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Patients with genital HPV lesion, as well as partners, usually present higher psychological stress, than the actual medical consequences of the lesion. Follow-up of these patients should be based on education and counseling. HPV molecular tests are not recommended as a follow-up test, or for screening partners. Development and implementation of protocols, by the centers or units, that follow these patients, are recommended.
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Andrologia , Condiloma Acuminado , Infecções por Papillomavirus , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/patologia , Consenso , Seguimentos , Humanos , Masculino , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Portugal , ReproduçãoRESUMO
INTRODUCTION: The G-spot, a putative erogenous area in the anterior vaginal wall, is a widely accepted concept in the mainstream media, but controversial in medical literature. AIM: Review of the scientific data concerning the existence, location, and size of the G-spot. METHODS: Search on Pubmed, Pubmed Central, Cochrane, clinicaltrials.gov and Google Scholar from inception to November 2020 of studies on G-spot's existence, location and nature. Surveys, clinical, physiological, imaging, histological and anatomic studies were included. MAIN OUTCOME MEASURE: Existence, location, and nature of the G-spot. RESULTS: In total, 31 eligible studies were identified: 6 surveys, 5 clinical, 1 neurophysiological, 9 imaging, 8 histological/anatomical, and 2 combined clinical and histological. Most women (62.9%) reported having a G-spot and it was identified in most clinical studies (55.4% of women); in 2 studies it was not identified in any women. Imaging studies had contradictory results in terms of its existence and nature. Some showed a descending of the anterior vaginal wall, that led to the concept of clitourethrovaginal complex. In anatomic studies, one author could systematically identify the G-spot, while another group did not find it. Studies on innervation of the vaginal walls did not systematically identify an area with richer innervation. CONCLUSION: The different studies did systematically agree on the existence of the G-spot. Among the studies in which it was considered to exist, there was no agreement on its location, size, or nature. The existence of this structure remains unproved. Vieira-Baptista P, Lima-Silva J, Preti M, et al. G-spot: Fact or Fiction?: A Systematic Review. Sex Med 2021;9:100435.
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The prolonged lockdown of health facilities providing non-urgent gamete cryopreservation-as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS-CoV-2 pandemic will be detrimental for subgroups of male infertility patients. We believe the existing recommendations should be promptly modified and propose that the same permissive approach for sperm banking granted for men with cancer is expanded to other groups of vulnerable patients. These groups include infertility patients (eg, azoospermic and cryptozoospermic) undergoing medical or surgical treatment to improve sperm quantity and quality, as well as males of reproductive age affected by inflammatory and systemic auto-immune diseases who are about to start treatment with gonadotoxic drugs or who are under remission. In both scenarios, the "fertility window" may be transitory; postponing diagnostic semen analysis and sperm banking in these men could compromise the prospects of biological parenthood. Moreover, we provide recommendations on how to continue the provision of andrological services in a considered manner and a safe environment. Our opinion is timely and relevant given the fact that fertility services are currently rated as of low priority in most countries.
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Andrologia/organização & administração , COVID-19 , Acessibilidade aos Serviços de Saúde/organização & administração , Necessidades e Demandas de Serviços de Saúde/organização & administração , Infertilidade Masculina/terapia , Avaliação das Necessidades/organização & administração , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/fisiopatologia , MasculinoRESUMO
The treatment of condyloma is generally a challenge in clinical practice. Although the spontaneous resolution rate is high, a significant proportion of patients seek treatment, not because of symptomatology, but mainly for aesthetic issues and concerns related to the transmission or worsening of existing lesions. The available treatments should be applied only for clinically evident macroscopic lesions. Ideally, available therapies should have rapid action onset and clearance, resolve symptoms, reduce recurrence rate and viral load, be effective in treating small lesions, and be well tolerated. However, none of the currently available treatments is clearly more effective than the others and there is no ideal treatment for all patients or for all condyloma. Therefore, the therapeutic decision should be based on the clinician's experience, available resources, lesion morphology, size, number and location, primary or recurrent lesions, disease severity, patient preference and expectations, patient's immune competence, convenience, tolerance, cost of treatment and results of previous therapies. The available treatments are divided into three groups: applied by the patient himself (imiquimod 3.75 or 5%, podophyllotoxin .5%, synecatekines 10% or 15%), applied by the health care provider (bi- and tricloacetic acids 80%-90%, intralesional interferon alpha, cryotherapy, surgical removal, electrofulguration, laser ablation) and experimental or alternative therapies (topical cidofovir, intralesional bleomycin, photodynamic therapy). Treatment methodologies can be further divided into their action - ablative or destructive treatment (cryotherapy, electrofulguration, laser ablation, surgical excision), cytotoxic or proapoptotic treatments (podophyllotoxin .5%, 5-fluoruracil, bleomycin) and immunomodulatory treatments (imiquimod 3.75% or 5%, synecatekines 10% or 15%, intralesional interferon alpha). The overall success rate of the various treatments available ranges from 23% to 94%. Only treatments that include cryotherapy or surgical excision are suitable in condyloma with any anatomical location and that have the highest success rate in monotherapy. Recurrences are common regardless of the treatment received. In contrast, immunomodulatory therapies despite having lower initial clearance rates appear to have higher probabilities of cure in the medium term, with low recurrence rates. Some treatments may be combined with each other and the effectiveness of combined therapies appears to be superior to monotherapy (proactive sequential treatment). The consensuses for the treatment of HPV also consider special situations: immunocompromised patients, meatus and intraurethral lesions and treatment of the partner.
