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1.
Molecules ; 24(20)2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31627373

RESUMO

Sweet potato anthocyanins are water-soluble pigments with many physiological functions. Previous research on anthocyanin accumulation in sweet potato has focused on the roots, but the accumulation progress in the leaves is still unclear. Two purple sweet potato cultivars (Fushu No. 23 and Fushu No. 317) with large quantities of anthocyanin in the leaves were investigated. Anthocyanin composition and content were assessed with ultra-performance liquid chromatography diode-array detection (UPLC-DAD) and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS), and the expressions of genes were detected by qRT-PCR. The two cultivars contained nine cyanidin anthocyanins and nine peonidin anthocyanins with an acylation modification. The acylation modification of anthocyanins in sweet potato leaves primarily included caffeoyl, p-coumaryl, feruloyl, and p-hydroxy benzoyl. We identified three anthocyanin compounds in sweet potato leaves for the first time: cyanidin 3-p-coumarylsophoroside-5-glucoside, peonidin 3-p-coumarylsophoroside-5-glucoside, and cyanidin 3-caffeoyl-p-coumarylsophoroside-5-glucoside. The anthocyanidin biosynthesis downstream structural genes DFR4, F3H1, anthocyanin synthase (ANS), and UDP-glucose flavonoid 3-O-glucosyltransferase (UFGT3), as well as the transcription factor MYB1, were found to be vital regulatory genes during the accumulation of anthocyanins in sweet potato leaves. The composition of anthocyanins (nine cyanidin-based anthocyanins and nine peonidin-based anthocyanins) in all sweet potato leaves were the same, but the quantity of anthocyanins in leaves of sweet potato varied by cultivar and differed from anthocyanin levels in the roots of sweet potatoes. The anthocyanidin biosynthesis structural genes and transcription factor together regulated and controlled the anthocyandin biosynthesis in sweet potato leaves.

4.
Neurosci Lett ; 711: 134406, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377244

RESUMO

The cochlea is the essential organ for hearing and includes both auditory sensory hair cells and spiral ganglion neurons. The discovery of inner ear stem cell brings hope to the regeneration of hair cell and spiral ganglion neuron as well as the followed hearing re-establishment. Thus the investigation on characteristics of inner ear stem/progenitor cells and related regulating clue is important to make such regeneration a reality. In addition, attempts have also been made to transplant exogenous stem cells into the inner ear to restore hearing function. In this review, we describe recent advances in the characterization of mammalian inner ear progenitor/stem cells and the mechanisms of regulating their proliferation and differentiation, and summarize studies that have used exogenous stem cells to repair damaged hair cells and neurons in the inner ear.

5.
Front Immunol ; 10: 1660, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379853

RESUMO

The loss of sensory hair cells in the cochlea is the major cause of sensorineural hearing loss, and inflammatory processes and immune factors in response to cochlear damage have been shown to induce hair cell apoptosis. The expression and function of Nfatc4 in the cochlea remains unclear. In this study, we investigated the expression of Nfatc4 in the mouse cochlea and explored its function using Nfatc4 -/- mice. We first showed that Nfatc4 was expressed in the cochlear hair cells. Cochlear hair cell development and hearing function were normal in Nfatc4 -/- mice, suggesting that Nfatc4 is not critical for cochlear development. We then showed that when the hair cells were challenged by ototoxic drugs Nfatc4 was activated and translocated from the cytoplasm to the nucleus, and this was accompanied by increased expression of Tnf and its downstream targets and subsequent hair cell apoptosis. Finally, we demonstrated that Nfatc4-deficient hair cells showed lower sensitivity to damage induced by ototoxic drugs and noise exposure compared to wild type controls. The Tnf-mediated apoptosis pathway was attenuated in Nfatc4-deficient cochlear epithelium, and this might be the reason for the reduced sensitivity of Nfatc4-deficient hair cells to injury. These findings suggest that the amelioration of inflammation-mediated hair cell apoptosis by inhibition of Nfatc4 activation might have significant therapeutic value in preventing ototoxic drug or noise exposure-induced sensorineural hearing loss.

