BXD recombinant inbred mice as a model to study neurotoxicity

BXD recombinant inbred (RI) lines represent a genetic reference population derived from a cross between C57BL/6J mice (B6) and DBA/2J mice (D2), which through meiotic recombination events possesses recombinant chromosomes containing B6 or D2 haplotype segments. The quantitative trait loci (QTLs) are the locations of segregating genetic polymorphisms and are fundamental to understanding genetic diversity in human disease susceptibility and severity. QTL mapping represents the typical approach for identifying naturally occurring polymorphisms that influence complex phenotypes. In this process, genotypic values at markers of known genomic locations are associated with phenotypic values measured in a segregating population. Indeed, BXD RI strains provide a powerful tool to study neurotoxicity induced by different substances. In this review, we describe the use of BXD RI lines to understand the underlying mechanisms of neurotoxicity in response to ethanol and cocaine, as well as metals and pesticide exposures. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Occupational And Environmental Human Lead Exposure In Brazil

The purpose of this paper is to present a review of data on assessment of exposure and adverse effects due to environmental and occupational lead exposure in Brazil. Epidemiological investigations on children lead exposure around industrial and mining areas have shown that lead contamination is an actual source of concern. Lead in gasoline has been phasing out since the 1980s, and it is now completely discontinued. The last lead mining and lead refining plant was closed in 1995, leaving residual environmental lead contamination which has recently been investigated using a multidisciplinary approach. Moreover, there are hundreds of small battery recycling plants and secondary smelting facilities all over the country, which produce focal urban areas of lead contamination. Current regulatory limits for workplace lead exposure have shown to be inadequate as safety limits according to a few studies carried out lately. © 2006 Elsevier Inc. All rights reserved.1032288297Alvarez-Leite, E.M., PRS, Z.L., Silveira, J.B., Silva, Z.L., Validade da correção dos valores de ALAU através da densidade urinária e da concentração de creatinina (1989) Rev Bras S. Ocup., 17, pp. 14-15Alves, M.A., Terra, N.N., Determination of serum lead concentration by atomic absorption spectrophotometry in subjects working in gas distribution in Santa Maria-RS (1983) Rev. Bras. S. Ocup., 11, pp. 53-57Araújo, U.C., Pivetta, F.R., Moreira, J.C., Occupational lead exposure assessment: a proposal for a strategy to monitor prevention of clinical and subclinical effects (1999) Cad. Saúde Publ., 15, pp. 123-131Azevedo, F.A., Queiroz, I.R., Kuno, R., Bastian, E.Y.O., Maluf, C.B., Campos, A.E.M., Diniz, K., Avaliação tóxico-epidemiológica da exposição ambiental da população infantil do Município de Cubatão (Sp-Brasil) a metais pesados: chumbo e mercúrio (1989) Rev. Bras. 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Saúde Publ., 16, pp. 225-230Carvalho, F.M., Barreto, M.L., Silvany-Netto, A.M., Waldron, H.A., Tavares, T.M., Multiple causes of anaemia among children living near a lead smelter in Brazil (1984) Sci. Total Environ., 35, pp. 71-84Carvalho, F.M., Silvany-Netto, A.M., Tavares, T.M., Lima, M.E.C., Waldron, H.A., Lead poisoning among children from Santo Amaro, Brazil (1985) Pan. Am. Health Organ. Bull., 19, pp. 165-175Carvalho, F.M., Silvany-Netto, A.M., Barbosa, A.C., Cotrim, A.R.L., Tavares, T.M., Erithrocyte