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J T Hsieh

Publications and source records attributed to J T Hsieh.

At least 37 records · Page 2Linked to original sources
PubMed2000

The growth inhibitory effect of p21 adenovirus on human bladder cancer cells.

PURPOSE: To evaluate whether p21 (WAF-1/CIP1) should be considered a potential candidate for human bladder cancer gene therapy, we determined: (1) the basal level of p21 expression in bladder cancer cell lines, (2) the response of bladder cancer cells to increased p21 expression following p21 adenovirus infection, and (3) the mechanism of growth inhibition produced by p21 overexpression. MATERIALS AND METHODS: Five established human bladder cancer cell lines and one primary culture derived from an invasive transitional cell carcinoma were used in this study. To examine the effect of p21 protein on the growth of human bladder cancer cells, a recombinant adenovirus vector system containing p21 cDNA, under the control of cytomegalovirus promoter, was constructed. A control virus containing p21 in an antisense orientation was used to eliminate potential artifacts caused by viral toxicity. RESULTS: Human bladder cancer cell lines exhibit variable endogenous p21 levels which correlate with the in vitro growth status. Significant, but highly variable increases in the steady-state level of p21 were detected in p21 adenovirus infected cells. Human bladder cancer cell lines responded heterogeneously to p21 adenovirus infection. Growth of the WH cell line was substantially inhibited in a dose and time-course dependent fashion. The mechanism of p21 growth inhibition was found to be due to G0/G1 arrest and not the induction of apoptosis. In contrast, p21 adenovirus failed to inhibit the growth of T24 bladder cancer cells because T24 cells were resistant to viral infection. The 253J bladder cancer cells exhibited marked sensitivity to adenovirus; substantial growth inhibition was seen with both sense and antisense p21 very early in the time course of infection. CONCLUSIONS: We found significant variation in the basal level of p21 protein expression in several human bladder cancer cell lines. Increased p21 expression as a result of adenoviral infection may be a potent growth suppressor in some human bladder cancer because it elicits cell cycle arrest in G0/G1 stage, but not the induction of apoptosis. Bladder cancer cells exhibit a wide spectrum of sensitivity to adenoviral infection that may be caused by the presence of viral receptor heterogeneity. This wide spectrum of sensitivity has significant basic scientific and clinical implications and warrants further study.

Adenoviridae↗
PubMed2000

The mismatch repair gene hMSH2 is mutated in the prostate cancer cell line LNCaP.

PURPOSE: Mismatch repair genes are responsible for the coordinated correction of misincorporated nucleotides formed during DNA replication. Inactivating and inherited mutations in the prototypic mismatch repair gene hMSH2 have been described in a cancer predisposition syndrome known as hereditary nonpolyposis colon cancer. Patients with hereditary nonpolyposis colon cancer are at increased risk for colon cancer and extracolonic cancers such as upper tract transitional cell carcinoma but not prostate cancer. We investigated expression of hMSH2 in prostate cancer cell lines using genetic and molecular analysis. MATERIALS AND METHODS: We used the 3 well described prostate cancer cell lines, DU145, LNCaP and PC3. Western blot analysis with monoclonal antibody to hMSH2 was used to assess expression. Southern blot and polymerase chain reaction of genomic DNA were used to identify genetic alterations in the hMSH2 gene. Single cell cloning, dinucleotide repeats and BAT-26 were used to assess the cell lines for microsatellite instability. RESULTS: The prostate cancer cell line LNCaP did not express hMSH2 and was found to have a homozygous deletion of hMSH2 exons 9 to 16, resulting in truncation of the protein. While microsatellite analysis did not reveal alterations at the BAT-26 locus, single cell cloning produced several LNCaP subclones with alteration at 1 dinucleotide repeat. CONCLUSIONS: The well described prostate cancer cell line LNCaP has a mutation in the hMSH2 gene, resulting in loss of expression and possible evidence of microsatellite instability. To our knowledge our finding is the first demonstration of a genetic alteration in hMSH2 in a prostate cancer cell line.

Base Pair Mismatch↗
PubMed2000

Post-traumatic, high-flow priapism treated with selective cavernous artery embolization and intracavernous streptokinase irrigation: a case report.

