Metal levels in waste pickers in Brasilia, Brazil: hair and nail as exposure matrices.

The aim of this cross-sectional study was to compare workplace conditions and metal exposures in 431 waste pickers who worked nearby at the Estrutural Dump in Brasilia utilizing hair (n = 310) and nail (n = 355) as matrices of exposure. Waste pickers were grouped according to their workplace (open waste dump: G1 and sorting plants: G2). Hair and nail samples were collected and analyzed using ICP-MS. The work duration in the facilities was significantly different between the groups with averages of 16.46 (8.48) yrs and 9.26 (6.28) yrs for hair donors in G1 and G2, and 15.92 (7.72) yrs and 8.55 (5.77) yrs for toenail donors in G1 and G2, respectively. The arithmetic means (µg/g) of cadmium, copper, lead, and manganese in hair were significantly higher in G2 (0.076 ± 0.133; 19.61 ± 18.16; 2.27 ± .56 and 3.87 ± 5.59, respectively) compared to G1 (0.069 ± 0.235; 15.72 ± 15.18; 1.72 ± 4.04 and 3.65 ± 5.5, respectively). Concentrations of arsenic, barium, cadmium, copper, cobalt, lead, manganese, and molybdenum in nail were significantly higher in G2 (0.57 ± 0.39; 22.74 ± 42.06; 0.1 ± 0.08; 22.7 ± 51.60; 0.48 ± 0.45; 4.69 ± 9.43; 19.07 ± 20.75; 1.80 ± 1.76, respectively) compared to G1 (0.40 ± 0.28; 15.32 ± 22.31; 0.08 ± 0.11; 11.91 ± 16.25; 0.37 ± 0.37; 3.94 ± 15.04; 13.01 ± 19.08; 1.16 ± 1.80, respective. Our findings suggest that the studied population was exposed to toxic metals and indicates the need for chemical exposure prevention policies to monitor chemical risk exposures in waste pickers.

Sirtuins as molecular targets, mediators, and protective agents in metal-induced toxicity.

Metal dyshomeostasis, and especially overexposure, is known to cause adverse health effects due to modulation of a variety of metabolic pathways. An increasing body of literature has demonstrated that metal exposure may affect SIRT signaling, although the existing data are insufficient. Therefore, in this review we discuss the available data (PubMed-Medline, Google Scholar) on the influence of metal overload on sirtuin (SIRT) signaling and its association with other mechanisms involved in metal-induced toxicity. The existing data demonstrate that cadmium (Cd), mercury (Hg), arsenic (As), lead (Pb), aluminium (Al), hexavalent chromium (CrVI), manganese (Mn), iron (Fe), and copper (Cu) can inhibit SIRT1 activity. In addition, an inhibitory effect of Cd, Pb, As, and Fe on SIRT3 has been demonstrated. In turn, metal-induced inhibition of SIRT was shown to affect deacetylation of target proteins including FOXO, PGC1α, p53 and NF-kB. Increased acetylation downregulates PGC1α signaling pathway, resulting in cellular altered redox status and increased susceptibility to oxidative stress, as well as decreased mitochondrial biogenesis. Lower rates of LKB1 deacetylation may be responsible for metal-induced decreases in AMPK activity and subsequent metabolic disturbances. A shift to the acetylated FOXO results in increased expression of pro-apoptotic genes which upregulates apoptosis together with increased p53 signaling. Correspondingly, decreased NF-kB deacetylation results in upregulation of target genes of proinflammatory cytokines, enzymes, and cellular adhesion molecules thus promoting inflammation. Therefore, alterations in sirtuin activity may at least partially mediate metal-induced metabolic disturbances that have been implicated in neurotoxicity, nephrotoxicity, cardiotoxicity, and other toxic effects of heavy metals.

Region-specific air pollutants and meteorological parameters influence COVID-19: A study from mainland China.

