DOCSLIB.ORG

POXVIRUS INFECTIONS in NORTH AMERICAN PINNIPEDS By

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
POXVIRUS INFECTIONS in NORTH AMERICAN PINNIPEDS By POXVIRUS INFECTIONS IN NORTH AMERICAN PINNIPEDS By HENDRIK HANS NOLLENS A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2005 Copyright 2005 by Hendrik Hans Nollens ACKNOWLEDGMENTS Funding for this work was provided in part by the UF College of Veterinary Medicine Batchelor Foundation, by a grant from the Florida Fish and Wildlife Conservation Commission, and by John H. Prescott Marine Mammal Rescue Assistance grant number NA03NMF4390410 to E.J. All samples were collected under NMFS Scientific Research Permit nos. 932-1489-00 and 1054-1731-00. Sample collection protocols were approved by the University of Florida Institutional Animal Care and Use Committee (IACUC C403). I would like to thank the staff at The Marine Mammal Center (CA), the Marine Mammal Stranding Center (NJ), Animal Health Center (British Columbia), Mystic Aquarium (CT), Sea World of Orlando (FL), SeaWorld of San Diego (CA) and the Virginia Marine Science Museum (VA) for their participation in this study. I thank Dr. John Wise and Dr. Carie Goertz at the Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, for supplying the seal and sea lion cell cultures. Dr. Andy Mercer of the University of Otago, New Zealand, was very generous with his advice on virus isolation and interpretation of electron microscopy images. Dr. Robert DeLong of the National Marine Mammal Lab, Seattle WA, kindly provided me with sera from free-ranging sea lions. The cidofovir was provided by Chimerix, La Jolla CA. Special thanks go to Dr. Susan D’Costa, Dr. Cindy Prins, Dr. Sayuri Kato, Dr. Steve Cresawn, Dr. Nissin Moussatche, Brad Dilling, Travis Bainbridge, Dr. Marty iii Haulena, Denise Greig, Dr. Brian Stacy, Dr. Charles Courtney, Dr. Deke Beusse, Dr. Greg Bossart, Linda Green, Diane Duke, Sally O’Connell and Courtney Watkins for their assistance, in various ways, with this project. I am greatly indebted to the members of my supervisory committee: Dr. Elliott Jacobson, Dr. Richard Condit, Dr. Frances Gulland, Dr. Jorge Hernandez, Dr. Paul Klein and Dr. Mike Walsh. I thank them for their invaluable advice, ideas, support and above all their confidence in my ability all the way through this project. It truly has been a pleasure working with them. iv TABLE OF CONTENTS page ACKNOWLEDGMENTS ................................................................................................. iii LIST OF TABLES............................................................................................................ vii LIST OF FIGURES ........................................................................................................... ix ABSTRACT.........................................................................................................................x CHAPTER 1 INTRODUCTION ..........................................................................................................1 2 PARAPOXVIRUSES OF SEALS AND SEA LIONS MAKE UP A DISTINCT SUBCLADE WITHIN THE GENUS PARAPOXVIRUS...........................................6 Introduction...................................................................................................................6 Materials and Methods .................................................................................................8 Animals and Samples ............................................................................................8 Polymerase Chain Reactions (PCR)......................................................................9 Viral Sequence Analyses.....................................................................................10 Results.........................................................................................................................13 Animals and Samples ..........................................................................................13 Viral Sequence Analyses.....................................................................................13 Discussion...................................................................................................................15 3 PATHOLOGY AND PRELIMINARY CHARACTERIZATION OF A PARAPOXVIRUS ISOLATED FROM A CALIFORNIA SEA LION.....................27 Introduction.................................................................................................................27 Materials and Methods ...............................................................................................28 Case Histories......................................................................................................28 Pathologic Studies ...............................................................................................29 Cell Cultures........................................................................................................30 Virus Isolation .....................................................................................................30 Virus Morphology ...............................................................................................31 Molecular Characterization of the Virus .............................................................32 Results.........................................................................................................................33 Pathologic Studies ...............................................................................................33 Virus Isolation .....................................................................................................34 Virus Morphology ...............................................................................................34 Molecular Characterization of