Remembering Charles B. Huggins' Nobel Prize for Hormonal Treatment of Prostatic Cancer at its 50th Anniversary.

Charles B. Huggins received the Nobel Prize in 1966. Based on archival sources from the Nobel archive we have found that nominators emphasised the practical therapeutic applications of his discoveries that were showing 25 yr after his key publications.

Acute epididymitis induces alterations in sperm protein composition.

OBJECTIVE: To use a proteomic approach to evaluate possible postinflammatory alterations in the protein composition of motile sperm in patients 3 months after acute epididymitis. DESIGN: Prospective case-control study. SETTING: University medical school research laboratory. PATIENT(S): Eight patients 3 months after acute unilateral epididymitis and 10 healthy controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Proteome analysis of sperm samples collected by swim-up from control and acute epididymitis patients analyzed by two-dimensional gel electrophoresis and subsequent protein identification by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry; immunofluorescence staining for mitochondrial ATP synthase subunit ß (ATP5B), α-tubulin (TUBA1A), and tubulin-ß2c (TUBB4B) for validation purposes. RESULT(S): Proteome analysis identified 35 proteins in sperm from epididymitis patients that were down-regulated, irrespective of subcellular localization and biologic function. Furthermore, immunofluorescence microscopy confirmed ATP5B, TUBA1A, and TUBB4B were less abundantly expressed in epididymitis samples compared with controls. CONCLUSION(S): Despite normal semen parameters observed by conventional semen analysis in patients after epididymitis, significant changes to sperm protein composition were observed. These changes may be implicated as additional factors contributing to subfertility/infertility in men after episodes of epididymitis.

Interview with Oswalt Kolle (1928-2010): German sex education pioneer.

INTRODUCTION: Alfred Kinsey (1894-1956) was the first pioneer of scientific sexology after World War II with his surveys on human sexuality in the male (1948) and the female (1953), which underwent worldwide translations and also had a major impact in Europe. AIM: To clarify the role of the journalist Oswalt Kolle (1928-2010) as the promoter of sex education in Germany and Western Europe in the late 1960s. METHODS: The information is almost exclusively based on a live interview taken with the time witness Oswalt Kolle in February 2010. This scientific technique of oral history is well established in the field of history research today. RESULTS: Kolle has a strong family background in the medical field as his father was a well-known psychiatrist and his grandfather a prominent bacteriologist. Before starting an interest in sex education, Kolle was a successful journalist by interviewing celebrities but turned into one of the most important critics against the restricted views on sex in Germany and Western Europe in the 1960s. His books and films on sexuality were translated into at least 12 languages and were major blockbusters for at least a decade. CONCLUSIONS: Oswalt Kolle had more influence on the public awareness and practice of sexuality in Western Europe and especially Germany than any other single person in his time.

Highlights from the history of sexual medicine.

INTRODUCTION: Today, we have a clear concept of sexual medicine and how to define this medical discipline. But historically, the unification of sexuality and medicine was not a given condition. Medicine was mainly focused on human reproduction and how to prevent and treat sexually transmitted diseases. Hardly any other aspect would have met the interest of medical doctors for centuries. METHODS: Historical review that can only highlight developments and milestones of sexual medicine and is not intended to be encyclopedic. RESULTS: Perhaps, the first true medicalization of sexuality was the dreadful anti-masturbation campaign led by doctors, beginning with Tissot, since the middle of the 18th century. In the 2nd half of the 19th century, first pioneers like the physician Paolo Mantagazza were systematically addressing issues related to human sexuality. This highly developing scientific field and medical community were destroyed after 1933 by the political influence of the national socialists in Europe. After World War II, a new era started with the works of Alfred Kinsey and other sexologists mainly in the United States of America. CONCLUSIONS: The term sexual medicine was established around 1970, most likely in Europe, and subsequently resulted in a new worldwide academic and clinical speciality.

Non-genomic effects of androgens on isolated human vascular and nonvascular penile erectile tissue.