A 54-year-old man developed priapism shortly after a blunt perineal trauma. An arteriocavernous fistula caused the high-flow priapism, and was detected on both color Doppler sonography and selective phaloarteriography. Selective embolization of the left cavernous artery with Gelfoam was performed to seal the fistula, resulting in immediate detumescence. However, the penis remained firm despite returning to almost normal size. No fistula was detected by subsequent color Doppler sonography and phaloarteriography examination. Intracavernous irrigation with 200,000 U streptokinase was applied to treat residual firmness 2 weeks after embolization. Successful sexual intercourse was reported 3 months later. The combination of selective cavernous artery embolization and intracavernous streptokinase irrigation was effective for the treatment of the high-flow priapism in this case.

Arteries↗
PubMed1999

The role of DOC-2/DAB2 protein phosphorylation in the inhibition of AP-1 activity. An underlying mechanism of its tumor-suppressive function in prostate cancer.

DOC-2/DAB2, a novel phosphoprotein with signal-transducing capability, inhibits human prostatic cancer cells (Tseng, C.-P., Ely, B. D., Li, Y., Pong, R.-C., and Hsieh, J.-T. (1998) Endocrinology 139, 3542-3553). However, its mechanism of action is not understood completely. This study delineates the functional significance of DOC-2/DAB2 protein phosphorylation and demonstrates that in vivo activation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate (TPA) induces DOC-2/DAB2 phosphorylation, including a serine residue at position 24. Mutation of Ser(24) to Ala reduced DOC-2/DAB2 phosphorylation by PKC. Using a synthetic Ser(24) peptide (APS(24)KKEKKKGSEKTD) or recombinant DOC-2/DAB2 as substrates, PKCbetaII, PKCgamma, and PKCdelta (but not casein kinase II) directly phosphorylated Ser(24) in vitro. This indicates that DOC-2/DAB2 is a PKC-specific substrate. Since expression of wild-type DOC-2/DAB2, but not the S24A mutant, inhibited TPA-induced AP-1 activity in prostatic epithelial cells, phosphorylation of Ser(24) appears to play a critical role in modulating TPA-induced AP-1 activity. Taken together, these data suggest that PKC-regulated phosphorylation of DOC-2/DAB2 protein may help its growth inhibitory function.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Structural analysis of the C-CAM1 molecule for its tumor suppression function in human prostate cancer.

BACKGROUND: Recently, we demonstrated that expression of C-CAM1, an immunoglobulin (Ig)-like cell adhesion molecule (CAM), was diminished in both prostate intraepithelial neoplasia and cancer lesions, indicating that loss of C-CAM1 expression may be involved in the early events of prostate carcinogenesis. Also, increased C-CAM1 expression can effectively inhibit the growth of prostate cancer. Structurally, C-CAM1 represents a unique CAM with a potential signal transducing capability. In this study, we further analyzed the functional domain of C-CAM1 for controlling its tumor suppression function. METHODS: Recombinant adenoviruses expressing a series of C-CAM1 mutants were generated, such as AdCAMF488 (mutated C-CAM1 containing Tyr-488 --> Phe-488), AdCAMH458 (intracellular domain deletion mutant containing 458 amino acids), AdCAMG454 (intracellular domain deletion mutant containing 454 amino acids), and AdCAMDeltaD1(C-CAM1 mutant containing first Ig domain deletion). After in vitro characterization of each virus, human prostate cancer cells infected with these viruses were subcutaneously injected into athymic mouse. Both tumor incidence and volume were measured for determining the tumor suppression function for each mutant. RESULTS: In vivo tumorigenic assay indicated that AdCAMDeltaD1 without cell adhesion function still retained its tumor suppression activity. In contrast, both AdCAMH458 and AdCAMG454 decreased or lost their tumor suppression activity. CONCLUSIONS: Our data indicate that the intracellular domain of the C-CAM1 molecule is critical for inhibiting the growth of prostate cancer, suggesting that C-CAM1 interactive protein(s) may dictate prostate carcinogenesis.

Adenosine Triphosphatases↗
PubMed1999

Induction of apoptosis and G2/M cell cycle arrest by DCC.

The Deleted in Colorectal Cancer gene (DCC) encodes a cell surface receptor that belongs to the Ig superfamily. Inactivation of the DCC gene has been implicated in human tumor progression. However, little is known about the biological function of the DCC protein. In the present study, we demonstrated that expression of DCC activated caspase-3 and programmed cell death, or induced G2/M cell cycle arrest in tumor cells. In some cell lines, apoptosis was evident within 24 h of DCC expression. Timing of the appearance of apoptotic cells coincided with that of the cleavage of poly (ADP-ribose) polymerase, a substrate of caspase-3. Expression of the apoptosis inhibitory gene Bcl-2 was not able to abrogate the DCC-induced apoptosis. In the G2/M cycle arrest cells, cdk1 activity was inhibited. Our results suggest that the DCC protein may transduce signals resulting in activation of caspases or inhibition of Cdk1. These data provide a possible mechanism by which DCC suppresses tumorigenesis.

