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1.
J Colloid Interface Sci ; 561: 348-357, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31735412

RESUMEN

DNA formylation (5-formylcytosine, 5fC) is a major epigenetic modification involved in alterations in the DNA double helix structure and protein identification. Due to the low amount in all mammalian tissues and cells, it is necessary to develop a rapid, sensitive and efficient method for detecting 5fC for further understanding the biological functions of 5fC. Thus, a novel PEC biosensor was constructed using P-g-C3N4-WS2 nanocomposite as photoactive material. Firstly, AuNPs/P-g-C3N4-WS2/ITO electrode was prepared as substrate electrode. Secondly, the probe DNA and complementary DNA (containing 5fC base) was modified to the electrode surface based on the formation of Au-S bonds between AuNPs and thiol group on the probe DNA and hybridization, respectively. Finally, the amino functionalized MnO2 nanoflowers were further modified to the electrode surface by covalent interaction between the aldehyde group on the 5fC and the amino group on MnO2 nanoflowers. The sensitive and specific detection of 5fC can be achieved by oxidizing ascorbic acid with MnO2 nanoflowers and quenching the photoactivity of P-g-C3N4-WS2 nanocomposite. The sensor has a detection range of 0.01-200 nM and a detection limit of 3.8 pM. Moreover, this sensor has excellent detection specificity, stability and reproducibility.


Asunto(s)
Citosina/análogos & derivados , Técnicas Electroquímicas , Electrodos , Grafito/química , Compuestos de Manganeso/química , Nanocompuestos/química , Compuestos de Nitrógeno/química , Óxidos/química , Compuestos de Tungsteno/química , Técnicas Biosensibles , Citosina/análisis , Oro/química , Nanopartículas del Metal/química
2.
Transplant Proc ; 50(1): 142-144, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29407298

RESUMEN

We report the first case of a ganciclovir-resistant cytomegalovirus (CMV) involving the gastrointestinal tract that was successfully treated with high-dose valganciclovir. A kidney transplant recipient developed drug-resistant CMV colitis which was initially treated with valganciclovir, but his CMV was found to have major resistance to ganciclovir and cidofovir due to UL97 and UL54 mutations. The patient was switched to intravenous foscarnet 40 mg/kg given every twelve hours. However, foscarnet had to be discontinued after 4 days of treatment due to acute kidney injury. Patient was restarted on valganciclovir at a higher target dose of 1800 mg twice a day based on the creatinine clearance. CMV became undetectable 2 weeks after valganciclovir treatment was completed. High-dose valganciclovir along with immune suppression reduction may be a treatment option for CMV colitis with ganciclovir resistance due to dual UL97 and UL54 gene mutations.


Asunto(s)
Antivirales/administración & dosificación , Colitis/tratamiento farmacológico , Infecciones por Citomegalovirus/tratamiento farmacológico , Ganciclovir/análogos & derivados , Proteínas Virales/genética , Adulto , Cidofovir , Colitis/virología , Citomegalovirus/efectos de los fármacos , Citomegalovirus/genética , Infecciones por Citomegalovirus/virología , Citosina/administración & dosificación , Citosina/análogos & derivados , ADN Polimerasa Dirigida por ADN/genética , Farmacorresistencia Viral/genética , Foscarnet/administración & dosificación , Ganciclovir/administración & dosificación , Humanos , Trasplante de Riñón , Masculino , Mutación , Organofosfonatos/administración & dosificación , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Valganciclovir , Proteínas Virales/efectos de los fármacos
3.
Transplant Proc ; 49(5): 1048-1052, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28583524

RESUMEN

BACKGROUND: Data on drug-resistant cytomegalovirus (CMV) infection in solid organ transplantation (SOT) are not often reported from resource-limited settings. We aimed to investigate the epidemiology and outcomes of this infection in SOT recipients at our institution. METHODS: This was a retrospective study conducted from January 2012 to May 2015. We included all SOT recipients who were suspected for drug-resistant CMV infection. Genotypic assay for UL97 gene mutation was analyzed by real-time polymerase chain reaction. Patients were reviewed for demographic data, clinical presentation, virologic data, treatment, and outcomes. RESULTS: The population consisted of 18 (12 kidney, 6 liver) SOT recipients with a median age of 20 years (interquartile range [IQR], 1-49); 44% were male. Anti-CMV resistance testing was analyzed at a median time of 23 days (IQR, 14-33) after initiation of anti-CMV therapy with a median CMV load of log 3.79 copies/mL (IQR, 3.37-4.58). During a median period of 2 years (IQR, 1-3), 6 SOT recipients were identified with UL97 gene mutation in codon 460, conferring ganciclovir (GCV) resistance. Patients with UL97 gene mutation had a longer mean duration of CMV DNAemia compared with those without mutation (263 vs 107 days; P = .04). All patients received high-dose GCV. Two patients received foscarnet and cidofovir. Two patients died (non-CMV-related), and 4 patients developed opportunistic infections other than CMV. CONCLUSIONS: GCV-resistant CMV infection in SOT recipients is an emerging clinical problem in resource-limited country. Those with UL97 mutation CMV infection have prolonged duration of CMV DNAemia. Clinicians should be aware of this condition when caring for SOT recipients.


