114,105 results match your criteria CNS & Neurological Disorders - Drug Targets [Journal]


Successful use of an immune checkpoint inhibitor in a patient with myasthenia gravis in remission.

Muscle Nerve 2019 Apr 24. Epub 2019 Apr 24.

Department of Medicine IV, Hematology and Oncology, University of Halle.

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http://dx.doi.org/10.1002/mus.26495DOI Listing

ACYLOXYACYL HYDROLASE MODULATES DEPRESSIVE-LIKE BEHAVIORS THROUGH ARYL HYDROCARBON RECEPTOR.

Am J Physiol Regul Integr Comp Physiol 2019 Apr 24. Epub 2019 Apr 24.

Urology, Northwestern University, United States.

Corticotropin-releasing factor (CRF) regulates stress responses, and aberrant CRF signals are associated with depressive disorders. expression is responsive to arachidonic acid (AA), where CRF is released from the hypothalamic paraventricular nucleus (PVN) to initiate the hypothalamic-pituitary-adrenal axis, culminating in glucocorticoid stress hormone release. Despite this biologic and clinical significance, regulation is unclear. Read More

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http://dx.doi.org/10.1152/ajpregu.00029.2019DOI Listing

Impact of introduction of non-invasive prenatal testing on uptake of genetic testing in fetuses with central nervous system anomalies.

Prenat Diagn 2019 Apr 24. Epub 2019 Apr 24.

Department of Obstetrics and Gynaecology, Mount Sinai Hospital and University of Toronto, Toronto, Canada.

Objective: To evaluate the impact of introduction of non-invasive prenatal testing (NIPT) on the uptake of invasive testing in pregnancies complicated by fetal central nervous system (CNS) anomalies.

Methods: Retrospective review of all singleton pregnancies complicated by fetal CNS anomalies seen at a single tertiary center between 2010 and 2017. Cases who had undergone invasive testing or NIPT prior to the diagnosis of the CNS anomaly were excluded. Read More

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http://dx.doi.org/10.1002/pd.5466DOI Listing

Evolving evidences of calreticulin as a pharmacological target in neurological disorders.

ACS Chem Neurosci 2019 Apr 24. Epub 2019 Apr 24.

Calreticulin (CALR), a lectin-like ER chaperone, was initially known only for its house-keeping function, but today it is recognized for many versatile roles in different compartments of a cell. Apart from canonical roles in protein folding and calcium homeostasis it performs a variety of non-canonical roles, majorly in CNS development. In past, studies have linked Calreticulin with various other biological components which are detrimental in deciding the fate of neurons. Read More

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http://pubs.acs.org/doi/10.1021/acschemneuro.9b00158
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http://dx.doi.org/10.1021/acschemneuro.9b00158DOI Listing
April 2019
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A five-CpG signature of microRNA methylation in non-G-CIMP glioblastoma.

CNS Neurosci Ther 2019 Apr 23. Epub 2019 Apr 23.

Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Air Force Medical University, Xi'an, China.

Aims: DNA methylation has been found to regulate microRNAs (miRNAs) expression, but the prognostic value of miRNA-related DNA methylation aberration remained largely elusive in cancers including glioblastomas (GBMs). This study aimed to investigate the clinical and biological feature of miRNA methylation in GBMs of non-glioma-CpG island methylator phenotype (non-G-CIMP).

Methods: Prognostic miRNA methylation loci were analyzed, with TCGA and Rennes cohort as training sets, and independent datasets of GBMs and low-grade gliomas (LGGs) were obtained as validation sets. Read More

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http://dx.doi.org/10.1111/cns.13133DOI Listing

Helminths products directly modulate T cells that mediate experimental autoimmune encephalomyelitis.

Eur J Immunol 2019 Apr 23. Epub 2019 Apr 23.

School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.

Infection with helminths can protect against the development of autoimmune diseases and this has been associated with induction of anti-inflammatory innate immune responses and regulatory T cells. Here we demonstrate that helminth-derived products can directly target T cells, especially IL-17-secreting γδ T cells that play a key pathogenic role in CNS autoimmune disease. This article is protected by copyright. Read More

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http://dx.doi.org/10.1002/eji.201948147DOI Listing

Brain biopsy in suspected non-neoplastic neurological disease.

Acta Neurochir (Wien) 2019 Apr 23. Epub 2019 Apr 23.

Neuropathology Unit, Hospital de Santo Antonio, Centro Hospitalar e Universitario do Porto, Porto, Portugal.

Brain biopsy has a well-established role in the diagnosis of CNS neoplasia. Nevertheless, despite being essential for the diagnosis of some benign neurological diseases, little consensus exists regarding its indications for disease diagnosis and patient orientation. Our aim was to assess brain biopsy diagnostic yield in patients with neurological deterioration of unknown etiology, to identify the clinical characteristics associated with an increased likelihood of achieving a diagnostic biopsy as well as the characteristics linked to a particular diagnosis. Read More

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http://dx.doi.org/10.1007/s00701-019-03910-8DOI Listing

A novel mouse model of adult T-cell leukemia cell invasion into the spinal cord.

