Tamoxifen induces toxicity, causes autophagy, and partially reverses dexamethasone resistance in Jurkat T cells.

Estrogens demonstrate biological activity in numerous organ systems, including the immune system, and exert their effects through estrogen receptors (ER) of two types: intracellular ERα and ERß that activate transcriptional factors and membrane G protein-coupled ER GPER. The latter is capable to mediate fast activation of cytosolic signaling pathways, influencing transcriptional events in response to estrogens. Tamoxifen (TAM), widely used in chemotherapy of ERα-positive breast cancer, is considered as an ERα antagonist and GPER agonist. TAM was shown to possess "off-target" cytotoxicity, not related to ER in various tumor types. The present work was designed to study biological effects of TAM on the glucocorticoid (GC)-resistant cell line Jurkat, derived from acute lymphoblastic leukemia of T lineage (T-ALL). We have shown that T-ALL cell lines, in contrast to healthy T cells, express only GPER, but not ERα or ERß. TAM compromised mitochondrial function and reduced the viability and proliferation of Jurkat cells. Additionally, TAM induced autophagy in a GPER-dependent manner. Gene expression profiling revealed the up-regulation of autophagy-related gene ATG5. Interestingly, TAM sensitized Jurkat cells to dexamethasone (DEX) treatment, which may be related to its capacity to cause autophagy. We suggest that TAM-based adjuvant therapy may represent a novel strategy in T-ALL patients handling.

Prolonged cold ischemia: risk factor for acute rejection in renal grafting of cadaveric kidney transplantation.

BACKGROUND: Exposure of renal grafting to prolonged cold ischemia time (CIT) and the association with acute rejection (AR) are known. However, there is no evidence in Mexico about this topic. Thus, the objective of this study was to evaluate prolonged CIT as a risk factor for AR in renal grafting of cadaveric kidney transplantation in a Mexican population. METHODS: A cross-sectional study was carried out. Clinical files of patients undergoing renal grafting using cadaveric kidneys were reviewed from July 1994-June 2004. Prolonged CIT (=12 h) as a risk factor for AR was evaluated. Other related variables were also examined. RESULTS: From 425 kidney transplantations, only 33 cases were cadaveric. Ten patients had AR. Prolonged CIT (OR 8.4; CI 1.5-44.2, p = 0.02) and azathioprine (AZA)-prednisone (PDN)-cyclosporine (CSA) combination (OR 9.1; CI 1.5-49.4, p = 0.02) were risk factors for AR. Anti-CD25 use (OR 0.6; CI 0.009-0.37, p = 0.001) and mycofenolate mofetil (MMF)-PDN-CSA combination (OR 0.1; CI 0.02-0.65, p = 0.02) were protective factors for AR. CONCLUSIONS: In a Mexican population, prolonged CIT and AZA-PDN-CSA combination were risk factors for AR. Meanwhile, anti- CD25 use and MMF-PDN-CSA combination were protective factors for AR in cadaveric kidney transplantations.

Isquemia fría prolongada, factor para rechazo agudo del injerto en trasplante renal cadavérico / Prolonged cold ischemia: risk factor for acute rejection in renal grafting of cadaveric kidney transplantation

Introducción: Es conocido que la exposición del injerto renal a tiempo prolongado de isquemia fría se asocia con rechazo agudo. Dado que no se encontró evidencia del tema en México, el objetivo de este estudio fue determinar el papel del tiempo de isquemia fría prolongado sobre el injerto en el trasplante renal cadavérico en población mexicana. Material y métodos: Estudio observacional, retrospectivo, transversal y analítico para el que se seleccionaron los expedientes de pacientes con trasplante renal entre julio de 1994 y junio de 2004. Se realizó análisis de diferentes variables para determinar su efecto sobre el rechazo agudo, entre ellas el tiempo prolongado de isquemia fría (≥ 12 horas). Resultados: De los 425 transplantes realizados, 33 fueron de donador cadavérico; 10 pacientes tuvieron rechazo agudo. El tiempo prolongado de isquemia fría (OR = 8.4, IC = 1.5-44.2, p = 0.02) y la combinación azatioprina (AZA)-prednisona (PDN)- ciclosporina (CSA) (OR = 9.1, IC = 1.5-49.4, p = 0.02) fueron factores de riesgo para rechazo agudo. El uso de antiCD25 (OR = 0.6, IC = 0.009-0.37, p = 0.001) y la combinación mofetil micofenolato (MMF)-PDN-CSA (OR = 0.1, IC = 0.02-0.65, p = 0.02) fueron factores protectores de rechazo agudo. Conclusiones: En una población mexicana, el tiempo de isquemia fría prolongado y la combinación AZA-PDN-CSA fueron factores de riesgo para rechazo agudo, mientras que el uso de antiCD25 y la combinación MMF-PDN-CSA fueron protectores para rechazo agudo en trasplantes renales de donadores cadavéricos.

BACKGROUND: Exposure of renal grafting to prolonged cold ischemia time (CIT) and the association with acute rejection (AR) are known. However, there is no evidence in Mexico about this topic. Thus, the objective of this study was to evaluate prolonged CIT as a risk factor for AR in renal grafting of cadaveric kidney transplantation in a Mexican population. METHODS: A cross-sectional study was carried out. Clinical files of patients undergoing renal grafting using cadaveric kidneys were reviewed from July 1994-June 2004. Prolonged CIT (=12 h) as a risk factor for AR was evaluated. Other related variables were also examined. RESULTS: From 425 kidney transplantations, only 33 cases were cadaveric. Ten patients had AR. Prolonged CIT (OR 8.4; CI 1.5-44.2, p = 0.02) and azathioprine (AZA)-prednisone (PDN)-cyclosporine (CSA) combination (OR 9.1; CI 1.5-49.4, p = 0.02) were risk factors for AR. Anti-CD25 use (OR 0.6; CI 0.009-0.37, p = 0.001) and mycofenolate mofetil (MMF)-PDN-CSA combination (OR 0.1; CI 0.02-0.65, p = 0.02) were protective factors for AR. CONCLUSIONS: In a Mexican population, prolonged CIT and AZA-PDN-CSA combination were risk factors for AR. Meanwhile, anti- CD25 use and MMF-PDN-CSA combination were protective factors for AR in cadaveric kidney transplantations.

[Comparison of sevoflurane/nitrous oxide and thiopental/fentanyl in anesthesia for minor gynecologic surgery]. / Comparación de sevoflurano-óxido nitroso y tiopental-fentanyl en anestesia para cirugía menor ginecológica.

We studied 40 patients undergoing minor gynaecological surgery, anaesthetized in random order with sevoflurane-nitrous oxide or thiopental-fentanyl. Operating conditions, pain, recovery and postoperative nausea and vomiting were assessed. For postoperative analgesia, all patients were given dypiron 1 g intravenous at the end of anaesthesia. Patients and gynaecologists were equally satisfied with both anaesthetic techniques. The time of surgery were higher in patients given sevoflurane, (7 versus 5 minutes) this women had recovery faster (17 versus 72 minutes) became orientated, followed orders (11 versus 19 minutes) and were able to walk (17 versus 60 minutes) significantly (p < 0.05) earlier than those given thiopental. Modified Aldrete scores were also higher in sevoflurane group within the first hour after anaesthesia, there were no differences in woke up (9 versus 12 minutes) vital constants, intrauterine bleeding, pain, and frequency of postoperative nausea and vomiting (10% versus 10%) between the two groups. We conclude that sevofluranenitrous-oxide is preferable to thiopental-fentanyl in ultra-short anaesthesia for minor gynaecological surgery.