Non-exposed Population Research Articles

Environmental pathways and human exposure to manganese in southern Brazil

The study of environmental pathways and human exposure to Manganese (Mn) in Southern Brazil was performed using two steps. The first step consisted of taking water samples from the surface of the Pardinho River. The average results from this technique showed a significant increase of pollutants, including increased levels of Mn, above the environmentally acceptable standard recommended by the Brazilian National Environment Council. Additionally, 64 soil samples were taken from areas with and without agricultural activity. Many results were above the mean crust and did not indicate significant differences of Mn levels between the sampled areas. For the second step, 12 families were selected and assessed for exposure to Mn in a region with high levels of Mn in the soil. Most of the analyzed foods contained amounts of Mn above the reference values, indicating that food can be an important source of exposure. The Mn content from the hair of most subjects studied was also high compared to reference values from non-exposed populations. Although the contamination appeared to come from a natural origin, the results found in the present study showed that the Mn levels present in the Pardinho River Basin are a relevant public health issue.

Noise-Induced Hearing Loss Still a Problem in Shipbuilders: A Cross-Sectional Study in Goa, India

Background:Workplace safety regulations seek to mitigate noise-induced hearing loss (NIHL), conventionally associated with the shipbuilding industry. Despite this, are workers still predisposed to NIHL?Aims:To study the prevalence of NIHL among noise-exposed subjects in the shipbuilding industry in Goa and to compare it with that among the non-exposed population working in the same industry in relation to certain relevant factors.Subjects and Methods:This is a cross-sectional study in the shipbuilding industry, Goa This study examined 552 workers: 276 shipbuilders and 276 office staff, of similar age, duration of employment and socio-economic status working at a shipbuilding enterprise. An interviewer-administered questionnaire was followed by audiometry. Values were presented as percentages, Mean (SD) and odds ratio (OR) and its 95% confidence interval (CI) (Woolfe's method). Fisher's exact test and binary logistic regression were used. P value of < 0.05 was taken as significant. SPSS version 16 was used.Results:NIHL was found in 17 (6%) shipbuilders, while no office staff was detected to have this condition (OR = 37.29, 95% CI 22.42-62.18). The shipbuilders with NIHL were 52.5 years of age and had been employed for 30.4 years, on an average. None of the 17 cases of NIHL were found to be using earplugs consistently; 11 reported using them “sometimes” and six “never” used them.Conclusions:NIHL continues to affect shipbuilders, owing their non-compliance to workplace regulation. Health education is the need of the hour.

The association between armed conflict, violence and mental health: a cross sectional study comparing two populations in Cundinamarca department, Colombia

BackgroundExposure to violence in general and to armed conflict in particular has been consistently associated with an increased prevalence of mental illness. Colombia has sustained an internal armed conflict for decades and is considered one of the most violent countries in the world. However, certain areas have been more exposed to the conflict than others.MethodsThis is a cross sectional study comparing two communities from different villages in the department of Cundinamarca, Colombia. One, Guasca, was directly impacted by armed conflict. The other one; Guatavita has never been affected by armed conflict. We applied two different instruments: the PHQ scale and a short standardized interview in order to estimate the prevalence of major psychiatric disorders and their link to violent events. Forty-two volunteers from each village were evaluated through a personal interview using these two instruments.FindingsOf the population surveyed in Guatavita, 2.4% reported direct exposure to violence compared to 23.8% from Guasca. In the population exposed directly to violent events, the prevalence of all disorders was greater than in the non-exposed population with an OR of 1.46 (95% CI 0.3809 - 5.5989) for anxiety; 4.54 (95% CI 1.1098 - 18.5984) for depression; 6.0 (95% CI 1.2298 - 30.2263) for somatization disorder; and 4.4 (95% CI 1.2037 - 16.0842) for alcohol abuse.InterpretationThere is a statistically significant association between the history of armed conflict, violence and the presence of mental illnesses, particularly depression, somatization disorder and alcohol abuse. Special attention should be paid to the detection, prevention and treatment of these disorders when dealing with populations exposed to violence and to armed conflict in particular.

