 mg/kg testosterone plus 20 mg/kg finasteride was evaluated. RESULTS: A correlation was observed between the DHT concentration and blood flow in the rat seminal vesicle after castration. The DHT concentration and blood flow decreased after castration to 31.6% and 37.9%, respectively, of the normal level at 6 hours. The decline in DHT concentration and blood flow decreased further thereafter to 2.2% and 18.1%, respectively, of the normal level at 72 hours. Both testosterone and DHT fully restored the organ blood flow in castrated rat seminal vesicles. However, the blood-flow-increasing effect of testosterone was attenuated by more than 50% when administered in combination with finasteride. Dehydroepiandrosterone did not increase seminal vesicle blood flow. CONCLUSIONS: The results of our study showed a strong correlation between the organ DHT concentration and blood flow in rat seminal vesicles. Of the various androgens, the most active androgen in the regulation of seminal vesicle blood flow was DHT.

Androgens↗

PubMed2005

Administration of extract of mushroom Phellinus linteus induces prostate enlargement with increase in stromal component in experimentally developed rat model of benign prostatic hyperplasia.

OBJECTIVES: To clarify the effect of the mushroom extract Phellinus linteus on noncancerous prostate cells using an experimentally developed rat benign prostatic hyperplasia model. A growing number of people take some natural herbal extracts for maintenance of their health. Among them, the extracts of certain mushrooms are believed to have a marked tumoricidal effect but low toxicity for normal tissues, and they are being drunk widely in Japan and Korea. However, until now, their effect on noncancerous benign prostate growth has not been examined. METHODS: The mushroom extract was administered daily for 5 weeks to experimentally developed benign prostatic hyperplasia rats. Prostate organ weight, histologic composition, and gene expression levels of sex hormone receptors, transforming growth factor-beta, vascular endothelial growth factor, and endothelial nitric oxide synthase were examined. RESULTS: Prostate weight increased significantly by 37% owing to treatment with the mushroom extract (P < 0.05). In particular, the stromal component of the prostate increased significantly by 80% (P < 0.05). A suppression of transforming growth factor-beta1 expression by 56% was observed with the mushroom extract treatment (P < 0.05). CONCLUSIONS: We found that the mushroom extract enlarged the prostate. The effect was suggested to be on the prostate stroma, which may be involved in transforming growth factor-beta1 regulation. Administration of mushroom extract should be considered carefully by those with an enlarged prostate.

Agaricales↗

PubMed2005

[Androstenedione].

Explore the source record for details and available documents.

Adrenal Hyperplasia, Congenital↗

PubMed2004

Direct regulation of prostate blood flow by vascular endothelial growth factor and its participation in the androgenic regulation of prostate blood flow in vivo.

Previous studies on prostate blood flow regulation have indicated that androgen regulates prostate blood flow. However, the mechanism responsible for this regulation is unknown. In the present study, we focused on the effects of vascular endothelial growth factor (VEGF), a key factor responsible for angiogenesis and androgenic blood flow regulation. We examined in vivo the effect of VEGF on prostate blood flow and its participation in the androgenic regulation of this blood flow using a castrated rat model following subcapsular intraprostatic injection method. We found that VEGF is involved in blood flow regulation with an activity equal to that of dihydrotestosterone (DHT). The effect of VEGF on prostate blood flow was already seen at 30 min after the administration. The elevating effect of DHT on castrated rat prostate blood flow was abolished by coadministration of DHT with neutralizing anti-VEGF antibody. The change in VEGF-A mRNA expression in response to androgen stimulation was examined by double-fluorescent probe quantitative PCR (Taqman PCR). The results showed that androgenic regulation of VEGF gene expression occurred shortly after androgen stimulation. VEGF gene up-regulation was abolished or down-regulated by coadministration of neutralizing anti-VEGF antibody. This is the first report on the importance of VEGF in the androgenic regulation signaling pathway that affects prostate blood flow. Alternative treatment targeted toward anti-VEGF activity as a substitute for ordinary antiandrogenic therapy may be effective against prostate diseases, especially those with androgen-independent and hyperhemorrhagic status.

Androgens↗

PubMed2004

Androgen-dependent blood flow control and morphological changes of the capillaries in rat prostate.

To clarify the effect of androgens on the microcirculation of the prostate, organ blood flow and ultrastructural features of the capillaries were investigated. In the ventral prostate (VP) of adult Wistar rats, organ blood flow was measured using a laser Doppler flowmetry, and the morphological features of the subepithelial capillaries were investigated and their luminal area was measured using transmission electron microscopy and a computed image analyzer at 1, 2, 3, and 7 days after castration, and 2 days after castration and gradational testosterone supplementation. The capillaries of the VP were classified into three types; oval opened (type 1), intermediate (type 2) and collapsed (type 3). Organ blood flow reduced from 40.5 to 27.7 mL/min/100 g (p < 0.0001) and the luminal area of the capillaries reduced from 13.5 to 4.5 microm2 (p < 0.0001) 2 days after castration. These reductions of the blood flow and the luminal area were gradationally prevented by testosterone supplementation. In the morphological features of the capillary, type 1 had rapidly shifted to types 2 and 3 after castration, and the shift of the capillary type was significantly prevented by the testosterone supplementation. These results clearly demonstrated that the androgen-dependent ultrastructural and morphological features in subepithelial capillaries revealed local microcirculatory conditions correlating the organ blood flow changes in VP.

