RESUMO
INTRODUCTION: A significant number of sensorineural hearing loss (SSNHL) patients had no noticeable hearing improvement after glucocorticoid (GC) treatment. In the present study, we examined expression of the nuclear factor erythroid 2-related factor 2 (NRF2) and histone deacetylase 2 (HDAC2) in peripheral blood mononuclear cells (PBMCs) of refractory SSNHL patients to study the role of NRF2-HDAC2 pathway in GC insensitivity hearing improvement after GC treatment, which is usually referred to as refractory SSNHL or GC insensitivity. MATERIALS AND METHODS: Forty-four refractory SSNHL patients were treated by intratympanic GC infusion. Hearing was tested in all patients before and after treatment by pure tone hearing test. NRF2/HDAC2 mRNA and protein levels were examined in PBMCs of refractory SSNHL patients before and after treatment. PBMCs from healthy volunteers were used as normal controls. RESULTS: According to the hearing improvement after treatment, patients were assigned into 2 groups: the intratympanic GC sensitive (IGCS) group (hearing recovery ≥15 dB HL) and the intratympanic GC insensitive (IGCI) group (hearing recovery <15 dB HL). Before treatment, the NRF2 mRNA level was lower in all patients than the normal control group. After treatment, NRF2 and HDAC2 mRNA and protein levels were increased in the IGCS group, while no significant change was observed in the IGCI group. CONCLUSION: Low response of NRF2/HDAC2 proteins is associated with GC insensitivity in SSNHL. We speculate that the NRF2-HDAC2 pathway affects GC sensitivity in SSNHL patients.
Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Audiometria de Tons Puros , Glucocorticoides/uso terapêutico , Perda Auditiva Neurossensorial/tratamento farmacológico , Histona Desacetilase 2/genética , Humanos , Leucócitos Mononucleares , Fator 2 Relacionado a NF-E2/genética , Resultado do TratamentoRESUMO
BACKGROUND Sudden sensorineural hearing loss (SSNHL) is currently treated with a combination of drugs, predominantly with glucocorticoids (GCs). However, the mechanisms of action of GCs in SSNHL are unknown. This study aimed to analyze the role of endoplasmic reticulum stress (ERS) in SSNHL pathogenesis and prognosis. MATERIAL AND METHODS In this study, we evaluated the expression and activation status of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-C/EBP homologous protein (CHOP) pathway in peripheral blood mononuclear cells (PBMCs) from patients with SSNHL and compared them with those in healthy controls. We also compared differences in expression of activating transcription factor 4 (ATF4) and CHOP before and after glucocorticoid treatment in patients with improved and unimproved SSNHL. RESULTS Treatment with GCs significantly improved hearing in 55% of patients with SSNHL. Levels of phosphorylated PERK (p-PERK) and phosphorylated eukaryotic initiation factor 2alpha were increased in PBMCs from patients with SSNHL compared with healthy controls. ATF4 and CHOP expression were also significantly elevated. After treatment, the amount of ATF4 and CHOP proteins in PBMCs in the patients whose SSNHL improved was significantly reduced compared with the levels measured before treatment in all patients with SSNHL. The expression of the ATF4 and CHOP proteins in PBMCs in the unimproved group, however, was not significantly changed relative to pretreatment levels. CONCLUSIONS ERS may play a significant role in the pathogenesis of SSNHL, and the responsiveness of the condition to GC-mediated mitigation of ERS may be one of the key factors that affect patient prognosis.
