NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics最新文献

{"title":"Noninvasive Measurement and Quantitation of Brain Iron in Parkinson’s Disease Using Adiabatic T2ρ and T1ρ High Field MRI Techniques","authors":"S. Michaeli,&nbsp;D. Sorce,&nbsp;G. Öz,&nbsp;K. Ugurbil,&nbsp;M. Garwood,&nbsp;P. Tuite","doi":"10.1016/j.nurx.2006.05.015","DOIUrl":"10.1016/j.nurx.2006.05.015","url":null,"abstract":"<div><p>Postmortem demonstration of increased iron in the substantia nigra (SN) is a well- appreciated finding in Parkinson’s disease (PD). It is thought that this iron may facilitate the generation of free radicals which are thought to play a role in dopamine neuronal loss. To date, however, researchers have been unable to confirm an <em>in vivo</em> difference of iron between those with PD and control subjects using magnetic resonance imaging (MRI). This may be due to the limitations of T1 and T2: two conventional MRI techniques that have been employed. Here, novel T2ρ and T1ρ MRI relaxation methods were used for the measurement of iron load and distribution <span>[1]</span>, <span>[2]</span>, <span>[3]</span>. T2ρ measurements are indicative of tissue iron content and distribution and measure molecular motion in local susceptibility gradients. T1ρ measurements, on the other hand, can be used to assess cellular loss. When applied at high magnetic fields these two methods may provide a noninvasive and reliable handle on iron accumulation and neuronal loss in PD. In our 4 Tesla magnet study, we found a significant change of the T1ρ and T2ρ relaxation time constants (both the distribution and absolute values) in the PD group versus controls. Relaxogram analysis of the T2ρ and T1ρ measurements demonstrated increased water and iron content, as well as changes in iron distribution in the SN. Therefore, high resolution MRI with T2ρ and T1ρ <em>provide unique information in Parkinson’s disease</em> patients as compared to conventional T1 and T2 measurements. This information may prove useful in evaluating the pathogenesis and severity of PD. Future studies are underway to correlate T1ρ, T2ρ, and Τ2 findings with simultaneous spectroscopy measurements of absolute concentration of NAA <span>[4]</span> to further assess iron accumulation and neuronal loss in controls and those with PD.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 3","pages":"Pages 408-409"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2006.05.015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54958962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a Rapid-Throughput Battery of Pheontypic Tests for Drug Candidate Evaluation in the Δ-7 Mouse Model of Spinal Muscular Atrophy","authors":"B. El-Khodor,&nbsp;N. Edgar,&nbsp;A. Chen,&nbsp;M.P. Heyes","doi":"10.1016/j.nurx.2006.05.023","DOIUrl":"10.1016/j.nurx.2006.05.023","url":null,"abstract":"<div><p>Spinal muscular atrophy (SMA) is characterized by selective loss of α-motor neurons and is caused by homozygous loss or mutation in the telomeric survival motor neuron (SMN1) gene. Currently, there are no specific treatments for SMA. Drugs that improve α-motor neuron survival and/or connectivity are potential therapeutic candidates. A high capacity and practical <em>in vivo</em> assessment system in the neonates (as early as the day of birth) is important to identify and evaluate therapeutic candidates. Key features of SMA are modeled in mice by deletion of the smn gene and insertion of the human SMN2 gene (smn^–/–; SMN2^+/+). Incorporation of the Δ7 gene into this SMA model improves survival into a more experimentally useful range of symptom progression, severity and drug administration protocols (see Le <em>et al., Hum. Mol. Genet.</em> 14: 845, <span>2005</span>). In the present study, SMA model mice (smn^–/–; SMN2^+/+; Δ7^+/+) and control mice (smn^+/+; SMN2^+/+; Δ7^+/+) were assessed daily for body weight and survival, and every other day for muscle tone, respiratory rate, gasping, degree of cyanosis, stomach milk content, and performance in a geotaxis test. Hind limb measures of strength, stamina, and general muscle tone were also evaluated. Around postnatal day 7, SMA mice showed lower body weights than controls and had a mean survival time of 13.5 days, as reported previously (<span>Le <em>et al.</em>, 2005</span>). SMA mice did not acquire the ability to perform the geotaxis test and exhibited consistently hypotonic hind limbs. Other parameters were more variable and impaired at later time points. Furthermore, there was a significant correlation between body weight change and survival, which predicted the day of death within a 1-2 day period. This battery of tests in the Δ7 mouse model of SMA provides a rapid throughput and efficient means to identify, evaluate, and develop candidate therapies as a prelude to human clinical trials.