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Age-related hearing loss (ARHL) impairs the quality of life in elderly persons. ARHL is associated with comorbidities, such as depression, falls, or frailty. Frailty syndrome is related to poor health outcomes in old age. ARHL is a potentially modifiable risk factor for frailty. Oxidative stress has been proposed as a key factor underlying the onset and/or development of ARHL and frailty. Cocoa has high levels of polyphenols and provides many health benefits due to its antioxidant properties. Male and female C57Bl/6J mice were randomly assigned to two study groups: animals receiving a cocoa-supplemented diet and the other receiving a standard diet. Then, at the ages of 6, 14, and 22 months, hearing and frailty were measured in all mice. Auditory steady-state responses (ASSR) threshold shifts were measured to different frequencies. The frailty score was based on the "Valencia Score" adapted to the experimental animals. The total antioxidant capacity and total polyphenols in urine samples were also measured. Significant improvements in hearing ability are observed in the cocoa groups at 6, 14, and 22 months compared to the no cocoa group. The cocoa diet significantly retards the development of frailty in mice. Cocoa increases the concentration of polyphenols excreted in the urine, which increases the total antioxidant capacity. In conclusion, cocoa, due to its antioxidant properties, leads to significant protection against ARHL and frailty.
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Cocoa, rich in polyphenols, has been reported to provide many health benefits due to its antioxidant properties. In this study, we investigated the effect of Cocoa polyphenols extract (CPE) against oxidative stress-induced cellular senescence using a hydrogen peroxide (H2O2)-induced cellular senescence model in three auditory cells lines derived from the auditory organ of a transgenic mouse: House Ear Institute-Organ of Corti 1 (HEI-OC1), Organ of Corti-3 (OC-k3), and Stria Vascularis (SV-k1) cells. Our results showed that CPE attenuated senescent phenotypes, including senescence-associated ß-galactosidase expression, cell proliferation, alterations of morphology, oxidative DNA damage, mitochondrial dysfunction by inhibiting mitochondrial reactive oxygen species (mtROS) generation, and related molecules expressions such as forkhead box O3 (FOXO3) and p53. In addition, we determined that CPE induces expression of sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3), and it has a protective role against cellular senescence by upregulation of SIRT1 and SIRT3. These data indicate that CPE protects against senescence through SIRT1, SIRT3, FOXO3, and p53 in auditory cells. In conclusion, these results suggest that Cocoa has therapeutic potential against age-related hearing loss (ARHL).
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Sirtuina 1 , Sirtuina 3 , Ratones , Animales , Sirtuina 1/metabolismo , Sirtuina 3/genética , Sirtuina 3/metabolismo , Polifenoles/farmacología , Peróxido de Hidrógeno/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Senescencia Celular , Estrés Oxidativo , Ratones TransgénicosRESUMEN
Presbycusis or Age-related hearing loss (ARHL) is a sensorineural hearing loss that affects communication, leading to depression and social isolation. Currently, there are no effective treatments against ARHL. It is known that cocoa products have high levels of polyphenol content (mainly flavonoids), that are potent anti-inflammatory and antioxidant agents with proven benefits for health. The objective is to determine the protective effect of cocoa at the cellular and molecular levels in Presbycusis. For in vitro study, we used House Ear Institute-Organ of Corti 1 (HEI-OC1), stria vascularis (SV-k1), and organ of Corti (OC-k3) cells (derived from the auditory organ of a transgenic mouse). Each cell line was divided into a control group (CTR) and an H2O2 group (induction of senescence by an oxygen radical). Additionally, every group of every cell line was treated with the cocoa polyphenolic extract (CPE), measuring different markers of apoptosis, viability, the activity of antioxidant enzymes, and oxidative/nitrosative stress. The data show an increase of reactive oxidative and nitrogen species (ROS and RNS, respectively) in senescent cells compared to control ones. CPE treatment effectively reduced these high levels and correlated with a significant reduction in apoptosis cells by inhibiting the mitochondrial-apoptotic pathway. Furthermore, in senescence cells, the activity of antioxidant enzymes (Superoxide dismutase, SOD; Catalase, CAT; and Glutathione peroxidase, GPx) was recovered after CPE treatment. Administration of CPE also decreased oxidative DNA damage in the auditory senescent cells. In conclusion, CPE inhibits the activation of senescence-related apoptotic signaling by decreasing oxidative stress in auditory senescent cells.
