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1.
HNO ; 69(8): 633-641, 2021 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-33502578

RESUMO

BACKGROUND: From spring 2020, SARS-CoV­2 began to spread worldwide, with what is now known as the first wave of the pandemic, starting in March 2020. This resulted in restructuring and shift of resources at many hospitals. The aim of our work was to detect the effects of the pandemic on the german Oto-Rhino-Laryngology (ORL) university hospitals in terms of research, student teaching and further specialist training. MATERIAL AND METHODS: The chairmen of the 39 ORL university hospitals in Germany were asked about the effects of the pandemic on research, student teaching and ORL specialist training (residency) in the period from March to April 2020 using a structured online survey. RESULTS: All 39 chairmen took part in the survey. Of these, 74.4% (29/39) stated that their research activities had deteriorated as a result of the pandemic. In 61.5% (24/39) pandemic-related research issues were addressed. All hospitals reported a restriction for in-house teaching and 97.5% (38/39) introduced new digital teaching methods. During the observation period, 74.4% of the chairmen did not see ORL specialist training (residency)at risk. CONCLUSION: Our results provide an insight into the heterogeneous effects of the pandemic. The fast processing of pandemic-related research topics and the introduction of innovative digital concepts for student teaching impressively demonstrates the great innovative potential and the ability of the ORL university hospitals to react quickly in order to maintain their tasks in research, student teaching and ORL specialist training in the best possible way even during the pandemic.


Assuntos
COVID-19 , Otolaringologia , Alemanha/epidemiologia , Hospitais Universitários , Humanos , Pandemias , SARS-CoV-2 , Estudantes , Ensino
2.
Laryngorhinootologie ; 99(10): 694-706, 2020 10.
Artigo em Alemão | MEDLINE | ID: mdl-32767296

RESUMO

INTRODUCTION: Since December 2019, the SARS-CoV-2 virus has been rapidly spreading worldwide. In Germany, an exponential increase in the number of infections was registered at the beginning of March 2020 and led to a call of the Ministry of Health to create more capacity for intensive medical treatment in hospitals. The aim of the present study was to determine the effects of the SARS-CoV-2 pandemic on Oto-Rhino-Laryngology (ORL) university hospitals regarding patient care. MATERIALS AND METHODS: An online survey was sent out to all chairmen of the 39 ORL university hospitals in Germany. The answers to the questions referred to the defined period from March 15th to April 15th 2020 and were carried out using the online survey tool "SurveyMonkey". 87 questions focused on general information, health care, and structural effects in the respective institution. RESULTS: All chairmen of the 39 university hospitals in Germany participated in the survey. The collected data prove the considerable impact on organizational, structural and medical aspects of patient care. For example, the surveyed clinics reported a decrease in outpatient cases by 73.8 % to 26.2 ±â€Š14.2 % and in surgical treatments by 65.9 % to 34.1 ±â€Š13.9 %. In contrast, emergency treatment remained unchanged or even increased in 80 % of the facilities and surgical treatment of emergency patients remained unchanged or even increased in more than 90 %. Emergency outpatient and surgical treatment of patients was provided throughout the pandemic in all facilities. In total, about 35 000 outpatients and about 12 000 surgical cases were postponed. As a result of the acute structural changes, the potential danger of falling below current treatment standards was seen in individual areas of patient care. DISCUSSION: The assessment of the impact of the SARS-CoV-2 pandemic is heterogeneous. The majority of the chairmen are critically aware of the risk of falling below current medical treatment standards or guidelines. In the phase of an exponential increase in the number of infections, significant changes in treatment processes had to be accepted for understandable reasons. However, with the currently significantly reduced number of infections, falling below treatment standards and guidelines should not be allowed to remain constant and tolerated. SUMMARY: This study shows a differentiated picture with regard to the effects of the SARS-CoV-2 pandemic on outpatient, inpatient and operative patient care at the ORL university hospitals in Germany and illustrates the importance of these institutions for ensuring patient care during this critical phase.


