Blood levels of metallic chemical element exposure patterns and associated factors in a population living in an Industrial District in Brazil.

AIM: to estimate the level of metallic chemical elements in the population living in the Steel company vicinity in Santa Cruz, Rio de Janeiro, Brazil; and estimate the association between exposure to the Steel company and the blood metals concentrations patterns. METHOD: A cross-sectional study was carried out on 463 individuals aged 18+ years old residing 1+ years in the Steel company vicinity. Mg, Be, Co, Ba, Ni, Cd, Al, and Pb were assessed in blood by DRC-ICP-MS. Metallic chemical element concentration patterns were obtained by exploratory factor analysis in the studied population. Exposure was set as the distance (Km) from each participant's residence to the Steel company in Santa Cruz, georeferenced by GPS. The outcome was set as the positive factor loadings in the factor analysis, including Mg and Be (Factor-1), Co, Ba, and Ni (Factor-2), Cd, Al, and Pb (Factor-4). Crude and adjusted OR, and their respective 95 %CI, were estimated to explore associations between independent variables and the exposures to metallic elements positively associated with the factors using polychotomous logistic regression. RESULTS: A reduction of 19 % was found between each km distance from the residence and the Steel company and P50 concentration of Cd, Al, and Pb (ORP50=0.81; 95 %CI:0.67-0.97), after adjusting by age, sex, and smoking. No statistically significant associations were observed for the distance from residences and the Steel company, after adjusting for age, gender, having a domestic vegetable garden and chewing gum for Mg and Be concentrations (Factor-1) (ORP50=0.84; 95 %CI:0.70-1.01; ORP75=1.10; 95 %CI:0.91-1.34); nor for Co, Ba and Ni (Factor-2) blood concentrations(ORP50=1.10; 95 %CI:0.91-1.33; ORP75=1.03; 95 %CI:0.84-1.26), in the adjusted analysis. CONCLUSIONS: For each Km distance from residences to the Steel company, a 19 % reduction in the risk of Cd, Al, and Pb blood concentration was observed in the population living in Santa Cruz, Rio de Janeiro, Brazil.

Corrigendum: Novel Zinc-Related Differentially Methylated Regions in Leukocytes of Women With and Without Obesity.

[This corrects the article DOI: 10.3389/fnut.2022.785281.].

Novel Zinc-Related Differentially Methylated Regions in Leukocytes of Women With and Without Obesity.

Introduction: Nutriepigenetic markers are predictive responses associated with changes in "surrounding" environmental conditions of humans, which may influence metabolic diseases. Although rich in calories, Western diets could be linked with the deficiency of micronutrients, resulting in the downstream of epigenetic and metabolic effects and consequently in obesity. Zinc (Zn) is an essential nutrient associated with distinct biological roles in human health. Despite the importance of Zn in metabolic processes, little is known about the relationship between Zn and epigenetic. Thus, the present study aimed to identify the epigenetic variables associated with Zn daily ingestion (ZnDI) and serum Zinc (ZnS) levels in women with and without obesity. Materials and Methods: This is a case-control, non-randomized, single-center study conducted with 21 women allocated into two groups: control group (CG), composed of 11 women without obesity, and study group (SG), composed of 10 women with obesity. Anthropometric measurements, ZnDI, and ZnS levels were evaluated. Also, leukocyte DNA was extracted for DNA methylation analysis using 450 k Illumina BeadChips. The epigenetic clock was calculated by Horvath method. The chip analysis methylation pipeline (ChAMP) package selected the differentially methylated regions (DMRs). Results: The SG had lower ZnS levels than the CG. Moreover, in SG, the ZnS levels were negatively associated with the epigenetic age acceleration. The DMR analysis revealed 37 DMRs associated with ZnDI and ZnS levels. The DMR of PM20D1 gene was commonly associated with ZnDI and ZnS levels and was hypomethylated in the SG. Conclusion: Our findings provide new information on Zn's modulation of DNA methylation patterns and bring new perspectives for understanding the nutriepigenetic mechanisms in obesity.

Determination of 17 potential endocrine-disrupting chemicals in human saliva by dispersive liquid-liquid microextraction and liquid chromatography-tandem mass spectrometry.