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Age-related hearing loss (ARHL) is an increasing and gradual sensorineural hearing dysfunction. Oxidative stress is an essential factor in developing ARHL; additionally, premature senescence of auditory cells induced by oxidative stress can produce hearing loss. Hydrogen peroxide (H2O2) represents a method commonly used to generate cellular senescence in vitro. The objective of the present paper is to study H2O2-induced senescence patterns in three auditory cell lines (House Ear Institute-Organ of Corti 1, HEI-OC1; organ of Corti, OC-k3, and stria vascularis, SV-k1 cells) to elucidate the intrinsic mechanisms responsible for ARHL. The auditory cells were exposed to H2O2 at different concentrations and times. The results obtained show different responses of the hearing cells concerning cell growth, ß-galactosidase activity, morphological changes, mitochondrial activation, levels of oxidative stress, and other markers of cell damage (Forkhead box O3a, FoxO3a, and 8-oxoguanine, 8-oxoG). Comparison between the responses of these auditory cells to H2O2 is a helpful method to evaluate the molecular mechanisms responsible for these auditory cells' senescence. Furthermore, this in vitro model could help develop anti-senescent therapeutic strategies for the treatment of AHRL.
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Currently, new treatments are required to supplement the current standard of care for head and neck squamous cell carcinoma (HNSCC). The phosphatidylinositol3-kinase (PI3K) signaling pathway is commonly altered and activated in HNSCC. PHT-427 is a dual PI3K-mammalian target of the AKT/PDK1 inhibitor; however, to the best of our knowledge, the effect of the PHT-427 inhibitor on HNSCC has not been investigated. This study aims to evaluate the antitumoral effect of PHT-427-loaded polymeric nanoparticles based on α-tocopheryl succinate (α-TOS). The in vitro activity of PHT-427 was tested in hypopharynx carcinoma squamous cells (FaDu) to measure the cell viability, PI3KCA/AKT/PDK1 gene expression, and PI3KCA/AKT/PDK1 levels. Apoptosis, epidermal growth factor receptor (EGFR), and reactive oxygen species (ROS) were also measured. The presence of PHT-427 significantly enhances its antiproliferative and proapoptotic activity by inactivating the PI3K/AKT/PDK1 pathway. Nanoparticles (NPs) effectively suppress AKT/PDK1 expression. Additionally, NPs loaded with PHT-427 produce high oxidative stress levels that induce apoptosis. In conclusion, these results are promising in the use of this nanoformulation as a PHT-427 delivery system for effective HNSCC treatment.
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The prognosis of patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC) is generally poor. New treatments are required to supplement the current standard of care. Paclitaxel (PTX), an effective chemotherapeutic for HNSCC, has serious side effects. A polymeric nanocarrier system was developed for the delivery of PTX to improve HNSCC treatment. This study aimed to evaluate the antitumor efficacy of PTX-loaded polymeric nanoparticles based on α-TOS (PTX-NPs) administered by direct intratumoral injection into a Hypopharynx carcinoma squamous cells (FaDu) tumor xenograft mouse model. The nanocarrier system based on block copolymers of polyethylene glycol (PEG) and a methacrylic derivative of α-TOS was synthesized and PTX was loaded into the delivery system. Tumor volume was measured to evaluate the antitumor effect of the PTX-NPs. The relative mechanisms of apoptosis, cell proliferation, growth, angiogenesis, and oxidative and nitrosative stress were detected by Western blotting, fluorescent probes, and immunohistochemical analysis. The antitumor activity results showed that compared to free PTX, PTX-NPs exhibited much higher antitumor efficacy and apoptosis-inducing in a FaDu mouse xenograft model and demonstrated an improved safety profile. Ki-67, EGFR, and angiogenesis markers (Factor VIII, CD31, and CD34) expression were significantly lower in the PTX-NPs group compared with other groups (p < .05). Also, PTX-NPs induced oxidative and nitrosative stress in tumor tissue. Direct administration of PTX-loaded polymeric nanoparticles based on α-Tocopheryl Succinate at the tumor sites, proved to be promising for HNSCC therapy.