Assuntos
Estresse do Retículo Endoplasmático , Perda Auditiva Neurossensorial/sangue , Perda Auditiva Neurossensorial/patologia , Leucócitos Mononucleares/patologia , Fator 4 Ativador da Transcrição/metabolismo , Adulto , Regulação para Baixo/genética , Estresse do Retículo Endoplasmático/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Feminino , Humanos , Masculino , Fator de Transcrição CHOP/metabolismo , Regulação para Cima/genética , eIF-2 Quinase/metabolismoRESUMO
BACKGROUND Repetition disorder can be used as an important criterion for aphasia classification, and damaged arcuate fasciculus in the dominate hemisphere has been reported to be closely related to repetition disorder, but the underlying neurological mechanism remains unclear. MATERIAL AND METHODS Fifteen stroke patients with poststroke aphasia and 9 healthy controls were included in the study. The value of fractional anisotropy (FA) in the dominate arcuate fasciculus in stroke patients and healthy controls were measured using DTI. We also assessed their repetition dysfunction with the Aphasia Battery of Chinese (ABC) assessment and calculated the correlation between the FA values in the dominate arcuate fasciculus and ABC scores of word repetition and sentence repetition. RESULTS There was a moderate correlation between the total score of repetition evaluation and the FA value of injured arcuate fasciculus in the dominant hemisphere (r=0.551, P=0.033). We found no correlation between the score of word repetition and the FA value of injured arcuate fasciculus in the dominant hemisphere (r=0.330, P=0.230), but there was a strong correlation between the score of sentence repetition and the FA value of injured arcuate fasciculus in the dominant hemisphere (r=0.795, P≤0.001). CONCLUSIONS We found that unintegrated left arcuate fasciculus might be related to the repetition dysfunction after stroke, especially sentence repetition deficit, which suggests that sentence repetition evaluation could be used to indicate the integrity of the arcuate fasciculus in the dominant hemisphere after stroke.
Assuntos
Afasia/diagnóstico por imagem , Afasia/fisiopatologia , Cérebro/fisiopatologia , Imagem de Tensor de Difusão , Fala/fisiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Substância Branca/fisiopatologia , Afasia/complicações , Cérebro/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Substância Branca/diagnóstico por imagemRESUMO
OBJECTIVE: The aim of this study was to understand parents' perspectives on caring for children who underwent liver transplantation in the intensive care unit transition period and to provide a reference for the development of targeted intervention strategies. METHODS: Thirteen parents of children who underwent liver transplantation at a tertiary hospital in Hangzhou, Zhejiang Province were chosen for in-depth semi-structured interviews via purposive sampling. The interview data were analyzed and summarized via content analysis. FINDINGS: Three themes were extracted, including a period of separation and suffering (being apart from child is tough, chilling atmosphere, and limited family access); being an overwhelming caregiver (hope coupled with worry, conflict of roles, and existential care dilemmas); and facing a new normal: searching for information and support (information on medical conditions, post-discharge care assistance, educational support, and peer support). CONCLUSION: For parents whose child underwent liver transplantation, the transition period from the intensive care unit to the general ward is challenging. Parents are burdened with several caregiving responsibilities and require a variety of information and support. It is advised that nurses should offer sufficient information and suitable educational approaches to enhance these parents' capacity to care for their children and assist children and their parents in making a smooth transition. IMPLICATIONS FOR CLINICAL PRACTICE: This study highlights parents' perspectives on caring for children with liver transplants transferred from the intensive care unit to a general ward. Transitional care is strenuous, evoking different feelings before and after transfer. The health care professionals should focus on the needs and challenges faced by parents who are caring for children with liver transplants during the intensive care unit transition period. To achieve this, it is critical to establish a supportive environment and provide suitable information and education for parents to enhance their caregiving abilities.
