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1.
J Clin Med ; 12(14)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37510885

RESUMO

Fibrosis is a disease condition characterized by abnormalities of the extracellular matrix, such as accumulation of the transforming growth factor ß, infiltration by myofibroblasts, deposition of collagen, and a generalized dysregulation of collagen maturation. It can severely impair the function of organs by replacing normal tissue with a highly collagenized matrix, thereby reducing the elasticity and compliance of tissues. Fibrotic diseases of the genitourinary tract present relevant problems in healthcare, and their principles of pathophysiology remain unclarified; hence, the armamentarium for prevention and treatment is limited. These diseases include renal fibrosis, Peyronie's disease and ureteral and urethral strictures due to perturbations in the process of wound healing in response to injuries. Such deteriorations may contribute to obstructive uropathies or sexual dysfunction. This review provides a brief overview of the most frequent fibrotic diseases of the genitourinary system and of how the pathophysiology is related to symptoms, and also highlights potential therapeutic strategies to address the abnormal deposition of collagen. Although the understanding of factors associated with fibrotic conditions of the urinary and genital tract is still limited, some beneficial advances have been made. Further research will serve to provide a more comprehensive insight into factors responsible for the development of fibrotic tissue deposition.

2.
Urol Oncol ; 41(8): 356.e19-356.e30, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37198025

RESUMO

BACKGROUND: Cisplatin-based chemotherapy (ChT) is the preferred perioperative treatment in muscle-invasive urothelial carcinoma of the urinary bladder (UCUB). Nevertheless, a certain number of patients are ineligible for platinum-based ChT. This trial compared immediate adjuvant vs. delayed gemcitabine ChT at progression in platinum-ineligible patients with high-risk UCUB. METHODS: High-risk platinum-ineligible UCUB patients (n = 115) were randomized 1:1 to adjuvant gemcitabine (n = 59) or gemcitabine at progression (n = 56). Overall survival was analyzed. Additionally, we analyzed progression-free survival (PFS), toxicity and quality of life (QoL). RESULTS: After a median follow-up of 3.0 years (inter quartile range [IQR]: 1.3-11.6), adjuvant ChT did not significantly prolong overall survival (OS) (HR: 0.84; 95% CI: 0.57-1.24; P = 0.375), with 5-year OS of 44.1% (95% CI: 31.2-56.2) and 30.4% (95% CI: 19.0-42.5), respectively. We noted no significant difference in PFS (HR: 0.76; 95% CI: 0.49-1.18; P = 0.218), with 5-year PFS of 36.2% (95% CI: 22.8-49.7) in the adjuvant group and 22.2% (95% CI: 11.5%-35.1%) when treated at progression. Patients with adjuvant treatment showed a significantly worse QoL. The trial was prematurely closed after recruitment of 115 of the planned 178 patients. CONCLUSIONS: There was no statistically significant difference in terms of OS and PFS for patients with platinum-ineligible high-risk UCUB receiving adjuvant gemcitabine compared to patients treated at progression. These findings underline the importance of implementing and developing new perioperative treatments for platinum-ineligible UCUB patients.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Adjuvantes Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/patologia , Cisplatino , Seguimentos , Gencitabina , Platina/uso terapêutico , Qualidade de Vida , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
3.
Aktuelle Urol ; 53(1): 54-59, 2022 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-32968994

RESUMO

BACKGROUND: Various life-prolonging therapy options are available for the treatment of metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: The optimal therapy sequence for mCRPC has been discussed for years. With the final results of the CARD study, important prospective data are available to enlighten the discussion about the therapy sequence. MATERIAL AND METHOD: CARD is a randomised phase IV trial in patients with mCRPC who were previously treated with docetaxel and an anti-androgen receptor (ARTA). The study showed significant efficacy benefits in favour of further treatment with cabazitaxel versus a second ARTA therapy. The study results are presented and discussed in the context of previous study data with regard to their importance for everyday clinical practice. RESULTS: The CARD study data confirm cabazitaxel as an effective therapy option for mCRPC patients previously treated with docetaxel and an ARTA. Cabazitaxel was safe to apply. The study results confirm the cross resistance between the two ARTAs Abiraterone and Enzalutamide. CONCLUSION: In mCRPC patients eligible for chemotherapy, the therapy sequence should be chosen so that the patients also receive cabazitaxel. A direct therapy sequence with two ARTAs should be avoided or, at least, only considered if other substances are contraindicated.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/uso terapêutico , Humanos , Masculino , Nitrilas/uso terapêutico , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Resultado do Tratamento
4.
Aktuelle Urol ; 53(5): 439-442, 2022 09.
Artigo em Alemão | MEDLINE | ID: mdl-34380148

