Pesticide exposure and gender discrepancy in breast cancer.

OBJECTIVE: It is biologically plausible that occupational and environmental pesticide exposure may contribute to breast cancer risk. Persistent chemical compounds, such as pesticides, tend to be lipophilic and are detected in human breast milk and adipose tissue. Therefore, the present systematic review aims to clarify the gender difference in breast cancer concerning pesticide exposure. MATERIALS AND METHODS: A total of 70 studies satisfied the inclusion criteria and were included in the systematic review. RESULTS: From the studies analyzed, it was observed that exposure to pesticides could be a risk factor for breast cancer in women, in particular in young women and in women who experienced menarche at a young age. In contrast, no association was found for breast cancer in men. Female breast cancer is correlated with estrogen receptor-negative tumor characteristics. Breast cancer in men was no correlated with pesticide exposure. CONCLUSIONS: Breast cancer in women has been linked to estrogen receptor positivity, but this positivity appears to be inversely related to fertility. The estrogen-like effects of organochlorine pesticides could be the cause of the observed gender differences.

Evaluation of the impact of the European Code against Cancer on awareness and attitudes towards cancer prevention at the population and health promoters' levels.

INTRODUCTION: The European Code against Cancer (ECAC) informs the public on steps to take to reduce their cancer risk. Despite over three decades of promotion, no systematic evaluation of its impact has yet been carried out. This study aimed to address the gap in knowledge regarding the impact of the ECAC. METHODS: An online survey targeting adults in the general population was conducted and analysed by age, gender, and country, both descriptive and mutually adjusted in logistic regression analyses. Additionally, semi-structured interviews with health promotion professionals from not-for-profit organisations in Europe were conducted and a qualitative thematic analysis was carried out for each interview. RESULTS: 8171 people from eight European countries responded to the survey. Although 70 % of respondents were aware of cancer prevention guidance, a low percentage of participants had previously heard about the ECAC (2% in UK to 21 % in Hungary and Poland). Females were more likely to make lifestyle changes to reduce their risk of cancer (odds ratio = 1.17; 95 % confidence interval: 1.05-1.29). Twenty-eight online semi-structured interviews with professionals were conducted covering 25 countries. Regional variation in the methods and target groups of the promotion and dissemination of the ECAC was reported. CONCLUSION: Whilst familiarity with the ECAC in the general public is low, professionals frequently use it as a basis for informing population-level actions. Future editions should be accompanied by a systematic evaluation of the ECAC investigating the impact upon society.

Bioavailability of phenolics from an oleuropein-rich olive (Olea europaea) leaf extract and its acute effect on plasma antioxidant status: comparison between pre- and postmenopausal women.

PURPOSE: Preclinical studies suggest a potential protective effect of oleuropein in osteoporosis, and one of the proposed mechanisms is the modulation of the oxidative stress. Oleuropein bioavailability and its effect on antioxidant status in pre- and postmenopausal women are unknown. The aim of the present study was to investigate the oral bioavailability of an olive leaf extract rich in oleuropein (40 %) and its effect on antioxidant status in postmenopausal women compared to premenopausal women. METHODS: Premenopausal (n = 8) and postmenopausal women (n = 8) received 250 mg of olive leaf extract, blood samples (t = 0, 1, 2, 3, 4, 6, 8, 12, 16 and 24 h) were taken, and 24-h urine divided into five fractions was collected. Olive-leaf-extract-derived metabolites were analyzed in plasma and urine by HPLC-ESI-QTOF and UPLC-ESI-QqQ, and pharmacokinetics parameters were determined. Ferric reducing antioxidant ability and malondialdehyde levels were measured in plasma. RESULTS: Plasma levels of hydroxytyrosol glucuronide, hydroxytyrosol sulfate, oleuropein aglycon glucuronide and oleuropein aglycon derivative 1 were higher in postmenopausal women. MDA levels were significantly decreased (32%) in postmenopausal women and inversely correlated with hydroxytyrosol sulfate levels. Postmenopausal women excreted less sulfated metabolites in urine than premenopausal women. CONCLUSIONS: Our results suggest that postmenopausal women could be a target population for the intake of olive phenolics in order to prevent age-related and oxidative stress-related processes such as osteoporosis.