OBJECTIVES: To evaluate non-genomic effects of testosterone and dihydrotestosterone (DHT) on isolated human cavernosal arteries (HCA) and corpus cavernosum (HCC) using organ-bath studies and radio-immunoassays (RIA), as non-genomic effects of androgens are reported for vascular smooth musculature and there is evidence that the relaxant response involves a modulation of cyclic nucleotide tissue levels. MATERIALS AND METHODS: The relaxation induced by the cumulative addition of testosterone and DHT (0.01-10 microm) was studied using circular segments of HCA and strip preparations of HCC. To evaluate the effects of testosterone and DHT on tissue levels of cAMP and cGMP, specimens were exposed to increasing concentrations of the hormones. Forskolin and sodium nitroprusside (SNP) served as reference compounds. RESULTS: Testosterone and DHT dose-dependently reversed the noradrenaline-induced tension of vascular segments and HCC strips. At the maximum concentration, testosterone and DHT reduced the mean (sd) tension to 79.8 (4.43)% and 83.9 (10.94)%, respectively. SNP and forskolin significantly stimulated the production of cGMP and cAMP. No effects of testosterone and DHT on cGMP and cAMP levels were detected. CONCLUSION: Rapid androgen-induced relaxation of HCA and HCC occurs via non-genomic mechanisms. In penile erectile tissue, non-genomic relaxant effects of testosterone and DHT are not mediated via modulation of cyclic nucleotide tissue levels. Additional studies are required to establish if non-genomic relaxant effects are important in ensuring a basal level of perfusion to maintain overall penile function.

[Pattison fascia: the forgotten eponym?]. / Pattison Faszie: Das vergessene Eponym?

Denonvilliers' fascia is known to every urologist as one of the most important structures of the pelvis separating the posterior surface of the prostate and the bladder from the anterior aspect of the rectum. Charles-Pierre Denonvilliers (1808-1872) introduced this "Aponévrose prostato-péritonéale" for the first time in 1836 in Paris, without discussing its surgical importance. Already in 1820 the Scotsman Granville Sharp Pattison (1791-1851) had described this "Fascia of the prostate gland" as a structure to be preserved during perineal lithotomy, a frequently performed procedure in those days. According to Pattison the intraoperative damage of this fascia and subsequent urine extravasation with infection of the anterior rectum was the main reason for the high mortality of this operation at that time. Therefore, it is surprising that the eponym of this fascia is not related with the name of Pattison today.

Early photo-illustration of a hermaphrodite by the French photographer and artist Nadar in 1860.

As early as 1860 the French photographer Gaspard Félix Tournachon, called Nadar (1820-1910), took a series of nine photographs depicting a young intersex patient. These illustrations were not published at their time and little is known about the patient and the role of the physicians involved in this case. The article discusses the available information on these artworks that today belong to the photographic collection of the Musée d'Orsay in Paris.

In vitro viability of human cavernosal endothelial and fibroblastic cells after exposure to papaverine/phentolamine and prostaglandin E1.

OBJECTIVE: To investigate the influence of commercially available vasoactive drugs on human cavernosal endothelial and fibroblastic cells in vitro, as although corporal fibrosis is a well known side-effect of intracavernosal injection therapy for erectile dysfunction, the possible detrimental effect of these agents on the endothelium lining the cavernosal vascular spaces is uncertain. MATERIALS AND METHODS: Cultured primary endothelial (13) and fibroblastic cells (12), obtained from potent patients undergoing penile surgery, were exposed to different physiological dilutions of prostaglandin E1 (PGE1), papaverine/phentolamine or the respective triple-mix of these agents for 30 min. Viable cells were counted and cell metabolic activity measured in these cultures 48 h after drug exposure. RESULTS: There was a significant dose-dependent decrease in the viable cell count after exposure to papaverine-containing formulations, probably because of the low pH of this substance. This cytotoxic effect was more pronounced in endothelial than in fibroblastic cells, and was not apparent in the PGE1 groups. The relative increase in cell metabolic activity in cultures affected by a moderate cytotoxic effect indicated a regenerative process. CONCLUSION: These comparative results in endothelial and fibroblastic cell cultures suggest that the endothelium rather than the interstitium of the corpus cavernosum is more sensitive to side-effects produced by intracavernosal injection therapy with papaverine. Thus, unfavourable consequences on the function of the endothelial layer might be as important as the risk of interstitial fibrosis. As these effects were not detected for PGE1 this drug should be preferred to papaverine in clinical practice.

