Sohn M, and Bosinski H. Gender identity disorders: Diagnostic and surgical aspects. J Sex Med 2007;4:1193–1208 Transsexualism is defined as a strong and persistent cross-gender identification with the patient's persistent discomfort with his or her sex and a sense of inappropriateness in the gender role of that sex (Diagnostic and Statistical Manual of Mental Disorders, fourth revision, text revision [DSM-IV-TR]). The disturbance is not concurrent with a physical intersex condition and causes clinical distress or impairment in social, occupational, or other important areas of functioning. The trained mental health professional is obliged to find out if the patient fulfills the criteria of an irreversible gender transposition and if he or she will benefit from medical (hormonal and surgical) sex-reassignment treatment. If a patient has absolved 12 months of real-life experience and at least 6 months of continuous hormonal treatment, the indication for surgical sex reassignment may be given. Genital sex-reassignment in male-to-female transsexuals includes vaginoplasty, preferably by inversion of penoscrotal skin flaps, clitoroplasty, and vulvoplasty. The operation may be performed in one or two sessions. In contrast to genital reassignment in male-to-female patients, no operative standards are available in female-to-male subjects. Recently, neophallus creation from sensate free forearm flaps has emerged as the most promising approach for those patients who want to have a neophallus. Other alternatives such as metoidoioplasty or neophallus reconstruction from regional flaps exist, but are also accompanied by multiple possible complications and re-interventions. Best results are to be expected when using multidisciplinary teams of plastic surgeons, urologists, gynecologists, and experts in sexual medicine in large volume centers.
The heme-enzyme soluble guanylyl cyclase (sGC) is an ubiquitous NO receptor, which mediates NO downstream signaling by the generation of cGMP. We studied the mechanism of action of the anthranilic acid derivatives 5-chloro-2-(5-chloro-thiophene-2-sulfonylamino-N-(4-(morpholine-4-sulfonyl)-phenyl)-benzamide sodium salt (HMR1766) (proposed international nonproprietary name, ataciguat sodium) and 2-(4-chloro-phenylsulfonylamino)-4,5-dimethoxy-N-(4-(thiomorpholine-4-sulfonyl)-phenyl)-benzamide (S3448) as a new class of sGC agonists. Both compounds activated different sGC preparations (purified from bovine lung, or crude from human corpus cavernosum) in a concentrationdependent and quickly reversible fashion (EC 50 ϭ 0.5-10 M), with mixed-type activation kinetics. Activation of sGC by these compounds was additive to activation by NO donors, but instead of being inhibited, it was potentiated by the heme-iron oxidants 1H-[1,2,4]-oxdiazolo[3,4-a]quinoxalin-1-one (ODQ) and 4H-8-bromo-1,2,4-oxadiazolo(3,4-d) benz(b)(1,4)oxazin-1-one (NS2028), suggesting that the new compounds target the ferric heme sGC isoform. Protoporphyrin IX acted as a competitive activator, and zinc-protoporphyrin IX inhibited activation of hemeoxidized sGC by HMR1766 and S3448, whereas heme depletion of sGC by Tween 20 treatment reduced activation. Both compounds increased cGMP levels in cultured rat aortic smooth muscle cells; induced vasorelaxation of isolated endothelium-denuded rat aorta, porcine coronary arteries, and human corpus cavernosum (EC 50 1 to 10 M); and elicited phosphorylation of the cGMP kinase substrate vasodilator-stimulated phosphoprotein at Ser239. HMR1766 intravenous bolus injection decreased arterial blood pressure in anesthetized pigs. All of these pharmacological responses to the new compounds were enhanced by ODQ and NS2028. Our findings suggest that HMR1766 and S3448 preferentially activate the NO-insensitive heme-oxidized form of sGC, which exists to a variable extent in vascular tissues, and is a pharmacological target for these new vasodilator drugs.The heterodimeric heme-protein soluble guanylyl cyclases (E.C. 4.6.1.2. pyrophosphate lyase, cyclizing; sGC) function as a receptor for the ubiquitous signaling molecule NO. Binding of NO to the ferrous heme activates the enzyme for rapid catalysis of cGMP formation from GTP (Koesling and Friebe, 1999). The second-messenger cGMP triggers several biological processes, such as a decrease in vascular tone and platelet activity, through an interaction with cGMP-specific protein kinases, phosphodiesterases, and ion channels (Munzel et al., 2003). A unifying concept of the molecular requisites for sGC activation has been put forward (Ignarro et al., 1984; Ballou A.M. was supported by grants from Hoechst-Marion-Roussel/Aventis and the German Research Council (SFB 553, project C10).Part of this work was published previously as a thesis (by A.T.) titled Kontrolle der glattmuskulä ren GC-Aktivitä t via NO-Sensitivitä t, Hä m-RedoxStatus und Proteinexpression, 2001 (ISBN 3-930...
