Protective Effect of Resveratrol in an Experimental Model of Salicylate-Induced Tinnitus.

To date, the effect of resveratrol on tinnitus has not been reported. The attenuative effects of resveratrol (RSV) on a salicylate-induced tinnitus model were evaluated by in vitro and in vivo experiments. The gene expression of the activity-regulated cytoskeleton-associated protein (ARC), tumor necrosis factor-alpha (TNFα), and NMDA receptor subunit 2B (NR2B) in SH-SY5Y cells was examined using qPCR. Phosphorylated cAMP response element-binding protein (p-CREB), apoptosis markers, and reactive oxygen species (ROS) were evaluated by in vitro experiments. The in vivo experiment evaluated the gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and auditory brainstem response (ABR) level. The NR2B expression in the auditory cortex (AC) was determined by immunohistochemistry. RSV significantly reduced the salicylate-induced expression of NR2B, ARC, and TNFα in neuronal cells; the GPIAS and ABR thresholds altered by salicylate in rats were recovered close to their normal range. RSV also reduced the salicylate-induced NR2B overexpression of the AC. These results confirmed that resveratrol exerted an attenuative effect on salicylate-induced tinnitus and may have a therapeutic potential.

Effect of Pre-Induced Mesenchymal Stem Cell-Coated Cellulose/Collagen Nanofibrous Nerve Conduit on Regeneration of Transected Facial Nerve.

(1) Objective: In order to evaluate the effect of a pre-induced mesenchymal stem cell (MSC)-coated cellulose/collagen nanofibrous nerve conduit on facial nerve regeneration in a rat model both in vitro and in vivo. (2) Methods: After fabrication of the cellulose/collagen nanofibrous conduit, its lumen was coated with either MSCs or pre-induced MSCs. The nerve conduit was then applied to the defective main trunk of the facial nerve. Rats were randomly divided into three treatment groups (n = 10 in each): cellulose/collagen nanofiber (control group), cellulose/collagen nanofiber/MSCs (group I), and cellulose/collagen nanofiber/pre-induced MSCs (group II). (3) Results Fibrillation of the vibrissae of each group was observed, and action potential threshold was compared 8 weeks post-surgery. Histopathological changes were also observed. Groups I and II showed better recovery of vibrissa fibrillation than the control group. (4) Conclusions: Group II, treated with the pre-induced MSC-coated cellulose/collagen nanofibrous nerve conduit, showed the highest degree of recovery based on functional and histological evaluations.

Hypertrophic Pachymeningitis of the Internal Auditory Canal Induced by a Labyrinthine Fistula Complicated With Cholesteatoma.

Hypertrophic pachymeningitis (HP) is defined by inflammation and thickening of the dura mater, and the etiologic factors are idiopathic or secondary to various conditions. To date, HP in the internal auditory canal (IAC) has rarely been reported. There have only been 3 reports of HP in the IAC. Magnetic resonance imaging showed enhancement of along the IAC and vestibule. After antibiotic treatment, enhancement was reduced with visible seventh and eighth nerves. The patient underwent tympanomastoidectomy. To our knowledge, this is the first case of HP associated with a labyrinth fistula complicated by cholesteatoma. We report MRI image with literatures.

Bioprinted Collagen-Based Cell-Laden Scaffold With Growth Factors for Tympanic Membrane Regeneration in Chronic Perforation Model.

With the recent development of bioprinting technology, various attempts have been made to replace bioprinting technologies and regenerative medicine are more directed towards transplantation/reconstructive surgeries only with the implantation of scaffolds. The purpose of this study is to determine whether the growth factors, human umbilical cord serum (hUCS) and bFGF (basic fibroblast growth factor), have a synergistic effect on eardrum regeneration, when used with a cell-printed scaffold in a chronic tympanic membrane perforation (TMP) model. In this study, in vitro cellular activities for bioprinted cell-laden collagen scaffolds using human adipose stem cells (hASCs) and supplemented with 10 [Formula: see text]/mL hUCS and 10 ng/mL bFGF were performed. The mixture of the growth factors in the cell-laden structures effectively affects various in vitro cellular responses including the proliferation of hASCs and the migration of keratinocytes due to the synergistic effect of the growth factors and hASCs. For the in vivo evaluation, a rat TMP model was used, and the TMP regeneration was assessed by otoscopic examination, hearing threshold measurement, and histologic examination. Although the cell-laden structure containing hUCS was more enhancing effect compared to the structure with bFGF, more synergistic effect in the structure using hUCS/bFGF was observed. Based on the results, we believe that the cell-laden structure incorporating hUCS and bFGF can induce significant regeneration of chronic tympanic membrane perforation.