Apoptosis↗
PubMed1999

Loss of adenoviral receptor expression in human bladder cancer cells: a potential impact on the efficacy of gene therapy.

There is great interest in the development of gene therapeutic strategies for the treatment of benign and malignant diseases. Recombinant adenovirus has a wide spectrum of tissue specificity and is an efficient vector delivery system. Successful gene delivery, however, requires viral entry into the target cells via specific receptor-mediated uptake. Recently, a cDNA clone (the coxsackie and adenovirus receptor [CAR]) encoding a 46-kDa protein was identified as the receptor for group C adenovirus (e.g., adenovirus type 2 and 5). Currently, little is known regarding the expression of adenoviral receptor in normal tissue and cancer. In this paper, we have documented a significant difference in viral receptor levels that may be due to transcriptional regulation of the CAR gene in several human bladder cancer cell lines. The differences in viral receptor levels in these cells correlated with their sensitivity to viral infection. Transfection of receptor-negative cell line with CAR cDNA led to increased virus binding and increased susceptibility to adenovirus-mediated gene delivery. Our results demonstrate that the expression of adenoviral receptor is variable among human bladder cancer cells. This variability may have a significant impact on the outcome of adenovirus-based gene therapy.

Adenoviridae↗
PubMed1999

Quantitative sensory testing in patients with incomplete spinal cord injury.

OBJECTIVE: To examine the utility of quantitative sensory testing (QST) to characterize sensory dysfunction in patients with spinal cord injury (SCI). DESIGN: Perceptual thresholds to warm, cold, cold pain, and vibratory stimuli were investigated using a modified method of "limits." METHOD: Three QST trials were administered to six lower leg dermatomes, on two different days, to estimate the reliability of measurement. SETTING: Regional Spinal Cord Injury Rehabilitation Center in Ontario, Canada. SUBJECTS: Twenty-one SCI patients with incomplete neurologic deficits and 14 able-bodied controls of similar age. RESULTS: ANOVA revealed significantly (p < .05) reduced perceptual threshold values (hypoesthesia) for warm, cold, and vibratory sensation in the SCI group. There were no differences between group mean values for cold pain because of the inclusion of patients with hypoalgesia and hyperalgesia. Intraclass correlation coefficient estimates of reliability revealed large between-subject variability in the SCI patients associated with relatively small trial-to-trial variability within each day of testing, and appreciable between-day variances. CONCLUSIONS: With QST in SCI there is a need for repeated measurements across days to establish stable baseline measures or outcomes following intervention. QST is a useful adjunct to clinical examination for assessment of preserved sensation.

Adult↗
PubMed1999

An in vivo evaluation of the therapeutic potential of sympatholytic agents on premature ejaculation.

OBJECTIVE: To evaluate the therapeutic potential of sympatholytic agents on premature ejaculation in an animal model, using monitoring of rat seminal vesicle pressure change in response to electrical stimulation of the lesser splanchnic nerve. MATERIALS AND METHODS: Male Wistar rats (aged 12-14 weeks) were injected intra-arterially with sympatholytic agents (phenoxybenzamine, prazosin, WB-4101, chloroethylclomidine, yohimbine and RX 821002) at various concentrations 10 min before electrical stimulation of the lesser splanchnic nerve. The change in phasic tension (triangle upmmHg) of the seminal vesicle induced by electrical nerve stimulation before and after the addition of sympatholytic agents was used for statistical analysis. The maximum inhibition and the concentration required to induce 50% inhibition of the maximal contractile response (IC50) were obtained from the concentration-response curves, and used to determine the potency of test agents. RESULTS: The seminal vesicle contractile response to electrical nerve stimulation was suppressed in a dose-dependent manner by all test drugs except RX 821002. The mean (sd) maximal inhibition was 78.4 (9. 3)% by 0.03 mg/kg of phenoxybenzamine, 77.1 (10.1)% by 0.03 mg/kg of WB-4101, 73.4 (6.0)% by 0.1 mg/kg of yohimbine, 67.9 (9.7)% by 0.1 mg/kg of prazosin, 75.5 (7.5)% by 3 mg/kg of chloroethylclomidine and 25.3 (4.8)% by 0.01 mg/kg of RX 821002. The potencies of WB-4101 (IC50 3 microgram/kg) and yohimbine (IC50 0.8 microgram/kg) were similar to that of phenoxybenzamine (IC50 0.5 microgram/kg) and much higher than that of prazosin (IC50 0.03 mg/kg) or chloroethylclomidine (IC50 0.3 mg/kg). CONCLUSIONS: Phenoxybenzamine, prazosin, WB-4101, chloroethylclomidine and yohimbine all inhibit the contractile response of the rat seminal vesicle to electrical nerve stimulation. As phenoxybenzamine is effective in treating premature ejaculation, the comparable in vivo potencies of WB-4101 and yohimbine strongly suggest that they have clinical therapeutic potential.