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 3","pages":"Page 411"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2006.05.023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54959373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dystonia Medical Research Foundation: 30 Years of Promoting Research and Therapy Development","authors":"","doi":"10.1016/j.nurx.2006.05.032","DOIUrl":"https://doi.org/10.1016/j.nurx.2006.05.032","url":null,"abstract":"<div><p>Dystonia is a neurological disorder of movement. It is characterized by involuntary contractions of various parts of the body causing discomfort and pain and, in more severe forms, incapacitating the affected individuals. Although the exact cause of the disease in unknown, several forms known as primary dystonias are inherited. Other, secondary dystonias result from brain injuries or exposure to toxic drugs. Dystonia often accompanies other neurological diseases. In North America alone, more than 300,000 people are affected by this disease, making it the third most common movement disorder. Due to its nature, the psychological and social impact of the dystonias is enormous. It is estimated that the total annual cost to the national economy can be counted in billions of dollars.</p><p>Thirty years ago, in response to the growing and unfulfilled needs of the dystonia community, the Dystonia Medical Research Foundation (DMRF) was established. One of the major goals of the Foundation is to promote and support basic and clinical research into the causes and mechanisms of the dystonias. The Foundation also supports efforts which aim at discovery and development of novel treatments and therapies. Since its founding, the DMRF-funded researchers have made major discoveries in the field. These efforts culminated in 1997, when the first dystonia-causing gene, DYT1, was cloned. Genetic studies indicate that there are at least 14 other genes causing inherited forms of the disease. The implications of gene discoveries are obvious. TorsinA, the product of DYT1 gene, has been extensively characterized. The knowledge about its structure, cellular localization, interactions, and physiological function provides an opportunity to identify viable targets for drug development. To explore these exciting possibilities, the DMRF began funding research aiming at the development of novel therapeutic agents and established the Cure Dystonia Initiative (CDI). The major goal of the CDI is to accelerate the development of more effective treatments for dystonia with the ultimate goal of finding a cure. The CDI is envisioned as a bridge between basic and translational research. As the CDI is still at its early stages, several research groups supported by the DMRF have already begun testing promising drug candidates which target pathogenic genes and proteins. Faithful to its tradition, the DMRF is committed to support basic and clinical research, as well as therapeutics development.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 3","pages":"Pages 414-415"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2006.05.032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138305831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Genetics of Addiction Vulnerability","authors":"George R. Uhl","doi":"10.1016/j.nurx.2006.05.006","DOIUrl":"10.1016/j.nurx.2006.05.006","url":null,"abstract":"<div><h3>Summary</h3><p>Classical genetic studies document strong complex genetic contributions to abuse of multiple addictive substances, to mnemonic processes that are likely to include those involved in substance dependence, and to the volumes of brain gray matter in regions that are likely to contribute to mnemonic/cognitive and to addictive processes. The working idea that these three heritable phenotypes are likely to share some of the same complex genetic underpinnings is presented. This review contains association-based molecular genetic studies of addiction that largely derive from my laboratory and their fit with linkage data from other laboratories. These combined results now identify many of the loci and genes that contain allelic variants that are likely to provide the heritable components of human addiction vulnerability. These data are also likely to have broad implications for neurotherapeutics. Drugs with potential abuse liabilities are widely used for indications that include pain, anxiety, sleep, seizure, and attentional disorders. There is increasing nonmedical use of these prescribed substances. Increasing information about addiction vulnerability gene variants should help to improve management of risks of dependence in individuals who receive such therapeutics. In addition, since mnemonic components that correlate well with individual differences in brain regional volumes are likely to play major roles in addiction processes, many addiction vulnerability genes are also good candidates to contribute to individual differences in mnemonic processes. Recently elucidation of addiction-associated haplotypes for the “cell adhesion” NrCAM gene illustrate several of these points.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 3","pages":"Pages 295-301"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2006.05.