Surgical results and factors affecting outcome in patients with fat-graft myringoplasty.

Objectives: We evaluated the closure rate after fat-graft myringoplasty (FGM) of perforations differing in size and location. We explored whether patient's factors and the FGM surgical technique influenced surgical outcomes. Methods: We retrospectively studied patients with tympanic membrane perforations who underwent FGM from March 2015 to March 2019. All procedures were performed by a single senior surgeon at our tertiary hospital. The patients who followed-up for at least 6 months after surgery were enrolled. We recorded hypertension and diabetes status, age, any prior ear surgery, any calcific plaques adjacent to the perforation, and perforation size and location. Results: A total of 150 patients were enrolled. Our success rate of FGM was 90%. Hypertension, diabetes, prior ear surgery history, and eardrum calcific plaques did not affect the surgical outcomes. There was no statistical difference in the surgical success rate according to the size (< 50%) or location of perforation. The closure rate was 97.2% in patients aged 1660 and 87.5% in patients aged > 60, respectively. However, FGM was successful in only two of six children (33.3%) aged ≤ 15 years, thus significantly less than in the other groups. Conclusion: FGM is a fast, safe, and efficient method for repairing tympanic membrane perforation. The surgical outcome is not significantly affected by underlying disease, perforation size or location, or by the condition of the tympanic membrane or older age. However, it may be poor in children with dysfunctional Eustachian tube.

Effect of Growth Factor-Loaded Acellular Dermal Matrix/MSCs on Regeneration of Chronic Tympanic Membrane Perforations in Rats.

The success rate of grafting using acellular dermal matrix (ADM) for chronic tympanic membrane was reported in previous studies to be lower than fascia or perichondrium. Combining mesenchymal stem cells (MSCs) and growth factor-loaded ADM for the regeneration of chronic TMP has not been reported so far. In this study, we hypothesized that combining growth factor-loaded ADM/MSCs could promote the recruitment of MSCs and assist in TMP regeneration. We evaluated the regeneration and compared the performance of four scaffolds in both in vitro and in vivo studies. MTT, qPCR, and immunoblotting were performed with MSCs. In vivo study was conducted in 4 groups (control; ADM only, ADM/MSC, ADM/MSC/bFGF, ADM/MSC/EGF) of rats and inferences were made by otoendoscopy and histological changes. Attachment of MSCs on ADM was observed by confocal microscopy. Proliferation rate increased with time in all treated cells. Regeneration-related gene expression in the treated groups was higher. Also, graft success rate was significantly higher in ADM/MSC/EGF group than other groups. Significant relationships were disclosed in neodrum thickness between each group. The results suggest, in future, combining EGF with ADM/MSCs could possibly be used as an outpatient treatment, without the need for surgery for eardrum regeneration.

Correlation of Intraoperative End-Tidal Carbon Dioxide Concentration on Postoperative Hospital Stay in Patients Undergoing Pylorus-Preserving Pancreaticoduodenectomy.

