Hikaru Aoki

Two Circulatory Routes Within the Human Corpus Cavernosum Penis: A Scanning Electron Microscopic Study of Corrosion Casts

The microvascular architecture of the human corpus cavernosum penis was studied by scanning electron microscopy of vascular corrosion casts. The corpus cavernosum was supplied by the penile deep artery. It gave off branches to become either arteries distributed within the corpus cavernosum or those directly supplying the corpus spongiosum urethrae. The former arteries further divided into small arteries which fell into two categories: 1) arteries breaking up into capillaries, and 2) arteries draining directly into the cavernous sinuses. The capillaries were collected into venular networks just beneath the tunica albuginea (the subalbugineal venular plexus), while the cavernous sinuses were collected into venules at the periphery of the corpus cavernosum. These postcavernous venules also received venules from the subalbugineal venular plexus, and left the corpus cavernosum. Thus, two circulatory routes are evident within the corpus cavernosum. These findings suggested that the penile erectile cycle is controlled by hemodynamic changes between these two routes within the corpus cavernosum.

In Vitro Contraction of the Canine Corpus Cavernosum Penis by Direct Perfusion with Prolactin or Growth Hormone

PURPOSE It is well established that hyperprolactinemia, most typically seen in prolactinoma patients, causes hypogonadism and impotence. There seems to be a good possibility that hyperprolactinemia causes impotence, at least partially via some intrinsic property of prolactin (PRL), rather than through its suppressive effects on the hypothalamic-pituitary-gonadal testosterone dynamics. In the present investigation, we used an in vitro canine model to attempt to clarify whether direct action of PRL on the corpus cavernosum penis may lead to erectile insufficiency. Growth hormone (GH) and placental lactogen (PL), both having close structural and functional homologies to PRL, were also studied. MATERIALS AND METHODS Isometric tension measurement with cavernous strips was performed in the presence or absence of 10(-5) to 10(-9) M. PRL, GH, or PL in the perfusion medium. The tension change induced by the test substances was normalized relative to that induced by 120 mEq KCl. RESULTS Both PRL and GH produced dose-related elevations (p < 0.01) of the cavernous tension, whereas PL and thiol-cleaved PRL in comparable doses were without effect (p > 0.05). When the tension rise produced by 120 mEq KCl was taken as 100%, the maximum contractions produced by PRL and GH were 80% and 110%. The minimum effective concentration was 10(-8) to 10(-7) M. for both PRL and GH. Pretreatment with indomethacin (10(-5) M.), but not tetrodotoxin (10(-5) M., partially suppressed (p < 0.05) the effects of PRL. CONCLUSION These results suggest that PRL and GH directly and specifically produced contraction of the corpus cavernosum penis, resulting in erectile insufficiency, and that the effect of PRL is partially mediated by prostaglandin.

Suppression by Prolactin of the Electrically Induced Erectile Response through its Direct Effect on the Corpus Cavernosum Penis in the Dog

PURPOSE Men become impotent when exposed to hyperprolactinemia. To clarify its mechanisms the effects of intracorporal infusion of prolactin on electrically induced penile erection were evaluated in 12 male dogs. MATERIALS AND METHODS Prolactin (10 micrograms./ml.) or control saline was directly infused into the corpus cavernosum penis 5 minutes before electrical pulse stimulation of the pelvic nerve and the intracorporal pressure was monitored. RESULTS In 8 dogs erection was markedly suppressed or completely abolished by prolactin. In the remaining 4, this effect of prolactin became manifest only when the ipsilateral internal pudenal artery was ligated. Saline infusion was without effect. CONCLUSIONS An excess of prolactin directly inhibited the smooth muscle relaxation of corpus cavernosum penis.

Significance of Staging Pelvic Lymphadenectomy for Prostatic Cancer

Staging pelvic lymphadenectomy in 31 cases in stages A2-C prostatic cancer was performed. In 15 of the cases (48%) lymph node invasion was found. Metastatic tendency strengthened with an increase in Gleason scores, although no metastases were found in 38% of the cases with Gleason scores of 8-10. Percutaneous fine-needle aspiration biopsy guided by lymphography was conducted in 14 cases and 17% were false-negative. Lymph node metastases were found in the common iliac lymph nodes in 47%, external iliac lymph nodes in 67% and internal iliac obturator lymph nodes in 100%. Prolonged lymph drainage in 4 cases (13%) and wound infection in 2 cases (3%) were found as postoperative complications, but they were all treated conservatively. So it was concluded that pelvic lymphadenectomy was a reasonable adjunct to total prostatectomy since it provided an accurate assessment of the anatomic distribution of disease, which could be of help in selecting treatment. Dissection of the lymph nodes of the internal iliac obturator was considered quite sufficient to establish the presence of any lymph node metastases.

