Extra-Virgin Olive Oil and Its Minor Compounds Influence Apoptosis in Experimental Mammary Tumors and Human Breast Cancer Cell Lines.

Breast cancer is the most common malignancy among women worldwide. Modifiable factors such as nutrition have a role in its etiology. In experimental tumors, we have observed the differential influence of high-fat diets in metabolic pathways, suggesting a different balance in proliferation/apoptosis. In this work, we analyzed the effects of a diet high in n-6 polyunsaturated fatty acids (PUFA) and a diet high in extra-virgin olive oil (EVOO) on the histopathological features and different cell death pathways in the dimethylbenz(a)anthracene-induced breast cancer model. The diet high in n-6 PUFA had a stimulating effect on the morphological aggressiveness of tumors and their proliferation, while no significant differences were found in groups fed the EVOO-enriched diet in comparison to a low-fat control group. The high-EVOO diet induced modifications in proteins involved in several cell death pathways. In vitro analysis in different human breast cancer cell lines showed an effect of EVOO minor compounds (especially hydroxytyrosol), but not of fatty acids, decreasing viability while increasing apoptosis. The results suggest an effect of dietary lipids on tumor molecular contexts that result in the modulation of different pathways, highlighting the importance of apoptosis in the interplay of survival processes and how dietary habits may have an impact on breast cancer risk.

Effects of diets high in corn oil or in extra virgin olive oil on oxidative stress in an experimental model of breast cancer.

Experimental evidence highlights the importance of dietetic factors on breast cancer. In this work we aimed to analyze the effects two oils, corn oil (rich in n-6 polyunsaturated fatty acids -PUFA-) and extra virgin olive oil (EVOO), on oxidative stress in an animal model of breast carcinogenesis. Female rats were fed a low-fat control, a high-corn oil, or a high-EVOO diet from weaning or after induction with 7,12-dimethylbenz[a]anthracene at 53 days. Animals were euthanized at 36, 51, 100 and 246 days of age. We analyzed antioxidant enzymes (mRNA and activity of superoxide dismutase, glutathione peroxidase and catalase), non-enzymatic capacity (oxidized and reduced glutathione) and DNA damage (8-oxo-dG) in tumors and mammary gland at different ages. We also analyzed lipid peroxidation (isoprostanes in serum and lipofuscin in liver). Results indicated a decrease in the enzymatic antioxidant capacity and increased oxidative stress in mammary gland of healthy young animals after a short period of high-fat diets intake, followed by an adaptation to chronic dietary intervention. After induction both diets, especially the one high in n-6 PUFA, increased the oxidized glutathione. In tumors no clear effects of the high-fat diets were observed, although in the long-term lipofuscin and 8-oxo-dG suggested greater oxidative damage by effect of the n-6 PUFA-rich diet. Considering the differential effects of these diets on mammary carcinogenesis that we have previously reported, this study suggests that these high-fat diets could have an effect on oxidative stress that would lead to different signaling pathways.

3P association (3PAs): Pituitary adenoma and pheochromocytoma/paraganglioma. A heterogeneous clinical syndrome associated with different gene mutations.

BACKGROUND: Pituitary adenomas (PA) associated with pheochromocytomas/paragangliomas (Pheo/PGL), also known as "the three P association" or "3PAs" could be the results of coincidence, but new evidence supports a common pathogenic mechanism in some patients. Our aim is to report the clinical data, surgical outcome, genetic findings of a large case series and review the current knowledge on this topic. METHODS AND RESULTS: In a retrospective multicentre study, we compiled 10 patients with PAs (6 new unreported cases). Six patients were female with mean age of 51.6 ±â€¯18.0 years. PA were: 6 acromegaly, 3 prolactinoma and 1 non-functioning PA (NFPA). Among the Pheo/PGL, 7 patients had a single tumour (4 Pheo and 3 PGL) and 3 patients had multiple or bilateral disease (2 PGL and 1 Pheo). Patients with GH-secreting PA and NFPA underwent surgery, while patients with prolactinoma received medical treatment (one patient required surgery). Unilateral adrenalectomy was carried out in all single Pheo and a bilateral procedure was performed in the patient with bilateral tumour. A single tumour was resected in two patients with multiple PGL. We found 3 germline pathogenic mutations: 2 in SDHB (c.166-170delCCTCA and a gross deletion involving exon 1) and 1 SDHD (p.P81L exon 3). Two variants of uncertain significance: 1 in MEN1 (c.1618C > T; p.Pro540Ser) and 1 in RET (c.2556C > G, p.Ile852Met), and finally a RETM918T somatic mutation in a Pheo tissue. CONCLUSION: We actively suggest considering the possibility of hereditary disease in all cases with 3PA and performing a complete genetic study.

