Therapeutic angiomyogenesis using human non-viral transduced VEGF₁₆₅-myoblasts

This article reviews the scientific development of angiomyogenesis using VEGF165-myoblasts, a patented biotechnology platform in regenerative medicine associated with Human Myoblast Genome Therapy (HMGT), also known as Myoblast Transfer Therapy (MTT). VEGF165-myoblasts are the leading biologics for angiomyogenesis. This review also compares the safety and efficacy of VEGF165-myoblasts transduced using adenoviral vectors, nanoparticles or liposomes, in anticipation of their application in clinical trials in the near future. VEGF165-myoblasts are differentiated myogenic cells capable of extensive division, natural cell fusion, nucleus transfer, cell therapy and genome therapy. Following transplantation they survive, develop and function to revitalize degenerative myocardium in heart failure and ischemic cardiomyopathy animal studies. VEGF165-myoblasts are second generation products of HMGT/MTT which replenishes live cells and genetically repairs degenerating myofibers in Type II diabetes, muscular dystrophies, aging dysfunction and disfigurement. Myoblasts have also been used to enhance skin and muscle appearance in cosmetology. We envision that VEGF165-myoblasts will provide better outcome than their non-tranduced counterparts. Myoblasts are not stem cells. Their competitive advantages over stem cells are presented.

Golding's Language View in Lord of the Flies and Darkness Visible

Beyond the stories,Golding spends much effort on an issue called"impotence of language"in his works,especially Lord of the Flies and Darkness Visible.Thus Golding's language view is worthwhile to research.With help of Lacan's theory of signifier and signified,this paper made a primary glance about Golding's language view within the two novels.

Erectile dysfunction and central obesity： an Italian perspective

Erectile dysfunction （ED） is a frequent complication of obesity. The aim of this review is to critically analyze the framework of obesity and ED, dissecting the connections between the two pathological entities. Current clinical evidence shows that obesity, and in particular central obesity, is associated with both arteriogenic ED and reduced testosterone （T） levels. It is conceivable that obesity-associated hypogonadism and increased cardiovascular risk might partially justify the higher prevalence of ED in overweight and obese individuals. Conversely, the psychological disturbances related to obesity do not seem to play a major role in the pathogenesis of obesity-related ED. However, both clinical and preclinical data show that the association between ED and visceral fat accumulation is independent from known obesity-associated comorbidities. Therefore, how visceral fat could impair penile microcirculation still remains unknown. This point is particularly relevant since central obesity in ED subjects categorizes individuals at high cardiovascular risk, especially in the youngest ones. The presence of ED in obese subjects might help healthcare professionals in convincing them to initiate a virtuous cycle, where the correction of sexual dysfunction will be the reward for improved lifestyle behavior. Unsatisfying sexual activity represents a meaningful, straightforward motivation for consulting healthcare professionals, who, in turn, should take advantage of the opportunity to encourage obese patients to treat, besides ED, the underlying unfavorable conditions, thus not only restoring erectile function, but also overall health.

The effect of platelet-rich plasma on cavernous nerve regeneration in a rat model

The aim of this study was to investigate the effect of platelet-rich plasma(PRP)on cavernous nerve(CN)regeneration and functional status in a nerve-crush rat model.Twenty-four Sprague-Dawley male rats were randomly divided into three equal groups:eight had a sham operation,eight underwent bilateral nerve crushing with no further intervention and eight underwent bilateral nerve crushing with an immediate application of PRP on the site of injury.Erectile function was assessed by CN electrostimulation at 3 months and nerve regeneration was assessed by toluidine blue staining of CN and nicotinamide adenine dinucleotide phosphate(NADPH)-diaphorase staining of penile tissue.Three months after surgery,in the group that underwent bilateral nerve crushing with no further intervention,the functional evaluation showed a lower mean maximal intracavernous pressure(ICP)and maximal ICP per mean arterial pressure(MAP)with CN stimulation than those in the sham group.In the group with an immediate application of PRP,the mean maximal ICP and maximal ICP/MAP were significantly higher than those in the injured control group.Histologically,the group with the application of PRP had more myelinated axons of CNs and more NADPH-diaphorase-positive nerve fibres than the injured control group but fewer than the sham group.These results show that the application of PRP to the site of CN-crush injury facilitates nerve regeneration and recovery of erectile function.Our research indicates that clinical application of PRP has potential repairing effect on CN and peripheral nerves.