protoporphyrin versus blood lead: relationship with iron status among children exposed to gross environmental pollution (1995) Environ. Res., 71, pp. 11-15Carvalho, F.M., Silvany Neto, A.M., Tavares, T.M., Costa, A.C.A., Chaves, C.R., Nascimento, L.D., Reis, M.A., Blood lead levels in children and environmental legacy of a lead foundry in Brazil (2003) Pan. Am. J. Pub. Health, 13, pp. 19-23Cordeiro, R., Lima Filho, E.C., The inadequacy of threshold values for preventing lead poisoning in Brazil (1995) Cad. Saúde Publ., 11, pp. 177-186Cordeiro, R., Lima Filho, E.C., Salgado, P.E.T., Neurological disorders in workers with low levels of lead in the blood. I: Peripheral neuropathy (1996) Rev. Saude Publ., 30, pp. 248-255Cordeiro, R., Lima Filho, E.C., Salgado, P.E.T., Santos, C.O., Constantino, L., Malatesta, M.L., Neurological disorders in workers with low levels of lead in the blood. II-Neuropsychological disorders (1996) Rev. Saúde Publ., 30, pp. 358-363Dabbas, M.A., Al-Zoubi, M.A., Blood lead level in the Jordanian population (2000) Saudi Med. J., 21, pp. 964-967De Capitani, E.M., Madureira, P.R., Moreira Filho, D.C., Vieira, R.J., Salgado, P.E.T., Peccinin, R.G., Morishita, R., Comparative study of chelation therapy for lead poisoned patients using RDTACaNa2 by two administration routes (2004) Rev. Bras. Med. Trab., 2, pp. 185-190Demarchi, A.C.C.O., Souza, L.C.D., Santos, L.S., Menezes, M.L., Evaluation of lead exposure in workers at industry in Bauru (1999) Salusvita, 18, pp. 27-36De Siqueira, M.E., Maia, P.P., De Oliveira, D.P., Luengo, D.M., Delta-aminolevulinic acid dehydratase activity in the general population of southern Minas Gerais, Brazil (2003) Ind. Health, 41, pp. 19-23Donni, V.L., Bagnoli, P., Bartoli, D., Bavazzano, P., Cavalli, I.P., Landucci, D., Marinari, M.G., Vitti, A., Blood lead levels in a non-professionaly-exposed population from six Tuscan provinces (1998) Ann. Ist Sup Sanita, 34, pp. 75-85Dos Santos, A.C., Colacciopo, S., Dal Bo, C.M., dos Santos, N.A., Occupational exposure to lead, kidney function tests, and blood pressure (1994) Am. J. Ind. Méd., 26, pp. 635-643Fernícola, N.A.G.G., Azevedo, F.A., Níveis de chumbo e atividade da desidratase do ácido δ-aminolevulínico (δ-ALA D) no sangue da população da grande São Paulo, Brasil (1981) Rev. Saúde Publ., 15, pp. 272-282Fischer, A.B., Georgieva, R., Nikolova, V., Halkova, J., Bainova, A., Hristeva, V., Penkov, D., Alandjiisk, D., Health risk for children from lead and cadmium near a non-ferrous smelter in Bulgaria (2003) Int. J. Hyg. Environ. Health, 206, pp. 25-38Flores, J., Albert, L., Environmental lead in México, 1990-2002 (2004) Rev. Environ. Contam. Toxicol., 181, pp. 37-109Fonseca, E.A., Problemas de hygiene e segurança do trabalho na indústria de acumuladores elétricos [Problems of industrial hygiene and safety in the acid lead battery workplaces] (1953) Arq. Fac. Hig. São Paulo, 7, pp. 87-100Franco-Netto, G., Alonzo, H.G.A., Cancio, J., Jost, M., Souza-Oliveira, S., Human health risk reduction due to lead exposure in Brazil (2003) Salud Publica Mex., 45, pp. s255-s258Freitas, C., Simonetti, M.H., Silva, M.R.P., Sakuma, A.M., Carvalho, M.F.H., Duran, M.C., Kira, C.S., De Capitani, E.M., Epidemiological investigation of children exposed to lead in the city of Bauru, São Paulo, Brazil (2002) Epidemiology, 14, pp. 565-566Gerhardsson, L., Kazantzis, G., Schultz, A., Evaluation of selected publications on reference values for lead in blood (1996) Scan. J. Work Environ. Health, 22, pp. 325-331Leroyer, A., Nisse, C., Hemon, D., Gruchociak, A., Salomez, J.L., Haguenoer, J.M., Environmental