Assuntos
Infecções por Coronavirus , Otolaringologia , Pandemias , Pneumonia Viral , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/terapia , Betacoronavirus , COVID-19 , Alemanha , Hospitais Universitários , Humanos , SARS-CoV-2
3.
HNO ; 68(11): 828-837, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-32514605

RESUMO

BACKGROUND: Since emergence of the new coronavirus in China in December 2019, many countries have been struggling to control skyrocketing numbers of infections, including among healthcare personnel. It has now been clearly demonstrated that SARS-CoV­2 resides in the upper airways and transmits easily via aerosols and droplets, which significantly increases the risk of infection when performing upper airway procedures. Ventilated COVID-19 patients in a critical condition in the intensive care unit may require tracheotomy for long-term ventilation and to improve weaning. However, the risk of secondary infection of medical personnel performing subsequent tracheostomy care remains unclear. OBJECTIVE: This study aimed to evaluate the risk of droplet dispersion during tracheostomy tube change and overview tracheostomy tube change in COVID-19 patients. MATERIALS AND METHODS: The current literature was reviewed, quantitative and qualitative analyses of droplet formation during tracheostomy tube change in n = 8 patients were performed, and an overview of and checklist for tracheostomy tube change were compiled. RESULTS: This study demonstrates that tracheostomy tube change, in particular insertion of the new tube, may cause significant droplet formation. The aerosolization of particles smaller than 5 µm was not analyzed. CONCLUSION: Our data, together with the current literature, clearly emphasize that tracheostomy care is associated with a high infection risk and should only be performed by a small group of well-trained, maximally protected healthcare personnel.


Assuntos
Infecções por Coronavirus/terapia , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Intubação Intratraqueal/efeitos adversos , Pneumonia Viral/terapia , Traqueostomia , Aerossóis , Betacoronavirus , COVID-19 , Humanos , Pandemias , SARS-CoV-2
4.
Strahlenther Onkol ; 194(12): 1124-1131, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30109361

RESUMO

BACKGROUND: Cochlea sparing can reduce late ototoxicity in head and neck cancer patients treated with cisplatin-based radiochemotherapy. In this situation, a mean cochlear dose (MCD) constraint of 10 Gy has been suggested by others based on the dose-effect relationship of clinical data. We aimed to investigate whether this is feasible for primary and postoperative radiochemotherapy in locoregionally advanced tumors without compromising target coverage. PATIENTS AND METHODS: Ten patients treated with definitive and ten patients treated with adjuvant intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy were investigated. The cochleae and a planning risk volume (PRV) with a 3 mm margin were newly delineated, whereas target volumes and other organs at risk were not changed. The initial plan was recalculated with a constraint of 10 Gy (MCD) on the low-risk side. The quality of the resulting plan was evaluated using the difference in the equivalent uniform dose (EUD). RESULTS: A unilateral MCD of below 10 Gy could be achieved in every patient. The mean MCD was 6.8 Gy in the adjuvant cohort and 7.6 Gy in the definitive cohort, while the non-spared side showed a mean MCD of 18.7 and 30.3 Gy, respectively. The mean PRV doses were 7.8 and 8.4 Gy for the spared side and 18.5 and 29.8 Gy for the non-spared side, respectively. The mean EUD values of the initial and recalculated plans were identical. Target volume was not compromised. CONCLUSION: Unilateral cochlea sparing with an MCD of less than 10 Gy is feasible without compromising the target volume or dose coverage in locoregionally advanced head and neck cancer patients treated with IMRT. A prospective evaluation of the clinical benefit of this approach as well as further investigation of the dose-response relationship for future treatment modification appears promising.


