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J Rajfer

Publications and source records attributed to J Rajfer.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effect of aging on nitric oxide-mediated penile erection in rats.

Aging is an important risk factor for impotence in men. Because nitric oxide (NO) appears to be the mediator of corpora cavernosal smooth muscle relaxation, we have examined in 5-, 20-, and 30-mo-old rats, designated "adult," "old," and "senescent," respectively, whether aging causes a decrease of erectile response that may correlate with lower NO synthase (NOS) in the penis. Electric field stimulation (EFS) of the cavernosal nerve showed that the maximum intracavernosal pressure (MIP) declined in the old and senescent rats to 80 and 51% of the adult value, respectively. A low systemic dose of the NOS inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME; 2 mg/kg), reduced the MIP by only 38% in the adult rats but decreased it in the old and senescent rats by 72 and 80%, respectively. In the absence of EFS, intracavernosal papaverine (phosphodiesterase inhibitor), or nitroglycerin (NO donor), caused a lower erectile response in the old and senescent rats compared with the adult animals (MIP: 41 and 14%, respectively; duration of the erection 46 and 21%, respectively). Tissue sections from old and senescent penises showed increasing degrees of sclerotic degeneration. In comparison with the adult rats, the penile soluble NOS activity per gram of tissue that is sensitive to L-NAME decreased significantly by 63% in the senescent rats but was elevated in the old rats. These results indicate that aging causes an erectile failure due to factors initially independent from an impairment of penile NO synthesis but which are compounded in the very old rats by the decrease of penile NOS activity.

Aging↗
PubMed1995

Reduction of penile nitric oxide synthase in diabetic BB/WORdp (type I) and BBZ/WORdp (type II) rats with erectile dysfunction.

Erectile dysfunction occurs frequently in human diabetes, and it is sometimes associated with hypogonadism. These conditions also develop in a model of insulin-dependent (type I) diabetes, the BB/WORdp (diabetic prone) rat but have not yet been investigated in the model of insulin-resistant (type II) diabetes, the BBZ/WOR rat. It is also unknown whether diabetes-related impotence is due to reduced levels of the mediator of penile erection, nitric oxide, caused by a decrease of nitric oxide synthase (NOS) in the penis. To clarify these questions, groups (n = 5-6) of diabetic BB/WORdp (insulin-maintained) and BBZ/WOR rats were age-matched with diabetic-resistant BB/WORdr and non-diabetic BB/WORdp rats and submitted to determinations of serum glucose, testosterone, and penile reflexes (cups and flips). Erectile dysfunction was found in all of type I and in most of type II diabetic animals (glycemias of 25.0 and 31.1 mM), at the selected mean ages of 310 and 180 days old, respectively. This was evidenced by over 95% decreases of erectile reflexes in both types of diabetes and was accompanied by 75% reduction of serum testosterone. Soluble NOS activity was measured in penile tissue from the diabetic rats with impaired erectile reflexes and in the corresponding controls, by the (3H)-L-arginine/citrulline conversion assay. The neuronal NOS isoform (nNOS) content was determined by a semiquantitative western blot assay. Both types of diabetes showed a marked decrease of penile NOS activity (74 and 55%, respectively), and a lower reduction of penile nNOS content (47 and 33%, respectively). No endogenous NOS inhibitor was detected in the diabetic type I penile cytosol by cross-mixing NOS activity assays. Our data support a common etiology for erectile dysfunction present in rats with types I and II diabetes mellitus and suggest that the etiology is related to a decrease of penile NOS derived in part from serum androgen deficiency.

Animals↗
PubMed1995

Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat.