Urolithins, ellagitannin metabolites produced by colon microbiota, inhibit Quorum Sensing in Yersinia enterocolitica: Phenotypic response and associated molecular changes.

The mammalian enteropathogen Yersinia enterocolitica produces two main N-acylhomoserine lactones (AHLs) involved in Quorum Sensing (QS)-mediated infection processes, such as virulence, biofilm maturation and motility. Ellagitannin (ET)-rich fruits exhibit anti-QS activity but in vivo effects against intestinal pathogens may be associated to the ETs gut microbiota derived metabolites, urolithin-A (Uro-A) and urolithin-B (Uro-B). In this work we show that urolithins, at concentrations achievable in the intestine through the diet, reduce the levels of N-hexanoyl-l-homoserine lactone (C6-HSL) and N-(3-oxo-hexanoyl)-l-homoserine lactone (3-oxo-C6-HSL) in Y. enterocolitica and inhibit QS-associated biofilm maturation and swimming motility. These inhibitory effects were not associated to downregulation of the expression of some of the genes involved in the synthesis of AHLs (yenI and yenR) or in motility (flhDC, fliA, fleB). Our results suggest that urolithins may exert antipathogenic effects in the gut against Y. enterocolitica and highlight the need to investigate the antipathogenic in vivo properties of plant derived metabolites.

Lack of effect of oral administration of resveratrol in LPS-induced systemic inflammation.

PURPOSE: The high mortality index due to sepsis and the lack of an effective treatment requires the search for new compounds that can serve as therapy for this disease. Resveratrol, a well-known anti-inflammatory natural compound, might be a good candidate for the treatment of sepsis. The aim of this work was to study the effects of oral administration of resveratrol, before and after sepsis initiation, on inflammation markers in a murine model of endotoxin-induced sepsis. METHODS: Sprague-Dawley male rats were treated with resveratrol the 3 days prior to LPS administration and 45 min later. Hematological parameters, TNF-α, IL-1ß and CINC-1, FRAP and TBARS levels were determined. Resveratrol and resveratrol-derived metabolites profile in plasma was compared after oral and intraperitoneal administration. RESULTS: Oral treatment with resveratrol had no apparent systemic protective effects. However, resveratrol reduced the levels of lipid peroxidation in the small intestine and colon. Importantly, the administration of LPS caused a decrease in resveratrol absorption. When resveratrol bioavailability after i.p. administration was compared to that observed after oral administration, a different profile of resveratrol metabolites was found in plasma. CONCLUSION: These results highlight the importance of studying the bioavailability of the assayed compounds in the experimental models used to be able to choose the best route of administration depending on the target organ and to determine which compounds or derived metabolites are effective treating the studied disease.

Prognosis of left-sided infective endocarditis in patients transferred to a tertiary-care hospital--prospective analysis of referral bias and influence of inadequate antimicrobial treatment.

The aims of this study were to compare the characteristics of adult patients with left-sided infective endocarditis (LSIE) diagnosed and treated in a tertiary-care hospital with those of patients referred from a second-level community hospital, and to establish the accuracy of diagnosis and adequacy of treatment in referred patients and the influence of this factor on outcome. A prospective observational cohort study was conducted at Hospital Universitari Vall d'Hebron, a 1000-bed teaching hospital in Barcelona (Spain) and a referral centre for cardiac surgery. One hundred and fourteen of 337 (34%) episodes of LSIE treated in our hospital occurred in transferred patients. As compared with patients diagnosed in our hospital, transferred patients acquired LSIE within the healthcare system less often (16.7% vs. 38.1%, p <0.001), were in better health (Charlson index 3 (interquartile range (IQR)) 1-4) vs. 4 (IQR 2-6), p <0.001), had more complications (94.7% vs. 78.9%, p <0.001), underwent more operations (69.3% vs. 22.1%, p <0.001), and experienced similar mortality (22.8% vs. 31.4%, p 0.100). Only 52 of 114 (45.6%) referred patients received an antimicrobial regimen included in the American, European or Spanish guidelines at the hospital of origin. After adjustment for congestive heart failure and staphylococcal infection in multivariate logistic regression, inadequate or no antimicrobial treatment at origin was a risk factor for in-hospital mortality (OR 3.3, 95% CI 1.1-10.0, p 0.030). Errors in the initial antimicrobial treatment prescribed for LSIE are associated with greater mortality.

