111,859 results match your criteria CNS Melanoma


(Pyrrolo-pyridin-5-yl)benzamides: BBB permeable monoamine oxidase B inhibitors with neuroprotective effect on cortical neurons.

Eur J Med Chem 2018 Nov 13;162:793-809. Epub 2018 Nov 13.

Bulgarian Academy of Sciences, Institute of Organic Chemistry, Centre of Phytochemistry, Acad. G. Bonchev Str., Bl. 9, Sofia, 1113, Bulgaria.

An extensive study was performed to develop a series of (pyrrolo-pyridin-5-yl)benzamides as reversible MAO-B inhibitors. Compounds 14 (NTZ-2020, hMAO-B IC = 1.11 nM, K = 0. Read More

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November 2018
3 Reads

The unique spatial-temporal treatment failure patterns of adjuvant gefitinib therapy: A post-hoc analysis of the ADJUVANT trial (CTONG 1104).

J Thorac Oncol 2018 Dec 3. Epub 2018 Dec 3.

Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address:

Introduction: Adjuvant gefitinib therapy prolonged disease-free survival (DFS) in patients with resected early-stage epidermal growth factor receptor (EGFR)-mutation positive non-small cell lung cancer (NSCLC) in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized.

Methods: Overall, 222 stage N1-N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Read More

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December 2018
2 Reads

Isolation and identification of endogenous RFRP1 and RFRP3 in the mouse hypothalamus.

J Neuroendocrinol 2018 Dec 6:e12668. Epub 2018 Dec 6.

Department of Biological Functions of Food, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.

Although RFamide-related peptide (RFRP) preproprotein sequence is known in mice, until now the molecular structure of the mature, functional peptides processed from the target precursor molecule has not been determined. In the present study we purified endogenous RFRP1 and RFRP3 peptides from mouse hypothalamic tissue extracts using immunoaffinity column conjugated with specific antibodies against the mouse C-terminus of RFRP-1 and RFRP-3. Employing liquid chromatography coupled with mass spectrometry (LC-MS) we demonstrated, that RFRP1 consists of 15 and RFRP3 of 10 amino acid residues (ANKVPHSAANLPLRF-NH and SHFPSLPQRF-NH , respectively). Read More

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December 2018
1 Read

Construction and efficient dye adsorption of supramolecular hydrogels by cyclodextrin pseudorotaxane and clay.

Soft Matter 2018 Dec 6. Epub 2018 Dec 6.

College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. China. and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, P. R. China.

Supramolecular hydrogels, which are usually used to develop excellent smart soft materials, are widely applied in miscellaneous fields due to their inherent reversible properties, unique functions and mechanical properties. Compared with covalently linked hydrogels, supramolecular hydrogels have advantages of easy preparation, stimulus responsiveness and good biocompatibility. Herein, after threading amino-modified β-cyclodextrins onto poly(propyleneglycol)bis(2-amionopropylether) (PPG-NH2) chains, the resultant pseudorotaxanes non-covalently interacted with a clay nanosheet (CNS) matrix to construct supramolecular hydrogels bearing negative charges, and the mechanical properties of these hydrogels were positively correlated with the number of amino groups on the pseudorotaxane. Read More

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December 2018
1 Read

Endoplasmic reticulum stress is transmissible in vitro between cells of the central nervous system.

J Neurochem 2018 Dec 6. Epub 2018 Dec 6.

Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV.

Improper protein folding and trafficking are common pathological events in neurodegenerative diseases that result in the toxic accumulation of misfolded proteins within the lumen of the endoplasmic reticulum (ER). While low-level stimulation of the unfolded protein response (UPR) is protective, sustained UPR activation resulting from prolonged ER stress can promote neurotoxicity. The cell-autonomous mechanisms of the UPR have been extensively characterized. Read More

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December 2018

eQTL of KCNK2 regionally influences the brain sulcal widening: evidence from 15,597 UK Biobank participants with neuroimaging data.

Brain Struct Funct 2018 Dec 5. Epub 2018 Dec 5.

UNATI, Institut Joliot, CEA, Université Paris-Saclay, Neurospin, CEA Saclay, Neurospin Bâtiment 145, 91191, Gif-sur-Yvette Cedex, France.

