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      • Trigonelline promotes auditory function through nerve growth factor signaling on diabetic animal models

        Castañ,eda, Rodrigo,Rodriguez, Isabel,Nam, Youn Hee,Hong, Bin Na,Kang, Tong Ho Elsevier 2017 Phytomedicine Vol.36 No.-

        <P>Conclusions: This study suggests that the enhanced hearing function produced by TRG may be mediated by NGF, providing a potential therapeutic strategy for diabetic hearing loss.</P>

      • Traditional oriental medicine for sensorineural hearing loss: Can ethnopharmacology contribute to potential drug discovery?

        Castañ,eda, Rodrigo,Natarajan, Sathishkumar,Jeong, Seo Yule,Hong, Bin Na,Kang, Tong Ho Elsevier 2019 Journal of Ethnopharmacology Vol.231 No.-

        <P><B>Abstract</B></P> <P><B>Ethnopharmacological relevance</B></P> <P>In Traditional Oriental Medicine (TOM), the development of hearing pathologies is related to an inadequate nourishment of the ears by the kidney and other organs involved in regulation of bodily fluids and nutrients. Several herbal species have historically been prescribed for promoting the production of bodily fluids or as antiaging agents to treat deficiencies in hearing.</P> <P><B>Aim of review</B></P> <P>The prevalence of hearing loss has been increasing in the last decade and is projected to grow considerably in the coming years. Recently, several herbal-derived products prescribed in TOM have demonstrated a therapeutic potential for acquired sensorineural hearing loss and tinnitus. Therefore, the aims of this review are to provide a comprehensive overview of the current known efficacy of the herbs used in TOM for preventing different forms of acquired sensorineural hearing loss and tinnitus, and associate the traditional principle with the demonstrated pharmacological mechanisms to establish a solid foundation for directing future research.</P> <P><B>Methods</B></P> <P>The present review collected the literature related to herbs used in TOM or related compounds on hearing from Chinese, Korean, and Japanese herbal classics; library catalogs; and scientific databases (PubMed, Scopus, Google Scholar; and Science Direct).</P> <P><B>Results</B></P> <P>This review shows that approximately 25 herbal species and 40 active compounds prescribed in TOM for hearing loss and tinnitus have shown <I>in vitro</I> or <I>in vivo</I> beneficial effects for acquired sensorineural hearing loss produced by noise, aging, ototoxic drugs or diabetes. The inner ear is highly vulnerable to ischemia and oxidative damage, where several TOM agents have revealed a direct effect on the auditory system by normalizing the blood supply to the cochlea and increasing the antioxidant defense in sensory hair cells. These strategies have shown a positive impact on maintaining the inner ear potential, sustaining the production of endolymph, reducing the accumulation of toxic and inflammatory substances, preventing sensory cell death and preserving sensory transmission. There are still several herbal species with demonstrated therapeutic efficacy whose mechanisms have not been deeply studied and others that have been traditionally used in hearing loss but have not been tested experimentally. In clinical studies, <I>Ginkgo biloba</I>, <I>Panax ginseng</I>, and <I>Astragalus propinquus</I> have demonstrated to improve hearing thresholds in patients with sensorineural hearing loss and alleviated the symptoms of tinnitus. However, some of these clinical studies have been limited by small sample sizes, lack of an adequate control group or contradictory results.</P> <P><B>Conclusions</B></P> <P>Current therapeutic strategies have proven that the goal of the traditional oriental medicine principle of increasing bodily fluids is a relevant approach for reducing the development of hearing loss by improving microcirculation in the blood-labyrinth barrier and increasing cochlear blood flow. The potential benefits of TOM agents expand to a multi-target approach on different auditory structures of the inner ear related to increased cochlear blood flow, antioxidant, anti-inflammatory, anti-apoptotic and neuroprotective activities. However, more research is required, given the evidence is very limited in terms of the mechanism of action at the preclinical <I>in vivo</I> level and the scarce number of clinical studies published.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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        Electrophysiological changes in auditory evoked potentials in rats with salicylate-induced tinnitus

        Castañ,eda, Rodrigo,Natarajan, Sathishkumar,Jeong, Seo Yule,Hong, Bin Na,Kang, Tong Ho Elsevier/North Holland 2019 Brain research Vol.1715 No.-