Asunto(s)
Infecciones por Citomegalovirus/epidemiología , Citomegalovirus/genética , Farmacorresistencia Viral/genética , Trasplante de Órganos/efectos adversos , Complicaciones Posoperatorias , Adulto , Antivirales/uso terapéutico , Cidofovir , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/virología , Citosina/análogos & derivados , Citosina/uso terapéutico , Femenino , Foscarnet/uso terapéutico , Ganciclovir/uso terapéutico , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Mutación , Organofosfonatos/uso terapéutico , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Tailandia/epidemiología , Adulto Joven
4.
J Drugs Dermatol ; 16(3): s49-s53, 2017 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-28301628

RESUMEN

Herpes labialis remains a common worldwide affliction. Recent advances in understanding the basic pathogenesis have led to new therapeutic intervention, both on-label and off-label. Aside from reducing the duration and symptomatology of acute outbreaks, another goal of treatment is to decrease the frequency of future episodes. Oral and topical acyclovir and its analogues are the mainstay of both chronic suppressive and episodic therapy. A new muco-adhesive formulation of acyclovir provides a decrease in outbreaks, probably due to a diminution of herpesvirus load in all reservoir sites. Acyclovir-resistant strains are rare in immunocompetent hosts; parenteral foscarnet and cidofovir are administered in this situation. Parenteral acyclovir is the drug of choice for eczema herpeticum, which may begin as herpes labialis in an atopic dermatitis patient. Thermotherapy may be beneficial, and a certified device to deliver heat is available outside the United States.

J Drugs Dermatol. 2017;16(3 Suppl):s49-53.

.


Asunto(s)
Antivirales/administración & dosificación , Antivirales/uso terapéutico , Herpes Labial/terapia , Herpesvirus Humano 1/efectos de los fármacos , Estomatitis Herpética/terapia , Carga Viral/efectos de los fármacos , Aciclovir/administración & dosificación , Aciclovir/uso terapéutico , Administración Oral , Administración Tópica , Adulto , Enfermedad Crónica/terapia , Cidofovir , Citosina/administración & dosificación , Citosina/análogos & derivados , Citosina/uso terapéutico , Farmacorresistencia Viral , Foscarnet/administración & dosificación , Foscarnet/uso terapéutico , Herpes Labial/complicaciones , Herpesvirus Humano 1/aislamiento & purificación , Herpesvirus Humano 1/fisiología , Humanos , Hipertermia Inducida , Infusiones Parenterales , Organofosfonatos/administración & dosificación , Organofosfonatos/uso terapéutico , Recurrencia , Estomatitis Herpética/complicaciones
5.
Hautarzt ; 68(Suppl 1): 6-10, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28197697

RESUMEN

The second part of this publication deals with varicella zoster virus (VZV) and presents an overview of new, rare, and atypical clinical manifestations, including photolocalized varicella, hemorrhagic bullae during varicella, the implication of VZV in immunoglobulin A vasculitis, VZV-related alopecia, ulcerative varicella skin lesions, childhood herpes zoster (HZ), prolonged prodromal pains, recurrent HZ, VZV implication in burning mouth syndrome, verruciform VZV lesions, the significance of satellite lesions during HZ, and late HZ complications, either neurological or internal. Furthermore, certain associations between the occurrence of HZ and subsequent internal pathologies, as well as risk factors for HZ and new developments in vaccination against HZ will be addressed.


