Monica Maria Bastos Paoliello

Manganese homeostasis in the nervous system

Manganese (Mn) is an essential heavy metal that is naturally found in the environment. Daily intake through dietary sources provides the necessary amount required for several key physiological processes, including antioxidant defense, energy metabolism, immune function and others. However, overexposure from environmental sources can result in a condition known as manganism that features symptomatology similar to Parkinsons disease (PD). This disorder presents with debilitating motor and cognitive deficits that arise from a neurodegenerative process. In order to maintain a balance between its essentiality and neurotoxicity, several mechanisms exist to properly buffer cellular Mn levels. These include transporters involved in Mn uptake, and newly discovered Mn efflux mechanisms. This review will focus on current studies related to mechanisms underlying Mn import and export, primarily the Mn transporters, and their function and roles in Mn‐induced neurotoxicity.

Manganese-induced parkinsonism and Parkinson’s disease: Shared and distinguishable features

Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson’s disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for manganism and idiopathic Parkinson’s disease (PD).

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.

Valores de referência para plumbemia em uma população urbana do Sul do Brasil

Objetivo. Descrever os valores de referencia para chumbo em sangue em uma populacao urbana do Municipio de Londrina, Estado do Parana, Brasil. Metodos. A populacao de referencia foi constituida por 520 voluntarios adultos avaliados de novembro de 1994 a dezembro de 1996. Os criterios de exclusao foram: exposicao ocupacional ao chumbo, exposicao atraves de habitos, fumar mais de 10 cigarros por dia e morar perto de industrias ou de locais que utilizam o chumbo em seus processos produtivos. Tambem foram excluidos individuos com valores de exames clinicos e laboratoriais fora da normalidade, doencas cronicas e disturbios cardiovasculares. Os teores de chumbo em sangue foram determinados por espectrofotometria de absorcao atomica com chama de ar-acetileno. O limite de deteccao obtido foi 1,23 mig/dL. Apos as analises de chumbo em sangue, foram determinados valor minimo, primeiro quartil, mediana, terceiro quartil e valor maximo; media geometrica; intervalo de confianca de 95%; intervalo experimental; e valor de referencia. Resultados. Os valores de referencia para plumbemia variaram de 1,20 a 13,72 mig/dL. A media geometrica foi igual a 5,5 mig/dL. Conclusoes. Em geral, os valores obtidos no presente estudo sao mais baixos do que aqueles obtidos em outros paises. Estudos adicionais deveriam enfocar a obtencao de valores de referencia em outras populacoes brasileiras que vivem em regioes mais industrializadas.

Environmental Contamination and Human Exposure to Lead in Brazil

Adverse effects caused by environmental lead pollution are well recognized. Being a widespread agent in the environment and a major harmful element to organic systems, mostly to children, lead has been investigated all over the world, aiming to improve measures regarding its control. The purpose of this chapter is to present a review of the situation of production, uses, assessment of exposure, and adverse effects from environmental lead contamination in Brazil. It also presents aspects of Brazilian legislation setting up maximum permissible levels of lead in several environmental compartments such as surface and drinking water, soils, sediment, urban air, and also in commercially sold food, vegetables, fish, and meat, in an effort to control industrial emissions. Epidemiological investigations on childrens lead exposure around industrial and mining areas are revised, showing that many situations where lead contamination is potentially present still need to be addressed by governmental agencies. In Brazil, lead was withdrawn from gasoline by the end of the 1980s, and the last lead mining and primary smelting plant was closed in 1995, leaving residual environmental lead contamination, which has recently been investigated using a multidisciplinary approach. Nevertheless, there are hundreds of small secondary battery recycling plants all over the country, running smelting facilities that produce local urban areas of lead contamination.

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.

Acute intentional and accidental poisoning with medications in a southern Brazilian city.

The expansion of the pharmaceutical market in the 20th century led to important changes in the consumption of medications worldwide. The objective of the current study was to analyze acute intentional and accidental poisoning with medications according to factors related to the individual, the poisoning, and the drug involved. This was a cross-sectional study that collected secondary data on all cases of acute poisoning with medications reported from 2003 to 2004 by the Poison Control Center at the Regional University Hospital in Maringá, Paraná State, Brazil. We studied a total of 546 cases of acute poisoning with medications. Females predominated among intentional cases (79.8%), and the 0-9-year age bracket was the most common among accidental cases (51.9%). The most frequently involved drugs were those acting on the central nervous system (57.2%), predominantly those requiring controlled prescriptions, especially among the intentional cases (66.2%). The results demonstrate the characteristics of acute poisoning from medications in Maringá, confirming the need for preventive measures that contribute to the rational use of medications.

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.

Toxicology of lead and its damage to mammalian organs

The toxicity of lead has been appreciated for centuries. Lead is a commonly used metal in industrialized nations, which results in the release of lead into the environment. Governmental agencies regulate the amount of lead permissible for workers to be exposed to; however, unregulated environmental lead exposure is a high concern. While essential metals have physiologic roles, there are no health benefits from lead intake. In this chapter, we discuss sources of lead exposure, the absorption, distribution, and elimination of lead from the human body, and molecular mechanisms of lead-induced toxicity. We also discuss the evidence on the association between lead exposure and blood pressure, and the influence of sociodemographic, lifestyle and environmental determinants of lead exposure in the general population. We highlight the effects on the nervous system, kidney, immune system, blood, reproductive system, and bones.

N-acetil-β-D-glicosaminidase como biomarcador precoce de disfunção renal para a exposição ocupacional ao chumbo inorgânico

OBJECTIVE: This study aimed to verify the enzymatic activity of N-acetyl-β-D-glucosaminidase (NAG) as a possible early biomarker of renal dysfunction due to occupational exposure to inorganic lead. MATERIALS AND METHODS: We selected a group of 30 males that had been exposed to inorganic lead in a battery factory in the state of Parana. This group comprised those employees whose blood lead levels were below 40 mg/dl. The control group consisted of 15 healthy adults of similar age and gender compared with the exposed group. Blood lead concentrations, d-aminolevulinic acid levels and urinary NAG activity were measured. RESULTS AND DISCUSSION: It was shown that urinary NAG activity was significantly higher (p < 0.05, U test of Mann-Whitney) in the exposed group in comparison to the control group, and there was a significant negative correlation (p < 0.05, Spearman Rank Order correlation) between the biological indicator of lead exposure and urinary NAG activity. CONCLUSION: The results showed that the increase of urinary NAG activity may be used as an early biomarker of the exposure to inorganic lead.