Las estatinas afectan la viabilidad de líneas celulares de leucemia y linfoma humanas in vitro / Statins affect the viability of leukemia cell lines in vitro and human lymphoma

Se ha propuesto que las estatinas inducen apoptosis sobre células tumorales. Para probar dicha hipótesis, se analizó el efecto de las estatinas atorvastatina, fluvastatina, lovastatina, mevastatina, pravastatina y simvastatina en el rango de concentraciones de 1 pM hasta 100 µM, sobre la viabilidad de las líneas celulares humanas Jurkat E6.1, Jurkat D1.1 (Linfoma T) , Daudi (Linfoma B), U937 (leucemia monocítica) y HL-60 (leucemia promielomonocítica) in vitro en cultivos de 48 horas, analizados por la técnica de hidrolización del compuesto bromuro de 3-(4,5-dimetiltiazol-2-il)-2,5-difenilltetrazolio (MTT). Lovastatina y mevastatina son los más potentes inductores de muerte celular independientemente del tipo celular (Ic 50 entre 12 y 50 µM). Para las otras estatinas se observan diferencias en el Ic50 según la línea celular atorvastatina (38,1 y 48,6 µM Jurkats, 55,3 µM Daudi y 100 µM para las otras líneas), pravastatina (25 µM HL-60, 55,6 y 60,7 µM Jurkats y > 100 µM Daudi y U937), simvastatina (25,1 µM Jurkat D1.1, 50,2 µM Jurkat E6.1, 45,2 µM Daudi y 51,3 µM HL-60, y > 100 µM U937) y para fluvastatina en todos los casos > 100 µM. La disminución de la viabilidad celular se revierte completamente cuando las células son incubadas con 10 µM mevalonato. Se concluye que la lovastatina y mevastatina son las más potentes inductoras de muerte seguida por atorvastatina, pravastatina y simvastatina cuyo efecto depende del tipo de línea celular y la fluvastatina no tiene efectos importantes en la viabilidad de las líneas celulares estudiadas

Statins have been proposed to induce apoptosis of tumor cells. In order to test this hypothesis, the effect of atorvastatin, fluvastatin, lovastatin, mevastatin, pravastatin, simvastatin on cell viability was assessed by in vitro culture for 48 hr, at concentrations ranging from 1 pM to 100 µM on human cell lines Jurkat E6.1, Jurkat D1.1 (T cell lymphoma), Daudi (B cell lymphoma), U937 (monocitic leukemia) and HL-60 (pro mielomonocitic leukemia) and analyzed the oxidation of (3-(4.5-Dimethylthiazol-2-yl)-2.5- diphenyltetrazolium bromide (MTT). Lovastatin and mevastatin are the most potent inductors of cell death independently of the cell type (Ic 50 between 12 and 50 µM). Differences in the Ic50 are observed depending on the cell line: atorvastatina (38.1 and 48.6 µM Jurkats, 55.3 µM Daudi y 100 µM for the others lines), pravastatin (25 µM HL-60, 55.6 y 60.7 µM Jurkats and > 100 µM Daudi and U937), simvastatin (25.1 µM Jurkat D1.1, 50.2 µM Jurkat E6.1, 45.2 µM Daudi and 51,3 µM HL-60, and > 100 µM U937) and for fluvastatin > 100 µM in all cases. The decrease in cell viability is reverted completely when the cells were incubated with 10 µM mevalonate. It is concluded that lovastatin and mevastatin are the most potent inductors of cell death followed by atorvastatin, pravastatin and simvastatin whose effect depends upon the cell type and fluvastatin does not have any important effects on cell viability on the cell lines studied