RESUMO

Rare benign tumours of the kidney comprise a group of very different histogenetic entities. We report a case of a 53-year-old woman who underwent laparoscopic nephrectomy because of a renal mass. The diagnosis of a rare and benign metanephric adenoma was confirmed by histopathology. With less than 200 documented cases, the metanephric adenoma described here is a rarity in everyday urological practice and cannot be distinguished from a malignant tumour of the kidney by clinical examination and/or imaging without histological assessment.


Assuntos
Adenoma , Neoplasias Renais , Tumor de Wilms , Adenoma/diagnóstico , Adenoma/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Rim/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Pessoa de Meia-Idade , Tumor de Wilms/diagnóstico , Tumor de Wilms/patologia , Tumor de Wilms/cirurgia
5.
Res Rep Urol ; 13: 139-145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777854

RESUMO

PURPOSE: Although it has been supposed that the NO/cyclic GMP system produces inhibitory signals to reduce the resistance of the bladder outlet and urethra during the micturition phase, little is known on the mechanisms controlling the function of urethral smooth muscle. The aim of the present study was to examine in the male and female urethra the expression of phosphodiesterase (PDE) isoenzymes, known as key proteins of the cyclic GMP/AMP signaling. METHODS: Urethral tissue was obtained from 4 female cadavers and 7 male patients (who had undergone gender reassignment surgery). The expression of mRNA encoding for PDE1A, 1B, 1C, 2A, 4B, 4D, 5A, 10A and 11A was investigated by means of real-time polymerase chain reaction. Western blot (WB) analysis was conducted to detect PDE isoenzymes. RESULTS: RT-PCR revealed relevant amounts of mRNA encoding for PDE1A, 2A, 4B, 5A, 10A and 11A in male and female urethral tissue. The expression of PDE1A, 2A, 4B and 10A was 2-fold higher in the female than in the male urethra, whereas the expression of PDE11A mRNA was 7-fold higher in the male tissue. In the WB experiments, immunosignals specific for PDE1A, PDE4A and 4B and PDE11A were of higher degree in the female than the male tissue specimens, while an almost equivocal expression of PDE2A, PDE5A and PDE10A was registered. CONCLUSION: On the level of mRNA and function proteins, different patterns of expression of PDE isoenzymes were registered in human male and female urethra. Future studies may clarify whether inhibition of PDE isoenzymes is likely to facilitate the relaxation of the outflow region in both sexes.

6.
J Clin Med ; 9(9)2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32947804

RESUMO

It is widely accepted that disorders of the male (uro)genital tract, such as erectile dysfunction (ED) and benign diseases of the prostate (lower urinary tract symptomatology or benign prostatic hyperplasia), can be approached therapeutically by influencing the function of both the vascular and non-vascular smooth muscle of the penile erectile tissue or the transition zone/periurethral region of the prostate, respectively. As a result of the discovery of nitric oxide (NO) and cyclic guanosine monophosphate (GMP) as central mediators of penile smooth muscle relaxation, the use of drugs known to increase the local production of NO and/or elevate the intracellular level of the second messenger cyclic GMP have attracted broad attention in the treatment of ED of various etiologies. Specifically, the introduction of vasoactive drugs, including orally active inhibitors of the cyclic GMP-specific phosphodiesterase (PDE) 5, has offered great advantage in the pharmacotherapy of ED and other diseases of the genitourinary tract. These drugs have been proven efficacious with a fast on-set of action and an improved profile of side-effects. This review summarizes current strategies for the treatment of ED utilizing the application of vasoactive drugs via the oral, transurethral, topical, or self-injection route.