Humoral response of captive zebra sharks Stegostoma fasciatum to salivary gland proteins of the leech Branchellion torpedinis

Parasitism by the marine leech Branchellion torpedinis is known to cause disease and mortality in captive elasmobranchs and is difficult to control when inadvertently introduced into public aquaria. Preliminary characterization of the salivary gland transcriptome of B. torpedinis has identified anticoagulants, proteases, and immunomodulators that may be secreted into host tissues to aid leech feeding. This retrospective study examined antigen-specific serum IgM responses in captive zebra sharks Stegostoma fasciatum to leech salivary gland extract. Antibody response was examined by ELISA and Western blot assays in 20 serum samples from six zebra sharks, with a 5 year history of leech infection, and 18 serum samples from 8 captive bred zebra sharks, with no history of leech exposure. ELISA demonstrated significantly higher serum IgM titers to salivary gland extract in exposed zebra sharks compared to the non-exposed population. No obvious trends in antibody titers were appreciated in exposed zebra sharks over a four-year period. One-dimensional and two-dimensional Western blot assays revealed IgM targeted specific salivary gland proteins within the 40, 55, 70 and 90 kD range. Antigenic proteins identified by liquid chromatography-tandem mass spectrometry and de novo peptide sequencing include a secreted disintegrin, metalloproteinase and thrombospondin motif containing protein (ADAMTS), tubulin, aldehyde dehydrogenase and two unknown proteins. Humoral immune responses to leech salivary gland proteins warrants further investigation as there may be options to exploit immune mechanisms to reduce parasite burdens in aquaria.

Environmental human silver exposure

Environmental exposure to silver (Ag) was assessed in occupationally non-exposed adult human population by analyzing Ag in the hair (H · Ag) and whole blood (WB · Ag). H · Ag was analyzed in 311 (123 men, M; 188 women, W); while WB · Ag was determined in 235 of these individuals (90 M, 145 W). Women had more H · Ag than men (M 0.05 vs. W 0.076), whereas WB · Ag concentrations in men and women were not significantly different. A natural distribution of the median derivatives was utilized to generate the dataset to fit the logistic sigmoid curve to assess the current human body burden of environmental Ag population exposure for M and W separately. The H · Ag (µg g−1) below 0.0105 for M and 0.0145 for W, reflects low level of environmental Ag exposure. The adaptive physiological saturation phase followed where H · Ag rose rapidly, first for M and then for W in parallel with biological assay. Both parallel saturation curves converged and plateaued at 0.215 for M and 0.965 for W (µg g−1). The current level of human environmental Ag exposure is low, but cases of high Ag exposure occurred sporadically. In conjunction with the medical histories overt clinical neural toxicity may be expected for H · Ag at 4 µg g−1and higher. There were no significant correlation between the H · Ag and WB · Ag.

Reduced lung function due to biomass smoke exposure in young adults in rural Nepal

This study aimed to assess the effects of biomass smoke exposure on lung function in a Nepalese population, addressing some of the methodological issues seen in previous studies. We carried out a cross-sectional study of adults in a population exposed to biomass smoke and a non-exposed population in Nepal. Questionnaire and lung function data were acquired along with direct measures of indoor and outdoor air quality. Ventilatory function (forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC) was significantly reduced in the population using biomass across all age groups compared to the non-biomass-using population, even in the youngest (16-25 yrs) age group (mean FEV(1) (95% CI) 2.65 (2.57-2.73) versus 2.83 (2.74-2.91) L; p=0.004). Airflow obstruction was twice as common among biomass users compared with liquefied petroleum gas users (8.1% versus 3.6%; p<0.001), with similar patterns for males (7.4% versus 3.3%; p=0.022) and females (10.8% versus 3.8%; p<0.001), based on the lower limit of normal. Smoking was a major risk factor for airflow obstruction, but biomass exposure added to the risk. Exposure to biomass smoke is associated with deficits in lung function, an effect that can be detected as early as the late teenage years. Biomass smoke and cigarette smoke have additive adverse effects on airflow obstruction in this setting.