BACKGROUND: Hypocapnia has been traditionally advocated during general anesthesia, even though it may induce deleterious physiological effects that result in unfavorable outcomes in patients. This study investigated the association between intraoperative end-tidal carbon dioxide (EtCO2) and length of hospital stay (LOS) in patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: The medical records of 759 patients from 2006 to 2015 were reviewed. The patients were divided into two groups based on the mean EtCO2 value during general anesthesia: the hypocapnia group (< 35 mmHg) and the normocapnia group (≥ 35 mmHg). The primary outcome was LOS between the groups. Secondary outcomes included the length of intensive care unit (ICU) stay, postoperative 30-day, 1-year, and 2-year mortality, and perioperative factors associated with LOS. RESULTS: A total of 727 patients were finally analyzed. The median LOS of the hypocapnia group was significantly longer than that of the normocapnia group (22 days vs. 18 days, respectively; p < 0.001). Postoperative mortality did not differ between the groups. Cox regression analysis revealed that hypocapnia was an independent risk factor for longer LOS (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.37-1.89; p < 0.001). Age and postoperative pancreatic fistula were also risk factors for a longer LOS. CONCLUSIONS: It was concluded that low levels of intraoperative EtCO2 during general anesthesia were associated with an increased LOS for patients undergoing PPPD.

Effects of fibrous collagen/CDHA/hUCS biocomposites on bone tissue regeneration.

Collagen- and bioceramic-based composites have been widely used in hard tissue engineering because they are analogous to the organic/inorganic constituents of native bones. However, biocomposites based on collagen and bioceramics show low mechanical stiffness and limited osteogenic activities. To elevate the low biophysical and biological activities, we have introduced a new biocomposite structure. Herein, we propose a biocomposite mimicking not only the physical structure of the extracellular matrix (ECM) structure but also the biochemical components of native bone tissues. Several components including fibrillated collagen, calcium-deficient hydroxyapatite (CDHA) obtained from α-tricalcium phosphate hydrolysis, and human umbilical cord serum (hUCS) were used to generate a unique structure of the biocomposite. The 3D-printed composites were topographically similar to the nanofibrous ECM and exhibited a mechanically stable structure. We also evaluated the in vitro biocompatibilities of the biocomposite using human adipose stem cells and found that the collagen/hUCS/CDHA scaffold accelerated the in vitro osteogenic differentiation of human adipose-derived stem cells and in vivo osteogenesis in a mastoid obliterated rat model.

Therapeutic Application of Mesenchymal Stem Cells for Cochlear Regeneration.

Hearing loss is one of the major worldwide health problems that seriously affects human social and cognitive development. In the auditory system, three components outer ear, middle ear and inner ear are essential for the hearing mechanism. In the inner ear, sensory hair cells and ganglion neuronal cells are the essential supporters for hearing mechanism. Damage to these cells can be caused by long-term exposure of excessive noise, ototoxic drugs (aminoglycosides), ear tumors, infections, heredity and aging. Since mammalian cochlear hair cells do not regenerate naturally, some therapeutic interventions may be required to replace the damaged or lost cells. Cochlear implants and hearing aids are the temporary solutions for people suffering from severe hearing loss. The current discoveries in gene therapy may provide a deeper understanding in essential genes for the inner ear regeneration. Stem cell migration, survival and differentiation to supporting cells, cochlear hair cells and spiral ganglion neurons are the important foundation in understanding stem cell therapy. Moreover, mesenchymal stem cells (MSCs) from different sources (bone marrow, umbilical cord, adipose tissue and placenta) could be used in inner ear therapy. Transplanted MSCs in the inner ear can recruit homing factors at the damaged sites to induce transdifferentiation into inner hair cells and ganglion neurons or regeneration of sensory hair cells, thus enhancing the cochlear function. This review summarizes the potential application of mesenchymal stem cells in hearing restoration and combining stem cell and molecular therapeutic strategies can also be used in the recovery of cochlear function.

Neuroprotective Effect of Valproic Acid on Salicylate-Induced Tinnitus.

