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Biomedical subjects

J Rajfer

Publications and source records attributed to J Rajfer.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Variability of venous anatomy of rat testis: application to experimental testicular surgery.

The venous drainage of the testis of the laboratory rat was observed in 31 animals. The right testicular (internal spermatic) vein drained directly into the right common iliac vein in 77.4%, and into the inferior vena cava in 22.6% of the animals. The left testicular vein drained into the left common iliac vein in all animals, but in 90.3% there was also an accessory branch of the testicular vein draining into the left renal vein. These observations suggest that in the rat the exact anatomy of the venous drainage of each testis should be identified prior to undertaking any surgical procedure on the testis where the venous vasculature plays a major role such as testicular transplantation or the creation of an experimental varicocele.

Animals↗
PubMed1992

Identification of motile sperm in caput epididymis. Intraoperative observations and clinical correlations.

This retrospective review of patients who underwent vasoepididymostomy demonstrates that motile sperm may be identified in the most proximal portion of the epididymis, and implies that induction of sperm motility may be independent of transit through the epididymis. Although further studies are needed, the data imply that it may not be necessary to identify motile sperm in the epididymal fluid to achieve a successful vasoepididymostomy.

Adult↗
PubMed1992

Effects of multiple injections of HCG on testis blood flow.

In attempting to determine whether or not multiple injections of human chorionic gonadotropin (hCG) augment testis blood flow, adult male rats were injected with three doses of 10 IU of hCG every other day and testis blood flow was determined on day 5, the day of the final injection. Testis blood flow (mL/100 g testis tissue/min +/- SEM) as measured by the 133Xe washout method increased from 10.8 +/- 1.3 to 20.4 +/- 4.5 (p less than 0.05) after the three doses of hCG. These observations suggest that multiple injections of hCG appear to have the same effect as a single dose of hCG in increasing testis blood flow. This supports the hypothesis that hCG should be administered to all patients undergoing orchiopexy in the hope that the increased perfusion of the gonad will make it less susceptible to ischemia during the surgical procedure.

Animals↗
PubMed1992

Laparoscopic occlusion of testicular veins for clinical varicocele.

Surgery via the laparoscope is now a reliable and cost-effective alternative to some open surgical procedures. Advances in videoendoscopy, incorporating optical magnification combined with the development of instruments with which to dissect, ligate, and transect blood vessels provide the urologist the opportunity to surgically correct a varicocele. In the outpatient setting, 4 patients (14-26 years of age) underwent laparoscopic ligation of the left internal spermatic veins for painful left varicocele. Carbon dioxide pneumoperitoneum was obtained using a Veress needle. A 10-mm laparoscope was placed intraperitoneally through a cannula inserted in the infraumbilical border. Utilizing two additional endosurgical ports (5 mm and 10 mm) through which 5-mm dissecting instruments and vaso-occlusive endoclips were placed, three veins were individually isolated and ligated in each of the 4 patients. In all 4 patients, the left testicular artery was visualized and preserved. There was no blood loss or other intraoperative complication. In each patient the varicocele was successfully corrected. Analgesic medication was not required postoperatively. We conclude that laparoscopic ligation of the internal spermatic veins is a safe and effective way of treating a varicocele without immediate postoperative sequelae. Long-term follow-up is necessary to determine the place of the endoscopic approach.

Adolescent↗
PubMed1992

Nitric oxide is a potent relaxant of human and rabbit corpus cavernosum.