Assuntos
Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Cóclea/efeitos dos fármacos , Cóclea/efeitos da radiação , Tratamentos com Preservação do Órgão , Neoplasias Otorrinolaringológicas/terapia , Radioterapia de Intensidade Modulada/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia Adjuvante/efeitos adversos , Cisplatino/uso terapêutico , Terapia Combinada , Estudos de Viabilidade , Feminino , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Otorrinolaringológicas/patologia , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador
5.
HNO ; 65(Suppl 1): 59-67, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27878601

RESUMO

BACKGROUND: High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as a long-term consequence. Here, a treatment regime was developed to limit permanent damage based on a preclinical animal model of acute noise trauma. AIM: To develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined. MATERIALS AND METHODS: A series of experiments with different impulse noise exposures were performed. Permanent hearing loss and hair cell density were assessed 14 days after exposure. Hearing and hair cell preservation were investigated as a function of the glucocorticoid dose. RESULTS: After impulse noise exposure, local application to the round window of the cochlea of high-dose prednisolone (25 mg/ml) or methylprednisolone (12.5 mg/ml) resulted in a statistically significant reduction in hearing loss compared with the control group. CONCLUSION: The local application of high doses of the drugs to the round window of the cochlea appears to be an effective treatment for acute noise trauma.


Assuntos
Percepção Auditiva/efeitos dos fármacos , Orelha Interna/efeitos dos fármacos , Orelha Interna/fisiopatologia , Glucocorticoides/administração & dosagem , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Perda Auditiva Provocada por Ruído/fisiopatologia , Administração Tópica , Animais , Doença Crônica , Cobaias , Perda Auditiva Provocada por Ruído/diagnóstico por imagem , Resultado do Tratamento
6.
HNO ; 64(11): 831-840, 2016 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-27742965

RESUMO

BACKGROUND: High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as a long-term consequence. Here, a treatment regime was developed to limit permanent damage based on a preclinical animal model of acute noise trauma. AIM: To develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined. MATERIALS AND METHODS: A series of experiments with different impulse noise exposures was performed. Permanent hearing loss and hair cell density were assessed 14 days after exposure. Hearing and hair cell preservation were investigated as a function of glucocorticoid dose. RESULTS: After impulse noise exposure, local application of high-dose prednisolone (25 mg/ml) or methylprednisolone (12.5 mg/ml) to the round window of the cochlea resulted in a statistically significant reduction in hearing loss compared to the control group. CONCLUSION: Local application of high doses of the drugs to the round window of the cochlea appears to be an effective treatment for acute noise trauma.


Assuntos
Glucocorticoides/administração & dosagem , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Perda Auditiva Provocada por Ruído/fisiopatologia , Janela da Cóclea/efeitos dos fármacos , Administração Tópica , Animais , Relação Dose-Resposta a Droga , Cobaias , Perda Auditiva Provocada por Ruído/diagnóstico , Resultado do Tratamento
7.
Pflugers Arch ; 467(12): 2571-88, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26208470

RESUMO

Volume homeostasis of the cochlear endolymph depends on radial and longitudinal endolymph movements (LEMs). LEMs measured in vivo have been exclusively recognized under physiologically challenging conditions, such as experimentally induced alterations of perilymph osmolarity or endolymph volume. The regulatory mechanisms that adjust LEMs to the physiological requirements of endolymph volume homeostasis remain unknown. Here, we describe the formation of an aquaporin (AQP)-based "water shunt" during the postnatal development of the mouse cochlea and its regulation by different triggers. The final complementary expression pattern of AQP5 (apical membrane) and AQP4 (basolateral membrane) in outer sulcus cells (OSCs) of the cochlear apex is acquired at the onset of hearing function (postnatal day (p)8-p12). In vitro, hyperosmolar perfusion of the perilymphatic fluid spaces or the administration of the muscarinic agonist pilocarpine in cochlear explants (p14) induced the translocation of AQP5 channel proteins into the apical membranes of OSCs. AQP5 membrane translocation was blocked by the muscarinic antagonist atropine. The muscarinic M3 acetylcholine (ACh) receptor (M3R) was identified in murine OSCs via mRNA expression, immunolabeling, and in vitro binding studies using an M3R-specific fluorescent ligand. Finally, the water shunt elements AQP4, AQP5, and M3R were also demonstrated in OSCs of the human cochlea. The regulation of the AQP4/AQP5 water shunt in OSCs of the cochlear apex provides a molecular basis for regulated endolymphatic volume homeostasis. Moreover, its dysregulation or disruption may have pathophysiologic implications for clinical conditions related to endolymphatic hydrops, such as Ménière's disease.