Endocrine-disrupting chemicals are a group of emerging contaminants that alters the function of the endocrine system, causing possible adverse health effects. In this study, a dispersive liquid-liquid microextraction method coupled with liquid chromatography-mass spectrometry for the simultaneous determination of 17 potential EDCs, bisphenols (A, S, P, AP, AF, Z), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-paraben), benzophenones (3, 1, 2, 8, 4-OH BP) and triclocarban, in human saliva samples was developed. Several parameters such as, type and volume of extraction and dispersive solvents, pH sample, ionic strength and, agitation, that affect extraction efficiency were investigated. Under the optimized conditions, the matrix-matched calibration curves of all analytes presented correlation coefficients higher than 0.99 (range level of 1-20 ng mL-1). The intra and inter-day coefficient of variation and relative standard deviation were lower than 20%, at 1 ng mL-1. The limits of detection and quantification ranged from 0.01 to 0.15 ng mL-1 and 0.05-0.40 ng mL-1, respectively. Finally, the proposed method was applied in the simultaneous determination of several endocrine-disrupting chemicals classes in 10 human saliva samples In conclusion, the proposed method is an attractive alternative for application in large-scale human biomonitoring studies.

Blood lead and cadmium levels in preschool children and associated risk factors in São Paulo, Brazil.

In Brazil, there are scarce data on lead (Pb) and cadmium (Cd) contamination, especially for more vulnerable populations such as preschool children. In this paper, we answer two questions: (1) What are the exposure levels of lead and cadmium in preschool children, in Sao Paulo, Brazil? and (2) What are the risk factors associated with this exposure? This cross-sectional study included 50 day care centers (DCCs), totaling 2463 children aged 1-4 years. Venous blood samples were analyzed by ICP-MS. Questionnaires were administered to the parents. Multiple logistic regression models were used to identify associations between blood lead levels (BLLs) and blood cadmium levels (BCLs) and potential risk factors. The geometric mean for BLLs was 2.16 µg/dL (95% CI: 2.10-2.22 µg/dL), and the 97.5th percentile was 13.9 µg/dL (95% CI: 10.0-17.3 µg/dL). For cadmium exposure, the geometric mean for BCLs was 0.48 µg/L (95% CI: 0.47-0.50 µg/L), and the 95th percentile was 2.57 µg/L (95% CI: 2.26-2.75 µg/L). The DCCs' geographic region was associated with high BLLs and BCLs, indicating hot spots for lead and cadmium exposures. In addition, it was found that the higher the vehicles flow, the higher were the BLLs in children. Red lead in household gates was also an important risk factor for lead exposure. Comparing these results with the findings of the Fourth National Report on Human Exposure to Environmental Chemicals by CDC-2013, it was found that in Brazilian preschool children the BLLs are almost three times higher (97.5th percentile) and the BCLs are almost twelve times higher (95th percentile) than those in U.S. children. This information is essential to formulate public health policies.

Chlorella vulgaris mixotrophic growth enhanced biomass productivity and reduced toxicity from agro-industrial by-products.

Algal wastewater remediation has become attractive for a couple of years now, however the effectiveness of genetic toxicity reducing of some by-products through microalgae are still not well reported. This study aimed to evaluate the growth, nutrients and toxicity removal of Chlorella vulgaris cultivated under autotrophic and mixotrophic conditions in three agro-industrial by-products. Mixotrophic culture using corn steep liquor showed higher cell concentration, specific growth rate, maximum cell productivity and biomass protein content when compared to cheese whey and vinasse. Nutrient removal results showed that C. vulgaris was able to completely remove corn steep liquor nutrients, while in cheese whey and vinasse culture this removal was not as efficient, observing remaining COD. This work evaluated for the first time the corn steep liquor and cheese whey genetic toxicity through Allium cepa seeds assay. These results demonstrate that corn steep liquor toxicity was totally eliminated by C. vulgaris cultivation, and cheese whey and vinasse toxicity were minimized. This study proves that the mixotrophic cultivation of C. vulgaris can increase cellular productivity, as well as it is a suitable and economic alternative to remove the toxicity from agroindustrial by-products.

Chrysobalanus icaco L. fruits inhibit NADPH oxidase complex and protect DNA against doxorubicin-induced damage in Wistar male rats.

