RESUMEN
BACKGROUND Morphea, also known as localized scleroderma, is a rare autoimmune connective tissue disease characterized by skin fibrosis. UVA1 phototherapy is an important asset in the reduction of clinical manifestations in morphea. There are studies claiming that UV light modulates the expression of some human endogenous retroviral sequences. The aim of this study was to determine if the expression of HERV-K10 gag element is lowered by UVA1 phototherapy in morphea, a disease in which such irradiation has a soothing effect. MATERIAL AND METHODS The expression levels of the HERV-K10 gag were assessed by real-time PCR (polymerase chain reaction) in peripheral blood mononuclear cells (PBMC) and skin-punch biopsies of healthy volunteers and 9 morphea patients before and after phototherapy. Additionally, correlations between the HERV-K10 gag expression and age, disease duration, the Localized Scleroderma Skin Severity Index (LoSSI), and antinuclear antibody (ANA) titers were assessed. RESULTS In PBMC, HERV-K10 gag mRNA was significantly elevated after UVA1 phototherapy compared to healthy controls. Most of the patients responded with an increased expression level of this sequence. However, we found no statistical evidence at this point that phototherapy indeed has an effect on the HERV-K10 gag expression (there were no statistical differences in PBMC of morphea patients before and after phototherapy). Similarly, there was no statistically relevant effect of the UVA1 on the expression of HERV-K10 gag in skin. CONCLUSIONS At this point, the effect of UVA1 phototherapy on the expression of HERV-K10 gag cannot be statistically confirmed.
Asunto(s)
Retrovirus Endógenos/efectos de la radiación , Productos del Gen gag/biosíntesis , Infecciones por Retroviridae/terapia , Esclerodermia Localizada/terapia , Terapia Ultravioleta/métodos , Adulto , Anciano , Estudios de Casos y Controles , Retrovirus Endógenos/genética , Retrovirus Endógenos/metabolismo , Femenino , Productos del Gen gag/genética , Productos del Gen gag/metabolismo , Humanos , Leucocitos Mononucleares/efectos de la radiación , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Infecciones por Retroviridae/sangre , Infecciones por Retroviridae/patología , Infecciones por Retroviridae/virología , Esclerodermia Localizada/sangre , Esclerodermia Localizada/patología , Esclerodermia Localizada/virología , Rayos UltravioletaRESUMEN
Non-human primates have assumed an important role in preclinical safety assessment studies, particularly in the evaluation of biopharmaceutical and immunomodulatory therapies. Naturally occurring simian retrovirus infections may adversely affect the suitability of primates for use in such studies. Various species of non-human primates are the natural hosts for six exogenous retroviruses, representing five genera within the family Retroviridae. Retroviruses establish persistent infections with a broad spectrum of pathogenic potential, ranging from nonpathogenic to highly pathogenic, depending on the variety of the host, virus, and environmental factors. In the context of immunotoxicology, in which the research objective is to specifically evaluate the effect of drugs or biologics on the immune system, the immune modulatory effects of simian retroviruses, which may be subtle or profound, may introduce significant confounding into the studies of immunotoxic effects utilizing non-human primates. Latent or subclinical retrovirus infections are common and research-related procedures may lead to virus reactivation or overt disease. Adverse effects of undetected retrovirus infections on preclinical research include the loss of experimental subjects (and potentially of statistical power) due to increased morbidity and mortality, virus-induced clinical abnormalities, histologic lesions, alteration of physiologic parameters and biologic responses, and interference with in vitro assays and/or cytolytic destruction of primary cell cultures. The aim of this review is to provide an overview of the key biological, clinical, and pathological features of several important simian retroviruses, with emphasis on viruses infecting macaques and other primate species commonly used in preclinical research, and a discussion of the implications of these infections for immunotoxicology and other preclinical research in primates. Adequate pre-study retrovirus screening is essential to exclude retrovirus-infected primates from research protocols.
Asunto(s)
Haplorrinos/virología , Sistema Inmunológico/efectos de los fármacos , Enfermedades de los Monos/virología , Infecciones por Retroviridae/veterinaria , Retrovirus de los Simios/patogenicidad , Infecciones Tumorales por Virus/veterinaria , Xenobióticos/toxicidad , Animales , Animales de Laboratorio , Evaluación Preclínica de Medicamentos , Sistema Inmunológico/fisiología , Sistema Inmunológico/virología , Enfermedades de los Monos/patología , Infecciones por Retroviridae/patología , Infecciones por Retroviridae/transmisión , Retrovirus de los Simios/aislamiento & purificación , Retrovirus de los Simios/fisiología , Pruebas de Toxicidad , Infecciones Tumorales por Virus/patología , Infecciones Tumorales por Virus/transmisión , Xenobióticos/clasificaciónRESUMEN
Friend murine leukemia virus (FMuLv) is an acutely oncogenic retrovirus, and its infection leads to erythroblastosis and leukemia in mice. This infection model is used in the search for new antiviral agents. In the present study, the authors have evaluated the potential of an extract of Phyllanthus amarus against FMuLv-induced erythroleukemia in BALB/c mice. Injection of newborn mice with FMuLv resulted in leukemia and animals died due to splenomegaly. Oral administration of P.amarus was found to enhance the life span of leukemia-harboring animals and decrease the incidence of anemia. The authors also performed a series of hematological, biochemical, histopathological, and gene expression analyses to evaluate the effect of P.amarus administration on erythroleukemia initiation and progression. The data obtained indicate that P.amarus administration could significantly decrease the progression of erythroleukemia. Treatment with P.amarus induced the expression of p53 and p45NFE2 and decreased the expression of Bcl-2 in the spleen of infected mice. Histopathological evaluations of the spleen demonstrated that administration of P.amarus decreased the infiltration of leukemic cells into the sinusoidal space when compared with the vehicle treated group. P.amarus is known to inhibit chemically induced neoplasm in different rodent models.The current results indicate that P.amarus has the ability to suppress virally induced cancers as well.