Assuntos
Aquaporina 5/metabolismo , Membrana Celular/metabolismo , Cóclea/metabolismo , Endolinfa/metabolismo , Animais , Aquaporina 4/genética , Aquaporina 4/metabolismo , Aquaporina 5/genética , Colinérgicos/farmacologia , Cóclea/efeitos dos fármacos , Homeostase , Humanos , Camundongos , Receptor Muscarínico M3/agonistas , Receptor Muscarínico M3/antagonistas & inibidores , Receptor Muscarínico M3/metabolismo , Água/metabolismo
8.
Neuroscience ; 284: 470-482, 2015 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-25316409

RESUMO

Human auditory nerve afferents consist of two separate systems; one is represented by the large type I cells innervating the inner hair cells and the other one by the small type II cells innervating the outer hair cells. Type I spiral ganglion neurons (SGNs) constitute 96% of the afferent nerve population and, in contrast to other mammals, their soma and pre- and post-somatic segments are unmyelinated. Type II nerve soma and fibers are unmyelinated. Histopathology and clinical experience imply that human SGNs can persist electrically excitable without dendrites, thus lacking connection to the organ of Corti. The biological background to this phenomenon remains elusive. We analyzed the pre- and post-somatic segments of the type I human SGNs using immunohistochemistry and transmission electron microscopy (TEM) in normal and pathological conditions. These segments were found surrounded by non-myelinated Schwann cells (NMSCs) showing strong intracellular expression of laminin-ß2/collagen IV. These cells also bordered the perikaryal entry zone and disclosed surface rugosities outlined by a folded basement membrane (BM) expressing laminin-ß2 and collagen IV. It is presumed that human large SGNs are demarcated by three cell categories: (a) myelinated Schwann cells, (b) NMSCs and (c) satellite glial cells (SGCs). Their BMs express laminin-ß2/collagen IV and reaches the BM of the sensory epithelium at the habenula perforata. We speculate that the NMSCs protect SGNs from further degeneration following dendrite loss. It may give further explanation why SGNs can persist as electrically excitable monopolar cells even after long-time deafness, a blessing for the deaf treated with cochlear implantation.


Assuntos
Neurônios/citologia , Gânglio Espiral da Cóclea/citologia , Adulto , Membrana Basal/citologia , Membrana Basal/metabolismo , Membrana Basal/patologia , Implante Coclear , Colágeno/metabolismo , Feminino , Humanos , Imageamento Tridimensional , Imuno-Histoquímica , Laminina/metabolismo , Masculino , Microscopia Confocal , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Neurônios/metabolismo , Neurônios/patologia , Células Satélites Perineuronais/citologia , Células Satélites Perineuronais/metabolismo , Células Satélites Perineuronais/patologia , Células de Schwann/citologia , Células de Schwann/metabolismo , Células de Schwann/patologia , Gânglio Espiral da Cóclea/metabolismo , Gânglio Espiral da Cóclea/patologia
9.
HNO ; 62(6): 423-31, 2014 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-24916350

RESUMO

BACKGROUND: Sound transduction in the cochlea critically depends on the circulation of potassium ions (K(+)) along so-called "K(+) recycling routes" between the endolymph and perilymph. These K(+) currents generate high ionic and osmotic gradients, which potentially impair the excitability of sensory hair cells and threaten cell survival in the entire cochlear duct. Molecular water channels-aquaporins (AQP)-are expressed in all cochlear supporting cells along the K(+) recycling routes; however, their significance for osmotic equilibration in cochlear duct cells is unknown. METHODS: The diffusive and osmotic water permeabilies of Reissner's membrane, the organ of Corti and the entire cochlear duct epithelium were determined. Expression of the potassium channel Kir4.1 and the water channel AQP4 in the cochlear duct was investigated by immunohistochemistry. RESULTS: The calculated water permeability values indicate the extent of AQP-facilitated water flux across the cochlear duct epithelium. Immunohistochemically, Kir4.1 and AQP4 were found to colocalize in distinct membrane domains of supporting cells along the K(+)-recycling routes. CONCLUSION: These observations suggest the presence of a rapid AQP-mediated water exchange between the endolymph, the cells of the cochlear duct and the perilymph. The subcellular colocalization of Kir4.1 and AQP4 in epithelial supporting cells indicates functional coupling of potassium and water flow in the cochlea. Finally, this offers an explanation for the hearing impairment observed in individuals with mutations in the AQP4 gene.