High-dose salicylate induces temporary moderate hearing loss and the perception of a high-pitched tinnitus in humans and animals. Previous studies demonstrated that high doses of salicylate increase N-methyl-d-aspartate (NMDA) receptor levels, resulting in a rise in Ca2+ influx and induction of excitotoxicity. Glutamate excitotoxicity is associated with failure in the maintenance of calcium homeostasis, mitochondrial dysfunction, and production of reactive oxygen species (ROS). Valproic acid (VPA) is widely used for the management of bipolar disorder, epilepsy, and migraine headaches, and is known to regulate NMDA receptor activity. In this study, we examined the beneficial effects of VPA in a salicylate-induced tinnitus model in vitro and in vivo. Cells were pretreated with VPA followed by salicylate treatment. The expression levels of NMDA receptor subunit NR2B, phosphorylated cAMP response element-binding protein-an apoptosis marker, and intracellular levels of ROS were measured using several biochemical techniques. We observed increased expression of NR2B and its related genes TNFα and ARC, increased intracellular ROS levels, and induced expression of cleaved caspase-3. These salicylate-induced changes were attenuated in the neuronal cell line SH-SY5Y and rat cortical neurons after VPA pretreatment. Together, these results provide evidence of the beneficial effects of VPA in a salicylate-induced temporary hearing loss and tinnitus model.

Oxidative stress-induced aberrant G9a activation disturbs RE-1-containing neuron-specific genes expression, leading to degeneration in human SH-SY5Y neuroblastoma cells.

Oxidative stress-induced neurodegeneration is one of several etiologies underlying neurodegenerative disease. In the present study, we investigated the functional role of histone methyltransferase G9a in oxidative stress-induced degeneration in human SH-SY5Y neuroblastoma cells. Cell viability significantly decreased on H2O2 treatment; however, treatment with the G9a inhibitor BIX01294 partially attenuated this effect. The expression of neuron-specific genes also decreased in H2O2- treated cells; however, it recovered on G9a inhibition. H2O2-treated cells showed high levels of H3K9me2 (histone H3 demethylated at the lysine 9 residue), which is produced by G9a activation; BIX01294 treatment reduced aberrant activation of G9a. H3K9me2 occupancy of the RE-1 site in neuron-specific genes was significantly increased in H2O2-treated cells, whereas it was decreased in BIX01294-treated cells. The differentiation of H2O2-treated cells also recovered on G9a inhibition by BIX01294. Consistent results were observed when used another G9a inhibitor UCN0321. These results demonstrate that oxidative stress induces aberrant activation of G9a, which disturbs the expression of neuron-specific genes and progressively mediates neuronal cell death. Moreover, a G9a inhibitor can lessen aberrant G9a activity and prevent neuronal damage. G9a inhibition may therefore contribute to the prevention of oxidative stress-induced neurodegeneration.

The Role of Stress Granules in the Neuronal Differentiation of Stem Cells.

creativecommons.org/licenses/by-nc-sa/3.0/. Cells assemble stress granules (SGs) to protect their RNAs from exposure to harmful chemical reactions induced by environmental stress. These SGs release RNAs, which resume translation once the stress is relieved. During stem cell differentiation, gene expression is altered to allow cells to adopt various functional and morphological features necessary to differentiate. This process induces stress within a cell, and cells that cannot overcome this stress die. Here, we investigated the role of SGs in the progression of stem cell differentiation. SGs aggregated during the neuronal differentiation of human bone marrow-mesenchymal stem cells, and not in cell lines that could not undergo differentiation. SGs were observed between one and three hours post-induction; RNA translation was restrained at the same time. Immediately after disassembly of SGs, the expression of the neuronal marker neurofilament-M (NFM) gradually increased. Assembled SGs that persisted in cells were exposed to salubrinal, which inhibited the dephosphorylation of eukaryotic translation initiation factor 2 subunit 1 (eIF2α), and in eIF2α/S51D mutant cells. When eIF2α/S51A mutant cells differentiated, SGs were not assembled. In all experiments, the disruption of SGs was accompanied by delayed NF-M expression and the number of neuronally differentiated cells was decreased. Decreased differentiation was accompanied by decreased cell viability, indicating the necessity of SGs for preventing cell death during neuronal differentiation. Collectively, these results demonstrate the essential role of SGs during the neuronal differentiation of stem cells.

