The Current Challenges for Drug Discovery in CNS Remyelination
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Application of HPLC Method in Determination of Miconazole Nitrate in Environmental Samples from El-Gharbia Governorate in Egypt
Journal of Analytical & Pharmaceutical Research Research Article Open Access Application of HPLC method in determination of miconazole nitrate in environmental samples from el-gharbia governorate in Egypt Abstract Volume 8 Issue 4 - 2019 This paper describes an enhanced High-performance liquid chromatography (HPLC) method for the analysis of miconazole in water samples. In this study, determination of Mohamed W Ibrahim,1 Ahmad A Mohamad,2 miconazole has been carried out according to standard method for water and wastewater Ahmed M Ahmed3 analysis. Samples of collected water were agriculture stream water, River Nile (Surface 1Department of Pharmaceutical Analytical Chemistry, Al-Azhar water samples) water and Hospital wastewater samples from El-gharbia governorate in University, Egypt Egypt. Miconazole was extracted by liquid-liquid extraction and analyzed by HPLC. The 2Department of Pharmaceutical Analytical Chemistry chromatographic separation was performed using a Phenomenex C8 column, flow rate of Department, Heliopolis University, Egypt 0.8mL/min, and UV detection at 220nm. The optimized HPLC system was achieved using 3Pharmacist Research Laboratories, Egypt mobile phase composition containing methanol: water (85:15v/v). The intra-day and inter- day precisions were lower than 0.58 while the accuracy ranged from 99.06% to 101.53%. Correspondence: Ahmed M Ahmed, Pharmacist Research Finally, liquid-liquid phase extraction in combination with HPLC is a sensitive and effective Laboratories, Ministry of health, Giza, Egypt, Tel +201119538119, method for the determination of Miconazole Nitrate in water samples. Miconazole was Email [email protected] observed in some agricultural streams and waste water samples of El-gharbia governorate Received: August 06, 2019 | Published: August 14, 2019 hospitals. -
4. Antibacterial/Steroid Combination Therapy in Infected Eczema
Acta Derm Venereol 2008; Suppl 216: 28–34 4. Antibacterial/steroid combination therapy in infected eczema Anthony C. CHU Infection with Staphylococcus aureus is common in all present, the use of anti-staphylococcal agents with top- forms of eczema. Production of superantigens by S. aureus ical corticosteroids has been shown to produce greater increases skin inflammation in eczema; antibacterial clinical improvement than topical corticosteroids alone treatment is thus pivotal. Poor patient compliance is a (6, 7). These findings are in keeping with the demon- major cause of treatment failure; combination prepara- stration that S. aureus can be isolated from more than tions that contain an antibacterial and a topical steroid 90% of atopic eczema skin lesions (8); in one study, it and that work quickly can improve compliance and thus was isolated from 100% of lesional skin and 79% of treatment outcome. Fusidic acid has advantages over normal skin in patients with atopic eczema (9). other available topical antibacterial agents – neomycin, We observed similar rates of infection in a prospective gentamicin, clioquinol, chlortetracycline, and the anti- audit at the Hammersmith Hospital, in which all new fungal agent miconazole. The clinical efficacy, antibac- patients referred with atopic eczema were evaluated. In terial activity and cosmetic acceptability of fusidic acid/ a 2-month period, 30 patients were referred (22 children corticosteroid combinations are similar to or better than and 8 adults). The reason given by the primary health those of comparator combinations. Fusidic acid/steroid physician for referral in 29 was failure to respond to combinations work quickly with observable improvement prescribed treatment, and one patient was referred be- within the first week. -
343747488.Pdf
Washington University School of Medicine Digital Commons@Becker Open Access Publications 6-1-2020 Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2 Simon Hsu Anna A Pimenova Kimberly Hayes Juan A Villa Matthew J Rosene See next page for additional authors Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Authors Simon Hsu, Anna A Pimenova, Kimberly Hayes, Juan A Villa, Matthew J Rosene, Madhavi Jere, Alison M Goate, and Celeste M Karch Neurobiology of Disease 139 (2020) 104817 Contents lists available at ScienceDirect Neurobiology of Disease journal homepage: www.elsevier.com/locate/ynbdi Systematic validation of variants of unknown significance in APP, PSEN1 T and PSEN2 Simon Hsua, Anna A. Pimenovab, Kimberly Hayesa, Juan A. Villaa, Matthew J. Rosenea, ⁎ Madhavi Jerea, Alison M. Goateb, Celeste M. Karcha, a Department of Psychiatry, Washington University School of Medicine, 425 