HTLV1/2 infection among renal dialysis patients in Egypt

Hemodialysis patients are one of the high risk groups for blood borne viral infection including HTLV1/2. This study was carried out on 171 chronic hemodialysis patients. From each patient, a serum sample and EDTA anticoagulated blood were collected. Serum was tested for anti HTLV1/2 antibodies by ELISA. Positive patients were confirmed by whole blood-PCR for detection of HTLV1/2 proviral DNA. Two [1.17%] patients were positive for both HTLV1/2 antibodies [by ELISA] and HTLV1/2 proviral DNA [by whole blood-PCR]. Interestingly, these two patients received more than 30 blood transfusions and were on hemodialysis for more than one year. Among patients who received 30 or more blood transfusions and those on hemodialysis for one year or more, the prevalence of HTLV1/2 positivity [by both ELISA and PCR] was 4.8% and 1.6%, respectively. A high frequency of HCV seropositivity [76%] was detected among our patients. Nevertheless, this frequency was not affected by the number of previously received blood transfusions [x[2] =3.48, P=0.481] or duration of hemodialysis [x[2] =3.21, P=0.073]. Two [1.17%] patients were positive for HBs antigen and they were transferred to the Fevers Hospital Hemodialysis Centre. This probably represents the tip of the iceberg as serum HBs antigen screening in the present setting is done every three months. Therefore, these two patients converted to HBs antigen seropositivity within the last three months only. Fortunately, none of our patients was anti HIV1/2 positive. These results suggest that HTLV1/2 infection occurs in hemodialysis patients in Egypt and the prevalence becomes more among those receiving 30 or more blood transfusions and those on hemodialysis for one year or more. Therefore, we recommend screening of blood for HTLV1/2 antibodies before transfusion to chronic hemodialysis patients. In addition, proper infection control should be stressed in hemodialysis centres. Interestingly, a high prevalence of HCV positivity occurred in our patients in spite of routine anti HCV screening of blood prior to transfusion. Therefore, exclusion of anti-HCV positive patients to separate hemodialysis centres is recommended to control the rapid spread of HCV infection among these vulnerable patients

The pathogenesis of tropical spastic paraparesis/human T-cell leukemia type I-associated myelopathy

Tropical spastic paraparesis/human T-cell leukemia type I-associated myelopathy (TSP/HAM) is caused by a human T-cell leukemia virus type I (HTLV-I) after a long incubation period. TSP/HAM is characterized by a chronic progressive paraparesis with sphincter disturbances, no/mild sensory loss, the absence of spinal cord compression and seropositivity for HTLV-I antibodies. The pathogenesis of this entity is not completely known and involves a multivariable phenomenon of immune system activation against the presence of HTLV-I antigens, leading to an inflammatory process and demyelination, mainly in the thoracic spinal cord. The current hypothesis about the pathogenesis of TSP/HAM is: 1) presence of HTLV-I antigens in the lumbar spinal cord, noted by an increased DNA HTLV-I load; 2) CTL either with their lytic functions or release/production of soluble factors, such as CC-chemokines, cytokines, and adhesion molecules; 3) the presence of Tax gene expression that activates T-cell proliferation or induces an inflammatory process in the spinal cord; 4) the presence of B cells with neutralizing antibody production, or complement activation by an immune complex phenomenon, and 5) lower IL-2 and IFN-gamma production and increased IL-10, indicating drive to a cytokine type 2 pattern in the TSP/HAM subjects and the existence of a genetic background such as some HLA haplotypes. All of these factors should be implicated in TSP/HAM and further studies are necessary to investigate their role in the development of TSP/HAM

HTLV-I antibody study in normal individuals and unselected hospital patients in Malaysia.

A serological investigation for human T cell leukemia virus I (HTLV-I) infection was carried out at the University Hospital, Kuala Lumpur. A total of 626 sera from a non-patient population and 1,038 sera from unselected in-patients were screened for HTLV-I antibodies using an enzyme-linked immunosorbent assay (ELISA). 27/1664 (1.6%) were found to be reactive. However, on Western blotting, only 2 sera were confirmed positive, both showing reactions for the major core (p19 and p24) and the envelope (gp46) proteins. Both of the serum samples were from unselected hospital patients. Most of the remaining sera which were reactive on screening showed indeterminate results on Western blotting. These were further tested by radioimmunoprecipitation assay (RIPA) and none of these sera gave a positive reaction. Therefore, only 2/1038 (0.19%) unselected patients could be confirmed to have antibodies to HTLV-I. None of the normal individuals screened showed a positive Western blot result. Our data indicate that HTLV-I infection is present in our population, but at a low prevalence rate.

HTLV-I associated myelopathy in Brazil: a preliminary report

Neste relato preliminar os autores registram a constataçäo de alta prevalência do soropositividade para anticorpos dirigidos ao HTLV-I detectados pelo método de Westernblot (37,5%) em amostra de 16 pacientes brasileiros com mielopatias crônicas de causa näo determinadas