Chrysobalanus icaco L. is an underexplored plant found in tropical areas around the globe. Currently, there is no apparent information regarding the effects C. icaco fruits may exert in vivo or potential role in health promotion. This study aimed at providing evidence regarding the in vivo influence of this fruit on antigenotoxicity, antimutagenicity, and oxidative stress in rats. Male Wistar rats were treated with 100, 200, or 400 mg/kg body weight (bw)/d C. icaco fruit for 14 d. Doxorubicin (DXR, 15 mg/kg bw, ip) was used for DNA damaging and as an oxidant to generate reactive oxygen species (ROS). Genomic instability was assessed by the comet assay and micronucleus (MN) test, while antioxidant activity was determined by oxidative burst of neutrophils. Chrysobalanus icaco fruit polyphenols were quantified and characterized by high-performance liquid chromatography coupled to a diode array detector and tandem mass spectrometer (HPLC-DAD-MS/MS). The concentrations of 19 chemical elements were determined by inductively coupled plasma-mass spectroscopy (ICP-MS). Significant amounts of polyphenols, magnesium, and selenium were found in C. icaco fruit. This fruit displayed in vivo antioxidant activity against DXR-induced damage in rat peripheral blood neutrophils, antigenotoxicity in peripheral blood cells, and antimutagenicity in bone-marrow cells and peripheral blood cells. Correlation analyses between endpoints examined indicated that the mechanism underlying chemopreventive actions of C. icaco fruit was attributed to inhibition of NADPH oxidase complex manifested as low levels of DNA damage in animals exposed to DXR. Data indicate that phytochemicals and minerals in C. icaco fruit protect DNA against damage in vivo associated with their antioxidant properties.

Iodine Nutritional Status in Schoolchildren from Public Schools in Brazil: A Cross-Sectional Study Exposes Association with Socioeconomic Factors and Food Insecurity.

INTRODUCTION: National programs of salt iodization were implemented in Brazil to combat iodine deficiency (ID) in children of school age. Currently, there are limited data in Brazil on those still vulnerable to this deficiency and the state of nutritional iodine status in the northeast region of Brazil, where children are vulnerable to malnutrition. OBJECTIVE: The aim of this study was to analyze the iodine nutritional status, household food insecurity, socioeconomic and demographic characteristics among schoolchildren from the public school system living in state the state of Bahia, Brazil. METHODS: A cross-sectional study was conducted on 1419 schoolchildren in Bahia between the ages of 6 and 14 years old. Anthropometric parameters, urinary iodine concentrations (UIC), and thyrotropin (TSH) measurements were evaluated from blood spots on filter paper. RESULTS: The mean UIC was 206.4 ± 80.5 µg/L, with a median of 221.6 µg/L, indicating sufficient iodine intake in the region. Low urinary iodide concentration (<100 µg/L) was detected in 12.3% of the schoolchildren (n = 174), with 6.2% with mild (<100 µg/L), 3.0% with moderate (20-49 µg/L), and 3.1% with severe ID (<20 µg/L). Moreover, 9.4% (n = 134) had a urinary iodide concentration of >300 µg/L, indicating the coexistence of excessive iodine intake (EII). The mean TSH was 1.0 ± 0.6 mIU/L. The body mass index category "overweight/obesity" was a protective factor against EII (odds ratio [OR] = 0.64 [confidence interval (CI) 0.4-1.0]; p = 0.07). Urban areas (73%) had a mean UIC of 213.1 ± 80 µg/L compared with 176.8 ± 76.1 µg/L in rural areas. The risk for EII increased in children living in a house with more than six people (OR = 1.62 [CI 0.9-2.6]; p < 0.05) and water consumption from shallow wells (OR = 1.70 [CI 0.9-3.1]; p = 0.09). The risk of ID was increased by 70% in schoolchildren who had moderate or severe food insecurity (OR = 1.70 [CI 0.9-3.0]; p > 0.05). CONCLUSION: A significant proportion of schoolchildren still have ID or EII in the northeast region of Brazil, emphasizing the importance of committed public policies to address this problem. Socioeconomic factors and the lack of education about nutritional importance of iodine were important influencing factors in the presence of ID in schoolchildren.