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Andrologia/normas , Antivirais/uso terapêutico , Condiloma Acuminado/terapia , Crioterapia , Fatores Imunológicos/uso terapêutico , Infecções por Papillomavirus/terapia , Verrugas/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Aminoquinolinas/uso terapêutico , Antimetabólitos/uso terapêutico , Condiloma Acuminado/virologia , Consenso , Tomada de Decisões , Humanos , Interferons/uso terapêutico , Ceratolíticos/uso terapêutico , Infecções por Papillomavirus/virologia , Podofilina/uso terapêutico , Podofilotoxina/uso terapêutico , Portugal , Guias de Prática Clínica como AssuntoRESUMO
The prevention of HPV-related diseases is an important healthcare issue due to its increasing incidence. Primary prevention is most important in males as it avoids initial infection and includes the use of condom, circumcision and vaccination. Primary prevention with vaccination is effective in decreasing HPV-related lesions in women up to 45 years old and the existing data for men comes from the experience from vaccinating women. Although it is the only vaccine that prevents cancer, the worldwide rates of vaccination in males is very low due to lack of information related to efficacy and side effects, lack of recommendation from the treating doctor, price and concern about encouragement of sexual promiscuity.
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Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Prevenção Primária , Andrologia , Condiloma Acuminado , Humanos , Masculino , Portugal , Sociedades Médicas , VerrugasRESUMO
HPV infection affects about 50% of sexually active individuals at least once in a lifetime. Diagnosis is made on careful inspection of the genital area and can be divided into benign lesions (genital warts or condyloma acuminatum) and pre-malignant lesions (intraepithelial neoplasia) that can lead to cancer (invasive neoplasia). Diagnostic recommendations are reviewed in Male, Female, Couple and in the immunocompromised host. Recent histological concepts are also discussed.
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Andrologia/normas , Condiloma Acuminado/diagnóstico , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Consenso , Feminino , Humanos , Masculino , Portugal , Reprodução , Sociedades MédicasRESUMO
Erectile dysfunction (ED) is a complication of diabetes, condition responsible for causing endothelial dysfunction (EDys) and hampering repair mechanisms. However, scarce information is available linking vasculogenesis mediated by Endothelial Progenitor Cells (EPCs) and diabetes-associated ED. Furthermore, it remains to be elucidated if glycemic control plays a role on EPCs functions, EPCs modulators, and penile vascular health. We evaluated the effects of diabetes and insulin therapy on bone marrow (BM) and circulating EPCs, testosterone, and systemic/penile Stromal Derived Factor-1 alpha (SDF-1α) expression. Male Wistar rats were divided into groups: age-matched controls, 8-weeks streptozotocin-induced type 1 diabetics, and insulin-treated 8-weeks diabetics. EPCs were identified by flow cytometry for CD34/CD133/VEGFR2/CXCR4 antigens. Systemic SDF-1α and testosterone levels were evaluated by ELISA. Penile SDF-1α protein expression was assessed, in experimental and human diabetic cavernosal samples, by immunohistochemical techniques. Diabetic animals presented a reduction of BM-derived EPCs and an increase in putative circulating endothelial cells (CECs) sloughed from vessels wall. These alterations were rescued by insulin therapy. In addition, glycemic control promoted an increase in systemic testosterone and SDF-1α levels, which were significantly decreased in animals with diabetes. SDF-1α protein expression was reduced in experimental and human cavernosal diabetic samples, an effect prevented by insulin in treated animals. Insulin administration rescued the effects of diabetes on BM function, CECs levels, testosterone, and plasmatic/penile SDF-1α protein expression. This emphasizes the importance of glycemic control in the prevention of diabetes-induced systemic and penile EDys, by the amelioration of endothelial damage, and increase in protective pathways. J. Cell. Biochem. 118: 82-91, 2017. © 2016 Wiley Periodicals, Inc.