Assuntos
Unidades de Terapia Intensiva , Transplante de Fígado , Pais , Pesquisa Qualitativa , Humanos , Transplante de Fígado/psicologia , Transplante de Fígado/métodos , Masculino , Pais/psicologia , Feminino , Criança , Adulto , Pré-Escolar , Unidades de Terapia Intensiva/organização & administração , China , Entrevistas como Assunto/métodos , Pessoa de Meia-Idade , Adaptação Psicológica , Lactente , Adolescente , Transferência de Pacientes/métodos , Transferência de Pacientes/normas , Transferência de Pacientes/estatística & dados numéricosRESUMO
Objectives: This study aimed to assess the knowledge, attitudes, and practices (KAP) and the training requirements of pediatric intensive care nurses regarding intra-abdominal pressure (IAP) monitoring, in order to provide a reference for the development of relevant training programs and operational procedures in clinical practice. Methods: This descriptive cross-sectional survey was conducted from April 2023 to June 2023. A convenience sample was created by recruiting 212 pediatric intensive care nurses in eight hospitals in Zhejiang Province. A self-developed IAP monitoring KAP assessment tool was used for evaluation, which included knowledge (14 items), attitude (6 items), and practice (8 items), three dimensions, 28 items. Results: The overall KAP score was 60.73 ± 8.35; the knowledge score was 7.84 ± 2.35, with a scoring rate of 56.0%; the attitude score was 25.16 ± 3.23, with a scoring rate of 83.9%; and the practice score was 28.44 ± 6.46, with a scoring rate of 69.3%. Nurses wh-o have received IAP monitoring training have higher KAP score, knowledge score and practice score than those who have not received it (P < 0.05). Nurses aged ≤ 30 showed better knowledge of IAP monitoring than those aged > 30 (P < 0.05). Among the participants, 55.7% of the nurses believed the current knowledge was insufficient to perform IAP measurement effectively. Difficulty in identifying the high-risk population of intra-abdominal hypertension (IAH) (64.6%), unfamiliarity with the operation process of IAP measurement (55.6%), and unreasonable nurse-patient ratio allocation (52.8%) were the main obstacles for nurses to monitor IAP. Conclusions: Pediatric intensive care nurses have a positive attitude towards IAP monitoring, but the knowledge level and practical behavior still need to be strengthened. In particular, the knowledge of published consensus definitions, measurement techniques, and frequency for IAP monitoring is inadequate. It is necessary to implement tailored IAP monitoring training based on their training needs and potential obstacles to promote the standardization and scientificity of IAP monitoring.
RESUMO
OBJECTIVE: To detect genetic cause of two Chinese siblings (patient 1 and 2) with Pendred syndrome. DESIGN: Patients and their parents underwent clinical and genetic evaluations. To identify genetic mutations, sequencing of SLC26A4 was carried out. STUDY SAMPLE: Two siblings and their parents. RESULTS: Clinical evaluations showed that patient 1 suffered from bilateral postlingual progressive sensorineural hearing loss with enlarged vestibular aqueduct and slight diffuse multinodular goiter with euthyroid, and patient 2 suffered from bilateral prelingual progressive sensorineural hearing loss with enlarged vestibular aqueduct and no goiter with euthyroid. Furthermore, the sequence analysis of SLC26A4 indicated that either of the two siblings presented a compound heterozygote for the c.919A>G mutation in the splice site of intron 7 and for the c.1548insC mutation in exon 14. Their mother was a heterozygous carrier of the splice site mutation in intron 7, and their father was a heterozygous carrier of the insertion mutation in exon 14. CONCLUSIONS: Mutation analysis identified a compound heterozygous mutation (c.919A>G/c.1548insC) in SLC26A4 in two Chinese siblings with Pendred syndrome. Also, c.1548insC was first reported in the Chinese population. Although the two siblings from the same family carried the same genotype, they presented different phenotypes.
