Changes in the extracellular matrix of the clitoris caused by aging: a stereological and comparative study

IntroductionThe clitoris is partially responsible for sexual arousal. The integrity of the extracellular matrix is essential for clitoral erection. Sexual dysfunction is a phenomenon associated with age.MethodsThe clitoris of cadavers of 20- to 80-year-old women was excised and histologically processed. Stereological analysis was performed to quantify the volumetric density of collagen, elastic fibers, and smooth muscle.ResultsA significant increase in collagen and a decrease in smooth muscle and elastic fibers were observed in older women.ConclusionsIn short, these changes caused by aging could contribute to female sexual dysfunction concerning clitoral orgasm.     

Organization of the fibrous connective tissue of the fallopian tubes in fertile and climacteric periods: a scanning electron microscopic and stereologic study

The extracellular matrix (ECM) of the fallopian tubes is subject to several changes due to hormonal influences and aging. However, there is a lack of studies regarding its arrangement in older women. We aimed to analyze the organization of ECMcomponents, including collagen and elastic fibers, in the fallopian tube’s ampulla from young and old women by means of scanning electron microscopical and stereological methods. Twenty-one samples were analyzed: 12 from female cadavers in a fertile age (G1) and 9 from the climacteric period (G2). Masson’s trichrome stain was used to observe collagen and smooth muscle, while Weigert’s Fuchsin-Resorcin was employed to observe elastic fibers. Statistical analysis was performed by the Wilcoxon-Mann-Whitney test with the aid ofthe R^© software. The tissue was also fixed for scanning electron microscopic analysis in a modified Karnovsky solution and the three-dimensional organization of fibrous connective tissue was observed and compared. Statistically significant differences (P < 0.01) were found in all stereologic comparisons of the extracellular matrix between the groups, which revealed a higher volumetric density of the fibrous tissue in the climacteric group. Scanning electron microscopy showed degenerative alterations of extracellular matrix. According to our results, aging caused significant changes to the elements of the extracellular matrix and the smooth muscle of the fallopian tubes.     

糖尿病性勃起功能障碍大鼠阴茎和脊髓nNOS及AchE表达的变化

目的：观察大鼠糖尿病性勃起功能障碍（ED）与腰骶段脊髓和阴茎神经源性一氧化氮合酶（nNOS）和乙酰胆碱酯酶（AchE）阳性神经元或神经纤维变化的相关性。方法：注射链脲佐菌素建立糖尿病大鼠模型,4周和12周后注射阿扑吗啡（APO）进行大鼠阴茎勃起功能实验,取大鼠阴茎和腰骶段脊髓,用ABC免疫组织化学法和组织化学法分别显示nNOS和AchE阳性神经元或神经纤维。结果：与对照组相比,糖尿病4周时,大鼠阴茎勃起次数无显著性差异;12周时显著性减少;糖尿病4周时,脊髓和阴茎nNOS和AchE阳性神经元或神经纤维均无显著变化,而12周时均显著减少。结论：糖尿病性ED的出现伴随脊髓和阴茎内NO和乙酰胆碱的减少。     

Remodeling of elastic fiber components in scleroderma skin

The skin of patients with scleroderma is characterized by an excess accumulation of collagen in the extracellular matrix of the fibrotic reticular dermis. Elastic fibers are also disrupted in this disease, however, in contrast to collagen, relatively few studies have provided information concerning the changes that occur to elastic fiber components in scleroderma. In the present study, the extracellular matrix in scleroderma skin was examined with a specific focus on the integrity of elastic fibers. Electron microscopic observations confirmed an excess of 10 nm microfibrils present in small bundles independent of amorphous elastin in the fibrotic reticular dermis. In the same area, a population of stellate-shaped fibroblasts was identified in close association with the dermal elastic fibers. In contrast to the uniform black appearance of the elastic fibers seen in the papillary dermis and in areas of the reticular dermis not infiltrated by these cells, the elastic fibers apposed to the cells were mottled in density and often almost electron-lucent. These observations suggest that the elastic fibers in the reticular dermis were being actively degraded. Results from this study provide evidence for disintegration of elastic fibers in the skin of scleroderma patients and suggest the possibility that degradation products from the elastic matrix in the diseased tissues may act as a feedback signal for increased matrix production.     