Assuntos
Aquaporinas/metabolismo , Água Corporal/metabolismo , Cóclea/fisiologia , Audição/fisiologia , Mecanotransdução Celular/fisiologia , Potássio/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia , Animais , Cobaias , Ativação do Canal Iônico/fisiologia
10.
Cell Death Dis ; 5: e1234, 2014 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-24853412

RESUMO

Hereditary retinal degeneration (RD) relates to a heterogeneous group of blinding human diseases in which the light sensitive neurons of the retina, the photoreceptors, die. RD is currently untreatable and the underlying cellular mechanisms remain poorly understood. However, the activity of the enzyme poly-ADP-ribose polymerase-1 (PARP1) and excessive generation of poly-ADP-ribose (PAR) polymers in photoreceptor nuclei have been shown to be causally involved in RD. The activity of PARP1 is to a large extent governed by its functional antagonist, poly-ADP-glycohydrolase (PARG), which thus also may have a role in RD. To investigate this, we analyzed PARG expression in the retina of wild-type (wt) mice and in the rd1 mouse model for human RD, and detected increased PARG protein in a subset of degenerating rd1 photoreceptors. Knockout (KO) animals lacking the 110 kDa nuclear PARG isoform were furthermore analyzed, and their retinal morphology and function were indistinguishable from wild-type animals. Organotypic wt retinal explants can be experimentally treated to induce rd1-like photoreceptor death, but PARG110 KO retinal explants were unexpectedly highly resistant to such treatment. The resistance was associated with decreased PAR accumulation and low PARP activity, indicating that PARG110 may positively regulate PARP1, an event that therefore is absent in PARG110 KO tissue. Our study demonstrates a causal involvement of PARG110 in the process of photoreceptor degeneration. Contrasting its anticipated role as a functional antagonist, absence of PARG110 correlated with low PARP activity, suggesting that PARG110 and PARP1 act in a positive feedback loop, which is especially active under pathologic conditions. This in turn highlights both PARG110 and PARP1 as potential targets for neuroprotective treatments for RD.


Assuntos
AMP Cíclico/metabolismo , Glicosídeo Hidrolases/deficiência , Degeneração Neural , Células Fotorreceptoras de Vertebrados/enzimologia , Degeneração Retiniana/enzimologia , Animais , Morte Celular , Nucleotídeo Cíclico Fosfodiesterase do Tipo 6/antagonistas & inibidores , Nucleotídeo Cíclico Fosfodiesterase do Tipo 6/genética , Modelos Animais de Doenças , Ativação Enzimática , Predisposição Genética para Doença , Glicosídeo Hidrolases/genética , Camundongos , Camundongos Knockout , Camundongos Mutantes , Mutação , Fenótipo , Inibidores de Fosfodiesterase/farmacologia , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Células Fotorreceptoras de Vertebrados/patologia , Poli(ADP-Ribose) Polimerase-1 , Poli Adenosina Difosfato Ribose/metabolismo , Poli(ADP-Ribose) Polimerases/deficiência , Poli(ADP-Ribose) Polimerases/genética , Isoformas de Proteínas , Degeneração Retiniana/genética , Degeneração Retiniana/patologia , Fatores de Tempo , Técnicas de Cultura de Tecidos
11.
Pflugers Arch ; 466(10): 1963-85, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24385019