Introduction Penile prostheses, introduced as the first effective organic treatment for erectile dysfunction over three decades ago, have an important role in the treatment of erectile dysfunction when other nonprosthetic treatment options have proven unsatisfactory. Although they are the least chosen and most invasive treatment option, they have the highest satisfaction rate of all available ED options and provide a predictable and reliable result. Aim To provide recommendations/guidelines concerning state-of-the-art knowledge for utilization of the penile prosthesis in the management of men with erectile dysfunction. Methods An International Consultation in collaboration with the major sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a 2-year period. There were 10 experts from seven countries concerning the Penile Implant for Erectile Dysfunction. Main Outcome Measure Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. Results Recommendations/guidelines for penile prosthesis (hydraulic, semi-rigid and soft silicone) insertion for management of men with erectile dysfunction were updated. Consensed issues included: criteria for patient selection, informed consent procedures, strategies for preoperative preparation, operative incisions/technical considerations and outcome results in terms of patient satisfaction and device survival. Updated information was reviewed concerning therapies for device failures, device insertion in scarred corporal bodies and strategies for managing implant infections. Conclusions There is a need for more research in developing management strategies for insertion of penile prostheses in men with ED.
The efficacy of the Catalyst vacuum device was objectively determined and the quality of the nocturnal erections improved in some patients. After application of a constriction ring an ischaemia of the penis developed. In contrast to previous reports, the increased penis volume during the application of the VD is caused not only by arterial inflow but also by venous backflow.
Despite the central and peripheral effects of androgens on the nervous system, the local effects of androgens in the corpus cavernosum penis and their importance for erectile function is still unclear. In this study corpus cavernosum biopsies of eight adult potent patients, aged 19-63 years, undergoing penile deviation surgery (group A) and 12 patients undergoing male-to-female transsexual surgery (group B) were immunostained for nuclear androgen and estrogen-alpha receptors. Additionally, primary corpus cavernosum endothelial cell cultures were obtained from six transsexual patients and exposed to testosterone, dihydrotestosterone, estradiol and progesterone likewise for 7 days. Total cell count was performed and cell metabolic activity was measured by a tetrazolium salt-based assay. Androgen and estrogen-alpha receptors were detected in stromal as well as in endothelial cells. Of all cell nuclei, 74.9% (SD 16.4) in group A and 63.5% (SD 17.1) in group B were positively stained for androgen receptors. The respective percentage of estrogen receptors was 11% (SD 9.5) and 21.2% (SD 12.6). An age-dependent difference in receptor distribution was not observed in either group. In the cell culture system only cultures exposed to testosterone and dihydrotestosterone showed a dose-dependent increase of cell metabolic activity compared to the cultures supplemented with estradiol and progesterone. The significant and age-independent high androgen and low estrogen-alpha receptor distribution found in both groups suggests a possible peripheral effect of androgens at the level of the corpus cavernosum penis in adult humans. This is supported by the observed effect of testosterone and dihydrotestosterone on cell count and endothelial cell metabolism in our cell culture system. The role of estrogens remains unclear.
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