DOCSLIB.ORG

Promising Drug Candidates and New Strategies for Fighting Against the Emerging Superbug Candida Auris

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Promising Drug Candidates and New Strategies for Fighting Against the Emerging Superbug Candida Auris microorganisms Review Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris Muriel Billamboz 1,2,*, Zeeshan Fatima 3, Saif Hameed 3 and Samir Jawhara 4,* 1 Inserm, CHU Lille, Institut Pasteur Lille, Université Lille, U1167—RID-AGE—Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement, F-59000 Lille, France 2 Junia, Health and Environment, Laboratory of Sustainable Chemistry and Health, F-59000 Lille, France 3 Amity Institute of Biotechnology, Amity University Haryana, Manesar, Gurugram 122413, India; [email protected] (Z.F.); [email protected] (S.H.) 4 UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, Centre National de la Recherche Scientifique, INSERM U1285, University of Lille, F-59000 Lille, France * Correspondence: [email protected] (M.B.); [email protected] (S.J.) Abstract: Invasive fungal infections represent an expanding threat to public health. During the past decade, a paradigm shift of candidiasis from Candida albicans to non-albicans Candida species has fundamentally increased with the advent of Candida auris. C. auris was identified in 2009 and is now recognized as an emerging species of concern and underscores the urgent need for novel drug development strategies. In this review, we discuss the genomic epidemiology and the main virulence factors of C. auris. We also focus on the different new strategies and results obtained during the past decade in the field of antifungal design against this emerging C. auris pathogen yeast, based on a medicinal chemist point of view. Critical analyses of chemical features and physicochemical descriptors will be carried out along with the description of reported strategies. Citation: Billamboz, M.; Fatima, Z.; Keywords: Candida auris; antifungal drugs; repurposed drugs; combinatorial therapy; natural Hameed, S.; Jawhara, S. Promising compounds; nanoparticles Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris. Microorganisms 2021, 9, 634. https://doi.org/10.3390/ microorganisms9030634 1. Introduction First identified in 2009 from the ear canal of a patient in Japan [1], C. auris is now recog- Academic Editor: Eric Dannaoui nized as an emerging species of concern [2,3], and more and more publications are related to C. auris studies (Figure1). When searching for “ Candida auris” key words on Scifinder, Received: 25 January 2021 fewer than 1000 reports have been compiled, most of them during the two last years, Accepted: 8 March 2021 proving the acceleration of research and clinical studies around this emerging pathogen. Published: 18 March 2021 Its emergence is defined by the occurrence of C. auris infections in a dozen of countries all around the world. In Europe, since 2015, sporadic epidemics have been reported in Publisher’s Note: MDPI stays neutral Spain [4], United-Kingdom [5], Germany, or Norway [6], for example. Simultaneously, with regard to jurisdictional claims in candidiasis caused by C. auris were reported in Korea [7], South Korea [8], India [9–11], published maps and institutional affil- South-Africa [12], or Kowait [13]. In the same period, the United States were also af- iations. fected [14–16]. This human pathogen is associated with severe invasive infections with high mortality rates ranging from 35 to 72% [8,12,17,18]. Since June 2016, governmental in- stitutions (Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control (ECDC), World Health Organization (WHO), Pan American Health Copyright: © 2021 by the authors. Organization (PAHO), National institute for Communicable Diseases (NICD) ... ) have Licensee MDPI, Basel, Switzerland. issued clinical alerts to health care facilities and provided interim guidelines for clinical This article is an open access article management, laboratory testing and infection control of C. auris [19,20]. This fungus poses distributed under the terms and significant challenges to microbiologists and clinicians because of its frequent multidrug conditions of the Creative Commons resistance; high transmissibility and severe outcomes coupled with misidentification by Attribution (CC BY) license (https:// standard biochemical identification systems such as Vitek 2 [21]. creativecommons.org/licenses/by/ 4.0/). Microorganisms 2021, 9, 634. https://doi.org/10.3390/microorganisms9030634 https://www.mdpi.com/journal/microorganisms Microorganisms 2021, 9, 634 2 of 40 Microorganisms 2021, 9, x 2 of 42 350 300 250 200 year 150 100 Number of publications per of publications Number 50 0 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 FigureFigure 1.1. Evolution of of annual annual reports reports dealing dealing with with C.C. auris auris studiesstudies (Scifinder (Scifinder search, search, keykey word word Candida auris, Data Compiled on 31 December 2020). Candida auris, Data Compiled on 31 December 2020). Moreover,Moreover, the the widespread widespread and and prolonged