Asunto(s)
Herpesvirus Humano 3/patogenicidad , Infección por el Virus de la Varicela-Zóster/virología , Adulto , Niño , Preescolar , Citosina/análogos & derivados , Citosina/uso terapéutico , Vacuna contra el Herpes Zóster/uso terapéutico , Humanos , Lactante , Terapia por Luz de Baja Intensidad , Persona de Mediana Edad , Organofosfonatos/uso terapéutico , Nucleósidos de Pirimidina/uso terapéutico , Recurrencia , Factores de Riesgo , Infección por el Virus de la Varicela-Zóster/diagnóstico , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Virulencia
6.
s.l; ANMAT; 2017. tab.
No convencional en Español | BRISA | ID: biblio-876905

RESUMEN

INTRODUCCIÓN: La cistitis hemorrágica (HC) es una complicación grave del trasplante de células madre hematopoyéticas (HSCT) y presenta una incidencia variable del 7 al 70%(1). Generalmente, la HC es una complicación dolorosa que prolonga la internación, aumenta el requerimiento de transfusiones de sangre y en sus formas severas puede causar obstrucción del tracto urinario. La ocurrencia de HC ha sido asociada con mayor mortalidad. Los factores predisponentes, incluyen: HSCT alogénico, edad avanzada en el trasplante, enfermedad de injerto contra huésped (GVHD), trombocitopenia, coagulopatía e infección viral. Las HC se clasifican en dos tipos: (1) inicio temprano, que ocurre dentro de las primeras 48 a 72 horas después de HSCT y generalmente debido a los efectos tóxicos de la quimioterapia; (2) inicio tardío, ocurre luego de 72 horas, usualmente de causa infecciosa, particularmente el virus BK (BKV)(2). La HC asociada al virus BK (BKV-HC) es una complicación frecuente luego de un trasplante alogénico de células hematopoyéticas. De acuerdo a su presentación clínica, se clasifica en diferentes grados de severidad: Grado I: Hematuria microscópica; Grado II: Hematuria macroscópica; Grado III: Hematuria macroscópica con presencia de coágulos en orina; Grado IV: Hematuria macroscópica con presencia de coágulos en orina y alteración de la función renal secundaria a obstrucción de las vías urinarias. TECNOLOGÍA: El cidofovir es un nucleósido análogo de citosina activo contra varios virus ADN. Ejerce una inhibición selectiva en la síntesis de ADN, suprimiendo la replicación viral. La EMA (European Medicines Agency) y la FDA (Food and Drug Administration) lo aprobaron para el tratamiento de la retinitis por citomegalovirus en adultos con síndrome de inmunodeficiencia adquirida y sin alteración de la función renal. El cidofovir causa nefrotoxicidad con daño a células tubulares proximales y aumento de la creatinina sérica. La nefrotoxicidad es muy frecuente y es dosis dependiente. La mayoría de las veces se recomienda la asociación con Probenecid vía oral para mantener una concentración plasmática útil de cidofovir que permita su administración semanal, disminuyendo la penetración y acumulación del cidofovir en las células renales y así atenuar su nefrotoxicidad. La modalidad de tratamiento varía en dosis y vías de administración. La vía intravesical se usa en casos de viruria con baja viremia y daño renal previo, aunque su efectividad es cuestionada. Por vía endovenosa, se usa en una dosis variable de 0,5 a 5 mg/kg, una o dos veces por semana. La elección de dosis y frecuencia depende de la severidad del cuadro y fundamentalmente, de la nefrotoxicidad. OBJETIVO: Evaluar la eficacia y seguridad de cidofovir en la HC por BK virus post HSCT. DISCUSIÓN: El cidofovir constituye una tecnología sanitaria experimental para el tratamiento de la HC-BKV. Se han utilizado diferentes dosis y vías de administración. La evidencia disponible sugiere que su eficacia para el tratamiento oscila entre el 60 y 100%. En el diseño de los estudios se constata que sólo en uno fue comparado vs tratamiento convencional pero fue un estudio descriptivo de dos grupos independientes. En este estudio, el cidofovir no fue superior en respuesta clínica ni en duración de la HC. La respuesta clínica de la HC en cuanto a disminución de hematuria, eliminación de coágulos y disuria, no siempre correlaciona con una significativa disminución de la carga viral en sangre o en orina. La mitad de los pacientes pos-trasplante presenta viruria y no desarrollan HC. Este aspecto no permite definir con absoluta certeza el grado de responsabilidad del virus ni del cidofovir en el desarrollo de la HC y su tratamiento. Se describen varios eventos adversos pero el más importante y serio, es la nefrotoxicidad que se relaciona con las dosis utilizadas y la duración del tratamiento. La función renal basal y la viruria/viremia deben ser tenidas en cuenta en la prescripción y vía de administración del cidofovir. Los criterios de elección de la ruta de administración local o sistémica no fueron expresamente definidos pero se relacionan con la ubicación del virus, la nefrotoxicidad y la función renal previa. El contexto peri-trasplante agrega varios tratamientos potencialmente nefrotóxicos que se suman al cidofovir y a la nefropatía derivada de la obstrucción urinaria por HC, lo que impone la necesidad de un extremo cuidado para la función renal. RECOMENDACIONES: El cidofovir es una opción terapéutica en el tratamiento de la HC-BKV y requiere control estricto de la función renal dado el alto riesgo de nefrotoxicidad. Es por ahora un tratamiento experimental. Su uso adecuado y en ámbito adecuado, es de estricta responsabilidad del médico tratante.