Adrenergic alpha-Antagonists↗
PubMed1999

Adenovirus-mediated p21((WAF1/SDII/CIP1)) gene transfer induces apoptosis of human cervical cancer cell lines.

p21((WAF1/SDII/CIP1)) (p21) arrests cell growth by inhibiting cyclin-depend kinases. To explore the potential of using p21 for the gene therapy of cervical cancer, we infected human papillomavirus (HPV)-positive cervical cancer cells (HeLa, SiHa, and Z172) and HPV-negative cervical cancer cells (C33A) with recombinant adenovirus encoding p21 cDNA. The results revealed that effective inhibition of cell growth could be achieved by sense p21 adenovirus but not antisense p21 adenovirus infection and occurred through apoptosis as measured by DNA fragmentation and chromatin condensation. Apoptosis was also observed in xenografts of human cervical cancer cells infected with sense p21 adenovirus, as confirmed by in situ terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). The apoptosis was not prevented by overexpression of the bcl-2 transgene. To sum up, the apoptotic effect suggests that p21 should be a tumoricidal agent instead of a tumoristatic agent in preventing cervical cancers. In addition, our report substantiates the combination of the high efficiency of adenovirus vector-mediated gene delivery and the apoptotic effect of p21.

Adenoviridae↗
PubMed1999

Fertilization capability of frozen epididymal sperm for intracytoplasmic sperm injection.

Both microsurgical epididymal sperm aspiration (MESA) and intracytoplasmic sperm injection (ICSI) are great advances in assisted reproductive techniques. By using the ICSI technique, frozen sperm from the epididymis can result in successful fertilization. The epididymal sperm retrieved via MESA can be cryopreserved for an in-vitro fertilization (IVF) procedure, thus, making repeat surgical retrieval of sperm unnecessary. We report a retrospective analysis of 24 ICSI cycles in 16 patients with obstructive or nonreconstructable azoospermia. Fresh epididymal sperm was used in 13 ICSI cycles and frozen-thawed epididymal sperm was used in the other 11. We compared the fertilization capability of ICSI using frozen-thawed epididymal sperm with fresh epididymal sperm. Eleven patients became pregnant and five of these pregnancies resulted from frozen epididymal sperm. The fertilization rate per oocyte was 58% with fresh sperm, and 66% with frozen-thawed sperm. The rate of clinical pregnancy for one embryo transfer was 46% with fresh sperm, and 45% with frozen-thawed sperm. There were no significant differences between fresh and frozen-thawed spermatozoa in the fertilization rate of oocytes or the clinical pregnancy rate. Our results suggest that we should cryopreserve supernumerary spermatozoa during a MESA/ICSI procedure in order to avoid repeated scrotal surgery.

Adult↗
PubMed1999

Cyst-like chylous coagulum in the urinary bladder of a patient with recurrent chyluria.

We report a rare case of recurrent chyluria in a 64-year-old man, who had undergone sclerosing therapy for chyluria with complete remission 40 years previously. The chyluria recurred 4 months before the present hospital admission. The patient presented with acute urine retention and weight loss of 6 kg during the past 6 months. Urine biochemistry studies showed elevated concentrations of albumin (0.7 g/dL), globulin (0.6 g/dL), cholesterol (0.59 mmol/L), and triglyceride (0.89 mmol/L), confirming the diagnosis of chyluria. Intravenous urography showed a substantial filling defect in the urinary bladder. Cystoscopy revealed milky urine flowing out of the right ureteral orifice, and a large chylous coagulum presenting as a cyst-like mass in the urinary bladder. The chyluria was successfully treated with sclerosing therapy with injection of 76% Urografin (Shering AG, Berlin, Germany) into the right upper urinary tract, and the chylous coagulum was evacuated endoscopically. No evidence of chyluria recurrence has been noted during a year of follow-up, and the patient has regained 6 kg of body weight. This particular presentation of chylous coagulum in a chyluria patient has not been previously reported in the literature.