S Euclid Avenue, St Louis, MO 63110, USA b Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA ARTICLE INFO ABSTRACT Keywords: Alzheimer's disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive APP decline. More than 200 pathogenic mutations have been identified in amyloid-β precursor protein (APP), presenilin PSEN1 1 (PSEN1) and presenilin 2 (PSEN2). Additionally, common and rare variants occur within APP, PSEN1, and PSEN2 PSEN2 that may be risk factors, protective factors, or benign, non-pathogenic polymorphisms. Yet, to date, no Alzheimer's disease single study has carefully examined the effect of all of the variants of unknown significance reported in APP, Cell-based assays PSEN1 and PSEN2 on Aβ isoform levels in vitro. -
Genetic Testing for Familial Alzheimer's Disease
Corporate Medical Policy Genetic Testing for Familial Alzheimer’s Disease AHS – M2038 File Name: genetic_testing_for_familial_alzheimers_disease Origination: 1/2019 Last CAP Review: 10/2020 Next CAP Review: 10/2021 Last Review: 10/2020 Description of Procedure or Service Alzheimer disease (AD) is a neurodegenerative disease defined by a gradual decline in memory, cognitive functions, gross atrophy of the brain, and an accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles (Karch, Cruchaga, & Goate, 2014). Familial Alzheimer disease (FAD) is a rare, inherited form of AD. FAD has a much earlier onset than other forms of Alzheimer disease with symptoms developing in individuals in their thirties or forties. Related Policies General Genetic Testing, Germline Disorders AHS – M2145 General Genetic Testing, Somatic Disorders AHS – M2146 ***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician. Policy BCBSNC will provide coverage for genetic testing for familial Alzheimer disease when it is determined the medical criteria or reimbursement guidelines below are met. Benefits Application This medical policy relates only to the services or supplies described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore member benefit language should be reviewed before applying the terms of this medical policy. -
Oligodendrocytes in Development, Myelin Generation and Beyond
cells Review Oligodendrocytes in Development, Myelin Generation and Beyond Sarah Kuhn y, Laura Gritti y, Daniel Crooks and Yvonne Dombrowski * Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast BT9 7BL, UK; [email protected] (S.K.); [email protected] (L.G.); [email protected] (D.C.) * Correspondence: [email protected]; Tel.: +0044-28-9097-6127 These authors contributed equally. y Received: 15 October 2019; Accepted: 7 November 2019; Published: 12 November 2019 Abstract: Oligodendrocytes are the myelinating cells of the central nervous system (CNS) that are generated from oligodendrocyte progenitor cells (OPC). OPC are distributed throughout the CNS and represent a pool of migratory and proliferative adult progenitor cells that can differentiate into oligodendrocytes. The central function of oligodendrocytes is to generate myelin, which is an extended membrane from the cell that wraps tightly around axons. Due to this energy consuming process and the associated high metabolic turnover oligodendrocytes are vulnerable to cytotoxic and excitotoxic factors. Oligodendrocyte pathology is therefore evident in a range of disorders including multiple sclerosis, schizophrenia and Alzheimer’s disease. Deceased oligodendrocytes can be replenished from the adult OPC pool and lost myelin can be regenerated during remyelination, which can prevent axonal degeneration and can restore function. Cell population studies have recently identified novel immunomodulatory functions of oligodendrocytes, the implications of which, e.g., for diseases with primary oligodendrocyte pathology, are not yet clear. Here, we review the journey of oligodendrocytes from the embryonic stage to their role in homeostasis and their fate in disease. We will also discuss the most common models used to study oligodendrocytes and describe newly discovered functions of oligodendrocytes. -
Investigation of Candidate Genes and Mechanisms Underlying Obesity