Asunto(s)
Humanos , Trasplante de Médula Ósea , Cistitis/complicaciones , Citosina/análogos & derivados , Citosina/uso terapéutico , Evaluación de la Tecnología Biomédica , Análisis Costo-Beneficio
7.
Nat Commun ; 7: 13077, 2016 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-27703148

RESUMEN

Elucidating the photophysical mechanisms in sulfur-substituted nucleobases (thiobases) is essential for designing prospective drugs for photo- and chemotherapeutic applications. Although it has long been established that the phototherapeutic activity of thiobases is intimately linked to efficient intersystem crossing into reactive triplet states, the molecular factors underlying this efficiency are poorly understood. Herein we combine femtosecond transient absorption experiments with quantum chemistry and nonadiabatic dynamics simulations to investigate 2-thiocytosine as a necessary step to unravel the electronic and structural elements that lead to ultrafast and near-unity triplet-state population in thiobases in general. We show that different parts of the potential energy surfaces are stabilized to different extents via thionation, quenching the intrinsic photostability of canonical DNA and RNA nucleobases. These findings satisfactorily explain why thiobases exhibit the fastest intersystem crossing lifetimes measured to date among bio-organic molecules and have near-unity triplet yields, whereas the triplet yields of canonical nucleobases are nearly zero.


Asunto(s)
Citosina/análogos & derivados , Oxígeno Singlete/química , Azufre/química , Antineoplásicos/química , Citosina/química , ADN/química , Diseño de Fármacos , Concentración de Iones de Hidrógeno , Simulación de Dinámica Molecular , Fotoquimioterapia , Fototerapia , Teoría Cuántica , ARN/química , Espectrofotometría , Termodinámica , Timina
8.
Nutrients ; 8(8)2016 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-27509522

RESUMEN

It is still unclear to which extent methyl-group intake during pregnancy can affect maternal global DNA (hydroxyl)methylation. Pregnancy methylation profiling and its link with methyl-group intake in a healthy population could enhance our understanding of the development of pregnancy related disorders. One hundred forty-eight women were enrolled in the MANOE (MAternal Nutrition and Offspring's Epigenome) study. Thiry-four women were enrolled before pregnancy and 116 during the first trimester of pregnancy. Global DNA (hydroxy)methylation in blood using LC-MS/MS and dietary methyl-group intake (methionine, folate, betaine, and choline) using a food-frequency questionnaire were estimated pre-pregnancy, during each trimester, and at delivery. Global DNA (hydroxy)methylation levels were highest pre-pregnancy and at weeks 18-22 of pregnancy. We observed a positive relation between folic acid and global DNA methylation (p = 0.04) and hydroxymethylation (p = 0.04). A high intake of methionine pre-pregnancy and in the first trimester showed lower (hydroxy)methylation percentage in weeks 11-13 and weeks 18-22, respectively. Choline and betaine intake in the first weeks was negatively associated with hydroxymethylation. Women with a high intake of these three methyl groups in the second and third trimester showed higher hyrdoxymethylation/methylation levels in the third trimester. To conclude, a time trend in DNA (hydroxy)methylation was found and women with higher methyl-group intake showed higher methylation in the third trimester, and not in earlier phases of pregnancy.


Asunto(s)
Betaína/administración & dosificación , Colina/administración & dosificación , Metilación de ADN , Dieta/efectos adversos , Ácido Fólico/administración & dosificación , Fenómenos Fisiologicos Nutricionales Maternos , Metionina/administración & dosificación , 5-Metilcitosina/sangre , Adulto , Bélgica , Betaína/metabolismo , Biomarcadores/sangre , Colina/metabolismo , Estudios de Cohortes , Citosina/análogos & derivados , Citosina/sangre , Dieta/etnología , Suplementos Dietéticos , Conducta Alimentaria/etnología , Femenino , Ácido Fólico/metabolismo , Humanos , Hidroxilación , Leucocitos/metabolismo , Estudios Longitudinales , Fenómenos Fisiologicos Nutricionales Maternos/etnología , Metionina/metabolismo , Embarazo , Estudios Prospectivos , Autoinforme
9.
J Gen Virol ; 97(6): 1414-1425, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26959283