Noradrenergic innervation of the penis in control and streptozotocin-diabetic rats: evidence of autonomic neuropathy

The noradrenergic sympathetic innervation of the penis of control and 4-month streptozotocin-diabetic rats was examined with the glyoxylic acid histofluorescence method. Noradrenergic varicosities were found in the corpora cavernosa in a dense subtunical plexus and in the perisinusoidal and trabecular regions of the erectile tissue, in the corpus spongiosum in perisinusoidal tissue, around large arteries and veins, and around small tortuous arterioles and small draining veins of the corpora cavernosa and spongiosum. Noradrenergic varicosities were diminished in number and fluorescent intensity in all regions of the penis of diabetic rats compared with controls. The subtunical plexus was absent, perisinusoidal and trabecular varicosities were sparse, and only occasional intermittent, discontinuous, dull fluorescent fibers or plexuses were found around the vessels. Quantitation with high-performance liquid chromatography revealed a significant reduction of norepinephrine in the penis of diabetic rats compared with controls. The present study suggests that long-term streptozotocin diabetes in the rat is accompanied by sympathetic autonomic neuropathy of the penis that seems to parallel changes in the noradrenergic content of penile corpora of men with diabetes and erectile impotence. The streptozotocin-diabetic rat merits further study to explore the relationship between noradrenergic innervation of the penis and erectile tissue.     

Sulcus nervi dorsalis penis: site of origin of Alcock's syndrome in bicycle riders?

This article introduces a hypothesis that the pudendal nerve compression syndrome, also known as the Alcock's syndrome in long-time duration bicycle riders might be caused by an irritation of the dorsal nerve of penis in a groove on the inferior ramus and the anterior surface of pubis, previously described by authors as the sulcus nervi dorsalis penis. Alcock's syndrome in bicycle riders has been characterized as a prolonged glans and penile insensitivity, genital numbness and an erectile dysfunction. Although no anorectal pain or disturbance of the bulbocavernosus reflex has been reported in these patients, we assume it cannot be caused by a compression of the pudendal nerve in pudendal (Alcock's) canal, hence by a compression of the dorsal nerve of penis in the sulcus nervi dorsalis penis. In future, if clinical studies confirm our hypothesis, it might be more sophisticated to evaluate this syndrome apart from the Alcock's syndrome and term it the dorsal nerve compression syndrome rather than the Alcock's syndrome.     

Distribution and function of nitric oxide-containing nerves in canine corpus cavernosum and spongiosum

Specimens of penile erectile tissue from the corpus cavernosum (CC) and corpus spongiosum (CS) of beagle dogs were investigated with reference to morphological and functional aspects of the nitric oxide (NO) system. Using immunohistochemistry, the smooth muscle bundles of the CC were found to contain a rich innervation, as seen by the pan-neuronal marker, protein gene product 9.5. A large number of nerves also stained positively for acetylcholine esterase. There was a moderate to rich supply of nerves containing NO synthase, which was frequently co-localized with vasoactive intestinal polypeptide. CS preparations from the proximal penis (the spongious bulb) had an innervation similar to that of the CC. However, CS preparations from the distal penis had a distinctly lower density of nerves than the proximal part, and spongious tissue from the glans penis was practically devoid of nerves. In isolated preparations of proximal and distal CC and CS, contracted by noradrenaline, electrical field stimulation (EFS) produced frequency-dependent relaxations. The responses were less pronounced in preparations from the distal penis, particularly in the CS. Pre-treatment with the NO-synthesis inhibitor N^G-nitro-L-arginine abolished all relaxations. Carbachol effectively relaxed noradrenaline-contracted strips. The responses were similar in proximal preparations from the CC and CS, and significantly less pronounced in strips from the distal penis. N^G-nitro-L-arginine significantly reduced the relaxant effect of carbachol. Preparations of spongious tissue from the glans penis did not react to high potassium solution, addition of noradrenaline, or EFS. The results demonstrate regional differences within the CS, both in innervation and functional responses.     