the Virus .............................................................35 Discussion...................................................................................................................36 v 4 SEROEPIDEMIOLOGY OF POXVIRUS INFECTIONS IN CAPTIVE AND FREE-RANGING CALIFORNIA SEA LIONS ........................................................46 Introduction.................................................................................................................46 Methods ......................................................................................................................48 Positive and Negative Reference Serum Samples...............................................48 ELISA Procedure.................................................................................................49 Diagnostic Performance (Sensitivity and Specificity) of ELISA........................53 Seroepidemiology of Parapoxvirus Infections ....................................................53 Results.........................................................................................................................56 Diagnostic Performance (Sensitivity and Specificity) of ELISA........................56 Seroepidemiology of Parapoxvirus Infections ....................................................56 Discussion...................................................................................................................58 5 RISK FACTORS ASSOCIATED WITH DEVELOPMENT OF POXVIRUS LESIONS IN HOSPITALIZED CALIFORNIA SEA LIONS...................................68 Introduction.................................................................................................................68 Materials and Methods ...............................................................................................70 Results.........................................................................................................................73 Discussion...................................................................................................................74 6 THERAPEUTIC POTENTIAL OF CIDOFOVIR FOR THE TREATMENT OF PARAPOXVIRUS INFECTIONS OF PINNIPEDS..................................................84 Introduction.................................................................................................................84 Materials and Methods ...............................................................................................87 Cell Cultures........................................................................................................87 Virus ....................................................................................................................87 Compounds and Concentrations..........................................................................89 CPE Reduction Assays........................................................................................89 Virus Yield Assay................................................................................................90 Cytotoxicity Assays.............................................................................................91 Results.........................................................................................................................92 CPE Reduction Assays........................................................................................92 Virus Yield Assay................................................................................................93 Cytotoxicity Assays.............................................................................................93 Discussion...................................................................................................................94
Load more

Recommended publications
  • Highlights of Prescribing Information
    HIGHLIGHTS OF PRESCRIBING INFORMATION --------------------------WARNINGS AND PRECAUTIONS--------------------­ These highlights do not include all the information needed to use • New onset or worsening renal impairment: Can include acute VIREAD safely and effectively. See full prescribing information renal failure and Fanconi syndrome. Assess creatinine clearance for VIREAD. (CrCl) before initiating treatment with VIREAD. Monitor CrCl and ® serum phosphorus in patients at risk. Avoid administering VIREAD (tenofovir disoproxil fumarate) tablets, for oral use VIREAD with concurrent or recent use of nephrotoxic drugs. (5.3) VIREAD® (tenofovir disoproxil fumarate) powder, for oral use • Coadministration with Other Products: Do not use with other Initial U.S. Approval: 2001 tenofovir-containing products (e.g., ATRIPLA, COMPLERA, and TRUVADA). Do not administer in combination with HEPSERA. WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH (5.4) STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS • HIV testing: HIV antibody testing should be offered to all HBV- infected patients before initiating therapy with VIREAD. VIREAD See full prescribing information for complete boxed warning. should only be used as part of an appropriate antiretroviral • Lactic acidosis and severe hepatomegaly with steatosis, combination regimen in HIV-infected patients with or without HBV including fatal cases, have been reported with the use of coinfection. (5.5) nucleoside analogs, including VIREAD. (5.1) • Decreases in bone mineral density (BMD): Consider assessment • Severe acute exacerbations of hepatitis have been reported of BMD in patients with a history of pathologic fracture or other in HBV-infected patients who have discontinued anti- risk factors for osteoporosis or bone loss. (5.6) hepatitis B therapy, including VIREAD. Hepatic function • Redistribution/accumulation of body fat: Observed in HIV-infected should be monitored closely in these patients.
