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Inhibition of prostaglandin synthase by pirprofen. Studies with sheep seminal vesicle enzyme.

1. Pirprofen, racemic 2-[3-chloro-4(3-pyrrolinyl) phenyl] propionic acid, was evaluated for its ability to inhibit the conversion of arachidonic acid into prostaglandin E2 by sheep seminal vesicle prostaglandin synthase in vitro. 2. The compound proved to be a potent inhibitor with a Ki value of about 1.2 muM. Like indomethacin, aspirin and certain other non-steroidal anti-inflammatory drugs, pirprofen inhibited the enzyme competively with respect to substrate. Unlike most non-steroidal anti-inflammatory drugs, however, pirprofen did not promote time-dependent inactivation of the enzyme. It behaved as a competitive, reversible inhibitor, whereas most of the other agents acted as competitive, irreversible inhibitors. 3. The results suggest that inhibition of prostaglandin synthesis accounts in large part for the pharmacological effects of pirprofen.

Animals↗

Purification and biochemical characterization of a recombinant mouse seminal vesicle trypsin inhibitor produced in Escherichia coli.

Escherichia coli cells were transformed with an expression vector constructed by inserting a DNA fragment encoding a Kazal-type trypsin inhibitor from mouse seminal vesicle into pGEX-2. The cloned cells were able to produce a high yield of a chimeric polypeptide made by fusing the trypsin inhibitor to glutathione S-transferase. The chimeric polypeptide could be purified through an affinity column of glutathione agarose beads. The purified protein could be digested with thrombin to release the recombinant trypsin inhibitor which could be further purified by HPLC of the thrombin digests on a reverse-phase C4 column. The recombinant trypsin inhibitor was homogeneous and showed trypsin inhibitor activity as strong as that of the naturally occurring trypsin inhibitor.

Amino Acid Sequence↗

Vitamin E and methylene blue in the prevention of abnormal pigmentation in the seminal vesicles of the castrated golden hamster.

The present work reports studies carried out in order to prove if prevention of the abnormal, yellow-brown pigment that is present in the seminal vesicles of the castrated hamster was possible by means of vitamin E (from 20 to 500 mg. per cent), methylene blue (126 mg. per cent), selenium dioxide (from 20 to 200 mcg per cent) and Licidril (dimethyl-aminoethyl-p-chlorophenox and acetate 1 per cent) given in the basic diet. Prepuberal hamsters (strain Ch CM) were used; they were fed during 120 experimental days Purina Laboratory Chow as a basic diet and were castrated at the beginning of the experiment. Results allow us to conclude that 100 to 500 mg per cent of vitamin E levels and methylene blue at the administrated level prevent the macroscopic evidence of this pigment whereas selenium dioxide and Licidril do not prevent the formation of this pigment at levels administrated. Further, in this work we discuss different aspects and implications of study results that establish the existence of important interrelations between physiology and pathology of the male hamster reproductive system and metabolism of vitamin E and methylene blue that is another not biological antioxidant.

Animals↗

The antimetastatic effect of IV-inoculated BCG on adenocarcinomas in the prostate-seminal vesicle complex of L-W rats.

Adenocarcinomas were induced in the prostate-seminal vesicle complex of Lobund-Wister (L-W) rats by a single IV inoculation of N-methyl-N-nitrosourea. This was followed by three slow-release S.C. implants of testosterone propionate, each at intervals of 2 months. Small (0.5 cm diameter) palpable tumors developed which enlarged during the following month to 3-4 cm diameter. At the latter stage, tumor cells spread via lymphatics to the lungs and/or by direct extension into the peritoneal cavity. Rats with small palpable tumors were inoculated IV with viable Bacillus Calmette-Guerin (BCG). One month later, the rats were killed and examined. Untreated rats with large tumors served as controls. Comparison of the two groups revealed that body weights and tumor sizes were similar and most of them had developed metastatic tumors in the peritoneal cavity. However, lung metastases were rare in the BCG-inoculated rats compared to controls. Spleen and liver weights were significantly heavier in the BCG-treated rats. It is speculated that an intra-vascular mechanism(s), engendered by BCG, immobilized the circulating tumor cells, but not those tumor cells that spread by direct extension from the primary tumor into the peritoneal cavity.