Association of glutathione S-transferase Ω 1-1 polymorphisms (A140D and E208K) with the expression of interleukin-8 (IL-8), transforming growth factor beta (TGF-β), and apoptotic protease-activating factor 1 (Apaf-1) in humans chronically exposed to arsenic in drinking water

Human exposure to arsenicals is associated with inflammatory-related diseases including different kinds of cancer as well as non-cancerous diseases like neuro-degenerative diseases, atherosclerosis, hypertension, and diabetes. Interindividual susceptibility has been mainly addressed by evaluating the role of genetic polymorphism in metabolic enzymes in inorganic arsenic (iAs) metabolism. Glutathione S-transferase omega 1-1 (GSTO1-1), which had been associated with iAs metabolism, is also known to participate in inflammatory and apoptotic cellular responses. The polymorphism A140D of GSTO1-1 has been not only associated with distinct urinary profile of arsenic metabolites in populations chronically exposed to iAs in drinking water, but also with higher risk of childhood leukemia and lung disease in non-exposed populations, suggesting that GSTO1-1 involvement in other physiologic processes different from toxics metabolism could be more relevant than is thought. We evaluated the association of the presence of A140D and E208K polymorphisms of GSTO1-1 gene with the expression of genes codifying for proteins involved in the inflammatory and apoptotic response in a human population chronically exposed to iAs through drinking water. A140D polymorphism was associated with higher expression of genes codifying for IL-8 and Apaf-1 mainly in heterozygous individuals, while E208K was associated with higher expression of IL-8 and TGF- gene, in both cases, the association was independently of iAs exposure level; however, the exposure to iAs increased slightly but significantly the influence of A140D and E208K polymorphisms on such genes expression. These results suggest an important role of GSTO1-1 in the inflammatory response and the apoptotic process and indicate that A140D and E208K polymorphisms could increase the risk of developing inflammatory and apoptosis-related diseases in As-exposed populations.

Variation in benchmark dose (BMD) and the 95% lower confidence limit of benchmark dose (BMDL) among general Japanese populations with no anthropogenic exposure to cadmium

The use of benchmark dose (BMD) and the 95% lower confidence limit of benchmark dose (BMDL) have been gaining popularity not only in experimental studies but also in epidemiological studies including those on toxicology of cadmium (Cd), a ubiquitous hazardous element in the environment. However, the reproducibility of BMD and BMDL values has seldom been examined. This study was initiated to determine whether consistent BMD and BMDL values are obtained for similar non-exposed populations, i.e., the populations with no anthropogenic exposure to Cd in a single nation of Japan. Cd (an exposure marker), α(1)-microglobulin (α(1)-MG), β(2)-microglobulin (β(2)-MG) and N-acetyl-β-D-glucosaminidase (NAG) (three effect markers of tubular dysfunction) levels in the urine of adult Japanese women from five previous publications of this study group were examined. Overall, data were available for 17,375 cases (in 16 prefectures) regarding Cd, α(1)-MG and β(2)-MG, and 6,409 cases (in ten prefectures) regarding NAG. The data were used to calculate BMD and BMDL values taking advantage of the hybrid approach (Budtz-Jǿrgensen et al. in Biometrics 57:698-706, 2001). It was possible to calculate BMD and BMDL values for α(1)-MG and β(2)-MG for all of the 16 prefectures with 17,375 cases, whereas the values for NAG were successfully calculated for nine prefectures with 5,843 cases. The application gave BMD values of 1.92, 2.46 and 2.32 μg Cd/g cr for α(1)-MG, β(2)-MG and NAG, respectively, and BMDL values of 1.83, 2.32 and 2.09 μg Cd/g cr. Large inter-prefectural variations were observed in the BMD and BMDL; there was about fourfold difference both in BMD and in BMDL calculated for α(1)-MG and β(2)-MG in 16 prefectures, and the variation was greater (i.e., by about sevenfold) in BMD and BMDL for NAG in nine prefectures. A survey of relevant literature revealed variation in BMD and BMDL values of similar folds as observed in the present analyses in five studies of Japanese populations. Multiple regression analyses taking BMD or BMDL as a dependent variable and age, CR concentration and Cd concentration as independent variables showed both BMD and BMDL were significantly influenced by Cd concentration in cases of α(1)-MG and β(2)-MG, whereas BMD and BMDL for NAG was by CR. Even when the analysis was conducted in a single nation, both BMD and BMDL for the Cd effect markers varied by ca. fourfold when examining α(1)-MG or β(2)-MG and the values varied by ca. sevenfold for NAG among Cd-non-exposed populations. The most influential factors in the study population may include urine density and Cd levels in the urine.