7.
Transl Androl Urol ; 9(3): 1286-1295, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32676412

RESUMO

BACKGROUND: Penile rehabilitation after nerve-sparing radical prostatectomy (nsRP) improves the functional outcome, i.e., erectile function and urinary continence. Masturbation as a concept of penile rehabilitation has been practically not investigated. The aim of this observational and explorative study was to evaluate the association between masturbation and the recovery of the functional outcome in patients after nsRP. METHODS: Patients after nsRP (11/2013-3/2016) with preoperative International Erectile Function Score-Erectile Function (IIEF-EF) of ≥22 and/or Erection Hardness Score (EHS) of ≥3 without neo- or adjuvant therapy were included in this analysis. Patients were classified according to their masturbation behavior (yes: m; no: nm). Chi-square tests were used to test for association between masturbation and functional outcome. The main outcome measures were rates of erectile function, morning erections, and urinary continence 6, 12, 24, and 36 months after nsRP. RESULTS: A total of 250 preoperatively potent patients with median age of 63.8 years (1st, 3rd quartile: 59.1, 69.6) at nsRP were included. After 24 months, m-patients had a numerically higher rate of moderate to good erectile function compared to nm-patients (47.5% vs. 37.5%; P=0.193) and had morning erections more often than nm-patients (54.6% vs. 34.9%; P=0.011). Urinary continence rate 12 months after nsRP was higher compared to nm-patients (12 months: 83.1% vs. 70.2%; P=0.042). CONCLUSIONS: Masturbation might be a promising approach of both erectile function and urinary continence recovery, and patients could be encouraged to masturbate after nsRP. However, due to the study design, causality cannot be concluded. Thus, masturbation as a possible concept of penile rehabilitation warrants further investigation.

8.
World J Urol ; 38(6): 1423-1435, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31506747

RESUMO

OBJECTIVES: The benign prostatic syndrome, comprising lower urinary tract symptomatology secondary to benign prostatic hyperplasia/enlargement, represents a major health care issue in westernized countries. The pharmacological management involves alpha-adrenoceptor antagonists, intervention into the hormonal control of prostate growth using inhibitors of the enzyme 5-alpha-reductase, and stimulation of the nitric oxide/cyclic GMP pathway by tadalafil, an inhibitor of the phosphodiesterase type 5. METHODS: This review summarizes the achievements which have been made in the development of drug candidates assumed to offer opportunities as beneficial treatment options in the management of the benign prostatic syndrome. RESULTS: A review of the literature has revealed that the line of development is focusing on drugs interfering with peripheral neuromuscular/neuronal mechanisms (nitric oxide donor drugs, agonists/antagonists of endogenous peptides, botulinum toxin, NX-1207), the steroidal axis (cetrorelix) or the metabolic turn-over (lonidamine), as well as the combination of drugs already established in the treatment of lower urinary tract symptomatology/benign prostatic hyperplasia (phosphodiesterase 5 inhibitor plus alpha-adrenoceptor antagonist). CONCLUSION: Many research efforts have provided the basis for the development of new therapeutic modalities for the management of lower urinary tract dysfunctions, some of which might be offered to the patients in the near future.


Assuntos
Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática/tratamento farmacológico , Antagonistas Adrenérgicos alfa/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Óxido Nítrico/antagonistas & inibidores , Hiperplasia Prostática/complicações , Transdução de Sinais/efeitos dos fármacos
9.
J Sex Med ; 17(2): 210-237, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31812683

