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1.
J Assist Reprod Genet ; 33(3): 335-348, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26843391

RESUMO

PURPOSE: Azoospermia is one of the major causes of male infertility and is basically classified into obstructive (OA) and non-obstructive azoospermia (NOA). The molecular background of NOA still largely remains elusive. It has been shown that the poly(A)-binding proteins (PABPs) essentially play critical roles in stabilization and translational control of the mRNAs during spermatogenesis. METHODS: In the present study, we aim to evaluate expression levels of the PABP genes, EPAB, PABPC1, and PABPC3, in the testicular biopsy samples and in the isolated spermatocyte (SC) and round spermatid (RS) fractions obtained from men with various types of NOA including hypospermatogenesis (hyposperm), RS arrest, SC arrest, and Sertoli cell-only syndrome (SCO). RESULTS: In the testicular biopsy samples, both PABPC1 and PABPC3 mRNA expressions were gradually decreased from hyposperm to SCO groups (P < 0.05), whereas there was no remarkable difference for the EPAB expression among groups. The expression levels of cytoplasmically localized PABPC1 and PABPC3 proteins dramatically reduced from hyposperm to SCO groups (P < 0.05). In the isolated SC and RS fractions, the EPAB, PABPC1, and PABPC3 mRNA expressions were gradually decreased from hyposperm to SC arrest groups (P < 0.05). Similarly, both PABPC1 and PABPC3 proteins were expressed at higher levels in the SC and RS fractions from hyposperm group when compared to the SC and RS fractions from either RS arrest or SC arrest group (P < 0.05). CONCLUSION: Our findings suggest that observed significant alterations in the PABPs expression may have an implication for development of different NOA forms.


Assuntos
Azoospermia/genética , Proteína I de Ligação a Poli(A)/genética , Proteínas de Ligação a Poli(A)/genética , Testículo/fisiologia , Adulto , Idoso , Biópsia , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Oligospermia/genética , Oligospermia/patologia , Proteína I de Ligação a Poli(A)/metabolismo , Proteínas de Ligação a Poli(A)/metabolismo , Síndrome de Células de Sertoli/genética , Síndrome de Células de Sertoli/patologia , Testículo/fisiopatologia
2.
J Sex Med ; 8(2): 540-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21054799

RESUMO

INTRODUCTION: In addition to the previously known lifelong and acquired premature ejaculation (PE) syndromes, the existence of two more PE syndromes has been suggested: natural variable PE and premature-like ejaculatory dysfunction. However, epidemiological studies investigating the prevalence of these four PE syndromes have yet to be conducted. AIM: To determine the prevalence of the complaint of ejaculating prematurely across the four PE syndromes. METHODS: This study, conducted between June 2009 and December 2009, was designed as a non-interventional, observational cross-sectional field survey. Participating couples were randomly selected from 17 provinces of Turkey. All participants were asked to complete a questionnaire including data regarding demographics, socioeconomic status, social and cultural factors, medical and sexual history, current medications, and ejaculation time. Subjects with a complaint of ejaculating prematurely were classified as lifelong, acquired, and natural variable PE, or premature-like ejaculatory dysfunction. MAIN OUTCOME MEASURES: The main outcome measures were prevalence of complaint of ejaculating prematurely in the general population and across the four PE syndromes. RESULTS: A total of 2,593 couples (mean age, 41.9±12.7 years for males and 38.2±12.1 years for females) were enrolled. Five-hundred twelve subjects (20.0%) complained of ejaculating prematurely. Fifty-eight (2.3%), 100 (3.9%), 215 (8.5%), and 131 (5.1%) subjects were classified as lifelong, acquired, and natural variable PE, and premature-like ejaculatory dysfunction, respectively. CONCLUSIONS: The prevalence of the complaint of ejaculating prematurely among Turkish men was 20.0%, with the highest PE syndrome being natural variable PE (8.5%) and premature-like ejaculatory dysfunction (5.1%).


Assuntos
Ejaculação , Disfunções Sexuais Psicogênicas/epidemiologia , Adulto , Idoso , Distribuição de Qui-Quadrado , Comorbidade , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Prevalência , Estatísticas não Paramétricas , Síndrome , Turquia/epidemiologia , Adulto Jovem
3.
J Sex Med ; 8(4): 1177-85, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21269396