Animal Model Exp Med 2019 Mar 29;2(1):64-67. Epub 2019 Jan 29.

Department of Veterinary Microanatomy School of Veterinary Medicine Rakuno Gakuen University Ebetsu Hokkaido Japan.

Adult T-cell leukemia (ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection, and 10%-25% of patients show central nervous system (CNS) involvement. CNS involvement significantly reduces survival and there are no effective treatments for CNS involvement. Therefore, an appropriate animal model is required to evaluate the inhibitory effects of novel drugs on the progression of ATL with CNS involvement. Read More

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http://dx.doi.org/10.1002/ame2.12053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431123PMC

Inflammasomes in neuroinflammatory and neurodegenerative diseases.

EMBO Mol Med 2019 Apr 23. Epub 2019 Apr 23.

VIB Center for Inflammation Research, Ghent, Belgium

Neuroinflammation and neurodegeneration often result from the aberrant deposition of aggregated host proteins, including amyloid-β, α-synuclein, and prions, that can activate inflammasomes. Inflammasomes function as intracellular sensors of both microbial pathogens and foreign as well as host-derived danger signals. Upon activation, they induce an innate immune response by secreting the inflammatory cytokines interleukin (IL)-1β and IL-18, and additionally by inducing pyroptosis, a lytic cell death mode that releases additional inflammatory mediators. Read More

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http://dx.doi.org/10.15252/emmm.201810248DOI Listing

Molybdenum disulfide nanoflowers mediated anti-inflammation macrophage modulation for spinal cord injury treatment.

J Colloid Interface Sci 2019 Apr 16;549:50-62. Epub 2019 Apr 16.

The First Affiliated Hospital, Biomedical Translational Research Institute, Jinan University, Guangzhou 510632, PR China. Electronic address:

Spinal cord injury (SCI) can cause locomotor dysfunctions and sensory deficits. Evidence shows that functional nanodrugs can regulate macrophage polarization and promote anti-inflammatory cytokine expression, which is feasible in SCI immunotherapeutic treatments. Molybdenum disulfide (MoS) nanomaterials have garnered great attention as potential carriers for therapeutic payload. Read More

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http://dx.doi.org/10.1016/j.jcis.2019.04.047DOI Listing

Sarcocystis species identification in cattle hearts destined to human consumption in southern Brazil.

Vet Parasitol Reg Stud Reports 2018 Dec 5;14:94-98. Epub 2018 Sep 5.

Laboratório de Doenças Parasitárias, prédio 44, sala 5149, Universidade Federal de Santa Maria (UFSM), Camobi, Santa Maria, RS 97105-900, Brazil.

Sarcocystis spp. are ubiquitous protozoan parasites that can form cysts in striated muscle and CNS of cattle. Cattle hearts are commonly infected by microscopic sarcocysts. Read More

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http://dx.doi.org/10.1016/j.vprsr.2018.09.002DOI Listing
December 2018

The Role of p.Ser1105Ser (in Gene) and p.Arg548Leu (in Gene) with Disease Status of Vietnamese Patients with Congenital Nephrotic Syndrome: Benign or Pathogenic?

Medicina (Kaunas) 2019 Apr 12;55(4). Epub 2019 Apr 12.

L'Hôpital Français de Hanoi, Ministry of Health, 1, Phuong Mai str., Dongda, Hanoi 100000, Vietnam.

: Congenital nephrotic syndrome (CNS), a genetic disease caused by mutations in genes on autosomes, usually occurs in the first three months after birth. A number of genetic mutations in genes, which encode for the components of the glomerular filtration barrier have been identified. We investigated mutations in , , , and genes that relate to the disease in Vietnamese patients. Read More

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http://dx.doi.org/10.3390/medicina55040102DOI Listing

Oxidative Stress: A Key Modulator in Neurodegenerative Diseases.

Molecules 2019 Apr 22;24(8). Epub 2019 Apr 22.

Nucleic Acids Research Lab, Department of Chemistry, University of Delhi (North Campus), Delhi 110007, India.

Oxidative stress is proposed as a regulatory element in ageing and various neurological disorders. The excess of oxidants causes a reduction of antioxidants, which in turn produce an oxidation-reduction imbalance in organisms. Paucity of the antioxidant system generates oxidative-stress, characterized by elevated levels of reactive species (oxygen, hydroxyl free radical, and so on). Read More

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http://dx.doi.org/10.3390/molecules24081583DOI Listing

The Effects of a Bacterial Endotoxin on Behavior and Sensory-CNS-Motor Circuits in .

Insects 2019 Apr 22;10(4). Epub 2019 Apr 22.

