Objectives-To obtain preliminary data on the effects of high-intensity exercise on functional performance in people with Parkinson's disease (PD) relative to exercise at low and no intensity; and to determine whether improved performance is accompanied by alterations in corticomotor excitability as measured through transcranial magnetic stimulation (TMS).Design-Cohort (prospective), randomized controlled trial. Setting-University-based clinical and research facilities.Participants-Thirty people with PD, 3 years or more since diagnosis, with Hoehn and Yahr stage 1 or 2.Interventions-Subjects were randomized to high-intensity exercise using body weight-supported treadmill training, low-intensity exercise, or a zero-intensity education group. Subjects completed 24 exercise sessions over 8 weeks and had 5 education classes over 8 weeks. Main Outcome Measures-UnifiedParkinson's Disease Rating Scales (UPDRS), biomechanic analysis of self-selected, fast walking, and sit-to-stand tasks; corticomotor excitability was assessed with cortical silent period durations (CSP) in response to single-pulse TMS.Results-A small improvement in total and motor UPDRS was observed in all groups. Highintensity group subjects demonstrated postexercise increases in gait speed, step and stride length, and hip and ankle joint excursion during self-selected and fast gait and improved weight distribution No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. SuppliersPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptArch Phys Med Rehabil. Author manuscript; available in PMC 2010 November 22. Published in final edited form as:Arch Phys Med Rehabil. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript during sit-to-stand. Improvements in gait and sit-to-stand measures were not consistently observed in low-and zero-intensity groups. Importantly, the high-intensity group demonstrated lengthening in CSP.Conclusions-The findings suggest the dose-dependent benefits of exercise and that highintensity exercise can normalize corticomotor excitability in early PD. KeywordsBasal ganglia; Central nervous system; Neuronal plasticity; Rehabilitation; Walking Both basic research and clinical studies suggest that high intensity (ie, high repetition, velocity, complexity) is a characteristic of exercise that may be important in promoting activitydependent neuroplasticity of the injured brain, includin...
This study aimed to establish the psychometric properties of parent ratings on the Chinese version of the Swanson, Nolan, and Pelham IV scale (SNAP-IV) in a school-based sample of 3534 students in grades 1 to 8 from two cities and two suburbs in Taiwan and 189 children diagnosed with attention deficit/hyperactivity disorder (ADHD) (aged 6 to 15) consecutively recruited from a medical center in Taipei. Parents completed the Chinese versions of the SNAP-IV, Strengths and Difficulties Questionnaire, and Child Behavior Checklist. The Chinese SNAP-IV demonstrated similar three factor structure (Inattention, Hyperactivity/Impulsivity, and Oppositional) as its English version, and satisfactory test-retest reliability (intraclass correlation = 0.59 approximately 0.72), internal consistency (alpha = 0.88 approximately 0.90), concurrent validity (Pearson correlations = 0.56 approximately 0.72), and discriminant validity. Boys scored higher than girls across the eight school grade levels. The SNAP-IV clearly distinguished children with ADHD from school-based participants. Comorbidity with oppositional defiant disorder/conduct disorder predicted higher SNAP-IV scores among children with ADHD. Our findings suggest that the Chinese SNAP-IV is a reliable and valid instrument for rating ADHD-related symptoms in both clinical and community settings in Taiwan.