Androgens are essential for the expression of normal libido in the male, but their role in the maintenance of the erectile response in humans is controversial. It has been shown previously in the rat that castration induces 1) loss of penile reflexes; and 2) considerable reduction in the erectile response to electric field stimulation (EFS) of the cavernosal nerve. Both of these effects can be reversed by testosterone replacement. The current study was performed to determine whether these testosterone effects are mediated via its conversion to dihydrotestosterone (DHT), and to what extent the synthesis of the mediator of penile erection, nitric oxide, is affected by castration and androgen replacement. Five-month-old rats were either castrated or left intact. The orchiectomized rats were implanted with SILASTIC brand silicon tubing (Dow Corning) containing testosterone or DHT with or without daily injections of the 5 alpha-reductase inhibitor finasteride. After 7 days, rats were submitted to EFS and the intracavernosal pressure was recorded. Castration reduced the EFS-induced erectile response by 50% in comparison with intact rats and testosterone restored this decrease to normal. When finasteride was given to these testosterone-treated castrate rats, erectile response was not restored. DHT was as effective as testosterone in restoring response to EFS in castrates and this effect was not decreased by finasteride. Nitric oxide synthase activity in the penile cytosol was measured by the arginine-citrulline conversion and was found to correlate with the EFS determinations. These results show that DHT is the active androgen in the prevention of erectile failure seen in castrated rats, and suggest that this effect may be mediated, at least partially, by changes in nitric oxide synthase levels in the penis.

Amino Acid Oxidoreductases↗
PubMed1995

The effect of zanoterone, a steroidal androgen receptor antagonist, in men with benign prostatic hyperplasia. The Zanoterone Study Group.

PURPOSE: Zanoterone (100 to 800 mg.) versus placebo was studied in 463 patients with benign prostatic hyperplasia. MATERIALS AND METHODS: Study end points were maximum urinary flow rate, American Urological Association symptom index, prostate volume, prostate specific antigen and sex steroid concentrations after 6 months of treatment. RESULTS: Mean increases in maximum urinary flow rate were 2 to 3-fold over placebo, although only the 200 mg. group had significant results (1.7 ml. per second, p = 0.026). There were no statistically significant differences between the zanoterone and placebo groups in symptom index or prostate volume. Estradiol and testosterone concentrations, and the incidence of breast pain and gynecomastia increased significantly with zanoterone compared with placebo. Prostate specific antigen levels decreased significantly. CONCLUSION: Zanoterone did not demonstrate a favorable risk-to-benefit profile for the treatment of benign prostatic hyperplasia.

Aged↗
PubMed1994

New device for visual neodymium:YAG laser prostate ablation: acute and chronic canine evaluation.

This canine study (n = 6) evaluated the acute and chronic effects of Nd:YAG laser prostatectomy using a Prolase II fiber. The Prolase II device consists of a 1,000 microns quartz fiber which directs a cone of Nd:YAG laser energy, at 45 degrees to the axis of the fiber, into the prostatic urethra under direct visual guidance [visual laser ablation of prostate, (VLAP)]. Under visual guidance and saline irrigation, 60 seconds of 60 watts of laser power was delivered at 3, 6, 9, and 12 o'clock positions (14,400 J). One canine was instrumented but received no laser energy (control). One prostate was harvested acutely. The remaining four laser-treated dogs were evaluated at 6 to 16 weeks. The histopathology of acute laser effects shows areas of necrosis with loss of glandular structures and stromal edema. Surrounding this area was a zone of degenerative glandular structures extending up to 12.6 mm into the prostate. Two of the four dogs developed urinary retention at 6.5 and 9 weeks. On examination, both were found to have fibrotic strictures at the distal prostatic urethra with markedly dilated proximal prostatic urethral lumens (1.98 and 2.8 cm). Two other dogs showed no signs of urinary retention at sacrifice. Histopathology, both the 6 and 16 week laser-treated animals without urinary retention demonstrated dilated prostatic urethras with maximum cross-sectional diameters of 1.52 and 1.50 cm, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Vein grafting of tunical incisions combined with contralateral plication in the treatment of penile curvature.

OBJECTIVE: To evaluate whether multiple incisions of Peyronie's plaque with placement of vein grafts to cover the tunical defects coupled with contralateral tunical plication is effective in straightening the penis while allowing preservation of normal erectile function. METHODS: Nine patients with Peyronie's disease and 2 patients with congenital curvature of the penis were surgically treated with a vein patch graft technique to correct their penile curvature. All patients underwent relaxing transverse incisions of their plaque with placement of a vein graft from the deep dorsal vein of the penis and/or the saphenous vein. Transverse relaxing incisions about 1 to 2 cm long were made on the tunica albuginea where a curvature was identified by an artificial erection. A corresponding size of the harvested vein was sewn into the defect created by the relaxing incisions. If there was evidence of a residual curvature after the vein grafts were sewn in, a plication of the contralateral surface of the tunica albuginea was performed. RESULTS: Of 10 patients who were potent preoperatively, 9 retained their potency post-operatively. Complete straightening of the erect penis occurred in 9 of 11 patients. Penile shortening occurred in three men. None of the patients permanently lost sensation in the shaft or glans of the penis. Two patients have anesthesia on part of the skin of the penile shaft. In all patients, the grafts were unable to straighten the penis 100 percent, thereby requiring at least one plication suture in the contralateral corpus. CONCLUSIONS: The use of vein grafts to cover multiple incisions of the tunica albuginea combined with contralateral corporeal plication is an easy alternative and an effective way to treat penile curvature while attempting to preserve erectile function.