Isolation of primary endothelial and stromal cell cultures of the corpus cavernosum penis for basic research and tissue engineering.

OBJECTIVES: Primary cell cultures derived from the corpus cavernosum are frequently used as in vitro models to define cellular mechanisms involved in erectile function. However, previous studies often lack detailed isolation protocols or a precise characterisation of the culture composition excluding especially contaminating fibroblasts. This study aimed at critically analysing and reproducing reported isolation methods, as well as establishing new procedures to receive highly pure and morphologically differentiated endothelial, smooth muscle and fibroblastic cells derived from the human penis. METHODS: We evaluated numerous isolation and enrichment techniques using cavernosal tissue from 57 patients. Assessment factors displayed the purity, cell yield, practicability and reproducibility. The purity in cultured cells was analysed using immunocytochemistry and Western blots. RESULTS: An enzymatic protocol was established for the isolation and cultivation of cavernosal endothelial cells with an impressive purity of 98.0+/-0.8%. In contrast, already published nearly pure smooth muscle cell cultures were not reproducible in our laboratory. Meaningful evidence for an overwhelming presence of fibroblasts in these widely accepted pure smooth muscle cell cultures is presented. CONCLUSION: Endothelial cell cultures derived from human corpora cavernosa are reproducible and reliable to serve for cell culture-based investigations of the endothelial dysfunction. The discrepancy in the purity of smooth muscle cell cultures might reflect laboratory and tissue source factors, lacking an exclusion of fibroblasts in other studies or changes in stromal phenotype under culture conditions. Further research is necessary to clarify a possible plasticity between smooth muscle cells and (myo)fibroblasts and assess functional properties.

Biological vascularized matrix for bladder tissue engineering: matrix preparation, reseeding technique and short-term implantation in a porcine model.

PURPOSE: We generated a vascularized, autologous, reseeded bladder substitute and evaluated immediate vascularization and perfusion of the graft after implantation to the recipient organism in a porcine model. MATERIAL AND METHODS: Acellular matrix was processed from porcine small bowel segments by subsequent mechanical, chemical and enzymatic decellularization, preserving the jejunal arteriovenous pedicles. In 2 separate steps the matrix was reseeded with primary bladder smooth muscle cells (SMCs) and urothelial cells (UCs), and its vascular structures were resurfaced with endothelial progenitor cells (EPCs). To evaluate graft perfusion short-term implantation was performed. RESULTS: The acellular scaffold was successfully repopulated with multilayers of ingrowing SMCs and superficial UCs. After reseeding the jejunal arteriovenous pedicles with EPCs and cultivation for 3 weeks the larger vessels as well as the intramural scaffold capillary network were repopulated with cell monolayers expressing endothelial specific proteins. Perfusion stagnation and implant thrombosis occurred within 30 minutes after the implantation of acellular scaffolds not reseeded with EPCs. In the EPC reseeded group the vascular system revealed intact perfusion and no relevant thrombus formation was observed after 1 or 3 hours. CONCLUSIONS: The current study of successful SMC and UC reseeding, vessel resurfacing with EPCs and short-term vascular patency represents the promising in vitro and in vivo basis for further evaluation of this biological vascularized matrix in chronic long-term large animal implantation experiments.

Nikolaj A. Bogoraz (1874-1952): pioneer of phalloplasty and penile implant surgery.

