Network of phosphatases and HDAC complexes at repressed chromatin.

Tight regulation of gene expression is achieved by a variety of protein complexes that selectively bind chromatin, modify it and change its transcription competency. Histone acetylases (HATs) and deacetylases (HDACs) play an important role in this process. They can generate transcriptionally active or inactive chromatin through the addition (HATs) or removal (HDACs) of acetyl groups on histones, respectively. Repo-Man is a Protein Phosphatase 1 targeting subunit that accumulates on chromosomes during mitotic exit and mediates the removal of mitotic histone H3 phosphorylations. It was shown recently that Repo-Man also regulates heterochromatin formation in interphase and that its depletion favours the switch between transcriptionally inactive and active chromatin, demonstrating that its role goes well beyond mitosis. Here, we provide the first link between a phosphatase and HDAC complexes. We show that genome-wide Repo-Man binding sites overlap with chromatin regions bound by members of the three HDAC complexes (Sin3a, NuRD and CoREST). We establish that members of the NuRD and Sin3a HDAC complexes interact with Repo-Man by mass spectrometry and that Repo-Man is in close proximity to SAP18 (Sin3a) in interphase as observed by the Proximity Ligation Assay. Altogether, these data suggest a mechanism by which Repo-Man/PP1 complex, via interactions with HDACs, could stabilise gene repression.

Malignant syphilis in an AIDS patient.

Malignant syphilis is an uncommon, but not unknown, ulcerative variation of secondary syphilis. The lesions typically begin as papules, which quickly evolve to pustules and then to ulcers with elevated edges and central necrosis. It is usually, but not mandatory, found in patients with some level of immunosuppression, such as HIV patients, when the TCD4(+) cell count is >200 cells/mm(3). Despite the anxiety the lesions cause, this form of the disease has a good prognosis. The general symptoms disappear right after the beginning of treatment, and lesions disappear over a variable period. This study reports the case of a 27-year-old man who has been HIV positive for 6 years, uses antiretroviral therapy incorrectly, has a TCD4(+) cell count of 340 cells/mm(3), a VDRL of 1:128 and itchy disseminated hyperchromic maculopapular lesions with rupioid crusts compatible with malignant syphilis.

[Study on the adverse reactions related to paclitaxel and docetaxel infusion]. / Estudio de las reacciones adversas relacionadas con la infusión de paclitaxel y docetaxel.

OBJECTIVE: To determine the incidence of paclitaxel and docetaxel infusion-associated reactions, and the likely causes that may trigger them. METHOD: Cohort study of the paclitaxel and docetaxel infusions carried out at a tertiary hospital from July of 2010 to December of 2011 (18 months). For each infusion, the clinical data and the drug-related data were recorded. When a reaction occurred during the infusion the following data were specified: type, severity, if treatment withdrawal was needed. The clinical charts and treatment orders were reviewed. The follow-up of the infusions were done by contacting the day-care hospital nurses. A descriptive study was done for the most relevant variables included in the follow-up and we analyzed if any of them could have had an influence on the occurrence of the reactions. RESULTS: During the study period, 357 paclitaxel and docetaxel infusions were administered to 92 patients: mean age 61.4 years (SD 11.1), 50.0% were female. 9 infusion reactions affecting 8 patients occurred, all of them caused by docetaxel (c2 = 8.3, p = 0.004); 14.5% of the patients receiving it, and always during the first or second treatment cycle. The variables significantly associated to the occurrence of the reaction were: lung cancer (p< 0.005), docetaxel-cisplatin regime (p< 0.005), receiving the drug as first line (p=0.021), and non-advanced disease (p = 0.014). CONCLUSIONS: At our hospital, docetaxel is the taxane that has provoked the most frequent safety problems during the infusion.

Objetivo: Determinar la incidencia de reacciones a la infusión de paclitaxel y docetaxel, y las posibles causas que pueden desencadenarlas. Método: Estudio de cohortes de las infusiones de paclitaxel y docetaxel realizadas en un hospital de tercer nivel, desde julio de 2010 hasta diciembre de 2011 (18 meses). Para cada infusión se registraron los datos clínicos del paciente y los referentes al taxano administrado. Ante la aparición de una reacción durante la infusión se especificó: tipo, gravedad y si ésta obligó a la suspensión del tratamiento. Se consultaron las historias clínicas y las órdenes médicas. El seguimiento de las infusiones se realizó contactando con las enfermeras de hospital de día. Se efectuó un estudio descriptivo de las variables más relevantes incluidas en el seguimiento y se analizó si alguna de ellas podía influir en la aparición de reacciones. Resultados: Durante el periodo de estudio, se administraron 357 infusiones de paclitaxel y docetaxel a 92 pacientes: media de edad 61,4 años (DE 11,1), 50,0% mujeres. Se detectaron 9 reacciones infusionales que afectaron a 8 pacientes, todas ellas causadas por docetaxel (c2 = 8,3, p = 0,004); el 14,5% de los pacientes que lo llevaron, y siempre durante el primer o segundo ciclo de tratamiento. Las variables asociadas significativamente a la aparición de reacciones fueron: neoplasia de pulmón (p< 0,005), esquema docetaxel-cisplatino (p < 0,005), recibir el fármaco en primera línea (p=0,021) y enfermedad no avanzada (p=0,014). Conclusiones: En nuestro centro hospitalario, docetaxel es el taxano que ha provocado más problemas de seguridad durante su infusión.