6.
Nat Commun ; 10(1): 3733, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31427575

RESUMO

Hearing loss is the most common sensory disorder. While gene therapy has emerged as a promising treatment of inherited diseases like hearing loss, it is dependent on the identification of gene delivery vectors. Adeno-associated virus (AAV) vector-mediated gene therapy has been approved in the US for treating a rare inherited eye disease but no safe and efficient vectors have been identified that can target the diverse types of inner ear cells. Here, we identify an AAV variant, AAV-inner ear (AAV-ie), for gene delivery in mouse inner ear. Our results show that AAV-ie transduces the cochlear supporting cells (SCs) with high efficiency, representing a vast improvement over conventional AAV serotypes. Furthermore, after AAV-ie-mediated transfer of the Atoh1 gene, we find that many SCs trans-differentiated into new HCs. Our results suggest that AAV-ie is a useful tool for the cochlear gene therapy and for investigating the mechanism of HC regeneration.

7.
Mol Cell ; 75(4): 807-822.e8, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31442424

RESUMO

mTORC2 controls glucose and lipid metabolism, but the mechanisms are unclear. Here, we show that conditionally deleting the essential mTORC2 subunit Rictor in murine brown adipocytes inhibits de novo lipid synthesis, promotes lipid catabolism and thermogenesis, and protects against diet-induced obesity and hepatic steatosis. AKT kinases are the canonical mTORC2 substrates; however, deleting Rictor in brown adipocytes appears to drive lipid catabolism by promoting FoxO1 deacetylation independently of AKT, and in a pathway distinct from its positive role in anabolic lipid synthesis. This facilitates FoxO1 nuclear retention, enhances lipid uptake and lipolysis, and potentiates UCP1 expression. We provide evidence that SIRT6 is the FoxO1 deacetylase suppressed by mTORC2 and show an endogenous interaction between SIRT6 and mTORC2 in both mouse and human cells. Our findings suggest a new paradigm of mTORC2 function filling an important gap in our understanding of this more mysterious mTOR complex.

8.
J Vestib Res ; 29(4): 171-179, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31450524

RESUMO

BACKGROUND: The activities and participation component of the International Classification of Functioning, Disability and Health (ICF) has gained increasing recognition in rehabilitation field. The vestibular activities and participation measure (VAP) was the first instrument using the ICF to evaluate activities and participation outcomes for vestibular research and clinical practice. OBJECTIVES: This study aimed to cross-culturally adapt the VAP into Chinese language and to examine the psychometric properties of the Chinese version of VAP (VAP-C). METHODS: A standard "forward-backward" translation procedure was followed and the results were presented to the panel of experts and consensus was sought. Internal consistency was assessed using Cronbach's alpha and test-retest reliability examined by intraclass correlation coefficient (ICC). Convergent validity was determined by calculating the Pearson's correlation coefficient between the VAP-C and the Visual Analog Scale (VAS) and the Dizziness Handicap Inventory (DHI). Discriminative validity for test subjects versus control subjects was evaluated by Receiver Operating Characteristic curve (ROC) analysis. RESULTS: Minor revisions were made during translation to ensure semantic equivalence and to suit Chinese culture. A total of 121 patients complaining of dizziness or vertigo due to peripheral vestibular disorders (test subjects) and 41 control subjects were enrolled. Cronbach's alpha was 0.94 for the VAP-C total scale and greater than 0.80 for the two subscales. ICC for the VAP-C total scale was 0.78, and for subscale one was 0.77 and subscale two 0.76. The VAP-C had strong correlations (r = 0.85-0.88) with the VAS and fair to moderate correlations (r = 0.23-0.53) with DHI. Through ROC analysis, we found the VAP-C discriminated significantly between patients and control subjects. Based on the estimate of Youden J, the optimal cut-off values for VAP-C total and the two subscales were established. CONCLUSIONS: The VAP-C shows evidence of reliability and validity, which can be applied for evaluating the impact of the vestibular disorder on patients' activities and participation in Chinese language populations.

