Bioética y Universidad en América Latina. Propuesta de una estructura para la formación integral profesional

En el presente trabajo hacemos una revisión del desarrollo de la bioética en América latina. Se señalan los enfoques que diversos autores apuntan para integrar la bioética en las universidades de la región. Asimismo se considera la importancia de integrar la bioética a la vida universitaria con la intención de fomentar una formación profesional integral con bases axiológicas robustas. Desde la revisión de la bioética y los avances en la región, se elabora una propuesta de estructura bioética en la universidad, la cual tendrá como intención mejorar los aspectos éticos en las carreras de grado y en el posgrado de todas las disciplinas que de alguna forma están relacionadas directa e indirectamente con la conservación de la vida humana y no humana desde el servicio profesional. Con ello se busca contribuir a mejorar la calidad de vida de los seres humanos

TNF-α/IL-1/NF-κB transduction pathway in human cancer prostate

TNFα exerts apoptosis throughout an intracellular transduction pathway that involves the kinase proteins TRAF-2 (integration point of apoptotic and survival signals), ASK1 (pro-apoptotic protein), MEK-4 (p38 activator and metastasis suppressor gene), JNK (stress mitogen activated protein kinase) and the transcription factor AP-1. TNFα also exerts proliferation by p38 activation, or when TRAF-2 simultaneously induces the transcription factor NF-κB by NIK. NIK and p38 may also be activated by IL-1. P38 activated several transcription factors such as Elk-1, ATF-2 and NF-κB. NIK also may activate NF-κB. The aim of the present article was to evaluate the different components of this TNFα/IL-1 transduction pathway in human prostate carcinoma (PC) in comparison with normal human prostate. In prostate cancer, pro-apoptotic TNFα/AP-1 pathway is probably inactivated by different factors such as p21 (at ASK-1 level) and bcl-2 (at JNK level), or diverted towards p38 or NIK activation. IL-1α enhances proliferation through IL-1RI that activates either NIK or p38 transduction pathway. P38 and NIK activate different transcription factors related with cell proliferation and survival such as ATF-2, Elk-1 or NF-κB. In order to search a possible target to cancer prostate treatment we proposed that inhibition of several proinflamatory cytokines such as IL-1 and TNFα might be a possible target for PC treatment, because decrease the activity of all transduction pathway members that activate transcription factors as NF-κB, Elk-1 or ATF-2.Ministerio de Educación y Cienci

Bioética e testes em animais. Uma revisão da praxis científica no México

This study examines the experimental use of non-human animals in Mexico from a bioethical approach. For this purpose, a survey was applied to researchers who develop research lines with animals (specifically chordates) to know the ethical and technical aspects related to their use. When analyzing the data, it was concluded that there is a partial use of the 3 R's of Russell and Burch, as well as irregularities related to the application of transport protocols, exclusive zones for experimentation, use of substances and tools in the slaughter process required by the NOM-062-ZOO-1999 and the Terrestrial Code.Este estudo examina o uso experimental de animais não humanos no México a partir de uma abordagem bioética. Para tanto, foi aplicado um questionário a pesquisadores que desenvolvem linhas de pesquisa com animais —especificamente cordados— para conhecer os aspectos éticos e técnicos relacionados ao seu uso. Ao analisar os dados, concluiu-se que há um uso parcial dos 3 R's de Russell e Burch, bem como irregularidades relacionadas à aplicação de protocolos de transporte, zonas exclusivas de experimentação, uso de substâncias e ferramentas no processo de abate exigido pelo NOM-062-ZOO-1999 e pelo Código Terrestre

Glucocorticoid receptor changes its cellular location with breast cancer development.

Glucocorticoids play a major role in attenuation of the inflammatory response and they are useful in the primary combination chemotherapy of breast cancer, since in vitro studies have demonstrated an antiproliferative effect in human breast cancer cells. In contrast, it was recently shown that glucocorticoids protect against apoptotic signals evoked by cytokines, cAMP, tumour suppressors, and death genes in mammary gland epithelia. Their actions are mediated by intracellular receptor (GR) that functions as a hormone-dependent transcription factor; however, no previous studies have been focused on GR expression in different pathologies of the human breast, and the possible relationship with that of mineralocorticoid receptor (MR) and COX-2. Also, the role of these proteins on tumoral breast epithelial cells remains unclear. Therefore, we examined GR, MR and COX-2 expression by immunohistochemistry and Western blot techniques in 142 samples of human breast obtained by total or partial mastectomy. We found that the percentage of positive patients presenting nuclear immunoreaction to GR decreased with tumor development, while all samples analyzed showed cytoplasmic immunoreactions to MR. All positive samples to COX-2 antibody showed cytoplasmic location, a higher immunoreaction being observed in benign breast diseases than in carcinomatous lesions. Thus, breast cancer progression is associated with the accumulation of GR in the cytoplasm of tumoral cells and the decrease of COX-2 expression

Human pregnane X receptor is expressed in breast carcinomas, potential heterodimers formation between hPXR and RXR-alpha.