Asunto(s)
Virus de la Leucemia Murina de Friend , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Leucemia Experimental/tratamiento farmacológico , Phyllanthus/química , Extractos Vegetales/uso terapéutico , Infecciones por Retroviridae/tratamiento farmacológico , Infecciones Tumorales por Virus/tratamiento farmacológico , Anemia/sangre , Anemia/tratamiento farmacológico , Animales , Recuento de Células Sanguíneas , Peso Corporal/efectos de los fármacos , Transformación Celular Viral/efectos de los fármacos , Progresión de la Enfermedad , Expresión Génica/genética , Hemoglobinas/análisis , Hemoglobinas/metabolismo , Leucemia Eritroblástica Aguda/sangre , Leucemia Eritroblástica Aguda/patología , Leucemia Experimental/sangre , Leucemia Experimental/patología , Hígado/efectos de los fármacos , Hígado/patología , Ratones , Ratones Endogámicos BALB C , Subunidad p45 del Factor de Transcripción NF-E2/genética , Tamaño de los Órganos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Infecciones por Retroviridae/sangre , Infecciones por Retroviridae/patología , Infecciones por Retroviridae/virología , Bazo/efectos de los fármacos , Bazo/metabolismo , Bazo/patología , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/genética , Infecciones Tumorales por Virus/sangre , Infecciones Tumorales por Virus/patología , Infecciones Tumorales por Virus/virología , Ácido Úrico/sangreRESUMEN
Evidence for interactive effects of chromium and selenium on the appearance of mammary tumors was obtained by exposing female virgin C3H mice infected with the murine mammary tumorvirus (MMTV) to subtoxic levels of Cr [as Cr(III) nitrate] and Se (as sodium selenite) in the supply water. Cr counteracted the inhibitory effect of Se on tumor development in a dose-dependent manner, shortened the tumor latency period, and accelerated tumor growth rates. Exposure to Cr also altered the levels of Se in the liver and kidneys of the mice, indicating that Cr interacts with Se and affects its organ distribution. Chromium must be added to the list of Se-antagonistic elements that weaken or abolish the antitumorigenic effects of Se. These findings are relevant to human cancer as previous studies revealed the age-corrected mortalities from breast and other major forms of cancer in different countries to be inversely correlated with the dietary Se intakes, and directly correlated with the estimated intakes of Cr and of other Se-antagonistic elements. The presence of these elements in foods must be taken into account when estimating the optimal dose of supplemental Se for cancer risk reduction.
Asunto(s)
Anticarcinógenos/antagonistas & inhibidores , Cromo/farmacología , Neoplasias Mamarias Experimentales/prevención & control , Virus del Tumor Mamario del Ratón , Selenio/antagonistas & inhibidores , Animales , Anticarcinógenos/metabolismo , Anticarcinógenos/farmacología , Cromo/metabolismo , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Femenino , Humanos , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos C3H , Infecciones por Retroviridae/metabolismo , Infecciones por Retroviridae/patología , Selenio/metabolismo , Selenio/farmacología , Factores de Tiempo , Infecciones Tumorales por Virus/metabolismo , Infecciones Tumorales por Virus/patologíaRESUMEN
The epidemiology of AIDS in Africa is discussed. Serological and clinical data on virology and population genetics are related to current theories of heterosexual transmission and to cultural practices involving the exchange or transmission of body fluids between individuals, such as female and male genital mutilation and indigenous or 'folk' medicine, as well as non-Western medical uses of medical syringes. A review of the relationship of autoimmune conditions, graft-vs-host disease and the retrovirus/oncogene involvement is presented. These data place in a new perspective concepts of widespread heterosexual infection and transmission of HIVs as well as their relation to AIDS in the context of the evolution of the human immune system.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/epidemiología , Infecciones por VIH/epidemiología , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/inmunología , África , Anticuerpos Antivirales/inmunología , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/patología , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/inmunología , Haití , Humanos , Estilo de Vida , Masculino , Compartición de Agujas/efectos adversos , Infecciones por Retroviridae/epidemiología , Infecciones por Retroviridae/patología , Enfermedades de Transmisión Sexual/epidemiología , Esterilización/normasRESUMEN
The role of passive immunity in bovine respiratory syncytial virus (BRSV) infections in neonatal calves was evaluated. Calves were divided into groups as follows: colostrum-deprived, sham-inoculated; colostrum-deprived, BRSV-inoculated; and colostrum-fed, BRSV-inoculated. Calves were inoculated with a low-passage field isolate of BRSV for 4 consecutive days by a combined respiratory tract route and were euthanized 6 days after receiving the last inoculation. Arterial oxygen tension (Pao2) decreased significantly over time in colostrum-deprived, BRSV-inoculated calves (P less than .01) and was significantly different among treatment groups (P less than .05). A significant decrease in arterial oxygen saturation was observed in this same group over time (P less than .01). Mean percentage of pneumonic lung volume (determined by computer data digitalization) was significantly greater in infected, colostrum-deprived calves compared with the other groups (P less than .01), and BRSV antigen was detected in these calves by avidin-biotin immunoperoxidase staining. Thus, passive immunity derived from colostrum feeding decreased the severity of BRSV infections in calves.