    [Show full text]
  • Guide for Common Viral Diseases of Animals in Louisiana
    Sampling and Testing Guide for Common Viral Diseases of Animals in Louisiana Please click on the species of interest: Cattle Deer and Small Ruminants The Louisiana Animal Swine Disease Diagnostic Horses Laboratory Dogs A service unit of the LSU School of Veterinary Medicine Adapted from Murphy, F.A., et al, Veterinary Virology, 3rd ed. Cats Academic Press, 1999. Compiled by Rob Poston Multi-species: Rabiesvirus DCN LADDL Guide for Common Viral Diseases v. B2 1 Cattle Please click on the principle system involvement Generalized viral diseases Respiratory viral diseases Enteric viral diseases Reproductive/neonatal viral diseases Viral infections affecting the skin Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. B2 2 Deer and Small Ruminants Please click on the principle system involvement Generalized viral disease Respiratory viral disease Enteric viral diseases Reproductive/neonatal viral diseases Viral infections affecting the skin Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. B2 3 Swine Please click on the principle system involvement Generalized viral diseases Respiratory viral diseases Enteric viral diseases Reproductive/neonatal viral diseases Viral infections affecting the skin Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. B2 4 Horses Please click on the principle system involvement Generalized viral diseases Neurological viral diseases Respiratory viral diseases Enteric viral diseases Abortifacient/neonatal viral diseases Viral infections affecting the skin Back to the Beginning DCN LADDL Guide for Common Viral Diseases v. B2 5 Dogs Please click on the principle system involvement Generalized viral diseases Respiratory viral diseases Enteric viral diseases Reproductive/neonatal viral diseases Back to the Beginning DCN LADDL Guide for Common Viral Diseases v.
    [Show full text]
  • Comparative Analysis, Distribution, and Characterization of Microsatellites in Orf Virus Genome
    www.nature.com/scientificreports OPEN Comparative analysis, distribution, and characterization of microsatellites in Orf virus genome Basanta Pravas Sahu1, Prativa Majee 1, Ravi Raj Singh1, Anjan Sahoo2 & Debasis Nayak 1* Genome-wide in-silico identifcation of microsatellites or simple sequence repeats (SSRs) in the Orf virus (ORFV), the causative agent of contagious ecthyma has been carried out to investigate the type, distribution and its potential role in the genome evolution. We have investigated eleven ORFV strains, which resulted in the presence of 1,036–1,181 microsatellites per strain. The further screening revealed the presence of 83–107 compound SSRs (cSSRs) per genome. Our analysis indicates the dinucleotide (76.9%) repeats to be the most abundant, followed by trinucleotide (17.7%), mononucleotide (4.9%), tetranucleotide (0.4%) and hexanucleotide (0.2%) repeats. The Relative Abundance (RA) and Relative Density (RD) of these SSRs varied between 7.6–8.4 and 53.0–59.5 bp/ kb, respectively. While in the case of cSSRs, the RA and RD ranged from 0.6–0.8 and 12.1–17.0 bp/kb, respectively. Regression analysis of all parameters like the incident of SSRs, RA, and RD signifcantly correlated with the GC content. But in a case of genome size, except incident SSRs, all other parameters were non-signifcantly correlated. Nearly all cSSRs were composed of two microsatellites, which showed no biasedness to a particular motif. Motif duplication pattern, such as, (C)-x-(C), (TG)- x-(TG), (AT)-x-(AT), (TC)- x-(TC) and self-complementary motifs, such as (GC)-x-(CG), (TC)-x-(AG), (GT)-x-(CA) and (TC)-x-(AG) were observed in the cSSRs.