RESUMEN

Feline herpesvirus type-1 (FHV-1) is the most common viral cause of ocular surface disease in cats. Many antiviral drugs are used to treat FHV-1, but require frequent topical application and most lack well-controlled in vivo studies to justify their clinical use. Therefore, better validation of current and novel treatment options are urgently needed. Here, we report on the development of a feline whole corneal explant model that supports FHV-1 replication and thus can be used as a novel model system to evaluate the efficacy of antiviral drugs. The anti-herpes nucleoside analogues cidofovir and acyclovir, which are used clinically to treat ocular herpesvirus infection in cats and have previously been evaluated in traditional two-dimensional feline cell cultures in vitro, were evaluated in this explant model. Both drugs suppressed FHV-1 replication when given every 12 h, with cidofovir showing greater efficacy. In addition, the potential efficacy of the retroviral integrase inhibitor raltegravir against FHV-1 was evaluated in cell culture as well as in the explant model. Raltegravir was not toxic to feline cells or corneas, and most significantly, inhibited FHV-1 replication at 500 µM in both systems. Importantly, this drug was effective when given only once every 24 h. Taken together, our data indicate that the feline whole corneal explant model is a useful tool for the evaluation of antiviral drugs and, furthermore, that raltegravir appears a promising novel antiviral drug to treat ocular herpesvirus infection in cats.


Asunto(s)
Antivirales/farmacología , Córnea/virología , Evaluación Preclínica de Medicamentos/métodos , Técnicas de Cultivo de Órganos/métodos , Varicellovirus/efectos de los fármacos , Cultivo de Virus/métodos , Aciclovir/farmacología , Animales , Gatos , Cidofovir , Citosina/análogos & derivados , Citosina/farmacología , Organofosfonatos/farmacología
10.
Antiviral Res ; 125: 71-8, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26526586

RESUMEN

Brincidofovir (BCV) is the 3-hexadecyloxy-1-propanol (HDP) lipid conjugate of the acyclic nucleoside phosphonate cidofovir (CDV). BCV has established broad-spectrum activity against double-stranded DNA (dsDNA) viruses; however, its activity against RNA viruses has been less thoroughly evaluated. Here, we report that BCV inhibited infection of Ebola virus in multiple human cell lines. Unlike the mechanism of action for BCV against cytomegalovirus and other dsDNA viruses, phosphorylation of CDV to the diphosphate form appeared unnecessary. Instead, antiviral activity required the lipid moiety and in vitro activity against EBOV was observed for several HDP-nucleotide conjugates.


Asunto(s)
Antivirales/química , Antivirales/farmacología , Citosina/análogos & derivados , Ebolavirus/efectos de los fármacos , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Organofosfonatos/química , Organofosfonatos/farmacología , Animales , Línea Celular Tumoral , Chlorocebus aethiops , Cidofovir , Citosina/química , Citosina/farmacología , Evaluación Preclínica de Medicamentos/métodos , Células HeLa , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/virología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Lípidos/química , Lípidos/farmacología , Masculino , Relación Estructura-Actividad , Células Vero , Replicación Viral/efectos de los fármacos
11.
Curr Opin Infect Dis ; 28(6): 589-95, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26524331

RESUMEN

PURPOSE OF REVIEW: The mainstay of antiviral therapy for the alpha-herpesviruses [herpes simplex virus (HSV)-1, HSV-2, and varicella zoster virus (VZV)] over the past 40 years has been the nucleoside analogues such as aciclovir. Although conventional antiviral therapy has reduced mortality in severe disease, novel agents are needed to address the emergence of resistance and toxicity associated with current second-line therapy. Treatment and prophylaxis of VZV and HSV reactivations remains a challenge. RECENT FINDINGS: A number of compounds have recently been evaluated in human clinical trials, amongst them brincidofovir, an intracellularly acting derivative of cidofovir currently undergoing phase III trials. The helicase-primase inhibitors are a new class of antiviral agent and may circumvent resistance to existing agents. Amenamevir and pritelivir are two examples of these agents that have been evaluated clinically along with novel nucleoside analogues such as valomaciclovir and FV-100. Tenofovir, an agent used in HIV and hepatitis B therapy, may also have a role in the prevention of HSV-2 acquisition and reduce viral shedding. SUMMARY: Although several novel antiviral agents have undergone clinical trials in recent years, all are yet to gain licensure. Brincidofovir appears to be the candidate with most promise for adoption into routine practice in the near future.