ACROSTART: A retrospective study of the time to achieve hormonal control with lanreotide Autogel treatment in Spanish patients with acromegaly / ACROSTART: Estudio retrospectivo del período de tiempo para lograr el control hormonal con lanreótida Autogel en pacientes con acromegalia en la práctica clínica española

Objectives: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline(R) Autogel(R)). Methods: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. Results: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. Conclusions: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals

Objetivos: El objetivo del estudio ACROSTART era determinar el período de tiempo para lograr la normalización hormonal (GH e IGF-I) en pacientes con acromegalia respondedores al tratamiento considerando los regímenes de lanreótida Autogel (Somatuline(R) Autogel(R)) utilizados en la práctica clínica. Métodos: Desde marzo de 2013 hasta octubre de 2013, en 17 hospitales españoles se analizaron los datos clínicos de 57 pacientes con acromegalia activa tratados con lanreótida durante ≥4 meses que lograron control hormonal (niveles de GH <2,5ng/ml y/o IGF-I normalizado en ≥2 evaluaciones). El objetivo principal fue determinar el período de tiempo desde el inicio del tratamiento con lanreótida hasta la normalización hormonal. Resultados: La mediana de edad de los pacientes fue 64 años, 21 pacientes eran hombres, 39 pacientes habían recibido cirugía, 14 pacientes habían recibido radioterapia. Los valores hormonales medianos al inicio del tratamiento con lanreótida fueron GH: 2,6ng/ml, IGF-I: 1,6×LSN. La dosis inicial más frecuente de lanreótida fue de 120mg (29 pacientes). Los principales regímenes iniciales fueron 60mg/4 semanas (n=13), 90mg/4 semanas (n=6), 120mg/4 semanas (n=13), 120mg/6 semanas (n=6), 120mg/8 semanas (n=9). Se administró un régimen de intervalo prolongado (≥6 semanas) en 25 pacientes. La duración media del tratamiento con lanreótida fue de 68 meses (7-205). El tiempo medio hasta lograr el control hormonal fue de 4,9 meses. Las inyecciones se manejaron sin asistencia médica en 13 pacientes. La mediana del número de visitas al endocrinólogo hasta el control hormonal fue 3. Cincuenta y un pacientes estaban "satisfechos"/"muy satisfechos" con el tratamiento y 49 pacientes no olvidaron ninguna dosis. Conclusiones: El tratamiento en la vida real con lanreótida Autogel condujo a un control hormonal temprano en pacientes que respondieron, con una alta adherencia al tratamiento y satisfacción con el tratamiento, a pesar de la disparidad de las dosis iniciales y los intervalos de dosificación

ACROSTART: A retrospective study of the time to achieve hormonal control with lanreotide Autogel treatment in Spanish patients with acromegaly.

OBJECTIVES: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline® Autogel®). METHODS: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. RESULTS: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. CONCLUSIONS: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals.

A high-corn-oil diet strongly stimulates mammary carcinogenesis, while a high-extra-virgin-olive-oil diet has a weak effect, through changes in metabolism, immune system function and proliferation/apoptosis pathways.