Adult↗
PubMed1994

Andrology.

Explore the source record for details and available documents.

Erectile Dysfunction↗
PubMed1993

Levels of nitric oxide metabolites do not increase during penile erection.

Cavernosal smooth muscle relaxation, one of the primary events in penile erection, is initiated by the synthesis and release of nitric oxide (NO) from the neurons of the cavernosa. The present study was undertaken to determine whether or not serum levels of NO metabolites rise during an erection. Since NO is rapidly converted into nitrites and nitrates, we measured these serum levels in the peripheral and cavernosal blood of 15 potent adult male volunteers who were exposed to erotic stimuli in order to elicit a penile erection. Our data demonstrate that both nitrite and nitrate levels in the peripheral and cavernosal blood do not appreciably change during and immediately following an erection. This indicates that the determination of whether or not abnormalities in the synthesis and release of NO play any role in erectile dysfunction will require alternative testing methods.

Adult↗
PubMed1993

Intraurethral prostaglandin E-2 cream: a possible alternative treatment for erectile dysfunction.

Prostaglandin E-2 (PGE-2) is an oxytocic agent in suppository form with vasodilatory effects similar to prostaglandin E-1 (PGE-1). Because some men find intracavernosal injections disagreeable, we investigated whether intraurethral PGE-2 may provide an alternative method for treating erectile dysfunction. A PGE-2 cream was made using PGE-2 suppositories (20 mg or 40 mg), 10 cc of 2% lidocaine (Xylocaine) jelly, and 40 cc of surgical lubrication. Two cc of the cream was instilled into the urethral meatus using a syringe, the cream was massaged down the urethra, and the urethra was occluded for five minutes. Treatment response was rated as no penile tumescence, partial tumescence, and full tumescence. Overall, 70 percent showed a response and 30 percent had full penile tumescence. Two of 4 men who had no tumescence using PGE-2 had a subsequent full tumescence using intracavernosal PGE-1 (15 mg), while 3 of 4 men with a partial tumescence with PGE-2 had a subsequent full tumescence using intracavernosal PGE-1 (15 mg). These data demonstrate that full penile tumescence may be achieved in impotent men using intraurethral PGE-2 cream. This pilot study supports the necessity for further investigations in a randomized double-blind manner in the use of intraurethral PGE-2 cream as a less invasive treatment alternative for erectile dysfunction.

Administration, Topical↗
PubMed1993

Up-regulation of the levels of androgen receptor and its mRNA by androgens in smooth-muscle cells from rat penis.

Smooth-muscle cells cultured from the penis of sexually immature (I-PSMC) and adult (A-PSMC) rats express similar high levels of the androgen receptor (AR) mRNA. This contrasts with the marked in vivo decline of both AR mRNA and androgen binding in the penile smooth muscle of adult rats, which appears to be responsible for the cessation of androgen-dependent penile growth upon sexual maturation. PSMC is therefore a good model to study putative down-regulators of AR expression as a function of cell proliferation in the smooth muscle of androgen-responsive vascular tissue. In order to determine whether AR protein levels in PSMC correlate with AR mRNA levels, the immunocytochemical detection of ARs and their androgen binding capacity were compared between I- and A-PSMC. The number of ARs and their protein half-lives suggested similar levels of translation of the AR mRNA in both cell lines. The effect of the synthetic analog methyltrienolone (R-1881) on androgen binding was studied in contact-inhibited androgen-deprived PSMC. In contrast to the postulated role of androgens as down-regulators of AR expression in rat penis, ARs were up-regulated in A-PSMC by R-1881. Contact inhibition of A-PSMC combined with serum depletion and androgen deprivation down-regulated AR mRNA levels, and dihydrotestosterone (DHT) counteracted this effect. These results suggest that the loss in A-PSMC of the age-dependent down-regulation of ARs observed in vivo in adult corpora cavernosa smooth muscle is related to the in vitro resumption of cell proliferation and that DHT acts directly on the penile smooth muscle as a positive modulator of AR levels.

