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The hexanic extract of Serenoa repens (HESr) has been in use for decades as an effective, safe and well-tolerated therapy for relieving bothersome lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH). This manuscript gives an overview of HESr as monotherapy for LUTS/BPH treatment and focuses on the currently available literature investigating the possible clinical benefits of HESr combination therapy with α-blockers. Combination therapy of HESr with α-blockers has been gaining significant interest in recent years, as an increasing body of evidence shows the beneficial pharmacological effects that HESr treatment can add to standard first-line treatment with α-blockers. By reducing persistent Prostatic Inflammatory Status (PIS), commonly present in LUTS/BPH patients, HESr complements the relaxation of prostate smooth muscle induced by α-blockers, thus providing additional symptom relief. Data suggest that patients harbouring PIS and having a specific clinical profile might especially benefit from the combination therapy. Future therapeutic efforts may take advantage of more personalised strategies for LUTS/BPH management.
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Conservative and medical treatments are considered the first step in ischemic priapism (IP) management, although there is no clear evidence regarding their efficacy. We conducted a systematic review on behalf of the EAU Guidelines panel on Sexual and Reproductive health to analyse the available evidence on the efficacy and safety of conservative and medical treatment for non-sickle cell disease-related IP. Databases searched for relevant literature investigating efficacy and safety of conservative measures and medical treatment for IP included Medline, EMBASE, Cochrane Libraries and clinicaltrial.gov published up to September 2021. Overall, 41 retrospective, 3 prospective single-arm studies and 3 randomized controlled trials met the inclusion criteria. Intracavernous injection with sympathomimetic (ICIs) agents were the most frequently utilized treatment with efficacy ranging from 0 to 100% of cases. The combination of ICIs with corporeal aspiration with or without irrigation with saline was successful in 70 to 100% of cases. Oral treatment with ß2 receptor agonist (e.g., terbutaline) showed mild to moderate efficacy. Conservative methods including ice pack, exercise, cold enema and ejaculation depicted lower effectiveness in resolving priapism (1-55%). Longer time interval from the onset to the resolution of IP was associated with higher rate of erectile dysfunction at follow-up (30-70%), especially after 24 h.
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The objective of this subset analysis was to evaluate and compare the efficacy and tolerability of two combination treatments for men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Data were from a real-world, open-label, prospective, and multicenter study performed in outpatient urology clinics. Men with moderate-to-severe LUTS/BPH received 6-month treatment with tamsulosin (TAM) in combination with either the hexanic extract of S. repens (HESr) or a 5-alpha-reductase inhibitor (5ARI). Changes in urinary symptoms and quality of life were measured using the IPSS and BII questionnaires, respectively. Treatment tolerability was assessed by recording adverse effects (AEs). Patients in the two study groups were matched using iterative and propensity score matching approaches. After iterative matching, data were available from 136 patients (n = 68 treated with TAM + 5ARI, n = 68 with TAM + HESr). After 6 months of treatment, mean (SD) IPSS total score improved by 7.7 (6.3) and 6.7 (5.0) points in the TAM + 5ARI and TAM + HESr groups, respectively (p = 0.272); mean BII total scores improved by 3.1 (2.9) and 2.9 (2.4) points (p = 0.751), respectively. AEs were reported by 26.5% and 10.3% of patients in the same groups, mostly affecting sexual function (p < 0.027). When used in a real-world setting to treat patients with moderate-severe LUTS/BPH, 6-month treatment with TAM + HESr was as effective as TAM + 5ARI, but with better tolerability.
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The endocannabinoid system is a complex lipid signaling network that has evolved to be a key regulator of pro-homeostatic pathways for the organism. Its involvement in numerous processes has rendered it a very suitable target for pharmacological studies regarding metabolic syndrome, obesity and other lifestyle-related diseases. Cannabinomimetic molecules have been found in a large variety of foods, most of which are normally present in the Mediterranean diet. The majority of these compounds belong to the terpene and polyphenol classes. While it is known that they do not necessarily act directly on the cannabinoid receptors CB1 and CB2, their ability to regulate their expression levels has already been shown in some disease-related models, as well as their ability to modulate the activity of other components of the system. In this review, evidence was gathered to support the idea that phytocannabinoid dietary intake may indeed be a viable strategy for disease prevention and may be helpful in maintaining the health status. In an era where personalized nutrition is becoming more and more a reality, having new therapeutic targets could become an important resource.
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Dieta Mediterrânea , Endocanabinoides/metabolismo , Alimentos , Humanos , Obesidade/prevenção & controleRESUMO
BACKGROUND: Bipolar Transurethral Enucleation of the Prostate (B-TUEP) is recommended as a first-choice treatment for benign prostatic obstruction in prostates >80 ml. Differently, B-TUEP is only considered as an alternative option after TURP for smaller prostates (30-80 ml). The aim of our study is to assess the relation between prostate size and surgical outcomes after B-TUEP. METHODS: We performed a retrospective analysis of data collected from 172 patients submitted to B-TUEP. Patients were segregated according to tertiles of prostate volume (PV) (≤60 ml, 61-110 ml, >110 ml). For each group we evaluated enucleation efficacy (enucleated weight/enucleation time), complication rates, urinary and sexual function parameters. Functional and sexual parameters were compared between groups at baseline, 1 and 3 months follow up. Descriptive statistics and linear and logistic regression models tested the association between PV and postoperative complications/outcomes. RESULTS: Operative time and weight of enucleated adenomas increased along with prostate volumes (all p≤0.01). Enucleation efficacy was higher in men with PV >110 ml compared to other groups (p≤0.001). Length of hospital stay, catheterization time and rates of postoperative complications, such as transfusion and clot evacuation rates and bladder neck/urethral strictures, were comparable between groups. Urinary symptoms improved at 1-and 3-months in each group as compared to baseline evaluation (all p<0.01) but they did not differ according to PV. In each group maximum urinary flow and post-void residual volume significantly improved at 3 months compared to baseline (all p≤0.01), without differences according to PV. Sexual symptoms were similar between groups at each follow up assessment. At multivariable linear and logistic regression analysis, prostate volume was not associated with postoperative functional outcomes and complications. Conversely, patient's comorbid status and antiplatelet/anticoagulation use were independently associated with postoperative complications. CONCLUSION: According to our findings, B-TUEP should be considered a "size independent procedure" as it can provide symptom relief in men with prostates of all sizes with the same efficacy and safety profile.
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Endoscopia/métodos , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Hiperplasia Prostática/patologia , Resultado do TratamentoRESUMO
Pasta is one of the basic foods of the Mediterranean diet and for this reason it was chosen for this study to evaluate its antioxidant properties. Three types of pasta were selected: buckwheat, rye and egg pasta. Qualitative-quantitative characterization analyses were carried out by HPLC-DAD to identify antioxidant compounds. The data showed the presence of carotenoids such as lutein and polyphenols such as indoleacetic acid, (carotenoids from 0.08 to 0.16 mg/100 g, polyphenols from 3.7 to 7.4 mg/100 g). To assess the effect of the detected metabolites, in vitro experimentation was carried out on kidney cells models: HEK-293 and MDCK. Standards of ß-carotene, indoleacetic acid and caffeic acid, hydroalcoholic and carotenoid-enriched extracts from samples of pasta were tested in presence of antioxidant agent to determine viability variations. ß-carotene and indoleacetic acid standards exerted a protective effect on HEK-293 cells while no effect was detected on MDCK. The concentrations tested are likely in the range of those reached in body after the consumption of a standard pasta meal. Carotenoid-enriched extracts and hydroalcoholic extracts showed different effects, observing rescues for rye pasta hydroalcoholic extract and buckwheat pasta carotenoid-enriched extract, while egg pasta showed milder dose depending effects assuming pro-oxidant behavior at high concentrations. The preliminary results suggest behaviors to be traced back to the whole phytocomplexes respect to single molecules and need further investigations.
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Antioxidantes/farmacologia , Análise de Alimentos , Rim/citologia , Animais , Antioxidantes/química , Sobrevivência Celular/efeitos dos fármacos , Cães , Ovos , Fagopyrum , Células HEK293 , Humanos , Células Madin Darby de Rim Canino , Estresse Oxidativo , SecaleAssuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Retenção Urinária , Humanos , Lasers , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/cirurgia , Masculino , Próstata , Hiperplasia Prostática/complicações , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/cirurgia , Túlio , Retenção Urinária/diagnóstico , Retenção Urinária/etiologiaRESUMO
PURPOSE: To review the role of a persistent prostatic inflammatory status (PIS) in the development and progression of benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS) and which medical therapies approved for LUTS/BPH may reduce persistent PIS. METHODS: Literature search in PubMed up to July 2019. RESULTS: The cause of histologically defined persistent PIS or chronic prostatic inflammation is multifactorial. It is evident in many men with LUTS/BPH, particularly in older men and in men with a large prostate volume or more severe (storage) LUTS. Additionally, persistent PIS is associated with an increased risk of acute urinary retention and symptom worsening. Of medical therapies approved for LUTS/BPH, the current evidence for a reduction of persistent PIS is greatest for the hexanic extract of Serenoa repens (HESr). This treatment relieves LUTS to the same extent as α1-adrenoceptor antagonists and short-term 5α-reductase inhibitors. Limited evidence is available on the effect of other mainstream LUTS/BPH treatments on persistent PIS. CONCLUSIONS: Persistent PIS plays a central role in both the development and progression of LUTS/BPH. In men with LUTS/BPH who have a high chance of harbouring persistent PIS, HESr will not only improve LUTS, but also reduce (underlying) inflammation. Well-designed clinical studies, with a good level of evidence, are required to better evaluate the impact of BPH/LUTS medical therapies on persistent PIS.
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Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Prostatite/tratamento farmacológico , Prostatite/etiologia , Humanos , Masculino , FitoterapiaRESUMO
BACKGROUND: A significant number of patients who require surgery for benign prostatic hyperplasia are under either anticoagulation (AC) or antiplatelet (AP) therapy. OBJECTIVE: To assess the efficacy and morbidity of holmium laser enucleation of the prostate (HoLEP) and bipolar transurethral enucleation of the prostate (B-TUEP) in patients who required AC/AP therapy. DESIGN, SETTING, AND PARTICIPANTS: This study included 296 (67.6%) and 142 (32.4%) patients who underwent HoLEP and B-TUEP, respectively. The AC/AP group included patients whose AP therapy was not interrupted pre-, peri-, and/or postoperatively, and patients who underwent perioperative AC therapy bridging with low-molecular-weight heparin. INTERVENTION: HoLEP and B-TUEP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We tested the hypothesis that AC/AP therapy had a limited impact on the efficacy of HoLEP and B-TUEP. To adjust for potential baseline confounders, propensity-score matching was performed. Clinical characteristics were compared among groups using the Kruskal-Wallis or chi-square test. Logistic regression analyses tested the association between clinical variables and the odds of Clavien-Dindo ≥2 complications after surgery. RESULTS AND LIMITATIONS: Overall, 28 (9.5%) and 46 (15.5%) patients in the HoLEP group and 15 (10.5%) and 24 (16.9%) men in the B-TUEP group had AC and AP therapy, respectively (p=0.9). HoLEP patients under either AC or AP therapy deserved longer catheter maintenance and a longer hospital stay (HS) than those without AC/AP therapy (all p≤0.01). Operative time, rates of postoperative complications, and 2-mo International Prostate Symptoms Score (IPSS) were similar between patients with and without AC/CP. Among B-TUEP patients, HS was longer (p=0.03) and the rate of complications was higher (p<0.001) in patients under AC or AP therapy. Postoperative haemoglobin drop and 2-mo IPSS were similar among groups and surgical techniques. Limitations are the retrospective nature of the study, and the lack of long-term complications and functional outcomes. CONCLUSIONS: HoLEP and B-TUEP can safely be performed in patients deserving continuous AP/AC therapy with only a slight increase in HS and catheterisation time. PATIENT SUMMARY: We assessed the safety and efficacy of holmium laser enucleation of the prostate (HoLEP) and bipolar transurethral enucleation of the prostate (B-TUEP) in men under chronic anticoagulation/antiplatelet therapy. Both HoLEP and B-TUEP could safely be performed as minimally invasive treatment options in this subset of patients at a high risk of bleeding from benign prostatic hyperplasia surgery.
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Anticoagulantes/uso terapêutico , Eletrocirurgia , Lasers de Estado Sólido/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Adulto , Humanos , Lasers de Estado Sólido/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Ressecção Transuretral da Próstata/efeitos adversos , Resultado do TratamentoRESUMO
Urologists can bridge the gender gap in life expectancy through the promotion of a holistic and streamlined approach to men's health that incorporates optimisation of lifestyle factors (smoking cessation, weight loss, diet) and comorbidities (treatment of hypertension, hypercholesterolaemia, and hypogo-nadism) and offers cancer screening.
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Expectativa de Vida , Saúde do Homem , Feminino , Humanos , Masculino , Papel do Médico , UrologiaRESUMO
OBJECTIVE: To investigate whether local injection of autologous adipose stromal vascular fraction (SVF) can prevent the development of fibrosis and elastosis in the tunica albuginea (TA) using a rat model of the acute phase of Peyronie's disease (PD). METHODS: A total of 24 male 12-week-old Sprague-Dawley rats were divided into three equal groups: sham; PD without treatment (transforming growth factor-ß [TGF -ß]); and PD treated with SVF 1 day after disease induction. Sham rats received two injections of vehicle into the TA 1 day apart. TGF -ß rats received TGF- ß1 injection and injection of vehicle 1 day later. SVF rats received TGF-ß1 injection, followed by SVF 1 day later. One month after treatment, all rats underwent measurement of intracavernosal pressure and mean arterial pressure during electrostimulation of the cavernous nerve. The rats were then killed and penises were harvested for histology and Western blot analysis. RESULTS: Erectile function was moderately reduced in the TGF-ß group and was significantly improved after SVF treatment (P < 0.05). PD rats developed areas of fibrosis with a significant upregulation of collagen III, collagen I and elastin protein expression. These fibrotic changes were prevented when treated with SVF. CONCLUSIONS: Local injection of SVF may represent treatment for the acute phase of PD.
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Induração Peniana/patologia , Induração Peniana/terapia , Células Estromais/transplante , Animais , Modelos Animais de Doenças , Injeções , Masculino , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1RESUMO
OBJECTIVE: To assess changes in the rate of incidental prostate cancer (PCa) after benign prostatic hyperplasia (BPH) surgery over the last decade. MATERIALS AND METHODS: We identified 1177 patients surgically treated for BPH (open prostatectomy, transurethral resection or holmium laser enucleation [HoLEP] of the prostate) in 2007-2016 at a single European academic center. Local polynomial regression was used to explore changes in the rate of incidental PCa detected after BPH surgery and of preoperative biopsy performed over time. Logistic regression analyses tested the association of incidental PCa diagnosis with year of surgery and preoperative biopsy. RESULTS: Incidental PCa was found in 6.4% (74) of cases, 67 (91%) with Grade group 1 disease. We observed an increased incidence of PCa diagnosis after BPH surgery over time (odds ratio [OR]: 1.12; 95%confidence interval [CI]: 1.02-1.24, Pâ¯=â¯.02) along with a concomitant decrease in the rate of preoperative prostate biopsies (OR: 0.83; 95%CI: 0.79-0.88, P < .0001). Patients undergoing a preoperative biopsy showed a lower risk of being diagnosed with PCa after surgery (OR: 0.29; 95% CI: 0.12, 0.72 Pâ¯=â¯.007). Patients treated with HoLEP had a higher chance of incidental PCa detection (OR: 2.28; 95%CI: 1.30-4.00; Pâ¯=â¯.004), although this may be related to the significantly higher number of HoLEP performed over the last years. CONCLUSION: The increased rate of low-risk PCa detected after BPH surgery in the last decade reflects the clinical practice changes in PCa screening and diagnosis leading to a reduced number of unnecessary biopsies and indolent cancer diagnosis.
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Achados Incidentais , Padrões de Prática Médica/tendências , Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/epidemiologia , Idoso , Biópsia , Humanos , Incidência , Lasers de Estado Sólido , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Padrões de Prática Médica/estatística & dados numéricos , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/estatística & dados numéricos , Próstata/patologia , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Ressecção Transuretral da Próstata/instrumentação , Ressecção Transuretral da Próstata/métodosRESUMO
To assess the rate and predictors of clinically meaningful improvements (CMI) in patients with lower urinary tract symptoms (LUTS) treated with either silodosin (SIL) alone or with a combination of SIL+ serenoa repens (Ser) hexanic lipidosterolic extract for ≥12 months. Data from 186 patients were collected. Patients completed the International Prostatic Symptoms Score (IPSS) at baseline and at follow-up assessment. Descriptive statistics and logistic regression models tested rates and predictors of CMI. Two CMI were assessed: 1) >3 points improvement in total IPSS from baseline to end (CMI#1); 2) >25% IPSS improvement from baseline to end (CMI#2). Overall, 93 (50%) patients were treated with SIL and SIL+ Ser, respectively. At a mean 13.5-mos follow-up [range: 12-20], mean IPSS scores were significantly lower in patients treated with SIL + Ser compared to those after SIL (p = 0.002). SIL + Ser patients more frequently achieved CMI#1 (69.9% vs. 30.1%, p = 0.001) and CMI#2 (68.8% vs. 31.2%, p < 0.001) compared SIL men. At multivariable analyses, younger age, IPSS severity and SIL + Ser (all p < 0.03) were independent predictors of CMI#1 and CMI#2. In conclusion, SIL + Ser therapy was more effective than SIL alone in improving IPSS scores in men with LUTS. SIL + Ser treatment led to CMIs in up to seven out of ten men.
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Indóis/administração & dosagem , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Hiperplasia Prostática/tratamento farmacológico , Serenoa/química , Agentes Urológicos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/isolamento & purificação , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Urinary tract infections (UTIs) are common in women and many patients with recurrent UTIs do not eradicate the condition albeit being treated with multiple courses of antibiotics. The use of nutritional supplements might reduce the risk of recurrent UTIs. However, the role of supplements taken as single agents appears to be limited. We hypothesized that a combination of cranberries, Lactobacillus rhamnosus, and vitamin C might produce a clinical benefit due to their additive or synergistic effects. We prospectively enrolled 42 consecutive women with recurrent UTIs treated with 120mg cranberries (minimum proanthocyanidin content: 32mg), 1 billion heat-killed L. rhamnosus SGL06, and 750mg vitamin C thrice daily for 20 consecutive d. Patients were advised to stop taking these supplements for 10 d and then to repeat the whole cycle three times. Patients were contacted three mo and six mo following the end of the administration of these supplements and evaluated with a semistructured interview and urinalysis. Responders were defined as the absence of symptoms and negative urinalysis or urine culture. Follow-up data were available for 36 patients. Overall, 26 (72.2%) and 22 patients (61.1%) were responders at the 3-mo and 6-month follow-up. No major side effects were recorded. The administration of cranberries, L. rhamnosus, and vitamin C might represent a safe and effective option in women with recurrent UTIs. PATIENT SUMMARY: We evaluated the effectiveness of cranberries, Lactobacillus rhamnosus, and vitamin C thrice daily for 20 consecutive d monthly for 3 mo for the management of recurrent urinary tract infections in women. Our results show that this approach might represent a safe and effective option.
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Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Suplementos Nutricionais , Lacticaseibacillus rhamnosus , Infecções Urinárias/prevenção & controle , Vaccinium macrocarpon , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Recidiva , Adulto JovemRESUMO
INTRODUCTION: Benign prostatic hyperplasia (BPH) is a disease affecting most of the elderly male. α1-blockers and 5-alpha reductase inhibitors are currently used to target lower urinary tract symptoms (LUTS). Moreover phytotherapeutic agents, including Serenoa Repens (SeR), have shown to have a role in ameliorating BPH/LUTS alone or in combination of other elements like Selenium (Se) and Lycopene (Ly). Areas covered: A literature review was performed using data from articles assessing the role of of SeR+Se+Ly in the management of LUTS secondary to BPH. Diverging evidence on SeR's efficacy is available. On one hand several studies have shown SeR efficacy in treating BPH/LUTS. SeR is effective in reducing prostate size, urinary frequency, dysuria, nocturia and in improving maximum urine flow-rate. On the other hand two long-term trials reported that SeR did not improve prostate size or urinary flow. SeR+Se+Ly in combination with tamsulosin is more effective than single therapies in improving IPSS and increasing maximal urinary flow-rate in patients affected by LUTS/BPH. Expert opinion: Despite great amount of preclinical and clinical studies, the use of SeR in BPH/LUTS is not sustained by clear evidence for a therapeutic efficacy but current data hint higher efficacy of of SeR+Se+Ly compared to SeR alone.
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Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática/tratamento farmacológico , Serenoa/química , Idoso , Animais , Carotenoides/administração & dosagem , Carotenoides/uso terapêutico , Quimioterapia Combinada , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Licopeno , Masculino , Fitoterapia/métodos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Hiperplasia Prostática/complicações , Selênio/administração & dosagem , Selênio/uso terapêuticoRESUMO
Restoring the bladder glycosaminoglycans layer has recently been introduced as prophylactic treatment for recurrent urinary tract infections. Herein, we analyze the latest main clinical and experimental studies to support this therapeutic option. An electronic research was carried out in the most common databases in order to identify any published studies. Retrieved studies were categorized as experimental or clinical according to their setting. For the clinical studies, the evidence level was assigned. A total of 13 laboratory studies showed how bladder glycosaminoglycans instillations act: attenuation of the inflammation process, reduction of bladder contraction amplitude and frequency, reduction of epithelium damage, and lower bacterial growth in urine and tissue samples. Likewise, two randomized clinical trials with grade 2 evidence level and two case series with grade 4 evidence level reported glycosaminoglycans as an alternative to reduce episodes and to prolong recurrence time in patients with recurrent urinary tract infections. At least 12 months of follow up was completed. No serious adverse events were reported. Compared with a placebo, in one randomized study a significantly higher maximum cystometric capacity was obtained, whereas in the other study a significant increase in quality of life scores was reported too. An improvement in the urinary symptoms score was reported by the two randomized trials. Although the clinical use of glycosaminoglycans replacement therapy for recurrent urinary tract infections is supported by a small number of clinical studies with different evidence levels, the laboratory studies show that glycosaminoglycans could have a protective role against inflammatory factors, supporting the idea "to restore the glycosaminoglycans bladder layer to prevent chronic disease course".