RESUMO

INTRODUCTION: To date, several aspects of inflatable penile prosthesis (IPP) surgical procedure have been poorly studied. AIM: The aim of this study was to review the evidence associated with IPP implantation and provide clinical recommendations on behalf of the European Society for Sexual Medicine (ESSM). Overall, 130 peer-reviewed studies and systematic reviews, which were published from 2007-2018 in the English language, were included. METHODS: MEDLINE and EMBASE were searched for randomized clinical trials, meta-analyses, and open-label prospective and retrospective studies. MAIN OUTCOME MEASURE: The panel provided statements exploring patients and partner expectations, satisfaction in male and phalloplasty cohorts, the impact of penile length, girth and implant type, reservoir placement, the influence of comorbidities, and social circumstances. Levels of evidence were provided according to the Oxford 2011 criteria and graded as for the Oxford Centre for Evidence-Based Medicine recommendations. RESULTS: In the preoperative setting, it is fundamental to identify and interact with difficult patients with the intention of enhancing the surgeon's ability to establish the surgeon-patient relationship, reduce physical and legal risk, as well as enhancing patient satisfaction. To address this need, the mnemonic Compulsive, Unrealistic, Revision, Surgeon Shopping, Entitled, Denial, and Psychiatric ("CURSED") has been suggested to identify patients who are at high risk of dissatisfaction. The current recommendations suggest improving glycemic control in patients with diabetes. Available evidence suggests evaluating transplant recipients with the criteria of Barry, consisting of stable graft function for >6 months, avoidance of intra-abdominal reservoir placement, and low-dose immunosuppression. HIV status does not represent a contraindication for surgery. Smoking, peripheral vascular disease, and hypertension may be associated with an increased risk of revision surgery. Patients with spinal cord injury may receive IPP. Patients aged ≥70 years, as well as obese patients, can be offered IPP. The IPP implantation can be performed in patients with stable Peyronie's disease. Ectopic high submuscular reservoir placement can be considered as an alternative method. CLINICAL IMPLICATIONS: There is a relevant lack of high-level data and definite conclusions in certain areas remain difficult to draw. STRENGTH & LIMITATIONS: All studies have been evaluated by a panel of experts providing recommendations for clinical practice. Because of lack of sufficient prospective data, some of the included studies are retrospective and this could be stated as a limitation. CONCLUSION: This ESSM position statement provides recommendations on optimization of patient outcome by patient selection, and individualized peri- and intra-operative management. ESSM encourages centers to collaborate and to create prospective, multicenter registries in order to address this topic of increasing importance. Osmonov D, Christopher AN, Blecher GA, et al. Clinical Recommendations from the European Society for Sexual Medicine Exploring Partner Expectations, Satisfaction in Male and Phalloplasty Cohorts, the Impact of Penile Length, Girth and Implant Type, Reservoir Placement, and the Influence of Comorbidities and Social Circumstances. J Sex Med 2020;17:210-237.


Assuntos
Doenças do Pênis/cirurgia , Implante Peniano/métodos , Prótese de Pênis , Comorbidade , Humanos , Masculino , Motivação , Satisfação do Paciente , Induração Peniana/cirurgia , Reoperação , Parceiros Sexuais
10.
Andrologia ; 51(9): e13349, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31482616

RESUMO

The nitric oxide (NO) pathway plays a role in maintaining the function of the prostate. An impairment in the activity of the NO system may have an impact in the manifestation of lower urinary tract symptomatology and benign prostatic hyperplasia. Arginase enzymes (Arg) counteract the generation of NO by depleting the intracellular pool of L-arginine, known to be the substrate of the NO synthases. This study investigated the expression of arginase type I and II in the human prostate. Nondiseased prostate tissue was obtained during pelvic surgeries (prostatectomy, cystoprostatectomy). Tissue sections were exposed to antibodies directed against Arg I and II, cGMP, the phosphodiesterase 5 and nNOS. The expression of mRNA transcripts encoding for Arg I and Arg II was investigated using molecular biology. Reverse transcriptase polymerase chain reaction (RT-PCR) revealed the presence of mRNA encoding for Arg I and II, immunofluorescence specific for Arg I was seen in the stromal smooth musculature, and labelling for PDE5 and cyclic GMP was also observed. Nerve fibres containing nNOS were identified running across the smooth musculature. Immunostainings for Arg II did not yield signals. These findings are in support of the notion that, in the prostate, Arg is involved in the modulation of the activity of the NO system.