RESUMO

INTRODUCTION: In addition to the previously defined "lifelong" and "acquired" premature ejaculation (PE), the existence of two more subtypes of PE, namely "natural variable PE" and "premature-like ejaculatory dysfunction," has been proposed. AIMS: To evaluate the diagnostic value of the Premature Ejaculation Diagnostic Tool (PEDT) and Arabic Index of Premature Ejaculation (AIPE) in a population-based study, in relation to their sensitivity across these four different PE syndromes and to assess the Premature Ejaculation Profile (PEP) scores of patients with lifelong, acquired, natural variable PE and premature-like ejaculatory dysfunction. METHODS: Between June 2009 and December 2009, couples were randomly selected from 17 provinces of Turkey. Subjects with the complaint of ejaculating prematurely were classified as lifelong, acquired, natural variable PE, and premature-like ejaculatory dysfunction according to the medical and sexual history they described. PE status was also assessed with PEDT, AIPE and PEP. The sensitivity, specificity, positive predictive value and negative predictive value were calculated for PEDT and AIPE in the study population whereas detection rates of these two questionnaires were also compared among the four PE syndromes. Moreover, PEP scores of patients with lifelong, acquired, natural variable PE and premature-like ejaculatory dysfunction were compared. Significance level was considered as P < 0.05. MAIN OUTCOME MEASURES: Scores obtained from PEDT, AIPE, and PEP questionnaires. RESULTS: A total of 2,593 couples were enrolled where 512 (20.0%) male subjects reported PE. PEDT, AIPE, and PEP measures of the PE patients indicated worse sexual function (P < 0.001 each). Mean scores obtained from questionnaires were significantly better in patients with premature-like ejaculatory dysfunction and they were the worst in patients with acquired PE (P < 0.001 each). The sensitivity values of PEDT and AIPE were 89.3 and 89.5, whereas their specificity values were 50.5 and 39.1, respectively. There were statistically significant differences in detection rates of PEDT and AIPE among the four PE syndromes (P = 0.006 and P < 0.001). They were higher in acquired and lifelong PE and lower in premature-like ejaculatory dysfunction. CONCLUSION: PEDT and AIPE can diagnose PE with high sensitivity, especially in patients with lifelong and acquired PE. The complaint of patients with acquired PE seems to be more severe than those complaining of lifelong, natural variable PE and premature-like ejaculatory dysfunction patients.


Assuntos
Ejaculação , Saúde do Homem , Comportamento Sexual , Disfunções Sexuais Fisiológicas/diagnóstico , Disfunções Sexuais Psicogênicas/diagnóstico , Adulto , Idoso , Andrologia , Estudos Transversais , Feminino , Indicadores Básicos de Saúde , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sensibilidade e Especificidade , Disfunções Sexuais Fisiológicas/classificação , Disfunções Sexuais Psicogênicas/classificação , Estatísticas não Paramétricas , Inquéritos e Questionários , Turquia
4.
Int J Impot Res ; 31(3): 231-238, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30710107

RESUMO

Low-intensity extracorporeal shockwave therapy (LI-ESWT) to the penis has recently emerged as novel therapeutic option in the treatment of erectile dysfunction (ED). Randomized-controlled studies investigating the effect of this new treatment modality revealed promising results in men with vasculogenic ED. However, the efficacy of LI-ESWT in men who develop ED following radical prostatectomy (RP) remains obscure due to the exclusion of this group in nearly all clinical trials. In this review, the authors synthesize the findings from available preclinical and clinical studies that examine the potential utility of LI-ESWT in men with post-RP ED.


Assuntos
Disfunção Erétil/terapia , Complicações Pós-Operatórias/terapia , Terapia por Ultrassom , Animais , Modelos Animais de Doenças , Disfunção Erétil/etiologia , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Prostatectomia/efeitos adversos
5.
Acta Histochem ; 109(2): 130-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17240430

RESUMO

The aim of the study was to determine the immunolocalisation of glial cell-derived neurotrophic factor (GDNF) and its receptor (GFRalpha1) in testicular dysfunction induced by experimental left varicocele. Male Wistar rats were divided randomly into two groups: a varicocele-induced group and a sham-operated group for 9, 11 and 13 weeks (each group n=6). After orchiectomy, part of the left testis from each animal was fixed, processed and embedded in paraffin wax for immunohistochemistry and the other part was fixed for ultrastructural investigations. GDNF immunoreactivity was localized in the interstitial space in Leydig cell cytoplasm and there was no significant difference (P=0.5) between the varicocele-induced groups at the various time points. GFRalpha1 localization was perinuclear in spermatids and cytoplasmic in Leydig cells. The decrease of GFRalpha1 immunoreactivity was significant (P=0.001) in varicocele-induced testis at 13 weeks when compared with the age-matched sham group. This is the first study to describe the immunolocalization patterns of GDNF and GFRalpha1 in a rat model of varicocele. Although there was no change in GDNF labelling at the different time points after varicocele, GFRalpha1 was significantly decreased in the 13-week group. Distribution of GDNF and its receptor GFRalpha1 in normal and varicocele-induced rat testes suggests both autocrine and paracrine regulation of spermatogenesis.


