Papers by Paula Sarcinelli

The enzyme acetylcholinesterase (EC 3.1.1.7, AChE) is present in all animals with neurons and mus... more The enzyme acetylcholinesterase (EC 3.1.1.7, AChE) is present in all animals with neurons and muscle cells, and many other proteins have the same sequence, with or without catalytic activity, allowing them to be used for phylogenetic and evolutionary studies. The great difference between substrates and inhibitor affinities makes it useful as a biomarker for genetic studies of various animals groups, especially insects. There are great differences among fish in AChE sensitivity to methyl-paraoxon (MP) in relation to terrestrial animals, and these differences can be related to evolution. The inhibition kinetic constants (IKC) for progressive irreversible inhibition of brain AChE with MP were determined in these two AChE sources as models for evaluating IKC as potential biomarkers in evolutionary and phylogenetic studies, especially among fish. IKC of brain AChE from six specimens of Mugil liza, a very common coastal fish, was collected from two of Brazil's lagoons in Rio de Janeiro State during 2005 at Araruama and 2007 at Saquarema. First samples were assayed at CESTEH -Fundação Oswaldo Cruz and the latter at Dept. Bioquímica -Universidade do Estado do Rio de Janeiro. The IKC was measured separately for each fish showing that these constants were maintained for all animals of the same species and that this methodology can be used in different laboratories without variations. The cerebral AChE of tainha was used as an example of a less sensitive enzyme (Concentration which inhibits 50% of enzyme activity after 30 minutes of incubation, or IC50, = 2118nM). The commercial hen (Gallus gallus domesticus) was used an example of a very highly sensitive enzyme to MP (IC50 = 26nM). Some tests were carried out to validate this methodology. The cerebral AChE of these two sources of enzyme was partially purified discarding the supernatant of the homogenate and solubilizing the pellet with Triton X-100 detergent. The AChE activity inhibition in these preparations by excess of the substrate acetylthiocholine, a typical AChE behaviour, proved the homogeneity of this preparation and that it is representative of the real AChE of each animal. Using MP allows checking out the solutions of inhibitor with colorimetric methods in the moment of use. The preparation of soluble AChE eliminates insoluble matters which confound the enzyme quantification. Some characteristics of mathematical calculations of IKC were defined to create a valid model that is able to be used for evolutionary and phylogenic studies of fish and other animals. The cerebral AChE of all terrestrial animals, whose results are available, is highly sensitive to MP. To compare with a similar recently evolved fish, a sample of baiacu (baiacu-arara, Lagocephalus laevigatus) was tested for IKC and the results (IC50 = 2243nM) indicated that evolutionary age of the fish does not correlate with sensitivity to organophosphorus compounds. The most sensitive AChE among the fish tested was a type of catfish (bagre-branco, Genidens barbus, IC50 = 606nM) and the enzyme of an older evolved fish, a small shark (cação-frango, Rhizoprionodon porosus), had an intermediate sensitivity (IC50 = 1280nM). Studies with other species correlated to those being more sensitive to MP have to be made to get adequate answers about the use of IKC for cerebral AChE inhibition by MP as a possible evolutionary and phylogenetic marker.

Agrotóxicos organoclorados (OC) são classificados como poluentes orgânicos persistentes e podem s... more Agrotóxicos organoclorados (OC) são classificados como poluentes orgânicos persistentes e podem ser determinados em uma ampla variedade de matrizes ambientais e biológicas. O controle da exposição a estes químicos é considerado um desafio para as autoridades de saúde pública, desde que o espectro de efeitos adversos às populações inclui desregulação do sistema endócrino e carcinogenicidade. O objetivo deste artigo é apresentar uma revisão sobre os métodos de análise de OC em amostras biológicas, e discutir os fatores que mais influenciam o monitoramento biológico. Os métodos para análise de resíduos de OC requerem alta sensibilidade, e a etapa de extração dos analitos da matriz é crítica para garantir a qualidade dos resultados. Muitos métodos são disponíveis tais como a extração líquido-líquido, utilização de cartuchos ou discos para extração em fase sólida, extração em fase sólida com micro fibras e extração com barra agitadora. A matriz biológica mais utilizada para detectar OC é o soro, que pode ser convenientemente obtida.