Assuntos
Arginase/metabolismo , Óxido Nítrico/metabolismo , Próstata/metabolismo , Arginase/análise , Arginase/genética , Arginina/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Músculo Liso/metabolismo , Fibras Nervosas/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Próstata/inervação , Próstata/cirurgia , Prostatectomia , RNA Mensageiro/metabolismo , Transdução de Sinais
11.
Andrologia ; 51(1): e13150, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30251438

RESUMO

Studies on erectile dysfunction (ED) have revealed a relationship between smooth muscle atrophy and the accumulation of collagen in the corpus cavernosum (CC). Transforming growth factor ß1 (TGF ß1) is a cytokine which has been proposed to be involved in the fibrotic process in the CC. We aimed to evaluate the course of TGF ß1 in the systemic and cavernous blood of 17 healthy males through different phases of the sexual arousal response (exemplified by the penile conditions flaccidity, tumescence, rigidity and detumescence). An enzyme-linked immunoassay was used to measure the concentration of TGF ß1 (ng/ml) in both the systemic and cavernous blood at the stages of flaccidity, tumescence and detumescence. TGF levels were significantly higher in the cavernous compartment than in the systemic blood. A linear decrease was evident in the cavernous blood when the flaccid penis became tumescent (24.3 ± 14.5 to 13.9 ± 6.5) and rigid (to 8.7 ± 3.1). At detumescence, TGF increased to 18.3 ± 10.4. In contrast, the levels in the systemic circulation remained unchanged. The results are in support of the hypothesis that the concentration of TGF ß1 in the CC is regulated by adequate blood flow and oxygenation.


Assuntos
Disfunção Erétil/sangue , Ereção Peniana/fisiologia , Pênis/irrigação sanguínea , Fator de Crescimento Transformador beta1/sangue , Adulto , Humanos , Masculino , Valores de Referência , Adulto Jovem
12.
Andrologia ; 50(7): e13049, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29781087

RESUMO

It has been assumed that ß-endorphin, belonging to the family of opiodergic neuropeptides, might facilitate the inhibition of the male sexual response; however, its role in the control of the penile erectile tissue remains to be elucidated. This study aimed to evaluate in healthy men the course of ß-endorphin in the systemic and cavernous blood through different stages of sexual arousal. Thirty-four (34) men were exposed to erotic stimuli to induce penile tumescence and rigidity. Blood was aspirated from the corpus cavernosum and a cubital vein during the penile conditions flaccidity, tumescence, rigidity and detumescence. Plasma levels of ß-endorphin were determined by means of radioimmunometric methods. The effects of ß-endorphin on isolated human penile erectile tissue were investigated in vitro. ß-endorphin did not induce a contractile response of the cavernous tissue or reverse the contraction induced by noradrenaline. ß-endorphin decreased in the systemic blood when the penis became tumescent and rigid and increased during detumescence. In the cavernous blood, no alterations in ß-endorphin concentrations were observed. The drop in ß-endorphin observed during tumescence and rigidity seems likely to reflect the inhibition of the opioidergic input with the beginning of sexual arousal.


Assuntos
Nível de Alerta/fisiologia , Ereção Peniana/fisiologia , Comportamento Sexual/fisiologia , beta-Endorfina/fisiologia , Adulto , Feminino , Humanos , Masculino , Norepinefrina/farmacologia , Pênis/efeitos dos fármacos , Pessoas Transgênero , beta-Endorfina/sangue
13.
Sex Med Rev ; 5(3): 387-392, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28372960

RESUMO

INTRODUCTION: Radical prostatectomy (RP) is the most common definitive invasive treatment option for localized prostate cancer. Although the different surgical procedures-open RP, laparoscopic RP, and robot-assisted laparoscopic RP-do not differ significantly for the results of postoperative erectile dysfunction (ED) and continence, the fear of losing erectile function (EF) is often an important factor for preoperatively sexually active men when deciding for or against a procedure. AIM: To review the available literature on rehabilitation of EF after RP and to evaluate the value of the "Kiel concept" against different strategies of phosphodiesterase type 5 inhibitor (PDE5i) low-dose treatments. METHODS: A review of the available literature up to January 2017 was undertaken using the key terms postsurgical ED, penile rehabilitation," PDE5i rehabilitation, and PDE5i daily dose treatment. MAIN OUTCOME MEASURES: As a main outcome measure we chose reviewed different concepts on the rehabilitation of EF after RP, taking into account the clinical background of the Kiel concept. RESULTS: The different therapeutic concepts for rehabilitation of EF after nerve-sparing RP are surprising. The most frequently applied method is application of different PDE5is. Despite different studies on efficacy, the issue of an optimal concept remains unresolved. The reason for this, among others, can be found in the difficulty of comparing different studies, which can vary with respect to the degree of nerve sparing, postoperative preservation of nocturnal erections, concomitant morbidity, and the number and experience of surgeons. CONCLUSION: In 86% of patients, the Kiel concept has been shown to support rehabilitation of EF after nerve-sparing RP with some form of therapeutic method. The Kiel concept is one therapeutic option among other comparable therapeutic options. Osmonov DK, Jünemann KP, Bannowsky A. The "Kiel Concept" of Long-Term Administration of Daily Low-Dose Sildenafil Initiated in the Immediate Post-Prostatectomy Period: Evaluation and Comparison With the International Literature on Penile Rehabilitation. Sex Med Rev 2017;5:387-392.


