BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common proliferative disease affecting men. Numerous minimally invasive technologies are being developed or are currently in use to obviate the need for transurethral surgery. The goal of the present study was to develop a novel molecular based approach for the treatment of BPH using recombinant p53 adenoviral vector. The over-expression of wt-p53 can cause cell apoptosis or cell growth arrest, thus preventing the uncontrolled cell proliferation underlying BPH pathophysiology. METHODS: Ad-CMV-p53, a replication-deficient recombinant adenovirus containing cytomegalovirus promoter driving p53 gene, was used. Human prostate stromal (PS) cells were evaluated for apoptosis (TUNEL assay), mRNA levels of key cell cycle regulators influencing apoptosis (p-53, Bax and Bcl-2) using quantitative RT-PCR and cytotoxicity after Ad-CMV-p53. Ad-CMV-p53 was unilaterally injected into rat ventral prostates and growth inhibition was measured by prostate weight 3 weeks after injection. RESULTS: In vitro exposure to Ad-CMV-p53 significantly inhibited the proliferation of PS cells, induced mRNA over-expression of both wt-p53 and Bax, and increased the proportion of apoptotic cells. A 30% decrease in average prostate weight was demonstrated in rodents after Ad-CMV-p53 injection. CONCLUSIONS: The results suggest that further investigation of molecular gene therapy with recombinant wt-p53 adenovirus for the treatment of BPH is warranted.

Adenoviridae↗

PubMedDate not supplied

Fluorescence in situ hybridization analysis of sex-chromosome mosaicism in azoospermic men.

A retrospective study was carried out to determine the prevalence of sex-chromosome mosaicism among azoospermic men and to evaluate the feasibility of using fluorescence in situ hybridization (FISH) technique to assess mosaicism and the origin of marker chromosomes. Nine hundred eighty patients with azoospermia who were referred to a male infertility clinic at a university hospital were karyotyped by G-banding using peripheral blood lymphocyte (PBL) metaphase spreads. When sex chromosome mosaic karyotype was detected, FISH analyses using sex chromosome-specific probes were performed. Seventeen of 980 patients showed evidence of sex chromosomal mosaic karyotype or mosaicism with marker chromosomes by G-banding studies of PBLs. Ten patients showed mosaicism in the number of sex chromosomes and 7 showed mosaicism with marker chromosomes. All 17 patients agreed to undergo FISH analysis. FISH confirmed mosaicism in 88.2% of these patients (15 of 17). Low-frequency mosaicism showing a frequency of less than 10% by G-banding was proved to be nonmosaicism by FISH. Marker chromosomes detected in 7 patients were proved to be derived from the Y chromosome by FISH analyses. From these data the prevalence of sex chromosome mosaicism confirmed by FISH analysis is 1.5% (15 of 980 patients). FISH analysis should be applied when mosaicism shows a frequency of less than 10% by the G-banding technique. Also, FISH analysis is indicated when a marker chromosome is detected by G-banding.

Animals↗

PubMedDate not supplied

Subsegmental transcatheter arterial embolization for hepatocellular carcinoma in the caudate lobe.

PURPOSE: To clarify the effectiveness of transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) in the caudate lobe of the liver. MATERIALS AND METHODS: Thirteen patients with HCC in the caudate lobe underwent TAE. TAE was performed by injection of the mixture of anticancer drugs (mitomycin C and doxorubicin or epirubicin) and iodized oil, followed by gelatin sponge particles. Arterial anatomy of the caudate branch, local recurrence rate, and survival rate were evaluated. RESULTS: From 31 TAEs for the caudate lobe, 22 subsegmental TAEs were successfully performed (71%). Local recurrence in the caudate lobe was seen in 10 patients (77%). Subsegmental TAE for the caudate lobe was repeated one to five times. Cumulative local recurrence rates were 33% and 75% within 3 and 6 months, respectively. Survival rates after first TAE for HCC in the caudate lobe were 89% and 74% for 1 and 3 years, respectively. CONCLUSION: Local recurrence rate after subsegmental TAE for HCC in the caudate lobe was high. However, repeated subsegmental TAE possibly improves the prognosis of HCC in the caudate lobe.

Aged↗

PubMedDate not supplied

Sertoli cell number in testes of azoospermic men: trends in biopsy specimens.

