The role of EVI1 in myeloid malignancies.

The EVI1 oncogene at human chr 3q26 is rearranged and/or overexpressed in a subset of acute myeloid leukemias and myelodysplasias. The EVI1 protein is a 135 kDa transcriptional regulator with DNA-binding zinc finger domains. Here we provide a critical review of the current state of research into the molecular mechanisms by which this gene plays a role in myeloid malignancies. The major pertinent cellular effects are blocking myeloid differentiation and preventing cellular apoptosis, and several potential mechanisms for these phenomena have been identified. Evidence supports a role for EVI1 in inducing cellular quiescence, and this may contribute to the resistance to chemotherapy seen in patients with neoplasms that overexpress EVI1. Another isoform, MDS1-EVI1 (or PRDM3), encoded by the same locus as EVI1, harbors an N-terminal histone methyltransferase(HMT) domain; experimental findings indicate that this protein and its HMT activity are critical for the progression of a subset of AMLs, and this provides a potential target for therapeutic intervention.

The effect of highly active antiretroviral therapy on outcome of central nervous system herpesviruses infection in Cuban human immunodeficiency virus-infected individuals.

With the rapid progress in the development of highly active antiretroviral therapy (HAART), the observed patterns in human immunodeficiency virus (HIV) encephalitis has changed, allowing herpesvirus (HV) infection to be controlled. HAART was first administered to HIV patients in Cuba in 2001. Consequently with the aim of investigate the behavior of the HVs causing neurological disorders in this population in the post-HAART era, the authors perform a clinical evaluation by a multiplex nested polymerase chain reaction (PCR) assay for simultaneous detection of human HVs--herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), and Epstein-Barr virus (EBV). The authors studied 241 samples of cerebrospinal fluid (CSF) received at the Sexually Transmitted Diseases Laboratory between 2001 and 2005 inclusive. Of the 241 CSF studied, 10.4% resulted positive for HV infections. Of these, 92% of patients were acquired immunodeficiency syndrome (AIDS) individuals at the C3 stage. CMV (44%), EBV (28%), and dual-HV (16%) infections were the most important agents identified. The principal clinical manifestations were fever, headache, vomiting, and focal abnormalities; the latter being associated with an increased risk of death. A statistically significant result was observed when central nervous system (CNS) disease evolution was compared between patients who were under HAART against those who were not, before they developed encephalitis. It was therefore concluded that it is more likely that HIV individuals receiving HAART have a better recovery of CNS infections than those who are not receiving it.

Distinct genotypic distribution of cytomegalovirus (CMV) envelope glycoprotein B (gB) in a Cuban cohort of patients with different CMV diseases.

To investigate the association between human CMV glycoprotein B (gB) genotypes and CMV disease, we retrospectively analysed 73 biological samples from 56 Cuban patients with different CMV-related diseases using a multiplex nested PCR for detection of the reported 5 CMV gB genotypes. All 4 main genotypes 1 to 4 were found in the clinical samples while no genotype 5 was detected. Among the individuals analysed, genotype gB-2 was the most prevalent (38%) followed by gB-1 (30%) and mixed infections (16%) being mainly detected among immunosuppressed patients (7 out of 9), although there was no association between mixed infections and CMV rejection in transplant recipients. Genotype gB-4 was the least frequent (5 patients), which was almost exclusively detected in mixed infections (4 out of 5, p<0.0001). Genotype gB-1 was more frequently detected in AIDS patients (47%) although it was not statistically significant, while 68% of transplant patients showed mixed infections (p<0.05). This study represents the first report of human CMV gB genotypes in Cuban patients; however, the study is limited by the small number patients, thus making it difficult to draw firm conclusions about the distribution of CMV genotypes in Cuba. Nevertheless, this preliminary report has allowed us to identify that the main 4 CMV genotypes are present in the Cuban population, with genotypes 2 and 1 being the most frequent strains.

Evaluación de la actividad antiviral de plantas medicinales frente al virus de la hepatitis B (VHB) en células PLC/PRF/5 / Evaluation of the antiviral activity of medicinal plants against the hepatitis B virus (HBV) in PLC/PRF/5 cells