Assuntos
Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/análise , Fatores Neurotróficos Derivados de Linhagem de Célula Glial/análise , Testículo/metabolismo , Varicocele/metabolismo , Animais , Imuno-Histoquímica/métodos , Masculino , Microscopia Eletrônica de Transmissão , Ratos , Ratos Wistar , Espermátides/metabolismo , Espermátides/ultraestrutura , Espermatogênese , Testículo/fisiopatologia , Testículo/ultraestrutura , Fatores de Tempo
6.
Curr Pharm Des ; 11(31): 4059-67, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16378511

RESUMO

Basic science research on erectile physiology has been devoted to investigating the pathogenesis of erectile dysfunction (ED) and has led to the conclusion that ED is predominately a disease of vascular origin. It is well recognized that the incidence of ED dramatically increases in men who suffer from diabetes mellitus, hypercholesterolemia, and cardiovascular disease. Endothelial nitric oxide synthase (eNOS) is an important factor in cardiovascular homeostasis, angiogenesis, and erectile function. Given the impact of endothelial-derived nitric oxide (NO) in vascular biology, a great deal of research over the past decade has focused on the role of NO synthesis from the endothelium in normal erectile physiology as well as in disease states. Loss of the functional integrity of the endothelium and subsequent endothelial dysfunction plays an integral role in the occurrence of ED. Therefore, a likely target of gene therapy for the treatment of ED is eNOS. This communication reviews the role of eNOS in erectile physiology and discusses the alterations in eNOS expression in various vascular diseases of the penis. Putative gene therapy interventions to restore eNOS expression and subsequent endothelial function may represent an exciting new therapeutic strategy for the future treatment of ED.


Assuntos
Disfunção Erétil/terapia , Terapia Genética/métodos , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Disfunção Erétil/etiologia , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Óxido Nítrico Sintase Tipo III/uso terapêutico
7.
Int Urol Nephrol ; 37(2): 295-7, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16142559

RESUMO

We report a case of 41-year-old man with idiopathic prostatic giant calculi presenting with voiding difficulty. To our knowledge this is the youngest case with idiopathic prostatic giant calculi reported in the literature. The etiopathogenesis of prostatic calculi are also discussed.


Assuntos
Cálculos/patologia , Doenças Prostáticas/patologia , Adulto , Humanos , Masculino
8.
Asian J Androl ; 17(5): 797-801, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25652632

RESUMO

The relationship between erectile dysfunction (ED) and chronic renal failure (CRF) has been reported in several studies. This study aimed to investigate whether the chronic use of sildenafil could enhance the erectile capacity in CRF-induced rats. In addition, we assessed the effect of that treatment on certain molecules, which have been suggested to play crucial roles in erectile physiology and CRF-related ED as well. Three groups of animals were utilized: (1) age-matched control rats, (2) CRF-induced rats, (3) CRF-induced rats treated with chronic administration of sildenafil (5 mg kg-1 p.o. for 6 weeks [treatment started after 6 weeks of CRF induction]). At 3 months, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue advanced glycation end products (AGE's)/5-hydroxymethyl-2-furaldehyde, malondialdehyde (MDA), cGMP (ELISA), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) (Western blot) analyses were performed in all rat groups. CRF-induced rats had a significant decrease in erectile function when compared to control rats (P < 0.05). The increase in both intracavernosal pressure (ICP) and area under the curve of CRF-induced rats treated with sildenafil (Group 3) was greater than CRF-induced rats (Group 2). Additionally, sildenafil treatment decreased AGE, MDA and iNOS levels, while it preserved nNOS and cGMP contents in CRF-induced penile tissue. Decreased AGE, MDA, iNOS and increased nNOS, cGMP levels at the sildenafil-treated group increased both ICP and Total ICP to CNS, which led to improve erectile function in CRF-induced rats. The results of the present study revealed the therapeutic effect of chronic sildenafil administration on erectile function in CRF-induced rats.