Epigenetics for ecotoxicologists

Do genes define your destiny? The field of epigeneticsexamines how genes and the environment interact to formthe basis of heredity and comes up with some surprisingfindings. We often think of deoxyribonucleic acid (DNA) asthe sole physical basis for heredity, the genetic code thatdetermines everything from eye and hair color to specificpersonality traits. The growing field of epigenetics suggeststhat this traditional paradigm is an oversimplification. Epi-genetics is the study of factors that are heritable, but whichoccur by mechanisms other than changes in the DNA codeitself. C.H. Waddington first used the term epigenetics in theearly 1940s to describe ‘‘the interactions of genes with theirenvironment, which bring the phenotype into being.’’ Epi-genetic marks are susceptible to environmental influences—both chemical and nonchemical—and can be inherited inways that may seem counterintuitive (see sidebar, ExpandingIdeas About Biological Inheritance). Effects of early lifeexperiences, such as parental care or nutrition, can showup later in life and even be passed on to future generations.This emerging area of research has interesting and importantimplications for the field of ecotoxicology—from basicscience to international policy.In classic genetics, genetic material is in the form of DNAand encodes all of the information necessary for life. Thisinformation is copied faithfully and passed down as cellsdivide. Every cell contains a complete copy of the DNAcode, but the pattern of gene expression—that is, whichgenes are turned ‘‘on’’ (expressed) or ‘‘off’’ (nonex-pressed)—determines the cell type and function. A skin cellon your arm contains the same DNA code as a nerve cell inyour brain, but their extreme differences in structure andfunction are due to the particular set of genes that each isexpressing. Epigenetics refers to an annotation in the form ofchemical marks on top of the DNA code; the prefix ‘‘epi’’comesfromaGreekwordmeaning‘‘over’’or‘‘above.’’Thesechemical marks, which are discussed in detail below, affectwhich genes are expressed and at what levels. Epigeneticmarks are highly influenced by the environment and can beinherited along with the genetic code as cells divide mitoti-cally, and in some cases meiotically, from one generation tothe next.Epigenetics is receiving significant attention in the field ofbiomedicine. A PubMed search for ‘‘epigenetic’’ revealedthat more than 1,300 review articles have been written on thetopic, of which more than 50% were published in the lastthree years alone. Epigenetics provides a mechanism for theBarker hypothesis, which postulates that nutrition and otherenvironmentalfactorsearlyindevelopmentcanaltersuscept-ibility to chronic diseases in adulthood. A classic exampleof this is that individuals who were conceived during theDutchWinterHunger(1944–1945)havepersistentepigeneticalterations on a characteristic gestational marker, the IGF2gene, as adults. Furthermore, individuals who experiencedthe Dutch Winter Hunger have higher rates of metabolicdisorders and cardiovascular disease, the epigenetic mecha-nisms of which are the focus of ongoing studies. Nutritionaldeprivation may also have an impact on human longevity;indeed, lifespanisnegativelycorrelated withfoodabundance

Assessment of environmental mercury discharge at a four-year-old artisanal gold mining area on Lombok Island, Indonesia