Assuntos
Disfunção Erétil/reabilitação , Inibidores da Fosfodiesterase 5/uso terapêutico , Prostatectomia/efeitos adversos , Citrato de Sildenafila/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Humanos , Masculino
14.
Expert Opin Investig Drugs ; 23(11): 1477-83, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25096243

RESUMO

INTRODUCTION: Over the last 20 years, basic and clinical research activities studying the male and female sexual responses have led to several pharmacological options to treat male erectile dysfunction (ED) and female arousal and orgasmic disorders. While some strategies exclusively focus on peripheral mechanisms--such as nitric oxide/cyclic GMP signaling, which is known to play a role in the control of genital vascular and nonvascular smooth muscle--others have considered the central pathways involved in mediating arousal and orgasmic functions in females as well as the induction of penile erection in males. Aside from dopaminergic agonists, drugs known to target the central melanocortin system have also been assumed to have a promising potential in the treatment of female and male sexual dysfunctions. AREAS COVERED: The present review summarizes the achievements that have been made in the clinical development of melanocortin receptor (MCR) agonists (melanotan I, melanotan II, bremelanotide) for the treatment of symptoms of sexual arousal and orgasmic disorders in adult females and ED in males. EXPERT OPINION: The data available at present have facilitated our understanding of how the melanocortin pathway regulates both the male and female sexual functions. Indeed the data warrant further investigation to demonstrate the impact of the activation of MCRs by specific agonists on penile erection and female arousal and orgasm function.


Assuntos
Disfunção Erétil/tratamento farmacológico , Receptores de Melanocortina/agonistas , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Adulto , Animais , Desenho de Fármacos , Disfunção Erétil/fisiopatologia , Feminino , Humanos , Masculino , Terapia de Alvo Molecular , Ereção Peniana/efeitos dos fármacos , Disfunções Sexuais Psicogênicas/fisiopatologia
15.
Eur J Pharmacol ; 741: 330-5, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25160741

RESUMO

Experimental and clinical studies have suggested a role for phosphodiesterase (PDE) isoenzymes in the control of the human lower urinary tract. This study aimed to investigate the expression of PDE isoenzymes and the effects of PDE inhibitors (PDE-Is) in isolated human urethral smooth muscle (USM). The expression of messenger ribonucleic acid (mRNA) specifically encoding for PDE isoenzymes and isoforms (1A, 1B, 1C, 2A, 4A, 4B, 4C, 4D, 5A and 11A) was analyzed by means of reverse transcriptase polymerase chain reaction (RT-PCR). Using a tissue bath technique, the effects of vinpocetine (PDE1-I), erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA-HCl=MEP1) (PDE2-I), rolipram (PDE4-I), sildenafil, vardenafil and tadalafil (PDE5-Is) (0.01-10µM) on the tension of USM induced by norepinephrine were investigated. The production of cyclic guanosine monophosphate (cyclic GMP) and cyclic adenosine monophosphate (cyclic AMP) was measured by means of radioimmunoassays. RT-PCR analysis revealed the expression of PDE1B, PDE1C, PDE4A, PDE4C, PDE4D, PDE5A and PDE11A. The tension induced by norepinephrine (NE) was reversed by the PDE inhibitors with the following rank order of efficacy: rolipram (mean: -39%)≥sildenafil (-35%)>vardenafil (-26%)>tadalafil (-20%)>vinpocetine (-16%)>MEP1 (-2%). The relaxing effects of the drugs were paralleled by an elevation in tissue levels of cyclic AMP and cyclic GMP. Selective inhibitors of PDE4 and PDE5 can antagonize the tension induced by alpha-adrenergic stimulation of USM. PDE inhibition might represent an interesting option to facilitate the relaxation of the human outflow region.