Metabolic Polymorphisms and Clinical Findings Related to Benzene Poisoning Detected in Exposed Brazilian Gas-Station Workers
International Journal of Environmental Research and Public Health, 2015
Benzene is a ubiquitous environmental pollutant and an important industrial chemical present in b... more Benzene is a ubiquitous environmental pollutant and an important industrial chemical present in both gasoline and motor vehicle emissions. Occupational human exposure to benzene occurs in the petrochemical and petroleum refining industries as well as in gas-station workers, where it can lead to benzene poisoning (BP), but the mechanisms of BP are not completely understood. In Brazil, a significant number of gas-station service workers are employed. The aim of the present study was to evaluate alterations related to BP and metabolic polymorphisms in gas-station service workers exposed to benzene in the city of Rio de Janeiro, Brazil. Occupational exposure was based on clinical findings related to BP, and metabolic polymorphisms in 114 Brazilian gas-station attendants. These workers were divided into No Clinical Findings (NCF) and Clinical Findings (CF) groups. Neutrophil and Mean Corpuscular Volume (MCV) showed a significant difference between the two study groups, and neutrophil has the greatest impact on the alterations suggestive of BP. The clinical findings revealed higher frequencies of symptoms in the CF group, although not all members presented statistical significance. The frequencies of alleles related to risk were higher in the CF group for GSTM1, GSTT1, CYP2E1 7632T > A, but lower for NQO1 and CYP2E1 1053C > T genotypes. Moreover, an association was found between GSTM1 null and alterations related to BP, but we did not observe any effects of other polymorphisms. Variations in benzene metabolizing genes may modify benzene toxicity and should be taken into consideration during risk assessment evaluations.

Epidemiological profile of Aldicab poisoning registered by the Forensic Medical Institute in the State of Rio de Janeiro from 1998 to 2005
pública. Estetraba-lho objetiva apresentar o perfil de mortalidade por Aldicarb no Estado do Rio ... more pública. Estetraba-lho objetiva apresentar o perfil de mortalidade por Aldicarb no Estado do Rio de Janeiro, referente ao período de 1998 a 2005. Através de um banco de dados secundários do Instituto Médico Legal Afrânio Peixoto (IMLAP/RJ),que contém resultados de laudos toxicológicos e características dos periciados, foi realizado um estudo descritivo. Foram detectados 746 casos positivos de intoxicação por Aldicarb. O sexo masculino (67,2%) prevaleceu sobre o feminino (32,8%). Quanto à idade, há um predomínio de intoxicação entre indivíduos adultos (56%). Emrelação à cor da pele, prevaleceu a cor branca (52,1%). O período com os maiores números de casos foi o de 1998 a 1999 (43,5%). O município com maior concentração de casos foi o Rio de Janeiro, com 440 (59,8%). Dos746casos, 601 (80,6%) tinham informações das circunstâncias, sendo que a maior prevalência de hospitalização foi para circunstância indeterminada com remoção do cadáver em via pública (45,1%). Sua comercialização e us...
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[Evaluation of risk factors related to lead exposure in children and adolescents from Rio de Janeiro]
Ciencia & saude coletiva
The importance of atmospheric lead in environmental global contamination is receiving increasing ... more The importance of atmospheric lead in environmental global contamination is receiving increasing scientific attention. The main exposure monitoring approach is biological, but the environmental one has a key role, since the environment is the major source of exposure. The study aimed to identify the contamination sources and potential risk factors of the exposure in a 64 subject group formed by 0-16 years-old children from an economically deprived community in Rio de Janeiro. Lead concentrations in soil, water, dust and air were determined and neurological and carcinogenic risk factors for ingestion and inhalation were calculated. Blood samples were collected and used in the analysis of Pb-B, ALA-D% and ALA-D genotyping. The observed neurological risk factor was 549 times higher than reference dose for dust and 554 times higher in the case of ingestion. The carcinogenic risk factor for ingestion was about 4 times. Mean Pb-B was 5.6 microg/dL and 40% of the children presented Pb-B le...
Adaptation of Method of Analysis of Methemoglobin as a Biomarker of Effect of Exposure to the Pesticide Diflubenzuron
Química Nova, 2015