Adenocarcinoma↗

Photoperiodic influence on the morphology and the androgen receptor level of the ventral prostate gland and seminal vesicles of the Djungarian hamster (Phodopus sungorus).

The influence of long (light:darkness LD 16:8) and short (LD 8:16) photoperiods on the morphology of the ventral prostate gland and the seminal vesicles of the Djungarian hamster was investigated. At LD 8:16, the wet weight of the glands was reduced to 15-20% of the values found in animals living in LD 16:8 conditions, the protein content was reduced to 3-4%. The glands showed distinct signs of atrophy and inactivity under short-day conditions. The androgen receptor levels were determined in both accessory sex glands. The receptor levels were comparable in both glands; the absolute values related to the whole glands remained about constant in animals living in long and short photoperiods despite a reduction of the androgen levels in short photoperiods.

Animals↗

Biological activities of a major protein secreted from the rat seminal vesicles after structural modification catalyzed by transglutaminase in vitro.

The immunosuppressive, anti-inflammatory and anti-thrombotic properties of SV-IV, a major protein secreted from the epithelium of rat seminal vesicles, were investigated after transglutaminase-catalyzed covalent incorporation of two molecules of spermidine (Spd) into the protein at the level of Gln-9 and Gln-86. The modified molecular form of the protein (Spd2-SV-IV) showed a more marked inhibitory activity on Con A-induced lymphocyte blastogenesis in comparison with the native protein, whereas no differences in the ability to inhibit the mixed lymphocyte reaction and to decrease the rat epididymal sperm immunogenicity were found between modified and native SV-IV. Spd2-SV-IV was also less effective than native SV-IV to inhibit platelet aggregation induced in vivo by different thrombogenic agents. In contrast, superimposable inhibitory tracings were observed in the in vitro platelet aggregation experiments performed with the two different molecular forms on the protein. Finally, Spd2-SV-IV was shown to retain unchanged the anti-inflammatory activity of native SV-IV.

Animals↗

Adjuvant radiotherapy in patients post-radical prostatectomy with tumor extending through capsule or positive seminal vesicles.

Between 1976 and 1989, 115 patients at UCLA had radical retropubic prostatectomy for clinically localized prostate cancer with positive surgical margins, penetration of tumor into or through the capsule, or positive seminal vesicles. Twenty-four of those received adjuvant radiotherapy after having recovered from surgery. Complications of adjuvant treatment were uncommon and included urethral strictures in 3 patients and transient leg edema in 1. No patient in this group has had proved clinical disease progression though 6 have isolated detectable serum prostate-specific antigen (PSA) values. Clinical disease-free survival at five and seven years was 92 percent. If detectable PSA is also considered as evidence of tumor recurrence, the corresponding disease-free survival rates were 75 percent at five years and 54 percent at seven years. The 91 patients who received no postoperative radiotherapy had a clinical disease-free survival of 67 percent at five years and 56 percent at seven years. Disease-free survival drops to 43 percent and 24 percent, respectively, if detectable follow-up PSA is considered an indicator of disease progression. The comparisons of the survivorship curves in this retrospective study for the two treatment groups are statistically significant both for disease-free survival (p = 0.041), and disease-free survival with undetectable PSA (p = 0.043). Adjuvant radiotherapy has a beneficial effect after radical prostatectomy in patients with local tumor extension.

Aged↗

Laparoscopic seminal vesicle and pelvic lymph node resection before high-dose three-dimensional conformal radiation therapy for localized prostate cancer. Results of a dosimetric study.

PURPOSE: To analyze the dosimetric implications of seminal vesicle (SV) resection at the time of laparoscopic pelvic lymph node (PLN) dissection in patients presenting with high-risk prostate cancer regarding PLN and SV involvement. PATIENTS AND METHODS: Between June and September 2005, twelve patients underwent laparoscopic SV resection and PLN dissection before delivering a total dose of 80 Gy through a three-dimensional conformal radiation therapy (3D-CRT). Dose-volume histograms (DVHs; rectum, bladder, femoral heads) were obtained from G1 (group 1 with SV) and G2 (group 2 without SV) according to either three- dimensional or intensity-modulated treatment planning. All DVH medians were compared using the nonparametric sign test. RESULTS: SV resection during laparoscopic PLN dissection was performed in all twelve patients without major complications. DVH obtained with three-dimensional and intensity-modulated treatment planning showed that the median doses of RV(25%) (25% of rectal volume), RV(50%), RFHV(5%) (5% of right femoral head volume) and LFHV(5%) (5% of left femoral head volume) in G1 were significantly higher compared to those obtained in G2. CONCLUSION: For patients presenting with high-risk prostate cancer, SV resection performed at the time of laparoscopic PLN dissection allows to significantly decrease the dose delivered to the rectum, using either three-dimensional or intensity-modulated treatment planning, and to reduce the risk of acute and late rectal toxicity.