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Quimiocina CXCL12/sangue , Complicações do Diabetes/sangue , Diabetes Mellitus Experimental/sangue , Impotência Vasculogênica/sangue , Testosterona/sangue , Animais , Complicações do Diabetes/terapia , Diabetes Mellitus Experimental/terapia , Impotência Vasculogênica/prevenção & controle , Masculino , Ratos , Ratos WistarRESUMO
BACKGROUND: Erectile dysfunction (ED) is a prevalent complication of diabetes, and oxidative stress is an important feature of diabetic ED. Oxidative stress-induced damage plays a pivotal role in the development of tissue alterations. However, the deleterious effects of oxidative stress in the corpus cavernosum with the progression of diabetes remain unclear. The aim of this study was to evaluate systemic and penile oxidative stress status in the early and late stages of diabetes. METHODS: Male Wistar streptozotocin-diabetic rats (and age-matched controls) were examined 2 (early) and 8 weeks (late) after the induction of diabetes. Systemic oxidative stress was evaluated by urinary H2 O2 and the ratio of circulating reduced/oxidized glutathione (GSH/GSSG). Penile oxidative status was assessed by H2 O2 production and 3-nitrotyrosine (3-NT) formation. Cavernosal endothelial nitric oxide synthase (eNOS) was analyzed by quantitative immunohistochemistry. Dual immunofluorescence was also performed for 3-NT and α-smooth muscle actin (α-SMA) and eNOS-α-SMA. RESULTS: There was a significant increase in urinary H2 O2 levels in both diabetic groups. The plasma GSH/GSSG ratio was significantly augmented in late diabetes. In cavernosal tissue, H2 O2 production was significantly increased in late diabetes. Reactivity for 3-NT was located predominantly in cavernosal smooth muscle (SM) and was significantly reduced in late diabetes. Quantitative immunohistochemistry revealed a significant decrease in eNOS levels in cavernosal SM and endothelium in late diabetes. CONCLUSIONS: The findings indicate that the noxious effects of oxidative stress are more prominent in late diabetes. Increased penile protein oxidative modifications and decreased eNOS expression may be responsible for structural and/or functional deregulation, contributing to the progression of diabetes-associated ED.
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Diabetes Mellitus Experimental/complicações , Endotélio Vascular/patologia , Disfunção Erétil/patologia , Miócitos de Músculo Liso/patologia , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Pênis/patologia , Animais , Células Cultivadas , Diabetes Mellitus Experimental/patologia , Progressão da Doença , Endotélio Vascular/metabolismo , Disfunção Erétil/etiologia , Imunofluorescência , Immunoblotting , Masculino , Miócitos de Músculo Liso/metabolismo , Pênis/metabolismo , Ratos , Ratos Wistar , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
INTRODUCTION: Peyronie's disease is an acquired penile deformity with a variety of presentations, caused by the formation of fibrous plaques within the tunica albuginea, leading to bio-mechanical and vascular abnormalities. The objective is to investigate the 18 years outcome of patients with Peyronie's disease treated with penile corporoplasty (Yachia technique) in our department. MATERIALS AND METHODS: One hundred and seventeen patients underwent surgical treatment for PD between 1991 and 2009 and were retrospectively evaluated. We used the Levine and Lenting's algorithm for surgical treatment. Data was obtained from medical records, clinical evaluation, and telephone interview. Post-operative follow-up was at 6 weeks and 12 months. The mean time of follow-up was 14 months (12-19 months). MAIN OUTCOME MEASURES: Patient demographic, co-morbidities, erectile function, penile curvature, and surgical intervention were documented. The main outcome measures of this study are postoperative complications, surgical purpose, and patients and partner's satisfaction rates. RESULTS: Surgical aim was obtained in 106 patients (success rate of 94.6%). Complications occurred in 4.5% of patients, but most of these were mild. At 6 weeks, complete straightening of the penis was achieved in 57 patients (50.9%), and partial straightening which allow sexual intercourse in 49 patients (43.7%). Nine patients report gland hypoesthesia and almost all report subjective perception of penis shortening (0.5 cm to 5 cm). Twenty-two patients developed recurrent deformity at 12 months follow-up, with compromise of sexual intercourse in 7 patients. Patients' responses to our questionnaire showed that overall 88.4% of the patients and partners were satisfied with the surgical results. CONCLUSION: According to the results of this long-term, retrospective study, surgical correction, using the Yachia technique, is an excellent option for patients with functional impairment from their Peyronie's disease, especially.