Prashanth et al. BMC Endocrine Disorders (2021) 21:80 https://doi.org/10.1186/s12902-021-00718-5 RESEARCH ARTICLE Open Access Investigation of candidate genes and mechanisms underlying obesity associated type 2 diabetes mellitus using bioinformatics analysis and screening of small drug molecules G. Prashanth1 , Basavaraj Vastrad2 , Anandkumar Tengli3 , Chanabasayya Vastrad4* and Iranna Kotturshetti5 Abstract Background: Obesity associated type 2 diabetes mellitus is a metabolic disorder ; however, the etiology of obesity associated type 2 diabetes mellitus remains largely unknown. There is an urgent need to further broaden the understanding of the molecular mechanism associated in obesity associated type 2 diabetes mellitus. Methods: To screen the differentially expressed genes (DEGs) that might play essential roles in obesity associated type 2 diabetes mellitus, the publicly available expression profiling by high throughput sequencing data (GSE143319) was downloaded and screened for DEGs. Then, Gene Ontology (GO) and REACTOME pathway enrichment analysis were performed. The protein - protein interaction network, miRNA - target genes regulatory network and TF-target gene regulatory network were constructed and analyzed for identification of hub and target genes. The hub genes were validated by receiver operating characteristic (ROC) curve analysis and RT- PCR analysis. Finally, a molecular docking study was performed on over expressed proteins to predict the target small drug molecules. Results: A total of 820 DEGs were identified between -
ANNOVERA™ (Segesterone Acetate and Ethinyl Estradiol Vaginal System) • Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Initial U.S
HIGHLIGHTS OF PRESCRIBING INFORMATION ANNOVERA™ no earlier than 4 weeks after delivery, in females who These highlights do not include all the information needed to use are not breastfeeding. Consider cardiovascular risk factors before ANNOVERA™ safely and effectively. initiating in all females, particularly those over 35 years. (5.1, 5.5) See Full Prescribing Information for ANNOVERA™. • Liver Disease: Discontinue if jaundice occurs. (5.2) ANNOVERA™ (segesterone acetate and ethinyl estradiol vaginal system) • Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Initial U.S. Approval: 2018 Treatment: Stop ANNOVERA™ prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir. ANNOVERA™ can be restarted 2 weeks following completion of this WARNING: CIGARETTE SMOKING AND regimen. (5.3) SERIOUS CARDIOVASCULAR EVENTS • Hypertension: Do not prescribe ANNOVERA™ for females with See full prescribing information for complete boxed warning. uncontrolled hypertension or hypertension with vascular disease. If • Females over 35 years old who smoke should not use used in females with well-controlled hypertension, monitor blood ANNOVERA™. (4) pressure and stop use if blood pressure rises significantly. (5.4) • Cigarette smoking increases the risk of serious cardiovascular • Carbohydrate and lipid metabolic effects: Monitor glucose in pre events from combination hormonal contraceptive (CHC) use. (4) diabetic and diabetic females taking ANNOVERA™. Consider an alternate contraceptive method for females with uncontrolled ----------------------------INDICATIONS AND USAGE-------------------------- dyslipidemias. (5.7) ANNOVERA™ is a progestin/estrogen CHC indicated for use by females of • Headache: Evaluate significant change in headaches and discontinue reproductive potential to prevent pregnancy. (1) ANNOVERA™ if indicated. (5.8) Limitation of use: Not adequately evaluated in females with a body mass index • Bleeding Irregularities and Amenorrhea: May cause irregular bleeding of >29 kg/m2. -
Cell Reprogramming Technologies for Treatment And
CELL REPROGRAMMING TECHNOLOGIES FOR TREATMENT AND UNDERSTANDING OF GENETIC DISORDERS OF MYELIN by ANGELA MARIE LAGER Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Thesis advisor: Paul J Tesar, PhD Department of Genetics and Genome Sciences CASE WESTERN RESERVE UNIVERSITY May 2015 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Angela Marie Lager Candidate for the Doctor of Philosophy degree*. (signed) Ronald A Conlon, PhD (Committee Chair) Paul J Tesar, PhD (Advisor) Craig A Hodges, PhD Warren J Alilain, PhD (date) 31 March 2015 *We also certify that written approval has been obtained from any proprietary material contained therein. TABLE OF CONTENTS Table of Contents……………………………………………………………………….1 List of Figures……………………………………………………………………………4 Acknowledgements……………………………………………………………………..7 Abstract…………………………………………………………………………………..8 Chapter 1: Introduction and Background………………………………………..11 1.1 Overview of mammalian oligodendrocyte development in the spinal cord and myelination of the central nervous system…………………..11 1.1.1 Introduction……………………………………………………..11 1.1.2 The establishment of the neuroectoderm and ventral formation of the neural tube…………………………………..12 1.1.3 Ventral patterning of the neural tube and specification of the pMN domain in the spinal cord……………………………….15 1.1.4 Oligodendrocyte progenitor cell production through the process of gliogenesis ………………………………………..16 1.1.5 Oligodendrocyte progenitor cell to oligodendrocyte differentiation…………………………………………………...22 -
Cellular and Molecular Signatures in the Disease Tissue of Early
Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of -
Membrane Topology of the C. Elegans SEL-12 Presenilin