Study of the efficacy of Korean Red Ginseng in the treatment of erectile dysfunction

Aim： To examine the treatment efficacy of Korean Red Ginseng （KRG） in impotent men with erectile dysfunction （ED）. Methods： A total of 60 patients presenting mild or mild to moderate ED were enrolled in a double-blind, placebo-controlled study in which the efficacies of KRG and a placebo were compared. The patients received either 1 000 mg （3 times daily） of KRG or a placebo. Results： The five-item version of the International Index of Erectile Function （IIEF-5） score after the treatment was significantly higher in the KRG group compared with that before the treatment （from 16.4±2.9 to 21.0±6.3, P 〈 0.0001）. In contrast, there was no difference before and after the treatment in the placebo group （from 17.0±3.1 to 17.7±5.6, P 〉 0.05）. In the KRG group, 20 patients （66.6%）, reported improved erection, significant in the global efficacy question （P 〈 0.01）; in the placebo group there was no significance. Scores on questions 2 （rigidity）, 3 （penetration）, 4 and 5 （maintenance）, were significantly higher for KRG than those for the placebo when those questions were answered after 12 weeks of each treatment （P 〈 0.01）. When the score in the KRG group was compared to the placebo group after the treatment, there was a significant improvement in total score （IIEF-5 score） in questions 3 and 5 for the KRG-treated group （P 〈 0.001 and P 〈 0.0001, respectively）. The levels of serum testosterone, prolactine and cholesterol after the treatment were not statistically significant different between the KRG and the placebo group （P 〉 0.05）. Conclusion： Our data show that KRG can be an effective alternative to the invasive approaches for treating male ED.

Determinants of male health： the interaction of biological and social factors

This review discusses the social and biological factors that may influence male development from conception to adulthood and also underlie the development of health disorders. It will provide assistance to those who may be considering the formulation of a male health policy. It aims to emphasize that social determinants function on a bio- logical background that is profoundly influenced by a male＇s genome, inherited from his parents. The importance of the male-specific reproductive disorders is emphasized, but these also affect somatic structures through the secretion of androgens secreted from the testes. In turn, the function of the cardiovascular and nervous systems can signifi- cantly influence reproductive processes such as erectile dysfunction.

Different hemodynamic responses by color Doppler ultrasonography studies between sildenafil non-responders and responders

Aim： To determine if there are different penile hemodynamic patterns between sildenafil non-responders and responders by using color Doppler ultrasonography. Methods： A total of 69 erectile dysfunction （ED） patients aged 22-79 years were enrolled into the present study. Thirty-eight （55.1%） men with ED who did not respond to four attempts of treatment with 100 mg sildenafil after re-education were classified as sildenafil non-responders. A com- bination of three vasodilator drugs, 1.25 mg papaverine, 0.4 mg phentolamine and 5 ug prostaglandin E1, was given by intracavernous injection before penile Doppler ultrasonography was carried out. The erectile response to intracavernous injection and vascular parameters including peak systolic velocity （PSV）, resistance index （RI）, end diastolic velocity （EDV） and cavernosa artery diameter （CD） were measured and the results between sildenafil nonresponders and responders were compared. Results： No statistical difference in vascular parameters measured by Doppler ultrasonography studies between non-responders and responders was noted. Sildenafil non-responders had a poorer penile rigidity response to intracavernous injection than responders （P 〈 0.05）. Among patients with adequate PSV （〉 30 cm/s） and abnormal EDV （〉 5 cm/s）, individuals in the non-responder group had fewer positive responses to intracavernous vasodilator injection than in the responder group （35.3% vs. 72.2%, P 〈 0.05）. Advanced age and comorbidity with diabetes mellitus were significantly associated with sildenafil non-response （P 〈 0.05）. Conclusion： Sildenafil non-responders were characterized by a poorer penile rigidity response to intracavernous injection and had an associated impaired veno-occlusive mechanism. Advanced age and comorbidity with diabetes mellitus were two common factors associated with non-response.