New Bioink Derived from Neonatal Chicken Bone Marrow Cells and Its 3D-Bioprinted Niche for Osteogenic Stimulators.

This study examined whether neonatal chicken bone marrow cells (cBMCs) could support the osteogenesis of human stromal cells in a three-dimensional (3D) extracellular bioprinting niche. The majority (>95%) of 4-day-old cBMCs subcultured 5 times were positive for osteochondrogenesis-related genes (Col I, Col II, Col X, aggrecan, Sox9, osterix, Bmp2, osteocalcin, Runx2, and osteopontin) and their related proteins (Sox9, collagen type I, and collagen type II). LC-MS/MS analysis demonstrated that cBMC-conditioned medium (c-medium) contained proteins related to bone regeneration, such as periostin and members of the TGF-ß family. Next, a significant increase in osteogenesis was detected in three human adipose tissue-derived stromal cell (hASC) lines, after exposure to c-medium concentrates in 2D culture (p < 0.05). To evaluate biological function in a 3D environment, we employed the cBMC-derived bioactive components as a cell-supporting biomaterial in collagen bioink, which was printed to construct a 3D hASC-laden scaffold for observing osteogenesis. Complete osteogenesis was detected in vitro. Moreover, after transplantation of the hASC-laden structure into rats, prominent bone formation was observed compared with that in control rats receiving scaffold-free hASC transplantation. These results demonstrated that substance(s) secreted by chick bone marrow cells clearly activated the osteogenesis of hASCs in 2D- or 3D-niches.

Effect of Bone Powder/Mesenchymal Stem Cell/BMP2/Fibrin Glue on Osteogenesis in a Mastoid Obliteration Model.

BACKGROUND/AIM: This study aimed to prospectively compare the osteogenesis of bone powder (BP) substances with and without mesenchymal stem cells (MSCs) and evaluate the synergistic effect of topically applied recombinant human bone morphogenic protein-2 (BMP2) on MSC-loaded BP using fibrin glue in a mastoid obliteration model. MATERIALS AND METHODS: To determine the expression of osteocyte-specific genes, total RNA was isolated from three MSC groups: Untreated MSCs, MSCs cultured with BP, and MSCs cultured with BP and BMP2. Real-time polymerase chain reaction was carried out with specific primers of osteogenesis-related genes runt-related transcription factor 2, osteocalcin, osteoprotegerin, osterix, alkaline phosphatase, transforming growth factor beta, and type I collagen. Live/dead staining was also performed. To observe the adhesion of MSCs to the BP, MSCs were treated with BP for 2 days and the surface was observed by scanning electron microscopy (SEM). Under general anesthesia, mastoid obliteration was performed in rats using three groups: treated with BP alone, BP/MSCs, and BP/MSC/BMP2. Before decapitation at 8 weeks post operation, in vivo micro computed tomography (micro CT) was performed. The bullae were dissected, fixed, and decalcified. followed by dehydration, paraffin embedding, and staining by hematoxylin and eosin and Masson's trichrome. RESULTS: SEM showed the MSCs to be well-attached to the superficial area of the BP. The expression of osteocyte-specific genes was the highest in the MSCs cultured with BP and BMP2, followed by cultured with BP only, and untreated MSCs. The BP/MSC/BMP2 group showed the highest radiodensity of bullae in microCT analysis. The microCT findings revealed that the BP/MSC/BMP2 group showed the most enhanced osteogenesis of the scaffold compared to the other two groups. No significant difference was found in osteoconductive osteogenesis between the control and BP/MSC groups. However, the BP/MSC/BMP2 group showed significantly enhanced osteoconductive osteogenesis and osteoinductive change of the BP as shown by hematoxylin and eosin staining. Histomorphometry of osteogenesis revealed that the difference between the BP/MSC/BMP2 group and the other two groups was statistically significant. CONCLUSION: A small amount of BMP2 is necessary during MSC loading to enhance the osteogenesis of BP and avoid complications associated with high doses of BMP2. These results may be applicable to mastoid obliteration in clinical practice.