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INTRODUCTION: Phosphodiesterase type 5 (PDE-5) inhibitor treatment for erectile dysfunction (ED) is frequently discontinued; adherence may vary depending on the initial regimen. AIM: To evaluate the effects of initiating treatment with tadalafil once a day (OaD), tadalafil on demand (pro re nata [PRN]), or sildenafil PRN on treatment adherence. METHODS: In this multicenter, open-label study, men (≥ 18 years) with ED, naïve to PDE-5 inhibitors, were randomized (1:1:1) to tadalafil 5 mg OaD, tadalafil 10 mg PRN, or sildenafil 50 mg PRN. An 8-week randomized treatment (RT) period (dose adjustment possible) was succeeded by 16 weeks of pragmatic treatment (switches between PDE-5 inhibitors allowed). MAIN OUTCOME MEASURES: Treatment adherence was measured as time to discontinuation of RT (any cause), estimated by Kaplan-Meier product-limit method. Treatment-group differences were estimated as hazard ratio (HR; Cox proportional hazards). RESULTS: Seven hundred seventy patients (mean age 53 years) were randomized to tadalafil OaD (N = 257), tadalafil PRN (N = 252), and sildenafil PRN (N = 261). Kaplan-Meier estimates for patients discontinuing RT were 52.2, 42.0, and 66.7%, respectively. Median time to discontinuation of RT was significantly longer for tadalafil OaD and PRN (130 and >168 days) compared with sildenafil (67 days) (HR [97.5% confidence interval]: 0.66 [0.51, 0.85] and 0.49 [0.37, 0.65]; P < 0.001). Reasons for discontinuation with significant differences between groups (P < 0.05) included "lack of efficacy (duration of erection)" (sildenafil 9.2% vs. tadalafil OaD 4.3%, PRN 2.8%), "time constraints due to short window of action" (sildenafil 4.2% vs. tadalafil OaD 0%, PRN 0.4%), and "feel medication controls my sexual life" (sildenafil 2.7% vs. tadalafil OaD 0%). No between-group differences were found in International Index of Erectile Function-Erectile Function domain change from baseline to end of RT (least squares mean: 9.4-10.0, P = 0.359) or discontinuations due to adverse events (1.2-1.6%). The most common adverse event (≥ 4%) was headache. CONCLUSIONS: ED patients assigned to tadalafil OaD or PRN adhered significantly longer to initial treatment than patients assigned to sildenafil PRN. Improvement of erectile function and safety profiles were similar in all three treatment groups.
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Carbolinas/administração & dosagem , Disfunção Erétil/tratamento farmacológico , Adesão à Medicação , Ereção Peniana/efeitos dos fármacos , Inibidores da Fosfodiesterase 5/administração & dosagem , Piperazinas/administração & dosagem , Sulfonas/administração & dosagem , Adulto , Idoso , Carbolinas/efeitos adversos , Esquema de Medicação , Substituição de Medicamentos , Europa (Continente) , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Inibidores da Fosfodiesterase 5/efeitos adversos , Piperazinas/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Purinas/administração & dosagem , Purinas/efeitos adversos , Recuperação de Função Fisiológica , Citrato de Sildenafila , Sulfonas/efeitos adversos , Tadalafila , Resultado do TratamentoRESUMO
Diabetes-induced metabolic derangements promote endothelial malfunction, contributing to erectile dysfunction (ED). However, it remains unclear which angiogenic molecular mechanisms are deregulated in diabetic corpus cavernosum (CC). We investigated early and late alterations in cavernosal angiogenic gene expression associated to diabetes. Angiogenic changes were assessed in penile tissue of streptozotocin-induced Wistar rats, in an early (2-week) and established stage (8-week) of diabetes. Differentially expressed genes were identified by microarrays and expression data validated by quantitative real-time PCR (qrt-PCR). At protein level, quantitative immunohistochemistry confirmed the arrays data and dual immunofluorescence for selected alterations and α-smooth muscle actin (α-SMA) identified the cellular location of target proteins. The selected differentially expressed genes were also evaluated in human non-diabetic and diabetic CC by quantitative immunolabeling. At 2-week diabetes there was no differential gene expression between non-diabetic and diabetic CC. At 8-week, 10 genes were found down-regulated in diabetics. The results were validated by qrt-PCR for the insulin-like growth factor-1 (Igf1) and the natriuretic peptide receptor-1 (Npr1) genes. Dual immunofluorescence for IGF-1/ α-SMA showed predominant localization of IGF-1 in SM. NPR-1 expression was diffuse and mostly present in trabecular fibroblasts and SM. Quantitative immunostaining confirmed the decreased expression of both proteins in diabetic tissues. Concordantly, we detected a significant reduction in IGF-1 and NPR-1 protein expressions in human diabetic samples. Microarray analysis identified 10 angiogenic-related molecules deregulated in CC of established diabetes. Among them, IGF-1 and NPR-1 were significantly down-regulated and might result in preventive/therapeutic targets for ED management.