Yohimbine in the treatment of orgasmic dysfunction

Aim： To study the effect of yohimbine in the treatment of men with orgasmic dysfunction. Methods： A 20-mg dose of yohimbine was first given to 29 men with orgasmic dysfunction of different aetiology in the clinic. Patients were then allowed to increase the dose at home （titration） under more favourable circumstances. The outcome and side effects were subsequently assessed. Results： The patients were classified into three groups of orgasmic dysfunction： primary complete （13）, primary incomplete （8） and secondary （8）. Nocturnal emissions were present in 75%, 40% and 50% of patients in the above groups, respectively （overall average 62%）. The men presented because of fertility problems （52%） or because they wanted to experience the pleasure of orgasm （48%）. Of the 29 patients who completed the treatment, 16 managed to reach orgasm and were able to ejaculate either during masturbation or sexual intercourse. A further three achieved orgasm, but only with the additional stimulation of a vibrator. A history of preceding nocturnal emissions was present in 69% of the men in whom orgasm was induced but only 50% who failed treatment. Of the patients, two have subsequently fathered children （one set of twins） and another 3 men were also cured. Side effects were not sufficient to cause the men to cease treatment. Conclusion： Yohimbine is a useful treatment option in orgasmic dysfunction.

Recent advancement in diagnosis of vasculogenic impotence

Several dynamic tests with vasoactive drags are available for evaluating penile vascular inflows and outflows,ranging from simple pharmacologic test to more invasive radiologic sets. However, there is still no perfect single testto reflect the penile vascular flow. All possible efforts should be exerted to get the greatest erectile effect to avoid anunderestimation of blood flow to the corpora due to incomplete relaxation of the trabecular smooth muscle.Appreciation of the type and frequency of anatomical variations and potential collateral routes is important in interpretingpenile arterograms and in evaluating the hemodynamic significance of suspected arterial disease. Choice of the vasculartests should always depend on the purpose of testing.

Efficacy and tolerability of vardenafil in Asian men with erectile dysfunction

Aim： To evaluate the efficacy and tolerability of vardenafil, a phosphodiesterase type-5 （PDE-5） inhibitor, in men of Asian ethnicity with erectile dysfunction （ED）. Methods： In this prospective, double-blind, multinational study, Asian men were randomized to receive vardenafil （10 mg） or placebo （4：1 ratio） for 12 weeks. The primary efficacy variables were the International Index of Erectile Function erectile function domain （IIEF-EF）, and Sexual Encounter Profile （SEP） questions related to penetration and intercourse completion. Significant mean improvements were required in all three measures to show positive benefits of vardenafil treatment. Secondary efficacy variables included the Global Assessment Question （GAQ） on erection improvement. Results： Least-squares mean baseline IIEF-EF domain scores （vardenafil 14.6, placebo 13.4） were consistent with moderate ED. After 12 weeks, vardenafil treatment was associated with significant increases from the baseline in IIEF-EF domain scores compared with the placebo （22.4 vs. 14.3; P 〈 0.001）. Vardenafil was associated with significant improvements from baseline in least squares （LS） mean success rates for SEP-2 （vardenafil 82.2 vs. placebo 43.6; P 〈 0.001） and SEP-3 （vardenafil 66.1 vs. placebo 24.0; P 〈 0.001）. Positive GAQ responses were reported by 81.8% of vardenafil recipients vs. 24.3% of placebo recipients. Adverse events were reported by 25.4% of the vardenafil group, the majority mild and transient. Conclusion： Vardenafil （10 mg） is a highly effective and well-tolerated treatment for moderate ED in Asian men. These results add to the increasing amount of data demonstrating the safety and efficacy of vardenafil for the treatment of ED in a range of patient populations.

Ventral phalloplasty

Aim： To present a simple technique during penile prosthesis implantation that promotes the perception of increased phallic length. Methods： The penoscrotal web is defined. A ＂check mark＂ incision is made with excision of scrotal tissue. Excellent exposure is provided for implantation of the cylinders, pump and reservoir. Wound closure is performed longitudinally. Results： This technique is a modified extension of surgeries described in the pediatric literature for webbed penis. Loss of penile length following penile implantation surgery is worrisome for patients suffering from erectile dysfunction （ED）. This technique helps with patient satisfaction, cosmetic results, and improves perception of penile length. Conclusion： Ventral phalloplasty is a safe, technically simple procedure that may be performed in concert with penile prosthesis implantation or as a stand alone procedure under＇certain circumstances.

