A 1-year follow-up study with C-VEMPs, O-VEMPs and video head impulse testing in vestibular neuritis

The aim of this paper was to evaluate prospectively, in a group of patients affected by VN, a diagnostic protocol employing C-VEMPs, O-VEMPs and vHIT together. The diagnosis of vestibular neurolabyrinthitis was based on the clinical history, absence of associated auditory or neurological symptoms, and a neuro-otological examination with an evaluation of lateral semicircular canal function using the Fitzgerald-Hallpike caloric vestibular test and ice test. Our series revealed an incidence of 55 % of superior and inferior vestibular neurolabyrinthitis, 40 % of superior vestibular neurolabyrinthitis and 5 % of inferior vestibular neurolabyrinthitis. These data, however, comprised different degrees of vestibular involvement considering the evaluation of each single vestibular end-organ with potential different prognosis. Four patients had only deficits of the horizontal and superior semicircular canals or their ampullary nerves. The implementation of C-VEMPs, O-VEMPs and vHIT in a vestibular diagnostic protocol has made possible to observe patients with ampullary VN, unidentifiable with other types of vestibular exams. The effect of age seems to have some impact on the recovery. When recovery firstly involves the utricular and saccular nerves and subsequently the ampullary nerves, it may be reasonable to expect a more favorable and successful outcome

Retinitis pigmentosa: evaluation of the vestibular system with cervical and ocular vestibular evoked myogenic potentials and the video head impulse test

OBJECTIVE: Retinitis pigmentosa (RP) represents a group of inherited disorders in which abnormalities of the photoreceptors lead to progressive visual loss. Night blindness, peripheral visual field loss, and eventual total blindness represent typical visual damage of such disease. No study has previously evaluated the presence of a "latent" vestibular deficit in patients with RP. STUDY DESIGN: Prospective study with caloric test, cervical vestibular evoked myogenic potentials (C-VEMPs), ocular vestibular evoked myogenic potentials (O-VEMPs), and video head impulse test (v-HIT). SETTING: Tertiary referral center. PATIENTS: 16 patients suffering from RP. INTERVENTION: Evaluation of vestibular dysfunction with caloric test, C-VEMPs, O-VEMPs, and the measurement of the vestibular-ocular reflex (VOR) using the v-HIT. RESULTS: Only five patients with RP showed normal values in all the vestibular tests performed. Three patients had an evident deficit at the caloric test, whereas eight (50%) of them had a normal caloric test but a pathological response in at least one of the other vestibular tests performed. No patient of the study showed a bilateral otolith or ampullary dysfunction. CONCLUSION: Our patients with RP unexpectedly showed pathological responses in at least one of the vestibular tests performed. Nowadays, in patients affected by RP, a vestibular diagnostic protocol must include VEMPs and v-HIT to confirm the vestibular damage and to identify selective damage of the vestibular nerve

Conociendo al perro cimarrón uruguayo

La publicación de este libro fue realizada con el apoyo de la Comisión Sectorial de Investigación Científica (CSIC) de la Universidad de la República. El trabajo que se presenta fue seleccionado por el Comité de Referato de Publicaciones de la Facultad de Veterinaria integrado por Luis Barros, José Luis Repetto y Celia Tasende.Capítulo 1. Primeros estudios de genética molecular en el perro cimarrón uruguayo / Silvia Llambí Dellacasa -- Capítulo 2. Estructura poblacional en el perro cimarrón uruguayo / Rosa Gagliardi, Silvia Llambí -- Capítulo 3. Caracterización racial del perro cimarrón / Gabriel E. Fernández de Sierra, Beatriz E. Mernies Falcone -- Capítulo 4. Estudios genealógicos en la raza canina cimarrón uruguayo / Mónica Martínez, Eileen Armstrong -- Capítulo 5. Etología clínica canina, agresividad y el cimarrón uruguayo / Juan Pablo Damián, María Belino, Ruben Rijo, Paul Ruiz -- Capítulo 6. Estacionalidad y carácterísticas reproductivas en perras cimarronas, Danilo Fila -- Capítulo 7. Diagnóstico genético de las anomalías del desarrollo sexual en caninos / Rody Artigas, María Montenegro, Silvia Llambí -- Capítulo 8. Estudio ecocardiográfico en la raza cimarrón / Benech, Pisón, Sehabiaga, Jiménez, Rossi -- Capítulo 9. Estudios farmacogenéticos en el perro cimarrón uruguayo / Rosa Gagliardi, Silvia Llambí -- Capítulo 10. Razas caninas españolas / M. Victoria Arruga Laviña, José Ignacio Bonafonte Zaragozano

Chanalyzer : a computational geometry approach for the analysis of protein channel shape and dynamics

Morphological analysis of protein channels is a key step for a thorough understanding of their biological function and mechanism. In this respect, molecular dynamics (MD) is a very powerful tool, enabling the description of relevant biological events at the atomic level, which might elude experimental observations, and pointing to the molecular determinants thereof. In this work, we present a computational geometry-based approach for the characterization of the shape and dynamics of biological ion channels or pores to be used in combination with MD trajectories. This technique relies on the earliest works of Edelsbrunner and on the NanoShaper software, which makes use of the alpha shape theory to build the solvent-excluded surface of a molecular system in an aqueous solution. In this framework, a channel can be simply defined as a cavity with two entrances on the opposite sides of a molecule. Morphological characterization, which includes identification of the main axis, the corresponding local radius, and the detailed description of the global shape of the cavity, is integrated with a physico-chemical description of the surface facing the pore lumen. Remarkably, the possible existence or temporary appearance of fenestrations from the channel interior towards the outer lipid matrix is also accounted for. As a test case, we applied the present approach to the analysis of an engineered protein channel, the mechanosensitive channel of large conductance