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Actinas/genética , Actinas/metabolismo , Corpo Caloso/patologia , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus/metabolismo , Disfunção Erétil/fisiopatologia , Fator de Crescimento Insulin-Like I/metabolismo , Receptores do Fator Natriurético Atrial/metabolismo , Animais , Corpo Caloso/metabolismo , Complicações do Diabetes/genética , Complicações do Diabetes/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus Experimental/genética , Endotélio/metabolismo , Endotélio/patologia , Disfunção Erétil/genética , Disfunção Erétil/metabolismo , Expressão Gênica , Humanos , Fator de Crescimento Insulin-Like I/genética , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Ratos , Ratos Wistar , Receptores do Fator Natriurético Atrial/genéticaRESUMO
Erectile dysfunction (ED) is a common problem in aged men; however, the molecular events involved in aging ED remain unclear. To better characterize the effects of aging in the penis, we evaluated cavernosal tissue remodeling capability and the downstream activation of the intracellular signaling mediator mitogen-activated protein p42/44 kinase (p42/44 MAPK). We used male Wistar rats, which were divided in groups of 2, 6, 12, 18, and 24 months old. Penile tissues were harvested and processed for protein isolation and immunohistochemical analysis. Cavernosal viability was assessed by TUNEL assay, and proliferation was analyzed by immunohistochemical detection of proliferating cell nuclear antigen (PCNA). Immunolocalization of the activated form of p42/44 MAPK was evaluated by immunofluorescence, and changes in its phosphorylation status were quantified by western blotting. p42/44 phosphorylation profile was also assessed in situ in human young and elderly cavernosal samples. With the advancement of age, experimental cavernosal tissue remodeling was affected by an age-dependent unbalance between the rate of apoptosis and proliferation, in all erectile components. Moreover, this turnover alteration was accompanied by significant modifications in the activation profile of the downstream effector p42/44 MAPK. In the youngest corporeal samples, p42/44 was mostly activated at perivascular sites, potentially mediating cell survival/proliferation. However, in elderly experimental erectile tissue, p42/44 phosphorylation shifted to trabecular fibroblasts, indicating a potential role in extracellular matrix (ECM) production. More importantly, the same differential pattern of p42/44 activation was observed in human young and aged cavernosal fragments, suggesting a distinct function of this protein with aging. We provided evidence for the first time that with the advancement of age, there is a differential activation of p42/44 MAPK in cavernosal tissue, which may promote ECM expansion and fibrosis, therefore compromising erectile function in the elderly.