Penile venous anatomy：application to surgery for erectile disturbance

AIM: The structure of the human penile venous system has been well studied, but disappointing outcomes of penile venous surgery in certain patients have called into question on the anatomy. We planned to extend the anatomic knowledge with the ultimate goal of improving operative success. METHODS: Thirty-five patients, who had undergone penile venous surgery, complained of poor erection developed gradually 6 months to 7 years postoperatively. Cavernosography was performed again during their return visit. Seven new patients underwent spongiosography followed by immediate cavernosography. Eleven male cadavers were carefully dissected. The anatomical findings were applied to venous surgery in 155 patients, who were then followed with the International Index of Erectile Function Questionnaire-5 (IIEF-5). RESULTS: Imaging observation demonstrated that the deep dorsal vein served as a common vessel of the corpora cavernosa and corpus spongiosum. A prominent cavernosal vein was found coursing along each corpus cavernosum distally to the glans, in contrast to its reported description as a short segment at the penile hilum. All cadavers had two sets of para-arterial veins sandwiching the dorsal artery. In 148 men available for follow-up, their mean IIEF-5 score was 9.3 preoperative and increased to 22.7 after the operation. The 88.5% (131/148) of the patients believed that venous stripping was a worthy treatment modality. Five cases required sildenafil to maintain their potentia, which was not working preoperatively. CONCLUSIONS: The failure of penile venous surgery has traditionally been ascribed to penile vein regeneration. However, our finding of a long and independent cavernosal vein and an independent set of para-arterial veins may be the principal cause in patients experiencing poor postoperative results.

Animal models for studying penile hemodynamics

Animal models for the study of erectile function monitoring the changes in intracavernous pressure (ICP) during penile erection was reviewed. The development of new models using small commercially-available experimental animals, rats and mice, in the last decade facilitated in vivo investigation of erectile physiology. The techniqueenabled to evaluate even subtle erectile responses by analyzing ICP and systemic blood pressure. Moreover, the method has been well improved and studies using conscious animal models without the influence of any drug or anesthesia are more appropriate in exploring the precise physiological and pharmacological mechanisms in erection. Also, more natural and physiological sexual arousal instead of electrical or pharmacological stimulation is desirable in most of the studies.This article reviewed the development of ICP studies in rats and mice.

Combination therapy for male erectile dysfunction and urinary incontinence

Urinary incontinence （UI） and erectile dysfunction （ED） are both very prevalent conditions. Insertion of an artificial urinary sphincter （AUS） and penile prosthesis （PP） is an effective and proven method of treatment for both conditions. With advancing age, as well as with increasing populations of patients radically treated for prostate cancer, the occurrence of both conditions found in the same patient is increasing. The purpose of this article was to analyze the available evidence for simultaneous surgical management of male ED and UI using prosthetic devices. The existing literature pertaining to dual implantation of AUS and PP was reviewed. The concomitant insertion of the PP with the male perineal sling was also considered. Concurrent ED and UI are increasingly seen in the post radical prostatectomy population, who are often younger and less willing to suffer with these conditions. Insertion of an AUS and PP, either simultaneously or as a two-stage procedure, appears to be a safe, efficacious and long-lasting method of treatment. The improvements in design of both the AUS and PP as well as the development of the single transverse scrotal incision have made simultaneous insertion of these prostheses possible. Dual implantation of the PP and male sling looks promising in a selected population. In conclusion, the insertion of the AUS and PP for the treatment of concurrent UI and ED is safe and effective. Simultaneous insertion of these prostheses in the same patient offers potential advantages in operative and recovery time and is associated with high patient satisfaction. Combination therapy should therefore be included in the arsenal of treatment of these conditions.

Long-term treatment with intracavernosal injections in diabetic men with erectile dysfunction

Aim： To assess the behavior of patients with diabetes mellitus （DM） and erectile dysfunction （ED） during 10 consecutive years of treatment with self-injection of vasoactive drugs. Methods： Thirty-eight diabetic men, including 12 with type Ⅰ and 26 with type Ⅱ diabetes, were followed up regularly for 10 years after they began self-injecting for severe ED. Real time rigidity assessment was used for the objective determination of the initial dosage and then doses were regulated in order to introduce an erection suitable for penetration and maintenance of erection for approximately 30 min. Patients were followed up every two months, and doses were increased only when the treatment response was not satisfactory. Results： The number of injections used per year by the patients was reduced each year （mean numbers： 50 in the first year and 22.5 in the 10th） and treatment shifted towards stronger therapeutic modalities （mixtures of vasoactive drugs instead of prostaglandin E1 alone）. Type Ⅰ diabetic men were standardized to a level of treatment as early as 5 years after the initiation of treatment. That level was finally reached by type Ⅱ patients after another 4-5 years. Conclusion： Treatment with self-injections of vasoactive drugs in diabetic men with severe El） is a safe and effective alternative in the long term. Diabetic men of both types show the same preferences in quality and quantity of treatment after 10 years. The key point for maintenance in treatment is the adjustment of the therapeutic method and dosage to optimal levels for satisfactory erections. （Asian J Androl 2006 Mar; 8： 219-224）

