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https://www.readbyqxmd.com/read/29777529/pharmacokinetics-of-ads-5102-amantadine-extended-release-capsules-administered-once-daily-at-bedtime-for-the-treatment-of-dyskinesia
#1
Robert A Hauser, Rajesh Pahwa, William A Wargin, Cindy J Souza-Prien, Natalie McClure, Reed Johnson, Jack T Nguyen, Rajiv Patni, Gregory T Went
BACKGROUND: Preclinical and clinical studies suggest amantadine immediate-release (IR) may reduce dyskinesia in Parkinson's disease (PD), although higher doses are associated with increased CNS adverse events (AEs). ADS-5102 is an extended release amantadine capsule formulation, designed for once-daily dosing at bedtime (qhs) to provide high concentrations upon waking and throughout the day, with lower concentrations in the evening. The pharmacokinetics (PK) of ADS-5102 were assessed in two phase I studies in healthy subjects, and a blinded, randomized phase II/III dose-finding study in PD patients...
May 18, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29776679/the-probability-that-catatonia-in-the-hospital-has-a-medical-cause-and-the-relative-proportions-of-its-causes-a-systematic-review
#2
REVIEW
Mark A Oldham
OBJECTIVE: The objective of this review is to determine the probability that catatonia in the hospital has a secondary cause ("medical catatonia") and to calculate the relative proportions of these causes stratified by hospital setting. METHODS: PRISMA systematic review of PubMed. RESULTS: Eleven studies were included. Hospital-wide, 20% of catatonia was medical. In acute medical and surgical settings, medical catatonia comprised more than half of cases...
April 9, 2018: Psychosomatics
https://www.readbyqxmd.com/read/29775896/dysregulated-network-of-mirnas-involved-in-the-pathogenesis-of-multiple-sclerosis
#3
REVIEW
Sanam Dolati, Faroogh Marofi, Zohreh Babaloo, Leili Aghebati-Maleki, Leila Roshangar, Majid Ahmadi, Reza Rikhtegar, Mehdi Yousefi
Multiple sclerosis (MS) is a chronic and organ-specific autoimmune disease in which immune cells act against the myelin sheath, resulting in central nervous system (CNS) damage. It has been revealed that miRNAs can play significant role in the pathogenesis of MS. These regulatory molecules lead to the activation of different signaling pathways, regulation of several transcriptional factors, influencing the differentiation of Th17 cells, development of Tregs and alteration from Th2 to Th1 response in MS. New studies have discovered that dysregulation of miRNAs may trigger abnormal immune responses leading consequently in the emergence of autoimmunity...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775734/defining-the-osteoarthritis-patient-back-to-the-future
#4
REVIEW
Geoffrey P Dobson, Hayley L Letson, Andrea Grant, Peter McEwen, Kaushik Hazratwala, Matthew Wilkinson, Jodie L Morris
The history of osteoarthritis (OA) is important because it can help broaden our perspective on past and present controversies. The naming of OA, beginning with Heberden's nodes, is itself a fascinating story. According to Albert Hoffa, R. Llewellyn Jones and Archibald Edward Garrod, the name OA was introduced in the mid-19th century by surgeon Richard von Volkmann who distinguished it from rheumatoid arthritis and gout. Others preferred the terms 'chronical rheumatism', 'senile arthritis', 'hypertrophic arthritis' or 'arthritis deformans'...
May 15, 2018: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29775730/an-integrated-biomanufacturing-platform-for-the-large-scale-expansion-and-neuronal-differentiation-of-human-pluripotent-stem-cell-derived-neural-progenitor-cells
#5
Gayathri Srinivasan, Daylin Morgan, Divya Varun, Nicholas Brookhouser, David A Brafman
Human pluripotent stem cell derived neural progenitor cells (hNPCs) have the unique properties of long-term in vitro expansion as well as differentiation into the various neurons and supporting cell types of the central nervous system (CNS). Because of these characteristics, hNPCs have tremendous potential in the modeling and treatment of various CNS diseases and disorders. However, expansion and neuronal differentiation of hNPCs in quantities necessary for these applications is not possible with current two dimensional (2-D) approaches...
