Cosmetics as endocrine disruptors: are they a health risk?

Exposure to chemicals from different sources in everyday life is widespread; one such source is the wide range of products listed under the title "cosmetics", including the different types of popular and widely-advertised sunscreens. Women are encouraged through advertising to buy into the myth of everlasting youth, and one of the most alarming consequences is in utero exposure to chemicals. The main route of exposure is the skin, but the main endpoint of exposure is endocrine disruption. This is due to many substances in cosmetics and sunscreens that have endocrine active properties which affect reproductive health but which also have other endpoints, such as cancer. Reducing the exposure to endocrine disruptors is framed not only in the context of the reduction of health risks, but is also significant against the background and rise of ethical consumerism, and the responsibility of the cosmetics industry in this respect. Although some plants show endocrine-disrupting activity, the use of well-selected natural products might reduce the use of synthetic chemicals. Instruments dealing with this problem include life-cycle analysis, eco-design, and green labels; in combination with the committed use of environmental management systems, they contribute to "corporate social responsibility".

Correlation between depression, anxiety, and polymorphonuclear cells' resilience in ulcerative colitis: the mediating role of heat shock protein 70.

BACKGROUND: To investigate whether anxiety and depression levels are associated with Heat Shock Protein 70 (HSP70) induction in the colon of patients with ulcerative colitis (UC). METHODS: The design was cross-sectional. Clinical activity was assessed by the Rachmilewitz Index (CAI). Three psychometric questionnaires were used: Zung Depression Rating Scale (ZDRS), Spielberg State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS). Colon biopsies were obtained from each affected anatomical site. Severity of inflammation was assessed by eosin/hematoxylin. Constitutive (HSP70c) and inducible (HSP70i) HSP70 expression were immunohistochemically studied. RESULTS: 29 UC patients were enrolled (69% men). Mean age was 46.5 years (SD: 19.5). Inflammation severity was moderate in 17 patients, severe in 6, and mild in 6. The mean number of years since diagnosis was 7.9 (SD: 6.5). The mean CAI was 6.4 (SD: 3.1). In active UC, there was downregulation of HSP70c in inflamed epithelium, without significant HSP70 induction. In 22/29 cases of active cryptitis, polymorphonuclear cells (PMN) clearly expressed HSP70i, with weak, focal positivity in the other 7 cases. Except for the hospital anxiety scale, scores in all psychometric tools were higher in patients with strong HSP70i immunoreactivity in the PMN. Logistic regression showed a strong positive relationship between HSP70i immunoreactivity in the PMN cells and scores in the trait anxiety, ZDRS, and hospital depression scales, (Odds ratios 1.3, 1.3, and 1.5; P = 0.018, 0.023, and 0.038; Wald test, 5.6, 5.2, and 4.3 respectively) and a weaker but significant positive correlation with the CAI (Odds ratio 1.654; P = 0.049; Wald test 3.858). CONCLUSION: HSP70 is induced in PMN cells of UC patients and its induction correlates with depression and anxiety levels.

Enhancer of zeste homologue 2 expression in breast carcinoma smears in relationship with p53, Ki-67 and other prognostic parameters.

BACKGROUND: The polycomb group protein enhancer of zeste homologue 2 (EZH 2) has been reported as a marker of aggressive breast cancer. The aim of this study was to investigate the correlation between the expression of EZH 2 with p53 and Ki-67 expression and other clinicopathological parameters in primary breast carcinomas in order to determine the role of the above marker as a prognosticator of tumor aggressiveness and patient outcome. PATIENTS AND METHODS: One hundred primary operable breast cancer patients were investigated in order to identify the expression of EZH 2, Ki-67 and p53 in imprint smears immunocytochemically. The prevalence of expression of these markers was then correlated with clinicopathological parameters. Follow-up was available for all patients. RESULTS: EZH 2 was expressed in 64% of the cases and correlated with higher levels of p53 (relative risk = 3.00, p < 0.0001) and Ki-67 (relative risk = 3.25, p < 0.0001). Malignant cells showed immunoreactivity for all markers in the nucleus. Univariate analysis revealed a strong association between EZH 2 protein expression and tumor grade and size, lymph node metastasis, and HER-2 and estrogen and progesterone receptor status. Multivariable statistical analysis revealed that lymph node metastasis was the main predictor for EZH 2 expression. Decreased patient survival was also significantly associated with EZH 2 expression (p < 0.0001). CONCLUSIONS: EZH 2 expression may be a marker of poor prognosis in breast carcinoma patients and has been suggested as a candidate for targeted therapy.

