Fludarabine induces apoptosis in chronic lymphocytic leukemia - the role of P53, Bcl-2, Bax, Mcl-1, and Bag-1 proteins

The expression of P53, Bcl-2, Bax, Bag-1, and Mcl-1 proteins in CD5/CD20-positive B-chronic lymphocytic leukemia (B-CLL) cells from 30 typical CLL patients was evaluated before and after 48 h of incubation with 10-6 M fludarabine using multiparametric flow cytometric analysis. Protein expression was correlated with annexin V expression, Rai modified clinical staging, lymphocyte doubling time, and previous treatment. Our main goal was to determine the predictive value of these proteins in CLL cells in terms of disease evolution. Bcl-2 expression decreased from a median fluorescence index (MFI) of 331.71 ± 42.2 to 245.81 ± 52.2 (P < 0.001) after fludarabine treatment, but there was no difference between viable cells (331.57 ± 44.6 MFI) and apoptotic cells (331.71 ± 42.2 MFI) before incubation (P = 0.859). Bax expression was higher in viable cells (156.24 ± 32.2 MFI) than in apoptotic cells (133.56 ± 35.7 MFI) before incubation, probably reflecting defective apoptosis in CLL (P = 0.001). Mcl-1 expression was increased in fludarabine-resistant cells and seemed to be a remarkable protein for the inhibition of the apoptotic process in CLL (from 233.59 ± 29.8 to 252.04 ± 35.5; P = 0.033). After fludarabine treatment, Bag-1 expression was increased in fludarabine-resistant cells (from 425.55 ± 39.3 to 447.49 ± 34.5 MFI, P = 0.012), and interestingly, this higher expression occurred in patients who had a short lymphocyte doubling time (P = 0.022). Therefore, we could assume that Bag-1 expression in such situation might identify CLL patients who will need treatment earlier.

Infecciones por virus herpes: drogas antiherpéticas: I / Herpesvirus infections: antiherpetic drugs: I

Aunque los antivirales sintéticos inhiben in vitro casi todos los virus del grupo herpes la terapia está virtualmente restringida a las infecciones por el virus herpes simplex y varicela zoster. Ninguna de estas drogas es realmente eficaz contra citomegalovirus; algunas tendrían cierta acción contra el virus Epstein-Barr. Las drogas antiherpéticas sólo actúan sobre el virus que replica, sin alcanzar al virus en estado de latencia. Deben ser usadas con precaución ya que aún no se han valorado sus efectos colaterales cuando se suministran por largos períodos. Las drogas antiherpéticas autorizadas por la FDA son: 1) la iododeoxiuridina en solución (0,1 por ciento) o unguento (0,5 por ciento) para uso oftálmico; 2) la trifluorotimidina en solución oftálmica (0,1 por ciento); 3) la adenina arabinosido en frasco ampolla de 1 gramo para uso intravenoso y 4) el aciclovir como unguento oftálmico (0,3 por ciento), crema dérmica (5 por ciento en base de propilenglicol al 40 por ciento), tabletas (400 y 200 mg) o jarabe para uso oral, frascos ampolla de 250 mg para uso intravenoso. El unguento dérmico es poco efectivo