Breast cancer is the most common malignancy in women worldwide, and dietary lipids are important environmental factors influencing its etiology. We have investigated the effects, and the mechanisms associated, of high-fat diets on 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors. Animals were fed a low-fat, a high-corn-oil (HCO) or a high-extra-virgin-olive-oil (HOO) diet from weaning or after induction. The HCO diet had a clear stimulating effect on mammary carcinogenesis, especially when dietary intervention started after induction, whereas the tumors from HOO diet groups exhibited clinical and morphological characteristics similar to those from low-fat controls. Transcriptomic and further protein and immunohistochemical analyses of tumors also indicated different modulatory effects of high-fat diets affecting relevant biological functions: metabolism, immunosurveillance and proliferation/apoptosis pathways. Thus, the results suggested different metabolic adaptations with increased glycolysis by effect of HOO diet. Moreover, leukocyte tumor infiltration and inflammation mediators showed increased cytotoxic T cells and decreased TGFß1 expression by the HOO diet, while the HCO one increased arginase expression and IL-1α plasma levels. Furthermore, the study of proteins controlling proliferation/apoptosis pathways (Sema3A, Stat5, Smad1, Casp3) suggested an increase in proliferation by the HCO diet and an increase of apoptosis by the diet rich in olive oil. In conclusion, the HCO diet clearly stimulated mammary carcinogenesis, especially in the promotion phase, and induced molecular changes suggesting increased tumor proliferation/apoptosis balance and a proinflammatory microenvironment. The HOO diet, despite being high fat, had a weaker effect on tumorigenesis probably related to metabolic adaptations, enhanced immunosurveillance and increased apoptosis.

Estudio retrospectivo para evaluar la eficacia y la seguridad de la radiocirugía en enfermedad de Cushing: 24 casos y revisión / Retrospective analysis to evaluate efficacy and safety of stereotactic radiosurgery in Cushing's disease: 24 cases and a review

Introducción: En los últimos años la radiocirugía (RC) se ha postulado como una buena alternativa terapéutica, por lo general de segunda línea, en el manejo de los adenomas hipofisarios productores de ACTH. Se realiza un estudio retrospectivo para evaluar la eficacia y la seguridad de dicho tratamiento en estos pacientes. Material y métodos: Se recogieron datos de los pacientes tratados mediante RC por adenoma hipofisario productor de ACTH entre 1996 y 2008, con al menos un año de seguimiento, analizando la tasa de normalización hormonal y mejoría clínica (estigmas del síndrome de Cushing, hipertensión arterial), así como la aparición de efectos adversos y de recidiva. Se consideró normalización hormonal -y por tanto curación- como una tasa normal de cortisol libre urinario (CLU) en 24 h (< 100 μg/día). Resultados: Treinta pacientes fueron tratados, de los que 24 entraron en el estudio. Todos ellos tenían cifras elevadas de CLU previamente al tratamiento con RC. La curación se consiguió en 12 (50%), en un promedio de 28meses, y en otros 3 pacientes se normalizaron las cifras de CLU con tratamiento con ketoconazol posterior. En todos mejoraron los estigmas de Cushing, y en 13 (de 14) mejoró la HTA. No se evidenció ningún caso de recidiva una vez instaurada la curación. Entre las complicaciones destacan 9 déficits hormonales nuevos (siendo el más frecuente el hipotiroidismo), una radionecrosis y un empeoramiento de la campimetría previa. No se encontró ningún caso de tumor radioinducido. Conclusiones: La RC es un tratamiento efectivo para aquellos pacientes con adenoma productor de ACTH en que la cirugía ha fallado o que no son candidatos a la misma, consiguiéndose buenas tasas de normalización hormonal y de control clínico de la enfermedad, con un bajo porcentaje de efectos adversos