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Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Nanopartículas/química , Paclitaxel/administración & dosificación , Paclitaxel/farmacología , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Química Farmacéutica , Portadores de Fármacos , Femenino , Ratones , Ratones Desnudos , Neovascularización Patológica/metabolismo , Polietilenglicoles/química , Polímeros/química , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND AND OBJECTIVE: Differential diagnosis of vertigo is a diagnostic challenge in the emergency setting. In our centre we have created a vertigo protocol to distinguish the different pathologies and their management in the emergency department. Our goal is to determine the efficacy of our hospital protocol in the diagnostic and therapeutic approach to acute vestibular syndrome. PATIENTS AND METHODS: It is a retrospective descriptive observational study on patients with a diagnosis of acute vestibular syndrome in the emergency department using our unclear origin vertigo protocol. All patients underwent an examination that included the HINTS protocol and had a minimum follow-up of 6 months. The results of the clinical assessments by the specialists were compared, as well as the physical examination with the different final diagnoses classified as peripheral, central and other-origin. RESULTS: We obtained 97 patients, with a mean age of 61.46 years. The final diagnoses were 26 patients for the peripheral group (26.8%), 38 for the other-origin group (39.2%) and 33 for the central group (34%). Stroke was found in 18 of the latter group, clinical-exploratory disagreement being the most frequent reason for activation of the protocol. CONCLUSIONS: Our protocol has proven to be a useful tool to differentiate a possible acute vestibular syndrome of central origin from a peripheral one, avoiding unnecessary imaging tests. The most frequent cause of activation of the protocol was clinical-exploratory disagreement seen by the ENT doctor.
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OBJECTIVE: To evaluate the incidence of certain symptoms in a population of health workers exposed to coronavirus disease 2019 patients. STUDY DESIGN: Case-control study. METHODS: The study was conducted at a tertiary care hospital from March 1 to April 7, 2020. Health workers with suspected coronavirus disease 2019 (COVID-19) infection were included. The presence of COVID-19 was detected by using real-time polymerase chain reaction (RT-PCR) methods. Positive and negative RT-PCR patients were used as case and control groups, respectively. This study analyzed the incidence of COVID-19 symptoms in both patient groups. Visual analog scales were used for self-assessment of smell and taste disorders, ranging from 0 (no perception) to 10 (excellent perception). RESULTS: There were 215 (60.6%) patients with positive RT-PCR and 140 (39.4%) patients with negative RT-PCR. The presence of symptoms such as hyposmia hypogeusia, dysthermia, and cough were strongly associated with a positive RT-PCR. The association of cough and subjective hyposmia had 5.46 times higher odds of having a positive test. The receiver operating characteristic (ROC) analysis showed that a fever higher than 37.45°C resulted in sensitivity and specificity of 0.65 and 0.61, respectively. A total of 138 cases (64.1%) and 114 cases (53%) had subjective hyposmia and hypogeusia, respectively. The 85.4% of these patients recovered olfactory function within the first 14 days of the onset of the symptoms. CONCLUSION: There is a significant association between positive RT-PCR and subjective hyposmia. The association of subjective hyposmia and cough increase significantly the odds of having a positive RT-PCR. The measurement of fever as the only method for screening of COVID-19 infection resulted in a poor association. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:2674-2679, 2020.
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Ageusia/epidemiología , Anosmia/epidemiología , COVID-19/complicaciones , Tos/epidemiología , SARS-CoV-2 , Adulto , Ageusia/virología , Anosmia/virología , Estudios de Casos y Controles , Tos/virología , Femenino , Personal de Salud/estadística & datos numéricos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y EspecificidadRESUMEN
During the SARS-CoV-2 pandemic, patients in intensive care units who are undergoing long-term intubation may require tracheostomy. There is controversy about indication and health care professionals' safety regarding the conventional or percutaneous technique. We performed a prospective analysis of a series of 27 consecutive patients with COVID-19 comparing both tracheostomy techniques, safety, and prognosis clinical markers. The results show that the techniques are equally safe, without cases of infection in surgeons. The Sequential Organ Failure Assessment score before surgery and the progression in ventilation support during the first 72 hours after tracheostomy are optimal prognostic markers for these patients.