Department of Biology, University of Kentucky, Lexington, KY 40506-0225, USA.

The effect of bacterial sepsis on animal behavior and physiology is complex due to direct and indirect actions. The most common form of bacterial sepsis in humans is from gram-negative bacterial strains. The endotoxin (lipopolysaccharide, LPS) and/or associated peptidoglycans from the bacteria are the key agents to induce an immune response, which then produces a cascade of immunological consequences. Read More

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http://dx.doi.org/10.3390/insects10040115DOI Listing

Administration of Vancomycin at High Doses in Patients with Post Neurosurgical Meningitis: A Comprehensive Comparison between Continuous Infusion and Intermittent Infusion.

Iran J Pharm Res 2018 ;17(Suppl2):195-205

Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Poor penetration of vancomycin into Central Nervous System (CNS) can lead to treatment failure. The aim of this study was to evaluate and compare CSF concentration and serum pharmacokinetics of high dose vancomycin by continuous infusion intermittent infusion in post neurosurgical meningitis patients. Twenty patients were divided into two groups. Read More

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January 2018

P300 values in patients diagnosed with primary Sjogren syndrome.

Somatosens Mot Res 2019 Apr 23:1-5. Epub 2019 Apr 23.

a Department of Neurology , Diskapi Yildirim Beyazit Egitim ve Arastirma Hastanesi , Ankara , Turkey.

Purpose: Primary Sjogren syndrome (PSS) is an autoimmune disease characterized by symptoms of a dry mouth and eyes, in which other organs and systems are widely involved. Central nervous system (CNS) involvement in PSS is reported in a wide range between 2.5-60%. Read More

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http://dx.doi.org/10.1080/08990220.2019.1604333DOI Listing

Rilpivirine as a potential candidate for the treatment of HIV-associated neurocognitive disorders (HAND).

J Mol Histol 2019 Apr 22. Epub 2019 Apr 22.

Catalysis and Peptide Research Unit, University of KwaZulu-Natal, Westville Campus, E-block, 6th floor, Room E1-06-016, Durban, South Africa.

As the HIV epidemic continues to contribute to global morbidity and mortality, the prevalence of HIV-associated neurological disorders (HAND) also continues to be a major concern in infected individuals, despite the widespread use of combination antiretroviral therapy. Therefore, current antiretroviral drugs should be able to reach therapeutic levels in the brain for the treatment of HAND. The brain distribution of the next-generation non-nucleoside reverse transcriptase inhibitor, rilpivirine (RPV) was investigated in healthy female Sprague-Dawley (SD) rats. Read More

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http://link.springer.com/10.1007/s10735-019-09826-y
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http://dx.doi.org/10.1007/s10735-019-09826-yDOI Listing
April 2019
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Dopaminergic Therapeutics in Multiple Sclerosis: Focus on Th17-Cell Functions.

J Neuroimmune Pharmacol 2019 Apr 23. Epub 2019 Apr 23.

Laboratory of Clinical Immunology, National Research Center Institute of Immunology of the Federal Medical-Biological Agency, 115478, Moscow, Russia.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with an autoimmune mechanism of development. Currently, one of the most promising directions in the study of MS pathogenesis are the neuroimmune interactions. Dopamine is one of the key neurotransmitters in CNS. Read More

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http://dx.doi.org/10.1007/s11481-019-09852-3DOI Listing

Blood vessels guide Schwann cell migration in the adult demyelinated CNS through Eph/ephrin signaling.

Acta Neuropathol 2019 Apr 22. Epub 2019 Apr 22.

Institut du Cerveau et de la Moelle Epinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM, U1127; CNRS, UMR 7225; Sorbonne Universités, Université Pierre et Marie Curie Paris 06, UM-75, Paris, France.

Schwann cells (SC) enter the central nervous system (CNS) in pathophysiological conditions. However, how SC invade the CNS to remyelinate central axons remains undetermined. We studied SC migratory behavior ex vivo and in vivo after exogenous transplantation in the demyelinated spinal cord. Read More

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http://dx.doi.org/10.1007/s00401-019-02011-1DOI Listing

Safety and Feasibility of Magnetic Resonance Imaging Simulation for Radiation Treatment Planning in Pediatric Patients: A Single Institution Experience.

Adv Radiat Oncol 2019 Apr-Jun;4(2):362-366. Epub 2018 Dec 21.

Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: This study aimed to report on the safety, feasibility, and workflow of using magnetic resonance imaging (MRI) simulation, while immobilized in the treatment position, for radiation therapy treatment planning in the pediatric population.

Methods And Materials: Between May and December 2017, 10 pediatric patients completed both MRI and computed tomography imaging simulation in treatment immobilization for radiation therapy planning for central nervous system disease. We report our initial institutional experience and workflow of the use of MRI simulation in immobilization for treatment planning in this population. Read More

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http://dx.doi.org/10.1016/j.adro.2018.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460291PMC
December 2018

Retinal alterations in a pre-clinical model of an autism spectrum disorder.