The grey and white matter volumes are known to reduce with age. This cortical shrinkage is visible on magnetic resonance images and is conveniently identified by the increased volume of cerebrospinal fluid in the sulci between two gyri. Here, we replicated this finding using the UK Biobank dataset and studied the genetic influence on these cortical features of aging. Read More

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December 2018
1 Read

Hindbrain induction and patterning during early vertebrate development.

Cell Mol Life Sci 2018 Dec 5. Epub 2018 Dec 5.

Koret School of Veterinary Medicine, The Robert H Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, 76100, Rehovot, Israel.

The hindbrain is a key relay hub of the central nervous system (CNS), linking the bilaterally symmetric half-sides of lower and upper CNS centers via an extensive network of neural pathways. Dedicated neural assemblies within the hindbrain control many physiological processes, including respiration, blood pressure, motor coordination and different sensations. During early development, the hindbrain forms metameric segmented units known as rhombomeres along the antero-posterior (AP) axis of the nervous system. Read More

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December 2018

Role of Macrophage Dopamine Receptors in Mediating Cytokine Production: Implications for Neuroinflammation in the Context of HIV-Associated Neurocognitive Disorders.

J Neuroimmune Pharmacol 2018 Dec 5. Epub 2018 Dec 5.

Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA.

Despite the success of combination anti-retroviral therapy (cART), around 50% of HIV-infected individuals still display a variety of neuropathological and neurocognitive sequelae known as NeuroHIV. Current research suggests these effects are mediated by long-term changes in CNS function in response to chronic infection and inflammation, and not solely due to active viral replication. In the post-cART era, drug abuse is a major risk-factor for the development of NeuroHIV, and increases extracellular dopamine in the CNS. Read More

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December 2018
1 Read

Mitochondrial Electron Transport Chain Complex Dysfunction in MeCP2 Knock-Down Astrocytes: Protective Effects of Quercetin Hydrate.

J Mol Neurosci 2018 Dec 6. Epub 2018 Dec 6.

Division of Neurobiology, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.

Astrocytes play the central role in CNS metabolism to support neuronal functions. Mehyl-CpG-binding protein 2 (MeCP2) is the global transcription factor with differential expression in neuronal and non-neuronal cells. MeCP2 mutation and downstream detrimental effects have been reported in astrocytes also in MeCP2-associated neurodevelopmental disorder-Rett syndrome. Read More

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December 2018
5 Reads

Risdiplam distributes and increases SMN protein in both the central nervous system and peripheral organs.

Pharmacol Res Perspect 2018 Dec 29;6(6):e00447. Epub 2018 Nov 29.

Roche Pharma Research and Early Development Roche Innovation Center Basel Switzerland.

Spinal muscular atrophy (SMA) is a rare, inherited neuromuscular disease caused by deletion and/or mutation of the Survival of Motor Neuron 1 ( gene. A second gene, , produces low levels of functional SMN protein that are insufficient to fully compensate for the lack of . Risdiplam (RG7916; RO7034067) is an orally administered, small-molecule pre-mRNA splicing modifier that distributes into the central nervous system (CNS) and peripheral tissues. Read More

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December 2018
1 Read

Radiotherapy in Patients with Mycosis Fungoides and Central Nervous System Involvement.

Case Rep Oncol 2018 Sep-Dec;11(3):721-728. Epub 2018 Nov 12.

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

Background: Involvement of the central nervous system (CNS) by mycosis fungoides (MF) is rare; however, it portends a poor prognosis. While aggressive multimodality therapy may improve outcomes, the role of radiation therapy (RT) is not well defined.

Objectives: We sought to explore the efficacy of RT in the management of CNS involvement by MF. Read More

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November 2018

Radiology learning or teaching subject areas vs modalities: students' perspective and experience at Albaha University.

Adv Med Educ Pract 2018 8;9:791-799. Epub 2018 Nov 8.

Radiology Department, Faculty of Medicine, Albaha University, Albaha, Saudi Arabia,

Introduction: In radiology learning, most of the integrated schools address the subject area as a theme, and several imaging modalities describe the findings. A few schools handle the imaging modalities as a separate theme wherein many subject areas are discussed.

Purpose: The aim of this study was to identify the differences in student achievement in imaging course using the two learning approaches: integration within modalities under the subject area and integration within the subject area under imaging modalities. Read More

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November 2018

Treatment of Epstein-Barr virus associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation with intrathecal donor lymphocyte infusion.