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Infecciones por Coronavirus/terapia , Seguridad del Paciente , Neumonía Viral/terapia , Traqueostomía/métodos , Anciano , Betacoronavirus , COVID-19 , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Puntuaciones en la Disfunción de Órganos , Pandemias , Pronóstico , Estudios Prospectivos , SARS-CoV-2RESUMEN
OBJECTIVE: This study aimed to evaluate the changes in the VOR gain after intratympanic gentamicin therapy and to correlate them with the mid-term effects on the control of vertigo, in a population of Menière's disease patients. STUDY DESIGN: The study design was a prospective "Outcomes research." SETTING: Tertiary referral center. PATIENTS: This study included 20 patients with unilateral Menière's disease refractory to medical therapy for at least 1 year, and treated with an on demand intratympanic gentamicin protocol. INTERVENTION: Therapeutic. MAIN OUTCOME MEASURE: Audiometry, caloric testing, and a vHIT before beginning the protocol were performed. Patients underwent weekly vHIT assessments until a significant gain reduction was observed. Subsequently we performed vHIT tests 1 month after the therapy completion, and then every 3 months for at least 1 year. RESULTS: Complete vertigo control (class A) was achieved in 14 patients at the 12-month follow-up assessment. We observed a significant reduction in VOR gain values at the 3-week follow-up assessment. We found a significant correlation between the 1-month posttreatment ipsilateral hVOR gain and the rate of vertigo recurrence after the first IT gentamicin treatment (p = 0.012; r = 0.400). At the mid-term assessment, 10 patients exhibited a significant partial recovery of the hVOR gain. CONCLUSIONS: The delayed effect of intratympanic gentamicin and the subsequent gain restoration are factors that may influence the patients' outcome. The feasibility of the vHIT system makes it a useful tool to monitorize the VOR changes.
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Antibacterianos/administración & dosificación , Gentamicinas/administración & dosificación , Enfermedad de Meniere/tratamiento farmacológico , Adulto , Anciano , Antibacterianos/uso terapéutico , Pruebas Calóricas , Femenino , Gentamicinas/uso terapéutico , Humanos , Inyección Intratimpánica , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
The aim of this work is to study, in an in vitro head and neck squamous cell carcinomas model the anti-angiogenic and anti-migratory properties of self-assembled polymeric nanoparticles (NPs) with demonstrated selective anticancer activity. The NPs are based on α-tocopheryl succinate (α-TOS) encapsulated in the hydrophobic core of the NPs. We analyzed the effect of the newly synthetized α-TOS-loaded NPs in proliferating endothelial cells and hypopharynx carcinoma squamous cells and measured markers of angiogenesis, apoptosis and reactive oxygen species (ROS). α-TOS-loaded NPs suppressed angiogenesis by inducing accumulation of ROS and inducing apoptosis of proliferating endothelial cells. These NPs also decrease the number and quality of capillary-like tubes in an in vitro three-dimensional (3D) experiment, decrease the production of the pro-angiogenic vascular endothelial growth factor and down-regulate the expression of its receptor. The anti-migratory efficacy of α-TOS is corroborated in hypopharynx carcinoma cells by decreasing the secretion of matrix metalloproteases 2 and 9 (MMP-2 and MMP-9) and inhibiting cell migration. These results confirm that α-TOS-based NPs not only present anticancer properties, but also antiangiogenic properties, therefore making them promising candidates for multi-active combinatorial anticancer therapy.
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Portadores de Fármacos/química , Nanopartículas/química , Polímeros/química , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , alfa-Tocoferol/química , alfa-Tocoferol/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Liberación de Fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Metaloproteinasas de la Matriz/metabolismo , Invasividad Neoplásica , Neovascularización Patológica/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , alfa-Tocoferol/uso terapéuticoRESUMEN
OBJECTIVES: To evaluate the prevalence and management of residual symptoms in recovered BPPV patients. METHODS: We performed a retrospective study on BPPV patients of any of the three semicircular canals. Exclusion criteria were multiple-canal BPPV, refractory BPPV, central nervous system pathologies or other vestibular diseases. Patients were treated with repositioning maneuvers until the vertigo disappeared and evaluated for symptoms of instability at 1 month after resolution. A dynamic computerized posturography was then performed on every patient complaining of residual instability. We analyzed demographic data, the affected semicircular canal, number of repositioning maneuvers, presence of anxiety disorders, and we correlated these variables with the presence of residual disequilibrium 1 month after vertigo resolution. RESULTS: We included 361 patients. Residual disequilibrium was found in 107 patients (29.6%) with no significant difference between the rates associated with the three semicircular canals (p = 0.73). The group who needed more than one repositioning maneuver (1 maneuver-229 patients, ≥ 2maneuvers-132 patients) showed a significantly higher prevalence of instability (17.9 vs. 50%; p < 0.0001). 47.2% of the patients with anxiety disorders presented with instability symptoms (p = 0,01). Patients older than 65 showed a significantly higher percentage of residual symptoms (23.3 vs. 34.8%; p = 0.03). CONCLUSIONS: Persistence of residual symptoms 1 month after the acute BPPV can be associated with certain risk factors that should be taken into consideration (age, number of repositioning maneuvers needed, anxiety and/or depressive disorders). These patients could benefit of treatment with vestibular rehabilitation.