Estudios preliminares de la estructura genética del perro cimarrón uruguayo usando microsatélites

Analizar la estructura poblacional en una muestra de perros “Cimarrón Uruguayo” usando marcadores moleculares tipo microsatélites. Materiales y métodos. Se analizaron treinta caninos de diferentes zonas de Uruguay con un set de nueve marcadores moleculares microsatélites empleando PCR. La estructura poblacional se analizó con el software de distribución libre “Structure”. Resultados. Según nuestros datos, los resultados preliminares muestran que no es posible establecer una subdivisión entre los animales de la muestra. Conclusiones. El estudio realizado apoya la hipótesis de que los perros que existen en la actualidad derivan del núcleo fundador que se refugió en la región noreste del país. La distribución de la raza entre las distintas áreas de Uruguay continúa hoy en día, no existe aislamiento entre los diferentes grupos de animales y el intercambio es constante

Down-Regulation of SOX2 Underlies the Inhibitory Effects of the Triphenylmethane Gentian Violet on Melanoma Cell Self-Renewal and Survival

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PO-099 Targeting the mitogen activated protein kinase ERK5 in human melanoma

Introduction Melanoma is the most aggressive skin cancer with a poor prognosis in advanced stages. Available treatments for melanoma are unsatisfactory, because rapidly lead to an acquired resistance in the majority of cases. Therefore, there is urgent need to identify novel possible targets involved in melanoma growth. ERK5/BMK1 is a member of the Mitogen-Activated Protein Kinases (MAPK) family and regulates cell functions critical for tumour development. Indeed, several studies reported a direct involvement of ERK5 in several types of cancer including prostate and breast cancer and hepatocellular carcinoma. However, no data have been reported about a possible role of ERK5 in melanoma. Material and methods Cell lines and patient-derived primary melanoma cells (wild type B-RAF: SSM2c and M26c; BRAFV600E: A375, SK-Mel-5, SK-Mel-28, 501-Mel, expressing; NRASQ61R: SK-Mel-2; MeWo) have been used for in vitro and in vivo experiments. HEK293T cells were used for protein overexpression. ERK5 inhibition was achieved using ERK5 and MEK5 inhibitors or lentiviral vectors encoding shRNA specific for ERK5. BRAF inhibition was achieved using Vemurafenib, a BRAFV600E inhibitor. Results and discussions In silico data analysis indicated that components of the ERK5 pathway are upregulated in up to 47% melanoma patients. Accordingly, we found that ERK5 is consistently expressed and active in commercial and patients derived melanoma cell lines. On that basis, we investigated the role of ERK5 in melanoma cell growth. In vitro , pharmacological or genetic inhibition of ERK5 decreased the number of viable cells in several melanoma cell lines. Moreover, xenografts performed using LV-shERK5-transduced A375 or SSM2c cells showed a reduced tumour growth when compared to those transduced with control LV-shC. We also found that oncogenic BRAF positively regulates expression, phosphorylation and nuclear localization of exogenous and endogenous ERK5. Accordingly, combined pharmacological inhibition of BRAFV600E and MEK5 is required to decrease nuclear ERK5, that is critical for the regulation of cell proliferation. Furthermore, the combination of MEK5 or ERK5 inhibitors with vemurafenib is more effective than single treatments in reducing 2D colony formation and growth of BRAFV600E melanoma cells and xenografts. Conclusion Our results identify ERK5 as a critical regulator of melanoma growth in vitro and in vivo , and point toward the possibility of targeting ERK5, alone or in combination with BRAF-MEK1/2 inhibitors, for the treatment of melanoma

The Hedgehog-GLI Pathway Regulates MEK5-ERK5 Expression and Activation in Melanoma Cells

Malignant melanoma is the deadliest skin cancer, with a poor prognosis in advanced stages. We recently showed that the extracellular signal-regulated kinase 5 (ERK5), encoded by the MAPK7 gene, plays a pivotal role in melanoma by regulating cell functions necessary for tumour development, such as proliferation. Hedgehog-GLI signalling is constitutively active in melanoma and is required for proliferation. However, no data are available in literature about a possible interplay between Hedgehog-GLI and ERK5 pathways. Here, we show that hyperactivation of the Hedgehog-GLI pathway by genetic inhibition of the negative regulator Patched 1 increases the amount of ERK5 mRNA and protein. Chromatin immunoprecipitation showed that GLI1, the major downstream effector of Hedgehog-GLI signalling, binds to a functional non-canonical GLI consensus sequence at the MAPK7 promoter. Furthermore, we found that ERK5 is required for Hedgehog-GLI-dependent melanoma cell proliferation, and that the combination of GLI and ERK5 inhibitors is more effective than single treatments in reducing cell viability and colony formation ability in melanoma cells. Together, these findings led to the identification of a novel Hedgehog-GLI-ERK5 axis that regulates melanoma cell growth, and shed light on new functions of ERK5, paving the way for new therapeutic options in melanoma and other neoplasms with active Hedgehog-GLI and ERK5 pathways