The general male population has shown a long-term decline in sperm count. Induced hormonal imbalance can produce adverse reproductive effects in men, especially decreases in sperm count. One suggested cause for a decreased sperm count is a reduction in the number of Sertoli cells. The authors assessed numbers of Sertoli cells in testicular biopsy specimens obtained from azoospermic men between 1989 and 1999. The number of Sertoli cells per tubular area or circumference did not vary by year of biopsy among the tissue samples during this 10-year period. Patient age, taken as a measure of exposure duration to hypothesized abnormal hormonal environment, did not affect the number of Sertoli cells. Since no reduction in the number of Sertoli cells was observed, other pathogenic factors may be the cause of long-term decreases in sperm count.

Adult↗

PubMedDate not supplied

Adenovirus-mediated p53 gene transfer to rat testis impairs spermatogenesis.

The tumor suppressor protein p53 participates in normal cell differentiation as well as induction of programmed cell death. The authors investigated the effect of p53 overexpression on spermatogenesis by transferring p53 gene into the rat testes. Replication-deficient recombinant adenovirus vectors were constructed to include cytomegalovirus (CMV) promoter driving wild-type p53 (Ad-CMV-p53) or beta-galactosidase (Ad-CMV-beta-gal). Virus was delivered to cells of the tubules by slow retrograde injection through the rete testis. At 0, 4, 7, and 14 days, testes were removed, weighed, and analyzed histopathologically, including immunohistochemistry for p53, Bcl-2, Bax, and interleukin-1beta converting enzyme (ICE). Testicular weight was decreased in Ad-CMV-p53 group at 14 days after injection, while no change occurred in phosphate-buffered saline-injected controls or Ad-CMV-beta-gal-infected testes. Beyond 4 days, cell degradation in tubules interfered with immunohistochemical observation in the Ad-CMV-p53 group. At 4 days, p53 was expressed mostly in spermatocytes. Bax showed greater expression in the p53 group than in the control or Ad-CMV-beta-gal group. ICE, expressed mostly in spermatids, was more abundant in the p53 group than in controls. Overall, p53 overexpression in the testis impaired spermatogenesis.

Adenoviridae↗

PubMedDate not supplied

Serum inhibin pro alphaC in infertile men.

Specific assays have been developed for bioactive inhibin dimers, inhibin A and B, and inhibin alpha-subunit precursor pro alphaC. To better understand the role of serum inhibin pro alphaC in infertile men, the authors measured these forms of inhibin in sera from 39 infertile men and analyzed inhibin relationships with serum gonadotropins, testosterone, and estradiol. All subjects had oligozoospermia. Inhibin A levels were undetectable in all subjects. Inhibin B concentrations were 117 +/- 59 pg/mL. Inhibit B concentrations correlated negatively with serum FSH (r = .584, p < .0001) and positively with sperm count (p < .01) and bilateral testicular volume (r = .607, p < .0001). The concentration of pro alphaC was 556 +/- 236 pg/mL (normal range, 446 +/- 28). Inhibin pro alphaC showed no correlation with serum FSH, LH, testosterone, sperm concentration, and bilateral testicular volume. In addition, inhibin pro alphaC was not correlated with inhibin B. Pro alphaC is unlikely to be a useful marker for spermatogenesis in infertile men compared with inhibin B.

Adult↗

PubMedDate not supplied

Inhibition of steroidogenesis in Leydig cells by exogenous nitric oxide occurs independently of steroidogenic acute regulatory protein (star) mRNA.

Nitric oxide (NO) plays multiple roles in the reproductive system. The authors studied the effect of NO on LH-stimulated steroidogenesis in primary cultures of rat Leydig cells, particularly seeking a link between inhibition of steroidogenesis and changes in expression of steroidogenic acute regulatory protein (StAR). Sodium nitroprusside (SNP), an NO generator, did not alter basal testosterone, but dose-dependently reduced testosterone production in the Leydig cells stimulated by LH (100 ng/mL) at 3 h after addition of SNP. Induction of StAR mRNA transcripts could be detected as early as 1 h after the addition of LH, but no effect was detected of SNP on LH induction of StAR mRNA. StAR, then, is not affected in the inhibition by NO of LH-stimulated steroidogenesis in Leydig cells.

Animals↗

PubMedDate not supplied

Evaluation of health-related quality of life in patients treated for erectile dysfunction with viagra (sildenafil citrate) using SF-36 score.

The effect of sildenafil on health-related quality of life (HRQOL) was evaluated. Forty men (61+/-8 years old, mean +/- SD) with erectile dysfunction (ED) were studied. Sexual satisfaction as well as HRQOL according to SF-36 scales was evaluated before and after treatment with Viagra (Sildenafil citrate) at a dose of 25 or 50 mg. After treatment with Viagra, scores increased for all scales; of these, physical functioning (PF), general health (GH), and role-emotional functioning (RE) showed significant differences from baseline scores. Patients who evaluated effectiveness of the treatment as excellent showed significantly better PF, role-physical functioning (RP), and GH scale scores than those who evaluated their outcome as good or poor (p<.05 for RP and GH; p < .01 in PF). Incomparison with the scores at baseline, patients who considered outcome of Viagra to be excellent also showed significant improvements in PF, GH, and RE. Viagra treatment can improve HRQOL as well as sexual function in many patients.