Coronavirus disease 2019 (COVID-19) was first detected in December 2019 in Wuhan, China, with 11,669,259 positive cases and 539,906 deaths globally as of July 8, 2020. The objective of the present study was to determine whether meteorological parameters and air quality affect the transmission of COVID-19, analogous to SARS. We captured data from 29 provinces, including numbers of COVID-19 cases, meteorological parameters, air quality and population flow data, between Jan 21, 2020 and Apr 3, 2020. To evaluate the transmissibility of COVID-19, the basic reproductive ratio (R0) was calculated with the maximum likelihood "removal" method, which is based on chain-binomial model, and the association between COVID-19 and air pollutants or meteorological parameters was estimated by correlation analyses. The mean estimated value of R0 was 1.79 ± 0.31 in 29 provinces, ranging from 1.08 to 2.45. The correlation between R0 and the mean relative humidity was positive, with coefficient of 0.370. In provinces with high flow, indicators such as carbon monoxide (CO) and 24-h average concentration of carbon monoxide (CO_24 h) were positively correlated with R0, while nitrogen dioxide (NO2), 24-h average concentration of nitrogen dioxide (NO2_24 h) and daily maximum temperature were inversely correlated to R0, with coefficients of 0.644, 0.661, -0.636, -0.657, -0.645, respectively. In provinces with medium flow, only the weather factors were correlated with R0, including mean/maximum/minimum air pressure and mean wind speed, with coefficients of -0.697, -0.697, -0.697 and -0.841, respectively. There was no correlation with R0 and meteorological parameters or air pollutants in provinces with low flow. Our findings suggest that higher ambient CO concentration is a risk factor for increased transmissibility of the novel coronavirus, while higher temperature and air pressure, and efficient ventilation reduce its transmissibility. The effect of meteorological parameters and air pollutants varies in different regions, and requires that these issues be considered in future modeling disease transmissibility.

Association of lead, cadmium and mercury with paraoxonase 1 activity and malondialdehyde in a general population in Southern Brazil.

Metal exposure is associated with increased oxidative stress (OS), which is considered an underlying mechanism of metal-induced toxicity. Malondialdehyde (MDA) is a final product of lipid peroxidation, and it has been extensively used to evaluate metal-induced OS. Pro-oxidant effects produced by metals can be mitigated by paraoxonase 1 (PON1), an antioxidant enzyme known to prevent cardiovascular disease and atherosclerosis. Among other factors, the Q192R polymorphism and the exposure to heavy metals have been known to alter PON1 activity. Here, we evaluated the association of blood lead (Pb), cadmium (Cd) and mercury (Hg) levels with PON1 activity, and with MDA concentrations in a randomly selected sample of Brazilian adults aged 40 years or older, living in an urban area in Southern Brazil. A total of 889 subjects were evaluated for blood Pb and Cd levels, and 832 were tested for Hg. Geometric mean of blood Pb, Cd and Hg was 1.93µg/dL, 0.06µg/L and 1.40µg/L, respectively. PON1 activity was significantly different among various genotypes: QQ (PON1=121.4U/mL), QR (PON1=87.5U/mL), and RR (PON1=55.2U/mL), p<0.001. PON1 genotypes were associated only with Cd blood levels. Those with QR genotype had Cd concentrations higher (0.07µg/L) than those with the RR genotype (0.04µg/L) with p=0.034. However, PON1 activity was not significantly associated with metal concentrations. Cluster analysis showed that men who reported to be current smokers and drinkers with higher blood Pb and Cd levels, had significantly lower PON1 activity than non-smokers or -drinkers, and women with lower Pb and Cd levels. RR genotype carriers had lower PON1 activity than those with the QR genotype, and had higher levels of Pb and Cd compared with other genotype carriers. For blood Hg, no association with PON1 activity or genotype was noted. We found low levels of Pb, Cd and Hg in environmentally exposed Brazilian adults. Cd concentrations were increased in subjects with QR genotype. Those with RR genotype had lower PON1 activity and higher levels of Pb and Cd than other genotype carriers. The results of cluster analysis suggested that smoking status exerts a significant influence on PON1 activity. Other studies with environmentally exposed populations are required to further clarify whether low blood levels of metals influence OS biomarkers.

Association between blood lead and blood pressure: a population-based study in Brazilian adults.