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Envelhecimento/metabolismo , Disfunção Erétil/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Pênis/metabolismo , Actinas/análise , Envelhecimento/patologia , Animais , Apoptose , Western Blotting , Contagem de Células , Proliferação de Células , Disfunção Erétil/patologia , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Pênis/patologia , Fosforilação , Antígeno Nuclear de Célula em Proliferação/análise , Ratos , Ratos WistarRESUMO
INTRODUCTION: Erectile dysfunction (ED) is a common disease that is mostly vasculogenic in nature. ED correlates with cardiovascular risk factors, with endothelial dysfunction being the common link. Hypertension (HTA) and insulin resistance are the most important determinants of arteriogenic ED, and are also components of the metabolic syndrome (MetS), which supports a strong association between MetS and ED. However, MetS and, specifically, obesity interference on penile hemodynamics is still controversial. AIM: To evaluate the impact of independent MetS criteria and obesity on penile duplex Doppler ultrasound (PDDU) parameters in men with ED. METHODS: Consecutive patients (n = 212) referred to a unit of PDDU were evaluated for cardiovascular risk factors and MetS (ATP III criteria). Body mass index and body fat percentage (BF%) were calculated. Each patient underwent a PDDU by the same investigator. Data are expressed as mean ± standard deviation, and statistical significance was considered at P level < 0.05. Statistical analysis of clinical, laboratory, and PDDU parameters was performed with SPSS® software. MAIN OUTCOME MEASURES: To evaluate the individual power of MetS clusters and obesity as predictive factors for penile hemodynamic changes namely mean peak systolic velocity (mPSV). RESULTS: MetS was present in 24.8% of men, and 80.8% of them presented penile hemodynamics alterations, with mPSV significantly lower comparatively to no MetS patients (29.0 vs. 35.4 cm/s, P = 0.004). Multivariate analysis demonstrated that, considering all MetS parameters, only HTA was significantly associated with diminished mPSV. However, after further adjustment for all cardiovascular risk factors, BF% remained the sole independent clinical factor for penile hemodynamics impairment. CONCLUSIONS: There is a strong association between MetS and ED, but within MetS criteria, only HTA was independently associated with the deterioration of penile hemodynamics parameters. Although the classical methods of evaluating obesity in MetS were not individually associated with PDDU impairment, BF% represented by itself an excellent predictor of vascular ED.
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Impotência Vasculogênica/etiologia , Síndrome Metabólica/complicações , Fatores Etários , Índice de Massa Corporal , Hemodinâmica , Humanos , Impotência Vasculogênica/diagnóstico por imagem , Impotência Vasculogênica/fisiopatologia , Modelos Lineares , Modelos Logísticos , Masculino , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Análise Multivariada , Pênis/irrigação sanguínea , Pênis/diagnóstico por imagem , Pênis/fisiopatologia , Fatores de Risco , Fumar/efeitos adversos , Estatísticas não Paramétricas , Ultrassonografia Doppler DuplaRESUMO
Experimental and clinical studies have reported that testosterone has a critical role in the maintenance of homeostatic and morphologic corpus cavernosum components, essential for normal erectile physiology. Although the exact mechanisms mediated by testosterone in erectile function are still under investigation, recent research has suggested an important role in the regulation of endothelial cell (EC) biological functions. Besides stimulating the production of EC mediators, testosterone is also thought to promote the vasculogenic reendothelialization process, mediated by bone marrow-derived endothelial progenitor cells. Additionally, testosterone seems to modulate other erectile tissue components, including trabecular smooth muscle cells, nerve fibers, and tunica albuginea structure, all essential for the erectile process. This paper summarizes current data regarding testosterone-induced cellular and molecular mechanisms that regulate penile tissue components, focusing particularly on the role of testosterone in endothelial health and erectile function.
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INTRODUCTION AND OBJECTIVES: Erectile dysfunction (ED) is a highly prevalent and age-related disease, caused by endothelial dysfunction and impaired cavernous angiogenesis. However, cellular and molecular changes involved in erectile pathophysiology in aging male remain to be elucidated. AIM: To characterize the vascular organization, concomitantly with analysis of the expression of vascular endothelial growth factor (VEGF), Angiopoietin 1 (Ang1) and Angiopoietin 2 (Ang2) in young and aged human corpus cavernosum. METHODS: Human penile fragments were removed from patients submitted to penile deviation surgery (11 cases; 58-70 years) and from potential organ donors (four cases; 18-28 years) without ED or risk factors for ED. Smooth muscle and connective tissue were assessed by Masson's trichrome staining and computer-assisted histomorphometry. Dual immunostaining for specific markers of endothelium (von Willebrand factor) and smooth muscle cell (alpha-actin), VEGF, Ang1 and Ang2 was assayed by fluorescence microscopy. Semi-quantification of expression of angiogenic factors was performed by Western blotting. MAIN OUTCOME MEASURES: Expression of VEGF and Angiopoietins in human corpus cavernosum, using a combination of histologic stainings, and molecular biology tools in order to achieve a better understanding of cavernosal tissue remodeling with aging. RESULTS: Aged human corpus cavernosum presented wider sinusoidal spaces, loss of muscle cell bundles, and increased connective tissue content. Ang1 was scarcely expressed in small clusters in smooth muscle cell cytoplasm with identical localization in both studied groups. VEGF expression was abundant in smooth muscle cell and its expression markedly decreased in aged tissue, contrasting with the expression of angiopoietins that increased in the aged corpus cavernosum. CONCLUSIONS: Immunoflourescent studies of cellular markers and growth factors help clarifying vascular organization and angiogenesis mechanisms in erectile tissue. Our findings demonstrate that the organization pattern of vascular endothelium and smooth muscle components of cavernosal tissue modifies during aging. Ang1 and Ang2 upregulation in human-aged penile tissue suggest a VEGF-independent vascular remodeling mechanism.