prolonged use use of of available available antifungal antifungal drugs drugs has has given given riserise to to multidrug multidrug resistance resistance that that alters alters the therapeuticthe therapeutic available available options. opti Itons. has It been has reported been re- thatported nearly that 90% nearly of C .90%auris ofisolates C. auris exhibit isolates resistance exhibit resistance to fluconazole, to fluconazole, around 30% around resistance 30% toresistance amphotericin to amphotericin B, and less B, thanand less 5% than resistance 5% resistance to echinocandins to echinocandins [22,23]. [22,23]. Under Under such compellingsuch compelling circumstances, circumstances,C. auris C. displaysauris displays all the all features the features of a “superbug”of a “superbug” and effortsand ef- areforts ongoing are ongoing to identify to identify newtherapeutic new therapeutic alternatives alternatives to fight to againstfight againstC. auris C. infections.auris infec- Aftertions. introducing After introducingC. auris C.genomic auris genomic epidemiology epidemiology and virulence and viru factors,lence thisfactors, review this aims review at compilingaims at compiling the different the strategiesdifferent strategies and results and obtained results during obtained the pastduring ten the years past in ten the fieldyears ofin antifungal the field of research antifungal against research emerging againstC. emerging auris from C. a medicinalauris from chemista medicinal point chemist of view. point To summarize,of view. To summarize, six complementary six complementary strategies have strate beengies developed, have been developed, from the most from attractive the most toattractive the less reported:to the less (i) reported: repurposing (i) repurposin of drugs;g (ii) of evaluation drugs; (ii) ofevaluation combination of combination drugs; (iii) discoverydrugs; (iii) of discovery new drug-candidates; of new drug-candidates; (iv) traditional (iv) traditional medicines medicines and natural andcompounds; natural com- (v)pounds; metal, (v) metalloids metal, metalloids and complexes; and complexes; (vi) others (vi) approaches others approaches including including nanoparticles nanopar- and irradiation.ticles and irradiation. Results and Results data will and be data analyzed will be from analyzed a chemical from approach a chemical based approach on chemical based featureson chemical and physicochemicalfeatures and physicochemical descriptors suchdescriptors as lipophilicity such as lipophilicity (expressed by(expressed logP) and by topologicallogP) and polartopological surface polar area (TPSA)surface inarea order (TPSA) to establish in order a comparison to establish between a comparison classes be- of compoundstween classes and of definecompounds potential and common define potential pharmacophoric common moieties.pharmacophoric moieties. 2.2.Candida Candida aurisaurisGenomic Genomic Epidemiology Epidemiology and and Virulence Virulence Factors Factors 2.1. Global View 2.1. Global View C. auris is taxonomically placed as a close relative to the Candida haemulonii since its C. auris is taxonomically placed as a close relative to the Candida haemulonii since its discovery in 2009 from the ear canal of a patient in Japan [1]. C. auris was isolated in all discovery in 2009 from the ear canal of a patient in Japan [1]. C. auris was isolated in all continents except Antarctica. Munoz et al. found that four of the five clades of C. auris are continents except Antarctica. Munoz et al. found that four of the five clades of C. auris are genetically related to other Candida species including C. haemulonii, C. duobushaemulonii, genetically related to other Candida species including C. haemulonii, C. duobushaemulonii, and C. psuedohaemulonii [24]. These five genetically distinct clades of C. auris correspond to: Cladeand C. I frompsuedohaemulonii India and Pakistan [24]. These (South five Asian), genetically Clade distinct II from Japanclades (Eastof C. Asian),auris correspond Clade III fromto: Clade South I from Africa India (African), and Pakistan Clade IV (South from VenezuelaAsian), Clade (South II from American) Japan (East and most Asian), recently Clade aIII potential from South Clade Africa V from (African), Iran [22 Clade,25]. OverIV from the Venezuela past ten years, (SouthC. Am auriserican)has been and isolatedmost re- acrosscently all a majorpotential continents, Clade V including from Iran elsewhere [22,25]. Over in Asia, the Africa, past ten North years, and C. South
Load more

Recommended publications
  • Electrophysiological and Behavioral Characterization Of