Background: In the past few years, stereotactic radiosurgery (SRS) has been suggested as a good alternative, second line therapy for the management of patients with ACTH-secreting pituitary adenomas. A retrospective study has been conducted in order to evaluate the efficacy and safety of this treatment in these patients. Material and methods: Data were collected on all patients treated with SRS for an ACTH-secreting pituitary adenoma between 1996 and 2008, and with at least one year of follow-up. An analysis was carried out by analysing the return to normal of the hormone levels and clinical improvement rates (including Cushing signs, arterial hypertension), as well as adverse effects, and disease relapse. A return to normal of the 24hour urinary free cortisol (24-UFC) levels (<100μg/day) without any ACTH-secretion suppressor drug treatment, was considered as cure or improvement. Results: A total of 30 patients were treated with SRS, of which 24 were included in the analysis. They all had high 24-UFC levels before the treatment. Cure was achieved in 12 (50%) in a mean of 28months, and in other 3 patients 24-UFC levels returned to normal with treatment with ketoconazole after the SRS. Cushing signs improved in all cases, as well as arterial hypertension in 13 out of 14 cases. There were relapses after cure consolidation. As far as adverse effects, it should be mentioned that there were 9 cases of new pituitary hormonal dysfunction (the most frequent being hypothyroidism), one radionecrosis, and one case of visual field defect impairment. Radiation-related neoplasm was not detected in any of the cases. Conclusions: SRS is an effective treatment for those patients with ACTH-secreting pituitary adenoma in whom surgery has failed, or in those that are not good candidates for it. It showed good rates of hormone levels returning to normal, as well as clinical disease control and a low level of adverse effects

Molecular Profiling and Malignant Behavior Define Two Rat Mammary Tumor Cell Lines as a Relevant Experimental Model.

Cancer cell lines have become a reliable tool in genetic and biochemical studies of breast cancer. Here, we described the behavior and novel molecular characterization of two cell lines derived from DMBA-induced rat mammary tumor, LA7 and RBA. LA7 cells have been identified as myoepithelial cells with stem cell properties, whereas the RBA cell line are epithelial cells that present mutational activated H-Ras, but are much less known. We evaluated the proliferation rate and molecular markers, several signaling pathways status related to proliferation, survival, inflammation, and apoptosis, as well as migration capacity, global DNA methylation levels, and stem cells populations. In fact, we found the A/T transversion in the c-Ha-Ras codon 61 as the activator mutation origin described in RBA cells. LA7 and RBA cells showed a high proliferation rate associated with overexpression of Cyclin D1, and resistance to apoptotic signals due to lack of expression of Bad. Moreover, neither of these two cell lines expressed steroid receptors, but they showed high migration capacity, all in accordance with an aggressive phenotype. We found global DNA methylation levels in LA7 and RBA cells lower than reference tissues analyzed, in addition to the presence of different stem cells populations in RBA cell line that differed in the expression of CD44 and CD24. These results revealed a malignant behavior associated with cancer stem cell phenotype. Since this profile is similar to a human triple-negative basal-like tumor, their extensive characterization presented herein increases their value as a good in vitro model. J. Cell. Biochem. 117: 2825-2834, 2016. © 2016 Wiley Periodicals, Inc.

[Retrospective analysis to evaluate efficacy and safety of stereotactic radiosurgery in Cushing's disease: 24 cases and a review]. / Estudio retrospectivo para evaluar la eficacia y la seguridad de la radiocirugía en enfermedad de Cushing: 24 casos y revisión.

BACKGROUND: In the past few years, stereotactic radiosurgery (SRS) has been suggested as a good alternative, second line therapy for the management of patients with ACTH-secreting pituitary adenomas. A retrospective study has been conducted in order to evaluate the efficacy and safety of this treatment in these patients. MATERIAL AND METHODS: Data were collected on all patients treated with SRS for an ACTH-secreting pituitary adenoma between 1996 and 2008, and with at least one year of follow-up. An analysis was carried out by analysing the return to normal of the hormone levels and clinical improvement rates (including Cushing signs, arterial hypertension), as well as adverse effects, and disease relapse. A return to normal of the 24 hour urinary free cortisol (24-UFC) levels (<100 µg/day) without any ACTH-secretion suppressor drug treatment, was considered as cure or improvement. RESULTS: A total of 30 patients were treated with SRS, of which 24 were included in the analysis. They all had high 24-UFC levels before the treatment. Cure was achieved in 12 (50%) in a mean of 28 months, and in other 3 patients 24-UFC levels returned to normal with treatment with ketoconazole after the SRS. Cushing signs improved in all cases, as well as arterial hypertension in 13 out of 14 cases. There were relapses after cure consolidation. As far as adverse effects, it should be mentioned that there were 9 cases of new pituitary hormonal dysfunction (the most frequent being hypothyroidism), one radionecrosis, and one case of visual field defect impairment. Radiation-related neoplasm was not detected in any of the cases. CONCLUSIONS: SRS is an effective treatment for those patients with ACTH-secreting pituitary adenoma in whom surgery has failed, or in those that are not good candidates for it. It showed good rates of hormone levels returning to normal, as well as clinical disease control and a low level of adverse effects.