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26124208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-dimensional Protein Electrophoresis: From Molecular Pathway Discovery to Biomarker Discovery in Neurological Disorders","authors":"Leila H. Choe,&nbsp;Brenda G. Werner,&nbsp;Kelvin H. Lee","doi":"10.1016/j.nurx.2006.05.001","DOIUrl":"10.1016/j.nurx.2006.05.001","url":null,"abstract":"<div><h3>Summary</h3><p>Two-dimensional protein electrophoresis (2-DE) has undergone many technical improvements in the past 30 years, resulting in an analytical method that is unparalleled in the resolution of complex protein mixtures and capable of quantifying changes in protein expression from a wide variety of tissues and samples. The technique has been applied in many studies of neurologic disease to identify changes in spot patterns that correlate with disease. The true power of the technique emerges when it is coupled to state-of-the-art methods in mass spectrometry, which enable identification of the protein or proteins contained within a spot of interest on a 2-DE map. Investigators have successfully applied the technique to gain improved understanding of neurologic disease mechanisms in humans and in animal models and to discover biomarkers that are useful in the clinical setting. An important extension to these efforts that has not been realized thus far is the desire to profile changes in protein expression that result from therapy to help relate disease-modifying effects at the molecular level with clinical outcomes. Here we review the major advances in 2-DE methods and discuss specific examples of its application in the study of neurologic diseases.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 3","pages":"Pages 327-335"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2006.05.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26121753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of 1-Octanol as a Novel Therapy for the Treatment of Ethanol-Responsive Essential Tremor","authors":"F. Nahab,&nbsp;M. Hallett","doi":"10.1016/j.nurx.2006.05.021","DOIUrl":"10.1016/j.nurx.2006.05.021","url":null,"abstract":"<div><h3>Background</h3><p>Essential tremor (ET) is a common movement disorder affecting 0.4% of the general population and up to 14% of people 65 years and older. Response to medications such as beta blockers and primidone may be of benefit, but are often accompanied by intolerable side effects. Response to ethanol, on the other hand, has a roughly 80% chance of significant tremor reduction, though daily use of this as a treatment has potentially serious medical, social, and legal consequences. Both ethanol and 1-octanol have been shown to reduce harmaline-induced tremor in rodents, an animal model of ET; however, 1-octanol does this at a dose much lower than that leading to intoxication, suggesting it may be useful in the treatment of essential tremor.</p></div><div><h3>Methods</h3><p>Our study population consists of adults with ethanol-responsive ET. Two formulations of 1-octanol have been utilized to date, a capsule containing 1-octanol adsorbed cellulose particles and a gelcap filled with 1-octanol in an oil-based vehicle. Primary outcome measures have included several measures including spiral drawings.</p></div><div><h3>Results</h3><p>Our initial findings have shown 1-octanol to be safe and effective in a placebo-controlled trial and in an open label dose-finding trial at doses up to 64 mg/kg. Two initial formulations of 1-octanol have shown an unstable shelf-life and/or poor systemic absorption. We have failed so far to develop an assay for octanol that will permit pharmacokinetic studies.</p></div><div><h3>Conclusions</h3><p>Octanol is a promising drug for ET, but there are problems in its development. We need to develop a satisfactory assay and a good formulation in order to proceed with further clinical trials. Lacking some of the necessary skills, our NIH team has now partnered with industry to speed up progress.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 3","pages":"Pages 410-411"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2006.05.021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54959319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Signal Detection Properties of 3 Outcome Scales Used in Clinical Trials of Patients with Generalized Anxiety Disorder","authors":"Q. Jiang,&nbsp;S. Ahmed,&nbsp;R. Pedersen,&nbsp;J. Musgnung,&nbsp;R. Entsuah","doi":"10.1016/j.nurx.2006.05.024","DOIUrl":"10.1016/j.nurx.2006.05.024","url":null,"abstract":"<div><h3>Introduction</h3><p>This analysis assessed correlations between the signal detection properties (drug vs placebo) of 3 outcome scales—the 14-item Hamilton Rating Scale for Anxiety (HAM-A), the Clinician Global Impression of Severity (CGI-S), and the Clinical Global Impression of Improvement (CGI-I)—in generalized anxiety disorder (GAD) clinical trials.</p></div><div><h3>Methods</h3><p>Data from 5 randomized, double-blind, placebo-controlled venlafaxine XR studies in adult patients with GAD were pooled and examined individually. For all rating scales, Pearson correlation coefficients were calculated for all patients at each visit and by treatment arm. To evaluate signal detection properties, effect sizes and <em>P</em> values based on the pooled and individual study data were examined for the 3 scales.