Humans↗

Cancer-specific survival and predictors of prostate-specific antigen recurrence and survival in patients with seminal vesicle invasion after radical prostatectomy.

BACKGROUND: The objectives of the current study were to determine the long-term biochemical recurrence (BCR) and cancer-specific survival (CSS) rates for men with seminal vesicle invasion (SVI) and to identify risk factors for freedom from BCR and CSS in patients who received treatment in the prostate-specific antigen era and who had SVI identified at the time of radical prostatectomy (RP). METHODS: Prospective clinical, pathologic, and outcome data were collected for 5377 men who underwent RP between June 1983 and August 2004. There were 936 patients who were excluded because they received treatment before RP. Multivariable analysis was used to identify the factors that predicted BCR and CSS. RESULTS: Among 4441 eligible patients, 387 patients (8.7%) had SVI, and 91 of those 387 patients (24%) had lymph node involvement (LNI). In total, 210 patients experienced BCR. For patients without LNI, the 10-year and 15-year freedom from BCR rates were 36% and 32%, respectively, and the corresponding CSS rates were 89% and 81%, respectively. For the 91 men who had SVI and LNI, the 10-year BCR-free probability was 10%, but the 10-year CSS probability was 74%. By 10 years, patients with LNI were 3 times more likely to die from cancer than from other causes; nonetheless, 66% of patients were alive despite their advanced stage. The preoperative prostate-specific antigen level, extracapsular extension, LNI, and Gleason grade were associated independently with BCR. Gleason scores of 8 to 10 and LNI were significant predictors of CSS. CONCLUSIONS: SVI does not invariably signal BCR or death from cancer in patients who undergo RP and pelvic lymph node dissection. Fifteen years later, approximately 33% of men with SVI and negative lymph nodes are expected remain free of BCR, and CSS was surprisingly good.

Aged↗

Suppression of rat epididymal sperm immunogenicity by a seminal vesicle secretory protein and transglutaminase both in vivo and in vitro.

The pretreatment of epididymal spermatozoa with SV-IV, one of the major secretory protein produced by the epithelium of adult rat seminal vesicles, was found to markedly decrease their ability to induce in vivo peritoneal macrophage activation, measured as class II major histocompatibility complex surface antigen expression, superoxide anion production, phagocytic activity, and antigen presentation. In addition, the treatment of spermatozoa with SV-IV produced a significant decrease of their immunogenicity evaluated in vitro by [3H]thymidine incorporation in splenocyte/spermatozoon co-culture. The concurrent presence of SV-IV and transglutaminase, an enzyme secreted in large amounts from the rat anterior prostate, amplified these phenomena. The suppression of the epididymal sperm immunogenicity is suggested to be of crucial importance for the prevention of the immune response to the sperm introduced in the immunocompetent female genital tract during coitus.

Animals↗

Prostaglandin H synthase dependent metabolism of diethylstilbestrol by ram seminal vesicle cell cultures.

