504 research outputs found
Area-preserving diffeomorphisms of the hyperbolic plane and K-surfaces in anti-de Sitter space
No full textTyrosine phosphorylation of band 3 protein in Ca++/A23187 -treated human erythrocytes
No full textHuman erythrocytes were induced to release membrane vesicles by treatment with Ca2+ and ionophore A23187. In addition to the biochemical changes already known to accompany loading of human erythrocytes with Ca2+, the present study reveals that tyrosine phosphorylation of the anion exchanger band 3 protein also occurs. The relationship between tyrosine phosphorylation of band 3 and membrane vesiculation was analysed using quinine (a non-specific inhibitor of the Ca(2+)-activated K+ channel, and the only known inhibitor of Ca(2+)-induced vesiculation) and charybdotoxin, a specific inhibitor of the apamin-insensitive K(+)-channel. Both inhibitors suppressed tyrosine phosphorylation of band 3. In the presence of quinine, membrane vesiculation was also suppressed. In contrast, at the concentration of charybdotoxin required to suppress tyrosine phosphorylation of band 3, membrane vesiculation was only mildly inhibited (16-23% inhibition), suggesting that tyrosine phosphorylation of band 3 is not necessary for membrane vesiculation. Phosphorylation of band 3 was in fact observed when erythrocytes were induced to shrink in a Ca(2+)-independent manner, e.g. by treatment with the K+ ionophore valinomycin or with hypertonic solutions. These observations suggest that band 3 tyrosine phosphorylation occurs when cell volume regulation is required
Reply to: “Experience with a New Index to Differentiate Parkinson's Disease and Progressive Supranuclear Palsy”
No full textOn the maximal dilatation of quasiconformal minimal Lagrangian extensions
No full textInternational audienceGiven a quasisymmetric homeomorphism ϕ of the circle, Bonsante and Schlenker proved the existence and uniqueness of the minimal Lagrangian extension f_ϕ : H^2 → H^2 to the hyperbolic plane. By previous work of the author, its maximal dilatation satisfies log K(f_ϕ) ≤ C||ϕ||_cr, where ||ϕ||_cr denotes the cross-ratio norm. We give constraints on the value of an optimal such constant C, and discuss possible lower inequalities, by studying two one-parameter families of minimal Lagrangian extensions in terms of maximal dilatation and cross-ratio norm
Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies
No full textRole and clinical utility of pramipexole extended release in the treatment of early Parkinson's disease
No full textEva-Maria Hametner, Klaus Seppi, Werner PoeweDepartment of Neurology, Innsbruck Medical University, Innsbruck, AustriaAbstract: The aim of this article is to provide a short review of the most relevant pharmacological and clinical data on pramipexole extended release (ER) as well as to address the clinical utility and potential advantages of a once-daily formulation especially in the treatment of early Parkinson's disease (PD). Pramipexole is widely established as a symptomatic treatment in early as well as advanced PD. The development of an ER formulation, with stable pramipexole plasma concentration over 24 hours, now offers a bioequivalent once-daily alternative. Double-blind randomized controlled trials in early and advanced PD, have established noninferiority of pramipexole ER compared with immediate release as well as superiority of both formulations over placebo. The overnight switch from the standard to the once-daily formulation was shown to be successful in >80% of patients without requiring any dose adjustments. Potential benefits of the prolonged-release design, which have not yet been formally demonstrated in the pivotal trial program, include improved compliance and a potential for better symptomatic control, particularly in patients with early disease that can be managed with monotherapy.Keywords: pramipexole, Parkinson's disease, extended release, compliance, contro
Pragmatic Approach on Neuroimaging Techniques for the Differential Diagnosis of Parkinsonisms