May 15, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29775619/proteomic-approach-to-profiling-immune-complex-antigens-in-cerebrospinal-fluid-samples-from-patients-with-central-nervous-system-autoimmune-diseases
#6
Nozomi Aibara, Kunihiro Ichinose, Miyako Baba, Hideki Nakajima, Katsuya Satoh, Ryuichiro Atarashi, Naoya Kishikawa, Noriyuki Nishida, Atsushi Kawakami, Naotaka Kuroda, Kaname Ohyama
BACKGROUND: Immune complexes (ICs) may clearly reflect immunological abnormalities caused by disease, especially for autoimmune diseases. Although ICs have been detected in cerebrospinal fluid (CSF) from patients with CNS autoimmune diseases, identities of antigens in such ICs have not been comprehensively determined. METHODS: We used immune complexome analysis, in which nano-liquid chromatography-tandem mass spectrometry is employed to comprehensively identify antigens incorporated into ICs in biological fluids, to characterize ICs in CSF samples from patients with CNS autoimmune diseases, and to find disease-specific IC antigen to a certain CNS autoimmune disease...
May 15, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29775591/disease-associated-microglia-a-universal-immune-sensor-of-neurodegeneration
#7
REVIEW
Aleksandra Deczkowska, Hadas Keren-Shaul, Assaf Weiner, Marco Colonna, Michal Schwartz, Ido Amit
A major challenge in the field of neurodegenerative diseases and brain aging is to identify the body's intrinsic mechanism that could sense the central nervous system (CNS) damage early and protect the brain from neurodegeneration. Accumulating evidence suggests that disease-associated microglia (DAM), a recently identified subset of CNS resident macrophages found at sites of neurodegeneration, might play such a protective role. Here, we propose that microglia are endowed with a dedicated sensory mechanism, which includes the Trem2 signaling pathway, to detect damage within the CNS in the form of neurodegeneration-associated molecular patterns (NAMPs)...
May 17, 2018: Cell
https://www.readbyqxmd.com/read/29775564/the-antibody-rhigm22-facilitates-hippocampal-remyelination-and-ameliorates-memory-deficits-in-the-cuprizone-mouse-model-of-demyelination
#8
Charlene Cui, Jing Wang, Ariana P Mullin, Anthony O Caggiano, Tom J Parry, Raymond W Colburn, Elias Pavlopoulos
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the CNS. In addition to motor, sensory and visual deficits, MS is also characterized by hippocampal demyelination and memory impairment. We recently demonstrated that a recombinant human-derived monoclonal IgM antibody, which is designated rHIgM22 and currently in clinical development for people with MS, accelerates remyelination of the corpus callosum in the brains of cuprizone-treated mice. Here, we investigated the effects of rHIgM22 in the hippocampus and on hippocampal-dependent learning and memory in the same mouse model of cuprizone-induced demyelination and spontaneous remyelination...
May 15, 2018: Brain Research
https://www.readbyqxmd.com/read/29774053/postherpes-simplex-encephalitis-a-case-series-of-viral-triggered-autoimmunity-synaptic-autoantibodies-and-response-to-therapy
#9
Harry Alexopoulos, Sofia Akrivou, Sotiria Mastroyanni, Maria Antonopoulou, Argirios Dinopoulos, Melpo Giorgi, Kostas Konstantinou, Evangelos Kouremenos, Maria Lariou, Dimitrios Naoumis, Efterpi Pavlidou, Evaggelos Pavlou, Konstantinos Voudris, Panayotis Vlachoyiannopoulos, Marinos C Dalakas
Background: Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens. Patient/Methods: Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29772459/tyrosine-kinase-inhibitors-for-brain-metastases-in-her2-positive-breast-cancer
#10
REVIEW
Renata Duchnowska, Sibylle Loibl, Jacek Jassem
Approximately 30-50% of advanced HER2-positive breast cancer patients will develop central nervous system (CNS) metastases, with an annual risk of around 10%, and a half of them will die from brain progression. An increased risk of brain metastases is also seen in patients with early HER2-positive breast cancer administered curative therapy. Brain metastases in HER2-positive breast cancer patients usually constitute the first site of recurrence. The administration of anti-HER2 monoclonal antibodies, trastuzumab and pertuzumab, considerably delays the onset of symptomatic brain disease: however, the limited penetration of these compounds into the CNS hinders their efficacy...