    Deletre et al. Parasites & Vectors (2015) 8:316 DOI 10.1186/s13071-015-0934-y RESEARCH Open Access Electrophysiological and behavioral characterization of bioactive compounds of the Thymus vulgaris, Cymbopogon winterianus, Cuminum cyminum and Cinnamomum zeylanicum essential oils against Anopheles gambiae and prospects for their use as bednet treatments Emilie Deletre1* , Fabrice Chandre2, Livy Williams3, Claire Duménil1, Chantal Menut4 and Thibaud Martin1,5 Abstract Background: Laboratory and field studies showed that repellent, irritant and toxic actions of common public health insecticides reduce human-vector contact and thereby interrupt disease transmission. One of the more effective strategies to reduce disease risk involves the use of long-lasting treated bednets. However, development of insecticide resistance in mosquito populations makes it imperative to find alternatives to these insecticides. Our previous study identified four essential oils as alternatives to pyrethroids: Thymus vulgaris, Cymbopogon winterianus, Cuminum cyminum, Cinnamomum zeylanicum. The objectives of this study were to identify active compounds of these essential oils, to characterize their biological activity, and to examine their potential as a treatment for bednets. Methods: We evaluated the electrophysiological, behavioural (repellency, irritancy) and toxic effects of the major compounds of these oils against Anopheles gambiae strain ‘Kisumu’. Results: Aldehydes elicited the strongest responses and monoterpenes the weakest responses in electroantennogram (EAG) trials. However, EAG responses did not correlate consistently with results of behavioral assays. In behavioral and toxicity studies, several of the single compounds did exhibit repellency, irritancy or toxicity in An. gambiae; however, the activity of essential oils did not always correlate with activity expected from the major components. On the contrary, the biological activity of essential oils appeared complex, suggesting interactions between individual compounds and the insect under study.
    [Show full text]
  • National Center for Toxicological Research
    National Center for Toxicological Research Annual Report Research Accomplishments and Plans FY 2015 – FY 2016 Page 0 of 193 Table of Contents Preface – William Slikker, Jr., Ph.D. ................................................................................... 3 NCTR Vision ......................................................................................................................... 7 NCTR Mission ...................................................................................................................... 7 NCTR Strategic Plan ............................................................................................................ 7 NCTR Organizational Structure .......................................................................................... 8 NCTR Location and Facilities .............................................................................................. 9 NCTR Advances Research Through Outreach and Collaboration ................................... 10 NCTR Global Outreach and Training Activities ............................................................... 12 Global Summit on Regulatory Science .................................................................................................12 Training Activities .................................................................................................................................14 NCTR Scientists – Leaders in the Research Community .................................................. 15 Science Advisory Board ...................................................................................................
    [Show full text]
  • Classification of Medicinal Drugs and Driving: Co-Ordination and Synthesis Report
    Project No. TREN-05-FP6TR-S07.61320-518404-DRUID DRUID Driving under the Influence of Drugs, Alcohol and Medicines Integrated Project 1.6. Sustainable Development, Global Change and Ecosystem 1.6.2: Sustainable Surface Transport 6th Framework Programme Deliverable 4.4.1 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Due date of deliverable: 21.07.2011 Actual submission date: 21.07.2011 Revision date: 21.07.2011 Start date of project: 15.10.2006 Duration: 48 months Organisation name of lead contractor for this deliverable: UVA Revision 0.0 Project co-funded by the European Commission within the Sixth Framework Programme (2002-2006) Dissemination Level PU Public PP Restricted to other programme participants (including the Commission x Services) RE Restricted to a group specified by the consortium (including the Commission Services) CO Confidential, only for members of the consortium (including the Commission Services) DRUID 6th Framework Programme Deliverable D.4.4.1 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Page 1 of 243 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Authors Trinidad Gómez-Talegón, Inmaculada Fierro, M. Carmen Del Río, F. Javier Álvarez (UVa, University of Valladolid, Spain) Partners - Silvia Ravera, Susana Monteiro, Han de Gier (RUGPha, University of Groningen, the Netherlands) - Gertrude Van der Linden, Sara-Ann Legrand, Kristof Pil, Alain Verstraete (UGent, Ghent University, Belgium) - Michel Mallaret, Charles Mercier-Guyon, Isabelle Mercier-Guyon (UGren, University of Grenoble, Centre Regional de Pharmacovigilance, France) - Katerina Touliou (CERT-HIT, Centre for Research and Technology Hellas, Greece) - Michael Hei βing (BASt, Bundesanstalt für Straßenwesen, Germany).