Diets high in corn oil or extra-virgin olive oil differentially modify the gene expression profile of the mammary gland and influence experimental breast cancer susceptibility.

PURPOSE: Nutritional factors, especially dietary lipids, may have a role in the etiology of breast cancer. We aimed to analyze the effects of high-fat diets on the susceptibility of the mammary gland to experimental malignant transformation. METHODS: Female Sprague-Dawley rats were fed a low-fat, high-corn-oil, or high-extra-virgin olive oil (EVOO) diet from weaning or from induction. Animals were induced with 7,12-dimethylbenz[a]anthracene at 53 days and euthanized at 36, 51, 100 and 246 days. Gene expression profiles of mammary glands were determined by microarrays. Further molecular analyses were performed by real-time PCR, TUNEL and immunohistochemistry. Carcinogenesis parameters were determined at 105 and 246 days. RESULTS: High-corn-oil diet increased body weight and mass when administered from weaning. The EVOO diet did not modify these parameters and increased the hepatic expression of UCP2, suggesting a decrease in intake/expenditure balance. Both diets differentially modified the gene expression profile of the mammary gland, especially after short dietary intervention. Corn oil down-regulated the expression of genes related to immune system and apoptosis, whereas EVOO modified the expression of metabolism genes. Further analysis suggested an increase in proliferation and lower apoptosis in the mammary glands by effect of the high-corn-oil diet, which may be one of the mechanisms of its clear stimulating effect on carcinogenesis. CONCLUSIONS: The high-corn-oil diet strongly stimulates mammary tumorigenesis in association with modifications in the expression profile and an increased proliferation/apoptosis balance of the mammary gland.

The Role of Dietary Extra Virgin Olive Oil and Corn Oil on the Alteration of Epigenetic Patterns in the Rat DMBA-Induced Breast Cancer Model.

Disruption of epigenetic patterns is a major change occurring in all types of cancers. Such alterations are characterized by global DNA hypomethylation, gene-promoter hypermethylation and aberrant histone modifications, and may be modified by environment. Nutritional factors, and especially dietary lipids, have a role in the etiology of breast cancer. Thus, we aimed to analyze the influence of different high fat diets on DNA methylation and histone modifications in the rat dimethylbenz(a)anthracene (DMBA)-induced breast cancer model. Female Sprague-Dawley rats were fed a low-fat, a high corn-oil or a high extra-virgin olive oil (EVOO) diet from weaning or from induction with DMBA. In mammary glands and tumors we analyzed global and gene specific (RASSF1A, TIMP3) DNA methylation by LUMA and bisulfite pyrosequencing assays, respectively. We also determined gene expression and enzymatic activity of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) and evaluated changes in histone modifications (H3K4me2, H3K27me3, H4K20me3 and H4K16ac) by western-blot. Our results showed variations along time in the global DNA methylation of the mammary gland displaying decreases at puberty and with aging. The olive oil-enriched diet, on the one hand, increased the levels of global DNA methylation in mammary gland and tumor, and on the other, changed histone modifications patterns. The corn oil-enriched diet increased DNA methyltransferase activity in both tissues, resulting in an increase in the promoter methylation of the tumor suppressor genes RASSF1A and TIMP3. These results suggest a differential effect of the high fat diets on epigenetic patterns with a relevant role in the neoplastic transformation, which could be one of the mechanisms of their differential promoter effect, clearly stimulating for the high corn-oil diet and with a weaker influence for the high EVOO diet, on breast cancer progression.