Serum cadmium levels in a sample of blood donors in the Western Amazon, Brazil, 2010-2011.

A cross-sectional study was conducted to determine the distribution of serum cadmium (Cd) levels in blood donors in Rio Branco, Acre State, Brazil. Blood samples were obtained from 922 volunteer blood donors from 18 to 65 years of age at the Hemoacre blood center in 2010-2011. Mean serum Cd was 0.37µg/L (95%CI: 0.33-0.41). Increased serum Cd was associated with lower schooling; individuals with less than five years of schooling showed a mean Cd of 0.61µg/L (95%CI: 0.34-0.89), compared to 0.34µg/L (95%CI: 0.28-0.40) among those with more than nine years of schooling. Mean serum Cd was three times higher among smokers. Smoking showed a positive association with Cd level, with an OR of 12.36 (95%CI: 7.70-19.84). Meanwhile, serum Cd was lower among individuals that regularly drank tea, as compared to non-tea drinkers. Serum Cd levels were mostly below the reference value (88.3% of participants). Mean serum Cd in the current study indicates that in general the population studied here is not exposed to worrisome Cd levels.

Serum cadmium levels in a sample of blood donors in the Western Amazon, Brazil, 2010-2011 / Niveis sericos de cadmio em uma amostra de doadores de sangue na Amazonia Ocidental, Brasil, 2010-2011 / Niveles sericos de cadmio en una muestra de donantes de sangre en la Amazonia occidental, Brasil, 2010-2011

A cross-sectional study was conducted to determine the distribution of serum cadmium (Cd) levels in blood donors in Rio Branco, Acre State, Brazil. Blood samples were obtained from 922 volunteer blood donors from 18 to 65 years of age at the Hemoacre blood center in 2010-2011. Mean serum Cd was 0.37µg/L (95%CI: 0.33-0.41). Increased serum Cd was associated with lower schooling; individuals with less than five years of schooling showed a mean Cd of 0.61µg/L (95%CI: 0.34-0.89), compared to 0.34µg/L (95%CI: 0.28-0.40) among those with more than nine years of schooling. Mean serum Cd was three times higher among smokers. Smoking showed a positive association with Cd level, with an OR of 12.36 (95%CI: 7.70-19.84). Meanwhile, serum Cd was lower among individuals that regularly drank tea, as compared to non-tea drinkers. Serum Cd levels were mostly below the reference value (88.3% of participants). Mean serum Cd in the current study indicates that in general the population studied here is not exposed to worrisome Cd levels.

Objetivou-se, por meio de estudo transversal, determinar a distribuição dos níveis séricos de cádmio (Cd) em doadores de sangue em Rio Branco, Acre, Brasil. O sangue foi obtido de 922 doadores voluntários entre 18 e 65 anos no Hemoacre, entre 2010-2011. A média da concentração de Cd foi de 0,37µg/L (IC95%: 0,33-0,41). Houve tendência de aumento com a diminuição do nível de escolaridade; indivíduos com menos de cinco anos de estudo apresentaram média de 0,61µg/L (IC95%: 0,34-0,89), enquanto aqueles com mais de nove anos de estudo obtiveram média de 0,34µg/L (IC95%: 0,28-0,40). A média da concentração de Cd apresentou-se três vezes maior entre os fumantes. O tabagismo demonstrou associação positiva com OR 12,36 (IC95%: 7,70-19,84). Já a concentração de Cd entre os indivíduos com hábitos de tomar chás apresenta- se menor quando comparada àqueles que não utilizam. Os níveis séricos de Cd foram, em sua maioria, abaixo do valor de referência (88,3% dos participantes). As médias encontradas no presente estudo indicam que, no geral, a população estudada não está exposta a níveis preocupantes de exposição ao Cd.