Assuntos
Disfunção Erétil/tratamento farmacológico , Falência Renal Crônica/fisiopatologia , Ereção Peniana/efeitos dos fármacos , Citrato de Sildenafila/farmacologia , Agentes Urológicos/farmacologia , Animais , GMP Cíclico/metabolismo , Modelos Animais de Doenças , Disfunção Erétil/etiologia , Disfunção Erétil/metabolismo , Disfunção Erétil/fisiopatologia , Produtos Finais de Glicação Avançada/metabolismo , Falência Renal Crônica/complicações , Falência Renal Crônica/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Pênis/efeitos dos fármacos , Pênis/metabolismo , Ratos , Citrato de Sildenafila/uso terapêutico , Agentes Urológicos/uso terapêutico
9.
J Androl ; 24(2): 239-45, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12634311

RESUMO

The etiologies of erectile dysfunction (ED) after nerve-sparing radical prostatectomy have not been clearly elucidated. The aim of this study was to evaluate the effects of cavernous nerve injury on cavernous fibrosis, and to consider measures to prevent irreversible damage to the cavernous tissues. Twenty male Sprague-Dawley rats constituted the study population. The animals were divided into 2 groups; group 1 consisted of sham-operated rats (n = 10), and group 2 consisted of rats that underwent incision of both cavernous nerves (n = 10). Three months later, all rats underwent intracavernous papaverine injection (300 and 600 mg), and intracorporal pressures were recorded. Transforming growth factor-beta(1) (TGF-beta(1)) messenger RNA (mRNA) expression from rat penile tissue was measured using reverse transcriptase-polymerase chain reaction. Hypoxia-inducible factor-1alpha (HIF-1alpha), TGF-beta(1), and collagen I and III protein expressions were determined by Western blot analysis and immunohistochemical staining. Erectile function as studied with intracavernosal papaverine injection and histological analysis of penile cross-sections at 3 months was similar in both groups. TGF-beta(1) mRNA expression, HIF-1alpha, TGF-beta(1), and collagen I and III protein expressions were significantly greater in the neurotomy group. Immunohistochemical staining for TGF-beta(1), HIF-1alpha, and collagen III were qualitatively more positive in the neurotomy group, whereas collagen I staining was similar. This study demonstrates an increase in TGF-beta(1), HIF-1alpha, and collagen III synthesis in rat cavernosal smooth musculature after cavernous neurotomies. In theory, cavernous fibrosis may be reduced by employing various vasoactive agents or interventions that increase oxygenation to the corporal tissues during the postoperative period.


Assuntos
Disfunção Erétil/etiologia , Hipóxia/etiologia , Pênis/inervação , Pênis/fisiopatologia , Animais , Western Blotting , Denervação , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/patologia , Fibrose , Plexo Hipogástrico , Hipóxia/tratamento farmacológico , Hipóxia/patologia , Imuno-Histoquímica , Masculino , Papaverina/farmacologia , Pênis/patologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta1 , Vasodilatadores/farmacologia
10.
Int Urol Nephrol ; 35(2): 207-8, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15072497

RESUMO

Colchicine has been reported to be a safe and effective medication in the treatment of early phase of Peyronie's disease (PD). However here we reported two patients, presenting with PD during high dose colchicine treatment for familiar mediterranean fever (FMF).


Assuntos
Anti-Inflamatórios/efeitos adversos , Colchicina/efeitos adversos , Induração Peniana/induzido quimicamente , Adulto , Anti-Inflamatórios/administração & dosagem , Colchicina/administração & dosagem , Febre Familiar do Mediterrâneo/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
12.
Am J Physiol Heart Circ Physiol ; 292(3): H1278-90, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17071732

RESUMO

Mesenchymal stem cells (MSCs) can be used in adult stem cell-based gene therapy for vascular diseases. To test the hypothesis that MSCs alone or endothelial nitric oxide synthase (eNOS)-modified MSCs can be used for treatment of erectile dysfunction (ED), syngeneic rat MSCs (rMSCs) were isolated, ex vivo expanded, transduced with adenovirus containing eNOS, and injected into the penis of aged rats. Histological analysis demonstrated that rMSCs survived for at least 21 days in corporal tissue after intracavernous injection, and an inflammatory response was not induced. Intracavernous administration of eNOS-modified rMSCs improved the erectile response in aged rats at 7 and 21 days after injection. The increase in erectile function was associated with increased eNOS protein, NOS activity, and cGMP levels. rMSCs alone increased erectile function of aged rats at day 21, but not at day 7, with the transplanted cells exhibiting positive immunostaining for several endothelial and smooth muscle cell markers. This change in rMSC phenotype was accompanied by upregulation of penile eNOS protein expression/activity and elevated cGMP levels. These findings demonstrate that an adenovirus can be used to transduce ex vivo expanded rMSCs to express eNOS and that eNOS-modified rMSCs improve erectile function in the aged rat. Intracavernous injection of unmodified wildtype rMSCs improved erectile function 21 days after injection through mechanisms involving improved endothelium-derived NO/cGMP signaling and rMSC differentiation into penile cells expressing endothelial and smooth muscle markers. These data highlight the potential clinical use of adult stem cell-based therapy for the treatment of ED.


