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Background: With the ongoing expansion of life-prolonging therapies approved to treat advanced prostate cancer, there is currently an unmet need to better understand real-world treatment patterns and identify optimal treatment sequencing for men with metastatic castration-resistant prostate cancer (mCRPC). Methods: In this retrospective, observational cohort analysis, patients with confirmed mCRPC were identified in the Auditron claims database and used to describe mCRPC treatment patterns and trends in the Brazilian private healthcare system from 2014 to 2019. Demographics and clinical characteristics, prostate cancer stage at diagnosis, and type and number of treatment lines were evaluated. The primary endpoint was identification of the drugs used in first-line therapies in mCRPC, and the secondary endpoint included a description of sequential lines of therapy (second and third lines) in mCRPC. Results: A total of 168 electronic patient records were reviewed. Docetaxel was the most frequently used first-line treatment (35.7%), followed by abiraterone (33.3%) and enzalutamide (13.1%). Docetaxel, abiraterone, and enzalutamide also accounted for 34.6%, 28.0%, and 15.0%, respectively, of second-line therapies. In third-line therapies, cabazitaxel (26.1%), enzalutamide (23.9%), docetaxel (15.2%), and abiraterone (15.2%) were most commonly prescribed. Irrespective of stage at diagnosis, treatment patterns were similar once the disease progressed to the metastatic castration-resistance stage. Conclusions: Docetaxel was the most frequently utilized therapy for mCRPC treatment, followed by abiraterone and enzalutamide. Although the current analyses provide real-world insights into treatment patterns for patients with mCRPC in Brazil, additional real-world data are needed to further validate and expand on these findings.
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Objective: To evaluate the effect of individual lower urinary tract symptoms (LUTS) and LUTS-specific bother on daily/leisure activities, work productivity and treatment behaviors and satisfaction in a Brazilian population reporting symptoms of the overactive bladder (OAB) syndrome.Methods: Secondary analysis of Brazil LUTS study data, including individuals ≥40 years old with a possible diagnosis of OAB, based on a score of ≥8 on the OAB-V8 questionnaire. Participants used a 5-point Likert scale to rate occurrence of LUTS during the previous month. Regression models were constructed to analyze association of symptom frequency and bother, controlled for demographics, comorbid conditions, habits and body mass index, to outcomes related to people's lives and treatment patterns.Results: This analysis included 5184 individuals (53% female), 24.4% of whom received a possible diagnosis of OAB. There was a greater likelihood of OAB symptoms in men reporting depression/anxiety (2.0 times), diabetes (1.8 times), or constipation (1.9 times) and women reporting depression/anxiety (2.6 times), constipation (1.7 times), and being overweight (1.4 times) or obese (1.8 times). Symptoms of all categories, including voiding, storage, and post-micturition, were associated with a negative impact on individuals' lives, quality of life and treatment-related outcomes. Treatment seeking for OAB was low among men and women overall (35.1 and 43.6%, respectively), with highest rates among individuals in the 60-69 age group.Conclusions: LUTS of all categories impacted all domains studied. These results highlight the importance of comprehensive LUTS assessment in OAB patients, including voiding, storage and post-micturition symptoms.