Indonesian artisanal and small-scale gold mining activities (ASGM) have been described for the islands of Borneo (Kalimantan) and Sulawesi. But the increased gold price over recent years has seen operations extend to the islands of Lombok and Sumbawa. For the current research, an environmental assessment was conducted across three new ASGM locations. Gold is recovered by miners through a two-stage process of whole-ore amalgamation and cyanidation. Waste (tailings) is discharged to land or sea with no concern for contaminants in the tailings. The gold grade of ore is up to 5000 mg kg(-1). The mean gold grade of the amalgamation tailings is 7 mg kg(-1), dropping to 1.2 mg kg(-1) for the cyanidation tailings. The mean mercury concentration of the amalgamation tailings is about 3000 mg kg(-1) and greater than 1600 mg kg(-1) for the cyanidation tailings. Samples of paddy rice grain collected adjacent to cyanidation tailings ponds showed methyl mercury concentrations greater than 100 ng g(-1). This is five times above the Chinese permissible level for total mercury in food crops. The mean total mercury concentration in hair of Lombok ASGM workers was greater than that in a non-exposed population; however there was no difference in methyl mercury concentration. This indicates the primary pathway of mercury exposure is inhalation of volatile mercury in the atmosphere. Future exposure may come from ingestion of methyl mercury contaminated rice where discharge of cyanide tailings to paddies continues. To protect the environment and to enhance the sustainability of ASGM, appropriate tailings management must be implemented. The gold grade of the tailings indicates that the residual value might be recoverable with appropriate technology. Ongoing research is investigating systems such as phytoextraction that might assist ASGM operators in Lombok and Sumbawa to improve their environmental performance.

Impacts of multidisciplinary actions on environmental lead exposure in Uruguay

Environmental lead contamination in Uruguay became a matter of public concern in 2001, when cases of children with blood lead levels (BLL) higher than 20 μg/dl appeared in some low-income neighborhoods of Montevideo, being 10 μg/dl the intervention reference BLL. The aim of this paper is to show the results of multidisciplinary actions taken by decisions makers in social, environmental and healthcare aspects, to minimize lead exposure risks. We evaluated changes in blood lead levels of different children and non-exposed adult populations before and after the actions were taken, from 2001 on. For children populations and non-exposed adults, we found a significant decrease of almost 50% in BLL compared with studies done before the actions were taken. The main action to consider was the phasing out process of leaded gasoline in our country among other. We conclude that the integration of inter and multidisciplinary actions promoted was of high impact on the population, bringing about a public sensitization and growing awareness of the lead environmental risks.

EXPOSURE ASSESSMENT AND HEALTH EFFECTS ASSOCIATED TO PESTICIDES BURIED NEAR AN URBAN COMMUNITY IN COLOMBIA

Background/aims: Organophosphate and organochlorine pesticides have been associated with neurological and respiratory effects in agricultural communities, but few studies have been conducted in buried pesticides deposited close to human settlements. An urban neighborhood and a school with &gt;1,500 children was settled in a former agricultural area of 44ha in Cartagena-Colombia. During construction, several containers with pesticides were found. Contaminated soils and containers were removed and confined to an area close by. Our objective was to evaluate exposure to and potential health effects of these buried pesticides on surrounding communities. Methods: Concentrations of pesticides in soil and air were determined. A health risk assessment was done modeling soil concentrations found at the pesticides confined area. Respiratory diseases data was obtained, and tests for pulmonary and neurological function were applied in children(n=389) and adults(n=440) at the exposed and a control area. Levels of pesticides in serum and their metabolites in urine were determined in a subsample of children. Results: Presence of DDT isomers and metabolites were found in one soil sample and chlorpyrifos was reported in one air sample. Risk modeling suggests risk inside the confined area by different routes of exposure. Although individuals at the exposed area reported more frequently severe dyspnea(children OR:2.97; IC95%:1.0-8.97) and wheezing (adults OR:2.10; IC95%:1.13-3.90) evidence of lung function effects was not demonstrated by spirometry. There were not differences in intellectual performance. Pesticides in blood serum were mostly below detection limits, and only significant levels of pp-DDE were found, although at concentrations similar to non-exposed populations. Conclusions: A confined area with buried pesticides but not direct contact with population is a potential source of risk. However, no evidence of exposure to pesticides was found in this area. Increased reports of respiratory symptoms could be explained by increased risk perception or other environmental exposures in the area.