lead exposure in a population of children in northern France: factors affecting lead burden (2000) Am. J. Ind. Med., 38, pp. 281-289Leite, E.M., Leroyer, A., Nisse, C., Haguenoer, J.M., De Burbure, C.Y., Buchet, J.P., Bernard, A., Urinary homovanillic acid and serum prolactin levels in children with low environmental exposure to lead (2002) Biomarkers, 7, pp. 49-57Liou, S.H., Wu, T.N., Chiang, H.C., Yang, T., Wu, Y.Q., Lai, J.S., Ho, S.T., Chang, P.Y., Blood lead levels in Taiwanese adults: distribution and influencing factors (1996) Sci. Total Environ., 180, pp. 211-219Mañay, N., Pereira, L., Cousillas, Z., Lead contamination in Uruguay (1999) Rev. Environ. Contam. Toxicol., 159, pp. 13-19Melo Mattos, S.V., Nicácio, M.A., Prado, G., Oliveira, M.S., Evaluation of exposure to lead inorganic compounds in workers of metroplotitan Belo Horizonte-1998 to 1993 (1994) Rev. Bras. S. Ocup., 22, pp. 7-16Mendes, R., Efeitos da exposição profissional ao chumbo em trabalhadores de duas regiões do estado da Bahia [Effects of lead occupational exposure in woekers from two regions of the state of Bahia] (1974) Rev. Bras. Saúde Ocup., 2, pp. 37-45Mendes, R., Effects of lead on workers living in areas with highly endemic intestinal helminthiasis (1977) J. Occup. Med., 19, pp. 498-499Menegotto, R.M., Paoliello, M.M.B., Occupational lead exposure and effects on hematological variables (2001) Rev. Bras. Toxicol., 14, pp. 31-34Minoia, C., Sabbion, E., Apostoli, P., Pietra, R., Pozzoli, L., Gallorini, M., Trace element reference values in tissues from habitants of the European Community: a study of 46 elements in urine, blood and serum of Italian subjects (1990) Sci. Total Environ., 95, pp. 89-105Monteiro, H.P., Abdalla, D.S.P., Arcuri, A.S., Bechara, E.J.H., Oxygen toxicity related to exposure to lead (1985) Clin. Chem., 31, pp. 1673-1676Montesanti, M., Morgantini, F., Landucci, C., Rossi, L., Biagi, C., Castelli, S., Livelli ematici di piombo nei bambini della Pianna di Lucca. Rilevazione del 1993 (1995) Minerva Pediatr., 47, pp. 119-125Morisi, G., Patriarca, M., Carrieri, M.P., Fondi, G., Tagi, F., Lead exposure: assessment of the risk for the general italian population (1989) Ann. Ist. Sup. Sanita, 25, pp. 423-426Muntner, P., Menke, A., DeSalvo, K.B., Rabito, F.A., Batuman, V., Continued decline in blood lead levels among adults in the United States: the National and Nutrition Examination Surveys (2005) Arch. Intern. Med., 165, pp. 2155-2161Oliveira, O.G., Cavalcanti, T., O problema do chumbo numa indústria gráfica [Lead problems in a printing industry] (1950) Mem. Inst. Osw. Cruz, 48, pp. 125-142Paoliello, M.M.B., De Capitani, E.M., Environmental contamination and human exposure to lead in Brazil (2005) Rev. Environ. Contam. Toxicol., 184, pp. 59-96Paoliello, M.M.B., Gutierrez, P.R., Turini, C.A., Matsuo, T., Mezzaroba, L., Barbosa, D.S., Carvalho, S.R.Q., Cascales, R.A., Reference values for lead in blood in an urban population in southern Brazil (2001) Pan Am. J. Pub. Health, 9, pp. 315-319Paoliello, M.M.B., De Capitani, E.M., Cunha, F.G., Matsuo, T., Carvalho, M.F., Sakuma, A., Fiqueiredo, B.R., Exposure of children to lead and cadmium from a mining area of Brazil (2002) Environ. Res., 88, pp. 120-128Paoliello, M.M.B., De Capitani, E.M., Cunha, F.G., Carvalho, M.F., Matsuo, T., Sakuma, A., Figueiredo, B.R., Determinants of blood lead levels in an adult population from a mining area in Brazil (2003) J. Phys., 107, pp. 127-130Pinto de Almeida, A.R., Carvalho, F.M., Spínola, A.G., Rocha, H., Renal dysfunction in Brazilian lead workers (1987) Am. J. Nephrol., 7, pp. 455-458Raghunath, R., Tripathi, R.M., Kumar, A.V., Sathe, A.P., Khandekar, R.N., Nambi, K.S.V., Assessment of Pb, Cd, Cu, and Zn exposures of 6- to 10-year-old children in Muambai (1999) Environ. Res., 80, pp. 215-221Salgado, P.E.T., Diagnóstico laboratorial da intoxicação pelo chumbo [Laboratory diagnosis of lead intoxication] (1976) Rev. Bras. Saúde Ocup., 5, pp. 21-34Sánchez-Cortez, J., Ilabaca-Marileo, M., Martín, M.A., Viñas, M.A., Bravo-Mendez, R., Prevalência de plomo em sangre, em niños escolares de Santiago de Chile (2003) Salud Publica Mex., 45, pp. s264-s268Sánchez-Molina, M., Rojas-Carrión, C., Patrón de descenso del plomo sanguíneo en la población costarricense (2003) Salud Publica Mex., 45, pp. s258-s261Santos Filho, E., Silva, R.S., Barreto, H.H.C., Inomata, O.N.K., Lemes, V.R.R., Sakuma, A.M., Scorsafava, M.A., Concentrações sanguíneas de metais pesados e praguicidas organoclorados em crianças de 1 a 10 anos (1993) Rev. Saúde Publ., 27, pp. 59-67Sepúlveda, A., Veja, J., Delgado, I., Exposición severa a plomo ambiental en una población infantil de Antofagasta, Chile (2000) Rev. Med. Chile, 128, pp. 221-232Silva, C.C., Mattos, R.C.O.C., Meyer, A., Moreira, J.C., Applicability limits of urinary-aminolevulinic acid as a screening test to evaluate professional intoxication by lead (2000) Cad. Saúde Publ., 16, pp. 225-230Silvany-Neto, A.M., Carvalho, F.M., Chaves, M.E.C., Brandão, A.M., Tavares, T.M., Repeated surveillance of lead poisoning among children (1989) Sci. Total Environ., 78, pp. 179-186Silvany-Neto, A.M., Carvalho, F.M., Tavares, T.M., Guimarães, G.C., Amorin, C.J.B., Peres, M.F.T., Lopes, R.S., Raña, M.C., Lead poisoning among children of Santo Amaro, Bahia, Brazil in 1980, 1985, and 1992 (1996) Pan Am. Health Organ. Bull., 30, pp. 51-62Spínola, A.G., Fernícola, N.A.G.G., Mendes, R., Intoxicação profissional por chumbo (1980) Medicina do Trabalho-Doenças Profissionais, pp. 437-460. , Mendes R. (Ed), Sarvier, São PauloTavares, T.M., Brandão, A.M., Chaves, M.E.C., Silvany-Neto, A.M., Carvalho, F.M., Lead in hair of children exposed to gross environmental pollution (1989) J. Environ. Anal. Chem., 36, pp. 221-230Yang, J.S., Kang, S.K., Park, I.J., Rhee, K.Y., Moon, Y.H., Sohn, D.H., Lead concentration in blood among the general population of Korea (1996) Int. Arch. Occup. Environ. Health, 68, pp. 199-202Zentner, L.E., Rondó, P.H., Lead contamination among pregnant Brazilian women living near a lead smelter (2004) Int. I. Gynaecol. Obstet., 87, pp. 147-148Zhang, Z.W., Moon, C.S., Watanabe, T., Shimbo, S., He, F.S., Wu, Y.Q., Zhou, S.F., Ikeda, M., Background exposure of urban populations to lead and cadmium: comparison between China and Japan (1997) Int. Arch. Occup. Health, 69, pp. 273-28

Lead Sources Of Human Exposure In Brazil [fontes De Exposição Humana Ao Chumbo No Brasil]

As result of increased environmental contamination, the interest on the accumulation of heavy metals in the human body and its harmful effects has increased. Some metals, such as lead, are non-essential elements and exert toxic effects on biological system. Despite the control measures established by law, acute and chronic intoxication by lead still happen in Brazil. Some sources of lead exposure are well known, such as industrial activities like mining and factories for batteries recycling. However, other sources, although common, are completely unknown by population. This article aims to present a review of past and current literature on the various lead sources of human exposure in Brazil.423301308Grandjean, P., Bach, E., Indirect exposures: The significance of bystanders at work and at home (1986) Am Ind Hyg Assoc J, 47, pp. 819-824Paoliello, M.M., De Capitani, E.M., Occupational and environmental human lead exposure in Brazil (2007) Environ Res, 103, pp. 288-297Franco-Netto, G., Alonzo, H.G., Cancio, J., Jost, M., de Souza-Oliveira, S., Human health risk reduction due to lead exposure in Brazil (2003) Salud Pública Mex, 45 (SUPPL. 