Serrated adenocarcinoma of the rectum associated with perianal Paget's disease: a case report

AIMS: To determine the incidence of mucinous metaplasia occurring in the foreskin or glans penis and any associated clinical or histopathological features. METHODS AND RESULTS: Following the recognition of two index cases, 100 other foreskin specimens were retrieved from the histopathology archives at Southampton General Hospital. The haematoxylin and eosin-stained slides were examined by a single observer to detect the presence of mucin-producing cells in the surface epithelium. The absence of mucinous metaplasia in negative cases was confirmed with mucin histochemistry. In total, four cases of mucinous metaplasia were identified, three involving the foreskin and one involving the glans penis. The age range was 51-80 years. Three cases were associated with Zoon's balanitis and the fourth showed mild non-specific balanitis. All four cases showed positive staining with both diastase periodic acid-Schiff and alcian blue. No mucin-producing cells were identified in non-inflamed or minimally inflamed specimens. CONCLUSIONS: Mucinous metaplasia of the penis is an uncommon but under-recognized condition. It is seen in the elderly and appears to be a metaplastic change associated with severe chronic inflammation, and possibly more specifically with Zoon's balanitis. Our study identified a case affecting the glans penis, a site not previously recorded.     

Ultrastructure of collagen fibers and distribution of extracellular matrix in the temporomandibular disk of the human fetus and adult

We quantitatively examined the distribution of these differences in extracellular matrices (collagen types I, III, and fibronectin) and elastic fibers under confocal laser scanning microscopy and electron scanning microscopy in terms of their contribution to the mechanics of the TMJ during development and in adults. Elastic fibers were found in the anterior and posterior bands in adults aged 40 years, and a few elastic fibers in the anterior band of the disk in adults aged 80 to 90 years. The extracellular matrix contents of the TMJ disk are shown in various detected levels in the anterior, intermediate, posterior bands of TMJ disk. During development, collagen fibers are arranged in a complex fashion from 28 weeks' gestation. These ultrastructures of the embryonic TMJ are resembled to that of adults aged the 40s, however the difference in extracellular matrix distribution found in embryonic stages and adults. They might reflect the differences in function between mastication and sucking or the changes in shape and form as results of functional disorders of the TMJ.     

Rapidly and slowly adapting mechanoreceptors in the glans penis of the cat

Sixty-one single mechanoreceptive fibers were surgically isolated from the dorsal nerve of the penis in anesthetized, mature, and sexually intact male cats. Impulse activity was recorded extracellularly. Receptive fields on the glans penis were stimulated with an accurate computer controlled mechanostimulator. Thirty-four units were categorized as rapidly adapting (RA) based on the absence of a response to sustained skin displacement. The remaining were slowly adapting (SA) units responding to sustained displacement. Most of the SA units were located in the distal smooth glans whereas RA units predominated in the proximal spiny glans. Displacement thresholds were significantly lower for RA units. All units encoded indentation velocity although the SA units were better suited to discriminate slowly moving stimuli. In addition, SA units encoded sustained displacement amplitude. Male cats with a denervated glans penis display disoriented mounting behavior disabling intromission. The presence of distally located SA mechanoreceptors suggests they may be the primary penile proprioceptors, mediating, along with the RA mechanoreceptors, successful completion of intromission.     

Degenerative processes of elastic fibers in sun-protected and sun-exposed skin: Immunoelectron microscopic observation of elastin, fibrillin-1, amyloid P component, lysozyme and α1-antitrypsin