Asunto(s)
Antivirales/uso terapéutico , Citosina/análogos & derivados , Farmacorresistencia Viral/efectos de los fármacos , Herpes Simple/tratamiento farmacológico , Herpes Zóster/tratamiento farmacológico , Organofosfonatos/uso terapéutico , Antivirales/farmacocinética , Antivirales/farmacología , Ensayos Clínicos como Asunto , Citosina/farmacocinética , Citosina/farmacología , Citosina/uso terapéutico , Descubrimiento de Drogas , Evaluación de Medicamentos , Herpes Simple/inmunología , Herpes Zóster/inmunología , Humanos , Pruebas de Sensibilidad Microbiana , Organofosfonatos/farmacocinética , Organofosfonatos/farmacología , Resultado del Tratamiento , Replicación Viral/efectos de los fármacos
12.
Epigenetics ; 10(5): 397-407, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25932923

RESUMEN

The mechanism responsible for developmental stage-specific regulation of γ-globin gene expression involves DNA methylation. Previous results have shown that the γ-globin promoter is nearly fully demethylated during fetal liver erythroid differentiation and partially demethylated during adult bone marrow erythroid differentiation. The hypothesis that 5-hydroxymethylcytosine (5 hmC), a known intermediate in DNA demethylation pathways, is involved in demethylation of the γ-globin gene promoter during erythroid differentiation was investigated by analyzing levels of 5-methylcytosine (5 mC) and 5 hmC at a CCGG site within the 5' γ-globin gene promoter region in FACS-purified cells from baboon bone marrow and fetal liver enriched for different stages of erythroid differentiation. Our results show that 5 mC and 5 hmC levels at the γ-globin promoter are dynamically modulated during erythroid differentiation with peak levels of 5 hmC preceding and/or coinciding with demethylation. The Tet2 and Tet3 dioxygenases that catalyze formation of 5 hmC are expressed during early stages of erythroid differentiation and Tet3 expression increases as differentiation proceeds. In baboon CD34+ bone marrow-derived erythroid progenitor cell cultures, γ-globin expression was positively correlated with 5 hmC and negatively correlated with 5 mC at the γ-globin promoter. Supplementation of culture media with Vitamin C, a cofactor of the Tet dioxygenases, reduced γ-globin promoter DNA methylation and increased γ-globin expression when added alone and in an additive manner in combination with either DNA methyltransferase or LSD1 inhibitors. These results strongly support the hypothesis that the Tet-mediated 5 hmC pathway is involved in developmental stage-specific regulation of γ-globin expression by mediating demethylation of the γ-globin promoter.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Citosina/análogos & derivados , Metilación de ADN/efectos de los fármacos , Células Eritroides/citología , Regiones Promotoras Genéticas/efectos de los fármacos , gamma-Globinas/metabolismo , 5-Metilcitosina/metabolismo , Animales , Animales Recién Nacidos , Antineoplásicos/farmacología , Ácido Ascórbico/farmacología , Azacitidina/análogos & derivados , Azacitidina/farmacología , Células de la Médula Ósea , Células Cultivadas , Citosina/metabolismo , Citosina/farmacología , Decitabina , Dioxigenasas/metabolismo , Células Eritroides/efectos de los fármacos , Células Eritroides/metabolismo , Histona Demetilasas/metabolismo , Humanos , Hidroxiurea/farmacología , Hígado/citología , Hígado/efectos de los fármacos , Papio anubis , Tranilcipromina/farmacología
13.
Transpl Infect Dis ; 17(1): 125-8, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25571908

RESUMEN

We report a 65-year-old heart transplant recipient who presented with conjunctivitis, likely acquired from a family member who worked at a daycare center during an outbreak of conjunctivitis. He developed a severe adenoviral pneumonitis, which was successfully treated with intravenous cidofovir combined with a reduction of immunosuppression.


Asunto(s)
Infecciones por Adenovirus Humanos/tratamiento farmacológico , Antivirales/uso terapéutico , Conjuntivitis/tratamiento farmacológico , Trasplante de Corazón/efectos adversos , Neumonía Viral/tratamiento farmacológico , Complicaciones Posoperatorias/tratamiento farmacológico , Adenovirus Humanos/efectos de los fármacos , Anciano , Cidofovir , Citosina/análogos & derivados , Citosina/uso terapéutico , Humanos , Huésped Inmunocomprometido , Terapia de Inmunosupresión/efectos adversos , Masculino , Organofosfonatos/uso terapéutico , Receptores de Trasplantes
14.
Auris Nasus Larynx ; 42(3): 218-20, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25454156