2), pp. S255-S258Brasil. Balanço mineral brasileiro. Chumbo. In: DNPM, editor: DNPM-MME, 2001Thornton, I., Culbard, E.B., Moorcroft, S., Watt, J.M., Wheatley, M., Thompson, M., Metals in urban dusts and soils (1985) Environ Technol, 6, pp. 137-144Toxicologic Profile for Lead - Update Statement (1999) Registry, p. 587. , ATSDR, USDoHHS-PHS-AfTSaD, editor. AtlantaQuitério, S.L., Silva, C.R.S., Vaitsman, D.S., Martinhon, P.T., Moreira, M.F.R., Araujo, U.C., Use of dust and air as indicators of environmental pollution in areas adjacent to a source of stationary lead emission (2001) Cad Saúde Publica, 17, pp. 501-508De Capitani, E.M., Ensweiler, J.M.S.A., Paoliello, M.M.B., (2009) Dados não publicadosMeyer, I., Heinrich, J., Trepka, M.J., Krause, C., Schulz, C., Meyer, E., The effect of lead in tap water on blood lead in children in a smelter town (1998) Sci Total Environ, 209, pp. 255-271Trepka, M.J., Heinrich, J., Krause, C., Schulz, C., Lippold, U., Meyer, E., The internal burden of lead among children in a smelter town - a small area analysis (1997) Environ Res, 72, pp. 118-130Lanphear, B.P., Matte, T.D., Rogers, J., Clickner, R.P., Dietz, B., Bornschein, R.L., The contribution of lead-contaminated house dust and residential soil to children's blood lead levels. A pooled analysis of 12 epidemiologic studies (1998) Environ Res, 79, pp. 51-68Lima, M., Pimentel, M., Brayner, F., Abreu, C., Lead released by handmade glazed ceramic food wares (2002) Rev Bras Toxicol, 15, pp. 19-23Paoliello, M.M., De Capitani, E.M., Environmental contamination and human exposure to lead in Brazil (2005) Rev Environ Contam Toxicol, 184, pp. 59-96Romano, J., Godinho, R., Alonso, C., Martins, M., Ethanol induced changes in the atmospheric lead in São Paulo Metropolitan Area, Brazil (1992) 9th Word Air Clean CongressFreitas, C.U., (2004) Vigilância de população exposta a chumbo no município de Bauru, São Paulo: Investigação de fatores de risco de exposição e avaliação da dinâmica institucional, , Universidade de São PauloPaoliello, M.M., De Capitani, E.M., da Cunha, F.G., Matsuo, T., Carvalho Mde, F., Sakuma, A., Exposure of children to lead and cadmium from a mining area of Brazil (2002) Environ Res, 88, pp. 120-128Silvany-Neto AM, Carvalho FM, Tavares TM, Guimaraes GC, Amorim CJ, Peres MF, et al. Lead poisoning among children of Santo Amaro, Bahia, Brazil in 1980, 1985, and 1992. Bull Pan Am Health Organ. 1996;30:51-62Jordão, C.P., Distribution of heavy metals in environmental samples near smelters and mining areas in Brazil (1999) Environ Technol, 20, pp. 489-498Cunha, F.G., (2003) Contaminação humana e ambiental por chumbo no Vale do Ribeira, nos Estados de São Paulo e Paraná, , Brasil. Universidade Estadual de CampinasMaio, F., Okada, I., Carvalho, M., Kira, C., Duran, M., Zenebon, O., Evaluation of the labelling, the minerals and inorganic contaminants in domestic and imported mineral water (2002) Rev Inst Adolfo Lutz, 61, pp. 227-232(1989) Assessing human health risks from chemically contaminated fish and shellfish: A guidance manual, , USEPA, Washington DCOkada, I.A., Sakuma, A.M., Maio, F.D., Dovidauskas, S., Zenebon, O., Evaluation of lead and cadmium