Assuntos
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Uretra/enzimologia , Adulto , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Masculino , Pessoa de Meia-Idade , Músculo Liso/efeitos dos fármacos , Músculo Liso/enzimologia , Técnicas de Cultura de Órgãos , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Diester Fosfórico Hidrolases/metabolismo , Uretra/efeitos dos fármacos
16.
J Sex Med ; 9(5): 1448-53, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22462626

RESUMO

INTRODUCTION: Several treatment regimens for rehabilitation of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) are currently discussed. The optimal and most cost-effective therapy is still not found yet. AIM: To evaluate the effect of vardenafil, a PDE5 inhibitor, dose escalation on recovery of EF after unilateral nsRP. METHODS: Thirty-six sexually active patients received a unilateral nsRP. All patients completed an International Index of Erectile Function-5 items (IIEF-5) questionnaire concerning EF preoperatively. Group 1 (N = 12 patients) received vardenafil 5 mg/day vs. group 2 (N = 12) who received vardenafil 10 mg/day at night beginning the day of catheter removal. A control of 12 patients underwent follow-up without PDE5 inhibitors. MAIN OUTCOME MEASURE: The IIEF-5 was the primary end point. IIEF-5 questionnaires were completed at baseline, 3, 6, and 12 months after nsRP. RESULTS: In group 1 (5 mg/day vardenafil) the IIEF-5 score decreased from a preoperative 22.4 mean score to 4.2 at 3 months, 8.9 at 6 months, and 13.4 mean score at 12 months after nsRP vs. preoperative 22.8, 4.1 at 3 months, 7.9 at 6 months, and 12.8 mean score at 12 months in group 2 (10 mg/day vardenafil). In the control group the preoperative IIEF-5 mean score of 21.9 decreased to 3.8 at 3 months, 6.1 at 6 months, and 8.9 at 12 months. Statistical evaluation showed significant difference in IIEF-5 score and time to recovery of EF between groups 1 and 3 and between groups 2 and 3 (P < 0.01). No statistical differences were found between groups 1 and 2. CONCLUSIONS: Daily low-dose vardenafil lead to significant improvement of recovery of EF. In this study doubling the dosage did not improve the recovery of EF further.


Assuntos
Disfunção Erétil/tratamento farmacológico , Imidazóis/uso terapêutico , Ereção Peniana/efeitos dos fármacos , Inibidores da Fosfodiesterase 5/uso terapêutico , Piperazinas/uso terapêutico , Prostatectomia/efeitos adversos , Idoso , Relação Dose-Resposta a Droga , Disfunção Erétil/etiologia , Humanos , Imidazóis/administração & dosagem , Masculino , Pessoa de Meia-Idade , Inibidores da Fosfodiesterase 5/administração & dosagem , Piperazinas/administração & dosagem , Prostatectomia/métodos , Sulfonas/administração & dosagem , Sulfonas/uso terapêutico , Inquéritos e Questionários , Triazinas/administração & dosagem , Triazinas/uso terapêutico , Dicloridrato de Vardenafila
17.
J Oncol ; 2009: 241270, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20069045

RESUMO

Cystic epithelial-stromal tumors of the prostate are rare, with 82 cases reported in literature. These cases have been published under a variety of diagnoses, including phyllodes tumor and prostatic stromal proliferation of uncertain malignant potential as well as a malignant tumor called "prostatic stromal sarcoma". We report a case of a 60-year-old man with the histological diagnosis of phyllodes tumor of the prostate in transurethral resection specimen.

18.
Cases J ; 1(1): 320, 2008 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-19014708

RESUMO

Iatrogenic fornix rupture caused during retrograde manipulation of the ureter is a rather rare or rarely diagnosed phenomenon. A 22 year-old female patient presented with a fornix rupture following endoscopic ureteral stone extraction under uretero-renoscopy, the rupture having become symptomatic two days later.