BACKGROUND: Environmental lead exposure among adults may increase blood pressure and elevate the risk of hypertension. The availability of data on blood lead levels (BLL) in adult Brazilian population is scarce and population-based studies are important for screening the population exposure and also to evaluate associations with adverse health effects. The goal of this study was to examine the association of BLL with blood pressure and hypertension in a population-based study in a city in Southern Brazil. METHODS: A total of 948 adults, aged 40 years or older, were randomly selected. Information on socioeconomic, dietary, lifestyle and occupational background was obtained by orally administered household interviews. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured according to the guidelines VI Brazilian Guidelines on Hypertension. BLL were measured by inductively coupled plasma mass spectrometry technique. Multiple linear and logistic regression models were performed to evaluate associations of BLL with SBP and DBP, and with the chance of hypertension and of elevated SBP and DBP. RESULTS: The geometric mean of BLL was 1.97 µg/dL (95%CI:1.90-2.04 µg/dL). After multivariable adjustment, participants in the quartile 4 of blood lead presented 0.06 mm/Hg (95%CI, 0.04-0.09) average difference in DBP comparing with those in quartile 1. Participants in the 90th percentile of blood lead distribution had 0.07 mmHg (95% CI, 0.03 to 0.11) higher DBP compared with those participants in the 10th percentile of blood lead. The adjusted OR for hypertension was 2.54 (95% CI, 1.17-5.53), comparing the highest to the lowest blood lead quartiles. Compared with participants in the 10th percentile of blood lead, participants in the 90th percentile presented higher OR for hypertension (OR: 2.77; 95% CI, 1.41 to 5.46). CONCLUSION: At low concentrations, BLL were positively associated with DBP and with the odds for hypertension in adults aged 40 or older. It is important to enforce lead exposure monitoring and the enactment of regulatory laws to prevent lead contamination in urban settings.

Blood manganese levels and associated factors in a population-based study in Southern Brazil.

Manganese (Mn) is an essential dietary nutrient for human health serving as a cofactor for many enzymes; however, exposure to excessive quantities of Mn may lead to toxicity with symptoms analogous to Parkinson's disease (PD). Population-based biomonitoring is an effective tool for characterizing the body burden of environmental or occupational pollutants, including Mn. The objective of this cross-sectional study was to (1) estimate reference values (RV) for blood Mn in an adult population and (2) assess the variables that were associated with higher blood metal levels. A total of 947 adults, aged 40 years or older, were randomly selected in a city in Southern Brazil. Information on socioeconomic, dietary, lifestyle, and occupational background was collected by trained interviewers. Blood Mn levels (µg/L) were analyzed by inductively coupled plasma-mass spectrometer (ICP-MS). The RV for blood Mn concentrations were obtained from the upper limits of the 95% confidence intervals (CI) of the 95th percentile distributions. Cluster analysis was performed to identify variables associated with high or low blood Mn concentrations. The RV for blood Mn levels in this study were 18.54 and 20.15 µg/L for men and women, respectively. Mn blood concentrations decreased with age and were higher in females compared to males. No marked association was noted between blood Mn and smoking or drinking habits, education levels and socioeconomic status. Diastolic blood pressure was higher in a group of women approximately 54 years of age associated with elevated blood Mn levels. Important reference data stratified by demographic and lifestyle factors that may prove useful for future surveillance of environmental exposure to Mn and health risks associated with this metal are presented.

Effects of Lead Exposure and Genetic Polymorphisms on ALAD and GPx Activities in Brazilian Battery Workers.