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Vértigo Posicional Paroxístico Benigno/epidemiología , Vértigo Posicional Paroxístico Benigno/terapia , Adulto , Anciano , Trastornos de Ansiedad/complicaciones , Vértigo Posicional Paroxístico Benigno/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Posicionamiento del Paciente , Prevalencia , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Canales SemicircularesRESUMEN
BACKGROUND: Recurrent tonsillitis might reduce the immunological capability of fighting against the infection of tonsil tissue. Polypodium leucotomos (Anapsos) immunomodulating effect has been subject of research in the last years. The aim of this research is to test the in vitro immunomodulating capacity of Anapsos in a child palatine tonsil explants model. METHODS: Palatine tonsils explants of children undergoing amigdalectomy were stimulated with mononuclear cells obtained from their own blood by density gradient centrifugation. Some were then treated with Anapsos while others rest untreated. Cytokines were measured by ELISA, immune cells activation was measured by flow cytometry and activation of immunoglobulins was appreciated by indirect immunofluorescence in tonsils tissue. RESULTS: Anapsos activates Natural Killers cells. It increases IL-2 and IFN-γ levels by the activation of Th2 lymphocytes, and IL-10, by the Th1 lymphocytes. Anapsos also increases immunoglobulins IgM, IgD and IgG4 by B-lymphocyte activation in tonsils tissue. CONCLUSION: Anapsos has an immunomodulating effect, both in humoral and cellular responses, which might benefit children suffering of recurrent tonsillitis as it could enhance their immune system. This effect might reduce the number of episodes suffered and therefore the number of children undergoing surgery.
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Citocinas/metabolismo , Glicósidos/inmunología , Inmunoglobulinas/metabolismo , Factores Inmunológicos/uso terapéutico , Leucocitos Mononucleares/inmunología , Tonsila Palatina/efectos de los fármacos , Tonsilitis/tratamiento farmacológico , Técnicas de Cultivo de Célula , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Leucocitos Mononucleares/metabolismo , Tonsila Palatina/inmunología , Tonsila Palatina/metabolismo , Polypodium , Tonsilectomía , Tonsilitis/inmunología , Tonsilitis/cirugíaRESUMEN
Dietary antioxidants, polyphenols, have been found to be beneficial in protecting against the generation of oxidative stress in various diseases associated with aging. Age-related hearing loss (AHL) is the number one neurodegenerative disorder on our aged population. Sprague-Dawley rats divided into five groups according to their age (3, 6, 12, 18 and 24 months old) and treated with 100 mg/day/kg body weight of polyphenols were used. Then, cochleae were harvested to measure caspase activities (- 3, - 8 and - 9), caspase-3 gene expression, ATP levels, Bax, BcL-2 and p53 levels. 8-OHdG levels (marker of DNA oxidative damage) and annexin-V were also measured in cochleae. Increased levels of caspase-3 and 9 in cochlea were observed with age and this effect was attenuated by polyphenol treatment. In addition, ATP and Bcl-2 levels in older rats were recovered after administration of polyphenols, while Bax and p53 levels protein decreased. Oral supplementation with polyphenols also reduces DNA oxidative damage of cochlear cell. Treatment with polyphenols inhibits the activation of age-related apoptotic signaling by decreasing oxidative stress inside the rat cochlea.