RESUMO

The cochlear duct epithelium (CDE) constitutes a tight barrier that effectively separates the inner ear fluids, endolymph and perilymph, thereby maintaining distinct ionic and osmotic gradients that are essential for auditory function. However, in vivo experiments have demonstrated that the CDE allows for rapid water exchange between fluid compartments. The molecular mechanism governing water permeation across the CDE remains elusive. We computationally determined the diffusional (PD) and osmotic (Pf) water permeability coefficients for the mammalian CDE based on in silico simulations of cochlear water dynamics integrating previously derived in vivo experimental data on fluid flow with expression sites of molecular water channels (aquaporins, AQPs). The PD of the entire CDE (PD = 8.18 × 10(-5) cm s(-1)) and its individual partitions including Reissner's membrane (PD = 12.06 × 10(-5) cm s(-1)) and the organ of Corti (PD = 10.2 × 10(-5) cm s(-1)) were similar to other epithelia with AQP-facilitated water permeation. The Pf of the CDE (Pf = 6.15 × 10(-4) cm s(-1)) was also in the range of other epithelia while an exceptionally high Pf was determined for an epithelial subdomain of outer sulcus cells in the cochlear apex co-expressing AQP4 and AQP5 (OSCs; Pf = 156.90 × 10(-3) cm s(-1)). The Pf/PD ratios of the CDE (Pf/PD = 7.52) and OSCs (Pf/PD = 242.02) indicate an aqueous pore-facilitated water exchange and reveal a high-transfer region or "water shunt" in the cochlear apex. This "water shunt" explains experimentally determined phenomena of endolymphatic longitudinal flow towards the cochlear apex. The water permeability coefficients of the CDE emphasise the physiological and pathophysiological relevance of water dynamics in the cochlea in particular for endolymphatic hydrops and Ménière's disease.


Assuntos
Aquaporina 4/metabolismo , Aquaporina 5/metabolismo , Permeabilidade Capilar , Ducto Coclear/metabolismo , Endolinfa/metabolismo , Perilinfa/metabolismo , Água/metabolismo , Animais , Aquaporina 4/genética , Aquaporina 5/genética , Membrana Celular/metabolismo , Epitélio/metabolismo , Cobaias , Masculino
12.
Neuroscience ; 189: 79-92, 2011 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-21621589

RESUMO

The water channel aquaporin-4 (AQP4) is expressed in the cochlea and is essential for normal hearing. Unlike other AQPs, multiple isoforms of AQP4 have been reported in diverse tissues, three of which, M1, M23, and Mz, function as water channels. In addition, these protein isoforms are found in higher order complexes. Morphologically these higher order complexes correspond to orthogonal arrays of particles (OAPs) that are found in cell membranes by freeze fracture analysis. Using RT-PCR, quantitative PCR and blue-native PAGE immunoblots we identified all functional AQP4 isoforms -M1, M23, and Mz- and the formation of higher-order complexes in the organ of Corti of the rat. Complementary freeze-fracture studies revealed OAPs distributed in the lateral and basal membrane domains of the cochlear duct supporting cells, specifically Hensen's cells and outer sulcus cells. The unique inter- and intracellular heterogeneity in size, density and shape of OAPs suggests exceptional physiological requirements for the maintenance of water homeostasis during auditory sensory transduction in the cochlea.


Assuntos
Aquaporina 4/metabolismo , Cóclea/metabolismo , Animais , Aquaporina 4/genética , Cóclea/citologia , Ducto Coclear/citologia , Ducto Coclear/metabolismo , Eletroforese em Gel Bidimensional , Técnica de Fratura por Congelamento , Órgão Espiral/citologia , Órgão Espiral/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de RNA/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
Cell Mol Life Sci ; 68(16): 2739-49, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21076990

RESUMO

INTRODUCTION: Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently. However, its role in the auditory system still remains elusive. Our previous results showed a deterioration of hearing with age in Tff3-deficient animals. RESULTS: Present detailed analysis of auditory brain stem response (ABR) measurements and immunohistochemical study of selected functional proteins indicated a normal function and phenotype of the cochlea in Tff3 mutants. However, a microarray-based screening of tissue derived from the auditory central nervous system revealed an alteration of securin (Pttg1) and serpina3n expression between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR, immunostaining and western blots. CONCLUSIONS: We found highly down-regulated Pttg1 and up-regulated serpina3n expression as a consequence of genetically deleting Tff3 in mice, indicating a potential role of these factors during the development of presbyacusis.