Prostaglandin H synthase (PHS) peroxidase dependent metabolic activation has been suggested to play a role in mediating adverse effects of various carcinogens. Recently, we derived a cell line from ram seminal vesicles (SEMV cells) to conduct studies on the PHS-mediated metabolism of estrogens and xenobiotics in intact cells with the goal of relating this to an endpoint for genotoxicity inducible in this in vitro model. The present paper describes the drug-metabolizing capability of SEMV cells which has been investigated using radiolabeled diethylstilbestrol (DES) and analysing culture extracts by means of reverse phase HPLC with on-line radioactivity detection and after enzymatic hydrolysis of conjugate fractions. The synthetic estrogen DES is converted to sulfate conjugates and to the oxidative metabolite Z,Z-dienestrol (Z,Z-DIES) in a time-dependent manner. Compounds expected to modulate PHS-dependent co-oxidation of DES increased (arachidonic acid) or inhibited (indomethacin) Z,Z-DIES formation of SEMV cells in culture. A comparison of rates of arachidonic acid turnover to prostaglandins on the one hand and DES oxidation on the other reveals that DES is oxidized despite the presence of competing endogenous cosubstrates of PHS peroxidase. The results clearly indicate that SEMV cells catalyze PHS-dependent oxidation of DES as well as carrying out phase II metabolism in the absence of detectable monooxygenase activity. These features and recent data showing that DES can induce micronuclei in SEMV cells makes them an attractive model for further investigations of the role of PHS in mediating the genotoxicity of DES and other xenobiotics.

Animals↗

Mass spectrometric evidence for the conversion of exogenous adrenate to dihomo-prostaglandins by seminal vesicle cyclo-oxygenase. A comparative study of two animal species.

We present conclusive mass spectrometric evidence for the synthesis of 1a,1b-dihomoprostaglandin E2 and 1a,1b-dihomoprostaglandin F2 alpha by sheep seminal vesicle microsomes and swine whole vesicular homogenates. Swine microsomes prepared according to standard procedure were catalytically inactive, possibly due to autoinactivation of the cyclo-oxygenase caused by metabolism of endogenous substrate released during the isolation procedure. Cyclo-oxygenase activity could be demonstrated, however, when the porcine vesicles were homogenized in the presence of exogenous substrate. Chemical and mass spectrometric evidence presented here allow unequivocal structural assignments.

Animals↗

Isolated seminal vesicle invasion imparts better outcomes after radical retropubic prostatectomy for clinically localized prostate cancer: prognostic stratification of pt3b disease by nodal and margin status.

OBJECTIVES: To examine the survival differences in men with seminal vesicle invasion (SVI) according to surgical margin (SM) and nodal (N) status to characterize the influence of isolated SVI on disease progression after radical retropubic prostatectomy for clinically localized prostate cancer. METHODS: We reviewed the records of 941 men who underwent radical retropubic prostatectomy for clinically localized prostate cancer between 1984 and 2002. Three groups with evidence of SVI (SM-/N-, SM+/N-, and N+) were analyzed to identify differences in age, preoperative prostate-specific antigen (PSA) level, biopsy Gleason score, surgical Gleason score, time to PSA progression, follow-up time, and cancer-specific and overall survival. Kaplan-Meier estimates and univariate and multivariate calculations were generated to examine differences in biochemical-free survival. RESULTS: Of 941 patients, 87 were identified with SVI; of these, 28 (32.2%) were SM-/N-, 35 (40.2%) were SM+/N-, and 24 (27.6%) were N+. The median follow-up for all patients was 70 months. The 5-year biochemical progression-free rate for SM-/N-, SM+/N-, and N+ patients was 71.9%, 36.6%, and 25.9%, respectively. The median time to PSA progression for SM-/N-, SM+/N-, and N+ patients was 26, 16, and 6 months, respectively. The clinical stage, pretreatment PSA level, and margin and node status were statistically predictive (P < 0.05) on univariate analyses; however, only positive margin status approached statistical significance on multivariate analysis (P = 0.06). The overall and cancer-specific 5-year survival rates for SM-/N-, SM+/N-, and N+ patients were 89% and 100%, 79% and 97%, and 78% and 86%, respectively. CONCLUSIONS: Isolated SVI is associated with lower rates of, and longer intervals to, biochemical failure compared with SVI with positive margins and/or regional lymph node involvement.

Aged↗

Porin from Pseudomonas aeruginosa induces apoptosis in an epithelial cell line derived from rat seminal vesicles.

Micromolar concentrations of porin, purified from the outer membranes of Pseudomonas aeruginosa, induced in vitro the classic morphological and biochemical signs of apoptosis in an epithelial cell line (SVC1) derived from the rat seminal vesicle secretory epithelium. The programmed cell death (PCD) was p53 independent and associated with significant decrease of bcl-2 expression, a marked increase of c-myc transcriptional activity, and an absence of the mRNA coding for tissue transglutaminase. The Ca(2+) influx, caused by the porin treatment of SVC1 cells, appears to play an important role in the triggering of apoptosis in our biological model. The possibility that the porin property of inducing PCD plays a role in the infertility of individuals chronically infected by gram-negative bacteria is discussed.

