The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease.

The aging process is driven by multiple mechanisms that lead to changes in energy production, oxidative stress, homeostatic dysregulation and eventually to loss of functionality and increased disease susceptibility. Most aged individuals develop chronic low-grade inflammation, which is an important risk factor for morbidity, physical and cognitive impairment, frailty, and death. At any age, chronic inflammatory diseases are major causes of morbimortality, affecting up to 5-8% of the population of industrialized countries. Several environmental factors can play an important role for modifying the inflammatory state. Genetics accounts for only a small fraction of chronic-inflammatory diseases, whereas environmental factors appear to participate, either with a causative or a promotional role in 50% to 75% of patients. Several of those changes depend on epigenetic changes that will further modify the individual response to additional stimuli. The interaction between inflammation and the environment offers important insights on aging and health. These conditions, often depending on the individual's sex, appear to lead to decreased longevity and physical and cognitive decline. In addition to biological factors, the environment is also involved in the generation of psychological and social context leading to stress. Poor psychological environments and other sources of stress also result in increased inflammation. However, the mechanisms underlying the role of environmental and psychosocial factors and nutrition on the regulation of inflammation, and how the response elicited for those factors interact among them, are poorly understood. Whereas certain deleterious environmental factors result in the generation of oxidative stress driven by an increased production of reactive oxygen and nitrogen species, endoplasmic reticulum stress, and inflammation, other factors, including nutrition (polyunsaturated fatty acids) and behavioral factors (exercise) confer protection against inflammation, oxidative and endoplasmic reticulum stress, and thus ameliorate their deleterious effect. Here, we discuss processes and mechanisms of inflammation associated with environmental factors and behavior, their links to sex and gender, and their overall impact on aging.

Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.

INTRODUCTION: Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERß), altered ERα/ERß ratio may constitute a marker of ovarian carcinogenesis progression. OBJECTIVE: To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC). METHODOLOGY: Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERß and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated. RESULTS: In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERß levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05). CONCLUSIONS: Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.

[Salivary cortisol among subjects with and without Cushing syndrome]. / Determinación de los niveles de cortisol salival en una muestra de sujetos de Santiago de Chile.

BACKGROUND: Salivary cortisol measurement is recommended as a screening mea-sure when a Cushing Syndrome is suspected. The proposed cut-off point for a probably diagnosis is 0.16 ug/dL. AIM: To determine salivary cortisol concentrations during the day inpatients with and without Cushing syndrome and with depression. MATERIAL AND METHODS: Salivary cortisol was measured by competitive enzyme immuno assay (EIA), in samples obtained at 8:00,15:00 and 23:00 h in 78 patients without Cushing syndrome, aged 40 +/- 15 years (28 males), 30 patients with depression aged 40 +/- 12 years (nine males) and four females with Cushing syndrome aged 42 +/- 17 years. RESULTS: Salivary cortisol was higher among patients with Cushing syndrome than the rest of patients. A salivary cortisol over the cut-off value of O.16 ug/dL was found in 42% of subjects without Cushing syndrome and in 33% of patients with depression. Median values among patients without Cushing syndrome, depression and with Cushing syndrome were 0.21 (range < 0.1-1.42), 0.2 (range 0,12-0.9) and 0.58 (range 0.37-1.1) ug/dL, respectively CONCLUSIONS: Salivary cortisol measured by EIA method was higher among patients with Cushing syndrome but there was a great overlap with values obtained in subjects without the syndrome.

Determinación de los niveles de cortisol salival en una muestra de sujetos de Santiago de Chile / Salivary cortisol among subjects with and without Cushing syndrome

Background: Salivary cortisol measurement is recommended as a screening mea-sure when a Cushing Syndrome is suspected. Theproposed cut-offpointfor aprobable diagnosis is 0.16 ug/dL. Aim: To determine salivary cortisol concentrations during the day inpatients with and without Cushing syndrome and with depression. Material and Methods: Salivary cortisol was measured by competitive enzyme immuno assay (EIA), in samples obtained at 8:00,15:00 and 23:00 h in 78 patients without Cushing syndrome, aged 40 ± 15years (28 males), 30 patients with depression aged 40 ± 12years (nine males) and four jemales with Cushing syndrome aged 42 ± 17 years. Results: Salivary cortisol was higher among patients with Cushing syndrome than the rest of patients. A salivary cortisol over the cut-off value of O.16 ug/dL was found in 42 percent of subjects without Cushing syndrome and in 33 percent of patients with depression. Median values among patients without Cushing syndrome, depression and with Cushing syndrome were 0.21 (range < 0.1-1.42), 0.2 (range 0,12-0.9) and 0.58 (range 0.37-1.1) ug/dL, respectively Conclusions: Salivary cortisol measured by EIA method was higher among patients with Cushing syndrome but there was a great overlap with values obtained in subjects without the syndrome.

Inmunodetección de FHIT y E-cadherina en fibroadenomas y cáncer ductal y lobulillar de mama / Inmunodetection of FHIT and E-cadherin in fibroadenomas and ductal and lobular human breast cancer

En Chile, el cáncer es la segunda causa de muerte después de las enfermedades cardiovasculares. Los principales cánceres asociados a muerte en mujeres fueron mama, estómago, vesícula biliar, broncopulmonar y cérvico uterino. Alteraciones de las E-cadherinas han sido relacionadas con varios tipos de cáncer, ya que uno de los principales eventos involucrados con su disfunción es el gatillar la invasión y metástasis del tumor. La inactivación del gen CDH1 ha sido demostrada en el cáncer gástrico difuso y el cáncer de mama lobulillar. Asimismo, la inactivación del gen FHIT parece estar asociado con la progresión a neoplasias más agresivas. Se realizaron determinaciones inmunohistoquímicas (IHQ) en fibroadenomas mamarios y cánceres previamente diagnosticados por RE, RPg y Her2, mostrando positividad en todos los casos. La detección (IHQ) de la expresión de FHIT y E-cadherina en tejidos con patologías benignas y malignizados, puede aportar una importante información diagnóstica y pronóstica en el cáncer de mama.

In Chile, cancer is the second leading cause of death after cardiovascular diseases. The major death-related cancers in women were breast, stomach, gallbladder, lung and cervical cancer. Alterations of E-cadherin have been linked to various cancers, as one of the main events involved in its dysfunction is the trigger of tumor invasion and metastasis. CDH1 gene inactivation has been demonstrated in diffuse gastric cancer and lobular breast cancer. Furthermore, inactivation of the FHIT gene to be associated with progression to more aggressive tumors. Immunohistochemistry (IHC) determinations were performed in fibroadenomas and breast cancers previously diagnosed by ER, PgR and Her2, showing positivity in all cases. Immunohistochemical detection of FHIT and E-cadherin expression in tissues with benign disease and malignant, may provide an important diagnostic and prognostic information in breast cancer.