Assuntos
Disfunção Erétil/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/enzimologia , Óxido Nítrico Sintase Tipo III/genética , Envelhecimento , Animais , Masculino , Ratos , Ratos Endogâmicos BN
13.
J Sex Med ; 3(2): 242-50; discussion 250-2, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16490017

RESUMO

OBJECTIVES: Accumulation of advanced glycation end products (AGEs) has been linked to many of the complications of diabetes mellitus, including erectile dysfunction (ED). Furthermore, it has been demonstrated that inhibitors of AGE formation, such as aminoguanidine, can prevent ED in diabetic animals. However, it is unknown whether late administration of a putative cross-link breaker, ALT-711, can reverse diabetic ED. We therefore compared ALT-711 and aminoguanidine in their ability to reverse ED in diabetic rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly divided into four groups: (i) age-matched controls; (ii) streptozotocin (STZ)-induced diabetic rats (60 mg/kg; intraperitoneal injection); (iii) STZ diabetic rats treated with ALT-711 (3 mg/kg/day, intraperitoneal injection); and (iv) STZ diabetic rats treated with aminoguanidine (1 gm/L in drinking water) during the final 6 weeks of 12 weeks of induced diabetes. At the end of 12 weeks, erectile response to cavernous nerve stimulation (CNS) was determined. Neuronal nitric oxide synthase (nNOS) contents were measured in all penises, and AGE levels were determined both in penile tissues and in serum samples. RESULTS: Erectile responses to CNS and penile nNOS protein content were significantly reduced, while AGE levels were elevated in the penises and serum of untreated diabetic animals. Treatment with ALT-711, but not with aminoguanidine, reversed ED and nNOS depletion and reduced serum and penile tissue AGE levels. CONCLUSIONS: These results suggest that cross-link breakers, such as ALT-711, are the optimal therapeutic approach, compared with treatment with inhibitors of AGE formation, in the reversal of diabetes-related ED.


Assuntos
Diabetes Mellitus Experimental/complicações , Angiopatias Diabéticas/complicações , Produtos Finais de Glicação Avançada/metabolismo , Guanidinas/administração & dosagem , Impotência Vasculogênica/tratamento farmacológico , Tiazóis/administração & dosagem , Animais , Angiopatias Diabéticas/induzido quimicamente , Relação Dose-Resposta a Droga , Imuno-Histoquímica , Impotência Vasculogênica/etiologia , Impotência Vasculogênica/prevenção & controle , Masculino , Ratos , Ratos Sprague-Dawley , Estreptozocina
14.
Urol Int ; 74(2): 140-6, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15756066

RESUMO

OBJECTIVE: To evaluate the factors influencing the results of endoureterotomy using cold-knife and cutting balloon dilatation, and permanent ureteral wall stents in patients with benign ureteral strictures after different operations affecting the ureter. MATERIALS AND METHODS: Over a 4-year period, in 18 patients, endoscopic cold-knife and Acucise endoureterotomies were performed in 13 and 7 renal units, respectively. Eight Memoterm permanent ureteral wall stents were inserted into 7 patients when endoureterotomy failed. Successful outcome was defined by the absence of re-stricture assessed both clinically and radiologically. RESULTS: The strictures were secondary to ureterolithotomy in 6, ureteroscopy in 3, gynecological procedures in 4, abdominal surgeries in 2, transplantation in 2 and continent urinary diversion in 1. The right and left ureters were unilaterally affected in 5 and 11 patients, respectively (5 of them had a solitary kidney), while the remaining 2 patients had bilateral ureteral strictures. We achieved total ureteral patency of 3 (43%) and 7 (54%) renal units with Acucise and cold-knife incision, respectively. Obstructive uropathy was resolved in 6 renal units (75%) of 8 using ureteral wall stents. CONCLUSION: Endoureterotomy with cold-knife or Acucise cutting balloon dilatation is effective in the treatment of iatrogenic ureteral strictures, but only in a selected group. Based on our results, the favorable prognostic criteria for endoureterotomy are the length (< or =1.5 cm), the nonischemic nature of the stricture and adequate renal function. As a salvage approach, permanent self-expanding ureteral wall stents with a 75% success rate may provide a satisfactory outcome for decompression of an obstructed system.


