Search results for "SPAST"
showing 10 items of 67 documents
Control of spasticity in a multiple sclerosis model using central nervous system-excluded CB1 cannabinoid receptor agonists
2014
The purpose of this study was the generation of central nervous system (CNS)-excluded cannabinoid receptor agonists to test the hypothesis that inhibition of spasticity, due to CNS autoimmunity, could be controlled by affecting neurotransmission within the periphery. Procedures included identification of chemicals and modeling to predict the mode of exclusion; induction and control of spasticity in the ABH mouse model of multiple sclerosis; conditional deletion of CB1 receptor in peripheral nerves; side-effect profiling to demonstrate the mechanism of CNS-exclusion via drug pumps; genome-wide association study in N2(129×ABH) backcross to map polymorphic cannabinoid drug pump; and sequencing…
A New Myohaptic Device to Assess Wrist Function in the Lab and in the Clinic – The Wristalyzer
2008
Wristalyzer is a portable robotic device combining haptic technology with electromyographic assessment. It allows to assess wrist motion in physiological and pathological conditions by applying loads and mechanical oscillations, taking into account the ergonomy and the angular positioning of the joints. The wristalyzer works in a free or loaded mode for assessment of metrics of motion and tremor, analyzes the behavior of the wrist joints and the associated muscle activities during delivery of mechanical oscillations, estimates the maximal voluntary contraction, assesses automatically the impedance of the wrist for assessment of rigidity or spasticity. Position, torques and electromyographic…
Cannabinoids in the management of spasticity associated with multiple sclerosis.
2008
Anna Maria Malfitano, Maria Chiara Proto, Maurizio BifulcoDipartimento di Scienze Farmaceutiche, Università degli Studi di SalernoAbstract: The endocannabinoid system and cannabinoid-based treatments have been involved in a wide number of diseases. In particular, several studies suggest that cannabinoids and endocannabinoids may have a key role in the pathogenesis and therapy of multiple sclerosis (MS). In this study we highlight the main findings reported in literature about the relevance of cannabinoid drugs in the management and treatment of MS. An increasing body of evidence suggests that cannabinoids have beneficial effects on the symptoms of MS, including spasticity and pai…
Evaluating the effect of spastin splice mutations by quantitative allele-specific expression assay
2010
Background: Mutations in the SPG4/SPAST gene are the most common cause for hereditary spastic paraplegia (HSP). The splice-site mutations make a significant contribution to HSP and account for 17.4% of all types of mutations and 30.8% of point mutations in the SPAST gene. However, only few studies with limited molecular approach were conducted to investigate and decipher the role of SPAST splice-site mutations in HSP. Methods: A reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and quantitative allele-specific expression assay were performed. Results: We have characterized the consequence of two novel splice-site mutations (c.1493 + 1G>A and c.1414−1G>A) in the SPAST gene…
A total of 220 patients with autosomal dominant spastic paraplegia do not display mutations in the SLC33A1 gene (SPG42).
2010
The most frequent causes of autosomal dominant (AD) hereditary spastic paraplegias (HSP) (ADHSP) are mutations in the SPAST gene (SPG4 locus). However, roughly 60% of patients are negative for SPAST mutations, despite their family history being compatible with AD inheritance. A mutation in the gene for an acetyl-CoA transporter (SLC33A1) has recently been reported in one Chinese family to cause ADHSP-type SPG42. In this study, we screened 220 independent SPAST mutation-negative ADHSP samples for mutations in the SLC33A1 gene by high-resolution melting curve analysis. Conspicuous samples were validated by direct sequencing. Moreover, copy number variations affecting SLC33A1 were screened by …
Human SPG11 cerebral organoids reveal cortical neurogenesis impairment
2018
Abstract Spastic paraplegia gene 11(SPG11)-linked hereditary spastic paraplegia is a complex monogenic neurodegenerative disease that in addition to spastic paraplegia is characterized by childhood onset cognitive impairment, thin corpus callosum and enlarged ventricles. We have previously shown impaired proliferation of SPG11 neural progenitor cells (NPCs). For the delineation of potential defect in SPG11 brain development we employ 2D culture systems and 3D human brain organoids derived from SPG11 patients’ iPSC and controls. We reveal that an increased rate of asymmetric divisions of NPCs leads to proliferation defect, causing premature neurogenesis. Correspondingly, SPG11 organoids appe…
Screening of hereditary spastic paraplegia patients for alterations at NIPA1 mutational hotspots.
2008
Item does not contain fulltext Mutations in NIPA1 cause hereditary spastic paraplegia type 6 (SPG6 HSP). Sequencing of the whole gene has revealed alterations of either of two nucleotides in eight of nine SPG6 HSP families reported to date. By analysing CpG methylation, we provide a mechanistic explanation for a mutational hotspot to underlie frequent alteration of one of these nucleotides. We also developed PCR RFLP assays to detect recurrent NIPA1 changes and screened 101 independent HSP patients, including 45 index patients of autosomal dominant HSP families. Our negative finding in this cohort for which several other causes of HSP had been excluded suggests NIPA1 alterations at mutation…
Lipid Droplets in the Pathogenesis of Hereditary Spastic Paraplegia
2021
Hereditary spastic paraplegias (HSPs) are genetically heterogeneous conditions caused by the progressive dying back of the longest axons in the central nervous system, the corticospinal axons. A wealth of data in the last decade has unraveled disturbances of lipid droplet (LD) biogenesis, maturation, turnover and contact sites in cellular and animal models with perturbed expression and function of HSP proteins. As ubiquitous organelles that segregate neutral lipid into a phospholipid monolayer, LDs are at the cross-road of several processes including lipid metabolism and trafficking, energy homeostasis, and stress signaling cascades. However, their role in brain cells, especially in neurons…
L'idrochinesiterapia nel recupero dell'arto superiore dopo allungamento dei flessori del gomito e asportazione di paraosteoartropatia di spalla in so…
2007
La spasticità, oltre a determinare alterazioni dei fisiologici schemi di movimento, siaccompagna a complicanze musoclo- scheletriche per le quali spesso si ricorre all'intervento chirurgico. La riabilitazione, partendo da un'accurata valutazione pre e postoperatoria del malato, da un lato mira al recupero e al mantenimento dell'articolarità, dall'altro al ripristino della motilità volontaria e della destrezza dei movimenti. L'idrochinesiterapia offre evidenti vantaggi nel trattamento di questi soggetti. In questo lavoro si espone la nostra esperienza su un paziente di 38 anni con esiti di trauma cranio-encefalico sottoposto dapprima ad intervento chirurgico sull'arto superiore ed in seguito…
[Ischemia with no obstructive coronary artery disease: microvascular angina and vasospastic angina].
2020
About 40% of patients undergoing coronary angiography for chest pain with anginal features have angiographically normal or near-normal coronary arteries. It was necessary to standardize all myocardial ischemia scenarios in stable patients in the absence of coronary artery disease, therefore the term INOCA (ischemia with non-obstructive coronary artery disease) was coined. The aim of this article is to summarize and to clarify the vast and controversial chapter of INOCA, in order to better understand the pathophysiological, nosographic, diagnostic and therapeutic aspects.