Animals↗

Improving bladder neck division in radical retropubic prostatectomy by prior dissection of the seminal vesicles and vasa deferentia.

OBJECTIVE: To develop a convenient technique for dividing the bladder neck during radical retropubic prostatectomy. METHOD: Before opening the bladder, we created a plane that separates the anterior surface of the seminal vesicles from the posterior wall of the bladder and ran an umbilical tape through the plane. The posterior bladder neck wall was later divided using this tape as a guide mark. RESULTS AND CONCLUSION: The posterior bladder neck was divided in a single, easy, and swift maneuver (less than 2 min) in 350 patients with no subsequent complications.

Humans↗

[Deferens unilateral agenesis associated with an absence of the epididymis, seminal vesicle and renal unit on the same side. A brief case].

Brief presentation of a series of considerations on the clinical history of a male with deferens unilateral agenesis associated to absence of epididymis, seminal vesicle and renal unit on the same side (all incidental findings in an asymptomatic male with no previous history who requested a vasectomy). For a better understanding of this entity, an outline of the wolffian ducts' organogenesis (urinary potentials/genital potentials) is made and reconsidered. The methodological mechanics followed in this case (performance of vasectomy on the one side, as well as comprehensive confirmation of absence of the other deferens, obtention and confirmation of azoospermia, and performance of a minimum set of tests to take down the particulars of the entity and to rule out associated conditions) are reviewed and discussed. Based on the "Brief case" approach, and on the documentation available in the clinical history, this paper will not go into details on the relationship of this entity with a mutation of the cystic fibrosis gen.

Abnormalities, Multiple↗

Steroid-binding properties of the rat seminal vesicle androgen receptor: short-term and long-term competition of various steroids with radioactive dihydrotestosterone.

Competition of 22 steroids with [3H]-dihydrotestosterone for the binding to the androgen receptor of the rat seminal vesicle has been studied. The effect of each competitor was determined in short term (1 h) and long term (67 h) incubations, and the results were evaluated by considering the kinetic aspects of competition. This approach made possible to investigate separately the ligand specificity of the association and dissociation parts of the steroid-receptor interaction. According to competitory behavior, the investigated steroids could be divided into three groups. In Group I, the association and dissociation rates of the competitors are close to that of 5 alpha-dihydrotestosterone. Steroids in Group II can still associate at a remarkable rate with the receptor, but the resulting complexes are much less stable than the 5 alpha-dihydrotestosterone-receptor complex. Finally, steroids of Group III do not exhibit significant binding. By correlating the binding characteristics and the structure of the test compounds it was possible to assess the significance of certain features of steroid molecules in the binding. Moreover, other correlations between the competitive behavior and some known biological activities of these steroids point to the potential usefulness of our procedure in the screening of synthetic steroids.

Animals↗

Phosphorylation of seminal vesicle protein IV on Ser58 enhances its peroxidase-stimulating activity.

In this study we show that SV-IV, a major immunomodulatory, anti-inflammatory, and sperm immunoprotective protein secreted from the rat seminal vesicle epithelium, acts in vitro as a substrate of protein kinase C (PKC) competing efficiently with H1 histone, a very well known PKC substrate. Electrospray mass spectrometry (ES-MS) analysis demonstrated that approximately 10% of the native SV-IV molecules were phosphorylated by PKC and that such a modification involved only a single serine residue (Ser58) out of the 22 occurring in the protein. Interestingly, this modification produced a substantial enhancement (approximately 50%) of the native SV-IV's ability to stimulate the activity of both horseradish peroxidase (POD) and selenium-dependent glutathione peroxidase (GPX), an enzyme that is known to protect the mammalian spermatozoa from oxidative stress and loss of motility in the female genital tract following ejaculation. In contrast, the phosphorylation of SV-IV on Ser58 did not produce any effect on the anti-inflammatory properties of SV-IV, as measured by its ability to inhibit the phospholipase A2.

Amino Acid Sequence↗