Assuntos
Criocirurgia , Stents , Obstrução Ureteral/cirurgia , Ureteroscopia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação
15.
J Sex Med ; 2(5): 709-15, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16422829

RESUMO

INTRODUCTION: Penile duplex Doppler ultrasound (PDDU) is currently the preferred method for the functional evaluation of penile hemodynamics. PDDU may be used to monitor objectively changes in penile vascular parameters in men who undergo treatment for Peyronie's disease (PD), including intralesional interferon alpha-2b (IFN alpha-2b). AIM: To investigate the impact of intralesional IFN alpha-2b therapy for PD on penile hemodynamics by using PDDU and to assess the objective role of PDDU in monitoring treatment outcomes. MATERIALS AND METHODS: Thirty-nine patients (20 in the placebo and 19 in the IFN alpha-2b treatment arm) were enrolled in this prospective, placebo-controlled, parallel study. Patients received either 10 mL saline or 5 x 10(6) units of IFN alpha-2b intralesional injections every other week for a total of six injections. Patients in each group were evaluated at baseline and after completion of treatment regarding changes in penile hemodynamic parameters, penile curvature, plaque size and density, pain on erection, and erectile function. Specific published criteria were used for PDDU measurements. Outcomes were statistically compared between each group by using Mann-Whitney U and chi-square tests. RESULTS: The mean age of the patients and the duration of PD were similar in both groups. The improvement in penile blood flow was significantly greater in IFN alpha-2b-treated patients than those in the placebo group. The number with the nonvascular classification increased significantly in the IFN alpha-2b arm from 31.5% to 57.8%. Additionally, improvements in penile curvature, plaque size and density, and pain on erection were better in the IFN alpha-2b group compared with the control. No significant improvement was observed in the erectile function domain in either group. CONCLUSION: This study reveals that intralesional IFN alpha-2b injections have a significant benefit on penile hemodynamic parameters. Moreover, intralesional IFN alpha-2b is an effective, minimally invasive treatment for PD, and PDDU is a useful adjunct to monitor objectively changes in penile vascular parameters. interferon alpha-2b injection therapy on penile hemodynamics in men with Peyronie's disease.


Assuntos
Interferon-alfa/uso terapêutico , Induração Peniana , Pênis/irrigação sanguínea , Adulto , Idoso , Vias de Administração de Medicamentos , Disfunção Erétil/diagnóstico , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Humanos , Injeções , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/farmacologia , Masculino , Pessoa de Meia-Idade , Induração Peniana/diagnóstico por imagem , Induração Peniana/tratamento farmacológico , Induração Peniana/fisiopatologia , Estudos Prospectivos , Proteínas Recombinantes , Ultrassonografia Doppler Dupla
16.
J Urol ; 174(5): 2054-9, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16217393

RESUMO

PURPOSE: We investigated the involvement of poly(adenosine diphosphate-ribose) (PAR) polymerase (PARP) activation in the development of erectile dysfunction and the therapeutic benefit of the potent PARP inhibitor INO-1001 (Inotek Pharmaceuticals Corp., Beverly, Massachusetts) in a bilateral cavernous nerve crush injury (BCNCI) model in rats. MATERIALS AND METHODS: Sprague-Dawley rats were divided into 3 groups, namely sham treated, BCNCI plus vehicle and BCNCI plus the PARP inhibitor INO-1001. One week after surgical intervention all groups underwent in vivo cavernous nerve stimulation. PAR activation, nitrotyrosine and inducible nitric oxide synthase were evaluated by immunohistochemistry and serum levels of INO-1001 were measured by high performance liquid chromatography. Penile tissues were analyzed for levels of malondialdehyde and myeloperoxidase. Data sets were statistically compared in all groups. RESULTS: Neurogenic mediated erectile responses were evaluated. Mean intracavernous pressure (ICP), the ICP-to-blood-pressure ratio and total ICP were significantly decreased in BCNCI plus vehicle rats. These values were not statistically different between the sham and PARP inhibitor treated groups. There was a marked decrease in PAR staining in the treatment group. There was a substantial increase in malondialdehyde tissue levels but not myeloperoxidase in response to BCNCI, which was unchanged with PARP inhibitor treatment. There was a marked increase in tyrosine nitration in the treatment group. Up-regulation of nitric oxide synthase and increased tyrosine nitration were not observed in the penile tissues of the treatment group. CONCLUSIONS: These data demonstrate that BCNCI in a rat model causes increased PARP activation, resulting in severe erectile dysfunction. Treatment with the PARP inhibitor INO-1001 decreases the degree of nitrosative stress, prevents PARP activation and provides significant cavernous neuroprotection, which in turn preserves erectile function.