Nitric oxide (NO) caused a potent, marked, and transient relaxation of precontracted strips of corpus cavernosum isolated from humans and rabbits. The relaxation response elicited by NO was very similar to the relaxation evoked by electrical field stimulation via the nonadrenergic-noncholinergic pathway. Sodium nitroprusside, nitroglycerin, and S-nitroso-N-acetylpenicillamine, which are nitrovasodilators known to generate NO, also caused marked concentration-dependent relaxation of corpus cavernosum. Relaxant responses to NO were enhanced by the cyclic GMP phosphodiesterase inhibitor M&B 22,948 and inhibited by oxyhemoglobin. Similarly, relaxation of corpus cavernosum in response to electrical field stimulation or acetylcholine was enhanced by M&B 22,948 and inhibited by oxyhemoglobin. NO stimulated cyclic GMP formation in corpus cavernosum and a close positive correlation was found between the magnitudes of relaxation and cyclic GMP formation. The data suggest that NO-elicited activation of guanylate cyclase and cyclic GMP formation represents the signal transduction mechanism responsible for relaxation and nonadrenergic-noncholinergic-mediated penile erection. These observations indicate that NO is a potent relaxant of human and rabbit corpus cavernosum and support our hypothesis that endogenous NO is the principal mediator of penile erection caused by nonadrenergic-noncholinergic stimulation.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1991

Noninvasive radiological diagnosis of renal vein thrombosis in renal transplantation.

Thrombosis of the allograft renal vein is a rare complication of renal transplantation. Of 557 consecutive renal transplants performed between January 1, 1985 and November 30, 1989, 3 cases occurred for an over-all incidence of 0.4%. In 2 cases the diagnosis was made preoperatively with renal scintigraphy and duplex Doppler sonography. No graft was salvaged, despite timely diagnosis in 2 patients. We conclude that the diagnosis of renal vein thrombosis in the renal allograft recipient should be suspected clinically and by the radiographic findings of absent perfusion on renal scintigraphy, and the detection of an arterial signal, albeit abnormal, on duplex Doppler sonography. When diagnosed, nephrectomy appears to be the only treatment.

Adult↗
PubMed1991

Effect of 5-alpha-reductase inhibitor, 4-MAPC, on testicular descent in male rat.

Testicular descent has been reported to be a dihydrotestosterone (DHT) dependent event. To further elucidate the role of DHT in the process of testicular descent, a group of rats were treated with the 5-alpha reductase inhibitor, 4-MAPC, from birth to day 28 of age and the incidence of testicular descent as well as ventral prostate weight was noted at day 29 of age. It was determined that in the doses used, 4-MAPC failed to prevent testicular descent. Because 4-MAPC inhibited ventral prostate weight by only 53% (as compared to a 75% inhibition by castration), the failure of the 4-MAPC to prevent testicular descent could be due to its inability to completely inhibit tissue 5-alpha reductase activity. The results of this study do not mitigate against the role of other nonhormonal factors working in tandem with DHT in the induction of testicular descent in this animal model.

5-alpha Reductase Inhibitors↗
PubMed1991

Effect of the antiandrogen, WIN 49,596, on the descent of the testis in the male rat.

Testicular descent in the male rat is believed to be an androgen dependent event with dihydrotestosterone the most likely active androgen. To provide further insight into the endocrinology of this important physiological event, we treated male rats with the antiandrogen, WIN 49596 (50 mg./kg./day), from day 1 to day 27 of age and evaluated its effect on the post-natal androgen-dependent events in this animal model. It was determined that while treatment with WIN inhibited the weights of the ventral prostate, seminal vesicles and penis when compared to those seen in castrate animals, the drug only caused a 19% (3/16) inhibition in the descent of the testes when compared to the control group (0/16; p = 0.112). These data together with those previously obtained in animals exposed to selective inhibitors of the 5-alpha reductase enzyme suggest that other factors possibly working in tandem with androgens play a predominant role in testicular descent in the rat.

5-alpha Reductase Inhibitors↗
PubMed1991

Expression of the androgen receptor gene in rat penile tissue and cells during sexual maturation.