Lead (Pb) is a toxic metal that is widely used by metallurgical industries such as car battery recycling. Exposure to the metal may modify the redox status of the cells and consequently result in changes in activities of important enzymes such as delta-aminolevulinic acid dehydratase (ALAD) and glutathione peroxidase (GPx). Similarly, genetic polymorphisms may modulate the activities of enzymes related to detoxification processes of the metal and may modify Pb body burden. Therefore, the aims of the present study were (i) to evaluate the correlation between blood lead levels (BLL) and activities of the enzymes ALAD and GPx, and (ii) to determine whether activities of these enzymes may be influenced by polymorphisms in ALAD and GPx genes in Brazilian automotive battery workers chronically exposed to Pb, as well as the effects of these polymorphisms on BLL. Our study included 257 participants; BLL were determined by inductively couple plasma-mass spectrometry (ICP-MS), and the activities of the enzymes ALAD and GPx were quantified spectrophotometrically; and genotyping of ALAD (rs1800435) and GPx-1 (rs1800668) polymorphisms was performed by TaqMan assays (real-time polymerase chain reaction, RT-PCR). Significant negative correlations were found between BLL and ALAD activity. Subjects who carried at least one polymorphic allele for ALAD gene displayed markedly lower ALAD activities, while no significant effect was observed regarding GPx-1 polymorphism and activity of the same enzyme. Further, ALAD and GPx-1 polymorphisms exerted no marked influence on BLL. Taken together, our results showed that BLL affected ALAD but not GPx activities, and these were not modulated by polymorphisms in ALAD and GPx gene. Further, the rs1800435 SNP showed a tendency to modulate ALAD activity, while the rs1800668 SNP did not modulate GPx activity in Brazilian automotive battery workers exposed to Pb.

Risk factors for lead exposure in adult population in southern Brazil.

In Brazil there is no systematic evaluation to access blood lead levels (BLL) in the general population and few studies with adults have been published. The aim of this study was to examine the socioeconomic, environmental, and lifestyle determinants of BLL in the adult Brazilian population. In total, 959 adults, aged 40 years or more, were randomly selected in a city in southern Brazil. Information on socioeconomic, dietary, lifestyle, and occupational background was obtained by interviews. A spatial analysis was conducted to discern whether there were any identifiable sources of exposure. BLL were measured by inductively coupled plasma-mass spectrometry. There was an adjustment for gender, age, race, education, income class, smoking status, alcohol consumption, occupation, and red meat or cow milk consumption (Model 1), and for occupation and gender (Model 2). The geometric mean of BLL was 1.97 µg/dl (95% CI: 1.9-2.04 µg/dl). In Model 1, BLL were positively associated with male gender, older age, and drinking and smoking habits, and less frequently with milk consumption. In Model 2, data showed higher BLL in non-white than white participants, in former smokers and individuals with current or former employment in lead (Pb) industries. The participants living in the area with more Pb industries had higher BLL (3.3 µg/dl) compared with those residing in other areas with no or fewer Pb industries (1.95 µg/dl). Despite the low BLL found in adults living in an urban area, Pb industries need to be monitored and regulatory laws implemented to prevent metal contamination in urban settings.

Leveraging artificial intelligence to advance the understanding of chemical neurotoxicity.

Neurotoxicology is a specialty that aims to understand and explain the impact of chemicals, xenobiotics and physical conditions on nervous system function throughout the life span. Herein, we point to the need for integration of novel translational bioinformatics and chemo-informatics approaches, such as machine learning (ML) and artificial intelligence (AI) to the discipline. Specifically, we advance the notion that AI and ML will be helpful in identifying neurotoxic signatures, provide reliable data in predicting neurotoxicity in the context of genetic variability, and improve the understanding of neurotoxic outcomes associated with exposures to mixtures, to name a few.

Retraction notice to "Use of ivermectin in the treatment of Covid-19: A pilot trial" [Toxicol. Rep. 8 (2021) 505-510].

[This retracts the article DOI: 10.1016/j.toxrep.2021.03.003.].

Relationship Between Elevated Hair Mercury Levels, Essential Element Status, and Metabolic Profile in Overweight and Obese Adults.