Phalloplasty and penile implants are outstanding pioneering procedures introduced in 1936 by the Russian surgeon Nikolaj A. Bogoraz and are thus of eminent interest to the urological and plastic surgeon. This article from the history of medicine will discuss his biography and scientific achievements during the first half of the 20th century.

Cytotoxicity of different intracavernous vasoactive drugs on cultured endothelial cells of human corpus cavernosum penis.

OBJECTIVES: To investigate the cytotoxic effect of prostaglandin E(1) (PGE(1)), a standard combination of papaverine/phentolamine, and a triple mixture of these agents on human cavernosal endothelial cells using a cell culture model. The endothelial layer of the corpus cavernosum plays an important role in signal transduction of penile erection and is directly exposed to vasoactive agents after intracavernous injection for erectile dysfunction. METHODS: Primary endothelial cells were obtained from the corpus cavernosum of 13 potent patients undergoing penile surgery. Cultured cells were exposed for 30 minutes to physiologic dilutions of 20 microg PGE(1), 30 mg papaverine/1 mg phentolamine, or the same dosages of the triple mixture of these agents, each dissolved in 5 to 50 mL sodium chloride. Lactate dehydrogenase release as a cytotoxicity marker was measured 6 hours after drug exposure, and the total cell metabolic activity was quantified after 48 hours with a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS)-based assay. Additionally, the amount of viable cells was identified with a dual fluorescent staining procedure. RESULTS: The initial release of lactate dehydrogenase was elevated up to 3.2-fold in the concentrated papaverine/phentolamine and triple mixture group compared with PGE(1) and the control. After 48 hours, the papaverine-containing formulations led to a significant dose-dependent decrease in the viable cell count and metabolic activity of the cultures that was not noticed with PGE(1). CONCLUSIONS: These in vitro data strongly suggest an unfavorable effect of vasoactive agents containing papaverine on cavernosal endothelial cells. Before fibrotic changes of the smooth muscle stroma, the functionally important endothelium of the corpus cavernosum might suffer significantly from intracavernous injection therapy. Therefore, papaverine should no longer be used for this indication.

Regenerative medicine in andrology: Tissue engineering and gene therapy as potential treatment options for penile deformations and erectile dysfunction.

Tissue engineering and gene therapy are currently investigated in animal studies for reconstructing penile tissue or treating erectile dysfunction. This review aims to examine these experimental efforts from the last years and tries to give a brief introduction to the basic methodology of these new techniques from the field of regenerative medicine.

Functional tissue engineering of autologous tunica albuginea: a possible graft for Peyronie's disease surgery.

OBJECTIVES: The aim of the present study was to generate a tissue engineered type of mechanically stable graft suitable for surgical replacement of the tunica albuginea penis. METHODS: Porcine fibroblasts isolated from open fascia biopsies were seeded on decellularized collagen matrices and then cultivated in a bioreactor under continuous multiaxial stress for up to 21 days (n=12). Static cultures without mechanical stress served as controls. Cell proliferation, cell alignment, and de novo synthesis of extracellular matrix proteins (proteoglycans, procollagen I, elastin) in these grafts was evaluated by hematoxylin-eosin, pentachrome, and immuno-staining. Additionally, the enzymatic isolation of porcine fibroblasts from X4mm skin punch biopsies (n=8) was evaluated. RESULTS: Mechanically strained cultures of fibroblasts showed a homogeneous multilayer matrix infiltration and a regular cell alignment in the direction of strain axis after 7 days, as well as a de novo production of extracellular matrix proteins compared to the static control. A large amount of viable fibroblasts was easily obtained from small skin punch biopsies. CONCLUSION: This study shows that continuous multiaxial stimuli improve proliferation and extracellular matrix synthesis of mature fibroblasts reseeded on a biological matrix making this a feasible autologous tissue engineered graft for penile surgery. For the clinical setting fibroblasts harvested from small skin biopsies can be a comfortable cell source.