Quantitative analysis of outflow pathway of corpora cavernosa by pressure flow technique.

Using a pressure flow technique, quantitative analysis of the physiological characteristics of the outflow pathway of the corpus cavernosum was carried out in 19 male dogs weighing 7.5 to 23.0 kg. Pressure flow curves were made on dogs whose pelvic nerve was stimulated electrically and on dogs left unstimulated. When a cyclical change in saline perfusion rate was applied without nerve stimulation, the variable of the intracorporeal pressure showed a large hysteretic loop, indicating that the resistance of the outflow canals to flow was altered by the distension of the sinusoidal space. In dogs whose pelvic nerve was stimulated, the pressure flow curves shifted to the left side in comparison with the outward phase of the pressure flow curve of animals without pelvic nerve stimulation, and this curve piled on the returning phase. No hysteretic relation was observed between the outward and returning phase of the pressure flow curve with pelvic nerve stimulation, but in the detailed analysis, in which the % flow rate was used instead of actual flow rate of saline perfusion, a small hysteretic loop based on the difference of the elasticity of the outlet canals was found. The distension of the corpora cavernosa and the pelvic nerve electrostimulation probably act as the triggers of the same occlusive mechanism in the outflow pathway. The percentage decrease in the blood flow in the outflow canal of the corpus cavernosum induced by the distension of the sinusoidal space or by the pelvic nerve electrostimulation was 69.6 +/- 14.4% (mean +/- SD).

Studies on the Site of Ethanol Action in Inducing Prolactin Release in Male Rats

Hypersecretion of prolactin (PRL) has been implicated as one of the factors that mediate ethanol-induced hypogonadism, but the site(s) in the central nervous system where ethanol acts to lead to the stimulation of PRL secretion is unknown. To clarify the site(s) of ethanol action, medial basal hypothalamic deafferentation (MBHD) or medial basal hypothalamic ablation (MBHA) were performed stereotaxically in male rats, and their PRL secretory capacity in response to acute ethanol administration was compared with that of intact or sham-operated controls. In intact control rats, plasma immunoreactive PRL concentration increased markedly (P < .001 v saline injection) following ethanol 400 to 500 mg/100 g body weight (BW) intraperitoneally (IP). The PRL response was dose-related and reached a maximum plateau level at 15 minutes. Plasma PRL returned to a near-basal level by 60 minutes. The response was blocked completely (P < .001) by pretreatment with dopamine (1 mg per rat), a specific inhibitor of adenohypophyseal PRL secretion. In sham-operated rats and in MBHD and MBHA rats, ethanol (500 mg/100 g BW IP) induced a significant (P < .001 to .05) elevation of PRL relative to the respective saline treatment. The basal level was significantly (P < .005) lower in the MBHD group (5.3 +/- 0.9 ng/mL) and significantly (P < .001) higher in the MBHA group (101.1 +/- 15.7 ng/mL) than in the sham group (17.2 +/- 5.9 ng/mL). These results suggest the following: (1) acute ethanol administration stimulates PRL secretion from the pituitary in a dose-related manner, (2) ethanol appears to have direct stimulatory effects on adenohypophyseal PRL secretion, and (3) extrahypothalamic brain areas exert a stimulatory influence and the hypothalamus an inhibitory influence on basal PRL secretion.