Degenerative processes of elastic fibers in sun-protected and sun-exposed skin were analyzed by light and electron microscopic (post-embedding) immunocytochemistry using antisera to elastin, fibrillin-1, amyloid P component, lysozyme and alpha1-antitrypsin. To assess the effect of aging and sun exposure, biopsy specimens of sun-protected skin (back) and severely and moderately sun-exposed skin (face and forearms) were obtained from a young age group (1-27 years), an adult group (31-56 years) and an old aged group (61-100 years). Elastin and fibrillin-1 were the essential components of elastic fibers; elastin being localized in the electron-lucent matrix and fibrillin-1 in the dense microfibrillar strands. Aging and sun exposure provoked degenerative condensed spots, which represented widened dense microfibrillar strands, in the matrix of altered elastic fibers in the reticular dermis. Amyloid P component was first deposited on the peripheral microfibrils, and then in the intermediate density zone of the spots. Lysozyme was observed in both the electron-dense core and in the intermediate density zone of the spots. Deposition of lysozyme correlated with basophilic degeneration of the elastic fibers. In the severely photodamaged facial skin of the aged, which showed solar elastosis in the upper reticular dermis, fibrillin-1 immunoreactivity was lost from the thickened and vacuolated elastic fibers that lacked condensed spots, and amyloid P component, lysozyme and alpha1-antitrypsin were diffusely deposited in the elastin-positive matrix. It seemed that amyloid P component deposition on the elastic fibers was closely associated with aging, while immunoreactive lysozyme was related to sun exposure. Vertically oriented, thin, elastic (oxytalan) fibers in the papillary dermis tended to decrease with age, with frequent deposition of amyloid P component but no lysozyme. In the facial skin of the aged, dermal papillae disappeared, with the formation of degenerative elastic globules beneath the dermal-epidermal junction. The present study demonstrated an intimate relationship between ultrastructural alterations and deposition of exogenous substances on the degenerative elastic fibers in sun-exposed and/or aged skin.     

Localization of vasoactive intestinal polypeptide in penile erectile tissue and in the major pelvic ganglion of the rat

Vasoactive intestinal polypeptide was localized by immunocytochemical techniques in the major pelvic ganglion and penile erectile tissue of the rat. Vasoactive intestinal polypeptide fibers were concentrated in penile crura with the density of innervation decreasing distally. The helicine arteries were very densely innervated while fewer fibers surrounded the deep artery of the penis. Intrinsic smooth muscle of the cavernous bodies received a moderate supply of vasoactive intestinal polypeptide immunoreactive fibers. Dorsal vascular structures, including the deep dorsal vein were innervated by vasoactive intestinal polypeptide fibers. Vasoactive intestinal polypeptide immunoreactive cell bodies were found in the major pelvic ganglion, concentrated on one end of the ganglion. Rectrograde studies with a dye injected into the penile crura indicated that neurons in major pelvic ganglion projected to the penis. Combined dye and immunofluorescent studies showed that all the dye-labeled neurons were immunoreactive for vasoactive intestinal polypeptide.

It is concluded that all vascular beds in the penis of the rat are innervated by vasoactive intestinal polypeptide fibers and that the extent of the innervation is related to the occurrence of smooth muscle. Neurons in the major pelvic ganglion probably are the main source of vasoactive intestinal polypeptide fibers to the penis.     

Ultrastructural distribution of sulfated complex carbohydrates in elastic cartilage of the young rabbit

Sulfated glycosaminoglycans are an integral component of elastic cartilage. We have investigated the ultrastructural distribution of sulfated complex carbohydrates (CC) in the mature cartilage and the perichondrium of young rabbit auricles using the high iron diamine-thiocarbohydrazide-silver proteinate (HID-TCH-SP) and the tannic acid-ferric chloride (TA-Fe) methods. In the mature cartilage, HID-TCH-SP stained intracellular Golgi saccules of the mature face, secretory granules, and the extracellular matrix granules, but staining was not discernible in collagen fibrils and osmiophilic elastic fibers consisting of only amorphous elastin. The HID and TA-Fe staining were similarly observed in matrix granules, whereas the elastic fibers and collagen fibrils lacked the staining. The pericellular matrix granules had a diameter of 34 +/- 5 nm (mean +/- SD; n = 30). Thiéry's periodate-TCH-SP (PA-TCH-SP) method stained vicinal glycol-containing CC in collagen fibrils but failed to stain matrix granules and elastic fibers. In the perichondrium, HID-TCH-SP staining of the organelles was less intense in the flattened chondrocytes when compared with those in large mature chondrocytes. The extracellular HID and HID-TCH-SP staining were observed in the matrix granules. The diameter of pericellular matrix granules (19 +/- 4 nm, mean +/- SD; n = 30) was significantly smaller when compared to those in the mature cartilage (P less than 0.001). The HID-TCH-SP staining was closely associated with collagen fibrils. However, the staining was not seen in collagen fibrils and osmiophilic elastic fibers consisting of elastin and microfibrils. The PA-TCH-SP method stained collagen fibrils and microfibrils but did not stain the amorphous elastin. Thus these studies demonstrate that sulfated CC are packaged in chondrocyte secretory granules and are released into the extracellular matrix to form matrix granules, but are not incorporated into collagen fibrils and elastic fibers.     