Assuntos
Povo Asiático/genética , Bócio Nodular/genética , Perda Auditiva Neurossensorial/genética , Audição/genética , Heterozigoto , Proteínas de Membrana Transportadoras/genética , Mutação , Adulto , Audiometria de Tons Puros , China/epidemiologia , Análise Mutacional de DNA , Éxons , Feminino , Predisposição Genética para Doença , Bócio Nodular/diagnóstico , Bócio Nodular/etnologia , Bócio Nodular/fisiopatologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etnologia , Perda Auditiva Neurossensorial/fisiopatologia , Hereditariedade , Humanos , Íntrons , Masculino , Linhagem , Fenótipo , Transportadores de Sulfato , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Objective: Tinnitus-a common clinical symptom-can be categorized into pulsatile tinnitus (PT) and non-PT. Among these, PT is usually associated with sigmoid sinus symptoms, such as sigmoid sinus wall defect or diverticulum, for which various surgical treatments are available. We have discussed the clinical efficacy of surgery for sigmoid sinus-associated PT via the transmastoid approach in this study. Methods: We conducted a retrospective review of 4 patients who underwent surgery for sigmoid sinus-associated PT via the transmastoid approach at Nanjing Drum Tower Hospital from January to December 2020. Of these, 2 patients had sigmoid sinus wall defect and 2 had sigmoid sinus diverticulum. Post-operative tinnitus grading and surgical efficacy were determined. Results: After surgery, PT dissolved in 3 patients, while tinnitus significantly decreased in 1 patient. During the follow-up period of 12-18 months, none of the 4 patients showed complications related to increased intracranial pressure or venous sinus thrombosis, and tinnitus symptoms disappeared in 3 patients without recurrence, although 1 patient occasionally developed tinnitus. Postoperative thin-slice CTA of the temporal bone indicated that the sigmoid sinus bone wall defect or diverticulum was completely repaired with a thick soft tissue coverage. Conclusion: Surgical repair of sigmoid sinus-associated PT via the transmastoid approach deserves clinical promotion as it exhibited better efficiency while being relatively less invasive.
RESUMO
Congenital temporal bone cholesteatoma is a rare lesion in otolaryngology.The disease is locally invasive and may lead to significant complications,including hearing lossï¼conductive or sensorineuralï¼, temporal bone destruction and intracranial invasion. This article reviews the characteristic symptoms of congenital temporal bone cholesteatoma, testing and imaging of the disease, stage and the current treatment options in order to promote awareness to this rare disease entity and perform early surgical treatment, effectively avoid the destruction of the temporal bone and its surrounding structures, thereby reducing the occurrence of complications. By improving the understanding of the disease and performing early surgical treatment, the destruction of the temporal bone and its surrounding structures can be effectively avoided, thereby reducing the occurrence of complications.
Assuntos
Colesteatoma , Surdez , Perda Auditiva , Humanos , Colesteatoma/diagnóstico , Colesteatoma/cirurgia , Colesteatoma/congênito , Osso TemporalRESUMO
This paper constructs a theoretical analysis model based on the theories of planned behaviour, consumer emotion and identity by surveying tourists in Zunyi city, China and employing structural equation modelling to explore the influence mechanisms of tourist motivation, satisfaction and place identity on the loyalty of 'red tourism'. The research results demonstrated a relationship between tourist motivation, satisfaction, place identity and tourist loyalty and thus confirmed the theoretical model. Tourist satisfaction and place identity are important means by which tourist motivation affects the loyalty of red tourism. However, tourist motivation cannot directly affect red tourism loyalty, though it can indirectly affect it via satisfaction and place identity. Tourist motivation not only directly influences the satisfaction of red tourism but also indirectly influences it through place identity. Furthermore, tourist motivation affects place identity. The mere recognition of place identity does not automatically attract tourists' loyalty but can, through their experiencing satisfaction, indirectly inspire it. Nevertheless, place identity can only directly affect tourist satisfaction, and tourist satisfaction can only directly affect red tourism loyalty.