Mol Autism 2019 15;10:19. Epub 2019 Apr 15.

3Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP 05508-000 Brazil.

Background: Autism spectrum disorders (ASD) affect around 1.5% of people worldwide. Symptoms start around age 2, when children fail to maintain eye contact and to develop speech and other forms of communication. Read More

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http://dx.doi.org/10.1186/s13229-019-0270-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466731PMC

Multiple subacute bilateral cerebral infarcts in a 9-year-old Nigerian male: a case of childhood primary angiitis of the central nervous system.

Pan Afr Med J 2018 10;31:99. Epub 2018 Oct 10.

Children's Emergency Room (CHER), Ward 12 (children's in-patient ward) and the Paediatric Neurology Clinic, Federal Medical Centre, Owerri, Nigeria.

A Primary Angiitis of the Central Nervous System (PACNS) is ill-defined, complex and rare in children. Clinical presentation is variable, diagnosis is challenging and it is life-threatening but treatable. The index case is a 9-year old male who presented with progressively slurred speech, progressive weakness of the limbs, hemifacial weakness and vomiting. Read More

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http://dx.doi.org/10.11604/pamj.2018.31.99.13898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462305PMC
October 2018

Preoperative Sleep Disturbance Exaggerates Surgery-Induced Neuroinflammation and Neuronal Damage in Aged Mice.

Mediators Inflamm 2019 18;2019:8301725. Epub 2019 Mar 18.

Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.

Postoperative cognitive dysfunction (POCD) is defined as new cognitive impairment (memory impairment and impaired performance) after surgery, especially in aged patients. Sleep disturbance is a common phenomenon before surgery that has been increasingly thought to affect patient recovery. However, little is known about the functional impact of preoperative sleep disturbance on POCD. Read More

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http://dx.doi.org/10.1155/2019/8301725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442479PMC

Effects of Epacadostat on Brain Extracellular Fluid Concentrations of Serotonin -- An Intracerebral Microdialysis Study in Sprague-Dawley Rats.

Drug Metab Dispos 2019 Apr 22. Epub 2019 Apr 22.

Incyte.

Epacadostat (EPAC) is an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor that has been examined in multiple clinical trials. The substrate for IDO1 is tryptophan and there is a theoretical concern that inhibition of IDO1 may increase the concentrations of tryptophan and subsequently serotonin, potentially leading to serotonin syndrome (SS). The objective of this study was to evaluate the effect of EPAC, either alone or with linezolid, a monoamine oxidase inhibitor (MAOI), on brain ECF concentrations of serotonin in rats, using microdialysis. Read More

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http://dx.doi.org/10.1124/dmd.118.084053DOI Listing

A neural signature of pattern separation in the monkey hippocampus.

Proc Natl Acad Sci U S A 2019 Apr 22. Epub 2019 Apr 22.

Center for Neural Science, New York University, New York, NY 10003

The CA3 and dentate gyrus (DG) regions of the hippocampus are considered key for disambiguating sensory inputs from similar experiences in memory, a process termed pattern separation. The neural mechanisms underlying pattern separation, however, have been difficult to compare across species: rodents offer robust recording methods with less human-centric tasks, while humans provide complex behavior with less recording potential. To overcome these limitations, we trained monkeys to perform a visual pattern separation task similar to those used in humans while recording activity from single CA3/DG neurons. Read More

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http://dx.doi.org/10.1073/pnas.1900804116DOI Listing
April 2019
1 Read

Sex-specific Tau methylation patterns and synaptic transcriptional alterations are associated with neural vulnerability during chronic neuroinflammation.

J Autoimmun 2019 Apr 19. Epub 2019 Apr 19.

Department of Neurology and Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, 94158, USA.

The molecular events underlying the transition from initial inflammatory flares to the progressive phase of multiple sclerosis (MS) remain poorly understood. Here, we report that the microtubule-associated protein (MAP) Tau exerts a gender-specific protective function on disease progression in the MS model experimental autoimmune encephalomyelitis (EAE). A detailed investigation of the autoimmune response in Tau-deficient mice excluded a strong immunoregulatory role for Tau, suggesting that its beneficial effects are presumably exerted within the central nervous system (CNS). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S08968411193001
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http://dx.doi.org/10.1016/j.jaut.2019.04.003DOI Listing
April 2019
2 Reads

Mechanisms of extramedullary relapse in acute lymphoblastic leukemia: Reconciling biological concepts and clinical issues.

Blood Rev 2019 Apr 17. Epub 2019 Apr 17.