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Eficiência , Sintomas do Trato Urinário Inferior/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Qualidade de Vida , Bexiga Urinária Hiperativa/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Objetivo: Avaliar a relação de custo-efetividade de mirabegrona como tratamento de primeira escolha de pacientes adultos com síndrome da bexiga hiperativa (SBH) comparada a antimuscarínicos orais comumente prescritos no manejo dessa condição. Métodos: O modelo de Markov foi utilizado, com ciclos mensais e horizonte temporal de um ano, para analisar a relação de custo-efetividade de mirabegrona em comparação a tolterodina, oxibutinina, darifenacina e solifenacina. Os pacientes iniciaram o modelo em tratamento com mirabegrona ou um dos comparadores, sendo distribuídos em cinco níveis de gravidade da doença, de acordo com a frequência miccional e número de episódios de incontinência, e a cada ciclo mensal poderiam melhorar, piorar ou permanecer no mesmo nível de severidade do ciclo anterior. Os resultados foram apresentados por meio de uma razão de custo-efetividade incremental. Resultados: Considerando a perspectiva do sistema de saúde suplementar, o custo total do tratamento com mirabegrona foi de R$ 2.455,26 e os parâmetros de efetividade em 0,491 e 0,498 (melhora na gravidade da incontinência e frequência miccional, respectivamente), sendo mais efetivo que os comparadores. Com relação à perspectiva pública, foi estimado um custo com o tratamento de R$ 1.396,01, com características similares de efetividade. De maneira geral, o tratamento com mirabegrona foi dominante quando comparado à tolterodina e custo-efetivo na comparação com os demais antimuscarínicos, em ambas as perspectivas analisadas. Conclusão: Mirabegrona demonstrou ser a melhor opção para tratamento de primeira escolha da SBH com potencial de redução de custos ao longo do tempo, tanto para o sistema público quanto para o sistema de saúde suplementar brasileiro.
Objective: To assess the cost-effectiveness of mirabegron as first-choice treatment in adult patients with of overactive bladder (OAB) compared to oral antimuscarinics, usually prescribed for this condition. Methods: A Markov model has been adopted, with monthly cycles and a one-year time horizon, to analyze the cost-effectiveness of mirabegron compared to antimuscarinic agents: tolterodine; oxybutynin; darifenacin; and solifenacin. The model started with patients receiving treatment with mirabegron or one of the comparators and then, they were assigned to five disease severity levels according to micturition frequency and number of incontinence episodes, and within each monthly cycle they could improve, worsen or remain at the same symptom severity level. Results were presented using an incremental cost-effectiveness ratio. Results: Considering the Brazilian private perspective, treatment with mirabegron resulted in a total cost of R$ 2,455.26 and effectiveness parameters at 0.491 and 0.498 (improvement in incontinence severity and micturition, respectively), being more effective than the comparators. Regarding the Brazilian public perspective, treatment with mirabegron resulted in a total cost of R$ 1,396.01 with similar effectiveness estimation. In general, a dominance was observed when mirabegron was compared to tolterodine and a cost-effectiveness profile against the other muscarinic antagonists, considering both health perspectives. Conclusion: Mirabegron has proven to be the best option for OAB first-line treatment with potential cost savings over time for both the public and private health care systems in Brazil.
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Bexiga Urinária , Análise Custo-Benefício , Agonistas Adrenérgicos beta , Antagonistas Muscarínicos , Bexiga Urinária HiperativaRESUMO
INTRODUCTION: Lower urinary tract symptoms (LUTS) affect ≥60% of adult men and are associated with erectile dysfunction (ED) and sexual dissatisfaction. AIM: The aim of this study was to evaluate the relationship among male LUTS, ED, and sexual satisfaction. METHODS: This was a secondary analysis of the Brazil LUTS study, a cross-sectional, epidemiological survey conducted by telephone interview in 5 cities in Brazil. This analysis included men aged ≥40 years. MAIN OUTCOME MEASURE: LUTS were identified using International Continence Society definitions. LUTS severity was assessed using the International Prostate Symptom Score questionnaire. Erectile function was assessed using the International Index of Erectile Function-5 (IIEF-5) questionnaire and sexual satisfaction was rated on a 5-point scale. RESULTS: 2,433 men participated in the study. Of 2,183 men reporting data on LUTS, 873 (40%) had LUTS "about half the time" or more. The prevalence of ED and sexual dissatisfaction was 14.4% and 7.8%, respectively. The proportion of men reporting ED and sexual dissatisfaction was higher among men with LUTS (24.6% and 13.8%, respectively) than men without LUTS (8.7% and 4.5%, respectively; P < .001). LUTS severity was negatively correlated with IIEF-5 scores (r = -0.199; P < .001); we estimated a 0.431-point decrease in IIEF-5 score per 3-point increase in International Prostate Symptom Score. Increased age and the presence of LUTS were associated with a greater chance of ED and sexual dissatisfaction; depression/anxiety and diabetes were associated with a greater chance of sexual dissatisfaction only. Among men with LUTS, urgency with fear of leaking, urgency urinary incontinence, and nocturnal enuresis were associated with a greater chance of ED, whereas slow stream and urgency urinary incontinence were associated with a greater chance of sexual dissatisfaction. CONCLUSION: These results demonstrate that the presence of LUTS is associated with an increased chance of ED and sexual dissatisfaction in Brazilian men and reinforce the importance of a comprehensive assessment of these conditions. Gomes CM, Averbeck MA, Koyama M, et al. Association Among Lower Urinary Tract Symptoms, Erectile Function, and Sexual Satisfaction: Results from the Brazil LUTS Study. Sex Med 2019;8:45-56.
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AIMS: To report on the impact of lower urinary tract symptoms (LUTS) on treatment-related behaviors and quality of life in Brazilian adults greater than or equal to 40 years. METHODS: Data were from a computer-assisted telephone survey conducted in Brazil between 1 September and 31 December 2015 (Brazil LUTS study). Participants were adults greater than or equal to 40 years with landlines living in major cities from five geographical regions in Brazil. Participants rated how often they experienced individual LUTS during the previous month and associated bother, and the impact on quality of life (QoL), treatment seeking, treatment, treatment satisfaction, and treatment discontinuation. Multiple logistic regression models were adjusted to analyze the simultaneous effects of predictor variables on each dependent variable. RESULTS: When the presence of LUTS was defined as symptoms occurring less than half the time or more, one-quarter of respondents sought treatment but 6% fewer actually received treatment. Of these, around 25% reported dissatisfaction with treatment and almost 10% reported treatment discontinuation. The occurrence of some symptoms and, in particular, the resultant bother were significantly related to worse QoL and to treatment-related outcomes, such as treatment seeking, actual treatment, treatment dissatisfaction, and treatment discontinuation. Symptoms of all three categories were associated with all these domains for both sexes. CONCLUSIONS: This is the first population-based study carried out in South America showing that treatment seeking and treatment rates for LUTS are low. Since the LUTS prevalence is high, this reinforces the importance of a comprehensive medical assessment, focusing on the resulting bother, for more appropriate and personalized patient management.
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Sintomas do Trato Urinário Inferior/terapia , Aceitação pelo Paciente de Cuidados de Saúde , Satisfação do Paciente , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Feminino , Humanos , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
OBJECTIVES: To compare reconstructed area and surface roughness of 3D models acquired using nine image acquisition protocols. Radiation dose was also compared among acquisition protocols. METHODS: A dry craniofacial specimen was scanned using three CT devices (a cone beam CT, a 16-channel fan beam CT, and a 64-channel fan beam CT), with three different acquisition protocols each. Nine 3D models were manufactured using polylactic acid. Surface roughness and reconstructed area were determined for each 3D model. The radiation dose during acquisitions was measured using lithium crystals. ANOVA was used to compare the data among the 3D models. Linear function optimization techniques based on stochastic variables were applied to identify the most suitable protocol for use. RESULTS: For surface roughness, statistically significant differences were observed among all 3D models and the specimen. For reconstructed area, CBCT and one CT-16 channel protocols originated 3D models statistically significant different from the specimen. Higher radiation doses were observed with fan beam CT acquisitions. CONCLUSIONS: All three CT devices were suitable for 3D printing when used at full resolution. The highest reconstruct area vs. radiation dose ratio was found for 64-channel CT devices.
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AIMS: The objective of this study was to evaluate the expression of bladder receptors in patients with defunctionalized bladder (DB) and to assess voiding behavior after refunctionalization. METHODS: A total of 68 pretransplant patients were divided in two groups: DB (diuresis <300 mL/24 h; n = 33) and NDB (non-DB; diuresis ≥300 mL/24 h; n = 35). A sample of mucosa and detrusor at the site of the future ureteral implantation was collected. The following receptors were assessed by real-time polymerase chain reaction (qRT-PCR): M2 , M3 , α1D , ß3 , P2X2 , P2X3 , TRPV1, TRPV4, TRPA1, and TRPM8. At 3, 6, and 12 months after transplant patients answered IPSS and ICIQ-OAB questionnaires and filled a 3-day 24 h frequency/volume chart (FVC) at 6 and 12 months. RESULTS: The expression of all receptors in the mucosa and in the detrusor was similar in both groups, except from α1D , which was overexpressed in the detrusor of DB relatively to NDB group. ICIQ-OAB symptom score was similar between the groups at 3, 6, and 12 months. There was a reduction of this score in both groups with time. The same pattern was found for IPSS score. Bother scores were similar between groups. No difference was observed for all FVC parameters between DB and NDB patients. CONCLUSION: Gene expression of bladder receptors involved in micturition control was similar in patients with or without DB. Bladder behavior had a similar pattern independently of pretransplant residual diuresis. These findings question the relevance of the term DB in pretransplant patients.
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Transplante de Rim/efeitos adversos , Transplantados , Doenças da Bexiga Urinária/fisiopatologia , Micção , Adulto , Feminino , Expressão Gênica , Humanos , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Mucosa/efeitos dos fármacos , Período Pós-Operatório , Inquéritos e Questionários , Bexiga Urinária/inervação , UrodinâmicaRESUMO
AIMS: We performed the first large population-based study to evaluate lower urinary tract symptoms (LUTS) in Brazil. The study objective was to assess the prevalence and bother of LUTS in the population aged ≥40 years in five major cities of Brazil. METHODS: This study was conducted as a telephone survey with assessment of LUTS using a standardized protocol, which included the International Prostate Symptom Score (IPSS) and, for overactive bladder (OAB), the OAB-V8 questionnaire. Participants were asked to rate how often they experienced individual LUTS and the degree of associated bother. RESULTS: Of the 5184 participants, 53% were women, and the age group with most participants (34%) was 50-59 years. The prevalence of LUTS (symptoms occurring less than half the time or more) was 75%: 69% in men and 82% in women. There was a statistically significant association between the frequency and bother intensity of each symptom (P < 0.001). The prevalence of OAB was similar in men and women (25% and 24%, respectively). According to the IPSS questionnaire, moderate-to-severe symptoms were present in 21% of men and 24% of women. LUTS detrimentally affected quality of life in many individuals: 39% would be "mostly dissatisfied," "unhappy," or consider it "terrible" to spend the rest of their life with their urinary condition as it is currently. CONCLUSIONS: This was the first nationwide, population-based epidemiological study of LUTS to be performed in Brazil. LUTS are highly prevalent and often bothersome among men and women aged ≥40 years.
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Sintomas do Trato Urinário Inferior/epidemiologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
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.
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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
Al enfrentarnos a casos que tienen relación con tumores de cabeza y cuello, hay que tener en cuenta la gran diversidad de presentaciones de las neoplasias, histopatología y topografía anatómica de las mismas. Sumado a esto intervendrán factores etiológicos o de riesgo, que darán distintas características epidemiológicas, sintomatológicas, tanto en la forma de progresión de la enfermedad, como en su pronóstico y plan de tratamiento. En este trabajo los autores presentan un caso clínico de una paciente femenino de 25 años con una maxilectomia, por mixoma odontogénico, en su variable histológica de Fibromixoma Odontogénico, ubicado en el seno maxilar derecho. El tratamiento rehabilitador protésico, se realiza con una prótesis obturatriz esquelética, preparando los pilares paralelizados, con los principios de un eje único y preciso de inserción y retiro...
When dealing with neck and head cancer patients, we must consider the many different types of such tumors that appear when conducting histopathologic and anatomic topography assessment. To this we must add etiological or risk factors that will result in various epidemiological and symptomatological characteristics, both regarding the progression of the disease and the prognosis and treatment plan. In this work a clinical case is presented: a 25-year-old female patient who underwent right maxillectomy for an odontogenic myxoma (fibromyxoma) located in her right maxillary sinus. Prosthetic rehabilitation is done with framework obturator prosthesis. The remaining teeth are prepared by creating parallel pillars to obtain a single and accurate axis for insertion and removal...
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Humanos , Implante de Prótese Maxilofacial , Neoplasias Maxilares/cirurgia , Prótese MaxilofacialRESUMO
INTRODUCTION: Painful bladder syndrome/interstitial cystitis (PBS/IC) pathogenesis is not fully known, but evidence shows that glycosaminoglycans (GAG) of bladder urothelium can participate in its genesis. The loss of these compounds facilitates the contact of urine compounds with deeper portions of bladder wall triggering an inflammatory process. We investigated GAG in urine and tissue of PBS/IC and pure stress urinary incontinence (SUI) patients to better understand its metabolism. MATERIALS AND METHODS: Tissue and urine of 11 patients with PBS/IC according to NIDDK criteria were compared to 11 SUI patients. Tissue samples were analyzed by histological, immunohistochemistry and immunofluorescence methods. Statistical analysis were performed using t Student test and Anova, considering significant when p < 0.05. RESULTS: PBS/IC patients had lower concentration of GAG in urine when compared to SUI (respectively 0.45 ± 0.11 x 0.62 ± 0.13 mg/mg creatinine, p < 0.05). However, there was no reduction of the content of GAG in the urothelium of both groups. Immunofluorescence showed that PBS/IC patients had a stronger staining of TGF-beta, decorin (a proteoglycan of chondroitin/dermatan sulfate), fibronectin and hyaluronic acid. CONCLUSION: the results suggest that GAG may be related to the ongoing process of inflammation and remodeling of the dysfunctional urothelium that is present in the PBS/IC.
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Cistite Intersticial/metabolismo , Glicosaminoglicanos/metabolismo , Incontinência Urinária por Estresse/metabolismo , Adulto , Idoso , Biópsia , Creatinina/urina , Cistite Intersticial/patologia , Feminino , Imunofluorescência , Glicosaminoglicanos/análise , Humanos , Ácido Hialurônico/urina , Imuno-Histoquímica , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Bexiga Urinária/patologia , Incontinência Urinária por Estresse/patologia , Urotélio/metabolismo , Urotélio/patologiaRESUMO
Introduction: Painful bladder syndrome/interstitial cystitis (PBS/IC) pathogenesis is not fully known, but evidence shows that glycosaminoglycans (GAG) of bladder urothelium can participate in its genesis. The loss of these compounds facilitates the contact of urine compounds with deeper portions of bladder wall triggering an inflammatory process. We investigated GAG in urine and tissue of PBS/IC and pure stress urinary incontinence (SUI) patients to better understand its metabolism. Materials and Methods: Tissue and urine of 11 patients with PBS/IC according to NIDDK criteria were compared to 11 SUI patients. Tissue samples were analyzed by histological, immunohistochemistry and immunofluorescence methods. Statistical analysis were performed using t Student test and Anova, considering significant when p < 0.05. Results: PBS/IC patients had lower concentration of GAG in urine when compared to SUI (respectively 0.45 ± 0.11 x 0.62 ± 0.13 mg/mg creatinine, p < 0.05). However, there was no reduction of the content of GAG in the urothelium of both groups. Immunofluorescence showed that PBS/IC patients had a stronger staining of TGF-beta, decorin (a proteoglycan of chondroitin/dermatan sulfate), fibronectin and hyaluronic acid. Conclusion: the results suggest that GAG may be related to the ongoing process of inflammation and remodeling of the dysfunctional urothelium that is present in the PBS/IC. .
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Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Cistite Intersticial/metabolismo , Glicosaminoglicanos/metabolismo , Incontinência Urinária por Estresse/metabolismo , Biópsia , Creatinina/urina , Cistite Intersticial/patologia , Imunofluorescência , Glicosaminoglicanos/análise , Ácido Hialurônico/urina , Imuno-Histoquímica , Reação em Cadeia da Polimerase em Tempo Real , Bexiga Urinária/patologia , Incontinência Urinária por Estresse/patologia , Urotélio/metabolismo , Urotélio/patologiaRESUMO
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.
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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
BACKGROUND: The pathophysiology of male lower urinary tract symptoms (LUTS) is highly complex and multifactorial. The shift in perception that LUTS are not sex or organ specific has not been followed by significant innovations regarding the available drug classes. OBJECTIVE: To review pathophysiologic mechanisms and clinical and experimental data related to the development of new pharmacologic treatments for male LUTS. EVIDENCE ACQUISITION: The PubMed database was used to identify articles describing experimental and clinical studies of pathophysiologic mechanisms contributing to male LUTS and, supported by them, new pharmacotherapies with clinical or experimental evidence in the field. EVIDENCE SYNTHESIS: Several pathologic processes (eg, androgen signaling, inflammation, and metabolic factors) and targets (eg, the urothelium, prostate, interstitial cells, detrusor, neurotransmitters, neuromodulators, and receptors) have been implicated in male LUTS. Some newly introduced drugs, such as phosphodiesterase type 5 inhibitors and ß3-adrenergic agonists, have just started broad use in clinical practice. Drugs with potential benefit, such as vitamin D3 receptor analogs, gonadotropin-releasing hormone antagonists, cannabinoids, and drugs injected into the prostate, have been evaluated in experimental studies and have progressed to clinical trials. However, safety and efficacy data for these drugs are still scarce. Some compounds with interesting profiles have only been tested in experimental settings (eg, transient receptor potential channel blockers, Rho-kinase inhibitors, purinergic receptor blockers, and endothelin-converting enzyme inhibitors). CONCLUSIONS: New pathophysiologic mechanisms of male LUTS are described that lead to the continuous development of new pharmacotherapies. To date, few drugs have been added to the current armamentarium, and several are in various phases of clinical or experimental investigation.
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Descoberta de Drogas/tendências , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Terapia de Alvo Molecular , Agentes Urológicos/uso terapêutico , Animais , Previsões , Humanos , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/metabolismo , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Transdução de Sinais/efeitos dos fármacos , Resultado do TratamentoRESUMO
La rehabilitación integral del paciente mutilado facial implica un gran desafío, el poderle brindar un tratamiento económicamente accesible y en el mismo medio donde el paciente vive es de importancia capital.Independientemente de la cobertura de salud que el paciente tenga, de su nivel socioeconómico ó de su lugar de residencia en el territorio nacional.El objetivo de este artículo es la divulgación de los logros alcanzados en la descentralización de la Prótesis Buco Maxilo Facial en nuestro País, fruto del trabajo conjunto entre dos Instituciones, la Universidad de la República y la Administración de los Servicios de Salud del Estado.
The rehabilitation of facial maimed patients, means a great challenge. The chance to provide accessible and economic care in the same environment where the patient lives, is paramount, regardless the health coverage the patient might have, his socioeconomic status residence place in the country.The aim of this article is the dissemination of the achievements of the decentralization of Maxillofacial Prosthetics care, that is a joint work between of two institutions, the University of the Republic and the Administration of State Health Services.
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Política , Prótese Maxilofacial , Sistemas Locais de SaúdeRESUMO
Among crocodilians, Crocodylus rhombifer is one of the world's most endangered species with the smallest natural distribution. In Cuba, this endemic species coexists with the American crocodile (Crocodylus acutus). Hybridization between these two species is well known in captivity and might occur in the wild, but has never been demonstrated genetically. Here, we combined molecular data with environmental, geographic, and fossil data to infer the evolutionary history of Crocodylus in the Cuban Archipelago, and to evaluate genealogical support for species boundaries. We analyzed seven microsatellite loci plus DNA sequence data from nuclear (RAG-1) and mitochondrial (cytochrome b and cytochrome oxidase I) genes from 89 wild-caught individuals in Cuba, Grand Cayman Island, Jamaica, and Central America, and two samples from zoo collections. Microsatellites showed evidence of introgression, suggesting potential hybridization among Cuban groups. In Cuba, C. acutus contained one mitochondrial DNA (mtDNA) haplotype, whereas C. rhombifer contained two haplotypes. MtDNA data showed that C. acutus is paraphyletic with respect to C. rhombifer, revealing 1% sequence divergence between species within Cuba vs. 8% divergence between Cuban forms and mainland C. acutus. We suggest that hybridization has been a historical as well as a current phenomenon between C. acutus and C. rhombifer. These findings suggest that long-term conservation of crocodiles in Cuba will require identification of genetically pure and hybrid individuals, and a decrease in anthropogenic activities. We also recommend more extensive morphological and genetic analyses of Cuban population to establish clear boundaries of the hybrid zone between C. acutus and C. rhombifer.
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Jacarés e Crocodilos/genética , Evolução Molecular , Alelos , Jacarés e Crocodilos/metabolismo , Animais , Sequência de Bases , Análise por Conglomerados , Conservação dos Recursos Naturais , Cuba , Citocromos b/química , Citocromos b/genética , DNA Mitocondrial/química , DNA Mitocondrial/genética , Complexo IV da Cadeia de Transporte de Elétrons/química , Complexo IV da Cadeia de Transporte de Elétrons/genética , Variação Genética , Proteínas de Homeodomínio/química , Proteínas de Homeodomínio/genética , Hibridização Genética , Repetições de Microssatélites/genética , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase/veterinária , Alinhamento de SequênciaRESUMO
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.
Assuntos
Indutores da Angiogênese/administração & dosagem , Cistite/terapia , Células Endoteliais/transplante , Neovascularização Fisiológica/efeitos dos fármacos , Lesões Experimentais por Radiação/terapia , Bexiga Urinária/irrigação sanguínea , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Administração Intravesical , Análise de Variância , Animais , Colágeno/metabolismo , Cistite/genética , Cistite/metabolismo , Cistite/patologia , Cistite/fisiopatologia , Células Endoteliais/metabolismo , Feminino , Fibrose , Regulação da Expressão Gênica , Neovascularização Fisiológica/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Lesões Experimentais por Radiação/genética , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/fisiopatologia , Ratos , Ratos Endogâmicos Lew , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Fator de von Willebrand/metabolismoRESUMO
PURPOSE: We reproduced a non-bacterial experimental model to assess bladder inflammation and urinary glycosaminoglycans (GAG) excretion and examined the effect of dimethyl sulfoxide (DMSO). MATERIALS AND METHODS: Female rats were instilled with either protamine sulfate (PS groups) or sterile saline (control groups). At different days after the procedure, 24 h urine and bladder samples were obtained. Urinary levels of hyaluronic acid (HA) and sulfated glycosaminoglycans (S-GAG) were determined. Also to evaluate the effect of DMSO animals were instilled with either 50% DMSO or saline 6 hours after PS instillation. To evaluate the effect of DMSO in healthy bladders, rats were instilled with 50% DMSO and controls with saline. RESULTS: In the PS groups, bladder inflammation was observed, with polymorphonuclear cells during the first days and lymphomononuclear in the last days. HA and S-GAG had 2 peaks of urinary excretion, at the 1st and 7th day after PS injection. DMSO significantly reduced bladder inflammation. In contrast, in healthy bladders, DMSO produced mild inflammation and an increase in urinary HA levels after 1 and 7 days and an increase of S-GAG level in 7 days. Animals instilled with PS and treated with DMSO had significantly reduced levels of urinary HA only at the 1st day. Urinary S-GAG/Cr levels were similar in all groups. CONCLUSIONS: Increased urinary levels of GAG were associated with bladder inflammation in a PS-induced cystitis model. DMSO significantly reduced the inflammatory process after urothelial injury. Conversely, this drug provoked mild inflammation in normal mucosa. DMSO treatment was shown to influence urinary HA excretion.
Assuntos
Cistite Intersticial/urina , Glicosaminoglicanos/urina , Ácido Hialurônico/urina , Protaminas/uso terapêutico , Animais , Biomarcadores/urina , Cistite Intersticial/tratamento farmacológico , Dimetil Sulfóxido/farmacologia , Modelos Animais de Doenças , Feminino , Ratos , Ratos WistarRESUMO
PURPOSE: The bladder is normally impermeable to possible hostile environmental factors and toxic urinary wastes. Any disruption of the permeability barrier would permit the leakage of urine constituents into the underlying cells layers and subsequent inflammation. Protamine sulfate, which increases urothelial permeability, is used in experimental models of cystitis. We examined whether protamine sulfate alone could cause bladder inflammation or if the association of protamine sulfate and urine is needed for this condition. MATERIALS AND METHODS: Female Wistar rats (Center for the Development of Experimental Models for Medicine and Biology, Federal University of São Paulo, São Paulo, Brazil) had the bladder catheterized and instilled with protamine sulfate (10 mg) or sterile saline for 30 minutes. To exclude urine other groups of rats underwent bilateral nephrectomy and the same procedure was used. One day after instillation the bladders were removed for histopathology. Edema and vascular congestion were graded from 0-none to 3-severe. Polymorphonuclear and mast cells were counted. The Kruskal-Wallis test was performed for statistical analysis. RESULTS: Intravesical instillation of protamine sulfate in nonnephrectomized rats led to inflammation, in contrast to findings in rats instilled with saline. On the other hand, nephrectomized rats showed no inflammatory changes following the instillation of protamine sulfate or saline. The mast cell count was similar in all groups. CONCLUSIONS: Bladder inflammation in this experimental model of urothelial injury was not due to protamine sulfate alone. The association of protamine sulfate and urine was necessary to trigger the inflammatory cascade. Thus, urine indeed has an important role in the development of bladder inflammation in an environment of higher urothelial permeability.
Assuntos
Cistite Intersticial/patologia , Cistite Intersticial/fisiopatologia , Urina , Urotélio/patologia , Administração Intravesical , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Inflamação/patologia , Inflamação/fisiopatologia , Mastócitos/patologia , Nefrectomia , Probabilidade , Protaminas/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Sensibilidade e EspecificidadeRESUMO
PURPOSE: We reproduced a non-bacterial experimental model to assess bladder inflammation and urinary glycosaminoglycans (GAG) excretion and examined the effect of dimethyl sulfoxide (DMSO). MATERIALS AND METHODS: Female rats were instilled with either protamine sulfate (PS groups) or sterile saline (control groups). At different days after the procedure, 24 h urine and bladder samples were obtained. Urinary levels of hyaluronic acid (HA) and sulfated glycosaminoglycans (S-GAG) were determined. Also to evaluate the effect of DMSO animals were instilled with either 50 percent DMSO or saline 6 hours after PS instillation. To evaluate the effect of DMSO in healthy bladders, rats were instilled with 50 percent DMSO and controls with saline. RESULTS: In the PS groups, bladder inflammation was observed, with polymorphonuclear cells during the first days and lymphomononuclear in the last days. HA and S-GAG had 2 peaks of urinary excretion, at the 1st and 7th day after PS injection. DMSO significantly reduced bladder inflammation. In contrast, in healthy bladders, DMSO produced mild inflammation and an increase in urinary HA levels after 1 and 7 days and an increase of S-GAG level in 7 days. Animals instilled with PS and treated with DMSO had significantly reduced levels of urinary HA only at the 1st day. Urinary S-GAG/Cr levels were similar in all groups. CONCLUSIONS: Increased urinary levels of GAG were associated with bladder inflammation in a PS-induced cystitis model. DMSO significantly reduced the inflammatory process after urothelial injury. Conversely, this drug provoked mild inflammation in normal mucosa. DMSO treatment was shown to influence urinary HA excretion.