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Envejecimiento/efectos de los fármacos , Cóclea/efectos de los fármacos , Polifenoles/farmacología , 8-Hidroxi-2'-Desoxicoguanosina , Adenosina Trifosfato/metabolismo , Envejecimiento/metabolismo , Envejecimiento/patología , Animales , Anexina A5/metabolismo , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Cóclea/metabolismo , Cóclea/patología , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Estrés Oxidativo/efectos de los fármacos , Presbiacusia/metabolismo , Presbiacusia/patología , Presbiacusia/prevención & control , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers worldwide and is associated with poor survival and significant treatment morbidity. The immune profile in patients with HNSCC is immunosuppressive and presents cytokine-mediated adaptive immune responses, triggered apoptosis of T cells, and alterations in antigen processing machinery. Bacille Calmette-Guerin (BCG) immunotherapy has been used successfully as a treatment for several types of cancer. In the present study, we sought to determine the antitumor effect of soluble mediators from peripheral blood mononuclear immune cells (PBMCs) activated with BCG vaccine in a three-dimensional coculture model of HNSCC growth using FaDu hypopharynx carcinoma squamous cells. BCG activation of PBMCs led to an increase in CD4+ and CD8+ lymphocyte subsets concomitant with an elevation in the levels of the antitumor cytokines IL-6, TNF-α and IFN-γ, and a EGFR in FaDu cells. In addition, coculture with BCG-activated PBMCs reduced FaDu proliferation and increased cytotoxicity and apoptosis in parallel with an increase in caspase-3 activity and p53 expression. Finally, conditioned medium from BCG-activated PBMCs reduced the levels of the angiogenic factors vascular endothelial growth factor and angiopoietin-2 produced by human aortic endothelial cells (HAECs), and inhibited their proliferation and differentiation into capillary-like structures. Taken together, these results demonstrate that BCG vaccination induces antitumor responses in an HNSCC in vitro model and suggest that the BCG vaccine could be an effective alternative therapy for the treatment of HNSCC.
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Vacuna BCG/administración & dosificación , Vacuna BCG/inmunología , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/terapia , Inmunoterapia/métodos , Leucocitos Mononucleares/inmunología , Neovascularización Patológica/terapia , Angiopoyetina 2/metabolismo , Carcinoma de Células Escamosas/patología , Células Cultivadas , Técnicas de Cocultivo/métodos , Medios de Cultivo Condicionados , Citocinas/metabolismo , Células Endoteliales/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , Factores Inmunológicos/administración & dosificación , Modelos Biológicos , Neovascularización Patológica/patología , Subgrupos de Linfocitos T/inmunología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To evaluate vestibular restoration and the evolution of the compensatory saccades in acute severe inflammatory vestibular nerve paralysis, including vestibular neuritis and Ramsay Hunt syndrome with vertigo. STUDY DESIGN: Prospective. SETTING: Tertiary referral center. PATIENTS: Vestibular neuritis (nâ=â18) and Ramsay Hunt syndrome patients with vertigo (nâ=â13) were enrolled. INTERVENTION: After treatment with oral corticosteroids, patients were followed up for 6 months. MAIN OUTCOME MEASURES: Functional recovery of the facial nerve was scored according to the House-Brackman grading system. Caloric and video head impulse tests were performed in every patient at the time of enrolment. Subsequently, successive video head impulse test (vHIT) exploration was performed at the 1, 3, and 6-month follow-up. RESULTS: Eighteen patients with vestibular neuritis and 13 with Ramsay Hunt syndrome and associated vertigo were included. Vestibular function was significantly worse in patients with Ramsay Hunt syndrome than in those with vestibular neuritis. Similar compensatory saccades velocity and latency values were observed in both groups, in both the caloric and initial vHIT tests. Successive vHIT results showed a significantly higher vestibulo-ocular reflex gain recovery in vestibular neuritis patients than in Ramsay Hunt syndrome patients. A significantly faster reduction in the latency, velocity, and organization of the compensatory saccades was observed in neuritis than in Ramsay Hunt syndrome patients. CONCLUSIONS: In addition to the recovery of the vestibulo-ocular reflex, the reduction of latency, velocity and the organization of compensatory saccades play a role in vestibular compensation.