levels in milk in environmental contamination in the Vale do Paraiba Region, southeastern Brazil] (1997) Rev Saude Publica, 31, pp. 140-143Machado, I., Maio, F., Kira, C., Carvalho, M., Pb, C., Hg, Cu and Zn in mangrove oyster Crassostrea brasiliana Cananéia estuary, São Paulo, Brazil (2002) Rev Inst Adolfo Lutz, 61, pp. 13-18Pereira, O., Henriques, M., Zenebon, O., Sakuma, A., Kira, C., (2002) Determination of Pb, Cd, Hg, Cu and Zn levels in molluscus (Crassostrea brasiliana, Perna perna and Mytella falcate) Rev Inst Adolfo Lutz, 61, pp. 19-25Sakuma, A., Scorsafava, M., Zenebon, O., Tiglea, P., Fukumoto, C., Hortaliças comercializadas em São Paulo: Aspectos da contaminação por chumbo, cádmio e zinco. (1989) Rev Inst Adolfo Lutz, 49, pp. 81-84Garrido, N.S., Pregnolatto, N.P., Murata, L.T.F., Silva, M.R., Nunes, M.C.D., Antunes, J.L.F., Avaliação dos níveis de arsênio, chumbo e cádmio em corantes e pigmentos utilizados em embalagens para alimentos no período de 1982 a 1989. (1991) Rev Inst Adolfo Lutz, 51, pp. 63-68Garrido, N.S., Pregnolato, N.P., Murata, L.T.F., Silva, M.R., Nunes, M.C.D., Engler, V.M., Determinação de chumbo e cádmio em artigos escolares. (1990) Rev Inst Adolfo Lutz, 50, pp. 291-296Stewart, D.D., Notes on some obscure cases on poisoning by lead chromate manifested chiefly by encephalopathy (1887) Med News, pp. 676-681. , 1Glenn, W., Chrome yellow considered as a poison (1889) Science, 13, pp. 347-349Ajab, H., Yasmeen, S., Yaqub, A., Ajab, Z., Junaid, M., Siddique, M., Evaluation of trace metals in tobacco of local and imported cigarette brands used in Pakistan by spectrophotometer through microwave digestion (2008) J Toxicol Sci, 33, pp. 415-420Brasil, Ministério da Saúde. Secretaria Nacional de Assistência à Saúde. Instituto Nacional do Câncer. Coordenação Nacional de Controle de Tabagismo e Prevenção Primária de Câncer (Contapp). Falando sobre Tabagismo. Ministério da Saúde. Rio de Janeiro: 3 o ed. 1998Elevated blood lead levels among internationally adopted children - United States, 1998 (2000) MMWR Morb Mortal Wkly Rep, 49, pp. 97-100Kaul, B., Lead exposure and iron deficiency among Jammu and New Delhi children (1999) Indian J Pediatr, 66, pp. 27-35Gogte, S.T., Basu, N., Sinclair, S., Ghai, O.P., Bhide, N.K., Blood lead levels of children with pica and surma use (1991) Indian J Pediatr, 58, pp. 513-519Dunbabin, D.W., Tallis, G.A., Popplewell, P.Y., Lee, R.A., Lead poisoning from Indian herbal medicine (Ayurveda) (1992) Med J Aust, 157, pp. 835-836Hayes, E.B., The hazard of lead in children (1995) Environmental Medicine, pp. 383-397. , Brooks SM, editor, St Louis: MosbyAl-Ashban, R.M., Aslam, M., Shah, A.H., Kohl (surma): A toxic traditional eye cosmetic study in Saudi Arabia (2004) Public Health, 118, pp. 292-298Al-Saleh, I., Nester, M., DeVol, E., Shinwari, N., Al-Shahria, S., Determinants of blood lead levels in Saudi Arabian schoolgirls (1999) Int J Occup Environ Health, 5, pp. 107-114Busse, F., Omidi, L., Timper, K., Leichtle, A., Windgassen, M., Kluge, E., Lead poisoning due to adulterated marijuana (2008) N Engl J Med, 358, pp. 1641-164

Arsenic Exposure Assessment Of Children Living In A Lead Mining Area In Southeastern Brazil [avaliação Da Exposição De Crianças Ao Arsênio Em área De Mineração De Chumbo Na Região Sudeste Do Brasil]