May 9, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29772377/impact-of-steroid-hormones-e2-and-p-on-the-nlrp3-asc-casp1-axis-in-primary-mouse-astroglia-and-bv-2-cells-after-in-vitro-hypoxia
#11
Alexander Slowik, Leoni Lammerding, Adib Zendedel, Pardes Habib, Cordian Beyer
Clinical and animal model studies have demonstrated the neuroprotective and anti-inflammatory effects of 17beta-estradiol (E2) and progesterone (P) in different disease models of the central nervous system (CNS) including ischemic stroke. Inflammasomes are involved in the interleukin-1 beta (IL1beta) maturation, in particular, NLRP3, the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and the active caspase-1 (Casp1) form. Recently, we showed that administration of E2 or P selectively regulated these components after experimental ischemic stroke in rats...
May 14, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29771386/immunotherapy-in-cns-cancers-the-role-of-immune-cell-trafficking
#12
Nivedita M Ratnam, Mark R Gilbert, Amber J Giles
Glioblastoma (GBM) is a highly malignant CNS tumor with very poor survival despite intervention with conventional therapeutic strategies. Although the CNS is separated from the immune system by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), emerging evidence of immune surveillance and the selective infiltration of GBMs by immune suppressive cells indicates that there is breakdown or compromise of these physical barriers. This in turn offers hope that immunotherapy can be applied to specifically target and reduce tumor burden...
May 15, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29770863/siv-latency-in-macrophages-in-the-cns
#13
Lucio Gama, Celina Abreu, Erin N Shirk, Suzanne E Queen, Sarah E Beck, Kelly A Metcalf Pate, Brandon T Bullock, M Christine Zink, Joseph L Mankowski, Janice E Clements
Lentiviruses infect myeloid cells, leading to acute infection followed by persistent/latent infections not cleared by the host immune system. HIV and SIV are lentiviruses that infect CD4+ lymphocytes in addition to myeloid cells in blood and tissues. HIV infection of myeloid cells in brain, lung, and heart causes tissue-specific diseases that are mostly observed during severe immunosuppression, when the number of circulating CD4+ T cells declines to exceeding low levels. Antiretroviral therapy (ART) controls viral replication but does not successfully eliminate latent virus, which leads to viral rebound once ART is interrupted...
May 17, 2018: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/29770253/simultaneous-cerebrospinal-fluid-and-hematologic-metastases-in-a-high-grade-ependymoma
#14
Daniel Diaz-Aguilar, Sergei Terterov, Alexander M Tucker, Shaina Sedighim, Rudi Scharnweber, Stephanie Wang, Catherine Merna, Shayan Rahman
Background: Ependymomas are relatively uncommon tumors that constitute about 7% of all primary intracranial neoplasms. Among these, high-grade ependymomas are locally aggressive and recur most commonly at the primary site following resection. Ependymomas are also known to be the one glial neoplasm that tends to frequently metastasize inside and outside the central nervous system (CNS) that complicates workup and management. Metastasis due to surgical manipulation is common and neurosurgeons should be well-versed in the most effective methods to remove these tumors in order to avoid such metastases...
