Cytotoxic effect of the pentacyclic oxindole alkaloid mitraphylline isolated from Uncaria tomentosa bark on human Ewing's sarcoma and breast cancer cell lines.

Preparations from Uncaria tomentosa, a South American Rubiaceae, have been used in the Peruvian traditional medicine for the treatment of infective, inflammatory and tumoral processes. In this study, the pentacyclic oxindole alkaloid mitraphylline was isolated from the dried inner bark of this plant species, and its structure elucidated by analysis of NMR spectroscopic data. Mitraphylline was differentially identified from its stereoisomeric pair isomitraphylline by (15)N-NMR. Its antiproliferative and cytotoxic effects have been tested on human Ewing's sarcoma MHH-ES-1 and breast cancer MT-3 cell lines, using cyclophosphamide and vincristine as reference controls. A Coulter counter was used to determine viable cell numbers, followed by the application of the tetrazolium compound MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium] an inner salt. A colorimetric method was employed to evaluate cell viability in this cytotoxic assay. Micromolar concentrations of mitraphylline (5 microM to 40 microM) inhibited the growth of both cell lines in a dose-dependent manner. The IC (50) +/- SE values were 17.15 +/- 0.82 microM for MHH-ES-1 and 11.80 +/- 1.03 microM for MT-3 for 30 hours, smaller than those obtained for the reference compounds. This action suggests that the pentacyclic oxindole alkaloid mitraphylline might be a new promising agent in the treatment of both human sarcoma and breast cancer.

Prevention of cytomegalovirus disease using pre-emptive treatment after solid organ transplant in patients at high risk for cytomegalovirus infection.

BACKGROUND: The use of pre-emptive or prophylactic treatment to control cytomegalovirus (CMV) replication after solid organ transplant (SOT) remains controversial. The aim of this study was to evaluate whether administration of pre-emptive treatment to control viral replication guided by a highly sensitive diagnostic tool is an effective approach for preventing CMV disease, even in high-risk transplant recipients. METHODS: Plasma samples from eight SOT patients were tested using antigenaemia and real-time PCR (RT-PCR) assays. Pre-emptive treatment was administered guided by RT-PCR when viral load values were >1,000 copies/ml. RESULTS: All patients developed episodes of CMV infection, but none of them developed CMV disease or indirect effects. No patient in this study died or experienced graft rejection. Treatment was needed in 10 replication episodes. At the end of treatment, four had undetectable levels and the other six were cleared 3 weeks later. In 42.6% of tested samples RT-PCR was more sensitive for detecting viral infection. CONCLUSIONS: Pre-emptive monitoring of SOT patients at high risk for CMV infection protected patients from developing CMV disease during the first 6 months after transplant. The use of this sensitive method for guiding pre-emptive treatment diminished viral load early enough that it did not have consequences for patient health.

[Descriptive study of infectious complications in 109 consecutive liver transplant recipients]. / Estudio descriptivo de las complicaciones infecciosas en 109 receptores de trasplantes hepáticos consecutivos.

INTRODUCTION: Infectious disease is a common, serious complication in liver transplant recipients. The etiology of these infections undergoes changes related with technical advances, prophylaxis, and local epidemiology. METHODS: Prospective study in patients who underwent liver transplantation from July 2003 to December 2005 at the Hospital Universitario Virgen del Rocío. An observational description of infections occurring during the first 2 years following transplantation was carried out. RESULTS: The incidence of infection was 1.32 episodes per patient over follow-up (443 +/- 248 days). The most frequent infections were surgical site (16%), cytomegalovirus (CMV) (14%), and urinary tract (11%). Etiologies included bacterial (64%), viral (31%), and fungal (5%) causes. The most common pathogens were CMV (21%), Escherichia coli (20%), among which, 40% were extended-spectrum beta-lactamase ESBL-producers, and Enterococcus spp. (11%). More than half the infectious episodes (58%) occurred in the first 4 months after transplantation. The 30-day mortality rate was 18%. In the group with infection, patient and graft survivals were 75% and 73% at the end of follow-up, and in the group without infection, survival was 80% in both cases (P=NS). CONCLUSIONS: The most common infectious syndromes following liver transplantation were surgical site infection, CMV infection, and urinary tract infection. Bacteria were the most commonly isolated microorganisms, and there was a high rate of ESBL-producing E. coli.