Assuntos
Motivação , Turismo , China , Emoções , Análise de Classes LatentesRESUMO
Purpose: Drawing on the motivation theory, this study investigated the effect and consequences of personal motivation and innovative climate on innovative behavior among university students in mainland China. The study also examined whether the effect of personal motivation and innovative climate on Chinese university students' innovative behavior is heterogeneous between disciplines and place of residence. Methods: A quantitative study was conducted to test the hypotheses. Data were collected from 245 undergraduate students at Chinese universities with paper-based questionnaires. Self-report scales were used to measure levels of personal motivation, innovative climate, and innovative behaviors. A confirmatory factor analysis was used to test the scale and questionnaire's reliability and validity. The logistic model was applied to analyze the data and test the hypotheses. Results: Personal motivation and innovative climate have significant effects on Chinese university students' innovative behavior. The effect of personal motivation and innovative climate on students' innovative behavior is heterogeneous between disciplines and place of residence. Further, extrinsic motivation serves as a positive incentive. Mentor support, good academic climate, and knowledge sharing affect students' innovative behavior positively. However, insufficient guaranteed resources has a significant negative influence. The data demonstrated no statistically significant difference between intrinsic motivation and students' innovative behavior. Conclusion: This study contributes to the empirical literature on mechanisms that influence innovative behavior by testing the relation between personal motivation, innovative climate, and innovative behavior on the part of Chinese university students. In addition, these findings also provide evidence for ways to improve university students' innovative consciousness and innovative ability, as well as universities' management practice of innovative education.
RESUMO
Noise- induced hearing loss usually refers to auditory impairment which is caused by long-term exposure to noise. The occupational noise problem is serious and urgently needs to be addressed, along with the lack of effective treatments. Recent studies have shown that the imbalance between oxidation and antioxidation is the source of the disease. To correct the redox reaction imbalance and to maintain an equilibrium of the redox reaction have always been the research focus of the prevention and treatment in noise induced hearing loss. This article reviews antioxidant therapy and prevention in noise induced hearing loss, including antioxidants, antioxidant enzymes and herbal medicine.
Assuntos
Perda Auditiva Provocada por Ruído , Ruído Ocupacional , Doenças Profissionais , Antioxidantes/uso terapêutico , Perda Auditiva Provocada por Ruído/prevenção & controle , Humanos , Ruído Ocupacional/efeitos adversos , Ruído Ocupacional/prevenção & controleRESUMO
Aphasia is characterized by the disability of spontaneous conversation, listening, understanding, retelling, naming, reading, or writing. However, the neural mechanisms of language damage after stroke are still under discussion. This study aimed to investigate the global and nodal characterization of the functional networks in patients with aphasic stroke based on resting-state functional MRI (fMRI). Twenty-four right-handed patients with aphasia after stroke and 19 healthy controls (HC) underwent a 3-TfMRI scan. A whole-brain large-scale functional connectivity network was then constructed based on Power's atlas of 264 functional regions of interest, and the global and nodal topological properties of these networks were analyzed using graph theory approaches. The results showed that patients with aphasia had decreased in small-worldness (sigma), normalized clustering coefficient (gamma), and local efficiency (E loc) values. Furthermore, E loc was positively correlated with language ability, retelling, naming, and listening comprehension in patients with aphasia. Patients with aphasia also had decreased nodal degree and decreased nodal efficiency in the left postcentral gyrus, central opercular cortex, and insular cortex. Our results suggest that the global and local topology attributes were altered by injury in patients with aphasic stroke. We argue that the local efficiency of brain networks might be used as a potential indicator of basic speech function in patients with aphasia.
RESUMO
We previously reported that dysregulation of histone deacetylase 2 (Hdac2) was associated with the prognosis of sudden sensorineural hearing loss. However, the underlying molecular mechanisms are poorly understood. In the present study, we developed an acute hearing loss animal model in guinea pigs by infusing lipopolysaccharides (LPS) into the cochlea and measured the expression of Hdac2 in the sensory epithelium. We observed that the level of Hdac2 was significantly decreased in the LPS-infused cochleae. The levels of apoptosis-inhibition genes Bcl-2 and Bcl-xl were also decreased in the cochlea and correlated positively with the levels of Hdac2. Caspase3 or TUNEL-positive spiral ganglion neurons, hair cells, and supporting cells were observed in the LPS-infused cochleae. These in vivo observations were recapitulated in cell culture experiments. Based on bioinformatics analysis, we found miR-204-5p was engaged in the regulation of Hdac2 on Bcl-2. Molecular mechanism experiments displayed that miR-204-5p could be regulated by Hdac2 through interacting with transcription factor Sp1. Taken together, these results indicated that the Hdac2/Sp1/miR-204-5p/Bcl-2 regulatory axis mediated apoptosis in the cochlea, providing potential insights into the progression of acute hearing loss. To our knowledge, the study describes a miRNA-related mechanism for Hdac2-mediated regulation in the cochlea for the first time.