    [Show full text]
  • Antifungals, Topical
    Therapeutic Class Overview Antifungals, Topical INTRODUCTION The topical antifungals are available in multiple dosage forms and are indicated for a number of fungal infections and related conditions. In general, these agents are Food and Drug Administration (FDA)-approved for the treatment of cutaneous candidiasis, onychomycosis, seborrheic dermatitis, tinea corporis, tinea cruris, tinea pedis, and tinea versicolor (Clinical Pharmacology 2018). The antifungals may be further classified into the following categories based upon their chemical structures: allylamines (naftifine, terbinafine [only available over the counter (OTC)]), azoles (clotrimazole, econazole, efinaconazole, ketoconazole, luliconazole, miconazole, oxiconazole, sertaconazole, sulconazole), benzylamines (butenafine), hydroxypyridones (ciclopirox), oxaborole (tavaborole), polyenes (nystatin), thiocarbamates (tolnaftate [no FDA-approved formulations]), and miscellaneous (undecylenic acid [no FDA-approved formulations]) (Micromedex 2018). The topical antifungals are available as single entity and/or combination products. Two combination products, nystatin/triamcinolone and Lotrisone (clotrimazole/betamethasone), contain an antifungal and a corticosteroid preparation. The corticosteroid helps to decrease inflammation and indirectly hasten healing time. The other combination product, Vusion (miconazole/zinc oxide/white petrolatum), contains an antifungal and zinc oxide. Zinc oxide acts as a skin protectant and mild astringent with weak antiseptic properties and helps to
    [Show full text]
  • Prediction of Premature Termination Codon Suppressing Compounds for Treatment of Duchenne Muscular Dystrophy Using Machine Learning
    Prediction of Premature Termination Codon Suppressing Compounds for Treatment of Duchenne Muscular Dystrophy using Machine Learning Kate Wang et al. Supplemental Table S1. Drugs selected by Pharmacophore-based, ML-based and DL- based search in the FDA-approved drugs database Pharmacophore WEKA TF 1-Palmitoyl-2-oleoyl-sn-glycero-3- 5-O-phosphono-alpha-D- (phospho-rac-(1-glycerol)) ribofuranosyl diphosphate Acarbose Amikacin Acetylcarnitine Acetarsol Arbutamine Acetylcholine Adenosine Aldehydo-N-Acetyl-D- Benserazide Acyclovir Glucosamine Bisoprolol Adefovir dipivoxil Alendronic acid Brivudine Alfentanil Alginic acid Cefamandole Alitretinoin alpha-Arbutin Cefdinir Azithromycin Amikacin Cefixime Balsalazide Amiloride Cefonicid Bethanechol Arbutin Ceforanide Bicalutamide Ascorbic acid calcium salt Cefotetan Calcium glubionate Auranofin Ceftibuten Cangrelor Azacitidine Ceftolozane Capecitabine Benserazide Cerivastatin Carbamoylcholine Besifloxacin Chlortetracycline Carisoprodol beta-L-fructofuranose Cilastatin Chlorobutanol Bictegravir Citicoline Cidofovir Bismuth subgallate Cladribine Clodronic acid Bleomycin Clarithromycin Colistimethate Bortezomib Clindamycin Cyclandelate Bromotheophylline Clofarabine Dexpanthenol Calcium threonate Cromoglicic acid Edoxudine Capecitabine Demeclocycline Elbasvir Capreomycin Diaminopropanol tetraacetic acid Erdosteine Carbidopa Diazolidinylurea Ethchlorvynol Carbocisteine Dibekacin Ethinamate Carboplatin Dinoprostone Famotidine Cefotetan Dipyridamole Fidaxomicin Chlormerodrin Doripenem Flavin adenine dinucleotide
    [Show full text]
  • NINDS Custom Collection II