Bone Marrow Transplant 2018 Dec 5. Epub 2018 Dec 5.

Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, 450008, Zhengzhou, China.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective measure for the treatment of hematological disease. With the progress and widespread use of allo-HSCT, Epstein-Barr virus (EBV) related central nervous system (CNS) diseases have gotten more and more attention because of its poor prognosis and overall survival. Since currently there is no standard treatment for patients with EBV-associated CNS diseases and reported therapies are heterogeneous with mixed results, we attempted to develop a novel therapeutic method. Read More

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December 2018
2 Reads

Non-nociceptive roles of opioids in the CNS: opioids' effects on neurogenesis, learning, memory and affect.

Nat Rev Neurosci 2018 Dec 5. Epub 2018 Dec 5.

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, Shirley and Stefan Hatos Center for Neuropharmacology, University of California, Los Angeles, CA, USA.

Mortality due to opioid use has grown to the point where, for the first time in history, opioid-related deaths exceed those caused by car accidents in many states in the United States. Changes in the prescribing of opioids for pain and the illicit use of fentanyl (and derivatives) have contributed to the current epidemic. Less known is the impact of opioids on hippocampal neurogenesis, the functional manipulation of which may improve the deleterious effects of opioid use. Read More

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December 2018
1 Read

Human pharmacology of positive GABA-A subtype-selective receptor modulators for the treatment of anxiety.

Acta Pharmacol Sin 2018 Dec 5. Epub 2018 Dec 5.

Centre for Human Drug Research, Leiden, 2333 CL, The Netherlands.

Anxiety disorders arise from disruptions among the highly interconnected circuits that normally serve to process the streams of potentially threatening stimuli. The resulting imbalance among these circuits can cause a fundamental misinterpretation of neural sensory information as threatening and can lead to the inappropriate emotional and behavioral responses observed in anxiety disorders. There is considerable preclinical evidence that the GABAergic system, in general, and its α2- and/or α5-subunit-containing GABA(A) receptor subtypes, in particular, are involved in the pathophysiology of anxiety disorders. Read More

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December 2018

Serotonin receptors of 5-HT2 type in the hypothalamic arcuate nuclei (ARC) positively regulate liver cytochrome P450 via stimulation of the growth hormone-releasing hormone - growth hormone (GHRH-GH) hormonal pathway.

Drug Metab Dispos 2018 Dec 5. Epub 2018 Dec 5.

Institute of Pharmacology, Polish Academy of Sciences

Our recent study carried out after local injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine into the arcuate nuclei (ARC) of the hypothalamus suggested a positive influence of the serotonergic innervation of the ARC on growth hormone secretion and growth hormone-dependent expression of cytochrome P450. The aim of our present study was to determine the effect of the activation of the 5-HT1 or 5-HT2 type receptors in the ARC on the expression and activity of cytochrome P450 in the liver of male rats. The serotonergic agonists 5-CT (5-carboxyamidotryptamine, a 5-HT1 type receptor agonist) or DOI (2,5-dimethoxy-4-iodoamphetamine, a 5-HT2 type receptor agonist) were injected into the ARC for 5 days. Read More

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December 2018
1 Read

Eradication of central nervous system leukemia of T-cell origin with a brain-permeable LSD1 inhibitor.

Clin Cancer Res 2018 Dec 5. Epub 2018 Dec 5.

Stem Cell Regulation, Jichi Medical University

Purpose: Lysine-specific demethylase 1 (LSD1) regulates several biological processes via the bifunctional modulation of enhancer functions. Recently, we reported that LSD1 overexpression is a founder abnormality of T-cell leukemogenesis and is maintained in fully transformed T-cell acute lymphoblastic leukemia (T-ALL) cells. On the basis of this finding, we attempted to develop novel LSD1 inhibitors effective for T-ALL with central nervous system (CNS) involvement. Read More

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December 2018

CNS phenotype in X linked Charcot- Marie-Tooth disease.

J Neurol Neurosurg Psychiatry 2018 Dec 5. Epub 2018 Dec 5.

MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, UK.

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December 2018

Persistent reduction in sialylation of cerebral glycoproteins following postnatal inflammatory exposure.