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Envelhecimento/fisiologia , Angiopoietina-1/análise , Angiopoietina-2/análise , Pênis/patologia , Fator A de Crescimento do Endotélio Vascular/análise , Actinas/análise , Adolescente , Adulto , Idoso , Western Blotting , Endotélio Vascular/patologia , Humanos , Impotência Vasculogênica/patologia , Masculino , Microscopia Confocal , Microscopia de Fluorescência , Pessoa de Meia-Idade , Músculo Liso/patologia , Adulto Jovem , Fator de von Willebrand/análiseRESUMO
OBJECTIVE: To evaluate the expression of the angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietins (Ang) 1 and 2, in normal human penile erectile tissue. MATERIALS AND METHODS: Penile fragments were removed from four young healthy organ donors (aged 17-28 years), and processed for immunohistochemical studies for VEGF, Ang1 and Ang2, and their specific receptors (VEGFR1 and 2, and Tie2, respectively). Molecular analysis was used to confirm the expression of VEGF and Angs in erectile tissue. RESULTS: VEGF and VEGFR1 expression was restricted to smooth muscle cells (SMCs). VEGFR2 was detected mainly in the endothelium lining and to a lesser extent in the SMC. Ang1 had a scattered distribution mostly in the perivascular SM layer, showing co-localization with VEGF. Tie2 was faintly detected in the endothelial cells. Ang2 was not detected by immunohistochemical studies, but the use of the same antibody in molecular analysis confirmed Ang2 expression in human corpus cavernosum. CONCLUSIONS: We show for the first time the co-localization of VEGF and Ang1 in the SMC, suggesting an interaction for vessel stabilization. Ang2 seems to be available for neoangiogenesis, if challenged. Studies of endothelial markers, growth factors and specific receptors are useful for understanding vascular organization and angiogenesis in normal human erectile tissue. This knowledge will be fundamental for developing newer therapeutic approaches to prevent or even cure erectile dysfunction.
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Angiopoietina-1/metabolismo , Angiopoietina-2/metabolismo , Pênis/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Humanos , Immunoblotting , Impotência Vasculogênica/etiologia , Impotência Vasculogênica/prevenção & controle , Masculino , Neovascularização Fisiológica/fisiologia , Pênis/irrigação sanguínea , Adulto JovemRESUMO
INTRODUCTION: Erectile dysfunction (ED) is a common complication of diabetes. Endothelial cell (EC) dysfunction is one of the main mechanisms of diabetic ED. However, loss of EC integrity has never been assessed in human diabetic corpus cavernosum. AIM: To identify and quantify apoptotic cells in human diabetic and normal erectile tissue and to compare these results with each patient's clinical data and erection status. METHODS: Eighteen cavernosal samples were collected, 13 from diabetics with ED and 5 from nondiabetic individuals. Cavernosal structure and cell proliferation status were evaluated by immunohistochemistry. Tissue integrity was assessed by terminal transferase dUTP nick end labeling assay, an index of apoptotic cell density (ACD) established and compared with each patient age, type of diabetes, arterial risk factors number, arterial/veno-occlusive disease, response to intracavernous vasoactive injections (ICI), and penile nitric oxide release test (PNORT). MAIN OUTCOME MEASURES: Establish an index of ACD and correlate those results with patient clinical data. RESULTS: Nondiabetic samples presented few scattered cells in apoptosis and an ACD of 7.15 +/- 0.44 (mean apoptotic cells/tissue area mm(2) +/- standard error). The diabetic group showed an increased ACD of 23.82 +/- 1.53, and apoptotic cells were located specifically at vascular sites. Rehabilitation of these endothelial lesions seemed impaired, as no evidence of EC proliferation was observed. Furthermore, higher ACD in diabetic individuals correlated to poor response to PNORT and to ICI. CONCLUSIONS: We provided evidence for the first time that loss of cavernosal EC integrity is a crucial event involved in diabetic ED. Furthermore, we were able to establish a threshold between ACD values and cavernosal tissue functionality, as assessed by PNORT and vasoactive ICI.