On the ultrastructure of the developing elastic cartilage in the rat external ear

Summary Selected ultrastructural features of chondrocytes and the extracellular matrix in the developing elastic cartilage of the external ear were studied in rat fetuses and young animals. The cytoplasmic lipid droplets were first observed in the 19-day fetus. They increase in number and size during the first post-natal week. The elastogenesis proceeds in the sequence: oxytalan fibers (17-day fetus), elaunin fibers (1-day rat), elastic fibers (5-day rat). Intermediary stages between the randomly oriented individual microfibrils and bundles of microfibrils (oxytalan fibers) were also observed.     

保留龟头的肿瘤切除术对T1期阴茎癌患者疗效及性功能的影响

目的 分析T1期阴茎癌行保留龟头的肿瘤切除术加腹腔镜腹股沟淋巴结清扫术对患者疗效及性功能的影响。方法 回顾性分析我院及中山大学附属肿瘤医院自2014年1月~2018年6月收治的8例行保留龟头的阴茎肿瘤切除术（保留龟头组）与10例行阴茎部分切除术（部分切除组）的T1期阴茎癌患者临床资料,术后随访了解其局部及远处复发情况,采用国际勃起功能指数问卷（ⅡEF-5）、性满意指数（ISS）问卷分别在术后6个月评估患者的勃起功能和性满意度,对数据进行统计学分析。结果随访6月~5年,1例保留龟头患者出现原发肿瘤复发,其余患者均未见肿瘤复发及转移。术后6个月,保留龟头组的患者ⅡEF-5评分为（24.48±1.89）分,与术前的（24.53±2.41）分比较,差异无统计学意义（P＞0.05）,但高于阴茎部分切除组患者的（21.59±3.26）分,差异有统计学意义（P＜0.05）;保留龟头组的ISS评分为（36.38±16.11）分,与术前的（38.27±14.38）分比较,差异无统计学意义（P＞0.05）,但低于阴茎部分切除组患者的（57.63±15.63）分,差异有统计学意义（P＜0.05）。结论 对于T1期的阴茎癌患者,保留龟头的手术加上腹腔镜腹股沟淋巴结清扫术安全有效,并可使患者维持更好的性功能和满意度。     

勃起状态下阴茎感觉阈值测量在原发性早泄诊断中的研究

目的比较阴茎头振动感觉阈在勃起前后的变化,并进一步观察勃起状态下正常人和早泄患者的阴茎头振动感觉阈的差异,从而评估勃起状态下阴茎感觉阈值测量在原发性早泄诊断中的价值。方法使用生物振动测试仪,对62例正常志愿者（对照组）及97例早泄患者（早泄组）阴茎勃起前后的振动感觉阈进行测定,测定部位为示指、阴茎头、阴茎干、阴囊4部位的皮肤。结果正常人和早泄患者在阴茎勃起状态下,其阴茎头、阴茎干的振动感阈值都显著低于未勃起状态下的振动感阈值（P〈0.01）。在勃起状态下,早泄患者的阴茎头、阴茎干的振动感阈值都显著低于正常人的振动感阈值（P〈0.01）。结论无论是正常人还是早泄患者,阴茎头、阴茎干的振动感阈值在勃起前后有显著的统计学差异。在勃起状态下进行阴茎感觉阈值测量对原发性早泄的诊断具有一定的价值。     