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 8.94μg/L.262391398Navarro, M., Sánchez, M., López, H., López, M.C., Arsenic contamination levels in waters, soils and sludges in Southeast Spain (1993) Bull Environ Contam Toxicol, 50, pp. 356-362Das, D., Chatterjee, A., Mandal, B.K., Samanta, G., Chakraborti, D., Chanda, B., Arsenic in ground water in six districts of West Bengal, India: The biggest arsenic calamity in the world. Part 2. Arsenic concentration in drinking water, hair, nails, urine, skin-scale and liver tissue (biopsy) of the affected people (1995) Analyst, 120, pp. 917-924Hopenhayn-Rich, C., Biggs, M.L., Smith, A.H., Kalman, D.A., Moore, L.E., Methylation study of a population environmentally exposed to arsenic in drinking water (1996) Environ Health Perspect, 104, pp. 620-628Chowdhury, U.K., Biswas, B.K., Chowdhury, T.R., Samanta, G., Mandal, B.K., Basu, G.C., Groundwater arsenic contamination in Bangladesh and West Bengal, India (2000) Environ Health Perspect, 108, pp. 393-397Meza, M.M., Kopplin, M.J., Burgess, J.L., Gandolfi, A.J., Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, Mexico (2004) Environ Res, 96, pp. 119-126Tseng, C.H., Huang, Y.K., Huang, Y.L., Chung, C.J., Yang, M.H., Chen, C.J., Arsenic exposure, urinary arsenic speciation and peripheral vascular disease in blackfoot disease-hiperendemic villages in Taiwan (2005) Toxicol Appl Pharmacol, 206, pp. 299-308Caceres, D.D., Pino, P., Montesinos, N., Atalah, E., Amigo, H., Loomis, D., Exposure to inorganic arsenic in drinking water and total urinary arsenic concentration in a Chilean population (2005) Environ Res, 98, pp. 151-159Mandal, B.K., Chowdhury, T.R., Samanta, G., Mukherjee, D.P., Chanda, C.R., Saha, K.C., Impact of safe water for drinking and cooking on five on five arsenic-affected families for 2 years in West Bengal, India (1998) Sci Total Environ, 218, pp. 185-201Le, X.C., Cullen, W.R., Reimer, K.J., Determination of urinary arsenic and impact of dietary arsenic intake (1993) Talanta, 40, pp. 185-193Le, X.C., Cullen, W.R., Reimer, K.J., Human urinary arsenic excretion after one-time ingestion of seaweed, crab, and shrimp (1994) Clin Chem, 40, pp. 617-624Christian, W.J., Hopenhayn, C., Centeno, J.A., Todorov, T., Distribution of urinary selenium and arsenic among pregnant women exposed to arsenic in drinking water (2006) Environ Res, 100, pp. 115-122Hirano, S., Kobayashi, Y., Cui, X., Kanno, S., Hayakawwa, T., Shraim, A., The accumulation and toxicity of methylated arsenicals in endothelial cells: Important roles of thiol compounds (2004) Toxicol Appl Pharmacol, 198, pp. 458-467Aposhian, H.V., Zakharyan, R.A., Avran, M.D., Sampayo-Reyes, A., Wollenberg, M.L., A review of the enzimology of arsenic metabolism and a new potencial role of hidrogen peroxide in the detoxication of the trivalent arsenic species (2004) Toxicol Appl Pharmacol, 198, pp. 327-335Mandal, B.K., Ogra, Y., Suzuki, K.T., Identification of dimethylarsinous and monomethylarsenous acids in human urine of the arsenic-affected areas in West Bengal, India (2001) Chem Res Toxicol, 14, pp. 371-378Sur, R., Dunemann, L., Method for the determination of five toxicologically relevant arsenic species in human urine by liquid chromatography-hydride generation atomic absorption spectrometry (2004) J Chromatogr B Analyt Technol Biomed Life Sci, 807, pp. 169-176Akter, K.F., Chen, Z., Smith, L., Davey, D., Naidu, R., Speciation of arsenic in ground water samples: A comparative study of CE-UV, HG AAS and LC-ICP MS (2004) Talanta, 68, pp. 406-415Hsueh, Y.M., Hsu, M.K., Chiou, H.Y., Yang, M.H., Huang, C.C., Chen, C.J., Urinary arsenic speciation in subjects with or without restriction from seafood dietary intake (2002) Toxicol Lett, 133, pp. 83-91Guo, T., Baaser, J., Tsalev, D.L., Fast automated determination of toxicologically relevant arsenic in urine by flow injection-hydride generation