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Apoptose/fisiologia , Diabetes Mellitus Tipo 2/epidemiologia , Endotélio Vascular/patologia , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/epidemiologia , Impotência Vasculogênica/tratamento farmacológico , Impotência Vasculogênica/epidemiologia , Vasodilatadores/uso terapêutico , Contagem de Células , Disfunção Erétil/diagnóstico , Humanos , Impotência Vasculogênica/diagnóstico , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/administração & dosagem , Óxido Nítrico/farmacologia , Pênis/efeitos dos fármacos , Qualidade de Vida/psicologia , Fatores de RiscoRESUMO
Introduction. Erectile dysfunction is a common problem in aged men; however, which vascular cavernosal alterations occur with age progression remain unclarified. Aim. Using cavernosal tissue from rats of various ages, we aimed to thoroughly assess erectile vascular-associated morphologic, immunohistological, and morphometric alterations during aging. Methods. Male Wistar rats were divided according to age in groups of 2, 6, 12, 18, 24 months old (N = 5). Cavernosal tissue of all groups was collected and processed for morphologic evaluation, immunodetection of alpha-smooth muscle actin and von Willebrand factor and morphometric quantification of vascular and smooth muscle cell (SMC) areas. Main Outcome Measures. The morphometric assessment of age-related alterations in cavernosal vascular and SMCs using the ImageJ image-processing program. Results. Morphologic and immunohistological evaluation showed a similar structure of erectile tissue among all age groups, divided in two cavernosal bodies containing numerous sinusoidal vascular spaces surrounded by SMCs. Additionally, we observed a reduction of SMC content and an increase in the caliber of vascular spaces, with aging. This was confirmed by the morphometric quantification of the vascular and SMC areas (mean area x10(3) microm(2) +/- x10(3) standard error). Two-month-old animals had a mean vascular area of 4.21 +/- 0.51, approximately 3.5-fold less than the 6-month-old group. The differences increased when comparing the youngest groups with the 12-, 18-, and 24-month-old animals, with mean measurements of 18.99 +/- 1.91, 25.23 +/- 2.76, and 26.34 +/- 2.97. Conversely, SMC areas progressively decreased between 2- and 6-month-old animals, from 6.75 +/- 0.90 to 6.38 +/- 1.24. The elderly 12-, 18-, and 24-month-old groups presented an approximated 1.5-fold reduction on SMCs area, showed by the respective measurements of 4.11 +/- 0.50, 4.01 +/- 0.35, and 4.02 +/- 0.44. Conclusions. We demonstrated that cavernosal angioarchitecture was modified with aging. The decrease in SMCs and the considerable enlargement of vascular lumens may limit the basic function of penile vascular tree in the elderly.
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Envelhecimento/patologia , Disfunção Erétil/patologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Pênis/patologia , Animais , Imageamento Tridimensional/métodos , Imuno-Histoquímica/métodos , Masculino , Pênis/anatomia & histologia , Pênis/metabolismo , Ratos , Ratos WistarRESUMO
Aging and hypogonadic states are known risk factors for erectile dysfunction (ED), contributing together to vascular damage of penile tissue. In the present study, VEGF-specific membrane receptor (VEGFR-1/Flt-1 and VEGFR-2/Flk-1) expression was studied by confocal immunofluorescence in the corpus cavernosum of control rats, rats aged 12 and 18 months, and orchidectomized Wistar rats (90 days of bilateral orchidectomy). Immunocytochemical results demonstrated VEGFR-2 expression restricted to the endothelium in both control and orchidectomized rats. Aged animals (12 and 18 months) presented enlarged vessels with intense VEGFR-2 endothelial staining. On the other hand, VEGFR-1 was demonstrated in smooth muscle fibers, particularly in those that surround vessel endothelium, the endothelial expression being very low in control and orchidectomized rats. However, in the aged rats, a shift resulting in a VEGFR-1 and VEGFR-2 co-localization in the endothelial cell was observed. The findings suggest an upregulation of VEGFR-1 in the corpora cavernosa during aging in the rat, which is evident from an increased expression by endothelial cells.