Application of mesenchymal stem cell for tympanic membrane regeneration by tissue engineering approach.

Regeneration is a biological process of cell renewal that takes place in damaged tissues or organs. It is naturally stimulated by the release of different growth factors, cytokines, surface molecules, and stem cells at the wounded sites. The tympanic membrane (TM) is an essential component of the hearing process in the auditory system, which can amplify and transmit sound vibrations through a chain of mobile ossicles. Middle ear infection, external sound pressure, insertion of sharp objects into the ear, and severe trauma are the main causes of TM perforations (TMPs), which could result in deficient hearing function. So far, otolaryngologists have employed surgical procedures (myringoplasty or tympanoplasty) to close the perforated eardrum. Because of limitations such as side effects, discomfort, and high cost to patients, there is a need for better alternatives to surgical procedures. Tissue engineering is a promising tool that can overcome the operational risk and restore, maintain, and improve the function of the TM using a range of biocompatible scaffolds, commercially available growth factors, and stem cells. Currently, multipotent mesenchymal stem cells (MSCs) are a good therapeutic option for the treatment of TMPs because of their self-renewing, and autocrine and paracrine activities. As there are fewer risks of isolation in the use of MSCs for the treatment of TMPs, they are more advantageous for tissue regeneration. The delivery of either MSCs alone or a combination of MSCs with biomaterials and growth factors (GFs) at the ruptured TM sites may enhance the activation of epithelial stem cell markers and increase the migration and proliferation of keratinocytes resulting in faster closure of TMPs. This review focuses on the current strategies used to treat TMPs and the importance of MSCs in TM regeneration. Particularly, we have discussed the synergistic effect of MSCs and scaffolds or GFs or scaffolds/GFs in TM regeneration. Finally, with the advancement of tissue engineering technologies such as 3D and 4D bioprinting, MSCs can be used to design patient-specific scaffolds, which may contain physical and chemical guidance cues to improve the extent and rate of targeted tissue regeneration.

Memantine Attenuates Salicylate-induced Tinnitus Possibly by Reducing NR2B Expression in Auditory Cortex of Rat.

Memantine, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, suppresses the release of excessive levels of glutamate that may induce neuronal excitation. Here we investigated the effects of memantine on salicylate-induced tinnitus model. The expressions of the activity-regulated cytoskeleton-associated protein (ARC) and tumor necrosis factor-alpha (TNFα) genes; as well as the NMDA receptor subunit 2B (NR2B) gene and protein, were examined in the SH-SY5Y cells and the animal model. We also used gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and noise burst prepulse inhibition of acoustic startle, and the auditory brainstem level (electrophysiological recordings of auditory brainstem responses, ABR) and NR2B expression level in the auditory cortex to evaluate whether memantine could reduce salicylate-mediated behavioral disturbances. NR2B was significantly upregulated in salicylate-treated cells, but downregulated after memantine treatment. Similarly, expression of the inflammatory cytokine genes TNFα and immediate-early gene ARC was significantly increased in the salicylate-treated cells, and decreased when the cells were treated with memantine. These results were confirmed by NR2B immunocytochemistry. GPIAS was attenuated to a significantly lesser extent in rats treated with a combination of salicylate and memantine than in those treated with salicylate only. The mean ABR threshold in both groups was not significant different before and 1 day after the end of treatment. Additionally, NR2B protein expression in the auditory cortex was markedly increased in the salicylate-treated group, whereas it was reduced in the memantine-treated group. These results indicate that memantine is useful for the treatment of salicylate-induced tinnitus.