9.
Neurogastroenterol Motil ; 31(10): e13677, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31323174

RESUMO

OBJECTIVE: This study was to inspect the antidepressant-like effect of prebiotics and probiotics, and to explore the effect of modulating gut microbiota on the serotonin (5-HT) metabolism. METHODS: Fifty rats were separated into control and other four groups randomly. The four groups underwent the chronic unpredictable mild stress (CUMS) intervention with or without prebiotics and probiotics (Bifidobacterium longum, L. rhamnosus) treatment. After weighted, the animals underwent a series of behavioral tests comprising the sucrose preference test (SPT) and the forced swimming test (FST). Central and colonic serotonin levels and relative metabolism factors were measured and analyzed. Microbiota was examined by 16S rRNA gene pyrosequencing. RESULTS: CUMS intervention caused a decrease in body weight, an increase in FST, and a decrease in SPT. Prebiotics and probiotics all ameliorated the CUMS-induced loss of weight and depressive-like behaviors to a certain extent, especially L. rhamnosus. Compared with the group of CUMS intervention, the rats of probiotics and probiotics treatment had a tendency to reduce colonic 5-HT and increase 5-HT in frontal cortex and hippocampus. However, there was no significant difference in peripheral blood 5-HT among these groups. Furthermore, CUMS caused noteworthy gut microbiota variations at the phylum and other levels in rats. Remarkably, there were considerable relations of perturbed gut microbiota with the changed metabolism of 5-HT. CONCLUSION: In conclusion, these findings implied that prebiotics and probiotics have antidepressive effects, and a considerable effect on the regulation of 5-HT metabolism, especially L. rhamnosus.

10.
BMJ Open ; 9(6): e026711, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31217316

RESUMO

INTRODUCTION: Benign paroxysmal positional vertigo (BPPV) is recognised as the leading cause of peripheral vertigo in adults. The canalith repositioning procedure (CRP) can be used for effective treatment of BPPV. However, some patients experience residual dizziness (RD) even after successful CRP, resulting in a significant negative impact on their daily function and quality of life. Exercise-based vestibular rehabilitation (VR) has been proven as an effective method for managing dizziness and has been applied in patients with various vestibular disorders. However, the efficacy of VR to specifically target RD post-BPPV is unknown. This study aims to investigate the efficacy of VR, compared with betahistine or VR plus betahistine treatment, in the treatment of patients experiencing RD after successful CRP. METHODS AND ANALYSIS: A randomised single-blinded controlled trial will be carried out to determine the efficacy of VR compared with betahistine or VR plus betahistine treatment in mitigating RD and improving balance function. Patients with BPPV who experience RD after successful CRP will be recruited. Participants will be randomised into one of three groups to receive VR, betahistine or VR plus betahistine. There will be 61 participants in each group. The primary outcomes will be changes in the patient's daily function as measured by the Vestibular Activities and Participation questionnaire and balance ability assessed by computerised dynamic posturography. The secondary outcomes will be dizziness-related handicap, otolith function and duration of RD symptoms. Outcome measures will be noted at baseline and at 2, 4 and 8 weeks post-randomisation. This study has the potential to reduce unnecessary anti-vertigo drug prescriptions and may lead to a general consensus regarding the use of VR as a first-line treatment for RD in patients with BPPV. ETHICS AND DISSEMINATION: This trial received ethical approval from the Institutional Review Board of Eye and ENT Hospital of Fudan University (reference number 2017046). The study results will be disseminated via peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: NCT03624283; Pre-results.

11.
Fish Shellfish Immunol ; 92: 1-10, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31141718

RESUMO

Rimicaris exoculata (Decapoda: Bresiliidae) is one of the dominant species of hydrothermal vent communities, which inside its gill chamber harbors ectosymbioses with taxonomic invariability while compositional flexibility. Several studies have revealed that the establishment of symbiosis can be initiated and selected by innate immunity-related pattern recognition receptors (PRRs), such as C-type lectins (CTLs). In this research, a CTL was identified in R. exoculata (termed RCTL), which showed high expression at both mRNA and protein levels in the scaphognathite, an organ where the ectosymbionts are attached outside its setae. Linear correlationships were observed between the relative quantities of two major symbionts and the expression of RCTL based on analyzing different shrimp individuals. The recombinant protein of RCTL could recognize and agglutinate the cultivable γ-proteobacterium of Escherichia coli in a Ca2+-dependent manner, obeying a dose-dependent and time-cumulative pattern. Unlike conventional crustacean CTLs, the involvement of RCTL could not affect the bacterial growth, which is a key issue for the successful establishment of symbiosis. These results implied that RCTL might play a critical role in symbiotic recognition and attachment to R. exoculata. It also provides insights to understand how R. exoculata adapted to such a chemosynthesis-based environment.