    ACACETIN ACEBUTOLOL HYDROCHLORIDE ACECLIDINE HYDROCHLORIDE ACEMETACIN ACETAMINOPHEN ACETAMINOSALOL ACETANILIDE ACETARSOL ACETAZOLAMIDE ACETOHYDROXAMIC ACID ACETRIAZOIC ACID ACETYL TYROSINE ETHYL ESTER ACETYLCARNITINE ACETYLCHOLINE ACETYLCYSTEINE ACETYLGLUCOSAMINE ACETYLGLUTAMIC ACID ACETYL-L-LEUCINE ACETYLPHENYLALANINE ACETYLSEROTONIN ACETYLTRYPTOPHAN ACEXAMIC ACID ACIVICIN ACLACINOMYCIN A1 ACONITINE ACRIFLAVINIUM HYDROCHLORIDE ACRISORCIN ACTINONIN ACYCLOVIR ADENOSINE PHOSPHATE ADENOSINE ADRENALINE BITARTRATE AESCULIN AJMALINE AKLAVINE HYDROCHLORIDE ALANYL-dl-LEUCINE ALANYL-dl-PHENYLALANINE ALAPROCLATE ALBENDAZOLE ALBUTEROL ALEXIDINE HYDROCHLORIDE ALLANTOIN ALLOPURINOL ALMOTRIPTAN ALOIN ALPRENOLOL ALTRETAMINE ALVERINE CITRATE AMANTADINE HYDROCHLORIDE AMBROXOL HYDROCHLORIDE AMCINONIDE AMIKACIN SULFATE AMILORIDE HYDROCHLORIDE 3-AMINOBENZAMIDE gamma-AMINOBUTYRIC ACID AMINOCAPROIC ACID N- (2-AMINOETHYL)-4-CHLOROBENZAMIDE (RO-16-6491) AMINOGLUTETHIMIDE AMINOHIPPURIC ACID AMINOHYDROXYBUTYRIC ACID AMINOLEVULINIC ACID HYDROCHLORIDE AMINOPHENAZONE 3-AMINOPROPANESULPHONIC ACID AMINOPYRIDINE 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE HYDROCHLORIDE AMINOTHIAZOLE AMIODARONE HYDROCHLORIDE AMIPRILOSE AMITRIPTYLINE HYDROCHLORIDE AMLODIPINE BESYLATE AMODIAQUINE DIHYDROCHLORIDE AMOXEPINE AMOXICILLIN AMPICILLIN SODIUM AMPROLIUM AMRINONE AMYGDALIN ANABASAMINE HYDROCHLORIDE ANABASINE HYDROCHLORIDE ANCITABINE HYDROCHLORIDE ANDROSTERONE SODIUM SULFATE ANIRACETAM ANISINDIONE ANISODAMINE ANISOMYCIN ANTAZOLINE PHOSPHATE ANTHRALIN ANTIMYCIN A (A1 shown) ANTIPYRINE APHYLLIC
    [Show full text]
  • FEMA GRAS 29 December 2019 SUPPLEMENTARY INFORMATION 1
    SUPPLEMENTARY INFORMATION 1: Identity for Natural Flavor Complexes as Evaluated by the Expert Panel The Identification Description as Reviewed by the FEMA FEMA No.1 FEMA Primary Name Expert Panel Rebaudioside M ≥80%; Rebaudioside D 5-20%; Total 4895 Rebaudioside M steviol glycosides ≥95%. Glutamic acid 35-40%; Other amino acids 1-2%; Total Corynebacterium glutamicum corn nitrogen 6-7%; Aliphatic primary alcohols, aldehydes, 4907 syrup fermentation product carboxylic acids, acetals and esters containing additional oxygenated functional groups 1-2%; Minerals 9-11% Inosine 5´-monophosphate 20-25%; Amino acids 7-8%; Corynebacterium stationis corn 4908 Minerals 23-25%; water 28-37%; Other nucleotides 1-2%; syrup fermentation product Total nitrogen 5-8% Supraglucosylated steviol glycosides 70-80%; Rebaudioside Glucosylated steviol glycosides, 4909 A 14-20%; Steviol glycosides not further glucosylated, each 70-80% individually, not to exceed 3%; Maltodextrin 3-10% Supraglucosylated steviol glycosides 30-40%; Rebaudioside Glucosylated steviol glycosides, A 5-8%; Not more than 4% stevioside; All other individual 4910 40% steviol glycosides not further glucosylated <3%; Maltodextrin 45-60% Stevioside 70-80%; Rebaudioside A 13-18%; Steviobioside 1- 3%; Rebaudioside C 2-3%; Total glycosides (including 4911 Stevia extract stevioside, 70% Rebaudioside D, Rebaudioside B, Rebaudioside F, Dulcoside A, and Rubusoside) <3% Derived from hibiscus blossom calyces (Hibiscus sabdariffa L.) , Hibiscus blossom extract is measured as water 30-60%; 4912 Hibiscus
    [Show full text]
  • A Screening-Based Approach to Circumvent Tumor Microenvironment
    JBXXXX10.1177/1087057113501081Journal of Biomolecular ScreeningSingh et al. 501081research-article2013 Original Research Journal of Biomolecular Screening 2014, Vol 19(1) 158 –167 A Screening-Based Approach to © 2013 Society for Laboratory Automation and Screening DOI: 10.1177/1087057113501081 Circumvent Tumor Microenvironment- jbx.sagepub.com Driven Intrinsic Resistance to BCR-ABL+ Inhibitors in Ph+ Acute Lymphoblastic Leukemia Harpreet Singh1,2, Anang A. Shelat3, Amandeep Singh4, Nidal Boulos1, Richard T. Williams1,2*, and R. Kiplin Guy2,3 Abstract Signaling by the BCR-ABL fusion kinase drives Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myelogenous leukemia (CML). Despite their clinical activity in many patients with CML, the BCR-ABL kinase inhibitors (BCR-ABL-KIs) imatinib, dasatinib, and nilotinib provide only transient leukemia reduction in patients with Ph+ ALL. While host-derived growth factors in the leukemia microenvironment have been invoked to explain