RESUMO
Cisplatininduced cytotoxicity, such as nephrotoxicity, neurotoxicity and ototoxicity, restricts the clinical application of this compound. Panax notoginseng Saponins (PNS) exhibit potent free radical scavenging and antioxidant activity. PNS have been demonstrated to reduce cisplatininduced nephrotoxicity and neurotoxicity. The present study investigated the ability of PNS to protect the auditory HEIOC1 cell line against ototoxicity induced by cisplatin. PNS induced activation of the AKT/nuclear factor erythroid 2related factor 2 (Nrf2) signaling pathway. Following pretreatment with PNS, HEIOC1 cells were treated with cisplatin and cultured for 24 h. The viability of HEIOC1 cells was examined using a Cell Counting Kit8 assay. Double staining analysis was used to measure cell apoptosis. The ability of PNS to reduce reactive oxygen species (ROS) levels was assessed by flow cytometry. The levels of phosphorylated (p)AKT, heme oxygenase 1 (HO1), NAD(P)H quinone dehydrogenase 1 (NQO1), glutamatecysteine ligase catalytic (GCLC) and Nrf2 were measured by western blotting. HEIOC1 cells that were pretreated with PNS exhibited significantly increased cell viability compared with that noted in cells treated only with cisplatin. In addition, PNS suppressed the induction of apoptosis and ROS production following cisplatin treatment. The upregulation of NQO1, HO1 and GCLC expression in PNSpretreated cells was associated with pAKT levels and the activation of Nrf2. These findings suggested that PNS protected auditory cells against ototoxicity induced by cisplatin by activating AKT/Nrf2 signaling. PNS may serve as a potential candidate in regulating cisplatininduced cytotoxicity.
Assuntos
Cisplatino/toxicidade , Células Ciliadas Auditivas/citologia , Ototoxicidade/metabolismo , Panax notoginseng/química , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/metabolismo , Masculino , Camundongos , Modelos Biológicos , Fator 2 Relacionado a NF-E2/metabolismo , Ototoxicidade/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
BACKGROUND: Over the last decade, more and more otologists have been using the intratympanic perfusion of steroids to treat SSHL, tinnitus, and vertigo. However, results of the treatment in the literature are controversial because most of the reports were retrospective and uncontrolled. Therefore a prospective random single-blind trial was conducted at the Affiliated Drum Tower Hospital of Nanjing University Medical School, P. R. China. The results were compared with oral carbamazepine treatment. Carbamazepine is a medication routinely used to treat tinnitus. MATERIAL/METHODS: Seventy-nine patients (84 ears) with subjective tinnitus which failed to respond to a minimum of four-week systemic medical therapy were assigned to a study group and a control group by a random, single-blind method. The study group was further randomly divided into two subgroups. The participants in the study group received either 0.5-ml intratympanic injections of prednisolone (study group 1) or dexamethasone (study group 2). The patients in the control group only took carbamazepine. The effective rates at the end of the therapy and the control rates at the end of a six-month follow-up were analyzed statistically. RESULTS: There were no statistical differences in the effective and control rates among the three groups. CONCLUSIONS: Intratympanic steroid injection has positive effects similar to those of oral carbamazepine in subjective tinnitus. Intratympanic steroid injection may be considered an alternative treatment for subjective tinnitus.
