Navegando por Palavras-chave "UL97"

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    The emergence of cytomegalovirus resistance to ganciclovir therapy in kidney transplant recipients
    (Elsevier B.V., 2006-12-20) Nogueira, Eliana; Ozaki, Kikumi S.; Tomiyama, Helena; Granato, Celso F. H.; Camara, Niels O. S.; Pacheco-Silva, Alvaro; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Transplant recipients that have not been previously exposed to the cytomegalovirus (CMV) are highly susceptible to viral diseases while under immunosuppression therapy. CMV disease requires prolonged therapy, facilitating the emergence of resistant strains. Persistence of positive antigenemia represents clinical evidence of the presence of resistant strains, although its frequency is unknown. These strains may present amino acid deletions or Substitutions in conserved regions of the UL97 protein, point mutations in the DNA polymerase (UL54), or both. in this study we aimed to analyze the prevalence of mutations associated with ganciclovir resistance in transplant recipients. Fifteen kidney transplant recipients and four kidney-pancreas transplant recipients, with a positive and oscillating CMV viremia detected by sequential antigenemia test, were enrolled. the UL97 gene was amplified by Nested-PCR and enzymatically digested in samples of these patients in order to detect mutations in the most common codons, such as 460 (M460V), 594 (A594V) and 595(L595S/F). the end-product fragments were further sequenced. Nine (47.4%) out of 19 patients presented with mutations in UL97 at codons L595S (55.6%), A594V (11.1%), A595F/A594V (11.1%) and L595S/A594V (22.2%). None presented with Mutation at the M460V codon. Renal transplant patients with oscillation in viral load for more than 2 weeks might have developed viral resistance to anti-drug therapy. Its detection might aid physicians in their clinical plan of tapering the patient's immunosuppression. (c) 2006 Elsevier B.V. All rights reserved.
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    Genotipagem do citomegalovírus humano para pesquisa de resistência primária aos antivirais em transplantados renais
    (Sociedade Brasileira de Patologia ClínicaSociedade Brasileira de PatologiaSociedade Brasileira de Citopatologia, 2004-02-01) Carraro, Emerson [UNIFESP]; Granato, Celso Francisco Hernandes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The aim of this study was to detect by PCR/RFLP HCMV strains containing specific UL97 or UL54 mutation in patients without previous therapy. Samples from 20 renal transplant recipients with HCMV infection at the moment of the diagnosis. From all the patients blood, saliva and urine samples were collected to investigate the possible occurrence of distinct mutations in different body sites. Although no HCMV strains with mutations conferring drug resistance were detected, the PCR/RFLP methodology was considered an adequate and practical tool to detect alterations in viral genes from different body fluids. The absence of drug resistant viral strains in the analyzed samples do not preclude its appearance in the near future, since the use of antiviral drugs in this setting is more widespread in the recent years. We suggest a periodic evaluation of the sensitivity pattern to antiviral drugs in order to monitor its occurrence.
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    The use of sirolimus in ganciclovir-resistant cytomegalovirus infections in renal transplant recipients
    (Blackwell Publishing, 2007-09-01) Ozaki, Kikumi Suzete; Camara, Niels Olsen Saraiva; Nogueira, Eliana; Pereira, Mauricio Galvao; Granato, Celso; Melaragno, Claudio; Camargo, Luis Fernando Aranha; Pacheco-Silva, Alvaro; Universidade Federal de São Paulo (UNIFESP); Hosp Rim & Hipertensao; Hosp Israelita Albert Einstein
    Background: the widespread use of prophylactic ganciclovir and anti-lymphocyte/thymocyte therapies are associated with increased induction of ganciclovir-resistant cytomegalovirus (CMV) strains. the use of sirolimus has been associated with a lower incidence of CMV infection in transplant recipients. We questioned whether it could also be effective as a therapeutic treatment of resistant CMV infection.Methods: Patients with ganciclovir-resistant CMV infections determined clinically and by DNA sequencing analysis were enrolled. Antigenaemia and DNA sequencing were used to diagnosis and follow the mutations.Results: Nine transplant patients were given sirolimus plus mycophenolate mofetil (n = 4) or a calcineurin inhibitor (n = 5). Seven out of nine recipients were CMV IgG negative before transplantation. We observed a rapid decrease in antigenaemia levels, reaching zero in eight out of nine (88.9%) patients within a median of 20.3 +/- 10.1 d. Graft function remained stable and no patient presented acute rejection or recurrence of the CMV infection.Conclusions: This suggests that the use of sirolimus plus ganciclovir therapy could be useful in ganciclovir-resistant CMV infections.