Differential rates of proliferation and apoptosis in nasal polyps correspond to alterations in DNA spatial distribution and nuclear polarization as observed by confocal microscopy.

The study aimed to investigate the expression of p53, Bcl-2 and Ki-67 in relation to the histologic and nuclear qualitative and spatial characteristics of chronic rhinosinusitis with polyposis (CRP). Imprint smears obtained from surgically removed nasal polyps of 20 patients were studied. The polyps were classified according to their histological characteristics as: hyperplasia (simple and pronounced) and squamous metaplasia. The expression of p53, Bcl-2 and Ki-67 was assessed by immunocytochemistry. DNA spatial distribution and nuclear orientation were studied by staining with propidium iodide and examined by confocal microscopy. Positive immunoreaction for p53, Ki-67 and Bcl-2 was observed in 50, 65, and 50% of polyp's smears, respectively. For each diagnosis, the rates were simple hyperplasia 60, 80 and 30%, pronounced hyperplasia 80, 100 and 40%, metaplasia 0, 0 and 100%, respectively. Abnormal chromatin distribution and nuclear disorientation was observed in three cases of pronounced hyperplasia combined with positive immunoreaction for Ki-67 and p53 and negative immunoreaction for Bcl-2. CRP demonstrated different proliferation and apoptotic rates, according to their histology. Nuclear characteristics observed by confocal microscopy are associated with the immunocytochemical markers of proliferation and apoptosis.

Contribution of nuclear morphometry by confocal laser scanning microscopy to the diagnosis of malignant bile duct strictures.

OBJECTIVE: To determine the clinical utility of nuclear morphometry by confocal laser scanning microscopy for the diagnosis of malignant biliary strictures. STUDY DESIGN: The study included 51 patients with bile duct strictures who underwent endoscopic retrograde cholangiopancreatography (ERCP). Based on the initial workup, 6 patients were diagnosed with benign strictures, and 12 patients had malignant strictures, while in the remaining 33 cases the diagnoses were inconsistent, due mainly to inadequate samples. Smears from ERCP brushings were stained for DNA with propidium iodide. Nuclear morphometry was assessed on images acquired by a confocal laser scanning microscope. Three parameters-nuclear volume, nuclear shape and nuclear staining intensity-were calculated. Based on these features, a distinctive nuclear morphometric pattern was attributed to the malignant nuclei, and its predictive value was assessed prospectively in the 33 undiagnosed cases. RESULTS: After an overall median follow-up period of 8 months, 19 patients were diagnosed with malignant strictures, and 14 patients were considered to have benign strictures. With respect to the prediction of malignancy, the sensitivity of the described method was 78%, the specificity was 63%, the positive predictive value was 64%, and the negative predictive value was 80%. CONCLUSION: Nuclear morphometry may provide significant information for the diagnosis of malignant bile duct strictures when conventional cytology fails to.

Insulinlike growth factor I receptor and estrogen receptor beta expressions are inversely correlated in colorectal neoplasms and affected by the insulin resistance syndrome.

The present study aimed at evaluating the modulation of insulin-like growth factor I receptor (IGF-IR) and estrogen receptor beta (ER-beta) expression and their correlation during tumorigenesis of sporadic colorectal cancer, with particular interest in the insulin resistance syndrome. In a series of 100 individuals (54 men and 46 women; mean age, 67.3 +/- 9.4 years) with colorectal neoplasms, classified as early adenomas (n = 25), advanced adenomas (n = 44), and adenocarcinomas (n = 31), IGF-IR and ER-beta expression was quantified in formalin-fixed, paraffin-embedded biopsy specimens, using confocal laser scanning microscopy and a computer-based method for assessment of immunofluorescent staining. All individuals were evaluated for insulin resistance markers (hyperglycemia, dyslipidemia, central obesity, and arterial hypertension), and 50 (26 men and 24 women; mean age, 68.2 +/- 9.0 years) were diagnosed with the insulin resistance syndrome. For the sequence of early adenoma-advanced adenoma-adenocarcinoma, a gradual increase in IGF-IR expression and a gradual decrease in ER-beta expression were observed. The partial correlation coefficient between IGF-IR and ER-beta expression, controlled for age, sex, insulin resistance, type of lesion, and location of lesion was 0.295 (P = .004, 2-tailed significance). Analysis of variance demonstrated that the effect of the insulin resistance syndrome on IGF-IR and ER-beta expression was significant (P = .007 and P = .018, respectively). The results suggest the combined effect of IGF-I and estrogens in colorectal cancer, with a distinctive role in individuals with the insulin resistance syndrome.

Exposure to multiple environmental agents and their effect.