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Herpes Zóster Ótico/tratamiento farmacológico , Vértigo/tratamiento farmacológico , Neuronitis Vestibular/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Adulto , Anciano , Antiinflamatorios/uso terapéutico , Pruebas Calóricas , Nervio Facial/fisiopatología , Femenino , Estudios de Seguimiento , Prueba de Impulso Cefálico , Herpes Zóster Ótico/complicaciones , Herpes Zóster Ótico/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recuperación de la Función , Reflejo Vestibuloocular , Movimientos Sacádicos , Vértigo/complicaciones , Vértigo/fisiopatología , Pruebas de Función Vestibular , Neuronitis Vestibular/fisiopatologíaRESUMEN
UNLABELLED: Age-related hearing loss (AHL) -presbycusis- is the number one neurodegenerative disorder and top communication deficit of our aged population. Experimental evidence suggests that mitochondrial dysfunction associated with reactive oxygen species (ROS) plays a central role in the aging process of cochlear cells. Dietary antioxidants, in particular polyphenols, have been found to be beneficial in protecting against the generation of ROS in various diseases associated with oxidative stress, such as cancer, neurodegenerative diseases and aging. OBJECTIVES: This study was designed to investigate the effects of polyphenols on AHL and to determine whether oxidative stress plays a role in the pathophysiology of AHL. METHODS: Sprague-Dawley rats (n=100) were divided into five groups according to their age (3, 6, 12, 18 and 24months old) and treated with 100mg/kg/day body weight of polyphenols dissolved in tap water for half of the life of the animal. Auditory steady-state responses (ASSR) threshold shifts were measured before sacrificing the rats. Then, cochleae were harvested to measure total superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, reactive oxidative and nitrogen species levels, superoxide anions and nitrotyrosine levels. RESULTS: Increased levels of ROS and RNS in cochlea observed with age decreases with polyphenol treatment. In addition, the activity of SOD and GPx enzymes in older rats recovered after the administration of polyphenols. CONCLUSION: The reduction in oxidative and nitrosative stress in the presence of polyphenols correlates with significant improvements in ASSR threshold shifts.
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Envejecimiento/efectos de los fármacos , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Polifenoles/farmacología , Presbiacusia/tratamiento farmacológico , Animales , Cóclea/efectos de los fármacos , Cóclea/metabolismo , Potenciales Evocados Auditivos , Glutatión Peroxidasa/metabolismo , Masculino , Presbiacusia/fisiopatología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
INTRODUCTION: The presentation of a down-beating nystagmus force to discard vascular pathology of brain and cervical joint with magnetic resonance imagine (MRI). Recent studies support the low profitability of this study and is subjected that this oculomotor sign has a peripheral origin especially when the patient has a benign paroxysmal positional vertigo (BPPV) with affection of the superior semicircular canal. AIM: To evidence the profitability of MRI in a population of patients with positional down-beating nystagmus. PATIENTS AND METHODS: We present a retrospective study with 42 consecutive patients. A complete clinical history and physical examination was performed. All of them perform vestibular tests (caloric and rotatory), cranial and cervical MRI. RESULTS: Fifty-two percent of patients present clinical manifestations and physical exploration compatible with BPPV. MRI was normal in 67%. We found spondylopathy in 26% and vascular cerebral pathology in 5%. Prevalence of type I Arnold-Chiari malformation was 9% in our population. None of them was founded when the main symptom was suggestive of BPPV. Results obtained of vestibular tests didn't contribute additional information to give an ethiologic diagnosis. CONCLUSION: The profitability of vestibular tests and MRI in our population with down beating nystagmus was very low. We must evaluate the real necessity of this test with the clinical context.