J Neuroinflammation 2018 Dec 5;15(1):336. Epub 2018 Dec 5.

Department of Paediatrics, Sainte-Justine Hospital Research Center, Université de Montréal, Montreal, H3T 1C5, QC, Canada.

Background: The extension of sepsis encompassing the preterm newborn's brain is often overlooked due to technical challenges in this highly vulnerable population, yet it leads to substantial long-term neurodevelopmental disabilities. In this study, we demonstrate how neonatal neuroinflammation following postnatal E. coli lipopolysaccharide (LPS) exposure in rat pups results in persistent reduction in sialylation of cerebral glycoproteins. Read More

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December 2018

Eomes-expressing T-helper cells as potential target of therapy in chronic neuroinflammation.

Authors:
Shinji Oki

Neurochem Int 2018 Nov 30. Epub 2018 Nov 30.

Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan. Electronic address:

Reserch progresses in understanding the pathogenicity of multiple sclerosis (MS) in the last couple of decade has enabled us to develop new drug entities available in the clinic. However, we still have not succeeded in preventing conversion from relapsing-remitting MS (RR-MS) to secondary progressive MS (SP-MS) and curing this intractable form of MS. Furthermore, diagnosis is usually retrospective and subjective, relying on gradual worsening of neurological signs/symptoms. Read More

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November 2018

Problematic Internet use two decades later: apps to wean us off apps.

Authors:
Elias Aboujaoude

CNS Spectr 2018 Oct 29:1-3. Epub 2018 Oct 29.

Department of Psychiatry and Behavioral Sciences,Stanford University School of Medicine,Stanford,California,USA.

Two decades of research into problematic Internet use have not yielded an established definition, much less an accepted treatment algorithm that is based on the psychopharmacological and psychotherapeutic interventions that have been tested. Meanwhile, technology-mediated tools that purport to curb unnecessary use of Internet-related technologies and the associated negative consequences are gaining in popularity, despite the lack of rigorous clinical trials into their efficacy and safety. Some popular new offerings that vary in browser, operating system and platform compatibility are reviewed. Read More

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October 2018

Do cognitive and neuropsychological functioning deficits coincide with hippocampal alteration during first-psychotic episode?

CNS Spectr 2018 Dec 3:1-7. Epub 2018 Dec 3.

1Bronx-Lebanon Hospital Center,Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York,USA.

Background: Numerous studies shown that structural hippocampal alterations are present in subjects at high risk of developing psychosis or schizophrenia. These findings indicate that in a subset of patients undergoing first-psychosis episode (FPE), hippocampal volume alterations are accompanied by associated cognitive and neuropsychological deficits. The combination of psychological deficits and neuroanatomical alterations, in turn, appears to increase treatment complexity and worsen clinical outcomes. Read More

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December 2018

Granulocyte-Macrophage Colony-Stimulating Factor as a Therapeutic Target in Multiple Sclerosis.

Neurol Ther 2018 Dec 1. Epub 2018 Dec 1.

Division of Clinical Neuroscience, Section of Clinical Neurology, University of Nottingham, Nottingham, UK.

Multiple sclerosis is an inflammatory neurodegenerative disease of the central nervous system (CNS) and the most frequent cause of non-traumatic disability in adults in the Western world. Currently, several drugs have been approved for the treatment of multiple sclerosis. While the newer drugs are more effective, they have less favourable safety profiles. Read More

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December 2018

Headache in the course of multiple sclerosis: a prospective study.

J Neural Transm (Vienna) 2018 Nov 30. Epub 2018 Nov 30.

Neuroimmunological Section, Department of Neurology, University of Rostock, Rostock, Germany.

Multiple sclerosis (MS) is the most common immune-mediated inflammatory disease of the central nervous system (CNS). Early diagnosis and treatment is important to prevent progression of disability in the course of the chronic disease. Therefore, correct and fast identification of early symptoms is vital. Read More

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November 2018

B-Cell Receptor-Associated Protein 31 Regulates the Expression of Valosin-Containing Protein Through Elf2.

Cell Physiol Biochem 2018 Nov 30;51(4):1799-1814. Epub 2018 Nov 30.