Assuntos
Adenosina Difosfato Ribose/metabolismo , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/enzimologia , Indóis/farmacologia , Poli(ADP-Ribose) Polimerases/efeitos dos fármacos , Análise de Variância , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Disfunção Erétil/patologia , Imuno-Histoquímica , Masculino , Óxido Nítrico Sintase/análise , Óxido Nítrico Sintase/metabolismo , Pênis/lesões , Pênis/inervação , Peroxidase/análise , Peroxidase/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Probabilidade , Ratos , Ratos Sprague-Dawley , Valores de Referência , Sensibilidade e Especificidade
17.
J Sex Med ; 2(2): 187-97; discussion 197-8, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16422885

RESUMO

INTRODUCTION: Superoxide anion may contribute to erectile dysfunction (ED) in diabetes mellitus by reducing cavernosal nitric oxide (NO) bioavailability. The purpose of this study was to determine if gene transfer of extracellular superoxide dismutase (EC-SOD) can reduce superoxide anion formation and determine if this reactive oxygen species may contribute to diabetes-related ED in an experimental model of diabetes. METHODS: Three groups of animals were utilized: (1) control; (2) streptozotocin (STZ)-diabetic rats [60 mg/kg intraperitoneally (ip)] intracavernosally injected with AdCMVbetagal (negative control); and (3) STZ-rats intracavernosally injected with AdCMVEC-SOD. Two months after ip injection of STZ, groups 2 and 3 were transfected with the adenoviruses and 2 days after transfection, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Confocal microscopy for superoxide anion and von Willebrand Factor (vWF) was performed in the STZ-diabetic rat. Superoxide anion production, total SOD activity, and cyclic guanosine monophosphate (cGMP) levels were measured in each experimental group of rats. RESULTS: Confocal microscopy demonstrated superoxide in smooth muscle and endothelial cells of the STZ-rat cavernosum and colocalized with vWF in the endothelium. Higher superoxide anion levels and decreased cGMP levels were found in the penis of STZ-rats at a time when erectile function was reduced. Two days after administration of AdCMVEC-SOD, superoxide anion levels were significantly lower in the penis of STZ-rats. Total SOD activity and cavernosal cGMP was increased in the penis of EC-SOD-transfected rats. STZ-rats transfected with AdCMVEC-SOD had a peak intracavernosal pressure (ICP) and total ICP to CNS that was similar to control rats. CONCLUSIONS: These data demonstrate that in vivo adenoviral gene transfer of EC-SOD can reduce corporal superoxide anion levels and raise cavernosal cGMP levels by increasing NO bioavailability thus restoring erectile function in the STZ-diabetic rat.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Disfunção Erétil/metabolismo , Terapia Genética , Pênis/metabolismo , Superóxido Dismutase/farmacologia , Superóxidos/metabolismo , Adenoviridae/genética , Animais , Modelos Animais de Doenças , Estimulação Elétrica , Endotélio Vascular/metabolismo , Guanosina Monofosfato/metabolismo , Masculino , Microscopia Confocal , Músculo Liso Vascular/metabolismo , Pênis/inervação , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina , Superóxido Dismutase/genética , Transfecção
18.
Urol Int ; 68(4): 255-60, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12053028

RESUMO

UNLABELLED: IINTRODUCION: The ideal diagnosis and therapeutic agent for erectile dysfunction (ED) would be an oral drug taken prior to color Doppler ultrasound (CDU) examination and sexual intercourse. In the present study we have investigated if the efficacy of oral sildenafil is optimal in the diagnosis of underlying pathology of ED. MATERIAL AND METHODS: The study group comprised of 41 patients with ED. Firstly, all patients underwent CDU examinations after the combined intracavernosal injection of 60 mg of papaverine and sexual stimulation (CIS). Secondly, these patients were examined after taking 50 mg of oral sildenafil citrate combined with self-manual and visual sexual stimulation. RERSULTS The differences of peak systolic velocity values were statistically significant between CIS and sildenafil (right: 40.7 +/- 2.9 vs. 28.7 +/- 3.3; left: 41.2 +/- 3.3 vs. 25.7 +/- 2.4; p < 0.001) in patients with normal penile vascular system. However, end-diastolic velocity and resistance index values were not significant between the same groups. In addition, there were not significant differences for peak systolic and end-diastolic blood flow velocities and resistances index with CIS and sildenafil in cases with vasculogenic ED. CONCLUSIONS: Sildenafil citrate plus visual sexual stimulation is not reliable as CIS to make accurate interpretation of penile vascular status using CDU. On the other hand, in some cases suspected of psychogenic ED after detailed sexual history, sildenafil might be tried as an initial step of the functional evaluation with CDU in order to prevent prolonged erection risk with intracavernosal injection of vasoactive agents.