Adult↗

PubMedDate not supplied

Erectile function after brachytherapy with external beam radiation for prostate cancer.

The effect of therapeutic modalities on sexual potency is an important consideration for patients choosing a treatment for prostate cancer. We assessed erectile function after iridium-192 (1r-192) high-dose rate (HDR) brachytherapy with external beam radiation therapy (EBRT), and examined the efficacy of sildenafil after this treatment. Forty-two prostate cancer patients (T1c to T3bN0M0) were treated with 22Gy HDR brachytherapy with 36.8Gy EBRT without neoadjuvant hormone therapy. Erectile function was assessed using a 5-item version of the International Index of Erectile Function questionnaire (IIEF-5), pre, 3 and 12 months after treatment, Potency was defined as an IIEF-5 score > or = 11. Ten patients with potency before HDR brachytherapy with EBRT with or without neoadjuvant hormone therapy requested Sildenafil 3 months after treatment. The mean IIEF-5 score of all patients was 10.5 +/- 8.5, 4.5 +/- 5.3 (p < 0.001), and 3.8 +/- 4.7 (p < 0.001), pre, 3 and 12 months after treatment, respectively. Seventeen (40.4%) patients were potent before treatment. The mean IIEF-5 score of those patients was 15.8 +/- 3.2, 9.6 +/- 5.1 (p = 0.04), and 11.3 +/- 6.1 (p = 0.06), pre, 3 and 12 months after treatment, respectively. Ten of 17 (58.8%) patients maintained their potency 12 months after treatment. In 10 patients with potency before treatment who were treated with sildenafil, the mean IIEF-5 score increased from 6.2 +/- 3.5 at 3 months to 13.6 +/- 5.1 (p < 0.001) at 12 months after treatment. Eight of 10 (80%) patients treated with sildenafil had recovered 12 months after treatment. HDR brachytherapy with EBRT can be performed with favorable results for maintaining potency.

Adult↗

PubMedDate not supplied

Clinical efficacy and safety of sildenafil in elderly patients with erectile dysfunction.

Erectile dysfunction (ED) is a common medical disorder affecting elderly men. Sildenafil citrate has been shown to be an effective and well-tolerated oral agent for treating ED in the general population of adult men with ED of broad-spectrum etiology. Elderly men are more likely to have concomitant medical problems than the general population of men with ED. In this study, we examined the efficacy and safety of sildenafil administration in elderly patients with ED. Forty-four elderly men with ED (> or = 60 years old) of broad-spectrum etiology were treated with 25 mg or 50 mg doses of sildenafil citrate. Age ranged from 60 to 78 years (65 +/- 4.5; means +/- S.D.). Mean follow-up period was 12.3 +/- 6.5 months, with a range of 1 to 25 months. Primary efficacy assessments were performed using the International Index of Erectile Function 5 (IIEF5) before their first dose of sildenafil and after at least 4 weeks of therapy. Serum testosterone was measured before treatment. The mean IIEF5 among all patients increased from 8.5 +/- 3.9 to 20 +/- 4.2 after sildenafil use (P < 0.0001). In patients younger than 70 years, the IIEF5 score increased from 9.5 +/- 5.0 to 17 +/- 4.3 while in patients 70 years and older, the score increased from 8.2 +/- 3.6 to 21 +/- 3.9, a near normalization. The rate of improvement in younger men was higher than in older men. Serum testosterone before treatment was similar in the two groups. The most commonly experienced adverse events were flushing and dyspepsia, which occurred in 6.8% and 2.3%, respectively. No patients discontinued sildenafil treatment due to adverse events. In conclusion, oral sildenafil is efficacious and well tolerated by elderly men with ED, even among those older than 70 years.

Aged↗

PubMedDate not supplied

Differential regulation of inhibin subunits by germ cells in human testes.