El objetivo de utilizar un estudio transversal para determinar la distribución de los niveles séricos de Cd en los donantes de Río Branco no expuestos al metal. Se obtuvo sangre de 922 voluntarios de entre 18 y 65 años en Hemoacre entre 2010-2011. La concentración media de Cd fue 0,37µg/L (IC95%: 0,33-0,41). Hubo una tendencia de aumento según el nivel educativo: las personas con menos de cinco años de estudio tenían una media de 0,61µg/l (IC95%: 0,34-0,89), mientras que quienes contaban con más de nueve años de escolaridad poseían un promedio 0,34µg/L (IC95%: 0,28-0,40). La concentración promedio de Cd se presentó tres veces mayor entre los fumadores. El consumo de cigarrillos mostró una asociación positiva con OR 12,36 (IC95%: 7,70-19,84). Ya la concentración de Cd en las personas con hábitos de tomar té era más pequeña en comparación con aquellos que no lo toman. Los niveles séricos de Cd fueron en su mayoría por debajo del valor de referencia (88,3% de los participantes). Los medios encontrados en este estudio indican que, en general, la población no está expuesta a niveles preocupantes de Cd.

Proteomic analysis of low- to high-grade astrocytomas reveals an alteration of the expression level of raf kinase inhibitor protein and nucleophosmin.

Proteomic approaches have been useful for the identification of aberrantly expressed proteins in complex diseases such as cancer. These proteins are not only potential disease biomarkers, but also targets for therapy. The aim of this study was to identify differentially expressed proteins in diffuse astrocytoma grade II, anaplastic astrocytoma grade III and glioblastoma multiforme grade IV in human tumor samples and in non-neoplastic brain tissue as control using 2-DE and MS. Tumor and control brain tissue dissection was guided by histological hematoxylin/eosin tissue sections to provide more than 90% of tumor cells and astrocytes. Six proteins were detected as up-regulated in higher grade astrocytomas and the most important finding was nucleophosmin (NPM) (p<0.05), whereas four proteins were down-regulated, among them raf kinase inhibitor protein (RKIP) (p<0.05). We report here for the first time the alteration of NPM and RKIP expression in brain cancer. Our focus on these proteins was due to the fact that they are involved in the PI3K/AKT/mTOR and RAS/RAF/MAPK pathways, known for their contribution to the development and progression of gliomas. The proteomic data for NPM and RKIP were confirmed by Western blot, quantitative real-time PCR and immunohistochemistry. Due to the participation of NPM and RKIP in uncontrolled proliferation and evasion of apoptosis, these proteins are likely targets for drug development.

A fast ultrasound-assisted extraction procedure for trace elements determination in hair samples by ICP-MS for forensic analysis.

An ultrasound-assisted extraction method is proposed for the determination of trace elements in hair samples by inductively coupled plasma-mass spectrometry (ICP-MS) for forensic investigation. Prior to analysis, 25mg of hair samples were accurately weighed into (15 mL) conical tubes. Then, 2 mL of 20% HNO(3) is added to the samples, sonicated at 2 min (50W, 100% amplitude), and then further diluted to 10 mL with Milli-Q water. Resulted diluted slurries are centrifuged and the analytes are directly determined in the supernatant. Calibrations against aqueous solutions were carried out with rhodium as internal standard. The method was successfully applied for the extraction of Al, As, Ba, Be, Cd, Co, Cr, Cu, Mn, Pb, Tl, U, V and Zn with a method detection limit (3s, n=20) of 0.1, 0.4, 0.2, 0.09, 0.08, 0.04, 0.1, 2.9, 1.0, 0.9, 0.04, 0.05, 0.1 and 4.2 ng/g, respectively. Method accuracy is traceable to Certified Reference Materials (CRMs) 85 and 86 human hair from the International Atomic Energy Agency (IAEA). Additional validation data are provided based on the analysis of hair samples from the trace elements intercomparison program operated by the Institut National de Sante' Publique du Quebec, Canada. The proposed method is very simple and can be applied for forensic purposes with the elimination of sample digestion step prior to analysis. Then, a considerable improvement in the sample throughput is archived with the use of the proposed method.

Determination of trace elements in biological samples by inductively coupled plasma mass spectrometry with tetramethylammonium hydroxide solubilization at room temperature.