The pancreatic ATP-sensitive potassium (K ATP ) channel, a complex of four sulfonylurea receptor 1 (SUR1) and four potassium channel Kir6.2 subunits, regulates insulin secretion by linking metabolic changes to -cell membrane potential. Sulfonylureas inhibit K ATP channel activities by binding to SUR1 and are widely used to treat type II diabetes. We report here that sulfonylureas also function as chemical chaperones to rescue K ATP channel trafficking defects caused by two SUR1 mutations, A116P and V187D, identified in patients with congenital hyperinsulinism. Sulfonylureas markedly increased cell surface expression of the A116P and V187D mutants by stabilizing the mutant SUR1 proteins and promoting their maturation. By contrast, diazoxide, a potassium channel opener that also binds SUR1, had no effect on surface expression of either mutant. Importantly, both mutant channels rescued to the cell surface have normal ATP, MgADP, and diazoxide sensitivities, demonstrating that SUR1 harboring either the A116P or the V187D mutation is capable of associating with Kir6.2 to form functional K ATP channels. Thus, sulfonylureas may be used to treat congenital hyperinsulinism caused by certain K ATP channel trafficking mutations. ATP-sensitive potassium (K ATP )1 channels present in the plasma membrane of pancreatic -cells play a central role in mediating glucose-induced insulin secretion (1-4). The activity of K ATP channels, which regulates -cell membrane potential, is determined by the relative concentrations of intracellular ATP and ADP. When the blood glucose level rises, the increased intracellular [ATP/ADP] ratio favors K ATP channel closure, resulting in membrane depolarization, Ca 2ϩ influx, and insulin secretion. When the blood glucose level falls, the above molecular events reverse, and insulin release is stopped. In the event where K ATP channels fail to open during glucose starvation, -cell membrane potential remains depolarized, and insulin secretion persists, leading to severe hypoglycemia. These symptoms are found in patients suffering from congenital hyperinsulinism (5), also known as persistent hyperinsulinemia hypoglycemia of infancy (PHHI) (6). Indeed, mutations in the K ATP channel genes, sulfonylurea receptor 1 (SUR1) and the inward rectifier potassium channel Kir6.2, that lead to a loss of channel function have been shown to be major causes of PHHI (4, 6).The pancreatic K ATP channel complex consists of four poreforming Kir6.2 subunits and four regulatory SUR1 subunits (7-10). Gating of K ATP channels occurs as a result of the interplay between both channel subunits and intracellular ATP and ADP. Binding of ATP to the Kir6.2 subunit inhibits channel activity, whereas binding of Mg 2ϩ -complexed ATP or ADP to the SUR1 subunit stimulates channel activity (11)(12)(13)(14). SUR1 is a member of the ATP-binding cassette transporter family; it has three transmembrane domains: TM0, TM1, and TM2, and two large cytoplasmic nucleotide binding domains: NBD1 and NBD2 (15,16). Structure-function studies sugges...
Depression was quite common in this Chinese rural geriatric population. The prevalence rate was twice as high when judged by depression symptomatology rather than clinical diagnosis. The critical risk factors were functional impairments, poor cognitive abilities and the presence of chronic physical illnesses.
The inactivation of the ClC-0 chloride channel is very temperature sensitive and is greatly facilitated by the binding of a zinc ion (Zn2+) from the extracellular side, leading to a Zn2+-induced current inhibition. To further explore the relation of Zn2+ inhibition and the ClC-0 inactivation, we mutated all 12 cysteine amino acids in the channel and assayed the effect of Zn2+ on these mutants. With this approach, we found that C212 appears to be important for the sensitivity of the Zn2+ inhibition. Upon mutating C212 to serine or alanine, the inactivation of the channel in macroscopic current recordings disappears and the channel does not show detectable inactivation events at the single-channel level. At the same time, the channel's sensitivity to Zn2+ inhibition is also greatly reduced. The other two cysteine mutants, C213G and C480S, as well as a previously identified mutant, S123T, also affect the inactivation of the channel to some degree, but the temperature-dependent inactivation process is still present, likewise the high sensitivity of the Zn2+ inhibition. These results further support the assertion that the inhibition of Zn2+ on ClC-0 is indeed due to an effect on the inactivation of the channel. The absence of inactivation in C212S mutants may provide a better defined system to study the fast gating and the ion permeation of ClC-0.
ClC channels are a family of protein molecules containing two ion-permeation pores. Although these transmembrane proteins are important for a variety of physiological functions, their molecular operations are only superficially understood. High-resolution X-ray crystallography techniques have recently revealed the structures of two bacterial ClC channels, but whether vertebrate ClC channel pores are similar to those of bacterial homologues is not clear. To study the pore architecture of the Torpedo ClC-0 channel, we employed the substituted-cysteine-accessibility method (SCAM) and used charged methane thiosulfonate (MTS) compounds to modify the introduced cysteine. Several conclusions were derived from this approach. First, the MTS modification pattern from Y512C to E526C in ClC-0, which corresponds to residues forming helix R in bacterial ClC channels, is indeed consistent with the suggested helical structure. Second, the ClC-0 pore is more accessible to the negatively charged than to the positively charged MTS compound, a pore property that is regulated by the intrinsic electrostatic potential in the pore. Finally, attempts to modify the introduced cysteine at positions intracellular to the selectivity filter did not result in larger MTS modification rates for the open-state channel, suggesting that the fast gate of ClC-0 cannot be located at a position intracellular to the Cl− selectivity filter. Thus, the proposal that the glutamate side chain is the fast gate of the channel is applicable to ClC-0, revealing a structural and functional conservation of ClC channels between bacterial and vertebrate species.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.