The cessation of rat and human penile growth at completion of sexual maturation appears to be related to a tissue-specific decrease in the number of androgen receptors (AR) in the penis. To find out whether this is due to either transcriptional or translational regulation of the AR gene, we determined the levels of AR mRNA by Northern blots in the corpora cavernosa from groups of 16-, 19-, 22-, 27-, 52-, and 90-day-old rats. The AR mRNA rapidly decreases with age and is nearly undetectable in the 52- and 90-day-old rats, paralleling the decline in AR number. The persistence of a low amount of AR mRNA in the adult penis was confirmed by reverse transcription/polymerase chain reaction amplification of total RNA, and its level was estimated by a semiquantitative modification of this procedure at less than 1/25th of that found in the youngest rats. Smooth muscle cells derived from the 16- and 90-day-old corpora cavernosa express in the AR gene in vitro in approximately the same levels, suggesting that there are factors in culture that up-regulate the AR mRNA. Our results are compatible with the assumption that the age-dependent decrease in AR in the rat penis is due to transcriptional regulation, although they do not exclude the less likely alternative of a selective effect on AR mRNA stability and support the use of this model for studying tissue-specific factors controlling the developmental expression of the AR gene.

Animals↗
PubMed1990

Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle.

In the presence of functional adrenergic and cholinergic blockade, electrical field stimulation relaxes corpus cavernosum smooth muscle by unknown mechanisms. We report here that electrical field stimulation of isolated strips of rabbit corpus cavernosum promotes the endogenous formation and release of nitric oxide (NO), nitrite, and cyclic GMP. Corporal smooth muscle relaxation in response to electrical field stimulation, in the presence of guanethidine and atropine, was abolished by tetrodotoxin and potassium-induced depolarization, and was markedly inhibited by NG-nitro-L-arginine, NG-amino-L-arginine, oxyhemoglobin, and methylene blue, but was unaffected by indomethacin. The inhibitory effects of NG-substituted analogs of L-arginine were nearly completely reversed by addition of excess L-arginine but not D-arginine. Corporal smooth muscle relaxation elicited by electrical field stimulation was accompanied by rapid and marked increases in tissue levels of nitrite and cyclic GMP, and all responses were nearly abolished by NG-nitro-L-arginine. These observations indicate that penile erection may be mediated by NO generated in response to nonadrenergic-noncholinergic neurotransmission.

Animals↗
PubMed1990

Nutritional and metabolic effects of gonadotropin-releasing hormone agonist treatment for prostate cancer.

Cancer commonly leads to weight loss associated with increased glucose production and protein breakdown. Medical or surgical castration results in decreased muscle mass, increased fat mass, and weight gain. The aim of this study was to evaluate the changes in body composition, protein metabolism, hepatic glucose production, (HGP), and basal energy expenditure in 10 men with advanced stage C and D prostate cancer receiving a gonadotropin-releasing hormone (GnRH) agonist (Buserelin). Metabolic parameters and nutritional status were determined at 0, 2, 6, and 12 months of therapy. Baseline measurements of plasma leucine appearance (76.2 +/- 5.4 microM/kg/h) and HGP rates (80.1 +/- 2.9 mg/m2/min) were greater than previously reported for normal volunteers. GnRH agonist therapy in prostate cancer patients was associated with a significant reduction in serum testosterone, dihydrotestosterone (DHT), luteinizing hormone (LH), and cortisol, and significant increases in triiodothyronine (T3) and free triiodothyronine (free T3). Neither basal energy expenditure nor plasma leucine appearance rates were changed over time, but there were significant linear reductions in HGP rates (80.1 +/- 2.9 mg/m2/min, mean +/- SEM; 79.9 +/- 2.3, 73.7 +/- 3.4, 72.5 +/- 2.3; P less than .01; baseline, 2, 6, and 12 months, respectively, by repeated measures ANOVA). In all patients, significant increases in body weight, triceps skin fold, cholesterol, and fat mass were noted. Total body water content was not significantly increased after the 12-month period; therefore, the weight gain seen in these patients was water-free tissue, ie, fat mass.

Aged↗
PubMed1990

Kinetics of cyclosporine A-induced inhibition of succinate-coenzyme Q dehydrogenase in rat renal cortical mitochondria.