    [Show full text]
  • ICD-9 Diagnosis Codes Effective 10/1/2011 (V29.0) Source: Centers for Medicare and Medicaid Services
    ICD-9 Diagnosis Codes effective 10/1/2011 (v29.0) Source: Centers for Medicare and Medicaid Services 0010 Cholera d/t vib cholerae 00801 Int inf e coli entrpath 01086 Prim prg TB NEC-oth test 0011 Cholera d/t vib el tor 00802 Int inf e coli entrtoxgn 01090 Primary TB NOS-unspec 0019 Cholera NOS 00803 Int inf e coli entrnvsv 01091 Primary TB NOS-no exam 0020 Typhoid fever 00804 Int inf e coli entrhmrg 01092 Primary TB NOS-exam unkn 0021 Paratyphoid fever a 00809 Int inf e coli spcf NEC 01093 Primary TB NOS-micro dx 0022 Paratyphoid fever b 0081 Arizona enteritis 01094 Primary TB NOS-cult dx 0023 Paratyphoid fever c 0082 Aerobacter enteritis 01095 Primary TB NOS-histo dx 0029 Paratyphoid fever NOS 0083 Proteus enteritis 01096 Primary TB NOS-oth test 0030 Salmonella enteritis 00841 Staphylococc enteritis 01100 TB lung infiltr-unspec 0031 Salmonella septicemia 00842 Pseudomonas enteritis 01101 TB lung infiltr-no exam 00320 Local salmonella inf NOS 00843 Int infec campylobacter 01102 TB lung infiltr-exm unkn 00321 Salmonella meningitis 00844 Int inf yrsnia entrcltca 01103 TB lung infiltr-micro dx 00322 Salmonella pneumonia 00845 Int inf clstrdium dfcile 01104 TB lung infiltr-cult dx 00323 Salmonella arthritis 00846 Intes infec oth anerobes 01105 TB lung infiltr-histo dx 00324 Salmonella osteomyelitis 00847 Int inf oth grm neg bctr 01106 TB lung infiltr-oth test 00329 Local salmonella inf NEC 00849 Bacterial enteritis NEC 01110 TB lung nodular-unspec 0038 Salmonella infection NEC 0085 Bacterial enteritis NOS 01111 TB lung nodular-no exam 0039
    [Show full text]
  • Novel Therapeutics for Epstein–Barr Virus
    molecules Review Novel Therapeutics for Epstein–Barr Virus Graciela Andrei *, Erika Trompet and Robert Snoeck Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium; [email protected] (E.T.); [email protected] (R.S.) * Correspondence: [email protected]; Tel.: +32-16-321-915 Academic Editor: Stefano Aquaro Received: 15 February 2019; Accepted: 4 March 2019; Published: 12 March 2019 Abstract: Epstein–Barr virus (EBV) is a human γ-herpesvirus that infects up to 95% of the adult population. Primary EBV infection usually occurs during childhood and is generally asymptomatic, though the virus can cause infectious mononucleosis in 35–50% of the cases when infection occurs later in life. EBV infects mainly B-cells and epithelial cells, establishing latency in resting memory B-cells and possibly also in epithelial cells. EBV is recognized as an oncogenic virus but in immunocompetent hosts, EBV reactivation is controlled by the immune response preventing transformation in vivo. Under immunosuppression, regardless of the cause, the immune system can lose control of EBV replication, which may result in the appearance of neoplasms. The primary malignancies related to EBV are B-cell lymphomas and nasopharyngeal carcinoma, which reflects the primary cell targets of viral infection in vivo. Although a number of antivirals were proven to inhibit EBV replication in vitro, they had limited success in the clinic and to date no antiviral drug has been approved for the treatment of EBV infections. We review here the antiviral drugs that have been evaluated in the clinic to treat EBV infections and discuss novel molecules with anti-EBV activity under investigation as well as new strategies to treat EBV-related diseases.
