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Cns diseases

Chelsea A O'Driscoll, Leah A Owens, Erica J Hoffmann, Madeline E Gallo, Amin Afrazi, Mei Han, John H Fechner, James J Schauer, Christopher A Bradfield, Joshua D Mezrich
BACKGROUND: Autoimmune diseases have increased in incidence and prevalence worldwide. While genetic predispositions play a role, environmental factors are a major contributor. Atmospheric particulate matter (PM) is a complex mixture composed of metals, nitrates, sulfates and diverse adsorbed organic compounds like polycyclic aromatic hydrocarbons (PAHs) and dioxins. Exposure to atmospheric PM aggravates autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus, among others...
October 1, 2018: Environmental Research
Bruna Donida, Bárbara Tauffner, Marco Raabe, Maira F Immich, Marcelo A de Farias, Diego de Sá Coutinho, Andryele Zaffari Machado, Rejane Gus Kessler, Rodrigo V Portugal, Andressa Bernardi, Rudimar Frozza, Dinara J Moura, Fernanda Poletto, Carmen Regla Vargas
Lysosomal Storage Disorders (LSDs) are characterized by an abnormal accumulation of substrates within the lysosome and comprise more than 50 genetic disorders with a frequency of 1:5000 live births. Nanotechnology may be a promising way to circumvent the drawbacks of the current therapies for lysosomal diseases. The blood circulation time and bioavailability of the enzymes or drugs could be improved by inserting them in nanocarriers, which could decrease and/or avoid the need of frequent intravenous infusions along with the minimization or elimination of associated immunogenic responses...
October 10, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Damian Miles Bailey
Rising atmospheric oxygen (O2 ) levels provided a selective pressure for the evolution of O2 -dependent micro-organisms that began with the autotrophic eukaryotes. Since these primordial times, the respiring mammalian cell has become entirely dependent on the constancy of electron flow with molecular O2 serving as the terminal electron acceptor in mitochondrial oxidative phosphorylation. Indeed, the ability to "sense" O2 and maintain homeostasis is considered one of the most important roles of the central nervous system (CNS) and likely represented a major driving force in the evolution of the human brain...
October 13, 2018: Journal of Physiology
Bingmei M Fu
The blood-brain barrier (BBB) is a dynamic barrier essential for maintaining the microenvironment of the brain. Although the special anatomical features of the BBB determine its protective role for the central nervous system (CNS) from blood-borne neurotoxins, however, the BBB extremely limits the therapeutic efficacy of drugs into the CNS, which greatly hinders the treatment of major brain diseases. This chapter summarized the unique structures of the BBB; described a variety of in vivo and in vitro experimental methods for determining the transport properties of the BBB and the permeability of the BBB to water, ions, and solutes including nutrients, therapeutic agents, and drug carriers; and presented recently developed mathematical models which quantitatively correlate the anatomical structures of the BBB with its barrier functions...
2018: Advances in Experimental Medicine and Biology
J Singh, M Cerghet, L M Poisson, I Datta, K Labuzek, H Suhail, R Rattan, Shailendra Giri
Identification of non-invasive biomarkers of disease progression in multiple sclerosis (MS) is critically needed for monitoring the disease progression and for effective therapeutic interventions. Urine is an attractive source for non-invasive biomarkers because it is easily obtained in the clinic. In search of a urine metabolite signature of progression in chronic experimental autoimmune encephalomyelitis (EAE), we profiled urine at the chronic stage of the disease (day 45 post immunization) by global untargeted metabolomics...
October 12, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Stefanie Kuerten, Leila J Jackson, Joel Kaye, Timothy L Vollmer
Growing evidence indicates that B cells play a key role in the pathogenesis of multiple sclerosis (MS). B cells occupy distinct central nervous system (CNS) compartments in MS, including the cerebrospinal fluid and white matter lesions. Also, it is now known that, in addition to entering the CNS, B cells can circulate into the periphery via a functional lymphatic system. Data suggest that the role of B cells in MS mainly involves their in situ activation in demyelinating lesions, leading to altered pro- and anti-inflammatory cytokine secretion, and a highly effective antigen-presenting cell function, resulting in activation of memory or naïve T cells...
October 12, 2018: CNS Drugs
Christopher A Shaw
In the following, I will consider the impact of aluminum on two major systems, the central nervous system (CNS) and the immune system, across the life span. The article will discuss the presence of aluminum in the biosphere, its history, and the sources of the element. These include food, water cosmetics, some vaccines, and a range of other sources. I will also consider aluminum's unique chemistry. Finally, in humans and animals, I will consider how aluminum may impact the CNS at various levels of organization and how it may be involved in various neurological disease states across the life span...