12.
Environ Int ; 129: 239-246, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31146158

RESUMO

Brominated flame retardants (BFRs) such as tetrabromobisphenol A (TBBPA) and hexabromocyclododecanes (HBCDs) are of ecological concern due to their ubiquitous presence and adverse effects. There is a paucity of data on environmental fate of such compounds in mangrove wetlands, which are unique ecosystems in coastal intertidal areas and act as natural sinks for many pollutants. In this study, mangrove plants and sediments were collected from an urban nature reserve in South China to investigate bioaccumulation and translocation of TBBPA and HBCDs. The mean (range) concentrations of TBBPA and ΣHBCD in roots, stems and leaves were 67 (

Assuntos
Hidrocarbonetos Bromados/metabolismo , Bifenil Polibromatos/metabolismo , China , Retardadores de Chama/análise , Hidrocarbonetos Bromados/análise , Plantas/metabolismo , Bifenil Polibromatos/análise
13.
Exp Mol Med ; 51(5): 58, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123246

RESUMO

Wnt and FGF are highly conserved signaling pathways found in various organs and have been identified as important regulators of auditory organ development. In this study, we used the zebrafish lateral line system to study the cooperative roles of the Wnt and FGF pathways in regulating progenitor cell proliferation and regenerative cell proliferation. We found that activation of Wnt signaling induced cell proliferation and increased the number of hair cells in both developing and regenerating neuromasts. We further demonstrated that FGF signaling was critically involved in Wnt-regulated proliferation, and inhibition of FGF abolished the Wnt stimulation-mediated effects on cell proliferation, while activating FGF signaling with basic fibroblast growth factor (bFGF) led to a partial rescue of the proliferative failure and hair cell defects in the absence of Wnt activity. Whole-mount in situ hybridization analysis showed that the expression of several FGF pathway genes, including pea3 and fgfr1, was increased in neuromasts after treatment with the Wnt pathway inducer BIO. Interestingly, when SU5402 was used to inhibit FGF signaling, neuromast cells expressed much lower levels of the FGF receptor gene, fgfr1, but produced increased levels of Wnt target genes, including ctnnb1, ctnnb2, and tcf7l2, while bFGF treatment produced no alterations in the expression of those genes, suggesting that fgfr1 might restrict Wnt signaling in neuromasts during proliferation. In summary, our analysis demonstrates that both the Wnt and FGF pathways are tightly integrated to modulate the proliferation of progenitor cells during early neuromast development and regenerative cell proliferation after neomycin-induced injury in the zebrafish neuromast.

14.
Hear Res ; 379: 79-88, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31103816

RESUMO

Myosin VI is an actin-associated molecular motor vital for auditory and vestibular function. It is encoded by MYO6 located on chromosome 6q13 in human. Pathogenic variants in MYO6 have been associated with both dominant and recessive forms of hearing loss. However, the molecular mechanisms remain unclear. We established a humanized knock-in mouse model, Myo6-C442Y, to mimic the p.C442Y missense variant identified in human patients with autosomal dominant nonsyndromic hearing loss designated as DFNA22. We characterized hearing and inner ear morphologies of Myo6-C442Y and wild-type control mice. We found that both homozygous and heterozygous Myo6-C442Y mice exhibited hearing loss from three weeks after birth that rapidly progressed to profound deafness by six to nine weeks of age. The hearing loss corresponded to the degeneration of hair cells in the organ of Corti. We also observed disorganized stereocilia with irregular morphological features by immunohistochemistry and scanning electron microscopy. Additionally, hearing loss and inner-ear morphological anomalies were more pronounced and deteriorated more drastically in homozygous than in heterozygous Myo6-C442Y mice, indicating a semi-dominant inheritance pattern. Heterozygous Myo6-C442Y mice recapitulated the progressive postlingual sensorineural deafness in human, thus providing a useful model for elucidating the role myosin VI plays in the mammalian auditory system. Furthermore, the late-onset hearing loss of this mouse model may provide a therapeutic window for the emerging gene therapy, a promising strategy to treat certain forms of genetic deafness.