Effect of High Fat Diets on Body Mass, Oleylethanolamide Plasma Levels and Oxytocin Expression in Growing Rats.

Obesity prevalence in developed countries has promoted the need to identify the mechanisms involved in control of feeding and energy balance. We have tested the hypothesis that different fats present in diet composition may contribute in body weight gain and body indexes by regulation of oxytocin gene (oxt) expression in hypothalamus and Oleylethanolamide (OEA) levels in plasma. Sprague-Dawley rats were fed two high fat diets, based on corn (HCO) and extra virgin olive oil (HOO) and results were compared to a low fat diet (LF). LC-MS/MS analysis showed an increasing trend of OEA plasma levels in HOO group, although no significant differences were found. However, body weight gain of LF and HOO were similar and significantly lower than HCO. HCO rats also had higher Lee index than HOO. Rats fed HOO diet showed higher levels of hypothalamic oxt mRNA expression, which could indicate that oxytocin may be modulated by dietary lipids.

Dietary extra-virgin olive oil and corn oil differentially modulate the mRNA expression of xenobiotic-metabolizing enzymes in the liver and in the mammary gland in a rat chemically induced breast cancer model.

High extra-virgin olive oil (EVOO) and corn oil diets differentially modulate experimental mammary carcinogenesis. We have investigated their influence on the initiation stage through the modulation of the expression of xenobiotic-metabolizing enzymes (XMEs) in the liver and the mammary gland. Female Sprague-Dawley rats were fed a low-fat (LF), high corn oil (HCO), or high EVOO (HOO) diet from weaning and gavaged with 7,12-dimethylbenz(a)anthracene (DMBA). The HCO diet increased the mRNA levels of the phase I enzymes CYP1A1, CYP1A2 and, to a lesser extent, CYP1B1, in the liver. The Aryl hydrocarbon receptor (AhR) seemed to be involved in this upregulated CYP1 expression. However, a slight trend toward an increase in the mRNA levels of the phase II enzymes GSTP1 and NQO1 was observed with the HOO diet. At least in the case of GSTP1, this effect was linked to an increased Nrf2 transactivation activity. This different regulation of the XMEs expression led, in the case of the HCO diet, to a balance between the production of active carcinogenic compounds and their inactivation tilted toward phase I, which would stimulate DMBA-induced cancer initiation, whereas the HOO diet was associated with a slower phase I metabolism accompanied by a faster phase II detoxification, thus reducing the output of the active compounds to the target tissues. In the mammary gland, the differential effects of diets may be conditioned by the state of cell differentiation, sexual maturity, and hormone metabolism.

Guía para el diagnóstico y tratamiento de la insuficiencia suprarrenal en el adulto / Guidelines for the diagnosis and treatment of adrenal insufficiency in the adult

La insuficiencia suprarrenal (IA) es un trastorno que se caracteriza por un déficit de glucocorticoides, al que se asocia en ocasiones un déficit de mineralocorticoides y/o andrógenos adrenales. Puede ser consecuencia de enfermedades intrínsecas del córtex adrenal (IA primaria), de procesos hipofisarios que afecten a la secreción de corticotropina (IA secundaria) o de trastornos hipotalámicos que afecten la secreción de la hormona liberadora de corticotropina (IA terciaria). Se trata de una entidad de baja prevalencia pero con elevado impacto sobre la salud individual, dado que entraña riesgo vital en ausencia de tratamiento y efectos deletéreos para la salud en caso de tratamiento inadecuado. En la actualidad no hay ninguna guía de práctica clínica para el manejo de esta enfermedad, por este motivo, a partir de una propuesta de la junta directiva de la Sociedad Española de Endocrinología y Nutrición (SEEN), se constituyó un grupo de trabajo dependiente del Área de Conocimiento de Neuroendocrinología de la SEEN, al que se encomendó la tarea de actualizar el diagnóstico y tratamiento de la IA del adulto. En cumplimiento de esta labor, el grupo de trabajo ha elaborado la presente guía, que, basándose en una revisión exhaustiva de la bibliografía, pretende dar respuesta a los interrogantes que se platean en el manejo de esta enfermedad. Se trata, por tanto, de un documento de carácter eminentemente práctico, cuya intención principal es servir de guía a los profesionales que se dedican al cuidado de los pacientes con IA