INTRODUCTION: All children are exposed to multiple physical, chemical and biological challenges that can result in adverse health effects before and after birth. In this context, the danger of multiple exposures cannot be assessed from a single-chemical approach as used in classical toxicology. AIM: To open up a 'negotiation space' for the problem of multiple exposure to environmental stressors, defined as any physical, chemical or biological entity that can induce an adverse response. In this context, two further questions obtain: to what extent can synergistic risks be assessed, and how far could potential adverse effects be prevented by enhanced regulation? METHODS: A discussion of two general approaches is taken: 1) the investigation of mixtures such as smoking or air pollution without specifying the individual agents, and 2) the investigation of individual substances with a focus on possible interactions in the context of dose to receptor. RESULTS: Although mixtures of compounds can have effects, it may not be possible to ascribe causation to a single compound. Furthermore, cumulative low-dose insult can, in some circumstances, be more toxic than a single high-dose exposure, e.g. endocrine disruptive effects of a combination of PCBs and dioxins which disrupt the thyroid hormone status; this tends to contradict elements of classical toxicology, . These cumulative insults may further combine with heavy metals and can disrupt the heme synthesis. It is possible that groups of pollutants could be used to test their cumulative capacity to multiple stress-susceptible receptor targets as is done in smoking and air pollution. This methodology could be used for further groups of potential pollutants, for example those associated with cleaning products, or cosmetics. Testing individual substances with a focus on interactions means that not only chemicals but also concurrent diseases should be taken into account. We suggest that the enhanced regulation of potential multiple stressors falls into two discrete categories. The first comprises a more precautionary approach (as demonstrated by the banning of chemicals such as some brominated flame retardants in Europe). The second comprises a more 'permissive' liberal approach involving the initial study of an individual compound, and subsequent interrogation of that compound in combination with another (as demonstrated by lowering the carcinogenicity of aflatoxin by vaccination against hepatitis B). CONCLUSIONS: It is necessary to define and study groups of multiple stressors as in US EPA's Framework for Cumulative Risk Assessment (U.S. EPA 2003). Recent increased knowledge of the greater sensitivity of the unborn baby, the infant and the child, has led to general recognition that a higher degree of precaution is now needed in regulating for multiple stressors on the young. The more liberal permissive approach proceeding from established effects of the individual exposures is becoming less acceptable now that we know that there is much we do not understand about chronic effects of stressors during the early development phases. Conflicts over which approach to take may have to be resolved through engagement and negotiation with a wide community of stakeholders. This "community of interest" may include fundamental research scientists, practicing clinical paediatricians, patient groups, and others concerned with the health and wellbeing of infants and children.

Chemical Pesticides and Human Health: The Urgent Need for a New Concept in Agriculture.

The industrialization of the agricultural sector has increased the chemical burden on natural ecosystems. Pesticides are agrochemicals used in agricultural lands, public health programs, and urban green areas in order to protect plants and humans from various diseases. However, due to their known ability to cause a large number of negative health and environmental effects, their side effects can be an important environmental health risk factor. The urgent need for a more sustainable and ecological approach has produced many innovative ideas, among them agriculture reforms and food production implementing sustainable practice evolving to food sovereignty. It is more obvious than ever that the society needs the implementation of a new agricultural concept regarding food production, which is safer for man and the environment, and to this end, steps such as the declaration of Nyéléni have been taken.

Sun lotion chemicals as endocrine disruptors.

Ultraviolet solar radiation is a well-known environmental health risk factor and the use of sun lotions is encouraged to achieve protection mainly from skin cancer. Sun lotions are cosmetic commercial products that combine active and inactive ingredients and many of these are associated with health problems, including allergic reactions and endocrine disorders. This review focuses on their ability to cause endocrine and reproductive impairments, with emphasis laid on the active ingredients (common and less common UV filters). In vitro and in vivo studies have demonstrated their ability to show oestrogenic/anti-oestrogenic and androgenic/anti-androgenic activity. Many ingredients affect the oestrous cycle, spermatogenesis, sexual behaviour, fertility and other reproductive parameters in experimental animals. Their presence in aquatic environments may reveal a new emerging environmental hazard.

Prognostic value of COX-2, P53, and EZH-2 evaluated by quantitative image analysis in premalignant and malignant breast lesions.