2018: Surgical Neurology International
https://www.readbyqxmd.com/read/29770137/gut-microbiota-confers-resistance-of-albino-oxford-rats-to-the-induction-of-experimental-autoimmune-encephalomyelitis
#15
Suzana Stanisavljević, Miroslav Dinić, Bojan Jevtić, Neda Đedović, Miljana Momčilović, Jelena Đokić, Nataša Golić, Marija Mostarica Stojković, Đorđe Miljković
Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29769839/a-novel-association-of-polymorphism-in-the-itga4-gene-encoding-the-vla-4-%C3%AE-4-subunit-with-increased-risk-of-alzheimer-s-disease
#16
Vladimira Durmanova, Zuzana Parnicka, Juraj Javor, Gabriel Minarik, Lubomir Vrazda, Barbora Vaseckova, Karin Gmitterova, Maria Kralova, Jan Pecenak, Peter Filipcik, Ivana Shawkatova
Alzheimer's disease (AD) is the most prevalent cause of dementia in elderly people worldwide. Many studies support the hypothesis that the inflammation of the CNS contributes to the neurodegeneration and disease progression. The integrin molecule α 4 β 1, also known as very late antigen 4 (VLA-4), belongs to adhesion molecules that activate the inflammatory process through the migration of immune cells into the CNS. Therefore, the objective of our study was to analyze the association between two polymorphisms located in the ITGA4 gene encoding the α 4 subunit of VLA-4 and the risk of AD...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29769699/a-stocked-toolbox-for-understanding-the-role-of-astrocytes-in-disease
#17
REVIEW
Akshata Almad, Nicholas J Maragakis
Our understanding of astrocytes and their role in neurological diseases has increased considerably over the past two decades as the diverse roles of these cells have become recognized. Our evolving understanding of these cells suggests that they are more than support cells for neurons and that they play important roles in CNS homeostasis under normal conditions, in neuroprotection and in disease exacerbation. These multiple functions make them excellent candidates for targeted therapies to treat neurological disorders...
May 16, 2018: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29769372/iglon5-mediated-neurodegeneration-is-a-differential-diagnosis-of-cns-whipple-disease
#18
Hugo Morales-Briceño, Belinda Cruse, Alessandro F Fois, Ming-Wei Lin, Jocelyn Jiang, Dev Banerjee, Ron Grunstein, Winny Varikatt, Michael Rodriguez, Claire Shepherd, Victor S C Fung
No abstract text is available yet for this article.
May 16, 2018: Neurology
https://www.readbyqxmd.com/read/29769333/microglia-are-critical-in-host-defense-against-prion-disease
#19
James A Carroll, Brent Race, Katie Williams, James Striebel, Bruce Chesebro
Microglial cells in the central nervous system play important roles in neurodevelopment and resistance to infection, yet microglia can become neurotoxic under some conditions. An early event during prion infection is the activation of microglia and astrocytes in the brain prior to damage or death of neurons. Previous prion disease studies using two different strategies to manipulate signaling through the microglial receptor CSF-1R reported contrary effects on survival from prion disease. However, in these studies, reduction of microglial numbers and function were variable, thus confounding interpretation of the results...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29768873/macrophages-as-nanocarriers-for-drug-delivery-novel-therapeutics-for-central-nervous-system-diseases
#20
Zeng-Pan-Pan Ye, Xiao-Lin Ai, Andrew M Faramand, Fang Fang
Many central nervous system (CNS) diseases were thought to be untreatable due to the presence of the blood-brain barrier (BBB). The chemokine gradients secreted from CNS parenchyma can induce macrophage migration to the brain, induce firm adherence to the endothelium of BBB, and eventually to enter the brain parenchyma. Macrophages migrating into CNS can promote neuron regeneration, induce inflammation and angiogenesis. These properties can potentially allow macrophages to act as carriers for drug/nano formulations across the BBB, and reach the potential target sites...
January 1, 2018: Journal of Nanoscience and Nanotechnology
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