Adrenal insufficiency (AI) is a disease characterized by a deficient production or action of glucocorticoids, with or without deficiency in mineralcorticoids and/or adrenal androgens. It can result from disease intrinsic to the adrenal cortex (primary AI), from pituitary diseases that hamper the release of corticotropin (secondary AI) or from hypothalamic disorders that impair the secretion of the corticotropin-releasing hormone (tertiary AI). It is a disease with a low prevalence but its impact on the affected individual is very high as it can be life-threathening if not treated or lead to health problems if inadequately treated. However, currently there are no specific guidelines for the management of this disease. Therefore, at the proposal of the Spanish Society of Endocrinology and Nutrition (SEEN) board, a task-force under the Neuroendocrinology Knowledge Area of the SEEN was established, with the mandate of updating the diagnosis and treatment of AI. In fulfilment of this mandate the task-force has elaborated the present guide that, based on a comprehensive review of literature, is intended to provide an answer to questions related to the management of this disease. It is, therefore, an essentially practical document, mainly aimed at guiding the health professionals involved in the care of IA patients

Guidelines for the diagnosis and treatment of adrenal insufficiency in the adult.

Adrenal insufficiency (AI) is a disease characterized by a deficient production or action of glucocorticoids, with or without deficiency in mineral corticoids and/or adrenal androgens. It can result from disease intrinsic to the adrenal cortex (primary AI), from pituitary diseases that hamper the release of corticotropin (secondary AI) or from hypothalamic disorders that impair the secretion of the corticotropin-releasing hormone (tertiary AI). It is a disease with a low prevalence but its impact on the affected individual is very high as it can be life-threathening if not treated or lead to health problems if inadequately treated. However, currently there are no specific guidelines for the management of this disease. Therefore, at the proposal of the Spanish Society of Endocrinology and Nutrition (SEEN) board, a task-force under the Neuroendocrinology Knowledge Area of the SEEN was established, with the mandate of updating the diagnosis and treatment of AI. In fulfilment of this mandate the task-force has elaborated the present guide that, based on a comprehensive review of literature, is intended to provide an answer to questions related to the management of this disease. It is, therefore, an essentially practical document, mainly aimed at guiding the health professionals involved in the care of IA patients.

Ontogeny of the major xenobiotic-metabolizing enzymes expression and the dietary lipids modulatory effect in the rat dimethylbenz(a)anthracene-induced breast cancer model.

Breast cancer is the most common malignancy in women worldwide. Environmental factors such as xenobiotic exposure and lifestyle and nutrition play a key role in its etiology. This study was designed to evaluate the age-related changes in the expression of major xenobiotic-metabolizing enzymes (XMEs) in the rat liver and the mammary gland in the dimethylbenz(a)anthracene-induced breast cancer model. The influence of dietary lipids on the ontogeny of XMEs was also evaluated. mRNA and protein levels of phase I (CYP1A1, CYP1A2, and CYP1B1) and phase II (NAD(P)H:quinone acceptor oxidoreductase 1 and GSTP1) enzymes were analyzed, as well as their regulation by AhR and Nrf2, respectively. Results showed differences in the phase I enzymes expression, whereas little changes were obtained in phase II. High corn oil and olive oil diets differentially influenced the expression of age-related changes, suggesting that the different susceptibility to xenobiotic exposure depending upon the age may be modulated by dietary factors.

Neurocognitive function in acromegaly after surgical resection of GH-secreting adenoma versus naïve acromegaly.

Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better neurocognitive state. Overall, this data suggests that the effects of chronic exposure to GH/IGF-I hypersecretion could have long-term effects on brain functions.