BACKGROUND: Cytological differential diagnosis of atypical hyperplasia and well differentiated breast carcinoma may be challenging, because sometimes there is an overlap between the cytomorphological features of these lesions. The aim of the study was to investigate COX-2, EZH-2, p53 expression in carcinomas and the gray zone of breast cytology categories of atypical hyperplastic lesions with regard to biological behavior of the tumor. METHODS: FNA speciments from 100 patients with breast hyperplastic lesions and cancer were investigated by immunocytochemistry and a quantitative analysis for COX-2, p53, and EZH-2. RESULTS: Extent of staining for COX-2 correlated with percentage of positive for EZH-2 (P < 0.0001) and p53 nuclei (P < 0.001). The intensity of COX-2 was lower in the carcinoma group (118.57 ± 12.43) than in the hyperplastic (127.16 ± 11.71) group (P = 0.006). On the contrary the mean value of staining extent was greater in the adenocarcinoma cases (15.96 ± 13.03) than in hyperplastic (4.04 ± 1.94) cases (P < 0.0001). The percentage of EZH-2 and p53 positive cells correlated with the histological type of the lesions (P = 0.001 and P = 0.011, respectively). There was also a statistically significant relation between tumor size and expression of COX-2 (P = 0.007) and EZH-2 (P = 0.010). CONCLUSION: Our study showed that the expression of COX-2, EZH-2, and p53 as determined by immunocytochemistry at quantitative level may be a predictor for distinguishing cytologically atypical hyperplastic from malignant breast lesions and may be regarded as potential prognostic factor in breast cancer patients.

Fibroblast activation protein and its prognostic significance in correlation with vascular endothelial growth factor in pancreatic adenocarcinoma.

Fibroblast activation protein (FAP), a selective protein for tumor stromal fibroblasts, is expressed in >90% of human epithelial carcinomas. A characteristic feature of pancreatic cancer is an extensive fibrotic or desmoplastic reaction surrounding the primary tumor. The present study aimed to evaluate the expression levels of FAP and vascular endothelial growth factor (VEGF) and determine their correlation in pancreatic adenocarcinoma. Confocal laser scanning microscopy and conventional immunohistochemical analysis were used to quantify FAP and VEGF expression levels in formalin­fixed and paraffin­embedded tissue biopsies from 46 patients (male, 26; female, 20; mean age, 66 years; age range, 53­80 years) with pancreatic adenocarcinoma stage IIA or IIB. The expression levels of FAP in the neoplastic and adjacent normal tissue were significantly higher in stage IIB patients, compared with stage IIA patients. FAP expression was correlated with positive lymph nodes, resulting in poor prognosis for stage IIB patients. The partial correlation coefficient between FAP and VEGF expression levels was 0.39 (P=0.007), and the two factors had an effect on patient survival. Multivariate analysis demonstrated the prognostic superiority of FAP over VEGF, which is considered to be the most consistently reproducible molecular marker with prognostic value in resected pancreatic adenocarcinoma. Due to the limited beneficial effect of current systemic therapies for pancreatic adenocarcinoma, targeting FAP may be a potential therapeutic strategy and requires further investigation.

Indoor air quality in a bar/restaurant before and after the smoking ban in Athens, Greece.

In this study we compared indoor air pollutant concentrations in a bar/restaurant in Greece before and after the enactment of a smoking ban legislation of 2008. This was done to investigate whether the separation of the venue into smoking and non-smoking areas will have an impact on workers and customers from secondhand smoke (SHS) exposure (null hypothesis). The study was completed within an 8-month period beginning in March 2010 and ending on November 2010. We compared the average of the measured PM0.1 concentrations in the smoking zones between the pre-ban and post-ban periods. Overall reduction in the number of particles was 18% between pre-ban and post-ban periods. The mean of the 36 total CO2 measurements for the pre- and the post-ban period was 611ppm. We calculated the ventilation rates per occupant (Vo in l/s/occ) and found it to be higher in the post-ban period (19.4l/s/occ), thus complying with the ASHARAE standard for Vo of 15l/s/occ at maximum occupancy, than in the pre-ban period (10.7l/s/occ). The mean of the 36 total CO measurements for the pre-ban period was 2 ppm. CO measurements in the post-ban period were less than the detection limit of 1 ppm. Emissions of nitrogen dioxide and formaldehyde weren't detected in any of the zones. It was observed there was about 50% distribution of pollutants from the smoking zones to the smoke-free zones. The smoking ban effect on the occupancy levels was initially reduced by 16%, but based on other similar studies this transition period will be followed by an increase in the occupancy. Passive smoking and associated risks were significantly reduced but not totally eliminated, indicating the need for stronger enforcement or complete partition between smoking and non-smoking areas.

Children exposure to trace levels of heavy metals at the north zone of Kifissos River.