O uso indiscriminado de agrotóxicos tem trazido uma gama de efeitos indesejáveis para os seres hu... more O uso indiscriminado de agrotóxicos tem trazido uma gama de efeitos indesejáveis para os seres humanos e o ambiente. Estima-se que dois terços dos agrotóxicos existentes sejam utilizados na agricultura. Este estudo visa avaliar o perfil socioeconômico e os processos executados pelos trabalhadores agrícolas de Paty do Alferes (RJ), a fim de identificar possíveis práticas e costumes que favoreçam a exposição ocupacional e/ou a contaminação ambiental, principalmente da água usada para consumo. Foram realizadas entrevistas com 40 agricultores, por meio da aplicação de questionários padronizados com questões sobre características socioeconômicas, informações de orientações sobre o uso de agrotóxicos, uso de agrotóxicos e noções de perigo, contaminação ambiental por agrotóxicos e agrotóxicos mais utilizados nas culturas praticadas. As práticas relatadas pelos agricultores, como não ler o rótulo das embalagens e não adotar medidas para diminuir o uso de agrotóxico, aliadas à falta de assistência técnica especializada gera, além de efeitos nocivos à saúde, uma tendência ao descuido em relação à contaminação ambiental. O desenvolvimento da agricultura sustentável deve ser estimulado, pois contribuirá para a conservação do ambiente e a minimização dos efeitos negativos desses compostos na saúde humana e ambiental.
Engenharia Sanitaria e Ambiental, 2009

Pesticidas: Revista de Ecotoxicologia e Meio Ambiente, 2014
O objetivo deste trabalho foi avaliar o processo de contaminação ambiental por glifosato na área ... more O objetivo deste trabalho foi avaliar o processo de contaminação ambiental por glifosato na área rural da Serrinha do Mendanha, comunidade periurbana, caracterizada pela presença de pequenos produtores agrícolas que utilizam de modo intensivo o herbicida de interesse para a pesquisa. Efetuou-se a avaliação do processo de trabalho dos agricultores locais mediante aplicação de questionário. A partir dos resultados obtidos pode-se afi rmar que o glifosato constitui contaminante ambiental na área estudada e que houve grande exposição ao produto em algum momento da sua aplicação sem a devida proteção. Sugerem-se estudos posteriores que avaliem a água, o ar e matrizes biológicas a fi m de investigar os efeitos da exposição ao glifosato sobre a saúde dos trabalhadores atuantes na Serrinha do Mendanha. As informações fornecidas pelos próprios agricultores indicaram a exposição do trabalhador ao produto pelas vias dérmica e respiratória. Além disso, a dispersão pelo ar pode atingir as casas, contaminando crianças, mulheres e outros moradores que sequer trabalham na agricultura. Como os trabalhadores não consomem a mesma água usada para a irrigação da lavoura, não se pode afi rmar que ocorra exposição ao glifosato por ingestão. Verifi cou-se também consumo elevado de outros princípios ativos na região, juntamente com o glifosato, cuja interação pode gerar efeito sinérgico desconhecido sobre a saúde humana e ambiental.
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[Evaluation of risk factors related to lead exposure in children and adolescents from Rio de Janeiro]
Ciência & saúde coletiva
The importance of atmospheric lead in environmental global contamination is receiving increasing ... more The importance of atmospheric lead in environmental global contamination is receiving increasing scientific attention. The main exposure monitoring approach is biological, but the environmental one has a key role, since the environment is the major source of exposure. The study aimed to identify the contamination sources and potential risk factors of the exposure in a 64 subject group formed by 0-16 years-old children from an economically deprived community in Rio de Janeiro. Lead concentrations in soil, water, dust and air were determined and neurological and carcinogenic risk factors for ingestion and inhalation were calculated. Blood samples were collected and used in the analysis of Pb-B, ALA-D% and ALA-D genotyping. The observed neurological risk factor was 549 times higher than reference dose for dust and 554 times higher in the case of ingestion. The carcinogenic risk factor for ingestion was about 4 times. Mean Pb-B was 5.6 microg/dL and 40% of the children presented Pb-B le...
Cadernos Saúde Coletiva, 2013