2018: Advances in Experimental Medicine and Biology
Allison Soung, Robyn S Klein
Neurotropic RNA virus infections cause a major neurological disease burden. Due to the morbidity and mortality rates of viral encephalitides worldwide, there is a need to develop clinical treatments. Features of the central nervous system (CNS), including interconnected cell types and limited regeneration, provide unique challenges. Viral encephalitis and antiviral immunity can disrupt the CNS environment, leaving patients with poor neurological outcomes despite virologic control. The cellular mechanism(s) underlying neurological recovery are not fully understood, but involve neuroimmune interactions that, until recently, primarily focused on microglia...
October 9, 2018: Trends in Molecular Medicine
Adjmal Nahimi, Martin B Kinnerup, Michael Sommerauer, Albert Gjedde, Per Borghammer
Noradrenergic neurons in both the peripheral nervous system and in the central nervous system (CNS) undergo severe degeneration in patients with Parkinson's disease (PD). This loss of noradrenaline may play essential roles in the occurrence of a wide range of prevalent non-motor symptoms and can further complicate the lives of PD patients. In vivo molecular imaging of noradrenaline may provide insights into to the extent of degeneration of noradrenergic neurons and subsequent depletion of noradrenergic projections...
2018: International Review of Neurobiology
Muharrem Yunce, Nargiz Muganlinskaya, Stephen Selinger
INTRODUCTION: Intravascular large B-cell lymphoma (IVLBCL) is an uncommon disease with a poor prognosis if not diagnosed early. It can present with central nervous system (CNS) manifestations. The diagnosis of IVCBCL is difficult to make given its varied clinical manifestations and the lack of a specific diagnostic modality. CASE PRESENTATION: We report an interesting case of IVLBCL presenting as bilateral strokes. The diagnosis was made by a random skin biopsy, which confirmed IVLBCL...
October 2018: Medicine (Baltimore)
S Jarius, A B Wuthenow, B Wildemann
The term 'neuromyelitis optica' (NMO, Devic syndrome) is used to refer to a syndrome characterized by optic neuritis and myelitis. For many decades NMO was classified as a clinical variant of multiple sclerosis (MS). Recent research has shown, however, that NMO differs from MS in terms of immunopathogenesis, clinical presentation, and optimum treatment. In most cases, NMO is caused by autoantibodies to aquaporin-4 or myelin oligodendrocyte glycoprotein. While the history of classic MS has been studied extensively, only relatively little is known about the early history of NMO...
September 6, 2018: Journal of the Neurological Sciences
Luke Masha, Shareez Peerbhai, David Boone, Fisayomi Shobayo, Aman Ghotra, Bindu Akkanti, Yelin Zhao, Igor Banjac, Igor D Gregoric, Biswajit Kar
Abnormalities in markers of liver injury after venoarterial extracorporeal membrane oxygenation (VA-ECMO) initiation are of unclear distribution and clinical significance. This study included all consecutive adult patients from a single institution who underwent VA-ECMO cannulation between May 2012 and September 2016 and had liver function panels drawn during their admission (n = 223). Data points include: age, sex, body mass index, diagnosis, duration of ECMO cannulation, duration of hospitalization, pre-ECMO cardiac arrest, central nervous system (CNS) injury, the presence of chronic kidney disease or acute renal failure, renal replacement therapy utilization, lactate levels, duration of pre-ECMO intubation, admission and peak bilirubin/aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase (ALP) levels, and time to peak bilirubin/AST/ALT/ALP in relation to cannulation...
October 9, 2018: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
Shuichi Yanai, Shogo Endo
As the population of older individuals grows worldwide, researchers have increasingly focused their attention on identifying key molecular targets of age-related cognitive impairments, with the aim of developing possible therapeutic interventions. Two such molecules are the intracellular cyclic nucleotides, cAMP and cGMP. These second messengers mediate fundamental aspects of brain function relevant to memory, learning, and cognitive function. Consequently, phosphodiesterases (PDEs), which hydrolyze cAMP and cGMP, are promising targets for the development of cognition-enhancing drugs...