Evaluating the ototoxicity of an anti-MRSA peptide KR-12-a2 / Avaliando a ototoxicidade de um peptídeo anti-MRSA KR-12-a2

Abstract Introduction Methicillin-resistant staphylococcus aureus is an emerging problem for the treatment of chronic suppurative otitis media, and also for pediatric tympanostomy tube otorrhea. To date, there are no effective topical antibiotic drugs to treat methicillin-resistant staphylococcus aureus otorrhea. Objective In this study, we evaluated the ototoxicity of topical KR-12-a2 solution on the cochlea when it is applied topically in the middle ear of guinea pigs. Methods The antimicrobial activity of KR-12-a2 against methicillin-resistant staphylococcus aureus strains was examined by using the inhibition zone test. Topical application of KR-12-a2 solution, gentamicin and phosphate buffered saline were applied in the middle ear of the guinea pigs after inserting ventilation tubes. Ototoxicity was assessed by auditory brainstem evoked response and scanning electron microscope examination. Results KR-12-a2 produced an inhibition zone against methicillin-resistant staphylococcus aureus from 6.25 µg. Hearing threshold in the KR-12-a2 and PBS groups were similar to that before ventilation tube insertion. However, the gentamicin group showed elevation of the hearing threshold and there were statistically significant differences compared to the phosphate buffered saline or the KR-12-a2 group. In the scanning electron microscope findings, the KR-12-a2 group showed intact outer hair cells. However, the gentamicin group showed total loss of outer hair cells. In our experiment, topically applied KR-12-a2 solution did not cause hearing loss or cochlear damage in guinea pigs. Conclusion In our experiment, topically applied KR-12-a2 solution did not cause hearing loss or cochlear damage in guinea pigs. The KR-12-a2 solution can be used as ototopical drops for treating methicillin-resistant staphylococcus aureus otorrhea; however, further evaluations, such as the definition of optimal concentration and combination, are necessary.

Resumo Introdução O staphylococcus aureus resistente à meticilina é um problema emergente não só para a otite média supurativa crônica, mas também para casos de otorreia crônica em crianças com tubo de ventilação. Até o momento, não há antibióticos tópicos efetivos para a otorreia causada por staphylococcus aureus resistente à meticilina. Objetivo Nesse estudo, avaliamos a ototoxicidade da solução tópica de KR-12-a2 na cóclea quando aplicada topicamente na orelha média de cobaias. Método A atividade antimicrobiana de KR-12-a2 contra cepas de staphylococcus aureus resistente à meticilina foi avaliada utilizando-se o teste de zona de inibição de crescimento. Foram aplicados na orelhas médias de 3 grupos de cobaias, ou solução tópica de KR-12-a2, ou gentamicina ou solução salina tamponada com fosfato após timpanostomia. A ototoxicidade foi avaliada através do exame auditivo de potencial evocado auditivo de tronco encefálico e por microscopia eletrônica de varredura. Resultados O KR-12-a2 produziu uma zona de inibição contra o staphylococcus aureus resistente à meticilina a partir de 6,25 µg. Alterações do limiar de audição no grupo KR-12-a2 e no grupo com solução salina foram semelhantes aos observados antes da inserção do tubo de ventilação. No entanto, o grupo gentamicina apresentou um limiar auditivo mais elevado, estatisticamente significativo em comparação ao grupo solução salina ou ao grupo KR-12-a2. Nos achados da microscopia eletrônica, o grupo KR-12-a2 apresentou células ciliadas externas intactas. No entanto, o grupo gentamicina apresentou perda total das células ciliadas externas. Em nosso experimento, a solução de KR-12-a2 aplicada topicamente não causou perda auditiva ou dano coclear em cobaias. Conclusão Em nosso experimento, a solução de KR-12-a2 aplicada topicamente não causou perda auditiva ou dano coclear em cobaias. A solução de KR-12-a2 pode ser utilizada como gotas otológicas para o tratamento da otorreia causada por staphylococcus aureus resistente à meticilina; no entanto, são necessárias outras avaliações, para a definição da concentração e das associações ideais.