The human pregnane X receptor (hPXR) is an orphan nuclear receptor that induces transcription of response elements present in steroid-inducible cytochrome P 450 gene promoters. This activation requires the participation of retinoid X receptors (RXRs), needed partners of hPXR to form heterodimers. We have investigated the expression of hPXR and RXRs in normal, premalignant, and malignant breast tissues, in order to det. whether their expression profile in localized infiltrative breast cancer is assocd. with an increased risk of recurrent disease. Methods: Breast samples from 99 patients including benign breast diseases, in situ and infiltrative carcinomas were processed for immunohistochem. and Western-blot anal. Results: Cancer cells from patients that developed recurrent disease showed a high cytoplasmic location of both hPXR isoforms. Only the infiltrative carcinomas that relapsed before 48 mo showed nuclear location of hPXR isoform 2. This location was assocd. with the nuclear immunoexpression of RXR-alpha. Conclusion: Breast cancer cells can express both variants 1 and 2 of hPXR. Infiltrative carcinomas that recurred showed a nuclear location of both hPXR and RXR-alpha; therefore, the overexpression and the subcellular location changes of hPXR could be considered as a potential new prognostic indicator

Prognostic value of inhibitors of apoptosis proteins (IAPs) and caspases in prostate cancer: caspase-3 forms and XIAP predict biochemical progression after radical prostatectomy

Background: The expression status of apoptotic regulators, such as caspases and inhibitors of apoptosis proteins (IAPs), could reflect the aggressiveness of tumors and, therefore, could be useful as prognostic markers. We explored the associations between tumor expression of caspases and IAPs and clinicopathological features of prostate cancer – clinical and pathological T stage, Gleason score, preoperative serum PSA levels, perineural invasion, lymph node involvement, surgical margin status and overall survival – and evaluated its capability to predict biochemical progression after radical prostatectomy. Methods: Protein expression of caspases (procaspase-8, cleaved caspase-8, procaspase-3, cleaved caspase-3, caspase-7 and procaspase-9) and IAPs (cIAP1/2, cIAP2, NAIP, Survivin and XIAP) was analyzed by immunohistochemistry in radical prostatectomy samples from 84 prostate cancer patients. Spearman’s test, Kaplan-Meier curves, and univariate and multivariate Cox proportional hazard regression analysis were performed. Results: cIAP1/2, cIAP2, Survivin, procaspase-8, cleaved caspase-8, procaspase-3 and caspase-7 expression correlated with at least one clinicopathological feature of the disease. Patients negative for XIAP, procaspase-3 or cleaved caspase-3 had a significantly worse prognosis. Of note, XIAP, procaspase-3 and cleaved caspase-3 were predictors of biochemical progression independent of Gleason score and pathological T stage. Conclusions: Our results indicate that alterations in the expression of IAPs and caspases contribute to the malignant behavior of prostate tumors and suggest that tumor expression of XIAP, procaspase-3 and cleaved caspase-3 may help to identify prostate cancer patients at risk of progression

Unusual winter Saharan dust intrusions at Northwest Spain: Air quality, radiative and health impacts

[EN] Saharan air masses can transport high amounts of mineral dust particles and biological material to the Iberian Peninsula. During winter, this kind of events is not very frequent and usually does not reach the northwest of the Peninsula. However, between 21 and 22 February 2016 and between 22 and 23 February 2017, two exceptional events were registered in León (Spain), which severely affected air quality. An integrative approach including: i) typical synoptic conditions; ii) aerosol chemical composition; iii) particle size distributions; iv) pollen concentration; v) aerosol optical depth (AOD); vi) radiative forcing and vii) estimation of the impact of aerosols in the respiratory tract, was carried out. In the global characterization of these events, the exceedance of the PM10 daily limit value, an increase in the coarse mode and a rise in the iron concentration were observed. On the 2016 event, an AOD and extinction-related Ångström exponent clearly characteristic of desert aerosol (1.1 and 0.05, respectively) were registered. Furthermore, pollen grains not typical of flowering plants in this period were identified. The chemical analysis of the aerosol from the 2017 event allowed us to confirm the presence of the main elements associated with mineral sources (aluminum, calcium, and silica concentrations). An increase in the SO42−, NO3− and Cl− concentrations during the Saharan dust intrusion was also noted. However, in this event, there was no presence of atypical pollen types. The estimated dust radiative forcing traduced a cooling effect for surface and atmosphere during both events, corroborated by trends of radiative flux measurements. The estimated impact on the respiratory tract regions of the high levels of particulate matter during both Saharan dust intrusions showed high levels for the respirable fractionSIThis study was partially supported by the Spanish Ministry of Economy and Competitiveness (Grant TEC2014-57821-R), the University of León (Programa Propio 2015/00054/001 and 2018/00203/001) and the AERORAIN project (Ministry of Economy and Competitiveness, Grant CGL2014-52556-R, co-financed with European FEDER funds). F. Oduber acknowledges the grant BES-2015-074473 from the Spanish Ministry of Economy and Competitiveness. C. Blanco-Alegre acknowledges the grant FPU16-05764 from the Ministry of Education, Culture and Sports, Spain. The authors gratefully acknowledge the NOAA Air Resources Laboratory (ARL) for the provision of the HYSPLIT transport and dispersion model and/or READY website (http://www.ready.noaa.gov) used in this study. The authors would also like to express their gratitude to the Naval Research Laboratory for providing the NAAP aerosol map and NASA for the satellite image used in the graphical abstract. The data from the MAPAMA network are property of the Office for Quality and Environmental Evaluation (DGCEA, in its Spanish acronym), belonging to the Ministry of Ecologic Transition. The data were supplied as a result of an agreement between the Spanish Ministry of Agriculture, Food and the Environment and the Scientific Research Council for sponsoring studies related to air pollution by particulate matter and metals in Spain. We thank AERONET network and specially Victoria E. Cachorro Revilla and Carlos Toledano for establishing and maintaining the Valladolid AERONET site used in this investigation. We also thank to Philippe Dubuisson for allowing the use of GAME model, as well as the Laboratoire d'Optique Atmosphérique (University of Lille