CNRS, IGDR (Institut de Génétique et Développement de Rennes), Univ Rennes, UMR 6290, Rennes F-35000, France; Pediatric Hematology Department, University Hospital, Rennes, France. Electronic address:

Long-term survival rates in childhood acute lymphoblastic leukemia (ALL) are currently above 85% due to huge improvements in treatment. However, 15-20% of children still experience relapses. Relapses can either occur in the bone marrow or at extramedullary sites, such as gonads or the central nervous system (CNS), formerly referred to as ALL-blast sanctuaries. Read More

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http://dx.doi.org/10.1016/j.blre.2019.04.003DOI Listing

Sanctuary site central nervous system relapse-refractory DLBCL responding to nivolumab and lenalidomide.

Oral Oncol 2019 Apr 19. Epub 2019 Apr 19.

Department of Pathology, Gujarat Cancer Research Institute, Gujarat, Ahmedabad, India.

Despite improvement in survival in diffuse large B-cell lymphoma (DLBCL) with the introduction of rituximab, central nervous system (CNS) relapse continues to represent a clinical challenge. In diffuse large B-cell lymphoma (DLBCL), the incidence of CNS relapse is only ∼5% in unselected cohorts. Immunotherapy is the treatment that either boosts the patient's own immune system or uses man-made versions of the normal parts of the immune system to kill lymphoma cells or slow their growth. Read More

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http://dx.doi.org/10.1016/j.oraloncology.2019.04.010DOI Listing
April 2019
3.607 Impact Factor

The role of dopamine D3 receptors in the mechanism of action of cariprazine.

CNS Spectr 2019 Apr 23:1-9. Epub 2019 Apr 23.

Department of Pharmacological and Biomolecular Sciences,Università degli Studi di Milano,Milan,Italy.

Cariprazine is a new atypical antipsychotic drug (APD) with a unique pharmacodynamic profile, different from both typical and atypical APDs. Specifically, cariprazine acts as a partial agonist at the dopamine (DA) D2 and D3 receptors and serotonin 5-HT1A receptors, and as an antagonist at the 5-HT2B receptors. Moreover, it shows moderate affinities for adrenergic, histaminergic, and cholinergic receptors that are involved in mediating the side effects characteristic of typical APDs. Read More

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http://dx.doi.org/10.1017/S109285291900083XDOI Listing

Emotional distress, brain functioning, and biobehavioral processes in cancer patients: a neuroimaging review and future directions.

CNS Spectr 2019 Apr 23:1-22. Epub 2019 Apr 23.

Psycho-oncology, Champalimaud Clinical and Research Center,Champalimaud Foundation,Lisbon,Portugal.

Despite emerging evidence that distress and adversity can contribute to negative health outcomes in cancer, little is known about the brain networks, regions, or circuits that can contribute to individual differences in affect/distress states and health outcomes in treated cancer patients. To understand the state-of-the-science in this regard, we reviewed neuroimaging studies with cancer patients that examined the associations between negative affect (distress) and changes in the metabolism or structure of brain regions. Cancer patients showed changes in function and/or structure of key brain regions such as the prefrontal cortex, thalamus, amygdala, hippocampus, cingulate cortex (mainly subgenual area), hypothalamus, basal ganglia (striatum and caudate), and insula, which are associated with greater anxiety, depression, posttraumatic stress disorder (PTSD) symptoms, and distress. Read More

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http://dx.doi.org/10.1017/S1092852918001621DOI Listing

Clinical implications of directly switching antidepressants in well-treated depressed patients with treatment-emergent sexual dysfunction: a comparison between vortioxetine and escitalopram.

CNS Spectr 2019 Apr 23:1-14. Epub 2019 Apr 23.

Department of Psychiatry & Neurobehavioral Sciences,University of Virginia, Charlottesville, Virginia,USA.

Objective: The objective of this work was to describe treatment-emergent sexual dysfunction (TESD) and tolerability following a switch from selective serotonin reuptake inhibitor (SSRI: citalopram, paroxetine, or sertraline) monotherapy to vortioxetine or escitalopram monotherapy in adults with well-treated major depressive disorder (MDD) and SSRI-induced sexual dysfunction.

Methods: Data were analyzed from the primary study, an 8-week, randomized, double-blind, head-to-head study in which participants with well-treated depressive symptoms but experiencing TESD with SSRIs were directly switched to flexible doses (10/20 mg) of vortioxetine or escitalopram. Sexual functioning was assessed by the Changes in Sexual Functioning Questionnaire-14 (CSFQ-14), efficacy by the Montgomery-Åsberg Depression Rating Scale scores (MADRS) and Clinicians Global Impression of Severity/Improvement (CGI-S/CGI-I), and tolerability by adverse events. Read More

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http://dx.doi.org/10.1017/S1092852919000750DOI Listing

A different aspect of the unexpected death of Mozart at the age of 35 years.

CNS Spectr 2019 Apr 23:1-4. Epub 2019 Apr 23.

President of Brandenburg Medical School - Theodor Fontane,Campus Neuruppin, Germany and Senior Professor of Health Services Research at Witten/Herdecke University,Germany.