October 11, 2018: Molecular Neurobiology
Mohd Babu Khan, Bhagath Kumar Palaka, Tuleshwori Devi Sapam, Naidu Subbarao, Dinakara Rao Ampasala
Acetyl-cholinesterase enzyme (AChE) is a known target for identifying potential inhibitors against Alzheimer diseases (AD). Therefore, it is of interest to screen AChE with the CNS-BBB database. An AChE enzyme is a member of hydrolase family is activated by acetylcholine (ACh), so, targeting the AChE enzyme with the potential inhibitor may block the binding of the ACh. In this study we carried out virtual screening of drug-like molecules from Chemical Diversity Database particularly CNS-BBB compounds, to identify potential inhibitors using Glide docking program...
2018: Bioinformation
Haijun Wang, Guobin Song, Haoyu Chuang, Chengdi Chiu, Ahmed Abdelmaksoud, Youfan Ye, Lei Zhao
Fibrosis is formed after injury in most of the organs as a common and complex response that profoundly affects regeneration of damaged tissue. In central nervous system (CNS), glial scar grows as a major physical and chemical barrier against regeneration of neurons as it forms dense isolation and creates an inhibitory environment, resulting in limitation of optimal neural function and permanent deficits of human body. In neurological damages, glial scar is mainly attributed to the activation of resident astrocytes which surrounds the lesion core and walls off intact neurons...
January 2018: International Journal of Immunopathology and Pharmacology
Pingyuan Wang, Jia Zhou
Great success has been achieved in small molecule drug discovery programs, making extraordinary contributions for human health, especially in targeted therapy. Taking anticancer drug discovery as an example, small molecules traditionally inhibit the target protein enzyme activities and induce cancer cell apoptosis through the target binding. However, the target protein within tumor cells often recovers its activities, leading to acquired drug-resistance through the overexpression of the target protein or the generation of new mutations in the target protein [1]...
October 9, 2018: Current Topics in Medicinal Chemistry
Kustrimovic Natasa, Marino Franca, Marco Cosentino
Parkinson's disease (PD) is the second most common neurodegenerative disorder among elderly population, and it is depicted by the degeneration of dopaminergic neurons in the midbrain which is progressive. Up to the present time, the precise cause remains ill-defined and the mechanism of neurons death indeterminate. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidences have been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD...
October 9, 2018: Current Medicinal Chemistry
Malte Borggrewe, Corien Grit, Wilfred F A Den Dunnen, Saskia M Burm, Jeffrey J Bajramovic, Randolph J Noelle, Bart J L Eggen, Jon D Laman
V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA) is a negative checkpoint regulator (NCR) involved in inhibition of T cell-mediated immunity. Expression changes of other NCRs (PD-1, PD-L1/L2, CTLA-4) during inflammation of the central nervous system (CNS) were previously demonstrated, but VISTA expression in the CNS has not yet been explored. Here, we report that in the human and mouse CNS, VISTA is most abundantly expressed by microglia, and to lower levels by endothelial cells...
October 11, 2018: Glia
Sherrie L Aspinall, Sydney P Springer, Xinhua Zhao, Francesca E Cunningham, Carolyn T Thorpe, Todd P Semla, Ronald I Shorr, Joseph T Hanlon
OBJECTIVES: To examine the association between central nervous system (CNS) medication dosage burden and risk of serious falls, including hip fractures, in individuals with a history of a recent fall. DESIGN: Nested case-control study. SETTING: Veterans Health Administration (VHA) Community Living Centers (CLCs). PARTICIPANTS: CLC residents aged 65 and older with a history of a fall or hip fracture in the year before a CLC admission between July 1, 2005, and June 30, 2009...
October 11, 2018: Journal of the American Geriatrics Society
Suguru Tamura, Keisuke Kawamoto, Hiroaki Miyoshi, Takaharu Suzuki, Takayuki Katagiri, Takuya Kasami, Hiroki Nemoto, Shukuko Miyakoshi, Hironori Kobayashi, Yasuhiko Shibasaki, Masayoshi Masuko, Kengo Takeuchi, Koichi Ohshima, Hirohito Sone, Jun Takizawa
Erdheim-Chester disease (ECD), a rare form of non-Langerhans cell histiocytosis, is characterized by the infiltration of foamy CD68+ and CD1a- histiocytes into multiple organ systems. Central nervous system (CNS) involvement has recently been reported to be a poor prognostic factor when treating ECD with interferon alpha. We report the case of a 66-year-old Japanese patient with ECD involving the CNS who harbored the BRAF V600E mutation and also concomitantly developed polycythemia vera with the JAK2 V617F mutation...
October 10, 2018: Journal of Clinical and Experimental Hematopathology: JCEH
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