RESUMO
OBJECTIVE: Overactive bladder (OAB) is a condition that has physical, social, psychosocial, and financial impacts. Transcutaneous tibial nerve stimulation (TTNS) is a modality that stimulates the nerve root fibers of L5-S3, the same spinal segments of the parasympathetic nervous system as the bladder. This scoping review aims to identify current literature available on the feasibility and outcomes of TTNS as a first-line treatment option for OAB. MATERIALS AND METHODS: A scoping review of six electronic data bases was performed to identify full-text articles from 2015 that explored the impact of TTNS on OAB and bladder dysfunction in people aged >18 years. RESULTS: A total of 15 articles met the inclusion criteria. TTNS was compared with sham treatment, parasacral stimulation, pelvic floor muscle training (PFMT), anticholinergic medication, and percutaneous tibial nerve stimulation (PTNS). Heterogeneity in treatment application and parameters existed, with variations in treatment duration, frequency of use, and treatment settings such as pulse width (µs) and frequency (Hz). Results indicated that TTNS has efficacy equal to PFMT and PTNS in the management of OAB; however, it is not as efficacious as anticholinergic medication. CONCLUSIONS: TTNS is a promising first-line management option for people with OAB, particularly in the older population and for those with neurogenic bladder. It can provide symptomatic relief from urinary incontinence, frequency, urgency, and nocturia, while avoiding the bothersome side effects of more invasive or pharmaceutical therapies. Heterogeneity in treatment parameters limits generalizability and translation of the most appropriate clinical application and should be considered in future trials.
Assuntos
Estimulação Elétrica Nervosa Transcutânea , Bexiga Urinária Hiperativa , Humanos , Bexiga Urinária Hiperativa/terapia , Resultado do Tratamento , Estimulação Elétrica Nervosa Transcutânea/métodos , Nervo Tibial , Antagonistas ColinérgicosRESUMO
High-content image-based screening was developed as an approach to test a small-molecule library of compounds targeting signal transduction pathways for antiviral activity against multiple highly pathogenic RNA viruses. Of the 2843 compounds screened, 120 compounds exhibited ≥60% antiviral activity. Four compounds (E225-0969, E528-0039, G118-0778, and G544-0735), which were most active against Rift Valley fever virus (RVFV) and showed broad-spectrum antiviral activity, were selected for further evaluation for their concentration-response profile and cytotoxicity. These compounds did not show any visible cytotoxicity at the highest concentration of compound tested (200 µM). All four of these compounds were more active than ribavirin against several viruses. One compound, E225-0969, had the lowest effective concentration (EC50 = 1.9-8.92 µM) for all the viruses tested. This compound was 13- and 43-fold more inhibitory against RVFV and Chikungunya virus (CHIKV), respectively, than ribavirin. The highest selectivity index (>106.2) was for E225-0969 against CHIKV. Time-of-addition assays suggested that all four lead compounds targeted early steps in the viral life cycle (entry and/or replication) but not virus egress. Overall, this work demonstrates that high-content image analysis can be used to screen chemical libraries for new antivirals against highly pathogenic viruses.
Assuntos
Antivirais/farmacologia , Ensaios de Triagem em Larga Escala/métodos , Testes de Sensibilidade Microbiana/métodos , Vírus de RNA/efeitos dos fármacos , Vírus de RNA/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Antivirais/química , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/normas , Ensaios de Triagem em Larga Escala/normas , Humanos , Testes de Sensibilidade Microbiana/normas , Microscopia de Fluorescência , Reprodutibilidade dos Testes , Bibliotecas de Moléculas Pequenas , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
PURPOSE: Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, has a wide range of beneficial properties. The purpose of this study was to test the protective role of CAPE in 661W cells (in vitro) against H(2)O(2)-mediated cell death and in albino rats (in vivo) against various light conditions. METHODS: The 661W cells were pretreated with CAPE and then stressed with H(2)O(2). Cell death was measured with lactate dehydrogenase (LDH) release assay, and mRNA and proteins were analyzed. Sprague Dawley rats were raised on either a control or CAPE (0.02%) diet and exposed to various light conditions for short or long periods. Retinal histology, mRNA, protein, lipid composition, and retinal function by electroretinography (ERG) were measured at the end of feeding. RESULTS: Pretreatment of 661W cells with CAPE reduced H(2)O(2)-mediated cell death in a dose-dependent manner and induced expression of heme oxygenase-1 (Ho1). Albino rats fed with CAPE had greater expression of Ho1 and intercellular adhesion molecule 1 (Icam1), less expression of FOS-like antigen (Fosl) and lipoxygenase 12 (Lox12) genes in the retina, less translocation of nuclear factor kappaB protein to the nucleus, and a lower molar ratio of n-3 polyunsaturated fatty acids. Further, the ERGs of the retinas of CAPE-fed rats were significantly higher than those of the control-fed rats when raised in dim light. CONCLUSIONS: CAPE can activate the antioxidative gene expression pathway in retinal cells in vitro and in vivo. Feeding CAPE to albino rats can enhance ERG responses and change the lipid profile in the rats' retinas.
Assuntos
Ácidos Cafeicos/farmacologia , Proteínas do Olho/genética , Expressão Gênica/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Albinismo , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Eletrorretinografia , Proteínas do Olho/metabolismo , Ácidos Graxos Ômega-3/análise , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio/farmacologia , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , L-Lactato Desidrogenase/análise , L-Lactato Desidrogenase/metabolismo , Luz , Lipoxigenases/genética , Lipoxigenases/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Álcool Feniletílico/farmacologia , Células Fotorreceptoras de Vertebrados/citologia , Células Fotorreceptoras de Vertebrados/metabolismo , Própole/química , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-DawleyRESUMO
Age-related macular degeneration (AMD) is a complex disease that has potential involvement of inflammatory and oxidative stress-related pathways in its pathogenesis. In search of effective therapeutic agents, we tested curcumin, a naturally occurring compound with known anti-inflammatory and antioxidative properties, in a rat model of light-induced retinal degeneration (LIRD) and in retina-derived cell lines. We hypothesized that any compound effective against LIRD, which involves significant oxidative stress and inflammation, would be a candidate for further characterization for its potential application in AMD. We observed significant retinal neuroprotection in rats fed diets supplemented with curcumin (0.2% in diet) for 2 weeks. The mechanism of retinal protection from LIRD by curcumin involves inhibition of NF-kappaB activation and down-regulation of cellular inflammatory genes. When tested on retina-derived cell lines (661W and ARPE-19), pretreatment of curcumin protected these cells from H(2)O(2)-induced cell death by up-regulating cellular protective enzymes, such as HO-1, thioredoxin. Since, curcumin with its pleiotropic activities can modulate the expression and activation of many cellular regulatory proteins such as NF-kappaB, AKT, NRF2, and growth factors, which in turn inhibit cellular inflammatory responses and protect cells; we speculate that curcumin would be an effective nutraceutical compound for preventive and augmentative therapy of AMD.