A simple method for sample preparation of biological samples for trace elements determination by inductively coupled plasma mass spectrometry (ICP-MS) is described. Prior to analysis, 75 mg of the biological samples were accurately weighed into (15 mL) conical tubes. Then, 1 mL of 50% (v/v) tetramethylammonium hydroxide (TMAH) solution was added to the samples, incubated at room temperature for 12 h and the volume made up to 10 mL with a solution containing 0.5% (v/v) HNO(3), 0.01% (v/v) Triton X-100 and 10 microg L(-1) of Rh. After preparation samples may be stored at -20 degrees C during 3 days until the analysis by ICP-MS. With these conditions, the use of the dynamic reaction cell was only mandatory for chromium determination. Method detection limits were 0.2145, 0.0020, 0.0051, 0.0017, 0.0027, 0.0189, 0.02, 0.5, 0.1, 0.0030, 0.0043, 0.0066, 0.0009, 0.020, 0.0043, 0.1794, 0.1 microg(-1) for Al, As, Ba, Cd, Co, Cr, Cu, Fe, Mg, Mn, Mo, Pb, Sb, Se, Sr, V and Zn, respectively. Validation data are provided based on the analysis of six certified reference materials (CRMs) purchased from the National Institute of Standards and Technology (NIST) and National Research Council Canada (NRCC). Additional validation was provided by the analysis of brain, kidney, liver and heart samples collected from rats and analyzed by the proposed method and by using microwave digestion.

Exploiting dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS) for sequential determination of trace elements in blood using a dilute-and-shoot procedure.

Inductively coupled plasma mass spectrometry with quadrupole (q-ICP-MS) and dynamic reaction cell (DRC-ICP-MS) were evaluated for sequential determination of As, Cd, Co, Cr, Cu, Mn, Pb, Se, Tl, V and Zn in blood. The method requires as little as 100 microL of blood. Prior to analysis, samples (100 microL) were diluted 1:50 in a solution containing 0.01% (v/v) Triton X-100 and 0.5% (v/v) nitric acid. The use of the DRC was only mandatory for Cr, Cu, V and Zn. For the other elements the equipment may be operated in a standard mode (q-ICP-MS). Ammonia was used as reaction gas. Selection of best flow rate of ammonium gas and optimization of the quadrupole dynamic band-pass tuning parameter (RPq) were carried out, using a ovine base blood for Cr and V and a synthetic matrix solution (SMS) for Zn and Cu diluted 1:50 and spiked to contain 1 microg L(-1) of each element. Method detection limits (3 s) for (75)As, (114)Cd, (59)Co, (51)Cr, (63)Cu (55)Mn, (208)Pb, (82)Se, (205)Tl, (51)V, and (64)Zn were 14.0, 3.0, 11.0, 7.0, 280, 9.0, 3.0, 264, 0.7, 6.0 and 800 ng L(-1), respectively. Method validation was accomplished by the analysis of blood Reference Materials produced by the L'Institut National de Santé Publique du Quebec (Canada).

Determination of indinavir in human plasma and its use in pharmacokinetic study

We report the development and validation of a new sensitive, accurate and precise HPLC method with ultraviolet detection for the determination of indinavir sulfate (IND) in human plasma and its application to a bioequivalence study of a new generic formulation. The extraction of IND from plasma samples was achieved by using liquid-liquid extraction with a mean recovery of 73.9 percent. The lower limit of quantification was 0.05 µg/mL. Bioequivalence between the products was determined by calculating 90 percent confidence intervals (CI) for the ratio of Cmax, AUC0-t and AUC0-inf values for the test and reference products, within the 0.80-1.25 interval proposed by ANVISA and FDA. Therefore the medications are bioequivalent and inter-exchangeable.

Foi desenvolvido e validado um novo método, sensível, exato e preciso por Cromatografia a Líquido de Alta Eficiência com detecção em UV para a determinação do sulfato de indinavir (IND) em plasma humano. O fármaco foi extraído do plasma através de extração líquido-líquido obtendo recuperação média de 73.9 por cento, com limite inferior de quantificação de 0.05 µg/mL. O método foi aplicado em estudo de farmacocinética para verificar a bioequivalência entre um novo medicamento genérico e seu produto de referência. A bioequivalência entre os produtos foi determinada calculando-se um intervalo de confiança (IC) de 90 por cento para a razão das médias do produto teste e referência compreendidas entre o intervalo de 0.80-1.25 proposto pela ANVISA e O FDA. Os produtos estudados são bioequivalentes e, portanto, intercambiáveis.