Encoding mu-opioid receptor biased agonism with interaction fingerprints.

Opioids are potent painkillers, however, their therapeutic use requires close medical monitoring to diminish the risk of severe adverse effects. The G-protein biased agonists of the µ-opioid receptor (MOR) have shown safer therapeutic profiles than non-biased ligands. In this work, we performed extensive all-atom molecular dynamics simulations of two markedly biased ligands and a balanced reference molecule. From those simulations, we identified a protein-ligand interaction fingerprint that characterizes biased ligands. Then, we built and virtually screened a database containing 68,740 ligands with proven or potential GPCR agonistic activity. Exemplary molecules that fulfill the interacting pattern for biased agonism are showcased, illustrating the usefulness of this work for the search of biased MOR ligands and how this contributes to the understanding of MOR biased signaling.

Bisphenol-A exposure and risk of breast and prostate cancer in the Spanish European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: We designed a case-cohort study within the EPIC-Spain cohort. Study population consisted on 4812 participants from 4 EPIC-Spain centers (547 breast cancer cases, 575 prostate cancer cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Borgan II weighted Cox regression was used to estimate hazard ratios. RESULTS: Median follow-up time in our study was 16.9 years. BPA geometric mean serum values of cases and sub-cohort were 1.12 ng/ml vs 1.10 ng/ml respectively for breast cancer and 1.33 ng/ml vs 1.29 ng/ml respectively for prostate cancer. When categorizing BPA into tertiles, a 40% increase in risk of prostate cancer for tertile 1 (p = 0.022), 37% increase for tertile 2 (p = 0.034) and 31% increase for tertile 3 (p = 0.072) was observed with respect to values bellow the limit of detection. No significant association was observed between BPA levels and breast cancer risk. CONCLUSIONS: We found a similar percentage of detection of BPA among cases and sub-cohort from our population, and no association with breast cancer risk was observed. However, we found a higher risk of prostate cancer for the increase in serum BPA levels. Further investigation is needed to understand the influence of BPA in prostate cancer risk.

Bisphenol A exposure and risk of ischemic heart disease in the Spanish European Prospective Investigation into cancer and nutrition study.

BACKGROUND: Cardiovascular disease, particularly ischemic heart disease (IHD), is the leading cause of mortality worldwide. Bisphenol A (BPA) is considered an endocrine disruptor and obesogen, present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident IHD in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: We designed a case-cohort study within the EPIC-Spain cohort. The population consisted of 4636 participants from 4 EPIC-Spain centers (946 IHD cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Follow-up was performed by linking with national and regional databases and reviewing patients' clinical records. Cox Proportional Hazards Models were used for the statistical analyses. RESULTS: Median follow-up time was 16 years and 70% of the participants showed detectable BPA values (>0.2 ng/ml). Geometric mean (GM) values of cases and sub-cohort were 1.22 ng/ml vs 1.19 ng/ml respectively (p = 0.90). Cox regression models showed no significant association of BPA serum levels and IHD, acute myocardial infarction or angina pectoris risk. CONCLUSIONS: We evidenced a similar percentage of detection of BPA among cases and sub-cohort participants from our population, and no clear association with IHD risk was observed. However, further investigation is needed to understand the influence of BPA on IHD risk.

Bisphenol-A in the European Prospective Investigation into Cancer and Nutrition cohort in Spain: Levels at recruitment and associated dietary factors.

Bisphenol A (BPA) is considered an endocrine disruptor and it is present in numerous products of daily use. The aim of this study was to analyze serum BPA concentrations in a subcohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC), as well as to identify potential predictors of the exposure. The population consisted on 3553 subjects from 4 EPIC-Spain centres and BPA levels were measured in serum samples by UHPLC-MS/MS. Almost 70% of the participants showed detectable BPA values (>0.2 ng/ml), with a geometric mean of 1.19 ng/ml (95% CI: 1.12-1.25). By sex, detectable percentages were similar (p = 0.56) but with higher serum levels in men (1.27 vs 1.11 ng/ml, p = 0.01). Based on the adjusted regression models, a 50 g/day increase in the consumption of added fats and oils were associated with 43% lower BPA serum levels, while sugar and confectionary was associated with 25% higher levels of serum BPA. We evidenced differential exposure levels by province, sex and age, but not by anthropometric or lifestyle characteristics. Further investigation is needed to understand the influence of diet in BPA exposure.

Estudio de las propiedades antimicrobianas de la Camellia sinensis en un modelo microbiano oral / Estudo das propriedades antimicrobianas da Camellia sinensis em um modelo microbiano oral / Study of the antimicrobial properties of Camellia sinensis in an oral microbial model

Objetivo: Determinar el efecto antibacteriano in vitro del extracto de Camellia Sinensis (té verde) sobre un modelo de microflora oral. Materiales y métodos: Fueron utilizados dos extractos etanólicos de té verde de diferente procedencia (Perú y China), en concentraciones de 16, 8, 4, 2, 1, 0.5 y 0.25mg/ml. Se evaluaron la concentración mínima y máxima inhibitoria sobre cepas de S. mutans, S. mitis, C. albicans, C. tropicalis, S. aureus,F. nucleatum, L. rhamnosus, L. casei, C. glabrata y E. faecalis. Los datos obtenidos fueron analizados estadísticamente utilizando la prueba estadística Kruskal Wallis con un nivel de significancia de 5%. Resultados: La C. sinensis mostró un efecto bacteriostático para las cepas de S. mutans, y fungiestático para C. albicans, C. tropicalis y C. glabrata. (p<0.05). Conclusión: El extracto etanólico de 16mg/ml de Camellia Sinensis presenta efecto inhibitorio sobre cepas de S. mutans, C. albicans, C. tropicalis y C. glabrata.