15.
Zhongguo Zhong Yao Za Zhi ; 44(6): 1220-1226, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30989987

RESUMO

The aim of this study was to observe the effect of baicalin on the growth state of attention deficit hyperactivity disorder animal model and its regulation on Ca MKⅡand ERK1/2.In the present study,a total of 40 SHR rats were randomly divided into model group,methylphenidate hydrochloride group,and low,medium,and high dose baicalin groups,with 8 rats in each group.Eight WKYrats were selected as a normal control group.The methylphenidate hydrochloride group(0.07 g·L~(-1))and the low(3.33 g·L~(-1)),medium(6.67 g·L~(-1)),and high dose(10 g·L~(-1))baicalin groups received corresponding drugs by gavage administration according to the body weight(0.015 m L·g~(-1)),while the normal group and the model group received the same volume of normal saline by gavage.Thegavage administration lasted for 4 weeks,twice a day.The body weight of the rats and the amount of remaining feed were weighed daily,and the growth state of the rats was statistically evaluated weekly.Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structures.The Ca MKⅡand ERK1/2 protein and mRNA expression levels were detected with Western blot and Real-time PCR methods,respectively.RESULTS: showed that baicalin did not affect the normal eating and weight gain of rats,and the weight gain of rats was even more significant than that in the normal group(P<0.05).In the study of its effects on Ca MKⅡand ERK1/2 protein expression in rat synaptosomes,the expression of both proteins in each drug-administered group was higher than that in the model group(P<0.05);besides,the expression levels of Ca MKⅡand ERK1/2 protein were significantly increased in both baicalin high dose group and the methylphenidate hydrochloride group(P<0.05).The relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosome was detected by PCR.The results showed that medium and high doses of baicalin and methylphenidate hydrochloride significantly increased the relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosomes of SHR rats(P<0.05).In conclusion,baicalin does not affect the normal growth and development of SHR rats,so it is safe for administration.Both baicalin and methylphenidate hydrochloride could up-regulate the relative expression of Ca MKⅡand ERK1/2 in mRNA and protein,and the pharmacodynamic stability of baicalin is in a dose-dependent manner to certain extent.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Animais , Modelos Animais de Doenças , Flavonoides , Peptídeos e Proteínas de Sinalização Intracelular , Sistema de Sinalização das MAP Quinases , Proteínas Serina-Treonina Quinases , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
16.
Chemosphere ; 227: 315-322, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30995592

RESUMO

Polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane (DBDPE), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCDD) and dechlorane plus (DP) were measured in sediments collected from three mangrove wetlands of the Pearl River Estuary (PRE) in South China. This study aims to investigate the distribution of these halogenated flame retardants (HFRs) and the correlations between HFRs and microbial community structure in mangrove sediments. Concentrations of PBDEs, DBDPE, BTBPE, TBBPA, HBCDD and DP in mangrove sediments ranged from 6.97 to 216.1, 3.70-26.0, 0.02-0.73, 0.02-37.5, 0.44-127.5 and 0.07-2.23 ng/g dry weight, respectively. Higher levels of PBDEs, BTBPE, HBCDD and DP were observed in sediments from Futian mangrove wetland of Shenzhen, the only nature reserve located in the downtown of China. The highest concentration of TBBPA found in mangrove sediments from Guangzhou was proximate to a ferry terminal and a dockyard where TBBPA is widely used in the coatings. PBDEs were the predominant HFRs in mangrove sediments, with an average contribution of 63.0%. Mangrove sediments from Guangzhou and Zhuhai showed an enrichment of (-)-α-HBCDD, (-)-ß-HBCDD and (-)-γ-HBCDD. Concentrations of HFRs in mangrove sediments from Guangzhou increased significantly from 2012 to 2015, which was probably due to the establishment and rapid development of Nansha Free Trade Zone of Guangzhou. Redundancy analysis showed that HFRs may cause a shift of microbial community structure in mangrove sediments and the variations were significantly correlated with TBBPA, syn-DP and BTBPE.


Assuntos
Monitoramento Ambiental/métodos , Estuários , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Microbiota/efeitos dos fármacos , Áreas Alagadas , China , Retardadores de Chama/farmacologia , Halogenação , Hidrocarbonetos Clorados/análise , Compostos Policíclicos/análise , Rios
17.
World Neurosurg ; 126: e688-e693, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30844532

RESUMO

OBJECTIVE: Neurorrhaphy with interpositional graft is a practical technique to achieve facial reanimation when the continuity of the facial nerve is interrupted and a large gap between the proximal and distal stump exists. The aim of this study was to report long-term outcomes of neurorrhaphy for facial reanimation with interpositional graft. The roles of some variable factors in the outcome of neurorrhaphy with interpositional graft were also evaluated and compared. METHODS: A retrospective case series from a single tertiary referral center comprised 23 patients with facial nerve interruptions who underwent neurorrhaphy with interpositional graft using either end-to-end anastomosis or end-to-side hypoglossal-facial technique. Preoperative data (age, sex, primary lesion, interval from paralysis to surgery, facial nerve function), intraoperative data (surgical approach, graft and type of neurorrhaphy), and postoperative data (facial nerve function) were collected and analyzed. RESULTS: Mean follow-up time was 26.6 ± 11.9 months. Patients who underwent neurorrhaphy for facial reanimation within 1 year after onset of facial paralysis were more likely to achieve House-Brackmann grade ≤3 compared with patients who underwent neurorrhaphy >1 year after onset of facial paralysis (odds ratio = 23.85, P = 0.04). No other factors were associated with improved outcomes. CONCLUSIONS: Early neurorrhaphy with interpositional graft (≤1 year) for facial reanimation resulted in better final facial nerve function outcomes compared with a delayed procedure.