College of Life and Health Science, Northeastern University, Shenyang,

Background/aims: B-cell receptor-associated protein 31 (Bap31) is an evolutionarily conserved, ubiquitously expressed, polytopic integral membrane protein in the endoplasmic reticulum (ER) that is involved in the regulation of apoptosis, protein transport and degradation. Patients with Bap31 mutations exhibit symptoms similar to those exhibited by patients with central nervous system (CNS) diseases, such as deafness, dystonia, and intellectual disability. The present study aimed to investigate the function of Bap31 in CNS diseases by identifying a CNS disease-related gene regulated by Bap31 and exploring the underlying molecular mechanism. Read More

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November 2018

Immune cells and CNS physiology: Microglia and beyond.

J Exp Med 2018 Nov 30. Epub 2018 Nov 30.

Center for Brain Immunology and Glia, University of Virginia, Charlottesville, VA

Recent advances have directed our knowledge of the immune system from a narrative of "self" versus "nonself" to one in which immune function is critical for homeostasis of organs throughout the body. This is also the case with respect to the central nervous system (CNS). CNS immunity exists in a segregated state, with a marked partition occurring between the brain parenchyma and meningeal spaces. Read More

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November 2018
1 Read

Developmental venous anomaly in adult patients with diffuse glioma: A clinically relevant coexistence?

Neurology 2018 Nov 30. Epub 2018 Nov 30.

From the Departments of Neurosurgery (A.R., M.Z., E.D., G.Z.-B., J.P.), Neuroradiology (M.E., S. Porelli, C.O), and Neuropathology (A.T.-E., P.V.), Sainte-Anne Hospital; Paris Descartes University (A.R., M.E., S. Porelli, A.T.-E., M.Z., E.D., G.Z.-B., S. Puget, P.V., C.O., J.P.), Sorbonne Paris Cité; Inserm (A.R., M.E., M.Z., E.D., P.V., C.O., J.P.), U894, IMA-Brain, Centre Psychiatrie et Neurosciences; Departments of Neuro-oncology (M.S.) and Neurosurgery (L.C.), Pitié-Salpêtrière Hospital; and Department of Pediatric Neurosurgery (S. Puget), Necker Hospital, Paris, France.

Objective: To determine the prevalence of developmental venous anomaly in adult patients with diffuse glioma.

Methods: We performed a retrospective cohort study (2010-2016) of consecutive adult patients harboring a supratentorial diffuse glioma in 2 centers: Sainte-Anne Hospital (experimental and control sets) and Pitié-Salpêtrière Hospital (external validation set). We included 219 patients with diffuse glioma (experimental set), 252 patients with brain metastasis (control set), and 200 patients with diffuse glioma (validation set). Read More

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November 2018
5 Reads

Pharmacokinetics and brain distribution of amitraz and its metabolites in rats.

Environ Toxicol Pharmacol 2018 Nov 23;65:40-45. Epub 2018 Nov 23.

Zoetis, Inc., Veterinary Medicine Research and Development, Kalamazoo, MI, 49007, USA.

Amitraz is an acaricide and insecticide widely used in agriculture and veterinary medicine. Although central nervous system (CNS) toxicity is one of major toxicities following oral ingestion of amitraz, the understanding of the cause of the toxicity is limited. This study evaluated the systemic and brain exposure of amitraz and its major metabolites, BTS27271, 2',4'-formoxylidide, and 2,4-dimethylaniline following administration of amitraz in male Sprague-Dawley rats. Read More

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November 2018

The discovery of VU0652957 (VU2957, Valiglurax): SAR and DMPK challenges en route to an mGlu PAM development candidate.

Bioorg Med Chem Lett 2018 Nov 1. Epub 2018 Nov 1.

Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA; Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA. Electronic address:

This letter describes the first account of the chemical optimization (SAR and DMPK profiling) of a new series of mGlu positive allosteric modulators (PAMs), leading to the identification of VU0652957 (VU2957, Valiglurax), a compound profiled as a preclinical development candidate. Here, we detail the challenges faced in allosteric modulator programs (e.g. Read More

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November 2018

The NMDA receptor intracellular C-terminal domains reciprocally interact with allosteric modulators.