19.
World J Urol ; 26(6): 623-6, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18629503

RESUMO

OBJECTIVES: Sacral neuromodulation having become established as an essentially effective new therapeutic modality, both in patients with anticholinergic-therapy refractory overactive bladder (OAB) and with chronic urinary retention. It is important to establish which patients might profit from this kind of therapy in order to ensure, by means of a peripheral nerve evaluation (PNE) test, that the implantation of a permanent stimulating device is effective. In a retrospective study we compared the urodynamic outcome of two different techniques (implantation of the permanent neurostimulation electrodes so-called "two-stage-implantation" vs. conventional PNE). METHODS: We performed a sacral nerve stimulation in 53 patients (30 urinary retention, 23 OAB syndrome). In 42 patients, we performed a conventional PNE, 11 patients received "two-stage-implantation" with implantation of the permanent electrodes. RESULTS: In 20 cases the conventional PNE-test (cPNE) was successful (47.6% of all cPNE). The response rate of "two-stage-implantation" (permanent electrodes) was 81.8%. In patients with overactive bladder the bladder capacity was increased by 30% with cPNE (P = 0.068) versus 52% when permanent electrodes were used (P = 0.017). Bladder instabilities were reduced by ca. 75%. In urinary retention, the cPNE versus permanent electrodes led to an increase of the maximum detrusor pressure by 68 versus 94% with reduction of residual urine by 71% (P = 0.068) versus 66% (P = 0.042). CONCLUSIONS: The results of this study show that application of permanent quadripolar electrodes during PNE prior to chronic neuromodulator implantation leads to significantly higher responder rates and enables more efficient patient selection.


Assuntos
Terapia por Estimulação Elétrica/métodos , Bexiga Urinária Hiperativa/diagnóstico , Bexiga Urinária Hiperativa/terapia , Urodinâmica , Eletrodos Implantados , Feminino , Humanos , Plexo Lombossacral/fisiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Bexiga Urinária/inervação , Bexiga Urinária/fisiologia
20.
BJU Int ; 101(10): 1279-83, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18284406

RESUMO

OBJECTIVE: To evaluate the effect of low-dose sildenafil for rehabilitating erectile function after nerve-sparing radical prostatectomy (NSRP), as the delay to recovery of erectile function after NSRP remains under debate. PATIENTS AND METHODS: Forty-three sexually active patients had a NSRP; at 7-14 days after surgery they had a Rigiscan (Dacomed Corporation, Minneapolis, MN, USA) measurement of nocturnal penile tumescence and rigidity (NPTR). To support the recovery of spontaneous erectile function, 23 patients with preserved nocturnal erections received sildenafil 25 mg/day at night. A control group of 18 patients were then followed but had no phosphodiesterase-5 inhibitors. The International Index of Erectile Function (IIEF)-5 questionnaire was completed 6, 12, 24, 36 and 52 weeks after NSRP. RESULTS: Of the 43 patients, 41 (95%) had one to five erections during the first night after catheter removal. In the group using daily sildenafil the mean IIEF-5 score decreased from 20.8 before NSRP to 3.6, 3.8, 5.9, 9.6 and 14.1 at 6, 12, 24, 36 and 52 weeks after NSRP, respectively. In the control group the respective scores were 21.2, decreasing to 2.4, 3.8, 5.3, 6.4 and 9.3. There was a significant difference in IIEF-5 score and time to recovery of erectile function between the groups (P < 0.001), with potency rates of 86% vs 66%. CONCLUSION: The measurement of NPTR after NSRP showed erectile function even the 'first' night after catheter removal. In cases of early penile erection, daily low-dose sildenafil leads to a significant improvement in the recovery of erectile function.


Assuntos
Disfunção Erétil/prevenção & controle , Ereção Peniana/efeitos dos fármacos , Pênis/inervação , Inibidores de Fosfodiesterase/administração & dosagem , Piperazinas/administração & dosagem , Prostatectomia/reabilitação , Sulfonas/administração & dosagem , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana/fisiologia , Pênis/cirurgia , Prostatectomia/métodos , Neoplasias da Próstata/reabilitação , Neoplasias da Próstata/cirurgia , Purinas/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Citrato de Sildenafila , Inquéritos e Questionários , Resultado do Tratamento
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