Assuntos
Proteínas de Fase Aguda/metabolismo , Proteínas de Transporte/metabolismo , Mucinas/genética , Presbiacusia/metabolismo , Serpinas/metabolismo , Proteínas de Fase Aguda/genética , Proteínas de Fase Aguda/fisiologia , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Cóclea/metabolismo , Regulação para Baixo , Orelha Interna/metabolismo , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Mucinas/deficiência , Mucinas/metabolismo , Fenótipo , Securina , Serpinas/genética , Serpinas/fisiologia , Fator Trefoil-3 , Regulação para Cima
14.
Neuroscience ; 168(4): 957-70, 2010 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-19747527

RESUMO

Aquaporins are membrane water channel proteins that have also been identified in the cochlea. Auditory function critically depends on the homeostasis of the cochlear fluids perilymph and endolymph. In particular, the ion and water regulation of the endolymph is essential for sensory transduction. Within the cochlear duct the lateral wall epithelium has been proposed to secrete endolymph by an aquaporin-mediated flow of water across its epithelial tight junction barrier. This study identifies interspecies differences in the cellular distribution of aquaporin 5 (AQP5) in the cochlear lateral wall of mice, rats, gerbils and guinea pigs. In addition the cellular expression pattern of AQP5 is described in the human cochlea. Developmental changes in rats demonstrate longitudinal and radial gradients along the cochlear duct. During early postnatal development a pancochlear expression is detected. However a regression to the apical quadrant and limitation to outer sulcus cells (OSCs) is observed in the adult. This developmental loss of AQP5 expression in the basal cochlear segments coincides with a morphological loss of contact between OSCs and the endolymph. At the subcellular level, AQP5 exhibits polarized expression in the apical plasma membrane of the OSCs. Complementary, the basolateral membrane in the root processes of the OSCs exhibits AQP4 expression. This differential localization of AQP5 and AQP4 in the apical and basolateral membranes of the same epithelial cell type suggests a direct aquaporin-mediated transcellular water shunt between the perilymph and endolymph in the OSCs of the cochlear lateral wall. In the human cochlea these findings may have pathophysiological implications attributed to a dysfunctional water regulation by AQP5 such as endolymphatic hydrops (i.e. in Meniere's disease) or sensorineural hearing loss (i.e. in Sjögren's syndrome).


Assuntos
Aquaporina 5/metabolismo , Cóclea/metabolismo , Endolinfa/metabolismo , Perilinfa/metabolismo , Animais , Animais Recém-Nascidos , Membrana Celular/metabolismo , Cóclea/crescimento & desenvolvimento , Epitélio/crescimento & desenvolvimento , Epitélio/metabolismo , Feminino , Gerbillinae , Cobaias , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Ratos , Especificidade da Espécie , Frações Subcelulares/metabolismo
15.
J Med Genet ; 46(4): 277-80, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19357117

RESUMO

Mutations in the large GPR98 gene underlie Usher syndrome type 2C (USH2C), and all patients described to date have been female. It was speculated that GPR98 mutations cause a more severe, and eventually lethal, phenotype in males. We describe for the first time two male patients with USH2 with novel GPR98 mutations. Clinical characterization of a male patient and his affected sister revealed a typical USH2 phenotype in both. GPR98 may have been excluded from systematic investigation in previous studies, and the proportion of patients with USH2C probably underestimated. GPR98 should be considered in patients with USH2 of both sexes.