Skeletal muscle adaptations in elastic resistance-trained young men and women

Skeletal muscle adaptations (fiber-type composition, cross-sectional area, myosin heavy chain (MHC) content, and capillarity) were assessed in the vastus lateralis muscle of young men and women after 8 weeks of training with the Sportcord, an elastic resistance device. Ten men [mean (SD) age 20 (1.1) years] and 13 women [20 (1.2) years] performed two sets each to failure of single leg squats and leg extensions at approximately 50 repetitions x min(-1). Biopsy samples were taken from the right vastus lateralis muscle before and after training. Six fiber types (I, IC, IIC, IIA, IIAB, and IIB) were classified using myofibrillar ATPase histochemistry. Training with the Sportcord caused a small, but significant, increase in one-repetition maximum using free weights and a large increase in repetitions to failure. In addition, elastic resistance training caused an increase in the percentage of fibers classified as type IIAB for both men and women, and a decrease in the percentage of type IIB fibers in the men. MHC analysis supported these findings (a significant increase in the percentage of MHCIIa for the men). The cross-sectional areas ofboth the type I and IIAB + IIB fibers increased after training for the men, whereas no area changes were found for the women. The capillary:fiber ratio and capillary contacts per fiber type increased significantly for the men, and similar trends were noted for the women. Capillary density did not change in either the men or the women. These data suggest minor changes in fiber type composition (IIB-->IIAB), fiber size, and capillarization following short-term training with elastic resistance. Although muscular changes did occur using the Sportcord, the extent of these changes was less than those reported previously for short-term resistance-training programs using free weights.     

Macro/microscopic distribution of the dorsal nerve of penis in human glans penis

This study aimed to elucidate the macroscopic and microscopic distributions of the dorsal nerve of penis (DNP) that provides the greatest sensitivity over the glans penis. The glandes of 23 penises of formalin-embalmed cadavers were investigated to confirm the macroscopic and microscopic distributions of the DNP within the glans penis by whole-mount Sihler's staining and histological sectioning. Superficial regions of the mid-glans were reconstructed in three dimensions to define the microstructure of terminal branches of the DNP that project towards the skin surface. A mean of 6.7 bundles of the DNP consisting of several nerve fibres converged linearly towards the distal end of the penis, rather than diverging laterally as they travelled. Lateral branches of the DNP extended linearly to the distal end with ramifications, while dorsomedial branches of the DNP gave off nerve fibres to the dorsum of the mid-glans and the corona. The intrastromal ramifications of the DNP were more developed in the distal half of the glans penis than the proximal glans containing the corpus cavernosum. These ramifications gave rise to radial nerve fibres that project towards the skin surface to form a plexiform network of terminal branches in the dermis. Linear projections of the main branches of the DNP throughout the glans and fine networks of terminal branches in the dermis were distinctly visualized in the human penis.     

Male sexual function after autologous blood or marrow transplantation.

Although endocrine dysfunction has been reported in survivors of allogeneic bone marrow transplantation (alloBMT), data for autologous BMT (autoBMT) recipients are lacking. Because information on male potency in particular is scanty, we prospectively assessed male sexual function after autoBMT. We identified 16 men who were < or =50 years of age at the time of evaluation and disease free for at least 6 months after autoBMT. Nine had Hodgkin's disease, 4 had acute myelogenous leukemia, and 3 had non-Hodgkin's lymphoma. Blood samples were assayed for luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Patients were surveyed with a modified version of the Pyschosocial Adjustment to Illness Scale regarding erectile dysfunction and loss of interest in sexual activities. Seventy five percent of the men reported normal interest in sexual activities and 87.5% reported normal erectile function; however, 4 of 16 reported a moderate loss of interest in sexual activities, and another 2 of 16 reported frequent loss of erectile function. All 4 men with decreased libido and both men with impaired erectile function had Hodgkin's disease. Fourteen (88%) of 16 patients had an elevated FSH level, 7 (47%) of 15 had elevated LH, and 6 (38%) of 16 had decreased testosterone levels. Decreased testosterone levels correlated with a moderate or total loss of libido (P = .008) and a diagnosis of Hodgkin's disease (P = .01). Thus, after transplantation, most men have abnormal levels of gonadotrophins. Decreased levels of testosterone and symptoms of sexual dysfunction correlated with a diagnosis of Hodgkin's disease and may be related to the induction and salvage therapy received prior to autoBMT.