Project description:The symptoms of Meniere's disease (MD) are generally considered to be related to endolymphatic hydrops (EH). There are many recent reports supporting the possibility that vasopressin (VP) is closely linked to the formation of EH in Meniere's disease. Based on this, we developed a clinically relevant animal model of Meniere's disease in which a VP type 2 receptor agonist was administered after electrocauterization of the endolymphatic sac. We report live imaging of the internal structure, and functional changes of the inner ear after electrocauterization of the endolymphatic sac and administration of a VP type 2 receptor agonist. In this model, the development of EH was visualized in vivo using optical coherence tomography, there was no rupture of Reissner's membrane, and low-tone hearing loss and vertiginous attacks were observed. This study suggested that acute attacks are caused by the abrupt development of EH. This is the first report of live imaging of the development of EH induced by the administration of a VP type 2 receptor agonist.
Project description:BackgroundWe sought to develop a novel non-contrast multiparametric MRI (mpMRI) protocol employing several complementary techniques in a single scan session for a comprehensive functional and structural evaluation of diabetic kidney disease (DKD).MethodsIn the cross-sectional part of this prospective observational study, 38 subjects ages 18‒79 years with type 2 diabetes and DKD [estimated glomerular filtration rate (eGFR) 15‒60 mL/min/1.73 m2] and 20 age- and gender-matched healthy volunteers (HVs) underwent mpMRI. Repeat mpMRI was performed on 23 DKD subjects and 10 HVs. By measured GFR (mGFR), 2 DKD subjects had GFR stage G2, 16 stage G3 and 20 stage G4/G5. A wide range of MRI biomarkers associated with kidney haemodynamics, oxygenation and macro/microstructure were evaluated. Their optimal sensitivity, specificity and repeatability to differentiate diabetic versus healthy kidneys and categorize various stages of disease as well as their correlation with mGFR/albuminuria was assessed.ResultsSeveral MRI biomarkers differentiated diabetic from healthy kidneys and distinct GFR stages (G3 versus G4/G5); mean arterial flow (MAF) was the strongest predictor (sensitivity 0.94 and 1.0, specificity 1.00 and 0.69; P = .04 and .004, respectively). Parameters significantly correlating with mGFR were specific measures of kidney haemodynamics, oxygenation, microstructure and macrostructure, with MAF being the strongest univariate predictor (r = 0.92; P < .0001).ConclusionsA comprehensive and repeatable non-contrast mpMRI protocol was developed that, as a single, non-invasive tool, allows functional and structural assessment of DKD, which has the potential to provide valuable insights into underlying pathophysiology, disease progression and analysis of efficacy/mode of action of therapeutic interventions in DKD.
Project description:Defects in several different connexins have been associated with several different diseases. The most common of these is deafness, where a few mutations in connexin (Cx) 26 have been found to contribute to over 50% of the incidence of non-syndromic deafness in different human populations. Other mutations in Cx26 or Cx30 have also been associated with various skin phenotypes linked to deafness (palmoplanta keratoderma, Bart-Pumphrey syndrome, Vohwinkel syndrome, keratitis-ichthyosis-deafness syndrome, etc.). The large array of disease mutants offers unique opportunities to gain insights into the underlying function of gap junction proteins and their channels in the normal and pathogenic physiologies of the cochlea and epidermis. This review focuses on those mutants where the impact on channel function has been assessed, and correlated with the disease phenotype, or organ function in knock-out mouse models. These approaches have provided evidence supporting a role of gap junctions and hemichannels in K(+) removal and recycling in the ear, as well as possible roles for nutrient passage, in the cochlea. In contrast, increases in hemichannel opening leading to increased cell death, were associated with several keratitis-ichthyosis-deafness syndrome skin disease/hearing mutants. In addition to providing clues for therapeutic strategies, these findings allow us to better understand the specific functions of connexin channels that are important for normal tissue function. This article is part of a Special Issue entitled: The communicating junctions, roles and dysfunctions.