The kinetic mechanism of succinate-coenzyme Q dehydrogenase (Complex II) inhibition by cyclosporine A (CS) on rat renal cortical mitochondria was investigated. CS showed two modes of inhibition of Complex II of the mitochondrial electron transport system: (a) a mixed linear noncompetitive inhibition of resting succinate-limited and ADP-stimulated respirations suggesting that CS binds to Complex II at a different site than the substrate, affecting the dissociation constant for the enzyme-substrate complex and (b) a competitive inhibition of the DNP-stimulated electron transport system suggesting competition with the oxidized form of a component of Complex II. CS action to renal mitochondrial Complex II limits its function, an effect which may be related to CS nephrotoxicity.

Adenosine Diphosphate↗
PubMed1990

Long-term effects of prepubertal testicular vessel ligation on testicular function in the rat.

To determine the effects of unilateral testicular vein and artery ligation in the immature rat on the function and final location of the testis at adulthood, 10-day-old male rats underwent either a sham operation or unilateral ligation of these vessels of the still undescended testis. Testicular location, blood flow, size and histology as well as ventral prostate weights were measured 50 days later at adulthood. At age 60 days, it was determined that all testes were descended into the scrotum, and there were no differences in testis and ventral prostate weights, intratesticular sperm counts and mean seminiferous tubular area between the control and sham operated animals. However, there was an 18% reduction in testicular blood flow (ml. per 100 gm. per minute +/- standard error of mean) in the operated animals when compared to the sham (20.43 +/- 1.10 versus 16.69 +/- 0.74, p less than 0.02). These data indicate that although there is a slight but significant reduction in testicular blood flow at adulthood when the testicular artery and vein are ligated early in life, this diminution is not sufficient to alter the ultimate location, testicular weight and spermatogenic function of the testis. This would suggest that after ligation of the main testicular vessels to the immature testis, the collateral blood supply is able to compensate with time to allow normal growth and development of the testis. These experimental observations provide additional support for the 2-staged approach to the high undescended testis whereby the testicular vessels are initially ligated and a subsequent procedure is performed to place the undescended testis into the scrotum.

Animals↗
PubMed1990

Cavernosography following clinical failure of penile vein ligation for erectile dysfunction.

In an attempt to determine what occurs to the venous circulation of the penis after ligation of the deep dorsal vein, 9 men with veno-occlusive dysfunction who underwent deep dorsal penile vein ligation and failed to achieve normal erectile function postoperatively consented to a postoperative cavernosogram. Preoperatively, the deep dorsal vein was visualized in all 9 patients, the cavernous vein in 2 and the corpus spongiosum in 1. Postoperatively, the deep dorsal vein was visualized in 1 patient, the cavernous vein in 1 and the corpus spongiosum in 8. These observations suggest that either the inability to identify a cavernous-spongiosal communication preoperatively or the induction of such a communication postoperatively may lead to a clinical failure in patients who undergo deep dorsal penile vein ligation.

Adult↗
PubMed1990

Correlation between penile angiography and duplex scanning of cavernous arteries in impotent men.

During the diagnostic evaluation of patients with vasculogenic impotence duplex scanning has been proposed as a reliable noninvasive method to evaluate the cavernous arteries. However, the sensitivity and specificity of this test have never been elucidated. To provide insight into the clinical value of this test 25 men who presented with impotence and failed to respond to 60 mg. intracavernous papaverine were evaluated with duplex scanning and the results of this modality were compared to penile angiography. The cavernous arteries were considered normal by duplex scanning if the artery demonstrated either a 60% or greater increase in diameter and/or a peak flow velocity of greater than 25 cm. per second 5 minutes after papaverine injection. Penile angiography was considered normal if both cavernous arteries were visualized and appeared to be normal radiographically (after intracorporeal papaverine). In the 25 patients studied there was no significant difference in peak flow velocity between patients with normal or abnormal cavernous arteries by angiography. In addition, arterial dilatation (more than 60%) after papaverine injection did not correlate with the results of the angiogram. These data demonstrate that duplex scanning of the cavernous arteries does not correlate well with what is observed by penile angiography in a selected population of men with vasculogenic erectile dysfunction. Since penile angiography itself has limitations in the evaluation of the penile arteries, the reliability of duplex scanning to identify cavernous artery dysfunction needs additional confirmation.

Adult↗