Human Penile Hemodynamics Studied by a Polarographic Method

Observations of the tissue oxygen tension alteration were made using an open tip type oxygen electrode polarographic method as an index of blood flow change in the penile skin, corpus cavernosum and thigh skin of 16 males aged 20-26 years (average age: 20.5 years). In another five males aged 18-21 (average age: 19.8 years) the relationship between corpus cavernosum tissue oxygen tension alteration and penile circumference change in the erection process was observed. This relation was obtained in the penile circulation model, and penile hemodynamics were ascertained. In the flaccid penis the corpus cavernosum contains low-oxygen blood and there is a blockade at the vascular tree in the corpus cavernosum. In the tumescence phase the blood flow of the corpus cavernosum increased suddenly by the relief of cavernosum vascular blockade. During the penile tumescence phase the increased inflow and outflow persisted in corpus cavernosum, and in penile skin the blood also increased initially, but gradually decreased as penile circumference increased. After erection was attained it is thought that resistance to inflow occurred by outflow pathway contraction. In the detumescence phase, a decrease of inflow and a concomitant increase of outflow occurred and the reopening of outflow is thought to be necessary for prompt penile detumescence.

Antitumor effects of oral administration of an interferon-inducing pyrimidinone, Bropirimine, on murine renal-cell carcinoma

Bropirimine [2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone] is a low-molecular-weight compound that acts as an inducer of interferon in several animal species. Experiments were designed to explore the possibility of using this drug for the treatment of renal-cell carcinoma (RCC). Euthymic BALB/c mice were inoculated with murine RCC (Renca) cells and given graded doses of Bropirimine p.o. for 5 consecutive days beginning on day 1 following tumor inoculation. These mice were killed and tumors were excised on day 21. Bropirimine significantly (P<0.01) inhibited the tumor growth at a daily dose of 1,000 or 2,000 mg/kg. No adverse effect or toxicity was noted at 1,000 mg/kg, and at 2,000 mg/kg there was only a marginal body-weight reduction without any other appreciable side effect. In addition to the inhibition of tumor growth, there was a small yet significant (P<0.05) increase in the duration of survival (in days) in the Bropirimine-treated animals. When the treatment was delayed to begin on day 6 following tumor inoculation, Bropirimine did not suppress tumor growth in euthymic mice, pointing to the importance of the timing of the treatment. In athymic nude BALB/c mice lacking T-cells or T-cell function, Bropirimine also inhibited tumor growth (P<0.01). The antitumor effect of this drug was abolished by pretreatment with anti-asialo GM1 serum, which eliminated natural killer (NK) activity in euthymic mice. In vivo treatment with Bropirimine augmented the cytotoxicity of lymphocytes isolated from the spleens or lungs of the tumor-bearing mice, which were active against Renca and YAC-1 cells in vitro. This activity was NK-cell-dependent as judged on the basis of the results of the in vitro complement-dependent cytotoxicity assay. Since Bropirimine induced interferon (IFN)-α/β production, significantly (P<0.05) elevating its serum concentration, and since this drug mimics the effects of IFN-α/β, it seemed likely that the Bropirimine-induced NK cell augmentation we found was mediated by IFN-α/β. These results suggest that Bropirimine, a booster of NK activity, may have potential as an adjunct to other therapeutic modalities in the treatment of human RCC.

Combined effects of intraperitoneal administration of recombinant interleukin-2 and streptococcal preparation OK-432 in murine tumors.

The combined effects of rIL-2 and OK-432 were investigated against a Meth-A tumor, a syngeneic tumor of inbred BALB/c mice. An analysis of the effector cells was also performed. The treatment resulted in an inhibition in vivo of tumor growth and increased survival of the Meth-A tumor-bearing mice. Splenic cells obtained from Meth-A inoculated mice which received combination therapy were not only NK-sensitive YAC-1 and LAK-sensitive EL-4 cells, but also NK-resistant Meth-A cells, as shown in a 4-h 51Cr-release assay. Syngeneic killer cell activity against Meth-A cells was abolished almost completely with anti-Thy 1.2 treatment and about 70% of the activity was abolished with anti-asialo GM1 treatment in a complement-dependent cytotoxic assay. It was not changed by the removal of macrophages and B cells from the splenic cells. Mice which survived for 60 days after the start of therapy rejected Meth-A inoculation when rechallenged, suggesting the establishment of a specific immunity. Combination therapy appeared to be beneficial against Meth-A cells and T-cells appeared to play a determining role in the treated Meth-A bearing mice. It was suggested that more than two populations of killer cells exist in the spleen treated with the combined therapy and they may have the same characteristics as activated T and NK cells with or without specific killer T-cells.

SURGICAL TREATMENT OF RENAL CELL CARCINOMA EXTENDING INTO THE VENA CAVA

Background: