Patient-Derived Upper Tract Urothelial Carcinoma Organoids as a Platform for Drug Screening.

Upper tract urothelial carcinomas (UTUCs) are rare entities that are usually diagnosed at advanced stages. Research on UTUC pathobiology and clinical management has been hampered by the lack of models accurately reflecting disease nature and diversity. In this study, a modified organoid culture system is used to generate a library of 25 patient-derived UTUC organoid lines retaining the histological architectures, marker gene expressions, genomic landscapes, and gene expression profiles of their parental tumors. The study demonstrates that the responses of UTUC organoids to anticancer drugs can be identified and the model supports the exploration of novel treatment strategies. This work proposes a modified protocol for generating patient-derived UTUC organoid lines that may help elucidate UTUC pathophysiology and assess the responses of these diseases to various drug therapies in personalized medicine.

Caffeine as a Factor Influencing the Functioning of the Human Body-Friend or Foe?

Nowadays, caffeine is one of the most commonly consumed substances, which presents in many plants and products. It has both positive and negative effects on the human body, and its activity concerns a variety of systems including the central nervous system, immune system, digestive system, respiratory system, urinary tract, etc. These effects are dependent on quantity, the type of product in which caffeine is contained, and also on the individual differences among people (sex, age, diet etc.). The main aim of this review was to collect, present, and analyze the available information including the latest discoveries on the impact of caffeine on human health and the functioning of human body systems, taking into account the role of caffeine in individual disease entities. We present both the positive and negative sides of caffeine consumption and the healing properties of this purine alkaloid in diseases such as asthma, Parkinson's disease, and others, not forgetting about the negative effects of excess caffeine (e.g., in people with hypertension, children, adolescents, and the elderly). In summary, we can conclude, however, that caffeine has a multi-directional influence on various organs of the human body, and because of its anti-oxidative properties, it was, and still is, an interesting topic for research studies including those aimed at developing new therapeutic strategies.

The Effect of Castration on Peripheral Autonomic Neurons Supplying Mammalian Male Genitourinary System.

This review paper deals with the influence of androgens (testosterone) on pelvic autonomic pathways in male mammals. The vast majority of the relevant information has been gained in experiments involving castration (testosterone deprivation) performed in male rats, and recently, in male pigs. In both species, testosterone significantly affects the biology of the pathway components, including the pelvic neurons. However, there are great differences between rats and pigs in this respect. The most significant alteration is that testosterone deprivation accomplished a few days after birth results some months later in the excessive loss (approximately 90%) of pelvic and urinary bladder trigone intramural neurons in the male pig, while no changes in the number of pelvic neurons are observed in male rats (rats do not have the intramural ganglia). In the castrated pigs, much greater numbers of pelvic neurons than in the non-castrated animals express CGRP, GAL, VIP (peptides known to have neuroprotective properties), and caspase 3, suggesting that neurons die due to apoptosis triggered by androgen deprivation. In contrast, only some morpho-electrophysiological changes affecting neurons following castration are found in male rats. Certain clinicopathological consequences of testosterone deprivation for the functioning of urogenital organs are also discussed.

Pharmacokinetics of UGN-101, a mitomycin-containing reverse thermal gel instilled via retrograde catheter for the treatment of low-grade upper tract urothelial carcinoma.

PURPOSE: To evaluate the pharmacokinetic properties of UGN-101, a mitomycin-containing reverse thermal gel used as primary chemoablative treatment for low-grade upper tract urothelial carcinoma (UTUC), in a subset of patients participating in a phase 3 clinical trial. METHODS: Pharmacokinetic parameters (Cmax, Tmax, AUC(0-6), λz, t½, and AUCinf) were evaluated in six participants (male or female, ≥ 18 years) with biopsy-proven, low-grade UTUC who received the first of 6 once-weekly instillations of UGN-101 to the renal pelvis and calyces via retrograde ureteral catheter. Plasma samples were collected prior to instillation and 30 min, 1, 2, 3, 4, 5, and 6 h post-instillation. Safety was assessed by laboratory evaluations, physical exam, and adverse event monitoring. RESULTS: The mean age of the six participants was 69 years; most were male (5/6) and Caucasian (5/6). Mean (SD) Cmax was 6.24 (4.11) ng/mL and mean Tmax was 1.79 (1.89) hours after instillation. Mean apparent t½ following instillation was 1.27 (0.63) hours. Mean total systemic exposure to mitomycin up to 6 h post-instillation was 20.30 (19.69) ng h/mL. At 6 h post-instillation, mitomycin plasma concentrations of 5/6 participants were < 2 ng/mL. There were no clinically important adverse events or changes in laboratory values in any participant after a single instillation of UGN-101. CONCLUSION: The reverse thermal gel formulation of UGN-101 is associated with higher concentration and extended dwell time of mitomycin in contact with the urothelium of the upper urinary tract while limiting systemic absorption of mitomycin. REGISTRATION: NCT02793128; registered June 8, 2016.

Degarelix as a neoadjuvant hormonal therapy for acute urinary tract toxicity associated with external beam radiotherapy for intermediate- and high-risk prostate cancer: a propensity score matched analysis.

BACKGROUND: In prostate cancer treatment, lower urinary tract symptoms significantly improve with luteinizing hormone-releasing hormone antagonists use compared with agonists. However, it is unclear whether luteinizing hormone-releasing hormone antagonists can decrease acute urinary tract toxicity during external beam radiotherapy. This study aimed to assess whether luteinizing hormone-releasing hormone antagonists used as neoadjuvant therapy reduced acute urinary tract toxicity during external beam radiotherapy compared with luteinizing hormone-releasing hormone agonists. METHODS: The study included 78 patients who underwent intensity-modulated radiation therapy for intermediate- and high-risk prostate cancer between April 2013 and January 2020. Irradiation was initiated after 3-6 months of neoadjuvant therapy. Androgen deprivation therapy was given to the intermediate-risk group for 6 months and the high-risk group for 2-3 years. The European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group toxicity grading scale was used to evaluate the urinary tract system toxicity. Relevant clinical factors were used in matching patients based on propensity scores to enable comparison between the groups. RESULTS: Each group had 27 matched patients. There was no reduction in urinary tract toxicity with the use of luteinizing hormone-releasing hormon antagonists (P = 0.624). For patients with an International Prostate Symptom Score of ≥11 at the start of treatment, 18 patients in each group were matched. Significantly lower scores were observed in the luteinizing hormone-releasing hormon antagonist group (P = 0.041). CONCLUSIONS: Luteinizing hormone-releasing hormon antagonists may reduce acute urinary tract toxicity during prostate cancer external beam radiotherapy compared with luteinizing hormone-releasing hormon agonists, in particular in patients with moderate to severe symptoms at the start of treatment.

Functional Evaluation of Upper Urinary Tract with Diuretic Mercaptoacetyltriglycine Renal Scans in Patients with Benign Prostatic Obstruction before and after Surgical Intervention: A Pilot Study.

INTRODUCTION: We investigated which benign prostatic hyperplasia-related lower urinary parameters are related to upper urinary tract obstruction and whether transurethral prostatectomy could improve upper urinary tract obstruction. MATERIALS AND METHODS: Patients with prostate size over 30 g and urodynamically proven bladder outlet obstruction were enrolled in this prospective observational study. Bladder wall thickness and prostate size were measured by ultrasonography. A urodynamic study with laboratory tests including serum creatinine, prostate-specific antigen, and urinalysis was performed. Finally, a diuretic scintigraphy using mercaptoacetyltriglycine was performed. Tests except the urodynamic evaluation were repeated after transurethral prostatectomy. RESULTS: In total, 24 patients were enrolled, and 19 patients completed the present study. The mean values of age (yrs), prostate size (mL), bladder thickness (mm), bladder compliance (ΔmL/Δpr), and the bladder outlet obstruction index were 68.42 ± 8.25, 72.29 ± 32.78, 4.42 ± 1.14, 50.17 ± 32.15, and 82.11 ± 34.68, respectively. The mean T1/2 (min) was 17.51 ± 16.34 on the left side and 15.30 ± 11.96 on the right side. Statistical analysis showed that bladder compliance and bladder thickness were preoperatively related to upper urinary tract obstruction (p = 0.001 and p = 0.007, respectively). Diuretic mercaptoacetyltriglycine scan in 19 patients showed improvement 6 months after prostate surgery. Clinically significant proteinuria was associated with upper urinary tract obstruction, and proteinuria was also improved after prostate surgery. CONCLUSION: Storage-phase bladder dysfunction could be a reliable urodynamic factor for the indication of upper urinary tract obstruction in patients with benign prostatic hyperplasia, and upper urinary tract obstruction with subsequent kidney damage could be improved by surgical decompression of benign prostatic obstruction.

Transcriptomic analysis of the mechanisms of alleviating renal interstitial fibrosis using the traditional Chinese medicine Kangxianling in a rat model.

Renal interstitial fibrosis (RIF) is currently recognized as a crucial mechanism of the pathogenesis of chronic kidney disease (CKD). Kangxianling (KXL, anti-fibrin) is a traditional Chinese medicine that has been proven to significantly reduce the levels of ECM deposition and inhibit renal fibrosis. To characterize the mechanisms and drug targets of KXL, we established a RIF rat model and treated the rats with KXL and losartan. Histological analyses validated the establishment of the RIF model and the treatment effect of KXL. Multiple levels of transcriptomic datasets were generated using lncRNA, mRNA and microRNA sequencing of kidney tissues. Functional annotations and pathway analyses were performed to unravel the therapeutic mechanisms. A multi-level transcriptomic regulatory network was built to illustrate the core factors in fibrosis pathogenesis and therapeutic regulation. KXL and losartan significantly reduced the progression of RIF, and a better therapeutic effect was shown with higher concentrations of KXL. According to the cluster analysis results of the RNA-seq data, the normal control (NC) and high concentration of KXL (HK) treatment groups were the closest in terms of differentially expressed genes. The WNT, TGF-ß and MAPK pathways were enriched and dominated the pathogenesis and therapy of RIF. miR-15b, miR-21, and miR-6216 were upregulated and miR-107 was downregulated in the fibrosis model. These small RNAs were shown to play critical roles in the regulation of the above fibrosis-related genes and could be inhibited by KXL treatment. Finally, based on the lncRNA datasets, we constructed a mRNA-lncRNA-miRNA coexpression ceRNA network, which identified key regulatory factors in the pathogenesis of kidney fibrosis and therapeutic mechanisms of KXL. Our work revealed the potential mechanism of the Chinese medicine Kangxianling in inhibiting renal interstitial fibrosis and supported the clinical use of KXL in the treatment of kidney fibrosis.

The Urinary Microbiome and Anticancer Immunotherapy: The Potentially Hidden Role of Unculturable Microbes.

Several urinary disorders, including overactive bladder, urinary incontinence, and interstitial cystitis, are often characterized by negative urine cultures. The application of metagenomics (i.e., 16S rRNA microbial profiling or whole-genome shotgun sequencing) to urine samples has enabled the identification of previously undetected bacteria, contributing to the discovery and characterization of the urinary microbiome. The most frequent species isolated are Lactobacillus (15%), Corynebacterium (14.2%), Streptococcus (11.9%), Actinomyces (6.9%), and Staphylococcus (6.9%). Although several studies are emerging in this context, the role of urinary microbiota in the pathogenesis of infections and in tumor carcinogenesis remains unclear. Furthermore, data on the activity of gut microbiota in modulating sensitivity to immune checkpoint inhibitors in advanced cancer patients suggest that the influence of urinary microbiota on tumor response to anticancer therapy should also be investigated. Moreover, its possible relationship with tumor mutational burden, which is in turn correlated with response to immunotherapy, should be the focus of future studies. Of note, the effect of antibiotics on this complex scenario seems to deserve careful consideration.

Bisdemethoxycurcumin protects against renal fibrosis via activation of fibroblast apoptosis.

Renal fibrosis is the common final outcome of nearly all progressive chronic kidney diseases (CKD) that eventually develop into end-stage renal failure, which threatens the lives of patients. Currently, there are no effective drugs for the treatment of renal fibrosis. However, studies have shown that certain plant natural products have a fibrosis-alleviating effect. Thus, we have screened a large number of natural products for their ability to protect against renal fibrosis and found that bisdemethoxycurcumin has a good therapeutic effect in renal fibrosis according to the data obtained in a mouse model of unilateral ureteral obstruction (UUO). The results indicate that bisdemethoxycurcumin can efficiently attenuate renal fibrosis induced by UUO. Additional studies of the bisdemethoxycurcumin mechanism of action in the treatment of renal fibrosis demonstrated that the therapeutic effect of bisdemethoxycurcumin is mediated by the specific induction of fibroblast apoptosis at a concentration of 20 µM. bisdemethoxycurcumin can efficiently protect against renal fibrosis both in vitro and in vivo. This discovery will provide new ideas for renal fibrosis treatment in clinics and a new direction for the development of effective drug therapy of renal fibrosis.

Development of an in silico prediction model for chemical-induced urinary tract toxicity by using naïve Bayes classifier.

The urinary tract toxicity is one of the major reasons for investigational drugs not coming into the market and even marketed drugs being restricted or withdrawn. The objective of this investigation is to develop an easily interpretable and practically applicable in silico prediction model of chemical-induced urinary tract toxicity by using naïve Bayes classifier. The genetic algorithm was used to select important molecular descriptors related to urinary tract toxicity, and the ECFP-6 fingerprint descriptors were applied to the urinary tract toxic/non-toxic fragments production. The established naïve Bayes classifier (NB-2) produced 87.3% overall accuracy of fivefold cross-validation for the training set and 84.2% for the external test set, which can be employed for the chemical-induced urinary tract toxicity assessment. Furthermore, six important molecular descriptors (e.g., number of N atoms, AlogP, molecular weight, number of H acceptors, number of H donors and molecular fractional polar surface area) and toxic and non-toxic fragments were obtained, which would help medicinal chemists interpret the mechanisms of urinary tract toxicity, and even provide theoretical guidance for hit and lead optimization.

Coconut Water: An Unexpected Source of Urinary Citrate.

PURPOSE: Coconut water has long been touted for its medicinal qualities including natural hydration. We sought to determine whether its consumption would induce changes to urinary lithogenic factors beyond changes in urine volume. MATERIALS AND METHODS: After Institutional Review Board approval, volunteers with no prior history of nephrolithiasis were recruited. Each participant was randomized initially to either the coconut water or the water phase of the study. Participants kept meticulous food and fluid intake logs during the first phase of the study and were asked to replicate that diet for the second phase. For each phase the participant consumed 2L of either Taste of Nirvana® pure coconut water or tap water daily for four days. Participants were not restricted to consume additional fluid of their choice during their assigned study phase. During days 3 and 4 of each phase the participant collected a 24-hour urine specimen. Coconut water citrate and malate content were measured and were used along with the beverage pH to calculate the total alkali content of the coconut water. Supersaturation levels were calculated using Equil2. Nonparametric paired analysis using the Wilcoxon test was performed for statistical analysis. RESULTS: There were 4 adult male and 4 adult female participants. Each individual's 24-hour urine collection had a creatinine excretion within 20% of the mean for each subject's four samples corroborating that all samples were collected properly. The two samples from each phase for each individual were averaged. The coconut water itself was also analyzed and it was calculated to have a total alkali content of 13.8 mEq/L. Consumption of coconut water significantly increased urinary citrate (29%, p=0.02), urinary potassium (130%, p=0.01), and urinary chloride (37%, p=0.03), without affecting urine pH (p=0.16) or volume beyond that of tap water (p=1.00). CONCLUSIONS: Coconut water consumption increases urinary potassium, chloride, and citrate in nonstone forming individuals.

Community-Acquired Urinary Tract Infection by Escherichia coli in the Era of Antibiotic Resistance.

Urinary tract infections (UTIs) caused by Escherichia coli (E. coli) are the most common types of infections in women. The antibiotic resistance of E. coli is increasing rapidly, causing physicians to hesitate when selecting oral antibiotics. In this review, our objective is to ensure that clinicians understand the current seriousness of antibiotic-resistant E. coli, the mechanisms by which resistance is selected for, and methods that can be used to prevent antibiotic resistance.

High Consumption of Green Tea Suppresses Urinary Tract Recurrence of Urothelial Cancer via Down-regulation of Human Antigen-R Expression in Never Smokers.

BACKGROUND/AIM: Smoking is a risk factor for carcinogenesis and progression of urothelial cancer (UC). Green tea polyphenol inhibits these malignant behaviors and suppresses human antigen R (HuR) expression, which is associated with malignant aggressiveness. This study aimed to clarify the anti-cancer effects of green tea based on the smoking status of UC patients. PATIENTS AND METHODS: Three hundred and sixty (260 with bladder cancer, BC and 100 with upper tract UC) patients were divided into three groups based on consumption of green tea: low (<1 cup/day, n=119), middle (1-4 cup/day, n=160), and high (>5 cup/day, n=81). HuR immunoreactivity was evaluated immunohistochemically in formalin-fixed specimens. RESULTS: In never smokers, multivariate analysis showed that the frequency of green tea consumption was a significant predictor (middle: hazard ratio, HR, 0.36, p=0.002; high: HR, 0.20, p=0.003) of urinary tract recurrence. A high consumption of green tea was associated with low rates of urinary tract recurrence and up-grading in UC patients. In BC, high consumption was associated with a lower risk of up-grading (p=0.011) and up-staging (p=0.041) in recurrent cancer. HuR expression in the high-consumption group was lower (p=0.019) than that in other groups. These significant findings were not detected in ever smokers. CONCLUSION: High consumption of green tea suppressed urinary tract recurrence and the risks of up-grading and up-staging by recurrence in never smokers. Our results suggested that HuR expression played important roles in such mechanisms.

Physician assessed and patient reported urinary morbidity after radio-chemotherapy and image guided adaptive brachytherapy for locally advanced cervical cancer.

BACKGROUND AND PURPOSE: The EMBRACE study is a prospective multi-institutional study on MRI guided adaptive brachytherapy (IGABT) in locally advanced cervix cancer (LACC). This analysis describes early to late urinary morbidity assessed by physicians and patients (PRO). MATERIAL AND METHODS: A total of 1176 patients were analysed. Median follow up (FU) was 27 (1-83) months. Morbidity (CTCAE v.3) and PRO (EORTC QLQ-C30&CX24) was prospectively assessed at baseline (BL), and during FU. RESULTS: The most frequent symptoms were frequency/urgency, incontinence, and cystitis with grade 2-4 prevalence rates of 4.3%, 5.0% and 1.7% and grade 1-4 prevalence rates of 24.5%, 16.1% and 5.8% at 3-years. The most frequent PRO endpoints were "urinary frequency" and "leaking of urine". Prevalence of "Quite a bit" or "very much" bother fluctuated from 14.0% to 21.5% for "frequency", while "leaking of urine" increased from 4.6% at BL to 9.3% at 3-years. Actuarial 3-year incidence of grade 3-4 urinary morbidity was 5.3% with most events being urinary frequency, incontinence and ureteral strictures. Grade 3-4 fistula, bleeding, spasm and cystitis were all <1.0% at 3/5-years. No grade 5 toxicity occurred. CONCLUSION: Urinary grade 3-4 morbidity with IGABT was limited. Urinary morbidity grade 2-4 comprises mainly frequency/urgency, incontinence and cystitis and has considerable prevalence in PRO. Various urinary morbidity endpoints have different patterns of manifestation and time course.

Healthcare-Associated Infections after Lower Urinary Tract Endoscopic Surgery: Analysis of Risk Factors, Associated Microorganisms and Patterns of Antibiotic Resistance.

OBJECTIVES: To review the incidence of healthcare-associated infections/urinary tract infection (UTI), risk factors, microorganisms isolated and antibiotic resistances in patients who underwent lower urinary tract endoscopic surgery (LUTES) in a tertiary care hospital. METHODS: A prospective observational study was carried out including 1,498 patients who undergo LUTES. Patients with and without UTI after surgery were compared. We analysed infection incidence, risk factors, microorganisms isolated and antibiotic resistances. RESULTS: Postoperative UTI incidence was 4.7%. Risk factors found: higher American Society of Anesthesiologists classification (OR 2.82; 95% CI 1.8-4.5; p < 0.00), immunosuppression (OR 2.89; 95% CI 1.2-7.2; p = 0.01), indwelling urinary catheter prior admission (OR 2.6; 95% CI 1.6-4.2; p < 0.00) and postoperative catheterization longer than 2 days (OR 1.74; 95% CI 1.7-4.3; p < 0.00). Transurethral resection of the bladder (TURB) had the highest infection rates (5.5%). Microorganisms isolated were Pseudomonas aeruginosa (23.5%), Escherichia coli (17.6%), Klebsiella pneumoniae and Enterococcus spp (11.8%). Resistance rates for flourquinolones varied between 28 and 80%, and Carbapenem-resistant Enterobacteriaceae rose up 20%. CONCLUSIONS: Low percentage of UTI after endoscopic surgery was registered. TURB was the procedure with highest infection rate. Pseudomonas aeruginosa stands out as the most frequently isolated microorganism. Patient comorbidities, previous urinary catheter and postoperative catheter were identified as risk factors.

Urinary Tract and Gynecologic Malignancies.

BACKGROUND: The close anatomical relationship of the urogenital system is a significant, and sometimes limiting, factor in oncogynecology. Reducing adverse effects (treatment-associated toxicity) is an integral part of cancer treatment. Radical surgery, as well as oncological therapy, which represent milestones in the treatment of such malignancies, may require tailoring the extension of the intervention in order to preserve other non-gynecological structures. Despite the progress in minimally invasive surgery, and evolution of radiotherapy and systemic therapy, treatment-related complications remain; indeed, their increasing prevalence in women raises questions about quality of life. AIM: Here, we highlight the modalities used to treat gynecological cancer and discuss the most common urological adverse effects related to these interventions. Knowledge of side effects, as well as methods of prevention, is fundamental if we are to preserve quality of life. CONCLUSION: reatment of gynecological cancer is based on cooperation between members of the multidisciplinary team. From this point-of-view, combination of two radical modalities (mainly surgery and radiotherapy) remains problematic. However, the patients prognosis, and plans for other possible oncological therapies, play an essential role in management of urological adverse effects related to cancer treatment. Key words: gynecologic neoplasms - complication - urinary tract - quality of life This work was supported by project PROGES Q40. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 27. 9. 2018 Accepted: 21. 10. 2018.

Comparación entre ciprofloxacina y antibióticos de otros grupos farmacológicos para el tratamiento de infecciones del tracto urinario / Comparison between ciprofloxacine and antibiotics of other pharmacological groups for urinary tract infection treatment / Comparação entre a ciprofloxacina e outros antibióticos grupos farmacológicos para o tratamento de infecções do tracto urinário

ResumenIntroducción. Las infecciones de tracto urinario son un tema común en los servicios de consulta externa y emergencias de los centros de salud. El uso inadecuado e irracional de antibióticos puede favorecer la aparición de cepas resistentes y limitar la capacidad de respuesta de estos fármacos. Este artículo busca revisar el uso de quinolonas (específicamente ciprofloxacina) con antibióticos de otros grupos farmacológicos y comparar efectividad y resistencia bacteriana.Método. A partir de la metodología que señala la práctica clínica basada en la evidencia para las revisiones rápidas, se estableció una pregunta clínica a la que se le procuró responder mediante la búsqueda de investigaciones primarias en bases de datos electrónicas como MEDLINE, PubMed, Cochrane Library Plus y el Journal of Infection.Resultado. Según el tipo de bacteria y cepa analizada, hay presencia de resistencia a diversos antibióticos. Las infecciones de origen comunitario han sido tratadas con betalactámicos, nitrofurantoína, trimetoprimsulfametoxasol y fluoroquinolonas (especialmente ciprofloxacina).Conclusión. No se determinó si las quinolonas son más efectivas que los antibióticos que pertenecen a otros grupos farmacológicos

AbstractIntroduction. Urinary tract infections are a common reason of consultation in medical practical in ambulatory and emergency rooms in centers of health. The inadequate and irrational use of antibiotics can favor the appearance of resistant bacterial strain and limit the capacity of response of these medicines. This article seeks to review the use of quinolones (specifically ciprofloxacine) with antibiotics of other pharmacological groups and to compare efficiency and bacterial resistance.Method.From the methodology that indicates the clinical practice based on the evidence for the rapid reviews, there was established a clinical question to which response was tried to give by means of the search of primary investigations in electronic databases like MEDLINE, PubMed, Cochrane Library Plus and the Journal of Infection.Result. According to the type of bacterium and analyzed bacterial strain there is presence of resistance to diverse antibiotics. The infections of community origin have been treated by beta-lactamics, nitrofurantoine, trimetoprimsulfametoxasol and fluoroquinolones (specially ciprofloxacine).Conclusion. It was not possible to determine if the quinolonas are more effective than the antibiotics that belong to other pharmacological groups.

ResumoIntrodução. As infecções do trato urinário são um tema comum nos serviços de consulta externa e emergências dos centros de saúde. O uso inadequado e irracional de antibióticos pode favorecer o aparecimento de cepas resistentes e limitar a capacidade de resposta destes medicamentos. Este artigo busca revisar o uso de quinolonas (especificamente ciprofloxacina) com antibióticos de outros grupos farmacológicos e comparar efetividade e resistência bacteriana.Método. A partir da metodologia que aponta a prática clínica baseada na evidência para as revisões rápidas, se estabeleceu uma pergunta clínica que se procurou responder mediante pesquisas primárias em bases de dados eletrônicas como MEDLINE, PubMed, Cochrane Library Plus e o Journal of Infection.Resultado. Segundo o tipo de bactéria e cepa analisada, há presença de resistência a diversos antibióticos. As infecções de origem comunitária tem sido tratadas com betalactâmicos, nitrofurantoína, trimetoprimsulfametoxasol e fluoroquinolonas (especialmente ciprofloxacina).Conclusão. Não se determinou se as quinolonas são mais eficazes que os antibióticos que pertencem a outros grupos farmacológicos

Manejo de infecciones del tracto urinario / Management of the urinary tract infections

ResumenLas infecciones del tracto urinario (ITU) suelen ser una causa frecuente de consulta a los diversos servicios de medicina general. Ciertas condiciones como el embarazo, estados de inmunosupresión, sexo masculino y/o malformaciones del aparato genitourinario favorecen la complicación de esta patología, lo que requiere un manejo oportuno y específico.Son diversos los agentes etiológicos causantes de este cuadro, donde son el orden de frecuencia la Escherichia coli, Proteus mirabilis y Klebsiella neumoniae. Para su adecuado abordaje, una completa historia clínica y un adecuado examen físico dirigido son indispensables y de forma coadyuvante diversas guías avalan la realización del urocultivo como método estándar de oro para un diagnóstico certero.En cuanto a manejo farmacológico compete, el uso de antibióticos se reserva para casos específicos, algunos como el Trimetoprim sulfametoxazol, que anteriormente era la primera línea de elección, han caído en desuso debido al aumento en la resistencia bacteriana. Por otra parte, medicamentos como la nitrofurantoína continúan dando adecuados resultados tras su utilización. Por último, drogas como la fosfomicina, betalactámicos y algunas fluoroquinolonas ofrecen respuestas variables en el manejo de las cistitis. Finalmente, condiciones específicas como la pielonefritis presentan como manejo de primera línea el uso de fluoroquinolonas por el grado de compromiso asociado. El presente artículo pretende actualizar al médico general sobre el manejo y tratamiento actual para las infecciones urinarias con el fin de asegurar la adecuada evolución de sus pacientes.

AbstractUrinary tract infections (UTI) are a common cause to visit an emergency service or general medicine, this disease is more frequently in women and it does not difference between economical status. Certain conditions such as pregnancy, immunosuppression, being male, and/or malformations in the urinary tract can lead to many complications that require an urgent an accurate management.Is well known that there are several pathogens who can produce this disease, the most commons in order of appearance are Escherichia coli, Proteus mirabilis and Klebsiella neumoniae. For an accurate management, as in all the diseases, is well know the importance of a good clinical history, a truthful physical examination, but the physician can also use many other tools such as the urine culture, which is indeed the gold standard for the diagnosis.In the pharmacological field the use of antibiotics is reserved only to certain cases. There are some drugs like the Trimethoprim sulfamethoxazole, year ago the first step to treat an UTI, that have lost their effectiveness due the rise in bacterial resistance; on the other side drugs such as nitrofurantoin are still useful, and other drugs like the fosfomycin, beta-lactams and some fluoroquinolones are able to handle some cystitis. Finally, specifics conditions such as the pyelonephritis require the use of fluoroquinolonas due the complexity of the condition. This article pretends in a short and precisely way to update the physicians in the management, diagnosis and treatment of the UTI, having as a goal guarantee the evolution of their patients.

Is testosterone important in LUT function in men and women? ICI-RS 2015.

AIM: This review article is a collaborative report based upon the Authors' presentations and Group discussion on the role of testosterone (T) in the male and female lower urinary tract (LUT) which took place at the 6th International Consultation on Incontinence Research Society's (ICI-RS) annual meeting, in Bristol, UK (September 8-10, 2015). METHODS: It comprises overviews and opinions on both the current state of knowledge of the role of T in LUT function and dysfunction in both sexes. RESULTS: Results from animal studies suggest that T treatment may be beneficial for disorders of the LUT in women including urinary incontinence and pelvic organ prolapse. The need for clinical studies to evaluate the effect of T treatment in peri- and post-menopausal women, taking into account the type of applied androgen, the application form, timing and dosage, is especially emphasized. In males, findings on the impact of T on the male external urethral sphincter underscores that there is still much to learn about its role in male LUT physiology. The important topic of the use of T therapy in the treatment of enuresis in the young, both sexes, is also discussed. The importance of understanding the steroidogenic pathways linking T with estradiol is discussed as being of paramount importance in researching the unique actions of T in the LUT. CONCLUSION: The overall conclusion is that further research into the role of T in LUT function and dysfunction across genders and age groups (young to old) is extremely important. Neurourol. Urodynam. 36:859-862, 2017. © 2017 Wiley Periodicals, Inc.

Oral ketamine induced pathological changes of the urinary tract in a rat model.

INTRODUCTION: In recent years, prolonged ketamine abuse has been reported to cause urinary tract damage. However, there is little information on the pathological effects of ketamine from oral administration. We aimed to study the effects of oral ketamine on the urinary tract and the reversibility of these changes after cessation of ketamine intake. METHODS: Rats were fed with illicit (a concoction of street ketamine) ketamine in doses of 100 (N=12), or 300 mg/kg (N=12) for four weeks. Half of the rats were sacrificed after the 4-week feeding for necropsy. The remaining rats were taken off ketamine for 8 weeks to allow for any potential recovery of pathological changes before being sacrificed for necropsy. Histopathological examination was performed on the kidney and urinary bladder. RESULTS: Submucosal bladder inflammation was seen in 67% of the rats fed with 300 mg/kg illicit ketamine. No bladder inflammation was observed in the control and 100 mg/kg illicit ketamine groups. Renal changes, such as interstitial nephritis and papillary necrosis, were observed in rats given illicit ketamine. After ketamine cessation, no inflammation was observed in the bladder of all rats. However, renal inflammation remained in 60% of the rats given illicit ketamine. No dose-effect relationship was established between oral ketamine and changes in the kidneys. CONCLUSION: Oral ketamine caused pathological changes in the urinary tract, similar to that described in exposure to parenteral ketamine. The changes in the urinary bladder were reversible after short-term exposure.