Cadernos Saúde Coletiva, 2014
Atualmente, a substância utilizada para o combate do vetor da dengue é o diflubenzuron, um larvic... more Atualmente, a substância utilizada para o combate do vetor da dengue é o diflubenzuron, um larvicida que possui como principal efeito no ser humano a formação demetemoglobina. A determinação do percentual de metemoglobina (MHb) no sangue permite estabelecer a relação com a exposição ao diflubenzuron, sendo utilizada como indicador de efeito. O objetivo do presente trabalho foi avaliar a efetividade do uso da MHb como indicador da exposição ao diflubenzuron por meio da determinação de sua concentração no sangue de guardas de endemias atuantes em dois municípios do Estado do Rio de Janeiro. Para a avaliação da MHb, foi utilizado o método de análise preconizado por Evelyn-Malloy, a espectrofotometria no visível λ máx =630 nm, e as informações complementares foram obtidas por intermédio da aplicação de questionários semiestruturados. Foi observado que a maioria dos trabalhadores não fazia uso de Equipamento de Proteção Individual (EPI) e atuava em condições de trabalho insalubres e sem treinamento adequado. Houve redução de cerca de 0,05% da concentração da MHb após a exposição ao diflubenzuron, com correlação inversa deste indicador de efeito com a variável fumo (R= -0,742; p=0,035). Dado que a MHb pode ser formada após exposição a diversas substâncias químicas e considerando as dificuldades na logística de execução desta análise, estudos sobre novos biomarcadores mais sensíveis e seletivos são necessários.
Cadernos Saúde Coletiva, 2014
Cad. Saúde Colet., 2014, Rio de Janeiro, 22 (1): 8-15
Ciência & Saúde Coletiva, 2002
Avaliação dos fatores de risco relacionados à exposição ao chumbo em crianças e adolescentes do Rio de Janeiro
Ciência & Saúde Coletiva, 2009
Page 1. ARTIGO ARTICLE 2039 1 Centro de Estudos da Saúde do Trabalhador e Ecologia Humana, Escola... more Page 1. ARTIGO ARTICLE 2039 1 Centro de Estudos da Saúde do Trabalhador e Ecologia Humana, Escola Nacional de Saúde Pública, Fiocruz. Rua Leopoldo Bulhões 1480/302, Manguinhos. 21041-210 Rio de Janeiro RJ. [email protected] ...
Influência de fatores socioeconômicos na contaminação por agrotóxicos, Brasil
Revista de Saúde Pública, 2001
Objetivo A elevada utilização de agrotóxicos, sem os cuidados necessários, tem contribuído para a... more Objetivo A elevada utilização de agrotóxicos, sem os cuidados necessários, tem contribuído para a degradação ambiental eo aumento das intoxicações ocupacionais, sendo um dos principais problemas de saúde pública no meio rural brasileiro. O objetivo do trabalho é avaliar a ...

International Journal of Hygiene and Environmental Health, 2009
In Brazil, where the use of pesticide grows rapidly, studies that evaluate the impact of pesticid... more In Brazil, where the use of pesticide grows rapidly, studies that evaluate the impact of pesticide exposure on cancer incidence and mortality are very scarce. In this study, we evaluated the degree of correlation between pesticide sales in 1985 in eleven Brazilian states and cancer mortality rates during 1996-1998. Information of all cancer deaths occurred in men 30-69 years old from 1996 to 1998 were collected from National Mortality System. Single and multiple linear regression coefficients were obtained to assess the relationship between per capita sales of pesticides in 1985, specificsite cancer mortality rates (prostate, soft tissue, larynx, leukemia, lip, esophagus, lung, pancreas, bladder, liver, testis, stomach, brain, non-Hodgkin's lymphoma, and multiple myeloma) during 1996-1998, and several covariates. In addition, states were stratified into three groups according to tertiles of pesticides sales and cancer mortality rate ratios (MRR) were then calculated using first tertile as reference. Finally, a factor analysis was performed to reveal unapparent relationships between pesticide use and cancer mortality. Pesticide sales showed statistically significant correlation with the mortality rates for the cancers of prostate (r ¼ 0.69; p ¼ 0.019), soft tissue (r ¼ 0.71; p ¼ 0.015), leukemia (r ¼ 0.68; p ¼ 0.021), lip (r ¼ 0.73; p ¼ 0.010), esophagus (r ¼ 0.61; p ¼ 0.046), and pancreas (r ¼ 0.63; p ¼ 0.040). Moderate to weak correlations were observed for the cancers of larynx, lung, testis, bladder, liver, stomach, brain, and NHL and multiple myeloma. In addition, correlation between pesticide sales and specific-site cancer mortality rates was reinforced by multiple regression analysis. For all specific-sites, cancer mortality rates were significantly higher in the states of moderate (2nd tertile) and high (3rd tertile) pesticide sales, with MRR ranging from 1.11 to 5.61. Exploring hidden relationships between pesticide sales and cancer mortality in Brazil, through a factor analysis, revealed that affluence; public policies and lifestyle behaviors may explain almost 70% of the variance of the studied association. The results suggest that population exposure to pesticides in the 1980s in some Brazilian States may have been associated with selected cancer sites observed a decade later.