Biochem Pharmacol 2018 Nov 29. Epub 2018 Nov 29.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, 68198-5800 USA. Electronic address:

N-Methyl-D-aspartate receptors (NMDARs) have multiple prominent roles in CNS function but their excessive or insufficient activity contributes to neuropathological/psychiatric disorders. Consequently, a variety of positive and negative allosteric modulators (PAMs and NAMs, respectively) have recently been developed. Although these modulators bind to extracellular domains, in the present report we find that the NMDAR's intracellular C-terminal domains (CTDs) significantly influence PAM/NAM activity. Read More

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November 2018
5.009 Impact Factor

Spatiotemporal Control of CNS Myelination by Oligodendrocyte Programmed Cell Death through the TFEB-PUMA Axis.

Cell 2018 Nov 21. Epub 2018 Nov 21.

Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Nervous system function depends on proper myelination for insulation and critical trophic support for axons. Myelination is tightly regulated spatially and temporally, but how it is controlled molecularly remains largely unknown. Here, we identified key molecular mechanisms governing the regional and temporal specificity of CNS myelination. Read More

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November 2018

Involvement of central nervous system in adult patients with acute myeloid leukemia: Incidence and impact on outcome.

Semin Hematol 2018 Oct 21;55(4):209-214. Epub 2018 Feb 21.

Hematology, Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy.

Incidence and effect on outcome of central nervous system (CNS) involvement in adult patients with acute myeloid leukemia (AML) is not clearly defined. To address this issue, 103 consecutive adult patients with newly diagnosed AML, regardless of neurologic symptoms, were submitted to a routine explorative lumbar puncture. Cerebrospinal fluid (CSF) samples were collected from 65 males and 38 females. Read More

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October 2018

Cerebrospinal fluid interleukin (IL)-10 and IL-10:IL-6 ratio as biomarkers for small B-cell lymphoproliferations with leptomeningeal dissemination.

Semin Hematol 2018 Oct 6;55(4):179-181. Epub 2017 Jul 6.

Department of Biological Hematology, Pitie-Salpetriere Hospital, Paris, France; Centre de Recherche des Cordeliers, Cell Death and Drug Resistance in Lymphoproliferative Disorders, Paris, France.

We here report for the first time that low levels of interleukin (IL)-10 do not exclude lymphomatous meningitis (LM) in B-cell lymphoproliferative disorders (CLPD). Unexpectedly, IL-10 levels and IL-10:IL-6 ratio in CLPD differed from the levels observed in diffuse large B-cell lymphoma (DLBCL). We report the usefulness of adding the IL-10:IL-6 ratio in order to potentially reveal more aggressive lymphomas: either a transformation or an association with another "hidden" lymphoma such as primary CNS lymphoma (PCNSL). Read More

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October 2018

Primary CNS lymphoma patient-derived orthotopic xenograft model capture the biological and molecular characteristics of the disease.

Blood Cells Mol Dis 2018 Nov 16;75:1-10. Epub 2018 Nov 16.

Institut Curie, Site Saint-Cloud Hematology, Saint-Cloud, France. Electronic address:

Primary CNS lymphomas (PCNSL) are rare and poor prognosis diffuse large B-cell lymphomas. Because of the brain tumor environment and the restricted distribution of drugs in the CNS, specific PCNSL patient-derived orthotopic xenograft (PDOX) models are needed for preclinical research to improve the prognosis of PCNSL patients. PCNSL patient specimens (n = 6) were grafted in the caudate nucleus of immunodeficient nude mice with a 83% rate of success, while subcutaneous implantation in nude mice of human PCNSL sample did not generate lymphoma, supporting the role of the brain microenvironment in the PCNSL physiopathology. Read More

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November 2018

Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement: a prospective, multicentre, single-arm phase 2 study.

Lancet Haematol 2018 Dec;5(12):e609-e617

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD, USA. Electronic address:

Background: MYC gene rearrangement is present in approximately 10% of aggressive B-cell lymphomas, with half also harbouring a BCL2 gene rearrangement. Multiple retrospective studies of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone or prednisolone) have shown a worse outcome in patients with MYC rearrangement (alone or with rearrangement of BCL2 or BCL6, or both) than in patients without MYC rearrangement, and suggest improved outcomes after more intensive treatment. We aimed to determine the outcome of dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; DA-EPOCH-R), an intensive infusional treatment regimen, in untreated aggressive B-cell lymphoma with MYC rearrangement. Read More

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December 2018

National survey of bladder and gastrointestinal dysfunction in people with spinal cord injury.