Assuntos
Disfunção Erétil/diagnóstico por imagem , Piperazinas , Ultrassonografia Doppler em Cores , Vasodilatadores , Administração Oral , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Pênis , Purinas , Citrato de Sildenafila , Sulfonas
19.
Urology ; 62(1): 105-9, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12837432

RESUMO

OBJECTIVES: To assess the long-term functional outcome, patient and partner satisfaction, and predictive factors for unfavorable results in men treated with a surgical approach for severe Peyronie's disease. METHODS: Sixty-one patients underwent surgical treatment for Peyronie's disease between 1997 and 2001 and were retrospectively evaluated. All patients were assessed preoperatively with a detailed sexual and medical history, focused physical examination, and penile duplex ultrasonography. Nineteen patients underwent penile plaque excision/incision and grafting with Tutoplast cadaveric pericardial grafting material (group 1). Penile prosthesis implantation and manual modeling was performed in 31 patients (group 2a), and 11 men were treated with penile prosthesis implantation and pericardial grafting (group 2b). RESULTS: The mean follow-up of the patients was 21.9 +/- 13.6 months (range 12 to 48). Complete penile straightening was achieved in 15 patients (78.9%) in the excision/incision and grafting group. In the 42 men who underwent reconstruction using penile prosthesis implantation (group 2a,b), penile curvature resolved completely in 37 patients (88%). Long-term postoperative residual curvatures greater than 30 degrees occurred in 3 patients (15.7%) and 2 patients (4.8%) in groups 1 and 2a,b, respectively. One penile prosthesis (2.3%) was explanted in the second group for erosion. Patient responses to our questionnaire showed that overall 83.6% of the patients and 76.9% of the partners were satisfied with the surgical result. CONCLUSIONS: According to the results of this long-term, retrospective study, pericardial grafting can be used successfully after plaque excision/incision procedures in men undergoing surgical treatment for severe Peyronie's disease. In patients with Peyronie's disease and erectile dysfunction, implantation of a penile prosthesis and correction of the curvature with a graft can provide an acceptable, functionally straight penis without any increased risk of complications compared with penile prosthesis implantation alone.


Assuntos
Satisfação do Paciente , Induração Peniana/cirurgia , Prótese de Pênis/psicologia , Procedimentos de Cirurgia Plástica/psicologia , Parceiros Sexuais/psicologia , Adulto , Idoso , Disfunção Erétil/etiologia , Disfunção Erétil/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana , Implante Peniano , Pericárdio , Complicações Pós-Operatórias , Estudos Retrospectivos , Transplante Heterotópico , Resultado do Tratamento
20.
BJU Int ; 94(3): 429-32, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15291881

RESUMO

OBJECTIVE: To assess the accumulation of advanced glycation end products (AGEs) in streptozotocin (STZ)-induced diabetic rat cavernosal tissue, and to determine whether the protective effect of aminoguanidine (AG) on erectile function is related to the timing of treatment, as the accumulation of AGEs in the penis may be important in the pathogenesis of diabetes mellitus-induced erectile dysfunction, and prolonged treatment with AG (a selective AGE inhibitor), prevents erectile dysfunction in this situation. MATERIALS AND METHODS: Harlan Sprague-Dawley rats were divided into groups 1-4, i.e. age-matched controls; STZ diabetic rats (60 mg/kg intraperitoneal) given free access to water; STZ diabetic rats treated with AG (1 g/L per day in the drinking water) immediately after inducing diabetes; and STZ-diabetic rats treated with AG 1 month after inducing diabetes, respectively. Two months after inducing diabetes the intracavernosal pressure was measured after cavernosal nerve stimulation, and cavernosal AGE (5-hydroxy methyl furfural, 5-HMF) levels assessed. RESULTS: Cavernosal tissue 5-HMF levels from groups 2 and 4 were significantly higher than in group 1 (control). The expression of 5-HMF in group 3 was similar to that in group 1. Diabetic rats had significantly lower erectile function than controls, while groups 3 and 4 (treated with AG) had normal erectile function, as measured by cavernosal nerve stimulation. CONCLUSIONS: The effect of AG on AGE levels seems to be time-dependent; that the 1-month treatment with AG improved erectile function with no change in AGEs suggests that AG has protective effects on the penile vasculature through alternative pathways.


Assuntos
Diabetes Mellitus Experimental/complicações , Inibidores Enzimáticos/uso terapêutico , Disfunção Erétil/prevenção & controle , Produtos Finais de Glicação Avançada/metabolismo , Guanidinas/uso terapêutico , Pênis/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Produtos Finais de Glicação Avançada/análise , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
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