atomic absorption spectrometry (1997) Anal Chim Acta, 349, pp. 313-318Ma, M., Le, X.C., Effect of arsenosugar ingestion on urinary arsenic speciation (1998) Clin Chem, 44, pp. 539-550Farmer, J.G., Johnson, L.R., Assessment of occupational exposure to inorganic arsenic based on urinary concentrations and speciation of arsenic (1990) Br J Ind Med, 47, pp. 342-348Hinwoodd, A.L., Sim, M.S., Klerk, N., Drummer, O., Gerostamoulos, J., Bastone, E.B., Are 24-hour urine samples and creatinine adjustment required for analysis of inorganic arsenic in urine in population studies? (2002) Environ Res, 88, pp. 219-224Hwang, Y.H., Bornschein, R.L., Grote, J., Menrath, W., Roda, S., Urinary arsenic excretion as a biomarker of arsenic exposure in children (1997) Arch Environ Health, 52, pp. 139-147Gong, Z., Lu, X., Cullen, W.R., Le, X.C., Unstable trivalent arsenic metabolites, monomethylarsonous acid and dimethylarsinous acid (2001) J Anal At Spectrom, 16, pp. 1409-1413Santos, E.C.O., Jesus, I.M., Brabo, E.S., Fayal, K.F., Sá Filho, G.C., Lima, M.O., Exposição ao mercúrio e ao arsênio em Estados da Amazônia: Síntese dos estudos do Instituto Evandro Chagas/FUNASA (2003) Rev Bras Epidemiol, 6, pp. 171-185Silva, R.H.P., (1997) Geoquímica E Impacto Ambiental Do Arsênio No Vale Do Ribeira (SP-PR) [Dissertação De Mestrado], , Campinas: Instituto de Geociências, Universidade Estadual de CampinasMatschullat, J., Borba, R.P., Deschamps, E., Figueiredo, B.R., Gabrio, T.E., Schwenk, M., Human and environmental contamination in the iron quadrangle, Brazil (2000) Applied Geochem, 15, pp. 181-190Rosa, R.T., (1999) Arsênio E Metais Associados Na Região Aurífera Do Piririca, Vale Do Ribeira, São Paulo, Brasil [Dissertação De Mestrado], , Campinas: Instituto de Geociências, Universidade Estadual de CampinasToujague, R., (1999) Arsênio E Metais Associados Na Região Aurífera Do Piririca, Vale Do Ribeira, São Paulo, Brasil [Dissertação De Mestrado], , Campinas: Instituto de Geociências, Universidade Estadual de CampinasBraga, P.S., Figueiredo, B.R., (2002) Comportamento De Metais Pesados Em Solos Na Região Do Vale Do Ribeira (SP), p. 231. , In: Anais do 41o Congresso Brasileiro de Geologia. 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SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19

Common manifestations of COVID-19 are respiratory and can extend from mild symptoms to severe acute respiratory distress. The severity of the illness can also extend from mild disease to life-threatening acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection can also affect the gastrointestinal tract, liver and pancreatic functions, leading to gastrointestinal symptoms. Moreover, SARS-CoV-2 can cause central and peripheral neurological manifestations, affect the cardiovascular system and promote renal dysfunction. Epidemiological data have indicated that cancer patients are at a higher risk of contracting the SARS-CoV-2 virus. Considering the multitude of clinical symptoms of COVID-19, the objective of the present review was to summarize their pathophysiology in previously healthy patients, as well as in those with comorbidities. The present review summarizes the current, though admittedly fluid knowledge on the pathophysiology and symptoms of COVID-19 infection. Although unclear issues still remain, the present study contributes to a more complete understanding of the disease, and may drive the direction of new research. The recognition of the severity of the clinical symptoms of COVID-19 is crucial for the specific therapeutic management of affected patients. © 2020 Elsevier Lt