</p></div><div><h3>Results</h3><p>At pretreatment visits, for the HAM-A and CGI-S, respectively, 1837 and 1831 observations were available, with mean scores of 25.8 and 4.5, and the correlation coefficient between the 2 scales was 0.55 (<em>P</em> &lt; 0.0001). Correlation coefficients at week 1 were 0.69 (HAM-A/CGI-S), 0.66 (HAM-A/CGI-I), and 0.55 (CGI-S/CGI-I). Correlation coefficients increased each week, and at final visit were 0.83 (HAM-A/CGI-S), 0.84 (HAM-A/CGI-I), and 0.82 (CGI-I/CGI-S). All correlations were significant (<em>P</em> &lt; 0.0001) and were of comparable magnitude in the venlafaxine XR and placebo groups. Pooled effect sizes (venlafaxine XR <em>versus</em> placebo) were 0.37, 0.41, and 0.40 for HAM-A, CGI-S, and CGI-I, respectively (week 8 LOCF). Across studies, effect sizes ranged from 0.21 to 0.55, 0.23 to 0.68, and 0.26 to 0.59 for the HAM-A, CGI-S, and CGI-I, respectively. As with the pooled data, however, within studies, they were more consistent across the 3 outcome measures. All 3 outcome measures reached statistical significance (<em>P</em> &lt; 0.05) in 4 of 5 studies.</p></div><div><h3>Conclusions</h3><p>The 3 scales were consistently correlated in all studies, and the correlations increased during the conduct of the study. Effect sizes based on different scales in the same studies were more similar than effect sizes based on the same scale in different studies. Furthermore, no one scale stood out as having consistently better signal detection properties than the others.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 3","pages":"Page 411"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2006.05.024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54959524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CT Scan Hematoma Volume: A Surrogate Endpoint for the Effect of Treatment in Intracerebral Hemorrhage","authors":"B.E. Skolnick ,&nbsp;S.M. Davis ,&nbsp;N.C. Brun ,&nbsp;S.E. Mathew ,&nbsp;S.A. Mayer","doi":"10.1016/j.nurx.2006.05.029","DOIUrl":"10.1016/j.nurx.2006.05.029","url":null,"abstract":"<div><p>Intracerebral hemorrhage (ICH) represents approximately 15% of all strokes, with no approved therapeutic interventions available. The 30-day mortality rate is 35 to 50% and only 10 to 20% of survivors regain functional independence. Previous studies have indicated that substantial increase in hematoma volume occurs within the first hours after ICH onset. These studies also indicated that hematoma volume expansion is associated with neurological deterioration and was a critical determinant of 30-day mortality. Early interventions directed at reducing hematoma expansion would be of considerable value. However, no validated measurements exist to directly translate the impact of hematoma volume on clinical outcomes. Changes in hematoma volume as determined by computed tomography (CT) scan is a potential surrogate endpoint for clinical outcomes. A recent randomized, double-blind, parallel-group, placebo-controlled clinical trial (399 patients) evaluated the use of rFVIIa (recombinant activated coagulation Factor VII) to reduce expansion of ICH hematoma volume, also determined the inter- and intrareader variability of CT scan measurements. In addition, assessments of clinical outcomes (modified Rankin Score, mRS) and mortality were conducted.</p><p>A baseline CT scan was performed within 3 hours after symptom onset. Placebo or rFVIIa was administered within 1 hour after the baseline scan. CT scans were repeated at 24 hours and 72 hours post-treatment. Inter-reader and intrareader variability was assessed by comparison of ICH volumes measured on CT images by two independent neuroradiologists, masked to treatment.</p><p>A meta-analysis conducted on a hemostatic treatment–naïve ICH patient population pooled from four studies (<em>N</em> = 218) demonstrated that hematoma volume was an independent determinant of mortality (<em>p</em> &lt; 0.0001) and mRS (<em>p</em> = 0.0003). The results of a clinical trial using rFVIIa indicated that CT scan measurements of ICH volumes showed excellent intraclass correlations for interreader (0.9569) and intrareader variability (0.9844). Additionally, treatment with rFVIIa resulted in significant reduction in hematoma volume (<em>p</em> = 0.01), mortality (<em>p</em> = 0.02) as well as improved clinical outcome (<em>p</em> = 0.004, mRS) for rFVIIa-treated patients compared to placebo. Therefore, change in hematoma volume as determined by CT scan has potential as a clinically relevant surrogate measure, with value in the study of early hemostatic interventions in acute neurologic settings where brain hemorrhage is of significant concern.