Effect of diabetes and insulin treatment on nitric oxide synthase content in rat corpus cavemosum

Aim: To study the effect of diabetes mellitus and insulin treatment on rat penile nitric oxide synthase content.Methods: Male Wistar rats were divided at random into two groups: the Control (n = 8) and the Diabetic (n =17). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The diabetic animals were then ran-domly divided into two subgroups; diabetic rats without insulin treatment (n = 7) and diabetic rats with insulin treat-ment (n = 10). The neuronal nitric oxide synthase (nNOS) in the penile corpus cavernosum were assayed by immumo-histochemical staining with specific antibody to nNOS and the nNOS-positive nerve fibers were counted semiquantita-tively under a high power microscope. Results: The nNOS- positive nerve fibres in diabetic rats with treatment washigher than that in diabetic rats without treatment ( P < 0.05) and lower than that in the controls ( P < 0.01). ThenNOS-positive nerve fibres in diabetic rat without treatment were also lower than that in the controls ( P < 0.01). Con-clusion; In streptozotocin-induced diabetic rats, the nNOS content in the penile corpus cavernosum was significantlydecreased. Insulin treatment at the dose level employed partially restores the penile nNOS content in these rats.

The 5-year functional outcomes after radical prostatectomy： a real-life experience in Korea

We investigated the functional outcomes regarding erectile function and urinary continence up to 5 years following radical prostatectomy （RP） in a cohort of Korean men. We retrospectively analyzed the clinicopathologic data of 85 Korean men who received open uni- or bilateral nerve-sparing RP for clinically localized prostate cancer and were followed up for at least 5 years postoperatively. From medical records, patients＇ status regarding urinary and erectile function at baseline and postoperative followups after RP was assessed. At 24 and 60 months after RP, proportions of subjects continent （no pads used） were 89.4% and 97.6%, respectively （P = 0.007）. Excluding subjects （n = 24） who preoperatively reported having severe erectile dysfunction or lacked relevant informations, proportions of subjects capable of having vaginal intercourse regardless of erectile aid usage were 47.5% and 37.7% at 24 and 60 months from RP, respectively （P = 0.022）. Patient＇s age at surgery （P = 0.047） and salvage radiation therapy （P = 0.026） were observed to be significant predictors of having erections sufficient for intercourse at 60 months from RP in multivariate analysis. Our results showed that while patients＇ postoperative status regarding urinary continence at 2 years from RP is generally maintained or improved at 5 year point, erectile function was observed to significantly declined from 2 years to 5 years following RP. Such decline in erectile function following RP may be more significant among men who were relatively older at surgery or those who received salvage therapy during postoperative follow-ups.

Erectile dysfunction: on the efficacy of a phosphodiesterase inhibitor in patients with multiple risk factors

1 Introduction With the 1998 introduction of sildenafil (Viagra), the first available oral phosphodiesterase inhibitor, there

A PARALLEL STUDY ON THE EFFECTS IN TREATMENT OF IMPOTENCE BY TONIFYING THE KIDNEY WITH AND THAT WITHOUT IMPROVING BLOOD CIRCULATION

141 cases of functional impotence of the kidney-deficiency type were treated by tonifying the kidney. On them, 103 cases at the same time were treated by improving blood circulation and the other 38 cases by the former only. As a result the total effective rate and the markedly effective rate in the former were 84.46% and 46.60% respectively; but in the latter, 60.55% and 13.15%. A significant difference was found in Ridit analysis (P

Erectile dysfunction: on the efficacy of a phosphodiesterase inhibitor with concurrent sex therapy

1 Introduction Erectile dysfunction (ED) is a condition that affects perhaps 25 to 30 million men in the U.S.A. constituting