Does Monastic Life Predispose to the Risk of Saint Anthony's Fire (Herpes Zoster)?

The consequences of the epidemiology of varicella for zoster epidemiology are still debated. We therefore compared the frequency of herpes zoster in an adult population with virtually no varicella zoster virus (VZV) exposure with that in the general population (GP). We performed a national, multicenter, observational, exposed versus nonexposed, comparative study. The nonexposed population consisted of members of contemplative monastic orders (CMO) of the Roman Catholic Church living in 40 isolated monasteries in France. The exposed population consisted of a sample of the GP representative of the French population in terms of age group, sex, socio-occupational categories, and regions. The primary analysis population comprised 920 members of CMO (41.5% nuns; mean age, 64.2 years) and 1533 members of the GP (51.9% women; mean age, 64.6 years). The reported frequency of zoster was 16.2% among CMO and 15.1% in the GP (P = .27, adjusted for sex and age). The reported mean age of onset of zoster was 54.8 and 48.6 years, respectively (P = .06). This study failed to demonstrate an increased risk or earlier onset of zoster in members of CMO not exposed to VZV, compared with that in the GP. Although adults highly exposed to VZV could have a reduced risk of zoster, compared with the GP, our results suggest that the opposite is not true: adults not exposed to VZV are not at increased risk of zoster when compared with the GP, challenging the relevance of the assumptions and forecasts of current epidemiological models.

Cadmium and Other Metal Levels in Autopsy Samples from a Cadmium-Polluted Area and Non-polluted Control Areas in Japan

This study was initiated to examine accumulation of cadmium (Cd) and other metals in kidney and liver in autopsy samples and to compare the levels between those in an area with heavy Cd exposure and those in no-polluted areas in Japan. Data on Cd and other metals in kidney (cortex and medulla) and liver in 95 cases (87 women and eight men; the exposed) in a Cd-polluted area and 43 cases (21 women and 22 men; the controls) in non-polluted areas were cited from 15 previous publications to be summarized together with six unpublished cases. Cd levels in kidney cortex and medulla were significantly lower in the exposed (31.5 and 23.8 μg/g wet tissue as GM, respectively) than in the controls (82.7 and 36.4 μg/g, respectively), whereas Cd levels in liver was higher in the exposed (60.2 μg/g) than in the controls (8.1 μg/g). Exposed women had lower Cd in the cortex (29.9 μg/g) and medulla (22.7 μg/g) than exposed men (55.4 and 38.1 μg/g, respectively) as well as in cortex of control women (92.9 μg/g). Comparison with worldwide data other than Japan for non-exposed populations [19.1, 9.3, and 1.3 μg/g in cortex, medulla, and liver, respectively, as the inverse variance-weighted averages (IVWA) of GM values for each of 22 reports] suggests that the levels for the non-exposed Japanese (123.3, 33.5, and 3.9 μg/g as IVWA) tended to be higher than the levels in other countries, possibly reflecting high dietary Cd intake in the past.

Background Values for Essential and Toxic Elements in Children’s Nails and Correlation with Hair Levels

Human nails are an attractive matrix for assessing environmental exposures to toxic elements as well as the deficiency of essential elements since it is noninvasively collected and can be stored at room temperature. However, reference or baseline levels in nonexposed and healthy populations are not yet established. Then, the aims of this study were (a) to estimate background values for essential and toxic elements in nails from a healthy young population in southern Brazil and (b) to evaluate possible correlations between essential and toxic elements in nails. Furthermore, this report took part of a recent study of background values in the hair of a young population. Thus, correlations between chemical elements in nails and hair were also evaluated. Nails were collected from healthy children (n = 126), and element concentrations were determined by inductively coupled plasma mass spectrometry. This study provides new and reliable reference concentrations for toxic and essential elements in children's nails. The results can be used as reference values for epidemiological or clinical investigations based on trace elements in nails. Additionally, we also showed weak to strong correlations between Cu, Mg, Mn, Se, and Zn levels in nails and hair.