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 3","pages":"Page 413"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2006.05.029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54959822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"www.PDtrials.org: Increasing Parkinson’s Clinical Trial Awareness through the Internet","authors":"","doi":"10.1016/j.nurx.2006.05.034","DOIUrl":"https://doi.org/10.1016/j.nurx.2006.05.034","url":null,"abstract":"<div><p><em>PDtrials^⁎</em> is a national initiative dedicated to increasing education and awareness about clinical research by providing information to help people with Parkinson’s learn and make informed decisions about participating in clinical trials. <span>www.PDtrials.org</span><svg><path></path></svg> is a first-of-its-kind website that lists over 50 clinical studies seeking participants. It sees over 25,000 visits per month and has an email list of close to 2,500.</p><p><em>PDtrials</em> was initiated in response to a concern within the Parkinson’s community about the low levels of awareness and participation in clinical research. As many as one million people in the U.S. live with Parkinson’s yet less than one percent participate in clinical studies—far short of volunteers that researchers anticipate will be needed over the next two to three years.</p><p>In October 2005, the <em>PDtrials</em> campaign initiated a series of online marketing strategies to increase visibility for <span>www.PDtrials.org</span><svg><path></path></svg>. These included the development of a monthly HTML email newsletter—the <em>PDtrials</em> Bulletin and engaging in “viral” marketing, such as forwarding the <em>PDtrials Bulletin</em> to contacts throughout the community.</p><p>The results were an increase in average daily visitors from 465 in September 2005 to 822 in January 2006 and an increase in overall visits from 13,956 in September 2005 to 25,506 in January 2006. In addition, over 50% of <em>PDtrials Bulletin</em> recipients opened the email and clicked through from the <em>Bulletin</em> to <span>www.PDtrials.org</span><svg><path></path></svg>. This compares with a nonprofit industry standard of a 30% open rate and 3% click-through rate.</p><p>Various strategies have been employed to increase web traffic to <span>www.PDtrials.org</span><svg><path></path></svg>. The greatest success has been through online cultivation of individuals who have requested to receive information about clinical studies and who are thought to be interested.</p><p>*<em>PDtrials</em><span> is led by the Parkinson’s Disease Foundation in collaboration with the American Parkinson Disease Association, The Michael J. Fox Foundation for Parkinson’s Research, the National Parkinson Foundation, the Parkinson’s Action Network, The Parkinson Alliance and WE MOVE. The campaign is advised by the National Institute of Neurological Disorders and Stroke (NIH), the Parkinson Study Group, the Parkinson Pipeline Project and the Parkinson’s Institute.</span></p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 3","pages":"Page 415"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2006.05.034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138305832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox Proteomics in Some Age-Related Neurodegenerative Disorders or Models Thereof","authors":"D. Allan Butterfield ,&nbsp;Hafiz Mohmmad Abdul ,&nbsp;Shelley Newman ,&nbsp;Tanea Reed","doi":"10.1016/j.nurx.2006.05.003","DOIUrl":"10.1016/j.nurx.2006.05.003","url":null,"abstract":"<div><h3>Summary</h3><p>Neurodegenerative diseases cause memory loss and cognitive impairment. Results from basic and clinical scientific research suggest a complex network of mechanisms involved in the process of neurodegeneration. Progress in treatment of such disorders requires researchers to better understand the functions of proteins involved in neurodegenerative diseases, to characterize their role in pathogenic disease mechanisms, and to explore their roles in the diagnosis, treatment, and prevention of neurodegenerative diseases. A variety of conditions of neurodegenerative diseases often lead to post-translational modifications of proteins, including oxidation and nitration, which might be involved in the pathogenesis of neurodegenerative diseases. Redox proteomics, a subset of proteomics, has made possible the identification of specifically oxidized proteins in neurodegenerative disorders, providing insight into a multitude of pathways that govern behavior and cognition and the response of the nervous system to injury and disease. Proteomic analyses are particularly suitable to elucidate post-translational modifications, expression levels, and protein–protein interactions of thousands of proteins at a time. Complementing the valuable information generated through the integrative knowledge of protein expression and function should enable the development of more efficient diagnostic tools and therapeutic modalities. Here we review redox proteomic studies of some neurodegenerative diseases.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 3","pages":"Pages 344-357"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2006.05.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26122303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}