Assuntos
Mutação , Receptores Acoplados a Proteínas G/genética , Síndromes de Usher/genética , Análise Mutacional de DNA , Saúde da Família , Feminino , Humanos , Masculino , Linhagem , Síndromes de Usher/classificação , Síndromes de Usher/patologia , Adulto Jovem
16.
Ophthalmologe ; 106(6): 547-50, 2009 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-18709374

RESUMO

Rhinoorbitocerebral mucormycosis is a rare invasive fungal infection that is fatal when untreated. We describe an immunosuppressed patient with chronic lymphatic leukaemia who developed a severe rhinoorbitocerebral mucormycosis after allogeneic bone marrow transplantation. Due to the potentially fulminant course and fatal outcome, radical excision of the necrotic area in combination with antifungal therapy is necessary in the presence of suspicious clinical signs of mucormycosis despite a lack of histopathologic confirmation.


Assuntos
Hospedeiro Imunocomprometido/imunologia , Mucormicose/diagnóstico , Mucormicose/terapia , Doenças Orbitárias/diagnóstico , Doenças Orbitárias/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Mucormicose/imunologia , Doenças Orbitárias/imunologia , Resultado do Tratamento
18.
HNO ; 56(3): 288-300, 2008 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-18288464

RESUMO

Regenerative medicine offers the prospect of causal treatment of sensorineural hearing loss. In humans, the loss of sensory hair cells is irreversible and results in chronic hearing loss. Other vertebrates, particularly birds, have the capability to spontaneously regenerate lost sensory hair cells and restore hearing. In the bird model, regeneration of hair cells is based on the proliferation of supporting cells. In mammals, supporting cells have lost their proliferative capacity and are terminally differentiated. To gain an understanding about regeneration of hair cells in mammals, cell division of supporting cells has to be controlled. Gene disruption of the cell cycle inhibitor p27(Kip1) allows supporting cell proliferation in the organ of Corti in vivo. Furthermore, in vitro studies indicate that newly generated cells may differentiate into hair cells after p27(Kip1) disruption. Other current methods to induce hair cell regeneration include the gene transfer of Math1 and transplantation of stem cells to the inner ear.


Assuntos
Terapia Genética/tendências , Perda Auditiva Neurossensorial/terapia , Procedimentos Cirúrgicos Otorrinolaringológicos/tendências , Procedimentos de Cirurgia Plástica/métodos , Medicina Regenerativa/tendências , Transplante de Células-Tronco/tendências , Engenharia Tecidual/tendências , Terapia Genética/métodos , Humanos
19.
Eur J Surg Oncol ; 34(2): 227-31, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17448624

RESUMO

OBJECTIVE: It is impossible to precisely anticipate the crooked course of the transverse and sigmoid sinuses and their individual relationship to superficial landmarks such as the asterion during retrosigmoid approaches. This study was designed to evaluate this anatomical relationship with the help of a surgical planning system and to analyze the impact of these in vivo findings on trepanation placement in retrosigmoid craniotomies. METHODS: In a consecutive series of 123 patients with pathologies located in the cerebellopontine angle, 72 patients underwent surgical planning for retrosigmoid craniotomies based on 3D volumetric renderings of computed tomography venography. By opacity modulation of surfaces in 3D images the position of the asterion was assessed in relationship to the transverse-sigmoid sinus transition (TST) and compared to its intraoperative localization. We evaluated the impact of this additional information on trepanation placement. RESULTS: The spatial relationship of the asterion and the underlying TST complex could be identified and recorded in 66 out of 72 cases. In the remaining 6 cases the sutures were ossified and not visible in the 3D CT reconstructions. The asterion was located on top of the TST in 51 cases, above the TST in 4 cases, and below the TST in 11 cases. The location of the trepanation was modified in 27 cases due to the preoperative imaging findings with major and minor modifications in 10 and 17 cases, respectively. CONCLUSION: Volume-rendered images provide reliable 3D visualization of complex and hidden anatomical structures in the posterior fossa and thereby increase the precision in retrosigmoid approaches.


Assuntos
Craniotomia/métodos , Imageamento Tridimensional , Flebografia/métodos , Tomografia Computadorizada por Raios X/métodos , Seios Transversos/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Estudos de Coortes , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Monitorização Intraoperatória/métodos , Sensibilidade e Especificidade , Base do Crânio/anatomia & histologia , Base do Crânio/diagnóstico por imagem , Base do Crânio/cirurgia , Seios Transversos/cirurgia
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