TITLE: Nistagmo vertical inferior: es obligada la resonancia magnetica?Introduccion. La aparicion de un nistagmo vertical inferior clasicamente obliga a descartar una patologia vascular o de la union craneocervical mediante resonancia magnetica (RM). Estudios recientes demuestran una baja rentabilidad de esta prueba, ya que sugieren que este signo oculomotor puede tener una causa vestibular periferica, sobre todo cuando el paciente presenta un vertigo posicional paroxistico benigno (VPPB) del canal semicircular superior. Objetivo. Comprobar la rentabilidad de la RM en una poblacion de pacientes con nistagmo de posicion vertical inferior. Pacientes y metodos. Estudio retrospectivo de 42 pacientes consecutivos a los que se les realizo una historia clinica, exploracion fisica, y pruebas vestibulares caloricas y rotatorias. A todos ellos se les practico una RM craneal y cervical. Resultados. El 52% de los pacientes con nistagmo de posicion vertical inferior presentaba una clinica y exploracion fisica compatibles con VPPB del canal semicircular superior. La RM fue normal en un 67%, un 26% mostraba datos de espondilopatia y un 5% de microangiopatia cerebral no relacionados con la clinica del paciente. La prevalencia de malformacion de Arnold-Chiari de tipo I fue de un 9% en la poblacion estudiada, sin que nadie tuviera un antecedente reciente de VPPB. Los resultados obtenidos en las pruebas complementarias vestibulares no aportaron informacion adicional para llegar a un diagnostico etiologico. Conclusion. En los pacientes con un VPPB, la RM craneal y las pruebas vestibulares tienen una baja rentabilidad diagnostica, y se debe evaluar la necesidad real de esta prueba con el contexto clinico.
Asunto(s)
Imagen por Resonancia Magnética , Nistagmo Patológico/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Aging causes histological, electrophysiological and molecular changes in the cochlea. The free radical theory of aging, has obtained consensus, and the mitochondrion is reported to play a key role in aging as a major source of reactive oxygen species. In the last years, there has been a significant increase in the interest in polyphenols because of the antioxidant properties and their role in the prevention of various diseases associated with oxidative stress, including aging. The aim of this study was to evaluate the preventive effect of different polyphenols on ARHL with auditory-evoked potentials. 100 Healthy female Sprague-Dawley (SD) rats were used for this study. Five groups were created based on the age of the rats, in months: 3, 6, 12, 18 and 24 months old. Two additional groups were created based on the treatment received. In the control group, 50 animals were assigned to no treatment. In the treated group, 50 animals were given a vehicle mixture of polyphenols for the half of the life before euthanization. Nine frequencies were tested (0.5-16 kHz) with ASSR and tone-burst ABR, performed on all of the rats prior to sacrifice. 100-µs auditory clicks ABRs were also recorded. A significant decrease in the audition was detected with ABR and ASSR in both treated and non-treated groups, as the different groups became older. This deterioration was more accurately measured at acute frequencies. Significantly lower thresholds were observed in the treated rats in the 6, 12 and 18-month-old group in the treated rats compared with the control group. All of the thresholds elicited using the ASSR technique were lower than the thresholds obtained using the ABR, regardless of the stimulus type. The present study demonstrated the benefits of the polyphenols, which generated a significant protection against ARHL, with significantly improved ASSR and tone-burst ABR auditory thresholds in rats receiving treatment with polyphenols.
Asunto(s)
Envejecimiento , Percepción Auditiva/fisiología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Potenciales Evocados Auditivos/fisiología , Polifenoles/farmacología , Presbiacusia/prevención & control , Animales , Umbral Auditivo/fisiología , Modelos Animales de Enfermedad , Potenciales Evocados Auditivos/efectos de los fármacos , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Femenino , Pérdida Auditiva Sensorineural/diagnóstico , Estrés Oxidativo , Presbiacusia/diagnóstico , Presbiacusia/fisiopatología , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los ResultadosRESUMEN
The aim of this work is the preparation of an active nanovehicle for the effective administration of α-tocopheryl succinate (α-TOS). α-TOS is loaded in the core of nanoparticles (NPs) based on amphiphilic pseudo-block copolymers of N-vinyl pyrrolidone and a methacrylic derivative of α-TOS. These well-defined spherical NPs have sizes below 165 nm and high encapsulation efficiencies. In vitro activity of NPs is tested in hypopharynx squamous carcinoma (FaDu) cells and nonmalignant epithelial cells, demonstrating that the presence of additional α-TOS significantly enhances its antiproliferative activity; however, a range of selective concentrations is observed. These NPs induce apoptosis of FaDu cells by activating the mitochondria death pathway (via caspase-9). Both loaded and unloaded NPs act via complex II and produce high levels of reactive oxygen species that trigger apoptosis. Additionally, these NPs effectively suppress the vascular endothelial growth factor (VEGF) expression of human umbilical vein endothelial cells (HUVECs). These results open the possibility to use this promising nanoformulation as an α-TOS delivery system for the effective cancer treatment, effectively resolving the current limitations of free α-TOS administration.