RESUMEN

OBJECTIVE: Recurrent respiratory papillomatosis (RRP) has historically been and still continues to be a difficult disease to treat. The present study aimed to characterize current practices in the treatment of RRP in Japan. METHODS: A questionnaire was posted to the Department of Otolaryngology of all 80 central university hospitals in Japan. RESULTS: A total of 56 universities responded to the survey. Regarding the use of surgical instruments, a trend toward a preference for lasers (50 hospitals) rather than a microdebrider (16 hospitals) or cold instruments (20 hospitals) was observed. Among the 50 hospitals frequently performing laser surgery, a carbon dioxide (CO2) laser was most commonly used, followed by a potassium-titanyl-phosphate (KTP) laser. The most favored adjuvant therapy was traditional Chinese medicine. Eight of the 56 university hospitals had an experience of using cidofovir, involving a total of 28 patients. CONCLUSION: The present study demonstrated the current trends in the management of RRP based on a questionnaire survey in a geographical area other than the US and UK for the first time. Treatment trends were generally similar in all three areas except for the least popular use of cidofovir in Japan.


Asunto(s)
Antivirales/uso terapéutico , Citosina/análogos & derivados , Terapia por Láser/métodos , Medicina Tradicional China/métodos , Organofosfonatos/uso terapéutico , Otolaringología/tendencias , Infecciones por Papillomavirus/terapia , Pautas de la Práctica en Medicina/tendencias , Infecciones del Sistema Respiratorio/terapia , Cidofovir , Citosina/uso terapéutico , Desbridamiento , Manejo de la Enfermedad , Humanos , Japón , Láseres de Gas , Láseres de Estado Sólido , Encuestas y Cuestionarios
15.
Pediatr Transplant ; 18(7): E227-31, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25174393

RESUMEN

NC, with renal failure secondary to bilateral dysplastic kidneys, received an LRD renal transplant (tx) at 17 months of age. Her early post-tx course was complicated by persistently elevated blood polyoma BK virus DNA loads. A protocol biopsy at six months post-transplant revealed BKVAN. Blood viral loads did not respond to decreased immunosuppression or treatment with ciprofloxacin and leflunomide. Six months post-tx, her serum creatinine began to rise and we sought experimental therapy to prevent the loss of her graft. At seven months post-tx, with FDA approval under an eIND, the patient was started on a 36-wk course of treatment with the investigational drug. The patient is now more than 24 months after stopping treatment with CMX. BKV viral DNA loads remain at low, but still detectable levels. Urine viral loads have declined, but remain elevated. EBV DNA loads become undetectable. The patient's serum creatinine has declined back to a baseline of 0.5-0.7 mg/dL and has been stable for two yr. Renal function was preserved in association with the use of CMX001 to treat BKV nephropathy in a young pediatric kidney transplant recipient. There were no serious adverse events associated with the use of CMX001. This novel medication may be of value in the treatment of BKVAN in pediatric renal transplant recipients.


Asunto(s)
Virus BK , Citosina/análogos & derivados , Trasplante de Riñón , Organofosfonatos/uso terapéutico , Insuficiencia Renal Crónica/virología , Insuficiencia Renal/complicaciones , Insuficiencia Renal/cirugía , Administración Oral , Biopsia , Preescolar , Ciprofloxacina/uso terapéutico , Creatinina/sangre , Citosina/uso terapéutico , ADN Viral/análisis , Femenino , Humanos , Inmunosupresores/uso terapéutico , Isoxazoles/uso terapéutico , Leflunamida , Carga Viral
16.
Expert Rev Anti Infect Ther ; 12(10): 1171-8, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25120093

RESUMEN

CMX001 (hexadecyloxypropyl-cidofovir, Brincidofovir) is a broad spectrum, lipid conjugate of cidofovir that is converted intracellularly into the active antiviral, cidofovir diphosphate. The lipid conjugation results in oral bioavailability, higher intracellular concentrations of active drug, lower plasma concentrations of cidofovir and increased antiviral potency against dsDNA viruses.


Asunto(s)
Antivirales/uso terapéutico , Citosina/análogos & derivados , Infecciones por Virus ADN/tratamiento farmacológico , Organofosfonatos/uso terapéutico , Adenoviridae/efectos de los fármacos , Antivirales/química , Antivirales/farmacología , Citomegalovirus/efectos de los fármacos , Citosina/química , Citosina/farmacología , Citosina/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Virus del Molusco Contagioso/efectos de los fármacos , Organofosfonatos/química , Organofosfonatos/farmacología , Orthopoxvirus/efectos de los fármacos , Poliomavirus/efectos de los fármacos
17.
JAMA Otolaryngol Head Neck Surg ; 140(2): 155-9, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24288019