    [Show full text]
  • List of Codes Used to Identify Measures Reported in the QDFC
    List of Codes Used to Identify Measures Reported in the Quarterly Dialysis Facility Compare Reports July 2018 List of Codes Used to Identify Measures Reported in the Quarterly Dialysis Facility Compare Reports Table of Contents Table 1a: Transfusion Summary for Medicare Dialysis Patients, Codes Used for Exclusions 3 CARCINOMA 3 COAGULATION 5 HEAD/NECK CANCER 5 HEMOLYTIC OR APLASTIC ANEMIA 9 LEUKEMIA 11 LYMPHOMA 15 METASTATIC 27 MYELOMA, ETC. 29 OTHER CANCER 30 SICKLE CELL 34 SOLID ORGAN CANCER 34 Table 1b: Transfusion Summary for Medicare Dialysis Patients, Codes Used to Identify Transfusion Events .................................................................................................................. 45 REVENUE CENTER CODES 45 PROCEDURE CODES 45 VALUE CODES 46 HCPCS CODE 46 Table 2a: Vascular Access Measures (SFR and Long-Term Catheter) for Medicare Dialysis Patients Based on Medicare Claims, Codes Used for Exclusions ........................................... 46 Produced by The University of Michigan Kidney Epidemiology and Cost Center Page 1 of 135 List of Codes Used to Identify Measures Reported in the Quarterly Dialysis Facility Compare Reports July 2018 COMA 46 END STAGE LIVER DISEASE 48 METASTATIC CANCER 48 Table 2b: Standardized Fistulae Rate (SFR) for Medicare Dialysis Patients Based on Medicare Claims, Codes Used for Prevalent Comorbidities Adjusted in Model .................................... 50 ANEMIA 50 CORONARY ARTERY DISEASE 52 CONGESTIVE HEART FAILURE 55 CEREBROVASCULAR DISEASE 56 CHRONIC OBSTRUCTIVE PULMONARY DISEASE 68 DIABETES 69 DRUG DEPENDENCE 79 INFECTIONS (NON-VASCULAR ACCESS-RELATED): 93 PERIPHERAL VASCULAR DISEASE (INCLUDES ARTERIAL, VENOUS AND NONSPECIFIC DISEASES) 124 Table 3: Dialysis Adequacy ...................................................................................................
    [Show full text]
  • Client Services Manual Public Health Laboratory
    CLIENT SERVICES MANUAL PUBLIC HEALTH LABORATORY COUNTY OF SANTA CLARA 2220 MOORPARK AVE, 2ND FLOOR SAN JOSE, CA 95128 (P) 408.885.4272 | (F) 408.885.4275 http://www.sccgov.org/sites /sccphd/en-us/HealthProviders/Lab Patricia Dadone, Public Health Laboratory Director Sara H. Cody, MD, Health Officer and Public Health Director Table of Contents 1 GENERAL INFORMATION ............................................................................................... 1.1 ROLE .............................................................................................................................................................. 1.1 MISSION STATEMENT ..................................................................................................................................... 1.1 ABBREVIATIONS.............................................................................................................................................. 1.2 LABORATORY CERTIFICATIONS ........................................................................................................................ 1.4 CLIENT SERVICES ............................................................................................................................................ 1.5 Hours of Operation: .............................................................................................................................. 1.5 Supplies ..................................................................................................................................................
    [Show full text]
  • Modulation of NF-Κb Signalling by Microbial Pathogens
    REVIEWS Modulation of NF‑κB signalling by microbial pathogens Masmudur M. Rahman and Grant McFadden Abstract | The nuclear factor-κB (NF‑κB) family of transcription factors plays a central part in the host response to infection by microbial pathogens, by orchestrating the innate and acquired host immune responses. The NF‑κB proteins are activated by diverse signalling pathways that originate from many different cellular receptors and sensors. Many successful pathogens have acquired sophisticated mechanisms to regulate the NF‑κB signalling pathways by deploying subversive proteins or hijacking the host signalling molecules. Here, we describe the mechanisms by which viruses and bacteria micromanage the host NF‑κB signalling circuitry to favour the continued survival of the pathogen. The nuclear factor-κB (NF-κB) family of transcription Signalling targets upstream of NF‑κB factors regulates the expression of hundreds of genes that NF-κB proteins are tightly regulated in both the cyto- are associated with diverse cellular processes, such as pro- plasm and the nucleus6. Under normal physiological liferation, differentiation and death, as well as innate and conditions, NF‑κB complexes remain inactive in the adaptive immune responses. The mammalian NF‑κB cytoplasm through a direct interaction with proteins proteins are members of the Rel domain-containing pro- of the inhibitor of NF-κB (IκB) family, including IκBα, tein family: RELA (also known as p65), RELB, c‑REL, IκBβ and IκBε (also known as NF-κBIα, NF-κBIβ and the NF-κB p105 subunit (also known as NF‑κB1; which NF-κBIε, respectively); IκB proteins mask the nuclear is cleaved into the p50 subunit) and the NF-κB p100 localization domains in the NF‑κB complex, thus subunit (also known as NF‑κB2; which is cleaved into retaining the transcription complex in the cytoplasm.