The cause of the early death of Wolfgang Amadeus Mozart (1756-1791) at the age of 35 has been the source of much discussion in the medical community. Investigators attributed to Mozart nearly 150 different medical diagnoses. However, the neurosurgical aspect of the early death of Mozart has yet to be well-analyzed, and this subject was investigated herein. Read More

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https://www.cambridge.org/core/product/identifier/S109285291
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http://dx.doi.org/10.1017/S1092852918001736DOI Listing
April 2019
1 Read

Research progress in the biological activities of 3,4,5-trimethoxycinnamic acid (TMCA) derivatives.

Eur J Med Chem 2019 Apr 6;173:213-227. Epub 2019 Apr 6.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, 229 Taibai Road, Xi'an, 710069, China. Electronic address:

TMCA (3,4,5-trimethoxycinnamic acid) ester and amide are privileged structural scaffolds in drug discovery which are widely distributed in natural products and consequently produced diverse therapeutically relevant pharmacological functions. Owing to the potential of TMCA ester and amide analogues as therapeutic agents, researches on chemical syntheses and modifications have been carried out to drug-like candidates with broad range of medicinal properties such as antitumor, antiviral, CNS (central nervous system) agents, antimicrobial, anti-inflammatory and hematologic agents for a long time. At the same time, SAR (structure-activity relationship) studies have draw greater attention among medicinal chemists, and many of the lead compounds were derived for various disease targets. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.009DOI Listing
April 2019
2 Reads

Functional microglia neurotransmitters in amyotrophic lateral sclerosis.

Semin Cell Dev Biol 2019 Apr 19. Epub 2019 Apr 19.

Fondazione Santa Lucia IRCCS, Preclinical Neuroscience, Via Del Fosso di Fiorano 64, 00143, Rome, Italy. Electronic address:

Today neuroscience is dominated by the perspective that microglia are essential elements in any integrated view of the nervous system. A number of different neuroinflammatory conditions affect the CNS where microglia involvement, and particularly microgliosis, is not only a prominent feature, but also a pathogenic key mechanism of disease. On the other side, microglia can also constitute an important trigger of neuronal protection during neurodegenerative disorders. Read More

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http://dx.doi.org/10.1016/j.semcdb.2019.04.014DOI Listing
April 2019
1 Read

Discovery of Potent, Selective, and Brain-Penetrant 1 Η-Pyrazol-5-yl-1Η -pyrrolo[2,3- b]pyridines as Anaplastic Lymphoma Kinase (ALK) Inhibitors.

J Med Chem 2019 Apr 22. Epub 2019 Apr 22.

Anaplastic lymphoma kinase (ALK), a member of the receptor tyrosine kinase family, is predominantly expressed in the brain and implicated in neuronal development and cognition. However, the detailed function of ALK in the central nervous system (CNS) is still unclear. To elucidate the role of ALK in the CNS, it was necessary to discover a potent, selective, and brain-penetrant ALK inhibitor. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.8b01630DOI Listing

Pediatric guanfacine exposures reported to the National Poison Data System, 2000-2016.

Clin Toxicol (Phila) 2019 Apr 22:1-7. Epub 2019 Apr 22.

b Center for Health Equity and Quality Research, UF Health - Jacksonville , Jacksonville , FL , USA.

Introduction: The purpose of this study was to characterize the frequency, reasons for exposure, clinical manifestations, treatments, duration of effects, and medical outcomes of pediatric guanfacine exposures reported to the National Poison Data System (NPDS) from 2000 to 2016.

Methods: Data extracted from poison control center call records for pediatric (0-5 years, 6-12 years, and 13-19 years), single-substance guanfacine ingestions reported to NPDS between 2000 and 2016 was retrospectively analyzed.

Results: A total of 10927 cases were identified for analysis. Read More

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http://dx.doi.org/10.1080/15563650.2019.1605076DOI Listing
April 2019
1 Read

Identification of novel Adenosine Deaminase 2 gene variants and varied clinical phenotype in pediatric vasculitis.

Arthritis Rheumatol 2019 Apr 22. Epub 2019 Apr 22.

BC Children's Hospital Research Institute, BC Children's Hospital, Vancouver, BC, Canada.

Objectives: Individuals with deficiency of adenosine deaminase 2 (DADA2), a recently recognized autosomal recessive disease, present with various systemic vascular and inflammatory manifestations, often with early-onset age, or recurrent strokes. Their clinical features and histological findings overlap with those of childhood onset polyarteritis nodosa (PAN), a primary "idiopathic" systemic vasculitis. Despite similar clinical presentation, individuals with DADA2 may respond better to biologic therapy than traditional immunosuppression. Read More

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http://dx.doi.org/10.1002/art.40913DOI Listing

Microglia in the Neurovascular Unit: Blood-Brain Barrier-microglia Interactions After Central Nervous System Disorders.