18.
Adv Exp Med Biol ; 1130: 1-16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30915698

RESUMO

Cochlear hair cells are mechanoreceptors of the auditory system and cannot spontaneously regenerate in adult mammals; thus hearing loss due to hair cell damage is permanent. In contrast, hair cells in nonmammalian vertebrates such as birds and in the zebrafish lateral line have the ability to regenerate after hair cell loss. Many regulatory factors, including signaling pathways, transcription factors, and epigenetic regulators, play roles in hair cell regeneration in various species. In this chapter, we review the history of hair cell regeneration research, the methods used in the study of hair cell regeneration, the properties and modulating factors of inner ear stem cells, and the re-formation of cochlear ribbon synapses and hearing function recovery.


Assuntos
Orelha Interna , Células Ciliadas Auditivas/citologia , Regeneração , Animais , Aves , Células-Tronco/citologia , Peixe-Zebra
19.
Adv Exp Med Biol ; 1130: 17-36, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30915699

RESUMO

Hair cells are specialized sensory epithelia cells that receive mechanical sound waves and convert them into neural signals for hearing, and these cells can be killed or damaged by ototoxic drugs, including many aminoglycoside antibiotics, platinum-based anticancer agents, and loop diuretics, leading to drug-induced hearing loss. Studies of therapeutic approaches to drug-induced hearing loss have been hampered by the limited understanding of the biological mechanisms that protect and regenerate hair cells. This review briefly discusses some of the most common ototoxic drugs and describes recent research concerning the mechanisms of ototoxic drug-induced hearing loss. It also highlights current developments in potential therapies and explores current clinical treatments for patients with hearing impairments.


Assuntos
Células Ciliadas Auditivas/efeitos dos fármacos , Perda Auditiva/induzido quimicamente , Perda Auditiva/prevenção & controle , Aminoglicosídeos/toxicidade , Antineoplásicos/toxicidade , Diuréticos/toxicidade , Humanos , Platina/toxicidade
20.
Adv Exp Med Biol ; 1130: 109-128, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30915704

RESUMO

Tinnitus is one of the most common hearing disorders, with wide-ranging risk factors including age, hearing loss, noise exposure, inflammatory diseases or tumors of the ear, ototoxic drugs, head or cervical vertebra trauma, and psychological disorders (e.g., anxiety and depression). Tinnitus can be a lifelong disorder and will bring about annoyance, anxiety, depression, insomnia, hyperacusis, concentration difficulty, and, in some extreme cases, suicide. Not every tinnitus patient will require medical attention, and the majority often get accustomed to the phantom sound; however, about 20% of the sufferers will seek clinical intervention. As a matter of fact, evidence was rare for successful tinnitus treatment with a randomized clinical trial. With recent advances in neuroimaging approaches and development of novel tinnitus animal models, scientists have gained new insights into the neural basis of tinnitus. Current theories regarding mechanisms underlying tinnitus focus on abnormal activities in the central nervous system, such as elevated spontaneous neuronal firing rate and increased neuronal synchronization caused by the auditory deprivation, changes in the tonotopic map, auditory cortical reorganization, dysregulation of the limbic system, and the central auditory cortex. At the present, there is a lack of objective indicator of tinnitus, and the diagnosis battery for tinnitus mainly relies on subjective assessments and self-reports, such as case history, audiometric tests, detailed tinnitus inquiry, tinnitus matching, and neuropsychological assessment. While there is currently no golden standard treatment for tinnitus, counseling, psychotherapy, pharmacological approaches, masking devices, individualized sound stimulation, and cognitive behavioral therapy (CBT) are the most widely used strategies, and among these only CBT treatment has been shown to have a definite improvement effect on tinnitus in a large randomized controlled trial. In summary, this article reviews recent advances in understanding, diagnosis, and treatment of tinnitus.


Assuntos
Zumbido/diagnóstico , Zumbido/terapia , Animais , Córtex Auditivo/fisiopatologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
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