Chyle↗
PubMed1999

Attenuation of WAF1/Cip1 expression by an antisense adenovirus expression vector sensitizes glioblastoma cells to apoptosis induced by chemotherapeutic agents 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin.

Previous studies have shown that the negative cell cycle regulator WAF1/Cip1 is often overexpressed in human gliomas and that WAF1/Cip1 overexpression renders glioma cells resistant to chemotherapy agents. In this study, we investigated whether down-regulation of WAF1/Cip1 would sensitize gliomas to chemotherapy. An adenoviral vector expressing antisense WAF1/Cip1 was constructed and used to infect D54 glioma cells, which express a high level of endogenous WAF1/Cip1. After D54 cells were infected with antisense WAF1/Cip1 adenovirus, Western blotting revealed a significant decrease in the WAF1/Cip1 protein level. Down-regulation of WAF1/Cip1 alone resulted in the cells rounding up and detaching from plates. Electron microscopy revealed some nuclear fragmentation in antisense WAF1/Cip1-infected cells, indicating the initiation of apoptosis. The antisense WAF1/Cip1-infected cells were then treated with the chemotherapeutic agents 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin. Other cells were infected with sense WAF1/Cip1 adenovirus or control virus and served as controls. Trypan blue exclusion assay revealed significant cell death in antisense WAF1/Cip1-infected cells. In situ end-labeling assay by flow cytometry revealed that many cells died of apoptosis. Our results show that the attenuation of WAF1/Cip1 expression initiated glioma cell death and sensitized glioma cells to apoptosis induced by 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin. Thus, blocking WAF1/Cip1 production may serve as a useful chemosensitization regimen for treating glioma.

Adenoviridae↗
PubMed1998

An ex vivo evaluation of regulatory role of biogenic amines in rat seminal vesicle after pharmacological manipulation.

We studied the neural regulation of seminal vesicles (SV) by determining the changes of intraluminal pressure of rat SV in response to an electric stimulation of the lesser splanchnic nerve (LSN). After pharmacological manipulation with neurotoxin, the contents of monoamines and their metabolites in SV were estimated. In rats receiving electric stimulation of the LSN, an increase of intraluminal pressure was obtained with a reduction of the serotonergic turnover rate in SV. An intraperitoneal injection of DSP-4 (100 mg/kg), the noradrenergic neurotoxin, into rats decreased the level of norepinephrine (NE) in SV significantly but did not influence this functional response. Also, the intraluminal pressure was lowered by an intrathecal injection of 6-OHDA (20 microg/rat) to denervate spinal monoaminergic nerves in rats although the contents of monoamines in SV were not changed. This indicates that noradrenergic neurotransmission appears unimportant in this regulation. The lowering of intraluminal pressure in rats by 6-OHDA is mainly related to an attenuation of dopaminergic neuroregulation from the decrease of turnover rate of DA. Otherwise, an intrathecal injection of 5,7-DHT (60 microg/rat) to abolish spinal serotonergic nerves did not influence the level of monoamines in SV but increased the intraluminal pressure indicating an involvement of inhibitory regulation from spinal serotonergic pathway. These results suggest that contraction by electric stimulation of the LSN in Wistar rat SV is mainly regulated by the dopaminergic nervous pathway and an inhibitory regulation of the serotonergic nervous pathway from spinal cord while the noradrenergic nervous system seems unimportant for this regulation.

5,7-Dihydroxytryptamine↗
PubMed1998

Sustained improvements in neurological function in spinal cord injured patients treated with oral 4-aminopyridine: three cases.