RESUMEN

IMPORTANCE: Recurrent respiratory papillomatosis (RRP) is a common and often chronic disorder. Intralaryngeal bevacizumab has gained recent interest as an adjuvant therapy for RRP. However, no histologic model has been published describing the effects of bevacizumab on the vocal fold. OBJECTIVE: To investigate the histologic effects of bevacizumab injections into the vocal fold and compare these findings with those for cidofovir and saline control injections. DESIGN AND SETTING: In vivo animal study involving eighteen 1-year-old Yorkshire crossbreed pigs, with a blinded review of pathologic findings conducted in a veterinary research laboratory. INTERVENTIONS: The pigs were randomly divided into six study groups receiving 2.5 or 5.0 mg of cidofovir or bevacizumab alone or in combination. Each pig received an injection of 0.5 mL of the test drug in the right vocal fold and 0.5 mL of saline in the left vocal fold. These injections were performed 4 times during the course of 8 weeks. One pig from each group was killed humanely and the larynges harvested 2 weeks after the last injection. The remaining pigs were killed 4 months after the last injection on the remaining pigs. The vocal folds were fixed and stained with hematoxylin-eosin and trichrome and reviewed for histologic changes by 3 blinded pathologists. MAIN OUTCOMES AND MEASURES: Histologic changes to the vocal folds. RESULTS: Minimal inflammation, edema, and atypia were found in all treatment groups. No appreciable histologic differences were found among the 3 treatment groups and their controls. No difference was seen in the vocal folds that were harvested late (4 months) vs early (2 weeks) after last injection. No fibrosis was found in any of the specimens. CONCLUSIONS AND RELEVANCE: No histologic evidence suggests that intralaryngeal cidofovir or bevacizumab alone or in combination resulted in significant changes to the porcine vocal fold. Future studies may build on this model to test higher dosages and/or may combine injections with potassium titanyl phosphate laser therapy.


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacología , Citosina/análogos & derivados , Organofosfonatos/farmacología , Pliegues Vocales/efectos de los fármacos , Pliegues Vocales/patología , Animales , Bevacizumab , Biopsia con Aguja , Cidofovir , Citosina/farmacología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Inmunohistoquímica , Inyecciones Intralesiones , Modelos Animales , Distribución Aleatoria , Sensibilidad y Especificidad , Sus scrofa , Porcinos
19.
J Colloid Interface Sci ; 386(1): 291-9, 2012 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-22918045

RESUMEN

A new solid-phase extraction adsorbent was prepared by employing a two-step "grafting from" approach to anchor a multidentate N-donor ligand, 5-azacytosine onto hydrothermal carbon (HTC) microspheres for highly selective separation of U(VI) from multi-ion system. Fourier-transform infrared and X-ray photoelectron spectroscopies were used to analyze the chemical structure and properties of resultant HTC-based materials. The adsorption behavior of U(VI) onto the adsorbent was investigated as functions of pH, contact time, ionic strength, temperature, and initial U(VI) concentration using batch adsorption experiments. The U(VI) adsorption was of pH dependent. The adsorption achieved equilibrium within 30 min and followed a pseudo-second-order equation. The adsorption amount of U(VI) increased with raising the temperature from 283.15 to 333.15K. Remarkably, high ionic strength up to 5.0 mol L(-1) NaNO(3) had only slight effect on the adsorption. The maximum U(VI) adsorption capacity reached 408.36 mg g(-1) at 333.15K and pH 4.5. Results from batch experiments in a simulated nuclear industrial effluent, containing 13 co-existing cations including uranyl ion, showed a high adsorption capacity and selectivity of the adsorbent for uranium (0.63 mmol U g(-1), accounting for about 67% of the total adsorption amount).


Asunto(s)
Carbono/química , Citosina/análogos & derivados , Extracción en Fase Sólida , Uranio/química , Adsorción , Citosina/química , Calor , Microesferas , Estructura Molecular
20.
PLoS One ; 7(3): e32610, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22427855

RESUMEN

In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarracenia purpurea as the first effective inhibitor of poxvirus replication at the level of early viral transcription. With the renewed threat of poxvirus-related infections, our results indicate Sarracenia purpurea may act as another defensive measure against Orthopoxvirus infections.


Asunto(s)
Fitoterapia/historia , Fitoterapia/métodos , Extractos Vegetales/farmacología , Sarraceniaceae/química , Viruela/tratamiento farmacológico , Virus de la Viruela/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Animales , Canadá , Línea Celular , Cidofovir , Citosina/análogos & derivados , Citosina/uso terapéutico , Técnica del Anticuerpo Fluorescente , Células HeLa , Historia del Siglo XIX , Humanos , Técnicas In Vitro , Organofosfonatos/uso terapéutico , Conejos , Reacción en Cadena en Tiempo Real de la Polimerasa , Viruela/historia , Estados Unidos
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