    [Show full text]
  • Treatment of Warts with Topical Cidofovir in a Pediatric Patient
    Volume 25 Number 5| May 2019| Dermatology Online Journal || Case Report 25(5):6 Treatment of warts with topical cidofovir in a pediatric patient Melissa A Nickles BA, Artem Sergeyenko MD, Michelle Bain MD Affiliations: Department of Dermatology, University of Illinois at Chicago College of Medicine, Chicago, llinois, USA Corresponding Author: Artem Sergeyenko MD, 808 South Wood Street Suite 380, Chicago, IL 60612, Tel: 847-338-0037, Email: a.serge04@gmail topical cidofovir is effective in treating HPV lesions Abstract and molluscum contagiosum in adult patients with Cidofovir is an antiviral nucleotide analogue with HIV/AIDS [2]. Case reports have also found topical relatively new treatment capacities for cidofovir to effectively treat anogenital squamous dermatological conditions, specifically verruca cell carcinoma (SCC), bowenoid papulosis, vulgaris caused by human papilloma virus infection. condyloma acuminatum, Kaposi sarcoma, and HSV-II In a 10-year old boy with severe verruca vulgaris in adult patients with HIV/AIDS [3]. Cidofovir has recalcitrant to multiple therapies, topical 1% experimentally been shown to be effective in cidofovir applied daily for eight weeks proved to be an effective treatment with no adverse side effects. treating genital condyloma acuminata in adult This case report, in conjunction with multiple immunocompetent patients [4] and in a pediatric published reports, suggests that topical 1% cidofovir case [5]. is a safe and effective treatment for viral warts in Cidofovir has also been used in pediatric patients to pediatric patients. cure verruca vulgaris recalcitrant to traditional treatment therapies. There have been several reports Keywords: cidofovir, verruca vulgaris, human papilloma that topical 1-3% cidofovir cream applied once or virus twice daily is effective in treating verruca vulgaris with no systemic side effects and low rates of recurrence in immunocompetent children [6-8], as Introduction well as in immunocompromised children [9, 10].
    [Show full text]
  • Specimen Type, Collection Methods, and Diagnostic Assays Available For
    Specimen type, collection methods, and diagnostic assays available for the detection of poxviruses from human specimens by the Poxvirus and Rabies Branch, Centers for Disease Control and Prevention1. Specimen Orthopoxvirus Parapoxvirus Yatapoxvirus Molluscipoxvirus Specimen type collection method PCR6 Culture EM8 IHC9,10 Serology11 PCR12 EM8 IHC9,10 PCR13 EM8 PCR EM8 Lesion material Fresh or frozen Swab 5 Lesion material [dry or in media ] [vesicle / pustule Formalin fixed skin, scab / crust, etc.] Paraffin block Fixed slide(s) Container Lesion fluid Swab [vesicle / pustule [dry or in media5] fluid, etc.] Touch prep slide Blood EDTA2 EDTA tube 7 Spun or aliquoted Serum before shipment Spun or aliquoted Plasma before shipment CSF3,4 Sterile 1. The detection of poxviruses by electron microscopy (EM) and immunohistochemical staining (IHC) is performed by the Infectious Disease Pathology Branch of the CDC. 2. EDTA — Ethylenediaminetetraacetic acid. 3. CSF — Cerebrospinal fluid. 4. In order to accurately interpret test results generated from CSF specimens, paired serum must also be submitted. 5. If media is used to store and transport specimens a minimal amount should be used to ensure as little dilution of DNA as possible. 6. Orthopoxvirus generic real-time polymerase chain reaction (PCR) assays will amplify DNA from numerous species of virus within the Orthopoxvirus genus. Species-specific real-time PCR assays are available for selective detection of DNA from variola virus, vaccinia virus, monkeypox virus, and cowpox virus. 7. Blood is not ideal for the detection of orthopoxviruses by PCR as the period of viremia has often passed before sampling occurs. 8. EM can reveal the presence of a poxvirus in clinical specimens or from virus culture, but this technique cannot differentiate between virus species within the same genus.