Actin Cytoskeleton↗
PubMed1993

Testosterone down-regulates the levels of androgen receptor mRNA in smooth muscle cells from the rat corpora cavernosa via aromatization to estrogens.

Androgens down-regulate the levels of androgen receptors (AR) and AR mRNA in the penis and prostate of castrated rats, and are assumed to cause their decrease during sexual maturation in the penile smooth muscle of intact rats. In order to determine whether these effects occur directly at the target cell level, and to what extent they are due to testosterone (T) or to their metabolites, we have measured AR mRNA in cultures of smooth muscle cells from the adult rat corpora cavernosa treated in vitro with sex steroids. T at high concentrations (100 nM) acted like dihydrotestosterone (DHT) in increasing moderately the levels of AR mRNA in both proliferating and contact-inhibited cells. However, when conversion of T to DHT was blocked by the 5-alpha reductase inhibitor finasteride, the levels of AR mRNA were considerably down-regulated by T (10-500 nM), particularly in the contact-inhibited cells. Finasteride by itself was inactive. These effects in both types of cultures were inhibited by platelet derived growth factor (PDGF) (20 ng/ml), a growth factor that up-regulates AR mRNA levels, and by fadrozole (100 nM), an aromatase inhibitor of the T/estrogen conversion. Estradiol (50 nM) was even more potent than T in decreasing AR mRNA levels. With the exception of PDGF none of the treatments affected significantly cell growth, as measured by DNA synthesis and content. Our results indicate that it is possible to modulate in vitro AR mRNA levels in the penile smooth muscle cells, and that under normal conditions DHT and T act as moderate up-regulators. When DHT formation is inhibited, the aromatization pathway of T to estradiol will prevail and induce a pronounced down-regulation of AR mRNA levels. We assume that the in vivo AR down-regulation in the penile smooth muscle by androgens is an indirect effect mediated by a paracrine or endocrine mechanism elicited in another tissue.

Animals↗
PubMed1993

Cavernous artery obstruction following blunt trauma to the penis.

Erectile dysfunction following blunt trauma to the erect penis usually is associated with an injury to the tunica albuginea of the corpus cavernosum. We recently identified 2 patients with erectile dysfunction following bending of the penis during coitus whose only abnormality after a complete evaluation, including penile angiography, was a deep cavernous artery injury. We suggest that during examination of patients with erectile dysfunction following blunt injury to the erect penis a complete vascular evaluation, including penile angiography, may be necessary to detect an unrecognized injury to the deep cavernous arteries.

Adult↗
PubMed1993

Sodium bicarbonate alleviates penile pain induced by intracavernous injections for erectile dysfunction.

In an attempt to determine whether penile pain associated with intracorporeal injections could be due to the acidity of the medication, we performed a randomized study comparing the incidence of penile pain following intracorporeal injections with or without the addition of sodium bicarbonate to the intracorporeal medications. A total of 38 consecutive patients who presented to our clinic with impotence received 0.2 ml. of a combination of 3 drugs: 6 mg. papaverine, 100 micrograms. phentolamine and 10 micrograms. prostaglandin E1 with (pH 7.05) or without (pH 4.17) the addition of sodium bicarbonate (0.03 mEq.). Of the 19 patients without sodium bicarbonate added to the medication 11 (58%) complained of penile pain due to the medication, while only 1 of the 19 men (5%) who received sodium bicarbonate complained of penile pain. From these data we conclude that the penile pain following intracorporeal injections is most likely due to the acidity of the medication, which can be overcome by elevating the pH to a neutral level.

Adult↗
PubMed1993

Long-term results of penile vein ligation for impotence from venous leakage.

