Completely dispersible PEGylated gold nanoparticles under physiological conditions: modification of gold nanoparticles with precisely controlled PEG-b-polyamine.

A novel water-soluble, biocompatible polymer, poly(ethylene glycol)-block-poly((2-N,N-dimethylamino)ethyl methacrylate) (PEG-b-PAMA), possessing controlled molecular weight with a narrow molecular weight distribution, was synthesized by the atom-transfer radical polymerization (ATRP) method. PEG-b-PAMA having a short PAMA chain length was successfully synthesized under suitable polymerization conditions. Gold nanoparticles (GNPs) were modified using PEG-b-PAMA prepared under a variety of PEGylation conditions. Under alkaline conditions (pH >10) and an [N]/[GNP] ratio of more than 3300, the PEGylated GNPs (PEG-GNPs) showed complete dispersion stability, avoiding coagulation. The amino groups of the PAMA segment of the block copolymers were completely deprotonated above pH 10. This means that PEG-b-PAMA interacted with the GNP surface via multipoint coordination of the tertiary amino groups of PAMA, not electrostatically. The effect of the number of amino groups in the PAMA segment on GNP surface modifications was investigated by zeta potential and dynamic light scattering (DLS) measurements. When the PEG-GNPs were prepared in excess polymer solution, almost the same diameter was observed regardless of the PAMA chain length. After the PEG-GNPs were purified by centrifugation, the zeta potentials of all PEG-GNPs were shielded to almost 0 mV, indicating the effective modifications of the GNP surface by PEG-b-PAMA regardless of the chain length. However, the particle size and particle size distribution of the purified PEG-GNPs were strongly affected by the PAMA chain length. PEG-GNPs with longer PAMA segments underwent coagulation after purification, whereas PEG-GNPs with shorter PAMA segments increased their dispersion stability. The experimental results of the thermal gravimetric analysis confirmed that the PEG density on the GNP surface increased as the AMA units decreased to 3. Thus, the dispersion stability depended significantly on the PEG density on the GNP surface. GNPs modified with PEG-b-PAMA having short AMA units showed excellent dispersion stability under a variety of pH conditions. The excellent dispersion stability of the obtained PEG-GNP was also confirmed both in bovine serum albumin (BSA) solution and 95% human serum.

Effect of aldosterone on isolated human penile corpus cavernosum tissue.

OBJECTIVE: To clarify the physiological effects of aldosterone on human penile corpus cavernosum (hPCC) tissue, as aldosterone has a wider physiological action than just the maintenance of electrolyte balance, and there are mineralocorticoid receptors, i.e. aldosterone receptors, in hPCC tissue. MATERIALS AND METHODS: Specimens of hPCC were obtained from 10 patients (mean age 38 years, range 21-75), with informed consent and approval by the local ethics committee. One patient had a penectomy because of penile cancer, and nine had a penile biopsy because of erectile dysfunction. Patients with diabetes mellitus, hypertension or ischaemic heart disease were excluded. In a pharmacological study we evaluated the effect of aldosterone on the isolated hPCC tissues. RESULTS: Aldosterone caused no significant change in resting tension and did not affect the nitric oxide-dependent relaxation reaction. However, the dose-response curve of noradrenaline was shifted to the left when the strip preparation was treated with aldosterone (1 x 10(-5)M) for 20 min before administering noradrenaline. Moreover, the shift to the left was completely blocked when spironolactone (anti-aldosterone agent) was added as a pre-treatment. Pre-treatment with aldosterone also significantly extended the mean (SEM) time required to reach 50% relaxation of a noradrenaline-induced contraction, of 9.3 (1.5) min, vs the control, of 5.2 (1.0) min (P = 0.002). CONCLUSION: Aldosterone has no direct contractile action or a relaxant action on human penile cavernous tissue, but acts to significantly enhance the noradrenaline-induced contraction. The effect on the noradrenaline-induced contraction is probably caused by aldosterone enhancing the affinity of the alpha-receptors for noradrenaline in hPCC. We suggest that aldosterone acts to enhance contraction of hPCC tissue, and is one of the restraining factors for human penile erection.

Variations of the internal pudendal artery as a congenital contributing factor to age at onset of erectile dysfunction in Japanese.