J Neurotrauma 2018 Dec 1. Epub 2018 Dec 1.

University of Calgary Cumming School of Medicine, 70401, Departments of Physiology and Pharmacology, Clinical Neurosciences, Cardiac Sciences , Calgary, Alberta, Canada ;

Small-scale studies indicate that spinal cord injury (SCI) may lead to significant gastrointestinal and bladder dysfunction. However, how the prevalence of chronic disease related to these dysfunctions compares to non-SCI individuals and whether there are robust relationships to level and severity of injury are still unclear. Here, our goal was to provide high-level evidence on the association between bladder and gastrointestinal dysfunction and SCI using population-level data from the Canadian Community Health Survey (CCHS) and the SCI Community Survey. Read More

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December 2018

The Expressional Pattern of Invasion-Related Extracellular Matrix Molecules in CNS Tumors.

Cancer Invest 2018 Dec 3:1-12. Epub 2018 Dec 3.

a Department of Neurosurgery , University of Debrecen , Debrecen , Hungary.

Aim Of The Study: Astrocytomas are primary CNS malignancies which infiltrate the peritumoral tissue, even when they are low-grade. Schwannomas are also primary CNS tumors, however, they do not show peritumoral infiltration similarly to brain metastases which almost never invade the neighboring parts of brain. Extracellular matrix is altered in composition in various cancer types and is proposed to play an important role in the development of invasiveness of astrocytic tumors. Read More

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December 2018

mRNA expression of the P5 ATPase ATP13A4 is increased in Broca's Area from subjects with schizophrenia.

World J Biol Psychiatry 2018 Dec 3:1-23. Epub 2018 Dec 3.

a The Florey Institute for Neuroscience and Mental Health , Parkville , Victoria 3052 , Australia.

Objective: ATPase Type 13A4 (ATP13A4) is a cation-transporting, P-type ATPase that has been implicated in neurodevelopmental disorders. Our recent microarray study reported a significant increase in ATP13A4 mRNA levels in Brodmann's Area (BA) 9 in subjects with schizophrenia compared to controls. Following this discovery we have sought to determine whether ATP13A4 expression was altered in other regions of the CNS that are affected in schizophrenia. Read More

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December 2018

Nanostructured cubosomes in an in situ nasal gel system: an alternative approach for the controlled delivery of donepezil HCl to brain.

J Liposome Res 2018 Dec 2:1-27. Epub 2018 Dec 2.

b Department of Pharmaceutics, Marathwada Mitra Mandal's College of Pharmacy , Thergaon , Pune 411033, Maharashtra, India.

The purpose of this research was to develop cubosomal mucoadhesive in situ nasal gel to enhance the donepezil HCl delivery to the brain. Glycerol mono-oleate (GMO) and surfactant poloxamer 407 were used to prepare cubosomes. The developed formulations were characterized for particle size (PS), poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), transmission electron microscopy (TEM), in vitro drug release and in vivo bio-distribution study in blood and brain tissue. Read More

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December 2018

Regulation of brain drug metabolizing enzymes and transporters by nuclear receptors.

Drug Metab Rev 2018 Dec 2:1-27. Epub 2018 Dec 2.

b Center for Pharmacogenetics and Department of Pharmaceutical Sciences , University of Pittsburgh , Pittsburgh , PA 15261 , USA.

Nuclear receptors (NRs) belong to a family of ligand dependent transcription factors. The target genes of NRs include many drug metabolizing enzymes and transporters. The central nervous system (CNS) bears the expression of NRs, drug metabolizing enzymes and transporters. Read More

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December 2018
1 Read

Identification, Characterization and Quantification of Process-Related and Degradation Impurities in Lisdexamfetamine Dimesylate: Identifiction of Two New Compounds.

Molecules 2018 Nov 29;23(12). Epub 2018 Nov 29.

Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, No. 285 Gebaini Road, Shanghai 201203, China.