Exposure to depleted uranium does not alter the co-expression of HER-2/neu and p53 in breast cancer patients

BackgroundAmongst the extensive literature on immunohistochemical profile of breast cancer, very little is found on populations exposed to a potential risk factor such as depleted uranium. This study looked at the immunohistochemical expression of HER-2/neu (c-erbB2) and p53 in different histological types of breast cancer found in the middle Euphrates region of Iraq, where the population has been exposed to high levels of depleted uranium.FindingsThe present investigation was performed over a period starting from September 2008 to April 2009. Formalin-fixed, paraffin-embedded blocks from 70 patients with breast cancer (62 ductal and 8 lobular carcinoma) were included in this study. A group of 25 patients with fibroadenoma was included as a comparative group, and 20 samples of normal breast tissue sections were used as controls. Labeled streptavidin-biotin (LSAB+) complex method was employed for immunohistochemical detection of HER-2/neu and p53.The detection rate of HER-2/neu and p53 immunohistochemical expression were 47.14% and 35.71% respectively in malignant tumors; expression was negative in the comparative and control groups (p < 0.05).HER-2/neu immunostaining was significantly associated with histological type, tumor size, nodal involvement, and recurrence of breast carcinoma (p < 0.05), p53 immunostaining was significantly associated with tumor size, nodal involvement and recurrence of breast cancer (p < 0.05). There was greater immunoexpression of HER-2/neu in breast cancer in this population, compared with findings in other populations.Both biomarkers were positively correlated with each other. Furthermore, all the cases that co-expressed both HER-2/neu and p53 showed the most unfavorable biopathological profile.ConclusionP53 and HER-2/neu over-expression play an important role in pathogenesis of breast carcinoma. The findings indicate that in regions exposed to high levels of depleted uranium, although p53 and HER-2/neu overexpression are both high, correlation of their expression with age, grade, tumor size, recurrence and lymph node involvement is similar to studies that have been conducted on populations not exposed to depleted uranium. HER-2/neu expression in breast cancer was higher in this population, compared with results on non-exposed populations.

S02-02 - The Effects of Malnutrition in a Human Population on Addictive Behavior and Sex Ratio at Birth

The objective and aim of this case-control study was to replicate an earlier finding of a significant relationship between prenatal exposure to famine and substance use disorders later in life and to examine the sex ratio at birth in the study populations. We compared the number of addicted individuals in a population prenatally exposed to a severe hunger period with matched individuals in a non-exposed population. The gender distribution of patients with substance use disorders and healthy controls were calculated and all data were quantified as odds ratios. The findings confirm that prenatal exposure to famine is a risk factor to develop substance use disorder later in life. Men are at risk in particular by exposure to famine during the first trimester, women by exposure during the third trimester. The sex ratio men to women at birth was 3 : 1 in the patient groups compared to 1:1 in the healthy controls. The results were discussed in the light of the possible disastrious future consequences for the hunger regions in our world.

From cell to man: Evaluation of osteopontin as a possible biomarker of uranium exposure

Background Ore workers are conventionally monitored for exposure by measuring the uranium in their urine, but specific biomarkers of kidney damage still remain to be discovered. A recent toxicogenomics study allowed us to focus on osteopontin (OSTP) normally excreted in human urine and linked to mineral metabolism. Objectives We examined the association between osteopontin and uranium exposure both in vitro, in a human kidney cell model, and in the urine of exposed individuals. Methods OSTP was measured in supernatants of uranium-exposed HK2 cells to establish a dose–response curve and a time course experiment. Its role was studied through a gene extinction experiment. Uranium and OSTP were then monitored in the urine of exposed nuclear fuel industry workers and a chronically exposed population. These levels were compared with those found in a non-exposed population. Results The study of HK2 cells indicated that OSTP secretion decreased after uranium exposure in a concentration and time dependent manner, but its suppression does not affect cell sensitivity to uranium. In spite of wide inter-individual variability, this parameter decreases also in human urine when urinary uranium exceeds 30 μg/L after an acute exposure, a value considered to be critical for kidney damage. Conclusion This study reports how toxicogenomics can highlight putative toxicity biomarkers in an easy to access biological fluid. The decrease of urinary osteopontin in response to uranium exposure suggests kidney damage and would thus be complementary to current markers.

