The Cholesterol Metabolite 25-Hydroxycholesterol Activates Estrogen Receptor α-Mediated Signaling in Cancer Cells and in Cardiomyocytes

The hydroxylated derivatives of cholesterol, such as the oxysterols, play important roles in lipid metabolism. In particular, 25-hydroxycholesterol (25 HC) has been implicated in a variety of metabolic events including cholesterol homeostasis and atherosclerosis. 25 HC is detectable in human plasma after ingestion of a meal rich in oxysterols and following a dietary cholesterol challenge. In addition, the levels of oxysterols, including 25 HC, have been found to be elevated in hypercholesterolemic serum.Here, we demonstrate that the estrogen receptor (ER) α mediates gene expression changes and growth responses induced by 25 HC in breast and ovarian cancer cells. Moreover, 25 HC exhibits the ERα-dependent ability like 17 β-estradiol (E2) to inhibit the up-regulation of HIF-1α and connective tissue growth factor by hypoxic conditions in cardiomyocytes and rat heart preparations and to prevent the hypoxia-induced apoptosis.The estrogen action exerted by 25 HC may be considered as an additional factor involved in the progression of breast and ovarian tumors. Moreover, the estrogen-like activity of 25 HC elicited in the cardiovascular system may play a role against hypoxic environments

The ARGA study with general practitioners: impact of medical education on asthma/rhinitis management.

AIM: To evaluate the impact of a medical education course (MEC) on the behaviour of general practitioners (GPs) to treat asthma and allergic rhinitis (AR). METHODS: Data on 1820 patients (mean age 41 yrs ± 17 yrs) with asthma or AR were collected by 107 Italian GPs: 50% attended a MEC and 50% didn't (group B). The adherence for AR and asthma treatment was evaluated according to ARIA and GINA guidelines (GL). RESULTS: AR and asthma were diagnosed in 78% and 56% of patients; 34% had concomitant AR and asthma. Regardless of the MEC, the adherence to GL was significantly higher for AR than for asthma treatment (52 versus 19%). Group B GPs were more compliant to ARIA guidelines in the treatment of mild AR, whereas group A were more compliant in the treatment of moderate-severe AR; the adherence didn't differ between the groups for AR patients with comorbid asthma. Adherence to GINA GL for asthma treatment did not differ between GPs of groups A and B, independently from concomitant AR. Though insignificantly, group A were more compliant to GINA GL in the treatment of patients with only severe persistent asthma (63 versus 46%) as group B were for patients with severe persistent asthma and concomitant AR. CONCLUSIONS: GPs often tend to treat patients independently from GL. The impact of a single MEC did not improve adherence to GL in treating less severe AR and asthma patients, while there was a trend towards the opposite attitude in more severe AR patients without concomitant asthma

The ARGA study with general practitioners: impact of medical education on asthma/rhinitis management.

AIM: To evaluate the impact of a medical education course (MEC) on the behaviour of general practitioners (GPs) to treat asthma and allergic rhinitis (AR). METHODS: Data on 1820 patients (mean age 41 yrs ± 17 yrs) with asthma or AR were collected by 107 Italian GPs: 50% attended a MEC and 50% didn't (group B). The adherence for AR and asthma treatment was evaluated according to ARIA and GINA guidelines (GL). RESULTS: AR and asthma were diagnosed in 78% and 56% of patients; 34% had concomitant AR and asthma. Regardless of the MEC, the adherence to GL was significantly higher for AR than for asthma treatment (52 versus 19%). Group B GPs were more compliant to ARIA guidelines in the treatment of mild AR, whereas group A were more compliant in the treatment of moderate-severe AR; the adherence didn't differ between the groups for AR patients with comorbid asthma. Adherence to GINA GL for asthma treatment did not differ between GPs of groups A and B, independently from concomitant AR. Though insignificantly, group A were more compliant to GINA GL in the treatment of patients with only severe persistent asthma (63 versus 46%) as group B were for patients with severe persistent asthma and concomitant AR. CONCLUSIONS: GPs often tend to treat patients independently from GL. The impact of a single MEC did not improve adherence to GL in treating less severe AR and asthma patients, while there was a trend towards the opposite attitude in more severe AR patients without concomitant asthma

Impact of asthma and comorbid allergic rhinitis on quality of life and control in patients of Italian general practitioners.

OBJECTIVE: Asthma is a disease with elevated prevalence within the general population. Although general practitioners (GPs) are among the first health-care professionals to whom patients refer for their symptoms, there are few evaluations of this disease based on data provided by the GPs. The aim of this observational study is to assess the impact of asthma and comorbid allergic rhinitis on individual/social burden, quality of life, and disease control in asthmatic patients of Italian GPs. METHODS: Throughout Italy, 107 GPs enrolled 995 patients diagnosed with asthma and using anti-asthmatic drug prescriptions, or with asthma-like symptoms during the previous 12 months. Data were collected through questionnaires filled out by GPs and patients. RESULTS: Of the 995 asthmatic patients, 60.6% had concomitant allergic rhinitis (R+A), 39.4% had asthma alone. The latter, compared to those with R+A, showed significantly lower prevalence of intermittent asthma (37.5% vs. 55.6%) and higher prevalence of mild, moderate, and severe persistent asthma (28.4% vs. 23.2%, 28.7% vs. 18.8%, and 5.4% vs 2.4%, respectively). Individual/social burden due to asthma was frequent and increased with disease severity: 87.5% of severe persistent asthma patients reported at least one medical consultation in the last 12 months, 37.5% emergency department visits, 26.7% hospitalization, and 62.5% limitations in daily activities. Control and quality of life were inversely associated with disease severity and were worse in patients with R+A than in those with asthma alone. CONCLUSIONS: This study showed the negative impact of high severity levels and comorbid allergic rhinitis on quality of life of asthmatic patients and on individual/social burden due to asthma in an Italian GPs setting

Impact of asthma and comorbid allergic rhinitis on quality of life and control in patients of Italian general practitioners.

OBJECTIVE: Asthma is a disease with elevated prevalence within the general population. Although general practitioners (GPs) are among the first health-care professionals to whom patients refer for their symptoms, there are few evaluations of this disease based on data provided by the GPs. The aim of this observational study is to assess the impact of asthma and comorbid allergic rhinitis on individual/social burden, quality of life, and disease control in asthmatic patients of Italian GPs. METHODS: Throughout Italy, 107 GPs enrolled 995 patients diagnosed with asthma and using anti-asthmatic drug prescriptions, or with asthma-like symptoms during the previous 12 months. Data were collected through questionnaires filled out by GPs and patients. RESULTS: Of the 995 asthmatic patients, 60.6% had concomitant allergic rhinitis (R+A), 39.4% had asthma alone. The latter, compared to those with R+A, showed significantly lower prevalence of intermittent asthma (37.5% vs. 55.6%) and higher prevalence of mild, moderate, and severe persistent asthma (28.4% vs. 23.2%, 28.7% vs. 18.8%, and 5.4% vs 2.4%, respectively). Individual/social burden due to asthma was frequent and increased with disease severity: 87.5% of severe persistent asthma patients reported at least one medical consultation in the last 12 months, 37.5% emergency department visits, 26.7% hospitalization, and 62.5% limitations in daily activities. Control and quality of life were inversely associated with disease severity and were worse in patients with R+A than in those with asthma alone. CONCLUSIONS: This study showed the negative impact of high severity levels and comorbid allergic rhinitis on quality of life of asthmatic patients and on individual/social burden due to asthma in an Italian GPs setting