Preclinical trials of intravenously administered 4-Aminopyridine (4-AP) have demonstrated transient improvements in neurological function in patients with longstanding spinal cord injury (SCI). The present report describes three patients with SCI who responded favourably in preclinical trials and who were subsequently administered oral (capsule) 4-AP (10 mg b.i.d. or t.i.d.) over a 4 month interval. The three patients (two male: 1 female) all had incomplete tetraplegia (ASIA levels C and D) with the neurological level of the lesion between C5-C7. Following the administration of 4-AP the patients demonstrated marked and sustained reductions in upper (n = 1) or lower extremity (n = 2) spasticity. Other clinical benefits of 4-AP were reduced pain (n = 1), restored muscle strength (n = 3), improved sensation (n = 2), voluntary control of bowel function (n = 1), and sustained penile tumescence (n = 2). The patients exhibited improved hand function (n = 1), enhanced mobility in transfers and gait (n = 2), with improved energy and endurance. Only trivial side effects (transient light-headedness) were observed. In one case, the enhanced neurological function allowed the patient to stand with support for the first time post injury (16 years). The time course of therapeutic response to the initial dose matched the pharmacokinetic elimination profile derived from serum and urine analysis. There was no evidence of renal or hepatic toxicity with prolonged use. These results indicate a therapeutic benefit of oral 4-Aminopyridine in the management of various neurological deficits in a select group of SCI patients.

4-Aminopyridine↗
PubMed1998

The effect of biological dyes and contrast media on the vas deferens in Long Evans rats.

The conventional diagnostic procedure of vasography utilizes a contrast medium to evaluate the patency of the vas deferens. With the development of microsurgical reconstruction for obstructive azoospermia in the past two decades, intraoperative vasography with saline or biological dye injection has replaced the use of radiographic contrast media. However, there are few reports on the effect of biological dyes on the healthy vas deferens. Therefore, we used experimental vasography to evaluate histological changes and functional patency of the vas deferens after infusion with a contrast medium and biological dye. Four groups of 10 Long Evans male rats were injected by vasopuncture with 1% methylene blue, 1% gentian violet and 38% Urografin or saline into the vas deferens. The animals were killed 30 days later, and the vasa deferentia were excised and examined for histological changes and for functional patency. Vasopuncture with saline injection induced minimal change both at the puncture site and in the distal vas deferens. In both the Urografin- and methylene blue-injected groups, inflammation at the puncture site was found in 20-22% of cases, and 10-11% of cases revealed functional obstruction of the vasal lumen. In the gentian violet-injected group, severe histological and obliterated changes were found in all cases. Leakage of the dye and contrast medium or the sperm reaction may be responsible for the inflammation; otherwise, methylene blue and urografin did not seem to be harmful to the vas deferens. Although gentian violet is a blue dye, as is methylene blue, it has marked destructive effects on the vas deferens. It is concluded that some biological dyes used for vasal injection can cause occlusion of the vasal lumen, while inflammatory responses can occur from placing a needle transmurally.

Animals↗
PubMed1998

In vivo evaluation of serotonergic agents and alpha-adrenergic blockers on premature ejaculation by inhibiting the seminal vesicle pressure response to electrical nerve stimulation.

OBJECTIVE: To evaluate the effect of drugs on premature ejaculation using a rat animal model in which the seminal vesicle was electrically stimulated via its lesser splanchnic nerve and changes in the pressure response monitored. MATERIALS AND METHODS: Male Wistar rats (aged 12-14 weeks) were injected intravenously with prazosin and serotonergic agents (serotonin, clomipramine, fluoxetine, imipramine and indatraline) at various concentrations 10 min before electrical nerve stimulation (ENS) of the lesser splanchnic nerve; the initial increase in seminal vesicle pressure in response to ENS was then compared. RESULTS: The pressure response to ENS was reduced in the presence of prazosin or serotonergic agents. The mean (SEM) maximum inhibition values were 84.1 (8.9%) by fluoxetine at 0.1 mg/kg, 67.9 (8.7)% by prazosin at 0.1 mg/kg, 60.9 (11.0)% by serotonin at 3 mg/kg, 54.9 (4.6)% by clomipramine at 3 mg/kg, 30.0 (11.0)% by imipramine at 0.1 mg/kg, and 20.9 (4.3)% by indatraline at 0.1 mg/kg. From the concentration-response curve, the potency of prazosin was lower than that of fluoxetine, but was higher than that of serotonin or clomipramine. CONCLUSIONS: Like serotonin, fluoxetine and clomipramine can reduce the pressure response of the seminal vesicle to ENS. Among these inhibitory agents, including prazosin, fluoxetine was the most effective and may be valuable for the clinical treatment of ejaculatory dysfunction in man.

Adrenergic Uptake Inhibitors↗