Sexual dysfunction in fibromyalgia patients.

OBJECTIVE: To investigate the prevalence of sexual dysfunction in female patients with fibromyalgia (FM), the impact of FM on sexual activity and the factors associated with sexual dysfunction in these patients. METHODS: Thirty-one consecutive women with FM were enrolled; two groups of 20 aged-matched healthy women and 26 patients with rheumatoid arthritis (RA) were used as controls. Demographic features were recorded in all patients. A cross-sectional analysis of pain (100-mm VAS scale), anxiety and depression (as determined by the STAI and Beck Depression Inventory scales, respectively) was performed. Sexual function was assessed by the Changes in Sexual Functioning Questionnaire (CSFQ). RESULTS: FM and RA patients showed a significantly higher rate of sexual dysfunction compared to healthy controls. Sexual dysfunction was more frequent among FM patients (97%) than in RA patients (84%) but without statistical differences. A univariate analysis showed that age (p=0.0002), marital (p=0.036) and work status (p=0.048), pain intensity (p=0.007), level of anxiety (p=0.002), level of depression (p=0.0005), were significantly associated with sexual dysfunction in FM. However, only the intensity of depression was associated with the sexual dysfunction in patients with FM in the multivariate analysis (p=0.012). CONCLUSIONS: Sexual function was very frequently and severely affected in patients with FM and this impairment appeared to be particularly associated with the degree of depression. The recognition of this dysfunction and its inclusion for the multidisciplinary management of FM may contribute to improve quality of life of these patients.

Transcriptional changes in human Caco-2 colon cancer cells following exposure to a recurrent non-toxic dose of polyphenol-rich chokeberry juice.

Berries and red fruits are important dietary sources of polyphenols [1]. In vitro and animal studies have demonstrated the bioavailability and the anti-proliferative and anticarcinogenic properties of these fruits or of their phenolic components [2, 3]. Consumption of berries may contribute to the reduction of colon cancer by mechanisms not yet understood. Gene expression analysis using microarrays allows for a more comprehensive study of the possible molecular mechanisms by which food or food components may prevent certain cancers of the gastrointestinal tract [4]. The aim of this research is to investigate the anti-proliferative effects of a polyphenol-rich berry juice on a human model of colon cancer cells and its association to transcriptional changes in relation to colon cancer.

[Renal involvement in amyloidosis. Clinical outcomes, evolution and survival]. / Afectación renal en la amiloidosis. Características clínicas, evolución y supervivencia.