Between 1986 and 1991, 46 men with organic impotence documented by dynamic pharmacocavernosometry and cavernosography to have venous leakage underwent penile vein ligation. Despite initial improvement in erections allowing normal intercourse in 34 men (74%) within the first 6 months, long-term (more than 12 months) evaluation revealed sustained potency without adjunctive therapy in only 11 (24%). Of the remaining 35 men 6 (13%) progressed to a penile prosthesis, 8 (17%) required intracavernous vasoactive injection therapy and 21 (46%) have not sought further therapy despite continued impotence. Of the 14 patients who had isolated distal leakage 6 (43%) had sustained erectile function while only 5 of the 32 patients (16%) with proximal leakage maintained potency. Associated complications included penile shortening in 20 (43%) and penile hypoesthesia in 9 men (20%). Therefore, we conclude that the long-term success of penile vein ligation is poor, with only 24% of the patients able to have normal intercourse more than 1 year later, although those patients with distal penile shaft leakage appear to have a greater chance of success than those with more proximal leakage.

Adult↗
PubMed1993

Pulmonary migration of coils inserted for treatment of erectile dysfunction caused by venous leakage.

Embolization of penile veins by coils and/or detachable balloons has been reported as a possible effective form of treatment of venogenic erectile dysfunction. The major appeal for this avenue of therapy in these patients is the reported low morbidity and negligible rate of complications compared to an open operation. We describe a case of asymptomatic pulmonary migration of a coil placed for venous leakage in a patient in whom the procedure was conducted through the femoral vein rather than the deep dorsal vein. We conclude that patients undergoing coil embolization for venous leakage should be appraised of the potential for coil migration.

Adult↗
PubMed1993

Nitric oxide and cGMP: mediators of pelvic nerve-stimulated erection in dogs.

We sought to determine whether the L-arginine-nitric oxide-guanosine 3',5'-cyclic monophosphate (cGMP) pathway, known to mediate neurostimulation-induced smooth muscle relaxation in penile tissue of rabbits and humans in vitro, is operative also in vivo. Adult male dogs (n = 9) were subjected to direct electrical stimulation of the pelvic nerves to induce penile tumescence. Intracavernous injection of the nitric oxide-releasing substance S-nitroso-N-acetylpenicillamine resulted in similar tumescence. Intracavernous injection of a specific inhibitor of nitric oxide synthesis, NG-nitro-L-arginine, blocked pelvic nerve-stimulated tumescence, and this was partially reversed by intracavernous injection of the nitric oxide precursor L-arginine. Furthermore, neurostimulated tumescence was inhibited by methylene blue, an inhibitor of cytosolic guanylate cyclase and enhanced by M&B 22948, a cGMP phosphodiesterase inhibitor. These in vivo findings support the hypothesis that cavernous smooth muscle relaxation and penile tumescence are mediated by nitric oxide and cGMP.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1992

Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission.

BACKGROUND: Nitric oxide has been identified as an endothelium-derived relaxing factor in blood vessels. We tried to determine whether it is involved in the relaxation of the corpus cavernosum that allows penile erection. The relaxation of this smooth muscle is known to occur in response to stimulation by nonadrenergic, noncholinergic neurons. METHODS: We studied strips of corpus cavernosum tissue obtained from 21 men in whom penile prostheses were inserted because of impotence. The mounted smooth-muscle specimens were pretreated with guanethidine and atropine and submaximally contracted with phenylephrine. We then studied the smooth-muscle relaxant responses to stimulation by an electrical field and to nitric oxide. RESULTS: Electrical-field stimulation caused a marked, transient, frequency-dependent relaxation of the corpus cavernosum that was inhibited in the presence of N-nitro-L-arginine and N-amino-L-arginine, which selectively inhibit the biosynthesis of nitric oxide from L-arginine. The addition of excess L-arginine, but not D-arginine, largely reversed these inhibitory effects. The specific liberation of nitric oxide (by S-nitroso-N-acetylpenicillamine) caused rapid, complete, and concentration-dependent relaxation of the corpus cavernosum. The relaxation caused by either electrical stimulation or nitric oxide was enhanced by a selective inhibitor of cyclic guanosine monophosphate (GMP) phosphodiesterase (M&B 22,948). Relaxation was inhibited by methylene blue, which inhibits cyclic GMP synthesis. CONCLUSIONS: Our findings support the hypothesis that nitric oxide is involved in the nonadrenergic, noncholinergic neurotransmission that leads to the smooth-muscle relaxation in the corpus cavernosum that permits penile erection. Defects in this pathway may cause some forms of impotence.

Adult↗