this drug resistance, their relative contribution remains uncertain. Using genetically defined murine Ph+ ALL cells, we identified interleukin 7 (IL-7) as the dominant host factor that attenuates response to BCR-ABL-KIs. To identify potential combination drugs that could overcome this IL-7–dependent BCR-ABL-KI–resistant phenotype, we screened a small-molecule library including Food and Drug Administration–approved drugs. Among the validated hits, the well-tolerated antimalarial drug dihydroartemisinin (DHA) displayed potent activity in vitro and modest in vivo monotherapy activity against engineered murine BCR-ABL-KI–resistant Ph+ ALL. Strikingly, cotreatment with DHA and dasatinib in vivo strongly reduced primary leukemia burden and improved long-term survival in a murine model that faithfully captures the BCR-ABL-KI–resistant phenotype of human Ph+ ALL.
    [Show full text]
  • Therapeutic Class Overview Antifungals, Topical
    Therapeutic Class Overview Antifungals, Topical INTRODUCTION The topical antifungals are available in multiple dosage forms and are indicated for a number of fungal infections and related conditions. In general, these agents are Food and Drug Administration (FDA)-approved for the treatment of cutaneous candidiasis, onychomycosis, seborrheic dermatitis, tinea corporis, tinea cruris, tinea pedis, and tinea versicolor (Clinical Pharmacology 2018). The antifungals may be further classified into the following categories based upon their chemical structures: allylamines (naftifine, terbinafine [only available over the counter (OTC)]), azoles (clotrimazole, econazole, efinaconazole, ketoconazole, luliconazole, miconazole, oxiconazole, sertaconazole, sulconazole), benzylamines (butenafine), hydroxypyridones (ciclopirox), oxaborole (tavaborole), polyenes (nystatin), thiocarbamates (tolnaftate [no FDA-approved formulations]), and miscellaneous (undecylenic acid [no FDA-approved formulations]) (Micromedex 2018). The topical antifungals are available as single entity and/or combination products. Two combination products, nystatin/triamcinolone and Lotrisone (clotrimazole/betamethasone), contain an antifungal and a corticosteroid preparation. The corticosteroid helps to decrease inflammation and indirectly hasten healing time. The other combination product, Vusion (miconazole/zinc oxide/white petrolatum), contains an antifungal and zinc oxide. Zinc oxide acts as a skin protectant and mild astringent with weak antiseptic properties and helps to
    [Show full text]
  • New Natural Agonists of the Transient Receptor Potential Ankyrin 1 (TRPA1
    www.nature.com/scientificreports OPEN New natural agonists of the transient receptor potential Ankyrin 1 (TRPA1) channel Coline Legrand, Jenny Meylan Merlini, Carole de Senarclens‑Bezençon & Stéphanie Michlig* The transient receptor potential (TRP) channels family are cationic channels involved in various physiological processes as pain, infammation, metabolism, swallowing function, gut motility, thermoregulation or adipogenesis. In the oral cavity, TRP channels are involved in chemesthesis, the sensory chemical transduction of spicy ingredients. Among them, TRPA1 is activated by natural molecules producing pungent, tingling or irritating sensations during their consumption. TRPA1 can be activated by diferent chemicals found in plants or spices such as the electrophiles isothiocyanates, thiosulfnates or unsaturated aldehydes. TRPA1 has been as well associated to various physiological mechanisms like gut motility, infammation or pain. Cinnamaldehyde, its well known potent agonist from cinnamon, is reported to impact metabolism and exert anti-obesity and anti-hyperglycemic efects. Recently, a structurally similar molecule to cinnamaldehyde, cuminaldehyde was shown to possess anti-obesity and anti-hyperglycemic efect as well. We hypothesized that both cinnamaldehyde and cuminaldehyde might exert this metabolic efects through TRPA1 activation and evaluated the impact of cuminaldehyde on TRPA1. The results presented here show that cuminaldehyde activates TRPA1 as well. Additionally, a new natural agonist of TRPA1, tiglic aldehyde, was identifed