    [Show full text]
  • Annex I Summary of Product Characteristics
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 4 1. NAME OF THE MEDICINAL PRODUCT VISTIDE 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each vial contains cidofovir equivalent to 375 mg/5 ml (75 mg/ml) cidofovir anhydrous. The formulation is adjusted to pH 7.4. 3. PHARMACEUTICAL FORM Concentrate for solution for infusion 4. CLINICAL PARTICULARS 4.1 Therapeutic Indication Cidofovir is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) and without renal dysfunction. Until further experience is gained, cidofovir should be used only when other agents are considered unsuitable. 4.2 Posology and Method of Administration Before each administration of cidofovir, serum creatinine and urine protein levels should be investigated. The recommended dosage, frequency, or infusion rate must not be exceeded. Cidofovir must be diluted in 100 milliliters 0.9% (normal) saline prior to administration. To minimise potential nephrotoxicity, oral probenecid and intravenous saline prehydration must be administered with each cidofovir infusion. Dosage in Adults • Induction Treatment. The recommended dose of cidofovir is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over 1 hr) administered once weekly for two consecutive weeks. • Maintenance Treatment. Beginning two weeks after the completion of induction treatment, the recommended maintenance dose of cidofovir is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over 1 hr) administered once every two weeks. Cidofovir therapy should be discontinued and intravenous hydration is advised if serum creatinine increases by = 44 µmol/L (= 0.5 mg/dl), or if persistent proteinuria = 2+ develops. • Probenecid.
    [Show full text]
  • Silibinin Component for the Treatment of Hepatitis Silbininkomponente Zur Behandlung Von Hepatitis Composant De Silibinine Pour Le Traitement De L’Hépatite
    (19) & (11) EP 2 219 642 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/357 (2006.01) A61P 1/16 (2006.01) 21.09.2011 Bulletin 2011/38 A61P 31/12 (2006.01) (21) Application number: 08849759.9 (86) International application number: PCT/EP2008/009659 (22) Date of filing: 14.11.2008 (87) International publication number: WO 2009/062737 (22.05.2009 Gazette 2009/21) (54) SILIBININ COMPONENT FOR THE TREATMENT OF HEPATITIS SILBININKOMPONENTE ZUR BEHANDLUNG VON HEPATITIS COMPOSANT DE SILIBININE POUR LE TRAITEMENT DE L’HÉPATITE (84) Designated Contracting States: (56) References cited: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR WO-A-02/067853 GB-A- 2 167 414 HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR • POLYAK STEPHEN J ET AL: "Inhibition of T- cell inflammatory cytokines, hepatocyte NF-kappa B (30) Priority: 15.11.2007 EP 07022187 signaling, and HCV infection by standardized 15.11.2007 US 988168 P silymarin" GASTROENTEROLOGY, vol. 132, no. 25.03.2008 EP 08005459 5, May 2007 (2007-05), pages 1925-1936, XP002477920 ISSN: 0016-5085 (43) Date of publication of application: • MAYER K E ET AL: "Silymarin treatment of viral 25.08.2010 Bulletin 2010/34 hepatitis: A systematic review" JOURNAL OF VIRAL HEPATITIS 200511 GB, vol. 12, no. 6, (60) Divisional application: November 2005 (2005-11), pages 559-567, 11005445.9 XP002477921 ISSN: 1352-0504 1365-2893 • CHAVEZ M L: "TREATMENT OF HEPATITIS C (73) Proprietor: Madaus GmbH WITH MILK THISTLE?" JOURNAL OF HERBAL 51067 Köln (DE) PHARMACOTHERAPY, HAWORTH HERBAL PRESS, BINGHAMTON, US, vol.
    [Show full text]