The objective of the present study was to evaluate hair essential and trace element levels and metabolic risk markers in overweight and obese subjects in relation to body mercury burden. According to 2 × 2 factorial design a total of 440 adults were distributed to four groups: (i) low-Hg normal-weight subjects (n = 114); (ii) high-Hg normal weight subjects (n = 113); (iii) low-Hg overweight (BMI > 25) subjects (n = 110); (iv) high-Hg overweight (BMI > 25) subjects (n = 110). Hg-exposed groups consisted of subjects characterized by frequent seafood consumption (> 4 times/week) subsequently evaluated by hair analysis (> 0.58 µg/g). Dietary-exposed subjects were characterized by a more than 3-fold higher hair Hg content irrespectively of body weight values. Both low-Hg and high-Hg overweight subjects were characterized by significantly higher ALT activity, as well as elevated serum glucose, LDL, and triglyceride levels as compared to the respective groups of normal weight subjects. High Hg body burden had a more significant effect on metabolic parameters in overweight and obese adults. Particularly, high-Hg overweight subjects were characterized by significantly higher serum creatinine and uric acid levels, as well as increased GGT and CK activity as compared to low-Hg overweight counterparts. In addition, hair Mg, Mn, and Sr content in high-Hg overweight subjects was significantly lower than that in low-Hg normal weight and overweight examinees. In turn, high Hg levels in overweight subjects were associated with significantly higher hair Se and Zn levels when compared to unexposed overweight adults. Generally, the obtained data demonstrate that increased hair Hg levels in overweight and obese subjects is associated with adverse metabolic profile. It is proposed that observed metabolic alterations may be at least partially mediated by Hg-associated disturbances in essential trace element and mineral metabolism.

Use of ivermectin in the treatment of Covid-19: A pilot trial.

OBJECTIVES: In this randomized open-label trial pilot study we assessed the antiviral effects and safety of various doses of ivermectin in patients with mild clinical symptoms of COVID-19. METHODS: Patients were randomly assigned to receive standard of care (SOC) treatment at hospital admission; SOC plus ivermectin 100 mcg/kg; SOC plus ivermectin 200 mcg/kg; or SOC plus ivermectin 400 mcg/kg. The primary assessed endpoint was the proportion of patients who achieved two consecutive negative SARS-CoV-2 RT PCR tests within 7 days of the start of the dosing period. This study was registered at ClinicalTrials.gov (NCT04431466). RESULTS: A total of 32 patients were enrolled and randomized to treatment. SOC treatment together with ivermectin did not result in any serious adverse events. All patients exhibited a reduction in SARS-CoV-2 viral load within 7 days; however, those who received ivermectin had a more consistent decrease as compared to the SOC alone group, characterized by a shorter time for obtaining two consecutive negative SARS-CoV-2 RT PCR tests. CONCLUSIONS: Ivermectin is safe in patients with SARS-CoV-2, reducing symptomatology and the SARS-CoV-2 viral load. This antiviral effect appears to depend on the dose used, and if confirmed in future studies, it suggests that ivermectin may be a useful adjuvant to the SOC treatment in patients with mild COVID-19 symptoms.

Lead levels in milk and blood from donors to the Breast Milk Bank in Southern Brazil.

Brazilian scientific literature on the adverse effects of lead on the general population is still very limited. Lead, a potentially toxic substance, has become a public health problem due to its effects, mainly those affecting the central nervous system and on the synthesis of heme. The aim of this study is to evaluate the level of lead exposure of donors to the Breast Milk Bank in the city of Londrina, Parana, by estimating the levels of that metal in milk and blood samples. This is a cross-sectional study conducted during the period between January and July 2007. All mothers enrolled as donors in the Breast Milk Bank were included in this study. A total of 92 volunteers presenting the following inclusion criteria were evaluated in the project: volunteers who were healthy, without any chronic disease, full-term pregnancy, breastfeeding between the 15th and 210 th day after giving birth, and living in the city of the study. Lead in milk and blood was quantified using the inductive coupled plasma mass spectroscopy (ICP-MS) technique. All mothers signed a consent form approved by the Research Ethics Committee from Londrina State University. The median lead concentration in milk samples was 3.0 microg/L, varying from 1.0 to 8.0 microg/L. The median of lead in blood was of 2.7 microg/dl, varying from 1.0 to 5.5 microg/dl. In Spearman correlation analysis, significant but modest correlations could be observed between the concentration of lead in blood and in milk (r(s)=0.207, p=0.048), hemoglobin and ALAD activity (r(s)=-0.264, p=0.011), level of lead in blood and mother's age (r(s)=0.227, p=0.029). However, for hematocrit and hemoglobin, the correlation was higher (r(s)=0.837, p<0.001). No statistically significant associations were found between concentrations of lead in milk and blood and demographic variables studied, obtained through interviews and validated questionnaire. The mean of milk/blood lead ratio was equal to 0.11. In general, the values found in the present study are similar to those obtained in populations in other countries, and are within background levels.