Assuntos
Carbamazepina/administração & dosagem , Carbamazepina/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Zumbido/tratamento farmacológico , Administração Oral , Distribuição por Idade , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Vias de Administração de Medicamentos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Injeções , Pessoa de Meia-Idade , Zumbido/diagnósticoRESUMO
The relationship between the left arcuate fasciculus (AF) and stroke-related aphasia is unclear. In this retrospective study, we aimed to investigate the role of subcomponents of the left AF in predicting prognosis of aphasia after stroke. Twenty stroke patients with aphasia were recruited and received language assessment as well as diffusion tensor tractography scanning at admission. According to injury of the left AF, the participants were classified into four groups: group A (4 cases), the AF preserved intactly; group B (6 cases), the anterior segment injured; group C (4 cases), the posterior segment injured; and group D (6 cases), completely injured. After a consecutive speech therapy, language assessment was performed again. Changes of language functions among the groups were compared and the relation between these changes with segments injury of the AF was analyzed. After therapy, relatively high increase score percentage changes in terms of all the subcategories of language assessment were observed both in group A and C; by contrast, only naming in group B, and spontaneous speech in group D. Although no statistical difference was demonstrated among the four groups. In addition, there was no significant correlation between improvement of language function with segments injury of the AF. The predictive role of subcomponents of the left AF in prognosis of aphasia is obscure in our study. Nevertheless, it indicates the importance of integrity of the left AF for recovery of aphasia, namely that preservation of the left AF on diffusion tensor tractography could mean recovery potential of aphasia after stroke.
Assuntos
Afasia/diagnóstico por imagem , Imagem de Tensor de Difusão/estatística & dados numéricos , Via Perfurante/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto , Idoso , Afasia/etiologia , Afasia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Via Perfurante/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fala , Fonoterapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular CerebralRESUMO
OBJECTIVES: To investigate glucocorticoid receptor (GR) and histone deacetylase 2 (HDAC2) gene expression and protein levels in peripheral blood mononuclear cells (PBMCs) of patients with severe or profound sudden sensorineural hearing loss (SSNHL) and to explore the roles of GRs and HDAC2 in glucocorticoid (GC) insensitivity. METHODS: Fifty-five severe or profound SSNHL patients were enrolled in the study. According to hearing improvement after GC treatment, patients were assigned into two groups: GC-sensitive and GC-resistant. A normal reference group included 20 healthy volunteers without hearing loss. Quantitative real-time polymerase chain reaction and Western blot analyses were used to detect the relative expression of GRα, GRß, and HDAC2 in PBMCs at the mRNA and protein levels. RESULTS: The protein levels of GRs and HDAC2 in PBMCs of SSNHL patients were lower than the normal reference values before GC treatment. Compared with the GC-resistant group, both the mRNA and protein levels of GRα and HDAC2 were significantly increased in the GC-sensitive group after GC treatment. CONCLUSION: A lack of GRα and HDAC2 induction following steroid treatment in GC-resistant SSNHL patients may play a fundamental mechanistic role in GC insensitivity. Response of GRα and HDAC2 to steroid treatment may, thus, predict the prognosis of hearing improvement in SSNHL patients.
RESUMO
Glucocorticoids have been used to treat hearing loss and vestibular dysfunction for many years. However, some reports have indicated that a subset of patients with these disorders exhibit glucocorticoid insensitivity or resistance. A reduction in histone deacetylase 2 (HDAC2) activity and expression has been reported to play a critical role in glucocorticoid resistance. Here, we investigated the protective effects of aminophylline on HDAC2 expression and glucocorticoid sensitivity in lipopolysaccharide (LPS)-induced sudden sensorineural hearing loss in guinea pigs. We assessed hearing recovery in LPS-applied guinea pigs, which were either left untreated or were systemically treated with either dexamethasone, aminophylline, or a combination of the two. We utilized fluorescence microscopy and enzyme-linked immunosorbent assay to analyze the distribution patterns of HDAC2 and detect its levels in the cochlea. We used hematoxylin-eosin staining to examine cochlear histopathological changes. In the absence of treatment, significant hearing loss was detected in LPS-exposed animals. A synergistic effect was observed between aminophylline and dexamethasone in maintaining HDAC2 expression levels, preventing hearing loss in LPS-exposed animals and reducing cochlear damage. This study indicates that aminophylline can restore glucocorticoid sensitivity, which provides a new approach to treating patients with hearing disorders who are refractory to glucocorticoids.