This study evaluates the exposure level of primary school children at three different towns in northern Attica, near the banks of the Kifissos River, defining referential values of toxic heavy metals. Concentrations of five toxic metals (arsenic, cadmium, mercury, lead and nickel) were analyzed in water samples from the Kifissos River as well as in the scalp hair of children aged 11 to 12 years old living in the study area. Chronic low-level toxicity of lead and cadmium came into view in recent years as a problem of our civilization. Exposure to concentrations of arsenic (As), cadmium (Cd), mercury (Hg) and lead (Pb) poses a potential threat to humans and can cause effects on children's renal and dopaminergic systems without clear evidence of a threshold, a fact that reinforces the need to control all the potential heavy metal emissions into the environment in order to protect children's health. The results were analyzed with the IBM SPSS Statistics 20 for Windows. The possible influence of sex and area was examined. Statistical differences were observed by t-test between the log-transformed hair concentrations of lead (p=0.021), arsenic (p=0.016) and nickel (p=0.038) in children's scalp hair from the municipalities of Kifisia and Kryoneri. ANOVA one-way test confirmed the difference of Pb concentration in hair between girls and boys from the municipality of Kifisia (p=0.038). The t-test confirms the difference of heavy metal concentrations in river samples between the municipalities Kifisia and Philadelphia in comparison with the samples from Kryoneri. The observations suggest that children living at the municipality of Kifisia are exposed to higher concentrations of heavy metals than the others. Despite all the confounding factors, hair can be used as a biomarker in order to determine the exposure to heavy metals, according to standardized protocols.

Subsite-specific differences of estrogen receptor beta expression in the normal colonic epithelium: implications for carcinogenesis and colorectal cancer epidemiology.

OBJECTIVE: This study aimed at investigating whether a differential estrogen receptor beta (ER-beta) expression between the colonic subsites could correspond to a modification in proliferation, apoptosis, and adhesion of the normal colonocytes. METHODS: ER-beta, Ki-67, Bcl-2, and E-cadherin expressions were investigated immunohistochemically, in normal epithelium biopsies from the ascending and the descending colon of 53 individuals, who underwent colonoscopy for the investigation of anemia and in whom no local pathology was identified. RESULTS: ER-beta immunoreactivity has been shown to be stronger at the superficial epithelium than the crypts' base, the difference being important only for the ascending colon. In addition, ER-beta expression was higher in the superficial epithelium of the ascending colon than that of the descending colon. The variations of ER-beta expression did not correspond to the alterations in Ki-67, Bcl-2, and E-cadherin expression. CONCLUSION: A subsite-specific variation of ER-beta expression has been shown in the normal colonic epithelium. This modulation of ER-beta might account for some well established specificities of colorectal cancer epidemiology like the right-sided predominance of the neoplasm in women and its gradual shift to more proximal sites over time.

VEGF isoforms and receptors expression throughout acute acetaminophen-induced liver injury and regeneration.

Acetaminophen (APAP) is a widely-used analgesic and a known hepatotoxic agent. Vascular endothelial growth factor (VEGF) is a growth factor with multiple functional roles. VEGF plays an important role in angiogenesis and hepatic regeneration. The aim of this study was to determine the expression of VEGF isoforms and its receptors throughout liver regeneration after the administration of a toxic dose of APAP in rats. Ten groups of adult male rats received a dose of 3.5 g/kg b.w. of APAP per os. The rats were killed post administration at 0-288 h. Blood and liver tissue were extracted. Determination of serum transaminases and alkaline phosphatase activities was performed. Liver injury and regeneration were assessed with hematoxylin-eosin specimens, morphometric analysis, hepatic thymidine kinase assay and Ki-67 expression. Reverse transcription-polymerase chain reaction and immunohistochemical methods were used for assessment of VEGF isoforms and receptors differential expression. High activities of aspartate aminotransferase were observed at 24 and 36 h with another peak of activity at 192 h post administration. Alanine aminotransferase was highest at 36 h. Alkaline phosphatase was increased post 24 h being higher at 72,192 and 240 h. Centrilobular necrosis was observed at 48-72 h and thorough restoration of the liver microarchitecture was observed at 288 h. Liver regeneration lasted from 24-192 h according to the results from thymidine kinase activity and Ki-67 expression. VEGF and VEGF receptor-2 m-RNA levels presented with a three-peak pattern of expression at 12-24, 72-96 and 192-240 h post administration. Significant difference was noted between periportal and centrilobular immunohistochemical expression. VEGF proves to play a critical role during APAP-induced liver regeneration as it presents with three points of higher expression. The first two time points are associated with the initial inflammatory reaction to the noxious stimulus and the hepatocyte regenerative process where as the third one is indicative of the potential involvement of VEGF in processes of remodeling.