Neuron, Vol. 17, 1015±1021, November, 1996, Copyright 1996 by Cell Press Membrane Topology of the C. elegans SEL-12 Presenilin Xiajun Li* and Iva Greenwald*²³ [this issue of Neuron]; Thinakaran et al., 1996). In the *Integrated Program in Cellular, Molecular, Discussion, we examine the amino acid sequence in and Biophysical Studies light of the deduced topology. ² Department of Biochemistry and Molecular Biophysics Results ³ Howard Hughes Medical Institute Columbia University Sequence analysis suggests that SEL-12 and human College of Physicians and Surgeons presenilins have ten hydrophobic regions (Figure 1). In New York, New York 10032 this study, we provide evidence that a total of eight of these hydrophobic regions function as transmembrane domains in vivo. Below, we use the term ªhydrophobic Summary regionº to designate a segment of the protein with the potential to span the membrane, as inferred by hydro- Mutant presenilins cause Alzheimer's disease. Pre- phobicity analysis, and ªtransmembrane domainº to senilins have multiple hydrophobic regions that could designate a hydrophobic region that our data suggest theoretically span a membrane, and a knowledge of actually spans a membrane. the membrane topology is crucial for deducing the mechanism of presenilin function. By analyzing the activity of b-galactosidase hybrid proteins expressed Strategy in C. elegans, we show that the C. elegans SEL-12 We constructed transgenes encoding hybrid SEL- presenilin has eight transmembrane domains and that 12::LacZ proteins, in which LacZ was placed after each there is a cleavage site after the sixth transmembrane of ten hydrophobic regions identified by hydrophobicity domain. We examine the presenilin sequence in view analysis (see Figure 1). -
Product Monograph Entocort®
PRODUCT MONOGRAPH ENTOCORT® (budesonide) Controlled Ileal Release Capsules 3 mg Glucocorticosteroid for the Treatment of Crohn’s Disease Affecting the Ileum and/or Ascending Colon Tillotts Pharma GmbH Date of Preparation: Warmbacher Strasse 80 July 7, 2016 79618 Rheinfelden Date of Revision: Germany April 9, 2018 Importer/Distributor: C.R.I. 4 Innovation Drive Dundas, ON Canada, L9H 7P3 Control Number: 213259 PRODUCT MONOGRAPH NAME OF DRUG ENTOCORT® (budesonide) Controlled Ileal Release Capsules 3 mg THERAPEUTIC CLASSIFICATION Glucocorticosteroid for the Treatment of Crohn’s Disease Affecting the Ileum and/or Ascending Colon ACTIONS AND CLINICAL PHARMACOLOGY The active ingredient of ENTOCORT capsules, budesonide, is a potent non-halogenated synthetic glucocorticosteroid with high topical potency and weak systemic effects. The exact mechanism of action of glucocorticosteroids in the treatment of Crohn’s disease is not fully understood. Anti-inflammatory actions, such as the inhibition of inflammatory mediator release and inhibition of immunological cellular responses, are probably important. Data from clinical pharmacology studies and controlled clinical trials indicate that ENTOCORT capsules, at least partly, act topically. Budesonide undergoes an extensive degree (approximately 90%) of biotransformation in the liver to metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the major metabolites, 6β- hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% of that of budesonide. The metabolism of budesonide is primarily mediated by CYP 3A4, an isozyme of cytochrome P450. The favourable separation between topical anti-inflammatory and systemic effect is due to strong glucocorticosteroid receptor affinity and an effective first pass metabolism by the liver with a short half-life. A glucocorticosteroid with such a profile is of particular importance for the local treatment of inflammatory bowel diseases such as Crohn’s disease. -
Investigation of the Underlying Hub Genes and Molexular Pathogensis in Gastric Cancer by Integrated Bioinformatic Analyses
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Investigation of the underlying hub genes and molexular pathogensis in gastric cancer by integrated bioinformatic analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.20.423656; this version posted December 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The high mortality rate of gastric cancer (GC) is in part due to the absence of initial disclosure of its biomarkers. The recognition of important genes associated in GC is therefore recommended to advance clinical prognosis, diagnosis and and treatment outcomes. The current investigation used the microarray dataset GSE113255 RNA seq data from the Gene Expression Omnibus database to diagnose differentially expressed genes (DEGs). Pathway and gene ontology enrichment analyses were performed, and a proteinprotein interaction network, modules, target genes - miRNA regulatory network and target genes - TF regulatory network were constructed and analyzed. Finally, validation of hub genes was performed. The 1008 DEGs identified consisted of 505 up regulated genes and 503 down regulated genes.