    [Show full text]
  • Minimising Blood Stream Infection: Developing New Materials for Intravascular Catheters
    medicines Review Minimising Blood Stream Infection: Developing New Materials for Intravascular Catheters Charnete Casimero , Todd Ruddock, Catherine Hegarty, Robert Barber, Amy Devine and James Davis * School of Engineering, Ulster University, Jordanstown BT37 0QB, Northern Ireland, UK; [email protected] (C.C.); [email protected] (T.R.); [email protected] (C.H.); [email protected] (R.B.); [email protected] (A.D.) * Correspondence: [email protected]; Tel.: +44-(0)289-0366-407 Received: 30 July 2020; Accepted: 24 August 2020; Published: 26 August 2020 Abstract: Catheter related blood stream infection is an ever present hazard for those patients requiring venous access and particularly for those requiring long term medication. The implementation of more rigorous care bundles and greater adherence to aseptic techniques have yielded substantial reductions in infection rates but the latter is still far from acceptable and continues to place a heavy burden on patients and healthcare providers. While advances in engineering design and the arrival of functional materials hold considerable promise for the development of a new generation of catheters, many challenges remain. The aim of this review is to identify the issues that presently impact catheter performance and provide a critical evaluation of the design considerations that are emerging in the pursuit of these new catheter systems. Keywords: intravascular catheter; CRBSI; biofilm; CVC; antimicrobial; antifouling 1. Introduction Intravascular catheters are ubiquitous in contemporary care and it has been estimated that 30–80% of hospital patients will have a peripheral venous catheter (PVC) in place at some point during their stay [1–3].
    [Show full text]
  • Evaluating the Efficacy of Commonly Used Topical Anesthetics
    Scientic Article Evaluating the efficacy of commonly used topical anesthetics Shiva Roghani, DDS Donald F. Duperon, DDS, MS, MRCD Nazanine Barcohana, DDS Dr. Roghani is in private practice in Orange County, California; Dr. Duperon is Professor and Chair; and Dr. Barcohana is a resident, Department of Pediatric Dentistry, University of California, Los Angeles, California. Abstract Purpose: This study compared the efficacy of commonly used with 5% EMLA cream was also measured. It was found to be topical anesthetics using an objective measuring scale. insufficient. The first study investigating the application of Methods: The following were tested: 5% EMLA cream, 10% EMLA cream in the oral cavity was performed in Sweden by cocaine, 10% lidocaine, 10% benzocaine, 1% dyclonine, and a comparing its pain reduction effect during a needle insertion placebo. A special instrument was designed to serve the purpose of to a placebo. EMLA was found to be very effective in reducing pressure application on the gingiva to obtain a threshold discom- pain experience.4 fort level in grams before and after the topical delivery. The Rosivack et al.5 used a visual analogue scale in adult patients medicaments, in the quantity of 20 µL (2–3 drops) were placed to compare 20% Benzocaine, 5% Lidocaine, and a placebo on the maxillary anterior region using Beckman paper wicks in (saline) in reducing pain when a needle was inserted. In this the form of discs. The topical anesthetics were left on the gingiva study both 5% Lidocaine and 20% Benzocaine were found to for 3 min and off for another 3 min.
    [Show full text]