RESUMO
AIMS: The objective of this study was to evaluate the similarities and differences of the urethral morphological and functional changes following external urethral sphincter EUS injury in male and female rats. METHODS: 30 female and 30 male age-matched Wistar rats were used in the experiments. Half of them underwent electrocauterization of the surrounding tissues lateral to the urethra at the level of the (EUS) and the others, a sham operation. At 2, 6, and 16 weeks after surgeries they underwent anesthetized cystometry, measurement of leak point pressure (LPP) and their urethras were harvested for morphological analyses. RESULTS: There were no differences in cystometric parameters between sex-time-matched animals, ensuring normal bladder function in the manipulated animals. The mean LPP in male and female rats was lower compared with sham animals. Age-time-matched sham operated male rats exhibited a higher LPP compared with female rats. The reduction in LPP comparing electrocauterized and sham time-matched animals was more pronounced in male rats than in female rats. Electrocauterization produced urethral collagen deposition and nerve damage in both male and female animals. Muscle atrophy and disruption also occurred, being more evident in female rats. CONCLUSIONS: The urethras of male and female rats exhibited a similar morphological and functional response to electrocauterization. The time-course evaluation revealed that the male animal model is as reliable, reproducible and long-lasting as the female model. Intact males had a higher LPP than female rats and the nerve injury led to a more drastic impairment of this mechanism.
Assuntos
Uretra/lesões , Incontinência Urinária por Estresse/etiologia , Animais , Colágeno/metabolismo , Modelos Animais de Doenças , Eletrocoagulação , Feminino , Fibrose , Masculino , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Pressão , Ratos Wistar , Fatores Sexuais , Fatores de Tempo , Uretra/inervação , Uretra/metabolismo , Uretra/fisiopatologia , Incontinência Urinária por Estresse/metabolismo , Incontinência Urinária por Estresse/patologia , Incontinência Urinária por Estresse/fisiopatologia , UrodinâmicaRESUMO
PURPOSE OF REVIEW: Improved understanding of the pathogenesis of lower urinary tract symptoms (LUTS) has led to the development of new drugs to treat male LUTS. The review aims to give an overview to the new drugs and to compounds in the pipeline. RECENT FINDINGS: Tadalafil, a phosphodiesterase type 5 inhibitor, is a drug newly approved for the treatment of male LUTS and a true new challenger for the current standard treatment with alpha1 blockers, particularly in men with concomitant erectile dysfunction. Botulinum toxin and mirabegron, a beta3 agonist, might be of value in treating persistent storage LUTS. Intraprostatic injections with botulinum toxin, NX-1207, and PRX302, need further evaluation but might be treatment alternatives in the future. Similarly, vitamin D3 receptor analogues (e.g., elocalcitol), gonadotropin-releasing hormone antagonists (e.g., cetorelix), and modulators of the cannabinoid system (e.g., fatty acid amide hydrolase inhibitors) need further evaluation in clinical studies. Other compounds, such as transient receptor potential vanilloid antagonists, Rho kinase inhibitors, purinergic receptor blockers, and endothelin targeting drugs, are still at experimental stages. SUMMARY: Novel drugs for the treatment of male LUTS have been introduced recently. Clinical practice along with further trials will have to prove their value, along with other compounds that are still in their early phase of development.
Assuntos
Drogas em Investigação/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Inibidores de 5-alfa Redutase/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Animais , Drogas em Investigação/efeitos adversos , Humanos , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Antagonistas Muscarínicos/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Resultado do Tratamento , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Agentes Urológicos/efeitos adversosRESUMO
PURPOSE: The underlying pathology of radiation cystitis is cellular and vascular damage followed by increased fibrosis and inflammation. This study was to determine if neovascular-promoting therapy could reduce the pathological changes in the bladder wall associated with pelvic irradiation. METHODS: Adult female Lewis inbred rats were irradiated with a single dose of 20 Gy directed at their bladder. Four weeks later, 30 rats were divided equally into one of three treatment groups for bladder wall injection of: (1) PBS (Control); (2) PBS containing 50 ng vascular endothelial growth factor (VEGF (165)); or (3) PBS containing 1 × 10(6) rat endothelial cells (EC). Age-matched non-irradiated rats (n = 10) served as untreated controls. At either 1.5 or 3 months following radiation, bladders were analyzed for collagen deposition using Masson's Trichrome staining of collagen and muscle and vascularization using Von Willebrand factor staining of ECs. Quantitative-PCR was used to examine markers of angiogenesis, hypoxia, and fibrosis. RESULTS: The collagen/muscle ratio was doubled in the control group 3 months post-irradiation (P < 0.05 vs. non-irradiated bladders). Both ECs and VEGF inhibited increases in collagen content (P < 0.05 vs. control). Similarly, irradiation reduced bladder wall vessel counts compared to non-irradiated controls (P < 0.05) and both ECs and VEGF maintained vessel counts similar to that of non-irradiated controls (P < 0.05). PCR analysis showed a higher expression of neovascular markers (CD31, KDR) in the EC and VEGF groups compared to non-irradiated controls (P < 0.05). CONCLUSIONS: Angiogenesis therapy may be useful in the prevention and/or treatment of the underlying pathology of radiation cystitis.