The economic benefits of reducing physical inactivity: an Australian example

BackgroundPhysical inactivity has major impacts on health and productivity. Our aim was to estimate the health and economic benefits of reducing the prevalence of physical inactivity in the 2008 Australian adult population. The economic benefits were estimated as 'opportunity cost savings', which represent resources utilized in the treatment of preventable disease that are potentially available for re-direction to another purpose from fewer incident cases of disease occurring in communities.MethodsSimulation models were developed to show the effect of a 10% feasible, reduction target for physical inactivity from current Australian levels (70%). Lifetime cohort health benefits were estimated as fewer incident cases of inactivity-related diseases; deaths; and Disability Adjusted Life Years (DALYs) by age and sex. Opportunity costs were estimated as health sector cost impacts, as well as paid and unpaid production gains and leisure impacts from fewer disease events associated with reduced physical inactivity. Workforce production gains were estimated by comparing surveyed participation and absenteeism rates of physically active and inactive adults, and valued using the friction cost approach. The impact of an improvement in health status on unpaid household production and leisure time were modeled from time use survey data, as applied to the exposed and non-exposed population subgroups and valued by suitable proxy. Potential costs associated with interventions to increase physical activity were not included. Multivariable uncertainty analyses and univariate sensitivity analyses were undertaken to provide information on the strength of the conclusions.ResultsA 10% reduction in physical inactivity would result in 6,000 fewer incident cases of disease, 2,000 fewer deaths, 25,000 fewer DALYs and provide gains in working days (114,000), days of home-based production (180,000) while conferring a AUD96 million reduction in health sector costs. Lifetime potential opportunity cost savings in workforce production (AUD12 million), home-based production (AUD71 million) and leisure-based production (AUD79 million) was estimated (total AUD162 million 95% uncertainty interval AUD136 million, AUD196 million).ConclusionsOpportunity cost savings and health benefits conservatively estimated from a reduction in population-level physical inactivity may be substantial. The largest savings will benefit individuals in the form of unpaid production and leisure gains, followed by the health sector, business and government.

Genotoxicity of mercury: Contributing for the analysis of Amazonian populations

Mercury is an important source of environmental contamination affecting human beings throughout the world and especially in the Amazon. Riverside populations have been chronically exposed to relatively high levels of methylmercury for many years. Long-term effects of mercury exposure are not well known, but human genotoxicity was already showed in both in vitro and epidemiological studies. However, to date, only two studies were carried out in Amazonian populations with conflicting results and without comparing to a non-exposed population. Aiming to highlight this question and avoid interference factors, this work analyzed in vitro genotoxicity of mercury in blood lymphocytes of Amazonian individuals by two methods (micronucleus and chromosomal aberrations). Deleterious effects of low levels (1–500 μg/l or 0,004–2 μM) of methylmercury were only detected with the method to detect chromosomal aberrations. Mitotic index (proportion of cells in metaphase) was the parameter most sensible. Thus, this technique was applied for the analysis of an Amazonian non-exposed population (Panacauera) with similar social–economical characteristics of the exposed populations studied elsewhere. The mean of the mitotic index for Panacauera population was 0.0814 ± 0.0097. Inter-individual variability of this index had no relation with sex or age. This value was above those registered for some groups of exposed populations. This fact points to mercury as the main responsible for inhibiting the cell cycle and/or the loss of proliferative capacity of the cells. These results already support mitotic index as an essential parameter for the early diagnose of mercury genotoxicity in humans, and especially in Amazonian populations.