BACKGROUND: Systemic amyloidosis is a disease resulting from extracellular deposition of fibrillar protein in various organs. Main systemic amyloidosis are: primary (AL) and Secondary (AA). The kidney is usually involved, conferring and adverse prognosis. In the last decade there has been a change in the aetiology of AA amyloidosis. OBJECTIVES: To analyse the incidence of AL and AA amyloidosis in our current population as well as the aetiology of AA amyloidosis. To describe clinical outcomes, renal involvement and survival. PATIENTS AND METHODS: We performed a descriptive analysis of all cases of amyloidosis diagnosed from 1992 to 2004 in our hospital. Diagnosis was assessed on histological criteria: positivity Congo Red stain. Clinical data, renal involvement, dialysis treatment and survival were analysed. RESULTS: 76 cases, 44 women, mean age 70.7 +/- 12. Types: 55 AA (72%), 21 AL (28%) systemic amyloidosis. AA aetiology was: 66% rheumatic disorders, 28% infectious disease, 6% others. Incidence for AL was 4.6 and for AA 12.2 cases/million. Renal involvement was present in 75% at diagnosis (69% Creatinine clearance < 60 ml/min, 37% urinary protein > 3 g/24 hours). 21 cases (28%) progressed to renal disease stage V in the 8.1 +/- 9.8 months follow up period, and 14 cases started dialysis treatment (10 HD, 4 CAPD). In 7 cases (33%) dialysis was not indicated due to their poor clinical condition, short life expectancy and bad quality of life. Mean global survival at diagnosis was 55% and 40% at 12 and 24 months (AL 58% and 19%; AA 55% and 44%). Mean survival from the start of dialysis was 30% and 5% at 12 and 24 months. CONCLUSIONS: Although amyloidosis has a low incidence in our population, the kidney is usually involved. Rheumatological disorders are the principal aetiology of AA amyloidosis. Long term survival is poor, specially for AL.

Antimalarial myopathy: an underdiagnosed complication? Prospective longitudinal study of 119 patients.

OBJECTIVES: To evaluate the prevalence and incidence of antimalarial myopathy in patients with rheumatic diseases treated with antimalarial drugs. METHODS: Over a three year period, all patients with rheumatic diseases who were taking antimalarial drugs were studied. Serum muscle enzymes were assessed at the time of inclusion and every six months thereafter. Muscle strength, electromyography (EMG), and muscle biopsy were assessed in patients with a persistent muscle enzyme disturbances. RESULTS: 119 patients were included (111 chloroquine, eight hydroxychloroquine). Of these, 22 (18.5%) had a persistent muscle enzyme disturbance: lactate dehydrogenase 19/22 (86%); creatine kinase 7/22 (32%), and aldolase 3/22 (14%). Findings of antimalarial myopathy were detected in 3/15 biopsied patients (20%) by light microscopy and in all 15 by electron microscopy. Eleven patients had myopathy at the time of inclusion (prevalence 9.2%) and four patients developed muscle injury during follow up (annual incidence 1.2%). Muscle weakness was observed in 8 of 15 patients with biopsy proven myopathy, giving a prevalence of clinical antimalarial myopathy of 6.7%. All these patients also had a myopathic pattern on electromyography. CONCLUSIONS: The prevalence of antimalarial myopathy is higher than previously recognised when muscle enzyme determination is used as a screening method. When a persistent muscle enzyme disturbance is observed, clinical and electromyographic studies should be undertaken periodically to detect the development of clinical myopathy. In cases of clinical myopathy, an anatomical-pathological tissue study, including an ultrastructural study, is mandatory to confirm the diagnosis.

Giant cell (temporal) arteritis and secondary renal amyloidosis: report of 2 cases.

Renal involvement is unusual in giant cell (temporal) arteritis (GCA). Microscopic hematuria and minimal proteinuria responsive to steroid therapy have been described as the most frequent renal alterations. The nephrotic syndrome in GCA has been rarely reported. We describe 2 cases of GCA with nephrotic syndrome, one at the time of diagnosis, the other 2 years after treatment. Percutaneous renal biopsy in both cases disclosed secondary renal amyloidosis confirmed by permanganate sensitivity and immunohistochemical analysis. To our knowledge, cases of GCA and secondary amyloidosis have not been reported.

Bilateral optic neuritis in occupational exposure to trichloroethylene.

Central nervous system depression is the predominant response to acute trichloroethylene exposure. Cranial or peripheral nerves are also affected. The paper is a case report of a bilateral retrobulbar optic neuritis caused by occupational trichloroethylene poisoning. The urinary concentration of trichloroacetic acid one week after the onset of symptoms was positive. Visual fields and visual evoked potentials recovered eight months later. Other neurological diseases, such as multiple sclerosis were excluded.