Lead levels in human milk and children's health risk: a systematic review.

Lead (Pb), a naturally-occurring element and industrially-produced metal, is highly toxic to children, causing intellectual and behavioral deficits, hyperactivity, fine motor function deficits, decreased intelligence quotient, alteration of hand-eye coordination, and problems in reaction time. Children's exposure to Pb occurs mainly through ingestion of contaminated food, water and soil. Few discussions have been held on the magnitude and potential risk associated with exposure from the consumption of breast milk. Hence, this research was designed to systematically review the scientific literature on published epidemiologic studies, with an emphasis on the study designs and analytical procedures used for Pb assessment in breast milk. From a total of 112 selected articles published since the 1980s, 11 met the inclusion criteria. A review of the data indicated that Pb levels varied from 0.15 to 6.1 microg L(-1) in mature milk samples, from 0.48 to 14.6 microg L(-1) in colostrum samples, and were non-detectable in some samples. The milk/blood ratio, which estimates the mean efficiency transfer of lead from blood to milk, varied between 0.01 and 0.48. The heterogeneity of methods revealed by our assessment of published studies underscores the need for harmonization of study designs and sample collection and analysis protocols to reflect specific exposure scenarios. Human milk seems to be one of the relevant biological matrices for use as a biomarker for assessing children's health risk to Pb poisoning.

Toxicological profile of Amanita virosa - A narrative review.

Mushrooms account for a part of human diet due to their exquisite taste and protein content as well as their promising health effects unveiled by scientific research. Toxic and non-toxic mushrooms frequently share considerable morphological similarities, which mislead the collectors/consumers, resulting in mycotoxicity. Numerous mushroom species are considered "poisonous" as they produce dangerous toxins. For instance, members of the genus Amanita, especially A. phalloides, A. virosa and A. verna, are responsible for severe and even life-threatening noxious consequences. Globally, mushroom poisoning is a crucial healthcare issue as it leads to a considerable number of deaths annually. However, no definite antidote has been introduced to treat this poisoning. The present article discusses the characteristics of A. virosa in terms of epidemiology, mechanisms of toxicity, poisoning features and management.

[Causes of acute poisoning with medication in a southern Brazilian city]. / Determinantes nas intoxicações medicamentosas agudas na zona urbana de um município do Sul do Brasil.

Acute poisoning with medicines in Brazil has various causes, including a deficient national drug policy. The current study thus aimed to analyze socioeconomic variables, prescription characteristics, and forms of purchase or acquisition and storing of medicines by victims of acute unintentional poisoning. The data were collected during home visits to patients with a record of acute unintentional drug poisoning according to the Poison Control Center in Maringá, Paraná State, in 2004. The variables were related to the victim, the poisoning event, the product, and its household storage. For the 97 poisonings recorded during the study period, 72 families were interviewed, with the majority of the victims under 10 years of age (73.6%), males (54.2%), and from lower-income groups (63.9%). Many interviewees reported not having received information about the drug (76.5%). There was a significant association between lower-income status and inadequate drug storage (p < 0.05). A larger proportion of poisonings in higher-income families involved expired products (p < 0.05). Inadequate acquisition and storage of drugs may thus have facilitated the occurrence of poisonings.

Paraoxonase 1 (PON1) Q192R genotypes and their interaction with smoking strongly increase atherogenicity and the Framingham risk score.