        <P><B>Abstract</B></P> <P>Early-response auditory evoked potentials (AEPs) in humans are significantly altered in tinnitus. These changes are closely related to that seen in animals, leading to new approaches to study tinnitus based on objective parameters. The purpose of this study was to characterize the AEPs in animals with tinnitus, by assessing early to late latency responses. For behavioral evaluation, rats were trained using positive reinforcement to press a lever in the presence of an auditory stimulus and to not press during silence. The auditory brainstem response (ABR), middle latency response (MLR) and auditory late latency response (LLR) were correlated to the false-positive responses (pressing the lever during silence), after oral administrations of Sodium Salicylate (SS, 350 mg/kg). In the present study, SS significantly increased the hearing thresholds and reduced ABR peak I amplitudes across the frequency range (4–32 kHz). In contrast, increased amplitudes were observed for several peaks in ABR, MLR, and LLR. Moreover, reduced ABR latencies in response to 8, 16 and 24 kHz tone bursts were observed after SS administration. Similarly, the central evaluation also revealed significantly reduced latencies in MLR and LLR during SS administration. In contrast, increased latencies were observed for ABR latencies in response to 32 kHz tone bursts, and at the P1-N1 component of LLR. Correlational analysis revealed that latencies and amplitudes of peaks II and IV (8 and 16 kHz) of ABR, and N2 latency and P2-N2 amplitude of LLR were associated with behavioral tinnitus. We suggest that AEPs can be used in the rat to evaluate the reduced sensory input and the increased central gain in SS-induced tinnitus, as well as reduced latencies (8–16 kHz) to distinguish between hearing loss and tinnitus.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Objective parameters of the AEPs were identified in rats treated with SS. </LI> <LI> Reduced sensory input was shown by hearing thresholds and ABR peak I amplitudes. </LI> <LI> Reduced latencies were found in the ABR (8-24kHz), MLR and LLR in SS-induced tinnitus. </LI> <LI> Central gain was reflected by increased amplitudes in ABR, MLR, and LLR. </LI> <LI> Behavioral tinnitus was correlated to peak IV of ABR, and P2 and N2 of LLR. </LI> </UL> </P>

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      • Amelioration of Auditory Response by DA9801 in Diabetic Mouse

        Lee, Yeong Ro,Hong, Bin Na,Her, You Ri,Castañ,eda, Rodrigo,Moon, Hyo Won,Kang, Tong Ho Hindawi Publishing Corporation 2015 Evidence-based Complementary and Alternative Medic Vol.2015 No.-

        <P>Diabetes mellitus (DM) is a metabolic disease that involves disorders such as diabetic retinopathy, diabetic neuropathy, and diabetic hearing loss. Recently, neurotrophin has become a treatment target that has shown to be an attractive alternative in recovering auditory function altered by DM. The aim of this study was to evaluate the effect of DA9801, a mixture of <I>Dioscorea nipponica</I> and <I>Dioscorea japonica</I> extracts, in the auditory function damage produced in a STZ-induced diabetic model and to provide evidence of the mechanisms involved in enhancing these protective effects. We found a potential application of DA9801 on hearing impairment in the STZ-induced diabetic model, demonstrated by reducing the deterioration produced by DM in ABR threshold in response to clicks and normalizing wave I–IV latencies and Pa latencies in AMLR. We also show evidence that these effects might be elicited by inducing NGF related through Nr3c1 and Akt. Therefore, this result suggests that the neuroprotective effects of DA9801 on the auditory damage produced by DM may be affected by NGF increase resulting from Nr3c1 via Akt transformation.</P>

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        Preparation of air stable nanoscale zero valent iron functionalized by ethylene glycol without inert condition

        Ruiz-Torres, Claudio Adrian,Araujo-Martí,nez, René,Fernando,Martí,nez-Castañ,ó,n, Gabriel Alejandro,Morales-Sá,nchez, J. Elpidio,Guajardo-Pacheco, Jesú,s Mar& Elsevier 2018 Chemical Engineering Journal Vol.336 No.-

        <P><B>Abstract</B></P> <P>The use of nanoscale zero-valent iron has been widely studied in recent years for potential application in environmental engineering, due to its affinity for a large number of contaminants, which may be in aqueous or solid phase, and for its abundance, which makes it an attractive tool for environmental remediation. However, there exist some variables in the production of nZVI that complicate the generation of the material, such as the complex methodologies of synthesis and the cost of inert conditions like nitrogen or argon atmosphere, which have the purpose of preventing the oxidation and reducing the instability of the material under ambient conditions. As a simple and economical synthesis methodology, this work presents an optimized method to synthesize functionalized nanoscale zero-valent iron (nZVI) using ethylene glycol (EG) without need for inert conditions. The coordination of iron ions during the nZVI-EG synthesis and the functionalization mechanism of the nanoparticles were identified by UV–Vis absorption spectroscopy and Fourier transform infrared spectroscopy (FTIR). Functionalized nZVI showed increased dispersibility due to the effects of steric repulsion between the grafted polymers. Ethylene glycol functionalized nZVI showed stability against oxidation during dry atmospheric condition, while significant oxidation was observed in the case of unfunctionalized nZVI. This result was also correlated with actual capacity for contaminant reduction. Therefore, the possibility was verified of using ethylene glycol in an effective surface modification method to prepare air stable nZVI for environmental remediation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Air-stable nZVI could be prepared by ethylene glycol without inert condition. </LI> <LI> Smaller and narrower size distribution could be obtained by functionalization. </LI> <LI> The nZVI-EG exhibited a protection effect against oxidation in oxic conditions. </LI> <LI> The reaction kinetics was not hindered by the organic functionalization agent EG. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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