No full textBackground: Rapid advances in neuroimaging technologies in the exploration of the living human brain also apply to movement disorders. However, the accurate diagnosis of Parkinson's disease (PD) and atypical parkinsonian disorders (APDs) still remains a challenge in daily practice. Methods: We review the literature and our own experience as the Movement Disorder Society–Neuroimaging Study Group in Movement Disorders with the aim of providing a practical approach to the use of imaging technologies in the clinical setting. Results: The enormous amount of articles published so far and our increasing recognition of imaging technologies contrast with a lack of imaging protocols and updated algorithms for differential diagnosis. The distinctive pathological involvement in different brain structures and the correlation with imaging findings obtained with magnetic resonance, positron emission tomography, or single-photon emission computed tomography illustrate what qualitative and quantitative measures may be useful in the clinical setting. Conclusion: We delineate a pragmatic approach to discuss imaging technologies, updated imaging algorithms, and their implications for differential diagnoses in PD and APDs
Maximal surfaces in anti-de Sitter space, width of convex hulls and quasiconformal extensions of quasisymmetric homeomorphisms
No full textInternational audienceWe give upper bounds on the principal curvatures of a maximal surface of nonpositive curvature in three-dimensional Anti-de Sitter space, which only depend on the width of the convex hull of the surface. Moreover, given a quasisymmetric homeo-morphism φ, we study the relation between the width of the convex hull of the graph of φ, as a curve in the boundary of infinity of Anti-de Sitter space, and the cross-ratio norm of φ. As an application, we prove that if φ is a quasisymmetric homeomorphism of RP^1 with cross-ratio norm ||φ||, then ln K ≤ C||φ||, where K is the maximal dilatation of the minimal Lagrangian extension of φ to the hyperbolic plane
Multiple system atrophy
No full textMultiple system atrophy (MSA) is a rare neurodegenerative disease that is characterized by neuronal loss and gliosis in multiple areas of the central nervous system including striatonigral, olivopontocerebellar and central autonomic structures. Oligodendroglial cytoplasmic inclusions containing misfolded and aggregated α-synuclein are the histopathological hallmark of MSA. A firm clinical diagnosis requires the presence of autonomic dysfunction in combination with parkinsonism that responds poorly to levodopa and/or cerebellar ataxia. Clinical diagnostic accuracy is suboptimal in early disease because of phenotypic overlaps with Parkinson disease or other types of degenerative parkinsonism as well as with other cerebellar disorders. The symptomatic management of MSA requires a complex multimodal approach to compensate for autonomic failure, alleviate parkinsonism and cerebellar ataxia and associated disabilities. None of the available treatments significantly slows the aggressive course of MSA. Despite several failed trials in the past, a robust pipeline of putative disease-modifying agents, along with progress towards early diagnosis and the development of sensitive diagnostic and progression biomarkers for MSA, offer new hope for patients
Association of transient orthostatic hypotension with falls and syncope in patients with Parkinson disease
No full textOBJECTIVES: To assess the frequency of transient orthostatic hypotension (tOH) and its clinical impact in Parkinson disease (PD), we retrospectively studied 173 patients with PD and 173 age- and sex-matched controls with orthostatic intolerance, who underwent cardiovascular autonomic function testing under continuous noninvasive blood pressure (BP) monitoring. METHODS: We screened for tOH (systolic BP fall ≥20 mm Hg or diastolic ≥10 mm Hg resolving within the first minute upon standing) and classic OH (cOH, sustained systolic BP fall ≥20 mm Hg or diastolic ≥10 mm Hg within 3 minutes upon standing). In patients with PD, we reviewed the medical records of the 6 months preceding and following autonomic testing for history of falls, syncope, and orthostatic intolerance. RESULTS: tOH occurred in 24% of patients with PD and 21% of controls, cOH in 19% of patients with PD and in none of the controls, independently of any clinical-demographic or PD-specific characteristic. Forty percent of patients with PD had a history of falls, in 29% of cases due to syncope. Patients with PD with history of orthostatic intolerance and syncope had a more severe systolic BP fall and lower diastolic BP rise upon standing, most pronounced in the first 30-60 seconds. CONCLUSIONS: tOH is an age-dependent phenomenon, which is at least as common as cOH in PD. Transient BP falls when changing to the upright position may be overlooked with bedside BP measurements, but contribute to orthostatic intolerance and syncope in PD. Continuous noninvasive BP monitoring upon standing may help identify a modifiable risk factor for syncope-related falls in parkinsonian patients
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