OBJECTIVE: Paraoxonase 1 (PON1) polymorphisms are associated with an increased susceptibility to cardiovascular disease. PON1 Q192R polymorphism (rs662) partially determine PON1 hydrolytic activity and protect against oxidation of LDL and HDL. This study aimed to delineate the association of PON1 status (functional 192 genotype and plasma activity levels) and atherogenicity in urbans residents aged 40 years or more. MATERIALS AND METHODS: Anthropometric data, lipid profiles, the atherogenic index of the plasma (AIP) and Framingham score risk were measured. Three kinetic assays were conducted to assay PON1 status using phenylacetate and 4-(chloromethyl)phenyl acetate as substrates. RESULTS: Smoking per se did not significantly impact the AIP but the interaction PON1 genotype by smoking significantly increased the AIP. In subjects with the RR genotype smoking increased the AIP index from (estimated mean ± SEM) -0.038 ± 0.039 to 0.224 ± 0.094. The QR genotype increased the Framingham risk index by around 1.3 points. Smoking by RR genotype carriers significantly increased the Framingham risk score (17.23 ± 2.04) as compared to smoking (13.00 ± 1.06) and non-smoking (7.79 ± 0.70) by QQ+QR genotype carriers. The interaction RR genotype by smoking was a more important predictor (odds ratio = 7.90) of an increased Framingham risk score (> 20) than smoking per se (odds ratio = 2.73). The interaction smoking by RR genotype carriers significantly increased triglycerides and lowered HDL cholesterol. CONCLUSION: Smoking per se has no (AIP) or a mild (Framingham risk score) effect on atherogenicity, while the interaction smoking by PON1 RR genotype has a clinically highly significant impact on atherogenicity.

Paraoxonase 1 (PON1) Q192R genotypes and their interaction with smoking strongly increase atherogenicity and the Framingham risk score

ABSTRACT Objective Paraoxonase 1 (PON1) polymorphisms are associated with an increased susceptibility to cardiovascular disease. PON1 Q192R polymorphism (rs662) partially determine PON1 hydrolytic activity and protect against oxidation of LDL and HDL. This study aimed to delineate the association of PON1 status (functional 192 genotype and plasma activity levels) and atherogenicity in urbans residents aged 40 years or more. Materials and methods Anthropometric data, lipid profiles, the atherogenic index of the plasma (AIP) and Framingham score risk were measured. Three kinetic assays were conducted to assay PON1 status using phenylacetate and 4-(chloromethyl)phenyl acetate as substrates. Results Smoking per se did not significantly impact the AIP but the interaction PON1 genotype by smoking significantly increased the AIP. In subjects with the RR genotype smoking increased the AIP index from (estimated mean ± SEM) -0.038 ± 0.039 to 0.224 ± 0.094. The QR genotype increased the Framingham risk index by around 1.3 points. Smoking by RR genotype carriers significantly increased the Framingham risk score (17.23 ± 2.04) as compared to smoking (13.00 ± 1.06) and non-smoking (7.79 ± 0.70) by QQ+QR genotype carriers. The interaction RR genotype by smoking was a more important predictor (odds ratio = 7.90) of an increased Framingham risk score (> 20) than smoking per se (odds ratio = 2.73). The interaction smoking by RR genotype carriers significantly increased triglycerides and lowered HDL cholesterol. Conclusion Smoking per se has no (AIP) or a mild (Framingham risk score) effect on atherogenicity, while the interaction smoking by PON1 RR genotype has a clinically highly significant impact on atherogenicity.

Arsenic exposure assessment of children living in a lead mining area in Southeastern Brazil.

Environmental contamination by arsenic compounds in the Ribeira River Valley, São Paulo, Brazil has already been observed. Lead mining and refining activities had been carried on since late colonial times and finished recently, at the end of 1995. The source of As in the region is known to be mainly from arsenopirite geological presence in the lead ore. Chronic exposure to arsenic compounds may cause peripheral vascular disorders, hyperpigmentation, hiperkeratosis and cancer of the skin, bladder, lung, liver and other internal organs. The purpose of this study was to assess children exposure to arsenic from environmental sources in the region. Urine samples from children between 7 to 14 years old were collected at the following localities: Cerro Azul (Paraná); urban areas of Ribeira (São Paulo) and Adrianópolis (Paraná); Vila Mota neighborhood (rural area of Adrianópolis) and Serra neighborhood (Iporanga, São Paulo), identified as groups 1, 2, 3 and 4, respectively. Group 1 was considered as non-exposed control group. Toxicologically relevant forms of As were determined by atomic absorption spectrometry with hydride generation system. The median values of urine arsenic levels obtained in groups 1, 2, 3 and 4 were respectively: 3.60, 6.30, 6.41 e 8.94 microg/L.