Inhibin B is comprised of two dissimilar disulfide-linked subunits, termed alpha and betaB, and is physiologically more important than inhibin A in the male. The aim of this study was to investigate testicular expression of inhibin subtypes in infertile men to uncover any interaction between Sertoli cells and germ cells. Ten azoospermic patients with Sertoli cell only syndrome (SCO) and 39 oligozoospermic men were included in this study. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone concentrations were determined by chemiluminescence assays. The serum concentrations of inhibin B were measured by enzyme-linked immunosorbent assay. Immunohistochemical staining for the alpha-subunit, betaA-subunit, and betaB-subunit of inhibin were performed on testicular biopsy specimens. The results were that serum inhibin B was undetectable in azoospermic men with SCO, while it was 133.8 +/- 82.0 pg/ml in oligozoospermic men. There was little expression of betaA in the testes of any patient. Expression of inhibin alpha and betaB was observed in Sertoli cells. The percentage of Sertoli cells expressing inhibin alpha was similar in azoospermic patients with SCO (55.3% +/- 20.6%) and in oligozoospermic patients (42.8% +/- 30.4%). In contrast, expression of betaB in Sertoli cells of azoospermic patients (24.9% +/- 16.8%) was lower than in oligozoospermic men (43.4% +/- 25.5%: P = 0.0308). There are no significant correlations between testicular expression of inhibin betaB and the serum inhibin B concentrations. The expression of inhibin betaB by Sertoli cells is dependent on the coexistence of spermatogenic activity within these seminiferous tubules, explaining why the level of inhibin B is low in patients with SCO.

Adult↗

PubMedDate not supplied

Varicocele ligation on free testosterone levels in infertile men with varicocele.

We have analyzed the effects of varicocele ligation on free testosterone levels, and investigated the interrelationships between free testosterone and fertility. The records were retrospectively evaluated for 42 infertile patients who underwent varicocele ligation, with serum free testosterone levels, follicle stimulating hormone (FSH), lutenizing hormone (LH), testosterone, estradiol, prolactin, ejaculated volume, sperm concentration and motility before and after surgery. Serum free testosterone levels increased from 12.97+/-4.16 to 13.59+/-3.93 pg/mL, but the difference was insignificant. The differences before and after surgery of patients in sperm concentration and motility were also insignificant. However, in free testosterone increasing group, the sperm concentration and motility increased significantly, from 4.05+/-4.35 to 7.90+/-8.19 million/mL (P=0.01) and from 30.64+/-21.87% to 41.00+/-22.00%, respectively (P=0.03). The increase in serum free testosterone level by varicocele ligation results in a significant improvement in sperm concentration and motility.

Adult↗

PubMedDate not supplied

Screening of FSH receptor gene mutation (C566T) in azoospermic men in Japan.

To study the genetic mutation, which could cause problems in spermatogenesis, we screened the point mutations of the FSH receptor gene (C566T) in idiopathic azoospermic men in Japan. We performed mutational analysis of the FSH receptor in 54 Japanese patients diagnosed for azoospermia with Sertoli cell-only (SCO) syndrome (n = 33), hypospermatogenesis (n = 11) and maturation arrest (n = 10). For mutation screening of the FSH receptor, polymerase chain reaction (PCR) amplification from genomic DNA with flanking intronic primers were used. On BsmI digestion, all patients demonstrated homozygous, normal exon 7 alleles with 51 and 27 bp fragments. The absence of any 78 bp fragments demonstrated that no heterozygous or homozygous mutant alleles were present in any patients. None of the 54 patients showed a C566T FSH receptor mutation. We could not confirm that the genomic mutation of the FSH receptor (C566T) is a common cause in Japanese azoospermic patients.

Adult↗

PubMedDate not supplied

Chlamydia trachomatis detected by ligase chain reaction in the semen of asymptomatic patients without pyospermia or pyuria.

To determine whether an absence of leukocytes in semen and urine predicts an absence of Chlamydia trachomatis in asymptomatic infertile men, chlamydial DNA was detected in subjects' semen and urine by ligase chain reaction (LCR). Ninety-eight infertile men were studied, including 39 cases of oligozoospermia, 19 of azoospermia, 16 of asthenozoospermia, and 24 of normozoospermia. None of the subjects had pyospermia or pyuria. C. trachomatis was detected by LCR. Antichlamydial and antisperm antibody were also measured. C. trachomatis was detected by LCR in the semen of only 1 of 98 patients (1.02%), but not in the urine samples. In C. trachomatis-positive patients LCR, IgG, and IgA levels were higher than normal. No antisperm antibody was detected. Even if leukocytes are not observed in the semen and urine of asymptomatic infertile men, the presence of C. trachomatis in semen specimens is rarely observed. Therefore, it should be noted that the presence of C. trachomatis in such cases is addressed in the context of artificial insemination and other assisted reproductive technologies.

Antibodies, Bacterial↗