OBJECTIVE: To investigate the relationship between variations of the pelvic artery arrangement and the age at erectile dysfunction (ED) onset, as some men develop ED while relatively young, while others maintain erectile function into old age despite having cardiovascular diseases, thus congenital factors might be involved. PATIENTS AND METHODS: We examined 290 units of internal iliac arteries (IIA) in 145 patients showing repeated incomplete erectile response to intracavernosal injections with prostaglandin E(1). Patients with cardiovascular risk factors, neurological disease or pelvic injury were excluded. The pelvic artery arrangement, evaluated by three-dimensional computed tomographic angiography, was classified anatomically into five types: Type 1 (normal or basic type), in which the internal pudendal artery (IPA) originates from the anterior trunk at the level between the linea terminalis and the major ischial notch; Type 2, the IPA originates from the anterior trunk of the IIA at the level of the major ischial notch or more distally; Type 3, the IPA originates directly from the IIA at a level proximal to the linea terminalis; Type 4, the IPA originates together with the superior and inferior gluteal artery within 1 cm of each other; and Type 5, the penile blood supply is dependent on arteries other than the IPA, such as the obturator artery. RESULTS: Among the 290 units, eight could not be classified due to poor image quality. There were no statistically significant differences in blood flow parameters among the types of IIAs, but there was a statistically significant difference in the IPA type at the age of onset of ED. Type 1 (153 units or 53%) anatomy, was more common in patients who developed ED at an advanced age. Types 2, 3 and 4 were more common in patients with onset of ED at an early age (log-rank test P < 0.001, P = 0.044, P < 0.001, respectively). Compared with patients with the common type of IIAs bilaterally, patients with any of the variations bilaterally are at risk of early onset of ED (log-rank test: P = 0.002). CONCLUSION: In these anatomical studies, nearly half of all internal artery units are variations in type. Congenital factors might contribute to the development of ED. If a man has bilateral variation from the common type (Type 1), he might develop ED approximately 10 years earlier than those who are identical in every way except for their IPA (Type 1) arrangements.

Penile revascularization surgery for arteriogenic erectile dysfunction: the long-term efficacy rate calculated by survival analysis.

OBJECTIVE: To determine the subjective and objective outcomes (by survival analysis) after penile revascularization surgery in patients with arteriogenic erectile dysfunction (ED), selected by established strict criteria. PATIENTS AND METHODS: The study included 51 patients diagnosed with arteriogenic ED caused by localised arterial lesions and who had microscopic penile revascularization surgery between January 1996 and March 2002. Before surgery, all patients had a full examination, including a medical and sexual history, laboratory testing, intracavernosal pharmacological tests, colour Doppler ultrasonography (CDU), pharmacodynamic infusion cavernosometry and cavernosography, and digital subtraction angiography (DSA). Penile revascularization surgery was indicated only in patients aged <50 years and with no history of diabetes mellitus, hypertension or hyperlipidaemia. When there were communicating branches between the dorsal and cavernosal arteries, Hauri's procedure was used; when there were none or there was no evidence for them on both CDU and DSA because of severe narrowing or obstruction in the proximal common penile artery, the Furlow-Fisher modification of the Virag V procedure (FFV5) was used. The patency of the neo-arterial blood flow was assessed by CDU and effective rates calculated using the Kaplan-Meier method. The efficacy rate was recalculated whenever there was a recurrence. When occlusion of the neo-arterial blood was confirmed by CDU the date of occlusion was set as that midway between the last examination showing patency of the donor vessel and the latest examination indicating the occlusion. The patency period was the number of days from surgery to the date of occlusion. RESULTS: Of the 51 patients, 26 had Hauri's and 23 the FFV5 procedure (median age 32 years, range 21-49); in two patients with a previous pelvic fracture surgery was not possible because of scar formation in the dorsal area at the base of the penis. The mean (sd) subjectively estimated efficacy rate was 85.9 (6.3)% after 3 and 67.5 (10.7)% after 5 years of follow-up. The duration at 75% efficacy was 41.0 (5.6) months. The objectively estimated efficacy rate was 84.9 (7.3)% at 3 and 65.5 (13.5)% after 5 years of follow-up. The duration at 75% patency was 42.4 (9.5) months, and at 50% was 60.6 (19.4) months. There was no significant difference in subjective outcome between the FFV5 and Hauri procedures (P = 0.38, log rank test) and none objective outcome after surgery (P = 0.19, log rank test). Thirteen of the 18 patients in the Hauri group had venous dilatation in the deep dorsal, obturator, prostatic and the internal iliac veins. There were operative complications in four patients (hyperaemia of the glans in two, and one each with haemorrhage from the anastomosis site and scar contracture). CONCLUSIONS: The long-term efficacy rates (by the Kaplan-Meier method) of the Hauri and FFV5 procedures were both acceptable. The selection criteria gave acceptable outcomes from both procedures. Penile revascularization surgery is a treatment suitable only for young men and therefore attention must be given not only to the long-term outcome but also to long-term adverse events.