Animals↗

PubMed2004

Role of androgen on blood flow and capillary structure in rat seminal vesicles.

To clarify the effect of androgen on the microcirculation in seminal vesicles of adult Wistar rats, we investigated the organ blood flow and morphological features in the capillaries after castration and subsequent testosterone supplementation. Testosterone (T) was subcutaneously injected every 12 hours after castration and its doses were set to 10(-2), 10(-1), 10(0) and 10(1) mg/kg-body weight (T10(-2), T10(-1), T10(0) and T10(1) groups, respectively). Organ blood flow was measured using laser Doppler flowmetry, and the subepithelial capillaries were analyzed using transmission electron microscopy. The capillaries were morphologically classified into 3 types; oval opened (type 1), intermediate (type 2) and collapsed (type 3), and their luminal areas were measured using a computed image analyzer. The organ blood flow was significantly reduced from 36.3+/-5.1 to 21.9+/-2.7 ml x min(-1)/100 g tissue, and the luminal area of the capillaries was significantly reduced from 9.02+/-1.28 to 4.85+/-0.82 microm2 with the shift of the type 1 and type 2 to type 3 after castration. The reduction of the luminal area and the blood flow reduction, and shift of the capillary type were significantly protected by gradated testosterone supplementation. These results indicate that the maintenance of the blood flow and morphological profiles in capillaries depend on androgen-supplementation levels in seminal vesicles.

Animals↗

PubMed2003

The evaluation of rat prostate blood flow using a laser speckle flowmetry: a comparative study using the microsphere method in castrated and androgen-replenished rats.

To evaluate the accuracy and reliability of laser speckle blood flowmetry in the measurement of prostate blood flow, we performed a comparative study with the ordinary intra-arterial radioactive microsphere injection method using the well-known castrate-rat model. Adult male Wistar strain rats were used for the study. The rats were either only castrated or subcutaneous testosterone replenishment was followed subcutaneously 6 h after castration. The prostate blood flow was measured at different time courses after castration. The effect of a single androgen replenishment on prostate blood flow was also evaluated. The measurement of prostate blood flow was performed by both the radioactive microsphere injection method and laser speckle blood flowmetry, and then the outcomes were compared. Rapid reduction in prostate blood flow to 30% of the normal level was observed 24 h after castration in the measurements with the microsphere injection technique. The prostate blood flow decreased gradually after 24 h post-castration to 23 and 21% of the normal level at 48 and 72 h after castration, respectively. The laser speckle blood flowmetry also detected the decrease in prostate blood flow well, but in a more gradual manner. The prostate blood flow was 70, 52 and 35% of the normal level at 24, 48 and 72 h after castration, respectively. The effect of a single administration of testosterone to castrated rats had recovered the prostate blood flow to 74 and 98% of the normal level by measurement with the microsphere injection technique and laser speckle blood flowmetry, respectively. The different outcome in blood flow rate change between the methods can be explained according to their different mechanism of measurement, thus suggesting the capillary vessels are the early and most responsive portion for hormonal manipulation. In conclusion, the laser speckle blood flowmetry is a convenient and reliable method for evaluating prostate blood flow, especially when the organ is required for other biological and molecular assays, since the method does not require the excision of the organ for the measurement.

Androgens↗

PubMed2003

Genetic polymorphisms of estrogen receptor alpha, CYP19, catechol-O-methyltransferase are associated with familial prostate carcinoma risk in a Japanese population.

BACKGROUND: Estrogen is one of the crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. The authors evaluated the association between genetic polymorphisms in estrogen-related enzymes and receptors and the risk of developing familial prostate carcinoma. METHODS: In the current study, 101 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 114 healthy age and residence-matched male controls were enrolled. The genotypes of estrogen receptor (ER) alpha, aromatase (CYP19), and catechol-O-methyltransferase (COMT) genes were analyzed. RESULTS: For single polymorphisms, a significant association of the T/T genotype of the PvuII site in the ER alpha gene (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.97-5.99; P = 0.0028), and the C/T and T/T genotypes of the CYP19 gene (OR, 1.77; 95% CI, 1.02-3.09; P = 0.037) with prostate carcinoma risk, was observed. The G/A genotype of the COMT gene showed a weak tendency toward increased risk (OR, 1.48; 95% CI, 0.85-2.57; P = 0.18). Stratification of cases according to clinical stage and pathologic grade showed that the C/T and T/T genotypes of the CYP19 gene were associated significantly with high-grade carcinoma (OR, 2.59; 95% CI, 1.47-4.46; P = 0.048). The number of high-risk genotypes (the T/T in ER alpha, the C/T and T/T in CYP19, and the G/A in COMT) significantly increased the risk of developing prostate carcinoma (2 genotypes: OR, 3.00; 95% CI, 1.72-5.23; P = 0.008; 3 genotypes: OR, 6.30; 95% CI, 3.61-10.99; P = 0.002). CONCLUSIONS: Genetic polymorphisms of genes in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma.

Adult↗

PubMed2003

Hormonal and morphologic evaluation of the effects of antiandrogens on the blood supply of the rat prostate.

OBJECTIVES: To clarify the basic aspects of the regulation of the prostatic blood supply by antiandrogens, their effect on the prostatic blood supply was studied for both androgen content and morphology of true capillaries in the rat ventral prostate. The effectiveness of antiandrogens on the control of hemorrhagic status in prostatic diseases has been previously reported. METHODS: Androgen concentrations in the prostate were quantified after administration of chlormadinone acetate (CMA), finasteride, or flutamide. The prostatic blood supplies were measured after administration of CMA, finasteride, flutamide, or bicalutamide. The alpha-blockers, terazosin and tamsulosin, were included in the study as negative controls. The histologic changes in the capillaries of the ventral prostate were observed, and the luminal area was measured. RESULTS: The prostate dihydrotestosterone concentrations were decreased by the administration of all antiandrogens. Treatment with CMA, finasteride, flutamide, or bicalutamide reduced the prostatic blood supply by 50% to 65%. The parallel reduction in luminal areas of the true capillaries was observed in rats treated with CMA. Treatment with alpha-blockers did not affect the prostate androgen content, prostatic blood supply, or capillary luminal area. CONCLUSIONS: The reduction of the prostatic blood supply was suggested to be the result of a decrease in dihydrotestosterone content and the reduction in the luminal area of capillaries. The early reductive effect of antiandrogens on the prostatic blood supply suggests an alternative use for antiandrogens independent of their typical use for prostate volume regression. The results support the basic aspects of the advantage of preoperative treatment with CMA, flutamide, and bicalutamide, similar to finasteride, in reducing perioperative hemorrhage.

5-alpha Reductase Inhibitors↗

PubMed2002

[Chromophobe cell renal carcinoma: a case report].

We report a case of chromophobe cell carcinoma in a 41-year-old woman who was admitted to our hospital because of right upper abdominal pain. We performed right radical nephrectomy under the diagnosis of renal cell carcinoma. The cut surface appearance of the tumor was homogeneous, grey beige and solid. This tumor was diagnosed as chromophobe cell renal carcinoma after microscopic and immunohistochemical studies. We report our case with reference to the relevant literature.

Adult↗

PubMedDate not supplied

Changes in testosterone and dihydrotestosterone levels in male rat accessory sex organs, serum, and seminal fluid after castration: establishment of a new highly sensitive simultaneous androgen measurement method.

It is known that abnormal androgen dynamics in the tissues is a cause of androgen-dependent disorders. Investigation of tissue androgen levels could provide a clue to the elucidation of disorders. However, it is difficult to measure a trace amount of androgen in the tissues. We established a highly sensitive simultaneous quantification method of testosterone and dihydrotestosterone (DHT), which play the most important roles in the body among androgenic steroids in trace amounts, and investigated time course changes in testosterone and DHT levels in male accessory sex organs, serum, and seminal fluid after castration in rat models. In addition, changes in the testosterone/DHT ratio of male accessory sex organs and seminal fluid were observed. The simultaneous testosterone and DHT measurement method established by us was validated. Intra-assay variation and interassay precision and accuracy were all within +/-20%, and the quantification limits of testosterone and DHT were both 15.6 pg/g. With the use of this method, the testosterone and DHT levels in the prostate, seminal vesicles, and serum immediately after castration were similar to those previously reported. The testosterone and DHT levels were 350 pg/g and 605 pg/g, respectively; which showed dominance of DHT in seminal fluid, although it was not as marked as that in the male accessory sex organs. Androgens decreased with time after castration in the accessory sex organs, serum, and seminal fluid. In the prostate and seminal vesicles, testosterone and DHT decreased to about 50% and about 2% of the normal levels, respectively, 72 hours after castration. The serum levels were under the quantification limits 6 hours after castration and thereafter. In seminal fluid, the testosterone and DHT levels decreased to 49% and 35% of normal levels, respectively, 72 hours after castration. The testosterone/DHT ratio in the male accessory sex organs was lower in the prostate (0.06) than in the seminal vesicles (0.13) immediately after castration. In the seminal fluid, changes in the ratio were small compared with those in the accessory sex organs and serum. These results showed that our method was capable of measuring testosterone and DHT in very small amounts of samples such as prostate biopsy specimens, and it might provide a clue to the elucidation of the pathology of androgen-dependent disorders.

Animals↗