Objective: To determine the in vitro antibacterial effect of the extract of Camellia Sinensis (green tea) on an oral microflora model. Materials and methods: Two ethanolic green tea extracts of different origin (Peru and China) were used in con-centrations of 16, 8, 4, 2, 1, 0.5 and 0.25mg / ml. The minimum and maximum inhibitory concentrations were evaluated on S. mutans, S. mitis, C. albicans, C. tropicalis, S. aureus, F. nucleatum, L. rhamnosus, L. casei, C. glabrata and E. faecalis strains . The obtained data were statistically analyzed using the Kruskal Wallis statistical test with a significance level of 5%. Results: C. sinensis showed a bacteriostatic effect for the strains of S. mutans, and fungistatic for C. albicans, C. tropicalis and C. glabrata. (P <0.05). Conclusion: The 16mg / ml ethanolic extract of Camellia Sinensis has an inhibitory effect on strains of S. mutans, C. albicans, C. tropicalis and C. glabrata.

Objetivo: Determinar o efeito antibacteriano in vitro do extracto de Camellia Sinensis (chá verde) sobre um modelo de microflora oral. Materiais e métodos: Foram utilizados dois extractos etanólicos de chá verde de diferente procedência (Peru e China), em concentrações de 16, 8, 4, 2, 1, 0.5 y 0.25mg/ml. Avaliaram-se as concentrações mínima e máxima inibitórias sobre cepas de S. mutans, S. mitis, C. albicans, C. tropicalis, S. aureus,F. nucleatum, L. rhamnosus, L. casei, C. glabrata y E. faecalis. Os dados obtidos foram analisados estatisticamente utilizando o teste estadístico de Kruskal Wallis com um nível de significância de 5%. Resultados:C. Sinensis mostrou um efeito bacteriostático para S. Mutans e fun-goestático para C. albicans, C. tropicalis y C. glabrata. Conclusão: O extracto etanólico de 16mg/ml de Camelia Sinensisapresenta efeito inibitório sobre as cepas de S. mutans, C. albicans, C. tropicalis y C. glabrata.

Síndrome pulmón-rinón: serie de casosdel Hospital Universitario San Ignacio / Pulmonary - renal syndrome: case series Hospital Universitario San Ignacio

El síndrome pulmón-rinón ˜ (SPR) se define como la presencia de hemorragiaalveolar y glomerulonefritis rápidamente progresiva. Fue descrito, inicialmente, como síndromeantimembrana basal glomerular, aunque existen otros mecanismos más frecuentesimplicados en la lesión, tales como vasculitis ANCA (anticitoplasma de neutrófilo), lupuseritematoso sistémico, síndrome antifosfolípido, crioglobulinemia y microangiopatía trombótica.Objetivo: Describir la experiencia de nuestro centro en el manejo de pacientes con SPR,analizar las variables demográficas, clínicas y sus desenlaces.Métodos: Se revisaron las bases de datos de la Unidad de Nefrología y la historia clínicaelectrónica SAHI del Hospital Universitario San Ignacio.Resultados: Se identificaron un total de 14 pacientes que presentaron SPR, entre enero de2009 y agosto de 2011, todos, inicialmente, manejados en la unidad de cuidado intensivodel hospital, con un promedio de edad de 44 anos ˜ y 57% de sexo femenino. El diagnósticomás frecuente fue vasculitis ANCA positivo en 8 pacientes, lupus en 4, un caso decrioglobulinemia y uno de microangiopatía trombótica. La mayoría recibió tratamiento concorticosteroides, ciclofosfamida y plasmaféresis. La mortalidad fue de 66%.Conclusiones: Presentamos los resultados de 14 pacientes con SPR en nuestro centro. La causamás frecuente fue vasculitis ANCA. Su presentación suele ser agresiva y el tratamientoincluye uso de esteroides, ciclofosfamida y plasmaféresis...

Pulmonary- renal syndrome (PRS) is defined as the presence of alveolar hemorrhageand rapidly progressive glomerulonephritis. It was initially described as glomerularbasement membrane syndrome, although other more common causes and mechanisms areinvolved such as, anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA), systemiclupus erythematosus, antiphospholipid syndrome, cryoglobulinemia, and thromboticmicroangiopathy.Objective: To describe the experience in the treatment of patients with PRS in our centerand analyze the demographic, clinical variables, and outcomes.Methods: The databases of the Nephrology Unit and the electronic medical records of thehospital were reviewed, and a total of 14 patients with PRS between January 2009 and August2011 were identified.Results: A total of 14 cases managed in the intensive care unit of the hospital where analyze,of which 57% were woman and the mean age was 44 years. The most frequent diagnosiswas positive ANCA vasculitis in 8 patients, lupus in 4, one case of cryoglobulinemia, andother with thrombotic microangiopathy. Most of them were treated with corticosteroids andcyclophosphamide, with 10 patients also receiving plasmapheresis. The overall mortalitywas 66%.Conclusions: The results of 14 patients with PRS in our center are presented. The mostcommon cause of this was positive ANCA vasculitis. It is an aggressive disease and itstreatment included the use of steroids, cyclophosphamide and plasmapheresis...