Se evaluaron las propiedades antivirales de los extractos vegetales derivados a partir de las plantas: Calendula officinalis L, Psidium guajava L, Eucaliptos spp y Phyllanthus orbicularis HBK contra el virus de la hepatitis B. Se llevó a cabo a concentraciones subtóxicas en el sistema in vitro PLC/PRF/5 o células Alexander, línea celular que expresa constitutivamente el antígeno de superficie del virus (AgsHB). El parámetro de viabilidad celular se midió mediante el cálculo de los valores de concentración citotóxica media (CC50): Eucalyptus spp. mostró una menor toxicidad en las células, seguido de Psidium guajava L, Phyllanthus orbicularis, y finalmente Calendula officinalis que tuvo una toxicidad mucho mayor que los extractos anteriores. Posteriormente se estudió el comportamiento de la producción de AgsHB intracelular y extracelular de las células a diferentes concentraciones de los extractos durante 48 h de tratamiento. Los datos obtenidos mostraron actividad inhibitoria en el caso de Phyllanthus orbicularis, así como para el extracto de eucalipto. Con el extracto de guayaba la actividad fue menor que en los 2 casos anteriores, mientras que la caléndula no mostró ninguna inhibición a las concentraciones ensayadas, lo que indica la ausencia de la actividad buscada en este extracto

The antiviral properties of plants extracts derived from Calendula officinalis L., Psidium guajava L., Eucaliptus spp. y Phyllanthus orbicularis HBK against the hepatitis B virus were evaluated at subtoxic concentrations in the in vitro PLC/PRF/5 system or Alexander cells, a cell line expressing constitutively the virus surface antigen (AgsHB). The cell viability parameter that was measured by the calculation of the mean cytotoxic concentration values (CC50): Eucalyptus spp. showed a lower toxicity in the cells, followed by Psidium guajava L., Phyllanthus orbicularis, and finally Calendula officinalis that had a much higher toxicity than the previous extracts. Later on, it was studied the behaviour of the production of intracellular and extracellular HBsAg of the cells at different concentrations of the extracts during 48 hours of treatment. The data obtained showed an inhibitory activity in the case of Phyllanthus orbicularis, as well as for the eucaliptus extract. With the guava extract, the activity was lower than in the 2 previous cases, whereas calendula did not show any inhibition to the assayed concentrations, which proves the absence of the activity searched in this extract

Evaluación de la actividad antiviral de plantas medicinales frente al virus de la hepatitis B (VHB) en células PLC/PRF/5 / Evaluation of the antiviral activity of medicinal plants against the hepatitis B virus (HBV) in PLC/PRF/5 cells

Se evaluaron las propiedades antivirales de los extractos vegetales derivados a partir de las plantas: Calendula officinalis L, Psidium guajava L, Eucaliptos spp y Phyllanthus orbicularis HBK contra el virus de la hepatitis B. Se llevó a cabo a concentraciones subtóxicas en el sistema in vitro PLC/PRF/5 o células Alexander, línea celular que expresa constitutivamente el antígeno de superficie del virus (AgsHB). El parámetro de viabilidad celular se midió mediante el cálculo de los valores de concentración citotóxica media (CC50): Eucalyptus spp. mostró una menor toxicidad en las células, seguido de Psidium guajava L, Phyllanthus orbicularis, y finalmente Calendula officinalis que tuvo una toxicidad mucho mayor que los extractos anteriores. Posteriormente se estudió el comportamiento de la producción de AgsHB intracelular y extracelular de las células a diferentes concentraciones de los extractos durante 48 h de tratamiento. Los datos obtenidos mostraron actividad inhibitoria en el caso de Phyllanthus orbicularis, así como para el extracto de eucalipto. Con el extracto de guayaba la actividad fue menor que en los 2 casos anteriores, mientras que la caléndula no mostró ninguna inhibición a las concentraciones ensayadas, lo que indica la ausencia de la actividad buscada en este extracto(AU)

[Evaluation of the antiviral activity of medicinal plants against the hepatitis B virus (HBV) in PLC/PRF/5 cells]. / Evaluación de la actividad antiviral de plantas medicinales frente al virus de la hepatitis B (VHB) en células PLC/PRF/5.

Calendula officinalis L., Psidium guajava L., Eucaliptus spp. y Phyllanthus orbicularis HBK against the hepatitis B virus were evaluated at subtoxic concentrations in the in vitro PLC/PRF/5 system or Alexander cells, a cell line expressing constitutively the virus surface antigen (AgsHB). The cell viability parameter that was measured by the calculation of the mean cytotoxic concentration values (CC50): Eucalyptus spp. showed a lower toxicity in the cells, followed by Psidium guajava L., Phyllanthus orbicularis, and finally Calendula officinalis that had a much higher toxicity than the previous extracts. Later on, it was studied the behaviour of the production of intracellular and extracellular HBsAg of the cells at different concentrations of the extracts during 48 hours of treatment. The data obtained showed an inhibitory activity in the case of Phyllanthus orbicularis, as well as for the eucaliptus extract. With the guava extract, the activity was lower than in the 2 previous cases, whereas calendula did not show any inhibition to the assayed concentrations, which proves the absence of the activity searched in this extract.