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4.
Am J Clin Dermatol ; 14(6): 497-502, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23775427

ABSTRACT

Telaprevir and boceprevir are novel protease inhibitors recently approved for treatment of chronic hepatitis C virus infection, and have gained widespread use. Skin rash has been reported frequently in patients treated with telaprevir, but less commonly with boceprevir. Despite a high incidence in clinical trials, the telaprevir-related eruption has not been fully described in the literature. We describe six patients treated with telaprevir and three treated with boceprevir who developed skin rash related to the antiviral medication. Four patients treated with telaprevir developed laboratory abnormalities and/or systemic symptoms and five required discontinuation of their antiviral medication because of these adverse effects, including two patients who fit criteria for drug reaction with eosinophilia and systemic symptoms (DRESS). Patients with boceprevir-related rash had a milder course and none required discontinuation of the medication. This report confirms that cutaneous adverse effects from telaprevir and boceprevir are common. Patients treated with telaprevir may have a more severe course and more frequently require discontinuation of their antiviral therapy due to extensive rash or laboratory abnormalities. Dermatologists must be aware of these cutaneous adverse effects, as early intervention with topical corticosteroids and antihistamines may minimize the severity of the eruption and allow patients to complete antiviral therapy.


Subject(s)
Antiviral Agents/adverse effects , Drug Eruptions/etiology , Hepatitis C, Chronic/drug therapy , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Drug Eruptions/pathology , Drug Hypersensitivity Syndrome/etiology , Drug Hypersensitivity Syndrome/pathology , Female , Humans , Male , Middle Aged , Oligopeptides/adverse effects , Oligopeptides/pharmacology , Oligopeptides/therapeutic use , Proline/adverse effects , Proline/analogs & derivatives , Proline/pharmacology , Proline/therapeutic use , Severity of Illness Index
5.
Clin Infect Dis ; 57(6): e143-7, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23704119

ABSTRACT

BACKGROUND: The increase in popularity of tattoos has coincided with an increase in reports of cutaneous inoculation of nontuberculous (atypical) mycobacteria (NTM) during the tattooing process. We report 3 NTM infections in otherwise healthy persons who received tattoos, which prompted a multiagency epidemiologic investigation. METHODS: Tattoo artists involved were contacted and interviewed regarding practices, ink procurement and use, and other symptomatic clients. Additional patients were identified from their client lists with an Internet survey. RESULTS: Thirty-one cases of suspected or confirmed NTM inoculation from professional tattooing were uncovered, including 5 confirmed and 26 suspected cases. Clinical biopsy specimens from 3 confirmed infections grew Mycobacterium abscessus strains that were indistinguishable by pulsed-field gel electrophoresis testing. Another 2 skin specimens grew Mycobacterium chelonae, which also grew from a bottle of graywash ink obtained from the tattoo artist. CONCLUSIONS: The pathogenicity and antibiotic resistance patterns of certain NTM isolates highlight the importance of correct diagnosis and potential difficulty in treating infections. Enforcement of new standards for the regulation and use of tattoo inks should be considered.


Subject(s)
Mycobacterium Infections, Nontuberculous/etiology , Mycobacterium Infections, Nontuberculous/transmission , Nontuberculous Mycobacteria/isolation & purification , Skin Diseases, Bacterial/etiology , Tattooing/adverse effects , Antitubercular Agents/therapeutic use , Drug Resistance, Bacterial , Humans , Ink , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/drug effects , Skin Diseases, Bacterial/epidemiology , Skin Diseases, Bacterial/microbiology , Washington/epidemiology
6.
Nat Chem Biol ; 2(1): 33-8, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16408090

ABSTRACT

The actin cytoskeleton supports diverse cellular processes such as endocytosis, oriented growth, adhesion and migration. The dynamic nature of the cytoskeleton, however, has made it difficult to define the roles of the many accessory molecules that modulate actin organization, especially the multifunctional adapter protein annexin II. We now report that the compound withaferin A (1) can alter cytoskeletal architecture in a previously unknown manner by covalently binding annexin II and stimulating its basal F-actin cross-linking activity. Drug-mediated disruption of F-actin organization is dependent on annexin II expression by cells and markedly limits their migratory and invasive capabilities at subcytotoxic concentrations. Given the extensive ethnobotanical history of withaferin-containing plant preparations in the treatment of cancer and inflammatory and neurological disorders, we suggest that annexin II represents a feasible, previously unexploited target for therapeutic intervention by small-molecule drugs.


Subject(s)
Actin Cytoskeleton/drug effects , Annexin A2/metabolism , Cytoskeleton/drug effects , Ergosterol/analogs & derivatives , Microfilament Proteins/metabolism , Actin Cytoskeleton/metabolism , Actin Cytoskeleton/ultrastructure , Actins/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Binding Sites , Cattle , Cell Line , Cell Membrane/metabolism , Cytoskeleton/metabolism , Dose-Response Relationship, Drug , Ergosterol/metabolism , Ergosterol/pharmacology , Nervous System Diseases/drug therapy , Time Factors , Withanolides
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