Twelve impurities (process-related and degradation) in lisdexamfetamine dimesylate (LDX), a central nervous system (CNS) stimulant drug, were first separated and quantified by high-performance liquid chromatography (HPLC) and then identified by liquid chromatography mass spectrometry (LC-MS). The structures of the twelve impurities were further confirmed and characterized by IR, HRMS and NMR analyses. Based on the characterization data, two previously unknown impurities formed during the process development and forced degradation were proposed to be (2)-2,6-di-(lysyl)-amino--[(1)-1-methyl-2-phenyl ethyl]hexanamide (Imp-H) and (2)-2,6-diamino--[(1)-1-methyl-2-(2-hydroxyphenyl)ethyl] hexanamide (Imp-M). Read More

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November 2018

Preventive effects of ketone ester BD-AcAc on central nervous system oxygen toxicity and concomitant acute lung injury.

Diving Hyperb Med 2018 Dec;48(4):235-240

Department of Diving and Hyperbaric Medicine, Naval Medical University, Shanghai, P R China.

Background: Recent studies indicated that ketone ester R,S-1,3-butanediol acetoacetate diester (BD-AcAc) may be effective in preventing central nervous system oxygen toxicity (CNS-OT) and concomitant acute lung injury, a serious medical problem to be faced when breathing hyperbaric oxygen (HBO). This study aimed to further investigate the protective effects of BD-AcAc against CNS-OT and concomitant acute lung injury (ALI) in mice.

Methods: Mice were treated with BD-AcAc in peanut oil vehicle (2. Read More

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December 2018
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Diabetes insipidus secondary to tuberculous meningoencephalitis with hypothalamic involvement extending to the hypophysis: a case report.

Rev Soc Bras Med Trop 2018 Nov-Dec;51(6):865-867

Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, AM, Brasil.

The involvement of Mycobacterium tuberculosis in the central nervous system (CNS) is an uncommon and devastating manifestation of tuberculosis. We report a case of disseminated tuberculosis presenting as meningoencephalitis, hypothalamic involvement with extension to the hypophysis, and secondary insipidus diabetes diagnosed at autopsy. Read More

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December 2017

Direct CNS delivery of proteins using thermosensitive liposome-in-gel carrier by heterotopic mucosal engrafting.

PLoS One 2018 5;13(12):e0208122. Epub 2018 Dec 5.

Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, United States of America.

Delivering therapeutics across the blood-brain barrier (BBB) for treating central nervous system (CNS) diseases is one of the biggest challenges today as the BBB limits the uptake of molecules greater than 500 Da into the CNS. Here we describe a novel trans-nasal mucosal drug delivery as an alternative to the intranasal drug delivery to overcome its limitations and deliver high molecular weight (HMW) therapeutics efficiently to the brain. This approach is based on human endoscopic skull base surgical techniques in which a surgical defect is repaired by engrafting semipermeable nasal mucosa over a skull base defect. Read More

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December 2018
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Role of systemic high-dose methotrexate and combined approaches in the management of vitreoretinal lymphoma: A single center experience 1990-2018.

Am J Hematol 2018 Dec 5. Epub 2018 Dec 5.

Division of Hematology, Mayo Clinic, Rochester, Minnesota.

Vitreoretinal lymphoma (VRL) management remains a challenge. We present 72 patients with VRL, diagnosed at Mayo Clinic between 1990-2018. Three nondiffuse large B-cell lymphoma (DLBCL) histology cases were excluded. Read More

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December 2018
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Imaging of Childhood Inflammatory Brain Diseases.

Top Magn Reson Imaging 2018 Dec;27(6):409-431

Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada.

Brain has been considered as an immune-privileged site for centuries owing to the presence of blood-brain barrier, absent lymphatic drainage, and antigen-presenting cells. However, the present prevailing concept is of immune surveillance where brain is continuously surveyed by immune cells. However, the presence of immune cells in central nervous system (CNS) brings the risk of inflammation and autoimmunity involving both T and B cell mediated pathways. Read More

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December 2018
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A Double-Edged Sword:Complement Component 3 in Toxoplasma gondii Infection.

Proteomics 2018 Dec 4:e1800271. Epub 2018 Dec 4.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, 510642, P. R. China.

We artificially infected Sprague Dawley (SD) rats and Kunming (KM) mice with type II Toxoplasma gondii (T. gondii) strain Prugniaud (Pru) to generate toxoplasmosis, which is a fatal disease mediated by T. gondii invasion of the central nervous system (CNS) by unknown mechanisms. Read More

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December 2018
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