Association between serum levels of organochlorine pesticides and sex hormones in adults living in a heavily contaminated area in Brazil
International Journal of Hygiene and Environmental Health, 2014
Several studies have investigated the effects of organochlorine (OC) pesticides on adverse reprod... more Several studies have investigated the effects of organochlorine (OC) pesticides on adverse reproductive outcomes. However, few previous studies explored their effects on sex hormones. To examine the association between serum concentrations of OC pesticides and levels of sex hormones in adult population in a rural area in Brazil heavily contaminated with these pesticides. A cross-sectional study with 304 men and 300 women was undertaken. Wet weight serum concentrations of 19 OC pesticides (dichloro-diphenyl-trichloroethane [DDT] and hexachlorocyclohexane [HCH], among others) were determined in all participants. Testosterone levels were obtained for men and estradiol, progesterone, prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) for women. Associations between OC pesticides and sex hormones were evaluated using linear regression models. Prevalence of women with non-physiological hyperprolactinemia was 4%. After adjusting for serum lipids and confounders, heptachlor and o,p'-DDT concentrations in men were associated with lower testosterone levels, while peri- and postmenopausal women (N=77) showed inverse associations between LH and hexachlorobenzene (HCB), p,p'-DDT, p,p'-DDD (dichloro-diphenyl-dichloroethane), endosulfan 1 and 2, aldrin and mirex, as well as between FSH and p,p'-DDD, endosulfan 1 and aldrin. Premenopausal women (N=210) did not show statistically significant associations between OC pesticides and sex hormones. Inverse associations between OC pesticide concentrations and testosterone in men and LH and FSH in peri-/postmenopausal women, together with the high proportion of women with elevated prolactin, suggest that these OC compounds may have triggered anti-androgenic effects in men and estrogenic effects in women in this population.

Cholinesterase activities determination in frozen blood samples: an improvement to the occupational monitoring in developing countries
Human & Experimental Toxicology, 2000
1. Studies were carried out on rural workers in Brazil to determine the decrease in the activity ... more 1. Studies were carried out on rural workers in Brazil to determine the decrease in the activity of plasma butyrylcholinesterase (BChE), erythrocyte cholinesterase (AChE) associated with exposure to organophosphorus pesticides (OP). The goal of this work is to help prevent injury to these workers. 2. In developing countries the distance between area of pesticide use and reference laboratories is a drawback for analytical techniques, since cholinesterase activity determinations require fresh blood samples. Field methodologies can be a useful alternative to laboratory tests, however they are not as sensitive as those found in laboratories. 3. The modification of Ellman's Method presented in this paper allows blood samples to be frozen and maintain enzymatic stability: 7 days for AChE and 3 days for BChE. The proposed method is also more sensitive than Ellman's Method Modified by Magnotti (EMMM). 4. The results suggest that the Ellman Method Modified by Oliveira-Silva (EMMOS) is valid for monitoring procedures. This method represents an important contribution to the process of monitoring OP exposures, since the evaluations no longer have to be conducted near the site of OP use.
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Papers by Paula Sarcinelli