Role of preoperative air-bone gap in tinnitus outcome after tympanoplasty for chronic otitis media with tinnitus / Papel do gap aéreo-ósseo pré-operatório no desfecho do zumbido após timpanoplastia para otite média crônica com zumbido

Abstract Introduction Previous reports indicated that middle ear surgery might partially improve tinnitus after surgery. However, until now, no influencing factor has been determined for tinnitus outcome after middle ear surgery. Objective The purpose of this study was to investigate the association between preoperative air-bone gap and tinnitus outcome after tympanoplasty type I. Methods Seventy-five patients with tinnitus who had more than 6 months of symptoms of chronic otitis media on the ipsilateral side that were refractory to medical treatment were included in this study. All patients were evaluated through otoendoscopy, pure tone/speech audiometer, questionnaire survey using the visual analog scale and the tinnitus handicap inventory for tinnitus symptoms before and 6 months after tympanoplasty. The influence of preoperative bone conduction, preoperative air-bone-gap, and postoperative air-bone-gap on tinnitus outcome after the operation was investigated. Results and conclusion The patients were divided into two groups based on preoperative bone conduction of less than 25 dB (n = 50) or more than 25 dB (n = 25). The postoperative improvement of tinnitus in both groups showed statistical significance. Patients whose preoperative air-bone-gap was less than 15 dB showed no improvement in postoperative tinnitus using the visual analog scale (p = 0.889) and the tinnitus handicap inventory (p = 0.802). However, patients whose preoperative air-bone-gap was more than 15 dB showed statistically significant improvement in postoperative tinnitus using the visual analog scale (p < 0.01) and the tinnitus handicap inventory (p = 0.016). Postoperative change in tinnitus showed significance compared with preoperative tinnitus using visual analog scale (p = 0.006). However, the correlation between reduction in the visual analog scale score and air-bone-gap (p = 0.202) or between reduction in tinnitus handicap inventory score and air-bone-gap (p = 0.290) was not significant. We suggest that the preoperative air-bone-gap can be a predictor of tinnitus outcome after tympanoplasty in chronic otitis media with tinnitus.

Resumo Introdução Relatos anteriores indicaram que a cirurgia no ouvido médio pode melhorar parcialmente o zumbido após a cirurgia. No entanto, até agora, nenhum fator influenciador foi determinado para o resultado do zumbido após cirurgia de ouvido médio. Objetivo O objetivo deste estudo foi investigar a associação entre o gap aéreo-ósseo pré-operatório e o desfecho do zumbido após timpanoplastia do tipo I. Método Setenta e cinco pacientes com zumbido, com mais de 6 meses de sintomas de otite média crônica no lado ipsilateral que eram refratários ao tratamento médico foram incluídos nesse estudo. Todos os pacientes foram avaliados através de otoendoscopia, audiometria tonal/vocal, questionário utilizando a escala visual analógica e o questionário tinnitus handicap inventory para sintomas de zumbido antes e 6 meses após a timpanoplastia. A influência da condução óssea pré-operatória, gap aéreo-ósseo pré-operatório e pós-operatório sobre o desfecho do zumbido após a operação foi analisada. Resultados e conclusão Os pacientes foram divididos em dois grupos com base na condução óssea pré-operatória de menos de 25 dB (n = 50) ou mais de 25 dB (n = 25). A melhora do zumbido pós-operatória em ambos os grupos mostrou significância estatística. Pacientes com gap aéreo-ósseo pré-operatório inferior a 15 dB não apresentaram melhora no zumbido pós-operatório utilizando a escala visual analógica (p = 0,889) e o tinnitus handicap inventory (p = 0,802). Entretanto, pacientes com gap aéreo-ósseo pré-operatório maior do que 15 dB apresentaram melhoria estatisticamente significante no zumbido pós-operatório com a escala visual analógica (p < 0,01) e o tinnitus handicap inventory (p = 0,016). A mudança pós-operatória no zumbido mostrou significância em comparação com o zumbido pré-operatório usando a escala visual analógica (p = 0,006). No entanto, a correlação entre a redução no escore da escala visual analógica e gap aéreo-ósseo (p = 0,202) ou entre a redução no escore do tinnitus handicap inventory e gapaéreo-ósseo (p = 0,290) não foi significativa. Sugerimos que o gapaéreo-ósseo pré-operatório possa ser um preditor de desfecho do zumbido após timpanoplastia em otite média crônica com zumbido.