Assuntos
Aminofilina/farmacologia , Glucocorticoides/farmacologia , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/metabolismo , Lipopolissacarídeos/efeitos adversos , Animais , Cóclea/metabolismo , Cóclea/fisiopatologia , Sinergismo Farmacológico , Imunofluorescência , Cobaias , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/tratamento farmacológico , Histona Desacetilase 2/metabolismo , Substâncias Protetoras/farmacologiaRESUMO
OBJECTIVE: To evaluate the expression of histone deacetylase 2 (HDAC2) in peripheral blood mononuclear cells (PBMCs) from patients with sudden sensorineural hearing loss (SSNHL) who were refractory to systemic glucocorticoid treatment and to identify the relationship between the level of HDAC2 and glucocorticoid insensitivity. STUDY DESIGN: Prospective clinical study. SETTING: This study was conducted in Nanjing Drum Tower Hospital, Nanjing University Medical School. SUBJECTS AND METHODS: PBMCs were collected from 42 refractory SSNHL patients. After a 10-day intratympanic methylprednisolone perfusion (IMP) and systemic Ginkgo biloba extract treatment, the SSNHL patients were divided into 2 groups according to their hearing recovery after IMP (IMP sensitive and insensitive). Real-time polymerase chain reaction and HDAC2 protein assays were used to detect the relative expression levels of HDAC2 in PBMCs. The HDAC2 mRNA expression and protein levels in PBMCs collected from 17 volunteers were used as normal HDAC2 reference levels. RESULTS: Compared with normal reference levels, HDAC2 protein levels were significantly reduced, while the HDAC2 mRNA expression was much higher in all refractory SSNHL patients before IMP. HDAC2 mRNA expression and HDAC2 protein levels were significantly elevated in the IMP-sensitive group, while no change was observed in the IMP-insensitive group after IMP plus systemic antioxidant treatment. CONCLUSIONS: Reduced HDAC2 protein levels may be 1 of the mechanistic underpinnings of corticosteroid insensitivity in refractory SSNHL patients. IMP can increase HDAC2 protein levels and the expression of HDAC2 mRNA in IMP-sensitive patients. HDAC2 protein levels might be regulated through posttranslational modifications.
Assuntos
Glucocorticoides/farmacologia , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/enzimologia , Histona Desacetilase 2/biossíntese , Leucócitos Mononucleares/enzimologia , Metilprednisolona/farmacologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Injeção Intratimpânica , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Perfusão , Estudos Prospectivos , Falha de TratamentoRESUMO
OBJECTIVE: This article summarizes the matters warranting consideration in adult cochlear implants before and after operation with different deafness causes and investigates the impact of etiological variables that affect hearing and speech ability rehabilitation after cochlear implantation. METHOD: We retrospectively reviewed the preoperative data of 30 adults who have received cochlear implantation, switch on, and periodical post operative mapping. 'Nijmegen Cochlear Implant Questionnaire' was used for every patient during follow-up and test their hearing thresholds at one year after switched-on. The average score of every patient in the six aspects of questionnaire, along with the average hearing threshold, has been gathered. RESULT: The average hearing threshold of every patient is lower than 35 dBHL. The average score of 28 patients is more than or equal to 75 in the basic sound perception, advanced sound perception as well as self-esteem. The average score of 26 patients is more than or equal to 75 in capacity for action. Besides, as for sociability and speech ability, the average score of 22 patients is more than or equal to 75. CONCLUSION: Auditory perception can be greatly improved regardless of deafness causes, on the premise that appropriate candidate is selected. The primary disease should be brought under control before and after the operation. The influence of various causes to the language ability rehabilitation largely depends on the development of the language center at deafness onset. Self-esteem and social identity can be significantly enhanced after cochlear implantation in adult patients, particularly those with acquired deafness.