Neuroscience 2019 May 6;405:55-67. Epub 2018 Jul 6.

Faculty of Biology, Medicine and Health, AV Hill Building, The University of Manchester, United Kingdom. Electronic address:

Over the past few decades, microglial cells have been regarded as the main executor of inflammation after acute and chronic central nervous system (CNS) disorders, responding rapidly to exogenous stimuli during acute trauma or infections, or signals released by cells undergoing cell death during conditions such as stroke, Alzheimer's disease (AD) and Parkinson's disease (PD). Barriers of the nervous system, and in particular the blood-brain barrier (BBB), play a key role in the normal physiological and cognitive functions of the brain. Being at the interface between the central and peripheral compartment, the BBB is regarded as a sensor of homeostasis, and any disruption within the brain or the systemic compartment triggers BBB dysfunction and neuroinflammation, both contributing to the pathogenesis of cerebrovascular disease. Read More

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http://dx.doi.org/10.1016/j.neuroscience.2018.06.046DOI Listing

Educational attainment of childhood cancer survivors: A systematic review.

Cancer Med 2019 Apr 21. Epub 2019 Apr 21.

Institute of Health & Society, Newcastle University, Newcastle upon Tyne, United Kingdom.

Background: Advances in treatment mean that most children diagnosed with cancer during childhood survive. Therefore, it is increasingly important to examine the long-term consequences of childhood cancer, including educational attainment. This systematic review investigated whether the educational attainment of childhood cancer survivors differ from the cancer-free population. Read More

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http://dx.doi.org/10.1002/cam4.2154DOI Listing
April 2019
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[Central nervous system atypical teratoid/rhabdoid tumor without loss of nuclear expression of INI1].

Arkh Patol 2019 ;81(2):36-42

Acad. N.N. Burdenko National Medical Research Center of Neurosurgery, Ministry of Health of Russia, Moscow, Russia.

The paper describes a clinical case of atypical teratoid/rhabdoid tumor with preserved INI1 expression and SMARCA4 gene mutations in an 8-month-old girl. Genome-wide DNA methylation, hierarchical clustering, and next-generation sequencing were used to make a tumor diagnosis. However, BRG1 immunohistochemical examination may be recommended in the routine practice of diagnosis and study of childhood CNS malignant tumors. Read More

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http://dx.doi.org/10.17116/patol20198102136DOI Listing
January 2019
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Tau Protein and Zebrafish Models for Tau-Induced Neurodegeneration.

J Alzheimers Dis 2019 Apr 15. Epub 2019 Apr 15.

Clinical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.

Tauopathies are a specific type of slow and progressive neurodegeneration, which involves intracellular deposition of fibrillar material composed of abnormal hyperphosphorylation of the microtubule associated protein (MAP) tau. Despite many years of intensive research, our understanding of the molecular events that lead to neurodegeneration is far from complete. No effective therapeutic treatments have been defined, and questions surround the validity and utility of existing animal models. Read More

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http://dx.doi.org/10.3233/JAD-180917DOI Listing

A PET study in healthy subjects of brain exposure of C-labelled osimertinib - A drug intended for treatment of brain metastases in non-small cell lung cancer.

J Cereb Blood Flow Metab 2019 Apr 20:271678X19843776. Epub 2019 Apr 20.

1 Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.

Osimertinib is a tyrosine kinase inhibitor (TKI) of the mutated epidermal growth factor receptor (EGFRm) with observed efficacy in patients with brain metastases. Brain exposure and drug distribution in tumor regions are important criteria for evaluation and confirmation of CNS efficacy. The aim of this PET study was therefore to determine brain distribution and exposure of C-labelled osimertinib administered intravenously in subjects with an intact blood-brain barrier. Read More

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http://dx.doi.org/10.1177/0271678X19843776DOI Listing

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2B6 and Efavirenz-containing Antiretroviral Therapy.

Clin Pharmacol Ther 2019 Apr 21. Epub 2019 Apr 21.

Department of Internal Medicine, Meharry Medical College School of Medicine, Nashville, TN, USA.

The human immunodeficiency virus (HIV) type-1 non-nucleoside reverse transcriptase inhibitor, efavirenz, is widely used to treat HIV-1 infection. Efavirenz is predominantly metabolized into inactive metabolites by CYP2B6, and patients with certain CYP2B6 genetic variants may be at increased risk for adverse effects, particularly central nervous system toxicity and treatment discontinuation. We summarize the evidence from the literature and provide therapeutic recommendations for efavirenz prescribing based on CYP2B6 genotypes. Read More

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http://dx.doi.org/10.1002/cpt.1477DOI Listing

The Dual Role of HIV-1 gp120 V3 Loop-Induced Autophagy in the Survival and Apoptosis of the Primary Rat Hippocampal Neurons.

Neurochem Res 2019 Apr 20. Epub 2019 Apr 20.

Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, Guangdong Province, China.

HIV-1 gp120, an important subunit of the envelope spikes that decorate the surface of virions, is known to play a vital role in neuronal injury during HIV-1-associated neurocognitive disorder (HAND), although the pathological mechanism is not fully understood. Our previous studies have suggested that the V3 loop of HIV-1 gp120 (HIV-1 gp120 V3 loop) can induce neuronal apoptosis in the hippocampus, resulting in impairment in spatial learning and memory in Sprague-Dawley (SD) rats. In this study, we demonstrated that autophagy was significantly increased in rat primary hippocampal neurons in response to treatment of HIV-1 gp120 V3 loop. Read More

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http://dx.doi.org/10.1007/s11064-019-02788-3DOI Listing

Complex encephalopathy arising from the combination of opioids and gabapentin.

BMJ Case Rep 2019 Apr 20;12(4). Epub 2019 Apr 20.

Allegiance Health, Jackson, Michigan, USA.

The interactions between opioids and gabapentin are more clinically relevant than ever. Prescriptions dispensed for gabapentin increased from 39 million in 2012 to 64 million in 2018 in the USA and are ever increasing. Authors present a challenging case of these interactions. Read More

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http://dx.doi.org/10.1136/bcr-2018-228354DOI Listing
April 2019
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A retrospective study on clinical manifestations of neonates with FXIII-A deficiency.

Blood Cells Mol Dis 2019 Apr 11;77:78-81. Epub 2019 Apr 11.

Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

We assessed clinical presentations and the rate of central nervous system (CNS) bleeding in neonates with FXIIID who exhibited bleeding diathesis in the early days of their lives. A total of 27 neonates presented bleeding or abnormal clinical symptoms, diagnosed with FXIII deficiency were evaluated. Factor XIII concentrate was initiated as the first-line of treatment, and prophylactic therapy was given to all patients. Read More

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http://dx.doi.org/10.1016/j.bcmd.2019.04.006DOI Listing

Rewarding effects of 2-desoxypipradrol in mice.

Neurosci Lett 2019 Apr 18. Epub 2019 Apr 18.

Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi, 28159, Republic of Korea.

Desoxypipradrol (2-DPMP), a new psychoactive substance (NPS), acts as a norepinephrine-dopamine reuptake inhibitor (NDRI). NDRIs can be addictive due to their action mechanisms similar to cocaine and methamphetamine. However, there is a lack of scientific information regarding the exact dependency of 2-DPMP. Read More

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http://dx.doi.org/10.1016/j.neulet.2019.04.037DOI Listing

Association of opioid receptor gene polymorphisms with drinking severity and impulsivity related to alcohol use disorder in a Korean population.

CNS Neurosci Ther 2019 Apr 19. Epub 2019 Apr 19.

Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Aims: Recent evidence suggests that the opioid system is implicated in the pathophysiology of alcohol use disorder (AUD). We aimed to examine the genetic influence of opioid receptors on susceptibility to AUD and its clinical and psychological characteristics including harmful drinking behavior and various aspects of impulsivity in AUD patients.

Methods: Three μ-opioid receptor gene (OPRM1) variants and two κ-opioid receptor gene (OPRK1) variants were examined in 314 male patients with AUD and 324 male controls. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/cns.13138
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http://dx.doi.org/10.1111/cns.13138DOI Listing
April 2019
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Revisiting Tramadol: A Multi-Modal Agent for Pain Management.

Authors:
Ahmed Barakat

CNS Drugs 2019 Apr 19. Epub 2019 Apr 19.

Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt.

Tramadol-an atypical opioid analgesic-has a unique pharmacokinetic and pharmacodynamic profile, with opioidergic, noradrenergic, and serotonergic actions. Tramadol has long been used as a well-tolerated alternative to other drugs in moderate pain because of its opioidergic and monoaminergic activities. However, cumulative evidence has been gathered over the last few years that supports other likely mechanisms and uses of tramadol in pain management. Read More

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http://link.springer.com/10.1007/s40263-019-00623-5
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http://dx.doi.org/10.1007/s40263-019-00623-5DOI Listing
April 2019
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Peripheral and central nervous system distribution of the CGRP neutralizing antibody [I] galcanezumab in male rats.

Cephalalgia 2019 Apr 19:333102419844711. Epub 2019 Apr 19.

1 Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.

Objective: The objective of this investigation was to examine the distribution of galcanezumab and a control immunoglobulin 4 antibody containing the same constant regions as galcanezumab, into peripheral and central tissues.

Methods: Galcanezumab and a control immunoglobulin 4 antibody were radioiodinated with Iodine-125 to specific activities of 0.11 mCi/mg and 0. Read More

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http://journals.sagepub.com/doi/10.1177/0333102419844711
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http://dx.doi.org/10.1177/0333102419844711DOI Listing
April 2019
1 Read